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Biomedical subjects

K Wang

Publications and source records attributed to K Wang.

At least 307 records · Page 17Linked to original sources
PubMed1998

The effects of endocardial defibrillation on left ventricular function: a transoesophageal echocardiographic study.

This study evaluates the immediate effects of the endocardial electrical shocks delivered by a transvenous defibrillation system on left ventricular (LV) function in a pig model. A triple-lead system consisting of two endocardial electrodes, in the right ventricular apex and the junction of superior cava-right atrium, and a custom-made defibrillation can implanted subcutaneously in the thorax was set up in 10 close-chest pigs. Transesophageal echocardiography with two dimensional image, m-Mode, and pulse Doppler was performed at baseline and after several episodes of fibrillation/defibrillation (F/DF). Each animal underwent an average of 8 (range 6 to 11) episodes of ventricle F/DF for a total of 210 (range 165 to 290) joules of biphasic-waveform defibrillation shocks. Heart rate, blood pressure, LV end-systolic area, end-diastolic area and fractional area contraction, isovolumic relaxation time, and both ratios of velocities and time-velocity integrals in transmitral Doppler flow E and A waves were unchanged after the shocks. This animal study suggests that multiple countershocks up to 210 joules delivered by a transvenous defibrillation system do not cause LV global systolic and/or diastolic dysfunction.

Animals↗
PubMed1998

Can collagen type II sustain a methotrexate-induced therapeutic effect in patients with long-standing rheumatoid arthritis? A double-blind, randomized trial.

OBJECTIVE: Based on the results of two recently published, randomized, double-blind and placebo-controlled studies, a possible improvement in rheumatoid arthritis disease activity after oral tolerization with triple helical collagen type II has been suggested. The goal of this study was to go one step further and ask the question whether collagen type II can sustain the therapeutic effect induced by methotrexate, the most widely accepted disease-modifying anti-rheumatic drug in patients with long-standing rheumatoid arthritis. METHODS: Ninety-two patients with rheumatoid arthritis on stable therapy with methotrexate were enrolled in a 3 month double-blind, randomized and comparative study to examine the efficacy of oral triple helical collagen type II as compared to continuing methotrexate. The dose of methotrexate (or the respective placebo drug) and of concomitant corticosteroids was not changed and intra-articular corticosteroids were not allowed during the 3 months. The primary study endpoint was disease activity as measured by physician and patients. RESULTS: While patients under ongoing therapy with methotrexate had, as expected, no change in disease activity, almost all parameters of disease activity and outcome in patients under a daily oral dose of 0.5 mg triple helical collagen type II worsened significantly (highly significant difference in swollen joints, between the two groups, P < 0.0001). No significant differences in side-effects between the two groups during the study period could be demonstrated. CONCLUSIONS: Substitution of methotrexate with daily 0.5 mg of triple helical collagen type II in patients with rheumatoid arthritis leads to a significant increase in disease activity, suggesting that oral collagen type II at the given dose is not capable of sustaining the methotrexate-induced anti-inflammatory effect in patients with long-standing rheumatoid arthritis.

Administration, Oral↗
PubMed1997

Systolic and diastolic effects of variable atrioventricular delay in patients with complete heart block and normal ventricular function.

This study was designed to demonstrate the effects of varying the atrioventricular delay (AVD) on ventricular diastolic filling dynamics and the resultant stroke volume in patients with complete heart block and normal cardiac function. We studied 7 patients with normal cardiac function in whom a dual chamber pacemaker had been implanted because of complete heart block. Doppler and M-mode echocardiography was performed at 70, 100, 140, 180, and 220 ms, AVD with the device in DDD mode at a rate of 80 beats/min. The effects of these variable intervals on the contribution of the E and A waveform to the diastolic filling, on the stroke volume, and on the systolic intervals were evaluated. Optimization of this interval, with a 19% increase in stroke volume was achieved in the group of patients at an AVD of 140 ms. When considered individually, the AVD associated with the largest stroke volume, was 100 ms in 2 patients and 140 ms in the remaining 5. At this individual optimal AVD the ventricular septal contraction occurred 31 +/- 14 ms, before the end of the transmitral flow. The optimal AVD is, therefore, the one which synchronizes the ventricular and atrial systole so that the first ventricular septal contraction occurs after the peak of the A wave, just before the end of the transmitral flow. Because of the different functional cardiovascular status of the single patient, this parameter should be individualized; this can be clinically important as it may lead, in this patient population, to an improvement of the stroke volume up to 42%.

