Biomedical subjects
S J Potter
Publications and source records attributed to S J Potter.
Hartnup disorder: polymorphisms identified in the neutral amino acid transporter SLC1A5.
Hartnup disorder is an inborn error of renal and gastrointestinal neutral amino acid transport. The cloning and functional characterization of the 'system B0' neutral amino acid transporter SLC1A5 led to it being proposed as a candidate gene for Hartnup disorder. Linkage analysis performed at 19q13.3, the chromosomal position of SLC1A5, was suggestive of an association with the Hartnup phenotype in some families. However, SLC1A5 was not linked to the Hartnup phenotype in other families. Linkage analysis also excluded an alternative candidate region at 11q13 implicated by a putative mouse model for Hartnup disorder. Sequencing of the coding region of SLC1A5 in Hartnup patients revealed two coding region polymorphisms. These mutations did not alter the predicted amino acid sequence of SLC1A5 and were considered unlikely to play a role in Hartnup disorder. There were no mutations in splice sites flanking each exon. Quantitative RT-PCR of SLC1A5 messenger RNA in affected and unaffected subjects did not support systemic differences in expression as an explanation for Hartnup disorder. In the six unrelated Hartnup pedigrees studied, examination of linkage at 19q13.3, polymorphisms in the coding sequence and quantitation of expression of SLC1A5 did not suffice to explain the defect in neutral amino acid transport.
Novel fibroblast growth factor 2 transcripts are expressed in mouse embryos.
We have discovered two new exons in the mouse fibroblast growth factor 2 (FGF-2 or bFGF) gene that can be alternatively spliced to the second coding exon of the gene. The newly identified exons 1b and 1c are located at, respectively, approximately 19 and 32 kb downstream of the canonical exon 1a. Using RT-PCR analysis, mRNAs containing exon 1c and canonical exons 2 and 3 were identified in embryonic limb, placenta, face, carcass and ocular tissues. A 3.7-kb transcript present in placenta and embryonic limb hybridizes with an exon 1c-derived probe in Northern blot analysis. Alternative splicing of exon 1c to exon 2 creates a transcript for which the predicted alternative FGF-2 (altFGF-2) polypeptide contains a novel N-terminal domain. Our data indicate that in mouse embryos multiple novel mRNA variants are transcribed from the FGF-2 locus using alternative splicing. These data suggest that proteins arising from these alternative transcripts may play a role in mouse embryogenesis.
A longitudinal analysis of the distinction between for-profit and not-for-profit hospitals in America.
Have changes in the hospital industry forced not-for-profit hospitals to become more like for-profit hospitals in measures of efficiency and community service? As a result, are not-for-profit hospitals moving away from their community service missions? In recent years researchers have asserted that the once-salient distinctions between not-for-profit and for-profit hospitals are quickly eroding and that this convergence threatens the community service that not-for-profit hospitals have historically provided. Neo-institutionalists explain that regulatory changes often force differing organization types to pursue similar strategies (Fligstein 1991, 1985; DiMaggio and Powell 1983). Guided by this theory, the present research analyzes if regulatory changes and the implementation of similar strategies result in not-for-profit and for-profit hospitals having similar efficiency and community service outcomes.
The Omagh bombing--a medical perspective.
The bomb in Omagh on the 15th August 1998 was responsible for the largest loss of life of any single terrorist incident in the whole of the "Troubles" in Northern Ireland. However, the medical response to this tragedy provided an excellent opportunity for the civilian and military agencies to work together. As a consequence of this a number of lessons were drawn which are presented in the paper. Whatever the outcome of the peace process these lessons will have an important role in the future, since history would suggest that there is little possibility of the terrorist threat ever completely.
Special care units for Alzheimer's patients: their role in the nursing home market.
The Special Care Unit (SCU) is a new, rapidly proliferating mode of caring for people with Alzheimer's disease (AD). Approximately 10% of nursing homes within the U.S. have SCUs with the number expected to grow substantially in coming years. SCUs are largely unregulated and not uncontroversial. This article discusses their emergence over time, their origins, growth, and the call for standardization. Subsequent sections review the range of potential benefits and costs associated with SCUs, optimally defined as well as research evidence available on this mode of care. Recent cost-setting and reform pressures in the nursing home industry are discussed in the final sections along with the likely future of AD SCUs in this environment.
