Long-term ecosystem stress: the effects of years of experimental acidification on a small lake.

Experimental acidification of a small lake from an original pH value of 6.8 to 5.0 over an 8-year period caused a number of dramatic changes in the lake's food web. Changes in phytoplankton species, cessation of fish reproduction, disappearance of the benthic crustaceans, and appearance of filamentous algae in the littoral zone were consistent with deductions from synoptic surveys of lakes in regions of high acid deposition. Contrary to what had been expected from synoptic surveys, acidification of Lake 223 did not cause decreases in primary production, rates of decomposition, or nutrient concentrations. Key organisms in the food web leading to lake trout, including Mysis relicta and Pimephales promelas, were eliminated from the lake at pH values as high as 5.8, an indication that irreversible stresses on aquatic ecosystems occur earlier in the acidification process than was heretofore believed. These changes are caused by hydrogen ion alone, and not by the secondary effect of aluminum toxicity. Since no species of fish reproduced at pH values below 5.4, the lake would become fishless within about a decade on the basis of the natural mortalities of the most long-lived species.

Lower levels of thyrotropin-releasing hormone-degrading activity in human cord and in maternal sera than in the serum of euthyroid, nonpregnant adults.

Thyrotropin-releasing hormone (TRH)-degrading activity was investigated in human cord, maternal, and euthyroid adult sera by measuring (a) the rate of disappearance of TRH and (b) the rate of formation of degradation products. The rate of TRH degradation in cord and maternal sera was 25-33% of that in euthyroid adult serum. Concomitantly, in cord and maternal sera, the rate of formation of proline, a major TRH degradation product in serum, was one-quarter to one-third that in euthyroid adult sera. The differences were highly significant (P less than 0.001). The decreased levels of TRH-degrading activity in cord and maternal sera cannot be explained by (a) the presence of a dialyzable inhibitor, (b) the absence of an activator of TRH degradation, or (c) a reversal of the degradation process. There was no difference in the types of radioactive degradation products formed by cord, maternal, and euthyroid adult sera. The low level of TRH-degrading activity and its possible relationship to high thyrotropin-stimulating hormone levels in cord serum suggest that TRH-degrading activity may be a factor to consider in investigations of the perinatal pituitary-thyroid axis, but further studies are needed to determine the role of serum degradation of TRH in regulating physiological levels of TRH.

Progesterone receptor in the hypothalamic cytosol of female rats.

A progesterone (P)-binding component with a sedimentation coefficient of 8S has been demonstrated in hypothalamic cytosol from ovariectomized, estrogen-primed rats using both [H]P-containing sucrose-glycerol gradient analysis and dextran-coated charcoal adsorption of the preisolated 8S component. The association rate constant (K+1) was determined to be 1.90 +/- 0.38 (SD) X 10(6) M-1 min-1 at 0-2 C. The dissociation rate constant (K-1) was 1.86 x 10(-2) min-1, as calculated from the half-dissociation time [37.0 +/- 7.3 (SD) min]. The apparent dissociation constant (Kd) at 0-2 C was determined to be 6-10 nM by Scatchard plot analysis of data obtained from either direct [3HA]P binding or competition of the [3H]P binding by nonradioactive P and by calculating from K-1/K+1. The 8S binding component was protein in nature, and the concentration of binding sites was 12 fmol/mg cytosol protein. On a per U cytosol protein basis, the relative capacities of the specific 8S binding components were: uterus greater than pituitary greater than hypothalamus greater than hippocampus/amygdala greater than cerebral cortex. Competition studies showed a high specificity for P and 5 alpha-dihydroprogesterone. Corticosterone (C), although competing for the binding, had an affinity 8-fold less than P. Implantation of C in adrenalectomized, ovariectomized, estrogen-implanted rats suppressed the 8S binding of [3H]C without affecting the [3H]P binding. The binding of [3H]P to the cytoplasmic 8S component of hypothalamus was greater than that of combined hippocampus and amygdala, while the reverse was observed for the binding of [3H]dexamethasone. These results demonstrate in rat hypothalamic cytosol a tissue and hormone-specific, high affinity, 8S progesterone-binding protein which has many of the properties expected of a hormone receptor.

The affinity of catechol estrogens for estrogen receptors in the pituitary and anterior hypothalamus of the rat.

