The androgen receptor gene GGN microsatellite and prostate cancer risk.

The androgen receptor (AR) gene contains a polymorphic GGN microsatellite in exon 1, which encodes polyglycine in the amino terminus of the AR. Previous work has shown that a polymorphic region of CAG repeats also in exon 1 is inversely related to the ability of the AR to transactivate other genes and to prostate cancer risk. We investigated whether AR gene GGN repeat length is related to prostate cancer in a nested study of 582 cases and 794 controls matched on age and smoking status in the Physicians' Health Study. DNA was prepared from archived blood. Using PCR, the region surrounding the GGN repeat was amplified. Fluorescence-labeled primers were used such that the fragment produced could be sized using polyacrylamide gels and Genescan software. We estimated odds ratios and 95% confidence intervals from logistic models controlling for the matching variables for the relation between GGN repeat length and total prostate cancer and by stage/grade and by age at diagnosis. Among controls, the most frequent GGN repeat lengths were 23 (53.5%) and 24 (34.0%), with a range of 10-29. There was no statistically significant difference in the mean GGN repeat length between cases (23.13) and controls (23.05). However, cases had a narrower spread of repeats lengths (parametric test, P = 0.03; nonparametric test, P = 0.07) than controls, with fewer extreme lengths in either direction. The risk of total prostate cancer was slightly increased for a GGN repeat length of 23 compared to all others (odds ratio, 1.20; 95% confidence interval 0.97-1.49); risk did not vary by tumor stage/grade. For every one repeat deviation in either direction from 23, the risk of prostate cancer decreased by 8% (P = 0.04). Although the AR gene GGN repeat probably plays only a modest role in prostate cancer, the observed relation of this repeat with prostate cancer risk supports the evaluation of the effect of GGN repeat length on AR transactivation.

A polymorphism of the 5 alpha-reductase gene and its association with prostate cancer: a case-control analysis.

Prostate cancer (CaP) is the most commonly diagnosed, nondermatological cancer in the United States. The development and progression of CaP is influenced by androgens. 5 alpha-Reductase, type II, converts testosterone to dihydrotestosterone and is critical to the development of the prostate. A TA dinucleotide repeat polymorphism exists in the 3' untranslated region of the 5 alpha-reductase type II gene. 5 alpha-Reductase alleles with longer TA repeats are more common in African-Americans, the group with the highest incidence of CaP. It has been hypothesized that the longer TA repeat alleles might be associated with increased risk of CaP. We studied this potential association within the Physician's Health Study, a predominantly Caucasian cohort study. Using PCR we identified the TA genotype in 590 men with CaP and 802 age-matched controls. The frequency of each allele in the controls was TA(0), 0.87, TA(9), 0.13, and TA(18), 0.01. Homozygotes for the longer TA alleles, TA(9) and TA(18), were underrepresented among cases with an odds ratio of 0.47 (confidence interval, 0.20-1.12), but this was not statistically significant (P = 0.08, two tailed). Our analysis does not support the prior hypothesis that longer TA alleles confer an increased risk of CaP in a predominantly Caucasian population; in fact, longer TA alleles are more prevalent in men without CaP.

Penile mass caused by the newly described organism Mycobacterium celatum.

We report a penile infection in a man with the acquired immunodeficiency syndrome caused by a newly described infectious organism, Mycobacterium celatum. Mycobacterium tuberculosis is the only mycobacterial species previously reported to cause infection in the penis. This is only the third documented human infection with M celatum, and the first to involve the genitourinary system.

Physiological hyperinsulinemia inhibits myocardial protein degradation in vivo in the canine heart.

Myocardial protein turnover in vivo was examined in anesthetized dogs following a 16- or 36-hour fast and again during a hyperinsulinemic (2 mU/kg per minute) euglycemic clamp with or without amino acid replacement or during saline infusion. We measured myocardial phenylalanine balance and rates of protein synthesis and degradation, using the extraction of intravenously infused L-[ring-2,6-3H]phenylalanine and the dilution of its specific activity across the heart at isotopic steady state. After both a 16-hour (n = 19) and 36-hour fast (n = 10), there was net myocardial release of phenylalanine indicated by the negative balances for phenylalanine of -52 +/- 9 (p less than 0.001) and -38 +/- 9 (p less than 0.005) nmol/min, respectively. Overall, the basal rate of myocardial protein degradation was lower in the 36-hour-fasted animals (81 +/- 13 versus 121 +/- 12 nmol/min, p less than 0.05). Myocardial phenylalanine balance and rates of protein synthesis and degradation did not change during insulin and glucose infusion in the 36-hour-fasted animals (n = 10). In these animals, there was a 30-40% decline in plasma amino acid concentrations, including branched chain (p less than 0.001) and essential amino acids (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo measurement of myocardial protein turnover using an indicator dilution technique.

We applied a nondestructive tracer technique, previously developed for measuring skeletal muscle protein turnover, to the measurement of myocardial protein turnover in vivo. During a continuous infusion of L-[ring-2,6-3H]phenylalanine to anesthetized, overnight-fasted dogs, we measured the uptake of radiolabeled phenylalanine from plasma and the release of unlabeled phenylalanine from myocardial proteolysis using arterial and coronary sinus catheterization and analytic methods previously applied to skeletal muscle. Using these measurements, together with a model of myocardial protein synthesis that assumes rapid equilibration of tracer specific activity between myocardial phenylalanyl-tRNA and circulating phenylalanine, we estimated the rates of heart protein synthesis and degradation. The rate of heart protein synthesis was also estimated directly from the incorporation of labeled phenylalanine into tissue protein. The use of [3H]phenylalanine was compared with L-[1-14C]leucine in the measurement of heart protein turnover in dogs given simultaneous infusion of both tracers. Leucine uptake and release by the myocardium exceeded that of phenylalanine by 3.1 +/- 0.4- and 1.7 +/- 0.3-fold, respectively, consistent with leucine's 2.4-fold greater abundance in heart protein and its metabolism via other pathways. Phenylalanine is the preferred tracer for use with this method because of its limited metabolic fate in muscle. One theoretical limitation to the method, slow equilibration of circulating labeled phenylalanine with myocardial phenylalanyl-tRNA, was resolved by comparison of these specific activities after a 30-minute infusion of labeled phenylalanine in the rat. A second, empirical limitation involves precision in the measurement of the small decrements in phenylalanine specific activity that occur with each pass of blood through the coronary circulation. This was addressed by improving the precision of both the measurements of phenylalanine concentration and phenylalanine specific activity using high-performance liquid chromatography. We conclude that the in vivo measurement of phenylalanine tracer exchange across the myocardium permits the nondestructive estimation of heart protein turnover in the intact animal.