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Biomedical subjects

G R Bruns

Publications and source records attributed to G R Bruns.

At least 19 recordsLinked to original sources
PubMed1979

Modulatory effects of oestrogen on immunologic responsiveness. I. Inhibition of DNA synthesis in peripheral blood lymphocytes from patients with Peyronie's disease, prostatic cancer and transsexuals and a commentary.

A reduction in the phytohaemagglutinin-induced transformation of peripheral blood lymphocytes from patients with Peyronie's disease and prostate cancer and transsexuals cultured in autologous and homologous serum following the receipt of oestrogen therapy has been observed. Reduction of lymphocyte transformation in patients with prostatic cancer and without malignancy receiving oestrogen, i.e., Peyronie's disease and transsexuals, suggests that this reduction is related to the mode of therapy rather than to malignancy or a particular pathologic state. No direct evidence exists that the observed in vitro aberrations of lymphocytic responsiveness are reflective of host compromise, but these observations are of potential relevance in terms of their implications in the therapeutic management of patients with prostatic cancer and other hormonally-dependent tumours, e.g., of the breast, as well as responsive diseases, through their effect on cellular immunocompetence and suitability of hormonally treated patients as prospective candidates for adjuvant immunotherapy. The possible relevance of the present observations to the suggested association between uterine cancer and prolonged administration of diethylstilboesterol, as well as that between development of vaginal tumours in offspring and maternal ingestion during pregnancy, also remains of potential concern, pending further investigation.

DNA↗
PubMed1978

Inhibition of leukocyte migration by extracts of malignant prostatic tissue and correlation of degree of in vitro sensitization to clinical responsiveness in prostatic cancer patients.

In an attempt to evaluate the degree of in vitro cellular sensitization to tumor and its relationship to clinical responsiveness, direct leukocyte migration tests were carried out in patients with varying degrees of adenocarcinoma of the prostate employing pooled allogeneic extracts of normal, benign, and malignant prostatic tissue as a source of antigen. Cell-mediated immunity to presumably common prostatic tumor associated antigens was observed. The degree of sensitization of clinically significant specific reactivity of the patients' leukocytes to malignant prostatic tissue was greatest in patients with localized disease, low-grade tumor, and clinically inactive disease than in patients with advanced disease, high-grade tumor, and clinically active disease. Evaluation of the possible correlation of specific reactivity to malignant prostatic tissue as a prognostic index of clinical responsiveness revealed a positive correlation with the degree of sensitization in 3 (43 per cent) of 7 patients. Correlation in 4 patients was questionable because of observations of "stimulation" of migration rather than inhibition, suggested by some to be reflective of weak sensitization to tumor. Evaluation of a larger patient population as well as a prospective study of the relationship of the degree of sensitization and clinical responsiveness will be necessary before any definitive conclusions may be drawn regarding the present observations.

Adenocarcinoma↗
PubMed1978

Serum immunoglobulin E in pemphigus.

Immunoglobulin E levels in the sera of patients with pemphigus (12 with Brazilian pemphigus foliaceus (BPF) and 11 with pemphigus vulgaris (PV)) were determined by means of a solid phase radioimmunoassay. A significant increase in IgE level was observed in BPF patients compared to the level of IgE in PV patients and healthy adults. The implications of an elevated level of IgE with respect to other aberrations of immunologic responsiveness and the suggested infectious etiology of BPF are considered.

Complement C3↗
PubMed1977

Alterations in host responsiveness in patients with prostatic cancer following cryosurgery or transurethral resection.

Anesthesia, stress, trauma or the operation per se have been reported to result in alterations of host resistance in a wide range of diseases. The effect of such changes on the thymolymphatic system of patients with prostatic cancer is not known. While evaluating in vitro parameters of cellular immunologic responsiveness in patients with prostatic cancer, we have observed a depression two to seven days following cryosurgery or transurethral resection (TUR) of the proliferation of phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes (PBL). Contrary to the reduced proliferation of PBL cultured in autologous and homologous serum from patients receiving TUR, patients receiving cryosurgery, while also showing reduction in autologous serum, showed increased responsiveness when cultured in homologous serum. Although transient, depression of lymphocyte proliferation, particularly if involving tumor-cloned T-cells, may provide reduced surveillance to potential metastatic tumor cells leading to an alteration of tumor-host homeostasis. The potential of reduced surveillance, at least in the case of TUR, appears to be supported by observations that patients dying from prostatic cancer at our institution had an antecedent TUR. Identifying those patients with changes in responsiveness before surgery, as well as those prone to develop or undergo further reductions in responsiveness after surgery, would appear to be relevant in the management of patient with prostatic as well as other malignancies. Pre- and/or postoperative immunotherapy in such patients may be indicated.

Aged↗
PubMed1977

The effect of transurethral resection of the prostate on lymphocyte response in patients with prostatic cancer.

