Contributions of Ea(z) and Eb(z) MHC genes to lupus susceptibility in New Zealand mice

Membrane vesicles derived from external taste epithelia of channel catfish (Ictalurus punctatus) were incorporated into lipid bilayers on the tips of patch pipettes. Consistent with previous experiments (Teeter, J. H., J. G. Brand, and T. Kumazawa. 1990. Biophys. J. 58:253-259), micromolar (0.5-200 microM) concentrations of L-arginine (L-Arg), a potent taste stimulus for catfish, activated a nonselective cation conductance in some bilayers, which was antagonized by D-Arg. Two classes of L-Arg-gated receptor/channels were observed in reconstituted taste epithelial membranes: one with a unitary conductance of 40-60 pS, and the other with a conductance of 75-100 pS. A separate class of nonselective cation channels, with a conductance of 50-65 pS, was activated by high concentrations of L-proline (L-Pro) (0.1-3 mM), which is the range necessary to elicit neural responses in catfish taste fibers. The L-Pro-activated channels were not affected by either L- or D-Arg, but were blocked by millimolar concentrations of D-Pro. Conversely, neither L- nor D-Pro altered the activity of either class of L-Arg-activated channels, which were blocked by micromolar concentrations of D-Arg. These results are consistent with biochemical, neurophysiological, and behavioral studies indicating that taste responses of channel catfish to L-Arg are mediated by high-affinity receptors that are part of or closely coupled to nonselective cation channels directly gated by low concentrations of L-Arg, while responses to L-Pro are mediated by distinct, low-affinity receptors also associated with nonselective cation channels.     

Toward a (Dys)functional anthropology of drinking: ambivalence and the American Indian experience with alcohol

This article explores the complex and contradictory experiences of urban American Indian drinkers. While previous anthropological accounts have emphasized the functions served by American Indian drinking, the testimony of drinkers also documents their awareness of the destructive effects of heavy drinking, particularly the way in which it often interferes with their ability to meet social obligations. Nevertheless, people often continue to use alcohol, and this means that many are profoundly ambivalent about their drinking; they see it simultaneously as something that is embedded in certain important relationships, but also something that is destructive of much that they value. Drawing on interviews with 35 self-defined problem drinkers, this article details the ambiguous nature of the American Indian experience with alcohol, highlighting the need for a clinically sophisticated anthropology of alcohol.     

Y chromosome polymorphisms in native American and Siberian populations: identification of native American Y chromosome haplotypes

We have initiated a study of ancient male migrations from Siberia to the Americas using Y chromosome polymorphisms. The first polymorphism examined, a C-->T transition at nucleotide position 181 of the DYS199 locus, was previously reported only in Native American populations. To investigate the origin of this DYS199 polymorphism, we screened Y chromosomes from a number of Siberian, Asian, and Native American populations for this and other markers. This survey detected the T allele in all five Native American populations studied at an average frequency of 61%, and in two of nine native Siberian populations, the Siberian Eskimo (21%) and the Chukchi (17%). This finding suggested that the DYS199 T allele may have originated in Beringia and was then spread throughout the New World by the founding populations of the major subgroups of modern Native Americans. We further characterized Native American Y chromosome variation by analyzing two additional Y chromosome polymorphisms, the DYS287 Y Alu polymorphic (YAP) element insertion and a YAP-associated A-->G transition at DYS271, both commonly found in Africans. We found neither African allele associated with the DYS199 T allele in any of the Native American or native Siberian populations. However, we did find DYS287 YAP+ individuals who harbored the DYS199 C allele in one Native American population, the Mixe, and in one Asian group, the Tibetans. A correlation of these Y chromosome alleles in Native Americans with those of the DYS1 locus, as detected by the p49a/p49f (p49a,f) probes on TaqI-digested genomic DNA, revealed a complete association of DYS1 alleles (p49a,f haplotypes) 13, 18, 66, 67 and 69 with the DYS199 T allele, while DYS1 alleles 8 and 63 were associated with both the DYS199 C and T allele.     

