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Biomedical subjects

C W Chen

Publications and source records attributed to C W Chen.

At least 91 records · Page 5Linked to original sources
PubMed1995

Activation of phosphorylation of plasma membrane insulin-like growth factor-I receptors in the kidney of Syrian hamsters by diethylstilbestrol.

In the present work we have investigated activation of phosphorylation of plasma membrane insulin-like growth factor-I receptors (IGF-IR) by diethylstilbestrol (DES). Insulin-like growth factor-I (IGF-I) stimulated the activity of membrane protein tyrosine kinase(s) (PTK) in both normal and DES-treated hamster kidneys. The level of IGF-I-stimulated PTK(s) almost doubled after 15 days of DES treatment. Autophosphorylation experiments revealed that phosphorylation of a 95 kDa band (presumably the beta subunit of IGF-IR) was 2-fold higher in the membranes of kidney from DES-treated animals compared with controls. To understand the mechanism of activation of IGF-I-dependent PTK by DES, we investigated the relationship between the binding capacity of IGF-I to membrane proteins and the level of IGF-IR. The binding of [125I]IGF-I to membranes from the DES-treated group was 30% higher than that of age-matched normal kidney (P < 0.001). Scatchard analysis of the binding data for both normal and DES-treated hamster kidney revealed a single class binding site for IGF-I with a dissociation constant (Kd) of 4.1 and 4.6 nM and a maximum binding capacity (Bmax) of 1786 and 2086 fmol/200 micrograms protein respectively. Therefore, the difference observed in [125I]IGF-I binding between DES-treated and normal kidney membranes may be partially due to an increase in the number of IGF-I binding sites, with no change in the affinity of the receptors for IGF-I. An enhanced level of IGF-IRs in membranes from DES-treated animals was visualized by autoradiography following affinity labeling of membrane proteins subjected to SDS-PAGE. Under reducing conditions a molecular band of 132 kDa was evident. The 132 kDa band represents the alpha-subunit of IGF-IRs. Northern blot analyses revealed that DES treatment increased the level of IGF-IR mRNA 2-fold compared with that of controls. These findings suggest that an enhanced level of IGF-IR coupled with qualitative changes may be responsible for the activation of IGF-I-dependent PTK on DES exposure. Whether the stimulation of IGF-IR phosphorylation by exposure to a carcinogenic dose of DES may be a factor in the induction of renal cancer in Syrian hamsters is not clear.

Animals↗
PubMed1995

Effects of splint therapy in TMJ dysfunction: a study using magnetic resonance imaging.

This pilot study was undertaken to correlate clinical and MRI diagnoses in seven symptomatic TMJ dysfunction patients and to account, if possible, for the clinical improvement in the signs and symptoms after the use of a maxillary stabilizing splint. The symptomatic TMJs were evaluated by means of MRI prior to splint insertion. Sagittal open/closed, and coronal closed images were obtained with a 0.3 T Fonar MR Scanner. A follow-up MRI was taken after three months of splint therapy for the purposes of a comparative study. All subjects responded positively even at the early phase of splint treatment. By the end of the three month period, six subjects experienced full remission of pain in the TMJ and associated masticatory muscles with one subject experiencing only partial remission following therapy. Baseline MRI study revealed that only three subjects had anterior disc displacement while the other four subjects had normal disc/condyle relationships and morphology. In the follow-up MRI study, there were no signs of recapture of the three anteriorly displaced discs despite there being evidence of improved jaw movement and remission of pain symptoms. The use of MRI in this preliminary study indicates that some but not all TMJ pain dysfunction syndromes are caused by internal derangements of the joint. A larger MRI study using the same clinical parameters is indicated for future research.

Adolescent↗
PubMed1995

Rapidly fatal outcome of bacteremic Klebsiella pneumoniae pneumonia in alcoholics.

