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Biomedical subjects

C W Chi

Publications and source records attributed to C W Chi.

At least 109 records · Page 6Linked to original sources

Clinicopathologic comparisons between estrogen receptor-positive and -negative gastric cancers.

We report that a modified dextran-coated charcoal (DCC) assay, including the addition of sodium molybdate and 5% DCC stripping of endogenous hormone, detected higher estrogen receptors (ERs) than those by the conventional assay. ERs in 21 gastric adenocarcinoma were determined by the modified DCC assay; 13 patients had ERs of 2.5 to 520.2 fmol/mg protein with a mean dissociation constant of 1.9 x 10(-10) M. The remaining 8 patients had no detectable amount of the receptor. There were no differences between the ER-positive and ER-negative groups in clinico-pathologic characteristics such as age, sex, tumor size, location, gross appearance, invasive depth, invasion of lymph vessel or vein of stomach wall, nodal involvement, peritoneal dissemination, liver metastasis, and curability. Histological analysis, using Japanese, Lauren's, or Ming's classifications, all revealed no differences between the ER-positive and -negative groups. The survival rate was identical for the 2 study groups. These results suggest that the presence or absence of ERs in gastric adenocarcinoma does not correlate to either biologic or clinicopathologic characteristics of this tumor; the role of ERs in human gastric cancer remains to be elucidated.

Adenocarcinoma↗

Debrisoquine metabolism in Chinese patients with Alzheimer's and Parkinson's diseases.

We determined the oxidative phenotype and metabolic ratio of debrisoquine in 96 Chinese patients with Alzheimer's disease (n = 12), Parkinson's disease (n = 55), and using patients with stroke and cervical spondylosis as controls (n = 29). We did not find any difference in debrisoquine metabolic phenotype among Parkinson's disease, Alzheimer's disease, and control patients as judged by chi-square analysis. In addition, the metabolic ratio of all our patients was less than 12.6. The result suggested that Chinese patients with Parkinson's disease and Alzheimer's disease metabolize debrisoquine at a velocity not different from that of their Western counterparts even though the frequency distribution of debrisoquine metabolism phenotyping in these two populations is quite different.

Aged↗

The nontransformed progesterone and estrogen receptors in gastric cancer.

Contents of the progesterone receptors (PgR) and estrogen receptors (ER) in 18 gastric adenocarcinoma tissues were determined using both the dextran-coated charcoal (DCC) assay and enzyme immunoassay (EIA). PgR were found in 15 cancer tissues (range, 1.0-58.8 fmol/mg protein) and 12 normal mucosal tissues (range, 1.4-26.8 fmol/mg protein) by DCC assay, whereas only 6 cancer tissues (ranged, 0.2-3.3 fmol/mg protein) and 7 normal mucosal tissues (range, 0.1-0.8 fmol/mg protein) had measurable PgR by EIA analysis. Similar results were observed for ER. DCC assay found ER in 12 cancer tissues (range, 2.9-112.6 fmol/mg protein) and 12 normal mucosal tissues (range, 1.2-36.6 fmol/mg protein), whereas EIA measured ER in 16 cancer tissues (range, 0.1-3.5 fmol/mg protein) and 15 normal mucosal tissues (range, 0.1-4.8 fmol/mg protein). No significant correlation between DCC and EIA was observed for either PgR or ER. DCC assay and its modified procedures including 5% DCC stripping of cytosol and/or the addition of sodium molybdate in buffer were simultaneously measured in 5 gastric adenocarcinoma tissues and 1 gastritis cystica polyposa tissue (a precancerous lesion). Higher receptor levels were found by the modified procedures than by conventional method. Using the DCC procedure with addition of sodium molybdate in buffer for receptor analysis, PgR and ER were found in gastric tissues in six patients, with significantly increased levels of measurable PgR. The results suggest that PgR and ER may be involved in the physiology of normal and gastric cancer tissues; their clinical implications are worthy of further study.

Aged↗

Regulation of arginase production by glucocorticoid in three human gastric cancer cell lines.

Gastric cancer tissues have high levels of glucocorticoid receptors (GR) and arginase. To investigate the interrelation of glucocorticoid, GR and arginase, three human gastric cancer cell lines (AZ-521, NUGC-3, KATO-III) were treated with hydrocortisone in the presence or absence of a glucocorticoid antagonist RU38486. GR were found to be present in all three lines, and hydrocortisone significantly increased the production of total arginase in all 3 lines. The induction of arginase production by hydrocortisone was inhibited by RU38486. These findings suggest that the regulation of arginase production by hydrocortisone in gastric cancer cells is mediated through GR.