Inbreeding and congenital heart diseases in a north Indian population

The study was performed in six mohallahs (colonies) of Aligarh City (North India). All six mohallahs are predominantly inhabited by Qureshi (meat sellers, a highly endogamous group) Muslims. A total of 1721 infants and children up to the age of 6 years were examined to determine the incidence of congenital heart diseases (CHD) in relation to the degree of consanguinity of the parents. Around 43% of the subjects were the offspring of consanguineous marriages including second-cousin, first-cousin-once-removed and first-cousin. A higher percentage of CHD was found in the offspring of consanguineous marriages: about 3.37% out of 741 children as compared to 1.22% in 980 offspring of non-consanguineous marriages, whereas in the first-cousin offspring, the percentage of CHD rose to 4.41%. The differences were found to be statistically significant. The present study suggests a genetic influence and also casts doubt on the applicability of a polygenic threshold model to all forms of cardiac malformation.     

Differences in detection of alcohol use in a prenatal population (on a Northern Plains Indian Reservation) using various methods of ascertainment

Although Fetal Alcohol Syndrome (FAS) rates have been reported to be higher in American Indian populations, no screening tool has been validated for alcohol use in American Indian women. The objectives of this study were to compare the detection of prenatal alcohol use by a self-administered questionnaire to detection by clinical interview; and to ascertain whether the screening tool would increase detection of pregnant women who are abusing alcohol. The hospital records of the women were reviewed for any history of alcohol-related illnesses or injuries to compare with results obtained from the questionnaire. Seventy women attending their first prenatal clinic visit on a reservation were screened for alcohol use. There was a wide range in detection of prenatal alcohol use (20%-71% of the sample detected) depending on the method used. There was a large variation in sensitivities (7%-93%) of the individual questions in identifying patients detected as "high risk" by the clinicians. The T-ACE screening questions significantly increased detection of alcohol use compared to detection by the clinicians (p = 0.04 Fisher's exact test). Due to the large variation between different methods of detection, it is recommended that screening tools that increase detection of alcohol use should be combined with methods of higher specificity such as using questions about quantity and frequency of alcohol intake, medical chart review and clinical interview. We also found that various interpretations of the screening questions by the patients highlighted the need to tailor the wording of individual questions to the particular patient population.     

Movement of badgers (Meles meles) in a high-density population: individual, population and disease effects

The movement of 1763 badgers trapped between 36 social groups in Woodchester Park, Gloucestershire, over 18 years was analysed to determine the frequency and duration of moves, the factors associated with a predisposition to move and the spatial pattern of movements. Of those badgers whose capture history could be categorized, nearly half had moved. Of these, 73.1% were classified as 'occasional movers', 22.1% as 'permanent movers' and 4.8% as 'frequent movers'. Most adult badgers that moved made occasional moves (78.8%, n = 67). Cubs made all types of move including permanent moves (29%, n = 10). Seventy per cent of females were non-movers compared with 37% of males. Badgers were significantly more likely to move to smaller groups, whereas male badgers were significantly more likely to move to groups with a greater proportion of females. The spatial pattern of movement differed from the distribution of groups with bovine tuberculosis in the study area. However, temporal changes in movement were significantly related to the incidence of Mycobacterium bovis infection in the following year, indicating that as the movement of badgers between groups varies so does the incidence of bovine tuberculosis in the population. This finding is of central importance in the formulation of badger control policy.     

Reflections on a proposed theory of reservation-dwelling American Indian alcohol use: Comment on Spillane and Smith (2007).

In their recent article, N. Spillane and G. Smith (see record 2007-06095-002) suggested that reservation-dwelling American Indians have higher rates of problem drinking than do either non–American Indians or those American Indians living in nonreservation settings. These authors further argued that problematic alcohol use patterns in reservation communities are due to the lack of contingencies between drinking and “standard life reinforcers” (SLRs), such as employment, housing, education, and health care. This comment presents evidence that these arguments were based on a partial review of the literature. Weaknesses in the application of SLR constructs to American Indian reservation communities are identified as is the need for culturally contextualized empirical evidence supporting this theory and its application. Cautionary notes are offered about the development of literature reviews, theoretical frameworks, and policy recommendations for American Indian communities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Blood pressure comparison in a selected Native American and white population

