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Biomedical subjects

J Fear

Publications and source records attributed to J Fear.

17 recordsLinked to original sources

Isotopic ((13)C) fractionation during plant residue decomposition and its implications for soil organic matter studies.

Carbon isotopic fractionations in plant materials and those occurring during decomposition have direct implications in studies of short-and longer-term soil organic matter dynamics. Thus the products of decomposition, the evolved CO(2) and the newly formed soil organic matter, may vary in their (13)C signature from that of the original plant material. To evaluate the importance of such fractionation processes, the variations in (13)C signatures between and within plant parts of a tropical grass (Brachiaria humidicola) and tropical legume (Desmodium ovalifolium) were measured and the changes in (13)C content (signatures) during decomposition were monitored over a period of four months. As expected the grass materials were less depleted in (13)C (-11.4 to -11.9 per thousand) than those of the legume (-27.3 to -25.8 per thousand). Root materials of the legume were less (1.5 per thousand) depleted in (13)C compared with the leaves. Plant lignin-C was strongly depleted in (13)C compared with the bulk material by up to 2.5 per thousand in the legume and up to 4.7 per thousand in the grass. Plant materials were subsequently incubated in a sand/nutrient-solution/microbial inoculum mixture. The respiration product CO(2) was trapped in NaOH and precipitated as CaCO(3), suitable for analysis using an automated C/N analyser coupled to an isotope ratio mass spectrometer. Significant depletion in (13)C of the evolved CO(2) was observed during the initial stages of decomposition probably as a result of microbial fractionation as it was not associated with the (13)C signatures of the measured more decomposable fractions (non-acid detergent fibre and cellulose). While the cumulative CO(2)-(13)C signatures of legume materials became slightly enriched with ongoing decomposition, the CO(2)-C of the grass materials remained depleted in (13)C. Associated isotopic fractionation correction factors for source identification of CO(2-)C varied with time and suggested errors of 2-19% in the estimation of the plant-derived C at 119 days of incubation in a soil of an intermediate (-20.0 per thousand) (13)C signature. Analysis of the residual material after 119 days of incubation showed little or no change in the (13)C signature partly due to the incomplete decomposition at the time of harvesting. Copyright 1999 John Wiley & Sons, Ltd.

Journal Article↗

Distinct patterns of chemokine expression are associated with leukocyte recruitment in alcoholic hepatitis and alcoholic cirrhosis.

Alcoholic liver disease is associated with three histologically distinct processes: steatosis (parenchymal fat accumulation), alcoholic hepatitis (characterized by parenchymal infiltration by neutrophil polymorphs), and alcoholic cirrhosis (in which chronic inflammation and fibrosis dominate). Chemokines are cytokines that promote subset-specific leukoycte recruitment to tissues and could therefore play a crucial role in determining which leukocyte subsets are recruited to the liver in alcoholic liver disease. This paper reports that chemokine expression is increased in the liver of patients with alcoholic liver disease and, moreover, that distinct patterns of chemokine expression are associated with the different inflammatory responses to alcohol. Interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1 alpha), and MIP-1 beta were all detected in the parenchyma at sites of inflammation in alcoholic hepatitis, whereas in alcoholic cirrhosis, chemokines were restricted to inflammatory cells and endothelium in the fibrous septa and portal tracts. In alcoholic hepatitis, chemokine transcription was localized to sinusoidal cells, leukocytes, and fibroblasts in areas of parenchymal inflammation, but hepatocytes, despite staining strongly for chemokine protein, were negative. In alcoholic cirrhosis, chemokine mRNA was detected in portal tract endothelium, leukocytes, and fibroblasts. Thus, alcoholic hepatitis and alcoholic cirrhosis are associated with distinct patterns of chemokine expression that are likely to be important factors in determining whether a patient develops acute parenchymal inflammation and alcoholic hepatitis, or chronic septal inflammation and alcoholic cirrhosis.

Chemokine CCL2↗

Prevalence of hip problems in the population aged 55 years and over: access to specialist care and future demand for hip arthroplasty.

