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Biomedical subjects

A Webster

Publications and source records attributed to A Webster.

At least 55 records · Page 3Linked to original sources
PubMed1995

Social support, quality of life, immune function, and health in persons living with HIV.

The purpose of this study was to examine the relationship between social support and quality of life in individuals with HIV. Using a descriptive, correlational design, data were collected from 50 HIV-positive individuals who were: (a) participants in support groups at a behavioral medicine unit, (b) inpatient or respite care patients with HIV, or (c) respondents to advertisements at AIDS service organizations. Instruments used for data collection were the Personal Resource Questionnaire 85-Part 2 (Weinert, 1987), measuring perceived social support, and the Quality of Life Index (QLI) (Ferrans & Powers, 1985), measuring the sense of well-being in life including the satisfaction with and importance of life domains with four subscales: health and functioning, socioeconomic, psychological/spiritual, and family. The results of the study indicated that social support was significantly correlated with quality of life (r = 0.81, p < 0.0001). Further, HIV status (asymptomatic HIV, symptomatic HIV, AIDS) was significantly related to quality of life (p < 0.01). However, HIV status was not significantly related to social support. No significant relationship was found between CD4 counts and HIV status, CD4 counts and social support, or CD4 counts and perceived health status. However, CD4 counts were significantly correlated with scores on the QLI. The findings of the study indicate that social support and quality of life are significantly intercorrelated and that higher CD4 counts are related to quality of life in this sample of persons living with HIV. Further areas for research include evaluation of quality of life over the span of HIV disease and interventions aimed at enhancing or maintaining quality of life in persons across the spectrum of HIV disease.

Adult↗
PubMed1994

Adenovirus DNA binding protein: helix destabilising properties.

Adenovirus DNA binding protein is a multifunctional protein essential for viral DNA replication. To investigate the role of the DNA binding protein in this process its interaction with partial DNA duplexes was examined. Duplex regions of DNA, created when a short DNA strand is annealed to its complementary sequence present in the single stranded form of M13 phage DNA, were efficiently unwound by DNA binding protein in a reaction that required neither ATP nor MgCl2. The unwinding activity of DNA binding protein was reduced by conditions which increased the stability of DNA duplexes. DNA unwinding by DNA binding protein was highly co-operative and required the single stranded DNA to be completely coated with the protein. Completely double stranded DNA could also be unwound by DNA binding protein but this reaction was sensitive to the G+C content of the DNA and could only be observed with relatively short DNA duplexes up to 45 base pairs in length. When these short double stranded DNA molecules contained binding sites for the transcription factors NFI and NFIII addition of the cognate factor blocked DNA binding protein mediated unwinding of the particular DNA duplex. Cleavage of DNA binding protein with chymotrypsin and isolation of the 39,000 molecular weight C-terminal fragment indicated that the unwinding activity was located in this domain of the protein. In support of this contention a monoclonal antibody, which had previously been mapped to this region, specifically inhibited the DNA unwinding activity. These activities of DNA binding protein are likely to be involved in DNA replication, where the destabilisation of DNA duplexes could be important both during initiation and elongation.

Adenoviridae↗
PubMed1994

The protease of adenovirus serotype 2 requires cysteine residues for both activation and catalysis.

Sequence analysis and site-directed mutagenesis were used to study the mechanisms of activation and catalysis of the adenovirus type 2 (Ad2) protease. Primary structure alignments of proteases from 12 serotypes and previously elucidated inhibition profiles were used to target residues for mutagenesis. All conserved serine and cysteine residues were mutated separately and following expression in Escherichia coli their activity in a synthetic peptide assay was compared to that of wild-type recombinant protease. Mutants containing altered serine residues were active while mutations to cysteine-104 and cysteine-122 reduced activity by more than 95%. These results taken together with the known inhibition profile of the adenovirus protease confirm that it is a cysteine protease and suggest that one of these residues provides the active site nucleophile while the other is a part of the thiol-disulphide interchange mechanism previously reported to be involved in its activation.

Adenoviruses, Human↗
PubMed1994

Activation of adenovirus-coded protease and processing of preterminal protein.

