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Biomedical subjects

R C Morris

Publications and source records attributed to R C Morris.

At least 19 recordsLinked to original sources
PubMed1995

Activation of transfer RNA-guanine ribosyltransferase by protein kinase C.

Transfer RNA-guanine ribosyltransferase (TGRase) irreversibly incorporates queuine into the first position in the anticodon of four tRNA isoacceptors. Rat brain protein kinase C (PKC) was shown to stimulate rat liver TGRase activity. TGRase preparations derived from rat liver have been observed to decrease in activity over time in storage at -20 or -70 degrees C. Contamination of the samples by phosphatases was indicated by a p-nitrophenylphosphate conversion test. The addition of micromolar concentrations of the phosphatase inhibitors sodium pyrophosphate and sodium fluoride into TGRase isolation buffers resulted in a greater return of TGRase activity than without these inhibitors. Inactive TGRase preparations were reactivated to their original activity with the addition of PKC. In assays combining both TGRase and PKC enzymes, inhibitors of protein kinase C (sphingosine, staurosporine, H-7 and calphostin C) all blocked the reactivation of TGRase, whereas activators of protein kinase C (calcium, diacylglycerol and phosphatidyl serine) increased the activity of TGRase. None of the PKC modulators affected TGRase activity directly. Alkaline phosphatase, when added to assays, decreased the activity of TGRase and also blocked the reactivation of TGRase with PKC. Denaturing PAGE and autoradiography was performed on TGRase isolates that had been labelled with 32P by PKC. The resulting strong 60 kDa band (containing the major site for phosphorylation) and weak 34.5 kDa band (containing the TGRase activity) are suggested to associate to make up a 104 kDa heterodimer that comprises the TGRase enzyme. This was corroberated by native and denaturing size-exclusion chromatography. These results suggest that PKC-dependent phosphorylation of TGRase is tied to efficient enzymatic function and therefore control of the queuine modification of tRNA.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

Improved mineral balance and skeletal metabolism in postmenopausal women treated with potassium bicarbonate.

BACKGROUND: In normal subjects, a low level of metabolic acidosis and positive acid balance (the production of more acid than is excreted) are typically present and correlate in degree with the amount of endogenous acid produced by the metabolism of foods in ordinary diets abundant in protein. Over a lifetime, the counteraction of retained endogenous acid by base mobilized from the skeleton may contribute to the decrease in bone mass that occurs normally with aging. METHODS: To test that possibility, we administered potassium bicarbonate to 18 postmenopausal women who were given a constant diet (652 mg [16 mmol] of calcium and 96 g of protein per 60 kg of body weight). The potassium bicarbonate was given orally for 18 days in doses (60 to 120 mmol per day) that nearly completely neutralized the endogenous acid. RESULTS: During the administration of potassium bicarbonate, the calcium and phosphorus balance became less negative or more positive--that is, less was excreted in comparison with the amount ingested (mean [+/- SD] change in calcium balance, +56 +/- 76 mg [1.4 +/- 1.9 mmol] per day per 60 kg; P = 0.009; change in phosphorus balance, +47 +/- 64 mg [1.5 +/- 2.1 mmol] per day per 60 kg; P = 0.007) because of reductions in urinary calcium and phosphorus excretion. The changes in calcium and phosphorus balance were positively correlated (P < 0.001). Serum osteocalcin concentrations increased from 5.5 +/- 2.8 to 6.1 +/- 2.8 ng per milliliter (P < 0.001), and urinary hydroxyproline excretion decreased from 28.9 +/- 12.3 to 26.7 +/- 10.8 mg per day (220 +/- 94 to 204 +/- 82 mumol per day; P = 0.05). Net renal acid excretion decreased from 70.9 +/- 10.1 to 12.8 +/- 21.8 mmol per day, indicating nearly complete neutralization of endogenous acid. CONCLUSIONS: In postmenopausal women, the oral administration of potassium bicarbonate at a dose sufficient to neutralize endogenous acid improves calcium and phosphorus balance, reduces bone resorption, and increases the rate of bone formation.

Aged↗
PubMed1994

Mesenteric defects as a cause of intestinal volvulus without malrotation and as the possible primary etiology of intestinal atresia.

