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Biomedical subjects

S Chen

Publications and source records attributed to S Chen.

At least 1,279 records · Page 71Linked to original sources
PubMed1992

The pharmacology of a novel topical retinoid, BMY 30123: comparison with tretinoin.

Preclinical studies pertaining to the pharmacology and toxicology of BMY 30123 (4-acetamidophenyl retinoate) are reported. BMY 30123 is a novel compound which has topical retinoid activity. This compound exhibits lower toxicity, both local and systemic, than other clinically used topical retinoids such as tretinoin (all-trans retinoic acid) in animal models. BMY 30123 is effective in a number of retinoid sensitive skin models including the rhino mouse utriculi reduction assay, the mouse epidermal hyperplasia model and in the suppression of DNA synthesis in mouse skin stimulated with phorbol ester. BMY 30123 was equipotent with tretinoin in these topical models. In the rhino mouse model the ED30 values for BMY 30123 and tretinoin were 0.037 and 0.015 mM, respectively. In addition, BMY 30123 was active in the UVB-induced photodamaged mouse model, another retinoid sensitive model. One of the problems associated with topically applied tretinoin is local irritation. Therefore, for topical therapy to be optimal, it is important to reduce or minimize local irritation. Repeated applications of BMY 30123 to rabbit skin resulted in low skin irritation. The first perceptible signs of skin irritation produced by BMY 30123 occurred at a dose 10 times higher than that observed for tretinoin. BMY 30123 also exhibits low retinoid activity after oral or i.p. administration in mice and produced no signs of hypervitaminosis A-related toxicity at twenty times the no effect dose of tretinoin. Because retinoids are effective modulators of epidermal growth and differentiation, this compound should be useful for the treatment of cutaneous disorders that exhibit altered epidermal differentiation such as acne, psoriasis, ichthyosis and epithelial tumours.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1992

Transactivation of the major capsid protein gene of herpes simplex virus type 1 requires a cellular transcription factor.

The purpose of this investigation was to identify and characterize the regulatory elements involved in the transcriptional activation of the beta gamma (leaky-late or gamma 1) genes of herpes simplex virus type 1 (HSV-1) by using the major capsid protein (VP5 or ICP5) gene as model. Gel mobility shift assays with nuclear extracts from uninfected and infected HeLa cells enabled us to identify two major protein-DNA complexes involving the VP5 promoter. The mobilities of these two complexes remained unaltered, and no unique complexes were observed when infected cell nuclear extracts were used. DNase I and orthophenanthroline-Cu+ footprint analyses revealed that the two complexes involve a single binding site, GGCCATCTTGAA, located between -64 and -75 bp relative to the VP5 cap site. To determine the function of this leaky-late binding site (LBS) in VP5 gene activation, we tested the effect of mutations in this region by using transient expression of a cis-linked chloramphenicol acetyltransferase gene. Deletion of the above sequence resulted in a seven- to eightfold reduction in the level of transactivation of the chloramphenicol acetyltransferase gene by superinfection with HSV-1 or by cotransfection of HSV-1 immediate-early genes. From these results, we conclude that the LBS sequence and a cellular factor(s) are involved in the transactivation of the VP5 gene. A search of published gene sequences revealed that sequences related to the LBS exist in a number of other HSV-1, cytomegalovirus, retrovirus, and cellular promoters. Sequence homologies of binding sites and results of unpublished competition binding studies suggest that this leaky-late binding factor may be related to, or the same as, a ubiquitous cellular transcriptional factor called YY1 or common factor-1 (also known as NF-E1, delta, and UCRBP).

Base Sequence↗
PubMed1992

Induction and superinduction of messenger ribonucleic acid specific for aromatase cytochrome P-450 in cultured human skin fibroblasts.

