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Biomedical subjects

R Marcus

Publications and source records attributed to R Marcus.

At least 253 records · Page 14Linked to original sources
PubMed1984

Age-related changes in parathyroid hormone and parathyroid hormone action in normal humans.

We evaluated parathyroid function in 158 normal subjects, aged 23-85 yr. Calcium, phosphorus, creatinine, and cAMP were measured in blood and urine in the fasting state and after a 1-g oral calcium challenge. Serum immunoreactive PTH (iPTH) was measured with a goat antiserum developed against human PTH, using (43Tyr) human PTH-(44-68) as tracer and standards. With age, a decrease in total serum Ca (r = -0.14; P less than 0.05) was attributable to a fall in serum albumin (r = -0.40; P less than 0.001). Creatinine clearance fell from 124 ml/min at age 20 yr to 61 ml/min at age 80 yr (r = -0.44; P less than 0.001). iPTH rose with age in men (r = 0.21; P less than 0.05) and women (r = 0.31; P less than 0.001) from 29 pg/ml at age 20 yr to 48 pg/ml at 80 yr. iPTH was also correlated with creatinine clearance (r = -0.32; P less than 0.001. When renal function was controlled in the analysis, the regression of iPTH with age was no longer significant. Other significant correlations with age include a decrease in renal phosphorus reabsorption (r = -0.17; P less than 0.05) and an increase in urinary nephrogenous cAMP excretion (r = 0.34; P less than 0.01). The rise in nephrogenous cAMP was not accompanied by a change in total urinary cAMP, since plasma, and therefore filtered, cAMP decreased with age. Basal calcium excretion was stable, but the calciuric response to oral calcium decreased (r = -0.27; P less than 0.01). We conclude that loss of renal function is the major cause of rising iPTH levels with age.

Adult↗
PubMed1984

Assessment of adenosine 3',5'-monophosphate excretion and an oral calcium tolerance test in the diagnosis of mild primary hyperparathyroidism.

An oral calcium tolerance test was administered to 22 hyperparathyroid patients and 162 normal subjects to determine its value in the diagnosis of mild primary hyperparathyroidism. Basal urinary excretion of calcium was higher in patients [0.217 mg/100 ml glomerular filtrate (GF)] than in normal subjects (0.090 mg/100 ml GF), but there was 50% overlap between the two groups. Phosphorus excretion, expressed as the ratio of the maximal tubular reabsorption of phosphorus to the glomerular filtration rate, was lower in patients (2.77) than in normal subjects (3.7), but 38% of the patients fell within the normal range. Urinary excretion of total cAMP also failed to separate hyperparathyroid patients from normal subjects [5.8 +/- 0.32 (+/- SEM) nmol/100 ml GF in patients vs. 3.41 +/- 0.11 in normal subjects]. Determination of nephrogenous cAMP failed to increase the utility of cAMP as a predictor of hyperparathyroidism. In response to oral calcium, the elevation in serum calcium concentration was the same in both groups. The rise in urinary calcium was greater in patients, but showed 77% overlap with that in normal subjects. Conversely, serum immunoreactive PTH, measured with a midregion-specific RIA, was elevated in 90% of the patients. Some normal subjects also had high levels of PTH, but none of these had hypercalcemia. We conclude that the oral calcium tolerance test and measurement of urinary cAMP do not adequately distinguish hyperparathyroid patients from normal subjects. In the absence of renal insufficiency, the combination of hypercalcemia and elevated serum PTH concentration most accurately predicts the diagnosis of primary hyperparathyroidism.

Administration, Oral↗
PubMed1984

Conjugated estrogens in the treatment of postmenopausal women with hyperparathyroidism.

Fourteen postmenopausal women with mild hyperparathyroidism were given conjugated estrogens. Serum calcium levels became normal and urinary calcium excretion was reduced for up to 2 years in ten patients taking an average dose of 1.25 mg of estrogen daily. Hypercalcemia returned quickly when therapy was interrupted. Estrogen did not systematically alter serum immunoreactive parathyroid hormone or calcitriol levels or urinary excretion of cyclic adenosine monophosphate. Significant reductions in urinary hydroxyproline and serum alkaline phosphatase activity during estrogen therapy indicate that the major effect of therapy was to decrease bone turnover. Iliac crest biopsy specimens taken before estrogen therapy showed normal trabecular bone volume and excessive osteoid seams. Follow-up biopsy specimens were taken from six patients after 1 year on therapy. Bone volume remained stable, but hyperosteoidosis had improved in only one patient. Without understanding the long-term impact of untreated mild hyperparathyroidism on bone, the benefits of estrogen therapy on bone remain uncertain. However, therapy with conjugated estrogens provides sustained control of serum and urine calcium in most women with hyperparathyroidism and is a reasonable alternative in patients who are not surgical candidates.

