Biomedical subjects

C H Chen

Publications and source records attributed to C H Chen.

At least 271 records · Page 15Linked to original sources

PubMed1998

Anti-AIDS agents. 34. Synthesis and structure-activity relationships of betulin derivatives as anti-HIV agents.

Succinyl and 3'-substituted glutaryl betulin derivatives showed stronger anti-HIV activity and higher therapeutic index (TI) values than their dihydrobetulin counterparts, with ratios of 1.2:1 to 15:1 (cf. 7 and 15, 9 and 17, 10 and 18, 11 and 19, and 12 and 20). For various 3'-substituted glutaryl compounds, the order of anti-HIV effects, from strong to weak inhibition, was 3',3'-dimethyl, 3'-methyl, 3'-ethyl-3'-methyl, followed by 3',3'-tetramethylene glutaryl derivatives (10 > 9 > 11 > 12, 18 > 17 > 19 > 20). The most potent compound, 10, has two 3',3'-dimethylglutaryl groups and displays significant anti-HIV potency with an EC50 value of 0.000 66 microM and a TI of 21 515. Results for compounds (22 and 23) without a C-3 acyl group confirmed the importance of the C-3 acyl group to the anti-HIV effect. With 3',3'-tetramethylene glutaryl derivatives, triacyl 29 showed stronger inhibition than diacyl 12; in contrast, 3',3'-dimethylglutaryl compounds displayed opposite results. 3-Keto compounds (35 and 36) and 2,3-dihydro compounds (39 and 40) had EC50 values in the range of 4.3-10.0 microM, suggesting that A ring modification led to decreased potency. The reduced activity of amide (33 and 34), ester (41), and oxime (42) analogues suggested that the orientation and linkage of the C-3 acyl side chain play crucial roles in the potent anti-HIV activity. Finally, replacing the C-28 acyl group with a bulky non-carboxylic group produced a less potent compound (44). In the study of mechanism of action, our results indicated that fusion is not the primary target for the anti-HIV activity of 10. It appears to inhibit HIV replication at a late stage of the viral life cycle, i.e., after viral protein synthesis.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Human dynamin-like protein interacts with the glycogen synthase kinase 3beta.

Members of the dynamin superfamily are implicated in vesicle trafficking. Using human glycogen synthase kinase 3 beta (Gsk-3 beta) as bait in the yeast two-hybrid system, we identified a novel human dynamin-like protein IV (HdynIV). When the full-length cDNA of HdynIV was sequenced, it showed that HdynIV's carboxyl terminal lacks a proline-rich domain that can bind to Gsk-3 beta. By Northern blot analysis and isoform-specific PCR, we found that HdynIV is expressed ubiquitously in all human tissues examined. Two transcripts of 2.4 and 4.4 kb are shown to be more abundant in heart, brain, and skeletal muscle. Interestingly, the 2.4-kb transcript is expressed more distinctly in the fetal liver than in the adult liver, suggesting that this protein might play a role during development. In the present report, we have demonstrated that HdynIV interacts with the Gsk-3 beta through its carboxyl-terminal region, implying than HdynIV may also be involved in cell signaling.

Adult↗

PubMed1998

Which arterial and cardiac parameters best predict left ventricular mass?

BACKGROUND: Many cardiovascular and noncardiovascular parameters are thought to be determinants of left ventricular mass (LVM). Complicated interactions necessitate the simultaneous measurement and consideration of each to determine their individual and collective impact on LVM. We undertook such a comprehensive study. METHODS AND RESULTS: The influence of anthropometry, cardiac size and contractility, arterial structure and function, as well as indices of lifestyle, physical activity, and dietary salt intake on LVM (by two-dimensionally guided M-mode echocardiography) was analyzed in 1315 Chinese subjects who were either normotensive or had untreated hypertension. Effects of many cardiac and arterial factors were assessed. In univariate analysis, almost all measured noncardiovascular, cardiac, and arterial variables were significantly correlated with LVM. In multivariate linear regression analyses, when age, sex, body habitus, fasting serum C-peptide level, dietary salt, physical activity, and lifestyle were accounted for, the optimum multivariate linear regression main effects model had an adjusted model r2 of 0.740, with 98% of the model variance accounted for by the 5 independent determinants of LVM: stroke volume (49.6%), systolic blood pressure (30.7%), contractility (14.7%), body mass index (1.8%), and aortic root diameter (1.6%). Other proposed arterial indices were significant independent determinants of LVM only when blood pressure was removed from the model and, even then, these indices not only resulted in less powerful prediction but also accounted for only a very small percentage of the total variance of LVM. CONCLUSIONS: In a large population, we (1) confirmed that age, body habitus, and some indexes of arterial structure and function are independent determinants of LVM; (2) found aortic diameter to be an independent structural determinant of LVM; (3) demonstrated that the effects of the derived measures of arterial function were small and provided no better predictive power than blood pressure alone; and (4) showed that when the best measures of cardiac and vascular load were included, the single most potent predictor was an index of left ventricular size.

