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Biomedical subjects

C S Chen

Publications and source records attributed to C S Chen.

At least 19 recordsLinked to original sources

Current seroepidemiology of hepatitis D virus infection among hepatitis B surface antigen carriers of general and high-risk populations in Taiwan.

In order to assess the current seroepidemiology of hepatitis D virus (HDV) infection in Taiwan where hepatitis B virus (HBV) is hyperendemic, a total of 756 voluntary blood donors, 641 prostitutes, 1,014 patients with sexually transmitted diseases (STDs), and 628 drug abusers were studied. Radioimmunoassays were used for testing HBV infection markers and antibody against HDV (anti-HDV) among HBsAg carriers. The anti-HDV prevalence among HBsAg carriers was significantly higher in STD patients (9.6%), prostitutes (33.1%), and drug abusers (68.1%) than in blood donors from the general population (2.2%). The prevalence gradually increased with age in blood donors and STD patients, but reached a plateau at a young age in prostitutes and drug abusers. Males had a higher prevalence than females in blood donors (2.7% vs. 0), STD patients (8.2% vs. 7.5%), and drug abusers (69.0% vs. 57.1%), but the difference was not statistically significant. STD patients with syphilis had a higher prevalence (19.5%) than those affected with non-ulcerating STDs (5.3%). While unlicensed prostitutes had a lower prevalence (13.6%) than licensed prostitutes (44.9%), intravenous drug abusers had a higher prevalence (73.1%) than non-intravenous drug abusers (34.6%). There was a twofold increase in anti-HDV prevalence from 1986 to 1989 among prostitutes, but the prevalence remained unchanged in the general population and drug abusers. HDV infection remains limited to the high-risk groups and spread mainly by promiscuity and needle sharing in Taiwan.

Adult

cDNA cloning and gene expression of the major prolamins of rice.

A full-length cDNA (pS 18) encoding the 16 kDa rice prolamin composed of 158 amino acids was sequenced. Analysis of N-terminal amino acid sequence of a major rice prolamin indicated that an 18 amino acid signal peptide was removed from 16 kDa precursor prolamin to form the 14 kDa prolamin during seed development. Synthesis of the 16 kDa precursor prolamin began around 8 days after flowering (DAF), increased remarkably at 8-11 DAF and gradually reached maximum levels with the maturation of rice seeds.

Amino Acid Sequence

Levels of direct-acting mutagens, total N-nitroso compounds in nitrosated fermented fish products, consumed in a high-risk area for gastric cancer in southern China.

A high gastric cancer mortality in Fujian province (Peoples Republic of China) has been associated with the consumption of certain salted fermented fish products such as fish sauce (FS). We have investigated the levels and nature of N-nitroso compounds (NOC) and genotoxins present, before and after nitrosation, in 49 FS samples collected from villages in this high-risk area, pooled into six samples. The concentrations of total NOC before nitrosation ranged from 0.2 to 16 mumoles/l, and after nitrosation at pH 2 and pH 7, they rose by up to 4800- and 100-fold, respectively. In nitrosated samples, 40-50% of total NOC was not extractable into organic solvents; volatile N nitrosamines accounted for 1-2% and N-nitrosamino acids for 8-16% of total NOC. None of the FS samples exhibited genotoxic activity, but after nitrosation all were weakly active in the SOS chromotest. The highest SOS-inducing potency was observed with nitrosated ethyl acetate extracts of most samples. The formation of methylating agents was measured by incubation of nitrosated FS with DNA and subsequent analysis of 7-methylguanine adduct. 2 of the 6 nitrosated FS samples caused a slight increase in DNA methylation. 1 pooled home-made FS sample (the only one tested) contained tumour promoter-like substances, as measured by expression of certain EBV genes in Raji cells. HPLC fractionation of ethyl acetate extracts of FS samples allowed identification of three UV-absorbing peaks that, upon nitrosation, produced direct-acting genotoxins. This genotoxicity was partly ascribed to the formation of nitrite-derived arene diazonium cations that were characterized by a coupling reaction with N-ethyl-1-naphthylamine and thin-layer chromatography.