Adult↗
PubMed1997

Phosphorylation and regulation of the Na+/H+ exchanger through mitogen-activated protein kinase.

We examined mitogen-activated protein kinase-mediated phosphorylation and activation of the Na+/H+ exchanger isoform type 1. A rabbit skeletal muscle extract was fractionated by FPLC chromatography. Four main fractions had the ability to phosphorylate the carboxyl-terminal region of NHE1. Western blot analysis and immunoprecipitation showed that three of these were associated with MAP kinase-dependent phosphorylation. Phosphorylation studies using purified MAP kinase showed that the region involved was the carboxyl-terminal 178 amino acids of the protein and that the stoichiometry was 1 phosphate/mol of protein. In-gel kinase assays showed that cytosolic extracts from smooth muscle cells also phosphorylate the carboxyl-terminal of NHE1 and that the MAP kinase-dependent phosphorylation could be activated by PDGF and AngII. Mutant cell lines with an inducible dominant negative MAP kinase showed decreased serum activation of Na+/H+ exchange but normal hypertonic activation of the protein. The results show that MAP kinase is intimately involved in regulation of the Na+/H+ exchanger, possibly through phosphorylation of one amino acid of the carboxyl-terminal cytosolic domain.

Animals↗
PubMed1997

Ex vivo experiment on radiofrequency liver ablation with saline infusion through a screw-tip cannulated electrode.

PURPOSE: To investigate whether radiofrequency (RF) therapy with hypertonic saline infusion through a hollow screw-tip electrode can cause a lesion size suitable for liver tumor ablation. MATERIALS AND METHODS: RF tissue ablation of 180 sites was performed by using a hollow screw-tip electrode in 40 freshly excised swine livers. Under both power and temperature control modes, the ablation effects with and without various regimes of 5% hypertonic saline (1 ml/min) prior to and/or during the procedure were compared by measuring the size of lesions at dissection and confirmed by T1 and T2 weighted magnetic resonance (MR) imaging. RESULTS: The maximal lesion diameter of 5.5 cm was reached at 30 W with saline infusion 1 min prior to and during 12 min of ablation. The smaller sizes (P < 0.01) between 0.3 and 2.5 cm in diameter were met with noninfusion or preinfusion-only groups. The RF ablation lesions appeared as hyper- and hypointense areas on T1 and T2 MR images, respectively. CONCLUSIONS: RF ablation in combination with present hollow screw-tip electrode and saline infusion allows for necrotic development of suitable size for liver tumor ablation. Such ablated lesions can be visualized with MR imaging.

Animals↗
PubMed1997

Decreased endosomal delivery of major histocompatibility complex class II-invariant chain complexes in dynamin-deficient cells.

Major histocompatibility complex class II molecules are heterodimeric cell surface molecules which acquire antigenic peptides in the endosomal/lysosomal system. Invariant chain (Ii), a third chain which is associated with class II molecules intracellularly mediates the endosomal targeting, but it is debated whether class II molecules reach the endosomal system mainly from the trans-Golgi network or via the cell surface. Dynamin is a cytosolic GTPase which is necessary for the formation of clathrin-coated vesicles from the plasma membrane, but which is not required for vesicle formation from the trans-Golgi network. Here we have used HeLa cells expressing a dominant negative form of dynamin to show that inhibition of clathrin-mediated uptake from the plasma membrane leads to accumulation of transfected Ii-class II complexes at the cell surface, while delivery of such complexes to endosomes/lysosomes is decreased. Our data therefore suggest that in this experimental system the majority of Ii-class II complexes traverse the cell surface before they reach the endosomal system.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1997

Novel function of lecithin-cholesterol acyltransferase. Hydrolysis of oxidized polar phospholipids generated during lipoprotein oxidation.

