Autistic disorder: a review for the pediatric dentist

A combined analysis of two polymorphic enzymes, glutathione S-transferase mu (GST M1) and q (GST T1) and their implication as cancer risk factors was performed in a case-control study of lung and bladder cancers. Using a multiplex polymerase chain reaction (PCR) based method, the frequency of the homozygous deleted GSTM1 and GSTT1 genotypes was examined in 117 lung cancer patients, 67 urinary bladder cancer patients, and in a community-based sample of 248 healthy, unrelated individuals. In both cancer groups the frequency of the GSTM1 null genotype was higher in comparison with that of the control group (59% and 59.7% vs. 49.6%), but this increase did not reach statistical significance (p > 0.05). After grouping by the smoking status, among smokers in both cancer groups (62.1% in lung cancer and 71.4% in the bladder cancer group, respectively) there were statistically significantly (p < 0.05) increased frequencies of the GSTM1 deletion genotype as compared to the control group (49.6%). Smokers with absence of the GSTM1 gene were at an approximately 1.7-fold higher risk for lung cancer (odds ratio--OR = 1.67, 95% confidence interval--CI 95% = 1.0-2.7, p = 0.04) and an approximately 2.5-fold higher risk for bladder cancer (OR = 2.54, CI 95% = 1.2-5.5, p = 0.02). As related to GSTT1, our study demonstrated an overall GSTT1 effect on bladder cancer risk. Individuals with absence of the GSTT1 gene were at an approximately 2.5-fold higher risk of developing bladder cancer. In the lung cancer cases, the frequency of the putatively high risk GSTT1 null genotype was not increased as compared with controls. No effect of smoking was found on risk of lung and bladder cancer associated with the GSTT1 0/0 genotype. In combined analysis, the obtained results suggested that individuals who were both GSTM1 null and GSTT1 null may be at increased risk because they lack both enzymes. The findings suggest that the GSTM1 null genotype may be associated with susceptibility to lung and urinary bladder cancer in dependence on the exposure to carcinogens in cigarette smoke and that the GSTT1 null genotype is not a critical factor in mediating the risk of lung cancer, but may be associated with an increased susceptibility to bladder cancer.     

Glutathione S-transferase M1 and T1 and cytochrome P4501A1 polymorphisms in relation to the risk for benign and malignant head and neck lesions

BACKGROUND: Susceptibility to head and neck cancer in a particular individual may depend in part on the metabolic balance between Phase 1 enzymes, such as cytochromes P450 (CYPs), and Phase II enzymes, such as glutathione S-transferases (GSTs). Genetic variability in CYP and GST isoenzymes may contribute to individual differences in susceptibility to chemical carcinogenesis. GSTM1 and GSTT1 null genotypes as well as polymorphic variants in the CYP1A1 gene that may help determine the risk for head and neck cancer have been described in previous reports. METHODS: Polymorphisms of GSTM1, GSTT1, and CYP1A1 in whole blood were detected by polymerase chain reaction (PCR) in 185 patients with head and neck squamous cell carcinoma (HNSCC), 78 patients with benign head and neck lesions (BHNL), and 207 blood donors. RESULTS: GSTM1 null genotype was demonstrated to be equally frequent in patients with HNSCC (50.8%), patients with BHNL (47.4%), and blood donors (51.7%). GSTT1 null genotype occurred significantly more often in patients with BHNL (33.3%) as compared with blood donors (20.3%), demonstrating that lack of GSTT1 may be a risk factor for BHNL. Presence of the rare valine in the CYP1A1/Nco1 site was found in 33 patients with HNSCC (17.8%), in 20 patients with BHNL (25.6%), and in 34 blood donors (16.4%). The frequencies with which the presence of the rare cytosine nucleotide in the CYP1A1/Msp1 site was detected were 17.8%, 15.4%, and 15.9%, respectively. CONCLUSIONS: The occurrence of polymorphic variants in the GSTM1, GSTT1, and CYP1A1 genes did not differ between the groups investigated, therefore indicating no significant contribution to the development of head and neck cancer.     

