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Biomedical subjects

E Orwoll

Publications and source records attributed to E Orwoll.

18 recordsLinked to original sources
PubMed2000

Alendronate for the treatment of osteoporosis in men.

BACKGROUND: Despite its association with disability, death, and increased medical costs, osteoporosis in men has been relatively neglected as a subject of study. There have been no large, controlled trials of treatment in men. METHODS: In a two-year double-blind trial, we studied the effect of 10 mg of alendronate or placebo, given daily, on bone mineral density in 241 men (age, 31 to 87 years; mean, 63) with osteoporosis. Approximately one third had low serum free testosterone concentrations at base line; the rest had normal concentrations. Men with other secondary causes of osteoporosis were excluded. All the men received calcium and vitamin D supplements. The main outcome measures were the percent changes in lumbar-spine, hip, and total-body bone mineral density. RESULTS: The men who received alendronate had a mean (+/-SE) increase in bone mineral density of 7.1+/-0.3 percent at the lumbar spine, 2.5+/-0.4 percent at the femoral neck, and 2.0+/-0.2 percent for the total body (P<0.001 for all comparisons with base line). In contrast, men who received placebo had an increase in lumbar-spine bone mineral density of 1.8+/-0.5 percent (P<0.001 for the comparison with base line) and no significant changes in femoral-neck or total-body bone mineral density. The increase in bone mineral density in the alendronate group was greater than that in the placebo group at all measurement sites (P<0.001). The incidence of vertebral fractures was lower in the alendronate group than in the placebo group (0.8 percent vs. 7.1 percent, P=0.02). Men in the placebo group had a 2.4-mm decrease in height, as compared with a decrease of 0.6 mm in the alendronate group (P=0.02). Alendronate was generally well tolerated. CONCLUSIONS: In men with osteoporosis, alendronate significantly increases spine, hip, and total-body bone mineral density and helps prevent vertebral fractures and decreases in height.

Adult↗
PubMed2000

Bone density in Ehlers-Danlos syndrome.

Ehlers-Danlos Syndrome (EDS) is the most common inherited disorder of connective tissue recognized. The objectives of the present study were to determine bone mineral density (BMD) and biochemical markers of bone metabolism in EDS. Twenty-three subjects with Type III EDS and 23 matched controls underwent BMD measurement by dual-Energy X-ray absorptiometry (DXA) of the lumbar spine and femoral neck. Health history questionnaires and biochemical markers of bone and connective tissue metabolism were also assessed. No significant differences in BMD at the lumbar spine or differences in biochemical markers of bone and connective tissue metabolism were found between EDS subjects and controls. EDS subjects had a significantly decreased BMD at the femoral neck compared with controls, but this difference disappeared after adjustment for body height, weight and physical activity levels.

Absorptiometry, Photon↗
PubMed2000

Sex steroids modify working memory.

In the last ten years, numerous mechanisms by which sex steroids modify cortical function have been described. For example, estrogen replacement improves verbal memory in women, and animal studies have shown effects of estrogen on hippocampal synaptogenesis and function. Little is known about sex steroid effects on other aspects of memory, such as frontal lobe-mediated working memory. We examined the relationships between working memory and sex steroid concentrations and whether sex steroid supplementation would modify age-related loss of working memory in older men and women. Before hormone supplementation, working memory, tested with the Subject Ordered Pointing Test (SOP), was worse in older subjects than younger subjects, and there was no evidence of gender differences at either age. Testosterone supplementation improved working memory in older men, but a similar enhancement of working memory was not found in older women supplemented with estrogen. In men, testosterone and estrogen effects were reciprocal - with better working memory related to a higher testosterone to estrogen ratio. These results suggest that sex steroids can modulate working memory in men and can act as modulators of cognition throughout life.

Adult↗
PubMed1999

Homologous androgen receptor up-regulation in osteoblastic cells may be associated with enhanced functional androgen responsiveness.

