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S Clifton

Publications and source records attributed to S Clifton.

12 recordsLinked to original sources

Sequence, structure, and evolution of a complete human olfactory receptor gene cluster.

The olfactory receptor (OR) gene cluster on human chromosome 17p13.3 was subjected to mixed shotgun automated DNA sequencing. The resulting 412 kb of genomic sequence include 17 OR coding regions, 6 of which are pseudogenes. Six of the coding regions were discovered only upon genomic sequencing, while the others were previously reported as partial sequences. A comparison of DNA sequences in the vicinity of the OR coding regions revealed a common gene structure with an intronless coding region and at least one upstream noncoding exon. Potential gene control regions including specific pyrimidine:purine tracts and Olf-1 sites have been identified. One of the pseudogenes apparently has evolved into a CpG island. Four extensive CpG islands can be discerned within the cluster, not coupled to specific OR genes. The cluster is flanked at its telomeric end by an unidentified open reading frame (C17orf2) with no significant similarity to any known protein. A high proportion of the cluster sequence (about 60%) belongs to various families of interspersed repetitive elements, with a clear predominance of LINE repeats. The OR genes in the cluster belong to two families and seven subfamilies, which show a relatively high degree of intermixing along the cluster, in seemingly random orientations. This genomic organization may be best accounted for by a complex series of evolutionary events.

Base Sequence↗

An encyclopedia of mouse genes.

The laboratory mouse is the premier model system for studies of mammalian development due to the powerful classical genetic analysis possible (see also the Jackson Laboratory web site, http://www.jax.org/) and the ever-expanding collection of molecular tools. To enhance the utility of the mouse system, we initiated a program to generate a large database of expressed sequence tags (ESTs) that can provide rapid access to genes. Of particular significance was the possibility that cDNA libraries could be prepared from very early stages of development, a situation unrealized in human EST projects. We report here the development of a comprehensive database of ESTs for the mouse. The project, initiated in March 1996, has focused on 5' end sequences from directionally cloned, oligo-dT primed cDNA libraries. As of 23 October 1998, 352,040 sequences had been generated, annotated and deposited in dbEST, where they comprised 93% of the total ESTs available for mouse. EST data are versatile and have been applied to gene identification, comparative sequence analysis, comparative gene mapping and candidate disease gene identification, genome sequence annotation, microarray development and the development of gene-based map resources.

Animals↗

Above reproach: developing a comprehensive ethics and compliance program.

How can a healthcare organization improve the public's confidence in the conduct of its business operations? What can it do to ensure that it can thrive despite being the subject of public and governmental scrutiny and doubt? Healthcare providers must establish standards of conduct that are above reproach and ensure that those standards are clearly articulated and strictly adhered to. This article describes the merits of a comprehensive ethics and compliance program, suggests five basic elements of such a program--organizational support/structure, setting standards, creating awareness, establishing a mechanism for reporting exceptions, and monitoring and auditing--and then demonstrates how those elements should be applied in several high-risk areas. Fundamentally, an ethics and compliance program has two purposes: to ensure that all individuals in an organization observe pertinent laws and regulations in their work; and to articulate a broader set of aspirational ethical standards that are well-understood within the organization and become a practical guideline for organization members making decisions that raise ethical concerns. Every ethics and compliance program should contain certain fundamental aspects. First, the effort must have the active support of the most senior management in the organization. To instill a commitment to ethics and compliance absent a clear and outspoken commitment to such purposes by organization leaders is simply impossible. Second, an ethics and compliance program is fundamentally about organizational culture--about instilling a commitment to observe the law and, more generally, to do the right thing. Third, ethics and compliance are responsibilities of operating management (sometimes called line management). Although staff such as compliance officers are obligated to provide the necessary resources for a successful program and to design the program, such staff officers cannot achieve implementation and execution. Only operating managers can do that. Fourth, an ethics and compliance effort should be about the conduct of individuals, not about "checking the boxes" in a model plan or generating attractive written or educational materials. Such an effort is about individuals on a day-to-day basis knowing what is expected of them and doing it and about never compromising integrity, regardless of pressures faced. A great deal of progress has been made in healthcare organizations in the development of increasingly sophisticated ethics and compliance programs. A particularly energetic focus has been placed on these programs since formal government guidance regarding compliance programs was first issued in the laboratory area about two years ago and as more sophisticated automated monitoring tools have been developed. As ethics and compliance programs have become more sophisticated, certain best practices have been established. This discussion will set forth approaches to ethics and compliance in the context of what are believed to be illustrative best practices. Much of what is described here is descriptive of the efforts of Columbia/HCA Healthcare Corporation from October 1997 to the present; however, this article has been presented not as a mere descriptive piece but rather as a set of normative guidelines. We hope that other healthcare providers will find this to be of practical use. Provider settings pose certain unique challenges that are specifically addressed in this discussion; however, many of the issues raised can be adapted to other healthcare organizations. For simplicity's sake, because the authors of this article all work on a daily basis primarily with hospitals, the article is written from a hospital perspective.

