Search PubMed⌕ Search

Biomedical subjects

R C Morris

Publications and source records attributed to R C Morris.

At least 19 recordsLinked to original sources
PubMed1992

Metabolic acidosis reverses the increase in serum 1,25(OH)2D in phosphorus-restricted normal men.

We tested the hypothesis that in humans, metabolic acidosis can disorder the metabolism of 1,25-dihydroxyvitamin D [1,25(OH)2D] by impairing the capacity for a sustained physiological stimulus to increase renal production of this hormone. Specifically, in seven healthy men in whom restriction of dietary phosphorus had doubled their serum concentration of 1,25(OH)2D, we induced metabolic acidosis of moderate severity with oral NH4Cl, administered for 7 days. With induction of acidosis, the serum concentration of 1,25(OH)2D decreased sharply and remained decreased and near constant throughout the period of acidosis, the decrease amounting to one-half of the increment induced by phosphorus restriction alone. The serum concentration of free 1,25(OH)2D also decreased, since the measured free fraction of 1,25(OH)2D was unaffected by NH4Cl. The decrease in serum 1,25(OH)2D was accounted for by a 16% increase in its metabolic clearance rate and by a 19% decrease in its production rate. Metabolic acidosis induced a modest increase in the concentrations of blood ionized calcium and serum phosphorus. Multiple linear regression analysis revealed that serum levels of 1,25(OH)2D varied inversely and significantly with those of plasma hydrogen ion (R = -0.77, P < 0.001), but not with those of blood ionized calcium or serum phosphorus. These data demonstrate in humans that metabolic acidosis can substantially reverse the increase in serum concentration of 1,25(OH)2D induced by phosphorus restriction. The data provide evidence that acidosis can restrict the increase in renal production and serum concentration of 1,25(OH)2D effected by a sustained physiological stimulus.

Acid-Base Equilibrium↗
PubMed1991

Measurement of aortic blood flow by Doppler echocardiography: day to day variability in normal subjects and applicability in clinical research.

To assess the reliability of Doppler ultrasound for detecting serial changes in cardiac output in response to experimental interventions, the day to day variability of the minute distance of aortic flow was determined in seven normal subjects maintained in a tightly controlled environment with regard to diet and activities. Measurements were made at the same time on 5 to 6 sequential days from an apical window with use of both continuous wave and pulsed wave Doppler techniques. Two statistical measures of reliability were calculated, the intraclass coefficient of correlation (R), which varies between 0 (null reliability) and +1 (perfect reliability), and the 95% confidence interval for the error-free value of a single measurement. For sequential measurements of arterial pressure, 24 h urinary volume and sodium excretion and body weight, the intraclass coefficients of correlation ranged from 0.85 to 0.99, indicating low day to day variability consistent with tight environmental control. Continuous and pulsed wave modes were proved equally and highly reliable for measuring minute distance of aortic flow. However, continuous wave Doppler ultrasound provided acceptable signals more frequently than did the pulsed wave technique. For continuous wave Doppler ultrasound, R was 0.87 (p less than 0.00001); the 95% confidence interval was +/- 1.81 m/min (or 11% of the mean of all measurements), which indicates that this method can be used in a single individual to detect a greater than 11% change in minute distance measured once before and after an intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

1,25-dihydroxyvitamin D3 modulates growth of vascular smooth muscle cells.

