Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis.

Sequence variation in human genes is largely confined to single-nucleotide polymorphisms (SNPs) and is valuable in tests of association with common diseases and pharmacogenetic traits. We performed a systematic and comprehensive survey of molecular variation to assess the nature, pattern and frequency of SNPs in 75 candidate human genes for blood-pressure homeostasis and hypertension. We assayed 28 Mb (190 kb in 148 alleles) of genomic sequence, comprising the 5' and 3' untranslated regions (UTRs), introns and coding sequence of these genes, for sequence differences in individuals of African and Northern European descent using high-density variant detection arrays (VDAs).

pPAC-ResQ: A yeast-bacterial shuttle vector for capturing inserts from P1 and PAC clones by recombinogenic targeted cloning.

We have developed a method to capture inserts from P1 and P1 artificial chromosome (PAC) clones into a yeast-bacteria shuttle vector by using recombinogenic targeting. We have engineered a vector, pPAC-ResQ, a derivative of pClasper, which was previously used to capture inserts from yeast artificial chromosome clones. pPAC-ResQ contains DNA fragments flanking the inserts in P1 and PAC vectors as recombinogenic ends.

Antibiotic prophylaxis in orthognathic surgery: a 1-day versus 5-day regimen.

Purpose: The effect on infection rates of 1-day and 5-day administration of prophylactic antibiotics in orthognathic surgical procedures was compared.

Patients And Methods: A prospective, randomized, double-blind clinical trial using placebo was conducted. Thirty patients were distributed equally between two groups.

Differential efficiency of expression of humanized antibodies in transient transfected mammalian cells.

Transient transfections are commonly used in the preliminary assessment of comparative levels of expression, biologic activity, and affinity of recombinant antibody molecules, but apparent expression levels can vary up to 200-fold. We have compared the expression levels of various humanized antibodies and "mixed and matched" heavy and light chains in transiently transfected CHO cells using replicate, small-scale transfections within single or replicate experiments to control for variation in transfection efficiency. We have found that each antibody is expressed with a characteristic efficiency, determined by a combination of factors including the level of light-chain synthesis, heavy- and light-chain "compatibility," and CDR/framework interactions to provide a compact Fv module.

Genomic structure of the gene for the SH2 and pleckstrin homology domain-containing protein GRB10 and evaluation of its role in Hirschsprung disease.

Hirschsprung disease (HSCR), or congenital aganglionic megacolon, is the most frequent cause of congenital bowel obstruction. Germline mutations in the RET receptor tyrosine kinase have been shown to cause HSCR. Mice that carry null alleles for RET or for its ligand, glial cell line-derived neurotrophic factor (GDNF), both exhibit complete intestinal aganglionosis and renal defects.

Recombinogenic targeting: a new approach to genomic analysis--a review.

Currently, recombinational cloning procedures based upon methods developed for yeast, Saccharomyces cerevisiae, are being exploited for targeted cloning and in-vivo modification of genomic clones. In this review, we will discuss the development of large-insert vectors, homologous recombination-based techniques for cloning and modification, and their application towards functional analysis of genes using transgenic mouse model systems.

Chronic toxicity, oncogenicity, and mutagenicity studies with chlorotetrafluoroethane (HCFC-124).

The chronic toxicity, oncogenicity, and mutagenicity of chlorotetrafluoroethane (HCFC-124) were evaluated. In the chronic toxicity/oncogenicity study, male and female rats were exposed to 0, 2000, 10,000, or 50,000 ppm HCFC-124 for 6 hr/day, 5 days/week, for 2 years. Body weights were obtained weekly during the first three months of the study and every other week for the remainder of the study.

5-hydroxytryptamine3 (5-HT3) receptor-mediated depolarisation of the rat isolated vagus nerve: modulation by trichloroethanol and related alcohols.

The ability of 2,2,2-trichloroethanol (TCE) and related alcohols to modify the 5-hydroxytryptamine3 (5-HT3) receptor-mediated depolarisation of the rat isolated cervical vagus nerve were investigated by extracellular electrophysiological recording using the 'grease gap' technique. TCE at millimolar concentrations increased the magnitude of the 5-HT3 receptor-mediated depolarisations of the rat vagus nerve by a number of agonists (5-HT, phenylbiguanide (PBG), quipazine). Concentration response curves generated for the 5-HT3 receptor agonists.

Detailed analysis of a 17q21 microdissection library by sequence bioinformatics and isolation of region-specific clones.

A region-specific microdissection library originating from human chromosome 17q21, was constructed using the MboI linker-adaptor microcloning technique. DNA sequencing of 241 microclones resulted in the identification of 74 novel coding sequences, paralogs of known genes, and known, but previously unmapped, genes or expressed sequence tags that were "virtually" mapped to chromosome 17q21. By pooling the microclones as multiplexed hybridization probes, and by virtue of their origin on 17q21, we were able to identify approximately 150 P1 clones from the human Reference Library Data Base P1 Library that potentially map to chromosome 17q21.

Human GFRA1: cloning, mapping, genomic structure, and evaluation as a candidate gene for Hirschsprung disease susceptibility.

Congenital aganglionic megacolon, commonly known as Hirschsprung disease (HSCR), is the most frequent cause of congenital bowel obstruction. Germline mutations in the RET receptor tyrosine kinase have been shown to cause HSCR. Knockout mice for RET and for its ligand, glial cell line-derived neurotrophic factor (GDNF), exhibit both complete intestinal aganglionosis and renal defects.

Results of the National Dental Examining Board of Canada written examination and implications for certification.

