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Biomedical subjects

S Matthews

Publications and source records attributed to S Matthews.

At least 91 records · Page 5Linked to original sources
PubMed1998

Dissimilar phorbol ester binding properties of the individual cysteine-rich motifs of protein kinase D.

Protein kinase D (PKD) is a serine/threonine kinase that binds phorbol esters in a phospholipid-dependent manner via a tandemly repeated cysteine-rich, zinc finger-like motif (the cysteine-rich domain, CRD). Here, we examined whether the individual cysteine-rich motifs of the CRD of PKD (referred to as cysl and cys2) are functionally equivalent in mediating phorbol ester binding both in vivo and in vitro. Our results demonstrate that the cysl and cys2 motifs of the CRD of PKD are functionally dissimilar, with the cys2 motif responsible for the majority of [3H]phorbol 12,13-dibutyrate (PDB) binding, both in vivo and in vitro.

Animals↗
PubMed1998

Eliminating a region of respiratory syncytial virus attachment protein allows induction of protective immunity without vaccine-enhanced lung eosinophilia.

In a murine model of respiratory syncytial virus disease, prior sensitization to the attachment glycoprotein (G) leads to pulmonary eosinophilia and enhanced illness. Three different approaches were taken to dissect the region of G responsible for enhanced disease and protection against challenge. First, mutant viruses, containing frameshifts that altered the COOH terminus of the G protein, were used to challenge mice sensitized by scarification with recombinant vaccinia virus (rVV) expressing wild-type G. Second, cDNA expressing these mutated G proteins were expressed by rVV and used to vaccinate mice before challenge with wild-type respiratory syncytial virus (RSV). These studies identified residues 193-205 to be responsible for G-induced weight loss and lung eosinophilia and showed that this region was not was not necessary for induction of protective immunity. Third, mice were sensitized using an rVV that expressed only amino acids 124-203 of the G protein. Upon RSV challenge, mice sensitized with this rVV developed enhanced weight loss and eosinophilia. This is the first time that a region within RSV (amino acids 193-203) has been shown to be responsible for induction of lung eosinophilia and disease enhancement. Moreover, we now show that it is possible to induce protective immunity with an altered G protein without inducing a pathological response.

Animals↗
PubMed1998

Inequalities in self-rated health: explanations from different stages of life.

BACKGROUND: Inequalities in health are a major public-health concern. A greater understanding is needed on the relative importance of different causes. We investigated the contribution of risk factors identified at different life stages to inequalities in self-rated health. METHODS: We used data from 5606 men and 5799 women in the 1958 British birth cohort followed-up to age 33 years, on health behaviour, education, adolescent health, family structure and social support, work characteristics, and material circumstances. We assessed the contribution of different factors to social-class differences in self-rated health by adjustment of odds ratios (classes IV and V vs I and II). FINDINGS: Odds ratios of poor-rated health at age 33 were 3.15 for men and 2.30 for women, which decreased to 2.06 and 1.34, respectively, after adjustment for previously identified factors from birth to early adulthood. Adjustment for adult work characteristics, material circumstances, and health behaviour between ages 23 years and 33 years further decreased the odds ratios to 1.64 (men) and 1.11 (women). Most factors contributed to the reduction in odds ratios, although adolescent socioemotional adjustment, class at birth, educational qualifications, and psychosocial job strain were especially important. Additional key factors for men were adult smoking and job insecurity, and for women, housing during childhood, adult income, and age at first child. INTERPRETATION: There was no single cause of health inequality at age 33 years. Explanations spanned from early life to young adulthood. Policy implications include reduction of social differences in material circumstances and of differences in individual skills and resources acquired in early life.

Adult↗
PubMed1998

Establishing a KSHV+ cell line (BCP-1) from peripheral blood and characterizing its growth in Nod/SCID mice.

Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) sequences are present in primary effusion lymphomas (PEL). KSHV+ cell lines have been established from such lymphomas. Here we report the first description of the establishment of a KSHV+, EBV- cell line (BCP-1) from the peripheral blood of a patient with PEL. Using this cell line and a KSHV+, EBV+ PEL cell line (HBL-6) previously established from ascitic fluid, we investigated whether in nonobese diabetic/severe combined immunodeficiency disease (Nod/SCID) mice tumors representing PEL can be established. When injected intravenously (IV) into Nod/SCID mice, BCP-1 and HBL-6 infiltrated organs, with only occasional macroscopic tumor formation. Intraperitoneal injections (ip) led to the development of ascites and diffuse infiltration of organs, without obviously solid lymphoma formation, resembling the diffuse nature of human PEL. To investigate a possible mechanism for the peculiar phenotype of PEL, we examine the presence of adhesion molecules and homing markers on PEL cells before and after growing in mice. Both BCP-1 and HBL-6 cells lack expression of important cytoadhesion molecules including CD11a and CD18 (LFA1 alpha and beta chains), CD29, CD31, CD44, CD54 (ICAM-1), and CD62L and E (L and E selectins).

Animals↗
PubMed1998

Gender, work roles and psychosocial work characteristics as determinants of health.

This paper aims to identify gender similarities and differences in psychosocial work characteristics for those in and out of paid employment, to inform research on possible health-related effects. Specifically five questions are addressed: do women report poorer work characteristics than men; are gender differences related to specific characteristics; do work characteristics differ between full- and part-time women workers and between those in paid and unpaid work; are socio-economic gradients in work characteristics similar for men and women; and, if there are gradients, do they differ between women in paid and unpaid work? Analyses are based on the 33 year follow-up of the 1958 British birth cohort. Four psychosocial work characteristics were examined: learning opportunities, monotony, pace of work, and flexibility of breaks. Women reported more negative work characteristics than men, primarily because of differences in learning opportunities (26% lacked opportunity compared with 13% of men) and monotonous work (47 and 31% respectively). Women in full-time employment reported fewer negative characteristics (27%) than part-time (39%) or home-workers (36%). Home-workers had fewer opportunities for learning (36%) and greater monotony (49%) than paid workers (21 and 22% respectively), however fewer home-workers reported inability to control the work pace (11% compared to 23%) and inflexibility of breaks (21% compared to 47%). Socio-economic gradients in work characteristics were similar among men and women, except for flexibility of break times. A socio-economic gradient in work characteristics was found for full- and part-time workers, but not among home-workers. Differences in self reported health were also examined: a social gradient was found for all employment status groups, being strongest for home-workers despite the absence of a gradient in negative work characteristics. In conclusion, these marked gender differences in psychosocial work characteristics need to be considered in future research on work and health.

Adult↗
PubMed1998

Eukaryotic RNA polymerase subunit RPB8 is a new relative of the OB family.

RNA polymerase II subunit RPB8 is an essential subunit that is highly conserved throughout eukaryotic evolution and is present in all three types of nuclear RNA polymerases. We report the first high resolution structural insight into eukaryotic RNA polymerase architecture with the solution structure of RPB8 from Saccharomyces cerevisiae. It consists of an eight stranded, antiparallel beta-barrel, four short helical regions and a large, unstructured omega-loop. The strands are connected in classic Greek-key fashion. The overall topology is unusual and contains a striking C2 rotational symmetry. Furthermore, it is most likely a novel associate of the oligonucleotide/oligosaccharide (OB) binding protein class.

Amino Acid Sequence↗
PubMed1998

Caring for the carers during transplant surgery.

Staff working in theatre departments play a vital role in organ retrieval. However, many find involvement with organ donation uncomfortable and sometimes distressing. They may also have misunderstandings about what takes place before and after the retrieval operation. This article will examine the issue of organ donation from the perspective of the operating theatre staff and offer insight into the process of organ donation prior to and following the retrieval surgery.

Attitude of Health Personnel↗
PubMed1997

Origins of health inequalities in a national population sample.

