Biomedical subjects

M C Yu

Publications and source records attributed to M C Yu.

At least 127 records · Page 7Linked to original sources

PubMed1996

Bladder cancer epidemiology and pathogenesis.

The two major causes of bladder cancer, cigarette smoking and occupational exposure to arylamines, have been recognized for 4 decades. Recently, attention has turned increasingly toward molecular approaches that can help predict which individuals exposed to these factors are at greatest risk of developing bladder cancer and can help explain the wide variation in bladder cancer risk among populations with similar prevalences of exposure to these two known causes. The mechanism for the relationship between smoking and bladder cancer risk has not yet been fully elucidated, but most likely is due to the presence in cigarette smoke of low levels of the same carcinogenic arylamines known to induce bladder cancer in occupational settings. These arylamines undergo metabolic transformation and the activated forms can form adducts with DNA, a probable essential step in the carcinogenic process. Alternatively, these arylamines can be detoxified. Two of the enzymes involved in this detoxification, glutathione S transferase mu and N-acetyltransferase, are genetically controlled. There is now ample epidemiological evidence that variations in the genes that code for these enzymes can affect bladder cancer risk among individuals exposed to arylamines. Levels of arylamine adducts are strongly correlated with cigarette "dose" and can be substantially modified by these detoxifying enzymes.

Carcinogens↗

PubMed1995

A cohort study of serum testosterone and hepatocellular carcinoma in Shanghai, China.

A nested case-control study of HCC based on a cohort of 18,244 middle-aged men in Shanghai, China, who had been followed for an average of 5.3 years, was conducted. Our hypothesis dealt with the possible role of testosterone in the etiology of HCC, which shows a minimum of a 2- to 3-fold male excess in all populations world-wide. Seventy-six incident cases of HCC and 410 control subjects drawn from the cohort and individually matched to the cases by age (within 1 year), time of blood sample collection (within 1 month) and neighborhood of residence were assessed for serum HBsAg, anti-HBc, anti-HBs, anti-HCV and testosterone. Among controls, serum testosterone levels were similar between those who had no markers of HBV infection, those who were positive for anti-HBs only and those who were positive for anti-HBc but negative for HBsAg. However, the geometric mean level of testosterone in HBsAg-positive controls was 21% higher relative to HBsAg-negative controls and the difference was statistically significant (2-sided p = 0.0006). Relative to controls, HCC cases had a significantly higher mean level of testosterone at the time of recruitment (570 vs. 485 ng/dl, 2-sided p = 0.0005), but the difference was explicable on the basis of a higher proportion of HBsAg-positive individuals among cases than controls (p = 0.42 after adjustment for HBsAg status).

Age Factors↗

PubMed1995

Genetic variability of the human SRD5A2 gene: implications for prostate cancer risk.

Elevated dihydrotestosterone levels have been suggested to increase the risk of prostate cancer. The human SRD5A2 gene encodes the type II steroid 5 alpha-reductase, which converts testosterone to the more bioactive compound dihydrotestosterone. We have determined the distribution of a dinucleotide repeat in low-risk Asian-Americans, high-risk African-Americans, and intermediate-risk non-Hispanic Whites. We found this marker to be more polymorphic than previously reported, with some alleles being specific to African-Americans. Genetic variants of the SRD5A2 gene may play a role in predisposition to prostate cancer and in explaining the substantial racial/ethnic variability in risk.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1995

Analgesics and cancers of the renal pelvis and ureter.

To evaluate renal pelvis and ureter (RPU) cancer risk in relation to lifetime use of analgesics, a population-based case-control study was carried out in 3 areas of the United States. Among 502 cases and 496 controls diagnosed and interviewed during 1983-1986, no significant increases in risk were found for any of the non-prescription and prescription analgesics evaluated or among regular users of phenacetin, acetaminophen or aspirin. Neither cumulative lifetime ingestion nor duration of regular use of these 3 drugs, whether alone or in combination, was associated with significantly increased risk of RPU cancer, although a slight excess was observed among long-term users of acetaminophen. Risk was not increased among persons reporting highest cumulative dose and/or longest duration of phenacetin use. Although our study of RPU cancer is the largest to date, it was nonetheless limited by the small number of regular analgesic users and the relatively low response rates. Because of the relatively recent onset of widespread use of acetaminophen, its pharmacologic similarity to phenacetin, a known urothelial carcinogen, and the elevation in risk seen in long-term users, further surveillance of this analgesic is warranted.

