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Background Weight gain and hypoglycaemia are common adverse effects associated with anti-diabetic treatments. Aim Our aim was to evaluate the long-term effects of adjunctive exenatide therapy on weight loss and glycaemic control in patients with type 2 diabetes. Methods A review of medical records in a specialist diabetes clinic over 5 years identified 446 patients who were prescribed exenatide therapy. We examined change in glycosylated haemoglobin ( HbA1c), weight, albumin-creatinine ratio and hypoglycaemic medication during 24 months follow up. Results Subjects were aged 59 ± 10 years (49% women) and received exenatide in combination with oral agents and insulin (47%). During an average of 17 ± 14 months follow up, 51% (more women than men; odds ratio 1.69, 95% confidence interval 1.14-2.49) remained on treatment. Lack of efficacy (33%) and/or gastrointestinal (27%) side-effects were the main reasons for treatment cessation. At 24 months, there was a reduction in HbA1c of 0.7 ± 1.2% and weight loss of 4.3 ± 5.2 kg. Change in HbA1c was similar regardless of concurrent insulin therapy, yet insulin was associated with greater weight reduction (4.8 ± 5.3 vs 3.8 ± 5.1 kg, P = 0.016). Independent predictors of HbA1c response were higher baseline HbA1c, longer duration of diabetes and use of insulin or sulfonylureas at study end. Predictors of weight response were baseline use of insulin or thiazolidinediones, increased age, female sex and sulfonylurea or thiazolidinediones at study end. Longer exenatide treatment duration was favourable for reducing HbA1c and weight. Conclusions Exenatide is effective in reducing HbA1c and weight, regardless of concurrent insulin, and in a specialist diabetes outpatient clinic, is recommended for use in clinical practice. [ABSTRACT FROM AUTHOR]

Ancestral background, specifically African descent, confers higher risk for development of inhibitory antibodies to factor VIII ( FVIII) in haemophilia A. It has been suggested that differences in the distribution of FVIII gene ( F8) haplotypes, and mismatch between endogenous F8 haplotypes and those comprising products used for treatment could contribute to risk. Data from the Hemophilia Inhibitor Genetics Study ( HIGS) Combined Cohort were used to determine the association between F8 haplotype 3 (H3) vs. haplotypes 1 and 2 (H1 + H2) and inhibitor risk among individuals of genetically determined African descent. Other variables known to affect inhibitor risk including type of F8 mutation and human leucocyte antigen ( HLA) were included in the analysis. A second research question regarding risk related to mismatch in endogenous F8 haplotype and recombinant FVIII products used for treatment was addressed. Haplotype 3 was associated with higher inhibitor risk among those genetically identified ( N = 49) as of African ancestry, but the association did not remain significant after adjustment for F8 mutation type and the HLA variables. Among subjects of all racial ancestries enrolled in HIGS who reported early use of recombinant products ( N = 223), mismatch in endogenous haplotype and the FVIII proteins constituting the products used did not confer greater risk for inhibitor development. Haplotype 3 was not an independent predictor of inhibitor risk. Furthermore, our findings did not support a higher risk of inhibitors in the presence of a haplotype mismatch between the FVIII molecule infused and that of the individual. [ABSTRACT FROM AUTHOR]

This study represents the first report on the distribution of KIR genes in 205 unrelated healthy mestizo Venezuelan individuals. Genotyping analysis showed that all KIR genes are present in this population. Frequency of inhibitory killer cell immunoglobulin-like receptors (KIRs) exceeded 0.69, except for KIR2DL2 (0.29) and 2DL5 (0.37). Activating KIRs showed low frequencies (0.11–0.29), except for KIR2DS4 (0.68). Forty-five different KIR genotypes were identified, with a predominance of three genotypes found in 50.7% of the population of which 25.9% were individuals homozygous for haplotype A. The frequencies of KIR genes reflect the ethnic admixture existing in the mestizo Venezuelan population. [ABSTRACT FROM AUTHOR]

