Showing papers by "Worcester Foundation for Biomedical Research published in 1965"

Phenobarbital-induced increase in 6-beta-hydroxycortisol excretion: clue to its significance in human urine.

Abstract: 6β-Hydroxycortisol was first isolated from ethyl acetate extracts of urine of cortisol-treated subjects and found in elevated concentrations in the urine of a pregnant woman in 1954 (1). It was also isolated from urine of normal subjects (2), and was subsequently found in higher levels in toxemia of pregnancy (3), in the newborn (4) and in adrenocortical hyperfunction (5). The question of the significance of this urinary steroid has been the subject of several studies (6–9), and the hypothesis has been advanced that 6β-hydroxylation of cortisol is an alternate pathway in the disposition of cortisol, which takes prevalence when the main pathway of ring A reduction is impaired, as may occur during high levels of estrogens.

Splanchnic Extraction and Clearance of Aldosterone in Subjects with Minimal and Marked Cardiac Dysfunction1

Abstract: The metabolic clearance rate (MCR) and splanchnic extraction of aldosterone were measured by analyzing hepatic and peripheral venous plasma after a continuous infusion of the tritiated hormone. In 9 subjects with minimal cardiac dysfunction (cardiac outputs in the normal range), the MCR of aldosterone was 1330±140 (SE) liters of plasma per day and the splanchnic extraction was 89 ±3 (SE)%. In 7 subjects with marked cardiac dysfunction (cardiac outputs subnormal or rt. ventricular systolic blood pressures > 100 mm Hg), both the MCR [800±65 (SE) liters plasma/day] and splanchnic extraction [71±5 (SE)%] were significantly lower. Using 131I Rose Bengal, hepatic blood flow and splanchnic aldosterone clearance were measured simultaneously in most of the subjects. Extrasplanchnic clearance of the hormone was found to be significant but a minor component (17 ±4%) of the total metabolic clearance rate in subjects with both minimal and marked cardiac dysfunction. Some of the subjects with subnormal cardiac indices ...

Prostaglandin: release from the rat phrenic nerve--diaphragm preparation.

Abstract: Release of a substance that stimulates smooth muscle was detected from a phrenic nerve-diaphragm preparation from the rat upon direct and indirect stimulation. On thin-layer chromatography most of the active material behaved as a mixture of prostaglandins. The effect of electrical stimulation was mimicked by catecholamines but not by acetylcholine or eserine. The effect of nerve stimulation was not antagonized by d-tubocurarine.

Fertilizing life of ferret sperm in the female tract.

Abstract: For the determination of the fertilizing life of ferret sperm in the female tract, gonadotrophin was intraperitoneally injected to induce ovulation at various times after the deposition of epididymal sperm into the uterine horns. The animals were examined 48 or 60 hours after ovulation injection to assess the proportion of fertilized eggs, although a few of them were allowed to deliver young. Intraperitoneal injection of 50 hypophysectomized R.U. of sheep pituitary extracts or 90 I.U. of Human Chorionic Gonadotrophin invariably induced ovulation in ferrets that were in heat. Ovulation occurred about 24 to 36 hours after the administration of H.C.G. and an average of 14.5 eggs with a range of 8 to 24 eggs per animal was obtained. The average number of sperm in the cauda epididymides and the vasa deferentia of nine males was 219 millions with a range of 24 millions at the end of breeding season to 621 millions at the peak of breeding season. The percentage of total eggs that were fertilized was 73, 40, 24, 15, 3, and 0 when the ovulation injection was given at 0, 36, 72, 84, 96, and 108 hours after sperm deposition respectively. Since ovulation occurred 30 hours after ovulation injection the fertilizing life of ferret sperm in the female tract is therefore no more than 126 hours. The percentage of eggs fertilized was lower following the deposition of epididymal sperm than following mating (73% vs. 98%). There is evidence that the fertility of sperm in the female tract was higher if a large number of sperm was deposited, and that the penetration of sperm into the egg facilitated the denudation of the egg. The majority of the penetrated eggs (54 to 84%) were at the pronuclear stage 48 hours after insemination and ovulation injection (i.e., about 18 hours after ovulation), at 60 hours (30 hours after ovulation) the majority of them were either at pronuclear stage (26–100%) or at the 2-cell stage (46–57%), and at 70 hours (40 hours after ovulation) most of them were at the 4–6 cell stage. The morphology of fertilization in the ferret and the time sequence after sperm penetration were described.

Plasma concentration and biosynthesis of testosterone in the syndrome of feminizing testes.

