Glutathione S-transferases in human testicular germ cell tumors: changes of expression and activity.

Glutathione S-transferases are involved in the detoxification of carcinogens and xenobiotics and are potentially associated with the development of drug-resistance. Forty-six testicular germ cell tumors and 33 adjacent normal testicular tissue specimens were analyzed at the RNA level for the expression of glutathione S-transferase alpha and pi. Glutathione S-transferase alpha was expressed in 31 of the 33 normal testicular tissues (94%) but in only three of the 46 germ cell tumors (7%). Glutathione S-transferase pi mRNA was detected in all normal and malignant testicular tissue samples. Thirteen testicular germ cell tumors and eight normal testicular tissue samples were analyzed at the protein level. The mean specific activity of total cytosolic glutathione S-transferase in tumor tissue was decreased by about 80% as compared to normal testicular tissue. Protein analysis of the glutathione S-transferase subunits of normal testicular tissue demonstrated the presence of the glutathione S-transferase classes alpha, mu and pi, with a predominance of the mu class. In testicular germ cell tumors the glutathione S-transferase subunit pattern showed a predominance of glutathione S-transferase pi representing 88% +/- 3% of total glutathione S-transferase. Since all three glutathione S-transferase isoenzyme classes contribute to the resistance to antineoplastic drugs, the altered glutathione S-transferase isoenzyme pattern and the decrease of glutathione S-transferase activity may play a role in the high inherent drug sensitivity of human testicular germ cell tumors.     

Shoptalk and Gobbledegook : Daniel Verne, 1921–1996

Over 15 years ago, after reading many humorous statements inadvertently written by contributors to the Journal, I approached Dan Verne about the possibility of his preparing a series of matching cartoons to use in an editorial that I wanted to write. Dan, the consummate artist, as well as surgeon and teacher, gladly obliged. However, in the face of other pressing issues over the subsequent years, his cartoons and the idea for the editorial were relegated to the back burner. It is truly unfortunate that it had to be his untimely demise that reawakened the idea.This editorial is dedicated to the memory of this caring gentleman and scholar. I am sure that he would have enjoyed seeing his handiwork, and perhaps he would even have tossed me a cigar for my efforts.     

Pelvic granulocytic sarcoma

 Granulocytic sarcoma is an uncommon extraskeletal tumor most frequently associated with leukemia. We present a case of bone location with unusual pattern in a patient with no evidence of myeloproliferative disorder at presentation or follow-up.     

Titration of duration discrimination in behavioral pharmacology and toxicology

This study investigated a discrete-trial, titration duration discrimination procedure in behavioral pharmacology. Pentobarbital and d-amphetamine, measured with this procedure, selectively affected discrimination more than response tendencies. Pentobarbital also tended to affect selectively discrimination of longer durations, whereas d-amphetamine did not. Further experiments showed that (1) other algorithms for modulating stimulus duration are useful in behavioral pharmacology and toxicology, (2) threshold estimates are similar with the method of constant stimuli and the method of titration, and (3) this titration procedure permits the separate examination of drug effects upon discrimination and upon response tendencies; the fixed-interval procedure does not. Baseline variability was an important correlate of drug effects in that the endpoints with more variable baselines were also more sensitive to drugs.     

Erection and ejaculation in man. Assessment of the electromyographic activity of the bulbocavernosus and ischiocavernosus muscles

Electromyographic (EMG) recordings were obtained by concentric needle electrodes from the bulbocavernosus (BC) and ischiocavernosus (IC) muscles in 7 human volunteers during excitement to erection and subsequent ejaculation. Simultaneous registration of the time course and volume of each expressed spurt of semen was obtained using an aluminium pan suspended in front of the subject's penis on a force transducer the output of which was charted with the EMG activity. The BC and IC muscles showed no EMG activity during erection and detumescence cycles induced by visual sex stimulation. In 5 of 7 subjects, the first EMG burst of the BC in ejaculations induced by masturbation was not correlated with an expelled spurt of semen as were subsequent bursts. However, only 26 to 60% of the total number of EMG bursts were accompanied by expulsion of a spurt of semen. There thus appears to be a large safety factor in the striated muscle expulsive mechanism. Oral phenoxybenzamine treatment in 2 subjects did not significantly affect either the number of EMG bursts of the BC or the subjective pleasure of the orgasm but did significantly reduce the volume of semen expelled. Semen volume does not appear to be a unique determinant of the pleasure felt or the trigger for ejaculation.     

Antidepressant-associated maniform states in acute treatment of patients with bipolar-I depression

Medical records of 158 patients with bipolar depression were analysed for the incidence of a switch from depression to maniform states (mania and hypomania). Relation to psychopharmacological treatment was investigated. Thirty-nine (25%) patients of the total sample had switched to a maniform state during the treatment period in the hospital. Among that group the phenomenon occurred in 23 patients (15%) as a hypomania and in 16 patients (10%) as a mania. Patients with a switch were significantly more often treated with tricyclic antidepressants (TCA) than patients without switch (79.5% vs 51.3%). Mood stabilising medication might reduce the risk for switching, especially in patients treated with TCA; however, it seems not totally sufficient, since 59% of the switched patients received mood stabilisers. The switch phenomenon was not associated with sociodemographic or clinical data. Received: 23 September 1998 / Accepted: 28 September 1998     

Effect of conjugated estrogens on platelet function and prostacyclin generation in CRF

In a double-blind, randomized, placebo-controlled cross-over study, we investigated in seven patients with chronic renal failure the effect of conjugated estrogens (0.6 mg/kg/day for 5 days) on template bleeding time and on thromboxane A2 (TxA2), beta-thromboglobulin (beta-TG) and prostacyclin (PGI2) concentrations in blood emerging from the template bleeding time incisions. Administration of conjugated estrogens resulted in a significant shortening of the bleeding time in six out of seven patients with a maximum effect 7 and/or 14 days following treatment. Both TxA2 (measured as thromboxane B2, TxB2) and beta-TG release in bleeding time blood were significantly higher following administration of conjugated estrogens as compared to placebo administration. No difference was seen in endothelial PGI2 (measured as 6-keto-prostaglandin F1 alpha) formation when patients were treated with conjugated estrogens as compared to placebo administration over the 28 day observation period. We conclude that in patients with chronic renal failure, infusion of conjugated estrogens results in a significant shortening of the bleeding time together with an increase in platelet reactivity, as indicated by an increase of TxA2 and beta-TG concentration in the microvasculature. No effect was seen on PGI2 production, thereby excluding a major effect on vascular prostaglandin metabolism.