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Biomedical subjects

J G Bekesi

Publications and source records attributed to J G Bekesi.

At least 91 records · Page 5Linked to original sources

Therapeutic effectiveness of neuraminidase-treated allogeneic myeloblasts as immunogen in acute myelocytic leukemia.

Our chemoimmunotherapy study shows significantly longer remission and survival in acute myelocytic leukemia (AML) patients who have been immunized with neuraminidase-treated allogeneic myeloblasts as compared to patients who received chemotherapy alone or neuraminidase-treated myeloblasts plus MER. MER impairs the immunotherapeutic effectiveness of neuraminidase-treated allogeneic myeloblasts in AML patients. The in vivo and in vitro immunologic status in each arm of the protocol correlate well with the duration of remission and survival of the patient.

B-Lymphocytes↗

Specificity of tumor antigen recognition by T-lymphocytes in the leukocyte adherence inhibition (LAI) assay in patients with breast cancer.

In an attempt to enhance the specificity with LAI assay in the diagnosis of cancer, we explored the possibility of using highly purified, 51Cr-prelabeled-PBL-subpopulations in performance of the assay. Leukocyte separation was achieved in 2 stages which involved EAET rosetting for the isolation of T-lymphocytes followed by Percoll gradient for separation of monocytes. These procedures provided excellent cellular yield, viability and cellular enrichment. By comparing the reactivity of various isolated subpopulations from breast cancer patients we established the critical role of T-lymphocytes in the recognition of tumor antigen in the LAI reaction, i.e. T-lymphocytes exhibited a breast cancer extract-specific response, reflected in a significant reduction of leukocyte adherence, while B-lymphocytes did not respond. In contrast, monocytes of breast cancer patients showed a non-specific LAI response to several unrelated tumor extracts. Similarly, T-lymphocytes from all patients with benign breast diseases as well as from healthy subjects showed no LAI response while false positive responses were detected in the unseparated PBL and monocytes of these individuals. It is concluded, therefore, that a differential diagnosis of cancer can only be made if isolated T-lymphocytes from PBL are used in the LAI assay procedure.

Adult↗

Studies on the role of cellular immunity and genetics in the etiology of rapidly progressing breast cancer in Tunisia.

It has been suggested that poussée évolutive (PEV) or rapidly progressing breast cancer (RPBC) represents a failure in the host immune system to control the proliferation of breast cancer cells. To evaluate this possibility, we have performed in vivo and in vitro assays of cellular immunity in Tunisian patients with breast cancer. Studies of delayed hypersensitivity using microbial antigens and in vitro including lymphocyte transformation tests and measurements of B and T cells indicated that RPBC patients had an immune response comparable to that of breast cancer patients without evidence of rapid progression. Normal Tunisians were more immunocompetent, however, an appeared to have a higher level of immune activity than normal individuals in the United States. In a second, independent series, an increased frequency of blood group A was found in RPBC patients, suggesting a genetic predisposition to this form of breast cancer. However HLA typing for A, B and DRW antigens revealed no specific RPBC-associated HLA antigen. Our studies clearly demonstrate that RPBC, or PEV, is not a reflection of immunodeficiency.

Breast Neoplasms↗

Preoperative and postoperative immunological evaluation of patients with colorectal cancer.

Twenty-two patients with cancer of the colon and rectum were studied: preoperative and postoperative cell-mediated and humoral immune factors were assessed, and local concentration of immunoglobulins in tumor tissue and in normal mucosa were measured. Lymphocyte function was found to be reduced in 50% of stage A and B and 66% of stage D patients. On the other hand, when the lymphoblastogenesis was performed in the presence of normal AB plasma, a partial restoration of lymphocyte function was noted, indicating the presence of a serum blocking factor in the blood of these patients. While there was no apparent decrease of B cell subpopulation, 57% of the tested patients showed significant reduction of T lymphocytes. Marked reduction of serum immunoglobulin levels, specifically IgG and IgM, was observed preoperatively followed by a gradual return toward normal values after surgical resection of neoplastic growth. It is noteworthy that tumor tissue contained more IgG and IgA than normal mucosa. However, IgM was below detection level both in normal and tumor tissues.

