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Biomedical subjects

M A Bean

Publications and source records attributed to M A Bean.

At least 19 recordsLinked to original sources
PubMed1991

Prevention of transfusion-induced sensitization to minor histocompatibility antigens on DLA-identical canine marrow grafts by gamma irradiation of marrow donor blood.

Dogs given total-body irradiation and marrow transplants from DLA-identical littermates exhibit prompt and sustained hematopoietic engraftment. However, animals given three preceding blood transfusions from the marrow donor before transplant become sensitized and reject the marrow graft. Rejection is due to exposure to polymorphic minor non-DLA histocompatibility antigens expressed on blood mononuclear cells. We sought to determine whether heat treatment would prevent blood from sensitizing recipients in this model since heating blood to 45 degrees C for 45 min abrogates the ability of blood mononuclear cells to stimulate in mixed lymphocyte culture. Three of 4 evaluable dogs given heat-treated blood before transplant rejected their marrow grafts. To prevent possible reexpression/reacquisition of mononuclear cell functional activity in vivo after transfusion, subsequent dogs were given heated blood that was additionally exposed to 2000 cGy gamma irradiation. Eight of 10 evaluable dogs given blood treated in this fashion engrafted. Unexpectedly, 9 out of 10 evaluable dogs transfused with blood treated only with gamma irradiation also engrafted. These results demonstrate that treatment of blood with gamma irradiation alone or in combination with heat prevents transfusion-induced sensitization to minor histocompatibility antigens. Results from this canine model suggest that blood products be gamma irradiated before transfusion in patients who are transplant candidates in order to prevent sensitization to minor histocompatibility antigens and reduce the risk of marrow graft rejection.

Animals↗
PubMed1990

Suppressed antidonor MLC responses in renal transplant candidates conditioned with donor-specific transfusions that carry the recipient's noninherited maternal HLA haplotype.

Forty-seven patients with end-stage renal disease were entered into a donor-specific transfusion protocol consisting of three infusions of whole blood every two weeks prior to transplantation. Fourteen of the patients became sensitized following transfusion and were not transplanted. Thirty-one patients received a transplant from the DST donor and have an estimated two-year graft survival of 97%, three-year survival of 88%, and four-year survival of 69%. Cells of eleven of the 36 recipients tested in one-way MLC before and two weeks after completion of DST exhibited a significantly decreased antidonor MLC response. Deletion of CD8+ positive lymphocytes from suppressed MLCs resulted in restoration of antidonor MLC reactivity in four of six patients. An analysis of the family HLA profile in patients exhibiting a decreased donor-directed MLC response revealed a significant (P less than 0.02) association between decreased MLC reactivity following DST and the expression of noninherited maternal HLA antigens by cells of the transfusion donor. These alterations in cellular immune responses noted in some patients following DST are consistent with the appearance of specific antidonor T suppressor cells as a result of donor-specific transfusion.

Blood Transfusion↗
PubMed1979

Cell-mediated cytotoxicity for cultured autologous melanoma cells.

Peripheral blood lymphocytes from 32 patients with malignant melanoma were tested for cell-mediated cytotoxicity (CMC) against cultured autologous melanoma cells. Effector cells were prepared from venous blood by defibrination, gel sedimentation, nylon column filtration, and lysis of remaining erythrocytes with NH4Cl. Melanoma cells prelabelled with [3H])proline were used as target cells in a 40-h assay and CMC was evaluated against standards obtained with blood lymphocytes from the least reactive normal donor. Reproducible autologous CMC was detected in 18 of 32 patients in a series of 367 total tests. CMC correlated with tumor volume (5-500 cm3) but not with tumor stage or DNCB reactivity. Preliminary results indicated that autologous CMC was not affected by treatment with DTIC, dexamethasone, intralesional BCG, radiation therapy, or partial surgical excision. Lack of consistent CMC in 14 patients could not be attributed to a measurable decrease in general immune capacity or to increased resistance of the patients' melanoma cells to CMC in general. Fibroblasts were more resistant to CMC than melanoma cells, and therefore of questionable value for defining specificity in direct tests.

Adult↗
PubMed1979

Human blood T lymphocytes that suppress the mixed leukocyte culture reactivity of lymphocytes from HLA-B14 bearing individuals.

