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Biomedical subjects

Y H Li

Publications and source records attributed to Y H Li.

At least 91 records · Page 5Linked to original sources

Prognostic significance of elevated hemostatic markers in patients with acute myocardial infarction.

OBJECTIVES: The purpose of this study was to determine whether the elevated levels of hemostatic markers in the early phase of myocardial infarction may serve as risk factors for subsequent cardiac mortality. BACKGROUND: Increased plasma hemostatic markers were noted in acute myocardial infarction, indicating that the blood coagulation system is highly activated in those patients. However, there are few clinical data concerning the association between the elevated hemostatic markers and survival in patients with myocardial infarction. METHODS: Blood samples were obtained from 64 patients (mean age 67 +/- 11 years; 49 male) with acute myocardial infarction within 12 h after the onset of symptoms and before the initiation of any antithrombotic treatment. We measured plasma concentrations of fibrinopeptide A (FPA), prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) using the enzyme-linked immunosorbent assay method, and examined the associations between the level of these markers and survival with Cox proportional hazards models. RESULTS: The follow-up time was 27 +/- 17 months, and 19 patients died of cardiac causes during the follow-up. Univariate survival analysis identified Killip class IV (hazard ratio 4.86; 95% confidence interval [CI] 1.55-15.19), left ventricular ejection fraction (hazard ratio 0.94; 95% CI 0.90-0.99), FPA (hazard ratio 1.54; 95% CI 1.13-2.10), F1+2 (hazard ratio 2.03; 95% CI 1.17-3.53) and TAT (hazard ratio 1.88; 95% CI 1.27-2.79) as significant factors associated with cardiac mortality. In multivariate analyses, only FPA level (hazard ratio 1.84; 95% CI 1.03-3.30) and left ventricular ejection fraction (hazard ratio 0.93; 95% CI 0.88-0.98) were independent predictors of cardiac mortality. CONCLUSIONS: Elevated FPA in the early phase of myocardial infarction identifies patients with increased risk for subsequent cardiac death. This association appears to be independent of residual left ventricular function after infarction.

Adult↗

A modified Boyden chamber assay for tumor cell transendothelial migration in vitro.

We have developed a modified Boyden chamber system for assessing tumor cell transmigration across endothelial monolayer in vitro. This radiometric-based method allows us to take into account the cells which have traversed but detached from the filter, a significant fraction not included in the existing method of visual counting. The method was applied to examine six malignant and one non-malignant cell lines. The variable invasive potentials of these cells were found to correlate with their ability to disrupt the endothelial cell monolayers.

Biological Assay↗

Endotoxin-induced changes in IGF-I differ in rats provided enteral vs. parenteral nutrition.

The purpose of the present study was to determine whether acute changes in the insulin-like growth factor (IGF) system induced by mild surgical trauma/fasting or endotoxin [lipopolysaccharide (LPS)] are differentially modulated by total enteral nutrition (TEN) or total parenteral nutrition (TPN). Rats had vascular catheters and a gastrostomy tube surgically placed and were fasted overnight. The next morning animals randomly received an isocaloric, isonitrogenous (250 kcal. kg-1. day-1, 1.6 g N. kg-1. day-1) infusion of either TEN or TPN for 48 h. Then rats were injected intravenously with Escherichia coli LPS (1 mg/kg) while nutritional support was continued. Time-matched control animals were injected with saline. After mild surgical trauma and an 18-h fast, TEN was more effective at increasing plasma IGF-I levels than TPN. Subsequent injection of LPS decreased IGF-I in blood, liver, and muscle in both TEN- and TPN-fed rats compared with saline-injected control animals. However, this decrease was approximately 30% greater in rats fed TPN compared with those fed TEN. LPS-induced downregulation of IGF-I mRNA expression in liver and muscle was also more prominent in TPN-fed rats. The LPS-induced increase in plasma corticosterone and tumor necrosis factor-alpha was greater (2- and 1.6-fold, respectively) in TPN-fed rats, and these changes were consistent with the greater reduction in IGF-I seen in these animals. In similarly treated rats allowed to survive for 24 h after LPS injection, the LPS-induced increase in the urinary 3-methylhistidine-to-creatinine ratio was smaller in TEN-fed rats. In summary, LPS reduced systemic levels of IGF-I as well as IGF-I protein and mRNA in critical target organs. Enteral feeding greatly attenuated this response. Maintenance of higher IGF-I levels in TEN-fed rats was associated with a reduction in inflammatory cytokine levels and lower rates of myofibrillar degradation.