Mesenteric defects can lead to intestinal volvulus even when the midgut is normally rotated. There are two types of mesenteric defects: basilar, in which the entire base of the mesentery is involved, and segmental, in which only an isolated portion of the mesentery is affected. These defects can present at any age, and the clinical symptoms depend on the extent of the disease and the amount of intestine involved in the volvulus. In the newborn, the basilar defects have clinical signs and symptoms similar to those of midgut volvulus secondary to malrotation. Similar to midgut volvulus secondary to malrotation, this is a surgical emergency. In older patients, basilar defects can be misdiagnosed because of the normal placement of the ligament of Treitz and because of failure to consider mesenteric defects as a possible cause. The treatment for basilar mesenteric defects is intestinal fixation. Intestinal volvulus secondary to segmental defects always presents as intestinal obstruction. In the newborn, these lesions may be indistinguishable from intestinal atresia. Older children present with intestinal obstruction of an unknown cause. Resection of the affected intestine is the treatment for segmental mesenteric defects. Intestinal mesenteric abnormalities as a cause of intestinal atresia unifies under one etiology all the lesions observed in intestinal atresia. Although this theory does not rule out other causes of intestinal atresia, intestinal mesenteric defects may be the primary condition under which intestinal atresia occurs.

Child↗
PubMed1994

Soil permeability as a function of vegetation type and soil water content.

Soil permeability is important for estimating the rate of mass transport of 222Rn through soils and into basements (Nazaroff 1992). We measured permeability and soil water content on a set of nine plots consisting of three plots vegetated with common barley (Hordeum vulgare), three plots vegetated with Russian thistle (Salsola kali), and three bare plots. Soil moisture was consistently highest on the bare plots and lowest on the Russian thistle plots. Plots with vegetation had lower soil water content during the growing season. Permeability was consistently higher on Russian thistle plots. ANOVA showed that both soil water content and presence of Russian thistle had a significant impact on permeability but that presence of barley did not. The effect of vegetation and moisture on permeability may have significant effects on 222Rn transport in soils.

Permeability↗
PubMed1994

Genetic contamination of Dahl SS/Jr rats. Impact on studies of salt-sensitive hypertension.

The Dahl salt-sensitive rat (SS/Jr) is a widely used animal model of salt-sensitive hypertension. SS/Jr rats are believed to be highly inbred and uniformly sensitive to the hypertensinogenic effects of sodium chloride, but we have recently observed that SS/Jr rats from Harlan Sprague Dawley, Inc, exhibit considerable variability in their blood pressure response to supplemental dietary salt. To test the possibility that commercially available SS/Jr rats are genetically contaminated and therefore no longer fully inbred, we performed molecular genetic studies and blood pressure measurements in several groups of SS/Jr rats purchased from Harlan Sprague Dawley. We found molecular evidence of heterozygosity and/or atypical allelic variants involving loci on at least five different chromosomes. Many of the rats also failed to exhibit a salt-sensitive blood pressure phenotype. We conclude that SS/Jr rats being sold by the only commercial vendor of Dahl rats in the United States are genetically contaminated and resistant to the hypertensinogenic effects of salt. These findings raise serious questions about the interpretation of research conducted with SS/Jr rats obtained from Harlan Sprague Dawley.

Animals↗
PubMed1993

Mirror image reversal: is what we see what we present?

Many psychological explanations have been advanced to explain left-right reversal in mirror images, but Gregory and Haig have each proposed a physical explanation for the reversal: the first is based upon the physical rotation used to present the surface of the object to the mirror, and the second on the classical optics of reflection. These physical explanations are considered together with an explanation based on object symmetry. The apparent reversal of directional coordinates (eg left and right) that occurs in the mirror images of most objects is distinguished from reversals achieved by physical or mental rotation. It is also distinguished from the object-image match that can be achieved by mental or physical rotation of some symmetrical objects. It is concluded that the left-right reversal is not specifically optical, but is determined by multiple factors, including object symmetry, the conventional and gravitational positioning of top and bottom and back and front, and our greater familiarity with right-left than with top-bottom or back-front reversals.

Attention↗
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↗