Arginase↗

Hormonal therapy for stomach cancer.

Stomach cancer is one of the major cancers in Asia. Recent advances in diagnosis and surgical techniques have improved the survival of patients with gastric cancer. But radiation and chemotherapy had limited value in promoting the outcome of patients with gastric cancer. Hormonal therapy with tamoxifen had been tried with conflicting results. Previously, we have found that estrogen receptors (ER) were present in 50% cases of Chinese patients with gastric cancers. Recently, the amplification of c-erbB-2 oncogene and its overexpression have been found to correlate with the advancement of lung, ovarian, breast and gastric cancers. In addition, estrogen has been found to inhibit the expression of c-erbB-2 through ER in breast cancer cell lines. A hypothesis is that the same event may occur in ER-positive gastric cancer cell. Thus patients with gastric cancers whose tumors were positive for both ER and c-erbB-2 gene expression, may benefit from estrogen therapy rather than tamoxifen therapy.

Animals↗

Preparation of [131I]lipiodol as a hepatoma therapeutic agent.

An isotopic exchange method was used to label lipiodol with 131I. The labelling efficiency was > 92.5%, and the radiochemical purity of [131I]lipiodol was above 98% as determined by ITLC. The influencing factors e.g. the heating temperature, reaction time, pH and storage conditions were studied and the optimum conditions were determined. In a pilot study injecting [131I]lipiodol for the treatment of hepatoma, about 70% of hepatoma patients had a response to the treatment with a reduction of alpha-fetoprotein and decrease of hepatoma sizes. The overall median survival was 9 months (range 2-17 months).

Carcinoma, Hepatocellular↗

Primary structure and disulfide bridge location of arrowhead double-headed proteinase inhibitors.

Two arrowhead proteinase inhibitors (inhibitors A and B) were characterized and their primary structures were determined. Both inhibitors A and B are double-headed and multifunctional protease inhibitors. Inhibitor A inhibits an equimolar amount of trypsin and chymotrypsin simultaneously and weakly inhibits kallikrein. Inhibitor B inhibits two molecules of trypsin simultaneously and inhibits kallikrein more strongly than does inhibitor A. The amino acid sequences of inhibitors A and B were determined by sequencing the reduced and S-carboxamidomethylated proteins and their peptides produced by cyanogen bromide or proteolytic lysylendopeptidase or Staphylococcus aureus V8 protease cleavage. Inhibitors A and B consist of 150 amino acid residues with three disulfide bonds (Cys 43-Cys 89, Cys 110-Cys 119, and Cys 112-Cys 115) and share 90% sequence identity, with 13 different residues. Since the primary structures are totally different from those of all other serine protease inhibitors so far known, these inhibitors might be classified into a new protease inhibitor family.

Amino Acid Sequence↗

Chemical synthesis, molecular cloning, and expression of the gene coding for the Trichosanthes trypsin inhibitor--a squash family inhibitor.

The gene coding for a Trichosanthes trypsin inhibitor analog (Ala-6-TTI) in which methionine at position 6 was replaced by alanine was synthesized chemically. The synthetic gene was cloned into plasmid pWR590-1 and expressed in Escherichia coli as a fusion protein composed of beta-galactosidase fragment of 590 amino acid residues and (Ala-6)-TTI, with methionine as a connecting residue. After cyanogen bromide cleavage and reduction of the fusion protein, followed by refolding with trypsin-Sepharose 4B as a matrix and affinity chromatography on the immobilized enzyme, the fully active (Ala-6)-TTI was obtained. The trypsin inhibitory activity and amino acid composition of the recombinant (Ala-6)-TTI were consistent with those of the natural one. The (Ala-6)-TTI gene was also cloned into the secretion expression vector, pVT102U/alpha, in Saccharomyces cerevisiae. In order to make the reading frame of the gene compatible with the vector, a nucleotide was inserted into the (Ala-6)-TTI gene via site-directed mutagenesis. The secreted (Ala-6)-TTI was purified and found to be correctly processed at the junction between the alpha-factor leader peptide and (Ala-6)-TTI downstream. Of the two expression systems, the latter is more advantageous in the high yield (greater than 2 mg/liter), easy purification and needlessness of disulfide refolding.

Amino Acid Sequence↗

Effect of sodium butyrate on glucocorticoid-sensitive and -resistant P1798 lymphosarcoma.

