Barry E. Schwarz

Effect of Age on Gastric Acid Secretion and Serum Gastrin Concentrations in Healthy Men and Women

The effects of age on basal, meal-stimulated, and human gastrin-17-stimulated gastric acid secretion rates and serum pepsinogen concentrations were evaluated in 41 healthy men and women. Older subjects (ages 44-71 years; mean, 57 years) had higher mean basal, meal-stimulated, and gastrin-17-stimulated acid secretory rates and basal serum pepsinogen I and II concentrations than younger subjects (ages 23-42 years; mean, 33 years). Age-related differences in acid secretion were especially prominent in men, and age-related differences in serum pepsinogen I and II concentrations were more prominent in women. Higher gastric acid secretion rates in older subjects could not be explained by body size (height, weight, body surface area, or fat-free body mass) or by the higher incidence of infection with Helicobacter pylori. Using a multivariate linear regression model, age had an independent positive effect on acid secretion, and H. pylori infection had an independent negative effect. It was concluded that aging is associated with an increase in gastric acid secretion in humans, especially in men, while infection with H. pylori is associated with lower acid secretion rates.

The nature of the stimulatory role of the supernatant fraction on triglyceride synthesis by the α-Glycerophosphate pathway

Evidence is presented as to the nature and mechanism of the stimulatory effect of the supernatant fraction on the biosynthesis of triglycerides via the α-glycerophosphate pathway in the intestinal mucosa. When microsomes are employed as the enzyme source, the major lipid formed from either labeled palmitic acid orl-α-glycerophosphate is phosphatidic acid and only a limited amount of triglyceride is synthesized. The addition of the supernatant fraction to microsomes results in a stimulation of triglyceride biosynthesis at the expense of phosphatidic acid. Employing the same microsomal fraction, the reaction sequence was followed step by step and the intermediates were isolated. The results suggest that the stimulatory role of the supernatant fraction can be attributed to the presence ofl-α-phosphatidate phosphohydrolase (EC 3.1.3.4). The hydrolysis of the biosynthesized microsomal phosphatidic acid by the supernatant enzyme occurs at a faster rate than the hydrolysis of added phosphatidic acid prepared from egg lecithin. The initial acylation steps in the biosynthesis of triglycerides or phosphatidic acid via the glycerophosphate pathway occur only in the presence of fatty acid and the cofactors necessary for its activation. Under these conditions, fatty acyl-CoA will not substitute for the fatty acid activation system.

Estrogen Binding in the Rat and Human

The interaction of estrogens with human target tissues has received scant attention as compared with other species. Early reports demonstrated that radioactive estradiol is concentrated by the human uterus in vivo (1), and is specifically bound in cytosol prepared from human endometrium (2,3,M. However, a specific cytoplasmic 8S estrogen receptor similar to that found in the rat and other species has been demonstrated in human tissues only recently by Siiteri et al. (5). The possible role of estrone in estrogen action is uncertain although several reports have shown its formation in human uterine tissue (6,7). Our interest in this problem arose from studies which demonstrated that the estrogen target organs of the human postmeno-pausal female are exposed principally to estrone rather than estradiol (8,9)• Together with similar observations made in a variety of clinical conditions which are associated with a high incidence of endometrial carcinoma, such as the polycystic ovarian syndrome, severe obesity, liver disease, and a variety of ovarian tumors, these findings indicate that exclusive production of estrone is a common endocrinologic feature of this form of neoplasia. The possibility of a causal role for estrone in the development of endometrial cancer must therefore be considered. For these reasons investigations of the interaction of the human uterine estrogen receptor system with both estradiol and estrone have been carried out.

Initiation of human parturition: IV. Demonstration of phospholipase A2 in the lysosomes of human fetal membranes☆

In this study we sought to define the subcellular localization of phospholipase A2 in human fetal membranes. Others have postulated a role for decidual lysosomes in the initiation of human parturition. We hypothesized that if phospholipase A2 were localized within lysosomes of fetal membranes the accelerated expression of the activity of this enzyme could be prevented until such time as the metabolic events of parturition begin. At parturition a perturbation of the lysosomal membrane within the chorio-amnion could result in an increased release of free arachidonic acid through an accelerated activity of phospholipase A2. The results of this study suggest that at least a portion of phospholipase A2 in the chorion laeve and amnion is localized in the lysosomal fraction.

Initiation of human parturition: II. Identification of phospholipase A2 in fetal chorioamnion and uterine decidua

In this study, the presence of a phospholipase has been demonstrated in the human chorioamnion and uterine decidua. That the chorioamnionic enzyme is of the phospholipase A2 type was established by product identification following the incubation of the enzyme with either radioactive phosphatidylcholine or phosphatidylethanolamine. The potential relationship between the expression of the activity of this enzyme and the regulation of arachidonic acid release, prostaglandin formation, and the initiation of labor is considered.

