Biomedical subjects

Y T Lau

Publications and source records attributed to Y T Lau.

At least 37 records · Page 2Linked to original sources

PubMed1995

Density of muscarinic receptors in rat myocardium during early sepsis.

The muscarinic receptor changes in two subcellular fractions of rat myocardium during sepsis, the sarcolemma (SL) and light vesicles (LV), were studied. [3H]-quinuclidinyl benzilate ([3H]-QNB) was used as a radioligand. Sepsis was induced by cecal ligation and puncture (CLP). The septic rats had higher pulse rates and slightly higher blood glucose levels than control rats. The marker enzyme assays revealed that the SL fraction was enriched with 5'-nucleotidase and the Na(+)-K(+)-ATPase activity increased over 20-fold, while the LV fraction showed very little enrichment when compared with the homogenate. [3H]-QNB binding studies showed that Bmax increased by 58.8% in SL with no changes in LV during early sepsis (9 h post-CLP), but there was no significant change in the Kd value. These data indicate that muscarinic cholinergic receptors in rat heart SL increase during early sepsis. Since the muscarinic cholinergic receptors mediate parasympathetic modulation of myocardial contractility, changes in the number of muscarinic receptors in the cardiac SL may have a pathophysiologic significance in the development of hemodynamic changes during sepsis.

Animals↗

PubMed1995

Serum activity of angiotensin converting enzyme (ACE) is not affected by hepatitis B viral infection.

Activity of angiotensin converting enzyme (ACE) in the serum from healthy and hepatitis B-infected subjects were examined. Preservation of the serum samples for 32 days at -80 degrees C did not significantly alter the activity of ACE. We have determined the ACE activity in three groups: healthy subjects with negative hepatitis B surface antigen (HBsAg) and normal liver function or the (-,N) group, subjects exhibiting positive HBsAg and normal liver function or the (+,N) group, as well as subject with positive HBsAg and abnormal liver function or the (+,Ab) group. The healthy group (-,N) exhibited serum activity of ACE of 31.5 +/- 1.2(25) nmoles/min/ml serum. There was no difference in ACE activity whether surface antigen was present, i.e., between (-,N) and (+,N) groups. Although a slight (about 10%) elevation of ACE activity was observed in the third group (+,Ab), it was not significantly different from either (-,N) or (+,N) group. These results suggest the lack of association between the serum activity of ACE and hepatis B, however, further studies are required to clarify whether correlation exists between serum activity and liver function.

Adult↗

PubMed1995

Sodium transport in endothelial cells--a brief review.

Abnormalities in endothelial cell functions play a significant role in the pathogenesis of hypertension and altherosclerosis. Ion transport, particularly sodium (Na+) transport, serves important functions in both housekeeping and stimulus-response pathways in endothelial cells. Cell cultures provide useful experimental systems to investigate the operation and the regulation of various Na+ transporters. Among these Na+ transport systems, activities of Na+ pump, Na+-K+-Cl- cotransport, and Na+-H+ exchange have all been reported in cultured endothelial cells. Similar to those in other cells, these transport systems are responsible for the establishment and maintenance of ionic composition and volume of the endothelial cell. Alterations of intracellular Na+,H+, and/or cell volume can activate individual transport pathways and usually can serve as a feedback regulatory mechanism to achieve constant cellular volume and ions. In addition, hormones and vasoactive peptides modulate the activities of these transporters; physicochemical modifications of the membrane by cholesterol enrichment or oxidant stress also affect Na+ transport. The maintenance of Na+(or K+) gradients across plasma membrane by Na+ pump are important for nutrient uptake and protein synthesis in endothelial cells. Regulatory volume increase or decrease also occur and are mediated via activation of Na(+-)K(+-)Cl-cotransporter (and Na(+-)H+ exchanger, but significance unclear) or KCl loss, respectively. Na(+-)K(+-)Cl- cotransport is also altered by vasoactive peptide and may play a role in modulating vascular properties. Oxidant stress appears to alter all 3 systems: inhibit Na(+-)K(+-)Cl- cotransport and Na(+-)H+ exchange while stimulate Na+ pump, these changes may be part of the mechano-transduction pathway in endothelial cells.

Animals↗

PubMed1994

Transport of 2-aminoisobutyric acid in cultured endothelial cells.