Adult↗
PubMed1983

Age-related loss of trabecular bone in premenopausal women: a biopsy study.

We measured the trabecular bone volume (TBV) of 62 iliac crest biopsies taken from women admitted to lymphoma protocols at Stanford University between 1970-1981. All subjects were active, cycling premenopausal women, with bone marrows that were negative for tumor. Disease status was stage III or less in 90% of the subjects. Trabecular bone volume was negatively correlated with age, and the annual predicted loss of bone was 0.14-0.18% TBV, or 0.7% of the original bone volume. In addition, there was a substantial range of normal TBV at any given age, evident even during adolescence. This study demonstrates that TBV is lost from iliac crest throughout adult life. The large spread in TBV indicates further that factors operating during adolescence or even earlier may have an important impact on skeletal mass.

Adolescent↗
PubMed1983

Parathyroid hormone induces a calmodulin-dependent alteration in phosphodiesterase activity of rat kidney in vivo.

In the basal state cyclic nucleotide phosphodiesterase in cytosol of rat kidney cortex is characterized by at least two kinetically distinct activities, with Michaelis-Menten constant (Km) for cAMP of 3.3 X 10(-6) and 3.7 X 10(-5) M. Eight minutes after in vivo injection of parathyroid extract, and persisting over 4 h, phosphodiesterase showed only one apparent activity, Km = approximately 1 X 10(-5) M. This change in kinetic profile was mimicked by the ip injection of 10 mg/kg (Bu)2-cAMP, and was reversed by incubation of cytosol with trifluoperazine or EGTA. Incubation of control cytosol with purified calmodulin duplicated the effect of hormone injection. Chromatography of control cytosol over diethylaminoethyl-cellulose resolved two activity peaks. Peak I, corresponding to the high Km activity of whole cytosol, was stimulated by calmodulin, representing a change in maximum velocity but not in substrate affinity. In addition, calmodulin stimulated the hydrolysis by Peak I of 3',5'-cyclic guanosine monophosphate. Peak II activity was not altered by calmodulin. These studies demonstrate that PTH promotes a rapid and sustained alteration in phosphodiesterase kinetics which is mediated by calcium and calmodulin, and which reflects the activation of the high Km component of the enzyme.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1982

Role of glucagon as a contributor to glucose intolerance in acute and chronic uremia.

It has been suggested that increased sensitivity to glucagon may contribute to glucose intolerance in uremia. In order to evaluate this possibility systematically, we have assessed the effect of glucagon on hepatic glucose outflow, formation of cAMP, and activation of adenylate cyclase by livers obtained from acutely and chronically uremic rats and their respective sham operated controls. Glucagon infused at rates of 6 ng/min/kg rat resulted in minimal and equivalent increases in hepatic glucose outflow and cAMP accumulation when livers from acutely uremic and control rats were perfused for 30 min. However, at glucagon infusion rates of 18 ng/min/kg, glucose efflux from perfused livers of acutely uremic rats was significantly reduced (p less than 0.001) compared to perfused livers of control rats (4.64 +/- .9 vs 12.7 +/- 2.4 mumol/g liver) and cAMP accumulation was also significantly lower (p less than 0.01) (1352 +/- 222 vs 3100 +/- 348 pmol/g liver). Basal adenylate cyclase activity of hepatic membranes obtained from uremic and control rats was similar, and was stimulated by glucagon concentrations ranging from 10(-8) to 10(-6) at equivalent rates in both groups. In livers from chronically uremic rats, glucagon infused at rates of 6 ng/kg/min significantly increased hepatic glucose outflow (32.5 +/- 6.9 mumol/g liver). However this was not greater than that of control animals (37.6 +/- 9.2). Furthermore, cAMP accumulation was significantly lower (p less than .02) in chronically uremic rats than in controls, and activation of adenylate cyclase by glucagon was similar in both groups. These findings indicate that glucagon does not increase glucose efflux, cAMP accumulation or enhance activation of adenylate cyclase by isolated perfused livers from either acutely or chronically uremic rats. Thus, glucose intolerance in uremic rats does not appear to be due to increase hepatic glucose output resulting from increased sensitivity to glucagon.

