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Biomedical subjects

P Hsu

Publications and source records attributed to P Hsu.

At least 37 records · Page 2Linked to original sources
PubMed1995

Low CO2 stimulates inositol phosphate turnover and increased inositol 1,4,5-trisphosphate levels in piglet cerebral microvascular smooth muscle cells.

In contrast to hypercapnic dilation, hypocapnia-induced cerebral vasoconstriction does not involve prostanoids in newborn pigs. The hypothesis that increased pH or decreased CO2 tension increases inositol phosphate turnover in piglet cerebral microvascular smooth muscle (SM) cells was addressed to begin to assess the possibility that this second-messenger system is involved in hypocapnia-induced cerebral vasoconstriction. Cerebral microvascular SM cells in primary culture prelabeled with [3H]-myoinositol were stimulated for 30 sec with artificial cerebrospinal fluid of increased or normal pH, (7.80 vs 7.40), constant PCO2 36 mm Hg. Following extraction from cells, radiolabeled inositol phosphates were separated by HPLC. These metabolic alkalosis studies were repeated using an inositol 1,4,5-trisphosphate (Ins[1,4,5]P3 protein-binding assay (PBA). Respiratory alkalosis using aCSF with pH 7.60, PCO2 20 mm Hg versus control pH 7.40, PCO2 36 mm Hg was similarly tested with PBS measurement of Ins(1,4,5)P3. aCSFs of control pH 7.40, and PCO2s of 70, 36, or 25 mm Hg were studied both by [3H]-myoinositol (HPLC) and PBA to further determine the importance of CO2 tension, in the presence of fixed pH, on Ins(1,4,5)P3 production. When PCO2 was constant, inositol phosphate turnover (as measured by [3H]-Ins[1,4,5]P3 accumulation) increased when pH was increased from 7.40 to 7.80 at 30 sec of stimulation. Mean [3H]-Ins(1,4,5)P3 accumulation at pHs of 7.40 and 7.80, constant PCO2 of 36 mm Hg, were 2.9 +/- 0.7 and 4.1 +/- 0.8 cpm/micrograms protein, respectively. Ins(1,4,5)P3 levels for pH of 7.40 or 7.80 and constant PCO2 of 36 mm Hg, were 25.4 +/- 1.8 and 38 +/- 8 pmol/well, respectively, by PBA. Respiratory alkalosis also increased Ins(1,4,5)P3 levels. For pH of 7.40, PCO2 36 mm Hg and pH 7.60, PCO2 20 mm Hg, Ins(1,4,5)P3 levels were 37.6 +/- 16 and 64.1 +/- 25 pmol/well, respectively. Decreasing CO2 tension (from 70 mm Hg to 25 mm Hg) in the presence of fixed pH 7.40 failed to increase Ins(1,4,5)P3 levels. The present data demonstrate that decreased CO2 tension stimulates an increase in Ins(1,4,5)P3 production in piglet cerebral microvascular smooth muscle cells. Increasing pH via lower PCO2 increases the level of Ins(1,4,5)P3 even more than increasing pH with fixed base, but extracellular pH appears to be important since decreased PCO2 without changing extracellular pH had no effect. We conclude that the inositol phosphate second messenger system in cerebral microvascular smooth muscle responds appropriately to acute alkalosis to be involved in hypocapnia-induced cerebral vasoconstriction.

Alkalosis, Respiratory↗
PubMed1995

Dilator prostanoid-induced cyclic AMP formation and release by cerebral microvascular smooth muscle cells: inhibition by indomethacin.