Adult↗

PubMed1998

Sesquiterpenes from the leaves of Tithonia diversifolia.

Two new compounds, a germacrane sesquiterpene, 1-acetyltagitinin A (1), and a guaianane sesquiterpene, 8beta-isobutyryloxycumambranolide (2), were isolated from leaves of Tithonia diversifolia, together with two known compounds, methyl 3alpha-acetoxy-4alpha-hydroxy-11(13)-eudesmen-12-oa te and tagitinin A. The structures of compounds 1 and 2 were elucidated on the basis of spectral and chemical evidence.

Carbohydrate Sequence↗

PubMed1998

New diterpenes from the heartwood of Chamaecyparis obtusa var. formosana.

An abietane diterpene, 11,14-dihydroxy-8,11,13-abietatrien-7-one (1); a seco-abietane diterpene, obtuanhydride (2); and an isopimarane diterpene, 18,19-O-isopropylidene-18, 19-dihydroxyisopimara-8(14),15-diene (3) were isolated from the heartwood of Chamaecyparis obtusa var. formosana. The structures of these new compounds were elucidated by spectroscopic methods.

Abietanes↗

PubMed1998

Genetic polymorphism and Parkinson's disease in Taiwan: study of debrisoquine 4-hydroxylase (CYP2D6).

Debrisoquine 4-hydroxylase (CYP2D6) is one of the cytochrome P450 enzyme families that catalyze the breakdown of a variety of exogenous and endogenous compounds. Previous reports have suggested that genetic polymorphisms of debrisoquine 4-hydroxylase are associated with susceptibility to Parkinson's disease (PD) in Caucasians. To determine if CYP2D6 also confers susceptibility to PD in Chinese patients, we carried out a study of genetic association using three polymorphic markers of the CYP2D6 gene, 188C/T, 1934G/A (mutant B), and 4268G/C. No differences of allele or genotype frequencies of these three polymorphisms were detected upon comparison of primary PD patients (n=53) with normal controls (n=94). The 1934A allele (mutant B), which accounts for the majority of poor metabolizers in Caucasians, is extremely rare in Chinese. Our data do not support the suggestion that the CYP2D6 gene is related to PD susceptibility in Chinese.

Adult↗

PubMed1998

Structures and dynamic motion of laminin-1 as observed by atomic force microscopy.

Laminins are a family of multifunctional extracellular matrix glycoproteins that play important roles in the development and maintenance of tissue organization via their interactions with cells and other extracellular matrix proteins. To understand the structural basis of laminins' functions, we examined the motion of laminin-1 (Ln-1) in physiological buffers using atomic force microscopy. While many Ln-1 molecules assumed the expected cruciform structure, unexpected dynamic movements of the Ln-1 arms were observed in aqueous environments. These dynamic movements of the Ln-1 arms may contribute to the diversity of laminin functions.

Animals↗

PubMed1998

Nitric oxide activates Ca2+-activated K+ channels in cultured bovine adrenal chromaffin cells.

The effects of sodium nitroprusside (SNP) on Ca2+-dependent K+ (KCa) channels in cultured bovine adrenal chromaffin cells were investigated using single channel recording patch-clamp techniques. KCa channels were activated by application of 100 microM SNP to the extracellular side of cell-attached patches. Methylene blue (300 microM), an inhibitor of soluble guanylate cyclase, or H-8 (1 microM), a protein kinase inhibitor with relative specificity for cGMP-dependent protein kinase, diminished but did not completely abolish the SNP-induced KCa channel activation. Diethylamine/NO complex (DEA/NO), an NO donor, also activated KCa channels in cell-attached patches. Furthermore, application of 100 microM SNP or 100 nM DEA/NO to the intracellular surface of excised inside-out patches also activated KCa channels in the bath solution which contained 1 microM Ca2+. These results indicate that SNP is capable of activating the KCa channel via cGMP-dependent and -independent mechanisms. These studies demonstrate that NO may serve as an important regulatory mechanism for catecholamine secretion in chromaffin cells via the activation of KCa channels.

