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S J O'Brien

Publications and source records attributed to S J O'Brien.

At least 37 records · Page 2Linked to original sources
PubMed1998

Patterns of Y and X chromosome DNA sequence divergence during the Felidae radiation.

The 37 species of modern cats have evolved from approximately eight phylogenetic lineages within the past 10 to 15 million years. The Felidae family has been described with multiple measures of morphologic and molecular evolutionary methods that serve as a framework for tracking gene divergence during brief evolutionary periods. In this report, we compare the mode and tempo of evolution of noncoding sequences of a large intron within Zfy (783 bp) and Zfx (854 bp), homologous genes located on the felid Y and X chromosomes, respectively. Zfy sequence variation evolves at about twice the rate of Zfx, and both gene intron sequences track feline hierarchical topologies accurately. As homoplasies are infrequent in patterns of nucleotide substitution, the Y chromosome sequence displays a remarkable degree of phylogenetic consistency among cat species and provides a highly informative glimpse of divergence of sex chromosome sequences in Felidae.

Animals↗
PubMed1998

A primary care perspective of meningococcal disease.

BACKGROUND: It is generally agreed that pre-admission benzyl penicillin improves the outcome in infection by Neisseria meningitidis. Even so, only a minority of cases in Birmingham received such treatment. The aim of this study was, therefore, to determine the views of general practitioners (GPs) in Birmingham on the early management of meningococcal disease, including the use of parenteral antibiotics. METHODS: A standard semi-structured confidential questionnaire was posted to GPs on the list of Birmingham Family Health Services Authority. The questions covered the GPs' clinical experience of meningococcal infection and their views on the pre-hospital management of suspected cases of Neisseria meningitidis. RESULTS: Completed questionnaires were received from 372 GPs, a response rate of 70 per cent. Nearly all GPs said they carried benzyl penicillin in their on-call bag (353; 95 per cent) and would give it to a patient they suspected had meningococcal disease (361; 97 per cent). A total of 208 GPs (56 per cent) would not give parenteral chloramphenicol to a patient they suspected had meningococcal disease and a penicillin allergy, and only 25 (7 per cent) carried it as an alternative antibiotic. The most common reason for not giving chloramphenicol was unfamiliarity with dosages (132; 63.5 per cent). CONCLUSIONS: The vast majority of GPs in Birmingham would apparently give benzyl penicillin to a patient they suspected had meningococcal infection. No single issue emerged to explain why pre-admission administration of benzyl penicillin was so low. Further work is being carried out locally to help translate positive attitudes into a change in behaviour.

Adult↗
PubMed1998

Exclusive and persistent use of the entry coreceptor CXCR4 by human immunodeficiency virus type 1 from a subject homozygous for CCR5 delta32.

Individuals who are homozygous for the 32-bp deletion in the gene coding for the chemokine receptor and major human immunodeficiency virus type 1 (HIV-1) coreceptor CCR5 (CCR5 -/-) lack functional cell surface CCR5 molecules and are relatively resistant to HIV-1 infection. HIV-1 infection in CCR5 -/- individuals, although rare, has been increasingly documented. We now report that the viral quasispecies from one such individual throughout disease is homogenous, T cell line tropic, and phenotypically syncytium inducing (SI); exclusively uses CXCR4; and replicates well in CCR5 -/- primary T cells. The recently discovered coreceptors BOB and Bonzo are not used. Although early and persistent SI variants have been described in longitudinal studies, this is the first demonstration of exclusive and persistent CXCR4 usage. With the caveat that the earliest viruses available from this subject were from approximately 4 years following primary infection, these data suggest that HIV-1 infection can be mediated and persistently maintained by viruses which exclusively utilize CXCR4. The lack of evolution toward the available minor coreceptors in this subject underscores the dominant biological roles of the major coreceptors CCR5 and CXCR4. This and two similar subjects (R. Biti, R. Ffrench, J. Young, B. Bennetts, G. Stewart, and T. Liang, Nat. Med. 3:252-253, 1997; I. Theodoreu, L. Meyer, M. Magierowska, C. Katlama, and C. Rouzioux, Lancet 349:1219-1220, 1997) showed relatively rapid CD4+ T-cell declines despite average or low initial viral RNA load. Since viruses which use CXCR4 exclusively cannot infect macrophages, these data have implications for the relative infection of the T-cell compartment versus the macrophage compartment in vivo and for the development of CCR5-based therapeutics.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Influence of the CCR2-V64I polymorphism on human immunodeficiency virus type 1 coreceptor activity and on chemokine receptor function of CCR2b, CCR3, CCR5, and CXCR4.

