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Differences between studies in reported relative risks associated with smoking: an overview.

Reported Relative Risks associated with smoking differ between studies; these differences may reflect true biological differences between populations or may be research artifacts introduced by differences in factors such as amount smoked or smoking duration. The authors reviewed the literature published before June 1992 on relative risks associated with smoking for heart disease, stroke, lung cancer, and chronic obstructive lung disease. They quantified the effect of variables such as age, amount smoked, and smoking duration on reported relative risks. The main reasons for the variation in reported relative risks were: misclassification of former smokers as never smokers, the use of mortality rate ratios rather than incidence rate ratios, a possible period effect suggesting increasing relative risks over time, and differences in the amounts smoked. It is far more likely that these factors are responsible for the observed variation between studies than that the variations reflect true biological differences between populations. Using relative risks from other studies is therefore justified in calculating a population attributable risk if the studies are carefully selected and address factors such as amount smoked and period effects.

Cardiovascular Diseases↗

Geographic distribution of haplotype diversity at the bovine casein locus.

The genetic diversity of the casein locus in cattle was studied on the basis of haplotype analysis. Consideration of recently described genetic variants of the casein genes which to date have not been the subject of diversity studies, allowed the identification of new haplotypes. Genotyping of 30 cattle breeds from four continents revealed a geographically associated distribution of haplotypes, mainly defined by frequencies of alleles at CSN1S1 and CSN3. The genetic diversity within taurine breeds in Europe was found to decrease significantly from the south to the north and from the east to the west. Such geographic patterns of cattle genetic variation at the casein locus may be a result of the domestication process of modern cattle as well as geographically differentiated natural or artificial selection. The comparison of African Bos taurus and Bos indicus breeds allowed the identification of several Bos indicus specific haplotypes (CSN1S1*C-CSN2*A2-CSN3*AI / CSN3*H) that are not found in pure taurine breeds. The occurrence of such haplotypes in southern European breeds also suggests that an introgression of indicine genes into taurine breeds could have contributed to the distribution of the genetic variation observed.

Animals↗

Seasonal changes in body composition of Ctenomys talarum (Rodentia: Octodontidae): an herbivore subterranean rodent.

Ctenomys talarum is a subterranean herbivorous rodent whose burrow systems exhibit particular characteristics, distinct from other subterranean environments. We studied seasonal variation in body composition of C. talarum in relation to energetic requirements. Body lipid content seasonally changed in C. talarum, related to reproductive cycle and thermorregulatory mechanisms. A decrease in protein body content was found only in spring. Ash content of females was lowest when most of them are in post partum estro. Observed variations in water body content could be associated with plant water content and/or metabolic regulation. Our results show the occurrence of seasonal variations in body composition in C. talarum, which could be related to the high cost of reproduction and the subterranean life style of this species.

Animals↗

Time series forecasts of ambulance run volume.

To test the hypothesis that time series analysis can provide accurate predictions of future ambulance service run volume, a prospective stochastic time series modeling study was conducted at a community-based regional ambulance service. For all requests for ambulance transport during two sequential years, the time and date, total run time, and acuity code of the run were recorded in a computer database. Time series variables were formed for ambulance service runs per hour, total run time, and acuity. Prediction models were developed from one complete year's data (1994) and included four model types: raw observations, moving average, means with moving average smoothing, and autoregressive integrated moving average. Forecasts from each model were tested against observations from the first 24 weeks of the subsequent year (1995). Each model's adequacy was tested on residuals by autocorrelation functions, integrated periodograms, linear regression, and differences among the variances. A total of 68,433 patients were seen in 1994 and 32,783 in the first 24 weeks of 1995. Large periodic variations in run volume with time of day were found (P < .001). A model based on arithmetic means of each hour of the week with 3-point moving average smoothing yielded the most accurate forecasts and explained 54.3% of the variation observed in the 1995 test series (P < .001). Time series analysis can provide powerful, accurate short-range forecasts of future ambulance service run volume. Simpler, less expensive models performed best in this study.