Gamma-heavy chain disease associated with MALT lymphoma of the duodenum

BACKGROUND: Glutathione S-transferases (GSTs) are encoded by a superfamily of genes and play a role in the detoxification of potential carcinogens. In a nested case-control study, we investigated associations between genetic variability in specific GST genes (GSTM1, GSTT1, and GSTP1) and susceptibility to breast cancer. METHODS: In 1989, a total of 32 898 individuals donated blood samples to a research specimen bank established in Washington County, MD. Genotypes of blood specimen DNA were determined for 110 of 115 women with incident cases of breast cancer diagnosed during the period from 1990 through 1995 and up to 113 of 115 control subjects. Associations between specific genotypes and the development of breast cancer were examined by use of logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The GSTM1 homozygous null genotype was associated with an increased risk of developing breast cancer (OR = 2.10; 95% CI = 1.22-3.64), principally due to an association with postmenopausal breast cancer (OR = 2.50; 95% CI = 1.34-4.65). For GSTP1, the data were suggestive of a trend of increasing risk with higher numbers of codon 105 valine alleles (compared with isoleucine alleles); a 1.97-fold increased risk of breast cancer (95% CI = 0.77-5.02) was associated with valine/valine homozygosity. The risk of breast cancer associated with the GSTT1 homozygous null genotype was 1.50 (95 % CI = 0.76-2.95). The risk of breast cancer increased as the number of putative high-risk genotypes increased (P for trend <.001) (OR = 3.77; 95% CI = 1.10-12.88 for a combined genotype of GSTM1 null, GSTT1 null, and either GSTP1 valine heterozygosity or GSTP1 valine homozygosity). CONCLUSIONS: Our findings suggest that genetic variability in members of the GST gene family may be associated with an increased susceptibility to breast cancer.     

Association of glutathione S-transferase GSTM1 and GSTT1 null genotypes with clinical outcome in epithelial ovarian cancer

Epithelial ovarian cancer is generally associated with a poor outcome, although the mechanisms that determine survival and progression-free interval (PFI) are unclear. Data from ovarian tumors showing associations between (a) null genotypes at the glutathione S-transferase GSTM1 and GSTT1 loci and expression of p53 protein and (b) outcome and expression of p53 suggest that polymorphism at these loci is a factor determining outcome. Accordingly, we have studied the association between the GSTM1 null and GSTT1 null genotypes and survival and PFI in 148 women with epithelial ovarian cancer. Although we did not find an association between individual genotypes and outcome, women with both GSTM1 null and GSTT1 null genotypes demonstrated poorer survival (P = 0.001) and reduced PFI (P = 0.003). Thus, no cases with both these genotypes survived past 42 months postdiagnosis. In contrast, 43% of the women without this combination survived beyond this time. Because response to chemotherapy is a major factor determining outcome in ovarian cancer, we also examined the data for associations between the glutathione S-transferase genotypes and response to such treatment. Thus, in 78 patients treated with chemotherapy, the combination of GSTM1 null and GSTT1 null was associated with unresponsiveness to primary chemotherapy (P = 0.004); none of the eight patients with both these genotypes responded, compared with 38 of 70 (54%) of patients with other genotype combinations. The effect of the combination of genotypes on survival and PFI was lost in a multivariate model that included response to chemotherapy as a confounding factor. This suggests that the combination of GSTM1 null/GSTT1 null is associated with outcome because of its influence on response to chemotherapy. These preliminary findings may provide a basis for the selection of patients for treatment with chemotherapeutic agents.     

Polymorphic expression of the glutathione S-transferase P1 gene and its susceptibility to Barrett's esophagus and esophageal carcinoma

