Biomedical subjects

L Lin

Publications and source records attributed to L Lin.

At least 343 records · Page 19Linked to original sources

PubMed1991

Intracellular signaling pathway of endothelin-1.

The intracellular signaling pathway of endothelin-1 (ET-1) was studied in individual mesangial cells (MCs) and vascular smooth muscle cells (VSMCs) using microspectrofluorimetry of fura-2 ([Ca2+]i), SPQ ([Cl-]i), and bisoxonol (membrane potential). ET-1 elicited a five-fold increase in [Ca2+]i that showed immediate and sustained phases. Both the Ca(2+)-free medium and nifedipine pretreatment curtailed the sustained phase of the response to ET-1. ET-1 resulted in sustained membrane depolarization of MCs and VSMCs. This depolarization was not attributed to Na influx, as Na-free medium did not abolish it. A Cl(-)-channel inhibitor, IAA-94, blunted the depolarization and sustained elevation of [Ca2+]i in response to ET-1. In aortic rings, both nifedipine and IAA-94 attenuated ET-1-induced contraction. No additivity in the effect of nifedipine and IAA-94 was detected. Studies of SPQ fluorescence changes induced by ET-1 revealed an immediate and sustained increase in fluorescence intensity consistent with the decrease in [Cl-]i. The sustained but not immediate increase in SPQ fluorescence was virtually abolished in Ca(2+)-free medium with or without pretreatment with the intracellular Ca2+ chelator BAPTA. In conclusion, we hypothesize that ET-1 results in Ca2+ mobilization and Ca(2+)-dependent and -independent activation of Cl- channels. Ensuing Cl- efflux causes membrane depolarization and, in turn, activation of voltage-gated Ca2+ channels in MCs and VSMCs. The latter results in sustained elevation of [Ca2+]i that is indispensable for the full-scale contractile response to ET-1.

Animals↗

PubMed1991

Role of endothelin in the development of Dahl hypertension.

To evaluate the possible role of endothelin in the development and/or maintenance of hypertension in Dahl rats, we examined the responsiveness of isolated vascular smooth muscle and glomerular mesangial cells, as well as deendothelialized vascular ring preparations to endothelin-1 (ET-1). Production of immunoreactive endothelin (ir-ET) was studied in freshly isolated glomeruli and renal medullary slices. Both glomerular mesangial cells and vascular smooth muscle cells obtained from prehypertensive Dahl-S rats exhibited an exaggerated [Ca2+]i response to ET-1, as compared with cells obtained from Dahl-R rats. This was paralleled by the enhanced isometric contraction of vascular rings obtained from prehypertensive Dahl-S rats. ir-ET production was doubled in response to 0.1 mM ouabain in tissue samples obtained from prehypertensive Dahl-S, but not Dahl-R rats. This effect was not observed in tissues obtained from animals fed a 4% NaCl diet (hypertensive). Immunocytochemistry of ET distribution in the outer medullary stripe showed approximately a 40% higher fluorescence intensity in sections obtained from Dahl-S rats fed 4% NaCl diet as compared with Dahl-R rats fed the same diet. Northern blot analysis of poly(A)+ RNA extracted from medullae of prehypertensive Dahl-S and -R rats using a full-length cDNA probe for rat ET-1 revealed a marginal induction of pre-pro-ET-1 message in Dahl-S samples after 30 and 60 min of incubation with 0.1 mM ouabain. In conclusion, increased responsiveness of target cells to ET-1 and inducibility of ir-ET production in prehypertensive Dahl-S rats are in favor of a possible role of this peptide in the pathogenesis of Dahl hypertension. We hypothesize that ouabain-like factor(s) may trigger production of ET, thus serving as a link between high-salt intake and the development of hypertension in Dahl-S rats.

Animals↗

PubMed1991

Case-control study of cigarette smoking and primary hepatoma in an aflatoxin-endemic region of China: a protective effect.

