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Biomedical subjects

C Power

Publications and source records attributed to C Power.

At least 145 records · Page 8Linked to original sources

Neutrophil collagenase in sputum from patients with cystic fibrosis.

The potential role of neutrophil elastase in causing lung damage and exacerbating the inflammatory response in cystic fibrosis (CF) has received considerable attention. Although another potent neutrophil-derived enzyme, collagenase, is implicated in tissue destruction in several interstitial lung disorders, there has been no reference to this enzyme in CF. The objective of this study was to determine whether neutrophil collagenase is present in active form in CF sputum and, if so, whether it is related to disease severity. High levels of active collagenase were detected in sputum from patients with CF, and the majority of the enzyme present was of neutrophil origin. In a group of 16 patients with CF, negative relations between sputum collagenase activity and Shwachman score (r = -0.55, p < 0.05) and FEV1 (r = -0.59, p < 0.02) were noted, indicating an association between high collagenase activity and severity of disease. A positive correlation was observed between sputum collagenase and elastase activity (r = 0.62, p < 0.05). These results suggest that both neutrophil elastase and collagenase may play a significant role in lung destruction in CF.

Adolescent↗

Cytomegalovirus encephalitis in acquired immunodeficiency syndrome (AIDS).

Cytomegalovirus encephalitis (CMVE) is frequently diagnosed only at postmortem because its specific clinical features have not been fully identified. We have described the clinical, radiologic, and laboratory features of CMVE in a retrospective review of 14 autopsy-confirmed cases of CMVE and compared them with a control group of demented acquired immunodeficiency syndrome (AIDS) patients without CMVE. CMVE was more common among homosexual men, and a subacute onset was more typical (mean duration of presenting symptoms was 3.5 weeks versus 18 weeks in demented controls). Median survival times were 4.6 weeks for CMVE and 28 weeks for controls. CMVE was accompanied by prominent systemic CMV infection at autopsy, including CMV adrenalitis (92%), CMV pneumonitis (42%), systemic Mycobacterium avium intracellulare (MAI; 58%), and CMV retinitis (58%). Hyponatremia and MAI bacteremia were found in 58% of CMVE cases. Polymerase chain reaction (PCR) of CSF samples identified CMV genome in 33% of CMVE cases. CMVE was associated with periventricular enhancement on CTs and periventricular lesions with meningeal enhancement on MRI scans. CMVE should be particularly suspected in homosexual men presenting with subacute encephalopathy who have had AIDS for more than 1 year and have a history of systemic CMV infection. Other features supporting the diagnosis of CMVE include periventricular lesions, hyponatremia, and identification of CMV genome in CSF by PCR.

AIDS Dementia Complex↗

A model of human immunodeficiency virus encephalitis in scid mice.

Human immunodeficiency virus (HIV)-associated dementia complex is a common and devastating manifestation of the late phases of HIV infection. The pathogenesis of dementia complex is poorly understood and effective treatments have not been developed, in part because of the lack of an appropriate animal model. Mice with severe combined immunodeficiency (scid mice), which accept xenografts without rejection, were intracerebrally inoculated with human peripheral blood mononuclear cells and HIV. One to 4 weeks after inoculation, the brains of these mice contained human macrophages (some of which were HIV p24 antigen positive), occasional multinucleated cells, and striking gliosis by immunocytochemical staining. Human macrophages also were frequently positive for tumor necrosis factor type alpha and occasionally for interleukin 1 and VLA-4. Cultures of these brains for HIV were positive. Generally, human macrophages were not present in the brains of control mice, nor was significant gliosis, and HIV was not recovered from mice that received HIV only intracerebrally. Pathologically, this model of HIV encephalitis in scid mice resembles HIV encephalitis in humans and the data suggest that the activation of macrophages by infection with HIV results in their accumulation and persistence in brain and in the development of gliosis. This model of HIV encephalitis should provide insights into the pathogenesis and treatment of this disorder.

AIDS Dementia Complex↗

Intracerebral cytokine messenger RNA expression in acquired immunodeficiency syndrome dementia.

