Acceptability of screening for HIV seroprevalence in women with cervical pathology.
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Adult↗
Biomedical subjects
M A Johnson
Publications and source records attributed to M A Johnson.
Neurotrophic activity of interphotoreceptor matrix on human Y79 retinoblastoma cells.
A neurotrophic activity of adult monkey and bovine interphotoreceptor matrix (IPM) was examined by using cultured human Y79 retinoblastoma cells as a model system. The cells were stimulated for 7 days in suspension culture with soluble IPM components and then attached to poly-D-lysine substratum. IPMs from both species induced greater than 80% neuronal differentiation of Y79 cell aggregates after 11 days of attachment as adjudged morphologically by the extension of lengthy, neurite-like processes. Immunocytochemical studies indicate that differentiated Y79 cells had an increased level of expression of neuron-specific enolase and a concomitant decreased expression of glial fibrillary acidic protein. This neurotrophic activity cannot be ascribed to nerve growth factor, platelet-derived growth factor, fibroblast growth factor, epidermal growth factor, or transforming growth factor beta. Although the nature of the factor and its cellular source have yet to be characterized, it may be related to a recently described neurotrophic protein secreted by human fetal retinal pigment epithelial cells in culture. Our findings provide evidence supporting the neuroblastic potential of the Y79 cell line and indicate that the IPM contains a potent neurotrophic activity. Such factors may be important to normal differentiation and maintenance of function of the neural retina.
Animals↗
Phenotypic and functional similarities between 5-azacytidine-treated T cells and a T cell subset in patients with active systemic lupus erythematosus.
OBJECTIVE: Antigen-specific CD4+ T cells treated with DNA methylation inhibitors become autoreactive, suggesting a novel mechanism for autoimmunity. To test whether this mechanism might be involved in systemic lupus erythematosus (SLE), phenotypic markers for the autoreactive cells were sought. METHODS: Cloned normal T cells were treated with the DNA methylation inhibitor 5-azacytidine (5-azaC) and studied for altered gene expression. T cells from patients with active SLE were then studied for a similar change in gene expression, and cells expressing the marker were tested for autoreactivity. RESULTS: 5-azaC-treated normal T cells had increased CD11a (leukocyte function-associated antigen 1 alpha) expression relative to other membrane molecules. A T cell subset with similar CD11a expression was found in patients with active SLE. This subset contained cells that spontaneously lysed autologous macrophages, with a specificity similar to that of 5-azaC-treated cells.
Antigens, CD↗
Infectious laryngotracheitis virus growth, DNA replication, and protein synthesis.
The polypeptides associated with infection of primary chicken kidney (CK) cells with infectious laryngotracheitis virus (ILTV) were examined by metabolic labelling with [35S]methionine and SDS-PAGE. Polypeptide synthesis was followed over the first 24 h post-infection (p.i.) as this was shown to be the period of viable virus production. A total of 16 ILTV encoded or induced polypeptides were identified using metabolic labelling. The use of inhibitors of protein and DNA synthesis in conjunction with metabolic labelling and viral DNA replication studies enabled a cascade pattern of gene expression, similar to that of herpes simplex virus type 1 (HSV-1), to be established for ILTV. Representatives of alpha, beta, gamma 1 and gamma 2 classes of genes were identified. In contrast to infection with HSV types 1 and 2, which leads to a rapid inhibition of total host cell polypeptide synthesis, ILTV infection of CK cells did not result in a complete inhibition of cellular protein synthesis, with only a small number of host cell polypeptides absent from infected cells.
Animals↗
Is copper an antioxidant nutrient?
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Animals↗
Molecular determination of cell tropism of human immunodeficiency virus.
In the 10 years since AIDS was first identified, knowledge of the causative agent, human immunodeficiency virus (HIV), has advanced remarkably. Molecular biological analysis has had a greater impact on the investigation of HIV and AIDS than on that of any other disease. Unfortunately, the vast amount of material published on this subject has still not resulted in a thorough understanding of the pathogenesis of AIDS. Undoubtedly, part of the reason for the complexity of this disease stems from the ability of HIV to infect a large number of different cell types. To comprehend the mechanisms involved in the pathogenesis of AIDS, it is of great importance to understand the factors that control the cell tropism of the virus. In this review, we describe the known factors involved in the determination of the cell tropism of retroviruses and the ways by which molecular biological analysis of HIV has revealed the nature of the processes involved in control of the tropism of the virus for various cell types.
