Monoclonal antibody identification of a potentially lithogenic protein extracted from human renal calculi.

In an attempt to identify potentially lithogenic proteins, a detergent soluble extract of human renal calculi was used to produce a unique monoclonal antibody. The monoclonal antibody was found to detect the presence of a specific epitope in 77% of individually extracted kidney stones from our patients' stone bank at The Long Island Kidney Stone Unit, State University of New York, Stony Brook. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoprecipitation, and Western Blot analysis revealed this monoclonal antibody to be specific to a protein of 83,000 dalton molecular weight. A secondary source of protein reactive to the monoclonal antibody was subjected to enzyme kinetic studies, those studies suggested that the 83,000 dalton protein is a member of the protein-glutamine gammaglutamyltransferase (transglutaminase) family of enzymes. It was not determined in the present investigation whether a member of this family of enzymes initiates or is necessary for lithiasis.

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.

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.

In vitro effects of diethylstilboestrol and the LHRH analogue leuprolide on natural killer cell activity.

In a series of studies of the immunobiological sequelae of oestrogens, the in-vitro effect of diethystilboestrol (DES) and the luteinizing-hormone-releasing-hormone leuprolide (Lupron) on the lytic activity of natural killer (NK) cells have been evaluated. Ficoll-Hypaque gradient-isolated human peripheral blood mononuclear cells (PBMC) were pre-incubated with varying concentrations of DES and leuprolide and the degree of lysis for the human erythroleukemia K-562 cell line was evaluated in a 51Cr-release assay. PBMC pre-incubated with DES exhibited an 82% reduction in the ability of NK cells to lyse K-562 target cells compared with a negligible 3% increase with leuprolide (p less than 0.001) vs. untreated PBMC. The inhibitory effects of DES or leuprolide were not due to cytotoxicity since the viability of PBMC incubated for 18 and 24 h (corresponding to the DES/leuprolide preincubation time and the NK cell assay, respectively) was comparable to that of untreated (control) cells. These observations demonstrate the further suppressive effects of DES on components of immunosurveillance. Pending evaluation of the effect of leuprolide on the activity of NK cells for other target cells, and other parameters of immunologic responsiveness, leuprolide may prove to be a favorable alternative to DES, both in view of its reduced clinical side-effects, and because of the suggested absence of deleterious effects to the immune system. Maintenance of tumour-host equilibrium, and some degree of immunocompetency, in the presence of effective therapy with leuprolide, may prove beneficial in achieving more effective therapy in prostate cancer patients.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Leuprolide vs. diethylstilboestrol: effect on natural killer cells.

Recent studies suggest even low dosages of oestrogen currently used for treatment of prostate cancer increase cardiovascular morbidity. In addition, relapse following growth of hormone - insensitive cells, and the present observations of further evidence of immunosuppression demonstrated by the significant (p less than 0.001) effect of DES on the lytic activity of natural killer cells vs. the negligible effect of the luteinizing - hormone - releasing - hormone, leuprolide (Lupron) raises concern that the palliative effects of oestrogen therapy are possibly further compromised by a reduction in immunosurveillance to tumour, or equally important, by a decreased capacity to cope with infectious agents.

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.

Bilateral transitional cell carcinoma of the renal pelvis in the cancer family syndrome.

The cancer family syndrome is an unusual hereditary disease rarely associated with transitional cell carcinoma of the urinary tract. We describe the occurrence of this syndrome in a patient with bilateral transitional cell malignancies.

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.

Dinitrochlorobenzene contact sensitization in patients with end-stage renal disease.

Sixty-nine patients with end-stage renal disease (ESRD) on maintenance hemodialysis were evaluated by topical application of 2,4 dinitrochlorobenzene (DNCB). The initial sensitization dose consisted of 2,000 micrograms of DNCB; challenge doses consisted of 50 and 100 micrograms. Applications to the contralateral forearm in the absence of a spontaneous flare. Only 71% of the ESRD patients tested could be sensitized to DNCB, compared to 100% of normal controls. There was no correlation between DNCB reactivity and the helper/suppressor ratio of circulating lymphocytes in such patients. This study further documents uremic suppression of T-cell responsiveness as manifested by impaired DNCB contact sensitization.

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.