The pathogenesis of the dementia associated with human immunodeficiency virus (HIV) infection is unclear, but has been postulated to be due to indirect effects of HIV infection including the local production of cytokines. To determine which cytokines are produced in the nervous system and to identify any correlations with dementia, cytokine and HIV messenger RNA expression was analyzed by reverse transcriptase-polymerase chain reaction in the brains from 24 HIV-infected patients with and without dementia and 9 HIV-uninfected control subjects. Levels of tumor necrosis factor-alpha messenger RNA were significantly higher and levels of interleukin (IL)-4 messenger RNA were significantly lower in demented compared to nondemented HIV-infected patients. Demented patients also had lower IL-1 beta levels than did nondemented patients. No significant differences were detected in the amounts of leukemia inhibitory factor, IL-6, transforming growth factor-beta 1 and -beta 2, monokine induced by gamma interferon-2 (MIG-2), or interferon-gamma messenger RNAs. IL-10 and IL-2 messenger RNAs were undetectable in all brains examined. Cytokine messenger RNA levels in nondemented HIV-positive patients were similar to those in HIV-negative control subjects. HIV transcripts were more abundant in subcortical white matter than in the basal ganglia, cortex, or deep white matter. Our findings suggest a possible role for tumor necrosis factor-alpha in the development of neurological dysfunction. Increased levels of tumor necrosis factor-alpha messenger RNA were not associated with increased levels of IL-1 beta messenger RNA, suggesting differential regulation of these monokines in acquired immunodeficiency syndrome dementia.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Dementia Complex↗

Cerebral white matter changes in acquired immunodeficiency syndrome dementia: alterations of the blood-brain barrier.

The cause of acquired immunodeficiency syndrome (AIDS) dementia, which is a frequent late manifestation of human immunodeficiency virus (HIV) infection, is unknown but radiological and pathological studies have implicated alterations in subcortical white matter. To investigate the pathological basis of these white matter abnormalities, we performed an immunocytochemical and histological analysis of subcortical white matter from AIDS patients with and without dementia, from pre-AIDS patients (asymptomatic HIV-seropositive patients), and from HIV-seronegative control subjects. Reduced intensity of Luxol fast blue staining, designated "diffuse myelin pallor," was detected in 8 of 15 AIDS dementia patients, 3 of 13 AIDS nondemented patients, and none of the pre-AIDS patients (n = 2) or control subjects (n = 9). In contrast to Luxol fast blue staining, sections stained immunocytochemically for myelin proteins did not show decreased staining intensities in regions of diffuse myelin pallor. In addition, neither demyelinated axons nor active demyelination were detected in light and electron micrographs of subcortical white matter from brains of patients with AIDS dementia. An increase in the number of perivascular macrophages and hypertrophy of astrocytes and microglia occurred in brain sections from HIV-infected patients. These changes were not specific to dementia or regions of diffuse myelin pallor and they occurred in both gray and white matter. In contrast to the lack of myelin pathology in AIDS dementia brains, significant accumulations of serum proteins in white matter glia were detected in the brains of 12 of 12 patients with AIDS dementia and 6 of 12 AIDS patients without dementia. Serum protein-immunopositive cortical neurons were detected in the frontal cortex of 11 of 12 patients with AIDS dementia and 3 of 12 nondemented AIDS patients. Seronegative control subjects showed minimal serum protein immunoreactivity in both cortex and white matter. We conclude therefore that alterations in the blood-brain barrier and not demyelination contribute to the development of AIDS dementia.

AIDS Dementia Complex↗

Disability in young adults: the role of injuries.

STUDY OBJECTIVES: To describe the prevalence of disability in young adults and estimate the contribution that injuries make to disability. DESIGN: The study uses data from a British longitudinal survey, the National Child Development Study (1958 cohort). Disability at age 23 was ascertained from three questions asked in an interview with cohort members in 1981: these related to longstanding illness that limits activity, permanent disability following an accident after age 16, and registered disability. Lower and upper estimates of the contribution of injuries to disability were derived from ICD-9 codes allocated to the disabilities. SUBJECTS: These comprised 12,537 subjects, representing 76% of the target population, cohort members still alive and resident in Britain in 1981. MAIN RESULTS: Prevalence of disability according to the three definitions was: 46 per 1000 with limiting longstanding illness; 28 per 1000 with a permanent accident related disability of onset after age 16; and 10 per 1000 registered disabled. Combining all three definitions, the overall prevalence of disability was 68 per 1000, with men reporting more disability than women. It was estimated that an injury caused the disability for 16.7% of subjects, at the lower estimate, and 26.0% at the upper estimate (23.1% to 32.1% for men and 8.6% to 18.4% for women). For limiting longstanding illness of onset after 16, between 33.5% and 47.8% was due to an injury. Road accidents caused 31% of permanent accident related disability. Over one half of men and nearly three quarters of women reporting permanent accident related disability had not been admitted to hospital for their injury. CONCLUSIONS: Injuries are an important cause of disability in young adults, particularly injuries resulting from accidents after age 16. Accident prevention in the 16-24 group has the potential to reduce the prevalence of disability substantially.