Abstract: The concentration of plasma testosterone was found to be within the range for normal adult men in 3 typical instances of the feminizing testes syndrome. Gonadectomy resulted in a sharp decrease in plasma values of testosterone, although the lowest level reached was still somewhat above the range for castrated men and normal females. Evidence was obtained showing that the adrenal cortex contributed, in part, to the circulating level of testosterone. In vitro biosynthesis of testicular tissue showed it capable of synthesizing testosterone from progesterone and androstenedione and estrogens from testosterone and androstenedione. A phenolic steroid metabolite was also obtained from the latter 2 substrates which closely resembled the chromatographic characteristics of equilenin.

Estrogen and androgen production in vitro from 7-3-H-progesterone by normal and polycystic rat ovaries.

Abstract: In vitro conversion of 7-3Hprogesterone to estrogens and androgens by ovaries of normal and testosterone-sterilized rats (TSR) was studied. Ovaries were obtained from 21- to 350-day-old rats. In incubations of ovaries from normal rats, modest estrogen formation, but no conversion to androgens, could be demonstrated. A marked change in steroidogenesis was demonstrable in the polycystic ovary of the adult TSR; conversion to estradiol and estrone was increased, and testosterone and androstenedione accumulated in appreciable amounts. A pattern of ovarian steroidogenesis similar to that of the TSR was found in older control rats which spontaneously developed prolonged vaginal cornification. At 21 and 28 days of age, no significant difference between the 2 groups was detected. The primary derangement induced by the neonatal administration of testosterone is most probably an alteration in central nervous system regulation of gonadotropin secretion. The findings in the present study are therefore interpreted as e...

Plasma testosterone and estrogen levels, urine testosterone excretion, and sebum production in males with acne vulgaris.

Abstract: Testosterone levels in plasma and urine, plasma 17β-estradiol and estrone, and sebum production were measured in 26 males, age 17–21, with acne vulgaris and compared with similar measurements carried out in 16 normal males in the same age range. Sebum production was significantly higher in the subjects with acne. However, both plasma and urine testosterone values did not differ between the 2 groups. Plasma 17β-estradiol and estrone concentrations were both significantly elevated in the acne subjects. No positive correlation was observed between the elevated values for sebum production and plasma estrogens. The significance of the increased estrogen values in acne is unknown. The failure to demonstrate differences in plasma or urine testosterone in acne suggests that this disorder is not accompanied by increased androgen production.

Effects of enovid on blood clotting factors

Abstract: Cyclic medication with Enovid determines significant increases in some of the blood clotting factors that are also elevated during normal pregnancy, namely factors VII–X “complex,” VII “specific” and fibrinogen. Prothrombin and fibrinolysin are also increased significantly at variance with the findings reported during pregnancy. The increase in fibrinolysin then tends to maintain the homeostatic equilibrium. Factors V, VIII and X are not affected. The significance of the results in relation with thromboembolic disease are discussed.

Identification in Rabbit Urine of the 3-Glucuronoside-17-N-acetylglucosaminide of 17α-Estradiol

Abstract: Four rabbits were given large doses of estrone benzoate subcutaneously and a tracer dose of 16-14C-estrone intravenously. Extraction of the urine with butanol yielded a major radioactive product which was identified as the 3-glucuronoside-17α-N-acetylglucosaminide of estradiol. This confirms the indications of previous work that the rabbit excretes 17α-estradiol as a double glycoside. (Endocrinology 76: 600, 1965)

Estimation of Androstenedione in Human Peripheral Blood with 35S-thiosemicarbazide

Abstract: A double isotope derivative technique using 35S-thiosemicarbazide and 3H indicator for estimation of androstenedione in 10 ml peripheral plasma is described. Radiochemical isolation is achieved with 2 thin layer and 2 paper chromatographic steps utilizing pyruvic acid hydrolysis for further derivative formation. With this method, plasma from ovariectomized-adrenalectomized subjects or 10 ml water blanks give values of 0.015 ±0.006 (sd) μg/100 ml. Male plasma contains 0.075 ±0.004 (se) and female plasma contains 0.145 ±0.017 (se) in the follicular phase and 0.160 ±0.010 (se) μg/100 ml in the luteal phase of the cycle (values not corrected for mean blank). Accuracy and precision studies do not indicate the presence of a systematic error. A comparison of plasma levels of both androstenedione and testosterone suggests that minimal blood testosterone is converted to blood androstenedione, but the excess concentration of androstenedione in the female could indicate that this steroid may be a major peripheral pr...

