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H Jin

Publications and source records attributed to H Jin.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of early angiotensin-converting enzyme inhibition on cardiac gene expression after acute myocardial infarction.

BACKGROUND: ACE inhibition after myocardial infarction (MI) has been shown to have beneficial effects on cardiac anatomy and function. The purpose of this study was to examine the effects of ACE inhibition on cardiac gene expression after MI. METHODS AND RESULTS: Rats were randomized to receive captopril or no treatment 1 day after MI. Eight weeks later, cardiac function and hemodynamics were measured by use of indwelling catheters and perivascular flow probes. Myocardial gene expression was assessed with DNA microarrays and real-time reverse transcription-polymerase chain reaction. The ratios of heart and left ventricular weights to body weight were significantly increased by MI and normalized by captopril. Cardiac index and stroke volume index were lower in the untreated MI group than in sham controls but were normal in the MI+captopril group. Thirty-seven genes were found to be differentially expressed between the untreated MI group and sham controls; 31 were induced and 6 repressed. Captopril partially or completely inhibited changes in 10 of the genes. The 37 genes clustered into 11 functional groups, and 6 had >/=1 genes whose expression was modified by ACE inhibition. CONCLUSIONS: ACE inhibition after MI inhibits cardiac hypertrophy, preserves cardiac function, and attenuates changes in myocardial gene expression. Gene expression profiling reveals, however, that some elements of the pathophysiology may be unaffected by the treatment and be targets for new therapies.

Acute Disease↗
PubMed2001

Binding of pyridine coenzymes to the beta-subunit of the voltage sensitive potassium channels.

The beta-subunit of the voltage-sensitive K(+) channels shares 15-30% amino acid identity with the sequences of aldo-keto reductases (AKR) genes. However, the AKR properties of the protein remain unknown. To begin to understand its oxidoreductase properties, we examine the pyridine coenzyme binding activity of the protein in vitro. The cDNA of K(v)beta2.1 from rat brain was subcloned into a prokaryotic expression vector and overexpressed in Escherichia coli. The purified protein was tetrameric in solution as determined by size exclusion chromatography. The protein displayed high affinity binding to NADPH as determined by fluorometric titration. The K(D) values for NADPH of the full-length wild-type protein and the N-terminus deleted protein were 0.1+/-0.007 and 0.05+/-0.006 M, respectively - indicating that the cofactor binding domain is restricted to the C-terminus, and is not drastically affected by the absence of the N-terminus amino acids, which form the ball and chain regulating voltage-dependent inactivation of the alpha-subunit. The protein displayed poor affinity for other coenzymes and the corresponding values of the K(D) for NADH and NAD were between 1-3 microM whereas the K(D) for FAD was >10 microM. However, relatively high affinity binding was observed with 3-acetyl pyridine NADP, indicating selective recognition of the 2' phosphate at the binding site. The selectivity of K(v)beta2.1 for NADPH over NADP may be significant in regulating the K(+) channels as a function of the cellular redox state.

Animals↗
PubMed2001

Codon bias at the 3'-side of the initiation codon is correlated with translation initiation efficiency in Escherichia coli.

The codon that follows the AUG initiation triplet (+2 codon) affects gene expression in Escherichia coli. We have extended this analysis using two model genes lacking any apparent Shine-Dalgarno sequence. Depending on the identity of the +2 codon a difference in gene expression up to 20-fold could be obtained. The effects did not correlate with the levels of intracellular pools of cognate tRNA for the +2 codon, with putative secondary mRNA structures, or with mRNA stability. However, most +2 iso-codons that were decoded by the same species of tRNA gave pairwise similar effects, suggesting that the effect on gene expression was associated with the decoding tRNA. High adenine content of the +2 codon was associated with high gene expression. Of the fourteen +2 codons that mediated the highest efficiency, all except two had an adenine as the first base of the codon. Analysis of the 3540 E. coli genes from the TransTerm database revealed that codons associated with high gene expression in the two expression systems are over-represented at the +2 position in natural genes. Codons that are associated with low gene expression are under-represented. The data suggest that evolution has favored codons at the +2 position that give high translation initiation.

Codon↗
PubMed2001

Binding of pyridine nucleotide coenzymes to the beta-subunit of the voltage-sensitive K+ channel.