We examined the effects of 1,25-dihydroxyvitamin D3(1,25-(OH)2D3) on the proliferation of vascular smooth muscle (VSM) cells. Receptors for 1,25-(OH)2D3 were demonstrated in fresh rabbit aortic tissue and in cultured rat VSM using binding of [3H]-1,25-(OH)2D3 in sucrose density gradients of the tissue or cell homogenates. The receptor sedimented at 3.6 S, the sedimentation velocity of 1,25-(OH)2D3 receptors from other sources. 1,25-(OH)2D3 dramatically altered the growth of VSM, but this effect depended importantly on the basal conditions in which the cells were grown. In quiescent VSM deprived of serum for 72 h, 1,25-(OH)2D3 (0.1-10 nM), but not 25-(OH)D3 (up to 100 nM) increased thymidine incorporation up to 12-fold and cell number up to 2.6-fold compared with controls. The maximal effect of 1,25-(OH)2D3 on thymidine incorporation was similar to the maximal effect of the growth factors alpha-thrombin or PDGF. Furthermore, the effects of 1,25-(OH)2D3 and thrombin on thymidine incorporation in quiescent cells were markedly synergistic, yielding a 78-fold increase in thymidine incorporation when both agents were added simultaneously. In "nonquiescent cells" which were exposed to serum-free medium for only 24 h, 1,25-(OH)2D3 (10 nM) also increased DNA synthesis 10-fold compared with controls. However, in striking contrast to what was observed in quiescent cells, 1,25-(OH)2D3 diminished the mitogenic response to thrombin by as much as 50% in nonquiescent cells. 1,25-(OH)2D3 also modulated the transcription of c-myc in response to thrombin. In quiescent cells, transcription was enhanced by 1,25-(OH)2D3, whereas in nonquiescent cells, thrombin-induced c-myc transcription was blunted. Thus, 1,25-(OH)2D3 is a potent modulator of the growth of cultured VSM. The direction of this modulation depends strongly on the conditions under which the cells are cultured.

Animals↗
PubMed1991

Pathogenesis of secondary hyperparathyroidism in chronic renal insufficiency.

Hyperparathyroidism is recognized to be an invariable complication of chronic renal insufficiency. Biochemical and/or histological evidence of hyperparathyroidism occurs in many patients with mild renal insufficiency (glomerular filtration rate of 50-75 ml/min) and predictably so when the glomerular filtration rate is less than 40-50 ml/min. A reduction in the serum concentration of 1,25-dihydroxyvitamin D, the biologically active metabolite of vitamin D, can contribute to the pathogenesis of the hyperparathyroidism, at least in part, by decreasing gut absorption of calcium and by increasing the set point for calcium suppression of parathyroid hormone release. In patients with mild and moderate renal insufficiency, both the serum concentration of 1,25-dihydroxyvitamin D and that of immunoreactive parathyroid hormone are importantly determined by the dietary intake of phosphorus. The pathogenesis of secondary hyperparathyroidism in patients with severe renal insufficiency is complex and multifactorial.

Calcitriol↗
PubMed1990

Dietary potassium influences kidney maintenance of serum phosphorus concentration.

In studying the metabolic effects of diet potassium (K+) variation in normal humans, we noted that varying diet K+ within its normal range influenced inorganic phosphorus (Pi) homeostasis and serum calcitriol (1,25-dihydroxyvitamin D) levels. In six men who ingested a constant whole-foods diet containing (per 70 kg body wt) 27 mmol/day Pi and 52 mEq/day K+, we increased diet K+ to 156 mmol/day with supplements first of potassium bicarbonate (KHCO3) alone and then of potassium chloride (KCL) alone, each for eight days interrupted by an eight-day recovery period of no K+ supplement. Urine Pi decreased promptly with either K(+)-salt, each inducing a persisting retention of 7 to 10 mmoles Pi, which was dumped during recovery. Fasting serum [Pi] increased with either K+ supplement (P = 0.022, repeated measures analysis of variance); the composite mean serum [Pi] for the two K(+)-supplement periods exceeded that for the two periods without supplements (P less than 0.01, paired t-test). Conversely, the concentrations of serum calcitriol decreased with either K+ supplement (P = 0.020). Among subjects, the diet K(+)-induced increases in serum [Pi] correlated with those in plasma [K+] (r = 0.64, P = 0.027); the decreases in serum calcitriol concentration correlated with the increases in serum [Pi] (r = -0.69, P = 0.014). There were no significant differences among periods in serum parathyroid hormone, ionized calcium, urine cyclic AMP excretion, plasma renin activity, body weight, serum albumin, or creatinine clearance; plasma volume decreased slightly during KCL but not during KHCO3 periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Sodium-calcium interactions and salt-sensitive hypertension.

