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Biomedical subjects

H Han

Publications and source records attributed to H Han.

At least 127 records · Page 7Linked to original sources
PubMed1996

Protective effect of the specific endothelin-1 antagonist BQ610 on mechanical function and energy metabolism during ischemia/reperfusion injury in isolated perfused rat hearts.

Endothelin-1 (ET-1) has been suggested to be involved in the pathophysiology of ischemia/reperfusion injury, but direct proof for this is still sparse. We tested whether protection of high-energy phosphate metabolism contributes to the beneficial effects of ETA receptor antagonists during ischemia/reperfusion. In isolated, buffer-perfused rat hearts, isovolumic function was measured by a left ventricular (LV) balloon, and 31P nuclear magnetic resonance spectra were continuously recorded. Two protocols were performed: (a) 15-min control, 30-min total, global ischemia, and 15-min reperfusion; and (b) 15-min control, 15-min total, global ischemia, and 30-min reperfusion. Treatment with BQ610 (1.75 micrograms/min) or saline was started during control and continued throughout the protocol. BQ610 did not affect function or energy metabolism under control conditions. In BQ610-treated hearts subjected to 30-min ischemia, time to ischemic contracture was significantly delayed (treated 10.6 +/- 0.4 min; untreated 8.1 +/- 0.7 min), and end-diastolic pressure (EDP) remained lower (after 30-min ischemia 26 +/- 2 vs. 35 +/- 2 mm Hg). In addition, recovery of mechanical function in BQ610-treated hearts was accelerated during reperfusion. BQ610 did not affect ATP but significantly accelerated and increased creatine phosphate (51 +/- 7 vs. 37 +/- 3%) recovery on reperfusion after 30-min ischemia. BQ610-treated hearts subjected to 15-min ischemia also showed lower EDP during ischemia and accelerated recovery of mechanical function during reperfusion. However, in this case, there were no differences in high-energy phosphate concentrations between treated and untreated hearts. We conclude that the protective action of BQ610 on mechanical function during ischemia/reperfusion injury can be but is not consistently associated with beneficial effects on cardiac high-energy phosphate metabolism.

Adenosine Triphosphate↗
PubMed1995

Liquid-phase combinatorial synthesis.

A concept termed liquid-phase combinatorial synthesis (LPCS) is described. The central feature of this methodology is that it combines the advantages that classic organic synthesis in solution offers with those that solid-phase synthesis can provide, through the application of a linear homogeneous polymer. To validate this concept two libraries were prepared, one of peptide and the second of nonpeptide origin. The peptide-based library was synthesized by a recursive deconvolution strategy [Erb, E., Janda, K. D. & Brenner, S. (1994) Proc. Natl. Acad. Sci. USA 91, 11422-11426] and several ligands were found within this library to bind a monoclonal antibody elicited against beta-endorphin. The non-peptide molecules synthesized were arylsulfonamides, a class of compounds of known clinical bactericidal efficacy. The results indicate that the reaction scope of LPCS should be general, and its value to multiple, high-throughput screening assays could be of particular merit, since multimilligram quantities of each library member can readily be attained.

Amino Acid Sequence↗
PubMed1995

Human intestinal H+/peptide cotransporter. Cloning, functional expression, and chromosomal localization.