Adrenal Medulla↗

PubMed1998

Apical hypertrophic cardiomyopathy mimicking acute myocardial infarction.

Thrombolytic therapy was given to a 77-year-old man with typical ischemic chest pain and unequivocal electrocardiographic ST-segment elevations at the emergency department. The diagnosis of acute myocardial infarction was excluded during hospitalization and the patient was found to have apical hypertrophic cardiomyopathy with apical aneurysm formation and mid-ventricular obstruction.

Adrenergic beta-Antagonists↗

PubMed1998

Sequencing DNA using mass spectrometry for ladder detection.

Sequencing of DNA fragments of 130 and 200 bp using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for DNA ladder detection was demonstrated. With further improvement in mass resolution and detection sensitivity, mass spectrometry shows great promise for routine DNA sequencing in the future.

Bacteriophage lambda↗

PubMed1998

Induction of stress response and differential expression of 70 kDa stress proteins by sodium fluoride in HeLa and rat brain tumor 9L cells.

We herein demonstrate that sodium fluoride (NaF) acts as a stress response inducer on HeLa and 9L rat brain tumor cells. NaF is only slightly cytotoxic, and inhibitory to Ser/Thr-phosphatases but not to Tyr-phosphatases in both cell lines. After treatment with 5 mM NaF for 2 h, the phosphorylation levels of vimentin and an alkali-resistant 65-kDa phosphoprotein were enhanced, a common phenomenon detected in cells under a variety of stress conditions. Under an identical treatment protocol, in which the cells were treated with 5 mM NaF for 2 h and then allowed to recover under normal growing conditions for up to 12 h, NaF differentially induced the cytoplasmic/nuclear heat-shock protein70s (including both the inducible and the constitutively expressed members of this protein family) in HeLa cells and the endoplasmic reticulum residing heat-shock protein70 (the glucose-regulated protein with an apparent molecular weight of 78 kDa) in 9L cells. Electrophoretic mobility shift assays (EMSA) using probes containing well-characterized regulatory elements revealed the activation of the heat-shock factor in HeLa but not in 9L cells; this is in good agreement with the stress protein induction pattern. Additional differential induction of binding activities toward EMSA probes individually containing NF-KB, AP-2, and CRE-like elements were detected in NaF-treated cells. The possible involvement of these binding sites as well as the corresponding factors in the stress response are discussed.

Animals↗

PubMed1998

Herpesvirus saimiri transformation of HIV type 1 suppressive CD8+ lymphocytes from an HIV type 1-infected asymptomatic individual.

CD8+ T lymphocytes from HIV+ individuals can potently suppress HIV-1 replication in a noncytolytic manner. This suppression appears to be multifactorial and the molecules contributing have not been fully elucidated. As an approach to this question we used herpesvirus saimiri (HVS) to transform CD8+ T lymphocytes from an HIV+ asymptomatic donor to a continuously growing, activation-independent, IL-2-dependent phenotype. The transformed cell population, termed CD8(HVS), had an activated phenotype, contained HVS sequences, did not shed infectious HVS virus, and was polyclonal. The CD8(HVS) cells, despite the absence of detectable CTL activity, potently suppressed HIV-1 production by both autologous and heterologous CD4+ cells from infected donors. The CD8(HVS) cells in coculture also suppressed virus production from PBMCs acutely infected with syncytium-inducing (SI) strains or NSI primary isolates of HIV-1. The supernatants from the CD8(HVS) cells and their concentrates derived from these supernatants were suppressive to NSI primary isolates of HIV-1 but not to SI strains. Fractionation of these concentrates showed that the suppressive activity was associated with low molecular mass (6500- to 19,300-Da) protein species. Western blotting and ELISA indicated that the CC chemokines MIP-1alpha, MIP-1beta, and RANTES were present in these fractions. Antibody-blocking studies with antibodies to the CC chemokines indicated that a significant portion of the soluble HIV-suppressive activity was due to these molecules. However, these experiments also suggested the inhibitory activity of the CD8(HVS) cells in coculture is not due exclusively to the CC chemokines. The HVS-transformed cells provide a useful tool for the study of noncytolytic CD8+ T lymphocyte-mediated suppression of HIV-1.