China

Morphological changes in the respiratory system of mice after inhalation of mosquito-coil smoke.

Male ICR mice were exposed to mosquito-coil smoke with d-allethrin or without d-allethrin at airborne particles concentration of 1.27 mg/m3, 7 h/day, 7 days/week for 1, 3, 6, and 12 months. Additional groups of air exposure animals served as controls. At 1 month after exposure, the histopathological lesions included the loss of cilia, and the alteration of the alveolar pattern in the treated and the sham mice. Volume fractions of the type I and II cells were smaller (0.028 +/- 0.006, 0.044 +/- 0.002) in the treated group than those of the controls (0.049 +/- 0.008, 0.059 +/- 0.003). Fractions of the lumina of vessels and the vessel wall decreased in both the treated and the sham groups as compared to the control group. However, the volume fraction of alveolar air space increased significantly in both treated and sham groups as compared to the controls (0.619 +/- 0.022, 0.685 +/- 0.018 vs. 0.507 +/- 0.025). After 3- and 6-months exposure, the lesions observed in the trachea persisted. The intercellular fibrosis in the lung was increased in both the treated and sham groups at 6 months and became more severe at the later stages. At 12-months exposure, an increase in vascularity of the alveolar wall was observed and fine granular debris was frequently present in the alveolar space. The fraction volumes of the type II cells in the treated group and the type I cells in the sham group were significantly increased (0.059 +/- 0.010, 0.042 +/- 0.003) compared with those of the controls (0.038 +/- 0.008, 0.033 +/- 0.003). However, the fraction volume of air space and vessel lumen were not different among the three groups. Finally, there were no differences in the morphologic appearance of the airways and the lung periphery between the treated and the sham-exposed animals.

Allethrins

Subcapsular hematoma of spleen--a complication following extracorporeal shock wave lithotripsy for ureteral calculus.

Splenic trauma with hematoma following extracorporeal shock wave lithotripsy (ESWL) is very rare. We reported a case of subcapsular hematoma of spleen with impending rupture following ESWL for ureteral calculus. This case was noted to have liver cirrhosis and splenomegaly, and received a total of 2000 shock waves under 18 kilovoltage. The subcapsular hematoma occurred 2 months later. Splenectomy was undertaken for a symptomatic huge subcapsular hematoma and thrombocytopenia. We reviewed the literature and concluded that portal hypertension with severe coagulopathy are contraindications for ESWL, even in case with ureteral calculus.

Female

Molecular abnormalities of a human glucose-6-phosphate dehydrogenase variant associated with undetectable enzyme activity and immunologically cross-reacting material.

Among a large number of glucose-6-phosphate dehydrogenase (G6PD) variants associated with different severity of clinical manifestations, enzyme deficiency, and kinetic abnormalities found in humans, only one variant exhibits no measurable activity and lacks an immunologically cross-reacting material in blood cells and other tissues. The mRNA content of the patient's lymphoblastoid cells was found to be normal, and the size of mRNA was also normal (i.e., approximately 2.4 kb). Western blot hybridization indicated that the patient's cells did not produce cross-reacting material. The variant mRNA was reverse transcribed and amplified by PCR. Nucleotide sequencing of the variant cDNA showed the existence of three nucleotide base changes, i.e., a C----G at nucleotide 317 (counting from adenine of the initiation codon), which should cause Ser----Cys substitution at the 106th position (counting from the initiation Met); a C----T at nucleotide 544, which induces the Arg----Trp at the 182d position; and a C----T at nucleotide 592, which induces Arg----Cys at the 198th position of the protein. The existence of three mutation sites was confirmed by sequencing of selected regions of the variant gene. No base deletion or frameshift mutation was found in the variant cDNA. No nucleotide change was detected in the extended 5' region, which included the most distal cap site. When the variant cDNA was expressed in Escherichia coli, the G6PD activity was approximately 2% of that expressed by the normal cDNA, and cross-reacting material was undetectable. However, when the variant mRNA was expressed in the in vitro translation system of rabbit reticulocytes, the variant protein was produced. These results suggest that extremely rapid in vivo degradation or precipitation of the variant enzyme induced by the three amino acid substitutions could be the major cause of the molecular deficiency.

