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1.
CYP2D6 genotyping (CYP2D6*3, CYP2D6*4, CYP2D6*5, CYP2D6*13, CYP2D6*16 alleles and gene duplications) was previously performed on 1053 Caucasian and African-American lung cancer cases and control individuals and no significant difference in allele frequencies between cases and control individuals detected. We have carried out additional genotyping (CYP2D6*6, CYP2D6*7, CYP2D6*8, CYP2D6*9, CYP2D6*10, CYP2D6*17 alleles) and debrisoquine phenotyping on subgroups from this study to assess phenotype-genotype relationships. African-Americans showed significant differences from Caucasians with respect to frequency of defective CYP2D6 alleles, particularly CYP2D6*4 and CYP2D6*5. The CYP2D6*17 allele occurred at a frequency of 0.26 among 87 African-Americans and appeared to explain higher average metabolic ratios among African-Americans compared with Caucasians. CYP2D6*6, CYP2D6*8, CYP2D6*9 and CYP2D6*10 were rare in both ethnic groups but explained approximately 40% of higher than expected metabolic ratios among extensive metabolizers. Among individuals phenotyped with debrisoquine, 32 out of 359 were in the poor metabolizer range with 24 of these (75%) also showing two defective CYP2D6 alleles. Additional single strand conformational polymorphism analysis screening of samples showing large phenotype-genotype discrepancies resulted in the detection of three novel polymorphisms. If subjects taking potentially interfering drugs were excluded, this additional screening enabled the positive identification of 88% of phenotypic poor metabolizers by genotyping. This sensitivity was comparable with that of phenotyping, which identified 90% of those with two defective alleles as poor metabolizers.  相似文献   

2.
OBJECTIVES: CYP2D6 polymorphism of clinical relevance occurs with variable frequency in different ethnic groups. Since this polymorphism has not been studied in a North Indian population, the present study was undertaken. METHODS: One hundred healthy unrelated North Indian subjects received 30 mg dextromethorphan (DM) orally at bed-time. The amounts of DM and its metabolite, dextrorphan (DR), excreted in 8 h urine were estimated by high performance liquid chromatography. Metabolic ratio (DM/DR excreted in 8 h) was used as an index of the metabolic status of an individual. RESULTS: The analysis of the data by frequency distribution histogram, probit and NTV plots demonstrated bimodal distribution of the North Indian subjects with respect to hepatic CYP2D6. Out of 100 subjects, 97 were extensive metabolizers (EMs), whereas three were poor metabolizers (PMs). EMs and PMs excreted 29.82 and 2.67 micromol DR (mean value) and 2.59 and 8.82 micromol DM (mean value) in 8 h, respectively. MR and log MR was 197- and 2.2-fold higher in PMs versus EMs. The antimode value of zero was determined by visual observation in frequency distribution histogram and inflection point in probit plot. CONCLUSION: From this study, it can be concluded that the PM phenotype of CYP2D6 occurs with a frequency of 3% (95% confidence interval of 0.33%-6.33%) in North Indians.  相似文献   

3.
The postnatal development of serotonin (5HT)-immunoreactive axons was studied in the visual cortex of the cerebrum in both normal and microcephalic rats during early postnatal and young adult stages. Severe microcephaly in rat offspring was induced by prenatal exposure to methylazoxymethanol acetate (MAM), an anti-mitotic agent, on day 15 of gestation. From postnatal day 1 (PND 1) to PND 5, fine and short 5HT fibers were irregularly dispersed throughout the occipital cortex in both the control and MAM-treated rats (MAM-rats). A conspicuous aggregation of dot-like 5HT terminals was found in controls, but not in MAM-rats, in a shallow layer of the dorsomedial region of the occipital cortical plate. On PND 7, such an aggregation of 5HT terminals was found in both groups. The density of the aggregation increased up to PND 9, but then decreased gradually, finally becoming unrecognizable at around PND 15 in both groups. MAM-rats, however, always showed hyperaggregation of 5HT terminals when compared with controls on the same PND. The density of 5HT fibers gradually increased, and finally made up a network-like formation at PND 28 in both groups, its pattern was essentially identical to the abnormal distribution of 5HT fibers during the later stage. As a result, the network-like formation of 5HT fibers in the MAM-rats at PND 28 was markedly twisted and somewhat hyperdense. In Nissl-stained preparations from PND 9 to 15, the 5HT terminal aggregation in the control rats was precisely confined to the newly forming layer IV of the visual cortex. In the MAM-rats, on the other hand, the aggregation of 5HT terminals was not associated with a specific cortical layer because of a disarranged cytoarchitecture of the microcephaly.  相似文献   