Acetaminophen↗

PubMed1995

The CAG and GGC microsatellites of the androgen receptor gene are in linkage disequilibrium in men with prostate cancer.

The androgen receptor genotype was determined in the white blood cell DNA of 45 African-American, 39 non-Hispanic white, and 39 Asian (Chinese, Japanese) normal subjects and 68 patients with prostate cancer (57 whites), all of whom were residents of Los Angeles County. For each subject, we measured the number of repeats in the polymorphic CAG and GGC microsatellites of exon 1 of the androgen receptor gene. In normal subjects, the distributions of CAG and GGC microsatellites differed significantly among the races (two-sided P = 0.046 and < 0.0005, respectively). The prevalence of short CAG alleles (< 22 repeats) was highest (75%) in African-American males with the highest risk for prostate cancer, intermediate (62%) in intermediate-risk non-Hispanic whites, and lowest (49%) in Asians at very low risk for prostate cancer. High-risk African-Americans also had the lowest frequency (20%) of the GGC allele with 16 repeats; the comparable values for intermediate-risk whites and low-risk Asians were 57% and 70%, respectively. Consistent with the interracial variation in CAG and GGC distributions, there was an excess of white patients with < 22 CAG and not-16 GGC repeats relative to white controls (relative risk, 2.1; one-sided P = 0.08). We observed no association (linkage) between the two microsatellites among normal subjects. On the other hand, there was a statistically significant negative association between the numbers of CAG and GGC repeats among the prostate cancer patients studied (two-sided P = 0.008). Among the 47 subjects with short CAG alleles (< 22 repeats), 43% had long GGC alleles (> 16 repeats) whereas only 15% of the 20 subjects with long CAG alleles (> or = 22 repeats) had long GGC alleles. Overall, our data suggest a possible association between CAG and GGC microsatellites of the androgen receptor gene and prostate cancer development.

Adult↗

PubMed1995

Tyrosine hydroxylase- and dopamine-beta-hydroxylase-positive neurons and fibres in the developing human cerebellum--an immunohistochemical study.

Six human fetuses of gestational ages 16-28 weeks were employed. The immunocytochemical avidin-biotin-peroxidase complex method combined with the silver Bodian technique was used to evaluate the presence of tyrosine hydroxylase and dopamine-beta-hydroxylase neurons and afferent and efferent fibres in the cerebellum during development. Our results illustrated that by 16-18 weeks, immunoreactivity of the Purkinje cells and the granule cells was evident. By 23 weeks, the positive Purkinje cells were tightly packed together and the perinuclear granules began to extend into the processes. The positive cells next to Purkinje cells were the basket cells and stellate cells. By 26-28 weeks, all positive cells increased in number and size. Mossy and climbing fibres appeared early in development (16-18 weeks of gestation) and were seen synapsing with the positive granule cells. At the same time, some parallel fibres were observed. At later stages, the tyrosine hydroxylase- and dopamine-beta-hydroxylase-positive Purkinje cells were surrounded by abundant climbing fibres, while parallel fibres were also evident in the molecular layer. In the deep cerebellar nuclei, positive tyrosine hydroxylase and dopamine-beta-hydroxylase neurons were present by 16-18 weeks of development. Those in the dentate nucleus were more polymorphic but smaller in size. Some afferent fibres were also spotted around 16-18 weeks of gestation and their numbers increased later. Positive efferent fibres were present by 26 weeks. All these observations point to an early presence of tyrosine hydroxylase and dopamine-beta-hydroxylase components in cerebellar development.

Avidin↗

PubMed1995

Diet and breast cancer in Shanghai and Tianjin, China.