In 1994, following a request from the ten Provincial Licensing Authorities, the National Dental Examining Board of Canada (NDEB) implemented significant changes to the certification process for dentists seeking a license to practice in Canada. Prior to 1994, graduates of accredited Canadian dental programs were certified without further examination while graduates of United States and other international programs (non-Canadian, non-U.S.

Fluorescence in situ hybridisation with chromosome-specific centromeric probes: a sensitive method to detect aneuploidy.

Cytochalasin B-blocked binucleate human lymphocytes from female donors have been used to measure micronucleus induction and other aneuploidy events after treatment with colchicine, vinblastine or carbendazim. For the aneuploidy events, centromeric probes for 6 selected chromosomes (1, 8, X, 11, 17, 18) were used to measure chromosome loss, addition and non-disjunction in the interphase nuclei of these binucleate cells. The chromosomes were probed in pairs using Cy-3 (red) and FITC (green) labels for the 2 different centromeric regions.

Molecular haplotyping of genetic markers 10 kb apart by allele-specific long-range PCR.

Haplotypes, combinations of polymorphic markers in a chromosome, are critical for genome diversity research. However, their utility in population samplings is compromised by uncertain linkage phase determinations from unrelated individuals. Molecular haplotyping accomplishes direct phase determination by generation of hemizygous templates from diploid genomic samples.

Two group therapy models for clients with a dual diagnosis of substance abuse and personality disorder.

Objective: The relative effectiveness of two types of group therapy-the disease-and-recovery model and the cognitive-behavioral model-was examined in a public inpatient and outpatient setting with consumers who had a dual diagnosis of a personality disorder and a substance use disorder. Outcomes in four areas of problem severity were measured: alcohol use, drug use, social and family relations, and psychological functioning.

Methods: Using a quasiexperimental group design, 19 subjects in an inpatient mental health facility and 19 in a public outpatient facility were randomly assigned to the two experimental groups.

Maternal factors related to parenting practices, developmental expectations, and perceptions of child behavior problems.

Parenting practices of a representative sample of 1,056 urban mothers with very young children were studied via the Parent Behavior Checklist (Fox, 1994) and the Behavior Screening Questionnaire (Richman & Graham, 1971). Potential determinants of parenting practices were also addressed, including maternal age, marital status, education level, number of children living at home, and family socioeconomic status. Less positive parenting practices concerning nuturing and discipline were found among mothers who were younger, had more than one child living at home, were single, had a lower income level, and had lower educational attainment.

Human HOXB cluster and the nerve growth factor receptor gene: comparison with an orthologous chromosomal domain in mouse.

The structural organization and nucleotide sequence similarity of mammalian Antennapedia-class homeobox genes support the view that the four homeobox clusters (HOXA, B, C, and D on human chromosomes 7, 17, 12, and 2, respectively) arose through a combination of gene duplication and divergence to form a cluster, followed by several cluster duplications. The duplication events that gave rise to the four clusters appear to have involved chromosomal domains extending well beyond the borders of the clusters in either direction. This evidence arises from the observation that many genes closely linked to the homeobox clusters on different chromosomes show sequence similarity.

Atypical migratory stomatitis and Munchausen syndrome presenting as periorbital ecchymosis and mandibular subluxation.

Stomatitis areata migrans, unlike its analogue on the tongue, migratory glossitis, is not easily recognized and is so uncommon and varied in appearance that it may escape definitive diagnosis. It may be so puzzling to the clinician that the patient's credibility may be questioned. A detailed report of a case is presented in which an atypical migratory stomatitis went undiagnosed.

Evidence that the atypical 5-HT3 receptor ligand, [3H]-BRL46470, labels additional 5-HT3 binding sites compared to [3H]-granisetron.

1. The radioligand binding characteristics of the 3H-derivative of the novel 5-HT3 receptor antagonist BRL46470 were investigated and directly compared to the well characterized 5-HT3 receptor radioligand [3H]-granisetron, in tissue homogenates prepared from rat cerebral cortex/hippocampus, rat ileum, NG108-15 cells, HEK-5-HT3As cells and human putamen. 2.

The interaction of trichloroethanol with murine recombinant 5-HT3 receptors.

1. The effects of ethanol, chloral hydrate and trichloroethanol upon the 5-HT3 receptor have been investigated by use of electrophysiological techniques applied to recombinant 5-HT3 receptor subunits (5-HT3R-A or 5-HT3R-As) expressed in Xenopus laevis oocytes. Additionally, the influence of trichloroethanol upon the specific binding of [3H]-granisetron to membrane preparations of HEK 293 cells stably transfected with the murine 5-HT3R-As subunit and 5-HT3 receptors endogenous to NG 108-15 cell membranes was assessed.

Supports for community-based mental health care: an optimistic review of federal legislation.

For the past 50 years, federal legislation has been a key force in shaping the delivery of public mental health services. This article describes and summarizes recent relevant federal legislative initiatives and analyzes their potential in providing support, either explicit or implicit, for community-based mental health care for adults in the United States. These legislative mandates and options can be a source of optimism and ammunition for advocates and change agents as they continue to work vigorously to improve the mental health services system.

Evaluation of benomyl and carbendazim in the in vivo aneuploidy/micronucleus assay in BDF1 mouse bone marrow.

Benomyl and its active metabolite carbendazim were investigated in BDF1 mouse bone marrow to establish whether micronuclei induced by these fungicides are caused by clastogenic or aneugenic events. Micronuclei were evaluated for kinetochores using immunofluorescent antikinetochore antibodies. Kinetochore positive (K+) micronuclei are likely to arise from chromosome loss since they presumably contain intact kinetochores and are indicative of aneuploidy.