Base Sequence

[Thyroid function tests in acute drug intoxication].

It is well known that thyroid function tests may be changed in non-thyroidal illnesses. To understand the influence of acute drug intoxication on thyroid function tests, 31 drug intoxicated patients without previous thyroid disorders and systemic diseases were included in our study. T3, T4, TSH, and resin T3 uptake were checked as soon as they arrived at our emergency service and were compared to that of 58 healthy volunteers. Within 31 patients, 14 were intoxicated by organophosphorous compounds, 6 by sedatives and hypnotics, 3 by strong acid, 2 by paraquet, 2 by rodenticides (warfarin), 2 by lysol and the other 2 were intoxicated by acetaminophen. The mean T3 and TSH levels were significantly lower in the drug intoxicated group. Among the 31 patients, 14 (45.2%) had a low T3, 2 (6.5%) had a low T3 and T4, and 6 (19.3%) had an elevated T4. All of the patients with an elevated T4 were intoxicated by organophosphates. If we divided the 31 patients into 2 subgroups: organophosphate intoxicated group and non-organophosphate intoxicated group, T4 and FT4I were significantly higher in the former group. Thyroid function tests became normal after treatment in 27 patients, discharged in good general condition. T3 and T4 became extremely low in 4 patients before they expired. The present study confirms that acute drug intoxication, like other non-thyroidal illnesses, affects thyroid function tests. Acute organophosphate intoxication may cause transient hyperthyroxinemia.

Acute Disease

[Measurements of dose distribution in small fields of 10 MV X-rays].

Dose distribution measurement in small fields include: 1. Field size factor, 2. Percentage depth dose, 3. Isodose curves charts, 4. Tissue-phantom ratio, and 5. Penumbra width. Field size factor was measured by using different detectors and it was found that the dimension of detector must be less than half of the field size to avoid under-estimation. If a 0.6 cc cylindrical ion chamber was used for small fields measurement, it would under-estimate the field size factor by 19.7% for a 2x2 cm2 field. The percentage depth dose and the tissue-phantom ratio increased with increasing the field size. The penumbra width increased with increasing the field size which was larger for a square field than the corresponding circular field by less than 1 mm.

Humans

Topical application of local anesthetics for postoperative analgesia in children undergoing circumcision.

Circumcision often followed by severe pain during the postoperative period. Forty boys, ASA class I, presenting for day case circumcision were allocated randomly to receive either 4% prilocaine hydrochloride spray or 1.1% dipucaine ointment at the end of the operation. Analgesia was assessed by a single observer utilizing a three-point scale in recovery room. The parents were asked to complete the questionnaire 8h following operation and on the morning of the first postoperative day. At approximately 24h following operation an assessment of the child's activity level was made by the parents. The frequency of taking the oral analgesia was also recorded. Both topical analgesics provided satisfied analgesia during the postoperative period and no complication was noted. Only one patient in dipucaine group vomited in the recovery room. We conclude that topical use of prilocaine hydrochloride and dipucaine can provide a simple, safe and adequate analgesia for post-circumcision pain relief.

Administration, Topical

Enzymatic properties of the protein encoded by newly cloned human alcohol dehydrogenase ADH6 gene.