In mammalian small intestine, a H(+)-coupled peptide transporter is responsible for the absorption of small peptides arising from digestion of dietary proteins. Recently a cDNA clone encoding a H+/peptide cotransporter has been isolated from a rabbit intestinal cDNA library (Fei, Y.J., Kanai, Y., Nussberger, S., Ganapathy, V., Leibach, F.H., Romero, M.F., Singh, S.K., Boron, W. F., and Hediger, M. A. (1994) Nature 368, 563-566). Screening of a human intestinal cDNA library with a probe derived from the rabbit H+/peptide cotransporter cDNA resulted in the identification of a cDNA which when expressed in HeLa cells or in Xenopus laevis oocytes induced H(+)-dependent peptide transport activity. The predicted protein consists of 708 amino acids with 12 membrane-spanning domains and two putative sites for protein kinase C-dependent phosphorylation. The cDNA-induced transport process accepts dipeptides, tripeptides, and amino beta-lactam antibiotics but not free amino acids as substrates. The human H+/peptide cotransporter exhibits a high degree of homology (81% identity and 92% similarity) to the rabbit H+/peptide cotransporter. But surprisingly these transporters show only a weak homology to the H(+)-coupled peptide transport proteins present in bacteria and yeast. Chromosomal assignment studies with somatic cell hybrid analysis and in situ hybridization have located the gene encoding the cloned human H+/peptide cotransporter to chromosome 13 q33-->q34.

Amino Acid Sequence↗
PubMed1995

Endothelin-1 contributes to ischemia/reperfusion injury in isolated rat heart-attenuation of ischemic injury by the endothelin-1 antagonists BQ123 and BQ610.

A potential detrimental role of endothelin-1 in myocardial ischemia/reperfusion injury was studied by use of the endothelin-1 antagonists BQ123 and BQ610. Isolated isovolumetric rat hearts were perfused at constant pressure. BQ123 (7 micrograms/min) and BQ610 (1.75 micrograms/min) did not alter mechanical function or coronary flow and shifted dose-response curves for endothelin-1 significantly to the right. In rats subjected to 30 min of no-flow ischemia, the increase of left ventricular resting pressure was significantly delayed by BQ123 and BQ610 compared to control (BQ123: 20 +/- 2* mmHg, BQ610: 19 +/- 2* mmHg, control: 44 +/- 4 mmHg at 15 min of ischemia, respectively, *P < 0.05 v control). With reperfusion after 30 min of ischemia, recovery of left ventricular developed pressure was not significantly affected but tended to be better with endothelin-1 antagonist pretreatment (BQ123: 20 +/- 3 mmHg; BQ610: 19 +/- 3 mmHg, control 12 +/- 3 mmHg). However, in hearts subjected to 15 min of ischemia followed by reperfusion, recovery of left ventricular developed pressure was improved by BQ610 pretreatment (BQ610: 52 +/- 8* mmHg, control: 24 +/- 6 mmHg). We conclude: BQ123 and BQ610 effectively antagonize the coronary constrictive effect of endothelin-1. BQ123 and BQ610 delay the development of contracture during ischemia and may improve functional recovery during reperfusion. Our findings suggest that endogenous endothelin-1 may contribute to ischemia/reperfusion injury.

Animals↗
PubMed1995

The core Alzheimer's peptide NAC forms amyloid fibrils which seed and are seeded by beta-amyloid: is NAC a common trigger or target in neurodegenerative disease?

BACKGROUND: NAC is a 35-amino-acid peptide which has been isolated from the insoluble core of Alzheimer's disease (AD) amyloid plaque. It is a fragment of alpha-synuclein (or NACP), a neuronal protein of unknown function. We noted a striking sequence similarity between NAC, the carboxyl terminus of the beta-amyloid protein, and a region of the scrapie prion protein (PrP) which has been implicated in amyloid formation. RESULTS: NAC was prepared by chemical synthesis and was found to form amyloid fibrils via a nucleation-dependent polymerization mechanism. NAC amyloid fibrils effectively seed beta 1-40 amyloid formation. Amyloid fibrils comprising peptide models of the homologous beta and PrP sequences were also found to seed amyloid formation by NAC. CONCLUSIONS: The in vitro model studies presented here suggest that seeding of NAC amyloid formation by the beta-amyloid protein, or seeding of amyloid fibrils of the beta-amyloid protein by NAC, may occur in vivo. Accumulation of ordered NAC aggregates in the synapse may be responsible for the neurodegeneration observed in AD and the prion disorders. Alternatively, neurodegeneration may be caused by the loss of alpha-synuclein (NACP) function.