America's increasingly diverse older population needs clinicians to be familiar with ethnic and cultural issues pertaining to end-of-life care (EOLC). Although there has been some work addressing these issues among African-American, Hispanic-American, and some Asian-American populations, data on the Asian-Indian and Hindu populations remain sparse. This community-based exploratory study surveyed older Indo-Caribbean Hindu people (a subset of the Hindu population living in America) attending a senior center in Queens, New York. This study describes the demographic and health characteristics of this population and examines their attitudes, knowledge, and beliefs regarding some EOLC issues. Data on participants' demographic, medical, psychosocial, and cognitive status were obtained. Previously validated scales were used to collect data on subjects' acculturation, religiosity, and EOLC beliefs. Participants had a mean age±standard deviation of 71.1±5.1 years; 43% were married. Prevalent illnesses included diabetes mellitus (48%), hypertension (66%), and arthritis (57%). Subjects were socially connected, moderately acculturated, and religious. Scores on the Ethnicity and Attitudes Towards EOLC Survey indicated negative beliefs about life-sustaining or prolonging technology and positive attitudes about advance care directives (ACDs), truth-telling, and family involvement. The number of ACDs that had been completed and knowledge about ACDs was low. The Indo-Caribbean elder population in this study expressed attitudes and beliefs regarding EOLC similar to those of other ethnic elders. Many of these beliefs are in conflict with current EOLC practice patterns. This highlights the importance of being aware of differing attitudes to provide sensitive EOLC. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate possible associations of HLA polymorphisms with idiopathic inflammatory myopathy (IIM) in African Americans, and to compare this with HLA associations in European American IIM patients with IIM. METHODS: Molecular genetic analyses of HLA-A, B, Cw, DRB1, and DQA1 polymorphisms were performed in a large population of African American patients with IIM (n = 262) in whom the major clinical and autoantibody subgroups were represented. These data were compared with similar information previously obtained from European American patients with IIM (n = 571). RESULTS: In contrast to European American patients with IIM, African American patients with IIM, in particular those with polymyositis, had no strong disease associations with HLA alleles of the 8.1 ancestral haplotype; however, African Americans with dermatomyositis or with anti-Jo-1 autoantibodies shared the risk factor HLA-DRB1*0301 with European Americans. We detected novel HLA risk factors in African American patients with myositis overlap (DRB1*08) and in African American patients producing anti-signal recognition particle (DQA1*0102) and anti-Mi-2 autoantibodies (DRB1*0302). DRB1*0302 and the European American-, anti-Mi-2-associated risk factor DRB1*0701 were found to share a 4-amino-acid sequence motif, which was predicted by comparative homology analyses to have identical 3-dimensional orientations within the peptide-binding groove. CONCLUSION: These data demonstrate that North American IIM patients from different ethnic groups have both shared and distinct immunogenetic susceptibility factors, depending on the clinical phenotype. These findings, obtained from the largest cohort of North American minority patients with IIM studied to date, add additional support to the hypothesis that the myositis syndromes comprise multiple, distinct disease entities, perhaps arising from divergent pathogenic mechanisms and/or different gene-environment interactions. [ABSTRACT FROM AUTHOR]

The population distribution of alleles of the classical HLA class I loci in Cameroon has not been well studied but is of particular interest given the AIDS and malarial epidemics afflicting this population. We investigated the genetic diversity of HLA-A, HLA-B and HLA-C alleles in remote populations of Cameroon. Subjects from seven small, isolated, indigenous populations (N = 274) in the rainforest of southern Cameroon were typed for HLA-A, HLA-B and HLA-C alleles using a polymerase chain reaction/sequence-specific oligonucleotide probe assay and sequence analysis. Multiple alleles of the HLA-A (N = 28), HLA-B (N = 41) and HLA-C (N = 21) loci were identified, of which A*2301 [allele frequency (AF) = 12.8%], B*5802 (AF = 10.9%) and Cw*0401 (AF = 16.6%) were the most frequent individual alleles and A*02 (AF = 19.0%), B*58 (AF = 15.9%) and Cw*07 (AF = 22.4%) the most common serologically defined groups of alleles. Twenty-six (28.9%) alleles with a frequency of less than 1% (AF < 1%), 39 (43%) with a frequency of 2.0-15.0% (AF = 2.0-15.0%), three globally uncommon alleles [A*2612 (AF = 2.0%), B*4016 (AF = 0.7%) and B*4407 (AF = 1.4%)], and the A*2612-Cw*0701/06/18-B*4407 haplotype (haplotype frequency = 1.3%) were also identified. Heterozygosity values of 0.89, 0.92 and 0.89 were determined for HLA-A, HLA-B and HLA-C, respectively. The extensive allelic and haplotypic diversity observed in this population may have resulted from varied natural selective pressures on the population, as well as intermingling of peoples from multiple origins. Thus, from an anthropologic perspective, these data highlight the challenges in T-cell-based vaccine development, the identification of allogeneic transplant donors and the understanding of infectious disease patterns in different populations. [ABSTRACT FROM AUTHOR]

