PubMed Health⌕ Search

Biomedical subjects

M J Varkarakis

Publications and source records attributed to M J Varkarakis.

13 recordsLinked to original sources
PubMed1976

The response of the juxtaglomerular apparatus to stimuli effecting renin or erythropoietin release in canine renal allografts.

The functioning canine renal allograft produces plasma renin activity (PRA) and erythropoietin (ESF) activity and can maintain normal blood pressure and normal erythropoiesis. Moreover, in response to various provocative stimuli it can: (i) increase plasma renin activity in response to low sodium intake; (ii) suppress PRA in response to high sodium intake; (iii) produce increased serum erythropoietin in response to hypoxia. The granulation activity of the juxtaglomerular apparatus correlates best with the degree of graft rejection and with the PRA in groups manipulated by changing sodium balance. This is not the case with hypoxia. Thus, the juxtaglomerular apparatus, even in the presence of vascular changes seen with the severe degree of rejection in renal allografts, can respond to stimuli that can regulate renin release. Renin production by the transplanted kidney can be dissociated from ESF secretion. Blood pressure changes in the present model were not directly associated with increased PRA or juxtaglomerular apparatus activity. In such conditions hypertension can exist in the presence of suppressed PRA and without hypergranulation of the apparatus. The majority of correlations of this study thus establish a close association of the degree of juxtaglomerular index activity with PRA levels, rather than ESF.

Animals↗
PubMed1975

Prognosis of bladder carcinoma in patients treated with cystectomy.

Prognostic criteria for bladder tumors are the stage and grade of the tumor in the present series of 82 patients, in which all patients received the same treatment. These criteria are related and the combined evaluation increases the prognostic accuracy for the disease. In addition, the diameter and not the number of bladder tumors on primary diagnosis is an important prognostic sign. A significant number of tumors at the first clinical evaluation were apparently understaged and undergraded and to a lesser degree overstaged and overgraded as compared with cystectomy specimen evaluations. Despite the total cystectomy, even the patients with superficial bladder lesions, a significant number died from the bladder tumor and 1/4 of the patients had metastases at post mortem examination. The 5 year overall survival with total cystectomy was 40% and for 10 years 15%. Other adjuvant forms of therapy pre- and post-operatively must be assessed.

Adult↗
PubMed1975

Comparison and significance of respiration and glycolysis of prostatic tissue from various species.

The respiration and glycolysis of prostatic tissue from baboons, rhesus monkeys, dogs and rats were compared to the respiration and glycolysis in human prostatic tissue. All the primate prostates had a high glycolytic ability and a low respiration in contrast to the rat and dog prostate. Treatment of baboons with drugs clinically effective against prostatic cancer did not change the prostatic metabolism despite a marked prostatic atrophy. In vitro the drugs reduced respiration markedly. The metabolic similarity between the human and the baboon and rhesus monkey prostate indicates that nonhuman primates should be investigated in the evaluation of chemotherapeutic agents for treatment of prostatic cancer.

Animals↗
PubMed1975

Antiprostatic effects of a nitrogen mustard of estriol.

The chemical ester of a nitrogen mustard with estriol was tested for its antiprostatic effects in dogs and rats. The E33-mustard was shown to interfere with the uptake of labeled estriol in the dog prostate and by the ventral prostate of the rat; and to increase the uptake of the radioactivity associated with testosterone in the dog prostate. The weights of the ventral and dorsolateral prostates of the rat were significantly reduced following the administration of E3-mustard for 2 days. The results are interpreted to be very similar to those obtained with the mustard of E (Estracyt) and the effects are probably a combination of the actions of the released estrogen (D) and/or mustard, either adding individually or in concert.

Animals↗
PubMed1975

Direct effect of prostaglandins in renal function and renin release in the presence of renal ischemia in the dog.

