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Biomedical subjects

M C Yu

Publications and source records attributed to M C Yu.

At least 109 records · Page 6Linked to original sources
PubMed1997

Presence of antibodies to the hepatitis B surface antigen is associated with an excess risk for hepatocellular carcinoma among non-Asians in Los Angeles County, California.

Hepatocellular carcinoma (HCC) exhibits a more than 50-fold variation in incidence worldwide. High-risk regions include East Asia and sub-Saharan Africa, while non-Asians in the United States constitute a low-risk population. We assessed 111 cases of histologically confirmed HCC and 128 community control subjects among non-Asians of Los Angeles County for the presence in serum of hepatitis B surface antigen (HBsAg), antibodies to HBsAg (anti-HBs), antibodies to the hepatitis B core antigen (anti-HBc), HBV DNA, and antibodies to the hepatitis C virus (anti-HCV). Anti-HCV positivity was significantly associated with a 12.6-fold increase in HCC risk (95% confidence limits = 4.7, 33.6). As expected, the presence of serum HBsAg and the presence of anti-HBc in the absence of anti-HBs were both positively associated with the risk of HCC. But most interestingly, among our study subjects, the presence of anti-HBs in the absence of HBsAg and HBV DNA (indicative of a resolved infection) was significantly related to a 4.7-fold increased risk for HCC (95% confidence limits = 2.2, 9.4). Overall, any serological evidence of prior HBV exposure was associated with a 9.4-fold elevation in HCC risk (95% confidence limits = 4.7, 18.7). The data also demonstrate a synergistic effect of HBV and HCV infections on the risk of HCC. We estimate that about 55% of HCC cases occurring in non-Asians of Los Angeles can be attributed to infection by the hepatitis B and/or C viruses.

Adolescent↗
PubMed1997

Does hepatitis GB virus-C infection cause hepatocellular carcinoma in black Africans?

The newly cloned and characterized hepatitis GB virus-C (HGBV-C), which is the same virus as the independently discovered hepatitis G virus, has a global distribution, is transmitted parenterally, and causes chronic viremia. The pathological consequences of infection with HGBV-C are uncertain, and its hepatocarcinogenic potential is unknown. We used a case-control format to compare the prevalence of HGBV-C infection in 167 southern African blacks with hepatocellular carcinoma (HCC) and 167 race-, age-, and sex-matched hospital-based control subjects, and to test for possible interactive effects between this virus and hepatitis B and C viruses in the development of the tumor. The presence of HGBV-C ribonucleic acid was detected in serum samples by reverse transcription, amplification of the resulting complementary deoxyribonucleic acid by the polymerase chain reaction (PCR), and Southern hybridization using a probe from the NS3/helicase region of the genome. Serum samples were also tested for the presence of hepatitis B virus surface antigen, antibodies to hepatitis C virus, and hepatitis C virus ribonucleic acid. Individuals infected with HGBV-C did not have an increased relative risk of developing HCC (relative risk 0.9; 95% confidence limits 0.5, 1.7). Moreover, co-infection with HGBV-C did not further increase the risk of tumor development in patients who were chronically infected with hepatitis B and/or C viruses. HGBV-C is unrelated to hepatocellular carcinoma development in black Africans.

Black or African American↗
PubMed1997

The relative roles of hepatitis B and C viruses in the etiology of hepatocellular carcinoma in southern African blacks.

BACKGROUND & AIMS: Epidemiological studies have shown the relative roles of hepatitis B and C viruses in hepatocarcinogenesis to vary considerably among populations. The aim of this study was to define the independent and interactive roles of the two viruses in the genesis of hepatocellular carcinoma in southern African blacks. METHODS: Blood samples were taken from 231 black patients with hepatocellular carcinoma and matched controls treated at four Johannesburg hospitals. These were tested for hepatitis B surface antigen, antibodies to hepatitis C virus, and hepatitis C virus RNA. RESULTS: Relative to individuals without serological evidence of hepatitis B or C infection, those positive for hepatitis B surface antigen alone had a statistically significant 23.3-fold increased risk for hepatocellular carcinoma, whereas those positive for hepatitis C serology alone had a statistically significant risk of 6.6. A synergistic effect on risk was evident when both hepatitis B and C markers were present (relative risk, 82.5). Hepatitis B virus alone is estimated to cause 43% of hepatocellular carcinoma in southern African blacks, hepatitis C alone 5%, and coinfection with the two viruses 20%. CONCLUSIONS: Hepatitis B virus plays a predominant role in hepatocellular carcinogenesis in southern African blacks, with hepatitis C virus responsible for a smaller proportion of cases. Coinfection with the two viruses carries a synergistic risk of hepatocellular carcinoma formation.