Although androgens have myriad effects on the skeleton, the regulation of androgen action in bone is not well understood. Androgen receptors (ARs) are known to play an important role in mediating androgen action. We have examined the effects of androgens and other sex steroids on AR levels in osteoblastic cells in vitro using two clonal human cell lines, SaOS-2 and U-2 OS. AR protein levels were quantitated both by specific androgen binding studies and Western analyses, and AR messenger RNA was measured with RNase protection assays. Potential changes in AR functionality was assessed by reporter assays. Treatment of osteoblastic cells with the nonaromatizable androgen 5alpha-dihydrotestosterone (DHT) increased specific androgen binding 2-to 4-fold. Similar increases in AR protein levels were documented by Western analysis in both cell lines. The androgen-mediated increase in receptor levels was time and dose dependent as well as androgen specific. Steady-state AR messenger RNA levels were also increased by DHT. When AR concentrations in osteoblastic cells were elevated with exogenous receptor, there was an enhancement of DHT responsiveness, measured by increased trans-activation of an androgen-responsive promoter. Thus, androgen exposure increased androgen receptor protein levels and specific androgen binding in osteoblastic cells. Androgen action as measured by androgen-mediated transcriptional activation is enhanced in the presence of elevated AR levels. Consequently, these studies have revealed an additional means by which androgens may modulate skeletal metabolism.

Androgens↗
PubMed1998

Estrogen and sequential movement.

Normal movement depends in part on the brain's ability to produce and use dopamine, which regulates basal ganglia function. Behavioral, neuroanatomical, and neurophysiological data suggest that the basal ganglia are critical for the performance of sequential movement. Dopaminergic function is modulated by estrogen in animals and in humans. To test the hypothesis that estrogen modulates sequential movement, this study measured the reaction time (RT) and movement time (MT) of 15 women and 10 men in a choice RT task with sequential responses. Higher levels of estradiol in women's blood were associated with faster total movement time (RT plus MT). Testosterone levels in women's blood were not associated with keypressing performance. Hormone levels in men's blood were unrelated to keypressing performance. These results suggest that women's motor performance was affected by hormone levels, and that estrogen may interact with dopaminergic function in women.

Adult↗
PubMed1995

Early induction of alterations in cancellous and cortical bone histology after orchiectomy in mature rats.

Androgen deficiency is associated with low bone mass in humans and animals, but the remodeling alterations that lead to bone loss are unclear. Our objective was to define early responses in both cancellous and cortical bone to orchiectomy (ORX) using histomorphometry in sexually mature (4-month-old) rats. A total of 62 male rats, 4 months of age, were divided into six groups, sham operated (SH) or orchiectomized (ORX), and sacrificed 1, 2, or 4 weeks after ORX. Calcein was given 5 and 2 days before sacrifice to label mineralizing surfaces. Bone mineral density (BMD) was measured in excised femurs by dual energy X-ray absorptiometry (DEXA). Static and dynamic histomorphometry was evaluated in the cancellous bone of the proximal tibial metaphysis and lumbar vertebral bodies, and in the cortical bone of the tibial diaphysis. Osteopenia began to develop by 2 weeks after ORX, though weight gain and femur length did not change. Femoral BMD was significantly reduced and BMC decreased (NS) by 4 weeks after ORX (p < 0.05). Tibial and vertebral cancellous bone volume decreased 19% and 13%, respectively, while osteoblast and osteoclast surfaces, and numbers of osteoclasts, increased after ORX. At 2 weeks post-ORX, an increase in cancellous bone formation rate was attributable primarily to an increase in mineralizing surfaces and a smaller rise in mineral apposition rate. In contrast, cortical bone periosteal, but not endosteal, bone formation rate and mineralizing surfaces decreased. We conclude that ORX stimulates cancellous and diminishes periosteal bone turnover rapidly after ORX, with subsequent decreases in bone volume and mineral density. The clear divergence in cortical and cancellous bone responses to hypogonadism raises important questions regarding the control of bone formation and its role in defining the skeletal phenotype.

Absorptiometry, Photon↗
PubMed1994

Effects of vitamin D on insulin and glucagon secretion in non-insulin-dependent diabetes mellitus.