A nontransfused male patient with recurrent bladder carcinomata has been demonstrated to have blood T lymphocytes that suppress the MLC responsiveness of lymphocytes only from normal individuals positive for HLA-B14. Unexpectedly, this T-suppressor cell differs from three other reported blood T-suppressor cells arising in man in that it apparently does not require HLA-D locus compatibility between the suppressor cell and the lymphocyte being suppressed.

Epitopes↗
PubMed1978

Immunocompetence of patients with transitional cell carcinoma as measured by dinitrochlorobenzene skin tests and in vitro lymphocyte function.

Patients with transitional cell carcinoma of the bladder have a highly significant stepwise decrease in responsiveness to challenge with DNCB with advancing stage of disease. Seventy-five percent of those patients with superficial tumors are skin-test positive versus only 35% for those having tumors that are locally advanced and/or metastatic. MLC response and ability to stimulate in this culture as well as PHA and Con A response of blood leukocytes have been studied in relation to stage of disease and therapy. Recent irradiation appears to inhibit significantly MLC responsiveness, and PHA and Con A blastogenesis. Although responsiveness for this group of patients is decreased from normal, a further decrease occurs in responsiveness to Con A with advancing stage of disease. Blood leukocytes from some patients with urinary bladder carcinoma appear to have a decreased ability to function as stimulator cells in one-way MLC. This ability to stimulate returns to normal levels with tumor removal.

Carcinoma, Transitional Cell↗
PubMed1978

In vitro immune parameters in relation to clinical course in transitional cell carcinoma.

Longitudinal experiments were performed in which lymphocytes from patients were compared with simultaneously studied normals. Patient lymphocytes were examined for their ability to function as stimulator and responder cells in a one-way MLC. Additionally, lymphocyte mitogenic response to PHA and Con A were examined. We observed changes in these parameters that could be correlated with the clinical course of the patients.

Carcinoma, Transitional Cell↗
PubMed1978

Mixed leukocyte culture reactivity of lymph node cells regional to transitional cell carcinoma of the bladder.

Regional lymph node cells from some patients with bladder cancer exhibited a suppressive effect on the ability of autologous and allogeneic blood leukocytes to function as stimulator cells in one-way mixed leukocyte culture. The appearance of the suppressor activity was significantly correlated to advancing stage of disease and to the histology of the regional lymph nodes.

Carcinoma, Transitional Cell↗
PubMed1978

Factors that affect the results of microcytotoxicity testing in man.

A great number of variables affect the pattern of test results obtained in studies of cell-mediated cytotoxicity of blood lymphocytes for tumor cells in vitro. The classic microcytotoxicity test measures both cell destruction and effects on cell growth. Microcytotoxicity tests in which isotopically prelabeled target cells are used measure primarily cell destruction. The method of preparation of effector cells from human blood can greatly influence results of such tests. Perhaps the most clear-cut example of this influence is the effect of Tris--NH4Cl treatment of effector cells to lyse contaminating red blood cells. This treatment inactivates the lytic function of certain effector cell types. In addition, a major consideration that must be kept in mind is the difference in patients under study by different groups of investigators.

Cell Separation↗
PubMed1978

Function of cryopreserved human effector cells in antibody-dependent, cell-mediated cytotoxicity.

Cells active in an ADCC model were studied for their ability to withstand cryopreservation. For this model, we used the [3H]proline microcytotoxicity assay with fibroblast target cells and a serum containing lymphocyte-dependent antibody reactive with the alloantigens on those target cells. Human blood effector cells active in this system can be successfully cryopreserved with minor dimunition in function with standard techniques and concentrations between 9 and 12% DMSO.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1977

Occurrence of restricted suppressor T-cell activity in man.

Blood leukocytes from an immunologically hyporesponsive patient with urinary bladder carcinoma were found to be deficient in their ability to stimulate 3 of 27 responder leukocyte preparations from normal individuals in one-way mixed leukocyte culture (MLC). The patient's T-depleted leukocytes, however, functioned adequately as stimulator cells. T-enriched lymphocytes from this patient suppressed the MLC responsiveness of those three normals but not the responsiveness of other normals. The patient's cells suppressed the MLC responsiveness of only one of each of the parents of two of the normals who could be suppressed by the patient's leukocytes suggesting a possible genetic restriction to this suppressor cell activity.

HLA Antigens↗
PubMed1977

Prostatic adenocarcinoma: relationship of grade and local extent to the pattern of metastases.