Twenty-eight alcoholic patients with community-acquired pneumonia who were admitted to a referral medical center during a 3-year period were reviewed. All were men and with few exceptions were heavy smokers. The overall mortality was 64.3%. The most dramatic group was that of 11 patients (39.3%) with bacteremic Klebsiella pneumoniae pneumonia (BKPP), which had high mortality rate (100%), short onset of illness before hospital admission (42.6 +/- 8.2 h, mean +/- SD), and short survival time after the admission (24.6 +/- 7.9 h). All these 11 patients needed intensive care unit (ICU) management and ventilatory support. ARterial blood gas values showed marked hypoxemia and metabolic acidosis in most of these 11 patients, and presence of shock at arrival in the hospital was noted in 8 patients. Acute renal failure and disseminated intravascular coagulation developed in six patients. Chest radiographs showed pleural effusion and radiographic spread in nearly 50% of patients. Combination chemotherapy consisting of one aminoglycoside and one second- or third-generation cephalosporin was initiated in all patients. The rapidly fatal outcome of these 11 patients with BKPP despite management with adequate antibiotics and intensive care indicated the fulminant nature of this disease. High virulence of the microorganism, altered immune response, and increased susceptibility to infection may all have contributed to the fulminancy in this group of patients. The disease continues to present many difficulties in management.

Adult↗
PubMed1995

A molecular study of ocular herpes simplex infection in Kaohsiung, Taiwan. Part I: Cleavage pattern analysis.

In order to investigate the relationship between genotypes of herpes simplex virus (HSV) and its clinical pictures in herpes simplex virus keratoconjunctivitis (HSK), fifty nine strains of HSV isolates, collected in the Kaohsiung Medical College Hospital during January 1981 to July 1991, and F strain (ATCC VR-73), a standard HSV-1, were studied. The viruses were isolated from HSK patients. All 59 strains were identified as HSV-1 using immunofluorescence monoclonal antibody method. The HSV DNAs were extracted and digested by restriction enzymes, BamH I, Kpn I and Sal I, followed by electrophoresis, and photographing. Six kinds of DNA cleavage patterns were found in Taiwan. The majority were E subtype (56.4%) then A subtype (27.3%), D subtype (7.3%), F subtype (5.4%), G subtype (1.8%) and H subtype (1.8%). Subtypes B and C were not found in this study. The cleavage patterns of two recurrent cases belonged to E and A subtypes. The identical cleavage patterns of two bilateral infections all belonged to the E subtype.

Animals↗
PubMed1995

Effect of prostaglandins and nitric oxide on basal blood flow and acetylcholine-induced vasodilation in rat diaphragmatic microcirculation.

To assess the effect of prostaglandins and endothelium-derived relaxing factor (EDRF) on diaphragmatic microcirculation under basal conditions and after acetylcholine (ACh) stimulation, we studied a diaphragmatic preparation in anesthetized rats. With bicarbonate-buffered Ringer's solution suffusing the abdominal surface of the left costal diaphragm, laser-Doppler flowmetry was used to record microvascular blood flow (QLDF). Microvascular conductance (CLDF) was derived from QLDF by dividing by the systemic blood pressure. Drugs were applied to the surface of the diaphragm. Four series of experiments were performed. In Series 1 (n = 9), ACh (3 x 10(-5)-10(-3) mol/L) elicited a concentration-dependent increase in QLDF and CLDF. In Series 2 (n = 11), ACh-induced QLDF and CLDF changes were significantly attenuated after 30 minutes suffusion of indomethacin (10(-5) mol/L), although baseline QLDF and CLDF were little affected. In Series 3 (n = 7), following suffusion of N omega-nitro-L-arginine methyl ester (L-NAME) (10(-4) mol/L) for 30 minutes, there was no change in baseline QLDF and CLDF. The ACh-induced QLDF change was abolished, while there was still a slight increase in CLDF (172 +/- 26%) at high concentrations of ACh (10(-3) mol/L). In Series 4 (n = 5), co-administration of indomethacin (10(-5) mol/L) and L-NAME (10(-4) mol/L) for 30 minutes did not completely prevent the increase in CLDF (143 +/- 13%) induced by high concentrations of ACh (10(-3) mol/L). The data suggest low basal activities of both vasodilatory prostaglandins and EDRF in diaphragmatic microvascular beds of the anesthetized rat, while both mediators independently modulate microvascular responses to ACh.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1995

[The re-evaluation of the prevalence of trachoma in primary school children in Kaohsiung City].

