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Biomedical subjects

J P Roboz

Publications and source records attributed to J P Roboz.

7 recordsLinked to original sources
PubMed1979

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↗
PubMed1979

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↗
PubMed1977

Specific immunotherapy with neuraminidase-modified leukemic cells: experimental and clinical trials.

The data presented establish the therapeutic effectiveness of immunotherapy with neuraminidase-treated allogeneic myeloblasts in combination with sustaining chemotherapy in patients with acute myelocytic leukemia. The in vivo and in vitro immunologic tests indicate normal immunocompetence in patients receiving immunotherapy versus control patients treated with chemotherapy alone. These findings correlate well with the improved duration of remission as the direct result of the immunotherapy.

Animals↗
PubMed1976

Therapeutic effectiveness of neuraminidase-treated tumor cells as an immunogen in man and experimental animals with leukemia.

The immunogenicity of leukemia L1210 in DBA/2 Ha and 6C3HED lymphosarcoma tumor cells in C3H/f mice was significantly increased after treatment with V. cholerae neuraminidase. DBA/2 Ha and C3H/f mice repeatedly immunized with neuraminidase-treated tumor cells rejected subsequent challenge of 10(7) or 10(6) untreated tumor cells, respectively. Based on the 51Cr microcytotoxicity assay, both strains of mice showed strong complement-dependent antibody titers and cell-mediated immunity. Sera and splenic lymphocytes from immunized C3H/f mice neutralized the tumorigenicity of 6C3HED lymphosarcoma and protected the recipient C3H/f mice against the disease. Immune lymphocytes pretreated with anti-theta sera lost their ability to neutralize the tumorigenicity of lymphosarcoma, and they failed to be stimulated by T-cell mitogens. We studied the effectiveness of chemoimmunotherapy in DBA/2 Ha mice with leukemia L1210. A single near optimal dose of BCNU 2 days after implantation of 10(6) tumor cells increased the survival time. A single immunization with 2 X 10(7) neuraminidase-treated L1210 tumor cells 4 days after cytoreductive therapy increased survival and resulted in cures for 50% of animals. Immunization of mice with neuraminidase-treated tumor cells and MER produced indefinite survival in a larger percentage of mice than did either treatment alone. AKR mice with spontaneous leukemia treated with combination chemotherapy sustained an 180% increase in life-span. Combination chemotherapy plus immunization with neuraminidase-treated syngeneic or allogeneic (Gross virus-induced) E2G leukemia cells were highly effective in prolonging the life-span of the immunized leukemic AKR mice. The experimental data led to clinical trials in acute myelocytic leukemia with neuraminidase-treated a-logeneic myeloblasts. Patients with acute myelocytic leukemia were randomized into two groups after remission induction. The median remission duration of patients on sustaining chemotherapy alone was 19 weeks (8 patients), whereas six of nine patients who received neuraminidase-treated allogeneic myeloblasts remain in remission 79-132 weeks. Statistical analysis of the remission duration and survival of patients who received chemoimmunotherapy versus the control group shows highly significant differences.

AKR murine leukemia virus↗
PubMed1976

Treatment of spontaneous leukemia in AKR mice with chemotherapy, immunotherapy, or interferon.

AKR mice are genetically destined to develop Gross (RNA) virus-induced lymphatic leukemia. Leukemic AKR mice treated with combination vincristine, cyclophosphamide (Cytoxan), and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea sustained a 180% increase of life-span. Combination chemotherapy plus immunization with neuraminidase-treated allogeneic (Gross virus-induced) G2G leukemic cells intradermally resulted in 35% of animals surviving beyond 150 days without evidence of the disease. It is significant that allogeneic E2G leukemic cells as immunogen were as effective in prolonging the life-span of the immunized leukemic AKR mice as were syngeneic leukemic thymocytes. Virazole (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), an antiviral compound, alone showed no apparent antitumor effect. However, in experiments in which the clinically diagnosed leukemic AKR mice received a combination of cytoreductive therapy [vincristine plus prednisone or, more effectively, vincristine, Cytoxan plus 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea, followed by Virazole], there was a noticeable reduction of the viral titer, a delay in the reappearance of viable clonogenic cells, and an increase in the survival time for the leukemic AKR mice as compared to those receiving cytoreductive therapy alone. The effectiveness of purified mouse interferon in AKR mice was also examined. The decrease in the viral titer of animals that received interferon treatment was markedly greater than of those receiving a combination of cytoreductive therapy with Virazole or immunotherapy. The administration of mouse interferon had a direct effect on the appearance of the spontaneous leukemia in AKR mice. The median life-span of the control animals was 36 weeks, whereas 45% of the AKR mice treated with five doses of 5 X 10(4) units of interferon are still alive at 54 weeks of age. Thus, interferon not only reduces the Gross murine leukemia virus titer in the chronically infected AKR mice but also significantly delays the appearance of the primary lymphoma.

AKR murine leukemia virus↗
PubMedDate not supplied

Characteristics of immunity induced by neuraminidase-treated lymphosarcoma cells in C3H (MTV+) and C3H (MTV-) mice.

The immunogenicity of 6C3HED lymphosarcoma ascites tumor cells was greatly enhanced upon treatment with Vibrio cholerae neuraminidase. As a result, mammary tumor virus (MTV)-free C3H mice which had been repeatedly immunized with the treated cells resisted a challenge of 10(6) untreated viable cells inoculated i.p., whereas all control animals died after receiving less than 10 lymphosarcoma tumor cells. In contrast, there was no increase in the refractoriness to challenge when MTV-infected C3H mice were immunized. Incubation of 6C3HED lymphosarcoma cells with serum of splenic lymphocytes from the immunized MTV-free C3H mice neutralized their tumorigenicity and protected recipient MTV-free and MTV-infected C3H mice against the disease. As shown by the 51Cr microcytotoxicity assay, the complement-dependent cytotoxic antibody titer reached 1,024; 29% of the target cells were lysed by lymphocytes obtained from immune MTV-free C3H mice. When the immune lymphocytes were pretreated with anti-theta serum they lost their ability to neutralize the tumorigenicity of the lymphosarcoma, failed to be stimulated by the T cell mitogens, phytohemagglutinin and concanavalin A, and failed to achieve cytolysis of the lymphosarcoma target cells in vitro. These observations establish the central role of the theta-antigen-bearing immune lymphocytes in cell-mediated immunity in this system. Failure of the immune system in the immunized MTV-infected C3H mice to cope with the challenging lymphosarcoma, even at low cell numbers, was reflected, not in the absence of humoral response, but in the relatively low level of cell-mediated immunity. This was manifested in both the neutralization and in the vitro cell-mediated immunity assays. This apparent immunological deficiency observed in the MTV-infected C3H mice could be countered by the transfer of lymphocytes from MTV-free C3H mice immunized with neuraminidase-treated 6C3HED lymphosarcoma cells. The recipient MTV-infected C3H mice then rejected a subsequent challenge with lymphosarcoma tumor grafts.

Animals↗