This study aims to examine the effect of sodium butyrate on the viability and the level of glucocorticoid receptors and cells cycle progression in glucocorticoid-sensitive and -resistant P1798 cells. Our results indicated that low levels of sodium butyrate had no effect on either the viability or the receptor level. However, high-level (5 mM) sodium butyrate appeared to reduce cell viability as well as the glucocorticoid receptor level. On the other hand, sodium butyrate inhibited cell cycle progression in a dose-dependent manner. This response was similar in both the glucocorticoid-sensitive and -resistant P1798 cells. Results from this study suggested that the sodium butyrate induced effect may be cell cycle related.

Butyrates↗

Effect of aging on phosphate metabolites of rat brain as revealed by the in vivo and in vitro 31P NMR measurements.

Changes of phosphate metabolism in brains of neonate, weaning and adult rats were compared using both in vivo and in vitro nuclear magnetic resonance spectra. Ratios of phosphocreatine/nucleoside triphosphate (PCr/NTP) were the same in neonatal brain in both in vivo and in vitro studies, but not in weaning and adult brains. This discrepancy may have resulted from extended cerebral hypoxia due to slowed freezing of the brain by the increased skull thickness and brain mass in the weaning and adult rats. Variations in in vitro extraction condition for this age-related study may lead to systematic errors in the adult rats. Nevertheless, the phosphomonoester/nucleoside triphosphate (PME/NTP) ratios in extracts of brain from neonatal rats were higher than those obtained in vivo. In addition, the glycerophosphorylethanolamine plus glycerophosphorylcholine/nucleoside triphosphate (GPE+GPC/NTP) ratios, which were not measurable in vivo, showed age-dependent increase in extracts of rat brain. Some of the phosphomonoester and phosphodiester molecules in rat brain may be undetectable in in vivo NMR analysis because of their interaction with cellular components. The total in vitro GPE and GPC concentration in brain from neonatal rat was estimated to be 0.34 mmole/g wet tissue.

Aging↗

Hormonal therapy for hepatocellular carcinoma.

Hepatocellular carcinoma is not only the leading cause of male cancer death in Taiwan, but also one of the most common cancers in the world. The survival of hepatocellular carcinoma patients is very low, mainly due to the lack of effective treatments. Radiation and chemotherapies in general are not satisfactory: surgery itself is the most effective treatment for hepatocellular carcinoma but only on small resectable tumors. The overall prognosis is still poor. Previously, we have found that the level of glucocorticoid receptor and its mRNA in hepatocellular carcinoma was significantly higher than that of the adjacent liver tissue. This correlated well with the elevated serum alpha-fetoprotein levels in patients with hepatocellular carcinoma. Recently, a female hormone, progesterone, has been found to inhibit the expression of alpha-fetoprotein in hepatoma cells. In addition, progesterone has been used to treat a few hepatocellular carcinoma patients with promising responses. These results together with our hypothesis that the expression of alpha-fetoprotein is regulated by glucocorticoid receptor complex in proliferating hepatocellular carcinoma cells lead to the conclusion that steroid hormones and/or their antagonists may interfere with the function of glucocorticoid receptors in tumors, consequently regulate tumor growth. The potential of hormonal therapy for treatment of hepatocellular carcinoma is worthy of further investigation.

Carcinoma, Hepatocellular↗

Baclofen-induced frontal lobe syndrome: case report.

An 81-year-old man with cervical spondylotic myelopathy developed an acute frontal lobe like syndrome with prominent preservation and an abnormal electroencephalogram after being given seven doses (70 mg) of baclofen for spasticity. The clinical symptoms cleared up in 72 hours after the medication was discontinued.

Aged↗

A unique human IgE-binding epitope on the Bermuda grass pollen recognized by mouse lambda-type monoclonal antibodies.

A group of six mouse monoclonal antibodies (MoAbs) with the unusual lambda-type light chain were generated by fusion of NS-1 cells with splenic cells derived from BALB/c mice immunized with crude extracts of Bermuda grass pollen (BGP). Four of them were IgG1, one was IgG2b, and one was IgG3. Binding inhibition assay showed that they recognized the same (or very similar) epitope. Using sera from BGP-allergic patients, it was found that the specific binding between the IgE antibodies and the MoAb 26-11-fixed antigen could be blocked by MoAb 26-11 itself and another MoAb 9-13 in a dose-dependent manner. It appears that the epitope recognized by the lambda-type MoAbs is a human IgE-binding antigenic determinant. Further physico-chemical analyses showed that this epitope was stable under heat but sensitive to treatments of sodium periodate and proteinase K. Results from these studies indicate that this unique epitope which leads to the generation of lambda-type MoAbs is part of a glycoprotein.