Animals↗

Dipeptidyl peptidase III from rat liver cytosol: purification, molecular cloning and immunohistochemical localization.

Dipeptidyl peptidase III (DPP III) was purified to homogeneity from rat liver cytosol. The calculated molecular weight of the purified enzyme was 82845.6 according to TOF-MS and 82000 on non-denaturing PAGE, and 82000 on SDS-PAGE in the absence or presence of beta-mercaptoethanol. These findings suggest that the enzyme exists in a monomeric form in rat liver cytosol. The enzyme rapidly hydrolyzed the substrate Arg-Arg-MCA and moderately hydrolyzed Gly-Arg-MCA in the pH range of 7.5 to 9.5. The Km, k(cat) and k(cat)/Km values of DPP III at optimal pH (pH 8.5) were 290 microM, 18.0 s(-1) and 62.1 s(-1) x nM(-1) for Arg-Arg-MCA and 125 microM, 4.53 s(-1) and 36.2 s(-1) x nM(-1) for Ala-Arg-MCA, respectively. DPP III was potently inhibited by EDTA, 1,10-phenanthroline, DFP, PCMBS and NEM. These findings suggest that DPP III is an exo-type peptidase with characteristics of a metallo- and serine peptidase. For further information on the molecular structure, we screened a rat liver cDNA library using affinity-purified anti-rat DPP III rabbit IgG antibodies, determined the cDNA structure and deduced the amino acid sequence. The cDNA, designated as lambdaRDIII-11, is composed of 2640 bp and encodes 738 amino acids in the coding region. Although the enzyme has a novel zinc-binding motif, HEXXXH, DPP III is thought to belong to family 1 in clan MA in the metalloprotease kingdom. The DPP III antigen was detected in significant amounts in the cytosol of various rat tissues by immunohistochemical examination.

Amino Acid Sequence↗

Prognostic value of Doppler-derived mitral deceleration time in postinfarction patients with left ventricular ejection fractions of 35% or more.

Short Doppler-derived mitral deceleration time of early filling has been proved to be an independent predictor of poor prognosis in patients with left ventricular dysfunction. However, the prognostic value of Doppler-derived mitral deceleration time in postinfarction patients without overt left ventricular dysfunction is poorly understood. A total of 27 survivors of acute myocardial infarction with left ventricular ejection fractions of 35% or more, as determined by radionuclide ventriculography, were prospectively studied. Doppler study was performed 5 to 7 days after the index infarction. The patients were divided into two groups. Group A included 10 patients whose mitral deceleration time was 125 msec or less and group B consisted of 17 patients whose mitral deceleration time was 125 msec or more. The two groups were similar in terms of age and gender distribution and there were no statistically significant differences in coronary risk factors, peak creatine kinase concentration, location of infarction, Killip classification, thrombolytic therapy, left ventricular ejection fraction, or medications. After a mean follow-up period of 30 months, the rate of congestive heart failure (New York Heart Association, NYHA, class II or above) was significantly higher in group A (5/10) than in group B (1/17) (p < 0.01). These results suggest that a short mitral deceleration time could be a useful early predictor of the potential development of future congestive heart failure in postinfarction patients with left ventricular ejection fractions of 35% or more.

Blood Flow Velocity↗

Mechanism of intestinal absorption of an orally active beta-lactam prodrug: uptake and transport of carindacillin in Caco-2 cells.

