Biomedical subjects

S L Chen

Publications and source records attributed to S L Chen.

At least 73 records · Page 4Linked to original sources

PubMed1999

The nuclear receptor corepressor N-CoR regulates differentiation: N-CoR directly interacts with MyoD.

Classical ligand-activated nuclear receptors (e.g. thyroid hormone receptor, retinoic acid receptor), orphan nuclear receptors (e.g. Rev-erbAalpha/beta), Mad/Max bHLH (basic helix loop helix)-LZ proteins, and oncoproteins, PLZF and LAZ3/BCL6, bind DNA and silence transcription by recruiting a repressor complex that contains N-CoR (nuclear receptor corepressor)/SMRT (silencing mediator of retinoic acid and thyroid hormone receptor), Sin3A/B, and HDAc-1/-2 proteins. The function of the corepressor, N-CoR, in the process of cellular differentiation and coupled phenotypic acquisition, has not been investigated. We examined the functional role of N-CoR in myogenesis (muscle differentiation), an ideal paradigm for the analysis of the determinative events that govern the cell's decision to divide or differentiate. We observed that the mRNA encoding N-CoR was suppressed as proliferating myoblasts exited the cell cycle, and formed morphologically and biochemically differentiated myotubes. Exogenous expression of N-CoR (but not RIP13) in myogenic cells ablated 1) myogenic differentiation, 2) the expression of the myoD gene family that encode the myogenic specific bHLH proteins, and 3) the crucial cell cycle regulator, p21Waf-1/Cip-1 mRNA. Furthermore, N-CoR expression efficiently inhibits the myoD-mediated myogenic conversion of pluripotential C3H10T1/2 cells. We demonstrate that MyoD-mediated transactivation and activity are repressed by N-CoR. The mechanism involves direct interactions between MyoD and N-CoR; moreover, the interaction was dependent on the amino-terminal repression domain (RD1) of N-CoR and the bHLH region of MyoD. Trichostatin A treatment significantly stimulated the activity of MyoD by approximately 10-fold and inhibited the ability of N-CoR to repress MyoD-mediated transactivation, consistent with the involvement of the corepressor and the recruitment of a histone deacteylase activity in the process. This work demonstrates that the corepressor N-CoR is a key regulator of MyoD activity and mammalian differentiation, and that N-CoR has a multifaceted role in myogenesis.

Animals↗

PubMed1999

Inhibitory effect of ligustrazine on proliferation of rabbit vascular smooth muscle cells after arterial injury.

AIM: To study the inhibitory effect of ligustrazine (Lig) on growth of cultured rabbit aortic vascular smooth muscle cells (VSMC) after balloon injury. METHODS: Twenty New Zealand white rabbits were subjected to arterial injury with a balloon catheter (810 kPa for three consecutive inflations, 1 min each time). The uptake of [3H]thymidine in primary cultural VSMC incubated with rabbit serum, which obtained from the animals treated without or with Lig (40 mg.kg-1.d-1, i.v.) for 21 d (7 d before and 14 d after the injury procedure) was determined. The determination was performed in direct addition of TMP to culture as well. And histological cross-sections of the blood wall were also analyzed. RESULTS: After balloon injury the intimal thickening (77 +/- 23) microns and lumen diameter narrowing (877 +/- 118) microns in dilated sites were increased significantly than the normal adjacent wall [(41 +/- 13) microns, P < 0.01; (1033 +/- 175) microns, P < 0.05, respectively]. Treatment with Lig decreased both intimal thickening (56 +/- 16) microns (P < 0.05) and lumen diameter narrowing (1023 +/- 157) microns (P < 0.05). Lig inhibited [3H]thymidine uptake in VSMC incubated with the serum obtained from these rabbits. Direct addition of Lig inhibited [3H]thymidine uptake in cultured VSMC in a dose-dependent manner (40-4000) micrograms/well. CONCLUSION: Lig shows a pronounced inhibitory effect on VSMC proliferation after balloon injury.