Factors determining individual susceptibility to esophageal cancer or premalignant Barrett's epithelium are still largely unclear. An imbalance between phase I drug metabolism [e.g., cytochrome P450 (CYP)] and phase II detoxification [e.g., glutathione S-transferase (GST)] may contribute to the development of these diseases. Polymorphic variants in the CYP1A1 gene were described leading to increased levels of bioactive compounds, whereas polymorphisms in GST genes often resulted in impaired detoxification. We studied the frequencies of polymorphic variants in CYP1A1, GSTP1, GSTT1, and GSTM1 genes in 98 patients with Barrett's epithelium and 34 patients with esophageal cancer. The results were compared with those obtained from 247 healthy blood donors. DNA was extracted, and PCR-RFLP methods were used to detect genetic polymorphisms. Chi2 analysis, Spearman rank correlation, and Wilcoxon rank sum tests were used for statistical evaluation. Polymorphisms in CYP1A1, GSTM1, and GSTT1 occurred at an equal frequency in patients and controls. Occurrence of the polymorphic GSTP1b variant in the GSTP1 gene resulted in a significantly lower GST enzyme activity (P < 0.05), and GSTP1b was found significantly more often in patients with Barrett's epithelium (70%; P < 0.001) and patients with esophageal adenocarcinoma (76%; P = 0.005), as compared to healthy blood donors (41%). In conclusion, presence of the GSTP1b allele leads to lower GST enzyme activity levels and, consequently, impaired detoxification. This most important esophageal GST isoform may, therefore, contribute to the development of Barrett's epithelium and adenocarcinoma.     

Individual sensitivity to cytogenetic effects of 1,2:3,4-diepoxybutane in cultured human lymphocytes: influence of glutathione S-transferase M1, P1 and T1 genotypes

Although some blood parameters have been suggested to modulate in-vitro induction of sister chromatid exchanges by 1,2:3,4-diepoxybutane (DEB), a metabolite of 1,3-butadiene, the increased sensitivity has largely been assigned to a homozygous deletion of glutathione S-transferase T1 gene (GSTT1 null genotype). However, some DEB-sensitive individuals have been shown to be GSTT1 positive (having at least one undeleted GSTT1 allele). To examine potential causes for this overlap, we evaluated the effect of GSTM1, GSTP1, and GSTT1 genotypes, together with various life-style and blood parameters, on the DEB induction of sister chromatid exchanges and cells with chromosomal aberrations (aberrant cells) in lymphocyte cultures of 115 and 62 human donors, respectively. Our results supported the important role of the GSTT1 genotype in DEB sensitivity; 76% of cultures from GSTT1 null donors but only 4% of those from GSTT1 positive donors were DEB-sensitive, as defined by sister chromatid exchange measurements. The GSTT1 genotype also clearly affected DEB-induced aberrant cells, 92% of GSTT1 null and 8% of GSTT1 positive donors being sensitive to DEB. All individuals showing a high response to DEB in both sister chromatid exchange and aberrant cell analyses were GSTT1 null. Baseline aberrant cell measurements but not sister chromatid exchange measurements were marginally higher among GSTT1 null donors compared with GSTT1 positive donors. GSTM1 and GSTP1 genotypes had no influence on these cytogenetic end-points. Blood transaminases, gamma-glutamyl transferase, urea, creatinine and white blood cell count showed a clear negative association with DEB-induced aberrant cells, whereas wine drinkers had more aberrant cells than non-drinkers. A higher sister chromatid exchange-response to DEB was observed in lymphocytes from women and smokers than from men and non-smokers, respectively. Erythrocyte count correlated negatively with DEB-induced sister chromatid exchanges. Thus, a variety of parameters seemed to modulate the individual DEB-sensitivity together with the GSTT1 genotype. Although the known contributing factors accounted for a considerable part of individual variability in sister chromatid exchanges (59.4%) and aberrant cells (46.7%) in DEB treatment, they did not, however, fully explain the overlap in cytogenetic response between GSTT1 positive and null individuals.     

