Biomedical subjects

R Zigelman

Publications and source records attributed to R Zigelman.

9 recordsLinked to original sources

PubMed1996

Muscle cells produce a low molecular weight factor with anti-cancer activity.

The present study describes a new low molecular weight factor released by muscle cells, which inhibits proliferation of tumor cells in vitro and in vivo, is highly specific towards tumor cells, and has no observable effect on normal cells' proliferation. What first prompted us to investigate this factor was the observation that tumor metastases are extremely rare in striated muscles. Co-culturing of striated muscle cells with malignant cells led to marked morphological alterations in the latter, in contrast to the same cells when incubated without muscle cells. A conditioned medium of striated muscle cells was prepared and its effect tested on a variety of cells. This conditioned medium (CM) inhibited proliferation of tumor cell lines of murine (B16 melanoma, Madison 109 lung carcinoma, MCA-105 sarcoma, ESB lymphoma), or of human origin (HTB-38 adenocarcinoma, T47D breast carcinoma, CX1 colon carcinoma). The proliferation of normal cells (bone marrow cells, fetal liver erythroid cells) was not affected by the CM. Flow cytometric analysis of B16 melanoma cells following incubation with the CM revealed that 63% +/- 12 of the cells were in the G0/G1 phase of the cell cycle, compared to 47.8% +/- 8 of cells incubated with a medium (not conditioned) only. The activity of the CM and of certain fractions thereof was also demonstrated in vivo: they prevented tumor growth in mice inoculated intraperitoneally with MCA-105 sarcoma cells. Partial purification of the CM revealed that the active component was a non-proteinaceous compound with a molecular weight of about 500 D. The results clearly suggest that muscle cells produce a low molecular weight factor which can selectively inhibit the proliferation of tumor cells in vitro and in vivo. This factor is neither species nor tumor specific.

Animals↗

PubMed1996

Tyrosinase as an autoantigen in patients with vitiligo.

Vitiligo is considered an autoimmune disorder due to the generation and presence of autoantibodies directed against melanocyte antigens in the patients' sera. In the present study we point towards a newly defined autoantigen in vitiligo, the enzyme tyrosinase, which participates in the process of melanogenesis. Anti-tyrosinase antibodies were detected in the sera of seven patients with diffuse and 11 patients with localized vitiligo. Employing solid-phase ELISA to mushroom tyrosinase, we found that patients with diffuse vitiligo had significantly higher titres of IgG anti-tyrosinase autoantibodies than patients with localized disease or healthy subjects. These anti-tyrosinase autoantibodies have relatively high functional affinity to tyrosinase and can be recovered from vitiligo patients' sera by affinity purification. The anti-tyrosinase antibodies do not cross-react with other enzymes recognized as autoantigens in different autoimmune disorders and the autoantibodies do not block the enzymatic activity of tyrosinase, indicating that they are not reacting with the catalytic site of the enzyme. These data point to tyrosinase as an autoantigen in vitiligo and suggest that anti-tyrosinase titres can serve as a marker for disease activity.

Autoantibodies↗

PubMed1996

Reactivity to tyrosinase: expression in cancer (melanoma) and autoimmunity (vitiligo).

Anti-tyrosinase antibodies are found in the sera of patients with diffuse vitiligo, metastatic melanoma and in sera of patients with melanoma and hypopigmentation (MAH). The autoantigen is tyrosinase itself, the enzyme that participates in pigment (melanin) formation by both melanocytes and melanoma cells. The production of autoantibodies in both diseases is associated with the development of white patches on the patients' skin. The presence of these autoantibodies in patients with melanoma may suggest a better prognosis. Cross-antigenicity between melanoma cells and normal melanocytes is most probably the key mechanism leading to the appearance of MAH. Anti-tyrosinase antibodies are absorbed by melanocytes and by melanoma cells in all the 3 situations (melanoma, vitiligo, MAH). However, since the production of antibodies in vitiligo exceeds that in melanoma or MAH, the antibodies are detected in significantly higher levels only in vitiligo. It is suggested here that anti-tyrosinase antibodies may be responsible, or at least participate in destruction of normal melanocytes during the immune response to melanoma antigens. This mechanism may be responsible for the phenomenon of MAH in patients with melanoma, and for the formation of the autoimmune vitiligo. Anti-tyrosinase antibodies may serve for two clinical applications. One is a marker for monitoring and follow up of patients with melanoma treated by immune therapy. The second is active (or passive) immunotherapy. We have recently shown that C57BL/6J mice immunized with tyrosinase generated a high titer of antityrosinase antibodies, and following the inoculation of melanoma cells developed lower number of lung metastases, compared to the unvaccinated control group.