Ambulances↗

Transmission-blocking effects of sera from malaria-exposed individuals on Plasmodium falciparum isolates from gametocyte carriers.

Sera from donors exposed to malaria were tested for their ability to block the transmission of isolates from Cameroonian Plasmodium falciparum gametocyte carriers. Sera were selected from amongst Cameroonian and Gambian donors who had positive antibody reactivity against the surface of activated gametes and against epitopes of Pfs 48/45 (a potential transmission-blocking vaccine candidate antigen). Aliquots of washed blood from gametocyte carriers were resuspended in test and control sera and fed to An. gambiae mosquitoes via a membrane feeder. Comparisons of the prevalence and intensity of infections is dissected mosquitoes showed variations in the ability of sera to block the transmission of the different isolates. Sera were identified that had little or no blocking effect on the transmission of isolates unless the isolate was poorly infectious. Some sera completely blocked the transmission of some isolates whilst having little or no effect on others. The observed variation in transmission-modulating activity may have implications for the development of a transmission-blocking vaccine.

Adolescent↗

Functional and binding studies of insurmountable antagonism of 606A, a novel AT1-receptor antagonist in rabbit tissues.

Angiotensin AT1-receptor antagonists can be classified into two types, surmountable and insurmountable ones, based on the way they inhibit angiotensin II (AII)-induced vasoconstriction. To elucidate the causes of the difference, we studied how several antagonists associate with and dissociate from AT1-receptor sites by using rabbit adrenal cortical membrane. Four antagonists, 606A, EXP3174, CV11974, and E4177, showed equipotent competitive antagonism when they were added simultaneous with [125I]-AII in binding experiments. However, in AII-induced contraction studies with rabbit aorta, 606A, EXP3174, and CV11974 inhibited the contraction noncompetitively, whereas E4177 inhibited competitively. The longer the pretreatment period with EXP3174 or CV11974, the more effectively the antagonists suppressed AII-induced contraction. However, the suppression of contraction by 606A and E4177 changed little with the length of the pretreatment period. AII-induced contraction of 606A- or E4177-treated aorta recovered easily by washout, but that of CV11974-treated aorta was hard to recover by washout. These results obtained in the aorta were consistent with their characteristics observed in the AII binding study in the rabbit adrenal cortical membrane in cases of EXP3174 and CV11974. The differences between association rate with and dissociation rate from the AT1 receptor of E4177 and 606A were slight, in spite of the clear difference between their action in the contraction study. Because of the variations observed with the four compounds, mechanisms of insurmountable antagonism may not be uniform among AT1-receptor antagonists.

Angiotensin II↗

A possible non-sexual origin of mate preference: are male guppies mimicking fruit?

In most animals, the origins of mating preferences are not clear. The "sensory-bias" hypothesis proposes that biases in female sensory or neural systems are important in triggering sexual selection and in determining which male traits will become elaborated into sexual ornaments. Subsequently, other mechanisms can evolve for discriminating between high- and low-quality mates. Female guppies (Poecilia reticulata) generally show a preference for males with larger, more chromatic orange spots. It has been proposed that this preference originated because it enabled females to obtain high-quality mates. We present evidence for an alternative hypothesis, that the origin of the preference is a pleiotropic effect of a sensory bias for the colour orange, which might have arisen in the context of food detection. In field and laboratory experiments, adult guppies of both sexes were more responsive to orange-coloured objects than to objects of other colours, even outside a mating context. Across populations, variation in attraction to orange objects explained 94% of the inter-population variation in female mate preference for orange coloration on males. This is one of the first studies to show both an association between a potential trigger of a mate-choice preference and a sexually selected trait, and also that an innate attraction to a coloured inanimate object explains almost all of the observed variation in female mate choice. These results support the "sensory-bias" hypothesis for the evolution of mating preferences.

Animals↗

Mating propensities and variations in enzyme activities in long-term cage populations of Drosophila melanogaster.