Aged↗

Radioisotopic 51Cr-leukocyte adherence inhibition (LAI) assay. I. Demonstration of anti-tumor immunity in patients with breast carcinoma.

A simplified radioisotopic leukocyte adherence inhibition assay (51Cr-LAI assay) was used to determine tumor-directed immune responses in patients with cancer of the breast. Essential steps in development of this assay are the standardization of conditions for optimal 51Cr uptake by peripheral blood lymphocytes (PBL) and the inclusion of autologous or normal AB serum in the incubation media. A dextrose salt mixture (GNK) was found to enhance intracellular uptake of 51Cr significantly (8-fold) without affecting viability of the cells or without causing selective loss of lymphocyte subpopulations. The presence of 10% autologous or normal AB serum prevented non-specific LAI responses to unrelated tumor antigens. In a study of 46 preoperative patients with suspected breast cancer, clear and accurate prediction of the presence of cancer was achieved with this new assay. All patients with localized breast cancer showed significant adherence inhibition in response to allogeneic breast tumor extracts whereas normal control women and patients with benign diseases did not respond. Neither patients with cancer nor those with benign breast diseases reacted to extracts of benign breast tissue antigens. LAI reactivities appeared to be directed selectively against tumor-associated antigens (TAA) and reflect specific antitumor immunity. This short term (4 h) 51Cr-LAI assay provides reproducible and specific results analogous to those using tube-LAI assay. The test has the advantages of being accurate, sensitive and free from technical bias.

Adult↗

Comparative studies of interferon and three antiviral agents on neurotropic and oncogenic herpesviruses.

The antiviral effects of four compounds, phosphonoacetate, phosphonoformate, acycloguanosine, and purified human lymphoblastic interferon, were tested against two neurotropic herpesviruses, herpesvirus platyrrhine and herpes simplex virus, and two oncogenic herpesviruses, herpesvirus saimiri and herpesvirus ateles. All four compounds induced different degrees of inhibition of these herpesviruses. Phosphonoacetate and phosphonoformate at concentrations of 50 micrograms/ml or greater showed powerful antiviral activities. Interferon was more effective against herpesvirus saimiri and herpesvirus ateles, the two oncogenic viruses. Herpes simplex virus and the oncogenic herpesviruses were effectively inhibited by acycloguanosine, whereas herpesvirus platyrrhine proved to be resistant. The simian herpesviruses required a higher concentration of phosphonoformate, phosphonoacetate, and acycloguanosine for antiviral action. The antiviral action of all four compounds was contingent on the continued presence of the compounds in the infected cell culture medium.

Antigens, Viral↗

Alterations of a mouse mammary tumor virus glycoprotein with interferon treatment.

The effects of exogenous mouse interferon on the MJY-alpha mammary tumor cell line chronically infected with mouse mammary tumor virus (MMTV) were examined. Interferon at concentrations of 25 to 2,000 IU/ml in culture medium did not alter the growth rate or morphology of the cell layers. Electron microscopic examination of interferon-treated cells indicated a decrease in the numbers of A-type and budding B-type particles of MMTV. However, the levels of extracellular MMTV virions in the culture supernatants were not significantly reduced. Profiles of MMTV glycoproteins and nonglycosylated polypeptides obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of virions purified from interferon-treated cultures revealed increases in the relative levels of the 60,000-dalton glycoprotein, gp60.

Animals↗

Transplantation of human malignant mesothelioma into nude mice.

Human pleural malignant mesothelioma was successfully transplanted into nude mice from 2 of 3 patients. The tumor implants of the first generation grew in 6 of 20 mice (30%), with a take of implants of 17 of 32 (53%). Overall, tumors grew from 52 of 80 mice (65%) in a total of 169 of 266 implants (64%) during the first four generations. The mean delay between transplantation and tumor growth was 46 days (range, 18 to 104 days). Pathological examination by light and electron microscopy confirmed the nature of the growing tumors in nude mice. Pathology of transplanted tumors was grossly similar to the human tumors in both first- and second-generation transplants. Up to eight generations have been presently carried out with presence of a human karyotype in transplanted tumors. The potential usefulness of this model with particular reference to chemosensitivity of these tumors will be investigated.

