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Breed differences in the distribution of BoLA-A locus antigens in American cattle.

A total of 627 cattle representing seven breeds from south central Nebraska, USA were tested for 37 BoLA antigens which behave as products of 37 distinct alleles of the class I BoLA-A locus. Four antigens were absent from all breeds tested. The other antigens showed marked and statistically significant differences in breed distribution. There was no evidence for blank (null) alleles. The number of alleles in each breed ranged from 10 to 20. The Hereford and Simmental populations tested were less polymorphic than the Angus, Brown Swiss, Charolais, Gelbvieh and Limousin populations.

Alleles↗

Population data on two new HLA-D determinants, EI and RE.

Homozygous typing cells (HTC) for two new HLA-D determinants, EI and RE, defined by family studies, are described. The HLA-D typing experiments among more than 300 unrelated individuals showed phenotype frequencies of 0.045 for EI and 0.098 for RE. Since the tested population was also typed for its HLA-A and -B alleles, linkage disequilibrium parameters could be calculated: HLA-D type EI was statistically significantly associated with HLA-B13 and Bw17, HLA-D type RE with HLA-Bw40. These data support the working hypothesis that both EI and RE are new alleles of the HLA-D series.

Alleles↗

Dynamic position testing for the detection of esophageal acid reflux disease.

Currently the most widely accepted study for the detection of significant esophageal reflux disease is the 24-hr pH study. It is a problematic study, however. The data obtained from that study have to be analyzed by comparison to a normal tested population, revalued through a weighted scale, then judged against recorded symptoms in order to obtain a valid interpretation. Dynamic position acid reflux testing has recently been described as a better alternative. In this comparative study between dynamic position and 24-hr pH testing in 64 patients, the dynamic position study was found to be more definitive, more informative, and more efficient in the detection of significant esophageal acid reflux disease.

Exercise Test↗

No linkage or association of five polymorphisms in the interleukin-4 receptor alpha gene with atopic asthma in Italian families.

The literature contains conflicting reports on the association of common variants of the interleukin (IL)-4 receptor alpha (IL4RA) gene with atopic asthma. The purpose of the present study was to investigate the linkage and association of several gene polymorphisms with atopic asthma in a large series of well-characterized individuals. Analysis of five polymorphisms (I50V, E375A, C406R, S478P and Q551R) of the IL4RA gene was performed in 823 individuals from 182 families with atopic asthmatic children from north-east Italy. The subjects were tested for clinical asthma, total serum IgE level, skin prick test positivity to common aeroallergens, and bronchial hyperresponsiveness to methacholine. The frequency of the polymorphisms was similar to that reported for other populations. The 375, 406, 478 and 551 polymorphisms were in linkage disequilibrium, as previously reported. No linkage or transmission disequilibrium was observed in the families between any mutation and any of the phenotypes investigated. No multipoint haplotype was associated with any phenotype. In conclusion, the IL4RA gene does not seem to play an important role in genetic predisposition to atopic asthma in the population tested.

Adolescent↗

IgA antibodies to human tissue transglutaminase: audit of routine practice confirms high diagnostic accuracy.

BACKGROUND: The diagnostic accuracy of IgA tissue transglutaminase antibodies (TGA) for coeliac disease (CD) has been assessed following the introduction of the test into routine practice in 2002. METHODS: Specificity was assessed in serum samples received from 1554 adults for routine coeliac serology. The population for assessing sensitivity was 75 consecutive new adult diagnoses of CD. TGA was measured by enzyme-linked immunoassay using human tissue transglutaminase as antigen. Concordance between TGA and endomysial antibody (EMA) was also assessed. RESULTS: The prevalence of new diagnoses of CD in the population tested was 2.8% with similar proportions of new diagnoses in males and females. The positive predictive values at a cut-off of 3 units/mL were 0.77 for samples from Primary Care and 0.92 for samples from Hospital sources, with a sensitivity of 92%. At TGA <3 units/mL, EMA was usually negative; when TGA was >4.9 units/mL, EMA was rarely negative. CONCLUSIONS: We have assessed the role of TGA in routine clinical practice and confirmed high diagnostic accuracy. Sensitivity (92%) is identical to the sensitivity for EMA. IgA deficiency should be excluded in samples showing low absorbance readings in the TGA assay and interference from monoclonal and polyclonal IgA should be excluded in samples with slightly raised TGA levels and negative EMA. TGA is recommended as the first-line serological test for coeliac disease.

Adolescent↗

Effects of experimentally generated bull antisperm antibodies on in vitro fertilization.