Amino Acid Sequence↗
PubMed1995

Predominance of HLA-DRB1*0405 in Korean patients with rheumatoid arthritis.

OBJECTIVE: To identify the association of HLA-DR4 subtypes with rheumatoid arthritis (RA) in Koreans. METHODS: Ninety five patients with RA and 118 normal control subjects were examined for HLA-DR antigens by serology. Subtypes of HLA-DR4 were determined by allele specific oligonucleotide typing. RESULTS: The phenotype frequency of HLA-DR4 in RA patients was significantly greater than that in controls (60.0% versus 31.4%, odds ratio (OR) 3.28, 95% confidence interval (CI) 1.79 to 6.02 (p < 0.001)), but HLA-DR6 was decreased in RA patients (15.8% versus 32.2%, OR 0.39, 95% CI 0.19 to 0.81 (p < 0.001)). When DR4 was excluded from analysis of patients and controls, the allele frequency of DR1 was significantly increased in the patients compared with controls (11.3% versus 4.5%, OR 2.73, 95% CI 0.87 to 5.95 (p < 0.001)). Forty two of 57 DR4 positive patients (73.7%) possessed DRB1*0405, which was strongly associated with RA (44.2% of patients, versus 11.9% of controls: OR 5.88, 95% CI 2.81 to 12.47 (p < 0.001)). DRB1*0403 was not found in the patients, but was present in 8.5% of controls. Examining the third hyper-variable region at position 70-74 in the DRB1*04 chain by oligotyping, we found that 52 of 57 DR4 positive patients (91.2%) carried one of the conserved amino acid sequences QRRAA or QKRAA, known to be the epitope conferring predisposition to RA. CONCLUSION: This study confirms that RA is strongly associated with DR4, especially with DRB1*0405, and that the presence of the inferred QRRAA sequence may be important in susceptibility to RA in Koreans.

Adult↗
PubMed1995

Serum soluble HLA class I antigen levels in hemodialysis patients and following renal transplantation.

We measured the serum levels of soluble HLA class I antigen (sHLA-I) to evaluate the immune status of uremia and following renal transplantation. Twenty-one hemodialysis (HD) patients had serum samples collected for sHLA-I analysis before and after HD and also during the initial posttransplant period. The serum sHLA-I levels in patients undergoing HD were higher than in the normal controls (574.8 +/- 431.1 vs. 415.6 +/- 256.1 ng/ml, p < 0.05). In the HD patients, HD duration was not correlated with serum sHLA-I levels (r = 0.01, p > 0.05), and pre- and post-HD serum sHLA-I levels were not significantly different (574.8 +/- 431.1 vs. 568.3 +/- 398.4 ng/ml, p > 0.05). After successful renal transplantation, the serum sHLA-I levels decreased significantly (574.8 +/- 431.1 vs. 226.7 +/- 202.8 ng/ml, p = 0.0001) but increased significantly during the rejection period as compared to the prerejection period (642.8 +/- 296.1 vs. 305.5 +/- 194.7 ng/ml, p = 0.0002). In conclusion, sHLA-I levels are stable in uremic status and can be used as a parameter for monitoring acute graft rejection in renal transplantation.

Adult↗
PubMed1995

Angioplasty reduces pharmacologically mediated vasoconstriction in rabbit carotid arteries with and without vasospasm.