The effect of indomethacin on dilator prostanoid receptor-mediated cAMP formation was investigated using primary cultures of vascular smooth muscle cells from the newborn pig cerebral microvessels. Cerebral microvascular smooth muscle cells responded to dilator prostanoids (iloprost > PGE2) by increasing cAMP formation and release into the media (EC50 = 2 x 10(-8) M and 2 x 10(-7) M for iloprost and PGE2, respectively). Indomethacin inhibited iloprost- and PGE2-evoked increases in cAMP formation (IC50 = 10(-4) M) and release (IC50 = 10(-6) M) by microvascular smooth muscle cells (maximal inhibition 80-90%), whereas isoproterenol-induced cAMP formation was only slightly attenuated at the highest concentration of indomethacin used (10(-3) M). Aspirin was much less effective in inhibiting dilator prostanoid-induced cAMP formation and release by the cells. Direct analysis of prostacyclin receptor sites using [3H]iloprost as the ligand revealed saturable, high affinity (ED50 = 2 x 10(-8) M) and reversible binding to the membranes isolated from cerebrovascular smooth muscle cells. Indomethacin dose-dependently inhibited [3H]iloprost receptor binding (ID50 = 10(-4) M; maximal inhibition, 70%). The present data suggest that combination of highly effective inhibition of prostaglandin H synthase and receptor binding resulting in inhibition of dilator prostanoid-mediated cAMP formation in target cells may contribute to the increased efficacy of indomethacin compared with other prostaglandin H synthase inhibitors in blocking certain vasodilator responses associated with prostanoids.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

The dose-dependent effect of misoprostol on indomethacin-induced renal dysfunction in well compensated cirrhosis.

Misoprostol (200 micrograms) has been shown to acutely counteract the indomethacin-induced renal dysfunction in well compensated cirrhotic patients. The aim of this study was to determine if the prophylactic value of misoprostol was dose-dependent. Parameters of renal hemodynamics and tubular sodium and water handling were assessed by clearance techniques in 26 well compensated cirrhotic patients before and after an oral combination of 50 mg of indomethacin and various doses of misoprostol. The 200-micrograms dose was able to totally abolish the deleterious renal effects of indomethacin, whereas the 800-micrograms dose resulted in significant worsening of renal hemodynamics and sodium retention. These changes were maximal in the hour immediately after medications and slowly returned toward base-line levels thereafter. These results suggest that the renal protective effects of misoprostol is dose-dependent. However, until this apparent ability of 200 micrograms of misoprostol to prevent the adverse effects of indomethacin on renal function is confirmed with chronic frequent dosing, it would be prudent to avoid nonsteroidal anti-inflammatory therapy in patients with cirrhosis.

Diuresis↗
PubMed1994

Personal history, training, and worksite as predictors of back pain of nurses.

Back pain among nurses is a common problem. Prior studies of this problem have been based on cross-sectional or retrospective data. This 18-month prospective study involving nurses newly graduated from nursing school investigated personal, worksite, and training factors associated with future risk of back pain. Each nurse underwent a preliminary interview and periodic follow-ups to identify those with back injuries. Contingency tables and logistic regression analyses demonstrated that prior significant back pain episodes (evidenced by previous job changes because of back pain, frequent medication use, etc.) were associated with increased future risk. Training at nursing school or on the job did not have a protective effect. This pilot study therefore suggests factors useful in placement and counseling of new nurses and indicates the need for further implementation of mechanical lift assist device use.

Accidents, Occupational↗
PubMed1994

Renal response to a saline load in well-compensated alcoholic cirrhosis.

A total of 29 patients with well-compensated alcoholic cirrhosis and 9 healthy control subjects of similar age and sex were studied to assess their response to a challenge of 2 L of normal saline infused over a 1 hr period. Patients with cirrhosis had an adequate effective arterial blood volume in the basal state as assessed by neurohumoral markers of vascular filling. They also had a lower renal vascular resistance (p = 0.048) and a higher glomerular filtration rate (p = 0.014) than the controls, indicating the presence of renal vasodilation. Both groups were in sodium balance, but the patients with cirrhosis had a higher filtered load of sodium, an increased proximal tubular reabsorption of sodium (p = 0.015) and a decreased fractional excretion of sodium (p < 0.001). The administration of a saline load was not accompanied by any significant changes in the renal circulation in the patients with cirrhosis. They were unable to suppress their proximal tubular reabsorption of sodium to the same extent as the controls (p = 0.012), so by the fourth hour a significant difference in the rate of urinary excretion of sodium was evident. In the patients with cirrhosis, glomerular filtration rate before and after the saline load correlated significantly with indocyanine green extraction (r = 0.65; p = 0.002), whereas the tubular handling of sodium was dependent on antipyrine clearance (r = 0.80; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Dose-dependent effects of oral misoprostol on renal function in alcoholic cirrhosis.

