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Biomedical subjects

C T Hsu

Publications and source records attributed to C T Hsu.

At least 55 records · Page 3Linked to original sources

An investigation of whether polymorphisms of cytochrome P4502E1 are genetic markers of susceptibility to alcoholic end-stage organ damage in a Chinese population.

The human cytochrome P4502E1 gene (P4502E1), coding for an ethanol-inducible nitrosamine-metabolizing P-450, is involved in the metabolism of ethanol and many known carcinogens. Recently, restriction fragment length polymorphisms (RFLPs) within the P4502E1 have been suggested as genetic markers of susceptibility to alcohol-induced liver disease but the previous studies disagree whether alcoholics with c1 or c2 allele are more susceptible to alcohol-induced liver diseases. Using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, we determined the RsaI and PstI polymorphism of P4502E1 in 77 Chinese alcoholic patients (54 with alcohol-induced cirrhosis and 23 with acute alcohol-induced pancreatitis) and 164 non-alcoholics and compared them with previously published data. The PCR-RFLPs showed three P4502E1 genotypes: type A, homozygote c1/c1; type B, heterozygote c1/c2; and type C, homozygote c2/c2. The RsaI and PstI polymorphism of P4502E1 were completely linked in both Chinese alcoholics and nonalcoholic controls. The rare allele (c2) occurs at similar frequency of 0.232 and 0.234 (P > .05) in nonalcoholic controls and alcoholics, respectively. The genotype distributions of P4502E1 between Chinese alcoholics and nonalcoholics are not significantly different. The genotype and allele frequencies of P4502E1 for Chinese are significantly different from those of Swedes, European-Americans, and African-Americans, respectively (P < .00001), but very similar to Japanese (P > .05). In conclusion, ethnic variations exist between Asians and Caucasians and between Asians and African-Americans. No allelic variants at loci associated with RsaI/PstI RFLPs result in phenotypes displaying greater susceptibility to alcohol-induced cirrhosis or alcoholism in Chinese populations, which contradicts previous reports from Japanese groups.

Adult↗

Evolution rate of hepatitis delta virus RNA isolated in Taiwan.

The complete RNA sequences of hepatitis delta viruses (HDV) isolated at 3 years apart from a chronic delta hepatitis patient in Taiwan were determined. The sequence analysis showed an overall evolution rate of 3.18 x 10(-3) substitutions/nucleotide/year. The evolution rates in different parts of HDV RNA varied. The hypervariable region evolved faster (4.55 x 10(-3) substitutions/nucleotide/year) than the hepatitis delta antigen (HDAg)-coding region (2.60 x 10(-3) substitutions/nucleotide/year) and the autocatalytic region (1.11 x 10(-3) substitutions/nucleotide/year). These data are compatible with the previous finding that the hypervariable region is more divergent than the HDAg-coding region and the autocatalytic regions among the HDV isolates from different geographic areas. No substitution was found in the four previously identified conserved domains of HDV RNA, further confirming their functional importance in viral replication. The evolution rate of this HDV RNA is higher than that determined from the partial RNA sequences of two Japanese HDV isolates and similar to that found in a Lebanon isolate. Further, it was found that this HDV RNA retained the same microheterogeneities at 15 nucleotide positions detected in the RNA 3 years earlier. It is concluded that HDV RNA in patients' serum is extremely heterogeneous, and that the nucleotide substitutions in certain nucleotide positions likely have conferred evolutionary advantages for HDV. Viral sequence evolution is a possible mechanism for chronic HDV infection.

Adult↗

Sequence determination of hepatitis C virus genome isolated from Taiwan.

The partial genome sequence of the hepatitis C virus (HCV) was determined in the serum of a Taiwanese patient with chronic community-acquired type C hepatitis. The cDNA fragments synthesized with the HCV RNA as a template were amplified by polymerase chain reaction using specific oligonucleotide primers. The amplified fragments represented the regions coding for the putative core, matrix and envelope proteins as well as the N-terminal amino acid sequence of the nonstructural protein NS1, the partial nonstructural NS3 and NS4 proteins and the region of the partial 5'-end noncoding sequence. The cDNA fragments were cloned and sequenced. Sequence analysis of these clones showed that they share 83.7%, 93.2% and 93.6% similarity at the nucleotide level, and 86.6%, 94.1% and 92.9% homology at the amino acid level, with the previously published American, Japanese and Taiwanese isolates, respectively. Accordingly, the RNA genome we obtained is HCV type II, probably, the predominant subtype in Taiwan.