4.
The aims of this study were to identify differences in the centre of buoyancy (CB) and centre of mass (CM) locations of male and female collegiate swimmers, and to assess the influence that buoyancy has on freestyle kicking performance. Sixteen female collegiate swimmers (mean +/- s: age 19.1 +/- 1.2 years) had significantly more adipose tissue (20.2 +/- 4.4%) than 15 male collegiate swimmers (19.9 +/- 1.0 years, 12.6 +/- 3.8%). The ratio of the sum of abdominal and suprailiac skinfolds to the thigh skinfold was significantly greater for the males (2.07 +/- 0.37) than the females (1.31 +/- 0.32), implying that females had proportionately more fatty tissue caudally than males. The distance d between the centres of buoyancy and mass was significantly larger for the males (0.79 +/- 0.43 cm) than the females (0.16 +/- 0.34 cm). Both points were more caudal in the female subjects (59.9 +/- 0.7% and 59.8 +/- 0.7% of body height respectively) than in the male subjects (61.7 +/- 0.8% and 61.2 +/- 0.9% respectively). These data suggest that the difference in d may be attributed to the difference in the location of the centre of buoyancy, because the centre of mass difference was not significant and was characterized by a smaller effect size. The amount and distribution of adipose tissue accounted for a significant proportion of variance in d (R2 = 0.25 and 0.29 respectively). Males had a significantly higher proportional kick time, defined as the ratio of times to complete a 22.9 m sprint when kicking and swimming respectively, than females (1.57 +/- 0.09 and 1.51 +/- 0.13 respectively). This shows that the male swimmers kicked proportionally more slowly than the female swimmers. However, the distance d did not account for a significant proportion of variance in the proportional kick time. Therefore, our results do not support the notion that skilled male swimmers are at a performance disadvantage in terms of natural buoyancy characteristics.  相似文献   

5.
PURPOSE: To investigate the nature and reversibility of biochemical and functional changes in the retina encountered over a single generation of dietary n-3 polyunsaturated fatty acid deficiency in guinea pigs. METHODS: Dunkin-Hartley guinea pigs were fed for 16 weeks after weaning with diets supplemented with safflower seed oil (n-3 deficient) or canola oil (n-3 sufficient, control). A number of deficient animals were repleted at 6 weeks with canola oil for 5 or 10 weeks, or at 11 weeks for 5 weeks. Electroretinograms (0.8 and 4.3 log scot td x sec) were collected at 6, 11, and 16 weeks after weaning. Conventional waveforms (a- and b-waves), oscillatory potentials, and receptoral and postreceptoral subcomponents (PIII and PII, respectively) were evaluated. Cone pathway function was assessed with 30-Hz flicker at the brighter intensity. Retinal phospholipid fatty acids were measured by capillary gas-liquid chromatography. RESULTS: Electroretinographic amplitudes showed statistically significant losses in b- and a-waves after 6 and 16 weeks of dietary n-3 deficiency, respectively. The response amplitude to 30-Hz flicker was reduced 42% after 16 weeks. Retinal docosahexaenoic acid (DHA) levels of animals maintained on the safflower oil diet for 16 weeks were 42% of levels in age-matched control subjects. There were significant losses in maximum response amplitudes (R(mPIII) and R(mPII)), although the major effect was a reduction in sensitivity of the receptoral response. Complete functional recovery was observed only in animals repleted for 10 weeks. CONCLUSIONS: Functional deficits in PIII and PII of the electroretinogram were apparent in first-generation guinea pigs fed an n-3 deficient diet. These losses showed a correlation with age and retinal DHA level, although varying degrees of dependence on the DHA level were found. All functional deficits were reversed after 10 weeks of dietary n-3 repletion. The results suggest that DHA may serve several functional and structural roles in the retina and further emphasize the requirement for DHA in the normal development of vision.  相似文献   