To determine the prevalence of hip problems in the population aged 55+, a postal questionnaire was sent to a multistage stratified random sample of residents of a health district with an over-55 population of 210,000. An initial four page postal questionnaire produced an 86% response rate from 18,827 eligible cases. A subsequent detailed questionnaire (with a response rate of 78%) then determined the prevalence of severe pain and severe disability amongst those with hip problems. The prevalence of those with existing hip replacements is estimated at 32.1/1000 (95% CI 29.5-34.9). An estimated 13.5/1000 (95% CI 12.4-14.7/1000) displayed levels of pain and disability consistent with a current need to consider arthroplasty. In addition, it appears that the over 75s are less likely to have access to appropriate surgery. Unless health authorities and, increasingly, general practitioners consider purchasing more hip replacements, the prevalence pool of those who could benefit will inexorably rise.

Age Distribution↗

Outcome following stroke.

A community study based on an age-stratified sample of those aged 55 years and older in a northern health district in the United Kingdom has been used to consider the implications for purchasing health-care services for those who have survived a stroke. The study showed that while almost a quarter of those reporting a stroke had made a full recovery, a wide range of impairments and disabilities persisted. Almost half reported needing help at least daily. A logistic regression model to predict this level of dependency found that impairments, disabilities and other factors, such as locality, were also predictive of dependency. A second model predicting mobility handicap (dwelling restricted) was found to have a similar mix of predictors. These results show how purchasers must consider the broad outcome in terms of a continuum of impairment, disability and handicap. The results also show that handicap is a distinct concept that draws together many influences which act upon the individual.

Aged↗

Promotion of leukocyte transendothelial cell migration by chemokines derived from human biliary epithelial cells in vitro.

Biliary epithelial cells are the focus of inflammatory damage in several liver diseases, including allograft rejection wherein intrahepatic bile ducts are infiltrated and damaged by T cells and neutrophils. Locally secreted chemotactic cytokines (chemokines) are important signals for leukocyte recruitment to an inflammatory site and include interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1), potent chemotactic agents for neutrophils and monocyte or T cells, respectively. In this study, we demonstrate that primary cultures of human biliary epithelial cells (BECs) express and secrete IL-8 and MCP-1, both of which are upregulated rapidly and markedly in response to the proinflammatory cytokines IL-1 and tumor necrosis factor-alpha. Interferon-gamma had a differential effect by reducing IL-8 secretion but stimulating MCP-1 secretion. BECs cocultured in transwell chambers below confluent monolayers of endothelial cells promoted the transendothelial migration of neutrophils, which was blocked by antibodies to CD18 or CD11b but only partially inhibited by blocking antibodies to IL-8. We conclude that human BECs produce and secrete potent, functional chemokines when stimulated by proinflammatory cytokines. The ability of BECs to secrete chemokines and thus to promote leukocyte infiltration into portal tracts seems likely to be an important cause of bile duct damage in such conditions as liver allograft rejection and may explain the involvement of intrahepatic bile ducts in a number of inflammatory liver diseases.

Base Sequence↗

Hepatic expression of macrophage inflammatory protein-1 alpha and macrophage inflammatory protein-1 beta after liver transplantation.

Two local events that are crucial for T cell emigration into tissue are (1) activation of T cell integrins to permit binding to endothelial counter-receptors and (2) directed migration through the endothelium and into tissue in response to chemotactic factors. Because the chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha) and MIP-1 beta can activate adhesion and induce migration of T cells in vitro, we investigated their expression in human liver allografts to determine whether they might be involved in regulating the recruitment of T cells to allografts in vivo. Both chemokines were expressed strongly by infiltrating leukocytes during rejection and could be detected immunohistochemically on biliary epithelium, an important target for T cell mediated graft damage. Both chemokines, but particularly MIP-1 beta, were detected on the vascular and sinusoidal endothelium of rejecting liver allografts, where they were coexpressed with the T cell beta 1-integrin receptor vascular cell adhesion molecule-1. In situ hybridization with complementary ribonucleic acid probes showed no MIP-1 alpha or MIP-1 beta mRNA in normal liver but dramatic expression of both chemokines in infiltrating leukocytes and graft endothelium during rejection. Expression was reduced after successful corticosteroid treatment of rejection but persisted in patients progressing to chronic rejection. Increased MIP-1 alpha and MIP-1 beta mRNA expression was already found in biopsies taken at the end of the transplant operation, suggesting that early induction of chemokines, possibly in response to graft reperfusion, might promote the subsequent development of graft rejection. These data demonstrate for the first time that MIP-1 alpha and MIP-1 beta are (1) expressed in human liver allografts, (2) produced by endothelial cells in vivo, and (3) induced early after transplantation. They suggest that MIP-1 alpha and MIP-1 beta produced by graft infiltrating leukocytes and graft endothelium might play a crucial role in regulating T cell recruitment to liver allografts in vivo.