Angioplasty, Balloon, Coronary↗

PubMed1999

[Atrioventricular conduction changes in acute ischemic and reperfused coronary artery of cats].

Acute inferior wall infarction is frequently complicated by conduction disturbance, but the relationship between ischemia and atrioventricular (AV) conduction disturbance is not well understood. The present experiments were made on cats with heart efferent completely denervated. A, H and V waves were picked up by a template-machine algorithm from His bundle electrogram, AA interval (cardiac cycle length), AH interval (AV conduction time), HV and AV intervals were measured. Of 20 cats, 14 showed prolongation of AH interval (Group A), while not in 6 cats (Group B) after ligation of right coronary artery. A fast pacing of right atrium (AA interval = 267 ms) was produced in Group B and AH interval was also prolonged after ligation of the artery. By multiple-step pacing, the curve of AV nodal function shifted to the right, AH interval which induced AV nodal block was prolonged after ischemia. After reperfusion, AH interval was shortened both in Group A and B. The above results show that myocardial ischemia may cause abnormality of AV conduction and accommodation function. The abnormality appears to be a potential danger which will induce AV conduction block during tachycardia.

Animals↗

PubMed1998

Apoptosis is induced in aging SV40 T antigen-transformed human fibroblasts through p53- and p21CIP1/WAF1-independent pathways.

When comparing SV40 T antigen-transformed human fibroblasts of a younger generation (24 population doubling) and aging stage (58 population doubling), we found that detachment of cells from the culture surface occurred more frequently in aging cells. DNA fragmentation and chromatin condensation which are typical findings of apoptosis occurred more frequently in aging cells as compared to cells of a younger generation. There is no increase in the p53 level or decrease in the SV40 T antigen level in aging cells as compared to cells of a younger generation. Retinoic acid treatment which can effectively suppress p21 gene expression did not prevent apoptosis. These findings indicate that apoptosis that occurs due to aging-transformed human fibroblasts is mediated through p53- and p21-independent pathways.

Antigens, Polyomavirus Transforming↗

PubMed1998

Identification of a novel metastasis-suppressor region on human chromosome 12.

There is a critical need for markers that can be used to predict accurately the malignant potential of histological prostate cancers (J. T. Isaacs. Am. J. Pathol., 150: 1511-1521, 1997). Metastasis-suppressor genes are attractive candidates for marker development because, by definition, their loss should be associated with the acquisition of metastatic ability. In an effort to identify such genes, a single copy of human chromosome 12, tagged with the neomycin resistance gene, was introduced into highly metastatic Dunning AT6.1 prostate cancer cells by microcell-mediated chromosomal transfer. Thirty-two AT6.1-12 clonal cell lines were established and the region(s) of chromosome 12 retained was determined by sequence tagged site-based PCR analysis. Representative AT6.1-12 clones containing overlapping regions of chromosome 12 were characterized cytogenetically and were shown to have a normal complement of parental AT6.1 rat chromosomes. Fluorescence in situ hybridization, performed on representative AT6.1-12 hybrids, demonstrated a single human chromosome 12-specific signal. The metastatic ability of six representative clones was tested in immunodeficient mice. All of the AT6.1-12 clones showed the same in vivo growth rates as the control AT6.1-neo cells. Clonal cell lines that contained a conserved approximately 70-cM portion of chromosome 12 (e.g., AT6.1-12-8, -8-1, and -8-3), showed a >30-fold suppression in the number of macroscopic surface lung metastases. Mice that received injections of these cells developed a mean number 4 lung metastases whereas mice that received injections of other AT6.1-12 hybrids (lacking the approximately 70-cM region) or AT6.1-neo control cells, developed a mean number of 140 metastases. Interestingly, histological examination of the lungs of the mice that received injections of AT6.1-12-8 cells showed essentially no microscopic metastases. These findings suggest that a gene(s) encoded by the approximately 70-cM portion of human chromosome 12 suppresses an early step in the metastatic cascade.

