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Biomedical subjects

T S Chen

Publications and source records attributed to T S Chen.

At least 91 records · Page 5Linked to original sources
PubMed1994

Workshop studies on monoclonal antibodies reactive against porcine myeloid cells.

Investigators from eight laboratories analyzed the reactivity of 22 monoclonal antibodies (mAb) against porcine myeloid cells. Based on binding data, clustering analysis and inhibition studies, workshop mAb 74-22-15 (003) and 6F3 (007) were assigned a swine workshop cluster number 3 (SWC3). These mAb recognized macrophages and neutrophils; neutrophils; a monocyte/macrophage-specific mAb was not identified by this workshop.

Animals↗
PubMed1994

The preparation of zaragozic acid A analogues by directed biosynthesis.

Zaragozic acid A analogues are produced by an unidentified sterile fungus when it is exogenously supplied with 2-thiophenecarboxylic acid, 3-thiophenecarboxylic acid, 2-furoic acid, 2-fluorobenzoic acid, 3-fluorobenzoic acid, or 4-fluorobenzoic acid. The analogues carry 2-thiophenyl, 3-thiophenyl, 2-furyl, o-fluorophenyl, m-fluorophenyl, or p-fluorophenyl group, respectively, at C-6' of the C-1 alkyl side chain replacing the phenyl group of natural zaragozic acid A. All the new analogues of zaragozic acid A possess picomolar inhibitory activity against squalene synthase in vitro.

Bridged Bicyclo Compounds↗
PubMed1994

Effect of eradication of Helicobacter pylori on serum pepsinogen I, gastrin, and insulin in duodenal ulcer patients: a 12-month follow-up study.

OBJECTIVES: To understand the short-term and long-term effects of the eradication of Helicobacter pylori on serum pepsinogen I, gastrin, and insulin concentration, we studied 53 patients with endoscopically proven duodenal ulceration and H. pylori infection. METHODS: All patients received a 2-wk course of colloidal bismuth subcitrate, amoxycillin, and metronidazole, and endoscopy was performed at 1.5, 3, 6, and 12 months after entry. H. pylori status was assessed by a urease test and histology. RESULTS: Among 43 patients in whom H. pylori was eradicated throughout the follow-up year, the mean basal pepsinogen I was 108 ng/ml at pretreatment, decreasing significantly to 85, 77, 80, and 75 ng/ml at 1.5, 3, 6, and 12 months, respectively, at posttreatment. The basal gastrin was 100 pg/ml at pretreatment and fell significantly to 72, 64, 65, and 59 pg/ml, respectively, posttreatment. Of the four patients in whom the H. pylori was not eradicated, there was no significant change in the median basal pepsinogen I and gastrin concentration. Among the six patients in whom the H. pylori was again detectable within the follow-up year, the fallen serum concentration of pepsinogen I and gastrin returned to the pretreatment level. There was no significant change of basal insulin concentration after triple therapy in either the successfully eradicated or failed group. CONCLUSION: We conclude that H. pylori is the leading and direct cause of higher serum concentration of pepsinogen I and gastrin in duodenal ulcer patients.

Amoxicillin↗
PubMed1993

Limb salvage surgery for locally aggressive and malignant bone tumors.

Since 1983, 77 patients have had limb salvage surgery for locally aggressive or malignant bone tumor of the limbs or pelvis. Twenty-nine patients had locally aggressive lesions with giant cell tumors the most prevalent, and 48 patients had malignant lesions, of which osteosarcomas predominated. Resection with a wide margin could be achieved in most of the patients. A mobile joint reconstruction was performed in 57 patients and an arthrodesis in 14 patients. At follow-up, 14 patients have died of disease, 7 patients have survived with disease, and 56 patients (73%) have survived without disease. Local recurrences were encountered in 4 patients (5%). The overall functional results were classified as excellent in 11 patients, good in 45 patients, and fair in 9 patients. Twelve patients had poor results because of failure of the reconstruction or amputation due to complications. Twenty-seven complications were encountered, among which infection was the most serious. Careful selection of patients and consideration of procedure chosen to reconstruct the defect are important for a successful outcome. This decision is based on a number of factors related to the tumor and the patient. Presently, major neurovascular involvement, displaced pathological fracture, inappropriate biopsy incision, extreme youth of the patient, and infection were considered to be contraindications to resection in our institution. Although various procedures promise functional restoration, the reconstructive procedure should be individualized and designed to meet the needs of the patient.

