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Biomedical subjects

M A Bean

Publications and source records attributed to M A Bean.

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

Prognostic significance of regional lymph node histology in cancer of the bladder.

The regional lymph nodes from 47 patients with carcinoma of the bladder who had undergone radical cystectomy and bilateral pelvic lymphadenectomy were classified into 3 histologic patterns that correlated with immunologic function. Lymph nodes were designated as stimulated if they exhibited prominent germinal centers (B cell proliferation) and expansion of the deep cortex (T cell proliferation), depleted if they appeared markedly hypocellular and fibrotic, and unstimulated if they resembled a normal resting lymph node. Correlation of the histologic pattern with the extent of disease revealed that patients whose nodes appeared stimulated had fewer metastases (p less than 0.05) than those with either unstimulated or unstimulated combined with a depleted pattern. A markedly improved 5-year survival rate was seen in patients with a stimulated pattern (p less than 0.0001) compared to those patients who exhibited a depleted and/or unstimulated lymph node pattern. The survival advantage related to the stimulated pattern was observed primarily among patients with advanced disease. It is suggested that stimulated nodes reflect proliferation of T and B lymphocytes engaged in cell-mediated and humoral immune responses to the bladder tumor and that this favorably influenced survival in those patients. Patients whose lymph nodes showed a depleted pattern fared poorly despite the extent of the disease and those with an unstimulated pattern were intermediate in survival. A depleted pattern may represent a state of local immune paralysis, exhaustion of the draining lymph nodes as a result of exposure to excess tumor-derived products such as antigen or toxic substances or simply an atrophic node incapable of response. In the absence of a local immune response such patients might be expected to do poorly. These results suggest that morphologic evaluation of the lymph nodes regional to bladder cancer may provide a clue to their immunologic function and a more accurate guide to prognosis of patients with this neoplasm.

Adult↗

Decreased ability of blood leukocytes from patients with tumors of the urinary bladder to act as stimulator cells in mixed leukocyte culture.

Blood leukocytes from patients with active neoplasms of the urinary bladder were found to have a decreased ability to stimulate in one-way mixed leukocyte culture (MLC). The ability of the patients' leukocytes to act as stimulator cells in one-way MLC was assessed by simultaneous comparison to the ability of leukocytes from normal individuals to stimulate. In addition, the ability of the patients' leukocytes to act as responder cells in the one-way MLC was evaluated. Cells from 31 (56%) of 55 patients with active disease exhibited subnormal stimulatory activity in the MLC while 26 of these 31 patients (84%) had normal responsiveness. Cells from 9 of the 55 failed to respond normally. Poor stimulation occurred with both early and advanced disease, and the stimulatory activity increased after tumor removal in 12 of 15 patients who had previously shown subnormal stimulation. Six patients without active disease at the time of testing, in addition to the 55, exhibited normal levels of stimulation and responsiveness. This defective stimulatory activity is suggestive of an acquired, disease-related phenomenon and is not necessarily associated with decreased blood leukocyte responsiveness.

Adult↗

Antibody-dependent cell-mediated cytotoxicity for human monolayer target cells bearing blood group and transplantation antigens and for melanoma cells.

A sensitive assay for antibody-dependent cell-mediated cytotoxicity (ADCMC) was developed utilizing serum from a patient with gestational choriocarcinoma and the 3H-proline microcytotoxicity test for detection fo destruction of monolayer target cells. Conditions for optimal expression of ADCMC were investigated using serum from this patient and skin fibroblasts from her husband and daugther as target cells with semi-purified blood leukocytes from normal donors as effector cells. Factors critical for optimal expression of ADCMC in this assay are the selection of effector cell donors possessing high levels of activity in the presence of serum with known lymphocyte-dependent antibody. (LDA), the effector cell preparative technique, and incubation for up to 40 h. Tris-NH4Cl lysis of red blood cells was found significantly to reduce effector cell activity. Under optimal conditions, the LDA titer of this patient's serum was greater than 10(-4). The sensitivity of the assay was confirmed by the detection of LDA activity of an anti-blood-group antibody at dilutions not demonstrating hemagglutination, and by the induction of ADCMC for blood group A antigen-bearing target cells by normal sera of B and O blood groups. In a preliminary study of sera from 16 melanoma patients on the corresponding antologous tumor target cells, four had significant LDA. Further studies are under way to determine specificty, incidence, and relationship of LDA-positive autologous sera to course of disease.

