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Biomedical subjects

C H Chen

Publications and source records attributed to C H Chen.

At least 325 records · Page 18Linked to original sources

An inhibitory fragment derived from protein kinase Cepsilon prevents enhancement of nerve growth factor responses by ethanol and phorbol esters.

We have studied nerve growth factor (NGF)-induced differentiation of PC12 cells to identify PKC isozymes important for neuronal differentiation. Previous work showed that tumor-promoting phorbol esters and ethanol enhance NGF-induced mitogen-activated protein (MAP) kinase activation and neurite outgrowth by a PKC-dependent mechanism. Ethanol also increases expression of PKCdelta and PKCepsilon, suggesting that one these isozymes regulates responses to NGF. To examine this possibility, we established PC12 cell lines that express a fragment encoding the first variable domain of PKCepsilon (amino acids 2-144), which acts as an isozyme-specific inhibitor of PKCepsilon in cardiac myocytes. Phorbol ester-stimulated translocation of PKCepsilon was markedly reduced in these PC12 cell lines. In addition, phorbol ester and ethanol did not enhance NGF-induced MAP kinase activation or neurite outgrowth in these cells. In contrast, phorbol ester and ethanol increased neurite outgrowth and MAP kinase phosphorylation in cells expressing a fragment derived from the first variable domain of PKCdelta. These results demonstrate that PKCepsilon mediates enhancement of NGF-induced signaling and neurite outgrowth by phorbol esters and ethanol in PC12 cells.

Animals↗

Elucidating mechanisms of thermostabilization of poliovirus by D2O and MgCl2.

To understand a significant reduction in the loss of poliovirus infectivity by D2O and a combination of D2O and MgCl2 at 37-45 degrees C, this paper attempts to elucidate the mechanisms underlying the thermostabilization of poliovirus. Three serotypes of Sabin oral poliovirus vaccine strains were investigated. Temperature-dependent fluorescence emission intensity studies showed that the effects of D2O and MgCl2 on the stability and conformation of poliovirus are correlated with those of the infectivity of poliovirus. Fluorescence steady-state polarization revealed that the conformation of poliovirus capsid is sensitive to D2O medium and MgCl2 salt, and that the rigidity of poliovirus conformation is increased in their presence. The exposure of poliovirus tryptophan residues to water is modified by D2O and MgCl2, as evidenced by changes in fluorescence emission intensity excited at 295 nm. The involvement of hydrogen bonding in the D2O effect was demonstrated by the greatly increased value of relative fluorescence intensity. Conformational alteration was also shown by changes in the positive band (193-230 nm) of circular dichroism spectra. D2O and MgCl2 were also found to reduce the interaction of virus with water as examined by differential scanning microcalorimetry, leading to a decline in the extent of water penetration into the poliovirus capsid. All these observations were found to be more profound in a combination of D2O with MgCl2 than D2O or MgCl2 alone. By inducing a conformation favorable to maintaining the poliovirus assembly and by reducing virus-water interaction to decrease water penetration into the poliovirus capsid, D2O, MgCl2, or D2O-MgCl2 is able to exert its thermostabilization effect. Thus, to maintain the virus assembly and conformation of the virus and to reduce the swelling of the virus capsid are key factors in increasing the thermostability of poliovirus. These two factors are mutually complementary. The latter can provide a favorable environment for the formers and the formers, in turn, lead to the latter.

Calorimetry, Differential Scanning↗

Estimation of central aortic pressure waveform by mathematical transformation of radial tonometry pressure. Validation of generalized transfer function.

BACKGROUND: Central aortic pressures and waveform convey important information about cardiovascular status, but direct measurements are invasive. Peripheral pressures can be measured noninvasively, and although they often differ substantially from central pressures, they may be mathematically transformed to approximate the latter. We tested this approach, examining intersubject and intrasubject variability and the validity of using a single averaged transformation, which would enhance its applicability. METHODS AND RESULTS: Invasive central aortic pressure by micromanometer and radial pressure by automated tonometry were measured in 20 patients at steady state and during hemodynamic transients (Valsalva maneuver, abdominal compression, nitroglycerin, or vena caval obstruction). For each patient, transfer functions (TFs) between aortic and radial pressures were calculated by parametric model and results averaged to yield individual TFs. A generalized TF was the average of individual functions. TFs varied among patients, with coefficients of variation for peak amplitude and frequency at peak amplitude of 24.9% and 16.9%, respectively. Intrapatient TF variance with altered loading (> 20% variation in peak amplitude) was observed in 28.5% of patients. Despite this, the generalized TF estimated central arterial pressures to < or = 0.2 +/- 3.8 mm Hg error, arterial compliance to 6 +/- 7% accuracy, and augmentation index to within -7% points (30 +/- 45% accuracy). Individual TFs were only marginally superior to the generalized TF for reconstructing central pressures. CONCLUSIONS: Central aortic pressures can be accurately estimated from radial tonometry with the use of a generalized TF. The reconstructed waveform can provide arterial compliance estimates but may underestimate the augmentation index because the latter requires greater fidelity reproduction of the wave contour.