Control of biologic hazards

Spontaneous and diepoxybutane (DEB)-induced sister-chromatid exchanges (SCEs) were examined in whole-blood lymphocyte cultures of 3 men and 4 women. A strong increase in mean number of SCEs per cell with increasing DEB concentrations (0, 2, and 4 microM) was observed in cultures of all subjects, but 3 of the donors were clearly more sensitive than the others. The SCE measurements were repeated 2-6 times per donor over a period of 55 months to assess the stability of the individual SCE response. The results showed that SCE induction by DEB was steady in the individuals during the follow-up at each DEB dose, with no significant differences among the repeated experiments. At 4 microM DEB, the DEB-sensitive and -resistant donors could be reliably be differentiated from each other in all trials. As DEB-sensitivity has been suggested to be due to the lack of glutathione S-transferase (GST) T1, the donors were genotyped for the presence of GSTT1 and GSTM1 genes. The 3 individuals found to be DEB-sensitive were all of the GSTT1 null genotype, whereas the 4 DEB-resistant donors were GSTT1 positive, which supported the role of the GSTT1 gene in determining DEB-sensitivity. Three of the DEB-resistant and none of the DEB-sensitive had the GSTM1 null genotype. Thus, the lack of the GSTM1 gene was not associated with the DEB-sensitivity trait. In conclusion, the present findings show that individual SCE responses to treatment of cultured human lymphocytes with DEB can reliably be reproduced in repeated trials. The results confirm that the GSTT1 gene but not the GSTM1 gene is important in determining individual sensitivity to the in vitro genotoxicity of DEB.     

Genetic polymorphisms in carcinogen metabolism and their association to hereditary nonpolyposis colon cancer

BACKGROUND & AIMS: The phenotype of hereditary nonpolyposis colorectal cancer shows interfamilial and intrafamilial variation even in the presence of identical predisposing mutations, suggesting the existence of additional phenotype determinants. The modifying role of genetic polymorphisms in loci involved in carcinogen metabolism was studied. METHODS: We focused on colon cancers from kindreds sharing one of two predisposing mutations (mutation 1 or 2) in the mismatch repair gene MLH1 (78 and 14 tumors, respectively). Polymorphisms in N-acetyltransferase 1 (NAT1) and glutathione S-transferase (GST) M1 and GSTT1 were investigated. RESULTS: The NAT1 allele 10 was associated with lower median age at diagnosis in both groups. In mutation 1 group, the NAT1 allele 10 was a risk factor for distal tumor location, both alone (P = 0.028) and combined with the GSTT1-positive genotype (P = 0.008). On the other hand, the combined null genotype of GSTM1 and GSTT1 was associated with proximal tumors. Associations with tumor location were not observed in patients with mutation 2, probably reflecting a small sample size. CONCLUSIONS: The results suggest that genetic polymorphisms in carcinogen metabolism modify the age of onset and tumor location in individuals with inherited deficiency of DNA mismatch repair.     

Effect of race on outcome after kidney and kidney-pancreas transplantation in type 1 diabetic patients

OBJECTIVE: The racial impact on graft outcome is not well defined in diabetic recipients. The purpose of this study is to analyze our experience with kidney-alone (A) and kidney-pancreas (KP) transplantation in type 1 diabetic recipients and evaluate the impact of racial disparity on outcome. RESEARCH DESIGN AND METHODS: The records of 217 kidney transplants (118 KA, 99 KP) performed on type 1 diabetic patients between 1985 and 1995 at the Medical University of South Carolina and the University of Texas Medical Branch were reviewed. RESULTS: A total of 53 (31%) white patients and 15 (33%) black patients experienced at least one episode of biopsy-proven acute rejection of the renal graft (NS). Patient survival at 1, 2, and 5 years was similar in white (92, 87, 69%) and black (91, 91, 69%) patients (NS). Kidney graft survival at 1, 2, and 5 years in the KA group was 72, 62, and 42% in blacks, compared with 79, 76, and 53% in whites (NS). Kidney graft survival at 1, 2, and 5 years in the KP group was 92, 92, and 74% in blacks, compared with 83, 77, and 58% in whites (NS). Pancreas graft survival at 1, 2, and 5 years was 81, 81, and 81% in blacks, compared with 81, 75, and 62% in whites (NS). Cox regression analysis revealed that donor age > or = 40 years increased the risk of renal graft failure 6.2-fold (P = 0.0001), whereas the addition of a pancreas transplant to a kidney and a living-related transplant decreased the risk of failure of the kidney graft 0.2 (P = 0.005) and 0.1 times (P = 0.005). CONCLUSIONS: Our results suggest that when compared with whites, there may be a trend toward an improved kidney and pancreas graft outcome in blacks undergoing KP transplants. These findings suggest that diabetes may override the risk factors that account for the pronounced disparity in outcome observed between nondiabetic white and black recipients.     