Adult↗
PubMed1993

Significance of tumor thickness in soft palate carcinoma.

Tumor thickness is an important prognostic factor in tumors outside of the upper aerodigestive tract, such as cutaneous melanoma, colorectal carcinoma, and cervical carcinoma. Some studies have also suggested that tumor thickness may have similar prognostic value in the upper aerodigestive tract. This study examined the relationship between tumor thickness (measured with an ocular micrometer) and nodal disease and that between tumor thickness and survival in 44 patients with soft palate epidermoid carcinoma. There was a significant correlation between tumor thickness and nodal disease. None of the 24 lesions less than or equal to 2.86 mm had cervical adenopathy. All of the 15 lesions greater than or equal to 3.12 mm had palpable adenopathy. Tumor thickness correlated more directly with nodal disease than did T stage. Thicker lesions were associated with poorer survival. Tumor thickness is an important parameter in the head and neck and deserves further study.

Adult↗
PubMed1993

Cell-mediated hepatic injury in alcoholic liver disease. Veterans Affairs Cooperative Study Group 275.

BACKGROUND: The mechanism responsible for the initiation and perpetuation of alcoholic liver disease (ALD) remains poorly understood. This investigation attempted to elucidate the role of cell-mediated immune phenomena in the pathogenesis of ethanol-induced liver injury. METHODS: Frozen liver biopsy specimens from 144 patients with moderate to severe ALD were examined by the avidin-biotin immunoperoxidase technique for the expression of antigenic markers of T and B lymphocytes, natural killer cells, and class I and II MHC molecules in the tissue. RESULTS: Expression of CD3 by lymphocytes correlated significantly with regenerating nodules, intralobular inflammation, central sclerosis, and abnormalities of Kupffer cells. B cells were rarely present, and natural killer cells were absent. CD3+ lymphocytes expressed either CD4 or CD8 surface molecules. Enhanced class I MHC expression correlated significantly with portal inflammation, limiting plate erosion, vascular abnormalities, and hemosiderosis. Expression of class II MHC molecules correlated significantly with necrosis, bile stasis, and Mallory bodies. CONCLUSIONS: The distribution and persistence of CD4+ and CD8+ cells in actively advancing ALD, the enhanced MHC expression on hepatocytes, and their relationship to alcoholic hyalin and necrosis lend support to the hypothesis that a cytotoxic T lymphocyte-hepatocyte interaction plays a role, perhaps via lymphokine production, in the genesis or perpetuation of ALD.

CD3 Complex↗
PubMed1993

Different feedback regulation of hepatic cholesterol and bile acid synthesis by glycodeoxycholic acid in rabbits.

BACKGROUND: To explore the sexual difference in the feedback regulation of hepatic bile acid synthesis, glycodeoxycholic acid (GDCA) was administered to 15 male and 14 female rabbits. METHODS: After bile diversion, GDCA equivalent to the hepatic bile acid influx was infused intraduodenally. Biliary cholic acid output represented bile acid synthesis. Hepatic 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase and cholesterol 7 alpha-hydroxylase activities and steady state messenger RNA (mRNA) levels were determined. RESULTS: GDCA inhibited bile acid synthesis less in female than in male rabbits. Hepatic HMG-CoA reductase activity decreased 39% in males, but increased 48% in females. Hepatic cholesterol 7 alpha-hydroxylase activity decreased similarly in males and females, and mRNA levels decreased 86% in males but were unchanged in females. CONCLUSIONS: (1) Total bile diversion stimulated both hepatic cholesterol and bile acid synthesis by activating the rate-controlling enzymes and increasing mRNA levels. (2) GDCA decreased mRNA levels of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase in males, but mRNA levels did not decrease in females. (3) Bile acid synthesis was sustained in females because continued biosynthesis of cholesterol provided a substrate for cholesterol 7 alpha-hydroxylase and stimulus for enzyme formation.

Animals↗
PubMed1993

Microbial transformation of L-696,474, a novel cytochalasin as an inhibitor of HIV-1 protease.

