Dorothea Zucker-Franklin, M.D.

Possible role of maternal lymphocytes contained in breast milk in the development of autoimmune diseases
Cohen, AM; Pancake, BA; Zucker-Franklin, D
2005 MAR ;53(2):S389-S389, Journal of investigative medicine
— id: 51762, year: 2005, vol: 53, page: S389, stat: Journal Article,

Atlas of blood cells : function and pathology
Zucker-Franklin D; Grossi CE
Milano : Edi. Ermes, 2003,
— id: 1556, year: 2003, vol: , page: , stat: ,

Natural is not necessarily better
Zucker-Franklin, D
2003 NOV 17 ;17(22):8-8, Scientist
— id: 55423, year: 2003, vol: 17, page: 8, stat: Journal Article,

Localization of HTLV-I tax proviral DNA in mononuclear cells
Zucker-Franklin, Dorothea; Pancake, Bette A; Najfeld, Vesna
2003 Jul-Aug;31(1):1-6, Blood cells, molecules, & diseases
The tax sequence of HTLV-I is demonstrable in the skin and blood mononuclear cells of patients with mycosis fungoides, as well as in the mononuclear leukocytes of some healthy blood donors, but was not demonstrable when PCR/Southern analyses were carried out on preparations of high-molecular-weight genomic DNA. Therefore, it was postulated that tax DNA may not be integrated. To investigate this possibility fluorescence in situ hybridization was carried out on cells arrested in metaphase, using a probe containing the HTLV-I tax proviral DNA full-length open reading frame coding sequence. While metaphases prepared from C91PL cells, a cell line infected with HTLV-I, showed an abundance of chromosome-associated as well as extra-chromosomal signals, metaphases prepared with blood mononuclear cells from healthy tax sequence positive donors did not reveal any tax DNA associated with chromosomes. Such signals were readily detected extra-chromosomally. Although it has been demonstrated that transactivation of genes by gene products encoded by extra-chromosomal DNA may have nosocomial implications, whether transactivation by p40 tax generated from extra-chromosomal tax sequences is responsible for the development of neoplasia remains to be investigated
— id: 39149, year: 2003, vol: 31, page: 1, stat: Journal Article,

Prevalence of HTLV-I Tax in a subset of patients with rheumatoid arthritis
Zucker-Franklin, D; Pancake, B A; Brown, W H
2002 Mar-Apr;20(2):161-169, Clinical & experimental rheumatology
OBJECTIVE: In regions of the world where the human T cell lymphotropic virus type I (HTLV-I) is endemic, it is recognized that infection with this virus is associated with autoimmune diseases such as rheumatoid arthritis (RA). Moreover, mice transgenic for the HTLV-I Tax gene develop a disease akin to RA. The observation that about 8% of healthy American blood donors carry HTLV-I Tax in their lymphocytes (1) prompted studies to determine whether Tax positivity is more prevalent among patients with RA and if so, whether its sequence is homologous with prototypic HTLV-I Tax. This proved to be the case. Of 102 patients with RA tested, one was a carrier of HTLV-I and 25 had the Tax sequences in their mononuclear cells and antibodies to p40 Tax in their sera, while being negative for antibodies to the structural proteins of the virus. METHODS: Blood was collectedfrom 102 RA patients. Lysates of their mononuclear cells were assayed for HTLV-I Tax by PCR/Southern analysis, and in some positive cases Tax sequence analysis was performed. Antibodies to p40 Tax, the gene product of the Tax sequence, were detected by western blot assay using recombinant p40 Tax as antigen. Results Of the 102 patients tested, one proved to be a carrier of the virus, having antibodies and sequences for the viral structural proteins, gag and env in addition to p40 Tax. Twenty-five of the 101 HTLV-I/II seronegative patients carried both HTLV-I Tax sequences in their mononuclear cells and had antibodies to p40 Tax. Sequence analysis confirmed homology with HTLV-I Tax. CONCLUSION: The data show that the prevalence of HTLV-I Tax positivity among patients with RA is -3 times higher than among healthy blood donors. Since Tax is known to be involved in the development of numerous autoimmune diseases, the possibility that it is responsible for the development of RA in a subpopulation of patients with this disease is not remote
— id: 39423, year: 2002, vol: 20, page: 161, stat: Journal Article,

The role of interleukin-7 and interleukin-15 in cutaneous T-cell lymphoma
Zucker-Franklin, Dorothea
2002 May 1;99(9):3488-3488, Blood
— id: 61761, year: 2002, vol: 99, page: 3488, stat: Journal Article,

The role of human T cell lymphotropic virus type I tax in the development of cutaneous T cell lymphoma
Zucker-Franklin D
2001 Sep;941(3):86-96, Annals of the New York Academy of Sciences
Although it has been well established that the human T cell lymphotropic virus type I (HTLV-I) causes adult T cell leukemia/lymphoma (ATLL) in regions of the world where this virus is endemic, its role in the pathogenesis of cutaneous T cell lymphoma (CTCL) in the Western world has been less well established. Most patients with CTCL are negative for antibodies to the structural proteins of HTLV-I, and thus a causative role for this virus is usually dismissed. However, the Tax sequence of HTLV-I has been found in the peripheral blood mononuclear cells of practically all patients with CTCL. Such patients express Tax mRNA and have antibodies to p40Tax, the protein encoded by this sequence. Sequence analysis of a 159-bp region of Tax extracted from CTCL cells proved to be homologous with the same region prepared from a cell line infected with prototypic HTLV-I. By in situ PCR, Tax has been demonstrated in the lymphocytes infiltrating the skin as well as in the keratinocytes of such patients. Apart from the pathophysiologic and clinical interest of these studies, these observations may have therapeutic implications. In vitro, the proliferation of HTLV-I-transformed cells can be inhibited by antisense to HTLV-I Tax. Since Tax has not been identified in the normal human genome, antisense to Tax deserves serious consideration as a treatment modality for patients whose cells have been demonstrated to harborTax
— id: 26648, year: 2001, vol: 941, page: 86, stat: Journal Article,

Detection of the tax gene of HTLV-I in labial salivary glands from patients with Sjogren's syndrome and other diseases of the oral cavity [In Process Citation]
Mariette X; Agbalika F; Zucker-Franklin D; Clerc D; Janin A; Cherot P; Brouet JC
2000 May-Jun;18(3):341-347, Clinical & experimental rheumatology
OBJECTIVE: To confirm a possible association between Sjogren's syndrome (SS) and the tax gene of human T lymphotropic virus type I (HTLV-I). METHODS: We studied by PCR labial salivary glands (LSG) from 50 patients with definite SS and from 58 controls including 32 patients with LSG involved by other inflammatory processes and 26 normal LSG. Antibodies to HTLV-I and antibodies to the Tax protein were searched for in serum. RESULTS: We detected the tax gene of HTLV-I in LSG from 15/50 (30%) of patients with SS but also in specimens from 9/32 (28%) patients with LSG involved by other inflammatory processes (3/9 graft-versus-host disease, 5/19 extra-vasated cysts, 1/4 sarcoidosis) and from only 1/26 (4%) normal LSG. A 652 bp region, sequenced in 2 SS patients, was 98-98.5% homologous to the canonic sequence of tax HTLV-I. The HTLV-I gag, pol and env genes were never detected. The serum of the SS patients did not contain antibodies to HTLV-I. However, anti-Tax antibodies were detected in the serum of 18/25 (72%) SS patients, 10/10 (100%) patients positive for tax DNA in their LSG and 8/15 (53%) patients negative for tax DNA in their LSG. CONCLUSION: Our observations raise the possibility that a very low number of copies of the tax gene may be harbored innocuously in cells within the oral cavity in some healthy individuals, but that this gene may play a role as a co-factor in the development of SS or other diseases of oral cavity
— id: 15707, year: 2000, vol: 18, page: 341, stat: Journal Article,

Non-HIV Retroviral Associations with Rheumatic Disease
Zucker-Franklin D
2000 Apr;2(2):156-162, Current rheumatology reports
While the human T-cell lymphotropic virus type I (HTLV-I) is the recognized cause of adult T cell leukemia, it is also associated with non-neoplastic, ostensibly autoimmune conditions, such as tropical spastic paraparesis. Moreover,among carriers of HTLV-I, the virus is strongly implicated in the development of a type of arthritis, which resembles rheumatoid arthritis (RA). Mice transgenic for HTLV-I tax develop RA-like pathology and Sjogren's syndrome. Patients with RA and SS in HTLV-I nonendemic regions, such as the United States, are usually serologically negative for antibodies to the structural proteins of HTLV. However, they appear to harbor HTLV-I tax in their peripheral blood mononuclear cells three times as often as individuals who present as healthy blood donors. Because HTLV-I tax transactivates numerous inflammatory cytokines and is not normally found in the human genome, treatment with tax antisense oligonucleotides may provide a new therapeutic approach for selected RA patients proven to be HTLV-I 'tax only' positive
— id: 15706, year: 2000, vol: 2, page: 156, stat: Journal Article,

Transmission of human T-cell lymphotropic virus type 1 tax to rabbits by tax-only-positive human cells
Zucker-Franklin D; Pancake BA; Lalezari P; Khorshidi M
2000 Mar;7(2):274-278, Clinical & diagnostic laboratory immunology
The human T-cell lymphrotropic virus type 1 (HTLV-1) is causally related to adult T-cell leukemia and lymphoma and the neurodegenerative diseases tropical spastic paraparesis and HTLV-1-associated myelopathy. In the United States the prevalence of infection has been estimated to range from 0.016 to 0.1% on the basis of serologic tests for antibodies to the viral structural proteins. Blood from donors positive for antibodies to HTLV-1 or HTLV-2 is not used for transfusion. However, patients with the cutaneous T-cell lymphoma mycosis fungoides (MF) are HTLV-1 and -2 seronegative yet harbor proviral sequences identical to those that encode the HTLV-1 transactivating and transforming gene product p40tax in their peripheral blood mononuclear cells (PBMCs), and they usually have antibodies to p40(tax). Moreover, a study of 250 randomly selected blood donors revealed that approximately 8% of these seronegative individuals also had HTLV-1 tax sequences and antibodies to p40(tax), while they lacked sequences and antibodies related to gag, pol, or env. Thus, it seemed important to determine whether the 'tax-only' state can be transmitted by transfusion. To this end, PBMCs from HTLV-1 and -2 seronegative tax-only-positive MF patients or from healthy tax-only-positive blood donors were injected into adult rabbits, an established animal model for HTLV-1 infection. The PBMCs of all injected rabbits became tax sequence positive. These observations suggest that HTLV-1 tax can be transmitted by tax-only-positive mononuclear cells
— id: 57552, year: 2000, vol: 7, page: 274, stat: Journal Article,

Platelet production in the pulmonary capillary bed: new ultrastructural evidence for an old concept
Zucker-Franklin D; Philipp CS
2000 Jul;157(1):69-74, American journal of pathology
Although there is substantial evidence indicating that platelets are released from megakaryocytes in the capillary bed of the lung, this concept has not been universally accepted because much of the evidence has been indirect. To more definitively substantiate that platelet production takes place in the lungs, megakaryocyte and platelet production was accelerated in mice by phlebotomy or by administration of thrombopoietin, and ultrastructural analysis was performed on lung specimens. Intact megakaryocytes, megakaryocyte fragments with numerous demarcated platelet fields, dissociating intact platelets, and denuded megakaryocyte nuclei were seen in the pulmonary capillaries of mice. In addition, some megakaryocyte nuclei exhibited the morphological counterpart of apoptosis. These observations provide evidence for platelet release in the capillary bed of the lungs during stimulated as well as reactive thrombocytosis without precluding observations that some 'proplatelets' form in the sinusoids of the bone marrow before transmigration of intact megakaryocytes into the circulation
— id: 11624, year: 2000, vol: 157, page: 69, stat: Journal Article,

Passively acquired antibodies to HTLV-I p40Tax by blood transfusion or administration of intravenous immunoglobulin (IVIG)
Zucker-Franklin, D; Benjamin, LJ; Bussel, JB; Pancake, BA
2000 NOV 16 ;96(11):619A-+, Blood
— id: 55235, year: 2000, vol: 96, page: 619A, stat: Journal Article,

Absence of human T-lymphotropic virus type I tax sequences in a population of normal blood donors in the Baltimore, MD/Washington, DC, area: results from a multicenter study
Cowan EP; Nemo GJ; Williams AE; Alexander RK; Vallejo A; Hewlett IK; Lal RB; Dezzutti CS; Gallahan D; George K; Pancake BA; Zucker-Franklin D; McCurdy PR; Tabor E
1999 Aug;39(8):904-909, Transfusion
BACKGROUND: It was reported recently that sequences corresponding to the human T-lymphotropic virus type I (HTLV-I) tax gene were detected in peripheral blood mononuclear cells from 8 to 11 percent of healthy blood donors without detectable antibodies to HTLV-I. A multicenter blind study was conducted to determine if these results could be independently confirmed. STUDY DESIGN AND METHODS: Specimens were collected from 100 anti-HTLV-I-negative healthy blood donors and from 11 anti-HTLV-I- or anti-HTLV-II-positive individuals. All samples were coded and distributed to each of four independent testing laboratories for polymerase chain reaction analysis to detect sequences of the HTLV-I or HTLV-II tax gene, using detailed procedures specified by the laboratory reporting the original observation. Each laboratory also tested a dilution panel of a plasmid containing HTLV-I tax to determine the analytical sensitivity of the procedure. RESULTS: The analytical sensitivity of the screening methods permitted detection of as few as 1 to 10 copies of the tax gene. However, HTLV-I tax sequences could not be detected in any of the anti-HTLV-I-negative blood donors at more than one test site. CONCLUSION: HTLV-I tax sequences appear not to be present in this population of 100 blood donors negative for anti-HTLV-I
— id: 15708, year: 1999, vol: 39, page: 904, stat: Journal Article,

Hypopigmented mycosis fungoides associated with human T cell lymphotropic virus type I tax in a pediatric patient
Zucker-Franklin D; Kosann MK; Pancake BA; Ramsay DL; Soter NA
1999 May;103(5 Pt 1):1039-1045, Pediatrics
— id: 6106, year: 1999, vol: 103, page: 1039, stat: Journal Article,

Localization of HTLV-I tax in the nuclei of mononuclear leukocytes of healthy HTLV-I/II seronegative individuals
Zucker-Franklin, D; Pancake, BA; Najfeld, V
1999 NOV 15 ;94(10):440A-440A, Blood
— id: 54778, year: 1999, vol: 94, page: 440A, stat: Journal Article,

Platelet production in the pulmonary capillary bed: New evidence for an old concept
Zucker-Franklin, D; Philipp, CS
1999 AUG ;37(5):500-500, Thrombosis & haemostasis
— id: 54724, year: 1999, vol: 37, page: 500, stat: Journal Article,

Transendothelial migration of megakaryocytes in response to SDF-1 is mediated through VE-Cadherin resulting in apoptosis of megakaryocytes
Hamada, T; Liao, F; Hicklin, D; Witte, L; Bohlen, P; Dejana, E; Zucker-Franklin, D; Nachman, RL; Moore, MAS; Rafii, S
1998 NOV 15 ;92(10):585A-585A, Blood
— id: 53631, year: 1998, vol: 92, page: 585A, stat: Journal Article,

Detection of anti-tax HTLV-I antibodies in serum from patients with Sjogren's syndrome
Mariette, X; Zucker-Franklin, D; Agbalika, F; Brouet, JC
1998 SEP ;41(9):S326-S326, Arthritis & rheumatism
— id: 53748, year: 1998, vol: 41, page: S326, stat: Journal Article,

Prevalence and possible clinical implications of the HTLV-I tax carrier state
Pancake, BA; Zucker-Franklin, D
1998 MAR ;46(3):218A-218A, Journal of investigative medicine
— id: 53496, year: 1998, vol: 46, page: 218A, stat: Journal Article,

The effects of Mpl-ligand, interleukin-6 and interleukin-11 on megakaryocyte and platelet alpha-granule proteins
Philipp CS; Remmler J; Zucker-Franklin D
1998 Dec;80(6):968-975, Thrombosis & haemostasis
Thrombopoietin (Mpl ligand), interleukin-6 (IL-6), and interleukin-11 (IL-11) differ in their effects on megakaryocyte maturation and development. In the present study, the impact of these thrombocytopoietic cytokines on biochemical and structural granule and membrane components was examined. Western blotting was performed on equivalent amounts of isolated megakaryocyte or platelet protein and the relative intensities of the enhanced chemiluminescent-visualized bands were quantitated by densitometry. Megakaryocyte growth and development factor (MGDF), a recombinant thrombopoietin-related molecule, significantly increased megakaryocyte fibronectin (72%), thrombospondin (55%), von Willebrand factor (28%) and p-selectin (CD62p) (37%) when compared to equivalent amounts of protein from saline-treated controls (p<0.01). Megakaryocyte fibrinogen was not increased. Ultrastructurally, there was a marked increase in ribosomes and rough endoplasmic reticulum even in mature-appearing megakaryocytes. Platelets from MGDF-treated mice showed small increases in fibronectin (8%), and CD62p (18%), but did not show increases in other measured alpha-granule proteins. Neither IL-6 nor IL-11 increased megakaryocyte or platelet alpha-granule proteins over levels observed in saline controls. IL-11 treated megakaryocytes, while also exhibiting an increase in ribosomes, were characterized by prominent cytoplasmic fragmentation. The study demonstrates the impact of Mpl ligand in increasing synthesized megakaryocyte alpha-granule proteins and of IL-11 in promoting megakaryocyte fragmentation
— id: 15709, year: 1998, vol: 80, page: 968, stat: Journal Article,

Human T-cell lymphotropic virus type 1 tax among American blood donors
Zucker-Franklin D; Pancake BA
1998 Nov;5(6):831-835, Clinical & diagnostic laboratory immunology
In the United States, all blood used for transfusion is tested for the presence of antibodies to the structural components of the human T-cell lymphotropic viruses types 1 and 2 (HTLV-1 and -2). Based on such serologic tests, the prevalence of HTLV-1 infection is estimated to range from 0.016 to 0.1%. As a consequence of studies of patients with mycosis fungoides and some of their healthy relatives who are antibody negative but were found to carry the tax sequence of HTLV-1 in their lymphocytes and who had antibodies to the p40(tax) protein, a study was undertaken to determine the prevalence of the 'tax-only' state in 250 healthy blood donors and other volunteers. Using PCR and Southern analysis for cell lysates and using Western blotting for plasmas, 8.6% of the blood donors proved to be tax sequence positive and antibody positive. Sequence analysis of specimens from 22 individuals proved that 20 of the sequences were homologous with that of HTLV-1 while 2 resembled the HTLV-2 sequence. The latter were obtained from volunteers of Indian origin. The possible clinical significance of the tax-only carrier state is discussed
— id: 56398, year: 1998, vol: 5, page: 831, stat: Journal Article,

White cell reduction by filtration may significantly decrease human T-lymphotropic virus type 1 Tax sequences and Tax-encoded proteins in blood used for transfusion
Zucker-Franklin D; Pancake BA
1998 Mar;38(3):317-318, Transfusion
— id: 57299, year: 1998, vol: 38, page: 317, stat: Journal Article,

Evidence for transmission of defective human T cell lymphotropic virus type I(HTLV-I) by blood transfusion
Zucker-Franklin, D; Pancake, BA; Lalezari, P; Khorshidi, M
1998 NOV 15 ;92(10):52A-52A, Blood
— id: 53625, year: 1998, vol: 92, page: 52A, stat: Journal Article,

HTLV-I provirus in seronegative healthy blood donors
Zucker-Franklin D; Gorman JG
1997 Apr 5;349(9057):999-999, Lancet
— id: 15710, year: 1997, vol: 349, page: 999, stat: Journal Article,

Reexamination of human T cell lymphotropic virus (HTLV-I/II) prevalence
Zucker-Franklin D; Pancake BA; Marmor M; Legler PM
1997 Jun 10;94(12):6403-6407, Proceedings of the National Academy of Sciences of the United States of America
In the United States, blood donors are being screened for infection with human T cell lymphotropic viruses I and II (HTLV-I/II) by serologic means, which detect antibodies to the structural proteins of these viruses. Because patients with mycosis fungoides (MF) usually do not have such antibodies even though their cells harbor HTLV-I Tax and/or pol proviral sequences, it was questioned whether the prevalence of HTLV infection among healthy blood donors may also be underestimated by current means of testing. To examine this possibility, a study on specimens of relatives of mycosis fungoides patients (MFR) was begun. In addition, to collect data more expeditiously, a cohort of former injection drug users (IDUs) was tested by routine serologic methods, as well as by PCR/Southern blot analysis for Tax, pol, and gag proviral sequences and Western blot analysis for antibodies to the Tax gene product. To date, 6/8 MFRs and 42/81 (51.8%) of HIV-negative IDUs proved to be positive for HTLV, whereas routine serology identified none of the MFR and only 18/81 (22.2%) of the IDUs. Among the latter test subjects, the incidence of HTLV-I also proved to be 10 times higher than expected. Therefore, it is likely that among healthy blood donors infection with HTLV-I/II is more prevalent than is currently assumed. Since Tax is the transforming sequence of HTLV-I/II, testing for Tax sequences and antibodies to its gene product may be desirable in blood transfusion and tissue donor facilities
— id: 57010, year: 1997, vol: 94, page: 6403, stat: Journal Article,