Aflatoxin is believed to be a major causative agent in the high incidence of primary liver cancer seen in certain regions of the world. In Fujian Province, an aflatoxin-endemic region of China, we compared the cigarette smoking habits of 200 primary hepatoma patients with those of 200 matched nonhepatoma controls. We excluded from our study all individuals with evidence of hepatitis B virus serum antigen and/or alcoholic cirrhosis. Interestingly, two groups of hepatoma patients could be discerned. In patients more than 50 years of age, a significantly higher number of cases of primary hepatoma was found among nonsmokers than smokers (odds ratio = 2.06; 95% confidence interval = 1.32-3.20). In patients less than 50 years of age, this difference was not seen. Previous studies in the rat, mouse and duck had suggested that agents present in cigarette smoke might induce a cytochrome P450-mediated detoxication pathway, leading to protection against aflatoxin-induced primary liver cancer. Our clinical data in the present study are therefore consistent with the previous laboratory animal experiments.

Adult↗

PubMed1991

Dynamics of creatine kinase shuttle enzymes in the human heart.

Myocardial cytoplasmic creatine kinase subunits M and B, mitochondrial CK (CKMIT), and citrate synthase (CS) were determined in 10 locations of the normal human heart (n = 8) and in papillary muscles of patients operated on for mitral regurgitation (n = 6). Compared to atrial biopsies, septal and left ventricular biopsies showed higher activities for CS (P less than 0.0001), total CK (P less than 0.05) and CKMIT (P less than 0.0001). CKM was evenly distributed. CKB activity in the right septum and left ventricular locations were 0.5-1% of total CK and 4-5 times lower than those of the atria and the right ventricular free wall. Activities of CS, CKB and CKMIT in right septal biopsies did not differ from those in left ventricular locations. The activities of CS, total CK, and CKM in papillary muscle from patients operated on for mitral regurgitation did not differ from that of healthy papillary muscle. CKMIT was about 40% lower (P less than 0.02), whereas CKB was 15-20 times higher (P less than 0.0001) than in the healthy heart. In conclusion, adaptations within the creatine kinase system occur in the human heart in health and disease. Small amounts of CKB in the normal left ventricle, as opposed to the right ventricular free wall, might be related to differences in myocardial perfusion during the cardiac cycle. In disease, a decreased CKMIT and dramatically increased CKB may indicate a stressed intracellular energy transfer. CK enzyme activities in right septal biopsy specimens may be used as an indication of metabolic stress on the myocardium of the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

DNA typing for HLA-DR, and -DP alleles in a Chinese population using the polymerase chain reaction (PCR) and oligonucleotide probes.

We have determined alleles of HLA-DRB1, DRB3, DRB5, DQA1, DQB1, and DPB1 loci in 91 unrelated healthy individuals from North China. Group-specific PCR primers were employed for the analysis of subsets of DR1, DR2, DR4, DRw52, and DPB. With allele-specific probes, 22 DRB1, 8 DQA1, 13 DQB1, and 12 DPB1 alleles were found in this panel. Allele frequencies showed that 25.3% of the subjects had DR7 and 26.4% had DR9, only 5.5% had DRB1*0301 (DRw17). In the DR4 group, DRB1*0405 (Dw15, 8.8%) and 0406 (KT2, 9.9%) were the most prevalent alleles. DRB1*0404 (Dw14.1), 0407 (Dw13.2) and 0408 (Dw14.2) were absent and the other alleles of the DR4 group were rare. The most common DRw6 subset was DRB1*1401 (8.8%). DRB1*0802 and 0803 were present (2.2%, 6.6%), and DRB1*0801 was not found. Associations with DQA1 and DQB1 were generally similar to those found in other populations. DPB1*0501 was the most frequent (60.2%) allele at the DPB1 locus. Overall our study shows that the distribution of class II alleles in a population from Mainland China is quite different from other ethnic groups. The high frequency of the KT2 subset of DR4. (DRB1*0406) and of DPB1*0501 are the most striking features found. A new type of DR4 was determined in one subject. It was like DR4-Dw15 (DRB1*0405) but, according to our hybridization patterns, it encoded valine instead of glycine in position 86. It is now called DRB1*0410.

Alleles↗

PubMed1991

Saturable binding of anesthetics to nicotinic acetylcholine receptors. A possible mechanism of anesthetic action.