Animals↗

PubMed1998

The induction of apoptosis by SV40 T antigen correlates with c-jun overexpression.

Simian virus (SV40) T antigen shares many characteristics with adenovirus E1A which is known to induce apoptosis. To verify the potential of SV40 T antigen-mediated apoptosis, we stably expressed T antigen in immortalized human epithelial cells (Z172 and HaCaT). We found that SV40 T antigen could directly cause apoptosis in 22-27% of these cells under normal growth condition as measured by chromatin condensation and nucleosomal fragmentation. The apoptosis of HaCaT cells which contain mutant p53 suggests the p53-independent nature of T antigen-mediated apoptosis. T antigen-induced apoptosis was associated with increased expression of c-Jun protein. Moreover, the overexpression of c-jun alone in these cells also induced apoptosis, indicating that c-jun might play an important role in T antigen-induced apoptosis.

Adenovirus E1A Proteins↗

PubMed1998

Detection of anti-recombinant beta 2-glycoprotein 1 and anti-recombinant beta 2-glycoprotein 1 fifth-domain antibodies in sera from patients with systemic lupus erythematosus.

Two kinds of plasmid expression vectors which expressed beta 2-glycoprotein 1 (beta 2GP1) and the fifth domain of beta 2-glycoprotein 1 (beta 2GP1-D5) were constructed respectively in this study. The antigenicity of recombinant beta 2GP1 (r beta 2GP1) and beta 2GP1-D5 (r beta 2GP1-D5) was identified by immunoblots using rabbit anti-beta 2GP1 antibodies, and the recombinant proteins were purified. Both anti-r beta 2GP1 and anti-beta 2GP1-D5 antibodies in 112 patients were detected by ELISA using r beta 2GP1 and r beta 2GP1-D5 as coating antigens. A significant statistical correlation (r = 0.667, P < 0.01) between the levels of anti-beta 2GP1 and anticardiolipin (ACL) antibodies was found. The presence of anti-r beta 2GP1 antibodies was associated with an increased frequency of history of thrombosis and/or recurrent abortion; hence anti-r beta 2GP1 assay provided better specificity than conventional ACL assay. Detection of anti-r beta 2GP1 antibodies may be of potential value in evaluating the risk of thrombosis and/or symptoms associated with other antiphospholipid syndromes (APS). The binding of anti-r beta 2GP1 from the sera of patients with APS to r beta 2GP1 was inhibited by r beta 2GP1-D5. Meanwhile, of 28 patients who had positive anti-r beta 2GP1 antibodies in sera, 27 (96.4%) had positive anti-r beta 2GP1-D1 antibodies. This indicated that the antigenic epitope of beta 2GP1 may be located in its fifth domain.

Abortion, Habitual↗

PubMed1998

Skin injury in the operating room.

Skin injury occurring in the operating room may occur as a result of electrical current, thermal injury, chemical irritation and mechanical stress. Between 1 December 1996 and 28 February 1997, 19 cases of skin injury from a total of 3657 operations were noted in our hospital. These injuries tend to be ignored because of their early spontaneous healing. We suggest that medical staff should pay more attention to this complication and prevent it from occurring.

Adult↗

PubMed1998

The comparison of early fluid therapy in extensive flame burns between inhalation and noninhalation injuries.