Prostaglandins PGE-1 or PGA-1 (0.5 to 1 mug per min) were infused into the stenosed renal artery of anesthetized hypertensive dogs. Increased urine volume, sodium and potassium excretion, and p-aminohippurate clearance were found during the prostaglandin infusion period in the infused kidney as compared to the control periods before infusion. Creatinine clearance was increased during infusion of PGE-1. The noninfused, nonischemic kidney showed no effect at the time of infusion with PGE-1 but in the case of PGA-1, the p-aminohippurate and creatinine clearances and urine diuresis were decreased. As a result, the mean aortic blood pressure decreased. Both prostaglandins increased the renal vein renin in the infused kidney. PGA-1 did affect renin release of the noninfused kidney, but PGE-1, which is rapidly inactivated by the lung, did not have this effect. Renin release seems to be influenced by electrolyte diuresis operating through the macula densa mechanism. However, the lowering of blood pressure seen in this study cannot exclude the involvement of the stretch receptors (the juxtaglomerular cells) for renin release. The increased renin release after prostaglandin administration seems to be a protective renal mechanism against the drug-induced hypotension. It seems to be induced by the direct sodium and water diuretic effects of prostaglandins.

Animals↗
PubMed1975

Prostatic effects of a nonsteroidal antiandrogen.

The possible mechanisms for the antiprostatic effects of a nonsteroidal antiandrogen, SCH 13521 (4'-nitro-3'-trifluoromethylisobutyranilide), were investigated in rats and dogs. The influence of administered SCH 13521 on the deposition of the radioactivity associated with labeled testosterone, dihydrotestosterone, and estriol (E-3) in the prostate and other tissues of the dog, and rat was determined in short term experiments. SCH 13521 definitely interfered with the localization of the radioactivity of these steroids in the prostate and indicated a competitive situation between SCH 13521 and the steroids. Even though in vitro binding data were generally in accord with in vivo results, he descrepancies regarding E-3 and the more intense effects of SCH 13521 observed in vivo, as compared to those in vitro, lead us to suggest that a metabolite of the compound may also play an important competitive role in vivo. Of particular interest was the competition between SCH 13521 and estrogens in vitro (estradiol-17-beta) and in vivo (E-3). Sch 13521 greatly decreased the volume of prostatic secretion whereas id minor effects on prostatic 5-alpha-reductase and arginase activities. The latter is surprising, since both enzymes are very highly androgen-dependent. Thus, even though the mechanisms of action of SCH 13521 on the prostate may involve competition with androgens at the cellular level, we think that its competition with some estrogens points to a more complicated action than observed with other antiandrogens.

Androgen Antagonists↗
PubMed1975

Changes of renal ATPase enzymes in different types of kidney preservation.

After 24-hr storage of canine kidneys with extracellular or intracellular (Ursol) solutions, the cortical and medullary renal ATPase enzymes (total Na+ + K+ and Mg-ATPase, Na+ + K+ -ATPase, and Mg-ATPase) were examined. It was found that storage with extracellular solution decreased all cortical enzymes. This was not the case with intracellular solution or in kidneys cooled and stored without any solution. A decrease in the potassium concentration of the Ursol solution decreased cortical (Na+ + K+)-ATPase enzymatic activity. The medullary enzymatic changes were similar in the different groups, and lower than in unstored controls. It appears that the changes on the level of the ATPase enzyme system which is related to the cation transport system might play a significant role in explaining the different results seen in clinical or experimental renal preservation systems. These changes can be related to the injury of preservation due to environmental effects of the cation concentrations and to a lesser degree to the damage of the enzyme system which provides the energy for cation transport.

Adenosine Triphosphatases↗
PubMed1975

Morphological responses of benign human prostatic hypertrophic tissue to chemotherapeutic agents in an in vitro culture system.

The in vitro maintenance of hypertrophic tissue with fluid containing cytotoxic drugs showed more degenerative changes in prostatic epithelium and stroma of the tissue compared with concurrently cultured aliquots of control tissue. It is suggested that theses morphological changes can be related with functional activity of the tissue. The mechanism of such an action is at present unsettled, but an interference on known enzymatic systems regulating prostatic growth seems likely. This system provides an added technique for the evaluation of drugs considered for possible therapeutic testing in human prostatic cancer states.