The purpose of these experiments was to evaluate the potential for interaction between 2-hydroxyestrone and 2-hydroxyestradiol and estrogen receptors in rat pituitary and anterior hypothalamus. The 150,000 X g supernatant fractions of these tissues were prepared, the estrogen receptor-site concentration was measured, and the relative abilities of unlabelled estradiol, estrone, 2-hydroxyestradiol and 2-hydroxyestrone to compete with [3H]estradiol for estrogen binding sites was determined. From these results, and the previously determined association constant for [3H]estradiol, 10(10)M-1, the association constants of the other estrogens were calculated. The introduction of the 2-hydroxy group caused only a modest reduction in the affinity of these estrogens for the receptors. The association constants of the 2-hydroxy derivatives were within one order of magnitude of those of the parent compounds. These results demonstrate the potential for interaction between catechol estrogens and estrogen receptor in rat brain and pituitary of a magnitude which could be biologically significant.

The effects of dexamethasone on the peripheral plasma concentrations of androstenedione, testosterone and cortisol in the pregnant rhesus monkey.

The concentrations of androstenedione, testosterone and cortisol have been measured in the maternal peripheral plasma of normal pregnant rhesus monkeys (Macaca mulatta), and in rhesus monkeys treated daily with dexamethasone during late pregnancy. During the last 30 days of pregnancy, the mean plasma concentrations of androstenedione, testosterone and cortisol were about 1400-2000 pg/m1375-425pg/ml and 300-400 ng/ml, respectively. None of these steroids increased significantly before parturition. As there was no rise in maternal androgens in late pregnancy when plasma estrogens increase sharply, it suggested that his elevation of plasma estrogens is related to an increase of fetal precursors Dexamethasone treatment resulted in 90% suppression of plasma cortisol and 40%-60% suppression of androstendione and testosterone. As the suppression of maternal androgens was of lesser magnitude than the decline of plasma estrogens, and as the androgens did not continue to fall with continuing dexamethasone treatment as did the estrogens, these findings also suggest that the decline in plasma estrogens is related in large part to suppression and atrophy of the fetal adrenals.

Catechol estrogen formation by the human fetal brain and pituitary.

Homogenates of central neuroendocrine tissues from 2 male and 1 female midtrimester fetuses were incubated with (23H) estradiol-17beta. Metabolism at the C-2 position was monitored by measuring the tritium incorporated into water in the incubate. Liberation of tritium from the substrate by hypothalamus, limbic tissues, parietal cortex and pituitary occurred to the extent of 5.1-12.7%, 1.6-8.5%, 4.7-10.8%, and 0.9-4.1% of starting radioactivity, respectively. The nature of the product was confirmed by the isolation of 14C labelled 2-hydroxyestrone derivative from separate incubations with 14C-estrone as the substrate. With or without correction for weight of tissue incubated, catechol estrogen formation under these conditions occurs at levels similar to those seen in rat brain homogenates except that in contrast to the rat, the human cortex is also highly active.

The effects of dexamethasone and indomethacin on the outcome of pregnancy in the rabbit.

Pregnant rabbits were treated with indomethacin (8-10 mg/kh/day) or dexamethasone (1-2-1-8 mg/kh/day) during late gestation. The effects of these treatments on the concentrations of progesterone and prostaglandin F (PGF) in the peripheral plasma, and the outcome of gestation was studied. Treatment with indomethacin significantly prolonged the length of gestation (P smaller than 0-01) compared iwth control, untreated animals. In these treated animals, the plasma progesterone levels declined at a similar time to that in control rabbits but the increase in systemic PGF normally seen during late pregnancy was reduced. Dexamethasone treatemnt reliably induced premature delivery within 3-6 days. The plasma progesterone concentration fell rapidly during the first 24 h of dexamethasone administration, but in no animal was this associated with a significant increase in the plasma levels of PGF. These results are consistent with the suggestion that prostaglandins are involved in the normal initiation of parturition in the rabbit. They do not support the hypothesis that the effect of dexamethasone on the length of gestation is mediated through an increase in the production of prostaglandin F.

Measurements of plasma zinc. II. In malignant disease.

The plasma zinc and plasma copper was estimated in 81 patients with malignant disease. There was a striking decrease in plasma zinc levels in carcinoma of bronchus compared both with normals and most other types of malignancy.

Measurements of plasma zinc. I. In health and disease.

Zinc is an essential trace element. Previous methods of measuring zinc in clinical material have been difficult and reported findings must be treated with caution. Using atomic absorption spectroscopy it has been established that plasma zinc is one of the most uniform biochemical characteristics of normal adult blood. Sex and age differences in adult life are insignificant. Increased metabolic activity, on the other hand, induces a marked, immediate fall in plasma zinc level. The possible implications of this are discussed. Zinc levels in patients with diabetes mellitus, cardiovascular disease, and anaemia due to acute blood loss have been within normal limits. Plasma zinc is low in certain types of liver disease.

Pituitary gonadotropin responsiveness with danazol.