Although the major function of lecithin-cholesterol acyltransferase (LCAT) is cholesterol esterification, our previous studies showed that it can also hydrolyze platelet-activating factor (PAF). Because of the structural similarities between PAF and the truncated phosphatidylcholines (polar PCs) generated during lipoprotein oxidation, we investigated the possibility that LCAT may also hydrolyze polar PCs to lyso-PC during the oxidation of plasma. PAF acetylhydrolase (PAF-AH), which is known to hydrolyze polar PCs in human plasma, was completely inhibited by 0.2 mM p-aminoethyl benzenesulfonyl fluoride (Pefabloc), a new serine esterase inhibitor, which had no effect on LCAT at this concentration. On the other hand, 1 mM diisopropylfluorophosphate (DFP) completely inhibited LCAT but had no effect on PAF-AH. Polar PC accumulation during the oxidation of plasma increased by 44% in the presence of 0.2 mM Pefabloc and by 30% in the presence of 1 mM DFP. The formation of lyso-PC was concomitantly inhibited by both of the inhibitors. The combination of the two inhibitors resulted in the maximum accumulation of polar PCs, suggesting that both PAF-AH and LCAT are involved in their breakdown. Oxidation of chicken plasma, which has no PAF-AH activity, also resulted in the formation of lyso-PC from the hydrolysis of polar PC, which was inhibited by DFP. Polar PCs, either isolated from oxidized plasma or by oxidation of labeled synthetic PCs, were hydrolyzed by purified LCAT, which had no detectable PAF-AH activity. These results demonstrate a novel function for LCAT in the detoxification of polar PCs generated during lipoprotein oxidation, especially when the PAF-AH is absent or inactivated.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1997

Structural organization of the human dihydropyrimidine dehydrogenase gene.

Deficiency of the pyrimidine catabolic enzyme, dihydropyrimidine dehydrogenase (DPD), has been shown to be responsible for a pharmacogenetic syndrome in which administration of 5-fluorouracil is associated with severe and potentially life-threatening toxicity. Following the recent availability of the cDNA for DPD, there were initial reports of several molecular defects (point mutations, deletions due to exon skipping) that were suggested as a potential molecular basis for DPD deficiency, even before the complete physical structure of the DPD gene was known. To understand the mechanism responsible for DPD deficiency, we have determined the genomic structure and organization of the human DPD gene. The gene is approximately 150 kb in length, and it consists of 23 exons, ranging in size from 69 to 1404 bp. The sequences of intronic regions flanking the exon boundaries have been determined. The physical map of the DPD gene should permit development of rapid assays to detect point mutations or small deletions in the DPD gene associated with 5-fluorouracil toxicity.

Dihydrouracil Dehydrogenase (NADP)↗
PubMed1997

Experimental study of thrombogenicity and foreign body reaction induced by heparin-coated coronary stents.

BACKGROUND: Results of recent randomized clinical trials have revealed a significant reduction in angiographic restenosis rate when adjunctive stenting was performed after conventional coronary balloon angioplasty. The thrombogenicity of metal stents, however, remains a concern. In the present study, we compare the thrombogenicity of heparin-coated coronary stents with that of bare metallic coronary stents. METHODS AND RESULTS: Thrombogenicity of metallic coronary stents (four heparin-coated and eight bare stents) was studied in a rat arteriovenous shunt model with the use of 125I-labeled fibrinogen and 51Cr-labeled platelets. Total clot weight after 30-minute follow-up was significantly lower in the heparin-coated stents compared with the bare stents (8.1 +/- 3.7 versus 25.8 +/- 4.6 mg; P < .001). Relative 125I and 51Cr activities in the stents were significantly higher in the bare stents than in the heparin-coated stents (125I, 1.03 +/- 0.43 versus 0.18 +/- 0.04, P = .003; 51Cr, 17.5 +/- 6.8 versus 4.4 +/- 1.0, P = .004). Subsequently, heparin-coated and bare stents were randomly implanted in the right coronary artery of 20 domestic pigs. Angiographic parameters were similar between both groups at baseline and after 6-week follow-up. Morphometry also did not show a significant difference in lumen area (bare, 1.03 +/- 0.83 mm2; heparin-coated, 1.12 +/- 0.73 mm2; P = NS) or neointimal hyperplasia (bare, 1.01 +/- 0.81 mm2; heparin-coated, 1.21 +/- 0.57 mm2; P = NS). CONCLUSIONS: Heparin coating of metallic coronary stents decreases their thrombogenicity but does not improve late vessel patency and neointimal hyperplasia at follow-up in a porcine coronary model.

Animals↗
PubMed1997

Transgenic mice with p53-responsive lacZ: p53 activity varies dramatically during normal development and determines radiation and drug sensitivity in vivo.