BACKGROUND: Explanations for social inequalities in health are often explored but remain largely unresolved. To elucidate the origins of health inequalties, we investigated the extent to which adult-disease risk factors vary systematically according to social position over three decades of early life. METHODS: We used the 1958 birth cohort (all children born in England, Scotland, and Wales on March 3-9, 1958) with data up to age 33 years from parents, teachers, doctors, and cohort members (n = 11,407 for age 33 interview). FINDINGS: Social class of origin was associated with physical risk factors (birthweight, height, and adult body-mass index); economic circumstances, including household overcrowding, basic amenities, and low income; health behaviour of parents (breastfeeding and smoking) and of participants (smoking and diet); social and family functioning and structure, such as divorce or separation of participants or their parents, emotional adjustment in adolescence, social support in early adulthood; and educational achievement and working career, in particular no qualifications, unemployment, job strain, and insecurity. With few exceptions, there were strong significant trends of increasing risk from classes I and II to classes IV and V. Self-perceived health status and symptoms were worse in participants with lower class origins. INTERPRETATION: An individual's chance of encountering multiple adverse health risks throughout life is influenced powerfully by social position. Social trends in adult-disease risk factors do not emerge exclusively in mid-life, but accumulate over decades. Investment in educational and emotional development is needed in all social groups to strengthen prevention strategies relating to health behaviour, work-place environment, and income inequality.

Adult↗
PubMed1997

The three-dimensional solution structure of the matrix protein from the type D retrovirus, the Mason-Pfizer monkey virus, and implications for the morphology of retroviral assembly.

The Mason-Pfizer monkey virus (M-PMV) is the prototype of the type D retroviruses. In type B and D retroviruses, the Gag protein pre-assembles before association with the membrane, whereas in type C retroviruses (lentiviruses, BLV/HTLV group) Gag is targeted efficiently to the plasma membrane, where the particle formation occurs. The N-terminal domain of Gag, the matrix protein (MA), plays a critical role in determining this morphogenic difference. We have determined the three-dimensional solution structure of the M-PMV MA by heteronuclear nuclear magnetic resonance. The protein contains four alpha-helices that are structurally similar to the known type C MA structures. This similarity implies possible common assembly units and membrane-binding mechanisms for type C and B/D retroviruses. In addition to this, the interpretation of mutagenesis data has enabled us to identify, for the first time, the structural basis of a putative intracellular targeting motif.

Cell Membrane↗
PubMed1997

Comparing measures of health inequality.

Several methods are available to measure social inequalities in health. This paper discusses the advantages and disadvantages of different approaches, in particular the odds ratio, the slope and alpha. These methods are illustrated using data from subjects in the 1958 British birth cohort. The inequality measures are compared using health status at ages 23 and 33. Six health indicators are examined, including self-rated health, limiting long-standing illness, psychological health, respiratory symptoms, asthma and obesity. Two social indicators are compared, namely class at birth and educational qualifications. Conclusions do not differ substantially using the three methods for measuring inequality. However, consistent differences were evident between the measures of social position, with greater inequalities apparent for educational qualifications. Choice of social indicator therefore appears to be of primary importance in measuring health inequality.

Adult↗
PubMed1997

Detection of human herpesvirus 8 DNA in semen from HIV-infected individuals but not healthy semen donors.

OBJECTIVE: To ascertain the prevalence of Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus (HHV) type 8, and cytomegalovirus (CMV) DNA in semen was investigated. METHODS: Amplification by nested polymerase chain reaction was used to detect viral DNA sequences in samples from 24 HIV-infected gay men, 15 of them with Kaposi's sarcoma (KS), and 115 healthy donors. RESULTS: Six of the 24 HIV-infected patients had detectable HHV-8 DNA in their semen: three of the 15 patients with KS and three of the nine patients without KS. CMV DNA was detected in 20 semen samples from HIV-infected patients. None of the semen samples from healthy donors had detectable HHV-8 DNA and rates of CMV DNA detection were low (3%). CONCLUSIONS: The study demonstrates the presence of HHV-8 in semen from HIV-infected individuals with, or at risk, of developing KS and the potential for sexual transmission of the virus. We found no evidence of HHV-8 in the semen of HIV-uninfected donors.