Various aspects of adult diet have been linked to breast cancer development. These include intake of fat (risk factor), and intake of fibre, soy protein and vitamins A, C and E (protective factors). Results of previous studies have been inconsistent. We examined the possible associations between breast cancer and various indices of nutrient and food intake in two Chinese populations who are at relatively low risk for breast cancer (one-fifth the rate in US white women). Two case-control studies of breast cancer were conducted in the cities of Shanghai and Tianjin, China. In Shanghai, 534 women aged 20-69 years with histologically confirmed breast cancer were recruited, whereas in Tianjin 300 women aged 20-55 years with histologically confirmed breast cancer were interviewed. All controls were community controls who were individually matched to the cases by sex and age (case-control ratio = 1:1). All interviews were conducted in person. Findings from the two studies were similar, although the diets in Shanghai and Tianjin were different in many respects. Cases and controls were similar in their consumption of soy protein, measured either in absolute levels or as percentages of total protein. Overall, all components of dietary fat (saturated fat, monounsaturated fat, polyunsaturated fat) showed a modest, non-significant association with breast cancer after adjustment for energy intake and other non-dietary risk factors for breast cancer. Intake of crude fibre, carotene and vitamin C, on the other hand, exhibited strong, statistically significant inverse associations with breast cancer risk. The last three indices were highly correlated, rendering it impossible to disentangle their individual effects; they were closely associated with intake of green vegetables in the two study populations. Vitamin E intake was unrelated to breast cancer risk in Shanghai and Tianjin. In the multivariate logistic regression model which included all non-dietary risk factors for breast cancer and energy intake, Shanghai women in the lowest tertile of crude fibre intake and highest tertile of fat intake had a 2.9-fold increased risk for breast cancer relative to those in the highest tertile of crude fibre intake and lowest tertile of fat intake. The comparable relative risk in Tianjin women was 2.4. Our data indicate a strong protective effect against breast cancer development with intake of foods rich in fibre, vitamin C and carotene. Our results are also compatible with dietary fat having a modest, positive effect on breast cancer risk within the range of exposure experienced by women in China.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Evidence of an X-linked or recessive genetic component to prostate cancer risk.

We used data from a population-based cohort study of blacks, Hispanics, Japanese and whites to examine the frequency of prevalent prostate and breast cancer by family history status of first-degree relatives (parents and siblings). Independent of race, the age-adjusted relative risk for prevalent prostate cancer in subjects with affected brothers was approximately two times that in subjects with affected fathers (P < 0.00005). No such excess risk for breast cancer was observed among subjects with affected sisters compared to those with affected mothers (age- and race-adjusted relative risk = 1.10, P = 0.34). The magnitude of the relative risk for prostate cancer in sibling- versus parent-affected groups was significantly different from that of the comparable relative risk for breast cancer (P < 0.00005). An excess risk of prostate cancer in men with affected brothers compared to those with affected fathers is consistent with the hypothesis of an X-linked, or recessive, model of inheritance.

Breast Neoplasms↗

PubMed1995

Identification and characterization of a Bacteroides gene, csuF, which encodes an outer membrane protein that is essential for growth on chondroitin sulfate.

Bacteroides thetaiotaomicron can utilize a variety of polysaccharides, including charged mucopolysaccharides such as chondroitin sulfate (CS) and hyaluronic acid (HA). Since the enzymes (chondroitin lyases I and II) that catalyze the first step in breakdown of CS and HA are located in the periplasm, we had proposed that the first step in utilization of these polysaccharides was binding to one or more outer membrane proteins followed by translocation into the periplasm, but no such outer membrane proteins had been shown to play a role in CS or HA utilization. Previously we have isolated a transposon-generated mutant, CS4, which was unable to grow on CS or HA but retained the ability to grow on disaccharide components of CS. This phenotype suggested that the mutation in CS4 either blocked the transport of the mucopolysaccharides into the periplasmic space or blocked the depolymerization of the mucopolysaccharides into disaccharides. We have mapped the CS4 mutation to a single gene, csuF, which is capable of encoding a protein of 1,065 amino acids and contains a consensus signal sequence. Although CsuF had a predicted molecular weight and pI similar to those of chondroitin lyases, it did not show significant sequence similarity to the Bacteroides chondroitin lyase II, a Proteus chondroitin ABC lyase, or two hyaluronidases from Clostridium perfringens and Streptococcus pyogenes, nor was any CS-degrading enzyme activity associated with csuF expression in Bacteroides species or Escherichia coli. The deduced amino acid sequence of CsuF exhibited features suggestive of an outer membrane protein. We obtained antibodies to CsuF and demonstrated that the protein is located in the outer membrane. This is the first evidence that a nonenzymatic outer membrane protein is essential for utilization of CS and HA.