For years, trachoma screening has been a routine part of the health examination program for all primary school children. In order to ascertain the current prevalence of trachoma in primary school children, we used clinical examination, immunofluorescein-monoclonal antibody and McCoy cell culture technique to examine 771 children from 5 primary schools in Kaohsiung City. Using the results of the McCoy cell culture as a judgement standard, we found that 118 children (15.3%) had chlamydia trachomatis infections. The infection rates of children were statistically insignificant for sex, grade and location of school of children. Among the 118 infected children, most had none or mild (96.6%) conjunctival inflammation. Only 3 children (0.4%) had conjunctival cicatrization complications. These results showed that the repeated reinfections among these children were quite few. The McCoy cell culture was used to test the result of clinical diagnosis made by the senior ophthalmologists. The sensitivity of the clinical diagnosis was 50% and the predictive positive rate was 26.6%. It revealed that the diagnosis of trachoma made by clinical observation only was unreliable. The results of immunofluorescein-monoclonal antibody test showed that 120 children (15.6%) had trachomatous infections. Its sensitivity was 68.4%, and specificity was 91.7%. It revealed that more care should be taken in quality control of laboratory techniques. From these results, we conclude: 1) the trachomatous infections of primary school children in Kaohsiung City are not serious; the repeated infections among

Child↗
PubMed1994

Differential effects of nitric oxide synthesis inhibitor on rat diaphragmatic microcirculation under basal conditions and after vasodilator stimulation.

To assess the effect of endothelium-derived relaxing factor (EDRF) on the diaphragmatic microcirculation under basal conditions and after vasodilator stimulation, prepared diaphragms from anesthetized rats were studied. With bicarbonate-buffered Ringer's solution suffusing the diaphragm, the microcirculatory blood flow was recorded by laser-Doppler flowmetry (QLDF). Drugs were applied to the surface of the diaphragm. Five series of experiments were performed. In Series 1, the effects of acetylcholine (ACh, 10(-4) M) and sodium nitroprusside (SNP, 3 x 10(-6) M) were measured before and after 15 minutes suffusion of N omega-nitro-L-arginine methyl ester (L-NAME, 10(-4) M). Trend analyses revealed that the vasodilator effect of SNP was not affected, while that of ACh was abolished by L-NAME. In Series 2, both ACh and SNP elicited a concentration-dependent increase in QLDF. In Series 3, following 15 minutes suffusion with L-NAME (10(-4) M), there was no change in baseline QLDF and the ACh-induced QLDF change was abolished, while the effect of SNP was maintained. In Series 4, five minutes of pretreatment with L-arginine (L-arg, 10(-2) M), followed by co-administration of L-arg (10(-2) M) and L-NAME (10(-4) M) for another 15 minutes, did not prevent the inhibitory effect on ACh-induced QLDF change by L-NAME. In Series 5, 20 minutes application of L-arg (10(-2) M) alone did not affect baseline QLDF. Also, L-arg did not influence the ACh-induced vasodilating response, whereas it slightly increased the SNP-induced vasodilating response.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

Seroepidemiological study of coxsackievirus type A24 variant (CA24v) in Taiwan.

In October 1985 and June 1986, for the first time, Taiwan experienced two outbreaks of acute hemorrhagic conjunctivitis (AHC) caused by a variant of coxsackievirus A24 (CA24v). Sera of virologically and clinically confirmed cases were studied together with the pre- and post-epidemic serum samples by the microneutralization method (cut-off titer, 1:8). The serum samples included 16 cases of virologically confirmed AHC and 18 cases of clinically diagnosed AHC which were collected during the period of January to July, 1987 (i.e., 7 to 21 months after the epidemic). In the same period of time, 374 serum samples were randomly collected as a post-epidemic control group. Meanwhile, 206 serum samples, which were randomly collected in 1980, were studied as a pre-epidemic control group. The results showed that in terms of CA24v neutralizing antibody (NTAb) positivity, a significant difference was found between the pre- and post-epidemic random sample groups (5.3% vs. 28.1%, P < 0.001) while no significant differences among the virologically confirmed, the clinically diagnosed and the post-epidemic random sample groups were noticed (31.3% vs. 28.1%; 44.4% vs. 28.1%, P > 0.05). For comparison, the enterovirus 70 (EV70) NTAb of the samples was studied simultaneously. The results showed that the positive rate and geometric mean titer of CA24v NTAb were lower than those of EV70 even in the post-epidemic serum samples collected shortly after the CA24v epidemic.