Over the last half century, advances in treatment have changed the principal cause of death in burn patients from burn shock and wound sepsis to pulmonary sepsis, of which inhalation injury has always played a key role in morbidity and mortality. Even though Navar et al., Am. J. Surg. 1985;150:716-720 have noted that patients with inhalation injury had a mean fluid requirement of 5.8 ml/kg/% burn to achieve resuscitation from early burn shock, while patients without inhalation injury required only a mean fluid of 4.0 ml/kg/% burn, to achieve successful resuscitation in inhalation injured patients with minimum but adequate fluid has always been a challenge. To further define the difference of early fluid therapy between inhalation and noninhalation in extensively burned patients, a retrospective analysis was carried out in the Tri-Service General Hospital. Sixty-two flame burned patients (aged from 16 to 81 years-old with a mean age of 33.2+/-15.1 years: with burn size ranging from 30% to 98% TBSA with a mean burn size of 60.5+/-22.7%; 26 with inhalation injury; noninhalation 36) were reviewed during a 5-year period. The Parkland formula is the initial choice of fluid regimen with 4 ml/kg/% burn and the amount of replacement is monitored by urine output and is titrated to maintain urine output between 0.5 and 1.0 ml/kg/h. The mean amounts of fluid requirements of both inhalation and noninhalation burned patients were 3.1 +/- 1.0 and 2.3+/-0.8 ml/kg/% burn respectively (p < 0.05). Our study showed less fluid requirement for both inhalation and noninhalation injured patients in comparison with the Navar study and Parkland predictions in the first 24 h postburn. Furthermore, the inhalation injured patients definitely required volumes of fluid in excess of those required in noninhalation injured cases.

Adolescent↗

PubMed1998

Kinetics of inhibition of Penaeus penicillatus acid phosphatase by bromoacetic acid.

The kinetics of inhibition of penaeus penicillatus acid phosphatase by bromoacetic acid has been studied. The results show that inhibition of the enzyme by bromoacetic acid is a slow, reversible reaction. The microscopic rate constants for the reaction of inhibitor with the enzyme were determined. The presence of the substrate offers marked protection of this enzyme against inhibition by bromoacetic acid. The above results suggest that the histidine residue is essential for activity and are situated at the active site of the enzyme.

Acetates↗

PubMed1998

Genospecies identification and characterization of Lyme disease spirochetes of genospecies Borrelia burgdorferi sensu lato isolated from rodents in Taiwan.

Lyme disease spirochetes of the genospecies Borrelia burgdorferi sensu lato were identified and characterized for the first time in Taiwan. Seven isolates, designated TWKM1 to TWKM7, were purified from the ear tissues of three species of rodents captured from seven localities of Taiwan. The immunological characteristics of these Taiwan isolates were compared with those of other genospecies of Lyme disease spirochetes by analyzing the protein profiles and reactivities with B. burgdorferi-specific monoclonal antibodies (MAbs). The genospecies of these Taiwan isolates were also identified by the similarities in their plasmid profiles and differential reactivities with genospecies-specific PCR primers. Although two distinct protein profiles were observed among the seven Taiwan isolates, the MAb reactivities against the outer surface proteins of B. burgdorferi of all of these isolates were consistent with those of B. burgdorferi sensu lato. The similarities of the plasmid profiles also confirmed the identities of these Taiwan isolates. PCR analysis indicated that all of these Taiwan isolates were genetically related to the genospecies B. burgdorferi sensu stricto. These results demonstrate the first identification of Lyme disease spirochetes in Taiwan and also highlight the increasing demand for defining the reservoirs and vector ticks of B. burgdorferi. A serosurvey for Lyme disease infection in the human population of Taiwan may also be required.

Animals↗

PubMed1998

Molecular epidemiology of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae isolates in a district hospital in Taiwan.

Thirty-one of 104 clinical isolates of Klebsiella pneumoniae collected over a period of 8 months were found to be putative extended-spectrum beta-lactamase (ESBL) producers. Isoelectric focusing and an iodine overlay agar method were used for preliminary identification of the ESBLs. They were further identified by DNA sequencing. Seventy-one percent of the isolates were found to produce SHV-5. The variation in the ESBL patterns of these isolates was slight, with only five patterns being identified. The strains were typed by pulsed-field gel electrophoresis (PFGE), and 16 different genotypes were identified. When the PFGE patterns were analyzed by the algorithmic clustering method called the unweighted-pair group method using arithmetic averages, five clusters were found. However, significant genetic variations were found among 11 isolates and between each cluster. A plasmid of 36 kb was found in all clinical isolates and in the transconjugants. Our results indicate that the increase in the number of ESBL-producing K. pneumoniae isolates in this hospital is due mainly to the dissemination of a resistance plasmid rather than to the clonal spread of a few epidemic strains.

