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Biomedical subjects

S Boyle

Publications and source records attributed to S Boyle.

At least 19 recordsLinked to original sources
PubMed2000

An evolutionarily conserved germ cell-specific hnRNP is encoded by a retrotransposed gene.

The gene encoding heterogeneous ribonucleoprotein (hnRNP) G recently has been mapped to the X chromosome. All mammals have a Y chromosome-encoded homologue of HNRNP G called RBMY, which is implicated with a role in male fertility and is a candidate for the azoospermia factor gene. We have identified a new member of this gene family, HNRNP G-T, and have mapped it as a single-copy gene on chromosome 11. This gene contains an uninterrupted open reading frame and no introns, consistent with derivation from a retroposon. However, unlike many retroposon-derived genes, HNRNP G-T is not a pseudogene. An antiserum raised to the conceptual reading frame of HNRNP G-T showed that it encodes a protein that is highly expressed in germ cells and in particular in the nuclei of meiotic spermatocytes. Surprisingly, although this antiserum was raised against human hnRNP G-T protein, it can also detect a similar protein in the testis of several mammals. This suggests that the protein is highly conserved and that the retrotransposition event generating the HNRNP G-T gene pre-dated at least the common ancestor of mouse and man. The existence of an additional testis-specific hnRNP G family member provides evidence for the importance of these proteins in normal germ cell development.

Amino Acid Sequence↗
PubMed2000

A prospective study of dominance and coronary heart disease in the Normative Aging Study.

The purpose of this study was to examine the prospective relation between dominance, as assessed by a Minnesota Multiphasic Personality Inventory (MMPI-2)-derived dominance scale, and incidence of coronary heart disease (CHD), independent of participants' anger level. The study was performed in the VA Normative Aging Study, an ongoing cohort of older (mean age 61 years) men. A total of 1,225 men who were free of CHD in 1986 completed the MMPI-2. A factor analysis of selected MMPI items provided the basis for the construction of a dominance scale and an anger scale. During an average of 8 years of follow-up, 158 cases of incident CHD occurred, including 29 cases of fatal CHD, 69 cases of nonfatal myocardial infarction (MI), and 60 cases of angina pectoris (AP). Compared with men reporting the lowest levels of dominance (lower tertile), the multivariate-adjusted relative risk among men reporting the highest levels of dominance (upper tertile) was 1.80 (95% confidence interval [CI] 1.21 to 3.24) for combined nonfatal MI and fatal CHD. Additional adjustment for anger scores did not significantly alter this relation. There was no significant relation between dominance and AP. Our data suggest that dominance is an independent risk factor for CHD in older men.

Adult↗
PubMed2000

Re-modelling of nuclear architecture in quiescent and senescent human fibroblasts.

Spatial organisation of the genome within the nucleus can play a role in maintaining the expressed or silent state of some genes [1]. There are distinct addresses for specific chromosomes, which have different functional characteristics, within the nuclei of dividing populations of human cells [2]. Here, we demonstrate that this level of nuclear architecture is altered in cells that have become either quiescent or senescent. Upon cell cycle exit, a gene-poor human chromosome moves from a location at the nuclear periphery to a more internal site in the nucleus, and changes its associations with nuclear substructures. The chromosome moves back toward the edge of the nucleus at a distinctive time after re-entry into the cell cycle. There is a 2-4 hour period at the beginning of G1 when the spatial organisation of these human chromosomes is established. Lastly, these experiments provide evidence that temporal control of DNA replication can be independent of spatial chromosome organisation. We conclude that the sub-nuclear organisation of chromosomes in quiescent or senescent mammalian somatic cells is fundamentally different from that in proliferating cells and that the spatial organisation of the genome is plastic.

Cell Division↗
PubMed2000

Molecular analysis of phyllodes tumors reveals distinct changes in the epithelial and stromal components.