The microbiological transformation of L-696,474 [1], a novel cytochalasin that is an inhibitor of HIV-1 protease, was investigated using Actinoplanes sp. ATCC 53771. Six hydroxylated metabolites 2-7 of 1 were isolated and purified using reversed-phase hplc. All six metabolites were found to have undergone hydroxylation at the C-16 methyl group (C-22) of 1. Three of the compounds, 3, 4, and 5, were further hydroxylated at the para (C-29), the meta (C-28), and both the para and the meta, positions of the phenyl ring, respectively. Metabolites 6 and 7 were shown to result from vicinal dihydroxylation on both C-16 and its attached Me (C-22). The metabolite 7 was further hydroxylated on the meta position of the phenyl ring. The structures of the metabolites were established using spectroscopic techniques including ms, 1H nmr, 13C nmr, and various 2D nmr spectroscopy experiments.

Actinomycetales↗
PubMed1993

Molecular basis and haematological characterization of beta-thalassaemia major in Taiwan, with a mutation of IVS-1 3' end TAG-->GAG in a Chinese patient.

We studied 41 patients with beta-thalassaemia major and their parents by using a combination of polymerase chain reaction (PCR) amplification, slot-blot hybridization of allele-specific oligonucleotide (ASO), and direct genomic sequencing. Eight different point mutations were characterized. C to T substitution at nucleotide (nt) 654 of intervening sequences (IVS) 2, accounting for 46.3% of mutant beta-globin genes, is the most common mutation in Taiwan, followed by frameshift codons 41/42 with four nucleotides (TCTT) deletion for 31.7%, A to G substitution at position -28 of promotor area for 8.5%, A to T substitution at codon 17 for 6.1%, frameshift codons 27/28 (insertion of C) for 2.4%, G to T substitution at nucleotide 1 of IVS-1 for 2.4%, frameshift codons 71/72 (insertion of A) and IVS-1 3 end TAG-->GAG for 1.2%. The former four mutations showed no obvious difference between two major ethnic groups in Taiwan. As to mutations in each individual of beta-thalassaemia major, the incidence of compound heterozygotes of two different mutations is much higher than homozygotes of single mutation, 78.0% v 22.0%. Compound heterozygotes of C to T substitution at nt 654 of IVS-2 and frameshift codons 41/42 with four nucleotides deletion is the most common pattern of beta-thalassaemia mutations in each individual (41.5%). The results are somewhat different from other documented reports concerning the mutations of beta-thalassaemia in southern China. This is the first report of mutation of IVS-1 3' end TAG-->GAG which causes consensus change in Chinese people. Patients with heterozygotes of beta zero and -28 beta(+)-thalassaemia mutations would have a greater delay in initial transfusion in comparison to patients with homozygotes of both beta zero-thalassaemia mutation, but their initial clinical manifestation might be aggravated when combined with a glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and an insult such as exposure to infection and certain drugs.

Adolescent↗
PubMed1993

Microbial hydroxylation and glucuronidation of the angiotensin II (AII) receptor antagonist MK 954.

The microbial metabolism of MK 954 (Fig. 1), a novel nonpeptide angiotensin II receptor antagonist, was investigated using 40 microorganisms in an initial screen for cultures that will produce metabolites similar to those produced in the mammalian liver. The microbial transformation occurred under aerobic conditions in shake flasks incubated at 27 degrees C. Three metabolites of MK 954 were isolated and identified as the 1'-hydroxy M2, 3'-hydroxy M1, and glucuronic acid conjugated M3 derivatives. The structures of the metabolites were established by UV, 1H-NMR spectroscopy and FAB-MS spectrometry and are identical to metabolites produced by incubation of MK 954 with mammalian liver slices.

Actinomycetales↗
PubMed1993

Enzymatic synthesis and immunosuppressive activity of novel desmethylated immunomycins (ascomycins).

31-O-Desmethylimmunomycin O: methyltransferase (DIMT), an enzyme involved in the biosynthesis of immunomycin (ascomycin/FR-900520), was used to synthesize three analogs of this immunosuppressant compound. These compounds were assigned the following structures: 13-O-desmethyl-, 15-O-desmethyl- and 13,15-O-bisdesmethyl-immunomycins. Two of these compounds, namely, 15-O-desmethyl- and 13,15-O-bismethyl-immunomycins have novel structures and were examined for possible immunosuppressive activity by in vitro T-cell proliferation assay. The results showed that methylation of the C-15 hydroxyl is critical for full biological activity of the immunomycin.

Animals↗
PubMed1993

Expression of the beta 1 chain (CD29) of integrins and CD45 in alcoholic liver disease. The VA Cooperative Study Group No. 275.

