Biomedical subjects

L Yang

Publications and source records attributed to L Yang.

At least 613 records · Page 34Linked to original sources

PubMed1995

Epinephrine increases the severity of postresuscitation myocardial dysfunction.

BACKGROUND: Epinephrine has been the mainstay for cardiac resuscitation for more than 30 years. Its vasopressor effect by which it increases coronary perfusion pressure is likely to favor initial resuscitation. Its beta-adrenergic action, however, may have detrimental effects on postresuscitation myocardial function when administered before resuscitation because it increases myocardial oxygen consumption. In the present study, our focus was on postresuscitation effects of epinephrine when this adrenergic agent was administered during cardiopulmonary resuscitation. Postresuscitation myocardial functions were compared with those of a selective alpha-adrenergic agent, phenylephrine, when epinephrine was combined with a beta 1-adrenergic blocking agent, esmolol, and saline placebo. METHODS AND RESULTS: Ventricular fibrillation was induced in 40 Sprague-Dawley rats. Mechanical ventilation and precordial compression was initiated either 4 or 8 minutes after the start of ventricular fibrillation. The adrenergic drug or saline placebo was administered as a bolus after 4 minutes of precordial compression. Defibrillation was attempted 4 minutes later. Left ventricular pressure, dP/dt40, and negative dP/dt were continuously measured for an interval of 240 minutes after successful cardiac resuscitation. Except for saline placebo, comparable increases in coronary perfusion pressure were observed after each drug intervention. The number of countershocks required for restoration of spontaneous circulation was significantly greater for epinephrine-treated animals (10 +/- 8) when compared with phenylephrine-treated animals (1.8 +/- 0.4, P < .01) and with animals treated with epinephrine combined with esmolol (1.6 +/- 0.9, P < .01). After resuscitation, dP/dt40 and negative dP/dt were significantly decreased and left ventricular end-diastolic pressure was significantly increased in each animal when compared with prearrest levels. However, the greatest impairment followed epinephrine, and this was associated with significantly greater heart rate and the shortest interval of postresuscitation survival of 8 +/- 4 hours, whereas placebo controls survived for 12 +/- 11 hours. Phenylephrine-treated animals survived for 41 +/- 10 hours (P < .01 versus epinephrine), and animals that received a combination of epinephrine and esmolol survived for 35 +/- 11 hours (P < .01 versus epinephrine). When the duration of untreated cardiac arrest was increased from 4 to 8 minutes, the severity of postresuscitation left ventricular dysfunction was magnified, but disproportionate decreases in postresuscitation survival were again observed with placebo and epinephrine when compared with alpha-adrenergic agonists. CONCLUSIONS: In an established rodent model after resuscitation following cardiac arrest, epinephrine significantly increased the severity of postresuscitation myocardial dysfunction and decreased duration of survival. More selective alpha-adrenergic agonist or blockade of beta 1-adrenergic actions of epinephrine reduced postresuscitation myocardial impairment and prolonged survival.

Adrenergic Agonists↗

PubMed1995

Potential linkage disequilibrium between schizophrenia and locus D22S278 on the long arm of chromosome 22.

Locus D22S278 at 22q12 has been implicated in schizophrenia by sib-pair analysis. In order to replicate these results, we performed the transmission test for linkage disequilibrium (TDT) in 113 unrelated schizophrenic patients and their 226 parents. Evidence for potential linkage disequilibrium was obtained between schizophrenia and allele 243 of the marker AFM 182xd12 at the locus D22S278 (P = 0.02). The results of our study suggest a detectable oligogenic gene in a multigene system for schizophrenia closely linked to D22S278 on the long arm of chromosome 22. If confirmed by others, this finding could lead to the identification of a schizophrenia susceptibility gene.

Adolescent↗

PubMed1995

Effects of premature beats on repolarization of postextrasystolic beats.