CD8-Positive T-Lymphocytes↗

PubMed1998

Adaptation of visually guided behavior during reversed vision in schizophrenia: a preliminary study.

This preliminary study evaluated the adaptation of visually guided behavior to reversed vision in schizophrenia. The study included 54 patients who met DSM-III-R criteria for schizophrenia. Visuomotor reaction times (VRTs) during reversed vision were measured in six blocks of 35 consecutive trials. The VRTs of schizophrenics were compared with those of normal subjects. A good fit (R2 = 0.9981) for the adaptation process of VRTs during reversed vision was found with the equation y = 1030 + 1499/x, where x is the order of the block and y is the group mean VRT for each block. The VRTs in schizophrenics were significantly slower than those in normal subjects. However, the adaptation process to reversed vision essentially did not differ from normal. The adaptation of visually guided behavior during reversed vision may involve procedural learning; this task may thus be useful in evaluating such learning. The VRTs during reversed vision may be related to some aspects of symptoms in the patient with schizophrenia and may also be useful in predicting clinical outcome.

Adult↗

PubMed1998

Elucidation of biphasic alterations on acetylcholinesterase (AChE) activity and membrane fluidity in the structure-functional effects of tetracaine on AChE-associated membrane vesicles.

Tetracaine-induced biphasic structure-functional alterations were investigated in acetylcholinesterase (AChE)-associated membrane vesicles from the electric organ of Torpedo californica. Enzyme assays showed that tetracaine exhibits a biphasic effect on the activity of membrane-bound AChE: increasing it at low concentrations (< 12 mM) and decreasing it at high concentrations (> 12 mM). Fluorescence-polarization experiments demonstrated that tetracaine affects the fluidity of lipid hydrocarbon chains of these membranes in a biphasic manner: increasing it at < 20 mM and decreasing it at > 20 mM. This small molecule also alters the fluidity of the negatively charged lipid head group: increasing it at < 13 mM and remaining essentially at the same level at > 13 mM. The positively charged lipid head group is unaffected. Contrasting effects on AChE activity with changes in membrane fluidity showed that [tetracaine] for AChE activity is comparable to that for the fluidity of the negatively charged lipid head group (12 mM versus 13 mM), but lower than that for a biphasic effect on the fluidity of lipid hydrocarbon chains (12 mM versus 20 mM). Differential scanning microcalorimetry showed that, due to membrane protein-lipid interaction, the lipid-phase transition temperature (tml) is higher for AChE-associated membrane vesicles than for isolated lipids from these membranes. An overall disordering of the membranes by tetracaine, as inferred from the lowering of tml, was also demonstrated. These findings suggested that binding of tetracaine to the lipid polar head group and membrane protein-lipid interaction may contribute to a higher [tetracaine] in inducing a comparable biphasic effect on membrane fluidity. At high [tetracaine], charge interactions between the tetracaine cation and the negatively charged lipid head group may result in a new lipid phase in the membranes, which could reverse the increase in membrane fluidity, resulting in the observed biphasic effect. Although both tetracaine and alcohol are amphiphilic species, they exhibit distinctive structure-functional effects on the membranes, as shown by comparing the results obtained on tetracaine with those previously reported for alcohol. The present observations may have significant physiological implications and may be of importance in understanding the biochemical effects of tetracaine in correlation with its physiological impact.

1-Propanol↗

PubMed1998

Psychopathological dimensions in schizophrenia: a correlational approach to items of the SANS and SAPS.

Seventy DSM-III schizophrenic patients were assessed for positive and negative symptoms using Andreasen's scales for the assessment of positive and negative symptoms (SANS and SAPS) on admission. The correlation structure of the items in the SANS and SAPS was explored in dimension and item levels by use of correlation plots through a distinct analytical method displaying the proximity matrix. The results revealed at least three major dimensions of symptoms delineated as Negative Symptoms, Disorganized Thoughts and Delusions and Hallucinations. The latter two dimensions were derived from the SAPS, while Negative Symptoms comprised most of the items in the SANS. Items in Disorganized Thoughts were more correlated to Negative Symptoms than to the other items in the SAPS. 'Loss of ego boundary' delusions and experience of auditory hallucinations appeared as two sub-clusters in the group of Delusions and Hallucinations. The relative independence of persecutory, grandiose, religious, somatic and reference delusions gives support to the concept that paranoid schizophrenia stands as a distinct clinical subtype of schizophrenia. The graphical method introduced here well expresses the information of correlation matrix and is useful for exploring inter-item or inter-cluster associations.