Phyllodes tumors are fibroepithelial mammary lesions that tend to behave in a benign fashion but may undergo sarcomatous transformation. A study of clonality in these tumors has suggested that the epithelial component is polyclonal, but the stroma is monoclonal, and thus forms the neoplastic component of the lesion. In this study microsatellites on chromosome 1q and chromosome 3p were assessed for allelic imbalance (AI) in 47 phyllodes tumors; in all cases stroma and epithelium were analyzed separately. Ten of 42 (24%) phyllodes tumors showed AI at one or more markers on 3p, and 14 of 46 (30%) showed AI on chromosome 1. Five tumors had changes in both the epithelium and stroma. Eight tumors had changes only detectable in the stroma and eight, changes in the epithelium only. Three tumors exhibited low-level microsatellite instability in the epithelium but not in the stroma. The results show that AI on 3p and 1q does occur in phyllodes tumors and that it can occur in both the stroma and epithelium, sometimes as independent genetic events. These unexpected findings throw into doubt the classical view that phyllodes tumors are simply stromal neoplasms and raise questions about the nature of stromal and epithelial interactions in these tumors.

Alleles↗
PubMed2000

Expression and genomic characterization of protein phosphatase inhibitor-1: a novel marker for mesothelium in the mouse.

Protein phosphatase inhibitor-1 (inhibitor-1 or I-1) is involved in signal transduction and is an endogenous inhibitor of protein phosphatase-1. The mouse I-1 protein sequence has been deduced from cDNA and is strongly homologous to the published rat sequence. A mouse genomic library was screened, and the I-1 gene was characterized and localized by fluorescent in situ hybridization (FISH) to chromosome 15F. Protein expression in a range of embryonic and adult tissue was analysed using confocal microscopy. Inhibitor-1 is expressed by: the coelomic epithelium; the epithelial bounding layer of cells of the kidney, lung, liver, heart, intestine and gonad; and the surface ectoderm. The blast cells of the kidney do not express I-1. We conclude that I-1 is a marker for mesothelium.

Amino Acid Sequence↗
PubMed2000

The long-term psychological effects of a disaster experienced in adolescence: I: The incidence and course of PTSD.

Previous studies have shown that children and adolescents exposed to traumatic experience in a disaster can suffer from high levels of post-traumatic stress. The present paper is the first a series reporting on the long-term follow-up of a group of young adults who as teenagers had survived a shipping disaster-the sinking of the "Jupiter" in Greek waters-between 5 and 8 years previously. The general methodology of the follow-up study as a whole is described, and the incidence and long-term course of Post-Traumatic Stress Disorder (PTSD). It is the first study of its kind on a relatively large, representative sample of survivors, using a standardised diagnostic interview, and comparing survivors with a community control group. Survivors of the Jupiter disaster (N = 217), and 87 young people as controls, were interviewed using the Clinician Administered PTSD Scale (CAPS). Of the 217 survivors, 111 (51.7%) had developed PTSD at some time during the follow-up period, compared with an incidence in the control group of 3.4 % (N = 87). In the large majority of cases of PTSD in the survivors for whom time of onset was recorded, 90 % (N = 110), onset was not delayed, being within 6 months of the disaster. About a third of those survivors who developed PTSD (30%, N = 111) recovered within a year of onset, through another third (34 %, N = 111) were still suffering from the disorder at the time of follow-up, between 5 and 8 years after the disaster. Issues relating to the generalisability of these findings are discussed.

Adolescent↗
PubMed2000

The long-term psychological effects of a disaster experienced in adolescence: II: General psychopathology.