This study compared the frequency of blood pressure elevation in a selected Native American and white population. Three hundred individuals participated: 87 Native Americans, 210 whites, and 3 others. Data were gathered using a questionnaire that addressed residence, sex, age, race, occupation, height, smoking, alcohol use, tea/coffee consumption, medications, and past or present illness. Weight and blood pressure were measured by the researchers at the time of data collection. The sample mean for systolic blood pressure (SBP) was 124 mm Hg (SD 14.78) and diastolic blood pressure (DBP) was 77 mm Hg (SD 10.13). One-way analysis of variance showed age groups and sex to affect blood pressure significantly (P = 0.0001). Stepwise multiple regression indicated weight significantly predicted blood pressure (SBP multiple R = 0.39, P = 0.001; DBP multiple R = 0.43, P = 0.00001). The interaction of age, sex, tobacco, alcohol, and caffeine influenced SBP and DBP. Obviously, these findings have limited generalizeability due to the sampling frame used in this study.     

Characterization of native corticotropin-releasing factor receptor type 1 (CRFR1) in the rat and mouse central nervous system

Corticotropin releasing factor (CRF), the most important regulator of various responses to stress, acts through CRF receptors (CRFR). For their characterization in brain tissue of Sprague-Dawley rats and C57BL/6J mice, a recently described polyclonal antibody directed against the N-terminus of rat CRFR1 (rCRFR1) was used. The molecular weights of rat and mouse brain receptors were determined by Western blot analysis to be 80,000-76,000 and 83,000-79,000, respectively, whereas molecular weights of 72,000-59,000 were observed for CRFR1 from rat and mouse pituitary. Immunohistochemical analysis was performed with brain sections of naive rats and mice. Strong CRFR1 staining was detected in the cortex, cerebellum, mesencephalon and pons of both species, whereas weak staining was observed in amygdala and hippocampus. The striatum did not show immunoreactivity. The density of immunostaining was significantly lower in murine than in rat cortex. In contrast, in the pons and mesencephalon of mice, higher density of immunostaining was observed than in the same brain structures of rats. On the basis of the observed differences, it is suggested that CRFR1 is differentially processed in rats and mice. In addition, the density of CRFR1 staining differed between both species.     

Reference values of lipoprotein(a) in a French population

OBJECTIVES: The aim of this work is to study the effect of different biological factors that could affect Lp(a) level in a presumably healthy population and to establish reference limits. METHODS: We selected 723 subjects (367 men and 356 women) for the age interval 4 to 64 years for evaluation. RESULTS: The distribution of Lp(a) is not Gaussian; 50.5% of subjects had Lp(a) concentrations under 0.10 g/l and the value for the 75th percentile was 0.27 g/l and 0.57 g/l for the 90th percentile. No relationship was observed between Lp(a) concentration and cholesterolaemia, triglyceridaemia, glycaemia, inflammatory proteins (orosomucoide and CRP), overweight, tobacco consumption and oral contraceptive use. The menopause state in women was a factor correlated with increased Lp(a) but this increase was not significant. Moreover, alcohol consumption (more than 44 g per day in men and more than 22 g per day in women) was associated with lower Lp(a) values. Among familial cardiovascular risks, only paternal listing of hypertension was associated with Lp(a) concentration in men. CONCLUSION: The measurement of Lp(a) in a young subject could be used as a genetic marker of cardiovascular risk associated with abnormal lipid metabolism and thrombosis phenomena.     

Germ line polymorphisms in cytochrome-P450 1A1 (C4887 CYP1A1) and methylenetetrahydrofolate reductase (MTHFR) genes and endometrial cancer susceptibility

We describe here a case-control study to identify associations between polymorphisms at the methylenetetrahydrofolate reductase (MTHFR) and cytochrome P-450 1A1 (CYP1A1) genes and susceptibility to endometrial cancer. Accordingly, genotype frequencies in 80 endometrial carcinoma patients were compared with frequencies in 60 controls. DNA analysis suggest a significantly increased endometrial cancer risk with an alanine to valine substitution at nucleotide 677 of MTHFR gene with an odds ratio of 2.8 (95% confidence interval: 1.36-6.14, P = 0.002). Moreover, the tumors from patients with the valine allele were more undifferentiated (P = 0.03). On the other hand, a recently described mutation in exon 7 of CYP1A1 gene (threonine exchanged to asparagine in codon 461) showed a strong association with endometrial cancer risk with an odds ratio of 6.36 (95% confidence interval: 1.99-26.5, P = 0.0004). Thus, this study suggests that polymorphisms at MTHFR and a novel CYP1A1 variant could influence susceptibility to endometrial cancer, although larger sample sizes would be required to corroborate these findings.     