Adult↗

Polymorphism of alcohol and aldehyde dehydrogenase genes and alcoholic cirrhosis in Chinese patients.

Liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the principal enzymes responsible for the oxidation of ethanol, are polymorphic at the ADH2, ADH3 and ALDH2 loci in human beings. Our previous studies have shown that, compared with nonalcoholic individuals, Chinese alcoholic patients without liver disease had significantly lower frequencies of the ADH2*2 and ADH3*1 alleles, which encode high maximum velocity beta 2- and gamma 1-ADH subunits, respectively, as well as a lower frequency of the ALDH2*2 allele, which encodes an enzymatically inactive subunit. The data strongly suggest that genetic variation in both ADH and ALDH may influence drinking behavior and the risk of alcoholism developing through acetaldehyde formation. To further investigate the possible role of acetaldehyde in the pathogenesis of alcoholic liver disease, we determined the ADH and ALDH genotype frequencies in patients with alcohol-related cirrhosis (n = 27), viral hepatitis-related cirrhosis (n = 29) and gastric and duodenal ulcer without relevance to alcohol (n = 30). We developed a new restriction fragment length polymorphism method to genotype the mutant and normal ALDH2 alleles by using polymerase chain reaction-directed mutagenesis, which proved to be simpler and faster than the conventional detection methods that use hybridization with allele-specific oligonucleotide probes. We found that the frequencies of the alleles ADH2*2 (57%), ADH3*1 (78%) and ALDH2*2 (9%) in the alcoholic cirrhotic patients were significantly lower than those in the healthy controls and in the patients with cirrhosis from viral hepatitis and with gastric and duodenal ulcer.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Dehydrogenase↗

Genotyping of alcohol dehydrogenase at the ADH2 and ADH3 loci by using a polymerase chain reaction and restriction-fragment-length polymorphism in Chinese alcoholic cirrhotics and non-alcoholics.

We investigated the genotype of ADH2 and ADH3 in Chinese alcoholic cirrhotics and non-alcoholics by using a polymerase chain reaction and restriction-fragment-length polymorphism. This method is non-radioactive, easy to implement with good reproducibility. In the Chinese population, the frequencies of the ADH2*1 and ADH3*2 alleles were significantly higher in the alcoholic cirrhotic patients (53%; 23%) than in the viral hepatitis cirrhotics (32%; 8%) and the gastric and/or duodenal ulcer control patients (25%; 6%). On the other hand, the gastric and/or duodenal ulcer control patients and the viral hepatitis cirrhotic patients showed similar allele frequencies for the polymorphic ADH2 and ADH3 genes. These findings suggest that the alleles ADH2*2 and ADH3*1, coding for the high-Vmax beta 2-ADH and gamma 1-ADH, respectively, may play a protective role against alcoholism in Chinese patients.

Alcohol Dehydrogenase↗

The effect of chemical sympathectomy on acute liver injury induced by carbon tetrachloride in spontaneously hypertensive rats.

The effects of 6-hydroxydopamine (6-OHDA) on carbon tetrachloride (CCl4)-induced acute liver injury were examined in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Plasma glutamate-pyruvate transaminase (GPT) activity was increased in both strains after one dose of CCl4 administration, although the increase was more significant in SHR than in WKY. Pretreatment with 6-OHDA inhibited the increase in GPT activity after CCl4 administration in both strains and especially in SHR. 6-OHDA also reduced the noradrenaline (NA) content of the liver and increased the hepatic blood flow in both strains. It caused a greater decrease in blood pressure in SHR than in WKY. The results suggest that 6-OHDA blocks the sympathetic neural activity in the liver, resulting in vasodilatation and increase in hepatic blood flow and thereby alleviating the circulatory disturbance produced by CCl4 preventing acute liver damage, especially in SHR.