BACKGROUND AND PURPOSE: We tested the hypothesis that vasospastic arteries do not reconstrict after angioplasty because angioplasty decreases smooth muscle contractility. METHODS: Twenty-four rabbits had carotid angiography and placement of silicone elastomer sheaths around both carotid arteries in the neck. Sheaths were empty (control groups) or filled with clotted blood (vasospasm groups). Angiography was repeated 2 days later, and one carotid artery was dilated with a balloon catheter. Animals were killed 1, 5, or 28 days after angioplasty, and the carotid arteries were studied pharmacologically under isometric tension. RESULTS: Before angioplasty, there was significant vasospasm in the vasospasm groups but not in the control groups (P < .05, ANOVA). Angioplasty produced significant, long-lasting dilation of arteries in the vasospasm groups. One and 5 days after angioplasty, arteries from control and vasospasm groups that had angioplasty had significantly reduced contractions to serotonin, KCl, and caffeine compared with arteries not subjected to angioplasty. Twenty-eight days after angioplasty, contractions were reduced in arteries subjected to vasospasm compared with controls, but there were no differences between arteries with or without angioplasty. At all times after angioplasty, vasospasm significantly decreased acetylcholine-induced relaxations of arteries contracted with serotonin. Relaxations were further decreased by angioplasty in the vasospasm group 1 day after angioplasty. Arterial wall compliance was significantly decreased in the vasospasm and control groups at all times after angioplasty, although there were no significant differences between arteries with and without angioplasty. CONCLUSIONS: These results suggest that arteries do not reconstrict after angioplasty because angioplasty decreases smooth muscle contractility. There was no evidence that angioplasty disrupted the arterial wall matrix, as judged by the lack of increase in arterial wall compliance after angioplasty.

Acetylcholine↗
PubMed1995

TNFB gene polymorphism in patients with systemic lupus erythematosus in Korean.

OBJECTIVES: To elucidate the gene frequency of TNFB Ncol polymorphism and its association with HLA class II antigen in patients with systemic lupus erythematosus(SLE) in Korea. METHODS: We investigated the gene frequency of the TNFB alleles using DNA obtained from peripheral mononuclar cells in 141 healthy controls and in 58 patients with SLE. The polymorphisms of TNFB gene (735 bp) were studied by Ncol PCR-RELP. A portion of TNFB gene(735 bp) was amplified by PCR and its products were digested with Ncol restriction enzyme. The digested samples of amplified DNA were analyzed by agarose gel electrophoresis. TNFB*1 and TNFB*2 alleles were identified according to polymorphic fragments on Ncol restriction site in the first intron of the TNFB gene. The generic types of HLA-DRBI were also determined by PCR with sequence specific primers(SSP) using genomic DNA from the same subjects. RESULTS: The genotypic frequency of TNFB*2 homozygote was significantly increased in patients with SLE compared with controls(RR = 2.36, P = 0.011). The frequency of HLA-DRBI*15 was also significantly increased in patients (RR = 2.27, P = 0.029). However, the increased frequency of TNFB*2 homozygote was apparently increased in nephritis group (RR = 2.79, P = 0.035), whereas the significance of TNFB*2 homozygote was weakend in non-nephritis group. CONCLUSIONS: Our results suggest that genetic predisposition of TNFB*2 homozygote is another risk factor in Korean SLE, especially in DR2 negative patients. In addition, TNFB*2 homozygote could have a tendency for the development of nephritis in patients with SLE.

Base Sequence↗
PubMed1995

Histidine ameliorated brain edema and cardiac dysfunction during local thrombotic cerebral ischemia in rats.

AIM: To observe the effects of histidine (i.v. 5 mg.kg-1) on brain edema and cardiac disturbance after cerebral thrombosis. METHODS: Regional cerebral thrombosis was induced by photochemical method in rats. RESULTS: It was showed that the brain water content increased markedly (85.6 +/- 3.8%, P < 0.01); the left ventricular systolic pressure (LVSP, 17.9 +/- 1.5 kPa) and the maximal left ventricular contractility decreased (+dp/dtmax 645 +/- 110 kPa and -dp/dtmax 473 +/- 106 kPa, P < 0.05). In rats treated with histidine after photochemical reaction, the brain water content decreased (81.5 +/- 2.0%) while LVSP (21.2 +/- 1.1 kPa) and left ventricular +dp/dtmax and -dp/dtmax increased markedly (777 +/- 144 kPa and 604 +/- 157 kPa, respectively). CONCLUSION: Histidine has protective effects on the brain and cardiac function during cerebral thrombosis.