In humans with essential hypertension, salt-induced increases in blood pressure have been reported to correlate directly with salt-induced increases in intracellular free calcium [( Ca2+]i) in circulating mononuclear cells. These findings are consistent with the hypothesis that salt-induced increases in [Ca2+]i mediate the phenomenon of salt sensitivity. Circumstantial evidence suggests that salt-induced increases in intracellular sodium or in plasma levels of 1,25-dihydroxy vitamin D might mediate salt-induced increases in [Ca2+]i and blood pressure. However, in humans with salt-sensitive hypertension, it remains to be determined: (1) whether salt-induced increases in white blood cell [Ca2+]i reflect corresponding increases in vascular smooth muscle [Ca2+]i; (2) whether salt-induced increases in [Ca2+]i are a cause or consequence of salt-induced increases in blood pressure; and (3) whether salt-induced increases in 1,25-dihydroxy vitamin D or intracellular sodium precede salt-induced increases in [Ca2+]i.

Calcitriol↗
PubMed1990

Fine needle aspiration and frozen section of salivary gland lesions.

This report examines the role of fine needle aspiration (FNA) and frozen section (FS) examination in the management of salivary gland lesions, and is based on a review of 58 cases. FNA specimens were first classified as nonneoplastic, or as benign or malignant neoplasms. Identification of specific morphologic type of neoplastic lesions was attempted. Overall accuracy for assigning cases was 86%. Specific accuracy (histologic type of neoplasms predicted by FNA) was 72%. No inflammatory lesion was incorrectly diagnosed as neoplasm. Eight patients with histologically documented neoplasm had aspirates classified as nonneoplastic because the sample obtained was not representative. These data indicate that FNA is a highly specific method for identifying benign and malignant neoplasms. Applications of salivary gland FNA include (1) identification of nonneoplastic lesions that may respond to nonsurgical management, (2) identification of neoplasms that represent lymph node metastases rather than primary lesions of the salivary gland, (3) preliminary identification of lymphomas, and (4) preliminary separation of benign and malignant neoplasms.

Biopsy, Needle↗
PubMed1990

Production and metabolic clearance of 1,25-dihydroxyvitamin D in men: effect of advancing age.

To determine whether aging alters the metabolism of 1,25-dihydroxyvitamin D [1,25-(OH)2D] in men, we measured the serum concentrations, MCRs, and production rates of 1,25-(OH)2D in healthy old (age, 72 +/- 5 yr; n = 9) and young men (age, 34 +/- 5 yr; n = 9) consuming a constant metabolic diet and in whom the glomerular filtration rate was greater than 1.2 mL/s.1.73 m-2. The results indicate that when dietary calcium and phosphorus are normal and glomerular filtration rate is not reduced, the serum concentrations, MCRs, and production rates of 1,25-(OH)2D in old men [83 +/- 22 pmol/L; 0.62 +/- 0.10 mL/s.70 kg ideal BW (IBW); 51 +/- 12 fmol/s.70 kg IBW, respectively] and young men (90 +/- 20 pmol/L; 0.56 +/- 0.09 mL/s.70 kg IBW; 52 +/- 13 fmol/s.70 kg IBW, respectively) are equivalent. Indices of serum PTH, however, were elevated in the elderly men. These results suggest that aging per se has little or no effect on the serum concentration, MCR, or production rate of 1,25-(OH)2D in men. Maintenance of a normal production rate of 1,25-(OH)2D in elderly men, however, may require increased circulating PTH. Most observed declines in serum 1,25-(OH)2D in elderly men are probably a consequence of decreased functional renal mass.

Adult↗
PubMed1990

Normal diet NaCl variation can affect the renal set-point for plasma pH-(HCO3-) maintenance.