Adolescent↗
PubMed1994

Study on some biological and antigenic characteristics of CA24v isolates in Taiwan in 1985-1989.

In order to understand the relationship between the CA24v isolates which caused two epidemics of acute hemorrhagic conjunctivitis (AHC) in 1985-1986 and 1988-1989 in Taiwan, biological and antigenic characteristics were studied with four CA24v strains, L077/85, V116/86, 590/88 and 722/89, which were isolated during the epidemics. The prototype strain, EH24/70, was used for comparison. In terms of cross neutralization, kinetic neutralization, plaque assay and protein electrophoresis, no obvious differences were found between the isolates from the two epidemics though differences were found between these isolates and the prototype.

Conjunctivitis, Acute Hemorrhagic↗
PubMed1993

Regulatory concerns for the chemistry, manufacturing, and controls of oligonucleotide therapeutics for use in clinical studies.

It is important to remember that while a new class of therapeutic agents like oligonucleotides may introduce novel concerns, the basic regulatory issues regarding the chemistry, manufacturing, and controls of drug substances and drug products must be addressed. This article focuses on information that should be included in an Investigational New Drug Application (IND), a request to use an investigational drug in clinical studies. The regulatory challenge presented with oligonucleotide therapeutics is to prove the identity of the oligonucleotide, and demonstrate its quality, purity, and strength/potency using both those characteristics that are the same as all other drugs, as well as those that are unique. Most of the discussion will concern issues that are unique to oligonucleotides, or those topics that deserve more detailed attention than would be needed for more typical small molecule drugs. Regulatory issues will need to be evaluated so that safety concerns are addressed while not imposing undue burden on the sponsors of investigational drugs.

Clinical Trials as Topic↗
PubMed1993

The chromosomal DNA of Streptomyces lividans 66 is linear.

Two copies of a DNA sequence similar or identical to one end of the linear plasmid SLP2 were found on the Streptomyces lividans chromosome. Restriction mapping showed that these sequences represented free ends. Electrophoretic retardation and glass-binding studies indicated that the telomeres carry covalently bound proteins. Moreover, the chromosome migrated as an 8 Mb linear DNA in pulsed-field gel electrophoresis. A similar finding with the chromosomes of six other Streptomyces species suggested that a linear chromosome may be characteristic of the genus. The S. lividans chromosome can be circularized by joining the two ends by artificial targeted recombination or by spontaneous deletions spanning both telomeres. Thus the chromosome appears to be able to exist, in viable bacteria, as a linear or a circular molecule.

Bacterial Proteins↗
PubMed1993

The conjugative plasmid SLP2 of Streptomyces lividans is a 50 kb linear molecule.

The SLP2 plasmid had previously been demonstrated genetically to exist in Streptomyces lividans by its ability to promote conjugation and to elicit 'pocks' on recipient (SLP2-) cultures, but it had not been physically detected. Using pulsed-field gel electrophoresis, a 50 kb linear DNA was isolated from SLP2+ but not SLP2- strains of S. lividans, and from Streptomyces coelicolor and Streptomyces parvulus strains to which SLP2 had been transferred by conjugation or transformation. We conclude that this linear DNA is SLP2. The terminal fragments of SLP2 were cloned. The determined sequences revealed a 44bp imperfect terminal inverted repeat. The terminal 12bp sequence of SLP2 was identical to those of two other Streptomyces linear plasmids, pSLA2 and pSCL, and similar to the terminal sequences of another Streptomyces linear plasmid, SCP1. The termini of SLP2 DNA were resistant to digestion by lambda exonuclease and ExoIII. A truncated (probably crippled) copy of Tn4811 is present on the plasmid. While the SLP2 plasmid exists as a free form in the host, a 15.7 kb sequence corresponding to the segment of SLP2 from Tn4811 to the right terminus is also present (at a copy number similar to the free form) elsewhere in the genome of S. lividans. Furthermore, SLP2 is partially homologous to a newly discovered 650 kb linear plasmid in S. parvulus.

Base Sequence↗
PubMed1993

Armitage-Doll two-stage model: implications and extension.