Ceftazidime↗

PubMed1998

Synthesis, DNA cleavage and cytotoxicity of some novel cyclic peptide-2,6-dimethoxyhydroquinone-3-mercaptoacetic acid conjugates containing D-amino acids.

This paper reports an ongoing study of the use of small-ring-size cyclic peptides as carriers of a potential antitumor agent: 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA). Three new cyclic tripeptide-DMQ-MA conjugates--cyclo[D-Val-Lys(DMQ-MA)-gamma-aminobutyric acid (GABA)-], cyclo[Val-Lys(DMQ-MA)-GABA-] and cyclo[D-Val-D-Lys(DMQ-MA)-GABA-]--were synthesized. The isomeric cyclic tripeptide-DMQ-MA conjugates were designed and synthesized to study the effect of stereoisomerism of the conjugates on cytotoxicity. The cyclic peptides were synthesized by coupling protected amino acids in solution and the final cyclization performed by the pentafluorophenyl ester method as described previously. After removing the lysyl-Z protecting group of the cyclic peptides the conjugation was achieved by reacting with the pentafluorophenyl ester of DMQ-MA. Electron spin resonance (ESR) studies of these three cyclic tripeptide-DMQ-MA conjugates showed that hydroxyl radicals were generated as a non-linear function of L-ascorbic acid (AH2) concentration. The IC50 of the cyclic tripeptide-DMQ-MA conjugates against a human pulmonary carcinoma cell line (PC-9 cells) under the synergistic activation of AH2 ranges from 0.4 to 1.6 microM, which is significantly lower than the parent compound DMQ-MA (6.1 microM). Agarose gel electrophoresis showed that DMQ-MA and these cyclic peptide-DMQ-MA conjugates are capable of cleaving supercoiled plasmid DNA to open circular and linear forms, even in the absence of AH2. The effects of enantiomeric and diastereomeric variations of these cyclic tripeptide-DMQ-MA conjugates on the cytotoxicity against PC-9 cells were discussed.

Amino Acids↗

PubMed1998

Kinetics of inactivation of Penaeus penicillatus acid phosphatase during inhibition by N-bromosuccinimide.

In the present investigation, the inactivation by N-bromosuccinimide of acid phosphatase from penaeus penicillatus has been studied using the kinetic method of the substrate reaction during modification of enzyme activity as previously described by Tsou [(1988, Adv. Enzymemol. Related Areas Mol. Biol. 61, 381-436]. The results show that inactivation of the enzyme by N-bromosuccinimide is a slow, reversible reaction. The results also clearly show that the modification of the tryptophan residues of penaeus penicillatus acid phosphatase by high concentrations of N-bromosuccinimide led to the complete inactivation of the enzyme. The microscopic rate constants were determined for the reaction of the inactivator with the free enzyme and with the enzyme-substrate complex. Comparison of the obtained microscopic rate constants indicates that the presence of the substrate offers marked protection of the enzyme against inactivation by N-bromosuccinimide. The above results suggest that the tryptophan residue is essential for activity and may be situated at the active site of the enzyme.

Acid Phosphatase↗

PubMed1997

Human papillomavirus, cytomegalovirus and herpes simplex virus infections for cervical cancer in Taiwan.

Previously, we had reviewed 43 cases of invasive cancers, adenosquamous cell carcinoma and adenocarcinoma for HPV type infections. With the same cases we extended the investigation to cytomegalovirus (CMV) and herpes simplex virus (HSV) infections. Results show that the prevalence of CMV and HSV infections from these cases of cervical carcinoma was 67 and 76%, respectively, by polymerase chain reaction. The results of the analysis of the association of HPV, CMV and HSV with various clinical characteristics of cervical cancer patients indicated that the correlation between HSV infections and clinical stages of squamous carcinoma was marginally significant (P = 0.068). HSV infections seemed to have a higher association with cell keratinization pattern as compared with the other two viral infections.