Adult↗
PubMed1997

Alterations in DNA methylation are early, but not initial, events in ovarian tumorigenesis.

We compared global levels of DNA methylation as well as methylation of a specific locus (MyoD1) in ovarian cystadenomas, ovarian tumours of low malignant potential (LMP) and ovarian carcinomas to investigate the association between changes in DNA methylation and ovarian tumour development. As we realized that cystadenomas showed different methylation patterns from both LMP tumours and carcinomas, we verified their monoclonal origin as a means of confirming their true neoplastic nature. High-pressure liquid chromatographic (HPLC) analyses showed that global methylation levels in LMP tumours and carcinomas were 21% and 25% lower than in cystadenomas respectively (P = 0.0001 by one-way variance analysis). Changes in the methylation status of the MyoD1 locus were not seen in any of ten cystadenomas analysed but were present in five of ten LMP tumours and in five of ten carcinomas (P = 0.03). These findings suggest that alterations in DNA methylation are absent (or at least not as extensive) in ovarian cystadenomas, but are present in LMP tumours, the phenotypic features of which are intermediate between those of benign and malignant ovarian tumours. The results also emphasize the merit of distinguishing ovarian LMP tumours from cystadenomas, in spite of their similar clinical characteristics.

Blotting, Southern↗
PubMed1997

In vitro activity of ofloxacin against Mycobacterium tuberculosis.

For the past 3 years, ofloxacin has been widely used in treating patients with drug-resistant tuberculosis in Taiwan. To study its usefulness in treating these patients, 139 isolates of Mycobacterium tuberculosis from patients treated at the Taiwan Provincial Chronic Disease Control Bureau from September 1994 to September 1995 were tested to determine the in vitro antituberculosis activity of ofloxacin. Of these, 131 had not been previously exposed to ofloxacin, and 130 (99.2%) were susceptible to ofloxacin. Sixty-four isolates were found to be susceptible to all conventional antituberculosis drugs, and all of these were also susceptible to ofloxacin. Of the remaining 67 isolates that were resistant to one or more conventional antituberculosis drugs, 66 (98.5%) were susceptible to ofloxacin. There was no association between susceptibility to ofloxacin and susceptibility to conventional antituberculosis drugs among the isolates tested. Of the eight isolates of M. tuberculosis previously exposed to ofloxacin, seven (87.5%) were resistant. Our results indicate that patients with multidrug-resistant strains of M. tuberculosis who have not received prior ofloxacin treatment may be safely treated with ofloxacin even without knowing the result of pretreatment ofloxacin susceptibility tests. We also found that ofloxacin resistance emerges frequently. Therefore, an adequate combination of antituberculosis drugs, along with ofloxacin, should be prescribed to prevent the development of resistance to ofloxacin.

Anti-Infective Agents↗
PubMed1997

Strength of linkage disequilibrium between two vitamin D receptor markers in five ethnic groups: implications for association studies.

Markers in the 3' end of the vitamin D receptor gene have recently been associated with prostate cancer risk. To evaluate the adequacy of the commonly used BsmI restriction fragment length polymorphism as a marker of this locus, we genotyped 627 individuals from five ethnic groups for this marker, as well as for a polymorphic site in the 3' untranslated region of this gene. At the latter site, we identified 12 alleles, A13 to A24, of a poly(A) microsatellite. Allele size followed a bimodal distribution with distinct short (A13-A17) and long (A18-A24) allele populations. Poly(A) allele frequency differed by ethnicity, with the frequency of short alleles being highest in non-Hispanic whites (41%), intermediate in Hispanics and African-Americans (31 and 29%, respectively), and lowest in Japanese-Americans and Chinese (8 and 9%, respectively). In each of the ethnic groups, some degree of coupling was observed between BsmI B and short poly(A) alleles and between BsmI b and long poly(A) alleles. However, the strength of the linkage disequilibrium varied by ethnicity, with departures from complete disequilibrium producing disagreement between the BsmI and poly(A) genotypes. Genotypic disagreement was lowest in Japanese-Americans and non-Hispanic whites (6 and 7%, respectively), intermediate in Chinese and Hispanics (11 and 19%, respectively), and highest among African-Americans (37%), indicating that BsmI is not a good marker for the vitamin D receptor 3' untranslated region genotype in all populations. This finding may explain contradictory results from recent association studies using the BsmI marker.