Aromatase cytochrome P-450 (cytochrome P-450AROM) catalyzes the formation of aromatic C18 estrogenic steroids from C19 androgens. Several studies indicate that cytochrome P-450AROM activity is induced by glucocorticoids such as dexamethasone (DEX) and superinduced by DEX plus cycloheximide (CHX). We have used cultured human skin fibroblasts as a model system to investigate the regulation of aromatase gene expression. Whereas Northern blot analysis of total cellular RNA or poly (A)+ RNA from untreated strains of normal human skin fibroblasts failed to demonstrate any hybridization with a specific human placental cytochrome P-450AROM complementary DNA, analysis of RNA from cells treated with DEX demonstrated hybridization of the cytochrome P-450AROM complementary DNA to two transcripts of about 2.5 and 3.0 kilobases. Incubation of cells with DEX plus CHX resulted in a further increase in levels of cytochrome P-450AROM messenger RNA (mRNA) when compared to cells treated with DEX alone, suggesting that inhibition of protein synthesis superinduces transcription of the cytochrome P-450AROM gene. By contrast, levels of beta-actin mRNA were not affected by treatment with DEX and CHX. Treatment of cells with CHX alone did not produce a change in either aromatase activity or levels of cytochrome P-450AROM mRNA transcripts. These results indicate that aromatase activity is regulated by changes in the concentration of cytochrome P-450AROM mRNA, and imply that control of cytochrome P-450AROM gene expression is at the level of gene transcription. We conclude that the cytochrome P-450AROM gene is regulated by a complex mechanism that includes both positive and negative transcription factors.

Aromatase↗
PubMed1992

Identification of a promoter and a silencer at the 3'-end of the first intron of the human aromatase gene.

Aromatase, a cytochrome P-450, catalyzes the formation of aromatic C18 estrogenic steroids from C19 androgens. DNA sequence analysis of the human aromatase gene has revealed that a putative promoter sequence exists immediately up-stream of the second exon. Chloramphenicol acetyltransferase functional analyses of cells transfected with chloramphenicol acetyltransferase expression plasmids containing various DNA fragments derived from the 3'-end of the first intron of the aromatase gene were performed to show that a promoter indeed exists in this region. However, in all of the cell lines used in this study, MCF-7, JAR, OVCAR-3, and skin fibroblast, the function of this promoter was inhibited by a negative regulatory element situated up-stream from the promoter. The results further suggest that this inhibitory element behaves as a silencer element, in that it could inhibit a simian virus-40 promoter from a distance of several kilobases. This negative element worked in both orientations and inhibited the functions of several promoters, including the newly identified promoter situated in the 3'-end of the first intron of the human aromatase gene. Primer extension analysis has been performed to determine the potential transcription start site. The mechanism of the regulation of aromatase expression is known to be very complex. The presence of a promoter and a silencer at the 3'-end of the first intron may represent one additional way that aromatase expression is controlled in estrogen-producing cells.

Aromatase↗
PubMed1992

Cloning and sequence analysis of the cDNA encoding P-450 aromatase (P450arom) from a rainbow trout (Oncorhynchus mykiss) ovary; relationship between the amount of P450arom mRNA and the production of oestradiol-17 beta in the ovary.

The enzyme aromatase P-450 (P450arom) catalyses the conversion of androgen to oestrogen. A cDNA insert encoding P450arom was isolated from a rainbow trout (Oncorhynchus mykiss) ovary cDNA library. The insert was sequenced and found to contain an open-reading frame predicted to encode a protein of 522 amino acid residues. The deduced polypeptide is 52% homologous with human, mouse and rat P450arom and 53% homologous with that of chicken. The insert was confirmed to encode P450arom by introducing it into COS-1 monkey kidney tumour cells (COS-1 cells) and detecting the conversion of testosterone to oestradiol-17 beta by radioimmunoassay. The N-terminal region of the deduced polypeptide was 19 amino acids longer than that of the other four species, and was found by hydropathy plotting to be very hydrophobic. Northern blot analysis revealed 2.6 kb RNA transcripts which were present in the trout ovary during vitellogenesis and hybridized to the cDNA insert. In preparations from subsequent stages of ovarian development, no RNA transcripts hybridized to the probe. Since the RNA transcripts are present only during the stage of oestradiol-beta production by the ovarian follicles, oestradiol-17 beta production may be regulated, in part, by the amount of P450arom mRNA present.