Cytomegalovirus↗
PubMed1997

Structure-function studies of the human immunodeficiency virus type 1 matrix protein, p17.

The human immunodeficiency virus type 1 (HIV-1) matrix protein, p17, plays important roles in both the early and late stages of the viral life cycle. Using our previously determined solution structure of p17, we have undertaken a rational mutagenesis program aimed at mapping structure-function relationships within the molecule. Amino acids hypothesized to be important for p17 function were mutated and examined for effect in an infectious proviral clone of HIV-1. In parallel, we analyzed by nuclear magnetic resonance spectroscopy the structure of recombinant p17 protein containing such substitutions. These analyses identified three classes of mutants that were defective in viral replication: (i) proteins containing substitutions at internal residues that grossly distorted the structure of recombinant p17 and prevented viral particle formation, (ii) mutations at putative p17 trimer interfaces that allowed correct folding of recombinant protein but produced virus that was defective in particle assembly, and (iii) substitution of basic residues in helix A that caused some relocation of virus assembly to intracellular locations and produced normally budded virions that were completely noninfectious.

Amino Acid Sequence↗
PubMed1997

Social differences in health: life-cycle effects between ages 23 and 33 in the 1958 British birth cohort.

OBJECTIVES: The purpose of this study was to determine whether social differences in health persist or widen during early adulthood. METHODS: A longitudinal follow-up of the 1958 British birth cohort was investigated, using social class at birth and six health measures at ages 23 and 33. A slope of inequality was estimated to represent social differences in health. RESULTS: Social gradients in health were evident by age 23: the prevalence of poor health increased with decreasing social position. This was observed for several but not all health indicators. Social gradients persisted to age 33. The slope of inequality was greatest for malaise (odds ratio [OR] = 3.37 for men, 3.21 for women) and obesity (OR = 4.80 for men and 2.84 for women), both at age 23, and for self-rated health in women at age 23 (OR = 2.94) and age 33 (OR = 3.22). Inequality increased significantly between ages 23 and 33 for limiting illness in men, and lessened, although not significantly, for malaise, overweight, and obesity; social gradients remained constant for self-rated health, respiratory symptoms, and asthma or wheezing. CONCLUSIONS: Social gradients in health evident in this sample by age 23 persisted to age 33. Inequalities did not appear to widen consistently, but variable findings for several health measures suggest that inequalities reproduce through different pathways.

Adult↗
PubMed1997

Mutations in the consensus helicase domains of the Werner syndrome gene. Werner's Syndrome Collaborative Group.

Werner syndrome (WS) is an autosomal recessive disease with a complex phenotype that is suggestive of accelerated aging. WS is caused by mutations in a gene, WRN, that encodes a predicted 1,432-amino-acid protein with homology to DNA and RNA helicases. Previous work identified four WS mutations in the 3' end of the gene, which resulted in predicted truncated protein products of 1,060-1,247 amino acids but did not disrupt the helicase domain region (amino acids 569-859). Here, additional WS subjects were screened for mutations, and the intron-exon structure of the gene was determined. A total of 35 exons were defined, with the coding sequences beginning in the second exon. Five new WS mutations were identified: two nonsense mutations at codons 369 and 889; a mutation at a splice-junction site, resulting in a predicted truncated protein of 760 amino acids; a 1-bp deletion causing a frameshift; and a predicted truncated protein of 391 amino acids. Another deletion is >15 kb of genomic DNA, including exons 19-23; the predicted protein is 1,186 amino acids long. Four of these new mutations either partially disrupt the helicase domain region or result in predicted protein products completely missing the helicase region. These results confirm that mutations in the WRN gene are responsible for WS. Also, the location of the mutations indicates that the presence or absence of the helicase domain does not influence the WS phenotype and suggests that WS is the result of complete loss of function of the WRN gene product.

Asian People↗