The following study indicates that transurethral resection may affect the in vivo cellular aspects of the immune response in patients with prostatic cancer. This in vivo result seems to be supported by the fact that patients dying of carcinoma of the prostate at our institution usually had had an antecedent transurethral resection. Therefore, we emphasize that transurethral resection in patients with prostate cancer should be undertaken with clear-cut indications and with the knowledge that it may be an insult to the patient's immune system.

Aged↗
PubMed1976

Evaluation of cellular immunologic responsiveness in the clinical management of patients with prostatic cancer. I. Thymic-dependent lymphocytic blastogenesis.

Thymic-dependent lymphocytic blastogenesis of peripheral blood lymphocytes of 59 patients with varying stages of prostatic cancer to the non-specific plant mitogen, phytohaemagglutinin (PHA) and the correlation of their responsiveness with the clinical stage of malignancy and level of alpha2-globulin have been evaluated. Patients within each of the four stages of malignancy possessed statistically significant extrinsic (noted in 40 (68%) of 59 patients) and intrinsic (noted in 21 (47%) of 45 patients) aberrations of their lymphocytic responsiveness to PHA compared with the responsiveness of a control population of non-cancer patients. The observed aberrations were, however, not significantly different between each stage nor did they correlate with the stage of disease. Similarly, levels of alpha2-globulin, while significantly elevated within each stage, as compared with the levels in the control population, no significant differences or correlation with the stage of disease was observed. Of interest, perhaps pending further study, were observations of the increased frequency of the number of patients with a significant elevation of alpha2 with a progression of malignancy from localized to invasive and metastatic disease. A similar trend in the incidence of the association of aberrations of lymphocytic reactivity with elevated levels of alpha2 were also noted with a progression of disease. The present confirmatory observations of a recent study in this laboratory of diminished cellular responsiveness in patients with prostatic cancer may be of considerable relevance in directing the therapeutic management of the patient - lest the therapy selected be further debilitating providing reduced surveillance - metastization of tumour cells, and alteration of tumour-host homeostasis.

Adenocarcinoma↗
PubMed1976

Evaluation of cellular immunologic responsiveness in the clinical management of patients with prostatic cancer. II. Effect of oestrogen, cryosurgery and transurethral resection on thymic-dependent lymphocytic blastogenesis.

The effect of oestrogen, cryosurgery and transurethral resection (TUR) of the prostate on the blastogenic response of thymic-dependent peripheral blood lymphocytes (PBL) to the non-specific mitogen, phytohaemagglutinin (PHA) was evaluated as one in vitro criteria of each of these treatment modalities on the cellular immunologic responsiveness of 24 patients with prostatic cancer. A depression 5 days following receipt of oestrogen and 2-7 days following cryosurgery or TUR of the responsiveness of PHA-stimulated PBL was observed. Oestrogen-induced aberrations of responsiveness may not only be of relevance in prostatic cancer patients, but also suggested association between uterine cancer and prolonged administration of diethylstilboesterol and the development of vaginal tumours in offspring found in association with maternal ingestion during pregnancy. Particularly striking was that contrary to the reduced responsiveness of PBL cultured in autologous and homologous serum from patients receiving TUR, patients receiving cryosurgery, while also showing reduction in autologous serum, showed increased responsiveness when cultured in homologous serum. Although transient, depression of lymphocyte responsiveness, particularly if involving tumour-cloned T cells, may provide reduced surveillance to potential tumour cells leading to an alteration of tumour-host homeostasis. The potential of reduced tumour surveillance at least in the case of TUR, appears to be supported by observations that patients expiring from prostatic cancer at our institution had an antecedent TUR. The possibility of identifying those patients possessing aberrations of responsiveness prior to therapy, as well as those prone to develop or undergo further reduction in their responsiveness following the presently evaluated treatment modalities would appear to be of real and relevant concern in the management of the patient with prostatic, as well as other types of malignant neoplasms. The possibility of pre-operative and/or post-operative immunotherapy in such patients may be indicated pending further study.

Aged↗
PubMed1976

Evaluation of cellular immunologic responsiveness in the clinical management of patients with prostatic cancer. III. Inhibition of leucocyte migration.