BACKGROUND: A short-long-short sequence of cycle lengths predisposes to reentrant tachyarrhythmias. There is limited information about the effects of premature ventricular contractions (PVCs) on repolarization of postextrasystolic depolarizations (PEDs). Such information would contribute to understanding the mechanism for facilitating reentry with short-long-short cycle lengths. METHODS AND RESULTS: We introduced PVCs, over a range of coupling intervals and during a range of basic drive cycle lengths (BCLs), and determined PED repolarization. Our results from whole-animal experiments, isolated cell studies, and computer simulations are reported. In the whole-animal experiments, PED refractory periods (RPs) were longer than RPBCL. The greatest difference between RPPED and RPBCL (delta RPmax) occurred after short coupling interval PVCs and was 4.3 +/- 0.8, 4.2 +/- 0.8, and 2.1 +/- 0.5 ms (mean +/- SEM) during drives with short, intermediate, and long BCLs, respectively. The diastolic interval preceding the PED (DIPED) was inversely related to the coupling interval between the basic drive beat and the PVC and directly related to RPPED. PED action potential durations (APDs) of isolated canine myocytes were 9.8 +/- 4.9 ms (mean +/- SEM) longer than APD BCL (n = 19). The DiFrancesco-Noble membrane equations were used in simulations of action potential propagation in a one-dimensional cable, with stimulation protocols duplicating those in the animal experiments. PVCs prolonged APDPED, and APDPED was prolonged more during short than during long BCL drives. There was a direct relation between DIPED and APDPED. Analysis of the membrane currents over the time course of the PVCs and PEDs suggested that the ionic basis for PED repolarization prolongation was the interaction of Ito and Ik. Hyperpolarizing constant-current injections introduced immediately after the spike of isolated myocyte action potentials caused APD prolongation. This observation is consistent with the Ito and Ik interaction causing PED repolarization prolongation. CONCLUSIONS: PED repolarization prolongation could provide sites for unidirectional block to propagation of PVCs after PEDs and could facilitate initiation of reentrant tachyarrhythmias after short-long-short sequences of cycle lengths.

Action Potentials↗

PubMed1995

Heparin inhibits the expression of interleukin-11 and granulocyte-macrophage colony-stimulating factor in primate bone marrow stromal fibroblasts through mRNA destabilization.

Interactions between different cytokines, extracellular matrix components, and various cell types inside the bone marrow microenvironment are believed to play important roles in the regulation of hematopoiesis. We observed that both interleukin-1 (IL-1) and 12-O-tetradecanoylphorbol-13-acetate (TPA) can stimulate the expression of IL-11 and granulocyte-macrophage colony-stimulating factor (GM-CSF) genes in a primate bone marrow stromal fibroblast cell line, PU-34. We also found that IL-1 or TPA-stimulated IL-11 and GM-CSF expression in PU-34 cells can be abolished by heparin, a class of molecules related to extracellular matrix components, glycosaminoglycans. Because the growth inhibitory signals provided by extracellular factors were less understood, the mechanisms of heparin inhibition of IL-11 and GM-CSF gene expression were further investigated. Our data demonstrate for the first time that heparin did not alter the transcription of endogenous IL-11 and GM-CSF genes or an exogenous IL-11 promoter construct containing an AP-1 sequence. Instead, heparin facilitated the degradation of the corresponding mRNAs. Through RNA gel shift assays, heparin-mediated mRNA destabilization was tentatively linked to its competition for mRNA binding proteins both in the cell-free system and in intact cells. Collectively, our findings suggest that varying degrees of heparin inhibition may provide a novel mechanism for the regulation of cytokine expression during the growth and differentiation of different lineages of hematopoietic cells.

Animals↗

PubMed1995

Stimulatory effect of saponin from Panax ginseng on immune function of lymphocytes in the elderly.

We used the saponin Rg1 extracted from Panax ginseng to study its effects on lymphocytes of 10 young and 19 elderly persons. The proliferative response of lymphocytes cocultured for 72 h with PHA and saponin was measured by using MTT method and the 3H-TdR incorporation procedure. PHA and Rg1 had stimulative effects on the phenotype of lymphocytes (P < 0.001). Rg1 also increased the fluidity of lymphocyte membrane of the aged (P < 0.001). The CD25 and CD45RA positive cells of lymphocytes in the elderly were lower than those of the young people, 8.6% +/- 2.7% vs 10.43% +/- 3.5%; 20.95% +/- 15.5% vs. 50.86% +/- 4.2%, respectively. More CD45RO positive cells (41.5% +/- 13.9%) than CD45RA positive cell lymphocyte populations were seen in the aged. The CD45RO positive cells of the young people were 39.63% +/- 3.2%. We discussed the cause of declined immune function of lymphocytes of aged person and the mechanism of the effect of P. ginseng on lymphocytes.