Acute Disease↗

A modified removable suture in trabeculectomy.

We modified the closure of the scleral flap in trabeculectomy by using an externalized hemibow tie, easily removable in the early postoperative period. We used this externalized knot in 20 eyes of 17 patients undergoing trabeculectomy and in eight eyes of seven patients undergoing combined trabeculectomy and cataract extraction with intraocular lens implantation. The sutures were removed between 2 and 72 days after surgery (16.75 +/- 14.49 days). With a mean follow up of 11.36 months, the overall success rate was 78.6%. The sutures of nine eyes (32%) were removed due to elevated intraocular pressure and/or decreased bleb size. The immediate and long-term efficacies were 77% and 56%, respectively. The trabeculectomies we performed using this safe and simple technique, as compared with those using other methods of scleral flap closure, provided a lower incidence of postoperative complications due to overfiltration, and made it possible to increase the degree of filtration when needed during the early postoperative period.

Aged↗

Primary carcinoma of the gallbladder: a review of 10 years of experience at Tri-Service General Hospital.

Thirty-two cases of primary carcinoma of the gallbladder proven by surgery and pathological biopsy between January 1982 and June 1991 at the Tri-Service General Hospital, Taipei, were analyzed retrospectively. There were 16 male and 16 female patients with a mean age of 66.1 years. The most common clinical manifestations were right upper quadrant abdominal pain and poor appetite. The most common laboratory finding was an elevation of alkaline phosphatase. The preoperative diagnostic rate of this series was 46.9% (15/32 cases), through use of abdominal sonography, computed tomography, endoscopic retrograde cholangiopancreatography and celiac angiography. The coexisting gallstone incidence was 65.6% and the resectability rate, 59.4%. The histological classifications were adenocarcinoma with variable differentiation in 31 cases, and undifferentiated adenocarcinoma in one. The liver was the most common site for metastasis (53.1%), followed by lymph nodes at porta hepatis (21.9%), omentum (12.5%), peritoneum (9.4%), lung (6.3%), colon (3.1%) and duodenum (3.1%). According to the Nevin's staging system, three patients were in stage I and all survived more than five years. Of the two patients in stage II, one survived longer than five years and the other survived longer than seven months. There were three cases in stage III: one patient died of metastasis eight months postoperatively, while the other two cases lived for seven and nine and a half months respectively. There were 24 cases in stage IV and stage V, all of them died less than six months after diagnosis. Poor prognosis for patients with primary carcinoma of the gallbladder makes early diagnosis and treatment important.

Adenocarcinoma↗

Osteoclast-like giant cell tumour of the gallbladder.

We describe a rare carcinoma of the gallbladder containing osteoclast-like giant cells. Well-differentiated adenocarcinoma was found in the mucosa of the fundus, and osteoclast-like giant cells were present mainly in a haemorrhagic mass protruding from the mucosal surface. The metastatic hepatic tumour was composed chiefly, if not exclusively, of osteoclastoma-like cells, but minute carcinomatous elements were also present. There was an apparent transition between the giant cells and tubular structures in both the gallbladder tumour and hepatic tumour. However, ultrastructural study did not reveal any evidence of epithelial differentiation in the giant cells. Immunohistochemical studies suggested that the mononuclear and giant cells were mesenchymal and histiocytic in nature (vimentin and factor XIIIa positive). A few exceptional giant cells transforming from the fine tubular structure were positive for epithelial membrane antigen. In conclusion, the osteoclast-like giant cell tumour component was thought to represent mesenchymal metaplasia in pre-existent adenocarcinoma.

Adenocarcinoma↗

Ectopic production of prolactin in uterine cervical carcinoma.