Amino Acid Sequence↗

PubMed1995

A urinary marker of alcohol intake.

Previously, one of us (B. K. T.) developed an assay that measures levels of free ethanol and ethanol conjugates in urine and showed that the mean levels of these ethanol markers in confirmed alcoholics were at least 20-fold higher than those levels in control subjects. In this study, we assessed the relationship of these biomarkers with self-reported levels of alcohol intake in a multiethnic sample of Los Angeles County residents who were male and over the age of 35 years (n = 128; 40 non-Hispanic whites, 46 blacks, 17 Chinese, and 25 Japanese). Regardless of race, the mean levels of free, bound, and total (free plus bound) ethanol were lowest in nondrinkers, intermediate in weekly drinkers, and highest in daily drinkers (P = 0.0001 in all three statistical tests of differences in the three biomarkers). Stepwise discriminant analysis showed that of the three potential biomarkers, total ethanol best discriminates between the three classes of drinkers (non, weekly, and daily), and that additional inclusion of either free or bound ethanol in the discriminant function had negligible effect. Overall, mean level of total ethanol was 2.2 times higher in weekly than in nondrinkers; daily drinkers, in turn, showed a 4.2-fold increase in mean total ethanol relative to weekly drinkers. However, there was no correlation between any of the three biomarkers and self-reported level (in grams of ethanol) of average consumption in either weekly or daily drinkers whose mean intake was about 13 and 42 g of ethanol/day, respectively. As the level of urinary free ethanol and ethanol conjugates showed extraordinary differences among racial groups for a given level of self-reported ethanol intake, the data suggest possible interracial differences in the in vivo elimination rate of ethanol; this latter finding needs to be confirmed in larger studies.

Adult↗

PubMed1995

Glutathione S-transferase M1 genotype affects aminobiphenyl-hemoglobin adduct levels in white, black and Asian smokers and nonsmokers.

Cigarette smoking is the major cause of bladder cancer in men in the United States, and the arylamines contained in cigarettes smoke, including 4-amino-biphenyl (4-ABP), are believed to play an important role in the induction of bladder cancer among smokers. N-acetylation, which is catalyzed by the genetically controlled hepatic N-acetyltransferase enzyme displaying two phenotypes (slow versus rapid), is a detoxification pathway for arylamines with regard to bladder carcinogenesis. In Los Angeles, CA, non-Hispanic white (white), black, and Asian males have comparable smoking habits and yet dramatically different risks of bladder cancer (31 of 100,000 in whites, 16 of 100,000 in blacks, and 13 of 100,000 in Chinese and Japanese). Previously, we have demonstrated that the prevalence of slow acetylators (the high-risk phenotype) was highest in whites (54%), intermediate in blacks (34%), and lowest in Asians (14%). We also showed that mean 3- and 4-ABP hemoglobin adduct levels were significantly higher in cigarette smokers relative to nonsmokers, and that the level increased with increasing number of cigarettes smoke/day. Most importantly, slow acetylators consistently exhibited higher mean levels of ABP hemoglobin adducts relative to rapid acetylators, regardless of race and level of cigarette smoking. We assessed 151 residents of Los Angeles County (CA) who were either white, black, or Asian (Chinese or Japanese) and over the age of 30 years for their glutathione S-transferase M1 (GSTM1) genotype (null versus non-null), acetylator phenotype (slow versus rapid), levels of 3- and 4-ABP hemoglobin adducts, and current use of tobacco products. Whites (27%) had the highest prevalence of the highest risk profile (slow acetylator, GSTM1 null), followed by blacks (15%) and Asians (2.7%), and the difference was statistically significant (P = 0.006). Whites also had less than one-half the prevalence of the "protective" profile (rapid acetylator, GSTM1 non-null) relative to blacks and Asians (23 versus 57%; P = 0.0001). Regardless of race and level of cigarette smoking, mean levels of 3- and 4-ABP hemoglobin adducts were higher in subjects possessing the higher risk (GSTM1/acetylator profile. Mean level of 4-ABP hemoglobin adduct (adjusting for race, cigarette smoking, and acetylator phenotype) was significantly higher in subjects possessing the GSTM1-null versus GSTM1-non-null genotype (46.5 versus 36.0 pg/g Hb; P = 0.037). The comparable difference in mean levels of 3-ABP hemoglobin adduct was borderline significant (1.6 versus 1.1 pg/g Hb; P = 0.07). Thus, our results suggest that GSTM1 is involved in the detoxification of 3- and 4-ABP and may contribute to the racial variation in bladder cancer incidence among white, black, and Asian males in Los Angeles, CA.