To test the hypothesis that bull antisperm antibodies have the capacity to interfere with fertilization, antisperm antibodies were generated in three 13-mo-old Holstein bulls by auto-immunizing each bull with sperm three times. All bulls produced serum antisperm IgG1 and IgG2 antibodies. No serum antisperm IgA nor seminal plasma antisperm antibodies of any isotype could be detected by ELISA. Western blots were performed with immunopurified IgG1 and IgG2 from pre- and post-immunization sera from one test bull. Both post-immunization IgG1 and IgG2 recognized a 45-kDa sperm antigen. Serum samples from a normal bull stud population tested by ELISA had significantly higher levels of antisperm antibodies than did heifers. The bull stud serum samples giving the highest ELISA values differed from those of the immunized bulls in that their antisperm antibodies were of the IgM isotype only. Bull sperm were incubated with serum from the immunized and control bulls, then added to bovine oocytes in vitro. Incubation of sperm with post-immunization serum reduced in vitro fertilization rates (p < 0.01). This study demonstrated that antisperm IgG1 and IgG2 generated by sperm auto-immunizations reduced fertility in vitro, and therefore naturally occurring antisperm antibodies may affect fertility in bulls.

Animals↗

Frequency of the cystic fibrosis 3199del6 mutation in individuals heterozygous for I148T.

PURPOSE: To determine the carrier frequency of the 3199del6 cystic fibrosis (CF) mutation in individuals heterozygous for I148T in a large-scale CF testing population. METHODS: DNA samples from 439 consecutive I148T-heterozygous individuals were screened for the 3199del6 mutation using a laboratory-developed test. RESULTS: Genotyping revealed four samples heterozygous for the 3199del6 mutation (0.9%). The four samples positive for 3199del6 had an IVS 8 genotype of 7T/9T. The 3199del6 mutation was not observed after genotyping of 348 random, anonymous samples. CONCLUSION: The 3199del6 mutation occurs in 0.9% of individuals positive for the I148T mutation and <0.07% of chromosomes that are wild type for the ACMG panel mutations.

Base Sequence↗

Long-term habituation of the speech-elicited mismatch negativity.

A significant issue in the use of the mismatch negativity evoked potential (MMN) concerns its low signal-to-noise ratio (SNR). One can improve the noise level by increasing the number of samples included in the averaged response. However, improvement achieved in this way assumes that the signal, the MMN, remains stable for extended test times, an assumption which has not been tested. If the MMN is not stable, or exhibits habituation over the test session, then SNR would be adversely affected. MMN response magnitude was measured in 5-min intervals over the course of a test session in response to various speech syllable contrasts. Significant long-term habituation of MMN was observed for all three subject populations tested: young adults, school-age children, and guinea pigs. The time course of the habituation and the stimulus conditions under which it occurs have important implications for research and clinical applications of the MMN. Recording procedures that minimize habituation effects may be used to advantage to improve the signal-to-noise ratio of the MMN.

Adolescent↗

Statistical problems in assessing the true value of new in vitro diagnostic tests, with special reference to the chemiluminescent assay (CLA, MAST).

By virtue of familiarity and usage over many years, diagnostic tests may become established and be regarded as infallible "Gold Standards". In the case of allergic disease no test except perhaps allergen challenge can ever precisely reflect the clinical disease at the actual site of the allergic reaction. Thus when a new test is introduced there are no fixed values available for statistical comparison when directly comparing established tests with more recent additions. This is illustrated by many articles comparing the new multiple allergosorbent test system (CLA, MAST) which is a chemiluminescent assay, to other previously established tests. The major reports on CLA in the diagnosis of allergy are here discussed and summarized. Most trials have compared the accuracy of CLA with clinical history, with the skin prick test (SPT), the universally used in vivo method, or with RAST, the most common in vitro diagnostic method. CLA performed similarly to SPT and most CLA and RAST results matched; nevertheless in statistical analyses the problems of comparing diagnostic methods without a Gold Standard against which to judge become obvious-if two fallible methods disagree, which is correct? These statistical problems are discussed as well as other difficulties, such as the impact of the use of different allergen sources and the differing prevalence of allergies in the various test populations analysed.

Biometry↗

Characterization of immune suppression induced by polyribonucleotides.