Association of the expression of an SR-cyclophilin with myeloid cell differentiation.
The role of a 150-kD SR-cyclophilin (NK-TR1) in monocyte differentiation was investigated. Using an antipeptide monoclonal antibody, we have detected NK-TR1 in human peripheral blood monocytes and HL-60 cells. Unstimulated monocytes showed a low intracellular level of NK-TR1 protein that increased over 3 days of lipopolysaccharide + interferon-gamma treatment, consistent with the kinetics of monocyte differentiation. Normal HL-60 cells also had a low level of NK-TR1 protein, and exposure to 1.25% dimethyl sulfoxide (DMSO) resulted in a marked transient increase in expression that returned to basal levels before the development of granulocyte differentiation-associated biochemical changes. Phorbol myristate acetate, a promoter of monocytic differentiation in HL-60 cells, also caused a significant increase in NK-TR1 over basal levels. Transfection of a vector expressing NK-TR1 antisense RNA into HL-60 cells suppressed DMSO-mediated growth arrest. In addition, the development of a more mature phenotype, as measured by expression of CD16, and the ability to reduce nitroblue tetrazoleum dye was inhibited in transfectants when compared with controls. These results are consistent with the hypothesis that the NK-TR1 gene product is required for the progression towards a mature differentiated phenotype.
Primary structure and gene organization of human hepatitis A virus.
The RNA genome of human hepatitis A virus (HAV) was molecularly cloned. Recombinant DNA clones representing the entire HAV RNA were used to determine the primary structure of the viral genome. The length of the viral genome is 7478 nucleotides. An open reading frame starting at nucleotide 734 and terminating at nucleotide 7415 encodes a polyprotein of Mr 251,940. Comparison of the HAV nucleotide sequence with that of other picornaviruses has failed to reveal detectable areas of homology. However, a computer analysis of the putative amino acid sequence of HAV and poliovirus demonstrated the existence of short areas of homology in virion protein 3 (VP3) and throughout the carboxyl-terminal portion of the polyproteins. In addition, extensive protein structural homologies with poliovirus were detected.
Molecular cloning of AIDS-associated retrovirus.
Retroviruses cause a wide variety of diseases in avian and mammalian species. Human acquired immune deficiency syndrome (AIDS) leads to collapse of the immune system and death by a wide variety of opportunistic infections; unusual forms of cancer are associated with this syndrome. Retroviruses have been recovered from tissues of AIDS patients and from patients with related conditions. These similar newly-isolated viruses are lymphadenopathy-associated virus (LAV), human T-cell lymphotropic virus (HTLV-III) and AIDS-associated retrovirus (ARV-2). We have identified a RNA genome of approximately 9 kilobases (kb) in virions purified from the culture medium of a human T-cell tumour line infected with ARV-2. A cDNA probe made from viral RNA detected circular DNA molecules and proviral forms in infected cells. We prepared a library of infected cell DNA. Recombinant phage included those with a 9.5-kb proviral DNA and viral DNA permuted with respect to the single EcoRI site. Comparison of three ARV isolates from different AIDS patients revealed polymorphism of restriction endonuclease sites.
Access to and participation in breast cancer screening: a review of recent literature.
Recently, attention has been focused on the incentives for access to and participation in breast cancer screening programs. The Healthy People 2000 health goals for the nation calls for 60% of women aged 50 years and older to have had mammograms and clinical breast exams within the preceding 2 years. To achieve this objective, the incentives for access to and participation in breast cancer screening programs must be identified. The present review examines incentive-based hypotheses dealing with lower socioeconomic status, lack of insurance coverage, physician referral, and self-referral. Policy-oriented solutions that have attempted to correct the disincentives associated with low access and participation were analyzed. The sophistication of screening technology is of primary importance; however, this review provides additional information that can be used to ensure the implementation of quality mammography screening programs.