Recent controversies in the existence of saturable binding of general anesthetics in brain tissues prompted a careful examination of specific binding of anesthetics to neural receptors. We examined the binding of both local and general anesthetics using electron spin resonance and radioligand criteria. Our results suggested that the hydrophobic path, most probably through the lipid bilayer, figures importantly in the binding of the uncharged moieties of anesthetics. Competitive interactions by hydrophobic compounds for the high-affinity site in the nicotinic acetylcholine receptor led us to propose a hypothesis that includes a hydrophobic crevice of limited volume as part of the high-affinity site. Association of anesthetic at this crevice is in turn dependent on the anesthetic concentration in the lipid phase of the membrane. The hypothesis provides a mechanism for the saturable interaction of anesthetics with their protein target site in the membrane without violating the correlations expressed by the Meyer-Overton rule of anesthetic action.

Anesthesia↗

PubMed1991

Intracellular ramification of endothelin signal.

Effects of porcine 1-21 endothelin (ET-1) on [Ca2+]i, [Na+]i, and [Cl-]i and on membrane potential were studied in individual mesangial (MC) and vascular smooth muscle (VSMC) cells using microspectrofluorimetry of fura-2, SBFI, SPQ, and bis-oxonol, respectively. ET-1 increased [Ca2+]i by fivefold, showing an immediate and a sustained phase of response. Ca(2+)-free medium and nifedipine pretreatment significantly curtailed the sustained phase of response to ET-1. These findings were confirmed in studies of vascular ring preparations, demonstrating that Ca2+ influx may account for at least 50% of contraction. ET-1 caused immediate and sustained depolarization of MC and VSMC. This could not be attributed to Na+ influx, since fluorescence of SBFI was not affected by ET-1 and Na(+)-free medium did not abolish the ET-1-induced membrane depolarization. Studies of SPQ fluorescence changes induced by ET-1 revealed an increase in fluorescence intensity consistent with the decrease in [Cl-]i. A Cl- channel blocker, IAA-94, abolished changes in SPQ fluorescence and curtailed sustained phases of membrane depolarization and [Ca2+]i elevation in response to ET-1, but did not affect KCl-induced [Ca2+]i transients. IAA-94 also attenuated the ET-1-induced contraction of aortic rings. Microinjection of either calcium gluconate or inositol 1,4,5-trisphosphate (IP3) in SPQ-loaded cells resulted in an increase in fluorescence mimicking the effect of ET-1. These changes were blunted by pretreatment of cells with BAPTA and incubation in Ca(2+)-free medium. When IP3 was microinjected into fura-2-loaded MC, this resulted in immediate and sustained elevation of [Ca2+]i. In conclusion, generation of IP3 results in mobilization of intracellular Ca2+ stores and activation of Cl- channels. Ensuing Cl- efflux causes membrane depolarization and, in turn, activation of voltage-dependent Ca2+ channels, resulting in sustained elevation of [Ca2+]i which is indispensable for the full-scale contraction produced by ET-1.

Animals↗

PubMed1991

Role of prostanoids in renin-dependent and renin-independent hypertension.

We investigated the role of prostanoid-mediated pressor mechanisms in setting the level of blood pressure in renin-dependent and renin-independent models of hypertension in unanesthetized rats. Intravenous administration of a blocker of thromboxane A2/prostaglandin endoperoxide receptors, SQ29548 (2 mg/kg bolus injection plus 2 mg/kg/hr for 3 hours), reduced from 162 +/- 4 to 144 +/- 5 mm Hg (p less than 0.05) the blood pressure of rats with aortic coarctation-induced hypertension at 7-14 days after coarctation when plasma renin activity is greatly increased. In contrast, treatment with SQ29548 was without effect on the blood pressure of either normotensive or hypertensive rats (i.e., aortic coarctation-induced hypertension at 90-113 days after coarctation, deoxycorticosterone-salt-induced hypertension) having normal or depressed values of plasma renin activity. The blood pressure-lowering effect of SQ29548 in the early phase of aortic coarctation-induced hypertension was positively correlated with the prevailing plasma renin activity and could not be demonstrated in hypertensive rats pretreated with indomethacin. We attribute the hypotensive effect of SQ29548 to interference with pressor mechanisms that depend on activation of thromboxane A2/prostaglandin endoperoxide receptors and suggest that such prostanoid-mediated mechanisms are operational and contribute to an increase in blood pressure in angiotensin-dependent forms of hypertension. Also prostanoid-mediated vasodepressor mechanisms are operational in the early phase of aortic coarctation-induced hypertension since the blood pressure of rats pretreated with SQ29548 was increased by the subsequent administration of indomethacin. Accordingly, the blood pressure of rats with aortic coarctation-induced hypertension is influenced by the interplay of prostanoid-mediated pressor and vasodepressor mechanisms.