Acute Disease↗
PubMed1982

Age-related change in parathyroid hormone-dependent cyclic AMP formation in rat kidney.

Parathyroid hormone (PTH) dependent cyclic AMP (cAMP) accumulation was evaluated in renal cortex from 2- and 12-month-old rats. Basal cAMP was lower, and responses to PTH were greater at all concentrations of hormone in kidney from 2-month-old rats. This difference was obliterated by prior removal of parathyroid glands. cAMP responses to calcitonin and both basal and hormone-stimulated adenylate cyclase activity were the same at both ages. The results suggest progressive loss of responsiveness to PTH with age, but at a site other than the receptor-adenylate cyclase complex. Blunted cAMP accumulation in year-old rats most likely reflects agonist-specific desensitization.

Adenylyl Cyclases↗
PubMed1982

The relationship of dietary calcium to the maintenance of skeletal integrity in man-an interface of endocrinology and nutrition.

Calcium restriction reliably produces osteoporosis in animals, but the impact of dietary calcium on age-related bone loss in man is controversial. The opinion that calcium intake is not clearly related to bone mass or to osteoporosis is well-entrenched in the nutrition literature, and has been influential in setting recommended intakes for the American public. This position rests on the poor correlation between habitual calcium intake and the incidence of osteoporosis in some non-Western countries, and on demonstrations that young men can achieve calcium balance on low intakes. However, such data neglect a variety of factors which determine calcium nutriture. These include the efficiency of mineral utilization, gonadal status, and the effect of dietary protein. It has recently been demonstrated that calcium requirements increase during adult life in women. This increase is attributable in large measure, but not completely, to estrogen deprivation associated with the menopause. In addition, the American diet is abundant in protein, a situation which may be deleterious to bone. Based on the evidence currently available, it is reasonable to propose that adolescent and young women consume one gram of calcium daily, and that this intake be increased to 1500 mg to the time of menopause.

Adult↗
PubMed1981

des-Ser2 salmon calcitonin: a biologically potent synthetic analog.

We studied the biological activity of a synthetic analog of salmon calcitonin (SCT), from which the serine2 residue within the amino-terminal disulfide ring had been omitted (des-Ser2-SCT). This analog proved to be indistinguishable from SCT with respect to hypocalcemic activity in vivo, displacement of [125I]SCT from rat renal membranes, and accumulation of cAMP in incubated renal cortical slices, des-Ser2SCT was twice as potent as SCT with respect to adenylate cyclase activation in renal membranes. Since the deletion did not impair biological activity, it appears that the function of the intact ring structure does not critically depend on its encompassed peptide chain length.

Adenylyl Cyclases↗
PubMed1981

Harmful effects of carrageenan fed to animals.

An increased number of reports have appeared in the literature describing the harmful effects of degraded and undegraded carrageenan supplied to several animal species in their diet or drinking fluid. The harmful effects include foetal toxicity, teratogenicity, birth defects, pulmonary lesions, hepatomegaly, prolonged storage in Kupffer cells, ulcerative disease of the large bowel with hyperplastic, metaplastic, and polypoidal mucosal changes, enhancement of neoplasia by carcinogens, and, more ominously, colorectal carcinoma. Degraded carrageenan as a drug or food additive has been restricted in the United States by the FDA, but undegraded carrageenan is still widely used throughout the world as a food additive. Its harmful effects in animals are almost certainly associated with its degradation during passage through the gastrointestinal tract. There is a need for extreme caution in the use of carrageenan or carrageenan-like products as food additives in our diet, and particularly in slimming recipes.

Animals↗
PubMed1980

Parathyroid hormone as a calcium ionophore in bone cells: tests of specificity.

Parathyroid Hormone (PTH) stimulates calcium entry into bone cells in vitro, and this effect has been proposed to mediate the actions of PTH on bone. Using cells harvested from infant rat calvaria by collagenase digestion, we evaluated the sensitivity and specificity of this phenomenon. Calcium uptake was temperature dependent, and was increased by PTH over the concentration range 0.01 to 0.50 units/ml. A series of nonhormonal peptides obtained during the purification of a single batch of PTH was found to stimulate calcium uptake. In addition, isoproterenol, ACTH, calcitonin, and glucagon stimulated calcium uptake. In no case, however, was the degree of stimulation as great as that produced by biologically active PTH. Prostaglandins are also potent resorbers of bone, and a series of prostaglandins also stimulated calcium uptake into bone cells. These results are compatible with a calcium ionophore model of PTH and prostaglandin action on bone.