Bile Ducts↗

Interactions between dietary selenium, copper and sodium nitroprusside, a source of cyanide in growing chicks and laying hens.

1. Diets containing supplements of selenium (10 mg/kg as sodium selenite), copper (500 mg/kg as copper (II) sulphate) and sodium nitroprusside (SNP 300 mg/kg) as a source of cyanide, were fed singly and in all possible combinations to chicks from 14 to 35 d of age. 2. Both copper and SNP individually alleviated the growth depression caused by excess selenium but interacted adversely with one another. The effect of SNP was to decrease liver selenium but copper increased it. Despite this contrast it is suggested that both achieve their beneficial effects through influences on the fraction of liver selenium that can be reduced to volatile forms by hydrochloric acid and zinc. 3. In a second experiment the effects of diets containing additional selenium (2 mg/kg as sodium selenite or selenomethionine) with or without additional copper (100 mg/kg) or SNP (100 mg/kg) on selenium incorporation into eggs were compared. 4. SNP reduced incorporation from selenite whereas copper had no effect. However, copper reduced the incorporation from selenomethionine into protein fractions of egg white as much as SNP.

Analysis of Variance↗

Incorporation of selenium into egg proteins from dietary selenite.

1. The deposition of selenium in egg components has been investigated in two experiments in which sodium selenite was added to a conventional cereal-based layer diet. 2. Addition of graded amounts of selenite up to 4 mg Se/kg resulted in linear increases in the selenium content of egg white and yolk, and in protein fractions derived from them. The presence of selenium in yolk phosvitin indicates that deposition is not dependent upon the presence of cysteine. 3. Addition of sodium nitroprusside at 0.l5 and 0.3 g/kg to diets having an addition of selenite at the highest concentration, 4 mg Se/kg, resulted in substantial reductions in the selenium concentration in egg components. 4. Samples from eggs laid by hens receiving a diet containing an additional 8 mg selenite Se/kg were subjected to dialysis against sodium hydroxide or cysteine, or subjected to reduction with hydrochloric acid and zinc under anaerobic conditions. Comparisons were made with similar samples prepared from eggs laid by hens on the control diet. 5. Both sodium hydroxide and cysteine were more effective at extracting additional diet-derived selenium from whole white than from whole yolk. The proportion of selenium that could be extracted from the water-soluble or the high density fractions of yolk by either reagent was similar for both control and high selenium samples. However, neither reagent was effective at removing selenium from the ovalbumin or globin fractions of white from control eggs but substantial amounts were extracted from high selenium samples. 6. Most of the selenium was present in non-reducible forms in all samples. There was significantly more reducible selenium in ovalbumin from control eggs than from all other samples but even so non-reducible selenium accounted for two thirds of the selenium present. 7. The differential responses to chemical treatment suggest that selenium can be deposited in eggs in an unspecified number of different forms. These have still to be characterised but site of formation of egg proteins, liver or oviduct, has a bearing on the forms of selenium deposited.

Analysis of Variance↗

Are we making the most of the Stanford Health Assessment Questionnaire?

For many years, the Stanford Health Assessment Questionnaire (HAQ) has provided an effective measure of disability. Recently, some debate has emerged about whether or not the HAQ is an "ordinal' or "interval' scale. The opportunity to test its level of measurement arose when the scale was applied in a community survey which undertook a two-stage random sample using postal questionnaires to ascertain the health care needs of those with arthritis. The HAQ data are fitted to the Rasch model which tests for the presence of certain desirable characteristics of measurement, e.g. unidimensionality. The fit of the data to the model for those self-reporting rheumatoid arthritis (RA) was adequate. The transformed HAQ score, derived from the Rasch analysis, is compared with the ordinary HAQ (raw) score. This shows that, for those with RA, incremental units of the raw score at the margins of the scale reflect an increasing level of (dis)ability compared to similar units in the centre of the scale. Thus, the traditional HAQ score (range 0-3) is an ordinal score. The findings also indicate that scoring all 20 items may lead to greater sensitivity. Questions are also raised about the construct validity for those with other types of arthritis. For osteoarthrosis, the grip item does not appear to belong to the same underlying construct as the other items.