BACKGROUND/AIMS: Prostaglandins are important modulators of renal physiology, particularly when the effective circulatory volume is decreased. The aim of this study was to determine the dose-dependent effects of an oral prostaglandin E1 analogue, misoprostol, on renal function in patients with well-compensated alcoholic cirrhosis. METHODS: Renal hemodynamics and tubular function were assessed by clearance techniques, before and after 100-microgram, 200-microgram, 400-microgram, or 800-microgram oral doses of misoprostol. RESULTS: Overall, the results indicate that low-dose misoprostol is vasodilatory, natriuretic, and diuretic whereas high-dose misoprostol increases renal vascular tone and inhibits sodium and water excretion. The 200-microgram dose produced a transient but significant increase in the glomerular filtration rate and effective renal plasma flow and a decrease in renal vascular resistance. Urinary volume and urinary sodium excretion increased and urinary osmolality decreased. CONCLUSIONS: The results suggest that, in patients with well-compensated cirrhosis, the renal effects of misoprostol are determined by a bell-shaped dose-response curve. The renal vasodilatory, natriuretic, and diuretic potential of 200-micrograms of misoprostol suggests that it may be of therapeutic value in patients with cirrhosis.

Administration, Oral↗
PubMed1994

Nifedipine: its effects on renal hemodynamics and sodium homeostasis in well-compensated alcoholic cirrhosis.

Following the administration of 10 mg of nifedipine to 11 patients with well-compensated alcoholic cirrhosis, there was a significant fall in mean arterial blood pressure, accompanied by an increase in heart rate, presumably due to a significant decrease in systemic vascular resistance. Despite the fall in renal perfusion pressure, there was an increase in the effective renal plasma flow and a significant decrease in renal vascular resistance. The glomerular filtration rate was preserved, suggesting that the decrease in renal vascular resistance was due to a preferential decrease in afferent arteriolar tone. There were no significant changes in the filtered sodium load or the tubular reabsorption of sodium and urinary sodium, and urinary volume did not alter significantly. Although the current study indicates that nifedipine can improve the renal circulation in patients with cirrhosis, the significant effects on the systemic circulation suggest that its potential to reverse the intense renal vasoconstriction that can complicate the clinical course of advanced liver disease is unlikely to be of value in the treatment of the hepatorenal syndrome.

Aged↗
PubMed1994

Subject-based rating of hand-wrist stressors.

Subject-based rating (SBR) methods (eg, Borg Scales) have been applied to lifting and exertion estimation. SBR methods were applied to hand-wrist motions in this controlled experimental study of rapid motion. Seven normal volunteers performed lift actions with several combinations of wrist position (flexion-extension), repetition frequency, force, and grip type (precision vs power) using an experimental apparatus. Wrist position and frequency were confirmed using an electrogoniometer. Subjects rated the tasks along 5 scales. Analysis showed that grip type had the predominant effect on the subjective ratings, but the other factors were also rated. However, cycle times between 3 and 8 seconds were not well differentiated. The study indicates that SBR does validly reflect actual stressors and suggests that SBR may be useful for "screening" jobs for more intensive study.

Adult↗
PubMed1993

Indomethacin-induced renal dysfunction in patients with well-compensated cirrhosis.

BACKGROUND: Patients with cirrhosis and ascites are especially sensitive to the adverse renal effects of indomethacin-induced inhibition of prostaglandin synthesis. The aim of this study was to determine whether indomethacin affects renal function in patients with well-compensated cirrhosis. METHODS: Clearance techniques were used to assess renal hemodynamics and sodium and water homeostasis. RESULTS: The oral administration of 50 mg of indomethacin to well-compensated patients with alcoholic cirrhosis was followed by a significant decrease in glomerular filtration rate (GFR) and effective renal plasma flow because of a preferential increase in afferent arteriolar tone. Indomethacin was both antidiuretic and antinatriuretic due principally to decreased free water clearance and increased proximal tubular reabsorption of sodium. The acute changes in renal function were not sustained. Patients with a high basal GFR were particularly sensitive to the adverse renal effects of indomethacin. CONCLUSIONS: This study indicates that in patients with well-compensated cirrhosis renal prostaglandins are functionally active and may contribute to the pathogenesis of glomerular hyperfiltration. Nonsteroidal anti-inflammatory drugs should be used with caution in all patients with cirrhosis.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Prostanoid synthesis in response to high CO2 in newborn pig brain microvascular endothelial cells.