Immunoglobulin levels in psychiatric patients

In a study of 19 schizophrenic patients, 7 nonschizophrenic patients, and 31 controls, the authors found significantly higher mean serum levels of 1) immunoglobulin A in schizophrenic women then in control women and in schizophrenic blacks than in either schizophrenic whites or black controls. 2) immunoglobulin D in schizophrenic blacks than in schizophrenic whites, 3) immunoglobulin M in controls than in nonschizophrenic patients, and 4) immunoglobulin G (IgG) in schizophrenics whose urine was positive for phenothiazines than in schizophrenics whose urine was negative for phenothiazines. High serum levels of IgG were associated with no or mild hallucinations and low levels with moderate or severe hallucinations. Black female patients had significantly more severe hallucinaions than white female patients. The authors discuss the possible implications of these findings.     

Blacks supervising whites: A study of interracial difficulties in working together in a simulated organization.

Investigated interracial difficulties of blacks and whites working together, when blacks are in a supervisory position over whites. 45 groups of male undergraduates were supervised by blacks, and 45 were supervised by whites. In each group, 2 subordinates played a business game with either a black or a white supervisor and were observed by 2 white Os. Results indicate that (a) the performance ratings of black supervisors were significantly poorer than those of white supervisors; (b) subordinates supervised by blacks behaved differently than subordinates supervised by whites, and some of these behaviors appeared to hinder the effectiveness of the black supervisor; and (c) subordinates with negative racial bias gave poorer ratings to black supervisors than subordinates with liberal racial attitudes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Urinary total isothiocyanate (ITC) in a population-based sample of middle-aged and older Chinese in Singapore: relationship with dietary total ITC and glutathione S-transferase M1/T1/P1 genotypes

Isothiocyanates (ITCs), degradation products of glucosinolates (which occur naturally in a variety of cruciferous vegetables), have been shown to exhibit chemopreventive activity. These compounds are metabolized in vivo to form the corresponding dithiocarbamates, which are the major urinary metabolites of ITCs, by a pathway involving the glutathione S-transferase (GST) class of enzymes. Using a newly developed assay that measures total ITC (primarily ITC conjugates) in urine, we examined the relationships between cruciferous vegetable intake (obtained from a food frequency/portion size questionnaire administered in person); dietary total ITC level; GSTM1, GSTT1, and GSTP1 genotypes; and levels of total ITC in spot urine samples collected from 246 Singapore Chinese (111 men and 135 women), ages 45-74 years, who are participants of the Singapore Cohort Study on diet and cancer. Consumption level of cruciferous vegetables was high in study subjects (mean consumption = 345 times per year, mean daily intake = 40.6 g), which was >3 times the comparable level of intake in the United States. Mean daily intake of total ITC among study subjects was 9.1 micromol, and there was a 2.5-fold difference between the 25th and 75th percentile values. Seventy-three % of study subjects tested positive for ITC in urine, and there was a 4-fold difference between the 25th and 75th percentile values among the positive subjects. There was a highly significant positive association between dietary intake and urinary excretion levels of total ITC (two-sided P = 0.0003) that was stronger than the association between overall cruciferous vegetable intake and urinary ITC level, which also was statistically significant (P = 0.0004). There was no difference in urinary ITC levels between GSTM1-null and GSTM1-positive study subjects (P = 0.61) or between subjects with differing GSTP1 genotypes (P = 0.77), but urinary excretion of ITC was significantly higher among GSTT1-positive subjects, relative to GSTT1-null subjects (P = 0.006). The strength of the association between GSTT1 genotype and urinary total ITC level was highly dependent on the level of cruciferous vegetable consumption (or dietary ITC level) in study subjects. Among subjects in the lowest tertile of cruciferous vegetable intake, there was little evidence of an association between GSTT1 genotype and urinary total ITC level (P = 0.67). In contrast, there was a strong and statistically significant association between GSTT1 genotype and urinary total ITC among subjects in the highest tertile of cruciferous vegetable intake (P = 0.02), whereas those in the middle tertile of cruciferous vegetable consumption exhibited an association of intermediate strength (P = 0.04). These results suggest the presence of GSTT1 inducers in cruciferous vegetables.     

