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238


Possible role of maternal lymphocytes contained in breast milk in the development of autoimmune diseases [Meeting Abstract]

Cohen, AM; Pancake, BA; Zucker-Franklin, D
ISI:000227846600104
ISSN: 1081-5589
CID: 51762

Natural is not necessarily better [Editorial]

Zucker-Franklin, D
ISI:000186601900002
ISSN: 0890-3670
CID: 55423

Localization of HTLV-I tax proviral DNA in mononuclear cells

Zucker-Franklin, Dorothea; Pancake, Bette A; Najfeld, Vesna
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
PMID: 12850476
ISSN: 1079-9796
CID: 39149

Atlas of blood cells : function and pathology

Zucker-Franklin D; Grossi CE
Milano : Edi. Ermes, 2003
Extent: 2 v. ; 32cm
ISBN: 8870512525
CID: 1556

The role of interleukin-7 and interleukin-15 in cutaneous T-cell lymphoma [Letter]

Zucker-Franklin, Dorothea
PMID: 12001911
ISSN: 0006-4971
CID: 61761

Prevalence of HTLV-I Tax in a subset of patients with rheumatoid arthritis

Zucker-Franklin, D; Pancake, B A; Brown, W H
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
PMID: 12051394
ISSN: 0392-856x
CID: 39423

The role of human T cell lymphotropic virus type I tax in the development of cutaneous T cell lymphoma

Zucker-Franklin D
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
PMID: 11594585
ISSN: 0077-8923
CID: 26648

Passively acquired antibodies to HTLV-I p40Tax by blood transfusion or administration of intravenous immunoglobulin (IVIG) [Meeting Abstract]

Zucker-Franklin, D; Benjamin, LJ; Bussel, JB; Pancake, BA
ISI:000165256102661
ISSN: 0006-4971
CID: 55235

Platelet production in the pulmonary capillary bed: new ultrastructural evidence for an old concept

Zucker-Franklin D; Philipp CS
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
PMCID:1850212
PMID: 10880377
ISSN: 0002-9440
CID: 11624

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
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
PMID: 10895371
ISSN: 0392-856x
CID: 15707