6.
The mutant of CYP2D6*3 allele with A2637 deletion in exon 5 and the mutant of CYP2D6*4 allele G1934-->A, splice site defect are among the most common polymorphic alleles of CYP2D6 gene, resulting in a decreased or no activity of CYP isoenzyme. In this study, a reliable polymerase chain reaction-restriction fragment length polymorphism method for identification of CYP2D6*3 and CYP2D6*4 alleles was used to investigate the genotype and phenotype prevalence in the groups of normal controls, and of cirrhosis and cancer patients. The results showed none of 36 controls genotyped for 2D6*3 and 2D6*4 allele to have the 2D6*3 allele with frameshift mutation in exon 5, while 33% (n=12) were found to bear the 2D6*4 allele with G to A mutation at the intron 3-exon 4 junction. In breast cancer patients (n=35) genotyped for 2D6*3 and 2D6*4 alleles, none with 2D6*3 allele was found either, but 60% (n=18) were found to bear the 2D6*4 allele. In patients with head and neck squamous cell cancer, there was only one subject with 2D6*3 allele and he was heterozygous. Among them, as many as ten (40%) patients were found to bear 2D6*4 allele. In the cirrhosis group, none of the patients was found to have the 2D6*3 allele, while the CYP2D6*4 allele was found in 23% (n=6) patients. The phenotype predicted according to the genotype was as follows: in the control group, 3% of individuals were identified as poor metabolizers, 70% as extensive metabolizers, and 27% as heterozygote extensive metabolizers. In the group of breast cancer, 7% of the patients were identified as poor metabolizer, 57% as extensive metabolizer and 36% as phenotype. In squamous cell cancer and cirrhosis patients, the incidence of poor metabolizer was zero, and of heterozygotes extensive metabolizer 42% and 31%, respectively.  相似文献   

7.
The p450 hepatic microsomal enzyme system metabolizes exogenous drugs and carcinogens. Debrisoquine hydroxylase (CYP2D6), one member of the p450 hemoproteins, has polymorphic expression leading to poor metabolism of debrisoquine and similar compounds in approximately 7% of Caucasians. The genetic locus for this enzyme has been characterized, and the mutations responsible for the slowed metabolism have been identified. Epidemiological studies of the CYP2D6 phenotype suggest an association between the normal or rapid metabolism phenotype and increased risk of lung and bladder cancer. Preliminary data have also suggested an association with prostate cancer (CaP). We used a PCR-based assay to investigate possible associations between the CYP2D6 B allele, the most common genetic mutation responsible for the poor metabolism phenotype, and CaP. Using genomic DNA isolated from peripheral blood, we genetically typed 571 men with CaP and 767 matched controls, all participants in the Physician's Health Study. Relative to men homozygous for the wild-type allele, heterozygotes for the B allele have an odds ratio of 1.19 (95% confidence interval, 0.94-1.51) for CaP, and men homozygous for the B allele have an odds ratio of 1.37 (95% confidence interval, 0.86-2.20). When analyzed as a trend over zero, one, or two copies of the B allele, there emerges a possible association between the B allele and an increased risk of CaP of borderline statistical significance (P = 0.07).  相似文献   

8.
OBJECTIVE: To determine trends in gang homicides and the population at greatest risk for homicide by reviewing all gang-related homicides in Los Angeles County, California, from January 1979 to December 1994. DESIGN: Homicide files of the Los Angeles Police Department and the Los Angeles County Sheriff's Department from 1979 to 1994 involving violent street gang activity were reviewed. Gang files were reviewed for demographic data, weapons used, homicides by drive-by shootings, and times and geographic areas of occurrence. SETTING: Los Angeles County from January 1, 1979, to December 31, 1994. MAIN OUTCOME MEASURES: Age, race, and sex of gang-related homicide victims; frequency of weapon use; and the change in gang-related homicide rates during the study period. RESULTS: A total of 7288 gang-related homicides occurred in Los Angeles County from 1979 through 1994; 5541 of these homicides occurred in Los Angeles Police Department and Los Angeles County Sheriff's Department jurisdictions. During the study period, the proportion of all homicides that were gang related increased from 18.1% to 43.0% (P < .001). Of the 5541 gang-related homicide victims, 4580 (85.6%) were aged 15 to 34 years, 93.3% were African American or Hispanic, 5157 (93.2%) were male, 3559 (64.2%) were gang members, and 1408 (25.4%) occurred during drive-by shootings. Firearms were used in an increasing proportion of homicides, from 71.4% in 1979 to 94.5% in 1994. Homicides by semiautomatic handguns dramatically increased during the study period. Gang-related homicide rates for African-American males aged 15 to 19 years increased from 60.50 per 100,000 population per year in 1979 to 1981 to 192.41 per 100,000 population per year in 1989 to 1991. CONCLUSIONS: Gang-related homicides in Los Angeles County have reached epidemic proportions and are a major public health problem. To prevent gang violence, the root causes of violent street gang formation must be alleviated, the cycle of violent street gang involvement must be broken, and access to firearms must be limited.  相似文献   