Adult↗

PubMed1995

[Disseminated Strongyloides stercoralis infection mimicking pneumonia].

Strongyloides stercoralis is an intestinal nematode. In an immunocompetent host, Strongyloides infections usually produce only mild gastrointestinal symptoms. However, in an immunocompromised host, widespread dissemination of larvae to the extra-intestinal organs may occur. If unrecognized, the mortality rate is high. Here we report a case of disseminated strongyloidiasis in a chronic obstructive pulmonary disease (COPD) subject whose chest radiograph demonstrated multiple pneumonic patches and interstitial infiltrates. Strongyloides larvae were found in stool, sputum, and urine, and embryonated eggs were also found in sputum. The patient was treated successfully with mebendazole and alben albendazole. In conclusion, although high mortality rate is noted in disseminated strongyloidiasis, it is still a curable disease when early diagnosis and treatment could be made.

Animals↗

PubMed1995

MeIQx (2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline): metabolism in humans and urinary metabolites in human populations.

The metabolism of the heterocyclic amines has been extensively studied in rodents and limited studies have been conducted in nonhuman primates. A study has been undertaken on the metabolism of 2-amino-3,8-dimethylimadazo[4,5-f]quinoxaline (MeIQx) in human subjects consuming normal cooked foods. A variety of fish and meat products has been cooked in several ways and fed to human volunteers. Urine was collected and analyzed according to methods developed for this purpose. Earlier rodent studies using radioactive MeIQx had suggested that the principal urinary excretion products included unmetabolized MeIQx, MeIQx sulfamate and MeIQx N-glucuronide. Conditions were developed for HPLC analysis of the free amine and its conjugates in human urine and for total hydrolysis of the conjugates to the free amine. Extraction and cleanup from urine were made possible by the availability of suitable monoclonal antibodies to MeIQx which could be used for immunoaffinity chromatography. For sensitive detection of the amounts present in human urine, gas chromatographymass spectrometry (GC-MS) was used in the negative chemical ionization mode. These studies have demonstrated that the distribution of metabolites in humans strongly resembles that in the rat. The sulfamate and N-glucuronide appear to be predominant human metabolites, while no evidence could be found of N-acetyl MeIQx. Subsequent to the studies just described, the methods developed were applied to urines collected in an epidemiological study on aromatic amine metabolism in Los Angeles. The study includes African American, White, and Asian people who have been phenotyped for caffeine acetylator status.

Adult↗

PubMed1994

NPC and diet.

Explore the source record for details and available documents.

Adult↗

PubMed1994

Breast-feeding and breast cancer.

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Breast Feeding↗

PubMed1994

Acetylator phenotype, aminobiphenyl-hemoglobin adduct levels, and bladder cancer risk in white, black, and Asian men in Los Angeles, California.