Children and adolescents exposed to trauma can suffer major adverse psychological effects including not only post-traumatic stress but also other psychological disorders. This study investigates the long-term course of general psychopathology following trauma in adolescence using a standardised diagnostic interview and comparisons with a matched control group. Young people (N= 216) who as teenagers had survived a shipping disaster-the sinking of the "Jupiter" in Greek waters-between 5 and 8 years previously and 87 young people as matched controls were interviewed. The survivors showed raised rates of diagnosis in a range of anxiety and affective disorders during the follow-up period. The highest rates were among the survivors who had developed Post-Traumatic Stress Disorder (PTSD), and those survivors who had not were generally similar to the controls. Onset of anxiety and affective disorders varied between being indefinitely close to the disaster to years later. Differences in rates of disorder between the survivor and control groups had lessened by the time of follow-up but were still apparent, due to continuing distress among the survivors still suffering from PTSD, and to a lesser extent among those who had recovered from PTSD. Generalisability of the findings are discussed.

Adolescent↗
PubMed1999

Juxta-centromeric region of human chromosome 21 is enriched for pseudogenes and gene fragments.

A physical map including four pseudogenes and 10 gene fragments and spanning 500 kb in the juxta-centromeric region of the long arm of human chromosome 21 is presented. cDNA fragments isolated from a selected cDNA library were characterized and mapped to the 831B6 YAC and to two BAC contigs that cover 250 kb of the region. An 85 kb genomic sequence located in the proximal region of the map was analyzed for putative exons. Four pseudogenes were found, including psiIGSF3, psiEIF3, psiGCT-rel whose functional copies map to chromosome 1p13, chromosome 2 and chromosome 22q11, respectively. The TTLL1 pseudogene corresponds to a new gene whose functional copy maps to chromosome 22q13. Ten gene fragments represent novel sequences that have related sequences on different human chromosomes and show 97-100% nucleotide identity to chromosome 21. These may correspond to pseudogenes on chromosome 21 and to functional genes in other chromosomes. The 85 kb genomic sequence was analyzed also for GC content, CpG islands, and repetitive sequence distribution. A GC-poor L isochore spanning 40 kb from satellite 1 was observed in the most centromeric region, next to a GC-rich H isochore that is a candidate region for the presence of functional genes. The pericentric duplication of a 7.8 kb region that is derived from the 22q13 chromosome band is described. We showed that the juxta-centromeric region of human chromosome 21 is enriched for retrotransposed pseudogenes and gene fragments transferred by interchromosome duplications, but we do not rule out the possibility that the region harbors functional genes also.

Animals↗
PubMed1999

Differences in the localization and morphology of chromosomes in the human nucleus.

Using fluorescence in situ hybridization we show striking differences in nuclear position, chromosome morphology, and interactions with nuclear substructure for human chromosomes 18 and 19. Human chromosome 19 is shown to adopt a more internal position in the nucleus than chromosome 18 and to be more extensively associated with the nuclear matrix. The more peripheral localization of chromosome 18 is established early in the cell cycle and is maintained thereafter. We show that the preferential localization of chromosomes 18 and 19 in the nucleus is reflected in the orientation of translocation chromosomes in the nucleus. Lastly, we show that the inhibition of transcription can have gross, but reversible, effects on chromosome architecture. Our data demonstrate that the distribution of genomic sequences between chromosomes has implications for nuclear structure and we discuss our findings in relation to a model of the human nucleus that is functionally compartmentalized.

Cell Cycle↗
PubMed1999

Vaccination with live Escherichia coli expressing Brucella abortus Cu/Zn superoxide dismutase protects mice against virulent B. abortus.

Vaccination of mice with Escherichia coli expressing Brucella Cu/Zn superoxide dismutase (SOD) [E. coli(pBSSOD)] induced a significant level of protection against virulent Brucella abortus challenge, although this level was not as high as the one reached with B. abortus vaccine strain RB51. In addition, vaccination with E. coli(pBSSOD) induced antibodies to Cu/Zn SOD and a strong proliferative response of splenocytes when stimulated in vitro with a thioredoxin-Cu/Zn SOD fusion protein.

Animals↗
PubMed1998

A sequence-ready 3-Mb PAC contig covering 16 breakpoints of the Wilms tumor/anirida region of human chromosome 11p13.