Sera from 743 patients with uterine cervical carcinoma were assayed for levels of circulating prolactin (PRL). Markedly abnormal serum prolactin levels were observed in 30.8% (229/743) of patients. During the early stages of cancer, the degree of PRL elevation in serum and incidence of abnormal PRL levels are much greater than those found for carcinoembryonic antigen, which is generally considered to be a circulating cervical tumor marker. Surgical removal of cervical carcinoma resulted in normalization of serum PRL concentrations. Immunohistochemical staining techniques and primary tissue culture of cervical carcinoma were used to verify the presence of PRL in the uterine cervical carcinoma cells. Twenty-two of forty-nine cervical carcinoma tissue sections showed cytoplasmic staining for prolactin, while normal cervix tissues tested were negative. Production of prolactin was directly demonstrated in the early tissue cultures of cervical carcinoma. These studies show ectopic production of PRL by uterine cervical carcinoma. Prolactin production may be a potential marker for detecting early occult tumors or for gauging the effectiveness of therapy for human cervical carcinoma.

Carcinoembryonic Antigen↗

The role of the sympathetic nervous system in promoting liver cirrhosis induced by carbon tetrachloride, using the essential hypertensive animal (SHR).

The effects of the sympathetic nervous system on liver injury induced experimentally by carbon tetrachloride (CCl4) were examined in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). It was found that the SHR had an elevated catecholamine (CA) content in the adrenal gland without any treatment, and fluorescence histochemistry also revealed dense adrenergic innervations in the liver. Moreover, the SHR showed greater sensitivity to CCl4 stimulation in the sympathetic nervous system than the WKY, resulting in a decreased hepatic blood flow in the acute stage and a depleted CA in the adrenal gland, a lowered blood pressure (BP) and a released non-esterified fatty acid (NEFA) from peripheral adipose tissue in the chronic stage. Upon repetition of the CCl4 treatments twice a week for 4 weeks, the liver injury was more severe in the SHR than in the WKY. Plasma glutamate-pyruvate transaminase (GPT) activity was increased in both strains but more significantly in the SHR than in the WKY. Histological examination of the liver in the SHR showed established cirrhosis, whereas only bridging fibrosis was seen in the WKY. These results suggest that the pathogenesis of the liver damage induced by CCl4 in the SHR, is attributable to the enhanced response of the sympathetic nervous system that releases massive amounts of CA which then lead to vasoconstriction and metabolic changes that promote liver damage.

Animals↗

Helicobacter pylori, gastritis and duodenitis in the healing process of duodenal ulcer.

The occurrence of antral gastritis, duodenitis, gastric metaplasia and Helicobacter pylori (H. pylori) were compared between 63 endoscopically proven duodenal ulcer (DU) patients and 34 non-ulcer dyspepsia (NUD) patients with no ulcer history and no ulcer present as documented by endoscopy. The DU group showed a significantly higher rate of active antral gastritis (89% vs 41% p less than 0.05), a higher antral H. pylori carrying rate (76% vs 27% p less than 0.01), a higher rate of active chronic duodenitis (75% vs 32% p less than 0.05), and a higher rate of gastric metaplasia in the duodenal bulb (68% vs 27% p less than 0.05) than the NUD group. The H. pylori carrying rate in the bulb was 16% in the DU group and 0% in the NUD group. The difference is evident, although it is statistically insignificant. All 10 cases carrying H. pylori in the duodenum in the DU group had active chronic duodenitis with gastric metaplasia. Further evaluation of the variables (rate of active antral gastritis and duodenitis and the carrying rate of H. pylori in the antrum and bulb) showed no difference between different ulcer stages (active, healing, or scarred). The above findings strongly suggest a close relation between H. pylori and duodenal ulcer. However, the low occurrence rate of the bacteria in the bulb can only indicate a partial etiologic role of the bacteria in DU. No improvement in antral gastritis, duodenitis and H. pylori occurrence, despite the healing of an ulcer, is in agreement with the naturally high recurrence rate of duodenal ulcers.

Duodenal Ulcer↗

Early gastric cancer arising from localized Ménétrier's disease.

A case of early gastric cancer arising from Ménétrier's disease in the stomach is described. The patient was a 53-year-old man, who suffered from epigastralgia. Radiological and endoscopic examination demonstrated giant mucosal folds along the greater curvature of the stomach. On the distal margin, signet-ring cell carcinoma was demonstrated by biopsy. The coexistence of Ménétrier's disease and early gastric cancer has rarely been reported. Cases reported in the literature were reviewed and the increased malignant potential of Ménétrier's disease was discussed.