Immunophenotypic identification of Sezary cells in peripheral blood
Bogen SA; Pelley D; Charif M; McCusker M; Koh H; Foss F; Garifallou M; Arkin C; Zucker-Franklin D
1996 Dec;106(6):739-748, American journal of clinical pathology
Despite anecdotal literature that Sezary cells express the CD4+ CD7- immunophenotype, no formal validation has been published establishing the use of this immunophenotype for clinical or experimental purposes. Consequently, the only method presently available for Sezary cell identification is nuclear contour analysis, a labor-intensive procedure not generally available at most major medical centers. In this study, the accuracy of CD4+ CD7- subset quantitation for the identification of Sezary cells was examined. The study found that the percentage of CD4+ CD7- cells is elevated in many Sezary syndrome/MF patients relative to normal, healthy individuals. In addition, CD4+ CD7- enumeration correlates with enumeration by nuclear contour analysis in most patients (11 of 15) with elevated CD4/CD8 ratios. The CD4+ CD7- subset also correlates with the expression of other aberrant immunophenotypes, such as CD3low or CD4low. Lastly, CD4+ CD7- subset quantitation correlates with the number of clonal T lymphocytes, as measured using V beta-specific T-cell receptor monoclonal antibodies. The study found this method to be exceptionally accurate, with two caveats: (1) the absence of an expanded CD4+ CD7- subset in patients with a normal CD4/CD8 ratio is uninformative; and (2) in approximately 25% of patients with an elevated CD4/CD8 ratio, the Sezary cells are CD7+
— id: 15711, year: 1996, vol: 106, page: 739, stat: Journal Article,

Localization of human T-cell lymphotropic virus-1 tax proviral sequences in skin biopsies of patients with mycosis fungoides by in situ polymerase chain reaction
Khan ZM; Sebenik M; Zucker-Franklin D
1996 Apr;106(4):667-672, Journal of investigative dermatology
The histopathologic diagnosis of mycosis fungoides (MF), even when clinical manifestations of the disease seem convincing, is often tenuous. The observation that practically all patients with MF harbor human T cell lymphotropic virus type I (HTLV-I) proviral sequences in their circulating lymphocytes raised the possibility that such viral footprints could be detected in their cutaneous infiltrates. Application of in situ polymerase chain reaction (PCR) to skin biopsies of 11 of 12 patients demonstrated this assumption to be correct. In addition, cells suspected to be keratinocytes were also positive. None of 10 skin biopsies from a variety of sources used as controls, nor 3 lymph node biopsies from patients with B-cell lymphomas, showed any HTLV proviral sequences on in situ PCR. On the basis of these observations, it is concluded that in situ PCR carried out on skin biopsies of patients with presumptive MF may help to established the diagnosis
— id: 7010, year: 1996, vol: 106, page: 667, stat: Journal Article,

Demonstration of antibodies to human T-cell lymphotropic virus-I tax in patients with the cutaneous T-cell lymphoma, mycosis fungoides, who are seronegative for antibodies to the structural proteins of the virus
Pancake BA; Wassef EH; Zucker-Franklin D
1996 Oct 15;88(8):3004-3009, Blood
Although most patients with the cutaneous T-cell lymphoma, mycosis fungoides (MF), are seronegative for human T-cell lymphotropic virus-I or -II (HTLV-I/II) when tested by assays that measure only antibodies to the viral structural proteins, the majority of such patients harbor HTLV-I-related pol and tax proviral sequences that encode proteins not included in routinely used serologic tests. Tax mRNA has also been detected in their peripheral blood mononuclear cells (PBMC). Therefore, it seemed possible that these patients have antibodies to the tax protein. To investigate this, enzyme-linked immunosorbent assays (ELI-SAs) and Western blot assays were set up, using as antigens the full-length HTLV-I tax cloned from the prototypic HTLV-I-infected cell line, C91PL, and from PBMC of a MF patient, as well as a synthetic peptide made to the carboxy-terminal 20 amino acids of tax-I. Of 60 MF patients whose PBMC were shown to be positive for tax proviral DNA and mRNA, 50 (83%) were shown to have tax antibodies. The antigen derived from the MF patient was most useful in detecting such antibodies. These results demonstrate the need for including other HTLV-related antigens in addition to gag and env in serologic tests used to identify HTLV-infected individuals. The findings underscore the fact that individuals considered seronegative on the basis of currently used tests can be infected with HTLV
— id: 12514, year: 1996, vol: 88, page: 3004, stat: Journal Article,

The difficulty of detecting HTLV-1 proviral sequences in patients with mycosis fungoides
Pancake BA; Zucker-Franklin D
1996 Dec 1;13(4):314-319, Journal of acquired immune deficiency syndromes & human retrovirology
Although most patients with cutaneous T cell lymphomas, including mycosis fungoides (MF) and its leukemic variant, the Sezary syndrome, are seronegative for antibodies to the human T cell lymphotropic viruses (HTLV-I/II), it has recently been shown that > 95% of such patients harbor proviral DNA sequences related to the region of the HTLV genome that encodes the transregulatory/transforming gene, tax. However, the demonstration of HTLV sequences, even after amplification by polymerase chain reaction (PCR), has not been universally successful, and some investigators continue to question this observation. In an effort to resolve this controversy, we have compared published methodologies that have been less successful with techniques currently used in this laboratory. Major differences were found in (a) the nature of the cells used [freshly isolated versus cultured peripheral blood mononuclear cells (PBMC)] and (b) the methods used to prepare samples for PCR (whole cell lysates versus DNA extracts). PBMC from 10 different MF patients and the healthy daughter of 1 of the patients were subjected to comparative analyses. While all of the PBMC lysates were positive, the DNA extract from only one of these individuals revealed HTLV tax sequences. Studies were also conducted comparing cell lysates and DNA extracts of cultured cells derived from tax sequence-positive PBMC from seven different MF patients. The cells from four of the seven were shown to have retained tax sequences after varying times in culture, when whole-cell lysates were used as targets for PCR amplification and Southern analysis, whereas none of the DNA extracts were positive. It appears that the use of whole-cell lysates instead of DNA extracts and the use of fresh instead of cultured cells greatly enhance the ability to detect HTLV-1 tax sequences in specimens from MF patients
— id: 12462, year: 1996, vol: 13, page: 314, stat: Journal Article,

Determination of the true prevalence of infection with the human T-cell lymphotropic viruses (HTLV-I/II) may require a combination of biomolecular and serological analyses
Pancake BA; Zucker-Franklin D; Marmor M; Legler PM
1996 Nov;108(6):444-448, Proceedings of the Association of American Physicians
Infection with the human T-cell lymphotropic virus types I and II (HTLV-I/II) usually is determined by tests that detect antibodies to the viral structural proteins. However, recent studies revealed that patients with mycosis fungoides have proviral DNA sequences related to the HTLV transactivating-transforming gene tax, without having antibodies to the virus. These results raised the possibility that the prevalence of HTLV infection in the general population of the United States also may be underestimated. To reassess the prevalence of HTLV-I/II infection effectively, a population at increased risk for infection (i.e., a cohort of injection drug users [IDUs]) was studied. Paired sera and peripheral blood mononuclear cells (PBMCs) from 81 IDUs were subjected to testing by Western blot analysis for antibodies to the viral structural proteins gag and env and by polymerase chain reaction (PCR) Southern analysis to detect gag, pol and tax proviral DNA sequences. Western blot assays showed 1 of 81 IDUs to be positive for HTLV-I, 14 to be positive for antibodies to HTLV-II, and 3 to be HTLV-serotype indeterminate. When whole-cell lysates of PBMCs from these individuals were subjected to PCR and Southern analysis. 39 of 81 were found to have HTLV-related sequences. A total of nine IDUs were found to be infected with HTLV-I, a figure nearly 10 times higher than that estimated by serology alone. Bio-molecular analysis showed HTLV-II-specific proviral sequences in 21 IDUs. Three individuals were seropositive for HTLV-II but lacked PCR evidence of gag, pol and tax sequences. Thus, the overall prevalence of HTLV infection among this cohort was 59% (43 of 81) (i.e., more than twice the frequency predicted by serology, 18 of 81 or 22%). These results indicate that it may be necessary to incorporate biomolecular as well as serological methodologies to identify all persons infected with these retroviruses
— id: 9094, year: 1996, vol: 108, page: 444, stat: Journal Article,

Determination of the true prevalence of infection with the human T cell lymphotropic viruses (HTLV-I/II) may reouire a combination of biomolecular and serologic analyses
Pancake, BA; ZuckerFranklin, D; Marmor, M
1996 MAR ;44(3):A250-A250, Journal of investigative medicine
— id: 52956, year: 1996, vol: 44, page: A250, stat: Journal Article,

Increases in megakaryocyte (MK) alpha granule proteins occur with the administration of thrombopoietin but not with interleukin-11 (IL-11) or interleukin-6 (IL-6)
Philipp, CS; Remmler, J; Cisar, LA; Haluska, P; ZuckerFranklin, D
1996 NOV 15 ;88(10):121-121, Blood
— id: 52706, year: 1996, vol: 88, page: 121, stat: Journal Article,

Megakaryocyte and platelet structure in thrombocytopoiesis: the effect of cytokines [In Process Citation]
Zucker-Franklin D
1996 ;14 Suppl 1:1-17, Stem cells
This paper presents an overview of selected data which the author considers crucial to an understanding of structure/function relationships of megakaryocytes (MK) and platelets. The observation that platelet territories form within the MK cytoplasm and that, therefore, MK and platelet plasma membranes need not be structurally or antigenically identical is substantiated on the basis of results obtained with a variety of experiments. While the predominant site of MK fragmentation is still debated, it is generally accepted that such terms as 'proplatelets,' 'giant platelets' or 'megathrombocytes' refer to MK fragments consisting of more than one platelet territory. It is suggested that such fragments be called 'compound' platelets to convey a unifying concept. The terms 'young' or 'immature' could be reserved for platelets which still contain ribosomes, rough endoplasmic reticulum or other organelles not usually seen in circulating platelets. Finally, the structure changes induced by cytokines, such as interleukin 3 (IL-3), IL-6, IL-11 and thrombopoietin have been illustrated
— id: 11461, year: 1996, vol: 14 Suppl 1, page: 1, stat: Journal Article,

Effect of thrombopoietin on the development of megakaryocytes and platelets: an ultrastructural analysis
Zucker-Franklin D; Kaushansky K
1996 Sep 1;88(5):1632-1638, Blood
Megakaryocytopoiesis and platelet production can be assessed with reasonable accuracy by quantitative and functional analyses of circulating platelets. The evaluation of megakaryocytopoiesis in culture has remained unsatisfactory, particularly because platelet production is rarely observed. In mouse culture systems, megakaryocytes have been identified almost entirely by measurements of acetyl cholinesterase, size, and ploidy without concomitant assessment of maturation based on such criteria as the formation of granules, demarcation membranes, and cytoplasmic fragmentation. The availability of various thrombopoietic cytokines, in particular thrombopoietin (TPO), and their imminent clinical use has made a more detailed understanding of their effect on differentiation and maturation of the MK lineage more urgent. Therefore, ultrastructural analyses were performed on megakaryocyte-depleted serum-free mouse bone marrow cultures in the presence of TPO alone, TPO plus other cytokines, or under conditions in which TPO and/or other cytokines were blocked with neutralizing agents. These studies show that, while cytokines that use the gp130 receptor subunit may function synergistically with TPO, in the absence of TPO, such cultures do not yield morphologically recognizable MK. On the other hand, TPO alone is able to drive MK to full maturation as evidenced by the generation of granules, demarcation membranes, and cytoplasmic fragmentation into platelets
— id: 56902, year: 1996, vol: 88, page: 1632, stat: Journal Article,

HTLV-I and CTCL: The link is missing - Reply
ZuckerFranklin, D
1996 NOV ;107(5):784-784, Journal of investigative dermatology
— id: 52753, year: 1996, vol: 107, page: 784, stat: Journal Article,

Further definition of the cellular target of human thrombopoietin
Bruno, E; Murray, LJ; ZuckerFranklin, D; Fu, WC; Gearing, D; Hoffman, R
1995 NOV 15 ;86(10):1449-1449, Blood
— id: 53119, year: 1995, vol: 86, page: 1449, stat: Journal Article,

Interferon alpha (IFN) and AZT in patients with advanced mycosis fungoides (MF)
Frazein A; Hymes K; Zucker-Franklin D
1995 ;14:A1279-A1279, Proceedings (American Society of Clinical Oncology)
The incidence of MF has increased almost 3-fold in the past decade; chemotherapeutic agents in current use have proven to be of little benefit in advanced disease. Because of recent evidence that MF is an HTLV-I associated condition (NEJM 239:580, 1993) AZT and IFN, two agents known for their antiviral effects were used in this protocol. All patients (pts) had advanced MF and had detectable HTLV-I proviral sequences in their peripheral blood mononuclear cells. Pts were treated with IFN at 3 MU/day SC TIW and this dose was escalated to 10 MU TIW as tolerated. AZT was administered 200 mg po q 4 hr. Responses were assessed by clinical improvement (ie, relief of pruritus and erythroderma) and decrease in Sezary cell count assessed ultrastructurally. To date, 13 pts have been entered on this protocol. The average age was 61 and all pts had received at least two previous treatments for MF. 6 pts responded with dramatic relief of pruritus, 3 had stable disease, 3 had progressive disease and 1 pt was not evaluable (IFN given less than 3 wk). Favorable responses of 5 pts continues with average duration of greater than 15 mo. The response of the 6th pt lasted 14 mo. AZT was used in only 5 pts because the drug's untoward side effects did not seem warranted. AZT was discontinued in all these pts due to unacceptable toxicity (headache, nausea, myopathy). The Sezary cell count performed by EM corresponded with clinical improvement and appears to be the best objective criterion to assess response. In the 3 pts with the most dramatic improvement the count dropped by 36-72%, average 60%. Stable disease correlated with a stable Sezary cell count. In conclusion, IFN was well tolerated in pts with advanced MF and produced dramatic and durable responses. A larger multicenter trial is now needed to confirm these results. (C) American Society of Clinical Oncology 1997
— id: 6020, year: 1995, vol: 14, page: A1279, stat: Journal Article,

Thrombopoietin, the Mp1 ligand, is essential for full megakaryocyte development
Kaushansky K; Broudy VC; Lin N; Jorgensen MJ; McCarty J; Fox N; Zucker-Franklin D; Lofton-Day C
1995 Apr 11;92(8):3234-3238, Proceedings of the National Academy of Sciences of the United States of America
The development of megakaryocytes (MKs) from their marrow precursors is one of the least understood aspects of hematopoiesis. Current models suggest that early-acting MK colony-stimulating factors, such as interleukin (IL) 3 or c-kit ligand, are required for expansion of hematopoietic progenitors into cells capable of responding to late-acting MK potentiators, including IL-6 and IL-11. Recently, the Mp1 ligand, or thrombopoietin (Tpo), has been shown to display both MK colony-stimulating factor and potentiator activities, at potencies far greater than that of other cytokines. In light of these findings, we tested the hypothesis that Tpo is absolutely necessary for MK development. In this report we demonstrate that neutralizing the biological activity of Tpo eliminates MK formation in response to c-kit ligand, IL-6, and IL-11, alone and in combination, but that these reagents only partially reduce MK formation in the presence of combinations of cytokines including IL-3. However, despite the capacity of IL-3 to support the proliferation and initial stages of MK differentiation, elimination of Tpo prevents the full maturation of IL-3-induced MK. These data indicate that two populations of MK progenitors can be identified: one that is responsive to IL-3 but can fully develop only in the presence of Tpo and a second that is dependent on Tpo for both proliferation and differentiation. Thus, our results strongly suggest that Tpo is the primary regulator of MK development and platelet production
— id: 15713, year: 1995, vol: 92, page: 3234, stat: Journal Article,

The cutaneous T cell lymphoma, mycosis fungoides, is a human T cell lymphotropic virus-associated disease. A study of 50 patients
Pancake BA; Zucker-Franklin D; Coutavas EE
1995 Feb;95(2):547-554, Journal of clinical investigation
For nearly two decades it has been suspected that the cutaneous T cell lymphoma, mycosis fungoides (MF), and its leukemic variant, the Sezary syndrome, are caused by the human T lymphotropic virus (HTLV-I/II). Arguments against this concept included the finding that only a small number of MF patients have antibodies to HTLV-I/II and that attempts to detect proviral sequences by mere Southern hybridization of extracted DNA usually met with failure. However, we have reported repeatedly that HTLV-like particles emerge in blood mononuclear cell (PBMC) cultures of practically all patients with this disease. In several instances, the particles were identified as HTLV by immunoelectron microscopy as well as biomolecular analysis. With the assumptions that the virus in MF patients may have become detection by Southern hybridization alone, the extracts of freshly isolated PBMC of 50 consecutive patients were subjected to combined PCR/Southern analysis. Here we report the presence of HTLV pol and/or tax proviral sequences in 46 out of 50 (92%) of the patients tested. In addition, five of the patients, who lacked antibodies to HTLV-I/II structural proteins, were found to be seropositive for tax. It thus seems reasonable to conclude that MF/Sezary syndrome is an HTLV-associated disease and that lack of an immune response does not preclude infection with this type of virus
— id: 12804, year: 1995, vol: 95, page: 547, stat: Journal Article,

Patients with cutaneous T cell lymphoma (CTCL), thought to be seronegative for HTLV-1, frequently have antibodies to HTLV tax
Pancake, BA; Wassef, EH; ZuckerFranklin, D
1995 NOV 15 ;86(10):1073-1073, Blood
— id: 53116, year: 1995, vol: 86, page: 1073, stat: Journal Article,

Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoietin/MGDF in megakaryocyte development
Shivdasani RA; Rosenblatt MF; Zucker-Franklin D; Jackson CW; Hunt P; Saris CJ; Orkin SH
1995 Jun 2;81(5):695-704, Cell
Despite the importance of blood platelets in health and disease, the mechanisms regulating their formation within megakaryocytes are unknown. We generated mice lacking the hematopoietic subunit (p45) of the heterodimeric erythroid transcription factor NF-E2. Unexpectedly, NF-E2-/- mice lack circulating platelets and die of hemorrhage; their megakaryocytes show no cytoplasmic platelet formation. Though platelets are absent, serum levels of the growth factor thrombopoietin/MGDF are not elevated above controls. Nonetheless, NF-E2-/- megakaryocytes proliferate in vivo in response to thrombopoietin administration. Thus, as an essential factor for megakaryocyte maturation and platelet production, NF-E2 must regulate critical target genes independent of the action of thrombopoietin. These findings provide insight into the genetic analysis of megakaryocyte maturation and thrombopoiesis
— id: 15712, year: 1995, vol: 81, page: 695, stat: Journal Article,

Interaction of human immunodeficiency virus type 1, human T-cell leukemia/lymphoma virus type I (HTLV-I), and HTLV-II with in vitro-generated dendritic cells
Zucker-Franklin D; Fraig M; Grusky G
1995 May;2(3):343-348, Clinical & diagnostic laboratory immunology
Although it is known that impairment of dendritic cells (DC) plays a role in the pathogenesis and immunosuppression of retrovirus-associated diseases, it is not clear whether, or to what extent, these antigen-presenting cells themselves become infected. The realization that the cells can be generated in vitro in larger numbers than can be isolated from circulating blood or bone marrow raised the possibility that they could be used for therapeutic purposes. Therefore, we investigated whether DC generated in vitro from CD34 precursors are susceptible to infection when cocultured with human immunodeficiency virus type 1- or human T-cell leukemia/lymphoma virus-infected cell lines. While there appears to be a remarkable affinity of the viruses for the plasma membranes of the DC, interiorization or budding was not observed in 30 experiments carried out under a variety of conditions
— id: 6799, year: 1995, vol: 2, page: 343, stat: Journal Article,

INTERACTION OF HIV-I, HTLV-I AND HTLV-II WITH IN-VITRO-GENERATED DENDRITIC CELLS
ZUCKERFRANKLIN, D
1995 MAR 10 ;14(1-6):36-36, Journal of cellular biochemistry
— id: 86740, year: 1995, vol: 14, page: 36, stat: Journal Article,

THE EFFECT OF THROMBOPOIETIN ON THE MATURATION DIFFERENTIATION OF MEGAKARYOCYTES - AN ULTRASTRUCTURAL ANALYSIS
ZUCKERFRANKLIN, D; KAUSHANSKY, K
1995 JUN ;73(6):1073-1073, Thrombosis & haemostasis
— id: 86733, year: 1995, vol: 73, page: 1073, stat: Journal Article,

ANTIBODIES TO HTLV-I IN PATIENTS WITH THE CUTANEOUS T-CELL LYMPHOMA, MYCOSIS-FUNGOIDES
PANCAKE, BA; WASSEF, EH; ZUCKERFRANKLIN, D
1994 NOV 15 ;84(10):A520-A520, Blood
— id: 52289, year: 1994, vol: 84, page: A520, stat: Journal Article,

Persistently perplexing purpuras: thrombotic thrombocytopenic purpura and immune thrombocytopenic purpura
Zucker-Franklin D
1994 Nov 1;121(9):721-721, Annals of internal medicine
— id: 15714, year: 1994, vol: 121, page: 721, stat: Journal Article,

The effect of viral infections on platelets and megakaryocytes
Zucker-Franklin D
1994 Oct;31(4):329-337, Seminars in hematology
— id: 56737, year: 1994, vol: 31, page: 329, stat: Journal Article,