In humans who are ingesting abundant NaCl, blood pH (pHb) and plasma bicarbonate concentration [HCO3-)p) change little or imperceptibly in response to the ingestion of alkali salts. We tested the hypothesis that such tight homeostatic regulation is an artifact of eating a culturally imposed NaCl-enriched diet, not a fundamental physiological trait of humans. In five normal men ingesting a constant acid-producing diet with a low intrinsic NaCl content (0.15 mEq/kg of body weight per day), we measured plasma and urine acid-base composition during four 7-day periods in which the diet was supplemented as follows: no supplements----NaHCO3 only----NaHCO3 plus NaCl----NaCl only. Each sodium supplement was 2.0 mmol/kg body weight per day. With no supplements, pHb was 7.43 +/- 0.005 and (HCO3-)p was 25.0 +/- 0.4 mEq/L. When NaHCO3 only was added, pHb rose 0.02 (to 7.45 +/- 0.004; P less than 0.01) and (HCO3-)p rose nearly 4 mEq/L (to 28.9 +/- 0.6 mEq/L, P less than 0.001). The rise in (HCO3-)p was sustained predominantly by an increased rate of renal bicarbonate reabsorption. When NaCl was added, (HCO3-)p returned to the earlier level, despite continued NaHCO3 supplementation (24.9 +/- 0.6 mEq/L), and remained there when NaHCO3 supplementation was subsequently stopped (24.1 +/- 0.5 mEq/L). Thus, tight homeostatic regulation of plasma acid-base composition in response to a change in dietary base occurred only when dietary NaCl was abundant. To our knowledge, this is the first study in normal humans that demonstrates that diet NaCl variations within the normal range significantly influence plasma acid-base composition.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1990

Calcitonin gene-related peptide levels are elevated in patients with sepsis.

Calcitonin gene-related peptide (CGRP), an endogenous vasoactive peptide encoded by the calcitonin gene in nerve cells, is distributed throughout the cardiovascular system and is a potent vasodilator. Plasma levels of CGRP have been elevated in animal models with sepsis. This study was designed to determine whether plasma CGRP levels are elevated in patients with sepsis and perhaps contribute to the hyperdynamic cardiovascular state in sepsis. Plasma CGRP levels were obtained from normal healthy volunteers and from patients with sepsis. Volunteers were afebrile and had normal pulse and blood pressure. Patients with sepsis were selected according to the following criteria: (1) temperature higher than 38.5 degrees C, (2) white blood count greater than 14,000/ml, (3) positive blood culture of bacterial organisms, (4) hemodynamic parameters consistent with hyperdynamic sepsis, and (5) negative history of thyroid or other endocrine abnormalities. CGRP was extracted and assayed by radioimmunoassay for iodine 125-labeled human CGRP. In patients with sepsis, the cardiac index was 5.4 +/- 0.5 L/min/m2 (normal, 3.0); systemic vascular resistance was 7.1 +/- 0.5 mm Hg/L/min (normal, 16); oxygen delivery was 1496 +/- 137 ml/min (normal, 1000). Plasma CGRP levels were significantly elevated in the patients with sepsis, 14.9 +/- 3.2 pg/ml, compared to plasma CGRP levels in control volunteers, 2.0 +/- 0.3 pg/ml (p less than 0.0005). These elevated levels of CGRP may contribute to the decreased vascular resistance and increased cardiac output in the hyperdynamic septic state.

Adult↗
PubMed1989

Effects of vegetation, a clay cap and environmental variables on 222Rn fluence rate from reclaimed U mill tailings.

We measured 222Rn fluence rate and several environmental variables on two plots with U mill tailings buried beneath 30 cm of overburden and 20 cm of topsoil. An additional 30 cm of clay covered the tailings on one plot and each plot was subdivided into bare soil and vegetated subplots. We used linear correlation, two-way ANOVA and stepwise multiple regression to analyze the effects of the plot characteristics and the environmental variables on 222Rn fluence rate. The most important effect on 222Rn fluence rates from these plots was the combination of a clay cap and a vegetated surface. The mean annual fluence rate from the plot having both of these characteristics (520 +/- 370 mBq m-2 s-1) was over three times that of the vegetated plot without a clay cap (170 +/- 130 mBq m-2 s-1) and 18 times that of the bare plot with a clay cap (29 +/- 13 mBq m-2 s-1). The interaction effect may have been due to the growth of roots in the moist clay and active transport of dissolved 222Rn to the surface in water. This speculation is supported by the observation that on vegetated plots with a clay cap, moisture in the clay enhanced the fluence rate.

Air Pollutants↗
PubMed1989

The Zucker fatty rat as a genetic model of obesity and hypertension.