Vitamin D has been shown to increase insulin release from pancreatic islet cells in vitro, and to improve insulin secretion in vitamin D-deficient animals. Few attempts have been made to evaluate this issue directly in humans. We studied 35 otherwise healthy diabetic subjects in the early spring at the seasonal nadir of 25-hydroxyvitamin D [25(OH)D] concentrations (mean 35 +/- 7 nmol/L). Fasting glucose, insulin, C-peptide, and glucagon concentrations, and their responses to Sustacal stimulation were not related to indexes of mineral metabolism. In 20 subjects, a double-blinded, placebo-controlled, crossover trials of 1,25-dihydroxyvitamin D[1,25](OH)2D] treatment (1 micrograms/d for 4 d) had no effect on fasting or stimulated glucose, insulin, C-peptide, or glucagon concentrations. However, insulin and C-peptide responses to Sustacal after 1,25(OH)2D treatment were related to duration of diabetes (r2 = 0.28, P = 0.052 and r2 = 0.25, P = 0.002, respectively) in that short duration correlated with improvement after 1,25(OH)2D treatment. Hence, vitamin D nutrition, or 1,25(OH)2D therapy, had no major effect on glucose homeostasis in non-insulin-dependent diabetes mellitus.

Adult↗
PubMed1992

Effects of dietary protein deficiency on mineral metabolism and bone mineral density.

The effects of dietary protein restriction on mineral and bone metabolism are uncharacterized. We studied growing rats fed a diet low in protein (5%) for 4, 6, and 8 wks (n = 10 animals/group) and compared them with animals pair-fed with a protein-replete (18%) diet. The low-protein diet rapidly induced a profound hypocalciuria that persisted for greater than or equal to 8 wk. Serum calcium and phosphorus concentrations were not affected but serum total and free 25-dihydroxyvitamin D concentrations as well as gastrointestinal calcium absorption were lower in the low-protein animals. Skeletal dimensions were reduced in the protein-deprived rats but there were no significant differences in bone mineral content between control and low-protein animals at 4, 6, and 8 wks. Hence, dietary protein deprivation resulted in slower growth but bone mineral density was maintained when there was a marked reduction in urinary calcium excretion.

Animals↗
PubMed1991

Bone mineral density of the lumbar spine in women with endometriosis.

Young women with endometriosis have reduced cortical and trabecular bone mineral density of the wrist compared with age-matched controls. This conclusion was based on 41 subjects from one geographical location. The purpose of this study was to test this finding in a larger, more geographically diverse population. One hundred women with laparoscopically proven endometriosis were enrolled in this study for the evaluation of the efficacy of nafarelin, a gonadotropin-releasing hormone agonist. Patients were recruited from nine investigators across the United States and Canada, and bone mineral density of the lumbar spine was obtained at baseline, with 6 Hologic QDR (Hologic Inc., Waltham, MA) and a Lunar DPX (Lunar Radiation Corp., Madison, WI) instrument. The age of the women was 30.3 +/- 5.8 years (mean +/- SD); 91% were white. Bone mineral density of the lumbar spine was 1.1 +/- 0.11 g/cm2 (n = 85 Hologic QDR) and 1.2 +/- 0.93 g/cm2 (n = 15 Lunar DPX). Hologic bone mineral density was 104.8 +/- 11.0 and Lunar bone mineral density was 103.4% +/- 7.8% of normal values for age. To conclude, in a population based cross-sectional study of patients with endometriosis, we do not observe low bone mineral density of the lumbar spine by techniques that measure a combination of cortical and trabecular bone.

Adult↗
PubMed1986

Acute parathyroid hormone secretory dynamics: hormone secretion from normal primate and adenomatous human tissue in response to changes in extracellular calcium concentration.

PTH secretion has been evaluated extensively using short term incubation techniques, but these methods cannot be used to adequately evaluate the early phases of PTH secretion. We developed a dispersed cell perifusion system to study these acute secretory events. Responses to low calcium conditions were studied using dispersed cells from normal primate and adenomatous human parathyroid tissue. When these cell were perifused with 1.0 mM calcium medium, PTH secretion was stable, but increased within minutes in a dose-dependent manner in response to a lowering of extracellular calcium concentrations. Similarly, PTH secretion quickly declined when cells were exposed to higher extracellular calcium concentrations. In studies of cells from 11 human adenomas, the mean maximum secretion in response to 0.25 mM calcium conditions was 587 +/- 330% (+/- SD) of that in response to 1.0 mM calcium. The magnitude of the response to low calcium stimulation was variable, and cells from two additional adenomas failed to respond to low calcium stimulation despite responses to other secretogogues. Variation in the rate of increase in stimulated PTH secretion was also found among the adenomas examined (128 +/- 95% of baseline/min), and the rate of increase in PTH release and the eventual maximum rate of release were positively correlated. In studies of cells from 4 normal primates (rhesus macaque), the maximum response to 0.25 mM Ca2+ (544 +/- 118% of baseline) and the rate of increase in PTH secretion (95 +/- 35% of baseline/min) were similar to those in adenomatous human tissue. These results indicate that 1) acute PTH secretion can be studied in vitro, and that it appears to be similar to the in vivo process; 2) there is a wide variation among adenomatous tissues in the magnitude of secretion stimulated by low calcium concentrations; 3) in addition to varied magnitude of secretion, the rate at which hormone secretion increases in response to a low calcium stimulus varied among adenomas; and 4) PTH secretion from human adenomatous tissue is similar to that from normal primate tissue in both the rate and magnitude of response.