Accidents↗

Distribution of immunocompetent cells in the bronchial wall of clinically healthy subjects showing bronchial hyperresponsiveness.

BACKGROUND: Nearly all asthmatic subjects show bronchial hyperresponsiveness, in that the provocative concentration of histamine reducing forced expiratory volume in one second (FEV1) by 20% (PC20FEV1) is < or = 8 mg/ml histamine, and have underlying chronic inflammation of the bronchial wall mediated by T cells. The possible cause and effect relationship between these phenomena remains an enigma. As a proportion of clinically healthy subjects show bronchial hyperresponsiveness, this study was undertaken to determine whether they also show evidence of bronchial inflammation. METHODS: Bronchial biopsy specimens were obtained from 27 clinically healthy subjects with no history of lung disease. Samples were taken perioperatively before elective knee arthroscopy for sports injuries. Specimens were frozen and cryostat sections analysed immunocytochemically with monoclonal antibodies to identify the presence of T lymphocytes, antigen presenting cells, and the expression of HLA-DR. Double immunofluorescence studies were performed with monoclonal antibodies RFD1 and RFD7 to show the relative proportions of RFD1+ RFD7- antigen presenting cells, RFD1- RFD7+ mature phagocytes, and RFD1+ RFD7+ suppressor macrophages. Histological stains were performed to show the presence of eosinophils and mast cells. Three to four weeks after bronchoscopy spirometry was performed on these subjects to record FEV1, forced vital capacity (FVC), FEV1/FVC, and forced expiratory flow between 25% and 75% of vital capacity (FEF25-75). Bronchial hyperreactivity was recorded by determining PC20FEV1 to histamine. RESULTS: Nine of the 27 subjects showed bronchial hyperresponsiveness as defined by a PC20FEV1 of < or = 8 mg/ml histamine. Segregated subjects with and without bronchial hyperresponsiveness showed no difference in spirometric results. Immunohistological analysis showed no evidence of inflammation in either group. Numbers of T cells, eosinophils, and mast cells were the same in both groups as was the expression of HLA-DR antigen. No neutrophils were observed in any tissues. Interestingly, reduced numbers of macrophages with the phenotype of antigen presenting cells (monoclonal antibodies RFD1+ RFD7-) were recorded in the subjects with bronchial hyperresponsiveness, who also had a significant increase in the proportion of RFD1+ RFD7+ suppressor macrophages. CONCLUSIONS: Up to 30% of selected clinically healthy subjects may have a PC20FEV1 of < or = 8 mg/ml histamine. This physiological trait can exist in the absence of bronchial inflammation. This suggests that bronchial hyperresponsiveness as currently defined is not dependent on immunopathological changes in the bronchial wall and does not necessarily promote even subclinical inflammation.

Adult↗

Long-term psychosocial sequelae of chronic physical disorders in childhood.

OBJECTIVE: This study was designed to examine the long-term psychosocial sequelae of chronic physical disorders that begin during childhood. DESIGN: We analyzed data from a national birth cohort. 12,537 children were followed until age 23 years--76% of all born in Britain during one week in 1958. Of these, 1667 had a chronic disorder before age 16 and 1279 were included in the 23-year follow-up. MEASURES: Outcome measures included self-reported psychological disturbances between ages 16 and 23, scores on the Malaise Inventory, social class, educational qualifications, unemployment, and social activities. RESULTS: The total cumulative incidence rate before 16 years was 109.5 per 1000. Demographic comparisons showed that the group with chronic physical disorders was similar to those free of chronic disorders in all respects except the sex ratio. Men with chronic physical disorders had significantly higher relative risks for abnormal scores on the Malaise Inventory (1.52, confidence interval [CI] 1.13, 2.05); specialist psychological care (1.43, CI 1.00, 2.03); poor educational qualifications (1.26, CI 1.08, 1.47); periods of unemployment (1.20, CI 1.03, 1.41); and less social drinking (1.36, CI 1.15, 1.60). In contrast, women only had a significantly elevated risk for having seen a mental health specialist (1.32, CI 1.02, 1.71). Among the men some of the risks were further elevated for those in specific diagnostic groups. These findings are examined in the light of postulates about the impact of chronic physical disorders as a whole and in an attempt to explain the striking sex differences. For clinicians they provide further reason to justify concern about the psychosocial aspects of care for children with chronic disorders.