Five non-allelic genes which encode five types of alcohol dehydrogenase subunits have been identified in humans. An additional gene (ADH6) and cDNA, whose coding sequences were not highly analogous to any of the known alcohol dehydrogenase subunits, were recently cloned (Yasunami et al., Proc. Natl. Acad. Sci. USA 88, 7610-7614, 1991). The full-length ADH6 cDNA was expressed in the E.coli expression system and in the in vitro translation system of rabbit reticulocytes. The protein produced had its isoelectric point at pH 8.6, optimum pH at pH 10, and a lower Km for benzylalcohol than for ethanol and propanol. These characteristics are compatible to the properties of mu- or sigma-alcohol dehydrogenase isozyme existing in human stomach, indicating that ADH6 gene encodes the mu- or sigma-alcohol dehydrogenase subunit.

Alcohol Dehydrogenase

Breakpoint clustering in t(4;11)(q21;q23) acute leukemia.

Chromosome 11 band q23 is commonly involved in nonrandom chromosomal translocations in hematopoietic malignancies, especially in infant acute leukemias. By using pulsed-field gel electrophoresis (PFGE) with restriction endonuclease digests of DNA from both a leukemia cell line (RS4;11) bearing the t(4;11)(q21;q23) and from human/hamster hybrid cells, we have been able to construct a detailed restriction map of the chromosome 11q23 region and have localized the t(4;11) chromosome 11 breakpoint to a region located approximately 200 to 230 kb telomeric to the CD3 gamma region and approximately 580 kb centromeric to the PBGD gene. PFGE analyses of DNA from clinical leukemia specimens and cell lines indicated a tight clustering of breakpoints in all eight t(4;11) acute leukemias studied. These data strongly suggest that discrete genetic loci are interrupted on both chromosomes 4 and 11 in a manner likely to be critically involved in the pathogenesis of t(4;11) acute leukemias. To our knowledge, these results represent the first evidence of breakpoint clustering in t(4;11) acute leukemias. In contrast to t(4;11), other 11q23 abnormalities studied to date have frequently shown evidence for alternative breakpoint sites in 11q23.

Acute Disease

A modified Arg-Asp-Val (RDV) peptide derived during the synthesis of Arg-Glu-Asp-Val (REDV), a tetrapeptide derived from an alternatively spliced site in fibronectin, inhibits the binding of fibrinogen, fibronectin, von Willebrand factor and vitronectin to activated platelets.

Characterization of a side-product obtained during the synthesis of Arg-Glu-Asp-Val (REDV) with inhibitory activity in thrombin-activated platelet aggregation was carried out. The semipreparative column fractionation of REDV peptide was rechromatographed on an analytical HPLC column and revealed two peaks which were re-tested for inhibitory activity. Using amino acid analysis with sequencing and fast atom bombardment mass spectrometry (FABMS), the first peak was determined to be REDV with molecular mass of 517 Da, and the second peak was determined to be a modified RDV with a mass of 608 Da. The modified RDV peptide inhibited thrombin-induced platelet aggregation with an IC50 of 200 microM, and complete inhibition occurred at 600 microM. However, the REDV peptide did not inhibit platelet aggregation up to 1 mM concentration. The modified RDV peptide eluted platelet glycoprotein IIb-IIIa complex that had been bound to GRGDSP-agarose. These studies show that the modified RDV peptide interacts with the platelet glycoprotein IIb-IIIa complex. Based on the collision-induced dissociation (CID) mass spectral data analysis, the modified RDV peptide has been characterized to contain an N-terminus blocking group on the Arg residue. The origin of this blocking group is presumed to have originated from decomposition products of the phenylacetamidomethyl (PAM) resin used in the solid-phase synthesis of the target peptide Arg-Glu-Asp-Val.

Amino Acid Sequence

A human alcohol dehydrogenase gene (ADH6) encoding an additional class of isozyme.