6-Ketoprostaglandin F1 alpha↗

PubMed1991

Role of endothelium-derived prostanoid in angiotensin-induced vasoconstriction.

To test the hypothesis that prostanoids contribute to angiotensin II-induced vascular contraction, we compared the effect of angiotensin II on isometric tension development by rings of descending thoracic aorta bathed in Krebs' bicarbonate buffer with and without indomethacin (10 microM) to inhibit cyclooxygenase, CGS13080 (10 microM) to inhibit thromboxane A2 synthesis, or SQ29548 (1 microM) to block thromboxane A2/prostaglandin endoperoxide receptors. The comparisons were made in rings of aorta taken from normotensive rats and from rats with aortic coarctation-induced hypertension at 12 days and 90-113 days after coarctation. These rings released thromboxane B2, which was found to be endothelium dependent, increased in hypertensive rats, and stimulated by angiotensin II (10(-6) M) in normotensive rats and in hypertensive rats at 12 days after coarctation. The angiotensin II (10(-6) to 10(-5)M)-induced contraction of aortic rings was increased by about 30% at 12 days after coarctation and decreased at 90-113 days after coarctation. Removal of the endothelium increased the contractile effect of angiotensin II (10(-6) M) in aortic rings of normotensive rats and hypertensive rats at 90-113 days after coarctation but decreased the effect in aortic rings of hypertensive rats at 12 days after coarctation. In rats at 12 days after coarctation, the angiotensin II (10(-6) M)-induced contraction of aortic rings with endothelium was attenuated by indomethacin and SQ29548 but not by CGS13080. These data suggest that a prostanoid-mediated and endothelium-dependent mechanism of vasoconstriction contributes to the constrictor effect of angiotensin II in aortic rings of rats in the early phase of aortic coarctation-induced hypertension.

Acetylcholine↗

PubMed1991

Arachidonic acid elicits endothelium-dependent release from the rabbit aorta of a constrictor prostanoid resembling prostaglandin endoperoxides.

This study was designed to investigate the mediator(s) of endothelium-dependent arterial constrictor responses evoked by arachidonic acid in vitro. A segment of descending rabbit thoracic aorta was isolated and perfused (1-2 ml/min) with oxygenated Krebs' bicarbonate buffer. Changes in the vascular smooth muscle-contracting activity of the aortic effluent were detected by superfusion bioassay using either strips of rabbit aorta or rings of dog saphenous vein, both denuded of endothelium and exposed to indomethacin (10 microM). Arachidonic acid (5-50 micrograms) injected into the inflow of the perfused aorta caused a dose-related increase in the vascular smooth muscle-contracting activity of the aortic effluent, whereas arachidonic acid added directly into the aortic effluent did not. The arachidonic acid-induced elevation of vascular smooth muscle-contracting activity in the aortic effluent was not apparent when indomethacin (10 microM) was added to the aortic inflow to inhibit cyclooxygenase, when the endothelium of the perfused aorta was removed by rubbing, or when the thromboxane A2/prostaglandin H2 receptors of the vascular tissues used for bioassay were blocked with an antagonist (1 microM SQ29548), and was unaffected when an inhibitor of thromboxane synthase (10 microM CGS 13080) was added to the aortic inflow. This effect of arachidonic acid was accompanied by release of prostaglandin H2 (measured as prostaglandin F2 alpha after reduction with SnCl2) in amounts sufficient to elicit contraction of the vascular tissues used for bioassay and was attenuated when a reducing agent (2 mM FeCl2) that converts prostaglandin H2 to 12-heptadecatrienoic acid was added to the aortic effluent. Collectively, these observations suggest that arachidonic acid stimulates endothelium-dependent release from the perfused aorta of a prostanoid that contracts vascular smooth muscle via interaction with thromboxane A2/prostaglandin H2 receptors. The study also suggests that the prostanoid responsible for the vascular smooth muscle-contracting activity of the aortic effluent is a prostaglandin endoperoxide(s) rather than thromboxane A2.