The role of human T-cell lymphotropic viruses (HTLV-I and II) in cutaneous T-cell lymphomas
Zucker-Franklin D; Pancake BA
1994 Sep;13(3):160-165, Seminars in dermatology
Although an association between the human T cell lymphotropic viruses (HTLV-I and II) and cutaneous T cell lymphoma (CTCL) has long been suspected, only a minor fraction of patients with this disease have antibodies to the viral structural proteins. However, the consistent finding of HTLV-like particles in cultures of peripheral blood mononuclear cells (PBMC) from such patients has prompted a continued effort to find evidence linking the virus to this disease. Capitalizing on the increased sensitivity afforded by combining PCR amplification with detection by Southern blot hybridization, it became possible to demonstrate HTLV tax and/or pol proviral sequences in freshly isolated PBMC of most patients with mycosis fungoides. These observations suggest a possible role of the virus in the pathogenesis of CTCL, and may impact on diagnostic and therapeutic measures in the future
— id: 12904, year: 1994, vol: 13, page: 160, stat: Journal Article,

Cutaneous disease resembling mycosis fungoides in HIV-infected patients whose skin and blood cells also harbor proviral HTLV type I
Zucker-Franklin D; Pancake BA; Friedman-Kien AE
1994 Sep;10(9):1173-1177, AIDS research & human retroviruses
Two homosexual HIV-infected patients with lymphocyte counts of < 50 presented with intense pruritis, hyperpigmentation, and skin lesions clinically suggestive of the cutaneous T cell lymphoma, mycosis fungoides. On light microscopy, the skin biopsies were difficult to interpret because of the sparseness of the lymphocytic infiltrates. However, electron microscopy revealed typical Sezary cells in the peripheral blood and skin. Cultures of blood mononuclear cells of one of the patients generated HTLV-I-like particles. Although both patients lacked antibodies to HTLV, their blood and skin specimens proved to harbor tax and pol HTLV-I proviral sequences as shown by the polymerase chain reaction and Southern blot analysis. Dual infection with HIV and HTLV should be considered in the diagnostic work-up of patients at risk, even in the absence of demonstrable antibodies. Dual infections could result in clinical manifestations and evolution of disease not anticipated in patients who harbor only one of these retroviruses
— id: 7921, year: 1994, vol: 10, page: 1173, stat: Journal Article,

CUTANEOUS T-CELL LYMPHOMA IS ANOTHER HTLV-ASSOCIATED DISEASE - A STUDY OF 65 PATIENTS
ZUCKERFRANKLIN, D; PANCAKE, BA
1994 APR ;42(2):A127-A127, Clinical research
— id: 52483, year: 1994, vol: 42, page: A127, stat: Journal Article,

HIV and HTLV-1 dual infection in a patient with mycosis fungoides (MF)
Franklin DZ; Pancake BA; Kien AE
1993 Dec 12-16;1:155-155, National Conference on Human Retroviruses & Related Infections
Dual infection with HIV and HTLV-I/II is no longer rare among homosexual and intravenous drug-abusing populations. The clinical implications of this development cannot yet be fully assessed. A synergistic effect on disease evolution seems likely. Therefore, we report here a HIV-infected homosexual male who presented with skin lesions, proven to be typical of the cutaneous T-cell lymphoma, mycosis fungoides (MF). Like most patients with MF, he was seronegative for antibodies to HTLV-I/II. Although his blood CD4+ lymphocyte count was only 6/cmm, Sezary cells were seen among his PBMC and in the skin infiltrate. Lysates of these tissues were subjected to PCR/Southern blot analysis utilizing primers SK43, 44 and probe SK45 to detect HTLV- I/II tax. Primers SK110, 111 and probe SK112 were used to detect Type-I-specific pol sequences. This revealed 159bp HTLV-I/II tax bands and 186 bp HTLV-I-pol-related bands which co-migrated with identically prepared samples of HTLV- I and HTLV-II positive controls, while cell lysates of 6 healthy volunteers run in parallel were negative. EM of cultures generated from the patient's PBMC showed HIV and HTLV-like particles within 2 weeks. We believe this to be the first report of a dually-infected patient who has developed a HTLV-I-associated T helper cell cutaneous lymphoma
— id: 5986, year: 1993, vol: 1, page: 155, stat: Journal Article,

HTLV I/II tax sequences in peripheral blood of most patients with mycosis fungoides
Pancake BA; Coutavas EE; Franklin DZ
1993 Dec 12-16;1:95-95, National Conference on Human Retroviruses & Related Infections
Although a retroviral etiology for the cutaneous T-cell lymphoma, Mycosis Fungoides (MF), has long been suspected, efforts to demonstrate such a relationship have largely gone unrewarded. We therefore renewed efforts to examine this association by PCR/Southern hybridization analysis, employing primers SK43,44 and SK110,111 and probes SK45 and SK112, to detect HTLV-I/II tax and pol-I, respectively. We herein report the detection of HTLV-I/II tax and/or pol-l- related proviral DNA sequences in peripheral blood mononuclear cells (PBMC) isolated from 34 of 40 (85%) of the MF patients thus far tested. Such sequences have not been demonstrated in PBMC from healthy volunteers. Only 1 of 18 of these patients tested positive for antibodies to HTLV- I/II structural proteins. HTLV-I-like particles have been demonstrated in short-term cultures of PBMC from greater than 80% of these patients by EM. To date, only one MF patient infected with HTLV-II has been found (Zucker- Franklin, D. et al., Blood 80:1537, 1992). The occurrence of HTLV-I/II-related sequences and, in particular, tax, in circulating blood cells of such patients implicates HTLV infection and suggests a possible role for such virus(es) in the pathogenesis of this neoplasm
— id: 5993, year: 1993, vol: 1, page: 95, stat: Journal Article,

HTLV tax and mycosis fungoides
Pancake BA; Zucker-Franklin D
1993 Aug 19;329(8):580-580, New England journal of medicine
— id: 15715, year: 1993, vol: 329, page: 580, stat: Journal Article,

HIGH-INCIDENCE OF INFECTION WITH HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I (HTLV-I) IN PATIENTS WITH CUTANEOUS T-CELL LYMPHOMA
PANCAKE, BA; ZUCKERFRANKLIN, D
1993 NOV 15 ;82(10):A452-A452, Blood
— id: 52147, year: 1993, vol: 82, page: A452, stat: Journal Article,

In vivo effects of interleukin-6 on thrombopoiesis
Stahl CP; Zucker-Franklin D
1993 May 15;81(10):2819-2820, Blood
— id: 15716, year: 1993, vol: 81, page: 2819, stat: Journal Article,

Kaposi's sarcoma in a human immunodeficiency virus-negative patient with asymptomatic human T lymphotropic virus type I infection
Zucker-Franklin D; Huang YQ; Grusky GE; Friedman-Kien AE
1993 Apr;167(4):987-989, Journal of infectious diseases
— id: 8407, year: 1993, vol: 167, page: 987, stat: Journal Article,

MORE ON HTLV TAX AND MYCOSIS-FUNGOIDES - REPLY
ZUCKERFRANKLIN, D; PANCAKE, BA
1993 DEC 30 ;329(27):2035-2036, New England journal of medicine
— id: 52134, year: 1993, vol: 329, page: 2035, stat: Journal Article,

Specific ligation of surface alpha-D-galactosyl epitopes markedly affects the quantity of four major proteins secreted by macrophages
Warfel AH; Zucker-Franklin D
1992 Jul;52(1):80-84, Journal of leukocyte biology
Activated macrophages (M phi s) have terminal alpha-D-galactosyl (alpha D-Gal) residues on their membranes that are not apparent on resting cells. Ligation of these epitopes with Griffonia simplicifolia I-B4 (GSI-B4), a lectin that has specificity for alpha-D-Gal residues, alters selected M phi functions. To explore the mechanism(s) that may be responsible for some of the functional changes, alterations in the secretory pattern of [35S]methionine-labeled proteins were assessed when cells were cultured with or without this ligand. The proteins were identified by Western blots and quantitated. Interestingly, alpha-D-Gal ligation proved to decrease the secretion of some proteins while increasing the secretion of others. Some of the most significant changes were observed in four proteins: fibronectin and transglutaminase were down-regulated by 55 and 66% respectively, while plasminogen activator inhibitor type 2 was increased by 259% and collagenase was increased 1000-fold. These observations show that the emergence of new oligosaccharide epitopes, such as alpha-D-Gal, concomitant with M phi activation may serve to mediate the transduction of signals that cause quantitative changes in the elaboration of diverse M phi products. The biologic significance of the four identified proteins has been well established. Fluctuations in their levels are likely to play a role at sites of chronic inflammation
— id: 13550, year: 1992, vol: 52, page: 80, stat: Journal Article,

Apparent ineffectiveness of natural killer cells vis-a-vis retrovirus-infected targets
Zheng ZY; Zucker-Franklin D
1992 Jun 1;148(11):3679-3685, Journal of immunology
The role of NK cells in the defense against retroviral infections is ill defined. The discovery of the pathogenic human retroviruses and their epidemic spread have made more urgent a better understanding of how such infections may be naturally controlled. Therefore, a systematic study was undertaken to determine whether NK cells obtained from healthy individuals are able to recognize and lyse target cells that have been infected with HTLV-I, HTLV-II, or HIV. The studies demonstrated that NK cells can recognize retrovirus-infected cells as evidenced by rapid conjugation, but that neither freshly isolated, nor IL-2 stimulated cells cause lysis of such targets. As has been reported for NK-resistant tumor cells, removal of sialic acid residues rendered the retrovirus-infected target cells vulnerable to NK cell attack. Although these data do not suggest that boosting natural immunity would be a useful treatment modality for patients with AIDS or HTLV-related diseases, the observations may help to explain why the small number of cells that harbor retroviruses in patients with subclinical infection are not eliminated
— id: 13590, year: 1992, vol: 148, page: 3679, stat: Journal Article,

INTERACTION OF NATURAL-KILLER-CELLS WITH TARGETS HARBORING HUMAN RETROVIRUSES
ZHENG, YZ; ZUCKERFRANKLIN, D
1992 APR ;40(2):A229-A229, Clinical research
— id: 51984, year: 1992, vol: 40, page: A229, stat: Journal Article,

Clinical significance of platelet microparticles
Zucker-Franklin D
1992 Apr;119(4):321-322, Journal of laboratory & clinical medicine
— id: 15717, year: 1992, vol: 119, page: 321, stat: Journal Article,

Human lymphotropic retroviruses associated with mycosis fungoides: evidence that human T-cell lymphotropic virus type II (HTLV-II) as well as HTLV-I may play a role in the disease
Zucker-Franklin D; Hooper WC; Evatt BL
1992 Sep 15;80(6):1537-1545, Blood
The human T-cell lymphotropic virus type I (HTLV-I) is causally associated with adult T-cell leukemia, but its role in mycosis fungoides (MF) has remained enigmatic. The virus is suspect because a small percentage of patients with MF have antibodies to it, the cells of others harbor deleted HTLV-I proviral sequences, and particles resembling HTLV-I emerge in cultured blood lymphocytes obtained from most patients. An alternative possibility is that disparate lymphotropic retroviruses may infect or affect a population of epidermotropic lymphocytes, leading to the same outcome, ie, MF. In studies designed to identify the particles detected in lymphocyte cultures of nine patients with a diagnosis of skin involvement characteristic of MF, this concept has gained support. While the cells of four patients provided evidence of HTLV-I infection, molecular hybridization with HTLV-II-specific pol probes showed HTLV-II in the cells of another patient. The 103-bp fragment amplified by the HTLV-II-specific probe was sequenced and proved to have greater than 90% homology with the same fragment amplified from cells known to be infected with HTLV-II. A role for HTLV-II in MF has not been suggested heretofore. Therefore, HTLV-I, HTLV-II, and their incomplete forms may be found in cells of MF patients, suggesting new theories regarding the pathogenesis of this disease
— id: 57508, year: 1992, vol: 80, page: 1537, stat: Journal Article,

Characterization of glycoprotein IIb/IIIa-positive cells in human umbilical cord blood: their potential usefulness as megakaryocyte progenitors
Zucker-Franklin D; Yang JS; Grusky G
1992 Jan 15;79(2):347-355, Blood
A need for hematopoietic stem cells, particularly cells destined to enter the megakaryocyte (MK) series, prompted phenotypic analysis of mononuclear leukocytes in human cord blood. To this end, immunohistochemical, flow cytometric, and ultrastructural techniques were used. The immunogold silver enhancement method (IGS) for the detection of the MK-specific glycoprotein (GP) IIb/IIIa epitopes combined with a monocyte-specific stain for alpha-naphthyl butyrate esterase proved to be superior to flow cytometry (FACS) for precise quantitation of cell types in each sample. Immunoelectron microscopy afforded a description of distinctions between precursors bearing GPIIb/IIIa epitopes and other stem cells of the myeloid series. The number of presumed MK progenitors was surprisingly high, averaging 1.8% +/- 1.3% (range, 0.2% to 4.6%) by IGS and 4.1% +/- 3.0% (range, 0.2% to 9.3%) by FACS analysis. The occurrence of GPIIb/IIIa-positive denuded MK nuclei in cord blood was of interest, but was too small to affect these data. These observations should advocate a greater use of cord blood for restitution of MK/platelet-lineage-depleted patients as well as for experimental studies concerned with MK differentiation
— id: 13711, year: 1992, vol: 79, page: 347, stat: Journal Article,

Effects of human interleukin-6 on megakaryocyte development and thrombocytopoiesis in primates
Stahl CP; Zucker-Franklin D; Evatt BL; Winton EF
1991 Sep 15;78(6):1467-1475, Blood
Recombinant human interleukin-6 (IL-6) has previously been shown to increase platelet counts in mice and primates. To elucidate the mechanisms underlying this phenomenon, serial analyses were performed on megakaryocytes obtained from rhesus monkeys treated for 8 days with 30 micrograms/kg/d of recombinant human IL-6. Platelet counts increased to a maximum of 7.8 x 10(5)/microL with biphasic peaks on days 7 and 12 without significant changes in platelet volumes. Large increases in DNA content were seen by two-color flow cytometry and digital image analysis. Ploidy distribution underwent a significant shift between study days 3 and 11 (P less than .0001) with large increases in the frequency of 64N and 128N megakaryocytes. The modal ploidy increased from the normal 16N to 64N. Megakaryocyte size, as measured by area, was increased 2- to 2.7-fold. On day 3, multiple megakaryocytes were seen in endomitosis, along with an abundance of young cells with wide, organelle-free peripheral zones. The giant megakaryocytes seen on days 5 to 7 exhibited marked membrane hyperplasia that occupied much of the cell. Emperipolesis occurred frequently, as did megakaryocyte cell death. No giant platelets were seen. We conclude that IL-6 significantly alters the process of megakaryocyte maturation and thrombocytopoiesis, and that these effects, at least in the doses of IL-6 administered, should not be equated with the physiologic mechanisms operative during accelerated platelet production
— id: 15718, year: 1991, vol: 78, page: 1467, stat: Journal Article,

INVIVO EFFECT OF INTERLEUKIN-6 ON MEGAKARYOCYTE (MK) DEVELOPMENT
STAHL, CP; ZUCKERFRANKLIN, D; EVATT, BL; WINTON, EF
1991 APR ;39(2):A269-A269, Clinical research
— id: 51611, year: 1991, vol: 39, page: A269, stat: Journal Article,

Cystatin C and cathepsin B production by alveolar macrophages from smokers and nonsmokers
Warfel AH; Cardozo C; Yoo OH; Zucker-Franklin D
1991 Jan;49(1):41-47, Journal of leukocyte biology
The capacity of alveolar macrophages (AM) obtained from smokers and nonsmokers to secrete cathepsin B and its inhibitor cystatin C was examined because of the concept that an imbalance in the production of proteolytic enzymes and/or their inhibitors could be responsible for the lung damage seen in smokers. Quantitation of immunoprecipitates on Western blots showed that the amount of total cystatin C secreted into the culture medium by AM of smokers was significantly greater than the amount secreted by cells obtained from nonsmokers, whereas the difference between the amount of cathepsin B secreted by the AM of smokers and that from nonsmokers did not appear significant. The cystatin C found in the medium conditioned by AM of nonsmokers appeared to be more heterogeneous in molecular size, presenting either as a single band of about 14 Kd or as a high-molecular-weight triplet of about 69 Kd, 63 Kd, and 57.3 Kd. Furthermore, in some cases there were single or doublet bands at 14 Kd as well as the high-molecular-weight triplets. In contrast, smokers AM-conditioned medium uniformly possessed both the low-and the high-molecular-weight cystatin C. Cathepsin B was not detected in Western blots at its reported molecular weights but was identified at the exact area occupied by the higher molecular weight cystatin C, i.e., at bands corresponding to 69 Kd, 63 Kd, and 57.3 Kd. Therefore, it is clear that in culture media of AM, cystatin C and cathepsin B are present as proteinase-antiproteinase complexes. The observation also suggests that in smokers an excess of cystatin C may be elaborated, which, if further substantiated, would show for the first time a likely role for this proteinase inhibitor in vivo
— id: 14179, year: 1991, vol: 49, page: 41, stat: Journal Article,

Macrophage membrane glycoproteins that bind Griffonia simplicifolia I-B4: effect on cytotoxicity and protein secretion
Warfel AH; Zucker-Franklin D; Zheng ZY
1991 May;147(2):265-273, Journal of cellular physiology
Thioglycollate elicited peritoneal (TG-Mos) but not resident peritoneal Mos (R-Mos) were found to bind the lectin Griffonia simplicifolia isotype I-B4 (GSI-B4). This was demonstrated by ultrastructural studies and FACS analyses. Membranes from TG-Mos were isolated, separated on SDS-PAGE, electrotransferred onto nitrocellulose, and exposed to peroxidase-labeled GSI-B4. These procedures revealed two major membrane glycoproteins of molecular weights 180,000 and 94,000 daltons that bound the lectin GSI-B4 which has a specificity for recognizing terminal alpha-galactosyl residues. The presence of these epitopes on the two membrane glycoproteins was further substantiated by the fact that treatment of the membranes with alpha-galactosidase destroyed their capacity to bind GSI-B4 and that alpha-D-galactopyranoside but not N-acetyl-D-glucosamine competitively inhibited GSI-B4 from binding to the glycoproteins. Treatment of TG-Mos with GSI-B4 reduced the capacity of interferon (IFN) and lipopolysaccharide (LPS), or IFN alone, to induce Mo mediated cytotoxicity towards tumor cells by as much as 40%. GSI-B4 also caused alterations in the pattern of biosynthetically 35S-methionine labeled secreted proteins as early as 2 hours after contact with TG-Mos. Out of 35 discernible proteins on fluorograms of SDS-PAGE separated proteins, 5 were down-regulated and 9 were enhanced. It is suggested that the two novel Mo membrane proteins may play a role in regulating the response of Mo subpopulations to their humoral and cellular environments
— id: 14057, year: 1991, vol: 147, page: 265, stat: Journal Article,

Detection of human T-lymphotropic virus-like particles in cultures of peripheral blood lymphocytes from patients with mycosis fungoides
Zucker-Franklin D; Coutavas EE; Rush MG; Zouzias DC
1991 Sep 1;88(17):7630-7634, Proceedings of the National Academy of Sciences of the United States of America
Because of seronegativity and absence of a leukemic phase in most patients with mycosis fungoides, a role for the human T-lymphotropic virus type I (HTLV-I) in this disease has remained tenuous. Virus particles are not seen in fresh isolates of skin or blood lymphocytes and the malignant cells (Sezary cells) have been difficult to culture. The availability of growth factors and biomolecular techniques have prompted a renewed attempt to find evidence of virus infection in these patients. We report here the successful culture of blood lymphocytes of 17 patients with mycosis fungoides and 1 patient with the Sezary syndrome. The cells of 2 additional patients failed to grow after 4-6 weeks in vitro. Ultrastructural analysis of the cultures showed an abundance of HTLV-like particles in the specimens of 18 of the 20 patients. Preliminary immunohistochemical studies carried out with various antisera directed against HTLV-I and the polymerase chain reaction utilizing a probe for a conserved region of the pol gene of HTLV-I were positive on only a portion of the specimens. Although definitive characterization of this organism awaits further analysis, it seems likely that circulating lymphocytes of all patients with mycosis fungoides harbor a virus that morphologically resembles HTLV-I
— id: 13917, year: 1991, vol: 88, page: 7630, stat: Journal Article,

ULTRASTRUCTURAL-CHANGES IN MEGAKARYOCYTES ACCOUNTING FOR THE EFFECTS INDUCED BY THE ADMINISTRATION OF INTERLEUKIN-6
ZUCKERFRANKLIN, D; STAHL, CP
1991 JUN 5 ;65(6):1146-1146, Thrombosis & haemostasis
— id: 51570, year: 1991, vol: 65, page: 1146, stat: Journal Article,

CD4-independent, productive human immunodeficiency virus type 1 infection of hepatoma cell lines in vitro
Cao YZ; Friedman-Kien AE; Huang YX; Li XL; Mirabile M; Moudgil T; Zucker-Franklin D; Ho DD
1990 Jun;64(6):2553-2559, Journal of virology
Five hepatoma cell lines, including CZHC/8571, PLC/PRF/5, Hep3B, HepG2, and HUH7, were inoculated with three diverse isolates of human immunodeficiency virus type 1 (HIV-1). Productive infection was noted in all hepatoma cell lines, and expression of viral p24 antigen lasted for over 3 months, but its level decreased in proportion to the number of viable cells. HIV-1 antigens were also found in the cells by immunohistochemical staining and radioimmunoprecipitation assay, as were viral RNA by in situ hybridization and HIV-1-like particles by electron microscopy. Virus yield assays were also positive on supernatant fluids collected from hepatoma cultures inoculated with HIV-1. Despite their susceptibility to infection, all five hepatoma cell lines were negative for CD4 by immunofluorescence and for CD4 mRNA by slot-blot hybridization. In addition, HIV-1 infection of hepatoma cell lines was not blocked by anti-CD4 monoclonal antibody or soluble CD4. Together, these findings clearly demonstrate that all five hepatoma cell lines were susceptible to productive infection by HIV-1 in vitro via a CD4-independent mechanism
— id: 14766, year: 1990, vol: 64, page: 2553, stat: Journal Article,