Abdomen↗

Efficacy of organ preservation media enriched with nonlactate-generating substrate for maintaining tissue viability: a transplantation study.

BACKGROUND: Previously, isotonic solution (IS) enriched with beta-hydroxybutyrate, a nonlactate-generating substrate, was shown to be efficacious in maintaining tissues' ATP and metabolic activity under cold storage. The objective of this study was to verify these findings in terms of tissue viability in vivo. METHODS: Using a rabbit cornea transplantation model, efficacy of IS was studied and compared with McCarey-Kaufman medium, with or without beta-hydroxybutyrate, and other known media (Optisol and Likorol), with different properties and without beta-hydroxybutyrate. After storage at 4 degrees C for 6, 7, and 11 days, the corneas were grafted, and postoperative changes in corneal thickness, and endothelial cell density and morphology were monitored with a pachymeter and specular microscope. RESULTS: The experiments revealed that before grafting, IS effectively controlled tissue swelling for 7 days or longer, comparable to Optisol. When grafted, the IS-stored corneas deturgesced at high rates, with a short half-time (t1/2) for the de-swelling process, and the grafts remained thin and clear with an intact endothelium. This reflects excellent tissue viability. In the controls, the deturgescence process was extremely sluggish, with significantly lower rates and longer t1/2 (P= >0.01-0.05). Immediate swelling for 3-5 days after grafting was also observed with Optisol. These grafts had significant endothelium cell loss of 24-30% after 12 weeks (P= >0.01-0.02). CONCLUSIONS: IS is more efficacious than currently used media for sustaining the viability of donor corneas under cold storage. These findings may serve as a useful basis for future tests of IS in other organ storage systems.

3-Hydroxybutyric Acid↗

Further evidence of no association between Ser9Gly polymorphism of dopamine D3 receptor gene and schizophrenia.

Dopamine D3 receptor (DRD3) was demonstrated to have important implications in schizophrenia, because it binds antipsychotic drugs and is abundant in the limbic system of the brain. Several groups attempted to find an association between a serine-to-glycine polymorphism at codon 9 of the DRD3 gene (Ser9Gly) and schizophrenia; however, the results were inconsistent. We conducted a case-control association study in Han Chinese schizophrenic patients from Taiwan, to examine the relationship of this serine-to-glycine polymorphism and schizophrenia. We noted no significant differences of genotype distribution, allele frequencies, or homozygosity proportion of this polymorphism between schizophrenic patients (N = 178) and controls (N = 100). When patients were divided according to sex, or presence or absence of family history, the differences were still not significant. Our study does not support the contention that the Ser9Gly polymorphism of the DRD3 gene plays a major role in schizophrenia.

Alleles↗

Matrix-assisted laser desorption/ionization for sequencing single-stranded and double-stranded DNA.

The DNA sequence of a single-stranded and double-stranded template was determined. The templates were sequenced using the chain termination method and cycle sequencing method and detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The sequencing products were analyzed successfully without the laborious and expensive methods for removal of the template. Direct sequencing of the double-stranded template was achieved with minimal post-reaction purifications, which could be extremely important for mutation analysis and clinical diagnosis. A systematic study of the mechanisms and kinetics of sequencing reactions was also performed. The details of this analysis and directions for future improvements of the quality of sequencing are presented.

Base Sequence↗

Nutrient intake and protein metabolism: responses to feeding.

Lean tissue growth occurs when the rate of protein synthesis exceeds the rate of protein breakdown. Although absolute rates of protein synthesis and breakdown rise during growth from birth to maturity fractional rates fall. Both these processes are sensitive to nutrient intake but responses to feeding vary greatly amongst different tissues. Protein, carbohydrate and fat can all stimulate body protein accretion in immature animals and in children but the mechanisms by which they do so, and the energy expenditures involved, seem to be different.

Animals↗

Possible overlapping potentials of the auditory P50 in humans: factor analysis of middle latency auditory evoked potentials.