Aged↗

PubMed1995

Detection of basal acetylcholine in rat brain microdialysate.

A liquid chromatography-electrochemistry (LC-EC) method is described for the determination of basal acetylcholine (ACh) in microdialysate from the striatum of freely moving rats. This method is based on the separation of ACh and choline (Ch) by microbore liquid chromatography followed by passage of the effluent through a post-column immobilized enzyme reactor (IMER), containing acetylcholinesterase (AChE) and choline oxidase (ChO), and then the electrochemical detection of the hydrogen peroxide produced. Instead of the conventional platinum electrode generally used for the anodic detection of hydrogen peroxide, a peroxidase-redox polymer modified glassy carbon electrode operated at + 100 mV vs. Ag/AgCl has been used to detect the reduction of hydrogen peroxide. With this method, a detection limit of 10 fmol (injected) for ACh (S/N = 3:1) was obtained and the basal ACh concentration in striatal microdialysate was determined without using esterase inhibitors.

Acetylcholine↗

PubMed1995

Formation of membrane domains created during the budding of vesicular stomatitis virus. A model for selective lipid and protein sorting in biological membranes.

Vesicular stomatitis virus buds from domains of the plasma membrane that have a unique protein and lipid composition. Fluorescence digital imaging microscopy and resonance energy transfer were used to determine how the two viral envelope-associated proteins, the G and the M proteins, could alter the lateral distribution of lipids in large unilamellar vesicles and form domains. The G protein formed large domains in vesicles containing phosphatidic acid but not with phosphatidylserine, while the M protein formed domains enriched in both acidic phospholipids. Domains enriched in sphingomyelin were observed only when both the G protein and the M protein were present in vesicles containing phosphatidic acid. Phosphatidylcholine and gramicidin (chosen to represent a host membrane protein) were excluded from the domains. Cholesterol was induced to partition into the domains only in vesicles containing phosphatidic acid and sphingomyelin along with both of the proteins. Phosphatidylethanolamine was not enriched or depleted in the domains. Domains of similar composition were formed using vesicles made from dioleoylphospholipids and the lipids extracted from BHK-21 plasma membranes, indicating that the fatty acid composition was not as important as the polar head groups of the phospholipids. The phospholipid and cholesterol compositions of the domains formed by the G and the M proteins in vesicles were very similar to the composition of the viral envelope, suggesting that the domains represent the areas in the plasma membrane where the virus buds. This study provides a model for selective lipid and protein sorting that occurs in biological membranes.

Animals↗

PubMed1995

Isolation and photodynamic effects of hematoporphyrin derivative components: a chromatographic analysis of the starting materials.

Twenty different fractions of hematoporphyrin derivatives (HpD) and eight fractions of an HpD dimer mixture were isolated utilizing isocratic reversed-phase ion-pair high-performance liquid chromatography. These fractions were characterized by UV-visible and fluorescence spectrophotometry. Fluorescence quantum yields and photokill efficiency for each fraction in PTK2 epithelial cells were obtained. Results indicate that some part of the photoactivity exhibited by HpD may be due to impurities present in the HpD starting material, hematoporphyrin-IX dihydrochloride, depending on its source. It was also found that hematoporphyrin D, a commercial acetylated product formed during synthesis of HpD, contained a higher percentage of monomers than would be expected.

Animals↗

PubMed1995

Tyrosine phosphorylation and activation of JAK family tyrosine kinases by interleukin-9 in MO7E cells.