Adenoma↗
PubMed1985

Hypochlorite radioiodination of parathyroid peptides (hPTH1-34, [Tyr43]hPTH44-68).

Parathyroid hormone (PTH) radioimmunoassays have conventionally utilized [125I]bPTH1-84 as a radioligand, but more region-specific PTH assays are now possible with the use of recently available synthetic PTH peptides as standards and radioligands. A radioiodination procedure has been developed that utilizes hypochlorite as an oxidant and that is capable of producing PTH tracers of high specific activity (200 to 250 microCi/micrograms), prolonged stability, and excellent immunologic potency. Radioiodinated hPTH1-34 and [Tyr43]hPTH44-68 produced by hypochlorite iodination techniques can be used to develop sensitive and region-specific PTH assays of use in clinical and research situations.

Chemical Precipitation↗
PubMed1984

Resistance exercise and plasma beta-endorphin/beta-lipotrophin immunoreactivity.

Serum cortisol and plasma beta-endorphin/beta-lipotrophin hormone (LPH) immunoreactivity were measured in five males before and after endurance exercise (treadmill) and burst activity resistance exercise (weight lifting). Mean beta-endorphin/beta-LPH immunoactivity increased significantly following treadmill testing (p less than .05) and weight training (p less than .06). Post-exercise hormonal values were similar for the two activities. The hormonal changes previously reported with endurance activities also occur with burst activity exercise.

Endorphins↗
PubMed1981

Corticotropin/beta-lipotropin biosynthesis, processing, and release in Nelson's syndrome.

Biosynthesis and processing of ACTH/beta-lipotropin was studied in Nelson's syndrome pituitary tumor tissue grown in monolayer culture. Radiolabeled peptides were immunoprecipitated and fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS/PAGE). Important findings include: 1) a virtual absence of 13K ACTH or 3.5K beta-endorphin production; 2) evidence indicating the presence of a 24-26K ACTH and beta-LPH containing intermediate (which implies a different order of processing from that reported in the mouse); 3) An extremely rapid rate of turnover and release of ACTH and beta-lipotropin (beta-LPH) similar to that of the mouse AtT20/D16v pituitary tumors. The latter finding is consistent with an intrinsic pituitary cell defect in the pathogenesis of this disorder.

Adrenocorticotropic Hormone↗
PubMed1980

The distribution of forms of adrenocorticotropin and beta-endorphin in normal, tumorous, and autopsy human anterior pituiary tissue: virtual absence of 13K adrenocorticotropin.

To begin to define the nature of the biosynthesis and processing of ACTH and beta-endorphin in the human, anterior pituitary tissue (fresh normal and adenomatous, and autopsy) was extracted in acetic acid in the presence of protease inhibitors and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The gel slice eluates were assayed for ACTH and beta-endorphin immunoactivity. Human anterior pituitary tissue contained four major size classes of ACTH and three major size classes of beta-endorphin. We found that in all tissue sources examined there was a virtual absence of 13-15K ACTH, which is a major form in the rat and mouse. When comparing extracts obtained from fresh normal or adenomatous anterior pituitary tissue, we also found a drastic decrease in beta-lipotropin and beta-endorphin in extracts of autopsy human anterior pituitaries. These results suggest that the biosynthesis and processing of pituitary ACTH and beta-endorphin in the human may be different than in the mouse, and because of apparent postmortem proteolysis of beta-endorphin, human pituitary obtained at autopsy is probably not a good source of material for biochemical studies of pituitary tissue.

Adenoma↗