Synthetic polyribonucleotide complexes, which have been shown to be potent adjuvants to the immune response of animals and humans were tested for their capacity to activate cells involved in suppressing antibody synthesis. Poly A:poly U and poly I:poly C inhibited murine antibody forming spleen cells when given 1-6 days before antigenic stimulus. To determine the cellular and molecular mediators of this suppression, individual cell populations were isolated or deleted and the resulting cell populations tested for induction of suppression. When the natural killer (NK) cell population was rendered non-functional with anti-asialo GM1 antiserum no diminution in suppressive activity was observed. Further experiments implicated adherent cells as the population responsible for mediating suppression. Supernatants from poly A:poly U-treated adherent cells were found both to contain increased levels of prostaglandin E (PGE) and to induce a significant decrease in antibody production when added to in vitro spleen cell cultures. In addition, indomethacin, an inhibitor of the cyclo-oxygenase pathway of the arachidonic acid cascade was found to reverse the suppression of antibody induced by poly A:poly U. Thus, the polyribonucleotide complexes appear to suppress antibody synthesis by inducing macrophages to secrete PGE, a known immune suppressant.

Animals↗

Application of new two-sample tests to data from a randomized placebo-controlled heart-failure trial.

In a randomized placebo-controlled double-blind trial of 230 congestive heart failure patients, four treatments were evaluated for efficacy, with exercise tolerance time (ETT) as the primary outcome. Various two-sample tests were applied to the analysis of ETT data. It is shown in this paper that the conventional two-sample tests (t and rank-sum) are insensitive to situations where the effect of the experimental therapy is not consistent across a patient population. Tests recommended by O'Brien are more appropriate for these data. It is also shown that the application of the O'Brien tests led to the identification of sub-groups where the observed effect of the experimental therapy was most pronounced.

Adult↗

Nonimmune lymphocyte-macrophage interaction. I. Quantification by an automated colorimetric assay.

Previous studies have demonstrated a spontaneous, nonimmune interaction between lymphocytes and macrophages. This paper describes an automated colorimetric assay based on the dye, rose bengal, to quantify this interaction. The procedure entails allowing lymphocytes to adhere to preformed macrophage monolayers in the wells of microplates and then staining bound lymphocytes with rose bengal. Dye uptake and the consequent number of lymphocytes bound were quantified using an automated spectrophotometer developed for reading microplates. This procedure was used to confirm and extend the basic parameters of the system. The interaction was found to be temperature dependent but the kinetics and percentage of cells binding varied with the source of lymphocytes. However, all lymphocyte populations tested, namely, mature and immature thymocytes, T and B lymphocytes, and a range of thymoma cell lines, bound to macrophages. Furthermore, all macrophage populations examined had the ability to bind lymphocytes. The interaction also showed no strain specificity and generally lacked species specificity. It is proposed that the interaction is a highly dynamic process that enables lymphocytes to scan the surface of macrophages for self and/or foreign antigens.

Age Factors↗

Population studies on three Native Alaska population groups using STR loci.

Allele distributions for 13 short tandem repeat (STR) loci D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820, TH01, TPOX, CSF1PO and D16S539 were determined for three Native Alaskan population groups-Athabaskans, Inupiats, and Yupiks. Although genetic diversity is lower in the Native Alaskan populations compared with Caucasians and Africans, almost all loci are highly polymorphic in all three Native Alaskan groups. There was little evidence for departures from Hardy-Weinberg expectations (HWE) in any of the populations. Only two examples of detectable departures from HWE out of 39 locus-population tests performed were observed based on the exact test (Yupik, D8S1179, P=0.030; Yupik, D5S818, P=0.016). The F(ST) estimate overall 13 STR loci is 0.0309 for the Native Alaskan populations. Based on a genetic distance measure, Athabaskans are more closely related to Apaches and Navajos (all of the same linguistic group) than the other Native Alaskan groups. The F(ST) estimate for Athabaskans, Apaches and Navajos is 0.0180 and for Inupiats and Yupiks is 0.0167. The allele frequency data can be used for estimating DNA profile frequencies for Native Americans residing in Alaska.

Alaska↗

The genetics of phenylthiocarbamide perception.

The ability to taste the bitter compound phenylthiocarbamide (PTC) and related chemicals is bimodal, and all human populations tested to date contain some people who can and some people who cannot taste PTC. Why this trait has been maintained in the population is uncertain but this polymorphism may influence food selection, nutritional status or thyroid metabolism. The gene product that gives rise to this phenotype is unknown, and its characterization would provide insight into the mechanism of bitter taste perception. Although this trait is often considered a simple Mendelian trait, i.e. one gene two alleles, a recent linkage study found a major locus on chromosome 5p15 and evidence for an additional locus on chromosome 7. The development of methods to identify these genes will provide a good stepping-stone between single-gene disorders and polygenic traits.

Antimetabolites↗

Biomarkers of exposure in community settings.