Interleukin-9 (IL-9) is a T-cell-derived multifunctional cytokine that can stimulate the proliferation of a human megakaryocytic leukemia cell line, MO7E. Previous studies suggested that protein tyrosine phosphorylation may be involved in IL-9 signaling pathways. However, tyrosine kinases activated by IL-9 have not been identified. In this report we show that IL-9 induces tyrosine phosphorylation and activation of the JAK family tyrosine kinases including JAK1, JAK3, and Tyk2. The kinetic studies indicate that tyrosine phosphorylation and activation of JAK kinases induced by IL-9 occurred within 1 minute, peaked by 5 to 10 minutes, and persisted at least for 45 minutes. Furthermore, we show that signal transducers and activators of transcription (Stat) 91 or related protein and an 88-kD Stat 91-associated protein are rapidly tyrosine phosphorylated following IL-9 treatment. Gel shift assays confirm that nuclear extracts from MO7E cells stimulated with IL-9 specifically interact with a DNA element termed gamma activated site. These results suggest that actions of IL-9 may, in part, be mediated through JAK kinase-Stat signaling cascades.

Base Sequence↗

PubMed1995

Suppression of the functional activity of IL-2-activated lymphocytes by CGRP.

CGRP is a 37-amino acid neuropeptide found in the central and peripheral nervous systems as well as the nerve endings in lymphoid organs. Specific CGRP receptors are present on both T and B lymphocytes. There is increasing evidence that CGRP plays a role in regulation of the immune response. However, few investigations have examined the effects of CGRP on lymphocyte effector functions. In this report, CGRP (0.1 nM-1 microM) was shown to cause concentration-dependent inhibition of IL-2-activated lymphocyte growth inhibition of the fungus Candida albicans and cytotoxic activity for tumor cells. Maximum inhibition of lymphocyte activity by CGRP was 47.4% for the hyphae of C. albicans, 44.8% for a natural killer cell susceptible cell line, and 52.9% for a natural killer cell-resistant cell line. CGRP-mediated inhibition of lymphocyte function was mimicked by 8-bromo-cAMP (1 mM) and was correlated in a concentration-dependent manner with an increase in intracellular levels of cAMP. These increases were potentiated by pretreatment of the lymphocytes with 3-isobutyl-1-methylxanthine (0.5 mM, 10 min), an inhibitor of the cAMP phosphodiesterase. hCGRP 8-37, a selective blocker of the CGRP1 receptor, abrogated the effect of CGRP on lymphocyte function and on intracellular cAMP level elevation induced by rCGRP. CGRP had no direct effect on the capacity of IL-2-activated lymphocytes to adhere to the hyphae of C. albicans. However, both CGRP and 8-bromo-cAMP diminished the capacity of the lymphocytes to release cytoplasmic granular content when stimulated by the hyphae of C. albicans. These data show that CGRP inhibits functional activity of IL-2-activated lymphocytes and suggest that hCGRP8-37 may be a useful tool for assessing the role of CGRP in the immune system.

Animals↗

PubMed1995

Membrane domains containing phosphatidylserine and substrate can be important for the activation of protein kinase C.

The relationship between lipid domains and enzyme activity was studied via the direct visualization and quantitation of domains by fluorescence digital imaging microscopy. The substrate used in these experiments was a basic peptide derived from a prominent cellular substrate (MARCKS) of protein kinase C. The MARCKS peptide and phosphatidylserine, which were labeled by two different fluorophores, colocalized into domains in large vesicles (5-10 microns). Increasing the ionic strength disrupted the domains of the MARCKS peptide and phosphatidylserine, and this was accompanied by a decrease in protein kinase C activity. Dansylpolylysine, which inhibits protein kinase C, was similar to the MARCKS peptide in forming domains enriched in phosphatidylserine. The degree of enrichment of the MARCKS peptide in the phosphatidylserine domains decreased proportionally with protein kinase C activity when polylysine was added. Polylysine caused the MARCKS peptide to be displaced from the domains into the nondomain areas of the vesicles. This suggested that binding of the substrate to the vesicles was not the critical factor for protein kinase C activity, but rather it was the organization of the substrate into domains that was related to the activation of the enzyme. Gramicidin, which was chosen to represent a neutral membrane protein, was excluded from the domains with phosphatidylserine, and it had no effect on the enrichment of the domains or the enzyme activity. The results of this study show that the formation of membrane domains can be important for the activation of protein kinase C and the activity can be inhibited by disrupting the domains.

