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Biomedical subjects

R C Morris

Publications and source records attributed to R C Morris.

At least 37 records · Page 2Linked to original sources

Shadows and depth illusions.

The visual system uses shadows to compute perceived depth of features on an uneven surface, and in doing so makes the assumption of a single light source in most circumstances. Three illusory depth effects are described (depth reversal, accentuation, and flattening) that can be demonstrated with 3-D materials, and all of which are based on the single-source assumption. Ambiguous lighting conditions may produce moment-to-moment depth reversals and/or the subjective sensation of textural 'strangeness'. It is suggested that these are both subjective experiences which occur when the system cannot compute depth with certainty.

Cues↗

Effect of aging on the metabolism of phosphorus and 1,25-dihydroxyvitamin D in healthy men.

We tested the hypothesis that aging alters physiological regulation of the serum concentration of 1,25-dihydroxyvitamin D [1,25(OH)2D] by inorganic phosphorus. In seven elderly men [age 71 +/- 1 (SE) yr] and 9 young men (29 +/- 2 yr), dietary phosphorus was first normal, then increased and decreased within its normal range. At each intake of phosphorus, serum concentrations of 1,25(OH)2D in the elderly did not differ from those in young men, but fasting and 24-h mean serum concentrations of phosphorus were lower in elderly men. With phosphorus restriction, in each group serum 1,25(OH)2D increased by 47%, and 24-h mean serum phosphorus decreased by 0.6 +/- 0.1 mg/dl. Serum concentrations of 1,25(OH)2D varied inversely with 24-h mean serum phosphorus (R= -0.92, P<0.0001). Thus, in healthy elderly men in whom glomerular filtration rate is normal or near normal, serum concentrations of 1,25(OH)2D increase when dietary phosphorus is restricted; the magnitude of response at steady state is unaffected by aging, but the time course of response is delayed. At any level of serum phosphorus, serum 1,25(OH)2D is lower than that in young men, as reflected by a lower intercept of regression of serum 1,25(OH)2D on 24-h mean phosphorus.

Adult↗

Effect of age on blood acid-base composition in adult humans: role of age-related renal functional decline.

In 64 apparently healthy adult humans (ages 17-74 yr) ingesting controlled diets, we investigated the separate and combined effects of age, glomerular filtration rate (GFR, index of age-related renal functional decline), renal net acid excretion [NAE, index of endogenous acid production (EAP)], and blood PCO2 (PbCO2, index of respiratory set point) on steady-state blood hydrogen ion ([H+]b) and plasma bicarbonate concentration ([HCO3-]p). Independent predictors of [H+]b and [HCO3-]p were PbCO2, NAE, and either age or GFR, but not both, because the two were highly correlated (inversely). [H+]b increased with increasing PbCO2, NAE, and age and with decreasing GFR. [HCO3-]p decreased with increasing NAE and age but increased with increasing PbCO2 and GFR. Age (or GFR) at constant NAE had greater effect on both [H+]b and [HCO3-]p than did NAE at constant age (or GFR). Neither PbCO2 nor NAE correlated with age or GFR. Thus two metabolic factors, diet-dependent EAP and age (or GFR), operate independently to determine blood acid-base composition in adult humans. Otherwise healthy adults manifest a low-grade diet-dependent metabolic acidosis, the severity of which increases with age at constant EAP, apparently due in part to the normal age-related decline of renal function.

Acid-Base Equilibrium↗

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↗

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↗

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↗

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↗

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↗

Differential modulation of fos and jun gene expression by 1,25-dihydroxyvitamin D3.