Racial disparity in the association of p53 gene alterations with breast cancer survival

A significant black/white difference in breast cancer prognosis has been observed in the United States. Alterations of p53 tumor suppressor gene in breast cancer have been associated with poor prognosis. This study was designed to test the hypothesis that p53 gene alterations are related to the difference in prognosis between black and white breast cancer patients. Formalin-fixed paraffin-embedded breast tissue blocks were available from 45 black and 47 white patients for PCR-single strand conformation polymorphism analysis and DNA sequencing. The types of p53 gene alterations were compared between blacks and whites. Associations between p53 gene alterations and survival were also evaluated. Three missense, 2 nonsense, 1 microdeletion, 1 intron, and 4 silent mutations were detected in blacks, while 7 missense, 1 microdeletion, 1 silent mutation, and 3 polymorphisms were observed in whites. Among the point mutations, G:C to A:T transitions at non-CpG sites were found in 80.0% of blacks (8 of 10) and 62.5% of whites (5 of 8). Significantly poorer survival associated with p53 gene alterations was observed for blacks (P = 0.012), but not for whites. Black patients with p53 alterations had a significant 4-5-fold excess risk of death from breast cancer than those without p53 alterations. Adjustment for stage, age, tumor histopathology, receptor status, and adjuvant treatment did not change the excess risk. The findings suggest that the types of p53 gene alterations may contribute to the racial difference in breast cancer survival.     

Trends in alcohol consumption patterns among whites, blacks and Hispanics: 1984 and 1995

OBJECTIVE: To report national trends in alcohol consumption patterns among whites, blacks and Hispanics between 1984 and 1995, in relation to the recent decline in per capita consumption in the United States. METHOD: Data were obtained from two nationwide probability samples of U.S. households, the first conducted in 1984 and the second in 1995. The 1984 sample consisted of 1,777 whites, 1,947 blacks and 1,453 Hispanics; the 1995 sample consisted of 1,636 whites, 1,582 blacks and 1,585 Hispanics. On both occasions, interviews averaging 1 hour in length were conducted in respondents' homes by trained interviewers. RESULTS: Between 1984 and 1995, the rate of abstention remained stable among whites but increased among blacks and Hispanics. Frequent heavy drinking decreased among white men (from 20% to 12%), but remained stable among black (15% in both surveys) and Hispanic men (17% and 18%). Frequent heavy drinking decreased among white women (from 5% to 2%), but remained stable among black (5% in both surveys) and Hispanic women (2% and 3%). White men and women were two times more likely to be frequent heavy drinkers in 1984 than in 1995. CONCLUSIONS: The reduction in per capita consumption in the U.S. is differentially influencing white, black and Hispanic ethnic groups. The stability of rates of frequent heavy drinking places blacks and Hispanics at a higher risk for problem development than whites. This finding is, therefore, a concern to public health professionals and others interested in the prevention of alcohol-related problems among ethnic groups in the United States.     

Ethnic differences in the hypertensive heart and 24-hour blood pressure profile

Black hypertensive persons have been observed to have a greater degree of left ventricular hypertrophy than white hypertensives. However, previous studies have matched groups for blood pressure (BP) measured in the clinic, and it has been demonstrated that black hypertensives have an attenuated nocturnal BP dip. Clinic BPs may thus underestimate mean 24-hour BP in this group. To investigate whether the differences in left ventricular hypertrophy can be accounted for by the greater mean 24-hour BP in black hypertensives, 92 previously untreated hypertensives were studied with 24-hour ambulatory BP monitoring and echocardiography. The 46 black hypertensives (24 men and 22 women) were matched with the 46 white hypertensives for age, gender, and mean 24-hour BP. Despite similar mean 24-hour BPs (blacks, 142/93 mm Hg; whites, 145/92 mm Hg; P=.53/.66), the black group had a smaller mean nocturnal dip than the white group (blacks, 8/8 mm Hg; whites, 16/13 mm Hg; P<.01). In addition, mean left ventricular mass index (LVMI) was greater (blacks, 130 g/m2; whites, 107 g/m2; P<.001). Mean 24-hour systolic BP was significantly related to LVMI in both groups (blacks, r=.45, P<.01; whites, r=.56, P<.01). However, systolic BP dip correlated inversely with LVMI only in the black group (blacks, r=-.30, P<.04; whites, r=.05, P=.76). In a multiple regression model, LVMI was independently related to both mean daytime BP and mean nocturnal BP dip in black subjects but only to mean daytime BP in white subjects. In conclusion, the increased left ventricular hypertrophy observed in black hypertensives compared with white hypertensives is not accounted for by differences in mean 24-hour BP. However, LVMI in black hypertensives appears to be more dependent on nocturnal BP than that in white hypertensives; this, coupled with the attenuated BP dip in black hypertensives, suggests that the BP profile rather than 24-hour BP may be important in determining the differences in left ventricular hypertrophy.     