The human alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) gene family consists of five known loci (ADH1-ADH5), which have been mapped close together on chromosome 4 (4q21-25). ADH isozymes encoded by these genes are grouped in three distinct classes in terms of their enzymological properties. A moderate structural similarity is observed between the members of different classes. We isolated an additional member of the ADH gene family by means of cross-hybridization with the ADH2 (class I) cDNA probe. cDNA clones corresponding to this gene were derived from PCR-amplified libraries as well. The coding sequence of a 368-amino-acid-long open reading frame was interrupted by introns into eight exons and spanned approximately 17 kilobases on the genome. The gene contains a glucocorticoid response element at the 5' region. The transcript was detected in the stomach and liver. The deduced amino acid sequence of the open reading frame showed about 60% positional identity with known human ADHs. This extent of homology is comparable to interclass similarity in the human ADH family. Thus, the newly identified gene, which is designated ADH6, governs the synthesis of an enzyme that belongs to another class of ADHs presumably with a distinct physiological role.

Alcohol Dehydrogenase

Metabolic stereoisomeric inversion of ibuprofen in mammals.

Studies on the mechanism and enzymology of metabolic ibuprofen isomerization constituted the focus of this investigation. Comparative in vivo studies revealed that this biotransformation proceeded via a proton abstraction mechanism in all tested species of mammals, which is in agreement with the previous reports. Direct evidence supporting this conclusion stemmed from the in vitro epimerization of ibuprofen-CoA thioester in rat liver homogenates. Chemically synthesized (R)-ibuprofen-CoA thioester was rapidly transformed to its (S)-counterpart by subcellular hepatic preparations. Examination of this epimerase activity in various rat tissue homogenates indicated that this enzyme was highly tissue specific. This biochemical reaction mainly took place in the liver and kidney, whereas low levels of enzyme activity were associated with other tissues. Nevertheless, the liver and kidney homogenates failed to invert (R)-ibuprofen directly even in the presence of all the necessary cofactors. Presumably, the failure to characterize this bioconversion was due to the lack of enzymatic acyl-CoA synthesis in these homogenates. It is noteworthy that the '2-arylpropionyl-CoA epimerase' catalyzed the transformation from either direction and with high turnover rates. The catalytic efficiency of (S)-ibuprofen CoA epimerization appeared to be greater than that of the (R)-counterpart. These in vitro findings suggest that the step of acyl-CoA formation assume a pivotal role in controlling the stereoselectivity and efficiency of the in vivo metabolism. As the responsible acyl-CoA synthetase(s) in different species of animals may exert the reaction with different degrees of enantiomeric preference and efficiency, the resulting stereochemical outcome and metabolic rates of this bioinversion vary accordingly. Consequently, in guinea pigs, this biotransformation proceeds in both directions with nearly equal efficiency, whereas it is virtually unidirectional and slow in humans. Currently, the purification and characterization of this novel '2-arylpropionyl-CoA epimerase' from rat livers constitute the focus of this investigation.

Adult

Reactivity of synthetic peptide analogs of adhesive proteins in regard to the interaction of human endothelial cells with extracellular matrix.

Vascular endothelial cells, providing a nonthrombogenic surface to the lumenal aspect of blood vessels, are anchored to matrix adhesion molecules in the subendothelium through their respective receptors belonging to a superfamily of integrins. We analyzed the reactivity of synthetic peptide analogs of adhesive proteins toward human umbilical vein endothelial cells (HUVEC), assaying their detachment from extracellular matrix and attachment to extracellular matrix components in vitro. Synthetic peptide analogs Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP), Arg-Gly-Asp-Val (RGDV), Arg-Gly-Asp-Ser (RGDS), and Arg-Gly-Asp-Phe (RGDF), which are analogous to "cell adhesion sites" of fibronectin, vitronectin, von Willebrand factor, and alpha-chain of human fibrinogen, respectively, caused significant detachment of HUVEC from the extracellular matrix in vitro at the concentrations ranging from 0.5 to 1.5 mmol/L. They also interfered with attachment of HUVEC to surfaces coated with subendothelial extracellular matrix or its components. The synthetic peptide analog of HHLGGAKQAGDV, which is homologous to the gamma-chain of human fibrinogen sequence 400-411, did not cause any measurable effect on the integrity of HUVEC monolayers (detachment and attachment). "Hybrid" peptides bearing salient features of both sequences, ie, Ala-Lys-Gln-Arg-Gly-Asp-Phe (AKQRGDF) and Lys-Gln-Arg-Gly-Asp-Phe (KQRGDF), had an attenuated effect on the detachment of HUVEC from extracellular matrix. Thus, the integrity of the human endothelial cell monolayer anchored to the extracellular matrix, as measured in detachment and attachment assays, is disturbed by peptides containing RGD sequence whereas the synthetic peptide His-His-Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val (HHLGGAKQAGDV) is nonreactive.