The association of hypertension with obesity has long been recognized; however, because of the lack of suitable animal models of obesity and hypertension, the pathogenesis of the high blood pressure associated with obesity remains poorly understood. We hypothesized that the Zucker fatty rat, a widely studied model of obesity and insulin resistance, might also be characterized by hypertension. Mean arterial pressure directly measured in the unanesthetized, unrestrained obese (fatty) Zucker rat was significantly greater than in two strains of nonobese control rats, the lean Zucker rat and the Lewis rat. The greater blood pressure in the obese rats was not dependent on hyperphagia or increased body weight per se since moderate caloric restriction, achieved by pair-feeding with lean rats, decreased weight gain but did not attenuate hypertension. Pair-fed obese rats retained less sodium than lean control rats, suggesting that greater blood pressure in the obese rats is not a consequence of increased renal retention of sodium. A unique feature of the Zucker strain is that the increased blood pressure appears to be specifically associated with the obese genotype. The findings suggest that the obese Zucker rat might provide a useful experimental model of obesity and hypertension.

Animals↗
PubMed1989

Physiologic regulation of the serum concentration of 1,25-dihydroxyvitamin D by phosphorus in normal men.

We asked this question: in normal humans, is either a normal dietary intake or normal serum concentration of phosphorus a determinant of the serum concentration of 1,25(OH)2D? In seven normal men whose dietary phosphorus was decreased from 2,300 to 625 mg/d, each intake for 8-9 d, under strictly controlled, normal metabolic conditions, we measured serum concentrations of 1,25(OH)2D daily, and concentrations of phosphorus hourly throughout a 24-h period, before and after restriction. Decreasing dietary phosphorus induced: (a) a 58% increase in serum levels of 1,25(OH)2D; (b) a 35% decrease in serum levels of phosphorus measured in the afternoon; (c) a 12% decrease in the 24-h mean serum level of phosphorus; but, (d) no decrease in morning fasting levels of phosphorus. Serum concentrations of 1,25(OH)2D varied inversely and significantly with 24-h mean concentrations of phosphorus (r = -0.77, P less than 0.001). When these data are combined with those of our prior study in which dietary phosphorus was varied over an extreme range, the relationship between serum levels of 1,25(OH)2D and 24-h mean serum levels of phosphorus is even stronger (r = -0.90, P less than 0.001). In the aggregate, the results demonstrate that in normal men, dietary phosphorus throughout a normal range and beyond, can finely regulate the renal production and serum concentration of 1,25(OH)2D, and provide evidence that this regulation is mediated by fine modulation of the serum concentration of phosphorus.

Adult↗
PubMed1989

Endothelin-induced increases in vascular smooth muscle Ca2+ do not depend on dihydropyridine-sensitive Ca2+ channels.

Endothelin is a potent mammalian vasoconstrictive peptide with structural homology to cation channel-binding insect toxins. We tested the proposal that this peptide directly activates dihydropyridine-sensitive Ca2+ channels in cultured vascular smooth muscle (VSM) cells. First, we found that cell Ca2+ can be altered in VSM by activation of voltage-operated Ca2+ channels. KCl-induced depolarization and the dihydropyridine Ca2+ channel agonist (-) Bay K 8644 (10 microM) both raised cell Ca2+ more than twofold; the effect of KCl was blocked by the inhibitory enantiomer, (+) Bay K 8644 (40 microM). Similar responses were observed in Chinese hamster ovary (CHO) cells. Synthetic endothelin (4 x 10(-8) M) raised Ca2+ in VSM but not CHO cells from 100 +/- 17 to 561 +/- 34 nM within 12 s. Ca2+ subsequently fell to basal levels after 30 min. Half maximal Ca2+ response was at 4 x 10(-9) M endothelin. Unlike endothelin, thrombin raised Ca2+ in both VSM and CHO cells. The Ca2+ responses to endothelin and thrombin were not affected by nicardipine (1 microM), (+) Bay K 8644, or Ca2+-free solutions. Lastly, both hormones caused release of inositol phosphates in VSM cells. However, the response to thrombin was more than 10-fold larger and was more rapid than the response to endothelin; the thrombin response was sensitive to pertussis toxin, while the response to endothelin was not. Thus endothelin, like thrombin, raises cell Ca2+ in VSM by mobilization of intracellular stores and not by activation of dihydropyridine-sensitive Ca2+ channels. However, their receptors are distinct and they exhibit important differences in signal transduction.