Conflicting reports exist concerning the presence of a Na(+)-coupled amino acid transport system in cultured endothelial cells. We have employed a non-metabolizable analog, 2-aminoisobutyric acid (AIB), to investigate the activity of Na(+)-dependent amino acid transport in cultured human umbilical vein endothelial cells (HUVEC). We found a pronounced saturable, Na(+)-dependent component of AIB uptake in 'fresh' (non-starved) HUVEC. The Na(+)-dependent component accounted for 78% of total AIB uptake with a high sensitivity to external Na+. The accumulation of AIB was inhibited by ouabain preincubation, consistent with the energetics of Na(+)-coupled transport. Amiloride, an epithelial Na+ channel blocker, also inhibited AIB transport at high concentration. The results strongly support the presence of a Na(+)-coupled transport system of amino acid in HUVEC.

Amiloride↗

PubMed1994

Membrane permeability changes during Rana oocyte maturation.

A transition from an open system to a closed one must occur during the complex process of meiotic maturation of the amphibian oocyte. Membrane permeability to urea in Rana oocytes following progesterone stimulation was determined, and the largest decrease was found to coincide with germinal vesicle breakdown. These findings suggest that the timing of the disappearance of membrane permeability correlates with developmental events that prepare the oocyte for a hostile environment.

Animals↗

PubMed1994

Cholesterol enrichment inhibits Na+/K+ pump in endothelial cells.

We have previously shown that cholesterol enrichment reduces 3H-ouabain binding in cultured vascular endothelial cells. The present study aimed to determine the effect of cholesterol enrichment on ouabain-sensitive 86Rb (as a substitute for K+) influx, i.e. K+ transport via the pump, and to examine whether cellular K+ content was affected in human umbilical vein endothelial cells. 86Rb influx was inhibited by both ouabain and bumetanide in a dose-dependent manner. Consistent with an earlier report [1], inhibition achieved was greater for ouabain (approximately 70% at mM range) than for bumetanide (approximately 55% at 0.1 mM), indicating that K+ influx via Na+/K+ pump was greater than that via Na(+)-K(+)-Cl- cotransport in these cells. After incubation of 18 h or more with cholesterol-enriched liposomes (2:1 cholesterol to phospholipid ratio), a significant reduction (> 20%) of the ouabain-sensitive K+ influx and an increase in cellular cholesterol content were observed. The inhibitory effect was observed only at liposome concentrations above 2 mg/ml. Following 18 h incubation with 2 mg/ml cholesterol-enriched liposomes, cellular K+ content was significantly decreased. The phospholipid liposome treatment did not alter K+ content, suggesting that the inhibitory effect on Na+/K+ pump and the cellular K+ content reduction was not due to liposome fusion alone or to the phospholipid present. These findings indicate that cholesterol enrichment inhibits Na+/K+ pump and thus reduces cellular K+ content in endothelial cells, and may play a role in the widely observed abnormal endothelium-dependent vascular response induced by hypercholesterolemia.

Bumetanide↗

PubMed1994

[3H]ouabain binding to cultured endothelial cells: effect of cholesterol enrichment.

Binding experiments were performed with [3H]ouabain on cultured human umbilical vein endothelial cells (huvEC). Saturation studies yielded a binding capacity (Bmax) of 820 +/- 81 fmole/mg pr.(n = 4) and dissociation constant (KD) of 11.7 +/- 2.1nM (n = 4) in K(+)-free buffer for specific [3H] ouabain binding on these cells. External K+ inhibited this binding in a dose-dependent manner. The mean value of Bmax is equivalent to about 4 x 10(5) sites per cell, comparable with that of smooth muscle cell. These data demonstrated the presence of specific [3H]ouabain binding linked to Na+/K+ pump, consistent with the observations of ouabain-sensitive 86Rb uptake in huvEC. Effect of cholesterol enrichment was also studied. Incubation in media supplemented with cholesterol-phospholipid liposomes of molar ratio of 2:1 for 18 hours reduced the Bmax by 31% (P < 0.05) without significantly changed the value of KD. This reduction of [3H]ouabain binding appeared to be specific for cholesterol since liposome made with pure phospholipid did not alter binding. Recent findings indicate that cholesterol-enrichment and plasma lipoproteins enhance vascular contractile response, our results suggest that the cholesterol-enrichment of endothelial cells may also indirectly affect the vascular response via disturbing the function of Na+/K+ pump.

Binding Sites↗

PubMed1994

Erythrocyte Ca2+ pump is defective during sepsis.