Race-ethnic differences in stroke risk factors among hospitalized patients with cerebral infarction: the Northern Manhattan Stroke Study

African-Americans have an unexplained increased incidence and mortality from stroke compared with whites, and little is known about stroke in Hispanics. To investigate cross-sectional differences in sociodemographic and stroke risk factors, we prospectively evaluated 430 patients hospitalized for acute ischemic stroke (black 35%. Hispanic 46%, white 19%) over the age of 39 from Northern Manhattan. Blacks and Hispanics were younger than whites (mean ages, blacks 70, Hispanics 67, whites 80; p < 0.001) and were more likely to have less than 12 years of education than whites. Hypertension was more prevalent in blacks and Hispanics with stroke than whites (blacks 76%, Hispanics 79%, whites 63%; p < 0.05) and was often untreated in blacks. Left ventricular hypertrophy by ECG was more frequent in blacks (blacks 20%, whites 9%; p = 0.02). History of cardiac disease (atrial fibrillation, myocardial infarction, angina, and congestive heart failure) was less prevalent in both blacks and Hispanics. Black women were significantly more obese than white women (mean Quetelet Index percent, blacks 3.9%, whites 3.6%; p < 0.05). Heavy alcohol use was more often reported by blacks and Hispanics; cigarette smoking was increased only in blacks. Moreover, blacks were less likely to have visited a physician 1 year after their stroke (blacks 85%, whites 98%; p < 0.05), and Hispanics less often lived alone compared with whites. These cross-sectional differences suggest that the burden of stroke risk factors is increased in both blacks and Hispanics with stroke. Further studies controlling for stroke risk factors are needed to establish whether race-ethnicity is an independent determinant of stroke risk.     

Race specific altitude effects on blood pressure

Altitude affects blood pressure (BP) depending on duration and absolute altitude of exposure. Until now changes in BP during exposure to altitude were studied only in Caucasians. It is not known whether BP is affected differently in black and white people in response to altitude. During a 6-day climb on Kilimanjaro, BP was measured in five white and four black people. All participants (mean +/- s.d.: age 31 +/- 8 years, body mass index 22 +/- 2 kg/m2, BP 125 +/- 11/84 +/- 9 mm Hg) had previous similar experience of high-altitude mountaineering. In the base camp (3040 m) systolic BP (SBP) was similar in both groups (131 +/- 9 vs 119 +/- 8 mm Hg). During ascent until 4600 m SBP increased in all whites (6.5 +/- 2.2 mm Hg) and decreased in all blacks (-7.3 +/- 4.6 mm Hg; P = 0.02, blacks vs whites). During descent SBP returned to initial values in whites, whereas it decreased further in blacks. Diastolic BP (DBP) and heart rate remained constant in all participants. During ascent body weight increased in all whites (1.0 +/- 0.8 kg) and decreased in all blacks (-1.9 +/- 1.4 kg; P = 0.02, blacks vs whites) whereas it returned approximately to initial levels during descent: +0.8 +/- 0.4 kg in blacks and -1.0 +/- 1.3 kg in whites (P = 0.03, blacks vs whites). In this study changes in SBP and body weight during exposure to high altitudes varied between whites and blacks. Fluid balance, acclimatisation, physical fitness or genetics could explain these findings.     

Effects of different levels of integration on advertising preference and intention to purchase.