Animals↗
PubMed1988

Criterion-related versus non-criterion-related prompt training with severely mentally handicapped children.

Thirty-three severely mentally handicapped children were involved in a study to evaluate the effectiveness of three training programmes in teaching visual discriminations. Three matched sets of subjects each received both a size and an intensity discrimination with either: (1) size prompting; (2) intensity prompting; or (3) no prompting (trial-and-error training). The prompted groups therefore received both criterion-related (CR) and non-criterion-related (NCR) training. Order of presentation of the discriminations was counterbalanced across subjects. There was a significant main effect of training group with both size and intensity prompting groups making significantly fewer errors than the trial-and-error group (P less than 0.05 in both cases), but not differing significantly from each other. Significant linear trends for increasing errors across CR, NCR and trial-and-error training programmes were found for both the size discrimination (P less than 0.01), and intensity discrimination (P less than 0.05). More children acquired the discriminations when trained with a CR prompt than with a NCR prompt or trial-and-error procedure, and all four children who failed to acquire discriminations with NCR prompts subsequently acquired them when trained with a CR programme. The results are discussed in relation to cue discriminability and theoretical explanations involving overshadowing are considered.

Adolescent↗
PubMed1987

"Salt-sensitive" essential hypertension in men. Is the sodium ion alone important?

We investigated whether the anionic component of an orally administered sodium salt can influence the salt's capacity to increase blood pressure. In five men with essential hypertension in whom blood pressure was normal with restriction of dietary sodium chloride to 10 mmol per day (0.23 g of sodium per day), oral administration of sodium chloride for seven days, 240 mmol per day (5.52 g of sodium per day), induced significant increases in systolic and diastolic blood pressures, of 16 +/- 2 and 8 +/- 2 mm Hg (mean +/- SEM), respectively (P less than 0.05). An equimolar amount of sodium given as sodium citrate induced no change in blood pressure. Replacing supplemental sodium chloride with an equimolar amount of sodium as sodium citrate abolished the increase in blood pressure induced by sodium chloride. Both salts induced substantial and comparable sodium retention, weight gain, and suppression of plasma renin activity and plasma aldosterone, but supplemental sodium chloride increased plasma volume and urinary excretion of calcium, whereas sodium citrate did not. These preliminary findings demonstrate that the anionic component of an orally administered sodium salt can influence the ability of that salt to increase blood pressure, possibly by determining whether the salt induces an increase in plasma volume. Our observations in a small group of men with salt-sensitive hypertension will require confirmation in larger numbers of patients of both sexes.

Aged↗
PubMed1987

Pancreatitis and alcoholism disorder the renal tubule and impair reclamation of some low molecular weight proteins.

We sought to determine whether the clinical setting in which pancreatitis occurs affects the incidence and distribution of increased values of renal clearance of amylase relative to creatinine, CAm/CCr, and whether the increased values reflect a tubular disorder that impairs renal reclamation of certain low molecular weight proteins. We measured the renal clearance of three low molecular weight proteins (amylase, beta 2-microglobulin, and lysozyme) and urinary excretion of three lysosomal enzymes that originate from the renal tubule in three groups of patients (alcoholic pancreatitis, pancreatitis without alcoholism, and alcoholism without pancreatitis). When compared to normal controls, the mean CAm/CCr was significantly elevated in alcoholic pancreatitis (p less than 0.05) but not in equally severe pancreatitis without alcoholism nor in alcoholism without pancreatitis. The clearance ratio of beta 2-microglobulin was significantly increased in each of the three patient groups; mean clearance ratio of lysozyme was not significantly increased in any of the patient groups. Excretion of each of the three lysosomal enzymes was significantly increased in each of the patient groups. We conclude that the etiology of pancreatitis affects the distribution of values for CAm/CCr, impaired tubular reclamation of amylase is the mechanism of the increase in CAm/CCr, and a factor or factors associated with both pancreatitis and with alcoholism per se appear to disorder the renal tubule and to impair tubular reclamation of some but not all low molecular weight proteins-a novel finding of considerable potential significance.

Acetylglucosaminidase↗