DETECTION OF 2 NOVEL LECTIN-BINDING PROTEINS OF APPARENT BIOLOGICAL SIGNIFICANCE PRESENT ON STIMULATED MACROPHAGES
Warfel, AH; Zheng, ZY; Zuckerfranklin, D
1990 Apr;38(2):A244-A244, Clinical research
— id: 31953, year: 1990, vol: 38, page: A244, stat: Journal Article,

Internalization of human immunodeficiency virus type I and other retroviruses by megakaryocytes and platelets
Zucker-Franklin D; Seremetis S; Zheng ZY
1990 May 15;75(10):1920-1923, Blood
Direct infection of megakaryocytes and platelets by human immunodeficiency virus type I (HIV-I) or other retroviruses has not been demonstrated. To determine whether this could occur, murine bone marrow was co-cultivated with the amphotropic retrovirus-producing cell line PA317-N2, and freshly isolated normal human bone marrow and platelets were co-cultivated with HIV-infected H9 cells. In each case, ultrastructural analyses showed viruses within megakaryocytes and platelets. In murine specimens, the uptake of retrovirus was avid at all stages of differentiation. In human specimens, viral uptake was less frequent. These results suggest that direct infection of megakaryocytes could play a role in the pathophysiology of HIV-associated disease. In addition, these observations suggest that cells of the megakaryocyte lineage could serve as target cells in gene transfer experiments using retroviral-based vectors
— id: 15719, year: 1990, vol: 75, page: 1920, stat: Journal Article,

Atlas der Blutzellen : funktion und pathologie = Atlas of blood cells : function and pathology
Zucker-Franklin, Dorothea
Stuttgart : Fischer, 1990,
— id: 1558, year: 1990, vol: , page: , stat: ,

RETROVIRUS INFECTION OF BLOOD-LYMPHOCYTES IN PATIENTS WITH MYCOSIS-FUNGOIDES
Zuckerfranklin, D; Coutavas, E; Zouzias, D
1990 Apr;38(2):A283-A283, Clinical research
— id: 31955, year: 1990, vol: 38, page: A283, stat: Journal Article,

Cell surface-associated proteinases in NK cell-mediated cytotoxicity: enhancement of enzyme expression is unique to activation with interferon-alpha
Lavie G; Zucker-Franklin D
1989 Dec;124(2):202-211, Cellular immunology
The human NK cell-mediated cytotoxicity reaction is sensitive to proteinase inhibitors with specificity for chymotrypsin-like enzymes inhibitable by 1-tosylamide 2-phenylethyl chloromethyl ketone (TPCK). Evidence is presented in support of previous data suggesting that this type of cytotoxicity is attributable to enzymes associated with the surface membrane of the NK cell. Activation of the cells with IFN-alpha results in increased cytolytic activity, the suppression of which requires an almost two- to threefold increase in the concentration of proteinase inhibitors. Treatment of NK cells with IFN-alpha results in increased surface binding of [3H]diisopropyl fluorophosphate ([ 3H]DFP). This effect is not inhibited by cycloheximide (50 micrograms/ml), suggesting translocation of preexisting enzymes to the surface membrane. TPCK can compete with [3H]-DFP for binding to the cell surface and can abrogate the increase in [3H]DFP binding observed after IFN-alpha stimulation of the cells. Treatment with IFN-gamma does not increase cell surface-associated proteolytic activity and stimulation with IL-2 results in much smaller increments. The sensitivity of cytotoxicity to proteinase inhibitors is confined to the initial 2-5 min of the reaction. This suggests that cell surface-associated proteinases play a role in the programming of NK cells for lysis, whereas subsequent events may be dependent on secreted enzyme moieties
— id: 10426, year: 1989, vol: 124, page: 202, stat: Journal Article,

Phorbol ester-induced loss of membrane sialic acid: implications for tumor cytolysis by natural killer cells
Nabi ZF; Zucker-Franklin D; Baten A
1989 Mar;45(3):183-188, Journal of leukocyte biology
Freeze-fracture analysis has shown that treatment of cells with phorbol myristate acetate (PMA) results in a loss of intramembranous particles (IMP) associated with the external leaflet of their plasma membranes. It has also been demonstrated that phorbol esters markedly enhance the sensitivity of tumor targets to natural killer (NK) cells, although the mechanism underlying this phenomenon has remained unexplained. Since the ability of NK cells to recognize neoplasms appears to be inversely related to the concentration of sialic acid on the target cell surface, it seemed possible that phorbols affect membrane glycoproteins which have terminal carbohydrates bearing sialic acid residues. To investigate whether phorbol treatment could be responsible for the loss of sialic acid, four tumor cell lines were examined before and after exposure to PMA. A reduction in surface sialic acid was established by four different methods: 1) standard thiobarbituric acid analysis of cell hydrolysates, 2) metabolic labelling of cells with [3H]-mannosamine followed by treatment with neuraminidase, 3) chromatography of membrane extracts, and 4) freeze-fracture analysis of lectin-labelled intact cells. These observations suggest a mechanism whereby phorbols may facilitate NK-cell-mediated cytolysis. In addition, an entirely novel effect of these tumor-producing agents may have been uncovered
— id: 10700, year: 1989, vol: 45, page: 183, stat: Journal Article,

The relationship of alpha granules to the membrane systems of platelets and megakaryocytes
Zucker-Franklin D
1989 ;15(1):73-79, Blood cells
— id: 10743, year: 1989, vol: 15, page: 73, stat: Journal Article,

Megakaryocytes of human immunodeficiency virus-infected individuals express viral RNA
Zucker-Franklin D; Cao YZ
1989 Jul;86(14):5595-5599, Proceedings of the National Academy of Sciences of the United States of America
The pathogenesis of thrombocytopenia associated with human immunodeficiency virus (HIV) infection is not fully understood. Immune mechanisms provide a partial explanation but fail to account for a lack of compensatory megakaryocytosis, the rapid reversal after treatment with azidothymidine, and the ultrastructural aberrations seen in the megakaryocytes of patients with acquired immunodeficiency syndrome. Therefore, a direct effect of HIV on megakaryocytes was investigated. The bone marrow of HIV seropositive individuals was analyzed ultrastructurally, and the megakaryocytes of 10 thrombocytopenic patients were subjected to in situ hybridization with a HIV RNA probe. The structural aberrations in HIV megakaryocytes were distinct from those in HIV-negative immune thrombocytopenias, and the megakaryocytes of 10 of 10 patients examined by in situ hybridization unambiguously expressed viral RNA. Therefore, it is likely that direct infection of megakaryocytes with HIV-1 is one mechanism for the decrease in platelet production
— id: 10550, year: 1989, vol: 86, page: 5595, stat: Journal Article,

Structural changes in the megakaryocytes of patients infected with the human immune deficiency virus (HIV-1)
Zucker-Franklin D; Termin CS; Cooper MC
1989 Jun;134(6):1295-1303, American journal of pathology
Although immune mechanisms are known to be partially responsible for the thrombocytopenia of patients infected with HIV-1, an understanding of the mechanism underlying this disorder is incomplete. A casual observation that bone marrow biopsies of HIV-infected individuals seem to exhibit an unusually large number of denuded megakaryocyte nuclei (DN-MK) prompted a study comparing MK of 20 HIV-seropositive individuals with those of 10 patients with HIV-negative idiopathic thrombocytopenic purpura and 10 hematologically normal subjects. In normal marrows the number of DN-MK average 2.1 +/- 0.5 SE per 10 low power field. In patients with ITP the average number was 6.5 +/- 1.4 SEM, whereas HIV-ITP marrows had an average of 42.5 +/- 3.7 SEM. Electron microscopy of AIDS megakaryocytes exhibited ballooning of the peripheral zone to an extent not seen by us in any other myelodysplastic syndromes. These observations support the concept that the pathophysiology affecting MK/platelets in HIV-infection should not be equated with the destructive process underlying other immune thrombocytopenias
— id: 10591, year: 1989, vol: 134, page: 1295, stat: Journal Article,

The association of progressive, atrophying, chronic, granulomatous dermohypodermitis with Hodgkin's disease
Benisovich V; Papadopoulos E; Amorosi EL; Zucker-Franklin D; Silber R
1988 Dec 1;62(11):2425-2429, Cancer
The case of a patient with an unusual skin disorder--progressive, atrophying, chronic, granulomatous dermohypodermitis (PACGD)--who developed Hodgkin's disease is reported. A review of the literature revealed only two other cases of PACGD, one of which affected a patient who also was found to have Hodgkin's disease. In an additional report, the diagnosis of Hodgkin's disease was made in a patient who may have had the same dermatologic disorder. The case is reported because the association of these two rare diseases is believed to be more than a chance event
— id: 10879, year: 1988, vol: 62, page: 2425, stat: Journal Article,

Evidence for clonal development and stem cell origin of M7 megakaryocytic leukemia
Najfeld V; Zucker-Franklin D; Adamson J; Singer J; Troy K; Fialkow PJ
1988 Jun;2(6):351-357, Leukemia
Previous studies have shown that acute nonlymphocytic leukemias are clonal diseases in which there is heterogeneity in the pattern of stem cell differentiative expression. To determine whether M7 megakaryocytic leukemia is a clonal disease and to evaluate the differentiative expression of the cells involved by the leukemia we studied a patient with megakaryocytic leukemia who was heterozygous for the X-chromosome-linked glucose-6-phosphate dehydrogenase (G6PD). The diagnosis of megakaryocytic leukemia was based on results obtained with the immunogold method and ultrastructural studies with the monoclonal anti-Gplla/IIIb antibody, 10E5. Direct testing of blood and marrow mononuclear cells and blood platelets demonstrated only A-type G6PD, whereas skin exhibited both B and A enzymes. The results indicate that the megakaryocytic leukemia in this patient was clonal at the time of study. To determine the differentiative expression of the stem cells, granulocyte/macrophage colony forming units and erythroid burst forming units were cultured and the resultant colonies were tested for G6PD. The results indicate that the stem cells involved by the leukemia exhibited differentiative expression multipotent for the megakaryocytic and granulocytic pathways, but no definitive conclusion could be made regarding the erythroid lineage
— id: 15720, year: 1988, vol: 2, page: 351, stat: Journal Article,

Unmasking of cryptic natural killer (NK) cell recognition sites on chronic lymphocytic leukemia lymphocytes
Spitz DL; Zucker-Franklin D; Nabi ZF
1988 Jul;28(3):155-161, American journal of hematology
The sensitivity of chronic lymphocytic leukemia (CLL) lymphocytes to attack by natural killer (NK) cells has remained questionable. To clarify this issue, freshly isolated lymphocytes of 37 patients with B-CLL, five with WDLL and two with HCL, were tested with a standard cytotoxicity assay with NK cells from normal donors. All these targets were resistant to cytolysis by the effectors. Freeze-fracture analysis of CLL cell plasma membranes revealed that they have a larger number of intramembranous particles (IMP) associated with the external leaflet (E-face) than have normal lymphocytes. Unlike other neoplastic cells, exposure of CLL lymphocytes to phorbol esters or treatment with neuraminidase did not render them vulnerable to attack by NK cells, nor did 5 days of culture have an effect. Incubation of CLL lymphocytes with anti-Ig-mu (24-72 hr) or with 0.1% pepsin (15 min) resulted in 15% and 27% cytolysis, respectively. B-lymphocytes from the blood of healthy donors were not killed when treated similarly: These data establish that freshly isolated B-CLL lymphocytes are resistant to NK cytolysis but that in contrast to normal B-cells, they possess cryptic NK-recognition structures, which may be uncovered by surface modulation
— id: 11049, year: 1988, vol: 28, page: 155, stat: Journal Article,

Atlas of blood cells : function and pathology
Zucker-Franklin D
Philadelphia : Lea & Febiger, 1988,
— id: 1555, year: 1988, vol: , page: , stat: ,

NATURAL-KILLER CELLS RECOGNIZE ONLY ONE MEMBRANE GLYCOPROTEIN ISOLATED FROM B-CHRONIC LYMPHOCYTIC-LEUKEMIA LYMPHOCYTES
Zuckerfranklin, D; Baten, A
1988 Apr;36(3):A625-A625, Clinical research
— id: 31520, year: 1988, vol: 36, page: A625, stat: Journal Article,

Antigenic differences between human platelets and megakaryocytes
Hyde P; Zucker-Franklin D
1987 May;127(2):349-357, American journal of pathology
To investigate the apparent paradox in the observation that most patients with immune thrombocytopenias have normal or increased numbers of megakaryocytes (MKs), the extent of antigenic cross-reactivity between normal platelets and MK was examined. Indirect immunofluorescence and ultrastructural studies were carried out by means of four antisera specific for platelets: anti-GpIb, anti-GpIIb/IIIa, anti-PLA1, and an antiserum from a patient with quinidine-induced thrombocytopenia. Following incubation of freshly collected marrow with these antisera, MK were first identified by phase-contrast microscopy and then inspected for fluorescence. Almost all MKs were found reactive with the last three antisera, albeit to a variable extent. In contrast, only 24% reacted with anti-GpIb. The pattern of fluorescence, ie, rim, partial or cytoplasmic, appeared to be related to the extent of MK fragmentation. Only rim fluorescence of living MKs could be interpreted to indicate that the platelet epitope was exposed on the surface of the precursor cell. The observations suggest that platelet antigens are variably expressed on the plasma membranes of MKs. In a clinical setting, the heterogeneity among platelet target antigens and the extent to which these are exposed on MKs at various stages of maturation may dictate the severity of the thrombocytopenia and degree of ineffective thrombocytopoiesis
— id: 15721, year: 1987, vol: 127, page: 349, stat: Journal Article,

PHORBOL-ESTER INDUCED LOSS OF CELL-SURFACE SIALIC-ACID ENHANCES TARGET-CELL SENSITIVITY TO CYTOLYSIS BY NATURAL-KILLER (NK) CELLS
Nabi, Z; Zuckerfranklin, D
1987 Apr;35(3):A654-A654, Clinical research
— id: 31205, year: 1987, vol: 35, page: A654, stat: Journal Article,

Constitutive secretion of cystatin C (gamma-trace) by monocytes and macrophages and its downregulation after stimulation
Warfel AH; Zucker-Franklin D; Frangione B; Ghiso J
1987 Dec 1;166(6):1912-1917, Journal of experimental medicine
Cystatin C (gamma-trace) was found to be a constitutively secreted protein of isolated human monocytes and mouse peritoneal macrophages, as well as the histiocytic lymphoma cell lines U937, P388D.1, and J774. This proteinase inhibitor is not uniquely secreted by monocytes/macrophages, but was also identified in the conditioned media from several primary cells, including brain cells, and diverse established cell lines. In vitro treatment of resident mouse peritoneal macrophages with either LPS or IFN-gamma caused a downregulation in cystatin C secretion. Elaboration of this protein was also diminished by macrophages that had been stimulated by thioglycollate in vivo, and treatment of these cells with LPS led to further decline. It is suggested that, under some inflammatory conditions, downregulation of cystatin C may contribute to tissue pathology
— id: 9437, year: 1987, vol: 166, page: 1912, stat: Journal Article,

MONOCYTE MACROPHAGE SECRETION OF PROTEINASE-INHIBITOR CYSTATIN- C (GAMMA-TRACE) - ITS DOWN-REGULATION BY INFLAMMATORY STIMULI
Warfel, AH; Zuckerfranklin, D; Frangione, B; Ghiso, J
1987 Apr;35(3):A640-A640, Clinical research
— id: 31202, year: 1987, vol: 35, page: A640, stat: Journal Article,

Phorbol ester-induced loss of cell surface sialic acid enhances target cell sensitivity to cytolysis by natural killer (NK) cells
Zucker-Franklin D; Nabi ZF
1987 ;100:339-346, Transactions of the Association of American Physicians
— id: 11411, year: 1987, vol: 100, page: 339, stat: Journal Article,

Megakaryocyte ultrastructure. Its relationship to normal and pathologic thrombocytopoiesis
Zucker-Franklin D; Stahl C; Hyde P
1987 ;509:25-33, Annals of the New York Academy of Sciences
— id: 11417, year: 1987, vol: 509, page: 25, stat: Journal Article,

Novel monocyte-like properties of microglial/astroglial cells. Constitutive secretion of lysozyme and cystatin-C
Zucker-Franklin D; Warfel A; Grusky G; Frangione B; Teitel D
1987 Aug;57(2):176-185, Laboratory investigation
Evidence implicates cells belonging to the mononuclear phagocytic system (MPS) in the development of some forms of amyloidosis (10, 22). Whether or not the MPS is involved in central nervous system amyloidosis is not known. As a first step to address this issue, microglial and astroglial cells isolated from mouse brains were cultured and characterized as to the properties they may share with other members of the MPS. It was shown by light and electron microscopy that both cell types phagocytose latex particles, but that only microglial cells engulf immunoglobulin sensitized erythrocytes. By means of immunohistochemical, immunofluorescence, and immunoblotting techniques, it was established that the cells contain and secrete lysozyme as well as the proteinase inhibitor cystatin-C (-gamma trace). Cystatin-C was distributed in the cytoplasm and the nucleus and was strikingly associated with filaments and bundles of fibrils. Another enzyme, commonly used to distinguish cells belonging to the MPS, is alpha-naphthyl butyrate esterase. Shortly after their isolation, only the microglial cells were positive, but on continued culturing, increasing numbers of astroglial cells became positive for alpha-naphthyl butyrate esterase. By day 22, almost all of the cells were positive. Freshly isolated cells were negative for the monocyte-specific antigen Mac-1. However, after 4 days, cells with the morphology of microglia had become positive, whereas astroglia failed to exhibit this antigen with up to 22 days in culture. Thus, both astroglia and microglia have properties in common with cells of the MPS which may be useful for future studies. However, on fresh isolation only microglia were indistinguishable from monocytes for all features tested.
— id: 9590, year: 1987, vol: 57, page: 176, stat: Journal Article,

MEGAKARYOCYTE ULTRASTRUCTURE - ITS RELATIONSHIP TO NORMAL AND PATHOLOGICAL THROMBOCYTOPOIESIS
Zuckerfranklin, D
1987 Apr;13(2):228-229, Seminars in thrombosis & hemostasis
— id: 31356, year: 1987, vol: 13, page: 228, stat: Journal Article,

MODULATION OF CHRONIC LYMPHOCYTIC-LEUKEMIA (CLL) LYMPHOCYTE PHENOTYPES BY INVITRO INCUBATION WITH ALPHA-1 THYMOSIN - COMMENTARY - INVOLVEMENT OF LYMPHOCYTES-T IN B-CELL LYMPHOPROLIFERATIVE DISEASES
Zuckerfranklin, D
1987 Jul;12(2):453-455, Blood cells
— id: 31163, year: 1987, vol: 12, page: 453, stat: Journal Article,

Interferon inactivator(s) in patients with AIDS and AIDS-unrelated Kaposi's sarcoma
Ikossi-O'Connor MG; Chadha KC; Lillie MA; Bernstein Z; Zucker-Franklin D; Ambrus JL
1986 Nov;81(5):783-785, American journal of medicine
Interferon inhibitory activity was found in the plasma of 11 of 14 patients with the acquired immune deficiency syndrome (AIDS). This was not seen in 75 normal persons, including six whose specimens were randomly and blindly interspersed among the patient samples. Plasma from a single patient with the AIDS prodrome (AIDS-related complex), who later demonstrated AIDS, did not contain interferon inhibitors but did contain high levels of interferon. Three patients with AIDS-unrelated Kaposi's sarcoma had neither significant levels of interferon nor interferon inhibitory activity. The existence of interferon inhibitory activity in the plasma has to be taken into account when interferon preparations are administered therapeutically
— id: 15722, year: 1986, vol: 81, page: 783, stat: Journal Article,

CASE FOR THE PANEL - LYMPHOCYTE JUNCTIONS
MURRAY, AB; MAUBACH, PA; ERLANDSON, RA; GHADIALLY, FN; TONER, PG; ZUCKERFRANKLIN, D
1986 AUG ;10(4):377-380, Ultrastructural pathology
— id: 41374, year: 1986, vol: 10, page: 377, stat: Journal Article,

Phorbol-induced recruitment of lymphocytes for spontaneous cytolysis of natural killer-insensitive tumor targets
Nabi ZF; Zucker-Franklin D
1986 Jul;100(2):485-500, Cellular immunology
Natural killer (NK) cells lyse a variety of tumor cells in vitro whereas NK-depleted unsensitized lymphocytes do not have this effect. In studies designed to elucidate the NK phenomenon, a series of experiments was carried out to identify properties of NK-sensitive targets and compare these with those of NK-insensitive targets and with targets rendered sensitive by treatment with phorbol esters. Following brief exposure to phorbol-12-myristate-13-acetate (PMA), the targets were thoroughly washed, and then incubated with lymphocyte preparations which were either enriched for or depleted of NK cells. PMA treatment increased the susceptibility of sensitive targets to NK-enriched fractions by only 20-30%, but made the NK-cell-insensitive targets markedly vulnerable to these effectors (80% lysis). Unexpectedly, brief PMA exposure also rendered cells susceptible to lysis by NK-cell-depleted lymphocytes. Yet, such targets were not killed by monocytes or B lymphocytes. Elimination of T8 lymphocytes from the NK-depleted fractions abolished lysis. To explore whether PMA had induced membrane changes not detectable on electron microscopy of thin sections, freeze-fracture studies were carried out on target cells before and after treatment with PMA. Freeze-fracture replicas of target cells which had been exposed to PMA exhibited a 50% reduction of the intramembranous particles (IMP) on the external leaflet of the plasma membrane but no changes in the number or size of the IMP associated with the protoplasmic leaflet face. The exact relationship of the structural changes and enhanced susceptibility to cytolysis has not yet been established. However, the observation that normal and tumor cells can be rendered vulnerable to lysis by lymphocytes which have not been sensitized immunologically may have practical applications
— id: 15726, year: 1986, vol: 100, page: 485, stat: Journal Article,

