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Biomedical subjects

M J Gonder

Publications and source records attributed to M J Gonder.

At least 19 recordsLinked to original sources

Paradoxical effects of cyclosporine on concanavalin A-induced blastogenesis.

The effects of increasing in vitro cyclosporine concentrations (0, 50 100 or 200 ng./ml.) on lymphocyte blastogenesis, measured by incorporation of tritiated thymidine and induced by varying levels of concanavalin A (0, 0.25, 1.0 or 5.0 ng./ml.), were studied in regard to mean serum level of cyclosporine in 26 renal allograft recipients. Results were compared to similar data obtained in healthy controls. Patients were divided into group 1 (13 patients, mean serum cyclosporine trough level less than 150 ng./ml.) and group 2 (13 patients, cyclosporine level greater than 150 ng./ml.). With no cyclosporine added to the assay proliferation of lymphocytes obtained from all patients inversely correlated to the mean serum trough cyclosporine level at all stimulatory levels of concanavalin A (0.25 ng./ml., p less than 0.01; 1.0 ng./ml., p less than 0.001 and 5.0 ng./ml., p less than 0.001) and was significantly lower than in controls (p less than 0.0002). Whereas increasing in vitro cyclosporine concentrations has produced the expected increase in suppression of blastogenesis in controls and group 1, a paradoxical effect became evident in group 2. Under stronger stimulatory conditions (concanavalin A 1.0 or 5.0 ng./ml.) increasing in vitro cyclosporine concentrations were associated with significantly decreased suppression of blastogenesis (p less than 0.01) compared to group 1. These results confirm previous reports and suggest that the duality of effect of cyclosporine in this in vitro model may be related to its functional relationship to the calcium ion (Ca++)/calmodulin complex and to its cellular concentration/solubility curve. These considerations may be of importance in adjusting cyclosporine dosage based on serum trough levels of cyclosporine.

Cells, Cultured

Immunoquantitation of factor VIII-related antigen (von Willebrand factor antigen) in prostate cancer.

Metastasization may be associated with activation of haemostatic processes resulting in increased levels of circulating factor VIII-related antigen (FVIIIRAg) (von Willebrand factor antigen). To evaluate the relevancy of this in prostate cancer (PCa), the level of FVIIIRAg in the serum of patients with PCa, benign prostatic hypertrophy (BPH) and non-prostatic diseases was quantitated by a modified micro enzyme-linked immunosorbent assay. Significant (P less than 0.05) differences were noted between the level of FVIIIRAg in PCa and patients with BPH and other than prostatic disease. Noteworthy were elevated levels of FVIIIRAg in PCa patients with metastatic vs. localized disease. Consideration of the "unorthodox", but possibly more convenient use of routine serum specimens commonly available in the non-haematological laboratory vs. plasma for the quantitation of FVIIIRAg, in situations where an "absolute" level is not required, and of disseminated intravascular coagulation as contributory to the present observations, is given. Pending evaluation of a larger patient population these observations may be of prognostic value.

Adenocarcinoma

Antibodies to sperm in benign and malignant diseases of the prostate in man: incidence, disease-associated specificity, and implications.

Initial investigation demonstrated antibodies to sperm (ASA) in patients with benign prostatic hypertrophy (BPH) and prostate cancer (PCa). The occurrence of ASA under a variety of normal and pathological circumstances indicated the need for confirmation and extension, including delineation of their possible disease-associated specificity and implications. As countercurrent immunoelectrophoresis (CIEP) employing sonicated allogeneic sperm (Sp) extracts appeared most efficient from initial studies of ASA, CIEP was employed for the present further study of 200 serum specimens from patients with and without prostatic disease. While ubiquitous, the continuing presence of ASA in BPH and PCa, with a combined incidence in this study of 57 (52%) of 109 vs. 9 (10%) of 91 in the absence of prostatic disease remains provocative in view of the hypothesized role of Sp in the development of BPH and PCa. The presence, however, of ASA in patients with genitourinary neoplasms other than prostate, raises doubt as to their disease specificity. Implications of ASA, other than in their more commonly related role in infertility, including their cross-reactivity with foetal antigens and lymphocytes and higher incidence in association with tumours and the presence of tumour-associated immunity are considered. However, pending further investigation, the present data may most appropriately be viewed as being reflective of a host response (marker?) to aberrant genitourinary cellular alterations.

Adult

Relationship of blood groups and bladder cancer.