Animals↗
PubMed1980

Sonographic evaluation of iliac artery aneurysms.

Abdominal aortic aneurysms are not uncommon and their ultrasonic characteristics have become well-known. Ultrasonic detection of iliac artery aneurysms however, has not been well documented. Experience with 125 ultrasonic examinations for clinically suspected absoeminal aortic aneurysms is presented herein. Fifty-two abdominal aortic aneurysms were detected. Six unsuspected iliac artery aneurysms were demonstrated using a special oblique projection. Routine use of this oblique projection in patients with suspected abdominal aortic aneurysms is discussed.

Aged↗
PubMed1980

Insulin secretion improves following dietary control of plasma glucose in severely hyperglycemic obese patients.

Severely hyperglycemic obese patients show deficient insulin secretion as well as insulin resistance. To determine whether the secretory defect is reversible, we placed 7 hospitalized patients on severe caloric restriction for 4--12 wk. Insulin secretory responses to oral glucose and intravenous tolbutamide were assessed before and after the diet. On entry, mean fasting plasma glucose (FPG) was 326 +/- 23 mg/dl. The insulin response to oral glucose was completely flat, although modest secretion was evoked by tolbutamide. After initiating caloric restriction, FPG rapidly fell, reaching 150 +/- 21 mg/dl by 2 wk, and remained low throughout the duration of the diet period. At restudy, improved oral glucose tolerance was accompanied by significant increases in the insulin secretory responses to both glucose and tolbutamide. These results support the concept that control of plasma glucose concentration allows recovery of insulin secretion. The degree of weight loss necessary to achieve this effect was modest. Since blood glucose was effectively controlled by caloric restriction alone, exogenous insulin is probably not required in the initial management of most obese patients with severe hyperglycemia.

Aged↗
PubMed1980

Acute systemic toxicological tests of soft contact lens extractives.

The toxic potential of three major components of soft contact lenses was assessed in white mice. Accepted procedures for toxicological studies were used to evaluate the effects of 2-hydroxyethyl methacrylate, ethylene glycol, and methacrylic acid. No observable signs of gross toxicity were detected in any of the mice injected with the original doses. Larger doses of methacrylic acid produced ataxia, irregular breathing, convulsions, and death. From the concentrations of these chemicals normally occurring in contact lenses, no systemic toxic effects would be expected.

Animals↗
PubMed1980

Effects in vivo of vitamin D metabolites and 17 beta-estradiol on parathyroid hormone-dependent formation of adenosine 3',5'-monophosphate in rat bone.

We used an in vivo infusion technique to assess the hypothesis that vitamin D metabolites and estrogens modulate tissue responsiveness to parathyroid hormone via effects on the adenylate cyclase-cAMP system. After treatment with these agents for 3-4 days, rats were thyroparathyroidectomized. Twenty-four hours later, parathyroid extract (PTE) was infused, and cAMP in calvaria was measured. The response to PTE was achieved by 2 min and represented a 4-fold increase in the tissue concentration of cAMP at the highest dose of hormone tested. Treatment with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], did not affect cAMP levels in bone. However, 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3], either 0.25 or 1.25 micrograms daily, led to a major increase in PTE-stimulated cAMP formation, a result which persisted when carried out in chronically thyroparathyroidectomized animals. This effect did not reflect direct stimulation of adenylate cyclase or inhibition of cyclic nucleotide phosphodiesterase from bone by the vitamin metabolite, nor did it operate via the 1,25-(OH)2D3 receptor. 24,25-(OH)2D3 treatment also increased cAMP concentrations in renal cortical slices, but not in liver. Adenylate cyclase activity in kidneys from 24,25-(OH)2D3-treated rats was not different from that found in control tissue, but total cytosol phosphodiesterase activity was diminished. 17 beta-Estradiol, over a daily dose range of 2.5 micrograms to 5.0 mg, lowered basal cAMP levels but did not alter PTE-stimulated cAMP production. We conclude that modulation of PTH action in bone by estrogen does not involve modification of the acute cAMP response to PTH. Further, the results support the concept that there are unique actions of 24,25-(OH)2D3 on bone and kidney which are not duplicated by 1,25(OH)2D3.

24,25-Dihydroxyvitamin D 3↗