1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) modulates the mitogenic response to alpha-thrombin either positively or negatively in vascular smooth muscle (VSM) cells depending upon the time at which cells are exposed to 1,25-(OH)2D3. We now examine the impact of 1,25-(OH)2D3 on the induction by alpha-thrombin of c-jun and c-fos mRNA. When 1,25-(OH)2D3 and alpha-thrombin were added simultaneously to rat VSM cells, c-jun expression was enhanced by five-fold compared to cells exposed to thrombin alone. However, when cells were exposed to 1,25-(OH)2D3 for 48h prior to thrombin, c-jun expression after alpha-thrombin was reduced to less than 25% of the level in cells exposed to thrombin alone. c-fos expression after alpha-thrombin was unaffected by 1,25-(OH)2D3. Thus 1,25-(OH)2D3 dramatically alters the ratio of jun/fos mRNA produced during the mitogenic response and may thus modulate the response to mitogens.

Animals↗

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↗

The role of diagnostic laparoscopy in the management of trauma patients: a preliminary assessment.

This study evaluated the role and advantages of diagnostic laparoscopy (DL) compared with diagnostic peritoneal lavage (DPL) in 75 trauma patients who were prospectively studied with DL followed by DPL. Of these, 59 patients had blunt injuries and 16 stab wounds. Seventy patients (93%) had the procedures performed in the emergency department (ED); 41 (59%) of these were awake and under local anesthesia. Forty-two patients had negative DPL and DL results with no subsequent sequelae. Twenty-three patients had negative DPL results and abnormal DL results. Of these, 20 were managed nonsurgically, and three (DPL < 10,000 RBC) underwent surgery based solely on DL findings of diaphragmatic lacerations from stab wounds. These were repaired. All 23 had an uneventful course. Three patients had positive DPL and insignificant DL findings. Laparotomy and DL findings correlated. A splenectomy for iatrogenic injury unrelated to DL and two nontherapeutic laparotomies were performed. Seven patients demonstrated both positive DPL and significant DL findings, and all had therapeutic laparotomies. Management based on DL rather than DPL would potentially have improved care in 8% of cases (6 of 75). Reliance on DL improved care in 19% (3 of 16) of patients with stab wounds and possibly could have in 3% (2 of 59) of those with blunt injuries. Management using DL would have potentially improved care in 30% (3 of 10) of patients with positive DPL findings and 5% (3 of 65) with negative DPL findings. Diagnostic laparoscopy can be performed safely in stable patients under local anesthesia in the ED. It offers no advantage over DPL as a primary assessment tool in blunt trauma. It does have advantages in the management of stab wounds. Diagnostic laparoscopy has a role in redefining DPL criteria for laparotomy and, in selected patients, as an adjunct to DPL, allowing further diagnosis and potentially the treatment of injuries without laparotomy.

Abdominal Injuries↗

Potassium preserves endothelial function and enhances aortic compliance in Dahl rats.

It has recently been proposed that in rat models of genetic hypertension, supplemental dietary potassium preserves release of endothelium-derived relaxing factor independently of its capacity to either attenuate hypertension or increase plasma potassium. To test this hypothesis in Dahl salt-sensitive rats given sodium chloride (4%) for 3 weeks, we supplemented dietary potassium (2.1%) with either KCl (n = 16) or KHCO3 (n = 16). Compared with unsupplemented rats (n = 16), rats supplemented with either potassium salt had a lower mean arterial pressure and a greater release of endothelium-derived relaxing factor, as assessed from acetylcholine-induced relaxation of precontracted aortic rings. However, the maximum relaxation response to acetylcholine correlated inversely with blood pressure (r = -.82, P < .001), not only in the KCl (r = -.68, P < .002) and KHCO3 (r = -.77, P < .001) groups but also in unsupplemented rats (r = -.86, P < .001). With potassium supplementation, plasma potassium concentrations measured between 4 and 6 PM did not increase, but those measured between 4 and 6 AM did increase (P < .05). In isolated ring segments, aortic compliance was greater in both the KCl and KHCO3 groups than in unsupplemented rats (0.015 and 0.017 vs 0.009 mm2/mm Hg) (P < .01). This greater compliance could not be related to differences in blood pressure, plasma potassium, or collagen or elastin content of the aortic wall.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

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↗

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↗

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↗

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↗