To analyze the involvement of p53-dependent transcriptional activation in normal development and in response to DNA damage in vivo, we created transgenic mice with a lacZ reporter gene under the control of a p53-responsive promoter. Five independent strains showed similar patterns of transgene expression. In untreated animals, lacZ expression was limited to the developing nervous system of embryos and newborn mice and was strongly decreased in the adult brain. gamma-irradiation or adriamycin treatment induced lacZ expression in the majority of cells of early embryos and in the spleen, thymus and small intestine in adult mice. Transgene expression was p53 dependent and coincided with the sites of strong p53 accumulation. The lacZ-expressing tissues and early embryos, unlike other adult tissues and late embryos, are characterized by high levels of p53 mRNA expression and respond to DNA damage by massive apoptotic cell death. Analysis of p53-null mice showed that this apoptosis is p53 dependent. These data suggest that p53 activity, monitored by the reporter lacZ transgene, is the determinant of radiation and drug sensitivity in vivo and indicate the importance of tissue and stage specificity of p53 regulation at the level of mRNA expression.

3T3 Cells↗
PubMed1997

Molecular contacts between nebulin and actin: cross-linking of nebulin modules to the N-terminus of actin.

Nebulin, a giant actin binding protein, coextends with actin and is thought to form a composite thin filament in the skeletal muscle sarcomere. To understand the molecular interactions between nebulin and actin, we have applied chemical cross-linking techniques to define molecular contacts between actin and ND8, a two-module nebulin fragment that promotes actin polymerization and inhibits depolymerization by binding to both G- and F-actin. The formation of a 1:1 complex with a dissociation constant of 4.9 microM between ND8 and G-actin was demonstrated by fluorescence titration of dansyl-ND8 with G-actin. Treatment with a zero-length cross-linker, l-ethyl-3-[3-(dimethylamino) propyl]carbodiimide (EDC), cross-linked the ND8-G-actin complex covalently without impairing actin's ability to polymerize. End-labeling Western blot and sequence and mass analyses of purified conjugated peptides revealed the cross-linking between lysine 5 of ND8 and the two N-terminal acidic residues of G-actin. Similarly, we have shown by end-labeling that cross-linking of ND8 to F-actin occurred at the N-terminus of actin protomer. The binding of nebulin to the N-terminus of actin is likely to be significant in its ability to affect actin polymerization. Furthermore, the association of nebulin modules with the actin N-terminus in subdomain 1 supports the hypothesis that nebulin wraps around the outer edges of actin filaments where Sl, tropomyosin, and several actin binding proteins are known to interact.

Actins↗
PubMed1997

Synthesis, antitumor activity and acute toxicity of diammine/diamino-cyclohexane platinum(II) complexes with oxygen-ligating leaving group.

In order to clarify the relation between the reactivity of the leaving groups in cisplatin-like complexes and their activity / toxicity, six new complexes of the formula Pt(NH3)2X and Pt(dach)X (where X is selenato, anion of squaric acid, or demethylcantharic acid) have been synthesized and compared. These complexes have been characterized by elemental analysis, infrared spectroscopy, and conductivity measurements. Six human neoplastic cell lines (HCT, KB, BGC, HL-60, K-563 and Bel-7402) were used to screen these compounds. The results demonstrated that four of them have comparable IC50 and even lower IC50 in a few kinds of tumor cell lines compared to cisplatin. Their LD50 values showed that the toxicity of these platinum complexes is related to the reactivity of the leaving groups. All of these complexes have lower acute toxicity than cisplatin, but the anticancer activity is not affected.

Actins↗
PubMed1997

The study of iodine in Chinese total diets.

In this work, China was divided into four area groups according to their geographical positions and dietary habits. All foods were divided into 12 types and the iodine contents in various diets were determined using epithermal neutron activation analysis (NAA). The intakes for China were evaluated. The results indicate that the intakes of iodine in northern areas are slightly higher and in south areas lower than the lowest recommended intake, and the average intake in China is 166 micrograms/person per day, which is within the recommended range. In addition, one province were chosen from each area groups. The dietary intakes of iodine were investigated in different ages and sex using total mixed diet method. Our results indicate that the average iodine intake of four provinces was lower than the recommended value, which suggests that it is necessary to supplement iodine in foods in China.