Hypercapnia-induced cerebral vasodilation involves prostanoids in newborn pigs. However, the source of prostanoids has not been determined. The current study was designed to address the hypothesis that piglet cerebral microvascular endothelial cells increase their synthesis of prostanoids in response to high CO2. Microvascular endothelial cells, smooth muscle cells, and glia were isolated and grown in primary culture. They were identified morphologically and by indirect immunofluorescence staining. Cerebral microvascular endothelial cell cultures from newborn pigs produced equal amounts of 6-ketoprostaglandin (PG) F1 alpha (stable hydrolysis product of PGI2), PGE2 and a small amount of PGF2 alpha under basal conditions. Administration of calcium ionophore A23187 to the endothelial cells increased release of all three prostanoids in a dose- and time-dependent manner. Exposure of piglet cerebral microvascular endothelial cells to higher than normal CO2 increased the production of 6-keto-PGF1 alpha and PGE2 but not of PGF2 alpha. The enhanced prostanoid biosynthesis was concentration dependent, peaking at 14% CO2, and was detected during the first 10 min exposure to 14% CO2. Hypercapnia-induced increased synthesis of prostanoids was blocked dose dependently by the simultaneous addition of PGH synthase inhibitor indomethacin. High CO2 did not increase prostanoid production by cerebral microvascular smooth muscle cells or glia, although A23187 enhanced prostanoid formation by both cell types. These data show that high CO2 stimulates prostanoid synthesis by newborn pig cerebral microvascular endothelial cells, which is consistent with an involvement of cerebral vascular endothelium in hypercapnia-induced vasodilation.

Animals↗
PubMed1993

Personal risk assessment under the Americans with Disabilities Act. A decision analysis approach.

A decision analysis model was designed and implemented to facilitate job placement decisions. It identified relevant input parameters such as typical probability and severity of adverse outcomes for three targets--the worker himself or herself, the public, and productivity. In addition, specific factors that differentiate this specific decision instance from the "typical" are identified, including a person's specific health history, job site risk modifiers, and possible accommodation methods. Relevant societal values are also integrated, including relative importance of the three target groups (person, public, productivity) and discounting of the importance of future events. The system also includes a calculation engine to quantitatively integrate these input parameters for any number of events and modifiers to yield a single cost (expected negative utility value) for the instant situation. Cost represents risk of substantial harm, not financial cost. The decision analysis model is illustrated using a progressively more complex series of decision examples. In addition, the method of sensitivity analysis is applied, determining the extent to which the outcome is affected by varying the value assigned to an uncertain input parameter. This decision analysis approach is useful both as a heuristic (explaining the process) and as an aid in decision-making for a person with disabilities. The recently implemented Americans with Disabilities Act requires that a rational approach be utilized in such decisions, and such a model may facilitate this process.

Accidents, Occupational↗
PubMed1991

Developmental lead exposure inhibits adult rat retinal, but not kidney, Na+,K(+)-ATPase.