The beta-subunit of the voltage-sensitive K(+) (K(v)) channels belongs to the aldo-keto reductase superfamily, and the crystal structure of K(v)beta2 shows NADP bound in its active site. Here we report that K(v)beta2 displays a high affinity for NADPH (K(d) = 0.1 micrometer) and NADP(+) (K(d) = 0.3 micrometer), as determined by fluorometric titrations of the recombinant protein. The K(v)beta2 also bound NAD(H) but with 10-fold lower affinity. The site-directed mutants R264E and N333W did not bind NADPH, whereas, the K(d)(NADPH) of Q214R was 10-fold greater than the wild-type protein. The K(d)(NADPH) was unaffected by the R189M, W243Y, W243A, or Y255F mutation. The tetrameric structure of the wild-type protein was retained by the R264E mutant, indicating that NADPH binding is not a prerequisite for multimer formation. A C248S mutation caused a 5-fold decrease in K(d)(NADPH), shifted the pK(a) of K(d)(NADPH) from 6.9 to 7.4, and decreased the ionic strength dependence of NADPH binding. These results indicate that Arg-264 and Asn-333 are critical for coenzyme binding, which is regulated in part by Cys-248. The binding of both NADP(H) and NAD(H) to the protein suggests that several types of K(v)beta2-nucleotide complexes may be formed in vivo.

Amino Acid Sequence↗
PubMed2001

The Stanford Microarray Database.

The Stanford Microarray Database (SMD) stores raw and normalized data from microarray experiments, and provides web interfaces for researchers to retrieve, analyze and visualize their data. The two immediate goals for SMD are to serve as a storage site for microarray data from ongoing research at Stanford University, and to facilitate the public dissemination of that data once published, or released by the researcher. Of paramount importance is the connection of microarray data with the biological data that pertains to the DNA deposited on the microarray (genes, clones etc.). SMD makes use of many public resources to connect expression information to the relevant biology, including SGD [Ball,C.A., Dolinski,K., Dwight,S.S., Harris,M.A., Issel-Tarver,L., Kasarskis,A., Scafe,C.R., Sherlock,G., Binkley,G., Jin,H. et al. (2000) Nucleic Acids Res., 28, 77-80], YPD and WormPD [Costanzo,M.C., Hogan,J.D., Cusick,M.E., Davis,B.P., Fancher,A.M., Hodges,P.E., Kondu,P., Lengieza,C., Lew-Smith,J.E., Lingner,C. et al. (2000) Nucleic Acids Res., 28, 73-76], Unigene [Wheeler,D.L., Chappey,C., Lash,A.E., Leipe,D.D., Madden,T.L., Schuler,G.D., Tatusova,T.A. and Rapp,B.A. (2000) Nucleic Acids Res., 28, 10-14], dbEST [Boguski,M.S., Lowe,T.M. and Tolstoshev,C.M. (1993) Nature Genet., 4, 332-333] and SWISS-PROT [Bairoch,A. and Apweiler,R. (2000) Nucleic Acids Res., 28, 45-48] and can be accessed at http://genome-www.stanford.edu/microarray.

Animals↗
PubMed2001

Saccharomyces Genome Database provides tools to survey gene expression and functional analysis data.

Upon the completion of the SACCHAROMYCES: cerevisiae genomic sequence in 1996 [Goffeau,A. et al. (1997) NATURE:, 387, 5], several creative and ambitious projects have been initiated to explore the functions of gene products or gene expression on a genome-wide scale. To help researchers take advantage of these projects, the SACCHAROMYCES: Genome Database (SGD) has created two new tools, Function Junction and Expression Connection. Together, the tools form a central resource for querying multiple large-scale analysis projects for data about individual genes. Function Junction provides information from diverse projects that shed light on the role a gene product plays in the cell, while Expression Connection delivers information produced by the ever-increasing number of microarray projects. WWW access to SGD is available at genome-www.stanford. edu/Saccharomyces/.

Databases, Factual↗
PubMed2001

Geometrical rectification for images from a mobile large container inspection system.

The mobile large container inspection system (MLCIS) is a more flexible X-ray radiographic system than conventional fixed systems. Ideally, the X-ray detectors should be arranged along an arc with the source at the center. However, detectors of the MLCIS are arranged in an L-shaped frame and result in a factual image which is distorted compared with the ideal image. We propose a geometrical rectification algorithm to convert the factual image to the ideal image. We choose the dimension ratios of identical objects shown on the factual and processed images with our algorithm as a measure, and the results is desirable.

Journal Article↗
PubMed2001

gamma-Aminobutyric acid(A) receptor subunit expression predicts functional changes in hippocampal dentate granule cells during postnatal development.