Activities of Daily Living↗

Prevalence of self reported stroke in a population in northern England.

STUDY OBJECTIVE: The aim of this study was to determine the prevalence of stroke survivors in a health district population aged 55 years and over. DESIGN: This was a point prevalence study using two-stage postal questionnaires sent to an age stratified random sample of the population. SETTING: A district health authority in northern England with a resident population of 723,000. SUBJECTS: Altogether 18,827 residents aged 55 years or over. MAIN RESULTS: Prevalence was found to increase with age and, apart from the very elderly, males had a higher prevalence than females. Overall prevalence was found to be 46.8/1,000 (95% CI 42.5, 51.6). 23% of respondents reported full recovery from stroke. Cognitive impairments (33%), problems with lower limbs (33% for right leg; 27% for left leg) and speech difficulties (27%) were the most common residual impairments. CONCLUSIONS: Current guidelines to purchasers on the provision of services to those who have had a stroke may under-estimate prevalence rates by as much as 50%. This could lead to a shortfall in provision of services designed to support people in the months and years following their stroke.

Age Distribution↗

Prevalence of knee problems in the population aged 55 years and over: identifying the need for knee arthroplasty.

OBJECTIVE: To determine the prevalence of knee problems in people aged 55 years and over and identify those who should be considered for knee arthroplasty. DESIGN: Postal survey; questionnaires were sent to a multistage stratified probability sample of residents of North Yorkshire Health Authority aged 55 and over. SETTING: A health district with a population of 210,000 aged 55 and over. RESULTS: An initial four page postal questionnaire produced an 86% response rate among 18,827 eligible patients. A subsequent detailed questionnaire sent to 1277 patients with knee problems (with a response rate of 78%) then determined the prevalence of severe pain and severe disability. Pain and disability consistent with the need to consider arthroplasty was found in 20.4/1000 (95% confidence interval 18.0 to 23.1); of these, 4.1 (2.7 to 5.8)/1000 had extreme disability. Age and sex specific rates in men who might benefit from arthroplasty were, in those aged 55-64, 12.9 (8.4 to 19.0)/1000; aged 65-74, 12.1 (7.4 to 18.4)/1000; aged 75 and over, 20.3 (12.9 to 30.5)/1000. In women aged 55-64 the rates were 12.9 (8.6 to 18.7)/1000; aged 65-74, 19.6 (13.9 to 26.7)/1000; aged 75 years and over, 42.6 (34.3 to 52.4)/1000. CONCLUSIONS: Total knee replacement has until recently been considered unreliable and often seen as a last resort for many with severe knee problems. Advances in prosthesis design and surgical and anaesthetic techniques have transformed this procedure into a reliable option with a potential for reducing disability and dependency in a large number of people in the community. Understandably, the prevalence pool of those who may benefit is large; health authorities and, increasingly, general practitioners should consider purchasing more total knee replacement surgery to offer real choice to those in need.

Aged↗

Broad host range plasmids carrying the Escherichia coli lactose and galactose operons.

We have developed a number of broad-host-range plasmids that allow the expression of the Escherichia coli lac operon from any cloned promoter, and the creation of 'in phase' fusions between lacZ and other cloned genes. In a second series of constructions, the E. coli gal operon has been cloned into the broad-host-range vector and a plasmid carrying both the E. coli gal and lac genes is described. These plasmids have been transferred into Pseudomonas aeruginosa and Zymomonas mobilis and their effects on the utilisation of lactose and galactose have been investigated.

Escherichia coli↗

Observations on the fusion of chick embryo myoblasts in culture.

Chick embryo myoblasts were grown as monolayers in culture. The formation of myotubes from myoblasts occurred over a 15 hour period in vitro. Time-lapse cinemicrography was used to study the behaviour of myoblasts during fusion and particular attention was paid to the way in which myoblasts aligned themselves. It was found that fusion tended to follow end-to-end rather than side-to-side alignment of myoblasts. This observation suggests that cell orientation is an important factor in myogenesis. Branched myotubes were frequently observed in culture; an explanation of this is offered.

Animals↗