Ethics, Institutional↗

Genetic and physical mapping of the Lps locus: identification of the toll-4 receptor as a candidate gene in the critical region.

On the basis of 2093 meioses analyzed in two separate intraspecific backcrosses, the location of the mouse Lpsd mutation was circumscribed to a genetic interval 0.9 cM in size. A total of 19 genetic markers that lie in close proximity to the mutation were examined in mapping. Most of these were previously unpublished polymorphic microsatellites, identified by fragmentation of YAC and BAC clones spanning the region of interest. Lpsd was found to be inseparable from the microsatellite marker D4MIT178, and from three novel polymorphic microsatellites identified near D4MIT178. The mutation was confined between two novel microsatellite markers, herein designated "B" and "83.3." B lies centromeric to the mutation, and was separated by four crossovers in a panel of 1600 mice; 83.3 lies distal to the mutation and was separated by three crossovers in a panel of 493 mice. 66 BAC clones and one YAC clone were assembled to cover > 95% of the critical region. Estimates based on pulsed field gel electrophoresis and fluorescence in situ hybridization indicate that the The B-->83.3 interval is about 3.2 Mb in length. A minimal area of zero recombinational distance from Lpsd was also assigned, and found to occupy approximately 1.2 Mb of physical size. To identify gene candidates, nearly 40,000 sequencing runs were performed across the critical region. Selective hybridization and exon trapping were also employed to identify genes throughout the "zero" region. Only a single intact gene was identified within the entire critical region. This gene encodes the Toll-4 receptor, a member of the IL-1 receptor family.

Animals↗

Sequence analysis in the olfactory receptor gene cluster on human chromosome 17: recombinatorial events affecting receptor diversity.

A cosmid clone covering a region of high olfactory receptor (OR) gene density inside the OR gene cluster on human chromosome 17 (17p13.3) was subjected to shotgun automated DNA sequencing. The resulting 40-kb sequence revealed three known OR coding regions, as well as a new OR pseudogene (OR17-25), fused to one of the previously identified OR genes (OR17-24). The suggested mechanism for the generation of this doublet structure involves an initial duplication mediated by flanking repeats and a subsequent deletion via nonhomologous recombination. Sequence analysis further suggests that the two other OR genes present in the cosmid (OR17-40 and OR17-228) may have evolved by ancient tandem duplication of an 11-kb fragment, mediated by recombination between mammalian-wide interspersed repeats. The duplicated genes appear to be complete and potentially functional. Their conserved structure reveals a long upstream intron and a previously uncharacterized 5' noncoding exon. No additional genes could be discerned in the cosmid, suggesting that the cluster may be part of a dedicated OR subgenome.

Base Sequence↗

Membranous glomerulonephritis associated with sarcoidosis.

Two patients with sarcoidosis involving pulmonary hilar lymph nodes developed the nephrotic syndrome. Renal biopsy in both cases showed membranous glomerulonephritis. In one patient, there was an associated renal vein thrombosis.

Adult↗

The spectrum of liver diseases in alcoholism.

Liver biopsies obtained from 100 alcoholic patient attending a clinic primarily for the management of their alcoholism, have been reviewed. The morphological appearances have been correlated with histories of alcohol consumption and with clinical and biochemical findings. There were 77 men and 23 women. Eight biopsies appeared normal, 62 showed fatty liver with or without fribrosis, 17 had alcoholic hepatitis with or without fibrosis and 13 had alcoholic hepatitis with established cirrhosis. Patients with fatty liver had drunk as long and as heavily as those with alcoholic hepatitis, suggesting that some other factor in addition to alcohol is of importance in the development of alcoholic hepatitis. Clinical and biochemical abnormalities showed no constant relationship to histological findings. Thus liver biopsy would seem to be an essential part of the full clinical assessment of the alcoholic patient.

Adult↗