Adenocarcinoma↗

New monoclonal antibody against human cervical carcinoma with diagnostic and therapeutic potential.

A new murine monoclonal IgG3 antibody (Mab 1H10) was developed with specificity for human cervical carcinoma and several other tumor types. Antibody reactivity against a panel of tumor cell lines was examined by indirect immunofluorescence and quantified by flow cytometry. Mab 1H10 reacted with cervical, colorectal and bladder carcinoma cells and to a lesser extent melanoma and hepatocellular carcinoma cells but did not react with human fibroblasts, lymphocytes or RBCs. Mab 1H10, as assessed by immunohistochemical staining, bound 40/97 cervical carcinoma tissue samples, 8/16 colorectal carcinoma samples as well as a population of osteogenic sarcoma and lung, ovarian and bladder carcinoma tissues. Mab 1H10 did not react with any normal tissue or cell samples tested including cervix, ovary, breast, liver, colon, bladder, lung, spleen, cerebrum, lymphocytes or RBCs. Mab 1H10 may be useful for the targeting of drugs, toxins or radioisotopes to cervical carcinoma in humans.

Animals↗

Uterine malignancy developing after long term use of IUCD additional report of 2 cases: endometrial stromal sarcoma and leiomyosarcoma.

In our 2 previous papers published in this Journal, we had 5 cases of uterine malignancies developing after long term use of IUCD's. In the present paper 2 cases of such association are to be added. One case ATH with right adnexectomy was performed for persisting vaginal bleeding after 22 years of Lippes Loop application and recurrence 8 years after the first operation. Pathological diagnosis is endometrial stromal sarcoma. The other case is a leiomyosarcoma developing after 25 years of Lippes Loop application. Although no cause and effect relationship between IUCD use and uterine malignancy in human beings has been proved, the increase in such cases suggests to us that long term application should be avoided, particularly in view of the positive animal experiments. The successive detection of such cases in a relatively short period of time prompts us to make further studies to gain a deeper insight into such associations.

Female↗

Multiple myeloma in alcoholic liver cirrhosis.

A case of multiple myeloma (Bence Jones, lambda) associated with alcoholic liver cirrhosis is reported. A 56-year-old Japanese male died of hepatic failure and hypercalcemia. Autopsy revealed alcoholic liver cirrhosis and plasma cell myeloma. Immunoelectrophoretic analysis of his reserved serum disclosed the presence of M component of lambda Bence Jones protein. IgA and lambda light chain were demonstrated in the cytoplasm of the myeloma cells. Complications such as generalized amyloidosis, metastatic calcification, myeloma kidney and hemorrhagic pancreatitis were noted. The coexistence of multiple myeloma and liver cirrhosis has rarely been reported. On the basis of a review of the reported cases, a possible association between both diseases was discussed.

Humans↗

A Mobile Oocyte Incubation Unit (MOIU): a device for improvement of the gamete intrafallopian transfer (GIFT) program.

Forty couples with infertility due to various causes were selected for the gamete intrafallopian transfer (GIFT) program at our hospital. When the first 21 couples (Group A) had been treated in the program, the rate of pregnancy achieved was 23.8%, which did not seem satisfactory. This might have been caused by the distance between the embryo laboratory and the operating room. To eliminate this defect, a Mobile Oocyte Incubation Unit (MOIU) was designed. This is actually a compact laboratory that can be placed in the operating room. After the MOIU was utilized, the rate of pregnancy for the following 19 couples (Group B) increased to 42.1%. The MOIU has helped improve the performance of the GIFT program by increasing the stability of the pH value of the culture medium (Chetkowski R, et al.: J Vitro Fert Embryo Transfer 1985;2:207), lessening the exposure of the gametes to air and room temperature, and most importantly, shortening the time required for a GIFT procedure from 45-100 to 15-30 min. We expect that the MOIU will eventually become an integral part of the standard equipment for the GIFT program and make the program more successful and reliable in the treatment of infertility.

Adult↗