BACKGROUND: There is a large body of epidemiologic and experimental data that have identified a number of arylamines as human bladder carcinogens. Metabolic activation is required to biotransform these arylamines into their carcinogenic forms, and N-hydroxylation, which is catalyzed by the hepatic cytochrome P4501A2 isoenzyme, is generally viewed as the first critical step. On the other hand, the N-acetylation reaction, catalyzed by the hepatic N-acetyltransferase enzyme, represents a detoxification pathway for such compounds. The N-acetyltransferase enzyme is coded by a single gene displaying two phenotypes, slow and rapid acetylators. In the United States, cigarette smoking is a major cause of bladder cancer in men, and carcinogenic arylamines present in cigarette smoke are believed to be responsible for inducing bladder cancer in smokers. PURPOSE: Our purpose was to test the differences in three ethnic/racial groups for the prevalence of acetylator phenotypes and to ascertain whether slow acetylators actually have higher levels of activated arylamines in comparison with rapid acetylators. METHODS: One hundred thirty-three male residents of Los Angeles County who were either white, black, or Asian (Chinese or Japanese) and over the age of 35 years were assessed for their acetylator phenotype and levels of 3- and 4-aminobiphenyl (ABP) hemoglobin adducts. Subjects were either lifetime nonsmokers (n = 72) or current cigarette smokers of varying intensity (n = 61). RESULTS: The proportion of slow acetylators was highest among whites (54%), intermediate among blacks (34%), and lowest among Asians (14%). Similarly, geometric mean levels of both 3- and 4-ABP-hemoglobin adducts were highest in whites (1.80 and 49.2 pg/g hemoglobin [Hb], respectively), intermediate in blacks (1.54 and 38.5 pg/g Hb), and lowest in Asians (0.73 and 36.0 pg/g Hb). As expected, cigarette smokers had significantly higher mean levels of both 3- and 4-ABP-hemoglobin adducts relative to nonsmokers, and the levels increased with the number of cigarettes smoked per day (P < .0005 for both adducts). Slow acetylators consistently exhibited higher mean levels of ABP-hemoglobin adducts relative to rapid acetylators, independent of race and level of smoking. CONCLUSION: The present cross-sectional survey supports acetylation phenotype as an important determinant of bladder cancer risk and a possible major factor in the varying bladder cancer risk among whites, blacks, and Asians.

Acetylation↗

PubMed1994

An immunohistochemical study of the c-fos protooncogene in the developing human retina.

The localization and distribution of the protooncogene c-fos were studied immunohistochemically in the retina of human fetuses ranging in age from 15 to 40 weeks of gestation. The highest levels of immunoreactivity were observed in the retinae of younger fetuses, decreasing in intensity with increasing age. At 15 weeks of gestation intense immunoreactivity was observed in the inner nuclear layer while the photoreceptor cells exhibited moderate staining. At 26 weeks of gestation, immunoreactivity in the inner nuclear layer was reduced. The ganglion cells, amacrine cells and photoreceptor cells showed moderate immunopositivity throughout the 26-40 weeks period. The role of c-fos in development is discussed in the light of its other known functions.

Embryonic and Fetal Development↗

PubMed1993

Histologically benign or low-grade malignant tumors adjacent to high-grade ovarian carcinomas contain molecular characteristics of high-grade carcinomas.

It is presently not clear if ovarian carcinomas arise de novo or from benign precursors (cystadenomas) and if high-grade malignant tumors (carcinomas) develop from preexisting low-grade carcinomas. The presence of allelic losses on chromosome 11p15.5 distinguishes high-grade ovarian carcinomas from either low-grade carcinomas or cystadenomas. We therefore examined the distribution of such losses in different parts of heterogeneous tumors showing mixed histological grades or showing adjacent large histologically benign neoplasms. The results showed that all neoplastic areas, including those that were histologically benign or compatible with low-grade carcinomas, contained allelic losses at the above locus. This suggests that the morphologically less aggressive portions of these heterogeneous tumors were not typical cystadenomas or low-grade carcinomas and contained molecular abnormalities indicative of at least a predisposition to the high-grade carcinoma phenotype.

Alleles↗