Saturated Ca2+ extrusion rate through the Ca2+ pump of erythrocytes was determined by the cobalt-exposure method in normal subjects and septic patients. From 48 normal subjects, the value of Vmax of erythrocyte Ca2+ pump was 14.83 +/- 0.49 mmol/L cells/hr; from 29 sepsis patients, it was 9.49 +/- 0.59 mmol/L cels/hr, significantly (P < 0.001) lower than that from the erythrocytes of normal subjects. When the severity of sepsis was evaluated by the septic severity score (SSS), a significant correlation (P < 0.0001) was observed between the Vmax of Ca2+ pump and the patient's SSS, indicating that the inhibition of Ca2+ pump depended on the degree of the pathological development of sepsis. Since the ATP-dependent Ca2+ transport in rat liver plasma membrane is also reduced during the late stage of sepsis [Lau et al., Circ Shock 38:238-244, 1992], impairment of the activity of Ca2+ pump appears to have a general pathophysiological significance in the development of severe sepsis.

Adenosine Triphosphate↗

PubMed1994

Urea transport in frog oocytes: effect of osmotic stress and vasopressin.

The transport of water and urea across biological membranes are considered to traverse separate channels or pores. While vasopressin responsiveness correlates with increased urea/water permeability in some epithelia, oocytes provide a single cell system to determine the coupling relationship. Urea transport under isotonic and hypotonic conditions are determined in full-grown frog oocytes in follicles. We found that urea reached equilibrium distribution (ratio of 14C-urea concentrations inside and outside of the oocyte) rapidly and remained equilibrated over 20 h period, independent of external urea concentrations. Thus, urea uptake is not via an active transport system. While hypotonicity caused oocytes to swell, vasopressin did not exert additional effect. Under hypotonic conditions, distribution ratios of water and urea changed in different ways supporting the view that distinguishable channels (pathways) were involved. It appeared that no correlated changes due to vasopressin occurred under osmotic challenge. The response pattern to vasopressin was different between renal epithelia and frog oocyte.

Animals↗

PubMed1994

Changes of alpha 1-adrenergic receptors in human liver during intraabdominal sepsis.

We studied changes in alpha 1-adrenergic receptors in human liver plasma membranes during intraabdominal sepsis using [3H]prazosin as a radioligand. Human liver tissues were obtained from nonseptic patients undergoing elective abdominal surgery (control group) and from patients with sepsis requiring laparotomy as a therapeutic measure (septic group). Septic patients were further divided into three subgroups on the basis of septic severity scores: mild sepsis (< 21), moderate sepsis (22 to 32) and severe sepsis (> 33). Plasma membranes were prepared by means of sucrose gradient centrifugation and were purified fivefold on the basis of the enrichment of the activity of the marker enzyme, 5'-nucleotidase. [3H]prazosin-binding studies show that the maximal binding capacity was increased by 49.6% (p < 0.01) in mild sepsis, relatively unchanged in moderate sepsis and decreased by 33.4% (p < 0.05) in severe sepsis (in femtomoles per milligram: 193.7 +/- 5.7 for control [n = 6], 289.8 +/- 23.4 for mild sepsis [n = 4], 192.3 +/- 16.3 for moderate sepsis (n = 4), 129.1 +/- 18.3 for severe sepsis [n = 5]). We found a significant inverse correlation (r = 0.85, p < 0.01) between changes in the densities of alpha 1-adrenergic receptors and septic severity scores. These data indicate that alpha 1-adrenergic receptors in human liver plasma membranes undergo dynamic changes during the development of sepsis--that is, the receptor number increased in mild sepsis, returned to a normal level in moderate sepsis and finally decreased in severe sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

5'-Nucleotidase↗

PubMed1993

Biphasic intracellular redistribution of alpha 1-adrenergic receptors in rat liver during sepsis.