Human leukocyte antigen (HLA) variations may affect immune response to human papillomavirus infection and subsequent cervical neoplasia risk. We investigated the frequency and relationship between HLA-A-B and HLA-A-B-DR haplotypes among women with cervical cancer/high-grade lesions ( n = 365) and cytologically normal population controls ( n = 681) within three cervical neoplasia studies in the US and Costa Rica. Notable differences in haplotype frequencies were observed; the HLA-A*01-B*08 haplotype occurred in >5% of US Caucasians but in <1% of Costa Ricans. The most prevalent HLA-A*24-B*40-DR*04 haplotype in Costa Rica (5%) was found in <1% of US Caucasians. No HLA haplotype was significantly associated with cervical neoplasia, suggesting that individual allele associations reported to date (e.g. HLA-DR*13) are not likely explained by underlying haplotypes. [ABSTRACT FROM AUTHOR]

Twenty-two human major histocompatibility complex (MHC) region microsatellite (Msat) markers were studied for diversity and linkage disequilibrium (LD) with HLA loci in hematopoietic cell transplant recipients and their HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele-matched unrelated donors. These Msats showed highly significant LD over much of the MHC region. The Msat diversity of five common Caucasian haplotypes (HLA-A1-B8-DR3, A3-B7-DR15, A2-B44-DR4, A29-B44-DR7, and A2-B7-DR15) was examined using a new measure called ‘haplotype specific heterozygosity’ (HSH). Each of the five haplotypes had at least one Msat marker with an HSH value of zero indicating that only one Msat allele was observed for the particular HLA haplotype. In addition, the ability of Msats to predict HLA-A-B-DRB1 haplotypes was studied. Over 90% prediction probability of two common haplotypes (HLA-A1-B8-DR3 and HLA-A3-B7-DR15) was achieved with information from three Msats (D6S265/D6S2787/D6S2894 and D6S510/D6S2810/D6S2876, respectively). We demonstrate how the HSH index can be used in the selection of informative Msats for transplantation and disease association studies. Markers with low HSH values can be used to predict specific HLA haplotypes or multilocus genotypes to supplement the screening of HLA-matched donors for transplantation. Markers with high HSH values will be most informative in studies investigating MHC region disease-susceptibility genes where HLA haplotypic effects are known to exist. [ABSTRACT FROM AUTHOR]

Reviews of microsatellite markers in the human leukocyte antigen region have been very useful in addressing the needs of the immunogenetics community. Nevertheless, characterization of the same microsatellite loci in different laboratories can lead to seemingly contradictory results, particularly in terms of nomenclature. Here we provide an update of previous reports, as well as a standardized characterization of primers for microsatellites located within the major histocompatibility complex (MHC). A uniform and extended inventory of 378 primer pairs from published reports was performed as well as a standardized characterization of the corresponding microsatellite loci according to the extended full-length consensus sequence of MHC region. The literature-based approach was complemented by a sequence-based analysis of each reported microsatellite locus. Iterative electronic polymerase chain reaction runs and an original algorithm that characterizes patterns of repeats within sequence were used. The sequence of primers was corrected according to the consensus sequence. Table of synonymous names for individual microsatellite loci is provided. [ABSTRACT FROM AUTHOR]

Reports on the formation of a subcommittee to coordinate the naming of alleles of the genes encoding the killer-cell immunoglobulin-like receptors (KIR). Characteristics of the genes; Expression of the receptors encoded by the KIR genes; Method of naming KIR haplotypes.

Provides information on a study which evaluated the role of fire in altering vegetation structure in three plant communities in inland peninsular Florida. Methods; Results and discussion.