5α-Reductase activity in human placenta

Abstract The concentration of 5α-pregnane-3,20-dione in peripheral blood of pregnant women is higher than that found in blood obtained from nonpregnant women throughout the luteal phase of the ovulatory cycle. The in vitro synthesis of 5α-reduced pregnanes from [ 3 H]progesterone by placental tissue was investigated using tissue minces and homogenates in the presence of added nicotinamide-adenine dinucleotide phosphate. The metabolites, [ 3 H]5α-pregnane-3,20-dione and [ 3 H]3β-hydroxy-5α-pregnan-20-one, were isolated and characterized employing a combination of chromatographic techniques, derivative formation, and crystallization with authentic [ 14 C]5α-pregnane-3,20-dione and [ 14 C]3β-hydroxy-5α-pregnan-20-one to constant 3 H: 14 C ratios. In short-term incubations with placenta homogenates, the apparent pH optimum for the synthesis of 5α-pregnane-3,20-dione was 8.8. There was no evidence for the formation of 5β-reduced pregnanes from [ 3 H]progesterone by placental tissue. The in vitro metabolism of [ 3 H]progesterone by minces of five term placentas, during 1 hour incubations at pH 7.4, was studied. The rate of formation of 5α-pregnane-3,20-dione varied from 109 to 197 pmoles/gm placental tissue/hr.

A preliminary report of Norplant@ implant insertions in a large urban family planning program

During the 21-month period between August 1, 1991, and April 30, 1993, 2,358 women received Norplant system insertions in either Parkland Memorial Hospital or the Dallas Maternal Health and Family Planning clinics. Forty-three percent of these women were teenagers with 14% 16 years of age or less. Overall, 431 patients received Norplant implants insertions postpartum prior to discharge from the hospital. To date, 138 Norplant systems have been removed, with the proportion of contraceptive implant removals among teenagers being essentially the same as that in more mature women. Of the reasons given by women discontinuing the Norplant system, an unanticipated high incidence of pain in the arm containing the implants, hair loss, and mood changes were noted. We have found the Norplant system to be a highly effective and highly acceptable contraceptive method for a large number of indigent women.

Progesterone binding and metabolism in human fetal membranes.

At term lysosomes are perturbed allowing phospholopase A2 activity which results in hydrolysis of glycerophospholipids and the release of free aranchidonic acids may be converted to prostaglandin or prostaglandin-like substances which may diffuse to the myometrium to inhibit ATP-dependent calcium ions by the sarcoplasmic reticulum and thereby initiate myometrial contractions of human labor. It is suggested that the lysosomes are perturbed by an increase in progesterone-binding substance causing progesterone withdrawal in the fetal membranes which decrease enzymes that metabolize progesterone. The progesterone withdrawal alone or with estrogen stimulation perturbs the lysosomes. Another suggestion is that progesterone-binding substance in the chorion laeve or protein-progesterone complex may perturb fetal membrane lysosomes. In either case a unique protein with high progesterone affinity appears in the fetal membranes before the onset of parturition.

Mechanism of estrogen action studies in the human

The interaction of both estradiol and estrone with human endometrial tissue obtained during the proliferative phase of the menstrual cycle has been examined by in vivo and in vitro techniques. Infusions of the tritium-labeled steroids resulted in tissue: plasma concentration gradients for both steroids, although the tissue levels of estrone were generally lower than those of estradiol. Little if any conversion of estrone to estradiol within the tissue was observed. Sucrose density gradient ultracentrifugal analysis of cytoplasmic and nuclear extracts following incubations with [3H]-estradiol revealed the presence of 8S and 4–5S receptors, respectively. While cytoplasmic binding of estrone was observed, transfer to the nucleus, although possible, was not proven. The human estrogen receptor system was found to be more labile than that of other species. Finally, evidence has been obtained which suggests that intranuclear conversion of estradiol to estrone may constitute a “release” mechanism for estradiol turnover in target cells.

Adenylate cyclase from term human placenta and its regulation

The activation of placental AC by either Mg2+ or Mn2+, in the presence and absence of NaF, followed sigmoidal saturation kinetics. Mn2+ enhanced maximally the NaF-stimulated Mg2+-dependent AC activity. The apparent Km of Mg2+-dependent AC for ATP was 0.4 mM, with and without NaF addition. GTP and GMP-P(NH)P stimulated the Mg2+-dependent AC in a dose-dependent manner with half-maximal stimulation taking place at concentrations of approximately 2 microM. In the presence of GMP-P(NH)P (10 microM) the kinetics of the AC dependence on Mg2+ ion concentration changed from sigmoidal to hyperbolic. Most of the AC activity (greater than 83 per cent) was associated with the particulate fractions of placental homogenate. For better reproducibility, the AC assay was performed using sonicated particulate fraction preparations; sonication did not alter the response of AC to stimuli to a variety of agents used in these experiments; freezing and thawing, however, obliterated the stimulation by beta-adrenergic agonists. Placental AC activity was inhibited by p-hydroxymercuriphenyl sodium sulphonate in a dose-dependent fashion, and the inhibition was reversed by dithiothreitol. Mg2+-dependent AC was inhibited by 0.5 mM phenylhydrazine (95 per cent). Mg2+-dependent AC activity was responsive to stimulation by epinephrine, without and with GTP addition, with half-maximal stimulation taking place at a concentration of 2 microM. The stimulatory effect of epinephrine was blocked by propranolol in a dose-dependent manner but was not blocked by phentolamine. Oestrone, oestradiol-17 beta, 2-hydroxyoestreone, 2-hydroxyoestradiol-17 beta, dehydroepiandrosterone sulphate, and progesterone, as well as oxytocin, did not alter either the basal or GMP-P(NH)P-stimulated Mg2+-dependent AC activities. Preincubation of 20 000 g particulate fraction with either NaF or GMP-P(NH)P, followed by washing, resulted in preparations that remained stimulated without the requirement of any further additions.