In 100 consecutive cases of prostatic adenocarcinoma treated by pelvic lymphadenectomy and interstitial implantation of 125I the relationship of tumor stage, size and grade was analyzed relative to the incidence and site of metastases, and the response of the primary tumor to irradiation. High stage, large size and poor histological differentiation were associated with a significantly higher probability of pelvic node metastases. The response of the primary tumor to irradiation was significantly higher among patients with small stage B tumors and/or those with negative pelvic lymph nodes. Important determinants of metastases subsequent to 125I implantation were the large size of the primary tumor, poor histological differentiation, seminal vesicle invasion, large (more than 3 cc) volume of lymph node metastases and absence of local prostatic response to irradiation.

Adenocarcinoma↗
PubMed1977

Prostatic involvement by transitional cell carcinoma: pathogenesis, patterns and prognosis.

Prostatic involvement by transitional cell carcinoma of the bladder includes a spectrum of histologic patterns. Ductal only or ductal and acinar involvement occurs with or without stromal invasion. Stromal invasion may exist without glandular involvement. Invasive prostatic patterns are most frequent in the setting of high stage invasive bladder tumors and 5-year survival rates for these patients are low. Non-invasive in situ prostatic patterns are usually associated with low stage bladder tumors and 5-year survival approaches that predicted from radical cystectomy for low stage bladder tumor alone. When an invasive pattern is associated with a low stage bladder tumor the 5-year survival rate is determined by the prostatic lesion and is low. Although the survival rate is severely jeopardized by stromal prostatic invasion the prognosis is not hopeless. Preoperative radiotherapy followed by cystoprostatourethrectomy can be expected to produce a 20 per cent 5-year survival rate.

Carcinoma, Transitional Cell↗
PubMed1977

Some immunological considerations relevant to the study of human bladder cancer.

The likelihood that immunosurveillance, concomitant immunity, and immunodepression play a role in the development and spread of neoplasms of the urinary bladder is discussed. The circumstantial evidence for the existence of concomitant immunity to bladder cancer-associated antigens is briefly reviewed, and the implications of the hypothesis of Zinkernagel and Dougherty of a genetic restriction to the cytotoxicity of T-cells for virally determined target cell antigens and of the concept of immunoregulatory cells for our understanding of the immunology of bladder carcinoma are discussed.

Aged↗
PubMed1976

Ly phenotype of cytotoxic T cells for syngeneic tumor.

Our present and previous findings may be summarized as follows: The phenotype of C57BL/6 (B6) cytotoxic cells for allogeneic target cells is Thy-1+, Ly-1- Ly-2/3+, MSLA+, and Ig-. the phenotype of B6 cytotoxic cells for syngeneic tumor cells is Thy-1+, Ly-1+, Ly-2/3+, MSLA+, and Ig-. The phenotype of B6 cytotoxic cells for syngeneic tumor cells is Thy-1+, Ly-1+, Ly-2/3+, MSLA+, AND Ig-. Thus, differences in Ly phenotype appear to be exhibited not only by cytotoxic T cells as opposed to helper T cells, but also within subcategories of cytotoxic T cells.

Animals↗
PubMed1976

Immune evaluation with skin testing. A study of testicular, prostatic, and bladder neoplasms.

Fifty patients with testicular carcinoma, 45 with prostatic neoplasm, 84 with bladder carcinoma, and 13 with benign bladder papilloma were evaluated for skin reactivity to DNCB and other intradermal antigens. Correlation between pathologic staging and skin-test reactivity was sought. Reaction to DNCB among patients with testis tumors was more significantly depressed by chemotherapy than by the extent of retroperitoneal or distant metastatic disease indicating that skin testing as a means of following the course of disease or of predicting survival may be limited by alterations caused by chemotherapy. DNCB reactivity did not correlate with the prognosis for the different stages of disease, but follow-up studies of individual patient survival are needed for substantiation. Depression of DNCB reactivity exists among patients with prostatic carcinoma whether the disease is localized or widely metastatic. Only lengthy follow-up will determine if there is any correlation of reactivity with survival in individual patients. DNCB reactivity among patients with bladder tumors shows progressive reduction with increasing stage disease and lends support to the evidence suggesting immune deficiency in patients with bladder neoplasm.

Adolescent↗