Changes in the distribution of alpha 1-adrenergic receptors in two subcellular fractions, the plasma membrane and the light vesicle, of rat liver during sepsis were studied using [3H]prazosin binding and photoaffinity labeling with [125I]arylazidoprazosin in combination with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Sepsis was induced by cecal ligation and puncture (CLP). Septic rats exhibit two metabolically distinct phases: an initial hypermetabolic (hyperglycemic) phase (9 h after CLP; early sepsis) followed by a hypometabolic (hypoglycemic) phase (18 h after CLP; late sepsis). [3H]prazosin binding studies show that during early sepsis, the maximal binding capacity (Bmax) was increased by 35% in plasma membranes but was decreased by 28% in light vesicles; while during late sepsis, the Bmax was decreased by 30% in plasma membranes but was increased by 33% in light vesicles. The photoaffinity labeling studies revealed two major binding peptides with M(r) of 77,000 and 68,000 Da and one minor binding protein with M(r) of 39,000 Da. The total binding for the three labeled peptides during early sepsis was increased by 26% in plasma membranes but was decreased by 33% in light vesicles, while during late sepsis the total binding was decreased by 19% in plasma membranes but was increased by 35% in light vesicles. These data indicate that alpha 1-adrenergic receptors in the rat liver were externalized from light vesicles to plasma membranes during the hyperglycemic phase while they were internalized from surface membranes to intracellular sites during the hypoglycemic phase of sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Abnormalities of sodium transport in non-insulin-dependent diabetes: association with renal disease.

We investigated both sodium-lithium countertransport (Na-Li CT) and ouabain-sensitive sodium transport (Na pump) of erythrocytes in healthy subjects (group A), patients with non-insulin-dependent diabetes (NIDDM) without nephropathy (group B), patients in the proteinuric stage (group C), and those in the renal insufficiency stage (group D). Erythrocytes from all four groups had a similar initial water and ionic content and were loaded with similar degrees of Li and Na for efflux studies. There were no significant differences in erythrocyte Na-Li CT or Na pump among the four groups. However, the maximal rate of Na-Li CT was significantly higher in a group of subjects with essential hypertension when compared with groups A, B and C, consistent with the view that there is a genetic marker for essential hypertension. Ouabain-insensitive Na efflux (Na leak) of erythrocytes was found to be significantly higher in group D than in groups A or B. Also, a significant positive correlation existed between Na leak and urine protein levels of the subjects studied. Our results thus indicate that in contrast with insulin-dependent diabetic patients (IDDM) where an elevated Na-Li CT is observed, with diabetic nephropathy, Na-Li CT in NIDDM is apparently not associated with nephropathy; rather the ouabain-insensitive Na efflux appears to be correlated with the stages of nephropathy in NIDDM. The association suggests that the rate of ouabain-insensitive Na efflux may provide an index for assessing the degree of nephropathy in NIDDM patients.

Adult↗

PubMed1993

Vascular contractile properties in hypertension. I. A study of testing methods.

Abnormal contractile responses of blood vessels are observed widely in several hypertension models and are assumed to play a role in the etiology of essential hypertension. Inconsistent reports also exist due to different animals, preparations, and experimental techniques employed. In this investigation, we compared vascular response of normotensive Wistar-Kyoto rat (WKY) with that of spontaneously hypertensive rat (SHR) employing two experimental methods. Thoracic aorta obtained from age-matched animals were contracted by norepinephrine (NE) with either--single-dose method or cumulative-dose method. Differences in both reactivity (maximal tension) and sensitivity (ED50) to NE were observed. Although no significant differences were found between WKY and SHR with either method, the choice of the method employed could affect the outcome. For aorta from WKY, the reactivity to NE was similar for both methods; however, for aorta from SHR, the reactivity obtained by cumulative-dose method was significantly higher. Furthermore, the cumulative-dose method yielded higher sensitivity in both WKY and SHR when compared with that obtained by single-dose method. Taken together, the cumulative-dose method appeared to be a more sensitive method to determine contractile response. Nevertheless, no significant difference in either reactivity or sensitivity to NE in aorta was detected between WKY and SHR when cumulative-dose method was employed. These data indicate that aorta do not exhibit abnormal response to NE in SHR, consistent with earlier findings that not all tissue preparations behave similarly.

Animals↗

PubMed1992

Coordinated regulation of vascular endothelial cell growth and prostacyclin production by epidermal growth factor: evidence of clonal variations among rat aortic endothelial cells.

Rat aortic endothelial cells were found to exhibit clonal variations in response to EGF stimulation in cell growth and prostacyclin synthesis. EGF-induced growth and prostacyclin synthesis appeared to be regulated in a coordinated manner in that a clone with a higher response to EGF growth stimulation also exhibited a higher response to EGF-stimulated prostacyclin synthesis. This observation implies a possible involvement of prostacyclin synthesis in some of the biological effects of EGF on vascular endothelial cells.

Animals↗

PubMed1992

Erythrocyte sodium-lithium countertransport in Chinese: its relationship to family history of hypertension.