Amino Acid Sequence↗

PubMed1995

Properties of Auricularia auricula-judae beta-D-glucan in dilute solution.

A water-soluble glucan A was isolated from the fruit body of Auricularia auricula-judae. It is composed of a backbone chain of beta-(1-->3)-linked D-glucose residues, two out of three glucose residues being substituted at C-6 positions with a single glucose unit. The weight average molecular weight Mw, number average molecular weight Mn, and intrinsic viscosity [eta] of the fractionated samples were studied at 25 degrees C in water and in dimethylsulfoxide (DMSO). The Mark-Houwink equation was established as [eta] = 6.10 x 10(-4) Mw1.14 for the glucan A having Mw ranging from 9 x 10(5) to 1.6 x 10(6) in water. The values of [eta] in water are far higher than those in DMSO, but the values of Mn measured in water are the same as those in DMSO. Analysis of Mw and [eta] in terms of the known theories for rods and wormlike chains yielded 1030 +/- 100 nm-1, 90 +/- 20 nm, 1.3 +/- 0.3 nm, and 0.26 +/- 0.03 nm for molar mass per unit contour length ML, persistence length q, diameter d, and contour length h per main-chain glucose residue, respectively. The present data suggest that glucan A dissolves in water as single-stranded helical chains and in DMSO as semiflexible chains.

Antineoplastic Agents↗

PubMed1995

Increased expression of p21Sdi1 in adrenocortical cells when they are placed in culture.

Expression of the cell cycle inhibitor p21Sdi1/WAF1/Cip1 was investigated in a differentiated cell type, the adrenocortical cell, at different stages of culture, from the preparation of cells from the adrenal gland to senescence after long-term growth. In bovine adrenocortical cells, expression of SDI1 was much higher in culture than in vivo. Elevation of SDI1 mRNA, accompanied by elevation of the level of a protein reacting with anti-p21Sdi1 antibodies, was observed as early as 3 h after the start of the tissue dissociation procedure used to prepare cells for culture. This level of expression was then maintained during plating and subsequent long-term growth in culture. Growth and quiescence in bovine adrenocortical cells can be modulated by inclusion or removal of FGF from the culture medium. In these cells SDI1 mRNA was not increased by long-term mitotic quiescence resulting from FGF deprivation. In cultured fetal human adrenocortical cells, SDI1 mRNA was also detected at all stages of the culture life span, including 2 days after isolation of cells from the adrenal gland and plating in culture. Mid-life-span cells had higher SDI1 mRNA than senescent human fibroblasts. Clones of human adrenocortical cells nearing senescence in culture had somewhat higher SDI1 mRNA than early passage cells. Thus, SDI1 expression in adrenocortical cells is not associated with mitotic quiescence either in vivo or in vitro, yet isolation of the cells and culturing them exerts a powerful inductive influence on its expression.

Adrenal Cortex↗

PubMed1995

A quantitative investigation of immunocytochemically stained blood vessels in normal, benign, premalignant and malignant human oral cheek epithelium.

The present study was designed to determine whether increased vascularity occurs during malignant transformation of human oral cheek epithelium. Nine normal (N) samples were taken from the resection margins of benign lesions; the pathological lesions were classified as chronic inflammation (CI; n = 11), fibrous hyperplasia (FH; n = 12), lichen planus (LIP; n = 8), dysplasia (DYS; n = 5), squamous cell carcinoma (SCC; n = 25; well differentiated [SCCWD]; n = 10; moderately to poorly differentiated [SCCMPD]; n = 15) and epithelium adjacent to carcinomas (EAC; n = 6). Sections were stained with monoclonal antibody (mAb) against vimentin using an ABC immunoperoxidase technique. All blood vessels present within a depth of 0.9 mm of lamina propria were quantified irrespective of their morphology. The blood vessel parameters quantified were volume density (VVBV, CT), number per unit area (NABV, CT), length per unit volume (LVBV, CT) and mean transverse sectional area (ABV). VVBV, CT increased significantly between normal and all pathological groups. Amongst the pathological groups, statistical differences were detected between CI and SCC, CI and EAC, FH and SCCWD, FH and EAC, LIP and SCC, LIP and EAC, DYS and SCCWD and DYS and EAC. The EAC group had the highest VVBV, CT and the values of NABV, CT and LVBV, CT were significantly higher in all the pathological groups when compared with the normal group. No significant differences were detected between any of the pathological group. The parameter ABV increased significantly between normal and DYS, FH, SCC, EAC, FH and EAC, FH and SCC, CI and EAC, CI and SCC, LIP and EAC and LIP and SCC. Spearman rank correlations detected a positive correlation between the severity of oral lesions and all of the blood vessel parameters. We conclude that a mAb against vimentin improved the identification of smaller blood vessels and the blood vessel data suggest that angiogenesis occurs in premalignant and malignant lesions of human oral cheek epithelium. Angiogenesis seems to play an essential role in sustaining the actively growing and transforming cells.