Amino Acid Sequence

Deletion of pgi alters tryptophan biosynthesis in a genetically engineered strain of Escherichia coli.

Deletion of the structural gene for phosphoglucose isomerase (pgi) of Escherichia coli dramatically alters the path of glucose catabolism by diverting carbon into the hexose monophosphate shunt. The effect of this genetic alteration on the conversion of glucose to tryptophan by strains optimized for the biosynthesis of this amino acid was determined by using 13C-nuclear magnetic resonance spectroscopy in vivo. Pgi- strains converted glucose to tryptophan almost twice as efficiently as did their Pgi+ counterparts.

Chromosome Deletion

Metabolic inversion of stereoisomeric ibuprofen in man.

Metabolic stereoisomeric inversion of ibuprofen has both toxicological and clinical implications, and may represent a potential pitfall for patients with metabolic disorders. For those patients, reduced renal clearance in conjunction with metabolic bioactivation resulting from inversion may increase the plasma levels of the active species to an unpredictable degree. This will give rise to enhanced adverse consequences from the same mechanism as its antiinflammatory action, via inhibition of prostaglandin formation. In this study, an enantioselective HPLC technique has been established to scrutinize this unique biotransformation. It was found that ibuprofen epimerization in humans in virtually irreversible, from R to S, which is in agreement with the previous reports. Also, using rats as a model, we have prepared active subcellular hepatic preparations to effect this biotransformation. The "2-arylpropionyl-CoA epimerase" readily converts R-ibuprofen-CoA into its S-counterpart. Examination of the epimerase activity in various tissues indicated that this metabolism mainly occurred in the liver and kidney.

Adult

Acute relapsing pancreatitis in primary hyperparathyroidism with hypercalcemia aggravated after aspiration cytology: report of a case.

In 1957, Cope and his associates first noted 2 cases of pancreatitis associated with primary hyperparathyroidism. They emphasized the association of hyperparathyroidism and pancreatitis. Since then pancreatitis has become a diagnostic clue to primary hyperparathyroidism. We report herein a 39-year-old woman who had suffered from acute relapsing pancreatitis 3 times in the past 2 years. Hypercalcemia persisted throughout the course. A movable mass 3 x 3 cm in diameter was noted over the right thyroid area on physical examination. A hypoechogenic mass 3.5 x 2.7 x 1.4 cm was found between the right lobe of the thyroid and the carotid artery. Because of a persistently high serum level of Ca2+, normal saline and furosemide were infused; the serum Ca2+ decreased gradually. After aspiration of the suspected mass, the serum level of Ca2+ increased from 8.7 mg/dL to 18 mg/dL. Because of the impression of parathyroid adenoma, surgery was performed and a 3 x 2.5 x 1.5 cm well-encapsulated mass was excised without difficulty. Pathologic examination revealed a well-encapsulated parathyroid adenoma. This case reveals that primary hyperparathyroidism maybe one of the causes of pancreatitis, and aspiration cytology, although it may be helpful for the diagnosis, can aggravate the hypercalcemia.

Acute Disease