Animals↗

PubMed1991

Myocardial lactate dehydrogenase and its isoenzyme activities in transplanted human hearts.

Lactate dehydrogenase and its heart (H) and muscle (M) subunit activities were studied in right ventricular endomyocardial biopsies from eight transplanted human hearts and compared with five chronically failing hearts and six normal human hearts from brain-dead liver/kidney donors. Of the 17 transplant biopsies (taken 5-95 weeks postoperatively), only two showed histologic signs of chronic rejection: They were excluded from the group analysis. A higher proportion of the M subunit of lactate dehydrogenase (M%) was found in the transplanted and the chronically failing hearts than in the normal hearts, presumably reflecting increased myocardial anaerobic glycolytic stress. In the early post-transplantation period, M% was higher in the transplanted than in the chronically failing hearts. Thereafter M% gradually fell, but had not reached normal levels 1-2 years after transplantation. During that time it was similar to the values in the chronic-failure hearts. In the two biopsies with chronic rejection, M% was nearly twice as high as in contemporaneous biopsies showing mild or no rejection. Monitoring of enzymatic adaptation from endomyocardial biopsies may be of clinical interest.

Adolescent↗

PubMed1991

[Application of differential derivative spectrophotometry to the determination of total chlorogenic acid in Lonicera japonica Thunb. and yinqiao jiedu pian].

The total chlorogenic acid in Lonicera japonica and yinqiao jiedu pian was determined by differential derivative spectrophotometry in this paper. Quantitative analysis of this component in eight mixtures of medicinal herbs can be done without any separation. The average recovery of total chlorogenic acid is 100.40 +/- 1.82% (CV). The method features good reproducibility, favorable stability and high sensitivity.

Chlorogenic Acid↗

PubMed1990

Immunoaffinity purification and functional characterization of interphase and meiotic Drosophila nuclear lamin isoforms.

Three isoforms of a single nuclear lamin have been identified in Drosophila. Two, lamins Dm1 and Dm2, are present during interphase and are apparently in equilibrium with each other in vivo. The third, lamin Dmmit, is found in cells that have undergone nuclear envelope breakdown, either during meiosis or mitosis. All three isoforms were purified under nondenaturing conditions using a novel technique of immunoaffinity chromatography and their in vitro activities were examined. Interphase lamins Dm1 and Dm2 can assemble into filaments at physiologic ionic strength; assembly is reversible upon addition of concentrated NaCl. Negative staining of filaments formed in vitro shows long, unbranched bundles approximately 20 nm in diameter. Addition of specific antilamin antibodies blocks in vitro assembly completely. In contrast with lamins Dm1 and Dm2, lamin Dmmit remains soluble at physiologic ionic strength. These observations are consistent with the notion that lamina disassembly in vivo is due, at least in part, to changes in properties of the lamins themselves.

Animals↗

PubMed1990

In vitro dissolution and in vivo bioavailability of commercial levothyroxine sodium tablets in the hypothyroid dog model.

The objective of this study was to determine whether a correlation exists between the rate of in vitro dissolution and bioavailability of levothyroxine sodium (T4) tablets. Dissolution versus time profiles for Synthroid, the Flint brand of levothyroxine sodium, and two competitors' tablets (brands A and B) were generated using an official dissolution apparatus (USP), and 0.05 M phosphate buffer (pH 7.4) as the medium. These tablets were also utilized in single-dose crossover bioavailability studies in the hypothyroid dog model (n = 6). The average areas under the serum T4 concentration versus time curve from 0 to 8 h (AUC) for Synthroid, brand A, and brand B were 8.22, 6.32, and 8.70 ng-h/mL per dose (micrograms per kg body weight), respectively. Respective peak serum concentrations (Cmax) for each tablet formulation were 1.26, 1.07, and 1.36 ng/mL per dose. The corresponding dissolution rates, expressed as t50%, were 20.5, 3.06, and 14.1 min, respectively. Data analysis indicated no correlation between dissolution kinetic parameters and the bioavailability parameters AUC and Cmax. However, a linear relationship was observed between dissolution kinetics and both the time to reach maximal serum concentration (tmax) and the observed absorption rate constant (ka).

Animals↗

PubMed1990

Medium-chain-triglyceride lipid emulsion: metabolism and tissue distribution.