Environment-dependent reproductive isolation was established between cage populations (Bs) of Drosophila melanogaster originated from a Greek natural population (summer 1973) and maintained for about five years under different diets (poor-rich). The detected deviation from random mating involved no homogametic or heterogametic preference but rather, a significantly increased activity of males from populations maintained on the rich food medium. This observation indicates that the male parental investment is not negligible and under certain conditions sexual isolation can be a function not only of female behavior but also of male behavior. Differences also were found in various enzyme activities on the inter- and intra-population levels. Given those observations as well as the observed different behavioral patterns of Bs and Cs-Ds populations 19, a preliminary attempt was made to associate adaptive evolution with differences in enzyme activities. The differences in enzyme activities between populations reared on different media are not due to allozymic differences. It also was shown that in some populations environmental effects do not always elicit differences in enzyme activity. It was concluded, therefore, that the observed variations were the result of environmental effects interacting with modifier genes.

Animals↗

Variation in T cell responses to ovalbumin in cattle: evidence for Ir gene control.

Genetic control of immune responsiveness in cattle was investigated using an antigen-dependent T cell proliferation assay in vitro. Bovine T cell proliferative responses to ovalbumin were dependent upon major histocompatibility complex (MHC) class II molecules. Responses of an unrelated panel of animals to a limiting concentration of ovalbumin after a single immunization were compared. Two discrete patterns of response were observed. One group of animals had low or non-responses which were not significantly different from the preimmune levels. Another group of animals showed significant responses. After a second immunization the majority of low responders remained low responders. There was no significant correlation between bovine MHC class I BoLA haplotype and magnitude of response within this group of unrelated animals. However, the magnitude of the T cell responses by two half-sib family groups segregated with BoLA haplotypes inherited from the sire. In contrast no significant correlation with antibody responses in vivo could be demonstrated. We suggest that the observed variation in T cell response is linked to bovine MHC class II immune response (Ir) genes.

Animals↗

Variation through the cell cycle in the dose-response of DNA neutral filter elution in X-irradiated synchronous CHO-cells.

Dose-response curves for DNA neutral (pH 9.6) filter elution were obtained with synchronized CHO cells exposed to X-rays at various phases of the cell cycle. The dose response was similar in synchronized and plateau-phase G1 cells, as well as in cells that were arrested at the G1/S border using aphidicolin; it flattened as cells progressed into S phase and reached a minimum in the middle of this phase. An increase in DNA elution dose response, to values only slightly lower than those obtained with G1 cells, was observed as cells entered G2 phase. Significant alterations in the sedimentation properties of the DNA during S phase were also observed in Ehrlich ascites tumor cells using the neutral sucrose gradient centrifugation technique. A significant proportion of the DNA from S cells irradiated with 10 Gy sedimented at speeds (350S-700S) well above the maximum sedimentation speed expected for free sedimenting DNA molecules (Smax = 350S), indicating the formation of a DNA complex. DNA from G1, G1/S, or G2 + M cells sedimented as expected for free sedimenting molecules. These results indicate significant alterations in the physicochemical properties of the DNA--probably caused by DNA replication-associated alterations in DNA structure and chromatin conformation--as cells enter S phase, and are invoked to explain the observed variation in DNA elution dose response throughout the cycle. It is proposed that the formation of a complex DNA structure, resistant to the proteolytic enzymes and detergents used, affected the elution characteristics of the DNA and gave rise to the observed curvilinear DNA elution dose-response curves, as well as to the fluctuations in elution characteristics observed throughout the cell cycle.

Animals↗

Electrophoretic variability in island populations of Drosophila simulans and Drosophila immigrans.

Genetic structure and variability were investigated in several Hawaiian populations of D. simulans and D. immigrans. Genetic variability is lower in Hawaiian populations of D. simulans than in Texas populations, and allelic differences exist as well. For D. immigrans, Hawaiian and Korean populations are similar in variability, allelic content, and gene frequencies. Several hypothesis are advanced to account for the patterns in gene variation observed between island and continental populations of these two colonizing species.

Alcohol Oxidoreductases↗

Correlation between hordatine accumulation, environmental factors and genetic diversity in wild barley (Hordeum spontaneum C. Koch) accessions from the Near East Fertile Crescent.