Evidence for genetic linkage to alcohol dependence on chromosomes 4 and 11 from an autosome-wide scan in an American Indian population

A retrospective histopathologic review of 97 patients with basal cell carcinoma of the eyelid was performed to determine the prevalence and behavior of tumors with a mixed pattern of growth. A mixed type basal cell carcinoma was defined as a tumor having a significant nodular or ulcerative component combined with an infiltrative component. Histologic classification of the 97 tumors yielded four (4.1%) that were multicentric, 67 (69.1%) that were nodular, one (1%) that was ulcerative, 13 (13.4%) that were infiltrative, and 12 (12.4%) that were the mixed variant. Follow-up was obtained on 8 of the 12 patients with mixed basal cell carcinoma. Three tumors recurred, but there were no tumor-related deaths. One of these patients underwent numerous eyelid resections over a 2-year period and then underwent an orbital exenteration. The authors conclude that mixed type basal cell carcinomas are not infrequent and behave as aggressively as basal cell carcinomas of the morphea type. A greater awareness and recognition of mixed type basal cell carcinomas by ophthalmologists and pathologists should result in fewer recurrences and better patient management.     

The utility of the Kessler Screening Scale for Psychological Distress (K6) in two American Indian communities.

The Kessler Screening Scale for Psychological Distress (K6; Kessler et al., 2002) has been used widely as a screener for mental health problems and as a measure of severity of impact of mental health problems. However, the applicability and utility of this measure for assessments within American Indian communities has not been explored. Data were drawn from a large-scale epidemiological study conducted in cooperation with 2 American Indian populations. Participants (N = 3,084) were 15–54 years of age and living on or near their home reservations; each completed an interview that included a version of the Composite International Diagnostic Interview (Robins, Wing, Wittchen, & Helzer, 1988) and the K6. A measure of both physical- and mental-health-related quality of life—the Medical Outcome Study's Short Form–36 (Ware & Sherbourne, 1992)—was used to examine the importance of the K6 over and above psychiatric diagnoses. The K6 was shown to be an appropriate screening and severity measure for mood disorders in these 2 samples. It also predicted health-related quality of life over and above that predicted by diagnoses alone. Inclusion of a measure such as the K6 as a complement to more traditional dichotomous diagnoses in both research and clinical practice is recommended. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Beta thalassemia in Germany: molecular genetics and clinical phenotype in immigrant and in the native population

Dentin dysplasia, type II (MIM*125420) is an autosomal dominant disorder of dentin development. Clinically the primary dentition appears opalescent, and radiographically the pulp chambers are obliterated, resembling dentinogenesis imperfecta. However, unlike dentinogenesis imperfecta, the permanent teeth in dentin dysplasia, type II are normal in color and, on radiographs, have a thistle-tube pulp chamber configuration with pulp stones. The similarity of the primary dentition phenotype suggested that the gene for dentin dysplasia, type II is allelic with the gene for dentinogenesis imperfecta, Shields type II (DGII; MIM*125490), which has been localized to chromosome 4q13-q21. Twenty-four members of a three generation family in which ten members are affected with dentin dysplasia, type II were genotyped for microsatellite alleles specific for the area of chromosome 4q linked to DGII. Linkage was assessed by using the LINKAGE computer program, assuming autosomal dominant inheritance, a disease allele frequency of 0.0001, and complete penetrance. The maximum two-point LOD score (Zmax = 4.2 at theta = 0.0) was obtained with SPPI and D4S2691. Multipoint analysis gave a maximum LOD score of 4.33. The candidate region for dentin dysplasia, type II is approximately 14.1 cM, includes SPPI, D4S2691, D4S2690, D4S451, and D4S2456, and overlaps the most likely location of the DGII locus. A candidate gene for DGII should also be considered a candidate gene for dentin dysplasia, type II.     