The auditory P50 in humans may consist of overlapping potentials. To test this hypothesis, we manipulated the conditions of stimulus discrimination and motor response difficulty and evaluated the data by factor analysis. Twenty right-handed males (mean age 27 years) performed the following 4 tasks: (1) a counting task, (2) an easy Go, No-Go task, (3) a difficult Go, No-Go task, and (4) a choice reaction task. Middle latency auditory evoked potentials were obtained with 100 times summation triggered by the onset of the auditory stimulus. Four factors were extracted by factor analysis for a 0-100 ms time period. Factor 1, the maximum factor loading at 91 ms, corresponded to N1, and factor 4, the maximum factor loading at 23 ms, appeared to correspond to P30. The latency of the maximum factor loading in factor 2 was adjacent to that in factor 3, the latency of factor 2 being 12 ms earlier than that of factor 3. Factor 2 and factor 3 latencies were approximately 55 ms which corresponded to the P50. Factor 3 started rising at the point that factor 2 reached the maximum factor loading, and the factor score demonstrated a significant group difference only when analyzed by motor response criteria. These results suggest that the P50 in humans consists of overlapping potentials and that a part of the potential might relate to a motor response process.

Adult↗

Nephromegaly and elevated hepatocyte growth factor in children with biliary atresia.

Nephromegaly, a rarely mentioned but probably common situation, was studied in children with biliary atresia. We evaluated the length and the cross-sectional diameters of the kidney by ultrasound in 21 children with biliary atresia as well as in 50 healthy children. The ages ranged from 1 month to 10 years. Plasma hepatocyte growth factor (HGF) was measured in 18 children with biliary atresia and also in 18 age- and sex-matched normal controls. There was a significant nephromegaly (increase in the renal length and the kidney volume) in children with biliary atresia as compared with normal children (P < 0.001 by analysis of covariance). Plasma HGF levels were elevated in these patients (2.13 +/- 1.06 v 0.76 +/- 0.19 ng/mL in controls, P < 0.001) and had a positive correlation with the renal size after considering the effect of body height by multiple regression analysis (P = 0.0022 for renal length, and P < 0.001 for kidney volume). These results confirm the presence of large kidneys in biliary atresia and implicate the possible pathogenic role of HGF in such a condition. Nephromegaly in biliary atresia may provide a new in vivo model to study the mechanism of renal growth.

Biliary Atresia↗

Anti-AIDS agents--XXVII. Synthesis and anti-HIV activity of betulinic acid and dihydrobetulinic acid derivatives.

Two series of lupane-type triterpenoic acid derivatives were synthesized and evaluated for their inhibitory activity against HIV-1 replication in acutely infected H9 cells, based on the fact that betulinic acid (1) and dihydrobetulinic acid (9) were identified as anti-HIV agents. Among the derivatives, 3-O-(3',3'-dimethylsuccinyl)-betulinic acid (3) and 3-O-(3',3'-dimethylsuccinyl)-dihydrobetulinic acid (11) both demonstrated extremely potent inhibitory activity with EC50 values of < 3.5 x 10(-4) microM, and remarkable in vitro therapeutic index (TI) values of 20,000 and 14,000, respectively. 3-O-(3',3'-dimethylglutaryl)-betulinic acid (4) and-dihydrobetulinic acid (12), 3-O-diglycolyl-betulinic acid (5) and -dihydrobetulinic acid (13) and 3-O-glutaryl-betulinic acid (6) were also potent inhibitors of HIV replication with EC50 values ranging from 0.04 to 2.3 x 10(-3) microM and TI values from 292 to 2344. In addition, compounds 11 and 12 were also active against HIV replication in a monocyte cell line and in peripheral blood mononuclear cells. Our in vitro assay indicated that these compounds are not inhibitors of HIV-1 reverse transcriptase, whereas they inhibited syncytia formation completely in a concentration range of 20-40 micrograms/mL. However, 3-O-(2',2'-dimethylsuccinyl)-betulinic acid (2) was also found to be an inhibitor of HIV-induced membrane fusion with an IC100 value of 20 micrograms/mL, though it displayed significantly lower anti-HIV activity than foregoing compounds with an EC50 value of 2.7 microM and TI of 6.7. Further study is underway to determine the mechanisms of action of these compounds.

Anti-HIV Agents↗

Characteristics of non-participants and reasons for non-participation in a population survey in Kin-Hu, Kinmen.