Asian↗
PubMed1997

Presence of p53 mutations in primary nasopharyngeal carcinoma (NPC) in non-Asians of Los Angeles, California, a low-risk population for NPC.

Mutatins of the p53 tumor suppressor gene are rare in nasopharyngeal carcinoma (NPC) patients who reside in high-risk areas, such as Southeastern China. Among this high-risk group, a pre-existing infection with the EBV and consumption of Cantonese salted fish are closely associated with NPC. We investigated the prevalence of p53 mutations in 28 primary NPC specimens from white (including Hispanic) and African-American patients in Los Angeles, who are at low risk for NPC. Using PCR-based single-strand conformational polymorphism and direct sequencing, we found four mutations (14%) in exons 5-8 of the p53 gene in four patients. All were C-to-T transition mutations: two were present in exon 5-one at codon 142 [CCT (Pro)-->CTT (Leu)] and another at codon 144 [CAG (Gln)-->TAG (stop codon)]. The other two mutations were identified in exon 8: one at codon 273 [CGT (Arg)-->CAT (His)], a CpG site, and one at codon 271, a silent mutation [GAG (Glu)-->GAA (Glu)]. This is the first report investigating the presence of p53 missense mutations in NPC among a low-risk population. Our data indicate that p53 is also an infrequent event among NPC patients at low risk for the disease.

Adolescent↗
PubMed1997

Initial drug resistance of Mycobacterium tuberculosis in Taiwan.

The prevalence and mortality rate of pulmonary tuberculosis in adults are high in Taiwan. Because the emergence of drug-resistant tuberculosis is one of the major causes of this sustained high tuberculosis mortality, surveillance of initial drug resistance is important. We tested Mycobacterium tuberculosis isolates from 1,935 newly diagnosed tuberculosis patients from January 1990 through December 1995 at the Taiwan Provincial Chronic Disease Control Bureau. The overall initial drug resistance rate was 12.3%; 8.7% of isolates were resistant to only one drug, 2.6% to two drugs, 0.7% to three drugs, and 0.3% to four drugs. The resistance rates to individual drugs were: streptomycin, 5.7%; isoniazid, 9.2%; ethambutol, 0.7%; and rifampin, 1.5%. The frequency of multidrug-resistant M. tuberculosis (resistant to at least isoniazid and rifampin) was 1.2%. In view of the high initial isoniazid resistance rate and low initial ethambutol resistance rate, ethambutol should be added to the regimen for the initial treatment of tuberculosis in Taiwan. The emergence of multidrug-resistant M. tuberculosis is ominous and should be considered when treating patients in Taiwan.

Adolescent↗
PubMed1997

Chemopreventive potential of thiol conjugates of isothiocyanates for lung cancer and a urinary biomarker of dietary isothiocyanates.