Susceptibility to NK cell lysis is abolished in tumor cells by a factor which restores their contact inhibited growth
Nabi ZF; Zucker-Franklin D; Lipkin G; Rosenberg M
1986 Oct 1;58(7):1461-1465, Cancer
It is well recognized that physical contact between natural killer (NK) cells and tumor targets is necessary for cell lysis. Therefore, any modulation of the tumor cell surface that alters intercellular contact could affect NK cell cytotoxicity. To examine this hypothesis, a contact inhibitory factor (CIF), which had been shown to restore contact inhibition of growth to several malignant cell lines was tested for its ability to render such cells immune to recognition by NK cells. When three NK-sensitive melanoma and two NK-sensitive colon carcinoma targets were cultured with CIF, they did not only change morphologically, but also showed a 70% to 95% reduction in their sensitivity to lysis by NK cells. In addition, K562 cells, which grow in suspension and do not permit a morphologic evaluation of the CIF effect, also became resistant to lysis by NK cells after culture with CIF. CIF did not reduce the viability nor the cytotoxicity of NK cells. CIF did not contain interferon nor did the CIF-treated targets induce the production of interferon during the cytotoxicity assay. It is concluded that restoration of contact inhibition of growth and resistance to NK cell lysis are cell surface phenomena that may run in parallel
— id: 15723, year: 1986, vol: 58, page: 1461, stat: Journal Article,

Incomplete antigenic cross-reactivity between platelets and megakaryocytes: relevance to ITP
Stahl CP; Zucker-Franklin D; McDonald TP
1986 Feb;67(2):421-428, Blood
Immune thrombocytopenias are usually associated with normal or increased numbers of megakaryocytes in the marrow. Therefore, the mechanism(s) responsible for the destruction of circulating platelets may not affect megakaryocytes in the same way. One of the possibilities which could account for the differential effect on the cells would be the development of antibodies to components of platelet membranes which are not exposed on the surface of all megakaryocytes. To investigate this possibility, a rabbit antiserum specific for mouse platelets was tested against fresh and cultured mouse megakaryocytes by indirect immunofluorescence. This antiserum cross-reacted with 46% of fresh murine megakaryocytes and 54% of cultured megakaryocytes. Phase-contrast microscopy revealed the reacting megakaryocytes to be fully granulated with irregular contours and in the process of releasing platelets. Nonreactive megakaryocytes demonstrated smooth contours and lacked morphological evidence of thrombocytopoiesis. Electron microscopy showed that only in megakaryocytes (MK) with an irregular contour had the demarcation membrane system (DMS) reached continuity with the plasma membrane. Ultrastructural analysis of megakaryocytes from patients with ITP showed approximately 25% to 50% of megakaryocytes without evidence of injury, whereas 50% to 75% had extensive damage. In undamaged cells, platelet territories had not yet reached the peripheral zone. The DMS of damaged megakaryocytes opened to the exterior elaborating platelets. The observations suggested that some platelet antibodies react only with megakaryocytes which have reached the stage of thrombocytopoiesis. Relevant target antigens may not be exposed on all megakaryocytes before cytoplasmic fragmentation occurs
— id: 15727, year: 1986, vol: 67, page: 421, stat: Journal Article,

Down-regulation of macrophage lysozyme by lipopolysaccharide and interferon
Warfel AH; Zucker-Franklin D
1986 Jul 15;137(2):651-655, Journal of immunology
Lipopolysaccharide (LPS) treatment of resident mouse peritoneal macrophages (M phi) was found to suppress intracellular as well as secreted lysozyme (LZM). Interferon (IFN) had a similar effect. LZM was identified by the capacity of cell lysates or medium to lyse Micrococcus lysodeikticus, and by the presence of a 14.5 Kd protein band which co-migrated with human LZM in SDS-PAGE and which reacted positively in Western blots with antiserum to human LZM. The size of the 14.5 Kd band decreased sequentially with increasing concentrations of LPS to which the cells were exposed. Although the LPS influence on LZM levels was dose-dependent, the intracellular LZM pool responded more readily than secreted LZM. Maximal intracellular LZM suppression of 80% was obtained with 10 micrograms LPS, whereas secreted LZM was reduced by only 66%. An IFN concentration of 100 U reduced secreted LZM by 24%, whereas 10,000 U of IFN decreased the amount of LZM secreted by 71%. Thioglycolate-elicited M phi had 75% less intracellular LZM than untreated resident M phi. Moreover, thioglycolate-elicited M phi were hyporesponsive to the suppressive effects of LPS added in vitro. Because both LPS and IFN have been shown to stimulate numerous M phi functions, the data are of interest because they support the concept, based on other studies, that agents which are capable of enhancing some M phi activities may concomitantly down-regulate other functions
— id: 15725, year: 1986, vol: 137, page: 651, stat: Journal Article,

Loss of intercalated membrane particles by treatment with phorbols
Zucker-Franklin D; Nabi ZF
1986 Sep;83(18):6829-6833, Proceedings of the National Academy of Sciences of the United States of America
Because brief exposure to phorbol esters renders normal cells vulnerable to deformation and cytolysis by lymphocytes, it was postulated that these tumor promoters might cause a hitherto unrecognized physical alteration in membrane architecture. To investigate this possibility, four tissue culture cell lines (K-562 erythroleukemia cells, melanoma cells, N1121 adult fibroblasts, and normal fetal fibroblasts) and three blood cell types (lymphocytes, monocytes, and platelets) were subjected to freeze-fracture analysis before and after brief treatment with phorbol myristate acetate. Phorbol myristate acetate caused a 50% reduction of intramembranous particles associated with the external leaflet (E face) of the plasma membrane of every cell except platelets. In contrast, no change in size or number of intramembranous particles associated with the protoplasmic membrane leaflet (P face) was evident. Since the platelet membrane is known to be turned 'inside out,' as regards the partition coefficient of the intramembranous particles, the disparity between the results obtained with platelets and other cells may serve to determine the nature of intramembranous particles affected by phorbols. Also, since phorbols affect primarily glycolipids and/or glycoproteins anchored in the external membrane leaflet, these findings may provide a useful tool for future exploration of membrane structure
— id: 15724, year: 1986, vol: 83, page: 6829, stat: Journal Article,

Antigenic dissimilarity between platelet and megakaryocyte surface membranes
Zucker-Franklin D; Stahl C; Hyde P
1986 ;215:259-264, Progress in clinical & biological research
— id: 15728, year: 1986, vol: 215, page: 259, stat: Journal Article,

CONTACT INHIBITED GROWTH RENDERS TUMOR-CELLS RESISTANT TO NATURAL-KILLER CELL-LYSIS
ZUCKERFRANKLIN, D; LIPKIN, G; NABI, ZF; ROSENBERG, M
1986 APR ;34(2):A728-A728, Clinical research
— id: 41414, year: 1986, vol: 34, page: A728, stat: Journal Article,

Impaired Kupffer cell function precedes development of secondary amyloidosis
Fuks A; Zucker-Franklin D
1985 May 1;161(5):1013-1028, Journal of experimental medicine
It has been demonstrated previously that the acute phase reactant, serum amyloid A (SAA), is subject to degradation by surface membrane-associated proteinases of peripheral blood monocytes. However, monocytes obtained from the blood of patients with amyloidosis degraded SAA incompletely, leaving a cleavage product that, biochemically and immunologically, resembled the amyloid protein A (AA) deposited in their tissues. To investigate the role of fixed macrophages in amyloidogenesis and to establish more definitively that amyloid deposition is attributable to faulty processing of the precursor protein rather than aberrant synthesis, secondary amyloidosis was induced in C57BL/6J mice by serial injections of casein. Kupffer cells (KC) were isolated from livers of mice that had received 0, 8, 13, 18, and greater than 30 injections of the stimulant. The cells were cultured with SAA for 4, 8, and 18 h and then subjected to electron microscopy and enzyme analyses. The medium was analyzed by SDS-PAGE to determine the amount of residual SAA and/or the appearance of AA. KC of healthy animals degraded SAA completely whereas KC of stimulated mice showed increasing amounts of residual SAA and the appearance of the AA cleavage product. The AA peptide appeared in KC cultures early during the course of casein injections and before any amyloid could be demonstrated in the organs of the stimulated mice. The addition of KC isolated from healthy mice to cultures that had produced AA eliminated the abnormal peptide. The results, indicate that defective KC function precedes amyloidosis. The abnormal AA cleavage product formed by such cells is still susceptible to hydrolysis by normal cells. In addition, ultrastructural evidence is presented that suggests that KC may also play a role in fibrillogenesis of the AA protein
— id: 15729, year: 1985, vol: 161, page: 1013, stat: Journal Article,

MEGAKARYOCYTES AND PLATELETS HAVE DISPARATE SURFACE-MEMBRANE ANTIGENICITY - IMMUNOFLUORESCENT AND ULTRASTRUCTURAL ANALYSIS
Hyde, P; Zuckerfranklin, D
1985 ;33(2):A547-A547, Clinical research
— id: 30928, year: 1985, vol: 33, page: A547, stat: Journal Article,

Absence of a surface-connected canalicular system in bovine platelets
Zucker-Franklin D; Benson KA; Myers KM
1985 Jan;65(1):241-244, Blood
Human platelets possess a surface-connected canalicular system (SCCS) which has been postulated to subserve endocytosis as well as secretion. Platelets of most animal species studied to date, including those of cattle, function similarly. However, ultrastructural analysis of freeze-fractured bovine platelets or thin sectioned bovine platelets treated with electron-dense tracers failed to delineate a SCCS. This observation may throw an entirely new light on the role of this organelle
— id: 15731, year: 1985, vol: 65, page: 241, stat: Journal Article,

A substrate analog inhibitor for arylsulfatase reduces NK cell cytotoxicity
Zucker-Franklin D; Nabi ZF
1985 Jan 16;126(1):540-543, Biochemical & biophysical research communications
A synthetic aromatic sulfonate (I), which has been found to be an effective inhibitor of arylsulfatase, reduces NK-cell mediated cytotoxicity by ca. 60% at 10 microM concentration. At lower concentrations the effect is concentration dependent, but no further reduction of cytotoxicity is observed at concentrations above 10 microM
— id: 15730, year: 1985, vol: 126, page: 540, stat: Journal Article,

CYTOPLASMIC STRUCTURES IN ENDOTHELIAL-CELLS OF THE CHOROID [Discussion]
Zuckerfranklin, D
1985 ;8(4):379-379, Ultrastructural pathology
— id: 30818, year: 1985, vol: 8, page: 379, stat: Journal Article,

HOW CELL BIOLOGY HAS HELPED HEMATOLOGY - CURRENT STUDIES ON MEGAKARYOCYTES AND PLATELETS
ZUCKERFRANKLIN, D
1985 FEB ;39(2):41-41, European journal of cell biology
— id: 41513, year: 1985, vol: 39, page: 41, stat: Journal Article,

RECRUITMENT OF UNSENSITIZED LYMPHOCYTES FOR CYTOLYSIS OF TUMOR- CELLS
Zuckerfranklin, D; Nabi, ZF
1985 ;33(2):A611-A611, Clinical research
— id: 30936, year: 1985, vol: 33, page: A611, stat: Journal Article,

THE EFFECT OF PHORBOL-MYRISTATE ACETATE (PMA) ON TUMOR-CELL LYSIS BY NATURAL-KILLER (NK) CELLS AND NK-DEPLETED LYMPHOCYTES
NABI, ZF; ZUCKERFRANKLIN, D
1984 ;43(3):598-598, Federation Proceedings (Federation of American Societies for Experimental Biology)
— id: 41012, year: 1984, vol: 43, page: 598, stat: Journal Article,

Modulation of natural killer (NK) cells by autologous neutrophils and monocytes
Yang J; Zucker-Franklin D
1984 Jun;86(1):171-182, Cellular immunology
Although natural killer (NK) cell activity is remarkably stable in healthy individuals, the number and cytotoxicity of the cells fluctuate in disease. In man, regulatory mechanisms are virtually unexplored but depressed NK cell function accompanies most chronic diseases. A suppressive role of monocytes/macrophages has been reported. Since neutrophils (PMN) and monocytes (M) often respond reciprocally to pathologic stimuli, experiments were designed to investigate whether increments in PMN and M per se could influence NK cell function. Peripheral blood NK cells obtained by Percoll gradient centrifugation were either cocultured with various concentrations of autologous PMN or M or they were exposed to diffusates of these granulocytes in Millipore chambers. The treated NK cells were washed and then mixed with melanoma target cells in various effector:target cell ratios. It was observed that PMN diffusates augmented cytotoxicity whereas monocyte diffusates decreased the killing function of NK cells markedly and in a dose dependent fashion (P less than 0.001). The stimulatory effect of PMN diffusates was heat labile and not attributable to interferon. The inhibitory effect of M diffusates was heat stable, not due to prostaglandins or lysozyme, and irreversible within 6 hr of observation. Binding of effector to target cells was enhanced by PMN-media, and significantly inhibited by monocyte diffusates . It is therefore possible that factors elaborated by neutrophils and monocytes in vivo could also influence NK cell function
— id: 15733, year: 1984, vol: 86, page: 171, stat: Journal Article,

Thrombocytopoiesis--analysis by membrane tracer and freeze-fracture studies on fresh human and cultured mouse megakaryocytes
Zucker-Franklin D; Petursson S
1984 Aug;99(2):390-402, Journal of cell biology
The origin of platelets (Pt) from megakaryocytes (MK) is beyond question, but the mechanism whereby Pts are released from the precursor cell is still debated. A widely-held theory claims that the MK plasma membrane invaginates to form demarcation membranes (DMS), which delineate Pt territories. Accordingly, Pts would be derived mostly from the periphery of the MK, and the MK and Pt plasma membranes would have to be virtually identical. Since, on morphologic grounds, this theory is untenable, several aspects of thrombocytopoiesis were reexamined with the help of membrane tracer and freeze-fracture analyses of freshly-collected human and cultured mouse MK. To our surprise, freeze-cleavage of the MK plasma membrane revealed that the vast majority of intramembranous particles (IMP) remained associated with the protoplasmic leaflet (P face), whereas the partition coefficient of IMPs of the platelet membrane was the reverse. This is the first time that any difference between MK and Pt membranes has been determined. Replicas of freeze-fractured MK that were in the process of thrombocytopoiesis revealed an additional novel phenomenon, i.e., numerous areas of membrane discontinuity that appeared to be related to Pt discharge. When such areas were small, the IMP were lined up along the margin of the crevice. At a later phase, a labyrinth of fenestrations was observed. Thin sections of MK at various stages of differentiation showed that Pt territories were fully demarcated before connections of the DMS with the surface could be found. Therefore, the Pt envelope is probably not derived from invaginations of the MK plasma membrane. When living, MK were incubated with cationic ferritin or peroxidase at 37 degrees C, the tracers entered into the DMS but did not delineate all membranes with which the DMS was in continuity, suggesting the existence of distinctive membrane domains. Interiorization of tracer was not energy-dependent, but arrested at low temperatures. At 4 degrees C the DMS remained empty, unless there was evidence that Pts had been released. In such instances, the tracers outlined infoldings of peripheral cytoplasm that was devoid of organelles. Thus, the majority of Pts seem to originate from the interior of the MK, and the surface membranes of the two cells differ in origin and structure. The observations do not only throw new light on the process of thrombocytopoiesis, but also strengthen the possibility that MKs and Pts may be subject to different stimuli
— id: 15732, year: 1984, vol: 99, page: 390, stat: Journal Article,

Different enzyme classes associated with human natural killer cells may mediate disparate functions
Zucker-Franklin D; Yang J; Fuks A
1984 Mar;132(3):1451-1455, Journal of immunology
Previous studies have shown that degradation of the acute phase reactant serum amyloid A (SAA) is mediated by enzymes on the plasma membrane of lymphocytes and monocytes. The responsible enzymes had properties of neutral elastases. The present investigations were conducted to explore whether human NK cells enriched by Percoll gradient centrifugation have similar activity and if so, whether the same or different enzyme classes are responsible for proteolysis as well as for tumor cell lysis. Accordingly, human NK cells were enriched on discontinuous Percoll gradients after which the cells were incubated either with SAA or with [3H] proline-labeled melanoma cells at various effector to target cell ratios. When SAA degradation was followed by SDS-polyacrylamide gel electrophoresis, NK fractions proved to be as effective in digesting the protein as unfractionated mononuclear leukocytes. To characterize the enzymes that may be involved in cytotoxicity on the one hand, and SAA degradation on the other, the NK fractions were treated with the following inhibitors: diisopropylfluorophosphate (DFP), soybean trypsin inhibitor, N-p-tosyl-L-lysine chloromethylketone (TLCK), the elastase inhibitors elastatinal, Ac-Ala-Ala-Pro-Val-CH2Cl, Meo-Suc-Ala-Ala-Pro-Val-CH2Cl, and an inhibitor of aryl sulfatase, Na2SO4. Preincubation of the cells with DFP or elastase inhibitors abolished their ability to hydrolyze SAA but did not affect their ability to kill tumor cells. On the other hand TLCK, a potent inhibitor of cytotoxicity, did not bring about any reduction in the proteolysis of SAA. DFP and Na2SO4 diminished cytotoxicity partially. Elimination of NK cells by sorting after incubation of lymphocytes with the monoclonal antisera Leu-7 and Leu-11 abolished cytotoxicity as well as proteolysis. The observations are compatible with the concept that NK cells carry several enzymes with different substrate specificities that may be involved in disparate cellular functions
— id: 15734, year: 1984, vol: 132, page: 1451, stat: Journal Article,

IMPAIRED KUPFFER CELL-FUNCTION MAY PRECEDE DEPOSITION OF AMYLOID IN SECONDARY AMYLOIDOSIS
ZUCKERFRANKLIN, D; FUKS, A
1984 ;32(2):A566-A566, Clinical research
— id: 40986, year: 1984, vol: 32, page: A566, stat: Journal Article,

ULTRASTRUCTURAL, HISTOCHEMICAL AND FUNCTIONAL-CHANGES OF ISOLATED KUPFFER CELLS (KC) FROM MICE UNDERGOING CHRONIC ANTIGENIC-STIMULATION
ZUCKERFRANKLIN, D; FUKS, A
1984 ;36(3):426-426, Journal of leukocyte biology
— id: 40904, year: 1984, vol: 36, page: 426, stat: Journal Article,

Identification of elastases associated with purified plasma membranes isolated from human monocytes and lymphocytes
Fuks A; Zucker-Franklin D; Franklin EC
1983 Jan 25;755(2):195-203, Biochimica & biophysica acta
Studies were carried out to understand the pathogenesis of amyloid formation and to localize the elastase-like enzymes postulated to be associated with the surface of human peripheral blood monocytes and lymphocytes. These enzymes are known to degrade serum amyloid A and amyloid A proteins. Pure plasma membrane preparations were obtained by allowing cells to attach to polyacrylamide beads, followed by their disruption. The purity of the membranes was monitored by electron microscopy and enzyme determinations. The extracted membrane enzymes which have molecular weights of 56000 and 30000, respectively, were inhibited by DFP, MeO-Suc-Ala-Ala-Pro-Val-CH2Cl, Ac-Pro-Phe-Arg-CH2Cl . HCl, and elastinal but were not inhibited by EDTA or epsilon-amino caproic acid, thus exhibiting the properties of elastases. These enzymes cleave serum amyloid A to amyloid protein A. In some individuals, cleavage stops at this point, while in others a second step occurs, resulting in complete protein degradation. This activity was comparable whether monocyte or lymphocyte plasma membranes were employed. Since lymphocyte dependent cytotoxicity has also been attributed to surface proteases, it is likely that a spectrum of membrane associated enzymes mediate important physiologic function of these mononuclear leukocytes
— id: 15739, year: 1983, vol: 755, page: 195, stat: Journal Article,

Purification and characterization of actin from normal and chronic lymphocytic leukemia lymphocytes
Liebes LF; Stark R; Nevrla D; Grusky G; Zucker-Franklin D; Silber R
1983 Oct;43(10):4966-4973, Cancer research
Previous studies from this laboratory have shown actin to be a major protein of human lymphocytes (Stark, R., Liebes, L. F., Nevrla, D., and Silber, R. Biochem. Med., 27: 200-206, 1982). We now report the purification to homogeneity and characterization of actin from blood lymphocytes of normal subjects and patients with chronic lymphocytic leukemia. The recovery of the purified protein was about 20%. The properties of the lymphocyte actins were compared to each other and to those of rabbit skeletal muscle actin. Lymphocyte actin consisted of beta and gamma forms in a 2:1 ratio. The Mr 42,000 was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Normal and leukemic lymphocyte actin had similar polymerization properties as assessed by viscosity measurements at 25 degrees and 4 degrees, and the ultrastructural appearance of the filaments was the same. Similar patterns were observed between normal and chronic lymphocytic leukemia actin tryptic digests analyzed by high-performance liquid chromatography. The Vmax of the actin-activated myosin Mg2+ ATPase activity was compared using rabbit skeletal muscle heavy meromyosin and subfragment 1 preparations. The values obtained with rabbit skeletal muscle and normal lymphocyte actin were identical. The Vmax observed with chronic lymphocytic leukemia lymphocyte actin was 70% of that obtained with normal lymphocyte actin. The amount of actin needed to produce half-maximal activation (Kapparent) of heavy meromyosin and subfragment 1 were, respectively, 26 and 25 microM for normal lymphocytes and 18 and 24 microM for chronic lymphocytic leukemia lymphocytes. The anomalous ATP activation by actin did not reflect differences in B-:T-cell subpopulations between chronic lymphocytic leukemia and normal lymphocytes. The possible significance of the observed differences between the myosin Mg2+ ATPase activation by chronic lymphocytic leukemia and normal lymphocyte actin is discussed
— id: 15736, year: 1983, vol: 43, page: 4966, stat: Journal Article,