Affective Symptoms↗

Explaining social class differences in psychological health among young adults: a longitudinal perspective.

The relationship between psychological health and occupational class was investigated in the large British sample of 23-year-old subjects from the 1958 birth cohort study. Odds of poor psychological health indicated by (1) the Malaise Inventory and (2) seeking help for a psychological problem between ages 16 and 23] were significantly greater in classes IV and V than in classes I and II: odds ratios were (1) 3.90 and 5.84, (2) 2.32 and 2.33 for men and women, respectively. Explanations for these differences were examined using longitudinal data representing 'inheritance' at birth, socio-economic background, educational achievement, earlier health and behaviour. The analyses suggested that each of these contributes to class differences in psychological health. Behaviour at age 16 (identified from the Rutter Behaviour Scale) was particularly notable for both psychological measures, as were educational achievement (for Malaise) and unemployment (for psychological morbidity needing specialist help). Mechanisms by which such factors might operate are discussed. Having accounted for earlier circumstances, class differences were no longer significant, except for Malaise in women. In this case an odds ratio of more than twofold remained after adjusting for earlier circumstances.

Adult↗

A review of child health in the 1958 birth cohort: National Child Development Study.

In the week 3-9 March 1958, 98% of all births in England, Scotland and Wales (approximately 17,000) were studied in the Perinatal Mortality Survey. The follow-up of surviving children, known as the National Child Development Study, comprises four major sweeps at ages 7, 11, 16 and 23. Medical examinations were conducted at each age, except at 23 when health was self-reported. Details of the child's family background and socio-economic circumstances were recorded, together with assessments of their social development and educational attainment. Seventy-six per cent of the target population were interviewed at age 23. The health of subjects in the 1958 cohort has been described in over 200 publications but there is no comprehensive account of findings from birth to age 23. This overview attempts to redress this. As new data are gathered from the study subjects at age 33, opportunities will exist to investigate associations between childhood factors and health in midlife. Data on their partners and children will be included, allowing studies of inter-generational and family health. Further indications of changing illness patterns will be possible from comparisons with data collected on earlier and later born cohorts.

Accidents↗

T-cell dominated inflammatory reactions in the bronchi of asthmatics are not reflected in matched bronchoalveolar lavage specimens.

Samples of bronchoalveolar lavage (BAL) and endobronchial biopsies were obtained from five patients with clinically diagnosed asthma (ATS criteria). A comparison was made of the presence and distribution of immunocompetent lymphocytes and macrophages within each sample. Significantly raised numbers of T lymphocytes, CD45RO+ lymphocytes, RFD1+ macrophage-like cells and RFD7+ macrophages were seen in the bronchial biopsies. In contrast four out of five of the BAL specimens showed a normal differential cell count, the one exception being a patient exhibiting a degree of lymphocytosis. Further, immunocytological investigation demonstrated a normal distribution of T-cell subsets and macrophage subsets in asthmatic BAL with the exception that in four out of five of these patients a raised number of macrophage-like cells exhibiting phenotypic markers of monocytes was observed. Correlation between BAL and biopsy data was seen in the number of CD45RO+ T-cells present. No other parameters exhibited a significant correlation. Raised expression of HLA-DR was recorded in all asthmatic biopsies, yet lavage cells from the same patients failed to exhibit any increase of HLA-DR density over normal. It is concluded that the immune-associated inflammation present in endobronchial biopsies of clinically stable asthmatics is not reflected in bronchoalveolar lavage samples taken from the same patients.

Acute-Phase Reaction↗

Structural and functional studies of the endothelial activation antigen endothelial leucocyte adhesion molecule-1 using a panel of monoclonal antibodies.

We have produced a panel of mAb to the endothelial activation Ag endothelial leucocyte adhesion molecule-1 (ELAM-1), using both a conventional immunization protocol and one involving immunosuppression. By constructing ELAM-1 mutants we have demonstrated that seven of these antibodies recognize epitopes within the lectin domain of ELAM-1 and that one binds within the complement regulatory protein domains. These studies also suggest that the EGF-like domain is important in maintaining the conformation of the neighbouring lectin domain. In functional studies, U937 cells bound to Cos cells expressing either ELAM-1 or ELAM-1 with the complement regulatory protein domains deleted. No adhesion was observed to Cos cells expressing ELAM-1 mutants lacking either the lectin or EGF-like domains. The fact that antibodies directed against the lectin domain can inhibit adhesion suggest that this domain is directly involved in cell binding.