Antibodies, Anti-Idiotypic↗

Expression of T-cell differentiation antigens on effector cells in cell-mediated cytotoxicity in vitro. Evidence for functional heterogeneity related to the surface phenotype of T cells.

The cell-mediated cytotoxicity (CMC) of nonadherent cells from the peritoneal cavity (NAPC) of alloimmunized mice can be measured by the [3H]proline microassay. The exhibition of thymus-derived (T) cell antigens on these killer cells was studied by incubating them with the relevant T-cell antisera and complement (C), under optimal conditions for lysis, before performance of the CMC assay. Under these conditions, the following T-cell antigens were demonstrable on the killer population in terms of percent reduction in CMC by the respective antisera: (a) Thy-1.1 (83%) and Thy-1.2 (100%), (b) MSLA (86%), (c) NTA-RA (a T-cell antigen recognized by naturally occurring autoantibody of NZB mice) (62%), (d) Ly1.1 )58%, (e) Ly-2.1 (11%; considered a marginal result) and Ly-2.2 (63%), and (f) Ly-3.2 (77%). The following were not demonstrable: (g) TL, and (h) Ly-1.2. (i) The antigen Ly-3.1 was not studied. Omission of C deprived all T-cell antisera tested of their capacity to suppress CMC, indicating that the cell components recognized by such antisera may perform no direct function in CMC. On the assumption that all Ly+ cells are Thy-1+, it is clear that the T-cell members of the immune NAPC population must be heterogenous. This follows from the fact that the proportions of T cells lysed by different Ly antisera did not correspond with ensuing degree of loss of CMC capacity. The extremes were represented by anti-Ly-1.2 (74% Thy-1+ cells lysed, but no reduction in CMC) and Ly-3.2 (54% Thy-1+ cells lysed, with 77% reduction in CMC). From this initial survey it appears that the C57BL/6 mice killer T-cell population active in CMC in vitro is relatively rich in surface antigens of the Ly-2/Ly-3 category and relatively poor in representation of the Ly-1 surface antigens. It remains to be seen whether this killer cell phenotype, poor in Ly-1 and rich in Ly-2/Ly-3, is characteristic of the mouse generally. From these results it appears that subsets of T cells with different immunological functions may exhibit qualitative or quantitative differences in surface antigens specified by different Ly loci; this will be easier to assess in the future when the results of experiments with the same Ly antisera but dealing with T-cell functions other than CMC become available.

Animals↗

Cytotoxic reactions of murine lymphoid cells studied with a tritiated proline microcytotoxicity test.

A lymphocyte cytotoxicity (CTX) test with 3-H-proline-prelabeled target cells was used to detect the immune response of murine lymphoid cells to H-2 and tumor antigens. The specificity of the reaction was determined by simultaneous tests on unrelated target cells and, for reactions directed against H-2 antigens, by blocking experiments with alloantiserum directed against the H-2 antigens of the target cells. After a single intraperitoneal (ip) injection of allogeneic spleen cells, CTX of unfractionated peritoneal cellswas strong, with a sharp peak on day 5. Repeated ip immunization markedly increased the CTX of unfractionated peritoneal cells. The reaction was strongest when the test was done at 37 degrees C. Sometimes CTX should be detected after as little as 6 hours' incubation. CTX depended primarily on the absolute number of effector or target cells per area rather than on the ratio of effector to target cells. Both nonadherent and adherent peritoneal cells destroyed target cells specifically. The CTX of nonadherent peritoneal cells was increased by 2-mercaptoethanol. The CTX reaction depended on effector cells bearing Tyl-1. Destruction of "innocent bystander" target cells was seen with one of four combinations of unfractionated and nonadherent peritoneal cells from hyperimmune animals.

Animals↗

Camp lighthouse.

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Adolescent↗