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R Horton

Publications and source records attributed to R Horton.

At least 163 records · Page 9Linked to original sources

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National Institutes of Health (U.S.)↗

Activin and inhibin have opposite effects on steroid 5 alpha-reductase activity in genital skin fibroblasts.

The transforming growth factor beta (TGF-beta) superfamily includes several closely related peptides including the activins and inhibins. Since we recently reported that TGF-beta 1 and beta 2 are potent inducers of steroid 5 alpha-reductase (5 alpha R), we have now studied the effects of these other peptides using primary cultures of human scrotal skin fibroblasts. Recombinant human activin A or inhibin A were added to cultured cells (2 x 10(5) cells) for 2 days in a serum free media and 5 alpha R activity was measured by the %-conversion of tracer [3H]-testosterone to dihydrotestosterone (DHT) over a 4-h period. Activin significantly stimulated 5 alpha R activity in a dose related manner (control 3.0 +/- 0.4%, activin (1.2 x 10(-9) M) 6 +/- 0.7%, P < 0.01, (2.4 x 10(-9) M) 8.5 +/- 0.6%, P < 0.001). In comparison, androgen (DHT 10(-7) M) induction of 5 alpha R was 4.7 +/- 0.2%, P < 0.05. Combined exposure of fibroblasts to activin (1.2 x 10(-9) M) and androgen (10(-7) M) did not result in additive or synergistic effect on 5 alpha R activity. In contrast, exposure of cells to an androgen (10(-7) M) and TGF-beta (2 x 10(-10) M) led to synergistic effects on 5 alpha R activity (control 1.5 +/- 0.1%, DHT 2.6 +/- 0.2% TGF-beta 1 4.8 +/- 0.5, TGF-beta 1 + DHT 9.2 +/- 1.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗

Renin response to 12-hydroxyeicosatetraenoic acid is increased in diabetic rats.

Eicosanoids (prostaglandins) can alter renin secretion and angiotensin (ANG) II action. We have studied the effects of both prostacyclin and a lipoxygenase (LO) product, 12-hydroxyeicosatetraenoic acid (12-HETE), on renin in normal and streptozotocin-induced diabetic rats. 12-HETE is not only a potent inhibitor of basal renin secretion but also a key mediator of ANG II-induced renin inhibition. We have also examined the effects of ANG II on 12-HETE formation in normal and diabetic animals. Both plasma (3.9 +/- 0.9 vs. 0.8 +/- 0.1 ng ANG I.ml-1.h-1, P < 0.01) and tissue (38 +/- 6 vs. 21 +/- 2 ng ANG I.mg tissue-1.h-1, P < 0.05) renin activity levels were markedly reduced in diabetic animals. Iloprost (10(-6) mol/l), a stable analog of prostacyclin, had similar stimulatory effects on renin secretion in both normal and diabetic tissues, but the response was enhanced by LO inhibition in diabetic tissue. 12-HETE (10(-7) mol/l) had an exaggerated effect on renin inhibition in diabetic tissue (78 +/- 2% normal vs. 65 +/- 4% diabetic, P < 0.05). Similarly, ANG II (10(-8) mol/l) inhibition of renin was significantly enhanced in diabetic rats (P < 0.001). However, ANG II did not produce an exaggerated increase in 12-HETE in diabetic renal tissue. Insulin reversed the inhibitory effects of ANG II on renin in normal rats, but it blunted the effect of ANG II in diabetic rats. These studies suggest that, while the capacity of renal cortical tissue to synthesize 12-HETE in response to ANG II is not altered, 12-HETE and ANG II actions are exaggerated in diabetes, and this may contribute to reduced renin production.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Longterm follow-up of biliary stents for retained common bile duct stones in elderly patients.

Common bile duct (CBD) stones in elderly patients are best treated by endoscopic sphincterotomy (ES). If CBD clearance cannot be achieved endoscopically a biliary stent may be inserted. Although satisfactory short-term results have been reported, few reports on their longterm outcome are available. Over a 3-year period, January 1987 to December 1989, 100 patients with CBD stones were referred for endoscopic stone removal. In 14 of these patients (3 men, 11 women; median age 83 years, range 79-97 years) the CBD could not be cleared endoscopically and a stent was inserted. Twelve of the 14 patients were jaundiced and 5 had acute cholangitis (AC). The maximum diameter of the retained stones ranged from 10-42 mm with a median of 17 mm. Stent insertion resolved jaundice and sepsis in all cases and all patients were discharged from hospital. In-patient stay ranged from 1-82 days (median 12 days) and was significantly increased by the presence of acute cholangitis (P = 0.03, Mann-Whitney U-test). Longterm follow-up was obtained in 13 of the 14 patients (93%) by referral to their general practitioner and out-patient notes. Seven patients are alive and well (median follow-up 43 months, range 34-60 months). One of these 7 developed further jaundice owing to stent migration and had further ES and stone removal. Six patients died at 1, 3, 12, 32, 36 and 42 months following stent insertion from unrelated causes. One patient developed further AC requiring antibiotic treatment and another patient required stent replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