Host cellular responsiveness to tumour was evaluted in 37 patients with varying degrees of clinically active and inactive adenocarcinoma of the prostate by direct inhibition of leucocyte migration (ILM) employing saline extracts of pooled allogeneic normal, benign and malignant prostatic tissue as a source of antigen. The majority of these patients had received or were receiving conventional therapy at the time of evaluation. 13 (35%) prostatic cancer patients possessed clinically significant specific reactivity to malignant prostatic tissue, whereas only 1 (8%), of 13 control patients (11 healthy adults and 2 patients with carcinoma other than of the prostate: bladder and penis) possessed comparable reactivity. While the wide range of specific reactivity observed overall, including 'stimulation' of migration, compared with the mean percent ILM was very large, the SD of the mean specific percent ILM in the 13 prostatic cancer patients possessing clinically significant specific reactivity to malignant prostatic tissue, was most respectable. Since all reactions were allogeneic, these results indicated that prostatic cancer patients possessed cell-mediated immunity to presumably common prostatic tumour-associated antigens. Further evaluation disclosed that the incidence of patients possessing clinically significant reactivity to malignant tissue was almost identical regardless of the patient's stage of malignancy, histological grade of tumour, or clinical status. The degree of sensitization of clinically significant reactivity to malignant tissue was, however, greater in patients with localized disease, low grade tumour, and clinically inactive disease, than in patients with advanced disease, high-grade tumour, and clinically active disease. Evaluation of the possible correlation of specific reactivity to malignant prostatic tissue as a prognostic index of subsequent clinical responsiveness revealed a positive correlation with the degree of sensitization in 3 (43%) of 7 patients available for routine follow-up. Correlation in four patients was questionable due to the observations of 'stimulation' of migration rather than inhibition. While providing initial preliminary evidence of the presence of cell-mediated anti-tumour immunity in patients with prostatic cancer and promise of a possible prognostic index, the wide range in the variability of cellular responsiveness and the failure to identify clinically significant reactivity to malignant prostatic tissue in the majority (65%) of the patients evaluated, raises concern as to whether ILM employing saline extracts will provide the necessary in vitro assay of cellular responsivenss for the evaluation of prostatic cancer patients.

Adenocarcinoma↗
PubMed1976

Evaluation of cellular immunologic responsiveness in the clinical management of patients with prostatic cancer. IV. Leucocyte adherence inhibition.

As a possible alternate to existing in vitro assays of cell-mediated host responsiveness to tumour, a modification of the leucocyte adherence inhibition test employing peripheral blood lymphocytes (PBL), has been evaluated in patients with adenocarcinoma of the prostate. PBL from patients with prostatic cancer reacted to varying degrees with 3 M KC1 extracts of autologous and allogeneic prostatic tumours when cultured in the presence of homologous serum. When sensitized PBL and tumour extract were cultured in autologous serum, inhibition ('blocking') of the interaction of PBL and antigen was observed. 'Blocking' was not observed when the tumour extract was allogeneic with respect to the origin of PBL and serum. Cross-reactivity between individual tumours within a given tumour type is in keeping with observations of anti-tumour immunity in patients with other tumours. Observations suggestive of a specificity of 'blocking' for autologous tumour only, is somewhat unique and will require further confirmation. While preliminary, these results provide further evidence suggestive of anti-tumour cell-mediated immunity in prostatic cancer patients previously observed by inhibition of leucocyte migration. The observed 'blocking' effect of autologous serum may be analogous to that observed in the technically more complex colonly inhibition and lymphocyte cytotoxicity tests and may be indicative of one means by which the potential effects of sensitized PBL are inhibited in vivo.

Adenocarcinoma↗
PubMed1976

Hormonal therapy and alteration of lymphocyte proliferation.

Suppression of the blastogenic response of phytohemagglutinin-stimulated peripheral blood lymphocytes in autologous serum obtained from patients with prostatic cancer. Peyronie's disease, and transsexuals following estrogen therapy has been observed. Observations of suppression of blastogenesis in patients with prostatic cancer and without malignancy receiving estrogen suggests that this suppression would appear not to be associated with a particular pathologic state or malignancy per se but, rather, the given mode of therapy. The relevance of these observations to the effect of estrogen on cell-mediated responsiveness in patients with hormonally dependent tumors and to the suggested association between uterine cancer and prolonged administration of diethylstilbesterol and the development of vaginal tumors in offspring found in association with material ingestion during pregnancy remains speculative.

Estrogens↗
PubMed1975

Serum proteins in prostatic cancer. II. Effect on in vitro cell-mediated immunologic responsiveness.

The sera from patients with prostatic cancer have been observed to posses an unidentified factor capable of inhibiting the migration of leukocytes and the proliferative response to the nonspecific mitogen, phytohemagglutinin. Observation of inhibition of these two suggested in vitro correlates fo cell-mediated immunologic responsiveness emphasizes (1) the importance to the adjunctive diagnosis and prognosis of patients with malignancy of identifying the presence of abnormal serum proteins, and (2) the role of humoral inhibitory or "immunoregulatory" factors as potential abrogators of mechanisms of host resistance, for example, immunologic surveillance, and thus the degree to whcih the host may respond to his tumor.

Antilymphocyte Serum↗
PubMed1975

Effect of hormone therapy on immune response in patients with prostatic cancer.

Thirty-one patients with adenocarcinoma of the prostate had laboratory studies done for total proteins, serum immunoglobulins, white blood cell counts, lymphocyte blastogenesis, skin tests, acid phosphatase, and CEA (carcinoembryonic antigen). The 16 patients receiving no hormones had depressed total proteins, lymphocyte and monocyte counts, skin tests, and CEA compared with the 15 patients receiving hromones who had depressed serum immunoglobulins, white blood cell counts, lymphocyte blastogenesis, and acid phosphatase.

Adenocarcinoma↗