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Biomedical subjects

A Balsari

Publications and source records attributed to A Balsari.

At least 91 records · Page 5Linked to original sources
PubMed1984

The inhibition of lymphocyte stimulation by autologous human metastatic melanoma cells correlates with the expression of HLA-DR antigens on the tumor cells.

Previous studies indicated that peripheral blood lymphocytes from patients (Pt-PBL) with lymph node metastatic melanomas proliferated in vitro and developed into tumor-restricted cytotoxic lymphocytes in response to alloantigens or interleukin 2 (IL-2). However, Pt-PBL were not stimulated by irradiated autologous metastatic melanoma (Auto-Me) cells. In the present study we report that the lack of stimulatory activity of Auto-Me cells may be due to a suppressive effect exerted by Auto-Me cells on the responder lymphocytes. In fact, we found that in 62% of cases examined, the addition of 5-10% Auto-Me cells to Pt-PBL cultures strongly inhibited both proliferation and the generation of tumor cytotoxic lymphocytes induced by alloantigens or IL-2. The inhibition was dose-dependent and tumor-restricted, and was not due either to toxicity, medium depletion or IL-2 absorption by Auto-Me cells. Normal fibroblasts, K562 cells and autologous E-lymphocytes were not suppressive. Auto-Me cells were able to inhibit Pt-PBL responses only when added during the first 24 h of culture and not later. Phenotypic analysis of Auto-Me cells using monoclonal antibodies directed against HLA-A,B,C, HLA-DR and melanoma-associated antigens revealed that the expression of high levels of DR antigens on Auto-Me cells was associated with an elevated suppressive activity. Conversely, Auto-Me cells with low or undetectable levels of DR antigens were not inhibitory. Furthermore, the increased expression of DR antigens on Auto-Me cells obtained by in vitro treatment with human interferon gamma (IFN-gamma) also resulted in an increased suppressive activity. We conclude that HLA-DR+ metastatic melanoma cells can interfere with the generation of an anti-tumor immune response, thus potentially favoring the escape of the tumor from the host's control mechanism.

HLA-DR Antigens↗
PubMed1984

Primary but not metastatic human melanomas expressing DR antigens stimulate autologous lymphocytes.

Lymphocytes from melanoma patients were stimulated in mixed culture with autologous tumor cells (MLTC) in order to evaluate lymphocyte proliferation and subsequent cytotoxicity on autologous melanoma cells. It was found that melanoma cells from lymph node metastases were unable to induce autologous tumor-cytotoxic cells in 21 cases examined, in 15 of which MLTC also failed to induce lymphocyte proliferation. Patients' lymphocytes, however, were significantly stimulated by allogeneic irradiated lymphocytes and by interleukin 2. To investigate whether the lack of autologous stimulation was restricted to metastatic cells, the immune response of patients with only primary lesions of malignant melanoma was evaluated. It was found that primary melanoma cells were able to induce proliferation in 7 out of 9 (77%) patients, whereas positive cytotoxicity was obtained in 2 out of 4 patients tested. In order to see whether the presence of DR molecules was important for the stimulatory activity, melanoma cells were examined for the expression of DR antigens by indirect immunofluorescence with monoclonal antibodies. Positive autologous MLTC was found in all of six DR+ primary melanomas, whereas the two DR-tumors were unable to stimulate autologous lymphocytes. An anti-DR but not an anti-DC monoclonal antibody was able to block the proliferation of lymphocytes induced by an autologous primary melanoma. Neither MLTC nor cell-mediated killing was obtained with either DR+ or DR-metastatic melanoma. In 60% of the cases tested, however, DR+ metastatic melanoma cells were able to stimulate allogeneic lymphocytes of normal individuals. Increased expression of DR antigens was induced by in vitro treatment with human gamma-interferon in metastatic tumor cells; this caused an increase in the proliferation of allogeneic but not autologous lymphocytes. These findings indicate that primary but not metastatic DR+ melanoma cells are able to activate the proliferation and cytotoxicity of autologous peripheral blood lymphocytes, suggesting a potential role of DR antigens in regulating tumor-host relationships in melanoma patients.

Cytotoxicity, Immunologic↗
PubMed1984

Inhibition of human melanoma growth in nude mice by autologous, alloactivated peripheral blood lymphocytes.

Peripheral blood lymphocytes of melanoma patients were stimulated in vitro by a pool of allogeneic lymphocytes and shown to be cytotoxic against autologous melanoma cells. To evaluate the in vivo antitumor activity of the cytotoxic alloactivated autologous peripheral blood lymphocytes, tumor neutralization (Winn) assay was carried out by injecting such lymphocytes admixed with autologous melanoma cells in athymic BALB/c nude mice. In 3 of 6 cases, complete inhibition of tumor growth was obtained at lymphocytes to tumor cells ratio of 10:1 and in one case also of 5:1. In all cases the appearance of tumors was delayed and the growth rate was significantly reduced in a dose-dependent fashion as compared to control mice injected with tumor cells alone. We conclude that in vitro alloactivated peripheral blood lymphocytes can inhibit and/or impair the growth of autologous melanoma cells in nude mice.