A large body of evidence that links alterations of chromosome 11p13 to tumor formation and various developmental disorders has been accumulated. To address the underlying genetic events it would be helpful to have a comprehensive gene map of the region, and this is most readily achieved by generating the complete genomic sequence. Building upon previous mapping and YAC contig analysis we have established a 3-Mb sequence-ready PAC contig. It was constructed by chromosome walking and independently verified by fingerprint analysis of individual clones. The contig starts from the catalase gene on the centromeric side and reaches beyond the PAX6 gene at the 11p13/p14.1 boundary. Additional smaller contigs on either side were identified, but still have to be linked up. The 3-Mb contig spans the central region of deletions encompassing 16 chromosomal breakpoints in patients with WAGR syndrome (Wilms tumor, aniridia, genitourinary malformation, mental retardation), and its construction is an important step in facilitating functional analysis of these genes.

Chromosome Aberrations↗
PubMed1998

Molecular cloning of a human cDNA IGSF3 encoding an immunoglobulin-like membrane protein: expression and mapping to chromosome band 1p13.

We report the isolation and characterization of a novel cDNA IGSF3 that contains a 3648-bp open reading frame encoding an apparent immunoglobulin (Ig)-like membrane protein characterized by eight Ig domains. IGSF3 has an overall structural similarity and strong sequence similarity to V7, a human leukocyte surface protein. The IGSF3 mRNA is highly expressed in placenta, kidney, and lung, but is also present in a wide range of other human tissues. Although a small internal sequence of the IGSF3 cDNA hybridizes to a YAC derived from the centromeric region of chromosome 21, in situ hybridization experiments on human metaphase chromosomes show that the gene corresponding to the long cDNA that we cloned is located in chromosome band 1p13 and that related sequences are located on chromosomes 2 and 13. These data serve to emphasize the potential difficulties in transcriptional mapping in centromeric regions.

Amino Acid Sequence↗
PubMed1998

The Epstein-Barr virus nuclear protein SM is both a post-transcriptional inhibitor and activator of gene expression.

The Epstein-Barr virus (EBV) nuclear protein BS-MLF1 (SM) is expressed early after entry of EBV into the lytic cycle. SM transactivates reporter gene constructs driven by a wide variety of promoters, but the mechanism of SM action is poorly understood. In this study, we demonstrate that the SM protein inhibits expression of intron-containing genes and activates expression of intron-less genes. We demonstrate that SM has the predicted inhibitory effect on expression of a spliced EBV gene but activates an unspliced early EBV gene. SM inhibited gene expression at the post-transcriptional level by preventing the accumulation of nuclear and cytoplasmic RNA transcripts. Conversely, SM led to increased accumulation of nuclear mRNA from intron-less genes without affecting the rate of transcription, indicating that SM enhances nuclear RNA stability. The ratio of cytoplasmic to nuclear polyadenylated mRNA was increased in the presence of SM, suggesting that SM also enhances nucleo-cytoplasmic mRNA transport. The degree of transactivation by SM was dependent on the sequence of the 3'-untranslated region of the target mRNA. Finally, we demonstrate that the amino-terminal portion of SM fused to glutathione-S-transferase binds radioactively labeled RNA in vitro, indicating that SM is a single-stranded RNA binding protein. Importantly, the latent and immediate-early genes of EBV contain introns whereas many early and late genes do not. Thus, SM may down-regulate synthesis of host cell proteins and latent EBV proteins while simultaneously enhancing expression of specific lytic EBV genes by binding to mRNA and modulating its stability and transport.

Cell Line↗
PubMed1998

Waiting lists. The wrong target.

The numbers now waiting for treatment in the NHS are more than double what they were in 1948 despite huge increases in activity. Increased activity has not reduced the time patients wait. Mean waiting times in the 1990s were 13-14 weeks, the same as in the 1960s and 1970s. An increase in activity to reduce the numbers waiting for treatment may, in fact, increase the number being put on the waiting list. Government targets should concentrate on how long individual patients have to wait, rather than reducing the numbers on the waiting list.

Elective Surgical Procedures↗