Autoantibodies↗

PubMed1995

Characterization of biologically active antineutrophil cytoplasmic antibodies induced in mice. Pathogenetic role in experimental vasculitis.

OBJECTIVE: To investigate the pathogenetic role of antineutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis (WG). METHODS: BALB/c mice were immunized with human IgG ANCA from a patient with WG. Control mice were immunized with normal human IgG. Levels of mouse ANCA and other autoantibodies were determined. Mouse ANCA were tested for their ability to induce adhesion and respiratory burst of neutrophils. The mouse lungs and kidneys were examined for the development of vasculitis. RESULTS: Mice immunized with human ANCA developed anti-human ANCA and anti-anti-human ANCA (mouse ANCA), while the controls did not develop these antibodies. Mouse ANCA were capable of inducing adhesion of neutrophils to fibronectin and activating the respiratory burst in neutrophils. Moreover, the mice that were immunized with human ANCA developed perivascular mononuclear cell infiltrates in the lungs, suggesting vasculitis. CONCLUSION: The results suggest a pathogenic role of ANCA in WG, and may imply that activation of neutrophils is the initiating event in the development of vasculitis in WG.

Animals↗

PubMed1993

Vitiligo autoantibodies are effective against melanoma.

BACKGROUND: Vitiligo is a dermatologic disease characterized by local, dispersed, or diffuse white patches on the skin. The disease is defined as an autoimmune disorder because autoantibodies against membranal components of melanocytes are found in the patients' sera. The current study examined whether the autoantibodies reacting with the normal melanocytes could be a potent therapy against melanoma cells. METHODS: The three in vitro assays used to determine the antibody reactivities using a mouse melanoma cell line B-16-F10 and M-14 human melanoma cells as targets are as follows: enzyme-linked immunosorbent assay (ELISA), proliferation assay, and morphologic examination in the presence of antibodies purified from sera of patients with vitiligo. In the in vivo studies, experimental melanoma was intravenously induced in C57BL/6J mice, and the mice were treated by daily intraperitoneal injections with purified immunoglobulin G (IgG) fraction derived either from patients with vitiligo or from healthy subjects. RESULTS: The binding of IgG derived from patients with vitiligo was demonstrated by ELISA: Exposure of melanoma cells to the vitiligo autoantibodies was followed by inhibition of their proliferation capacity. In addition, morphologic alterations exemplified by detachment of the cells from their solid support associated with melanin release were observed in the B-16-F10 cells. Less metastatic foci developed in the lungs of the mice treated with the purified IgG fraction from the sera of patients with vitiligo compared with those treated with purified IgG fraction from healthy subjects. CONCLUSIONS: The results of this study point to the presence of anti-melanoma autoantibodies in the sera of patients with localized and diffuse vitiligo. These antibodies have a destructive effect on melanoma cells in vitro and in vivo.

Animals↗

PubMed1993

Interleukin-3 immunoassay in systemic lupus erythematosus patients: preliminary data.