Adolescent↗

PubMed1998

Structural characteristics of brain glutamate decarboxylase in relation to its interaction and activation.

The conformation, stability, cofactor interactions, and activation of a recombinant 65-kDa form of rat brain glutamate decarboxylase (GAD65) were investigated by using UV/visible spectrophotometry, fluorescence spectroscopy, circular dichroism, and differential scanning microcalorimetry. The enzyme was prepared from Sf9 insect cells infected with a recombinant baculovirus containing the entire GAD65 coding region. The UV/visible absorption spectrum of purified holoenzyme (holoGAD) exhibits two peaks in the range of 300-450 nm, which are due to the formation of a Schiff base when pyridoxal phosphate (pyridoxal-P) binds to GAD. Fluorescence emission intensity (excited at 295 or 280 nm) was substantially enhanced when pyridoxal-P was removed from holoGAD and quenched when pyridoxal-P was added to the apoenzyme (apoGAD). These observations implied that a significant enzyme conformational change occurs during the formation of holoGAD. Circular dichroism provided additional evidence for a conformational change, as the ellipticity of both negative (202-242 nm) and positive (188-202 nm) bands decreased when pyridoxal-P was removed from holoGAD. Secondary structure determination estimated that holoGAD contains a higher content of alpha-helix (34% versus 24%) and a lower content of beta-sheet (18% versus 30%) than apo-GAD. Differential scanning microcalorimetry indicated that holoGAD exhibits a much larger enthalpy and a 3 degrees C higher temperature of thermal unfolding than apoGAD, suggesting that holoGAD has a much tighter conformation and greater stability than apoGAD. A model describing the interaction of pyridoxal-P with GAD is presented, which proposes that an intermediate complex involving ionic interaction between the phosphate group of pyridoxal-P and the positive, charged residues in the active site of GAD maintains the pyridoxal-P molecule in an appropriate position in the active center. Simultaneously, this complex formation is accompanied by a moderate enzyme conformational change, providing a favorable configuration that enables the epsilon-amino of the active-site lysine to react with the aldehyde group of pyridoxal-P. The formation of active holoGAD involves a large enzyme conformational change, which leads to increased stability.

Animals↗

PubMed1998

Matrix-assisted laser desorption/ionization for short tandem repeat loci.

Matrix-assisted laser desorption/ionization was used for the detection of four base short tandem repeats (STR) for clinical samples using a time-of-flight mass spectrometer. Since STR plays an important role in genetic disease and human identification, this work indicates that laser desorption mass spectrometry has the potential to achieve rapid DNA typing for both forensic applications and genetic disease diagnosis.

DNA↗

PubMed1998

Identification of a novel point mutation (S65T) in alpha-galactosidase A gene in Chinese patients with Fabry disease. Mutations in brief no. 169. Online.

Fabry disease is an X-linked inborn error of sphingolipid catabolism resulting from deficient enzyme activity of alpha-galactosidase A. The molecular defects of human alpha-galactosidase A gene causing Fabry disease have been characterized, including gene rearrangement and point mutations, which show the genetic heterogeneity in Fabry disease. To characterize the molecular defects of these patients, each exon of alpha-galactosidase A gene including intron-exon junctions were PCR amplified using biotin-labelled primer and sequenced using magnetic beads solid-phase sequencing. A G to C transversion was identified in the last nucleotide of exon 1 in two unrelated Chinese patients. This mutation obliterates an EcoN1 restriction site. Family studies show close linkage with the affected family members. Screening of 100 alleles (22 males, 39 females) of unrelated normal Chinese can not find this mutation. This mutation not only changes the amino acid from serine to threonine, but also likely cause splicing defects. To our knowledge, this is the first report of mutation in Chinese patients with Fabry disease, and a novel mutation causing Fabry disease not reported in literature previously.

Adult↗