The chemokine receptors CCR5 and CXCR4 are used by human immunodeficiency virus type 1 (HIV-1) in conjunction with CD4 to infect cells. In addition, some virus strains can use alternative chemokine receptors, including CCR2b and CCR3, for infection. A polymorphism in CCR2 (CCR2-V64I) is associated with a 2- to 4-year delay in the progression to AIDS. To investigate the mechanism of this protective effect, we studied the expression of CCR2b and CCR2b-V64I, their chemokine and HIV-1 coreceptor activities, and their effects on the expression and receptor activities of the major HIV-1 coreceptors. CCR2b and CCR2b-V64I were expressed at similar levels, and neither molecule affected the expression or coreceptor activity of CCR3, CCR5, or CXCR4 in cotransfected cell lines. Peripheral blood mononuclear cells (PBMCs) from CCR2-V64I heterozygotes had normal levels of CCR2b and CCR5 but slightly reduced levels of CXCR4. CCR2b and CCR2b-V64I functioned equally well as HIV-1 coreceptors, and CCR2-V64I PBMCs were permissive for HIV-1 infection regardless of viral tropism. The MCP-1-induced calcium mobilization mediated by CCR2b signaling was unaffected by the polymorphism, but MCP-1 signaling mediated by either CCR2b- or CCR2-V64I-encoded receptors resulted in heterologous desensitization (i.e., limiting the signal response of other receptors) of both CCR5 and CXCR4. The heterologous desensitization of CCR5 and CXCR4 signaling by both CCR2 allele receptor types provides a mechanistic link that might help explain the in vivo effects of CCR2 gene variants on progression to AIDS as well as the reported antiviral activity of natural CCR2 ligands.

Cell Line, Transformed↗
PubMed1998

Comparative genomics: tracking chromosome evolution in the family ursidae using reciprocal chromosome painting.

The Ursidae family includes eight species, the karyotype of which diverges somewhat, in both chromosome number and morphology, from that of other families in the order Carnivora. The combination of consensus molecular phylogeny and high-resolution trypsin G-banded karyotype analysis has suggested that ancestral chromosomal fissions and at least two fusion events are associated with the development of the different ursid species. Here, we revisit this hypothesis by hybridizing reciprocal chromosome painting probes derived from the giant panda (Ailuropoda melanoleuca), domestic cat (Felis catus), and man (Homo sapiens) to representative bear species karyotypes. Comparative analysis of the different chromosome segment homologies allowed reconstruction of the genomic composition of a putative ancestral bear karyotype based upon the recognition of 39 chromosome segments defined by painting as the smallest conserved evolutionary unit segments (pSCEUS) among these species. The different pSCEUS combinations occurring among modern bear species support and extend the postulated sequence of chromosomal rearrangements and provide a framework to propose patterns of genome reorganization among carnivores and other mammal radiations.

Animals↗
PubMed1998

General outbreaks of infectious intestinal disease in England and Wales: 1995 and 1996.

One thousand nine hundred and nineteen general outbreaks of infectious intestinal disease in England and Wales were reported to the PHLS Communicable Disease Surveillance Centre (CDSC) between 1 January 1995 and 31 December 1996, compared with 1073 in the previous two years. A minimum data set was received for 1568 (82%) of the 1919 outbreaks. Over 40,000 people were affected and about 2% of those who were ill were admitted to hospital. Seventy-one deaths were reported. The duration of outbreaks varied between less than one day and 202 days (median six days) according to the pathogen. Small round structured virus (SRSV) (43%) and salmonellas (15%) were the most commonly reported pathogens. In almost a quarter of the outbreaks (24%) the aetiology was unknown. Over half the outbreaks (64%) were reported to be transmitted from person to person, most of which were due to SRSV and occurred in residential homes and hospitals. Twenty-two per cent of outbreaks were described as mainly foodborne, 51% of which were due to salmonellas. The number of outbreaks reported in each region ranged from 52 in Wales to 512 in Northern and Yorkshire.

Caliciviridae Infections↗
PubMed1998

European politicians need epidemiologists.

This paper reviews some of the recent discussions about public health policy in Europe. In particular it points to the interest in communicable diseases and the need to extend this interest into non-communicable fields. It draws attention to the consequential need for trained and continuously updated epidemiologists.

Epidemiology↗
PubMed1997

Cloning and chromosome mapping of the feline genes p21WAF1 and p27Kip1.