Danazol (17alpha-pregn-4-en-20-yno-[2,3-d]isoxazol-17-ol) was administered daily for 4 days to castrated female rats. As previously demonstrated, danazol lowered serum levels of luteinizing hormone (LH) in an apparent dose-dependent fashion. Animals which received danazol in a dose sufficient to lower serum LH responded to administered LH-releasing hormone (LHRH) with increases in serum LH levels which were not diminished as compared with those of control animals. Although these experiments do not preclude an effect of danazol directly on the pituitary, the results indicate that this agent probably lowers serum LH primarily by inhibition of hypothalamic LHRH secretion.

Danazol inhibits steroidogenesis.

Danazol was found to inhibit multiple enzymes of steroidogenesis directly in the pregnant mare serum (PMS)-treated hamster ovary and the rat testis and adrenal in vitro. In the PMS-treated hamster ovary, danazol inhibited 17alpha-hydroxylase, 17,20-lyase, and 3beta-hydroxysteroid dehydrogenase. In the rat testis, danazol inhibited 17alpha-hydroxylase, 17,20-lyase, 3beta-hydroxysteroid dehydrogenase, and 17beta-hydroxysteroid dehydrogenase. In the rat adrenal, danazol inhibited 3beta-hydroxysteroid dehydrogenase, 21-hydroxylase, and 11beta-hydroxylase. Two hours after a subcutaneous injection of 5 mg/kg of danazol to adult male rats, serum luteinizing hormone levels were significantly increased and serum testosterone levels were significantly suppressed. These findings suggest that in the rodent one of danazol's major pharmacologic effects is the direct inhibition of steroidogenesis.

Estradiol receptors in the pituitary and anterior hypothalamus of the rat: measurement by agar gel electrophoresis.

PIP: The reliability of agar gel electrophoresis in the measurement of high-affinity saturable estrogen-binding component in the cytosol of the rat pituitary gland and anterior hypothalamus was assessed. The available binding sites were determined in small samples with good precision and accuracy. Incubation with 100-fold competitor was more satisfactory than heat-treatment for measuring nonspecific binding. There was substantial, but incomplete, dissociation of albumin-estradiol complexes. The total number of estrogen binding sites in the anterior hypothalamus was approximately 15% greater in 28-day-old females than males (p .02). However, differences in the number of binding sites in the pituitary was not significant (p .02). The pituitary was found to contain twice as many binding sites as the anterior hypothalamus in both sexes. The latter finding is consistent with the importance of the direct action of estrogen on the pituitary in mediating pituitary function.^ieng

Perceptual studies on ultrasonic B-scan textures.

A pilot study of the perceptual characteristics of ultrasonic textured images is described. Scans of four models performed on four real-time machines optimised for display of a normal liver were used. A trial with 22 observers indicated that the model that gave images closest to the liver image varied between machines. A second, paired similarity test with five observers using all the model images was performed, with a cluster analysis of a multidimensional scaling procedure. This suggested that the prominent features of the textural images are often more closely related to the machines than to the models. Considerable further work is needed to confirm these pilot results and to identify the visual cues that are most significant in textured images.

Calcium metabolism in bone disease: effects of treatment with microcrystalline calcium hydroxyapatite compound and dihydrotachysterol.

Microcrystalline calcium hydroxyapatite compound (MCHC) was given orally together with small doses of dihydrotachysterol (DHT) to a number of patients with osteogenesis imperfecta (OI). Serial calcium and phosphate balances in three patients representing wide variations in severity of OI are presented over periods from eight months to two years. The combination of MCHC and DHT resulted in an immediate positive calcium balance which was maintained throughout the period of assessment in 2 cases. However, no radiological improvement could be demonstrated. Substituting calcium gluconate for MCHC resulted in a reduction of positive balance. No adverse effects were noted. The reasons why MCHC with DHT should result in increased calcium retention are discussed. This combination of MCHC and DHT could be of benefit in many common situations of bone demineralization, such as osteoporosis.

The assessment of continuing medical education.

There is a close link between audit of clinical competence and audit of continuing medical education. Some of the earlier assumptions about the organisation of continuing medical education need to be reviewed. The increasing provision of resources for continuing medical education by the NHS means that added safeguards are necessary to ensure that professional standards are not subordinated to service exigencies. The introduction of higher educational methodology into continuing medical education should be critically examined with awareness of the limitations and controversies concerning many methods of teaching and assessing educational outcome. The methodology of higher education may need to be substantially modified to suit the uniqueness of the clinical process and the problems of altering the behaviour of experienced and practising doctors. Criticism of behaviourist educational methods should be based on an understanding and knowledge of these methods. A new functional clinical educational domain is proposed which links educational methods with the clinical application of new learning.