Animals↗
PubMed1995

[Expression and significance of HBV DNA and its 5 antigens in liver cirrhosis].

Hepatitis B virus (HBV) DNA and its 5 antigens were studied in 225 cases of paraffin-embedded sections of human liver cirrhosis obtained by biopsy. HBxAg, pre-S1 and pre-S2 antigens were detected by immunohistochemical ABC method, HBsAg and HBcAg by PAP method. HBV DNA by in situ hybridization, and both HBV DNA and HBsAg, HBxAg or HBcAg by double labelling technique of immunohistochemistry and in situ hybridization respectively. The results showed that the positive rates were 70.0% (128/183) for HBsAg, 64.4% (85/132) for pre-S1 antigen, 61.4% (81/132) for pre-S2 antigen, 75.3% (113/150) for HBxAg, 22.4% (39/174) for HBcAg and 62.4% (58/93) for HBV DNA respectively. The double labelling positive rates were 37.3% (19/51) for both HBV DNA and HBsAg, 86.3% (44/51) for both HBV DNA and HBxAg and 39.2% (20/51) for both HBV DNA and HBcAg respectively. More than 80% of the cases with positive sections for HBV DNA and its 5 antigens were associated with liver cell dysplasia (LCD). The results of this study suggest that the occurrence and development of liver cirrhosis were closely related to chronic infection of HBV in China.

DNA, Viral↗
PubMed1994

Mapping RNA regions in eukaryotic ribosomes that are accessible to methidiumpropyl-EDTA.Fe(II) and EDTA.Fe(II).

Methidiumpropyl-EDTA.Fe(II) [MPE.Fe(II)] and EDTA.Fe(II) were used to investigate the structure of Drosophila melanogaster ribosomes. Cleavage reactions were performed on intact ribosomes in cell lysates in vitro and analyzed by primer extension with reverse transcriptase using oligodeoxynucleotide primers. Regions of 18S and 28S ribosomal RNAs (rRNAs) which are accessible to MPE.Fe(II) and EDTA.Fe(II) are located almost exclusively within expansion segments. The accessibility of these regions to cleavage indicates that they are likely exposed on the surface of eukaryotic ribosomes. These results provide information about the overall tertiary structure of rRNA in ribosomes.

Animals↗
PubMed1994

Different conformational families of pyrimidine.purine.pyrimidine triple helices depending on backbone composition.

Different helical conformations of DNA (D), RNA (R), and DNA.RNA (DR) hybrid double and triple helices have been detected using affinity cleavage analysis. Synthetic methods were developed to attach EDTA.Fe to a single nucleotide on RNA as well as DNA oligonucleotides. Cleavage patterns generated by a localized diffusible oxidant in the major groove on the pyrimidine strand of four purine.pyrimidine double helices consisting of all DNA, all RNA, and the corresponding hybrids reveal that the relative cleavage intensity shifts to the 5' end of the purine strand increasingly in the order: DD < DR < RD < RR. These results are consistent with models derived from structural studies. In six pyrimidine.purine.pyrimidine triple helices, the altered cleavage patterns of the Watson-Crick pyrimidine strands reveal at least two conformational families: (i) D + DD, R + DD, D + DR, and R + DR and (ii) R + RD and R + RR.

DNA↗
PubMed1994

Functional characterization and chromosomal localization of a cloned taurine transporter from human placenta.

