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Biomedical subjects

M A Bean

Publications and source records attributed to M A Bean.

At least 37 records · Page 2Linked to original sources
PubMed1987

Evidence for increased somatic cell mutations at the glycophorin A locus in atomic bomb survivors.

A recently developed assay for somatic cell mutations was used to study survivors of the atomic bomb at Hiroshima. This assay measures the frequency of variant erythrocytes produced by erythroid precursor cells with mutations that result in a loss of gene expression at the polymorphic glycophorin A (GPA) locus. Significant linear relations between variant frequency (VF) and radiation exposure were observed for three different variant cell phenotypes. The spontaneous and induced VFs agree with previous measurements of radiation-induced mutagenesis in other systems; this evidence supports a mutational origin for variant cells characterized by a loss of GPA expression and suggests that the GPA assay system may provide a cumulative dosimeter of past radiation exposures. VFs for some survivors differ dramatically from the calculated dose response, and these deviations appear to result primarily from statistical fluctuations in the number of mutations in the stem-cell pool. These fluctuations allow one to estimate the number of long-lived hemopoietic stem cells in humans.

Antibodies, Monoclonal↗
PubMed1986

Antigen-specific functions of a CD4+ subset of human T lymphocytes with granular morphology.

We previously showed that a small proportion of the CD4+ human lymphocytes express the C3bi receptor (CD11). In the present investigation these cells were found to have the homogeneous morphology of granular lymphocytes. Between 70 and 80% of the cells reacted with antibody Leu-7, but they did not express Fc receptors and had no spontaneous cytotoxic activity against the NK-sensitive cell line K562. The CD11+/CD4+ cells uniformly expressed CD3 and could be induced to express IL 2 receptors by activation with PHA or anti-CD3 antibody. Compared with unfractionated T cells, however, CD11+/CD4+ granular lymphocytes had a reduced ability to produce IL 2 after stimulation with PHA or anti-CD3 antibody. Nevertheless, the CD11+/CD4+ subset generated specific allocytotoxicity after stimulation with allogeneic cells and culture in IL 2. Furthermore, the CD11+/CD4+ cells also proliferated after stimulation with tetanus toxoid and PPD. Thus some cells of the CD11+/CD4+ subset are capable of antigen-specific responses. These results indicate that certain CD11+ cells with granular morphology are mature T lymphocytes.

Antigens↗
PubMed1986

Helper (OKT4) T cells from human T cell colonies produce potent colony-stimulating activity.

Confluent T cell colonies were grown by culturing blood mononuclear cells in double agar layers containing autologous plasma and phytohemagglutinin (PHA) for one week (37 degrees C, 5% CO2). The plates were then overlaid with serum-free alpha medium which was harvested after 24 h. This medium was demonstrated to have colony-stimulating activity (CSA) of greater potency than conventionally prepared PHA-leukocyte conditioned medium, which was prepared by incubating cells from the same donors. Removal of OKT4-positive cells using a monoclonal antibody and complement abolished CSA production by cells from T cell colonies while the removal of OKT8-positive cells had no effect.

Antibodies, Monoclonal↗
PubMed1985

Monoclonal antibody 9.3 and anti-CD11 antibodies define reciprocal subsets of lymphocytes.

We have previously described antibody 9.3 which recognizes a 44-kDa polypeptide designated Tp44 expressed on 70-80% of peripheral blood T cells, including nearly all CD4+ cells and some CD8+ cells. Whereas the 9.3+ population contains helper cells, cytotoxic T cell precursors and cytotoxic T cell effectors, the 9.3- population has been reported in several models to contain precursors for suppressor cells. In this report, we demonstrate that 9.3- lymphocytes express CD11, an antigen which is also present on monocytes and granulocytes. Among lymphoid cells, Tp44 and CD11 represent markers that identify reciprocal, nonoverlapping subsets, each of which contains both CD8+ cells and CD4+ cells. With Tp44 and CD11, and CD4 and CD8, the development and function of T cells can thus be examined within the framework of two distinct systems of reciprocally expressed antigens.

Antibodies, Monoclonal↗
PubMed1983

The cell surface phenotype of a naturally occurring human suppressor T-cell of restricted specificity: definition by monoclonal antibodies.

A series of murine monoclonal antibodies was used to characterize the surface phenotype of a naturally occurring E+ B14-specific suppressor cell present in the blood of a patient with recurrent superficial bladder carcinomas. This suppressor T cell is different from the few naturally occurring suppressors of MLC reported by others in that its function does not require HLA-D compatibility with the cells being suppressed. This patient's T cells had decreased proportions of T3+, 10.2+, 9.3+, and T4+ cells, a normal proportion of T8+ cells, and a markedly increased proportion of Ia-positive cells. The MLC-suppressor assay was used to test the functional activity of cell populations selectively depleted by treatment with monoclonal antibodies and C or enriched by panning. The B14-specific suppressor T cells in this patient expressed T cell markers recognized by monoclonal antibodies 9.6, T3, and the T cell subset marker identified by OKT8 (T8+) but not the subset marker identified by OKT4 (T4-). Ia antigens were present on a substantial portion of these suppressor T cells. Thus, this unique, naturally occurring suppressor T cell has a phenotype similar to that of other T suppressor cells in humans, adding validity to the concept of functionally distinct T cell compartments in human blood.

Antibodies, Monoclonal↗
PubMed1983

Suppression of the responsiveness of lymphocytes from cancer patients triggered by co-culture with autologous tumor-derived cells.

The question as to whether or not cancer patients have "tumor antigen"-induced suppressor T cells is of considerable interest and importance. As an approach to that question, the effect of addition of autologous irradiated tumor-derived cells (TDC) on the mixed lymphocyte response (MLR) of patients' lymphocytes (Ly) and of healthy donor Ly was tested. The rationale for these experiments was based on the fact that circulating antigen-responsive blood lymphocytes can be reactivated in vitro by exposure to the appropriate antigen. Thus, if there are circulating tumor "antigen"-reactive suppressor Ly, exposure to TDC as a source of the antigen should reactivate those cells. Reactivation of suppressor cells might result in diminished responsiveness to other stimuli such as alloantigens in the mixed leukocyte culture. We found that the addition of TDC to Ly cultures produced four distinct patterns of reaction. In 26 of the 74 different patient-tumor assays, the addition of autologous TDC to the patient cultures inhibited MLR, but the addition of the same TDC to cultures of Ly from healthy donors had no effect or increased their responsiveness (Specific Suppression). In 21 cases, the addition of autologous TDC to the patient cultures suppressed the MLR and the addition of the same TDC to control cultures suppressed the response of some but not all the healthy donors (Selective Suppression). In four cases, the addition of TDC to the cultures suppressed the MLR of the patients and all of the control donors (Nonspecific Suppression). In 23 cases, the addition of autologous TDC resulted in no suppression of the patient MLR or of any of the simultaneously tested normal donors (No Suppression). When TDC of patients with noninvasive bladder cancer were added to their own Ly cultures, only four of 11 produced specific or selective suppression compared to 11 of 12 when TDC came from patients with superficially invasive cancer. These data provide indirect evidence to support the hypothesis that human tumors induce circulating suppressor cells that may be reactivated in vitro by co-culture with TDC.

Cell Transformation, Neoplastic↗
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↗