Natural and synthetic isothiocyanates (ITCs) are versatile chemopreventive agents in many animal systems. We have shown that phenethyl ITC (PEITC) and 6-phenylhexyl ITC (PHITC) are potent inhibitors against lung tumorigenesis induced by tobacco nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in both mouse and rat. The mechanism by which these ITCs inhibited lung tumorigenesis is attributed to their ability to decrease cytochrome P450 (P450) enzyme activities involved in the activation of NNK. Recently, we have found that thiol conjugates of ITCs inhibit P450 enzymes and are effective inhibitors of lung tumorigenesis. This is significant because conjugation with cellular thiols is the major route of ITC metabolism via the mercapturic acid pathway in rodents and humans. The thiol conjugates are less pungent and potentially less toxic, and they are more soluble and chemically less reactive than ITCs. These properties raise the prospect of substituting thiol conjugates for ITCs as chemopreventive agents. Furthermore, although ample rodent studies have established that ITCs inhibit tumorigenesis, the protective role of dietary ITCs against human cancers has not yet been established. As a prerequisite for such human studies, we have developed an HPLC-based assay, based on the condensation reaction of ITCs or conjugates with 1,2-benzenedithiol, for measuring a cyclocondensation product in human urine as an uptake biomarker of total ITCs. This assay was validated using urine samples from subjects who had ingested a known amount of watercress or mustard in a controlled diet. The assay is convenient and rapid, showing promise for analyzing urine samples obtained from population-based studies. Results from two such studies are presented to illustrate the potential application of this biomarker in epidemiologic studies.

Animals↗
PubMed1996

An apparent lack of association between Helicobacter pylori infection and risk of gastric cancer in China.

Several prospective studies have shown a significant association between Helicobacter pylori seropositivity and the risk of gastric cancer. Only a small proportion of H. pylori-infected individuals will, however, develop gastric cancer, and it is unclear what effects other factors, such as diet, might have on the risk of cancer. Eighty-seven subjects with gastric cancer were identified during the first 6 years of follow-up (mean 2.4 years) of a cohort of middle-aged men from Shanghai, China. They were matched with 261 cancer-free controls, and serum samples from all subjects, obtained at recruitment, were assayed for anti-H. pylori IgG antibodies. Questionnaire data provided information on a wide range of socio-demographic life-style and dietary variables. H. pylori seropositivity rates in the cases and controls were 54% and 56%, respectively. Neither the overall risk of developing gastric cancer nor the risk of developing non-cardia gastric cancer was significantly associated with prior M. pylori seropositivity. Adjustment for any of the other medical, dietary or life-style variables studied had little effect on the risk of developing non-cardia gastric cancer; simultaneous adjustment for all of these factors yielded an odds ratio of 1.17. The results do not support the hypothesis that H. pylori plays a role in the process of gastric carcinogenesis in China. It is possible that this is an artefact resulting from the relatively short follow-up period to date.

Antibodies, Bacterial↗
PubMed1996

Morbidity and mortality in relation to cigarette smoking in Shanghai, China. A prospective male cohort study.

OBJECTIVE: To evaluate prospectively the health risk of cigarette smoking in middle-aged men in Shanghai, China. DESIGN: Prospective cohort study with annual follow-up. PARTICIPANTS: A total of 18 244 male residents of Shanghai, China, enrolled in the study during January 1, 1986, through September 30, 1989, and actively followed via annual visits. RESULTS: By September 30, 1993, 852 deaths and 554 incident cancer cases were identified during the follow-up period, which averaged 5.4 years per subject. The overall incidence rate for cancer was 568 per 100 000 man-years, with the 3 leading sites being lung (146/100 000), stomach (116/100 000), and liver (81/100 000). Forty-one percent of all deaths were from cancer. Stroke was the most frequent cause of death unrelated to cancer, with an age-adjusted rate 4.2 times higher than that of US white men (201/100 000 vs 48/100 000), followed by ischemic heart disease, with an age-adjusted rate one-fifth that of US white men (69/100 000 vs 366/100 000). Compared with lifelong nonsmokers, the relative risks in heavy smokers (20 or more cigarettes per day) after adjustment for alcohol consumption were 2.2 for any incident cancer, 9.4 for incident lung cancer, 6.7 for head and neck cancer, and 1.8 for liver cancer. In terms of mortality, heavy smokers were at a 60% greater risk of death relative to lifelong nonsmokers; there was a 2.3-fold excess risk of death from cancer and 2-fold to 3-fold excess risk of death from heart disease. CONCLUSIONS: Cigarette smoking is an important predictor of risk of cancer and mortality in men in Shanghai. Among the study subjects, 36% of all cases of cancer and 21% of all deaths could be attributed to cigarette smoking.

Cause of Death↗
PubMed1996

Genetic susceptibility to cancer from exogenous and endogenous exposures.