Wild barley shows a large morphological and phenotypic variation, which is associated with ecogeographical factors and correlates with genotypic differences. Diversity of defense related genes and their expression in wild barley has been recognized and has led to attempts to exploit genes from H. spontaneum in breeding programs. The aim of this study was to determine the variation in the accumulation of hordatines, which are Hordeum-specific preformed secondary metabolites with strong and broad antimicrobial activity in vitro, in 50 accessions of H. spontaneum from different habitats in Israel. Differences in the accumulation of hordatines in the seedling stage were significant between different H. spontaneum genotypes from different regional locations and micro-sites. Variation in the hordatine accumulation within genotypes was between 9% and 45%, between genotypes from the same location between 13% and 38%, and between genotypes from different locations up to 121%. Principal component analysis showed that water related factors explain 39%, temperature related factors explain 33% and edaphic factors account for 11% of the observed variation between the populations of H. spontaneum. Genetic analysis of the tested accessions with LP-PCR primers that are specific for genes involved in the biosynthetic pathway of hordatines showed tight correlations between hordatine abundance and genetic diversity of these markers. Multiple regression analyses indicated associations between genetic diversity of genes directly involved in hordatine biosynthesis, ecogeographical factors and the accumulation of hordatines.

Agmatine↗

Molecular weight diversity among murine class I antigens: both the mature cell surface forms and the unglycosylated polypeptides vary significantly in molecular weight.

The molecular weights of the fully glycosylated cell surface form and the unglycosylated polypeptide of five murine class I antigens (H-2Kb, Db, TL, Qa-1.1, and Qa-2) were compared by SDS-PAGE. Significant molecular weight diversity was observed for both forms among these molecules. The size of the fully glycosylated forms ranged from approximately 52,000 daltons (H-2Db) to 41,000 daltons (Qa-2), whereas the unglycosylated polypeptides ranged from 43,000 daltons (H-2Kb and TL) to 33,000 daltons (Qa-2). The magnitude of the size variation observed in the unglycosylated polypeptides implies that there are differences in the gene organization, RNA processing or post-translational modifications of various class I glycoproteins.

Animals↗

Geographic variation in surgical treatment for work-related carpal tunnel syndrome: does improved return to work matter?

Medical treatment of compensated work-related conditions has two objectives--improve injured workers' health status and allow safe and sustained return to work (RTW). Theoretically, the choice of treatment method should be based primarily on these objectives. Surgical treatment of work-related carpal tunnel syndrome (CTS) provides an opportunity to evaluate whether this occurs. The traditional method of open release has been complemented by an endoscopic procedure, particularly useful in work-related cases due to the anticipated benefit of earlier RTW. The objective of this study was to investigate the differences in surgical treatment for work-related CTS across eight US workers' compensation (WC) jurisdictions, and the factors associated with these differences. From all WC claims reported to a single insurer during the 1995-1999 period, we identified individuals with a one or two surgical procedures for work-related CTS. Among selected individuals (n=4,421), about 20% were treated using the endoscopic procedure; this percentage had a ten-fold variation across the eight jurisdictions. However, utilization of endoscopic release did not increase during the study period, despite reports of better RTW outcomes. The highly jurisdictional nature of the US WC system, with significant differences in reimbursement levels for endoscopic procedures, and geographical differences in medical training were among the potential contributors to the observed variation in utilization.

Carpal Tunnel Syndrome↗

Immunophenotypes by flow cytometry: a longitudinal study in healthy individuals.

Weekly blood samples from five healthy volunteers were obtained for 13 weeks to assess the variations in the immunological phenotypes of peripheral blood lymphocytes and monocytes. Monoclonal antibodies to eleven lymphocyte and two monocyte antigens were evaluated using two-color flow cytometry. Average week-to-week differences were less than 5% for all monoclonal antibodies and combinations except for I2+, NKH-1+, MO1+, and MO2+ cells. The observed variations presumably reflected both technical variables and responses of the immune system to daily environmental insults.