Aged↗
PubMedDate not supplied

Potential test systems for drugs against prostatic cancer.

A number of chemotherapeutic agents have been tested in two systems which could be useful as models in the search for effective drugs for cancer of the prostate. One system involved the effects of the administered drugs on rat prostatic 5 alpha-reductase and arginase activities. Since both enzymic systems are androgen dependent and essential for prostatic function and anatomy, the effectiveness of a drug in these systems could be indicative of its value in the treatment of prostatic cancer. Michaelis constants were obtained with Lineweaver-Burk plots and the conclusions are based on a comparison of these plots with those of the controls. Thus, the following results were obtained: (a) isophosphamide, bleomycin, and procarbazine produced definite inhibition of 5 alpha-reductase in either or both the ventral and dorsolateral glands of the rat; (b) 5-fluorouracil, vincristine, bleomycin, procarbazine, adriamycin, and hexamethyl-melamine inhibited arginase activity significantly in both glands; (c) streptozotocin and 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (NSC-45388) produced inhibition of arginase in the ventral gland only; (d) in contrast to the noncompetitive or uncompetitive inhibition of most of the drugs, particularly in the ventral gland, procarbazine, hexamethylmelamine, bleomycin, adriamycin, and NSC-45388 produced competitive inhibition of arginase in the dorsolateral gland; and (e) seven of the drugs led to an activation of 5 alpha-reductase (5-fluorouracil, vincristine, NSC-45388, hexamethylmelamine, CCNU, streptozotocin, and diglycolaldehyde). The second model system utilized the deposition of labeled estriol and testosterone in the dog prostate and the effects of drug therapy as a possible index of effectiveness in prostatic cancer. Streptozotocin and procarbazine definitely interfered with the deposition of both estriol and testosterone. On the basis of the data obtained, the model systems investigated by us could potentially serve as reliable indicators for the clinical use of drugs against cancer of the prostate.

Animals↗
PubMedDate not supplied

Tumor antigen and acid phosphatase isoenzyme in prostatic cancer.

Plasma and prostatic fluid from man, dog, and baboon were measured for carcinoembryonic antigen (CEA) by a radioimmunoassay technique. No CEA was detected in plasma, prostatic fluid, or seminal fluid in 12 dogs and three baboons. Elevated CEA (less than 2.5 ng/ml) was found in 13 of 20 human prostatic fluids. It was inferred that there was no immunologic cross-reactivity of CEA among man, dog, and baboon. CEA has been isolated and purified from liver tumors. Biochemical studies reveal that CEA consists of 60 percent carbohydrate and 40 percent protein. It contains the following carbohydrates: fucose, mannose, galactose, sialic acid, N-acetylglucosamine, and a small amount of N-acetylgalactosamine. The following amino acids were found in CEA: lysine, histidine, arginine, aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, valine, emthionine, isoleucine, leucine, tyrosine, phenylalanine, and cysteine. The amino acid sequence (first 30 amino acids) of the N-terminal has been determined. The N-terminal amino acid was lysine. Using this study as a model, other tumor antigens from prostatic tumor tissues are being investigated. The acid phosphatase isoenzyme from prostatic tissue was also studied. After a series of purifications, two chromatographic fractions were obtained. Treatment with neuraminidase removed the sialic acid content of the molecule, changed the isoelectric focusing patterns, and abolished the chromatographic heterogeneity. Sedimentation studies indicated a molecular weight of about 100,000. Biochemical studies showed that prostatic acid phosphatase isoenzyme is a glycoprotein which consists of 7 percent carbohydrate and 93 percent protein. It contains fucose, galactose, mannose, sialic acid, N-acetylglucosamine, and the following amino acids: aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, lysine, histidine, arginine, tryptophan, and cysteine. An antiserum to this purified prostatic acid phosphatase isoenzyme is being prepared in animals.

Acid Phosphatase↗