Antibodies, Monoclonal↗

Women's lung cancer mortality, socio-economic status and changing smoking patterns.

Mortality data from the OPCS Longitudinal Study were used to determine whether the conventional classification of married women by their husband's occupation under-estimates the extent of social differences in lung cancer among this group. Differences existed for social class measures but alternatives based on housing tenure and car access defined socio-economic differences wider than any other previously recorded for England and Wales: married women living in rented housing and without a car were two and a half times as likely to die from lung cancer than those in owner occupied housing with access to a car. In 1957 and 1974 mothers of children included in the 1958 cohort study showed parallel socio-economic differences in smoking patterns as well as in uptake and cessation rates. Data from the General Household Survey for 1982 similarly suggest that cigarette smoking is more sharply differentiated using household rather than occupational measures of class. This suggests that wide differences in mortality are likely to persist through the eighties and beyond.

Adult↗

Social and economic background and class inequalities in health among young adults.

This paper considers which socio-economic factors in childhood and early adulthood are most strongly associated with social class differences in health at age 23. Longitudinal data from the 1958 (NCDS) cohort were used for this purpose. By age 23 class gradients were evident for several health measures, including self-rated health, 'malaise', psychological morbidity and height. The contribution of earlier socio-economic background was established by assessing how far class differences in the health indicators were reduced by controlling for earlier circumstances. While class differentials were not eliminated after taking account of earlier circumstances, substantial reductions were associated with a number of factors in childhood, in particular social class, housing tenure, crowding, family size and receipt of free school meals. More recent experiences of unemployment and family formation were also important.

Adult↗

Pathological and molecular biological features of a myelopathy associated with HTLV-1 infection.

We report the pathological and molecular biological findings of human T-cell lymphotropic virus type 1 (HTLV-1) infection of the spinal cord in a patient with a chronic progressive myelopathy. Light microscopy disclosed loss of myelin and axons, thickening of blood vessels and a lymphocytic cell infiltrate in the spinal cord especially at the cervical and thoracic levels. Electron microscopy confirmed the vascular appearance seen with light microscopy but virus particles were not observed. The HTLV-1 gag gene could be amplified (by polymerase chain reaction) from cervical spinal cord tissue while not from elsewhere in the neuroaxis. The presence of HTLV-1 genomic material in spinal cord tissue has not been previously reported.

DNA, Viral↗

Secular trends in social class and sex differences in adult height.

Trends in social class and sex differences in adult mean height in Great Britain since the turn of the century were investigated using data from parents and offspring in the 1946 and 1958 British birth cohort studies (n = 50,000). There has been an increase of 1.09 cm per decade in the mean height of men but only 0.36 cm per decade in the mean height of women. On average men from non-manual origins were 1.97 cm taller than men from manual origins and the figure for women was 1.61 cm. Trends in class differences in height for those born between the beginning of the century and 1958 have been small; fluctuations have occurred over the period but were unsynchronized for men and women.

Adult↗

Family disruption in early life and drinking in young adulthood.

The relationship between family disruption early in life and subsequent drinking in young adulthood was examined in a large representative British sample. Contrary to popular belief, parental loss was not an antecedent to heavy drinking in young adults. This finding was observed within social class of origin groups and when the nature and timing of the disruption were considered separately.

Adult↗

T cell dominated inflammatory reactions in the bronchioles of asymptomatic asthmatics are also present in the nasal mucosa.

Endobronchial and nasal mucosa biopsies were obtained from 5 patients with clinically-stable, diagnosed asthma (ATS criteria). A comparison was made of the presence and distribution of immunocompetent lymphocytes and macrophages within each sample. The distribution of immunocompetent cells within the nasal biopsies of the asthmatic patients reflected a very similar inflammatory infiltrate to that seen in the bronchial biopsies. Significantly raised numbers of T lymphocytes, CD45RO + lymphocytes, RFD1 + macrophage-like cells and RFD7 + macrophages were seen in both the nasal mucosa and the bronchial biopsies. Increases in HLA-DR expression were also seen in the nasal mucosa biopsies from asthmatics although the increases over normal did not reach statistical significance. It is concluded that inflammation present in the nasal mucosa of asymptomatic asthmatics exhibits cellular characteristics also seen in endobronchial biopsies. This observation offers the possibility that mucosal biopsy may be an alternative and less invasive approach for studying the cells involved in the bronchial inflammatory reaction that possibly predisposes asthmatics to bronchial hyper-responsiveness.

Adolescent↗