A retrospective study correlating the blood groups of 141 patients with bladder cancer showed that patients with blood group A had lower grade tumors with lower mortality rates, and those with blood group O(H) had higher grade tumors and higher mortality rates.

ABO Blood-Group System

AIDS and hemophilia.

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Acquired Immunodeficiency Syndrome

Seminoma in an atrophic testis.

A rare case of a seminoma developing in an atrophic testis is described and the role of testicular atrophy in tumorigenesis is discussed.

Adult

Urologic considerations in the elderly.

The impact of urinary tract infections, incontinence, impotence, and malignant lesions of the urinary tract on the elderly is discussed. A palliative approach is often beneficial in this population; indications for urologic surgery in the elderly should be well-defined in order to maintain quality of life.

Aged

Interaction of prolactin and testosterone in the human prostate.

Three experiments were performed to determine whether human prolactin (hPr) affects prostatic uptake and metabolism of testosterone (T). 1) Patients with prostatic cancer were infused twice with radio-labelled androgens, the first time with basal hPR, the second time with oral thyrotrophin-releasing hormone (TRH)-elevated hPr. In 5/7, significant increases in metabolic clearance of dihydrotestosterone (DHT) and in conversion of T to DHT accompanied increased hPR. 2) The incorporation of labelled T into minced benign prostatic hypertrophy (BPH) tissue from subjects with high (40 ng/ml) hPR was measured and was found to be more than twice the uptake into tissue from those with low hPR (6.5 +/- 1.9 ng/ml). 3) Uptake and metabolism in vivo of a bolus of 3H-T by BPH and carcinomatous prostates was measured and was far greater in subjects whose hPR was elevated by chlorpromazine than in untreated controls. It is concluded that prolactin increases prostatic uptake and metabolism of T. It is suggested that the best management of prostatic cancer should include depletion of prolactin as well as androgen.

Dihydrotestosterone

Comparative performance of three radioimmunoassays for prostatic acid phosphatase.

Three commercial radioimmunoassays and one enzymatic assay for prostatic acid phosphatase (PAP) have been tested on 122 patients to determine their relative specificity, sensitivity, and diagnostic value. Each of the three radioimmunoassays was found to have special merits. For distinguishing Stage IV prostatic cancer from normal patients without prostatic disease, the Smith Kline (SKF) and New England Nuclear (NEN) assays provide more significant differences. The SKF test also best distinguishes all stages of prostatic cancer from benign prostatic hyperplasia (BPH), but is inferior to the Malinckrodt (MAL) assay for contrasting Stage IV prostatic cancer from BPH. Values obtained with the NEN assay best distinguish the stages of prostatic cancer. Only with the MAL assay are significantly higher PAP values obtained in patients with metastases to bone than those without positive bone scans. Viewed from the point of sensitivity, the SKF assay proves best at all levels of specificity examined in detecting all stages (I-IV), and Stage IV prostatic cancer. By none of the assays can estrogenized Stage III and IV cancer patients be distinguished from those not on estrogen.

Acid Phosphatase

Serum proteins in prostatic cancer. IV. Alterations and clinical response following cryoprostatectomy.

Evaluation of alterations in the level of the five major electrophoretic fractions of serum proteins (albumin, alpha 1-, alpha 2-, beta- and gamma-globulin) in 18 patients with prostatic cancer prior to and following cryoprostatectomy disclosed: (i) a progressive increase in the level of alpha 2- and beta-globulin and the incidence of patients possessing statistically significant (p less than 0.05) elevations in these proteins with a progression of the stage of their malignancy; (ii) a significant decrease in albumin, alpha 2- and beta-globulin and increase in alpha 1- and gamma-globulin from their preoperative levels following cryoprostatectomy in patients with metastatic disease (stage III) in association with a favorable clinical response; (iii) an overall significant decrease in albumin and alpha 2-globulin and increase in alpha 1-globulin from their preoperative levels and (iv) a general association of decreases in albumin (83% of the patients) and alpha 2-globulin (92%) and gamma-globulin (75%) with a favorable clinical response following cryoprostatectomy. Limited to study of a small patient population, the present results confirm earlier studies suggestive of a prognostic potential for alpha 2-globulin, as applied to stage identification in prostatic cancer once the initial diagnosis has been made. Pending confirmation and evaluation of a larger patient population, the observed alterations in serum protein, while not pathognomonic for prostatic cancer, and alterations of inhibitory ('immunoregulatory') factors, may provide adjunctive criteria for monitoring the clinical response following cryoprostatectomy.

Adenocarcinoma