The utilization and distribution of radioactively labeled lipid emulsions were evaluated in Sprague-Dawley rats. Animals received one of three lipid emulsions. Group 1 received [14C]medium-chain-triglyceride (MCT) lipid emulsion, group 2 received a 75%:25% (vol:vol) admixture of [14C]MCT: unlabeled long-chain-triglyceride (LCT) lipid emulsion, and group 3 received only [14C]LCT. The radioactive dose appearing in expired carbon dioxide and various body tissues was monitored over a 24-h period. Results indicate that MCT is oxidized more rapidly and completely than in LCT; approximately 90% of the MCT is converted to carbon dioxide with in 24 h compared with 45% for LCT. When MCT and LCT are administered together, the metabolism of MCT is slowed but remains more rapid than that of LCT. Removal of MCT from the blood was more rapid than was removal of LCT, and tissue radioactivity was lower.

Animals↗

PubMed1990

Gastric secretion pH measurement: what you see is not what you get!

We evaluated the accuracy of gastric secretion pH measurements as performed in three ICUs. The pH of 275 samples was measured with pH paper using established techniques. The pH of 85 additional samples was determined with a hand-held pH meter. All specimens also were measured using a research laboratory pH meter to learn the true pH. Analyses included mean and SD of the difference between the two measurements, the correlation coefficient (r value), and the concordance correlation coefficient. The pH meter values disagreed significantly with pH paper measurements. Measurements of gastric secretion pH with pH indicator paper do not guide therapy reliably. Inaccurate values derived from pH paper measurements could have resulted in inappropriate treatment in 28% of the samples tested. A portable, battery-powered pH meter accurately reproduced laboratory pH meter measurements and is a reasonable device for clinical use.

Gastric Acidity Determination↗

PubMed1990

Comparison of 18O exchange and pH stop-flow assays for carbonic anhydrase.

The hydration velocity of CO2 (0.002 M) catalyzed by bovine carbonic anhydrase (BCA) was measured at 25 degrees C and pH 7.4 by three different techniques: two initial-rate (steady-state) stop-flow methods, one using a glass pH electrode (in Hannover, method 1) and one using spectrophotometric measurements of a pH indicator (in Philadelphia, method 2), and an exchange method in which the disappearance of C18O16O from a bicarbonate solution was determined at equilibrium (in Philadelphia, method 3). The Michaelis-Menten constant (Km) and the inhibition constants for chloride (Ki,Cl) and ethoxzolamide (Ki,ez) were the same for methods 1, 2, and 3. The turnover numbers were 270,000, 400,000, and 555,000 s-1 by methods 1, 2, and 3, respectively. Values for CO2 hydration velocity measured by methods 2 and 3 on the same solution of BCA at the same time were the same. Km, maximal reaction velocity (Vmax), Ki,ez, and Ki,Cl obtained from normal human hemolysate at 37 degrees C and pH 7.2 by methods 2 and 3 were the same. Km and Vmax of the carbonic anhydrase isozyme CA III of homogenate from rabbit soleus were also identical by methods 1 and 3. According to Michaelis-Menten theory, the values of Km and Vmax obtained by method 3 should have been significantly smaller than those obtained by methods 1 and 2. We conclude that the catalytic step itself is apparently not rate limiting under physiological conditions and that method 3 can be used to obtain Michaelis-Menten characteristics of carbonic anhydrase.

Animals↗

PubMed1990

Myoglobin content and citrate synthase activity in different parts of the normal human heart.

Myoglobin (Mb) content and citrate synthase (CS) activity were determined in myocardial samples from nine human brain-dead organ donors with normal hearts. Six regions of each heart were analyzed: right and left atria, right ventricle, left ventricular subepicardium, subendocardium, and anterior papillary muscle. The Mb content was similar, whereas the CS activity was higher in the left than in the right heart at both atrial and ventricular levels. Mb content and CS activity were higher in ventricles than in atria. The subendocardial layer and papillary muscle of the left ventricle had a higher Mb content than the subepicardial layer, whereas CS activity was similar in these three locations. The results suggested a closer relationship between CS activity (oxidative potential) and work load than between Mb content and work load. Mb content may, instead, be related to intramuscular oxygen tension (PO2) on the basis of a comparison between our Mb data and those of others on regional variations in myocardial PO2.

Adolescent↗