Rates of sodium (Na+)-stimulated lithium (Li+) efflux (Na(+)-Li+ countertransport) and ouabain-sensitive Na+ efflux (Na+ pump) were determined in erythrocytes of Chinese normotensive and hypertensive subjects. Near-maximal rate of Na(+)-Li+ countertransport was found to be significantly higher in hypertensive than normotensive subjects. No significant difference was observed for the rate of Na+ pump between them. A second series of study involved normotensive subjects without and with hypertensive parent(s) (group A and B, respectively) and hypertensive subjects (group C). We found that the rate of Na(+)-Li+ countertransport in group A was significantly lower than that of group B and C, while no difference existed between group B and C. No significant difference was observed for the rate of Na+ pump among the three groups. Our results suggested that Na(+)-Li+ countertransport activity could be a genetic marker for essential hypertension in Chinese, similar to that as proposed in Caucasians.

Adult↗

PubMed1992

Calcium transport by rat liver plasma membranes during sepsis.

The effects of sepsis on the ATP-dependent Ca2+ transport in rat liver plasma membranes were investigated. Sepsis was induced by cecal ligation and puncture (CLP). Control rats were sham-operated. The results show that the ATP-dependent Ca2+ transport by liver plasma membranes was not affected during early sepsis (9 hr after CLP) but was decreased by 30-50% (P < 0.05) during late sepsis (18 hr after CLP). Kinetic analysis of the data indicates that during late sepsis, the Vmax values for ATP and for Ca2+ were decreased by 38.5% (P < 0.05) and 41.8% (P < 0.05), respectively, while the Km values for ATP and Ca2+ remained unchanged. Mg2+ stimulated ATP-dependent Ca2+ transport. The Mg(2+)-stimulated activity was unaffected during early sepsis but was decreased by 34-63% (P < 0.05) during late sepsis. These data demonstrate that ATP-dependent Ca2+ transport in rat liver plasma membranes was impaired during late sepsis and that the impairment is associated with a mechanism not affecting the affinity of the Ca2+ transporter for ATP and Ca2+. Since plasma membrane ATP-dependent Ca2+ transport plays an important role in the regulation of intracellular Ca2+ homeostasis in hepatocytes, an impairment in the ATP-dependent Ca2+ transport by liver plasma membranes during late sepsis may have a pathophysiological significance in contributing to the development of altered hepatic metabolism during septic shock.

Adenosine Triphosphate↗

PubMed1992

Sodium transport in hypertension.

Although most workers in the field agree that salt causes hypertension, but there is no well-established mechanism(s) explaining how salt works. Vast literature exists on abnormal sodium (Na+) transport processes in human and experimental hypertension from various cell systems. We examined the recent developments in the investigation of three important sodium transport pathways: Na+/K+ pump, Na+/Li+ countertransport and Na+/K+ cotransport in hypertension. The activities of these transporters may affect vascular reactivity or may serve as genetic marker for essential hypertension. Selected reports on the abnormalities of these transporters were summarized, potential problems in the interpretation of these data were discussed, and the current view about the physiological or pathophysiological meaning of these studies were presented. The multiple sites of defects and sometime conflicting reports on Na+ transport in hypertension also lead to alternative hypothesis associating membrane abnormalities with hypertension. Two models, considering membrane lipid bilayers and cellular calcium handling as primary sites of defect and the related evidence, were introduced. Finally, the role of natriuretic hormone (or endogenous Na+ pump inhibitor) in influencing Na+ transport was briefly discussed.

Animals↗

PubMed1992

Comparison of sodium transport processes of human and rat erythrocytes in hypertension.

Erythrocytes of normotensive and hypertensive humans, as well as Sprague-Dawley, Wistar-Kyoto and spontaneously hypertensive rats, were prepared to have similar ionic compositions adequate for determining the activities of lithium-sodium (Li-Na) countertransport and sodium (Na) pump. The rate of Li-Na countertransport was significantly higher in erythrocytes of hypertensive subjects. This activity was not detected in rat erythrocytes, at two different ages, and over a six-fold of lithium (Li) content. Activities of Na pump were not significantly different among various groups. Human cells, in general, had a higher activity than rat cells; among rat cells, spontaneously hypertensive rats had a higher rate of sodium pump. Both Na-independent Li efflux and ouabain-insensitive Na efflux were significantly higher in rat erythrocytes than in human cells. Thus, employing the same methods, we have determined that while the properties of Na pump were similar in human and rat erythrocytes, Li-Na countertransport did not operate in the erythrocytes of either normotensive or hypertensive rats.

Adult↗