MODULATION OF NATURAL-KILLER (NK) CELL-ACTIVITY BY POLYMORPHONUCLEAR LEUKOCYTES(PMN) AND MONOCYTES (M)
YANG, JS; ZUCKERFRANKLIN, D
1983 ;31(2):A486-A486, Clinical research
— id: 40689, year: 1983, vol: 31, page: A486, stat: Journal Article,

"Looking" for the cause of AIDS
Zucker-Franklin D
1983 Apr 7;308(14):837-838, New England journal of medicine
— id: 15737, year: 1983, vol: 308, page: 837, stat: Journal Article,

Amyloid in myeloma stem-cell culture
Zucker-Franklin D; Frangione B
1983 May 12;308(19):1164-1165, New England journal of medicine
— id: 9624, year: 1983, vol: 308, page: 1164, stat: Journal Article,

Reed-Sternberg cells cultured from morphologically unidentifiable precursors in the blood of patients with Hodgkin's disease
Zucker-Franklin D; Grusky G; Baez L
1983 Apr-Jun;1(2):127-138, Hematological oncology
In order to examine whether morphologically unidentifiable precursors of Reed-Sternberg cells (RSC) may circulate in the blood of patients with untreated Hodgkin's Disease (HD), mononuclear leukocytes were isolated from the blood of 33 consecutive patients and cultured in soft agar. Abnormal colonies containing multinucleated giant cells developed in the specimens of 12 patients. These cells had the light and electron microscopic appearance of RSC. They were positive for alpha-naphthyl acetate and alpha-naphthyl butyrate esterases, acid phosphatase and lysozyme, bespeaking their monocyte/macrophage lineage. The observations suggest that unidentifiable precursors of RSC could be responsible for hematogenous spread of the disease in some cases. Moreover, since RS-like cells developed in the specimens of 8 patients with stage I and II HD, it may be useful to evaluate whether soft agar colony culture would yield data of prognostic significance in patients with early disease
— id: 15738, year: 1983, vol: 1, page: 127, stat: Journal Article,

Arylsulfatase in natural killer cells: its possible role in cytotoxicity
Zucker-Franklin D; Grusky G; Yang JS
1983 Nov;80(22):6977-6981, Proceedings of the National Academy of Sciences of the United States of America
Ultrastructural cytochemistry of natural killer cells enriched by Percoll gradient centrifugation showed them to possess arylsulfatase (aryl-sulfate sulfohydrolase, EC 3.1.6.1). The enzyme was located in vesicles, granules, and the parallel tubular arrays, organelles characteristic for cytotoxic lymphocytes. Biochemically, peak enzyme activity correlated with the Percoll fractions containing cells with cytotoxicity for melanoma target cells. Treatment of natural killer cells with Na2SO4, a competitive inhibitor of arylsulfatase, suppressed cytotoxicity by almost 50%. Electron microscopy of effector-target cell conjugates, which had been permitted to incubate for only 30 min, disclosed numerous arylsulfatase-positive sites at the points of contact between the effector/target cell membranes. Thus, the enzyme was translocated to the surface before lysis of the target cell was morphologically evident. It is postulated that the parallel tubular arrays play a role in this translocation and that arylsulfatase may function in the degradation of cerebroside sulfate ester components of the target cell membrane to initiate the lytic event
— id: 15735, year: 1983, vol: 80, page: 6977, stat: Journal Article,

OCCURRENCE OF RIBOSOME LAMELLA COMPLEXES - REPLY
ZUCKERFRANKLIN, D
1983 ;309(10):616-616, New England journal of medicine
— id: 40641, year: 1983, vol: 309, page: 616, stat: Journal Article,

LYMPHOCYTES HAVE DIFFERENT SURFACE ENZYMES INVOLVED INDEPENDENTLY IN PROTEOLYSIS AND CYTOLYSIS
ZUCKERFRANKLIN, D; YANG, JS; FUKS, A
1983 ;31(2):A540-A540, Clinical research
— id: 40694, year: 1983, vol: 31, page: A540, stat: Journal Article,

Pathologic effects of plasma from patients with thrombotic thrombocytopenic purpura on platelets and cultured vascular endothelial cells
Burns ER; Zucker-Franklin D
1982 Oct;60(4):1030-1037, Blood
The pathologic hallmarks of thrombotic thrombocytopenic purpura (TTP) include endothelial cell proliferation and subendothelial hyalin deposits in the microvasculature leading to symptomatic thrombotic occlusions. Plasma or sera from three consecutive patients with TTP were subjected to multiple analyses to determine whether they induce endothelial injury and/or platelet activation, two pathogenic mechanisms that may account for this disorder. Sera were utilized in a microcytotoxicity assay against cultured human umbilical vein endothelial cells (EC). These cells were assessed ultrastructurally and with immunofluorescence techniques to ascertain the nature of inflicted cell damage. Control plasmas were obtained from healthy volunteers as well as patients with immune complex disease and the adult hemolytic uremic syndrome. In the presence of TTP serum, cell kill of 3H-proline-labeled EC averaged 42% versus 8.6% for control sera. Cytotoxicity induced by an IgG fraction of TTP sera averaged 70% versus 16.8% for control IgG. Removal of IgG by immune precipitation diminished cytotoxicity by 70%. Using indirect immunofluorescence, IgG was detected on EC incubated with TTP serum but not on EC treated with control serum. Ultrastructural changes became apparent within 30 min after exposure of cultured EC to TTP serum. Virtually every cell developed numerous cytoplasmic inclusions rarely seen in EC in the presence of normal serum. Prolonged incubation with the TTP serum led to progressive cytolysis, terminating with complete cytoplasmic and nuclear degeneration. Plasma from all three patients with TTP caused spontaneous aggregation of normal washed platelets as monitored by aggregometry. No spontaneous aggregation occurred in response to control plasmas. These results indicate that the sera of the three TTP patients studied were able to mediate time-dependent immune destruction of human cultured endothelial cells and that their plasmas were capable of causing spontaneous aggregation of normal human platelets in vitro. It would seem likely that these mechanisms are also operative in vivo to produce the endothelial destruction as well as the thrombotic vascular occlusions seen in this disorder
— id: 18201, year: 1982, vol: 60, page: 1030, stat: Journal Article,

Cytotoxicity of natural killer cells: correlation with emperipolesis and surface enzymes
Burns ER; Zucker-Franklin D; Valentine F
1982 Jul;47(1):99-107, Laboratory investigation
Cell-mediated cytotoxicity involving natural killer cells requires contact between effector and target cells for effective cytolysis. Ultrastructural studies of biopsies of primary human malignant melanoma showed mononuclear leukocytes to be located in close proximity to tumor cells and, on occasion, within the confines of the melanoma cell itself. This phenomenon, called emperipolesis, was examined in vitro to determine whether the same population of cells that exhibits emperipolesis is responsible for cytotoxicity. Since natural killer cells have been identified morphologically and functionally as large granular lymphocytes with surface receptors for the Fc portion of immunoglobulin (FcR+ cells), lymphocytes were depleted of FcR+ cells, and their cytotoxicity and ability to emperipolese were measured. Both of these properties were markedly diminished (88 and 85 per cent, respectively). Systematic comparison of emperipolesis and cytotoxicity from donors known to exhibit either high or low lymphocyte cytotoxicity showed perfect concordance. Ultrastructural analysis of in vitro emperipolesis revealed the emperipolesing lymphocytes to be FcR+ cells establishing identity with the large granular cells known to mediate cytotoxicity. The morphologic marker found in both FcR+ cells, purified by rosetting techniques, and in emperipolesed lymphocytes consisted of cytoplasmic parallel tubular arrays. Further studies designed to elucidate a mechanism for cytotoxicity and emperipolesis implicated cell surface proteases as mediators of these activities. Competitive inhibition of surface proteases with artificial and natural inhibitors markedly reduced both cytotoxicity and emperipolesis. Therefore, it is likely that lymphocytes that are FcR+ participate in cell-medicated cytotoxicity through mechanisms involving cell contact and enzyme-initiated damage of target cells. Emperipolesis represents one type of effector-target cell contact leading to cytotoxicity
— id: 61762, year: 1982, vol: 47, page: 99, stat: Journal Article,

DEMONSTRATION OF ELASTASE ACTIVITY ASSOCIATED WITH LYMPHOCYTE AND MONOCYTE SURFACE-MEMBRANES
Fuks, A; Zuckerfranklin, D; Franklin, EC
1982 ;30(2):A559-A559, Clinical research
— id: 30437, year: 1982, vol: 30, page: A559, stat: Journal Article,

ANAPLASTIC MALIGNANT ROUND CELL TUMOR OF CHEST WALL
Yunis, EJ; Jaffe, R; Battifora, H; Gould, VE; Pauli, B; Mackay, B; Steiner, GC; Zuckerfranklin, D; Rosai, J; Sibley, RK; Dehner, LP
1982 ;3(4):387-392, Ultrastructural pathology
— id: 30337, year: 1982, vol: 3, page: 387, stat: Journal Article,

Evolution of Sezary syndrome in the course of hairy cell leukemia
Zucker-Franklin D; Amorosi EL; Ritz ND
1982 Jun;59(6):1181-1190, Blood
A patient with a history of 'leukemia' for 19 yr and documented hairy cell (HC) leukemia for 10 yr developed mycosis fungoides and the Sezary syndrome. The manifestations of both diseases were diagnostic on clinical and pathologic grounds. Ultrastructural, immunohistochemical, and surface marker techniques proved the HC to have phenotypic characteristics of the T-helper subset of lymphocytes to which the Sezary cells (SC) also belonged. Both types of cells contained tartrate-resistant acid phosphatase. HC did not infiltrate the skin. SC did not contain ribosome lamellar complexes. Because of otherwise overlapping morphology and the apparent replacement of HC by SC, it is likely that the Sezary cells constituted a genetic variant of the original neoplastic clone represented by the hairy cells. Since the biologic and therapeutic implications of such clonal evolution may be important, subtle phenotypic changes should be looked for repeatedly in patients with these diseases
— id: 61763, year: 1982, vol: 59, page: 1181, stat: Journal Article,

NEW CONCEPT OF THROMBOCYTOPOIESIS AS REVEALED BY FREEZE-FRACTURE (FF) ANALYSIS OF CULTURED MEGAKARYOCYTES
Zuckerfranklin, D; Petursson, SR
1982 ;95(2):A270-A270, Journal of cell biology
— id: 30359, year: 1982, vol: 95, page: A270, stat: Journal Article,

PLASMA FIBRONECTIN LEVELS IN HEMOSTATIC DISORDERS MEASURED BY SOLID-PHASE RADIOIMMUNOASSAY
BAEZ, L; ZUCKERFRANKLIN, D; PEARLSTEIN, E; LACKNER, H
1981 JAN 20 ;29(2):A515-A515, Clinical research
— id: 98642, year: 1981, vol: 29, page: A515, stat: Journal Article,

Characterization of the cell population mediating cytotoxicity and emperipolesis in human malignant melanomas
Burns ER; Zucker-Franklin D; Valentine F
1981 ;94:366-371, Transactions of the Association of American Physicians
— id: 61770, year: 1981, vol: 94, page: 366, stat: Journal Article,

CHARACTERIZATION OF THE CELL-POPULATION MEDIATING CYTO-TOXICITY AND EMPERIPOLESIS IN HUMAN-MALIGNANT MELANOMA
BURNS, ER; ZUCKERFRANKLIN, D; VALENTINE, F
1981 ;29(2):A580-A580, Clinical research
— id: 40228, year: 1981, vol: 29, page: A580, stat: Journal Article,

Interaction of mononuclear leukocytes with malignant melanoma
Fujinami N; Zucker-Franklin D; Valentine F
1981 Jul;45(1):28-37, Laboratory investigation
Since it is well established that cellular immunity plays a role in the defense against melanoma, the morphologic aspects of this reaction warranted investigation. Accordingly, peripheral blood mononuclear cells obtained from healthy donors were incubated with human melanoma cells for 1 to 24 hours to examine, on the ultrastructural level, the cellular interaction that eventuates in cytolysis of the tumor cells. Within 1 hour of incubation, monocytes and lymphocytes were seen attached to approximately 40 per cent of the melanoma cells with marked interdigitation of cellular processes. After 4 hours of incubation, the percentage of tumor cells with attached leukocytes remained the same, but 2 to 9 per cent of the melanoma cells showed interiorized lymphocytes when kept in suspension, 10 to 25 per cent when maintained in culture dishes. Erythrocytes or fixed lymphocytes were not taken up by the melanoma cells nor were living lymphocytes seen in fibroblasts or endothelial cells which served as controls for the neoplastic cell lines. Thus, melanoma cells did not prove to be randomly phagocytic, and the interiorization displayed by lymphocytes--a process called emperipolesis--appears to be selective. It is postulated that emperipolesis may enhance the tumoricidal effect exerted by cytotoxic lymphocytes on melanoma cells
— id: 61768, year: 1981, vol: 45, page: 28, stat: Journal Article,

Factors affecting the release of proteases from peripheral blood monocytes
Fuks A; Zucker-Franklin D; Franklin EC
1981 Nov;14(5):577-579, Scandinavian journal of immunology
Serum amyloid A (SAA) protein is degraded by serine proteases associated with the external plasma membrane of peripheral blood monocytes. The plasma membrane-associated enzymes are serine proteases of high molecular weight. In addition, cells grown in suspension release enzymatic activity into the surrounding medium. The origin and nature of the released SAA degrading enzymes remains obscure, but they appear to belong to the general class of serine proteases. Conditions of culture were determined which minimized release of the secreted enzymes and will ultimately permit the characterization of the properties of the membrane associated enzymes uncontaminated with the cytoplasmic proteases. It seems likely that there are two compartments of proteases-one surface-associated and one cytoplasmic
— id: 61765, year: 1981, vol: 14, page: 577, stat: Journal Article,

Comparison of lipid composition and 1,6-diphenyl-1,3,5-hexatriene fluorescence polarization measurements of hairy cells with monocytes and lymphocytes from normal subjects and patients with chronic lymphocytic leukemia
Liebes LF; Pelle E; Zucker-Franklin D; Silber R
1981 Oct;41(10):4050-4056, Cancer research
In this report, we compare the lipid composition and fluorescence polarization properties of hairy cells with those of monocytes and lymphocytes from normal subjects and of lymphocytes from patients with chronic lymphocytic leukemia. For hairy cells, the cholesterol content was 4.66 +/- 1.49 (S.D.) mumol/10(9) cells, and the cholesterol/phospholipid ratio was 0.60 +/- 0.09. These were significantly higher than the values of normal lymphocytes, (cholesterol content, 2.75 +/- 0.65 mumol; cholesterol/phospholipid ratio, 0.50 +/- 0.07) or of chronic lymphocytic leukemia lymphocytes (cholesterol content, 1.76 +/- 0.43 mumol; cholesterol/phospholipid ratio, 0.44 +/- 0.07). Normal monocyte values (cholesterol content, 5.81 +/- 2.08 mumol; cholesterol/phospholipid ratio, 0.59 +/- 0.06) were similar to those of hairy cells. Using the probe 1,6-diphenyl-1,3,5-hexatriene, the fluorescence polarization value at 25 degrees for hairy cells was 0.302, compared to the value of 0.259 obtained with chronic lymphocytic leukemia lymphocytes. Intermediate values (0.294) were obtained with normal lymphocytes and monocytes. Fluorescence polarization values were higher in hairy cell membranes than in chronic lymphocytic leukemia lymphocyte membranes, indicating a low fluidity in the former cell, compatible with their higher cholesterol content and cholesterol/phospholipid ratio. These studies show that two neoplastic cells, hairy cells and chronic lymphocytic leukemia lymphocytes, differ markedly in membrane fluidity and that a high membrane fluidity does not necessarily occur in neoplasia
— id: 61766, year: 1981, vol: 41, page: 4050, stat: Journal Article,

BIOCHEMICAL-CHARACTERIZATION OF ACTIN FROM NORMAL AND LEUKEMIC LYMPHOCYTES
Liebes, L; Stark, R; Nevrla, D; Unger, P; Zuckerfranklin, D; Silber, R
1981 ;33(2):A214-A214, Biophysical journal
— id: 30290, year: 1981, vol: 33, page: A214, stat: Journal Article,

Atlas of blood cells : function and pathology
Zucker-Franklin D
Philadelphia : Lea & Febiger, 1981,
— id: 1554, year: 1981, vol: , page: , stat: ,

Endocytosis by human platelets: metabolic and freeze-fracture studies
Zucker-Franklin D
1981 Dec;91(3 Pt 1):706-715, Journal of cell biology
The mechanism by which platelets endocytose or release particulate or soluble substances is poorly understood. Engulfed materials enter the open canalicular system (OCS) by a process akin to phagocytosis, but fusion of platelet granules with the OCS is rarely observed. Secretion of granule contents, a concomitant of the 'release reaction' which occurs during platelet aggregation, does not take place by extrusion at the surface membrane as is true for other secretory cells. Some substances may be secreted without obvious granule loss. To examine whether structural properties of the platelet membrane could account for this unusual behavior, thin section and freeze-fracture analyses were performed on platelets which had undergone endocytosis under a variety of experimental conditions. After freeze-cleavage, most of the intramembranous particles (IMP) remain associated with the outer leaflet of the platelet plasma membrane. The sites where the OCS reaches the surface membrane are marked by pits on the cytoplasmic leaflet (P face) and by complementary protrusions on the outer leaflet (E face) of the membrane. Endocytosis of small particles and solutes takes place via these structures. This process is not energy dependent but arrested at 4 degrees C. Distension of the OCS does not appear to affect the size or number of the pits. On the other hand, large particles are taken up by membrane invagination without redistribution of IMP's and independent of the pits. This process is sensitive to metabolic inhibition. Thus, the studies have demonstrated the existence of two different pathways for platelet endocytosis which are postulated to be also involved in secretion. The selective release of substances contained in different granules may be related to the 'inside-out' structure of the plasma and OCS membranes
— id: 61764, year: 1981, vol: 91, page: 706, stat: Journal Article,

The presence of mast cell precursors in rat peripheral blood
Zucker-Franklin D; Grusky G; Hirayama N; Schnipper E
1981 Sep;58(3):544-551, Blood
Soft agar culture of mononuclear cell fractions prepared from rat peripheral blood yielded numerous colonies consisting of mast cells. The mast cell nature of the cells was established by ultrastructural and histochemical analyses as well as by the demonstration the the colonies contained histamine and that the cells possessed receptors for the Fc component of IgE. Stringent criteria for the distinction of mast cells from monocytes/macrophages that could have metachromatic inclusions were applied. The alcian-blue-safranin technique delineated the maturation of mast cell granules by showing the loss of alcian-blue and increase in safranin-positive organelles presumed to reflect the increase in N-sulfated polysaccharides representing heparin. The mast cells exhibited low or absent reactions for peroxidase, alpha-naphthyl butyrate, periodic acid Schiff, and Sudan black reacting lipid, whereas macrophages stained in parallel were positive for these substances. Since it is known that extracellular conditions may cause variations in phenotypic expression, the observations have led to the hypothesis that mast cells and macrophages may have a common precursor
— id: 61767, year: 1981, vol: 58, page: 544, stat: Journal Article,

Demonstration of membrane-bound proteolytic activity on the surface of mononuclear leukocytes
Zucker-Franklin D; Lavie G; Franklin EC
1981 Mar;29(3A Suppl):451-456, Journal of histochemistry & cytochemistry
The existence of proteolytic enzymes bound to the surface of migrating cells has often been surmised. That such enzymes are present on mononuclear leukocytes was suggested by studies showing that serum amyloid A (SAA), the presumed precursor of amyloid protein A, is degraded in the presence of monocytes without endocytosis and with only negligible activity in the cells' supernates. Experiments using immunofluorescence were designed to support this view. It was shown that SAA binds to the cells' surface at low temperatures, whereas binding at 37 degrees C could only be demonstrated when the cells were pretreated with the serine protease inhibitor, diisopropyl-fluorophosphate (DFP) or the elastase inhibitor Ac-Ala-Ala-Pro-Val-CH2Cl. Exposure of the cells to these inhibitors before incubation with SAA at 0 degrees C permitted detection of the protein for an indefinite period of time. At 37 degrees C the DFP-treated cells polarized and eventually lost the surface-bound protein. No interiorized SAA could be demonstrated. Radioautography of cells that had been treated with 3H-DFP revealed grains on the plasma membrane and in the cytoplasm of sectioned monocytes, whereas only 8-15% of lymphocytes were labeled. In lymphocytes radioactivity was restricted to the surface membrane. Additional experiments showed that alpha-naphthyl acetate esterase activity is also located on the surface of monocytes and a subpopulation of lymphocytes. These observations have led to the conclusion that some functions of mononuclear leukocytes may be mediated by enzymes associated with the external surface of these cells
— id: 61769, year: 1981, vol: 29, page: 451, stat: Journal Article,