A cDNA clone highly related to the rat brain taurine transporter has been isolated from a human placental cDNA library. Transfection of this cDNA into HeLa cells results in a marked elevation of taurine transport activity. The activity of the cDNA-induced transporter is dependent on the presence of Na+ as well as Cl-. The Na+/Cl-/taurine stoichiometry for the cloned transporter is 2:1:1. The transporter is specific for taurine and other beta-amino acids, including beta-alanine, and exhibits high affinity for taurine (Michaelis-Menten constant approximately 6 microM). The clone consists of a coding region 1863 bp long (including the termination codon), flanked by a 376 bp-long 5' non-coding region and a 625 bp-long 3' non-coding region. The nucleotide sequence of the coding region predicts a 620-amino acid protein with a calculated M(r) of 69,853. Northern-blot analysis of poly(A)+ RNA from several human tissues indicates a complex expression pattern differing across tissues. The principal transcript, 6.9 kb in size, is expressed abundantly in placenta and skeletal muscle, at intermediate levels in heart, brain, lung, kidney and pancreas and at low levels in liver. Cultured human cell lines derived from placenta (JAR and BeWo), intestine (HT-29), cervix (HeLa) and retinal pigment epithelium (HRPE), which are known to possess Na(+)- and Cl(-)-coupled taurine transport activity, also contain the 6.9 kb transcript. Somatic cell hybrid and in situ hybridization studies indicate that the cloned taurine transporter is localized to human chromosome 3 p24-->p26.

Amino Acid Sequence↗
PubMed1994

Visualization of RNA tertiary structure by RNA-EDTA.Fe(II) autocleavage: analysis of tRNA(Phe) with uridine-EDTA.Fe(II) at position 47.

To test whether intramolecular autocleavage of RNA labeled at a single nucleotide position with EDTA.Fe(II) is a useful approach for the investigation of tertiary structures of RNAs, yeast phenylalanine tRNA was synthesized with uridine-EDTA (*U) at position U47. Autocleavage of [*U47]tRNA(Phe) in the presence of Fe(NH4)2(SO4)2 and dithiothreitol produced a set of cleavage fragments which are in general agreement with the three-dimensional structure derived from x-ray analysis.

Base Sequence↗
PubMed1994

Morphological analysis of acute ulcerative colitis experimentally induced by dextran sulfate sodium in the guinea pig: some possible mechanisms of cecal ulceration.

This study in the guinea pig demonstrated that ulcerative colitis-like lesions were induced more rapidly and effectively than in other laboratory animals by the oral administration of dextran sulfate sodium (DSS). In all guinea pigs receiving 3% DSS solution, diarrhea was noted within 48h, and bleeding at 48-72h. Light microscopically, hemorrhagic and ulcerative lesions were observed in the cecum and proximal colon as early as 72h after administration. Lamina propria macrophages, gather in the subepithelial region under normal conditions, were markedly increased in number after DSS administration; by 96 h, they were approximately three times as many as in the control specimens. The cecal mucosa was also characterized, in earlier stages, by the obliteration of virtually all cryptal lumina because of the accumulation of mucous secretions, leading to the subsequent disappearance of the crypts. The obliteration of crypts, which preceded the increase of macrophages, is suggested to play a leading part in this ulceration.

Acute Disease↗
PubMed1994

Effects of LTD4 and its specific antagonist L-660,711 in isolated rat hearts with chronic myocardial infarction.

We investigated the effects of leukotriene (LT) D4 and its novel potent and selective antagonist L-660,711 on isolated rat hearts with chronic myocardial infarction. The left coronary artery was ligated permanently or for 30 or 60 min and followed by reperfusion. Hearts were isolated and perfused in the Langendorff mode 4 days, 4 wk, or 8 wk after the operation. Dose-response curves for LTD4 (12-240 ng/min) on coronary flow were shifted to the left in rats with permanent coronary occlusion for 8 wk or with coronary occlusion for 30 or 60 min and reperfusion for 4 wk. In contrast, dose-response curves were unchanged in rats 4 days after myocardial infarction. L-660,711 shifted dose-response curves for LTD4 on coronary flow to the right in all groups. The negative inotropic and chronotropic effects of LTD4 could be markedly attenuated by L-660,711 in all groups. Our findings suggest that the effect of LTD4 is enhanced in rat hearts with chronic myocardial infarction. L-660,711 effectively antagonized the vasoconstrictor effect of exogenous LTD4.

Angiotensin I↗