Amino Acid Sequence↗
PubMed1992

Patient-controlled analgesia for cancer pain: a long-term study of inpatient and outpatient use.

The safety and efficacy of patient-controlled analgesia for the long-term control of cancer pain was tested prospectively. Respiratory rates, mental status, and pain relief were recorded at baseline and compared with those during the study period. Patients had a lower analgesic demand (i.e., self-administered less morphine during the nighttime); specifically, dosing declined 48% from the daytime level. Respiratory rates did not change appreciably during the study and no cases of significant respiratory depression were encountered. Patients self-administered sufficient morphine to produce adequate but not complete pain relief in almost all trials. Pain relief was safely achieved by both intravenous and subcutaneous routes of administration in both the inpatient and outpatient settings. Mean 24-h morphine use stayed relatively constant even for patients receiving more than 2 weeks of treatment. In conclusion, patient-controlled analgesia is effective and safe therapy for the long-term control of severe cancer pain.

Adult↗
PubMed1992

Overexpression of rnc gene and purification of RNaseIII.

The reason for low content of RNaseIII in E. coli is that RNaseIII has a negative feedback action on its own synthesis by cutting off the transcripts of its own gene, rnc, at 5'-terminal. On this basis, the scheme for overproduction of RNaseIII was designed. The 5'-flanking sequence of rnc gene transcribing to form a secondary structure which could be degraded by RNaseIII was removed, and the whole coding sequence, including the translational initiation signal, was reserved and put under the control of lambda PL promoter. The constructed plasmid pCR21, which contain the recombined rnc gene, overproduced RNaseIII, which covered over 65% of the total cell protein and formed inclusive bodies in E. coli after induction at 42 degrees C. By using the characteristics of solubility of the protein, electrophoretic pure RNaseIII was obtained with a simple procedure, including lysis of the bacterial cells, washing precipitates of the lysate repeatedly at low temperature and low salt concentration, and dissolving and passing through Q-Sepharose FF column in high salt concentration at room temperature. The yield of purified RNaseIII was 10-12 mg per 100 ml culture, and lambda sib transcripts were cut at special sites. RNaseIII possessing the activity of binding ATP is reported.

Adenosine Triphosphate↗
PubMed1992

[Echocardiographic diagnosis and significance of atrial isomerism].

Forty-nine patients with atrial isomerism (right atrial isomerism 27, left atrial isomerism 22) diagnosed by 2DE of the abdominal great vessels were reported in this paper. Compared with the results of high kilovolt filtered chest film and autopsy, atrial situs determined by 2DE was concordant with bronchial morphology in 43 patients, 25 (93%) of right atrial isomerism, 18 (82%) of left isomerism. 25 patients who had angiocardiography or autopsy were associated with other cardiac malformations which were severe and complicated in right atrial isomerism. The results of this series showed that ultrasonography of the abdominal great vessels could be a reliable guide to the diagnosis of atrial isomerism, 2DE diagnosis is useful for angiocardiography.

Child↗
PubMed1992

The priming effect of ultraviolet B radiation on retinoic acid-stimulated collagen synthesis in the mouse photodamage model.