Adenoviruses code for a protease that is essential for infectivity and is activated by a disulfide-linked peptide, derived from the C terminus of the virus structural protein pVI (pVI-CT). The protease was synthesized at relatively high levels late in infection and was detected in both cytoplasmic and nuclear fractions of adenovirus-infected cells. DNA was not found to be a cofactor of the protease, as previously proposed (W. F. Mangel, W. J. McGrath, D. Toledo, and C. W. Anderson, Nature [London] 361:274-275, 1993), but a role for DNA in facilitating the activation of the protease by pVI-CT in vivo cannot be ruled out. Adenovirus preterminal protein is a substrate for the virus-coded protease, with digestion to the mature terminal protein proceeding via the formation of two intermediates. Each of the three cleavage sites in the preterminal protein was identified by N-terminal sequencing and shown to conform to the substrate specificity of adenovirus protease, (M,L,I)XGX-X. Functional studies revealed that preterminal protein and intermediates but not mature terminal protein associated with adenovirus polymerase, while only the intact preterminal protein and none of its digestion products bound to DNA. These results suggest that the virus-coded protease may influence viral DNA replication by cleavage of both genome-bound and freely soluble preterminal protein, with consequent alterations to their functional properties.

Adenoviridae↗
PubMed1993

The adenovirus protease is activated by a virus-coded disulphide-linked peptide.

In common with many other viruses, adenoviruses code for a protease essential for the development of infectivity. Recombinant adenovirus protease was active in crude in vitro complementation assays but was inactive with peptide or purified protein substrates. Activity was reconstituted by a component of adenovirus virions, which was identified as GVQSLKRRRCF, a peptide derived from the virus protein pVI. Synthetic peptides were used to demonstrate that the cysteine is essential and that the disulphide-linked dimer is required for activity. It is proposed that the adenovirus protease is a cysteine protease and that its activation by the peptide involves thiol-disulphide interchange, which serves to expose the active site cysteine. This represents a novel strategy for controlling the activity of a protease that is required for virus maturation.

Adenoviruses, Human↗
PubMed1993

The active adenovirus protease is the intact L3 23K protein.

The L3 23K protein was isolated from adenovirus type 2 and shown to cleave purified substrates, confirming that this protein is the adenovirus protease. Separate antisera, prepared against the amino- and carboxy-terminal regions of the 23K protein react with active protease, demonstrating that, contrary to previous reports, zymogen activation is not involved in the regulation of this enzyme. Molecular exclusion chromatography indicated that the protease is active as a monomer. Purified protease was shown to be inhibited by Zn2+ and Cu2+ and by some, but not all, recognized cysteine protease inhibitors, indicating participation of a thiol group and providing additional support to the suggestion that regulation of the enzyme involves a form of thiol-disulphide interchange.

Adenoviruses, Human↗
PubMed1993

Do general practitioners and general psychiatrists want to look after drug misusers? Evaluation of a non-specialist treatment policy.

A new means of monitoring drug misuse which was developed in the north west of England, but is now widely used throughout the United Kingdom, is described and evaluated. Report forms which had been specially designed and ensured the anonymity of drug misusers were widely distributed among doctors and non-medical health workers who may have had contact with drug misusers. The forms were returned post-free to a centre where they were entered on a customized drug misuse database. There were 2127 reports from the north west of England (population 3.99 million) relating to 1792 individuals over a 15-month period. However, despite intensive promotion of the project among doctors, the number of reports from doctors remained virtually unchanged over the 15 months despite a 33% increase in the overall number of reports. When the reports from three health districts, selected so as to be representative of the region demographically (total population 658,500, population aged 15-44 years 292,200), were considered there was a substantial fall (70%) in reports from general practitioners which was considerably greater than the 2% fall in all reports. In a linked study all the psychiatrists, 30% of probation officers and a one in six sample of general practitioners from the three selected health districts were approached for interview at the beginning of the 15-month period and again a year later. This structured enquiry about caseloads, treatment, and attitudes also revealed a fall in the number of drug misusers attended by general practitioners and general psychiatrists and a reduction in the services provided for them by general practitioners.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Value of routine surveillance cultures for detection of CMV pneumonitis following bone marrow transplantation.

The results of 5018 surveillance cultures for the detection of cytomegalovirus (CMV) from 177 patients undergoing allogeneic T cell-depleted bone marrow transplantation (BMT) were analysed to determine their value in predicting future development of CMV pneumonitis. Twenty-two patients were diagnosed as having CMV pneumonitis. The median times of a positive CMV culture result from urine, saliva or blood before disease in these patients were 32, 8 and 23 days, respectively. The positive predictive value of CMV viraemia for the development of CMV pneumonitis was 0.64. Multivariate analysis showed that recipient pretransplant CMV seropositivity and increasing recipient age were independent risk factors for CMV pneumonitis. By contrast, donor CMV seropositivity was protective against disease, supporting the hypothesis that immunity against CMV can be adopted from donor T cell-depleted marrow. It is concluded that detection of CMV viraemia in a surveillance protocol can predict subsequent CMV pneumonitis but that it is of low sensitivity. This might be improved by more frequent sampling or by the use of a more sensitive assay, such as the polymerase chain reaction, thus identifying individuals who may benefit from 'pre-emptive' therapy.