The aim was to characterize non-participants and to investigate reasons for non-participation in a health survey in Kin-Hu township, Kinmen, Republic of China. The non-participants represented 25.6% of the target population of 4,451 registered residents aged 30 and older. Baseline demographic characteristics and two-year mortality for the participants and non-participants were compared. A house-to-house visit was attempted to all of the non-participants for reasons of refusal. The mean age of the non-participants was significantly older than that of the participants (54.3 versus 48.5 years, p < 0.001). The response rate for women was significantly higher than that for men (77.2% versus 71.6%, p < 0.001). The probability of death was significantly different between the two groups (1.2% versus 8.8% for participants and non-participants, respectively, p < 0.001). Major reason for not having participated in the health survey was 'not notified or informed of the examination' (32.7%). These data suggest that non-participants were less healthy.

Adult↗

PYY and NPY: control of gastric motility via action on Y1 and Y2 receptors in the DVC.

The pancreatic polypeptide family of hormones and neurotransmitters including pancreatic polypeptide (PP), peptide YY (PYY) and neuropeptide Y (NPY) are emerging as potent central regulators of gastric function. There is, however, considerable debate concerning the mechanisms and even the direction of effects mediated by these peptides. Good evidence exists showing that PYY is the 'enterogastrone' released by the ileum after feeding which acts on vagal reflex control circuits to reduce gastric motility (i.e. the 'ileal brake'). However, equally convincing evidence is available to suggest that PYY and its close structural relative NPY may act in the same region of the brain to increase gastric motility through vagal mechanisms. We hypothesize that the confounding observations are due to agonist effects on two different receptor types-Y1 and Y2, which are both present in the dorsal vagal complex (DVC) but may be accessed differentially by peripheral humoral (PYY) vs central (NPY) pathways. In our initial approach to this problem, we studied the effects of NPY, PYY, Y1 and Y2 agonists microinjected into the DVC on gastric motility in the stimulated (by central thyrotropin-releasing hormone (TRH) and basal conditions. Our results show that Y2 agonist applied to the DVC during conditions of TRH-stimulated gastric motility mimicked the suppressive effects of PYY applied under the same conditions. Under basal conditions, Y2 agonist has no effect on motility. The DVC effect of the Y1 agonist is the opposite; Y1 agonist has no further effect to stimulate gastric motility in the TRH stimulated condition while Y1 agonist strongly stimulates motility from the basal condition. The effects of NPY depend upon the condition of study. Under TRH stimulation (maximal motility), NPY in the DVC reduces (but does not completely suppress) gastric motility while in the basal state, NPY is a strong activator of motility. These results are discussed in terms of the possible differential localization of Y1 vs Y2 receptors within the DVC and in terms of recent findings suggesting that PYY is rapidly converted to a Y2 agonist by a ubiquitous dipeptidyl aminopeptidase (DAP-IV).

Animals↗

Susceptibility of Pseudomonas aeruginosa of various pyocin types to the newly synthesized ampicillin derivative, N-(6,7-difluoroquinolonyl)ampicillin.

Six hundred and thirty-two isolates of Pseudomonas aeruginosa of 17 pyocin types were collected in 1993 in Taiwan. Types 1, 10, 3, 35 and 12 were the most common pyocin types identified in Taiwan with isolation frequencies of 47.3%, 24.4%, 7.6%, 3.6% and 2.2%, respectively. Several pyocin subtypes were determined. All pyocin types (one isolate of each tested) were resistant to ampicillin and nalidixic acid, but sensitive to fluoroquinolone antibiotics, such as norfloxacin and enoxacin, indicating that cross-resistance to quinolone antibiotics of nalidixic acid and fluoroquinolone derivatives has not developed. A new ampicillin derivative of 6,7-difluoroquinolonic acid, N-(6,7-difluoroquinolonyl)-ampicillin (AU-1), was synthesized by coupling ampicillin with 6,7-difluoroquinolonic acid (FP-3). Compound AU-1 was much more active than either ampicillin or FP-3 alone against all pyocin types of P. aeruginosa and induced filamentation in most growing cells.

Ampicillin↗

Bile duct hamartomas. A report of two cases.

Bile duct hamartomas (von Meyenburg's complexes) of the liver are usually detected at laparotomy or autopsy as an incidental finding, and usually they are multiple. We report two cases of proved bile duct hamartomas of the liver. The first was in a 65-year-old man whose initial sepsis and many hepatic lesions were interpreted as microabscess of the liver. The second patient was a 39-year-old man, a hepatitis B surface antigen carrier, in whom an incidental hepatic tumor was found. We suggest that liver biopsy be done in hepatic lesions with uncertain clinical features, because the histologic findings may change the treatment plan.

Adult↗