Absorption characteristics of carindacillin (CIPC) were investigated using Caco-2 cells, and the results were compared with those of its parent drug, carbenicillin (CBPC). Uptake of CBPC was not affected by the metabolic inhibitor or the change in extracellular pH. CBPC appeared to be taken up into Caco-2 cells by passive diffusion. In contrast, the uptake of CIPC was greater at lower extracellular pH and was inhibited in the presence of carbonyl cyanide p-(trifluoromethoxy)phenyl hydrazone, a protonophore. Also, transport of CIPC through Caco-2 cell monolayer was energy and temperature dependent. Moreover, the uptake and transport of CIPC were significantly inhibited in the presence of various monocarboxylic acids, which are the substrates of the monocarboxylic acid transport system(s), whereas the substrates of the oligopeptide transporter had no effect on the uptake or transport of CIPC. These results suggested that the absorption of CIPC may be mediated by the monocarboxylic acid transport system(s), not by the oligopeptide transporter. Furthermore, the uptake and transport of CIPC were approximately 40-fold greater than those of CBPC. Therefore, it is likely that the participation of a carrier-mediated transport in the absorption of CIPC may significantly contribute to the improved absorption of the prodrug over the parent drug.

Administration, Oral↗

Delayed treatment with diethyl maleate prevents E-selectin expression in human endothelial cells.

BACKGROUND: Polymorphonuclear leukocyte (PMN) infiltration is a significant contributor to tissue damage in many disease states and is known to occur through an orderly set of events. The endothelial cell adhesion molecule E-selectin is involved in the initial rolling of PMNs on the endothelium at sites of inflammation. We have previously shown that the glutathione depleting agent diethyl maleate (DEM) attenuates lung injury in a rodent model of intratracheal LPS stimulation. We hypothesized that DEM might attenuate E-selectin in LPS-treated human umbilical vein endothelial cells as a mechanism underlying this effect. Further, we investigated the role of delayed treatment with DEM on E-selectin expression. METHODS: Human umbilical vein endothelial cells were treated with DEM (100 to 400 mumol/L) before or after LPS stimulation (1 microgram/mL). Surface expression of E-selectin was examined using a cellular enzyme-linked immunosorbent assay. E-selectin mRNA transcripts were detected by Northern blot analysis. Nuclear factor-kappa B (NF-kappa B) activity was detected with gel shift assays. RESULTS: DEM significantly inhibited LPS-induced E-selectin surface expression and mRNA levels in a dose-dependent fashion, with complete inhibition at 250 mumol/L, without affecting cell viability. This inhibitory effect was seen even if DEM was added up to 60 minutes after LPS. DEM inhibited NF-kappa B nuclear translocation in a manner that mirrored protein and mRNA levels. CONCLUSIONS: Delayed treatment with DEM attenuates NF-kappa B nuclear translocation and E-selectin expression in human umbilical vein endothelial cells up to 60 minutes after the onset of LPS stimulation. Thus, DEM may represent an effective intervention for PMN-mediated organ injury even when given after an inflammatory insult.

Cells, Cultured↗

Prognostic determinants of infective endocarditis in the 1990s.

The clinical profiles of infective endocarditis (IE) might have changed in recent years, owing to the advent of transesophageal echocardiography, the introduction of new diagnostic criteria, and the increased frequency of intravenous drug abuse. In this retrospective study, we sought to identify factors affecting the in-hospital outcome of IE patients in a single tertiary referral center in the 1990s (1990-1997). Eighty-eight episodes of IE in 80 consecutive patients admitted from January 1990 through June 1997 were evaluated. Clinical variables that were significantly associated with in-hospital mortality in univariate analyses were entered into a multiple logistic regression model. A total of 22 patients (25%) died. Fatal episodes were significantly more likely than non-fatal episodes to involve older patients (> or = 50 years), use of coumadin, short interval between symptom onset and hospitalization (< 15 days), noncardiac shock, and complications of the heart, central nervous system, and kidneys. White blood cell counts and C-reactive protein concentrations were also significantly higher in fatal than in non-fatal episodes of IE. Multivariate analysis showed that in-hospital mortality was associated with noncardiac shock, neurological complications, cardiac complications, and older age (> or = 50 years). Compared with previous reports, our findings suggest that the clinical profiles of IE have undergone some changes in the 1990s. The most important prognostic predictors of in-hospital mortality in patients with IE were noncardiac shock and neurologic complications.

Adolescent↗

Pulmonary artery leiomyosarcoma.

