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Biomedical subjects

R Karp

Publications and source records attributed to R Karp.

48 records · Page 3Linked to original sources
PubMedDate not supplied

Spontaneous excision of a large composite transposable element of Drosophila melanogaster.

The TE1 family of transposable elements (TEs) of Drosophila consists of unusually large transposons, cytologically visible in larval polytene chromosomes as one or more bands. They are composite elements, as their termini consist of foldback (FB) sequences which are themselves transposable. The location of FB elements at the termini of transposable elements suggests that these sequences have a direct role in the genetic instability of TEs. To investigate the structural and phenotypic consequence of TE excision, we have cloned genomic DNA required for the expression of the no-ocelli (noc) gene of Drosophila; this gene has been mutated by the insertion of TE146, a member of the TE1 family carrying six polytene chromosome bands including functional copies of the white (w+) and roughest (rst+) genes. As reported here, our experiments indicate that the spontaneous excision of TE146, which results in the loss of the w+ and rst+ markers, can occur either as a single-step event or following a partial internal deletion. In either case, the end product is an imprecise excision in which a residual portion of the element, varying in size from 3 to 10 kilobases (kb), is left at the insertion site. These residual sequences share homology with the FB family. Furthermore, despite their imprecise nature, all these spontaneous excisions restore a wild-type noc+ phenotype.

Animals↗
PubMedDate not supplied

The antigonadotropic action of testosterone but not 7alpha-methyl-19-nortestosterone is attenuated through the 5alpha-reductase pathway in the castrated male rat pituitary gland.

The enzyme 5alpha-reductase plays a significant role in the prostate to amplify the action of testosterone (T) by converting it to a more potent androgen, dihydrotestosterone (DHT). The role of 5alpha-reductase in the testosterone feedback inhibition of gonadotropin secretion from the pituitary has not been elucidated. Therefore, we investigated the role of 5alpha-reductase on T action in in vitro and in vivo models. Castration has been reported to increase the 5alpha-reductase activity in pituitary glands. Hence, the effect of castration duration on the conversion of T to DHT by pituitary homogenates and the responsiveness of pituitary monolayer cell cultures to gonadotropin-releasing hormone (GnRH) challenge exposure were investigated. Incubation of [3H]-T with pituitary homogenates showed that the conversion of T to 5alpha-reduced metabolites was two- to threefold greater in pituitaries from rats who had been castrated for 14 days compared with those castrated for 1 day. In addition, the GnRH-stimulated release of LH from monolayer cell cultures of pituitaries from rats castrated for 1 day was twofold greater, whereas that from rats castrated for 2 weeks was six- to sevenfold greater compared with basal luteinizing hormone (LH) release. Hence we used rats castrated for 2 weeks to elucidate the role of 5alpha-reductase in T feedback inhibition. The inhibitory effects of the androgens T, 19-nortestosterone (19-NT), and 7alpha-methyl-19-nortestosterone (MENT) at 3 different concentrations (10(-9), 10(-7), and 10(-5) mol/L) on GnRH-stimulated LH release from monolayer cell cultures of pituitaries from rats castrated for 2 weeks were examined. All 3 androgens showed dose-dependent inhibition of LH release. MENT showed the greatest inhibition, followed by 19-NT and T. In the presence of finasteride (a 5alpha-reductase inhibitor), the inhibition of LH released by T and 19-NT were significantly greater. The inhibitory effect of MENT, which does not undergo 5alpha-reduction, was not altered by finasteride. In an in vivo study, rats castrated for 2 weeks received T with or without finasteride. There was a significantly greater suppression of serum LH in rats receiving T plus finasteride compared with those receiving T alone. These results suggested that 5alpha-reductase in the pituitary is not obligatory for the inhibitory action of T on gonadotropin secretion in the castrated rat. The action of MENT, a nonreducible androgen, on the pituitary is not affected by 5alpha-reductase.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMedDate not supplied

Long-term preservation of renal function in hypertensive heart transplant recipients treated with enalapril and a diuretic.

Hypertension and progressive deterioration in renal function are commonly seen in heart transplant recipients treated for the long term with cyclosporine. Because angiotensin converting enzyme inhibitors have been associated with amelioration of renal dysfunction in some patients with hypertension and preexisting mild-moderate kidney failure, we treated nine hypertensive recipients of orthotopic heart transplants with enalapril (11 +/- 2 mg/day) and furosemide (62 +/- 15 mg/day) for 23 +/- 4 months. Most of the enalapril dose was given at bedtime, which minimized nocturnal and early morning hypertension. In addition to controlling blood pressure (154 +/- 6/100 +/- 2 mm Hg before enalapril vs 120 +/- 5/81 +/- 2 mm Hg currently; p less than 0.001 for both systolic and diastolic blood pressures by paired t test), there has been no increase in serum creatinine level over 684 +/- 102 days of follow-up (1.88 +/- 0.20 mg/dl before enalapril vs 1.81 +/- 0.17 mg/dl currently; p greater than 0.70). This is unlikely to be caused by the reduction in daily cyclosporine dose (492 +/- 60 mg/day before enalapril to 305 +/- 47 mg/day currently) because there were no significant changes in mean blood cyclosporine level (which has been maintained between 100 and 500 ng/ml). Treatment of hypertension with enalapril and a diuretic after heart transplantation may help prevent or delay the impairment of renal function often seen during prolonged cyclosporine therapy.

Adult↗
PubMedDate not supplied

Perceptions of the impact of baccalaureate degrees for cytotechnologists.

The purpose of this study was to ascertain differences in the perceptions of medical directors, education coordinators and cytotechnologists of the impact of baccalaureate degrees for cytotechnologists on (1) career mobility, (2) salaries, (3) professional status, and (4) changes in cytotechnology education. Questionnaries were mailed to all medical directors and education coordinators of active, accredited cytotechnology programs and to a random sampling of cytotechnologists. The responses were statistically analyzed by computer and supported the following conclusions: (1) Education coordinators and cytotechnologists generally perceive a greater impact of degrees than do medical directors. (2) Education coordinators perceive more impact on career mobility from degrees than do medical directors. (3) Medical directors perceive less impact from degrees on professional status than do the other two groups. (4) There was little difference in perceptions of the impact of degrees on salaries and changes in cytotechnology education. (5) Degrees are perceived to have more impact on career mobility than on salaries, professional status or changes in cytotechnology education.

Attitude of Health Personnel↗