Animals↗

Immunologic dysfunction among PBB-exposed Michigan dairy farmers.

In 1973 inadvertent contamination occurred in a special farm feed supplement for lactating cows. Polybrominated biphenyls (PBBs) were used in place of magnesium oxide resulting in serious harm to farm animals, including cattle, chickens, geese, ducks. Farm families, accustomed to eating their own products, were most heavily exposed. To further study the impact of PBBs, 45 adult Michigan farm residents who were originally examined in a clinical field survey were further studied with respect to their immunologic status. For comparison, 46 dairy farm residents in Wisconsin, who had not eaten PBB-contaminated food, were examined, as were 79 healthy subjects in New York City. Abnormalities in the Michigan group included significant decrease in absolute numbers and percentages of T and B-lymphocytes and increased number of lymphocytes with no detectable surface markers ("null cells"). Significant reduction of in vitro immune function was noted in 35--40% of the Michigan farm residents who had eaten food containing PBB. Despite the absence of any apparent numerical reduction, both T and B lymphocyte subpopulations of peripheral blood lymphocytes showed evidence of functional defect. Ten of the 45 Michigan farmers studied showed impaired PHA-induced blastogeneic response, due to the decreased number and percent of T-cells in the PBLs. The decreased immune function detected among the PBB-exposed farm residents tended to affect families as a unit and was independent of exposed individuals' age or sex, speaking against the possibility of genetic predisposition.

Accidents↗

Impact of specific immunotherapy in acute myelocytic leukemia.

Our studies clearly show that significantly longer remission duration was attained in groups of AML patients immunized with neuraminidase treated allogeneic myeloblasts as compared to patients who received chemotherapy alone or neuraminidase treated myeloblasts plus MER. IT is clear that MER, albeit apparently active alone in certain other clinical studies impairs the immunotherapeutic value of neuraminidase treated allogeneic myeloblasts in AML patients. The in vivo and in vitro immunological tests results reflect the host's immunological status in each arm of the protocol and correlate well with the duration of remission achieved with specific vs. combination of specific plus adjuvant immunotherapy.

Drug Therapy, Combination↗

Impaired immune function and identification of polybrominated biphenyls (PBB) in blood compartments of exposed Michigan dairy farmers and chemical workers.

In 1973 PBB's were accidentally mixed into animal feed, resulting in marked toxic effects. Meat and dairy products were widely consumed in Michigan. To determine the impact of PBB's, 55 exposed Michigan farm residents, 11 Michigan chemical workers and 46 non-exposed Wisconsin farmers were examined. Abnormalities included decreased number of T-lymphocytes with concomitant increase of lymphocytes with no detectable surface markers, "null cells", and altered lymphocyte function. Data obtained from skin testing using standard recall antigens, showed no consistent correlation between the delayed cutaneous hypersensitivity response and the impaired lymphocyte function. PBB (hexa) in separated white blood cells and red cells was positively identified and quantified by gas chromatography-mass spectrometry. PBB and immunological abnormalities were not detected in non-exposed Wisconsin dairy farm residents.

Agricultural Workers' Diseases↗

Macrophage-like cell transformation and CFU(c) fluctuations in normal and leukemic human marrow cultures treated by phorbol diester.

Bone marrow from normal and chronic myeloid leukemia donors was grown in liquid cultures without feeder layers and with and without 12-u-tetradecanoyl-phorbol-13-acetate (TPA). In 24-96 hours most of the cells (60-70%) cultured with 10(-7) M and 10(-8) M TPA stuck to the bottom of the flasks and had a peculiar shape resembling macrophages possessing strong phagocytizing activity and surface markers of monocyte-macrophage lineage of differentiation. 10(-7) M and 10(-8) M TPA fully inhibited CFU(c) in cultures of normal marrow as well as of chronic myeloid leukemia (CML) patients; 10(-9) M and 10(-10) M exhibited individually varied partial suppression. Cultivation of bone marrow with 10(-11) M to 10(-13) M TPA led in some cases to statistically significant increase of CFU(c) on day 4 and day 7.

Bone Marrow↗