Animals↗
PubMed1984

Human renal antigen defined by a murine monoclonal antibody.

Fusion of spleen cells from a mouse immunized with a surgical specimen of a human renal carcinoma with murine P3 myeloma cells resulted in the establishment of a hybridoma cell line that secreted a monoclonal antibody (MKi-1), of IgG1 subclass, which preferentially reacted on kidney crude membrane (CM) preparations. This monoclonal antibody was tested by solid-phase radioimmunometric assay and immunofluorescence (IF) on a panel of tumor cell lines and on CM preparations and cell suspensions from surgical specimens of normal and neoplastic tissues. In addition, cryosections of normal and cancer tissues of various histologic types were tested by IF. The expression of the MKi-1 antigen was limited to normal kidney epithelium, renal cancers, some areas in the pancreas, the apical region of some breast ducts, and a proportion (5-50%) of activated lymphocytes. Electron microscopic study by the immunoperoxidase technique on fixed sections from normal kidney showed that MKi-1 stained the brush border of almost all proximal tubules. The molecule recognized by MKi-1 was a single polypeptide chain with a molecular weight of 140,000.

Animals↗
PubMed1983

Regulation of the macrophage content of neoplasms by chemoattractants.

Factor chemotactic for mononuclear phagocytes was found in supernatant fluids of cultured human and mouse tumor cells. In 11 mouse tumors there was a correlation observed between chemotactic activity and macrophage content of neoplastic tissues. Tumor-derived chemoattractants appear to participate in the regulation of tumor-associated macrophages.

Animals↗
PubMed1983

Immunochemical analysis of the determinant recognized by a monoclonal antibody (MBr1) which specifically binds to human mammary epithelial cells.

A monoclonal antibody (MBr1) raised against a membrane preparation (CM) of a human breast cancer line (MCF-7) and characterized as mammary gland epithelium associated (S. Mènard, E. Tagliabue, S. Canevari, G. Fossati, and M. I. Colnaghi. Generation of monoclonal antibodies reacting with normal and cancer cells of human breast. Cancer Res., 43:1295-1300, 1983), was used to biochemically define and partially purify its target antigen. The antigenic activity recognized by MBr1 was unaffected by treatment of MCF-7 cells with trypsin, protease K, or Vibrio cholerae neuraminidase and by heating at 100 degrees but was abolished by treatment with methanol. Since this behavior suggested a glycolipid nature of the MBr1-defined antigen, total lipids were obtained by chloroform:methanol or tetrahydrofuran:phosphate buffer extractions from crude membrane preparations of MCF-7 cells and of breast cancer surgical specimens. Total absorption of MBr1 activity was found by breast cancer lipid extracts, whereas no absorbing capability was detected with a series of highly purified acid and neutral glycolipids or with normal and neuraminidase-treated red blood cells of human, ox, and sheep species. The same pattern of inhibition of MBr1-binding activity was obtained with total lipid extract and both phases after diethyl ether partition. However, when the three extracts were chromatographed on diethylaminoethyl-Sepharose, the antigenic activity was recovered only in the neutral glycolipid fractions. Periodate oxidation of MCF-7 crude membrane preparation abolished MBr1-binding activity, suggesting that the carbohydrate portion of the molecule may constitute the antigenic determinant.

Antibodies, Monoclonal↗
PubMed1982

Lysis of autologous human melanoma cells by in vitro allosensitized peripheral blood lymphocytes.

Peripheral blood lymphocytes (PBL) of melanoma patients were sensitized in vitro with lymphocytes of a single donor or with a pool of lymphocytes of 5-20 different donors. After 6-7 days, the cytotoxic activity of the sensitized PBL was tested against cultured autologous tumor cells and lymphocytes in a 51Cr-release assay. Tumor lysis was observed in 13 of 16 cases in which patients' PBL (Pt-PBL) were stimulated by a pool of allogeneic lymphocytes and in five out of seven cases when single sensitization was performed. In no case was lysis of autologous normal lymphocytes or blasts seen. Cultivation of Pt-PBL with irradiated autologous tumor cells never led to the induction of lymphocytes cytotoxic to melanoma cells. Lysability by pool-activated autologous Pt-PBL of fresh cryopreserved tumor cells was compared to that of short-term cultured tumor cells, and no significant differences were observed. Cold-target inhibition experiments indicated that the cytotoxicity of Pt-PBL was tumor-restricted since only autologous melanoma cells but not lymphocytes were able to inhibit the reaction. These results indicate that activation of Pt-PBL is necessary in order to elicit or amplify their antitumor activity.