Pulmonary artery leiomyosarcoma is a rare but highly lethal disease, and can be mistaken for pulmonary thromboembolism. We report a case of pulmonary artery leiomyosarcoma managed with surgical resection, chemotherapy, and radiotherapy. A 57-year-old woman was admitted with complaints of aggravated dyspnea. She was initially treated with oxygen therapy and heparinization for a suspected pulmonary embolism. Echocardiography revealed a dilated right atrium and ventricle and severe tricuspid regurgitation, with an estimated systolic right ventricular pressure of 95 mm Hg; a shadow of a mass in the main pulmonary artery was also noted. Right ventriculography revealed a filling defect, and to-and-fro motion of the mass in the main pulmonary artery. The left pulmonary artery was almost totally occluded by the mass. The patient's condition improved dramatically after palliative excision of the mass and patch reconstruction of the outflow tract of the right ventricle with a bicuspid xenograft. Pathologic examination of the mass revealed leiomyosarcoma. Chemotherapy and radiotherapy were subsequently administered and follow-up imaging studies 3 months postoperatively revealed no recurrence of the tumor. The patient remains well, more than 1 year after treatment. This report emphasises that pulmonary artery sarcoma should be considered in the differential diagnosis in cases of suspected pulmonary thromboembolism.

Diagnosis, Differential↗

[Changes in the content and activity of HSC70/HSP68, proteinases and phosphatases during liver regeneration].

This article reports changes in acid and alkaline phosphatases (ACP and AKP), constitutive heat shock protein 70/induced heat shock protein 68 (HSC70/HSP68) and acid and neutral proteinases during liver regeneration (0-144 h) after 2/3 hepatectomy (partial hepatectomy, PH). Both ACP and AKP had two active peaks at 4 and 48 h, 16 and 96 h, respectively, which were followed by significant decrease. The content of HSC70/HSP68 also showed two peaks (16 and 96 h), of which the content after the second peak decreased more obviously than after the first peak. Moreover a 90 kD neutral proteinase was induced at the time from 2 to 6 h and a 27 kD acid proteinase was induced at 36 h. The results suggest that the ACP and the 90 kD neutral proteinase may participate in activating hepatocytes from G0-phase into G1-phase, and AKP and HSC70/HSP68 may play a role mainly in DNA synthesis, cellular metabolism and proliferation. Furthermore 27 kD acid proteinase may be involved in re-differentiation of hepatocytes and reconstruction of liver tissue.

Acid Phosphatase↗

Biodegradation and tumorigenicity of implanted plates made from a copolymer of epsilon-caprolactone and L-lactide in rat.

Flat plates made from a copolymer of epsilon-caprolactone and L-lactide (P-CL-LA) [50:50 (w/w), molecular weight 1.62 x 10(5); 20 x 10 x 1 mm size] were subcutaneously implanted into 50 young, male Wistar rats (P-CL-LA group). After 24 months the plates had become a mass of small pieces, which were concentrated in an area of 3 x 2 x 1 mm. For comparison, 50 rats were implanted with medical-grade polyethylene plates (PE group) while another set of 50 rats was subjected to the same operation but without an implant (Sham Op group). Tumors arose in 25 rats from the P-CL-LA group: 24 were malignant mesenchymal tumors at the implant sites. In the PE group, tumors appeared in 16 rats (14 at the implant sites and two ectopically). The average tumor latency was 578+/-84 days in the P-CL-LA group and 452+/-102 days in the PE group. There was no difference in tumor incidence between the P-CL-LA and PE groups (p < 0.05). In the Sham Op group, two malignant tumors appeared over 2 years. Pathologically, these induced tumors arose from the inflammatory cells surrounding the degrading fragments of P-CL-LA within the tissue capsule. This indicates that relatively slowly degrading material can induce malignant tumors at a similarly high rate to nonabsorbable medical grade PE, at least in this animal model.

Abdominal Neoplasms↗

Immunomodulatory effects of hypertonic resuscitation on the development of lung inflammation following hemorrhagic shock.