Adolescent↗

PubMed1995

[An epidemiological study on the relationship between musculoskeletal disorders and work load].

965 workers engaged in working tasks of work intensity grade 2, 3, 4 (based on Chinese National Standard) were investigated on the musculoskeletal disorders with a questionnaire. The lumbar vertebra of 136 randomly chosen workers were also radiologically examined. The result revealed that the prevalence of low-back disorders was 51.2% on average and it was obviously correlated with such factors as age, standing, previous back injury, education level, sport activity, work intensity, working posture, satisfaction with the tools as well as work condition and house work. Heavy work load and unneutral working posture were proved to be the main factors as revealed by the multifactor analysis and further supported by the findings of X-ray examination.

Adult↗

PubMed1995

Activity changes of ATP synthase and adenylate kinase in rat-liver mitochondria during the early phase after burn injury.

Using succinate as a substrate, the activities of ATP synthase and adenylate kinase in liver mitochondria of male Sprague-Dawley rats 30 min after 20 per cent full skin thickness burns were increased in comparison with the sham burn rats, suggesting that these two enzymes might contribute to the increased rates of ATP formation and oxidative phosphorylation coupling during the early phase after burn injury.

Adenylate Kinase↗

PubMed1995

Dielectric response of triplex DNA in ionic solution from simulations.

We have analyzed a 1.2-ns molecular dynamics simulation of 51 mM d(CG.G)7 with 21 Na+ counter-ions and 1 M NaCl in water. Via the dipole fluctuations, the dielectric constant for the DNA is found to be around 16, whereas that for the bases and sugars combined is only 3. The dielectric constant for water in this system is 41, which is much smaller than 71 for pure SPC/E water, because of the strong restriction imposed on the motion of water molecules by the DNA and the ions. Also addressed in the present work are several technical issues related to the calculation of the dipole moment of an ionic solution from molecular dynamics simulations using periodic boundary conditions.

DNA↗

PubMed1995

An international two-stage genome-wide search for schizophrenia susceptibility genes.

Schizophrenia is thought to be a multifactorial disease with complex mode of inheritance. Using a two-stage strategy for another complex disorder, a number of putative IDDM-susceptibility genes have recently been mapped. We now report the results of a two-stage genome-wide search for genes conferring susceptibility to schizophrenia. In stage I, model-free linkage analyses of large pedigrees from Iceland, a geographical isolate, revealed 26 loci suggestive of linkage. In stage II, ten of these were followed-up in a second international collaborative study comprising families from Austria, Canada, Germany, Italy, Scotland, Sweden, Taiwan and the United States. Potential linkage findings of stage I on chromosomes 6p, 9 and 20 were observed again in the second sample. Furthermore, in a third sample from China, fine mapping of the 6p region by association studies also showed evidence for linkage or linkage disequilibrium. Combining our results with other recent findings revealed significant evidence for linkage to an area distal of the HLA region on chromosome 6p. However, in a fourth sample from Europe, the 6p fine mapping finding observed in the Chinese sample could not be replicated. Finally, evidence suggestive of locus heterogeneity and oligogenic transmission in schizophrenia was obtained.

Chromosomes, Human, Pair 20↗