9.
BACKGROUND: Metabolic drug-drug interactions can occur between drugs that are substrates or inhibitors of the same cytochrome P450 (CYP) isoenzymes, but can be prevented by knowing which isoenzymes are primarily responsible for a drug's metabolism. m-Chlorophenylpiperazine (mCPP) is a psychopharmacologically active metabolite of four different psychiatric drugs. The present experiments were designed to identify the CYP isoenzymes involved in the metabolism of mCPP to its main metabolite p-hydroxy-mCPP (OH-mCPP). METHODS: The rate of production of OH-mCPP from mCPP was correlated with isoform activities in a panel of human liver microsomes, was assessed using a panel of individual complementary DNA-expressed human CYP isoenzymes, and was investigated in the presence of a specific inhibitor of CYP2D6. RESULTS: OH-mCPP production correlated significantly with CYP2D6 activity in human liver microsomes. Furthermore, incubations with microsomes from cells expressing CYP2D6 resulted in OH-mCPP formation, whereas no mCPP was formed from incubations with microsomes from cells expressing other individual isoforms. Finally, when the specific CYP2D6 inhibitor quinidine was preincubated with either human liver microsomes or cells expressing human CYP2D6, there was a concentration-dependent decrease in the production of OH-mCPP. CONCLUSIONS: These results confirm that CYP2D6 is the isoform responsible for the p-hydroxylation of mCPP, and indicate that caution should be exercised in coprescribing inhibitors or substrates of CYP2D6 with drugs that have mCPP as a metabolite.  相似文献   

10.
OBJECTIVES: The combination of carboplatin, methotrexate and vinblastine (M-CAVI) is an active and well-tolerated regimen for patients with bladder cancer who are ineligible for cisplatin-based regimens. We have prospectively randomized patients with locally advanced (T2-4 N0 M0) or locoregional (Tx N1 M0) bladder cancer suitable for subsequent surgical treatment to M-VAC or M-CAVI chemotherapy. METHODS: M-CAVI consisted of carboplatin (300 mg/m2 on day 1 and later adjusted to 4.5 mg/dl/min according to Calvert's formula), methotrexate (30 mg/m2 on days 1, 15 and 22) and vinblastine (3 mg/m2 on days 1, 15 and 22). After 3-4 cycles, the patients were assessed for surgical resection. RESULTS: To date, 60 patients have been included. There were 58 completely evaluable patients, 27 were randomized to M-VAC and 31 to M-CAVI. The overall response rates were similar for M-VAC (48%; confidence interval 95%, 26%-67%) and M-CAVI (45%; confidence interval 95%, 28%-62%). The pathological complete responses were similar for the M-VAC and M-CAVI regimens for both the group with locally advanced (27% vs 39%, p = NS) and locoregional (14% vs 14%, p = NS) bladder cancer. The median actuarial survival for the M-VAC treated group was 23 months and 18 months for the M-CAVI. M-VAC therapy was statistically significantly associated with more events of granulocytopenic fever, grade 2-3 nausea and vomiting, grade 2 alopecia and grade 3-4 mucositis. CONCLUSIONS: The results achieved in the 60 patients included in the study indicate that M-CAVI is better tolerated than M-VAC, although both treatment regimens have similar overall response rates, pathological response rates and survival in patients with locally advanced and locoregional bladder cancer.  相似文献   

11.
Parkinsonism-dementia complex (PDC), a neurodegenerative disorder in the Chamorro, Guam population, has been epidemiologically ascribed to the ingestion of the neurotoxin cycasin. This disease is characterized neuropathologically by the presence of abundant neurofibrillary tangles (NFTs). We analyzed a genetic risk factor of Alzheimer's disease (AD), apolipoprotein E, hypothesized to be linked to NFT formation, and a genetic risk factor of Parkinson's disease (PD), CYP2D6 mutation, linked to slower metabolism of exogenous toxins, in Chamorro, Guam individuals with and without PDC. The representation of the G-to-C mutation in exon 9 of the CYP2D6 gene was higher in Chamorro and Filipino than in Caucasian individuals, but this mutant allele had similar high frequencies in both PDC patients and healthy Chamorro individuals. We found no alleles of these genes associated with AD or PD to be overrepresented among those with PDC.  相似文献   