OBJECTIVES: In the active stages of alcoholic liver disease (ALD), we have shown previously an enhanced expression of either CD4 or CD8 molecules on CD3+T cells. Class I and II MHC molecules expression were enhanced on lymphocytes, and on the cell membrane of hepatocytes, thus suggesting that an intrahepatic antigen-dependent lymphocyte-hepatocyte interaction occurs. Here we report the pattern of expression of several additional molecules known to participate in nonspecific cell-cell adhesion preceding alloantigen recognition i.e., the beta 1 chain of integrins (CD29) and the isoforms of the leukocyte common antigen CD45RA and CD45RO. METHODS: Frozen liver samples from 38 patients with advanced ALD were examined immunohistochemically by the avidin-biotin-peroxidase complex method using monoclonal antibodies. Nine patients with alcoholic fatty liver and six patients with only hepatitis C infection were included as controls and studied in a similar manner. RESULTS: CD29 was strongly expressed on the cell membrane of hepatocytes in 18/20 patients with cirrhosis, in 17/18 with alcoholic hepatitis without cirrhosis, in 5/9 of fatty liver and in all six with hepatitis C. CD45RA was present in 5/18 cases of alcoholic hepatitis and in 3/20 cases of cirrhosis on the hepatocytes plasma membrane, in none of the controls, and rarely on lymphocytes. CD45RO was expressed on the surface of lymphocytes in 14/18 cases of alcoholic hepatitis, 13/20 patients with cirrhosis, in 5/9 of fatty liver and in one with hepatitis C. The CD45RO lymphocytes were predominantly CD8 positive. CONCLUSIONS: Our results indicate that in ALD the hepatocytes exhibit on their plasma membrane an enhanced expression of the beta 1 chain of the integrins and less commonly CD45RA. Furthermore, the expression of only CD45RO on the surface of lymphocytes favors the postulate that the intrahepatic lymphocytes in ALD are most likely of the "memory" type. The results of this study lend further support to the contention that a cell-cell contact precedes a cell-mediated mechanism in the pathogenesis of ALD.

Antigens, CD↗
PubMed1993

Age-related differences in gastric acid secretion and response of gastric inhibitory polypeptide after oral glucose in male rats.

Effects of aging on the secretion of gastric acid and the response of gastric inhibitory polypeptide (GIP) and insulin after oral glucose were studied. Male rats with the age of 3 and 20 months (mo) were fasted overnight before anesthetization with pentobarbital (25 mg/kg BW, ip). The right jugular vein was catheterized for pentagastrin infusion. A PE-320 cannula was introduced into the stomach through an incision in the duodenum and was ligated about 0.5 cm from the pylorus. The stomach was flushed through the esophagus cannula via a peristaltic pump with 10 ml saline at room temperature and then irrigated with saline. Acid output was determined by titration of the flushed perfusate with 0.01 N NaOH to pH 7.0. Basal secretions were collected for 45 min before intravenous infusion of pentagastrin (0.5 microgram/kg/min) for 90 min, then for an addition 45 min. In another experiment, rats were fasted for 4 hours before an oral glucose load (3.2 g/kg). Blood samples were collected from each animal via a jugular catheter at -10, 0, 10, 20, 30, 45, 60, and 90 min following glucose ingestion. The concentrations of plasma GIP, insulin and triiodothyronine (T3) were measured by specific radioimmunoassays. The plasma T3 concentration was decreased in male rats during aging. Pentagastrin infusion stimulated gastric acid secretion in both old and young rats. The spontaneous gastric acid secretion in 20 mo rats was not significantly different from that in 3 mo rats. However, the secretion of gastric acid in response to pentagastrin was greater in 20 mo rats than in 3 mo rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

The Whipples and their legacies in medicine.

George Whipple and Allen Whipple lived as contemporaries, but were not related. Their careers have many similarities. Both had the best available education and training. Both achieved distinction as administrator, educator and researcher. George Whipple founded the medical school at University of Rochester and was its first Dean for 32 years. Allen Whipple established a modern department of surgery at Columbia University and held the chair in surgery for 25 years. Both Whipples were published extensively and did extensive work on the gastrointestinal system. George Whipple's elucidation of the effect of liver on hemoglobin formation won for him a Nobel Prize. The work of Allen Whipple on the pancreas earned him the title of father of modern pancreatic surgical treatment. He also revitalized the surgical management of portal hypertension. Both Whipples were remembered with eponyms--George Whipple for his report on a small intestinal disease and Allen Whipple for his triad and operation. Both achieved international reputations and represented the finest embodiments of American medicine.

Education, Medical↗