We have demonstrated previously that all-trans retinoic acid (tRA) stimulates collagen synthesis in ultraviolet B (UVB)-exposed but not in nonirradiated hairless mouse skin, suggesting that UVB exposure is required to prime certain tRA-induced events. The current study investigated further whether this tRA stimulatory effect on collagen synthesis could be regulated quantitatively by the accumulative dose of UVB. Mice were irradiated with the total amount of 0.25 (low), 0.77 (medium) or 1.43 J/cm2 (high) UVB radiation over 2, 5 and 10 weeks, respectively. Post-irradiation, 50 microliters of 0.1% tRA was applied topically 5 times a week. An initial delay was observed before tRA-induced collagen stimulation was detected in all 3 treatment groups. The first statistically significant increase in collagen synthesis was observed at the 6th week of tRA treatment in the high-UVB group. In the groups receiving medium and low UVB doses, onset occurred at the 8th week. Furthermore, at the end of tRA treatment, the degree of collagen stimulation correlated positively with the total UVB dose applied (increasing 183%, 224% and 250% over the vehicle control in the low-, medium- and high-UVB groups). By contrast, no collagen stimulation was detectable in the non-irradiated animals treated with tRA for 10 weeks, as previously reported. Although the mechanism by which UVB exposure primes skin to respond to tRA for collagen synthesis still remains unknown, the data indicate that the accumulative UVB dose positively affects the length of the initial delay and the magnitude of the stimulatory effect of tRA on collagen synthesis in photodamaged skin.

Animals↗
PubMed1992

Comparative studies of the carbohydrate of human gamma-crystallins from fetal and adult lenses with agglutinins.

Using gel chromatography of Sephadex G-75 superfine connected with Sephadex G-50 fine column, three human gamma-crystallins (gamma 1, gamma 2, gamma 3) could be obtained. Seven agglutinins (LCA, SBA, DBA, PNA, BSL, RCA and UEA) were used to detect the sugar of sub-gamma-crystallins, which had been transferred to nitrocellulose membrane and finally stained with ABC reagents and the substrate of HPR. These results suggested that gamma 2- and gamma 3-crystallins contain sugar, but gamma 1-crystallin has no sugar. There is a decrease of carbohydrate of gamma 2 and gamma 3 as the development of the lens (esp. the former). It was postulated that in gamma-crystallins (gamma 2, gamma 3) the sugar components helped stabilizing the molecular structure (folding polypeptide, prevent protein breaking). The sugar components decreased with age by the post-translation modification.

Adult↗
PubMed1992

[Study on the meiotic mapping and functions of another new osmotic-sensitive gene-osm3 in Saccharomyces cerevisiae].

Another recessive nuclear gene mutation of Sacchromyces cerevisiae, osm3, which causes growth inhibition on hypertonic media, has been mapped on the chromosome II by tetrad analysis. Its second-division segregation frequency is about 51.01%, and the map distances between osm3 and the centromere of chromosome II is about 25.51 centimorgans and it is approximately 45 centimorgans far gene gall. The studies on the reverse mutation of osm3 indicated that this osmotic-sensitivity arises from a missense or nonsense mutation in OSM3 locus. The response of yeast to osmotic stress and the mechanism of osm3 gene function were investigated. The results indicated that high intracellular glycerol content is necessary for yeast to grow in hypertonic media; The gene product of osm3 is probably relative to the process of glycerol transportation. Finally, the effect of osmotic stress on fermentability was also discussed.

Chromosome Mapping↗
PubMed1992

[Effects of spleen on inducing portal hypertension and liver cirrhosis in rats].

The role of spleen on inducing the portal hypertension and cirrhotic rat by carbon tetrachloride (CCl4) and ethyl alcohol was studied. Totally 412 male rats were divided randomly into four groups: group A (n = 42) underwent splenectomy before induction by CCl4; group B (n = 42) underwent splenectomy after induction by CCl4 and alcohol of 4 weeks; group C (n = 42) received sham-splenectomy and group D (n = 14) served as a control group. Free portal pressure (FPP), function of liver, the index of spleen (weight of spleen/weight of body) as well as the spleen and liver biopsy were evaluated at different time. The results showed that, in group C, the index of spleen and the area of splenic white pulp had significant increase. The degree of hepatic damage, the number of the infiltrating cells and the degree of hepatic fibrosis were significantly greater in sham-operated animals than in others (group A and B). These results suggested that the spleen should be an immunomodulatic organ in playing an exacerbation role of hepatic cirrhosis, and the effect of splenectomy be a preventive role against the induced rat liver cirrhosis, at least, at certain stage.