90 black and 90 white male undergraduates evaluated 6 proposed advertisements in terms of attractiveness and likelihood of purchase of the product advertised. The advertisements differed in the degree of racial integration depicted, which was operationally defined by a 5-point continuum ranging from 0 whites and 4 blacks (0W-4B) to 4 whites and 0 blacks (4W-0B). The hypothesis that young blacks react negatively to integrated ads depicting tokenism (e.g., 3 whites to 1 black) and positively to ads depicting equality (e.g., 2 whites to 2 blacks) was supported with each of the dependent measures. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comprehensive analysis of risk factors for acquisition of Pseudomonas aeruginosa in young children with cystic fibrosis

Racial differences in insulin secretion and insulin sensitivity in healthy children were studied by administering a 2-hour hyperglycemic clamp (225 mg/dL) to 14 black and 16 white healthy adolescents (Tanner II-V), and 12 black and 11 white prepubertal children, matched for age, body mass index, and Tanner I pubertal development. In prepubertal children, fasting and first-phase insulin concentrations were higher in blacks compared with whites (14.7+/-1.3 vs 10.4+/-1.2, P=0.02, and 76.9+/-6.8 vs 52.1+/-6.4 microu/mL, P=0.016). There were no differences in second-phase insulin levels and insulin sensitivity index. In pubertal adolescents, first-phase and second-phase insulin concentrations were higher in blacks compared with whites (first-phase: 157.3+/-18.3 vs 77.0+/-8.7 microu/mL, P=0.0003; second-phase: 175.0+/-24.3 vs 108.7+/-8.8 microu/mL, P=0.012). Insulin sensitivity index was 35% lower in black adolescents compared with whites (P=0.02). These findings indicate that significant differences in insulin secretion and sensitivity are detectable early in childhood in healthy African-American vs American whites. However, genetic (race) vs environmental factors (physical activity/fitness, energy balance) should be carefully scrutinized as potential factors responsible for such differences.     

Absence of the glutathione S-transferase M1 gene increases cytochrome P4501A2 activity among frequent consumers of cruciferous vegetables in a Caucasian population

The cancer protective effect of cruciferous vegetables has been attributed to induction of phase II enzymes. But cruciferous vegetables also induce cytochrome P4501A2 (CYP1A2), which catalyzes the metabolic activation of various procarcinogens, including aromatic amines in tobacco. Thus, frequent intake of cruciferous vegetables could also result in cancer-enhancing effects. GSTM1 is involved in the detoxification of various carcinogens, but it also enhances the excretion of isothiocyanates and possibly other enzyme inducers in cruciferous vegetables. We, therefore, hypothesized that GSTM1 null genotype might be associated with increased CYP1A2 activity among frequent consumers of cruciferous vegetables because the excretion of CYP1A2 inducers contained in these vegetables may be partially inhibited in the absence of the GSTM1 enzyme. Three hundred twenty-eight non-Hispanic white residents of Los Angeles County (265 males and 63 females) were genotyped for the presence or absence of GSTM1 alleles and phenotyped for CYP1A2 activity. Information on usual dietary habits was obtained from these subjects through in-person interviews. Among frequent (at least once a week) consumers of broccoli, GSTM1 null individuals exhibited a 21% higher geometric mean level of CYP1A2 activity relative to GSTM1 non-null individuals (5.24 versus 4.32, two-sided P = 0.01). No such difference was observed in subjects who consumed broccoli less frequently (two-sided P = 0.39). This interactive effect of GSTM1 genotype and vegetable intake on CYP1A2 activity also was observed when overall intake of the five cruciferous vegetables under study (broccoli, cabbage, cauliflower, Brussels sprouts, and mustard greens) was examined. Among weekly consumers of cruciferous vegetables, GSTM1 null individuals showed a 16% higher geometric mean level of CYP1A2 activity relative to GSTM1 non-null individuals (5.03 versus 4.33, two-sided P = 0.02), whereas no difference was evident among those who consumed cruciferous vegetables less frequently (two-sided P = 0.35). Our results suggest that cruciferous vegetables contain CYP1A2 inducers, which are deactivated in the presence of GSTM1.