12.
OBJECTIVE: To determine the proportion of Los Angeles County (LAC) hospitals offering obstetrical services that have postpartum and postabortion rubella vaccination policies. DESIGN: A survey was sent to the infection control practitioners (ICPs) of all operational acute care hospitals (N = 133) in LAC in 1992. A remainder and second survey was mailed to ICPs who did not respond to the first mailing. RESULTS: Of 75 hospitals with obstetrical departments, 56 (75%) responded. Thirty-four (61%) of the 56 respondent hospitals had post-partum rubella vaccination policies. Of the 34 hospitals with policies, 30 (88%) accepted only a written record of rubella seropositivity as proof of immunity, 30 (88%) screened women with unknown immunity status before hospital discharge, and 32 (94%) vaccinated susceptible women before hospital discharge. Of the 32 hospitals that performed induced abortions, only two (6%) provided screening and vaccination services for these women. CONCLUSION: Only 61% of hospitals in LAC offering obstetrical services had postpartum rubella vaccination policies while only minimal screening and vaccination occurred in association with abortion services. Widespread implementation of postabortion screening and vaccination, and more stringent compliance with Advisory Committee on Immunization Practices recommendations for postpartum screening and vaccination in hospitals offering obstetrical services would reduce the number of rubella-susceptible women who have been missed by other prevention strategies.  相似文献   

13.
BACKGROUND: Esophageal perforation is one of the most dreaded complications in therapeutic gastrointestinal endoscopy. We assessed the frequency of esophageal perforation after endoscopic procedures in a highly specialized endoscopy unit and compared clinical outcomes in patients undergoing either surgical or conservative management. METHODS: From January 1985 to June 1996, 1011 instrumental endoscopic procedures (dilatation and bougienage) were performed in our department. The computerized complication database was searched to identify all patients with esophageal perforation during this same period, and their records were reviewed. RESULTS: Seventeen esophageal perforations (1.7%) occurred in the course of 1011 procedures. Four perforations resulted from balloon dilatation, and 13 were secondary to bougienage. Six patients were managed surgically (35%), all of them recovering uneventfully. Eleven patients were managed conservatively, mainly because they were unfit for surgery. Survival rate in this group was 82%; only two patients died, both of whom had underlying malignant disease. CONCLUSIONS: The current concept in management of esophageal perforations comprises surgical as well as medical treatment. In well-selected cases, non-operative treatment can be considered with favorable results.  相似文献   

14.
Parkinson's disease (PD) is thought to develop as a result of interactions between genetic susceptibility factors and environmental exposures. One candidate gene is CYP2D6, which codes for the debrisoquine 4-hydroxylase cytochrome P450. Impairment of debrisoquine 4-hydroxylase activity has been associated with an increased risk of PD in patients with younger age at disease onset. Genotyping studies in patients with an older age at onset have reported modest increases in risk associated with the CYP2D6 B and A alleles; however, the risk for young-onset PD has not been adequately evaluated. We designed a case-control study to investigate the role of nonfunctional CYP2D6 allelic risk factors for young-onset PD in a sizable patient population and compared the distributions of CYP2D6 genotypes between young-onset ( < or = 51 years) PD patients (n = 108) and controls (n = 236). In contrast with the results from genotyping studies conducted among patients with an older age at onset, there were no significant differences in CYP2D6 allelic frequencies between young-onset PD cases and controls. The frequency of the B allele was slightly lower in the young-onset PD cases than in the controls (0.14 versus 0.20) (X2 = 2.66, p = 0.10). The presence of one or more B alleles was not associated with an increased risk of young-onset PD (odds ratio 0.58; 95% CI 0.33 to 1.00), nor was the presence of one or more nonfunctional alleles (i.e., A, B, D, and D2) (odds ratio 0.68; 95% CI 0.41 to 1.13). This study suggests that the young-onset PD population may differ from the older-onset population with respect to risk factors.  相似文献   

15.
We investigated genetic polymorphism of the cytochrome P450 CYP 2D6 gene in 105 caucasian patients with idiopathic Parkinson's disease (IPD) and 15 patients with diffuse Lewy body disease (DLBD). The mutations of the CYP 2D6 gene associated with the poor metabolizer (PM) phenotype of the debrisoquine/sparteine polymorphism were analyzed in DNA by a polymerase chain reaction (PCR)-based DNA amplification combined with Xba I restriction fragment length polymorphism (RFLP) analysis. The rate of genotypically defined PM and the frequencies of the mutation D6-B were not significantly different in IPD and DLBD patients. This study fails to find a relationship between CYP 2D6 impairment and neuropathological lesions diffusion in IPD and DLBD. This study cannot exclude involvement of neuronal expression of CYP 2D6.  相似文献   