Animals↗
PubMed1992

[Quench effect of metallothionein on free radical signal in post-ischemic reperfusion of isolated rat hearts].

Signals of N-tert-butyl-phenyl-nitrone (PBN) spin adducts were observed during post-ischemic reperfusion in isolated rat hearts using electron spin resonance (ESR) spectroscopy and ESR spin-trap PBN. The intensity of signals was related to the time course of ischemia. The intensity of the signals produced during reperfusion after 40 minutes of ischemia was remarkably higher than that of 20 minutes of ischemia. Metallothionein (MT) did quench the adduct signals and the extent of quenching of the signals by this protein was dose-dependent. The signal intensity was decreased to 40% of corresponding control at the concentration of 5 x 10(-6) mol/L. It is a kind of endogenetic protein rich in cysteine residue and divalent metal ions. It is believed to be a promising cytoprotective drug in clinical medicine.

Animals↗
PubMed1992

Protective effects of berberine and phentolamine on myocardial reoxygenation damage.

The protective effects of berberine and phentolamine against anoxia and reoxygenation damage in isolated rat hearts have been investigated. Incorporation of berberine (24.5 mumol/L) in both anoxic and aerobic perfusion media resulted in a significant reduction of CPK release during the reoxygenation period, and the ultrastructural damage was reduced as compared with the control group; the myocytes in the berberine-treated group displayed mild intracellular edema, well-registered myofibrils without contracted bands, and swollen mitochondria with partially broken cristae but without dense bodies. Berberine did not inhibit calcium and sodium accumulation or magnesium and potassium loss. Treatment with phentolamine (6.6 mumol/L), an alpha-adrenoceptor antagonist, had similar effects, though the CPK release profile was shifted to the right and downwards. These results suggest that although berberine and phentolamine have some beneficial effects on myocardial reoxygenation injury, they may not abolish the injury. Therefore alpha-adrenoceptor stimulation may not be the major mechanism behind the injury.

Adrenergic alpha-Antagonists↗
PubMed1992

[A study on spontaneous closure of ventricular septal defect using 2 dimensional echocardiography].

The results of 2 dimensional echocardiographic (2DE) observation in 73 patients with clinically diagnosed spontaneous closure of ventricular septal defect (VSD) were reported. 2DE showed that aneurysm of the membranous septum formed at the defect portion in 54 patients (74%), tricuspid valve leaflet tissue adhered to the defect portion in 2 patients, coarse appearance of the membranous septum in 8 patients, no defect in 9 patients. There was no shunt flow detected in 59 patients, trivial shunt flow in 14 patients on Doppler echocardiography. All VSD were of the membranous and perimembranous inlet type. The results of this study suggested spontaneous closure of membranous VSD was related to the aneurysmal formation of the membranous septum and adhesion of tricuspid valve tissue.

Child↗
PubMed1992

Suggested mechanism for the modulation of the activity of NAD(P)H:quinone acceptor oxidoreductase (DT-diaphorase) by menadione: interpretation of the effect of menadione on 5'-[p-(Fluorosulfonyl)benzoyl]adenosine labeling of rat liver NAD(P)H:quinone acceptor oxidoreductase.

5'-[p-(Fluorosulfonyl)benzoyl]adenosine (5'FSBA) was previously shown to be an active site-directed affinity label of rat liver NAD(P)H:quinone acceptor oxidoreductase [Mol. Pharmacol. 35:818-822 (1989)]. Our recent study revealed that menadione, the substrate of this quinone reductase, had a magnifying effect on inactivation of the enzyme by 5'-FSBA. The dissociation constant for the initial reversible enzyme-inhibitor complex was significantly lower and the rate of inactivation was increased when menadione was present during the incubation. However, [14C]5'FSBA labeling was reduced in the presence of menadione. These results are presented and a possible mechanism for the enzyme is discussed.

Adenosine↗