Adult↗
PubMed1997

Site-directed mutagenesis of the sodium pump: analysis of mutations to amino acids in the proposed nucleotide binding site by stable oxygen isotope exchange.

A model for the active site of P type ATPases has been tested by site-directed mutagenesis of amino acids in two conserved sequences of Mg(2+)-dependent and Na(+)- and K(+)-stimulated ATPase. The mutants K501R, K501E, D586E, D586N, P587A, and P588A were expressed in yeast cells and compared with wild type. In addition to previously published assays of adenosine 5'-triphosphate binding and hydrolysis, measurements of 18O exchange between Pi and water have been used to identify steps in the E2 half of the reaction cycle affected by the mutations. The study supports the prediction that K501 in the KGAP sequence interacts with adenosine 5'-triphosphate. However, quantitative comparisons of the effect of mutation K501E on the activity with the effects of mutations to an enzyme of known structure that also catalyzes phosphoryl group transfer make a direct role for the positive charge on the side chain of K501 in catalysis by stabilizing the transition state unlikely. No evidence for the predicted interaction between D586 and the hydroxyl groups of ribose was found. However, the data do indicate that the spatial organization of the loop containing the DPPR sequence is critical for phosphorylation of the enzyme. A role for D586 in coordinating the Mg2+ that is required for activity is proposed.

Adenosine Triphosphate↗
PubMed1997

Fos and Jun expression in rat supraoptic nucleus neurons after acute vs. repeated osmotic stimulation.

Using a double-label immunofluorescence method, we analyzed the time course of the appearance of Fos and Jun in the nuclei of supraoptic nucleus (SON) neurons following intraperitoneal injection of hypertonic saline. Fos and Jun immunostaining appeared within 30 min, peaked at 90-120 min, and disappeared 4-5 h later. At all time points (30, 60, 120, 180, 240 min postinjection), colocalized Fos and Jun immunostaining was observed (> 90% colocalized staining in labeled neurons). At 4 h post-saline injection, some rats received a second injection of normal or hypertonic saline. A second injection of normal saline resulted in no Fos/Jun immunostaining 90 min later, while hypertonic saline induced combined Fos/Jun staining in only 17% of SON neurons. Of the remaining SON cells, 23% had staining to Fos alone and 4% of the cells stained for Jun only. In spite of the delivery of an effective second osmotic stimulus, determined by assessment of plasma osmolality and sodium content, SON neurons exhibited less colocalized Fos/Jun immunostaining, dramatically less Jun expression, and substantial, but attenuated, immunostaining for Fos. These results are discussed in the context of known negative feedback mechanisms that control the re-expression of these transcription factors.

Animals↗
PubMed1997

Clinical and angiographic outcome after implantation of a home-made stent for complicated coronary angioplasty.

To defray the escalating costs of coronary stenting, we handmade a balloon-expandable, stainless steel stent, which after experimental evaluation, was implanted in 156 patients undergoing PTCA complicated by a major dissection. The procedural success rate was 98%. The in-hospital course was characterized by a 1.3% cardiopulmonary mortality and a 4.5% nonfatal myocardial infarction rate, while emergency bypass surgery and early repeat PTCA were necessary in only one patient each (0.6%). Clinical 6-mo follow-up in 150 patients revealed no deaths and no myocardial infarctions, and the event-free survival rate was 82%. Six-month control angiography was performed in 93.3% of eligible patients and revealed a restenosis rate of 20%.

Aortic Dissection↗
PubMed1997

The molecular evolution of the vertebrate trypsinogens.

We expand the already large number of known trypsinogen nucleotide and amino acid sequences by presenting additional trypsinogen sequences from the tunicate (Boltenia villosa), the lamprey (Petromyzon marinus), the pufferfish (Fugu rubripes), and the frog (Xenopus laevis). The current array of known trypsinogen sequences now spans the entire vertebrate phylogeny. Phylogenetic analysis is made difficult by the presence of multiple isozymes within species and rates of evolution that vary highly between both species and isozymes. We nevertheless present a Fitch-Margoliash phylogeny constructed from pairwise distances. We employ this phylogeny as a vehicle for speculation on the evolution of the trypsinogen gene family as well as the general modes of evolution of multigene families. Unique attributes of the lamprey and tunicate trypsinogens are noted.

Amino Acid Sequence↗