16.
This prospective, double-blinded evaluation of 24 osteoarthritic patients undergoing bilateral total knee replacement compared the midvastus and standard parapatellar approaches. The midvastus approach was found to offer an early advantage in terms of less pain and earlier return to function. There were no significant complications associated with the midvastus approach. This approach should be a part of the knee surgeon's armamentarium.  相似文献   

17.
Racial/ethnic and socioeconomic disparities in the prevalence of childhood asthma have been reported nationally but few population-based studies in local and regional settings have been reported. To assess variation in the prevalence of childhood asthma and associated morbidity across race/ethnic and income groups in the Los Angeles County population, we analyzed data on a random sample of 6004 children (< or = 17 years old) enrolled in a countywide health survey from September 1999 through April 2000. The prevalence of childhood asthma was highest in blacks (15.8%), intermediate in whites (7.3%) and Asians (6.0%), and lowest in Latinos (3.9%; p < 0.001). These differences persisted after controlling for income, measures of health care access, and other covariates. Asthma prevalence was inversely related to income in all racial/ethnic groups except Latinos from Spanish-speaking households. Among children with asthma, blacks and Latinos were more likely than whites to report asthma-related limitations in physical activity and need for urgent medical services. These findings indicate marked disparities in asthma prevalence and related morbidity in this large urban child population and highlight the importance of efforts to identify high-risk subpopulations for focused prevention and treatment interventions.  相似文献   

18.
OBJECTIVES: We sought to determine whether a natural disaster affected total cardiovascular mortality and coronary mortality in an entire population. BACKGROUND: The effect of the January 17, 1994 Northridge Earthquake (NEQ) on all deaths and causes of deaths within the entire population of Los Angeles County is unknown. The purposes of our study were to analyze all deaths in this entire population before, during and after the NEQ and to determine whether the NEQ temporally and spatially altered death due to cardiovascular disease. METHODS: We analyzed all death certificate data (n = 19,617) from Los Angeles County during January of 1992, 1993 (control periods) and 1994, using International Classification of Diseases, 9th Revision codes for ischemic heart disease (IHD) and atherosclerotic cardiovascular disease (ASCVD), as well as other causes of death. RESULTS: There was an average of 73 deaths per day due to IHD and ASCVD during January 1 to 16, 1994; this increased to 125 on the day of the NEQ, and then decreased to 57 deaths per day from January 18 to 31 (p < 0.00001, before NEQ vs. day of NEQ; after NEQ vs. day of NEQ; and before NEQ vs. after NEQ). The NEQ was associated with an increase in deaths due to myocardial infarction and trauma but not cardiomyopathy, hypertensive heart disease, valvular heart disease, cerebrovascular disease or noncardiovascular causes. Based on plots of daily deaths due to IHD and ASCVD, the decrease in deaths during the 14 days after the NEQ (-144) overcompensated for the increase on the day of the NEQ (+55). Geographic analysis revealed a redistribution of deaths due to IHD and ASCVD toward the epicenter on the day of the NEQ. CONCLUSIONS: When an entire population simultaneously experiences a major environmental stress, there is an increase in death due to coronary artery disease (but not other cardiac causes), followed by a decrease that overcompensates for the excess of death. The overcompensation may represent a residual population that is more resistant to stress or a possible preconditioning effect of the stress, or both. This study supports the concept that cardiovascular events within an entire population can be triggered by a shared stress.  相似文献   

19.
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.  相似文献   

20.
The impact of the 1992 Los Angeles (LA) civil disturbances on psychosocial functioning was assessed as part of a larger project investigating the views and attitudes of residents in LA County. Random digit dialing methodology identified a household probability sample of 1,200 adults (age 18 or older) from LA County. Respondents completed a telephone interview 6 to 8 months after the disturbances. Respondents' degree of exposure to the disturbances, mental health impact of the disturbances, and mental health effects of chronic versus acute exposure to violence were assessed. Consistent with hypotheses, the impact of the disturbances was the worst in the South Central communities. Higher rates of posttraumatic stress disorder (PTSD) (both diagnostic level and subclinical symptomatology) were found among respondents who reported disturbance-related experiences. Exposure to an acute event (i.e., the disturbances) was predictive of current PTSD symptomatology after controlling for demographics, lifetime trauma, and other types of stressful events. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

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