Animals↗
Copper and selenium deficiencies do not enhance the cardiotoxicity in rats due to chronic doxorubicin treatment.
This study tests the hypothesis that Cu and Se deficiencies enhance doxorubicin-induced cardiotoxicity and anemia. Male Sprague-Dawley rats (n = 48) were fed Cu and Se-adequate (+Cu+Se), Cu-deficient (-Cu), Se-deficient (-Se) or Cu and Se-deficient (-Cu-Se) diets for 5.5 wk. Doxorubicin (4 mg/kg body wt) or saline was administered once weekly for the last 4 wk of the study. Copper deficiency was confirmed by 79% lower liver Cu, 67% lower liver Cu,Zn superoxide dismutase (Cu,Zn SOD) activity and 76% lower erythrocyte Cu,Zn SOD activity. Selenium deficiency was confirmed by 90% lower liver glutathione peroxidase activity. Rats fed the -Cu diet had greater reductions in hematocrit than did those fed the +Cu diet after administration of doxorubicin. Doxorubicin, Cu deficiency and Se deficiency all produced electrocardiographic abnormalities and ultrastructural anatomical lesions. However, the dietary deficiencies did not enhance doxorubicin-induced cardiotoxicity. Doxorubicin, but not Cu or Se deficiency, raised lipid peroxidation 16% in liver (P < 0.01) and 18% in heart (not significant). These data suggest that the cardiomyopathies caused by doxorubicin and Cu and Se deficiencies have some similarities, but cardiac changes may be related to mechanisms other than lipid peroxidation.
Animals↗
Cephaloridine nephrotoxicity is potentiated by selenium deficiency but not copper deficiency in rats.
Lipid peroxidation may contribute to the nephrotoxicity of cephaloridine, a beta-lactam antibiotic. Copper and Se may protect against free radical damage, and dietary Se deficiency potentiates cephaloridine nephrotoxicity. The objectives of this study were to further investigate potentiation of cephaloridine toxicity by Se deficiency and to determine whether Cu deficiency increases cephaloridine-induced injury. Weanling male Sprague-Dawley rats were fed adequate, Cu-deficient, Se-deficient, and Se and Cu-deficient diets for 4 wk and subsequently injected i.p. with cephaloridine (1200 mg/kg body wt) or saline. Nephrotoxic response to cephaloridine occurred, with increased plasma urea, kidney weight, excretion of urinary enzymes, and kidney lesions. Cephaloridine also increased plasma sorbitol dehydrogenase activity. Selenium deficiency depressed kidney glutathione peroxidase activity (78%) and potentiated cephaloridine nephrotoxicity. Copper deficiency did not increase cephaloridine nephrotoxicity; the small depression (13%) in kidney Cu,Zn-superoxide dismutase activity may not have been sufficient to impair antioxidant status. However, the marked depression in kidney glutathione peroxidase activity during Se deficiency may have impaired antioxidant status and enhanced cephaloridine-induced injury. In contrast to results in the kidney, neither Se deficiency nor Cu deficiency potentiated cephaloridine hepatotoxicity, as assessed by plasma SDH activity.
Animals↗
Relationship between herpes simplex virus ulceration and CD4+ cell counts in patients with HIV infection.