Nature of the giant cell in Hodgkin's disease
Zucker-Franklin D; Schinella R
1981 Jan-Mar;2(1):81-83, Ultrastructural pathology
— id: 66702, year: 1981, vol: 2, page: 81, stat: Journal Article,

Current concepts of the structure and pathogenesis of the amyloid diseases
Franklin EC; Lavie G; Zucker-Franklin D
1980 Jan-Mar;10(1):3-7, Ricerca in clinica e in laboratorio = Research in clinic & laboratory
— id: 61775, year: 1980, vol: 10, page: 3, stat: Journal Article,

Elastase-type proteases on the surface of human blood monocytes: possible role in amyloid formation
Lavie G; Zucker-Franklin D; Franklin EC
1980 Jul;125(1):175-180, Journal of immunology
A group of DFP-inhibitable serine proteases that are associated with the cell surface of human peripheral blood monocytes and degrade the amyloid precursor protein SAA has been partially characterized. Enzymes that resemble elastases in being inhibitable by Ac-Ala-Ala-Pro-Val-CH2Cl but differ from the secreted macrophage elastase in m.w. can be recovered from SDS gels in the region ranging from 58 to 72 x 10(3) daltons. These enzymes degrade SAA to a product similar in m.w. and antigenic properties to the amyloid A protein. When intact cells are labeled with 3H Ac-Ala-Ala-Pro-Val-CH2Cl at 4 degrees C for 3 min, a major 58 x 10(3) and two minor 48 and 65 x 10(3) dalton bands are seen. Another group of enzymes that digests SAA completely through a transient AA-like intermediate can be recovered from the 40 to 58 x 10(3) dalton region of the gels. These enzymes are only minimally inhibited by Ac-Ala-Ala-Pro-Val-CH2Cl. We suggest that both types of enzymes may be involved in the proteolytic processes that lead to amyloid formation in secondary amyloidosis
— id: 61773, year: 1980, vol: 125, page: 175, stat: Journal Article,

Human lymphocyte tubulin. Purification and characterization in normal and leukemic cells
Liebes LF; Fleit H; Zucker-Franklin D; Silber R
1980 Dec 1;633(2):245-257, Biochimica & biophysica acta
Tubulin has been purified from human blood and tonsil lymphocytes. Using gel filtration, the molecular weight of human lymphocyte tubulin was estimated to be 119000. The protein was shown to consist of two subunits, with molecular weights of 61000 and 58000 comparable to the alpha and beta polypeptides of human brain tubulin. A partial identity reaction was observed between lymphocyte tubulin and human tubulin when tested by double immunodiffusion against a rabbit anti-human brain tubulin antibody. In the presence of GTP, the purified protein polymerized to form microtubules. Tubulin was localized to the cell's juxtacentriolar region by immunofluorescence and electron microscopy. When assayed by a colchicine-binding assay corrected for time decay, the binding affinity was 1.50 +/- 0.86 . 10(6) M-1 and a level in normal lymphocytes of 1.21 . 10(2) +/- 0.79 g/g of soluble protein was determined. Since chronic lymphocytic leukemia lymphocytes have an anomalous capping behavior as well as an unusual susceptibility to colchicine toxicity, the properties and levels of tubulin were determined in these cells. Similar values were obtained for the level, decay rate, molecular weight, and Ka for colchicine as for normal lymphocytes. Chronic lymphocytic leukemia lymphocytes tubulin polymerized in a normal fashion. It thus appears that a decrease in the quantity for function of tubulin does not account for these anomalies in the chronic lymphocytic leukemia lymphocyte
— id: 61771, year: 1980, vol: 633, page: 245, stat: Journal Article,

ULTRASTRUCTURAL PATHOLOGY
MACKAY, B; FERRANS, VJ; HENRY, K; WEISS, L; ZUCKERFRANKLIN, D
1980 ;1(1):67-70, Ultrastructural pathology
— id: 50115, year: 1980, vol: 1, page: 67, stat: Journal Article,

Light-microscopic analysis of sectioned Sezary cells: an accurate alternative to electron microscopy
Myrie C; Zucker-Franklin D; Ramsey D
1980 Apr;99(1):243-252, American journal of pathology
The prognostic implications of circulating Sezary cells in mycosis fungoides (MF) are not known, and the significance of fluctuating Sezary cell counts in either MF or the Sezary syndrome has not been assessed. Such studies have been hampered by the inaccuracy of counts performed on routine blood smears and the unavailability of electron microscopy for routine purposes. The present studies conducted on the peripheral blood of 35 patients with either MF or the Sezary syndrome show that Sezary cell counts performed by light microscopy of sectioned Epon-embedded lymphocyte fractions are as accurate as those carried out at the ultrastructural level. In addition, the studies include preliminary observations concerning 20 patients whose Sezary cell counts were repeated over time intervals ranging from 3 months to over 5 years. The described method should facilitate the performance of blood and lymph node Sezary cell counts on a wider scale, which is a necessity if the significance of circulating Sezary cells is to be evaluated
— id: 61774, year: 1980, vol: 99, page: 243, stat: Journal Article,

Ultrastructural evidence for the common origin of human mast cells and basophils
Zucker-Franklin D
1980 Sep;56(3):534-540, Blood
Although the functional similarity of basophils and mast cells is widely accepted, their distinctive morphological features have been taken to indicate the existence of two different, albeit functionally complementary, cell systems. The recent demonstration that mast cells as well as basophils originate from the bone marrow raises the possibility that these cells derive from the same precursor. This report provides evidence for this theory by describing a distinctive 'intermediate' cell possessing the ultrastructural features typical of both basophils and mast cells. These cells were encountered in three patients with myeloproliferative diseases and may thus be more readily found in states of disturbed myelopoiesis. These observations have given impetus for the first comparative description of the ultrastructure of human basophils, human mast cells, and the newly recognized intermediate cell within a single report
— id: 61772, year: 1980, vol: 56, page: 534, stat: Journal Article,

THE SIGNIFICANCE OF SEZARY CELLS (SC) IN THE BLOOD OF PATIENTS WITH MYCOSIS-FUNGOIDES (MF)
Zuckerfranklin, D; Ramsay, D; Myrie, C
1980 ;28(2):A542-A542, Clinical research
— id: 28016, year: 1980, vol: 28, page: A542, stat: Journal Article,

INTERACTION OF MONONUCLEAR LEUKOCYTES WITH CULTURED MELANOMA CELLS
Fujinami, N; Zuckerfranklin, D
1979 ;38(3):993-993, Federation Proceedings (Federation of American Societies for Experimental Biology)
— id: 30034, year: 1979, vol: 38, page: 993, stat: Journal Article,

MEMBRANE-BOUND ELASTASE-LIKE PROTEASES ON MONOCYTES AND LYMPHOCYTES
Lavie, G; Zuckerfranklin, D; Franklin, EC
1979 ;38(3):1419-1419, Federation Proceedings (Federation of American Societies for Experimental Biology)
— id: 30149, year: 1979, vol: 38, page: 1419, stat: Journal Article,

PURIFICATION AND CHARACTERIZATION OF TUBULIN FROM HUMAN LEUKEMIC LYMPHOID-TISSUE
Liebes, L; Zuckerfranklin, D; Silber, R
1979 ;25(2):A35-A35, Biophysical journal
— id: 30052, year: 1979, vol: 25, page: A35, stat: Journal Article,

Capping and freeze-fracture analysis of Sezary cells
Zucker-Franklin D
1979 Jul;54(1):274-279, Blood
The functional integrity of blood and skin Sezary cells was examined in regard to motility, capping proficiency, and intramembranous particle (IMP) mobility. In contrast with chronic lymphocytic leukemia lymphocytes, which are relatively inert in these respects, variable proportions of Sezary cells are motile and are able to cap and cluster their IMP's. Since these functions may reflect a cell's propensity for diapedesis, these observations may help to explain the inverse relationship between the size of the skin infiltrate and the number of circulating Sezary cells often observed in this condition
— id: 61776, year: 1979, vol: 54, page: 274, stat: Journal Article,

Differences in the behavior of the membrane and membrane-associated filamentous structures in normal and chronic lymphocytic leukemia (CLL) lymphocytes
Zucker-Franklin D; Liebes LF; Silber R
1979 Jan;122(1):97-107, Journal of immunology
— id: 61777, year: 1979, vol: 122, page: 97, stat: Journal Article,

SURFACE ENZYME-ACTIVITY - ADDITIONAL MECHANISM OF MONONUCLEAR CELL-FUNCTION
Zuckerfranklin, D; Lavie, G; Franklin, EC
1979 ;27(2):A509-A509, Clinical research
— id: 30128, year: 1979, vol: 27, page: A509, stat: Journal Article,

An unusual case of a plasma cell neoplasm with an IgG3lambda myeloma and a gamma3 heavy chain disease protein
Adlersberg JB; Grann V; Zucker-Franklin D; Frangione B; Franklin EC
1978 Jan;51(1):85-96, Blood
A unique case of gamma3 heavy chain disease with two related serum proteins is reported. One molecule appears to be an IgG3lambda myeloma protein. The second molecule is a dimer of a shortened gamma3 heavy chain that has an unblocked amino terminus and lacks the VH and CH1 domains. Its probable origin as a synthetic product is discussed. The clinical and pathologic features of this patient resemble those of other patients with gamma heavy chain disease more than those of patients with multiple myeloma. It seems likely that the heavy chain disease protein is the result of a mutational event in the malignant clone originally producing the myeloma protein.
— id: 9661, year: 1978, vol: 51, page: 85, stat: Journal Article,

Degradation of serum amyloid A protein by surface-associated enzymes of human blood monocytes
Lavie G; Zucker-Franklin D; Franklin EC
1978 Oct 1;148(4):1020-1031, Journal of experimental medicine
Peripheral blood monocytes incubated in a serum-free medium degraded serum amyloid A (SAA) protein along three pathways. Of 20 normal subjects, 8 degraded SAA completely with no detectable intermediates. Eight subjects transiently produced an amyloid A (AA)-like intermediate which comigrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (PAGE) with tissue AA protein and reacted with antisera to AA, whereas four subjects yielded a persistent AA-like intermediate on PAGE. This group also failed to degrade tissue AA protein. Cells from 10 patients with amyloidosis fell into the second group. The responsible enzymes appear to be serine proteases because they are inhibited by disopropyl fluorophosphate. They were not affected by epsilon-amino caproic acid, L-1-tosylamide-2-phenylethyl chloromethyl ketone, or N-alpha-p-tosyl-L-lysine chlormethyl ketone. It appears possible that the enzymes are associated with the outer membrane of the cell because only a small fraction of the activity is secreted into the medium and because enzyme activity remains after fixation of the cells with glutaraldehyde which completely stops phagocytosis. Perhaps differences in patterns of proteolysis may play a role in the predisposition to amyloidosis
— id: 61778, year: 1978, vol: 148, page: 1020, stat: Journal Article,

DEGRADATION OF AMYLOID PRECURSOR (SAA) BY BLOOD MONOCYTES - ROLE IN PATHOGENESIS
Lavie, G; Zuckerfranklin, D; Franklin, EC
1978 ;26(3):A517-A517, Clinical research
— id: 29818, year: 1978, vol: 26, page: A517, stat: Journal Article,

Eosinophil function related to cutaneous disorders
Zucker-Franklin D
1978 Jul;71(1):100-105, Journal of investigative dermatology
A concise review of the ultrastructural features and physiological properties of eosinophils is presented with the aim of delineating those properties of eosinophils that set them apart from other granulocytes. It has become clear that eosinophols are subject to chemotaxis by attractants that do not affect other cells (e.g., histamine, ECF-A, ESP) and that they contain antiflogistic agents (arylsulfatase IIB, peroxidase) that neutralize specific substances known to elicit the inflammatory response. The mechanisms underlying eosinophilia in a variety of cutaneous disorders are analyzed in the light of this information
— id: 61779, year: 1978, vol: 71, page: 100, stat: Journal Article,

Ultrastructure of the fibrillar proteins in platelets
Zucker-Franklin D
1978 ;63:37-47, Supplementum ... ad Thrombosis & haemostasis
— id: 61782, year: 1978, vol: 63, page: 37, stat: Journal Article,

Transformation of monocytes into "fat" cells
Zucker-Franklin D; Grusky G; Marcus A
1978 May;38(5):620-628, Laboratory investigation
Human peripheral blood leukocytes, when cultured in soft agar give rise to giant (100 to 500 micrometer.) 'foam cells.' Investigation of the origin and properties of the cells proved that they were derived from monocytes in that the cells adherent to glass after 24 hours in culture were phagocytic, elaborated lysozyme and bore receptors for complement and immunoglobulin. The increment in size was accounted for primarily by large inclusions which on histochemical and biochemical analyses were shown to consist predominantly fo neutral fat. Transformation to fat cells took place in the absence of mitosis. Fc receptors were retained but complement receptors were lost. These observations suggest a role for monocytes in the replacement of hematopoietic tissue by fat in certain hypoplastic states. The cultured monocytes may also serve to facilitate the study of fat synthesis and metabolism in vitro
— id: 61780, year: 1978, vol: 38, page: 620, stat: Journal Article,

Platelet interaction with cartilage -- the role of proteoglycans in vitro and in vivo
Zucker-Franklin D; Rosenberg L
1978 ;63:321-336, Supplementum ... ad Thrombosis & haemostasis
— id: 61781, year: 1978, vol: 63, page: 321, stat: Journal Article,

PLATELET AND RED-CELL FRAGMENTS IN THROMBOCYTOPENIA - REPLY
Zuckerfranklin, D; Karpatkin, S
1978 ;298(6):341-341, New England journal of medicine
— id: 29860, year: 1978, vol: 298, page: 341, stat: Journal Article,

Mixed cryoglobulinemia-an immune complex disease often associated with hepatitis B virus infection
Levo Y; Gorevic PD; Kassab H; Zucker-Franklin D; Gigli I; Franklin EC
1977 ;90:167-173, Transactions of the Association of American Physicians
— id: 61787, year: 1977, vol: 90, page: 167, stat: Journal Article,

Association between hepatitis B virus and essential mixed cryoglobulinemia
Levo Y; Gorevic PD; Kassab HJ; Zucker-Franklin D; Franklin EC
1977 Jun 30;296(26):1501-1504, New England journal of medicine
In view of a high frequency of liver involvement in patients with essential mixed cryoglubulinemia, we looked for evidence for hepatitis B virus infection in 25 serum specimens and 19 cryoprecipitates obtained from 30 patients. Three of the 25 serum specimens contained Hbs Ag, and 12 had antibody. The frequency of positive results was increased to six and 11 of 19 respectively when cryoprecipitates were examined, and 14 of 19 (74 per cent) of the cryoprecipitates were positive for either HBs Ag or its antibody. Electron microscopy of four cryoprecipitates showed structures resembling the 20-nm and 27-nm spheres, tubules, as well as the Dane particles characteristic of hepatitis B virus infection. Since such infection appears to be involved in the pathogenesis of the syndrome, the term 'essential mixed cryoglobulinemia' should be replaced by 'mixed cryoglobulinemia secondary to hepatitis B virus' or perhaps to other viral infections
— id: 61783, year: 1977, vol: 296, page: 1501, stat: Journal Article,

MIXED CRYOGLOBULINEMIA, AN IMMUNE-COMPLEX DISEASE OFTEN ASSOCIATED WITH HEPATITIS B-VIRUS (HBV) INFECTION
LEVO, Y; GOREVIC, PD; KASSAB, H; ZUCKERFRANKLIN, D; GIGLI, I; FRANKLIN, EC
1977 ;25(3):A520-A520, Clinical research
— id: 39983, year: 1977, vol: 25, page: A520, stat: Journal Article,

HEPATITIS-B AND ESSENTIAL MIXED CRYOGLOBULINEMIA - REPLY
LEVO, Y; GOREVIC, PD; KASSAB, HJ; ZUCKERFRANKLIN, D; FRANKLIN, EC
1977 ;297(17):947-947, New England journal of medicine
— id: 39931, year: 1977, vol: 297, page: 947, stat: Journal Article,

LOCALIZATION OF FILAMENTOUS STRUCTURES IN NORMAL AND CHRONIC LYMPHOCYTIC-LEUKEMIA (CLL) LYMPHOCYTES EXPOSED TO ANTIBODY
Liebes, L; Silber, R; Zuckerfranklin, D
1977 ;50(5):172-172, Blood
— id: 29557, year: 1977, vol: 50, page: 172, stat: Journal Article,

Formation of lipid inclusions in normal human leukocytes
Lutas EM; Zucker-Franklin D
1977 Feb;49(2):309-320, Blood
Normal peripheral blood leukocytes left standing at room temperature develop large inclusions which increase in number and size with time of incubation. The formation and nature of these inclusions were investigated. At 0 hour the structures were present in only 1% of the cells, whereas at 48 hr, they were in virtually all neutrophils and monocytes. Ultrastructurally, the globules measured 0.5-1.5 mu in diameter and they were usually not membrane bound. Histochemical analysis indicated that they were lipid in nature. The inclusions were separated on a sucrose density gradient and their isolation was confirmed by electron microscopy. Thin-layer chromatography of the isolated globules suggested that they consisted predominantly of triglycerides. Since it is known that the cells synthesize triglycerides at rest, it was postulated that the structures may represent the storage form for free fatty acids which may be utilized for membrane synthesis during phagocytosis
— id: 61786, year: 1977, vol: 49, page: 309, stat: Journal Article,

STRUCTURE AND FUNCTION OF PROTEOGLYCANS
Rosenberg, L; Tang, LH; Zuckerfranklin, D
1977 ;174(SEP):77-77, Abstracts of papers (American Chemical Society)
— id: 29796, year: 1977, vol: 174, page: 77, stat: Journal Article,

Platelet interaction with modified articular cartilage. Its possible relevance to joint repair
Zucker-Franklin D; Drosenberg L
1977 Apr;59(4):641-651, Journal of clinical investigation
During studies concerned with the platelet-collagen interaction, it was observed that platelets did not adhere to bovine or human articular cartilage and that cartilage did not induce platelet aggregation in vivo or in vitro. To study the mechanism responsible for this observation, the role of proteoglycans was examined. Purified cartilage collagen proved to be fully active as a platelet aggregant. Addition of small amounts of proteoglycan subunit (PGS) blocked platelet aggregation, whereas chondroitin sulfate, a major glycosaminoglycan component of cartilage matrix, impaired platelet aggregation only at concentrations which resulted in a marked increase in viscosity. Moreover, PGS abolished aggregation of platelets by polylysine but did not prevent aggregation by ADP, suggesting that PGS may block strategically placed lysine sites on the collagen molecule. Treatment of fresh articular cartilage with proteolytic enzymes rendered the tissue active as a platelet aggregant. In vivo experiments demonstrated that surgical scarification of rabbit articular cartilage does not result in adhesion of autologous platelets. Treatment of rabbit knee joints with intraarticular trypsin 1 wk before the injection of blood resulted in adhesion and aggregation of platelets on the surface of the lesions. Since there is evidence from other studies that some degree of cartilage healing may take place after initiation of an inflammatory response, it is postulated that induction of platelet-cartilage interaction may eventuate in cartilage repair
— id: 61784, year: 1977, vol: 59, page: 641, stat: Journal Article,

Red-cell and platelet fragmentation in idiopathic autoimmune thrombocytopenic purpura
Zucker-Franklin D; Karpatkin S
1977 Sep 8;297(10):517-523, New England journal of medicine
We investigated the abnormal small-particle spike discerned in the platelet-rich plasma of patients with severe idiopathic autoimmune thrombocytopenic purpura. By electron microscopy, erythrocyte as well as platelet fragments were found in the 27,000 X g plasma sediment of 15 patients with severe disease. These fragments were not observed in the plasma sediment of 12 normal subjects, two healthy asplenic subjects, three patients with thrombocytopenia of nonimmunologic origin, and two with autoimmune thrombocytopenic purpura in remission. Weak complement sensitization of red blood cells was noted in seven out of 12 patients with the disease. Coating of red blood cells with IgG or IgM was not detected in these patients. Whereas erythrophagocytosis was conspicuously absent, phagocytosis of intact platelets as well as platelet fragments and other cellular debris was frequently observed. Autoimmune mechanisms may be directed against erythrocytes as well as platelets in most cases of severe idiopathic autoimmune thrombocytopenia
— id: 14974, year: 1977, vol: 297, page: 517, stat: Journal Article,

Congenital neutropenia: an intrinsic cell defect demonstrated by electron microscopy of soft agar colonies
Zucker-Franklin D; L'Esperance P; Good RA
1977 Mar;49(3):425-436, Blood
Congenital neutropenia (CN), a disease characterized by recurrent infections leading to death in infancy, shows a maturation arrest of the myeloid series at the promyelocyte-myelocyte level. The potential value of marrow transplantation in this disease would be determined by the nature of the underlying defect. However, studies to date have failed to define whether the defect is intrinsic in the cells or attributable to 'environmental' factors. Therefore, marrow of four patients with CN was cultured on soft agar, and the colonies were analyzed by a newly developed ultrastructural method. In parallel, patients' cells were used in feeder layers for normal marrow. Although the patients' colonies appeared grossly normal in size and number, electron microscopy showed only rare neutrophil colonies. These colonies contained markedly aberrant cells exhibiting asynchronous nucleocytoplasmic maturation, convoluted nuclei, excessive cytoplasm, and dearth of granules. Monocyte and eosinophil colonies differentiated normally. Patients' cells and sera supported growth of normal colonies. The studies have demonstrated unequivocally that the neutrophil cell line of patients with CN is intrinsically defective and suggest that attempts at marrow grafting are warranted
— id: 61785, year: 1977, vol: 49, page: 425, stat: Journal Article,