The past four decades of epidemiological research have yielded valuable information on the risks of populations to environmental exposures such as tobacco, asbestos, and dietary components. Prevention efforts have been focused on large-scale population-based interventions to minimize exposure to such external carcinogens. While some cancers are beginning to show a decline from changing environmental exposures, hormone-related cancers, such as breast and prostate, are becoming more prevalent. The development of these cancers appears to be closely related to endogenous exposures to circulating steroid hormones. Although prevention trials using antihormone agents are proving successful in some instances, the long-term control of these cancers necessitates a clearer understanding of the metabolism and transport of the relevant hormone in vivo. The revolution in molecular biology has provided powerful genetic tools for evaluating mechanisms of cancer causation as well as the potential to better define individual susceptibility. Using tobacco exposure as an example, we and others have demonstrated that polymorphisms in genes controlling aromatic amine metabolism provide at least a partial explanation for ethnic and individual susceptibility to bladder cancer. Similar studies have examined genetic polymorphisms in the metabolism of tobacco smoke and lung cancer risk, red meat and colorectal cancer, and aflatoxin and liver cancer. Our current studies have pursued a similar paradigm of genetic polymorphism and individual cancer susceptibility in prostate and breast carcinogenesis. We are evaluating polymorphisms in the steroid 5 alpha-reductase type II and androgen receptor genes in relation to prostate cancer based on the evidence that intracellular dihydrotestosterone is the critical "carcinogen." We are pursuing genetic polymorphisms affecting estradiol metabolism, including those in the 17 beta-hydroxysteroid dehydrogenase 2 and estrogen receptor genes as they relate to susceptibility to breast cancer. The potential role of a polymorphism in the cytochrome P450c 17 alpha gene in both breast and prostate cancers is also being examined.

Adult↗
PubMed1996

Immunohistochemical studies of GABA and parvalbumin in the developing human cerebellum.

The localization of GABA and parvalbumin was studied in the developing cerebellum of human fetuses from 16 to 28 weeks of gestation. The avidin-biotin complex immunohistochemical method combined with silver staining were used to reveal the presence of GABA- and parvalbumin-positive neurons and nerve fibres. As early as the 16th week of gestation, GABA immunopositivity was observed in the cerebellar cortex and the deep nuclei. GABA-positive neurons included Purkinje cells, stellate and basket cells of the cerebellar cortex and neurons in the deep nuclei. The gradient of immunoreactivity increased with the maturing cells, being weak at 16 weeks and becoming markedly pronounced at 28 weeks of gestation. GABA-immunopositive mossy fibres were observed in the granular cell layer at 16 weeks, and by 28 weeks, a robust fibre network was present in the cortex and deep nuclei. Immunohistochemical localization for parvalbumin indicates that weak immunoreactivity was observed in Purkinje cells, stellate and basket cells at 16 weeks of gestation, increasing in intensity with advancing age, notably in the Purkinje cells which had acquired an elaborate arbor of neurites at 28 weeks of gestation. In the deep nuclei, parvalbumin-positive cells and nerve fibres were observed throughout the 16 to 28 week period. These results indicate that GABA- and parvalbumin-positive neurons and fibres appeared as early as 16 weeks of gestation, expressing a high degree of immunoreactivity by the 28 week of fetal age.

Cerebellum↗
PubMed1996

Low prevalence of hepatitis C infection in hepatocellular carcinoma (HCC) cases and population controls in Guangxi, a hyperendemic region for HCC in the People's Republic of China.

Southern Guangxi, China has one of the highest incidences of hepatocellular carcinoma (HCC) in the world. Serum samples collected from subjects of an earlier case-control study (39 cases, 41 controls) and from a random sampling of a residential male cohort (n = 100) were tested for antibodies for the hepatitis C virus (anti-HCV) using ELISA version 2.0 with confirmation by RIBA version 2.0. Only one of 141 (0.7%, upper 95% confidence limit, 3.2%) control subjects and none of 39 (upper 95% confidence limit, 6.07%) HCC cases tested positive for anti-HCV. Our results indicate that hepatitis C infection is not an important environmental determinant of HCC risk in this hyperendemic region.

Adult↗
PubMed1996

p53 mutations in hepatocellular carcinoma related to oral contraceptive use.