Hypertonic resuscitation fluids are known to be effective in restoring circulating volume in the hypovolemic trauma patient. Previous studies have suggested that hypertonicity might exert effects on immune cells leading to an altered host response. The present studies evaluated the effect of hypertonic resuscitation on the development of lung injury in a hemorrhagic shock model in which antecedent shock primes for increased lung neutrophil sequestration in response to intratracheal LPS. Resuscitation with hypertonic saline significantly reduced albumin leak, bronchoalveolar lavage fluid neutrophil counts, and the degree of histopathologic injury compared with resuscitation with Ringer's lactate. Both in vivo and in vitro data suggest that this beneficial effect may be related to altered adhesion molecule expression by the neutrophil. Specifically, hypertonicity induced shedding of L-selectin and prevented LPS-stimulated expression and activation of CD11b, both of which might contribute to reduced sequestration in the lung. Impaired up-regulation of lung ICAM-1 may have also participated, although ex vivo studies suggest that alterations in neutrophils were sufficient to account for the effect. Lung cytokine-induced neutrophil chemoattractant did not differ between animals resuscitated with hypertonic saline vs Ringer's lactate. Considered together, these studies demonstrate a possible novel approach to inhibiting organ injury in disease processes characterized by neutrophil-mediated damage.

Adjuvants, Immunologic↗

No change of brain extracellular catecholamine levels after acute catechol-O-methyltransferase inhibition: a microdialysis study in anaesthetized rats.

Catechol-O-methyltransferase inhibitors have been newly introduced as adjunct drugs to the levodopa/dopa decarboxylase inhibitor therapy in Parkinson's disease. When given alone, catechol-O-methyltransferase inhibitors seem to affect behaviour. We wanted to determine whether the concentrations of free amine would be increased by catechol-O-methyltransferase inhibition with tolcapone and underpin the positive behavioural effects. To this end, dopamine and noradrenaline levels were analyzed in the microdialysis perfusion fluid collected from several brain regions in chloral hydrate anaesthetized rats. We also analyzed the turnover rate of catecholamines in the brain after single doses of tolcapone and entacapone using the alpha-methyl-p-tyrosine method. On their own, tolcapone (at 10 or 30 mg/kg) did not elevate dopamine or noradrenaline levels in any brain region studied although the formation of catechol-O-methyltransferase-dependent metabolites was strongly reduced. Neither tolcapone nor entacapone (at 30 mg/kg) affected the turnover rate of catecholamines. It seems that catechol-O-methyltransferase inhibitors do not alter behaviour by elevating extracellular levels of free catecholamines levels but other explanations are needed.

3,4-Dihydroxyphenylacetic Acid↗

Atrial dissociation after atrial compartment operation for chronic atrial fibrillation in mitral valve disease.

Atrial dissociation with segmental atrial arrhythmia is an interesting electrophysiological phenomenon. It was rarely reported before to be caused by anatomical exit block after cardiac surgery. We report the case of a 28-year-old patient who developed atrial disassociation after a surgical method for correcting atrial fibrillation--atrial compartment operation. The segmental atrial flutter was first found by Doppler echocardiography and proved later by detailed intracardiac mapping.

Adult↗

The protective effects of traditional Chinese medicine prescription, han-dan-gan-le, on CCl4-induced liver fibrosis in rats.

Han-Dan-Gan-Le, a Chinese medicine preparation composed of Salvia miltorrhiza, Radix paeoniae, Astragalus membranaceus, Stephania tetrandra, and dried leaves of Ginkgo biloba, has been used successfully to treat human liver fibrosis and cirrhosis for years. This study was designed to examine the mechanisms of the protection. Male Wistar rats were given CCl4 (1.2 ml/kg, 2 times/week), 20% fat diet, and 30% alcohol in drinking water (every other day) for 6 weeks. Han-Dan-Gan-Le (0.5 and 1.0 g/kg, p.o., daily for 6 weeks) was administered to rats simultaneously to examine the protective effects against CCl4-induced liver fibrosis. The experimentally-induced liver fibrosis and other morphological alterations were significantly ameliorated by Han-Dan-Gan-Le. Han-Dan-Gan-Le treatments decreased CCl4-induced hepatic collagen accumulation by more than 50%, and significantly increased urinary excretion of hydroxyproline. The CCl4-induced lipid peroxidation in liver and serum was ameliorated as a result of Han-Dan-Gan-Le treatment, possibly by restoring the activity of superoxide dismutase activity in liver and erythrocytes, In conclusion, Han-Dan-Gan-Le is effective in protecting against liver fibrosis. The mechanisms of the protection appear to be due to its antioxidant properties and the modulation of hepatic collagen metabolism.