Thymus-dependent lymphocytes in lymphoproliferative disorders of the skin (Sezary syndrome and mycosis fungoides)
Zucker-Franklin D
1976 Sep;67(3):412-418, Journal of investigative dermatology
— id: 61789, year: 1976, vol: 67, page: 412, stat: Journal Article,

The identification of eosinophil colonies in soft-agar cultures by differential staining for peroxidase
Zucker-Franklin D; Grusky G
1976 Dec;24(12):1270-1272, Journal of histochemistry & cytochemistry
There has been a need to easily quantitate the incidence of eosinophil colonies within soft agar cultures. This has been realized by layering of the agar with benzidine dihydrochloride that permits detection of peroxidase activity in cells. Eosinophil colonies can be specifically identified by the addition to the substrate of potassium cyanide, an inhibitor of enzyme activity in neutrophils and monocytes. The enumeration of eosinophil colonies can be accomplished by scanning fresh or embedded cultures with low power magnification
— id: 61788, year: 1976, vol: 24, page: 1270, stat: Journal Article,

TRANSFORMATION OF CULTURED MONOCYTES INTO FAT-CELLS
Zuckerfranklin, D; Grusky, G
1976 ;70(2):A410-A410, Journal of cell biology
— id: 29457, year: 1976, vol: 70, page: A410, stat: Journal Article,

ERYTHROCYTE FRAGMENTATION IN IDIOPATHIC-AUTOIMMUNE THROMBOCYTOPENIC PURPURA (ITP-ATP)
Zuckerfranklin, D; Karpatkin, S
1976 ;48(6):1006-1006, Blood
— id: 28725, year: 1976, vol: 48, page: 1006, stat: Journal Article,

SUBCLINICAL ERYTHROCYTE FRAGMENTATION IN IDIOPATHIC AUTOIMMUNE THROMBOCYTOPENIC PURPURA (ITP-ATP)
Zuckerfranklin, D; Karpatkin, S
1976 ;24(3):A481-A481, Clinical research
— id: 28760, year: 1976, vol: 24, page: A481, stat: Journal Article,

Microthrombocytosis and platelet fragmentation associated with idiopathic/autoimmune thrombocytopenic purpura
Khan I; Zucker-Franklin D; Karpatkin S
1975 Dec;31(4):449-460, British journal of haematology
Platelet volume distribution curves were obtained in 20 control subjects and in 21 patients with idiopathic/autoimmune thrombocytopenic purpura. A striking increase in microthrombocytes as well as megathrombocytes was noted in 86% of patients on one or more occasions, particularly in the prsence of severe thrombocytopenia. The entire spectrum of platelet volume distribution curves noted in patients could be reproduced experimentally in rabbits following intravenous injection of anti-platelet antibody. Differential centrifugation studies with control subjects revealed that microthrombocytes were light platelets and megathrombocytes were heavy platelets. Electron microscopy in patients with thrombocytopenia revealed that microthrombocytes were composed of intact small platelets as well as platelet fragments. It is concluded that severe peripheral destruction of platelets is associated with an increase in microthrombocytes as well as megathrombocytes
— id: 14981, year: 1975, vol: 31, page: 449, stat: Journal Article,

INDUCTION OF BLOOD EOSINOPHILIA BY PULMONARY EMBOLIZATION OF ANTIGEN-COATED PARTICLES - RELATIONSHIP TO CELL-MEDIATED-IMMUNITY
SCHRIBER, RA; ZUCKERFRANKLIN, D
1975 ;114(4):1348-1353, Journal of immunology
— id: 48826, year: 1975, vol: 114, page: 1348, stat: Journal Article,

Human lymphocytes: 5'-nucleotidase-positive and -negative subpopulations
Silber R; Conklyn M; Grusky G; Zucker-Franklin D
1975 Nov;56(5):1324-1327, Journal of clinical investigation
The enzyme, 5'-nucleotidase (5'N) (E.C.-3.1.3.5) is present in lymphocytes isolated from the blood of normal subjects. This activity is markedly decreased or not detectable in the cells from three-quarters of patients with chronic lymphocytic leukemia (CLL), while supranormal levels are found in less than 10% of the cases. To determine whether the decreased 5'N value in CLL represents a lower activity per cell or fewer enzyme-containing cells than in the normal, conditions were established for the histochemical measurement of 5'N in human lymphocytes. It was found that the cells isolated from the blood of normal subjects or patients with CLL consist of 5'N-positive and 5'N-negative subpopulations. Normal subjects who had high 5'N specific activity were shown to have a greater percentage of 5'N-positive cells than individuals with low 5'N activity. Patients with CLL who had no activity by standard chemical assay had no 5'N-positive cells, while the exceptional patient with CLL with a higher than normal specific activity showed an percentage of 5'N-positive cells. It is suggested that the selective proliferation of 5'N-positive and 5'N-negative populations may account for the heterogeneity of 5'N in CLL
— id: 61790, year: 1975, vol: 56, page: 1324, stat: Journal Article,

Cellular structure and function in normal and neoplastic lymphoid cells
Zucker-Franklin D
1975 Jan;135(1):55-60, Archives of internal medicine
In general, the ultrastructure of normal lymphocytes and plasma cells reflects their functional state. Similarly, in pathologic conditions, ultrastructural abnormalities may reflect specific functional derangements of the cells. The identification of some structural abnormalities may be clinically useful, even though their origin and biochemical composition is still obscure
— id: 61792, year: 1975, vol: 135, page: 55, stat: Journal Article,

Physiological and pathological variations in the ultrastructure of neutrophils and monocytes
Zucker-Franklin D
1975 Oct;4(3):485-508, Clinics in haematology
— id: 61791, year: 1975, vol: 4, page: 485, stat: Journal Article,

A method for the induction of blood eosinophilia with simple protein antigens
Schriber RA; Zucker-Franklin D
1974 Dec;14(3):470-474, Cellular immunology
— id: 61793, year: 1974, vol: 14, page: 470, stat: Journal Article,

INDUCTION OF EOSINOPHILIA BY TISSUE RETENTION OF ANTIGEN
Schriber, R; Zuckerfr[...], D
1974 ;33(3):645-645, Federation Proceedings (Federation of American Societies for Experimental Biology)
— id: 28379, year: 1974, vol: 33, page: 645, stat: Journal Article,

Eosinophil function and disorders
Zucker-Franklin D
1974 ;19:1-25, Advances in internal medicine
— id: 61798, year: 1974, vol: 19, page: 1, stat: Journal Article,

Properties of the Sezary lymphoid cell. An ultrastructural analysis
Zucker-Franklin D
1974 Aug;49(8):567-574, Mayo Clinic proceedings
— id: 61795, year: 1974, vol: 49, page: 567, stat: Journal Article,

The percentage of monocytes among "mononuclear" cell fractions obtained from normal human blood
Zucker-Franklin D
1974 Jan;112(1):234-240, Journal of immunology
— id: 61799, year: 1974, vol: 112, page: 234, stat: Journal Article,

Ultrastructural analysis of hematopoietic colonies derived from human peripheral blood. A newly developed method
Zucker-Franklin D; Grusky G
1974 Dec;63(3):855-863, Journal of cell biology
— id: 61794, year: 1974, vol: 63, page: 855, stat: Journal Article,

Granulocyte colonies derived from lymphocyte fractions of normal human peripheral blood
Zucker-Franklin D; Grusky G; L'Esperance P
1974 Jul;71(7):2711-2714, Proceedings of the National Academy of Sciences of the United States of America
— id: 61796, year: 1974, vol: 71, page: 2711, stat: Journal Article,

Ultrastructural, immunologic, and functional studies on Sezary cells: a neoplastic variant of thymus-derived (T) lymphocytes
Zucker-Franklin D; Melton JW 3rd; Quagliata F
1974 May;71(5):1877-1881, Proceedings of the National Academy of Sciences of the United States of America
— id: 61797, year: 1974, vol: 71, page: 1877, stat: Journal Article,

Leukemic cells with membrane properties of thymus-derived (T) lymphocytes in a case of Sezary's syndrome: morphologic and immunologic studies
Broome JD; Zucker-Franklin D; Weiner MS; Bianco C; Nussenzweig V
1973 Apr;1(3):319-329, Clinical immunology & immunopathology
— id: 61803, year: 1973, vol: 1, page: 319, stat: Journal Article,

The formation of amyloid-like fibrils in vitro from Bence Jones Proteins of the VlambdaI subclass
Linke RP; Tischendorf FW; Zucker-Franklin D; Franklin EC
1973 Jul;111(1):24-26, Journal of immunology
— id: 61800, year: 1973, vol: 111, page: 24, stat: Journal Article,

Morphologic, chemical, and immunologic studies of amyloid-like fibrils formed from Bence Jones Proteins by proteolysis
Linke RP; Zucker-Franklin D; Franklin ED
1973 Jul;111(1):10-23, Journal of immunology
— id: 61801, year: 1973, vol: 111, page: 10, stat: Journal Article,

Lymphocyte plasma membranes: analysis of proteins and glycoproteins by SDS-gel electrophoresis
Lopes J; Nachbar M; Zucker-Franklin D; Silber R
1973 Jan;41(1):131-140, Blood
— id: 18958, year: 1973, vol: 41, page: 131, stat: Journal Article,

Heterogeneity of 5'-nucleotidase activity in lymphocytes in chronic lymphocytic leukemia
Lopes J; Zucker-Franklin D; Silber R
1973 May;52(5):1297-1300, Journal of clinical investigation
— id: 61802, year: 1973, vol: 52, page: 1297, stat: Journal Article,

Use of tracer techniques in studies on immunoglobulin-producing cells
Zucker-Franklin D
1973 Mar;21(3):209-217, Journal of histochemistry & cytochemistry
— id: 61804, year: 1973, vol: 21, page: 209, stat: Journal Article,

GRANULOCYTE COLONIES DERIVED FROM LYMPHOCYTE FRACTIONS OF NORMAL HUMAN PERIPHERAL-BLOOD
Zuckerfr[...], D; Grusky, G; Lesperan[...], P
1973 ;42(6):1010-1010, Blood
— id: 28470, year: 1973, vol: 42, page: 1010, stat: Journal Article,

Antisera specific for human amyloid reactive with conformational antigens
Franklin EC; Zucker-Franklin D
1972 Jun;140(2):565-568, Proceedings of the Society for Experimental Biology & Medicine
— id: 61806, year: 1972, vol: 140, page: 565, stat: Journal Article,

Current concepts of amyloid
Franklin EC; Zucker-Franklin D
1972 ;15:249-304, Advances in immunology
— id: 61810, year: 1972, vol: 15, page: 249, stat: Journal Article,

Studies on the succinylation of erythrocyte membranes
Moldow CF; Zucker-Franklin D; Gordon A; Hospelhorn V; Silber R
1972 Jan 17;255(1):133-148, Biochimica & biophysica acta
— id: 61809, year: 1972, vol: 255, page: 133, stat: Journal Article,

Ultrastructure and immunofluorescence of mouse spleen cells obtained by discontinuous albumin gradient centrifugation
Waldo ED; Zucker-Franklin D
1972 Jun;108(6):1665-1674, Journal of immunology
— id: 61805, year: 1972, vol: 108, page: 1665, stat: Journal Article,

Electron microscope study of surface immunoglobulin-bearing human tonsil cells
Zucker-Franklin D; Berney S
1972 Mar 1;135(3):533-548, Journal of experimental medicine
— id: 61807, year: 1972, vol: 135, page: 533, stat: Journal Article,

The actin and myosin filaments of human and bovine blood platelets
Zucker-Franklin D; Grusky G
1972 Feb;51(2):419-430, Journal of clinical investigation
— id: 61808, year: 1972, vol: 51, page: 419, stat: Journal Article,

ULTRASTRUCTURE OF MOUSE SPLEEN CELLS OBTAINED BY DIFFERENTIAL CENTRIFUGATION
WALDO, E; ZUCKER-F.D
1971 ;30(2):A396-&, Federation Proceedings (Federation of American Societies for Experimental Biology)
— id: 112501, year: 1971, vol: 30, page: A396, stat: Journal Article,

The effect of the morphine analog levorphanol on phagocytosing leukocytes. A morphologic study
Zucker-Franklin, D; Elsbach, P; Simon, E J
1971 Nov;25(5):415-421, Laboratory investigation
— id: 41970, year: 1971, vol: 25, page: 415, stat: Journal Article,

Ultrastructural and immunofluorescence studies of the cells associated with mu-chain disease
Zucker-Franklin, D; Franklin, E C
1971 Mar;37(3):257-271, Blood
— id: 61811, year: 1971, vol: 37, page: 257, stat: Journal Article,

Immunophagocytosis of human amyloid fibrils by leukocytes
Zucker-Franklin D
1970 Aug;32(3):247-257, Journal of ultrastructure research
— id: 61813, year: 1970, vol: 32, page: 247, stat: Journal Article,

The submembranous fibrils of human blood platelets
Zucker-Franklin D
1970 Oct;47(1):293-299, Journal of cell biology
— id: 61812, year: 1970, vol: 47, page: 293, stat: Journal Article,

Intracellular localization of human amyloid by fluorescence and electron microscopy
Zucker-Franklin D; Franklin EC
1970 Apr;59(1):23-41, American journal of pathology
— id: 61814, year: 1970, vol: 59, page: 23, stat: Journal Article,

Increased lecithin synthesis during phagocytosis by normal leukocytes and by leukocytes of a patient with chronic granulomatous disease
Elsbach P; Zucker-Franklin D; Sansaricq C
1969 Jun 12;280(24):1319-1322, New England journal of medicine
— id: 28177, year: 1969, vol: 280, page: 1319, stat: Journal Article,

Electron microscopic study of isolated Kupffer cells
Mills DM; Zucker-Franklin D
1969 Feb;54(2):147-166, American journal of pathology
— id: 61816, year: 1969, vol: 54, page: 147, stat: Journal Article,

Physical, chemical, and ultrastructural studies of water-soluble human amyloid fibrils. Comparative analyses of nine amyloid preparations
Pras M; Zucker-Franklin D; Rimon A; Franklin EC
1969 Oct 1;130(4):777-796, Journal of experimental medicine
— id: 61815, year: 1969, vol: 130, page: 777, stat: Journal Article,

Microfibrils of blood platelets: their relationship TO MICROTUBULES AND THE CONTRACTILE PROTEIN
Zucker-Franklin D
1969 Jan;48(1):165-175, Journal of clinical investigation
— id: 61818, year: 1969, vol: 48, page: 165, stat: Journal Article,

The ultrastructure of lymphocytes
Zucker-Franklin D
1969 Jan;6(1):4-27, Seminars in hematology
— id: 61817, year: 1969, vol: 6, page: 4, stat: Journal Article,

Coexistence of polycythemia vera and biclonal gammopathy (gamma-GK and gamma-AL) with two Bence Jones proteins (BJK and BJL)
Dittmar K; Kochwa S; Zucker-Franklin D; Wasserman LR
1968 Jan;31(1):81-92, Blood
— id: 61822, year: 1968, vol: 31, page: 81, stat: Journal Article,

The characterization of soluble amyloid prepared in water
Pras M; Schubert M; Zucker-Franklin D; Rimon A; Franklin EC
1968 Apr;47(4):924-933, Journal of clinical investigation
— id: 61821, year: 1968, vol: 47, page: 924, stat: Journal Article,

Electron microscopic studies of human granulocytes: structural variations related to function
Zucker-Franklin D
1968 Apr;5(2):109-133, Seminars in hematology
— id: 61820, year: 1968, vol: 5, page: 109, stat: Journal Article,

Werner's syndrome. An analysis of ten cases
Zucker-Franklin D; Rifkin H; Jacobson HG
1968 Aug;23(8):123-135, Geriatrics
— id: 61819, year: 1968, vol: 23, page: 123, stat: Journal Article,

Secret in the white cell
Hirsch, James G; Cohn, Zanvil; Zucker-Franklin D
New York : Prism Productions, 1967,
— id: 1559, year: 1967, vol: , page: , stat: ,

Immunologic studies of proteins associated with subcellular fractions of normal human platelets
Nachman RL; Marcus AJ; Zucker-Franklin D
1967 Apr;69(4):651-658, Journal of laboratory & clinical medicine
— id: 61825, year: 1967, vol: 69, page: 651, stat: Journal Article,

Electron microscopic study of human basophils
Zucker-Franklin D
1967 Jun;29(6):878-890, Blood
— id: 61824, year: 1967, vol: 29, page: 878, stat: Journal Article,

Ultrastructure of thrombosthenin, the contractile protein of human blood platelets
Zucker-Franklin D; Nachman RL; Marcus AJ
1967 Aug 25;157(3791):945-946, Science
— id: 61823, year: 1967, vol: 157, page: 945, stat: Journal Article,

Studies on human platelet granules and membranes
Marcus AJ; Zucker-Franklin D; Safier LB; Ullman HL
1966 Jan;45(1):14-28, Journal of clinical investigation
— id: 61829, year: 1966, vol: 45, page: 14, stat: Journal Article,

The phagosomes in rheumatoid synovial fluid leukocytes: a light, fluorescence, and electron microscope study
Zucker-Franklin D
1966 Feb;9(1):24-36, Arthritis & rheumatism
— id: 61828, year: 1966, vol: 9, page: 24, stat: Journal Article,

The interaction of mycoplasmas with mammalian cells. I. HeLa cells, neutrophils, and eosinophils
Zucker-Franklin D; Davidson M; Thomas L
1966 Sep 1;124(3):521-532, Journal of experimental medicine
— id: 61827, year: 1966, vol: 124, page: 521, stat: Journal Article,

The interaction of mycoplasmas with mammalian cells. II. Monocytes and lymphocytes
Zucker-Franklin D; Davidson M; Thomas L
1966 Sep 1;124(3):533-542, Journal of experimental medicine
— id: 61826, year: 1966, vol: 124, page: 533, stat: Journal Article,

HUMAN PLATELET LIPIDS AND THEIR RELATIONSHIP TO BLOOD COAGULATION
MARCUS AJ; ZUCKER-FRANKLIN D
1965 Jun;42:500-504, Journal of the American Oil Chemists Society
— id: 61831, year: 1965, vol: 42, page: 500, stat: Journal Article,

ELECTRON MICROSCOPE STUDY OF THE DEGRANULATION OF POLYMORPHONUCLEAR LEUKOCYTES FOLLOWING TREATMENT WITH STREPTOLYSIN
ZUCKER-FRANKLIN D
1965 Sep;47:419-433, American journal of pathology
— id: 61830, year: 1965, vol: 47, page: 419, stat: Journal Article,

STUDIES ON SUBCELLULAR PLATELET PARTICLES
MARCUS AJ; ZUCKER-FRANKLIN D
1964 Mar;23:389-393, Blood
— id: 61834, year: 1964, vol: 23, page: 389, stat: Journal Article,

MULTIPLE MYELOMA. II. STRUCTURAL FEATURES OF CELLS ASSOCIATED WITH THE PARAPROTEINEMIAS
ZUCKER-FRANKLIN D
1964 Apr;124:165-198, Seminars in hematology
— id: 61833, year: 1964, vol: 124, page: 165, stat: Journal Article,

ELECTRON MICROSCOPE STUDIES ON THE DEGRANULATION OF RABBIT PERITONEAL LEUKOCYTES DURING PHAGOCYTOSIS
ZUCKER-FRANKLIN D; HIRSCH JG
1964 Oct 1;120:569-576, Journal of experimental medicine
— id: 61832, year: 1964, vol: 120, page: 569, stat: Journal Article,

THE ULTRASTRUCTURE OF CELLS IN HUMAN THORACIC DUCT LYMPH
ZUCKER-FRANKLIN D
1963 Oct;59:325-339, Journal of ultrastructure research
— id: 61835, year: 1963, vol: 59, page: 325, stat: Journal Article,

Virus-like particles in the lymphocytes of a patient with chronic lymphocytic leukemia
ZUCKER-FRANKLIN D
1963 Apr;21:509-512, Blood
— id: 61837, year: 1963, vol: 21, page: 509, stat: Journal Article,

PARTIAL PURIFICATION OF INTERMEDIATE COAGULATION PRODUCT I AND A STUDY OF ITS PROPERTIES
ZUCKER-FRANKLIN D; SPAET TH
1963 Aug;205:341-347, American journal of physiology
— id: 61836, year: 1963, vol: 205, page: 341, stat: Journal Article,

The physiology and pathology of leukocytes
Braunsteiner, Herbert; Zucker-Franklin, Dorothea
New York : Grune & Stratton, 1962,
'American edition prepared and revised by Dorothea Zucker-Franklin'
— id: 1557, year: 1962, vol: , page: , stat: ,

Haptoglobin hemoglobin metabolism in rabbits studied with I-131 and Fe59 labelled complexes
FRANKLIN EC; ORATZ M; ROTHSCHILD MA; ZUCKER-FRANKLIN D
1960 Oct;105:167-170, Proceedings of the Society for Experimental Biology & Medicine
— id: 61838, year: 1960, vol: 105, page: 167, stat: Journal Article,

Werner's syndrome: a clinical-roentgen entity
JACOBSON HG; RIFKIN H; ZUCKER-FRANKLIN D
1960 Mar;74:373-385, Radiology
— id: 61839, year: 1960, vol: 74, page: 373, stat: Journal Article,