Sequential part presentation: a method of studying visual form perception

Abstract: Everyday perception of a form's parts as simultaneous and joined is viewed as a perceptual achievement dependent on the central operations of analysis and integration. Experiments have been conducted which employ a method of stimulus presentation which assures that neural response simulates the hypothesized analysis operation, viz. sequential part presentation. Perceptual measures are employed which are assumed to reflect the hypothesized integration. In one experiment, interpart intervals between the sequentially presented sides of a line triangle were varied and 50% points determined for judgements of simultaneity and joining between the lines. In a second experiment, these thresholds were also determined, but for side part versus angle part presentation of the line triangle. With side part presentation, thresholds for both judgements of simultaneity and joining were found to be higher. It is concluded that normal perception of form, i.e., perception of parts as simultaneous and joined, can take place at larger intervals when sequential response is to side parts.

Fertilization and early development of Dorset Horn sheep in the spring and summer.

Abstract: The estrous cycles of 34 Dorset Horn ewes were observed during the spring and summer in East Anglia. The majority of sheep (22 out of 34) came in heat fairly regularly. In 26 out of 37 estrous cycles the duration was between 14 and 25 days. Laparotomy performed soon after estrus did not prolong the subsequent estrous cycle in the majority of animals. Failure of ovulation following estrus was not observed; the observations were made either at laparotomy or at autopsy. The rate of ovulation was 1.55 per cycle as assessed by counting the number of corporalutea in the ovary. The time of ovulation was estimated at about 30 to 40 hours after the onset of estrus. Following deposition of semen into the Fallopian tubes of nine ewes, either before or soon after ovulation, five eggs were recovered but none of these was found to be fertilized. Following intra-cervical insemination or mating 21 fertilized eggs, at different stages of division, were found in 11 out of 29 ewes. In 13 ewes out of 26 which were examined 5–17 days after mating 15 normal embryos were found. Photomicrographs of early sheep embryos are presented and the low fertility of sheep in summer is discussed.

Studies on vaginal, cervical and uterine histology.

Abstract: Among patients in the Caribbean area taking progesterone-estrogen combinations cyclically in oral contraception the rate of development of suspicious Papanicolaou smears was significantly lower than the rates observed in users of other contraceptive devices. Neither the progress of cervical anaplasia nor cervical carcinoma was significantly affected by the use of these drugs in the small number under observation. A significant reduction in endometrial dysplasia and endometritis was observed in the drug users.

Implantation of ferret ova fertilized by mink sperm

Abstract: Epididymal mink (Mustela vison) sperm were inseminated into the uterine horns of ferrets (Mustela furo) at various times before or after ovulation which was induced by intraperitoneal injection of H.C.G. The Fallopian tubes or uterine horns of each animal were examined at different times. The ova were recovered and examined microscopically for the evidence of fertilization at 60–66 hours. Cleavage of ova, blastocyst formation during 4–12 days, and the development of embryos during 22 to 42 days were also ascertained. The fertilization rate is rather low, ranging between 8–41%, probably depending on the number of sperm inseminated and the time of insemination in relation to ovulation. The cleavage rate is lower than either the ferret or mink ova, but no delayed implantation was observed as in the case of the mink. The fertilized ova developed and implanted, but degeneration occurred at various stages, although some of them went to advanced stages.

Gonadotrophin Content of Pituitaries of Rats in Constant Estrus Induced by Continuous Illumination

Abstract: LH and total gonadotrophin of the anterior pituitaries of cycling rats under normal lighting and rats in constant vaginal estrus (CVE) induced by continuous illumination were compared. The ovarian ascorbic acid depletion method and the uterine weight increase in immature mice were employed for LH and total gonadotrophin assays, respectively. Most of the rats placed in constant light developed continuous vaginal cornification within 30 days. There was an increase in pituitary weight and the ovaries were smaller than those of the controls. The pituitary LH content and concentration were markedly decreased in rats in CVE after 50 and 100 days of illumination. Administration of progesterone, SC-13664 (an antiestrogenic compound), or clomiphene or oophorectomy caused an increase in LH. The pituitary total gonadotrophin of rats in CVE was similar to that of normal rats and increased under treatment with SC-13664 or clomiphene and after oophorectomy. Progesterone caused no change.(Endocrinology 77: 529,1965)

Oxidation of Dimethyl Sulfoxide to Dimethyl Sulfone in the Rabbit.

Abstract: A white, crystalline compound was obtained from a butanol extract of the urine of rabbits injected subcutaneously with dimethyl sulfoxide. The melting point and infrared spectrum of the compound were identical with those of authentic dimethyl sulfone.