Testing the fit of population data to Hardy-Weinberg proportions is crucial in the validation of many current approaches in population genetic studies. In this paper, we tested fit to Hardy-Weinberg proportions using exact approaches for both the overall and individual heterozygote genotype data of four HLA Class II loci: DRB1, DQA1, DQB1, and DPB1, from 26 human populations. Eighty of 99 overall tests fit the Hardy-Weinberg expectation (73% for DRB1, 89% for DQA1, 81% for DQB1 and 81% for DPB1). Deviations from Hardy-Weinberg proportions were both locus and group specific. Although we could not rule out other mechanisms at work, the individual test results indicated that the departure was possibly partly due to recent admixture. Evidence for selection and other sources of deviation are also discussed. [ABSTRACT FROM AUTHOR]

There is increasing evidence for epistatic interactions between gene products (e.g. KIR) encoded within the Leukocyte Receptor Complex (LRC) with those (e.g. HLA) of the Major Histocompatibility Complex (MHC), resulting in susceptibility to disease. Identification of such associations at the DNA level requires comprehensive knowledge of the genetic variation and haplotype structure of the underlying loci. The LRC haplotype project aims to provide this knowledge by sequencing common LRC haplotypes. [ABSTRACT FROM AUTHOR]

This study deals with a quantification of pre- and post-fire seedling establishment and microsite characteristics in two Florida sand pine scrub sites burned in May 1993. In addition, life history characteristics related to seedling establishment are described for five perennial species - Calamintha ashei, Chapmannia foridana, Eriogonumfloridanum, Garberia heterophylla and Palafoxia feayi. Post-fire seedling establishment in sand pine scrub was sparse (median = 1, 12 seedling/ m2), with 17 of 35 species establishing seedlings. Chapmannia, Eriogonum, Garberia and Palafoxia resprouted and flowered after fire; Eriogonum and Garberia had strong post-fire seedling establishment responses within 19 months post-fire. Calamintha individuals werekilled by fire, but this species had a strong post-fire seedling establishment response, presumably from seeds in a soil seed bank. Eriogonum and Calamintha seedlings established preferentially in plots centered on conspecific adults. For these species with poor seed dispersal, spatial patterns of seedling establishment may be influenced moreby pre-fire adult plant location than by post-fire microsite conditions. Post-fire seedling density in sand pine scrub was much lower than in California chaparral and South African sand plain lowland fynbos. [ABSTRACT FROM AUTHOR]

Presents killer-cell immunoglobulin-like receptor (KIR) nomenclature report for the year 2002. Changes in names of KIR genes and proteins; Naming of KIR allele sequences; Official recognition of KIR alleles.

Objective: Although HLA-B27 is strongly associated with susceptibility to Reiter's syndrome (RS), recent data suggest that an additional modifying or susceptibility gene(s) acts in concert with HLA-B27 to contribute to disease pathogenesis. The recently described TAP genes (transporters associated with antigen processing) are potential candidates because they are polymorphic and their function is to transport antigenic peptides to be loaded in HLA class I molecules., Methods: TAP1 and TAP2 alleles were determined for 34 patients with RS (28 HLA-B27 positive, 6 HLA-B27 negative), and their frequencies were compared with those observed for 52 HLA-B27 positive and 80 random disease-free control subjects., Results: The allele frequency of TAP1C was greater in patients with RS (8 of 62, 13%) than in random controls (5 of 160, 3%) (P = 0.009). The frequency of TAP2A was greater in RS patients (51 of 66, 77%) than in random controls (88 of 160, 55%) (P = 0.002); likewise, the frequency was greater in HLA-B27 positive RS patients (41 of 54, 76%) than in HLA-B27 positive disease-free controls (49 of 94, 52%) (P = 0.004). Furthermore, the TAP2A allele was present in all RS patients (100%), whereas TAP2A was present in 79% (63 of 80) of the random controls (P = 0.003)., Conclusion: The association observed between TAP alleles and RS is independent of the presence of HLA-B27, and despite the physical proximity of TAP and HLA class II genes, linkage disequilibrium does not account for the observed associations between TAP and RS. Thus, TAP genes are genetically separated but functionally linked to class I genes, and both contribute to susceptibility to RS.