Animals↗

Isolation and characterization of an alanyl aminopeptidase from rat liver cytosol as a puromycin-sensitive enkephalin-degrading aminopeptidase.

Alanyl aminopeptidase (AAP-S) was purified to homogeneity from rat liver cytosol. The molecular weight of the purified enzyme was calculated to be approximately 100,000 on Sephacryl S-200 HR and to be 90,000 on SDS-PAGE in the presence of beta-mercaptoethanol. These findings suggested that the enzyme exists as a monomeric form in rat liver cytosol. The enzyme rapidly hydrolyzed the substrates Ala-, Tyr- and Met-MCAs, and moderately hydrolyzed Arg-, Lys-, Leu-, Phe- and Lys-Ala-MCAs at pHs ranging from 7.5to 8.0. The enzyme also hydrolyzed several amino acid 4-methyl-coumaryl-7-amide (MCA) substrates. The order for k(cat)/Km values of AAP-S at the optimal pH (pH 7.5) was Lys->Met->Arg->Ala->Leu->Phe->Tyr->Lys-Ala-MCAs. It was strongly inhibited by bestatin, leuhistin, actinonin, amastatin, 1, 10-phenanthroline, PCMBS, Zn2+, Cd2+, Co2+, Cu2+ and Hg2+, and puromycin. The amino acid sequence of the first 43 residues of the enzyme was determined as Pro1-Glu-Lys-Arg-Pro5-Phe-Glu-Arg-Leu-Pro10-Thr-Glu-Val-Ser-Pro 15-Ile-Asn-Tyr-Ser-Leu20-(Cys)-Leu-Lys-Pro-Asp25-Leu-Leu- Asp-Phe-Thr30-Phe-Glu-Gly-Lys-Leu35-Glu-Ala-Ala-Ala-Gln40 -Val-Arg-Gln-. This N-terminal amino acid sequence is almost identical with those of puromycin-sensitive enkephalin-degrading aminopeptidases in rat and human brains, and the mouse neuroblastoma cell line Neuro2A. These findings suggest that the AAP-S from rat liver cytosol is a puromycin-sensitive aminopeptidase. Furthermore, with immunohistochemistry the enzyme was strongly stained in the cytosol of the rat liver cells.

Amino Acid Sequence↗

Amebic liver abscess complicated with cardiac tamponade and mediastinal abscess.

Amebic pericarditis is an extremely rare complication of liver abscess and an uncommon etiology of sterile pericardial effusion with cardiac tamponade. The association of mediastinal abscess in this clinical setting has not been reported in the literature. Herein, we describe a case of amebic liver abscess complicated with mediastinal abscess and amebic pericarditis with cardiac tamponade. A 44-year-old man was admitted to our hospital because of shortness of breath for the previous 2 days. Cardiac tamponade was diagnosed and emergency pericardiectomy was performed. Chocolate-like pus was found in the pericardial sac and mediastinal space during surgery. Abdominal computed tomography revealed an ill-defined hypodense lesion over the left lobe of the liver, suggesting a liver abscess. Amebic liver abscess and pericarditis were diagnosed on the basis of a high serum titer of amebic antibodies on hemagglutination test. The patient was treated with metronidazole for 2 weeks and discharged in good condition. This case should alert clinicians to the possibility of amebic pericarditis in patients with cardiac tamponade associated with chocolate-like sterile pus in the pericardium and mediastinum. To establish the diagnosis of amebic pericarditis, one should investigate the presence of a liver abscess, a high serum titer of amebic hemagglutination antibodies, and the presence of Entamoeba histolytica trophozoites in the pericardium or pericardial aspirate.

Abscess↗