Profound alterations in the function of GABA occur over the course of postnatal development. Changes in GABA(A) receptor expression are thought to contribute to these differences in GABAergic function, but how subunit changes correlate with receptor function in individual developing neurons has not been defined precisely. In the current study, we correlate expression of 14 different GABA(A) receptor subunit mRNAs with changes in the pharmacological properties of the receptor in individual hippocampal dentate granule cells over the course of postnatal development in rat. We demonstrate significant developmental differences in GABA(A) receptor subunit mRNA expression, including greater than two-fold lower expression of alpha1-, alpha4- and gamma2-subunit mRNAs and 10-fold higher expression of alpha5-mRNA in immature compared with adult neurons. These differences correlate both with regional changes in subunit protein level and with alterations in GABA(A) receptor function in immature dentate granule cells, including two-fold higher blockade by zinc and three-fold lower augmentation by type-I benzodiazepine site modulators. Further, we find an inverse correlation between changes in GABA(A) receptor zinc sensitivity and abundance of vesicular zinc in dentate gyrus during postnatal development. These findings suggest that developmental differences in subunit expression contribute to alterations in GABA(A) receptor function during postnatal development.

Animals↗
PubMed2001

Disturbed expression of Fas/FasL on CD4(+) and CD8(+)T cells in Behcet's disease, Vogt-Koyanagi-Harada syndrome, and idiopathic anterior uveitis.

AIMS: To evaluate the expression of Fas/FasL antigen on peripheral blood T lymphocytes in patients with Behcet's disease, Vogt-Koyanagi-Harada (VKH) syndrome, and idiopathic anterior uveitis. METHODS: The expression of Fas and FasL on peripheral blood T lymphocytes was determined using flow cytometry in 26 patients with Behcet's disease (BD), 17 patients with VKH syndrome, 25 patients with idiopathic anterior uveitis, and 43 healthy individuals (controls). RESULTS: A higher proportion of CD4(+) T cells expressing Fas was noted in patients with Behcet's disease (25.70 +/- 7.32%), VKH syndrome (19.60 +/- 11.02%), and idiopathic anterior uveitis (20.81+/- 7.40%) compared with controls (14.02 +/- 6.30%). The expression of Fas on CD8(+) cells from patients with Behcet's disease (9.47 +/- 6.97%) and VKH syndrome (6.84+/- 5.5%) was also higher than that seen in controls (3.47+/- 2.75%). There was no difference in FasL expression on T cells between patients and controls except that a lower expression of FasL on CD8(+) T cells was noted in patients with idiopathic anterior uveitis. CONCLUSION: A disturbed expression of Fas and FasL on T cells is present in patients with Behcet's disease, VKH syndrome, and idiopathic anterior uveitis, which may be involved in the perpetuation and recurrence of uveitis.

Adult↗
PubMed2001

Fission yeast Aip3p (spAip3p) is required for an alternative actin-directed polarity program.

Aip3p is an actin-interacting protein that regulates cell polarity in budding yeast. The Schizosaccharomyces pombe-sequencing project recently led to the identification of a homologue of Aip3p that we have named spAip3p. Our results confirm that spAip3p is a true functional homologue of Aip3p. When expressed in budding yeast, spAip3p localizes similarly to Aip3p during the cell cycle and complements the cell polarity defects of an aip3Delta strain. Two-hybrid analysis shows that spAip3p interacts with actin similarly to Aip3p. In fission yeast, spAip3p localizes to both cell ends during interphase and later organizes into two rings at the site of cytokinesis. spAip3p localization to cell ends is dependent on microtubule cytoskeleton, its localization to the cell middle is dependent on actin cytoskeleton, and both patterns of localization require an operative secretory pathway. Overexpression of spAip3p disrupts the actin cytoskeleton and cell polarity, leading to morphologically aberrant cells. Fission yeast, which normally rely on the microtubule cytoskeleton to establish their polarity axis, can use the actin cytoskeleton in the absence of microtubule function to establish a new polarity axis, leading to the formation of branched cells. spAip3p localizes to, and is required for, branch formation, confirming its role in actin-directed polarized cell growth in both Schizosaccharomyces pombe and Saccharomyces cerevisiae.

Actins↗
PubMed2001

Apoptosis in atrophic skeletal muscle induced by brachial plexus injury in rats.