Adult↗

Estimation of allele frequencies at isoloci.

In some polyploid animals and plants, pairs of duplicated loci occur that share alleles encoding proteins with identical electrophoretic mobilities. Except in cases where these "isoloci" are known to be inherited tetrasomically, individual genotypes cannot be determined unambiguously, and there is no direct way to assign observed variation to a particular locus of the pair. For a pair of diallelic isoloci, nine genotypes are possible but only five phenotypes can be identified, corresponding to individuals with 0-4 doses of the variant allele. A maximum likelihood (ML) approach is used here to identify the set of allele frequencies (p, q) at the individual gene loci with the highest probability of producing the observed phenotypic distribution. A likelihood ratio test is used to generate the asymmetrical confidence intervals around ML estimates. Simulations indicate that the standard error of p is typically about twice the binomial sampling error associated with single locus allele frequency estimates. ML estimates can be used in standard indices of genetic diversity and differentiation and in goodness-of-fit tests of genetic hypotheses. The noncentral chi 2 distribution is used to evaluate the power of a test of apparent heterozygote deficiency that results from attributing all variation to one locus when both loci are polymorphic.

Alleles↗

Polymorphism in diazepam metabolism in Wistar rats.

We observed variations in the metabolism of diazepam in Wistar rats. We studied these variations carefully, and found that the variations are dimorphic and about 17% of male rats of Wistar strain we examined showed two times higher diazepam metabolic activities in their liver microsomes than the rest of animals at the substrate concentrations less than 5 microM. We classified them as extensive metabolizer (EM) and poor metabolizer (PM) of diazepam. No sex difference was observed in the frequency of appearance of EM. Activities of the primary metabolic pathways of diazepam were examined to elucidate the cause of this polymorphism in male Wistar rats. No significant differences were observed in activities of neither diazepam 3-hydroxylation or N-desmethylation between EM and PM rats, while activity of diazepam p-hydroxylation was markedly (more than 200 times) higher in EM rats, indicating that this reaction is responsible for the polymorphism of diazepam metabolism in Wistar rats. We examined the expression levels of CYP2D1, which was reported to catalyze diazepam p-hydroxylation in Wistar rats to find no differences in the expression levels of CYP2D1 between EM and PM rats. The kinetic study on diazepam metabolism in male Wistar rats revealed that EM rats had markedly higher V(max) and smaller K(m) in diazepam p-hydroxylation than those of PM rats, indicating the presence of high affinity high capacity p-hydroxylase enzyme in EM rats. As a consequence, at low concentrations of diazepam, major pathways of diazepam metabolism were p-hydroxylation and 3-hydroxylation in male EM rats, while in male PM rats, 3-hydroxylation followed by N-desmethylation. Due to this kinetic nature of p-hydroxylase activity, EM rats had markedly higher total CL(int) of diazepam than that of PM rats. Polymorphism in diazepam metabolism in humans is well documented, but this is the first report revealing the presence of the polymorphism in diazepam metabolism in rats. The current results infer polymorphic expression of new diazepam p-hydroxylating enzyme with lower K(m) than CYP2D1 in EM Wistar rats.

Animals↗

Structural polymorphism of mouse complement C2 detected by microscale peptide mapping: linkage to H-2.

Complement C2 was isolated from 17 mouse strains by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis and examined for structural polymorphism by using micro-peptide mapping. By comparing the peptide maps of tryptic digest of C2 from various strains, two allotypic variations were detected. B10 and 14 other mouse strains demonstrated C2.1 type, while a wild mouse line (M.Mol-Ohm) and one B10 congenic strain, B10.MOL.OHM, which carries the H-2 derived from M.Mol-Ohm, demonstrated C2.2 type. (B10 X B10.MOL.OHM)F1 demonstrated codominantly expressed C2 type (C2.1.2). Desialation of mouse C2 did not abolish the observed variation of mouse C2. It is concluded that an H-2-linked codominant locus controls the structure of mouse complement C2, further confirming the extensive homology of the major histocompatibility complex among higher vertebrate species.

Alleles↗