Cytotoxicity, Immunologic↗
PubMed1982

The fecal microbial population in the irritable bowel syndrome.

The focal microbial flora composition has been studied in patients affected by irritable bowel syndrome. The statistical analysis of the results showed a decrease of coliforms, lactobacilli and, to a lesser extent, bifidobacteria, as compared to control healthy individuals. Hypotheses on the cause of these modifications and their role in the maintenance and severity of the disease are discussed.

Bacteria↗
PubMed1981

Microplate enzyme-linked immunosorbent assay for bovine leukemia virus antibody.

A microplate enzyme-linked immunosorbent assay method was developed for the measurement of bovine immunoglobulin G antibody specific to the envelope antigen (glycoprotein 60) of bovine leukemia virus. The test was then performed on 440 serum samples from dairy cows belonging to herds in which bovine leukemia was suspected or which were leukemia free, and the results were compared with those obtained with the gel-diffusion technique.

Animals↗
PubMed1980

ELISA for toxoplasma antibody detection: a comparison with other serodiagnostic tests.

An ELISA method was developed for the measurement of toxoplasma IgG antibodies in human serum using antigen-coated polystyrene beads as a solid phase and anti human IgG-horse radish peroxidase conjugate as an enzymatic tracer. In order to assess ELISA sensitivity and specificity, a between methods comparison was made using 'conventional' serological tests as reference (dye-test, crossover-linked immunoassay, passive haemagglutination, indirect immunofluorescence). From an analysis of the group classifications obtained some considerations emerged: the ELISA specificity looks comparable with that of the 'reference' tests, as no sample classified as negative by all these tests was ELISA-positive, and vice versa; ELISA appears to correlate better with haemagglutination and immunofluorescence, on the basis of the respective class frequencies; in particular, the number of positives, which is much lower for the dye-test and crossover-linked immunoassay, suggests that a higher sensitivity is reached in the former cases.

Antibodies↗
PubMed1978

Use of gentamicin to prevent intestinal side effects of lincomycin therapy.

Mild to severe and persisting diarrhea and even colitis have been reported as a side effect of therapy with lincomycin and clindamycin. An alteration in the normal bowel flora with an overgrowth of coliforms and other antibiotic-resistant bacteria has been postulated as a mechanism for the development of diarrhea. Investigations were undertaken in men to observe whether the simultaneous administration of gentamicin was capable of preventing lincomycin-associated intestinal disturbances. Of the 30 subjects treated only with lincomycin 11 (36.6%) developed diarrhea. Of the 18 subjects treated with lincomycin and simultaneously with oral gentamicine, none developed diarrhea. Results of bacteriological examinations indicate that in subjects treated with lincomycin, some potentially pathogenic bacteria, like coliforms and clostridia, are still present in intestinal flora; the simultaneous absence of bifidobacteria and bacteriodes could result in the abolishment of the host resistance to the noxious activity of these endogenous bacteria, as some reported data of the literature suggest. Coliforms and the majority of clostridia strains are not present in subjects treated simultaneously with gentamicin.

Adult↗
PubMedDate not supplied

Adoptive immunotherapy of cancer with immune and activated lymphocytes: experimental and clinical studies.

Recent studies of passive adoptive immunotherapy of experimental tumors indicate that histologically different neoplasms can be cured by this procedure in mice, rats and guinea pigs. In this paper two main approaches of adoptive immunotherapy with lymphocytes are considered. One which makes use of specific tumor-immune cells and is applicable to immunogenic tumors, and the other which uses activated (allostimulated and/or IL-2-activated) lymphocytes and is applicable to immunogenic and non-immunogenic neoplasms. Experimental models of both approaches and results provided by them are reviewed. These studies indicate that transfer of tumor-reactive lymphocytes with or without the combined administration of IL-2 into syngeneic tumor-bearing animals can lead to the eradication of a disseminated neoplasia when certain conditions are met. In particular, it was found that high tumor burdens, delay of treatment and low number of transferred lymphocytes can adversely affect the results. It has also been shown that the therapeutic effect of treatment with anti-cancer drugs or irradiation may be significantly improved by the addition of adoptive immunotherapy. The successful treatment of immunogenic tumors often requires the inhibition of suppressor lymphocytes by Cy or irradiation. Non-immunogenic tumors can be successfully treated only by providing activated lymphocytes and high doses of IL-2. Recent findings of few available human studies of adoptive immunotherapy are also reviewed, and the problems of toxicity and possible therapeutic effects of infusion of autologous, activated lymphocytes and IL-2 are discussed.

Animals↗