OBJECTIVE: To establish the incidence of herpes simplex virus (HSV) ulceration in relation to CD4+ cell counts in HIV-infected patients. DESIGN: Swabs were taken from all ulcerated lesions in HIV-infected patients and cultured for HSV. CD4+ cell counts were performed at regular intervals. SETTING: The HIV unit at a London teaching hospital (the Royal Free Hospital, London, UK). PATIENTS: All HIV-infected patients (n = 500) attending the HIV unit. RESULTS: Two hundred and twenty-three swabs were obtained from 118 patients; 83 (37.2%) swabs from 62 (52.5%) patients were positive for HSV. Of 96 swabs taken from patients with CD4+ cell counts < 50 x 10(6)/l, 56 (58.3%) were positive for HSV, compared with 27 of 127 (21.2%) swabs from patients with higher CD4+ cell counts (P < 0.0001). Of patients with CD4+ cell counts < 50 x 10(6)/l, 37 of 47 (78.7%) had positive cultures compared with 25 of 71 (35.2%) of patients with higher counts (P < 0.0001). This trend was observed with swabs from all body sites; sufficient samples were available from oral and perianal lesions to demonstrate statistical significance (P < 0.0001 and P = 0.007, respectively). CONCLUSIONS: These results show a sharp rise in the incidence of HSV with CD4+ cell counts < 50 x 10(6)/l and thus provide important data for the design of studies of anti-HSV prophylaxis. Furthermore, since nearly 60% of all ulcers in patients with such low CD4+ counts are HSV-positive, we suggest appropriate empirical therapy on presentation.
AIDS-Related Opportunistic Infections↗
Laboratory control values for CD4 and CD8 T lymphocytes. Implications for HIV-1 diagnosis.
With the advent of standard flow cytometric methods using two-colour fluorescence on samples of whole blood, it is possible to establish the ranges of CD3, CD4 and CD8 T lymphocyte subsets in the routine laboratory, and also to assist the definition of HIV-1-related deviations from these normal values. In 676 HIV-1-seronegative individuals the lymphocyte subset percentages and absolute counts were determined. The samples taken mostly in the morning. The groups included heterosexual controls, people with various clotting disorders but without lymphocyte abnormalities as well as seronegative homosexual men as the appropriate controls for the HIV-1-infected groups. The stability of CD4% and CD8% values was demonstrated throughout life, and in children CD4 values less than 25% could be regarded as abnormal. The absolute counts of all T cell subsets decreased from birth until the age of 10 years. In adolescents and adults the absolute numbers (mean +/- s.d.) of lymphocytes, CD3, CD4 and CD8 cells were 1.90 +/- 0.55, 1.45 +/- 0.46, 0.83 +/- 0.29 and 0.56 +/- 0.23 x 10(9)/l, respectively. In patients with haemophilia A and B the mean values did not differ significantly. In homosexual men higher CD8 levels were seen compared with heterosexual men and 27% had an inverted CD4/CD8 ratio but mostly without CD4 lymphopenia (CD4 less than 0.4 x 10(9)/l). However, some healthy uninfected people were 'physiologically' lymphopenic without having inverted CD4/CD8 ratios. When the variations 'within persons' were studied longitudinally over a 5-year period, the absolute CD4 counts tended to be fixed at different levels. As a marked contrast, over 60% of asymptomatic HIV-1+ patients exhibited low CD4 counts less than 0.4 x 10(9)/l together with inverted CD4/CD8 ratios. Such combined changes among the heterosexual and HIV-1-seronegative homosexual groups were as rare as 1.4% and 3%, respectively. For this reason, when the lymphocyte tests show less than 0.4 x 10(9)/l CD4 count and a CD4/CD8 ratio of less than unity, the individuals need to be investigated further for chronicity of this disorder, the signs of viral infections such as HIV-1 and other causes of immunodeficiency.
Adolescent↗
Dystrophin or a "related protein" in Duchenne muscular dystrophy?
Previously we have shown low levels of dystrophin immunoreactivity in muscle from patients with DMD. According to the "frame-shift hypothesis" DMD muscle should not synthesize any dystrophin through to the C-terminus and it has been suggested that the protein detected is not dystrophin, but a related autosomal homologue. We have labelled serial sections of DMD muscle with specific monoclonal antibodies to the amino, rod and C-terminal domains of dystrophin and find labelling on the same individual fibres, allowing us to conclude that the protein detected is Xp21-encoded dystrophin. This has an impact on the interpretation of myoblast transfer experiments. The abundance (on blots) of "C-terminal dystrophin" appears lower than "rod dystrophin" in both BMD and DMD.
Antibodies, Monoclonal↗
Predicted and observed sizes of dystrophin in some patients with gene deletions that disrupt the open reading frame.