Biomonitoring is a valuable tool for assessing human exposures to chemical contaminants in the environment. Biomonitoring tests can be divided into biomarkers of exposure, effect, and susceptibility. In studies of community exposure to an environmental contaminant, biomarkers of exposure are most often used. The ideal biomarker should be sensitive, specific, biologically relevant, practical, inexpensive, and available. Seldom does a biomarker meet all of these criteria--most biomarkers represent a compromise of these criteria. In designing a community exposure study, consideration should also be given to the selection of the test population, the practicality of collecting biological samples, temporal or seasonal variations in exposure, the availability of background comparison ranges, and interpretation of the test results. Biomonitoring tests provide unequivocal evidence of exposure, but they do not typically identify the source of exposure. Furthermore, rarely do the test results predict a health outcome. For many chemicals, testing must be conducted soon after exposure has occurred. In spite of these limitations, the use of biomonitoring is finding wider application in many scientific disciplines. Recent advances in analytical techniques are expanding the utility of biomarker testing in public health investigations.

Biomarkers↗

The alcohol dehydrogenase polymorphism in populations of Drosophila melanogaster. I. Selection in different environments.

The allozyme polymorphism at the alcohol dehydrogenase locus in Drosophila melanogaster was studied in order to obtain experimental evidence about the maintenance of this polymorphism. Populations started with different initial allele frequencies from homozygous F and S lines showed a convergence of frequencies on regular food at 25 degrees, leading to values equal to those in the base populations. These results were interpreted as due to some kind of balancing selection. In populations kept at 29.8 degrees, a lower equilibrium F frequency was attained. Addition of ethanol and some other alcohols to the food gave a rapid increase in F frequency, and high humidity decreased the F frequency slightly. Combination or alternation of ethanol and high humidity had variable effects in the populations tested. For a further analysis of the allele-frequency changes, estimates were obtained for egg-to-adult survival under different conditions and for adult survival on ethanol-supplemented food. On ethanol food (both at regular and high humidity), egg-to-adult survival of SS homozygotes was considerably lower than that of the FF and FS genotypes. Under regular conditions of food, temperature and humidity, a tendency to heterozygote superiority was observed, while at high humidity a relative high survival of SS was noticed in some tests. Adult survival of SS was lower than that of FF, but FS was generally intermediate, though the degree of dominance differed between populations. The results are consistent with the hypothesis of the occurrence of selection at the Adh locus.

Alcohol Oxidoreductases↗

Comparison of antibody titers determined by hemagglutination inhibition and enzyme immunoassay for JC virus and BK virus.

A comparison of antibody titers to JC virus (JCV) or BK virus (BKV) was made by hemagglutination inhibition (HI) and enzyme immunoassay (EIA) with 114 human plasma samples. Antibody titers to JCV or BKV determined by HI were lower than those determined by EIA. Nevertheless, as HI titers increased so did EIA titers. When antibody data were compared by the Spearman rank correlation test, highly significant correlations were found between HI and EIA titers. Results obtained by plotting EIA antibody titers for JCV against those for BKV generally showed a reciprocal relationship, i.e., samples with high antibody titers to JCV had lower antibody titers to BKV and vice versa. Some samples, however, had antibody titers to both viruses. Of the samples tested, 25.4% (25 of 114) had HI and EIA antibody titers to JCV and BKV which were identical or closely related. This is not the scenario one would expect for cross-reactive epitopes shared by the two viruses, but one suggesting that these samples were from individuals who had experienced infections by both viruses. Adsorption with concentrated JCV or BKV antigen of sera with high antibody titers to both JCV and BKV and testing by JCV and BKV EIA gave results which support this conclusion. Although 52.6% (51 of 97) of the samples from the Japanese population tested had very high antibody titers (>/=40,960) to either JCV or BKV, none of the samples were found by a dot blot immunoassay to have antibodies which cross-reacted with simian virus 40. The results from this study, in agreement with those of others, suggest that humans infected by JCV or BKV produce antibodies to species-specific epitopes on their VP1 capsid protein, which is associated with hemagglutination and cellular binding.

Antibodies, Viral↗

Dorsal effect of the patella: incidence and distribution.

To determine the incidence and distribution of dorsal defect of the patella, the radiographs of 2,349 knees in 1,192 consecutive patients were evaluated. The defect was present in about 1% of the population. It may be found at any age from the preadolescent to the mature adult. Females were more commonly affected than males. The test population group was validated by concurrent tabulation and comparison with other series of two other bening lesions occurring at the knee: fabella and multipartite patella.

Adolescent↗