Oral contraceptives (OCs) are implicated in the development of hepatocellular carcinoma (HCC). Mitogenic stimulation may be the primary mechanism of tumorigenesis, but other factors may also contribute. Mutational spectrum analysis can provide insights into pathogenesis, therefore we analyzed the p53 tumor suppressor gene in 10 HCCs from women with a history of OC use. All were non-Asians whose average OC use was 6.7 years (range 2 months-13 years) and whose mean age at HCC diagnosis was 48.8 years (range 21-67 years). Each tumor was analyzed by immunohistochemistry, DNA sequencing and allelic deletion analysis. Three tumors were positive by p53 immunohistochemistry; allelic deletion analysis identified loss of heterozygosity in one of four informative cases. Two p53 point mutations were found in one tumor containing moderately and well-differentiated components; this patient was negative for all serological markers of hepatitis B and C infections. Both components showed p53 protein accumulation and a GTTval-->GCTala mutation at codon 274. In addition, a silent mutation (ACCthr-->ACTthr) at codon 140 of the p53 gene was detected in the moderately differentiated component of the tumor. These preliminary data indicate that p53 mutations are uncommon in OC-related HCCs. One of the two detected mutations was a G:C-->A:T transition at a non-CpG site, which is characteristic of DNA damage by free radicals. These data support a model whereby estrogens contribute to HCC development primarily through mitogen stimulation and secondarily by mutagenesis via hydroxyl radicals produced during estrogen metabolism. Confirmational analysis of a larger series is warranted.

Adult↗
PubMed1996

Mutational analysis of the input domain of the VirA protein of Agrobacterium tumefaciens.

The transmembrane sensor protein VirA activates VirG in response to high levels of acetosyringone (AS). In order to respond to low levels of AS, VirA requires the periplasmic sugar-binding protein ChvE and monosaccharides released from plant wound sites. To better understand how VirA senses these inducers, the C58 virA gene was randomly mutagenized, and 14 mutants defective in vir gene induction and containing mutations which mapped to the input domain of VirA were isolated. Six mutants had single missense mutatiions in three widely separated areas of the periplasmic domain. Eight mutants had mutations in or near an amphipathic helix, TM1, or TM2. Four of the mutations in the periplasmic domain, when introduced into the corresponding A6 virA sequence, caused a specific defect in the vir gene response to glucose. This suggests that most of the periplasmic domain is required for the interaction with, or response to, ChvE. Three of the mutations from outside the periplasmic domain, one from each transmembrane domain and one from the amphiphathic helix, were made in A6 virA. These mutants were defective in the vir gene response to AS. These mutations did not affect the stability or topology of VirA or prevent dimerization; therefore, they may interfere with detection of AS or transmission of the signals to the kinase domain. Characterization of C58 chvE mutants revealed that, unlike A6 VirA, C58 VirA requires ChvE for activation of the vir genes.

Acetophenones↗
PubMed1996

Treatment of multidrug-resistant tuberculosis in Taiwan.

Eighty-seven patients with multidrug-resistant tuberculosis (MDR-TB) diagnosed between 1988 and 1990 were treated with isoniazid and at least three other effective second-line drugs based on in vitro susceptibility tests. Of these patients, 10% failed to adhere to the regimen and 43% remained sputum positive after 6 months of treatment. Only 47% showed sputum conversion within 6 months of treatment and 12% of them relapsed during the first year of follow-up. From September 1987 to July 1989, 36 patients with MDR-TB were treated with a regimen containing rifabutin, isoniazid and at least three other susceptible drugs. Only 47% achieved a sustained sputum conversion. Four died during treatment due to disease progression. From March 1992 to July 1993, 17 cases of MDR-TB were treated with an ofloxacin-containing anti-TB regimen for 12-24 months. Two failed to adhere to the regimen for more than 1 month during the first 6 months of therapy. Among the remaining 15, 26% failed to achieve sputum conversion, 73% achieved bacterial conversion, 9 within 1 month and the other 2 within 2 months. No significant adverse effect was associated with ofloxacin use. We concluded that ofloxacin is a better choice among the more toxic and less potent second-line drugs, and should be used along with other anti-TB drugs in treating patients with MDR-TB.

Adult↗