Carcinoma, Squamous Cell↗

PubMed1997

Characterization of human N8 protein.

We have shown before that the N8 mRNA is expressed at higher levels in lung tumor and lung tumor-derived cell lines than normal lung cells. In this paper, we have characterized the N8 protein, and studied its properties. The N8 gene encodes a major 24 kDa protein and its expression correlates well with the N8 mRNA expression pattern observed in different cell lines. N8 protein is capable of forming a homodimer or multimeter in vitro. It is a phosphorylated cytoplasmic protein and phosphorylation occurs mainly at serine residues. N8 protein is expressed at higher levels in epithelial cells than in mesenchymal cells. N8 protein expression is induced in a fibroblast cell line expressing adenoviral Ela protein, which acquired epithelial-like characteristics. Furthermore, ectopic expression of N8 protein in NIH3T3 cells converts them into a spheroid form. These spheroids also have some of the characteristic features of epithelial cells. Taken together, these results suggest that the N8 protein may be associated with the development or maintenance of epithelial cell phenotype.

3T3 Cells↗

PubMed1997

20-Hydroxyeicosa-tetraenoic acid (20 HETE) activates protein kinase C. Role in regulation of rat renal Na+,K+-ATPase.

It is well documented that the activity of Na+,K+-ATPase can be inhibited by the arachidonic acid metabolite, 20-hydroxyeicosa-tetraenoic acid (20 HETE). Evidence is presented here that this effect is mediated by protein kinase C (PKC). PKC inhibitors abolished 20 HETE inhibition of rat Na+,K+-ATPase in renal tubular cells. 20 HETE caused translocation of PKC alpha from cytoplasm to membrane in COS cells. It also inhibited Na+,K+-ATPase activity in COS cells transfected with rat wild-type renal Na+,K+-ATPase alpha1 subunit, but not in cells transfected with Na+,K+-ATPase alpha1, where the PKC phosphorylation site, serine 23, had been mutated to alanine. PKC-induced phosphorylation of rat renal Na+,K+-ATPase, as well as of histone was strongly enhanced by 20 HETE at the physiologic calcium concentration of 1.3 microM, but not at the calcium concentration of 200 microM. The results indicate that phospholipase A2-arachidonic acid-20 HETE pathway can exert important biological effects via activation of PKC and that this effect may occur in the absence of a rise in intracellular calcium.

Animals↗

PubMed1997

Evidence for linkage of a candidate chromosome 1 region to human systemic lupus erythematosus.

Genetic susceptibility confers significant risk for systemic lupus erythematosus (SLE). The MHC region and other polymorphic loci have been associated with SLE. Because more compelling evidence for an involvement of a genetic locus includes linkage, we tested a candidate region homologous to a murine SLE susceptibility region in 52 SLE-affected sibpairs from three ethnic groups. We analyzed seven microsatellite markers from the human chromosome 1q31-q42 region corresponding to the telomeric end of mouse chromosome 1, the region where specific manifestations of murine lupus, including glomerulonephritis and IgG antichromatin, have been mapped. Comparing the mean allele sharing in affected sibpairs of each of these seven markers to their expected values of 0.50, only the five markers located at 1q41-q42 showed evidence for linkage (P = 0.0005-0.08). Serum levels of IgG antichromatin also showed evidence for linkage to two of these five markers (P = 0.04), suggesting that this phenotype is conserved between mice and humans. Compared to the expected random distribution, the trend of increased sharing of haplotypes was observed in affected sibpairs from three ethnic groups (P < 0.01). We concluded that this candidate 1q41-q42 region probably contains a susceptibility gene(s) that confers risk for SLE in multiple ethnic groups.

Adolescent↗