Neonatal lead exposure produces selective rod degeneration and functional deficits in adult hooded rats. Similar alterations occur following retinal exposure to ouabain. This study determined whether there were long-term effects of neonatal lead exposure on rat retinal or renal Na+,K(+)-ATPase (Na,K-ATPase) activity and employed in vitro studies to examine the mechanism of ionic lead (Pb2+)-induced inhibition of retinal Na,K-ATPase. Pups, exposed to lead only via the milk of dams consuming 0, 0.02, or 0.2% lead solutions, had mean blood lead concentrations of 1.2, 18.8, and 59.4 micrograms/dl at weaning, respectively, and 5-7 micrograms/dl as adults. Prior lead exposure produced significant dose-dependent decreases in isolated retinal Na,K-ATPase activity (-11%; -26%) whereas activity in the kidney was unchanged. In contrast, Na,K-ATPase from both isolated control tissues was inhibited by Pb2+. The half-maximal inhibitory dose (I50) of Pb2+ for retinal and renal Na,K-ATPase was 5.21 x 10(-7) and 1.25 x 10(-5) M, respectively. The Hill coefficient of the retina was 0.42 whereas it was 0.88 in the kidney. With MgATP as a substrate, the Pb(2+)-induced inhibition of retinal Na,K-ATPase was competitive and reversible with a Ki of 2.1 x 10(-7) M. Retinal and renal Na,K-ATPase were 20-fold and 1.1-fold more sensitive to inhibition by Pb2+ than by Ca2+, respectively. The Pb(2+)-induced inhibition of retinal Na,K-ATPase was antagonized by Na+, potentiated by Mg2+, not altered by K+ or Ca2+, and prevented by ATP. Kinetic and competition studies with the retinal Na,K-ATPase establish that the Pb(2+)-induced inhibition is complex. The increased sensitivity of retinal, compared to renal, Na,K-ATPase to inhibition following in vivo or in vitro lead exposure may relate to their different alpha subunit composition. This is speculated to play a fundamental role in the target organ toxicity of lead.

Administration, Oral↗
PubMed1991

Effects of ischemia/reperfusion on brain tissue prostanoids and leukotrienes in newborn pigs.

We investigated the hypothesis that cerebral prostanoid and peptidoleukotriene (LTs) (LTC4/D4/E4/F4) synthesis are increased during postischemic reperfusion of newborn pig brains. Prostanoids and LTs extracted from brain tissue were determined by RIA in sham-control piglets and at 1h, 3h, or 12h after a 20-min period of total cerebral ischemia. During reperfusion following ischemia, all regional brain tissue (cerebrum, brain stem and cerebellum) prostanoids (6-keto-PGF1 alpha, TXB2, PGE2 and PGF2 alpha) were increased at 1h compared with those in sham-control piglets. Only cerebral and brain stem 6-keto-PGF1 alpha and cerebral TXB2 remained elevated at 3h postischemia and all prostanoids returned to control levels by 12h postischemia. Brain tissue LTs were lower than prostanoids and were not altered 1, 3, or 12h following ischemia. These data indicate that 1) newborn pig brain tissue prostanoids are increased initially, and then returned to control levels at later stages of reperfusion following ischemia; 2) LTs are present in newborn pig brain tissue, but are not increased by ischemia/reperfusion injury and therefore probably do not play a significant role in cerebral ischemia-reperfusion injury.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Is the central dogma of flow cytometry true: that fluorescence intensity is proportional to cellular dye content?

Measurements and theoretical calculations of fluorescent emission from four samples of polystyrene microspheres (diameter 0.92, 1.63, 1.90 and 4.18 microns) containing the same fluorescent dye show a general dependence upon particle size, emission angle, and polarization conditions. However, for the excitation and detection conditions used in flow cytometry, the relative fluorescent intensities measured for the four particle sizes are proportional to the dye content to +10% accuracy, independent of particle size. Accordingly, the central dogma of flow cytometry 'that fluorescence is proportional to cellular dye content' is valid to this accuracy for these solid, highly refractive polymer particles. Most mammalian cells are much less refractive, therefore, should conform more closely to the central dogma.

Animals↗
PubMed1981

Construction and expression of recombinant plasmids encoding type 1 or D-mannose-resistant pili from a urinary tract infection Escherichia coli isolate.

Isolates of Escherichia coli from human urinary tract infections frequently express adherence properties found less often among normal intestinal isolates. These properties include adherence to human uroepithelial cells and primary monkey kidney cells, as well as D-mannose-resistant hemagglutination of human erythrocytes, and they are mediated by a pilus type different from type 1. The genes encoding this pilus type (pyelonephritis-associated pili, pap) and those encoding type 1 pili have been cloned from a urinary tract infection isolate of E. coli and transferred to an E. coli K-12 derivative. The recombinant plasmids were found to express functional pili and to endow the new host with all of the adherence properties of the urinary tract infection isolate. Both pilus types were found to be genetically distinct, and unlike the adherence genes from bovine, porcine, and human diarrheal isolates, both were found to be chromosomally encoded.

Adhesiveness↗