For investigation of the relation of cell cycle regulation with tumorigenesis in cats, we carried out molecular cloning of feline p21WAF1 and p27Kip1 cDNAs and chromosomal mapping of these genes on the cat genome. The feline p21WAF1 cDNA clone obtained in this study encoded 164 amino acids (aa) showing 83.5% and 76.8% sequence similarity with those of the human and mouse counterparts, respectively. The cat p27Kip1 cDNA clone isolated here encoded 198 aa, showing sequence similarities of 93.4% and 90.4% with its human and mouse counterparts, respectively. Using a panel of feline x rodent somatic cell hybrids, the feline CDKN1A (p21WAF1) and CDKN1B (p27Kip1) loci were assigned to feline chromosomes B2 and B4, respectively. Southern-blot analyses of 17 feline spontaneous leukemia and lymphoma cases using these cDNAs as probes did not reveal any rearrangements in either the p21WAF1 or the p27Kip1 gene. RT-PCR/SSCP (single strand conformation polymorphism) analysis of p27Kip1 cDNA did not uncover any amino acid substitutions in the 10 feline leukemia and lymphoma cases that were examined.

Amino Acid Sequence↗
PubMed1997

Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study.

The critical role of chemokine receptors (CCR5 and CXCR4) in human immunodeficiency virus-type 1 (HIV-1) infection and pathogenesis prompted a search for polymorphisms in other chemokine receptor genes that mediate HIV-1 disease progression. A mutation (CCR2-64I) within the first transmembrane region of the CCR2 chemokine and HIV-1 receptor gene is described that occurred at an allele frequency of 10 to 15 percent among Caucasians and African Americans. Genetic association analysis of five acquired immunodeficiency syndrome (AIDS) cohorts (3003 patients) revealed that although CCR2-64I exerts no influence on the incidence of HIV-1 infection, HIV-1-infected individuals carrying the CCR2-64I allele progressed to AIDS 2 to 4 years later than individuals homozygous for the common allele. Because CCR2-64I occurs invariably on a CCR5-+-bearing chromosomal haplotype, the independent effects of CCR5-Delta32 (which also delays AIDS onset) and CCR2-64I were determined. An estimated 38 to 45 percent of AIDS patients whose disease progresses rapidly (less than 3 years until onset of AIDS symptoms after HIV-1 exposure) can be attributed to their CCR2-+/+ or CCR5-+/+ genotype, whereas the survival of 28 to 29 percent of long-term survivors, who avoid AIDS for 16 years or more, can be explained by a mutant genotype for CCR2 or CCR5.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Growth of lion and puma lentiviruses in domestic cat cells and comparisons with FIV.

Feline immunodeficiency virus (FIV-Fca) is a lentivirus that causes gradual immunological deterioration in domestic cats. Lentiviruses related to FIV have been detected in several nondomestic feline species; the biologic significance of these viruses remains to be defined. To examine the in vitro cell tropism of these nondomestic cat lentiviruses, prototypical puma and lion lentiviruses (FIV-Pco and FIV-Ple) were cultured in a variety of feline cell cultures. A domestic cat T lymphoma cell line, 3201, best supported the replication of both FIV-Pco and FIV-Ple. Moreover, FIV-Ple was lytic for these cells. RT-PCR amplification of a conserved pol gene region demonstrated species-specific primer homology. Sequence and phylogenetic analyses of this amplification product confirmed the identity of the replicating viruses and classified two previously uncharacterized viruses within predictable lion and puma clades. Sequence analysis of a conserved pol region demonstrated homology with previously characterized FIV-Ple and FIV-Pco. Western blot analysis using domestic cat anti-FIV-Fca sera showed that both FIV-Pco and FIV-Ple were antigenically related, to differing degrees, to three serotypes of FIV-Fca. These studies demonstrate that though nondomestic cat lentiviruses differ significantly from FIV-Fca and that a viral-specific protocol may be necessary for sensitive viral detection, these viruses can replicate in cells of domestic cats. suggesting the potential for cross-species transmission.

Animals↗
PubMed1997

The tax gene sequences form two divergent monophyletic lineages corresponding to types I and II of simian and human T-cell leukemia/lymphotropic viruses.

Evolutionary associations of human and simian T-cell leukemia/lymphotropic viruses I and II (HTLV-I/II and STLV-I/II) are inferred from phylogenetic analysis of tax gene sequences. Samples studied consisted of a geographically diverse assemblage of viral strains obtained from 10 human subjects and 20 individuals representing 12 species of nonhuman primates. Sequence analyses identified distinct substitutions, which distinguished between viral types I and II, irrespective of host species. Phylogenetic reconstruction of nucleotide sequences strongly supported two major evolutionary groups corresponding to viral types I and II. With the type I lineage, clusters were composed of strains from multiple host species. A genetically diverse, monophyletic lineage consisting of eight new viral strains from several species of Asian macaques was identified. The second lineage consisted of a monophyletic assemblage of HTLV-II/STLV-II strains from Africa and the New World, including an isolate from a pygmy chimp (Pan paniscus) as an early divergence within the lineage. High levels of genetic variation among strains from Asian STLV-I macaque suggest the virus arose in Asia. Evidence of the origin of the type II virus is less clear, but diversity among HTLV-II variants from a single isolated population of Mbati villagers is suggestive but not proof of an African origin.