BACKGROUND: Skeletal muscle atrophy induced by denervation is associated with apoptosis. This study was undertaken to determine the role of apoptosis and the expression of apoptosis-associated genes in rat skeletal muscle made atrophic by brachial plexus injury, and to study the apoptotic signal transduction pathway. METHODS: An animal model of skeletal muscle atrophy was established in rats by severing the brachial plexus of one forelimb. Apoptosis of muscle cells was investigated with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate end labeling, flow cytometry, deoxyribonucleic acid (DNA) electrophoresis, and electron microscopy. The apoptosis-associated genes Fas, FADD, Caspase 8, c-myc, p53, and Bcl-2 were detected by immunohistochemistry and Northern blot. RESULTS: By terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate end labeling and flow cytometry we found that the percentage of apoptotic muscle cells was higher in atrophic than in healthy skeletal muscle (p < 0.05). DNA laddering could be seen in gel electrophoresis of DNA from atrophic muscle. By electron microscopy, we observed morphologic change of early apoptosis, such as aggregation of chromosomes, expansion of nucleic cistern, and contraction of the nucleus. Using immunohistochemistry, we determined that in atrophic muscle Fas, FADD, and Caspase-8 genes were highly expressed, whereas Bcl-2 was poorly expressed (p < 0.01). However, we did not detect a change in the expression of p53 or c-myc genes. Northern blots indicated that Fas messenger ribonucleic acid was higher and Bcl-2 messenger ribonucleic acid was lower in atrophic than in healthy muscle (p < 0.01). CONCLUSION: There are many more apoptotic cells in muscle atrophied as a result of brachial plexus injury than in healthy muscle, and apoptosis plays an important role in the pathogenesis of atrophy. The apoptotic signal may be transmitted from Fas to FADD to Caspase-8, with a decrease in Bcl-2 expression aggravating the process.

Animals↗
PubMed2001

Requirement of cysteines and length of the human respiratory syncytial virus M2-1 protein for protein function and virus viability.

The M2-1 protein of human respiratory syncytial virus (hRSV) promotes processive RNA synthesis and readthrough at RSV gene junctions. It contains four highly conserved cysteines, three of which are located in the Cys(3)-His(1) motif at the N terminus of M2-1. Each of the four cysteines, at positions 7, 15, 21, and 96, in the M2-1 protein of hRSV A2 strain was individually replaced by glycines. When tested in an RSV minigenome replicon system using beta-galactosidase as a reporter gene, C7G, C15G, and C21G located in the Cys(3)-His(1) motif showed a significant reduction in processive RNA synthesis compared to wild-type (wt) M2-1. C96G, which lies outside the Cys(3)-His(1) motif, was fully functional in supporting processive RNA synthesis in vitro. Each of these cysteine substitutions was introduced into an infectious antigenomic cDNA clone derived from hRSV A2 strain. Except for C96G, which resulted in a viable virus, no viruses were recovered with mutations in the Cys(3)-His(1) motif. This indicates that the Cys(3)-His(1) motif is critical for M2-1 function and for RSV replication. The functional requirement of the C terminus of the M2-1 protein was examined by engineering premature stop codons that caused truncations of 17, 46, or 67 amino acids from the C terminus. A deletion of 46 or 67 amino acids abolished the synthesis of full-length beta-galactosidase mRNA and did not result in the recovery of viable viruses. However, a deletion of 17 amino acids from the C terminus of M2-1 reduced processive RNA synthesis in vitro and was well tolerated by RSV. Relocation of the M2-1 termination codon upstream of the M2-2 initiation codons did not significantly affect the expression of the M2-2 protein. Both rA2-Tr17 and rA2-C96G did not replicate as efficiently as wt rA2 in HEp-2 cells and was restricted in replication in the respiratory tracts of cotton rats.

Amino Acid Sequence↗
PubMed2001

Endotoxin responsiveness and subchronic grain dust-induced airway disease.

Endotoxin is one of the principal components of grain dust that causes acute reversible airflow obstruction and airway inflammation. To determine whether endotoxin responsiveness influences the development of chronic grain dust-induced airway disease, physiological and airway inflammation remodeling parameters were evaluated after an 8-wk exposure to corn dust extract (CDE) and again after a 4-wk recovery period in a strain of mice sensitive to (C3H/HeBFeJ) and one resistant to (C3H/HeJ) endotoxin. After the CDE exposure, both strains of mice had equal airway hyperreactivity to a methacholine challenge; however, airway hyperreactivity persisted only in the C3H/HeBFeJ mice after the recovery period. Only the C3H/HeBFeJ mice showed significant inflammation of the lower airway after the 8-wk exposure to CDE. After the recovery period, this inflammatory response completely resolved. Lung stereological measurements indicate that an 8-wk exposure to CDE resulted in persistent expansion of the airway submucosal cross-sectional area only in the C3H/HeBFeJ mice. Collagen type III and an influx of cells into the subepithelial area participated in the expansion of the submucosa. Our findings demonstrate that subchronic inhalation of grain dust extract results in the development of chronic airway disease only in mice sensitive to endotoxin but not in mice that are genetically hyporesponsive to endotoxin, suggesting that endotoxin is important in the development of chronic airway disease.