The objective of this paper is twofold: (1) to provide insight on the simplified MVK model of carcinogenesis (a model proposed by Moolgavkar and colleagues) by revealing the relationship between the Armitage-Doll two-stage model and the simplified MVK model; and (2) to extend the Armitage-Doll two-stage model to one with time-varying (piece-wise constant) parameters. It is shown that the simplified MVK model is a special case of the Armitage-Doll two-stage model, and many applications of the simplified MVK model involving intermittent exposures or exposures to different compounds in different time periods can be derived easily from the Armitage-Doll two-stage model with piece-wise constant parameters. The limitations of the Armitage-Doll two-stage model are discussed.

Animals↗
PubMed1993

The unstable melC operon of Streptomyces antibioticus is codeleted with a Tn4811-homologous locus.

The melC operon of Streptomyces antibioticus is unstable, undergoing frequent spontaneous deletions. All the delta melC mutants analyzed also lost 2-kb V1 DNA, which contained two open reading frames (ORFs) homologous to ORF4 (a putative oxidoreductase gene) and ORF5 (a putative AraC-type regulatory gene) of Tn4811. The two ORFs may constitute an accessory unit of a different transposon.

Amino Acid Sequence↗
PubMed1993

Molecular epidemiology of a variant of coxsackievirus A24 in Taiwan: two epidemics caused by phylogenetically distinct viruses from 1985 to 1989.

In order to know the phylogenetic relationship and the route of transmission of a variant of coxsackievirus A24 (CA24v), an agent that caused four sequential outbreaks of acute hemorrhagic conjunctivitis from 1985 to 1989 in Taiwan, the nucleotide sequence variations in the virus-encoded proteinase 3C region (549 nucleotides) were studied with 19 isolates. The prototype strain (EH24/70), four isolates from Japan, and two isolates from Hong Kong were used for comparison. The nucleotide sequences of the Taiwan strains from the 1985-1986 and 1988-1989 epidemics were closely related within each epidemic, while they were more distantly related between strains from two epidemics. Phylogenetic analysis by the unweighted pairwise grouping method of the arithmetic average revealed that the 19 Taiwan isolates had diverged into two groups, 1985-1986 and 1988-1989 groups. The time at which these two groups diverged was estimated to be around May 1982, more than 3 years prior to the first appearance of the CA24v epidemic in Taiwan. On each occasion, the viruses caused a 2-year epidemic and then disappeared. The Taiwan isolates from 1985 to 1986 were closely related to the Japan isolates from 1985 to 1986 and the Taiwan isolates from 1988 to 1989 were phylogenetically close to the 1989 Japan isolates, indicating that Taiwan and Japan had two common-source outbreaks. However, none of the 1988 Taiwan isolates were phylogenetically close to the 1988 Japan or Hong Kong isolates. The evidence revealed that Taiwan has had two repeated but discontinuous introductions of CA24v since its first appearance in Taiwan in 1985. None of the other CA24v strains have been detected so far.

Base Sequence↗
PubMed1993

Bronchoprovocation test by forced oscillation technique: airway hyperresponsiveness in chronic cough and psychogenic dyspnea subjects.

By measuring the respiratory resistance (Rrs) with the forced oscillation technique, we evaluated the airway responsiveness to methacholine in four groups of subjects (30 normal, 21 asthmatic, 60 chronic cough, and 30 psychogenic dyspnea subjects). After evaluating the airway responsiveness of normal and asthmatic subjects, four patterns of dose-response curves were found. All of the asthmatic subjects were responders (types III and IV), whereas all but two of the normal subjects were nonresponders (types I and II). The responders had more bronchoconstriction than the nonresponders who presented with a significant decrease in FEV1 after the test. If airway hyperresponsiveness to methacholine was defined as Cmin < or = 12.5 mg/mL, then this test showed 100% sensitivity, 97% specificity, a positive predictive value of 95.5%, and a negative predictive value of 100%. According to these criteria, 18 of 60 (30%) chronic cough subjects and six of 30 (20%) psychogenic dyspnea subjects had airway hyperresponsiveness. We conclude that bronchoprovocation test by the forced oscillation technique is a simple, safe and time-saving tool for measuring airway hyperresponsiveness. We also found that airway hyperresponsiveness is a common finding in subjects with chronic cough, and is also present in some subjects with psychogenic dyspnea.

Adult↗