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Biomedical subjects

A Webster

Publications and source records attributed to A Webster.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Late BCNU lung: a light and ultrastructural study on the delayed effect of BCNU on the lung parenchyma.

We describe eight patients who developed interstitial pulmonary fibrosis following BCNU (carmustine) therapy for cerebral tumours. The fibrosis presented 12-17 (mean 14) years after exposure to the drug. A distinctive pattern of pulmonary fibrosis with involvement of the apices and subpleural areas was seen in one patient dying of the disease. Light microscopy showed interstitial elastosis and intra-alveolar fibrosis which was often focal with an associated mild lymphoplasmacytic infiltrate, intra-alveolar oedema, macrophages, and some neutrophils. Ultrastructural studies showed electron lucency of type I pneumocytes, with breaks in the cytoplasmic membranes leaving a bare basement membrane. Degenerative change was also seen in endothelial cell cytoplasm along with lipofuscin deposition. While BCNU pulmonary fibrosis has been described up to 2 years after treatment, this complication so late after therapy, though rare, has important implications for the follow-up of patients receiving this drug.

Astrocytoma↗
PubMed1991

Eliminating PCR contamination: is UV irradiation the answer?

The sensitivity of the polymerase chain reaction (PCR) can mean that even very low levels of contamination with the target DNA will result in a positive signal. At present this aspect is a major limitation in the use of PCR as a routine diagnostic method. By exposing PCR reagents to UV light, contaminating DNA can be inactivated, thus providing an opportunity to eradicate false positive reactions. UV irradiation was applied to PCR systems used for the detection of human cytomegalovirus (CMV) and human immunodeficiency virus (HIV) and shown to be effective in eradicating both laboratory encountered contamination and plasmid DNA (below 100 pg) added to PCR systems prior to UV exposure. The sensitivity of a PCR system to amplify the long terminal repeat (LTR) sequence of HIV-1 was not affected by the irradiation procedure; however, the ultimate sensitivity of a PCR system for the amplification of an early gene promotor sequence of the CMV genome was reduced 1000-fold. UV irradiation did not affect the size of the PCR product as determined by strand separating polyacrylamide gel electrophoresis of a 32P-labelled amplimer. Thus, a simple pre-exposure to UV light would seem a worthwhile step to incorporate into PCR protocols provided that the effects on sensitivity have been determined empirically for each PCR system.

Base Sequence↗
PubMed1991

Population dynamics of HIV within an individual after treatment with zidovudine.

A new mechanism is proposed for the apparent breakthrough of HIV that occurs approximately 6 months after the commencement of therapy with zidovudine (AZT). Using a simple mathematical model of the interacting population dynamics of HIV and its major host cell in the circulation (the CD4+ lymphocyte), predicted patterns of HIV plasma viraemia in the weeks following treatment with zidovudine are generated. These are in close agreement with observed patterns despite the fact that the model contains no mechanisms for the development of drug-resistant strains of virus. It is suggested that the patterns of viral abundance observed during the first 6 months after treatment may be the result of non-linearities in the interactions between HIV and CD4+ cells, and that it is only after the first post-treatment burst of viral production that drug resistance plays an important role.

AIDS-Related Complex↗
PubMed1991

p24 antigenaemia, CD4 lymphocyte counts and the development of AIDS.

A cohort of 111 HIV-infected haemophiliacs has been followed for up to 11 years, during which time 33 patients have been diagnosed with AIDS. Twenty-seven of the cohort developed detectable p24 antigenaemia while remaining free of AIDS. These patients experienced an increased risk of progression to AIDS compared with those patients who were persistently p24-negative (relative risk 7.24; P less than 0.0001, Cox proportional hazards model). The relative risk was reduced to 5.42 (P less than 0.0001) after adjustment for age and cytomegalovirus seropositivity. After adjustment for the patients' declining CD4 lymphocyte count during follow-up, the relative risk fell dramatically to 1.97 and became non-significant (P = 0.2). p24-antigenaemic patients tended to develop AIDS at levels of similar CD4 lymphocyte counts to those who were persistently p24-antigen-negative (median CD4 lymphocyte counts, 70 and 50 x 10(6)/l, respectively). These results suggests that the association between p24 antigenaemia and the rate of progression to AIDS can be explained largely by a more rapid decline in CD4 lymphocyte count among patients with p24 antigenaemia than in those without. The major pathological effects of increased plasma viral load, as detected by the presence or absence of p24 antigenaemia, appear to act via progressive CD4 lymphocyte depletion.

Acquired Immunodeficiency Syndrome↗
PubMed1991

More rapid progression to AIDS in older HIV-infected people: the role of CD4+ T-cell counts.