Animals↗

Analysis of allergenic components of Bermuda grass pollen by monoclonal antibodies.

A panel of 16 monoclonal antibodies (MoAbs) directed against Bermuda grass (Cynodon dactylon) pollen (BGP) were generated for identification and purification of the major allergenic components of the eliciting antigen (Ag). Radioimmunoprecipitation (RIP) analysis revealed that there were at least eight antigenic components with molecular weights (MW) ranging from 12 kilodalton (12 kDa) to 200 kDa. Each of these components has distinct biochemical characteristics based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and isoelectric focusing (IEF). Among them, Cyn d Bd67K and Cyn d Bd58K were basic proteins, Cyn d Bd35K consisted of at least four isomeric components with isoelectric points ranging from 6.2 to 7.2. The other antigens (Cyn d Bd68K, 48K, 38K, Cyn d Bd200K, Cyn d Bd46K, Cyn d Bd25K and Cyn d Bd12K) were all acidic proteins. The IgE binding capacity of all these antigens was determined with sera from 11 BGP-allergics by using a modified radioallergosorbent test. All but one of the antigens (Cyn d Bd200K) were found to react with human IgE from sera of BGP-allergic patients. Among those human IgE-binding molecules, Cyn d Bd35K reacted with allergic sera most frequently (10 of 11), followed by Cyn d Bd58K (8 of 11) and Cyn d Bd46K (7 of 11) respectively. Our results suggest that Cyn d Bd35K, Cyn d Bd58K, and Cyn d Bd46K are major allergens of BGP, and the MoAbs we obtained should be valuable tools for further purification of these allergens.

Allergens↗

HTLV-1-associated myelopathy: first case reported in Taiwan.

Taiwan is geographically, culturally, and socially close to southern Japan, which is an endemic area of human T-lymphotropic virus type 1-associated myelopathy (HAM). Taiwan, however, is not an endemic area of HAM. We report the first case of HAM in a native Taiwanese, a 61-year-old woman, without known HTLV-1 risk factors.

Female↗

Analysis of monoamines in the cerebrospinal fluid of Chinese patients with Alzheimer's disease.

We have established HPLC assay conditions that could measure the levels of 14 monoamines and their metabolites simultaneously. Monoamine levels in cerebrospinal fluids of 12 Chinese patients with Alzheimer's disease were compared with those in samples from patients with benign prostate hyperplasia. Of the 14 monoamines and metabolites, only three were found to be present in all samples. Although the levels of 5-hydroxy-3-indoleacetic acid (HIAA) and homovanillic acid (HVA) in cerebrospinal fluid of patients with Alzheimer's disease were lower, and the levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) higher, as compared to control patients, no significant differences were found between these two groups.

3,4-Dihydroxyphenylacetic Acid↗

Purification and preliminary characterization of new peptide inhibitor of insulin from pork pancreas.

A new active peptide was purified from the acid-alcohol extract of pork pancreas. It markedly suppressed the insulin activity detected by either in vivo mouse convulsion assay or in vitro free-fat cell assay. When the extract was subjected to chromatography on a carboxymethylcellulose column, the insulin fraction completely passed through the column, whereas the glucagon fraction was absorbed. The fact that the total apparent biological activity of insulin in the exclusive eluate was higher than in the original extract and the insulin radioimmunoactivity remained unchanged led to the discovery of a potent insulin inhibitor in the extract. The inhibitor was separated from glucagon and insulin in the extract by ion-exchange chromatography on a carboxymethylcellulose column followed by gel filtration on a Bio-Gel P-6 column and finally purified by reverse-phase high-performance liquid chromatography (HPLC) on a C-18 column. The antagonistic effect of this inhibitor on insulin was dose dependent with an ED50 of 2 x 10(-10) M, which was the same level used for insulin in vitro assay (1.7 x 10(-10) M). Amino acid analysis of the inhibitor showed that it was rich in arginine and glycine. It was estimated to be approximately 3000 Mr. The NH2-terminal of the peptide was proved to be blocked because it could not be degraded by Edman degradation. Based on the physicochemical and biochemical characteristics of the inhibitor and compared with other active peptides known to be in the pancreas, the inhibitor is probably a new active peptide that might play an important role in homeostasis of carbohydrate metabolism.

Adipose Tissue↗