Antibodies, Viral↗
PubMed1992

Risk factors for viral reactivation following bone marrow transplantation.

The identification of risk factors for viral reactivation following transplantation is essential in order that antiviral prophylactic regimes may be allocated rationally. In the pretransplant period qualitative serological assessment of recipient and donor is informative with regard to the risk of post-transplant reactivation and disease. In addition, the quantitative level of herpes simplex virus (HSV) IgG in the pretransplant recipient is predictive of post-transplant HSV excretion, although this relationship does not exist for other viruses of the herpes group. We discuss the value of surveillance cultures for cytomegalovirus in the post-transplant period in predicting the development of CMV disease, and how this may allow effective intervention to prevent what is a major cause of morbidity and mortality in the transplant population.

Antibodies, Viral↗
PubMed1992

Cytomegalovirus (CMV) infection, CD4+ lymphocyte counts and the development of AIDS in HIV-1-infected haemophiliac patients.

After a maximum of 11 years (median 8.3 years) from the time of HIV seroconversion, 25 out of 59 (42%) of CMV-seropositive haemophiliacs had progressed to AIDS, as opposed to eight out of 50 (16%) CMV seronegatives. The age-adjusted relative risk for AIDS among CMV seropositives was 2.4 (P = 0.03). In order to determine how this adverse effect is mediated, the mean rate of decline in serial CD4+ lymphocyte counts was studied. CD4+ lymphocyte counts tended to decline more rapidly in CMV seropositives than in seronegatives (-0.087 x 10(9)/l per annum versus -0.082 x 10(9)/l per annum), but this difference did not reach statistical significance. The average CD4+ lymphocyte count at the time of HIV seroconversion was estimated to be similar in CMV seropositives and negatives, because in HIV-1-negative haemophiliacs the CD4+ counts were virtually identical, after adjustment for age (0.94 x 10(9)/l and 0.97 x 10(9)/l, respectively). The median CD4+ cell count at which AIDS developed was higher in the CMV-seropositive group (0.07 x 10(9)/l) than in the seronegative group (0.04 x 10(9)/l), but this difference did not reach statistical significance. We conclude from these findings that the adverse effect of CMV is not wholly mediated via a more rapid loss of CD4+ cells. We discuss other processes that may be mediated by CMV, such as a functional deficiency of residual CD4+ cells, or dissemination of HIV in other organs, which may be important in determining the earlier onset of AIDS among CMV-seropositive subjects.

Acquired Immunodeficiency Syndrome↗
PubMed1992

The effect of pre-assessment information on clients' satisfaction, expectations and attendance at a mental health day centre.

An information sheet describing the nature of initial assessment sessions was sent to people referred to a mental health day centre. This study examines the effect of receiving the information on attendance at assessment, expectations of the session and subsequent satisfaction. A group of subjects who were sent the information were compared with a control group who were not. The former group were more likely to attend the initial appointment (82 per cent attended) than those who did not receive the information (57 per cent attended). Of those subjects who attended, the experimental group expressed greater satisfaction overall and with the session itself. There were no differences between the groups on other satisfaction measures, levels of state anxiety and expectations. It is concluded that the effect of the information sheet is most likely to be mediated by changes in satisfaction levels which may be raised by increased levels of personal attention.

Adult↗
PubMed1992

Proteolysis is a key process in virus replication.

Proteases were amongst the first enzymes to be isolated and crystallized, and the discovery of their existence in viruses and the realization of the vital role they play has given a new lease of life to one of the oldest topics in biochemistry. Already we have seen the discovery of new variations on well-studied reaction mechanisms and there is the promise of others to come that may be totally novel. When this is allied to the prospect of developing the knowledge which is beginning to accrue into a much needed antiviral therapy, it is clear that viral proteases and their key role in viral replication will be an increasing focus of attention for some time to come.

Animals↗
PubMed1991

Cytomegalovirus excretion after bone marrow transplantation cannot be predicted from the pre-transplant level of IgG antibodies.

The relationship of pre-bone-marrow transplant recipient and donor cytomegalovirus (CMV) antibody level to post-transplant recipient CMV excretion was investigated. CMV excretion was found to be related to pre-transplant recipient serological status, but not to level of antibody. This therefore contrasts with herpes simplex virus (HSV), for which pre-transplant antibody level in recipients predicts post-transplant HSV excretion.

Adolescent↗