The tendency for older people with HIV infection to progress more rapidly to AIDS than younger people was studied in a group of 111 anti-HIV-positive haemophiliacs followed for up to 10 years from seroconversion. After 7 years of seropositivity, those aged over 30 years at the time of the first positive anti-HIV test had a cumulative progression rate to AIDS of 50%, compared with only 12% for those aged 10-19 years (Kaplan-Meier estimates). Overall, the relative risk of developing AIDS by any given time after seroconversion was 1.45 for each 10 year increase in age (p = 0.002; 95% confidence limits of 1.15, 1.85; Cox proportional hazards model). After adjustment for the CD4+ T-cell count (median of 10 count measurements per patient, fitted as a time-dependent covariate), the relative risk fell to 1.31 but remained statistically significant (p less than 0.05; 95% confidence limits of 1.03, 1.67). This implies that older people may be at higher risk of progression than their younger counterparts, even if their CD4+ T-cell counts are the same. Hence, prophylaxis against opportunistic infections may be indicated at higher CD4+ T-cell counts in older people than in younger people.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Cytomegalovirus as a possible cofactor in HIV disease progression.

It has been suggested that cofactors in human immunodeficiency virus (HIV) disease, particularly other viral infections, may accelerate progression to the acquired immune deficiency syndrome (AIDS). We have shown that in a population of 108 HIV-infected hemophiliacs observed for up to 9 years after the first documented HIV seroconversion, coinfection with cytomegalovirus (CMV) adversely influenced the course of the disease; in particular, logistic regression analysis showed that the age-adjusted relative risk of developing AIDS in CMV-seropositive patients was 2.5 times that in CMV seronegatives (p = 0.02). A number of potential mechanisms for the interaction of HIV and CMV have been proposed. Several groups have reported interaction at a molecular level between HIV and other viruses, including CMV, through transactivation of the HIV genome. Mechanisms by which the two viruses might gain entry to the same cell have been identified in vitro; these include Fc receptor-mediated uptake of antibody-coated HIV by CMV-infected fibroblasts. There is also some evidence that coinfection with HIV and CMV can occur in vivo, within brain cells. Interaction between these two viruses might also occur indirectly through the production of cytokines, such as tumor necrosis factor. Identification of cofactors in HIV infection may help in understanding the pathogenesis of AIDS, and may provide an important opportunity for intervention in the progression of the disease, particularly when an infectious agent for which specific therapy is available is identified.

Cytomegalovirus↗
PubMed1989

Cytomegalovirus infection and progression towards AIDS in haemophiliacs with human immunodeficiency virus infection.

To examine whether cytomegalovirus (CMV) infection could accelerate progression of human immunodeficiency virus (HIV) infection to AIDS, serological studies were done on 108 HIV-infected haemophiliacs. In the 1.3-9 years from time of first recognised HIV seroconversion, the age-adjusted risk of CDC group IV disease in CMV-seropositive patients was 2.5 times that in CMV-seronegative patients. CMV-seropositive patients were also more likely to have detectable p24 antigenaemia. Survival analysis showed that CMV-seropositive patients were at greater risk of HIV disease than CMV-seronegative patients from about 2 years after HIV seroconversion. Thus CMV infection is associated with a more rapid progression to HIV disease.

Acquired Immunodeficiency Syndrome↗
PubMed1989

A dye-photosensitized reaction that generates stable protein-protein crosslinks.

Irradiation of fibrinogen with visible light for 30 s in the presence of 1-1000 microM fluorescein was found to crosslink fibrinogen both inter- and intramolecularly. Optimum crosslinking was achieved at dye concentrations of around 100 microM and the amount of crosslinking was shown to increase with pH. Crosslinking was inhibited in the presence of 50 microM tryptophan or tyrosine and enhanced in the presence of 5 mM histidine. Twice as much crosslinking was found to take place under anaerobic conditions. These observations are consistent with a dye-photosensitized reaction following the hydrogen abstraction pathway. The subunits of eukaryotic ribosomes and those of phosphorylase a were also crosslinked by the method described.

Amino Acids↗
PubMed1989

The influence of calcium ions on fibrinogen conformation.

The conformation of fibrinogen has been examined using the techniques of dye-photosensitized surface labelling and cross-linking. The results obtained suggest that fibrinogen is a flexible molecule and its conformation is influenced by the concentration of calcium ions. These effects are mediated through binding to the low-affinity calcium binding sites of fibrinogen. In particular the C-terminal regions of the [A]alpha chain are more exposed at higher calcium concentrations creating a molecule which is more liable to form inter-molecular interactions.

Calcium↗