Actins↗
PubMed2001

Impaired functional activity of alveolar macrophages from GM-CSF-deficient mice.

We hypothesized that pulmonary granulocyte-macrophage colony-stimulating factor (GM-CSF) is critically involved in determining the functional capabilities of alveolar macrophages (AM) for host defense. To test this hypothesis, cells were collected by lung lavage from GM-CSF mutant mice [GM(-/-)] and C57BL/6 wild-type mice. GM(-/-) mice yielded almost 4-fold more AM than wild-type mice. The percentage of cells positive for the beta(2)-integrins CD11a and CD11c was reduced significantly in GM(-/-) AM compared with wild-type cells, whereas expression of CD11b was similar in the two groups. The phagocytic activity of GM(-/-) AM for FITC-labeled microspheres was impaired significantly compared with that of wild-type AM both in vitro and in vivo (after intratracheal inoculation with FITC-labeled beads). Stimulated secretion of tumor necrosis factor-alpha (TNF-alpha) and leukotrienes by AM from the GM(-/-) mice was greatly reduced compared with wild-type AM, whereas secretion of monocyte chemoattractant protein-1 was increased. Transgenic expression of GM-CSF exclusively in the lungs of GM(-/-) mice resulted in AM with normal or supranormal expression of CD11a and CD11c, phagocytic activity, and TNF-alpha secretion. Thus, in the absence of GM-CSF, AM functional capabilities for host defense were significantly impaired but were restored by lung-specific expression of GM-CSF.

Animals↗
PubMed2001

Calcium-activated potassium current in single Novikoff cell.

The electrophysiological properties of the hemichannels of the gap junction in a single Novikoff cell was studied using patch-clamp whole-cell recording techniques. During the experiments, a transient outward current (peak current, Ip) was found to be evoked by the increment of depolarized pulses. Ip was voltage-dependent and could be inhibited partly by CsCl and tetraethylammonium (TEA), but was blocked completely by quinidine. When the intracellular free Ca2+ concentration ([Ca2+]i) was increased, the amplitude of Ip was enhanced. Adding 10 mmol/l EGTA in the pipette solution, Ip disappeared. When the cells were bathed in symmetrical high-K+ solution, Ip also completely disappeared. These results suggest that Ip is a calcium-activated potassium current, although it cannot be blocked by apamin.

Animals↗
PubMed2001

Association of depressive symptoms with worse functioning in schizophrenia: a study in older outpatients.

BACKGROUND: Subsyndromal depressive symptoms are highly prevalent and associated with substantial impairments of daily function in the general population. Depressive symptoms are common in schizophrenia. However, few studies have examined the relationship of functioning and well-being to the presence of depressive symptoms in schizophrenia. METHOD: 202 middle-aged or elderly outpatients with schizophrenia (DSM-III-R or DSM-IV criteria) were categorized by severity of depressive symptoms on the Hamilton Rating Scale for Depression (HAM-D) using previously validated cutoff points, i.e., HAM-D total score < or = 6 (low), from 7 to 16 (medium), and > or = 17 (high). We also assessed severity of positive and negative symptoms, movement disorders, neurocognitive performance, daily functioning, and health-related quality of well-being with standardized measures. RESULTS: A total of 11.4% of patients had HAM-D scores > or = 17, and 56.4% had HAM-D scores from 7 to 16. Even after adjusting for severity of other psychopathology, patients with more severe depressive symptoms had significantly worse everyday functioning (p < .02), except for physical functioning, and health-related quality of well-being (r = -.365, p < .001) than did those with lower HAM-D scores. These differences were unrelated to those in demographics, extrapyramidal symptoms, tardive dyskinesia, neurocognitive performance, or number of physical illnesses. CONCLUSION: The results suggest the importance of evaluating schizophrenia patients for the presence of depressive symptoms. Effectiveness of adjunct treatment of depressive symptoms with antidepressants and psychosocial management in improving functioning of schizophrenia patients deserves further study.

Age Factors↗