Amino Acid Sequence↗
PubMed1997

Nature and origin of polymorphism in feline MHC class II DRA and DRB genes.

Transcripts of the MHC class II DRA and DRB gene homologues of the domestic cat (Felis catus) were cloned and sequenced to compare the pattern and process of DR gene divergence. Homologous DRB exon 2 sequences from 36 feral domestic cats throughout the world plus from three species of Felidae (tiger cat, Iriomote cat, and Geoffroy's cat) were also determined. Limited variation in the domestic cat Feca-DRA gene was observed, but abundant variation in the Feca-DRB gene was seen comprising 61 distinct DRB alleles. Phylogenetic analyses resolved at least five monophyletic feline DRB allelic lineages (DRB*1 to *5), which are clearly distinct from those of human (HLA-DRB1 to 9 lineages), mouse (H-2Ebeta b, u, f), and dog DRB alleles. Approximately 80% of individual cats contained three to six distinct DRB sequences, indicating that feline MHC maintains two to three DRB loci. Five cats had three DRB sequences in a single allelic lineage, indicating the occurrence of recent gene duplication of feline DRB genes. DRB sequences isolated from three exotic cats demonstrated close association with a particular domestic cat DRB lineage, suggesting that these allelic lineages are derived from common ancestral alleles that existed prior to the divergence of these feline species about 10 to 15 million years ago. Patterns of synonymous and nonsynonymous nucleotide substitution rates that occurred in Ag recognition sites (ARS) and nonrecognition (NAR) sites demonstrated a strong role of natural selection--positive selection for Ag recognition sites and negative selection for nonrecognition sites of feline DRB sequences--in the process of evolution of DR molecules.

Amino Acid Sequence↗
PubMed1997

Phylogenetic reconstruction of the Felidae using 16S rRNA and NADH-5 mitochondrial genes.

The Felidae family represents a challenge for molecular phylogenetic reconstruction because it consists of 38 living species that evolved from a relatively recent common ancestor (10-15 million years ago). We have determined mitochondrial DNA sequences from two genes that evolve at relatively rapid evolutionary rates, 16S rRNA (379 bp) and NADH dehydrogenase subunit 5 (NADH-5, 318 bp), from multiple individuals of 35 species. Based on separate and combined gene analyses using minimum evolution, maximum parsimony, and maximum likelihood phylogenetic methods, we recognized eight significant clusters or species clades that likely reflect separate monophyletic evolutionary radiations in the history of this family. The clusters include (1) ocelot lineage, (2) domestic cat lineage, (3) Panthera genus, (4) puma group, (5) Lynx genus, (6) Asian leopard cat group, (7) caracal group, and (8) bay cat group. The results confirm and extend previously hypothesized associations in most cases, but in others, e.g., the bay cat group, suggest novel phylogenetic relationships. The results are compared and evaluated with molecular, cytogenetic, and morphological data to derive a phylogenetic synthesis of field evolutionary history.

Animals↗
PubMed1997

Do CuSums have a role in routine communicable disease surveillance?

The swift identification of outbreaks of infection is essential for effective control in the population. One of the functions of surveillance is to detect outbreaks but it could be argued that this is one of the weaker aspects of routine surveillance at present. This paper describes a technique which might meet this surveillance need. The CuSum technique allows rapid measurement of change from expected values based on historical data. It is very simple and seems to be a highly sensitive technique which can signal the need for further scrutiny of the data and/or for public health action, long before a change in incidence is apparent from raw data. This is particularly true for low-incidence infections where large functions can make interpretation difficult. CuSums represent a potentially useful adjunct to other surveillance methods in infection control.

Communicable Disease Control↗
PubMed1997

Comparative genomics: lessons from cats.

The genomics era, spear headed by dazzling technological developments in human and mouse gene mapping, has additionally provoked extensive comparative gene mapping projects for domestic species of several vertebrate orders. As the human genome project promises a one dimensional string of 100,000 genes and sequences, comparative mapping will extend that inference to a second dimension representing index species of the 20 living mammalian orders and to a third dimension by phylogenetic description of the genomes of mammal ancestors. We review here the remarkable extent of genome homology conservation among mammals illustrated by technology applications in the feline genome project.

Animals↗