The distirubtion of active genes (globin) and inactive genes (keratin) in fractionated chicken erythroid chromatin

Repeatable fractionation of sheared chromatin from purified populations of chicken erythroid cells has been achieved, based on the Bio-Gel procedure of Janowski et al. ((1972) Karolinska Symp. 5, 112). For reticulocytes, 3-5% of chromatin DNA is excluded from Bio-Gel A-50 m (peak I) and over 90% elutes in the included volume of the column(peak II). Peak I material has a higher protein/DNA ratio than peak II chromatin and the two fractions have melting profiles characteristic of "active" and "inactive" chromatin, respectively. In cells prelabeled with [3H]uridine or [3H]leucine there was very pronounced preferential association of radioactivity with the "active" peak I chromatin. The distribution of "active" (globin) and "inactive" (keratin) gene sequences in the DNA of fractions from peak I and peak II chromatin was determined with complimentary DNA (cDNA) probes to chicken globin mRNA and chicken feather keratin mRNA. While slight enrichment for globin gene sequences was found in peak I (relative to DNA in these fractions), some 80% of the total globin hybrid formed was found in peak II fractions. Experiments with the keratin cDNA probe showed that these genes were equally distributed in both chromatin fractions rather than being confined to the "inactive" peak II material. The hybridization data in particular question the validity of claims for fractionation of chromatin into "active" and "inactive" material.     

Plasma Lp(a), apolipoprotein(a) isoforms and acute myocardial infarction in men and women: a case-control study in the Jerusalem population

The relationship of Lp(a) with manifestations of coronary heart disease (CHD) has not been studied extensively in women. There is little information as to the association of the unique Lp(a) apolipoprotein moiety (apo(a)) with CHD in either men or women. We therefore assessed the association of the apo(a) polymorphism and of Lp(a) with first acute myocardial infarction (MI) in a population-based case-control study in Jewish residents of Jerusalem between the ages of 25 and 64. The patients consisted of 238 men and 47 women hospitalized for a first acute MI in the 4 hospitals of Jerusalem serving the population (70% response rate among all first MI patients). The control subjects comprised 318 men and 159 women sampled from the national population registry and who were free of CHD (75% response). Lp(a) and apo(a) were measured in plasma stored at -20 degrees C for 6-24 months. Among men, plasma Lp(a) concentrations were higher in cases than controls in both univariate and multivariate analyses. The elevated risk was limited to the upper fifth of the Lp(a) distribution (unadjusted odds ratio = 1.65, P < 0.01 vs. the lower four quintiles, multivariable odds ratio = 1.82, P < 0.01). Among women, Lp(a) was not elevated in acute MI patients. Apo(a) isoforms with a B, S1 or S2 band (associated with higher Lp(a) values and having lower molecular weights) were more prevalent in female MI cases than controls (unadjusted odds ratio = 2.5, P = 0.016). This association could not be attributed to the higher Lp(a) concentrations associated with these isoforms and was not seen in men. In conclusion, our study points to an association of the apo(a) isoforms with acute MI in women, not evident in this population sample in men. Previously described associations of elevated Lp(a) with acute MI were confirmed in men but not in women. While the role of chance and inadequate statistical power cannot be excluded, the suggestion of a sex difference in the strength of these associations deserves further investigation, as does the question of whether apo(a) phenotype contributes to risk independently of Lp(a) level.     

Epstein-Barr virus (EBV) and Hodgkin''s disease in a multi-ethnic population in Malaysia

The plant pathogenic fungus Verticillium dahliae produced extracellular alkaline protease activity when grown in liquid medium supplemented with a protein source. A serine protease was purified 80-fold in a single step, using cation-exchange chromatography, from the filtrate of cultures grown with skim milk as a protein source. N-terminal amino acid sequence analysis of the 30-kDa protein (VDP30) that copurified with the serine protease activity suggested that VDP30 is a trypsin-like protein. The purified enzyme hydrolyzed the synthetic substrate N alpha-benzoyl-DL-arginine p-nitroanilide hydrochloride (BAPNA), and the activity on BAPNA was inhibited by leupeptin, further verifying the trypsin-like nature of the enzyme.