Systemic lupus erythematosus (SLE) may be associated with thrombocytopenia on one hand and lymphoma on the other. Interleukin-3 (IL-3) may contribute to both conditions. IL-3 is a pleotrophic growth factor affecting the proliferation and differentiation of stem cells to committed progenitors of several hematopoietic lineages including megakaryocytes and lymphocytes. The serum level of IL-3 determined by ELISA was found to be higher in a cohort of 16 patients with SLE in comparison to health controls. The IL-3 levels were highest in 2 patients with SLE and lymphoma. Interestingly, low serum levels were detected in SLE patients with thrombocytopenia. Our preliminary results may point to the role of IL-3 in the hematopoietic changes observed in SLE.

Enzyme-Linked Immunosorbent Assay↗

PubMed1993

Prevention of fetal loss in experimental antiphospholipid syndrome by in vivo administration of recombinant interleukin-3.

Antiphospholipid antibodies are strongly associated with arterial and venous thrombosis and with fetal loss. Recently an experimental model for antiphospholipid syndrome (APLS) was established in our laboratory. In this model, mice are immunized passively or actively with anticardiolipin antibodies and acquire the syndrome, which is characterized by prolonged activated partial thromboplastin time (APTT), thrombocytopenia, low fecundity rate, and fetal loss. In a normal process of pregnancy, lymphokines affect fetal implantation and development. Cytokines from the colony stimulating factor family, like GM-CSF and IL-3, were shown to be positive signals for implantation and to promote placental development and fetal growth. Given our preliminary findings of low IL-3 in mice with APLS and the efficacy of IL-3 in preventing fetal loss in a strain of mice prone to fetal resorption, our aim in the present study was to examine the effect of murine recombinant IL-3 (mrIL-3) on pregnant mice induced with experimental APLS. Mice were passively transfused to the tail vein, 24 h following mating, with anticardiolipin antibodies. The mice were divided into two groups: one group was injected intraperitoneally with mrIL-3 on days 6.5, 8.5, and 10.5 after mating, while the control group was injected with PBS. When the mice were killed on day 15 of pregnancy a 32% +/- 4.2 resorption rate was observed in the anti-cardiolipin-immunized group, which was reduced to 4% +/- 0.3 following treatment with mrIL-3. The thrombocytopenia associated with the experimental APLS was also corrected following lymphokine administration. IL-3 may be effective in prevention of recurrent fetal loss in APLS.

Animals↗

PubMed1992

Interleukin-3-like activity levels in pregnant women: possible modulation by progesterone.

Human interleukin-3-like activity (IL-3-LA), a factor possessing similar characteristics to interleukin-3 and having clony stimulating factor (CSF) activity, has recently been defined. In the present study, IL-3-LA levels in the sera of women before and after delivery were examined. The results indicate a significant increase in IL-3-LA levels in women before delivery as compared to IL-3-LA levels after delivery or to non-pregnant healthy women. The ability of mononuclear cells from women before and after delivery to produce IL-3-LA was similar to that of mononuclear cells from cord blood. In addition, the effect of progesterone on in vitro IL-3-LA production was examined and a stimulatory dose-dependent effect was observed. These observations point to the hypothesis that during pregnancy IL-3-LA levels are modulated by progesterone. With placental loss, the IL-3-LA in the sera decreases, although the mononuclear cells previously affected by the hormone continue to produce cytokines.

Female↗

PubMed1989

Using an organizational development strategy to improve residency training.

Medical students' preferences for residencies in internal medicine are in decline. To attract outstanding students, departments of medicine must strive to improve the quality of their training programs. In the setting of a university-affiliated residency program, the authors employed a strategy based on organization development principles to identify remediable educational problems and to facilitate the process of solving these problems. Residents, attending physicians, and administrators used a consensus-building method, the nominal group technique, to develop problem lists ranked by two criteria--relative importance and potential for solution. Problems of high importance and high potential for solution were identified and assigned to committees of housestaff and faculty for action. Management plans consisting of short-term and long-term interventions were created to solve each problem. These plans were widely accepted and short-term interventions were successfully implemented. This strategy represents a pragmatic approach to improving internal medicine residency programs because it focuses limited institutional resources on problems that are both important and amenable to change.

Career Choice↗