Among 85 patients with Duchenne and Becker muscular dystrophy, 29 were found to have mutations which disrupted the open reading frame for dystrophin. Thus any dystrophin detected in this group of patients should consist of the severely truncated polypeptides that represent prematurely terminated translation products. Dystrophin was detected in blots from 17/29 biopsies and the observed sizes of the polypeptides were compared with predicted sizes calculated in two ways: if translation was terminated at the stop codon generated by each frameshifting deletion, and if the reading frame was restored and translation proceeded. In every case the observed size matched the size predicted on the basis of a restored reading frame. This was in accord with immunocytochemical labelling of scattered dystrophin positive fibres which were found on serial sections labelled with antibodies to both the rod and C-terminal domains. Thus analysis at the protein level supports genetic evidence of exon skipping as a mechanism which restores frameshifting mutations in some fibres.
Adolescent↗
Investigation of a female manifesting Becker muscular dystrophy.
Females manifesting Becker muscular dystrophy (BMD) are even more rarely observed than for the allelic condition Duchenne muscular dystrophy. The male proband has typical BMD with greatly raised CK activity and a myopathic muscle biopsy. His mother experienced walking difficulties from 35 years of age and has a myopathy with marked calf hypertrophy, a raised CK, and a myopathic muscle biopsy. Dystrophin analysis was undertaken on both the proband and his mother. Immunoblotting showed a protein of normal size but of reduced abundance in both. Immunocytochemical analysis in the proband indicated that the majority of the fibres showed weak dystrophin labelling and in his mother both dystrophin positive and dystrophin negative fibres were present. Non-random X inactivation at locus DXS255, was observed in DNA isolated from peripheral lymphocytes of the mother. Neither extended multiplex PCR performed on DNA from the proband nor analysis of lymphocyte derived mRNA showed a structural alteration in the dystrophin gene suggesting that an unusual mutation was responsible for BMD in this family.
Adult↗
Fulminant bronchopulmonary Kaposi's sarcoma.
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Adult↗
Resuscitation in HIV.
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Cardiopulmonary Resuscitation↗
Severe cytomegalovirus pneumonitis in HIV infected patients with higher than average CD4 counts.
BACKGROUND: Cytomegalovirus may replicate within the lungs both of recipients of transplants and of patients infected with the human immunodeficiency virus (HIV). A hypothesis formulated by this group was that a host damaging immune response might be provoked by cytomegalovirus infection and cause a severe pneumonitis in recipients of allogeneic transplants, whereas the progressive impairment of cellular immunity in patients with HIV disease would preclude a damaging immune response in the lungs, and thus protect these patients from severe cytomegalovirus pneumonitis. This study set out to discover whether severe cytomegalovirus pneumonitis arises in HIV infected patients. METHODS: Data were prospectively collected on severity of pneumonitis and infectious agents identified in consecutive respiratory episodes in HIV infected patients undergoing diagnostic bronchoalveolar lavage during 20 months. RESULTS: Eighty five episodes of pneumonitis occurred in 68 patients. Cytomegalovirus was identified as the only infectious agent in nine episodes (nine patients). Seven of the episodes were mild; all these patients had CD4 counts below 0.1 x 10(9)/1. The remaining two episodes were severe and ventilatory support was required. In both cases the CD4 counts were above 0.2 x 10(9)/1 and HIV infection appeared to have been acquired shortly before presentation. CONCLUSION: Although rare, severe cytomegalovirus pneumonitis may occur in HIV infected patients. Both patients with severe pneumonitis in this series had relatively well preserved immune function. These findings support the hypothesis that severe cytomegalovirus pneumonitis is an immunopathological condition.
Adult↗
Personality, life events and coping in the oldest-old.
This paper compares older adults in their sixties, eighties, and 100s on personality, experience of life events, and coping. A secondary goal was to test a structural model of adaptation. Participants (165) filled out a personality inventory, life-event lists, and coping and mental health measures. Results revealed differences in personality: centenarians scored higher on dominance, suspiciousness, and imagination. While centenarians scored lower on active behavioral coping than other age groups, they used cognitive strategies when coping with health and family events. Results from the structural equation model indicated that extraversion and anxiety predicted morale and mental health.
Adaptation, Psychological↗