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Biomedical subjects

M E Thomas

Publications and source records attributed to M E Thomas.

At least 19 recordsLinked to original sources
PubMed2005

Risk factors for the introduction of high pathogenicity Avian Influenza virus into poultry farms during the epidemic in the Netherlands in 2003.

An epidemic of high pathogenicity Avian Influenza (HPAI) occurred in the Netherlands in 2003. A census survey of 173 infected and 401 uninfected commercial poultry farms was carried out to identify factors associated with the introduction of the HPAI virus into poultry farms. Data on farm size, production characteristics, type of housing, presence of cattle and pigs were gathered by the National Inspection Service for Livestock and Meat from all farms included in this study. For each risk factor (RF) available for analysis, the Mantel-Haenszel odds ratio was calculated (stratified on farm size and housing type). We found an increased risk of HPAI virus introduction in layer finisher type poultry: OR = 2.05 (95% confidence interval, CI = 1.29-3.27). An explanation for this increased risk is the high number of contacts between these farms, especially via cardboard egg trays used for removal of eggs during the epidemic. Our analysis did not indicate significant differences between the infected and uninfected farms with regard to housing type, presence of cattle or pigs. Since layer finisher type farms are assumed to be at higher risk for HPAI virus introduction, more specific control measures might be applied in future outbreaks.

Animal Husbandry↗
PubMed2004

Manipulation of the renin angiotensin system in peripheral arterial disease.

The Heart Outcomes Prevention Evaluation (HOPE) study has provided evidence for the use of ramipril for secondary cardiac prevention for patients with peripheral arterial disease. Despite this many vascular surgeons and general practitioners are reluctant to prescribe ACE inhibitors in a group of patients perceived to have a high incidence of renal artery stenosis. This review aims to review the pathophysiology of the renin-angiotensin system and make evidence based recommendations for commencing ACE inhibitors as part of a comprehensive delivery of best medical therapy to patients with peripheral arterial disease.

Algorithms↗
PubMed1999

[An integrated quality policy for and by veterinarians: 1. Status of business].

Several initiatives are being developed by the livestock industry and veterinarians to improve quality. This article describes the term quality control. Although action has been taken to improve quality, at the moment there is no integrated policy of quality control for veterinarians. To date, initiatives have been limited to defining the preconditions for such policies and little has been done to establish the content of veterinary interventions.

Animal Husbandry↗
PubMed1999

[An integrated quality policy for and by (cattle) veterinarians: 2. A comparison with the quality policy of family physicians].

The core of the integrated quality control policy of Dutch general practitioners is the development of treatment guidelines. These guidelines are the basis for assessing interventions and for improving quality. General practitioners took the initiative to prepare these guidelines without there being external pressure on them to do so. The quality control policy strengthens the position of this professional group by diminishing differences in therapeutic approach. The procedures followed for establishing guidelines, such as those for human medicine, are described and may be of use to veterinarians.

Animals↗
PubMed1999

Proteinuria induces tubular cell turnover: A potential mechanism for tubular atrophy.

BACKGROUND: Proteinuria and tubular atrophy have both been closely linked with progressive renal failure. We hypothesized that apoptosis may be induced by tubular cell exposure to heavy proteinuria, potentially leading to tubular atrophy. Apoptosis was studied in a rat model of "pure" proteinuria, which does not induce renal impairment, namely protein-overload proteinuria. METHODS: Adult female Lewis rats underwent intraperitoneal injection of 2 g of bovine serum albumin (BSA, N = 16) or sham saline injections (controls, N = 8) daily for seven days. Apoptosis was assessed at day 7 in tissue sections using in situ end labeling (ISEL) and electron microscopy. ISEL-positive nuclei (apoptotic particles) were counted in blinded fashion using image analysis with NIH Image. Cell proliferation was assessed by detection of mRNA for histone by in situ hybridization, followed by counting of positive cells using NIH Image. RESULTS: Animals injected with saline showed very low levels of apoptosis on image analysis. BSA-injected rats had heavy proteinuria and showed both cortical and medullary apoptosis on ISEL. This was predominantly seen in the tubules and, to a lesser extent, in the interstitial compartment. Overall, the animals injected with BSA showed a significant 30-fold increase in the number of cortical apoptotic particles. Electron microscopy of tubular cells in a BSA-injected animal showed a progression of ultrastructural changes consistent with tubular cell apoptosis. The BSA-injected animals also displayed a significant increase in proximal tubular cell proliferation. This increased proliferation was less marked than the degree of apoptosis. CONCLUSION: Protein-overload proteinuria in rats induces tubular cell apoptosis. This effect is only partially balanced by proliferation and potentially provides a direct mechanism whereby heavy proteinuria can induce tubular atrophy and progressive renal failure.

Animals↗
PubMed1998

B-cell chronic lymphocytic leukaemia with CD8 expression: report of 10 cases and immunochemical analysis of the CD8 antigen.

We report 10 cases of B-cell chronic lymphocytic leukaemia (B-CLL) with expression of the T-cell antigen CD8. The majority of patients had typical B-cell CLL with stable and non-progressive stage A(O) disease except for more common expression of lambda light chain and CD25. Two patients had progressive disease and required therapy, one with atypical morphological and phenotypic features. The incidence of CD8 expression was approximately 0.5% of B-CLL patients from our institutions. Immunoprecipitation of the CD8 antigen from four of these B-CLLs showed identity to the CD8 antigen expressed on T cells with precipitation of CD8alpha bands of molecular weight approximately 34 kD. In view of the known intracellular signalling mechanism of CD8 using the tyrosine kinase p56-lck, we studied p56-lck expression by Western blot and found lack of consistent expression of the CD8 surface antigen, with most lacking p56-lck. Our report indicates that CD8 expression in B-CLL is probably underrecognized but is not a marker of disease progression. The CD8 on the B-CLL surface is immunochemically identical to the antigen on T cells, but is not accompanied by its usual signalling mechanism of p56-lck tyrosine kinase and therefore is unlikely to be a functionally active receptor.

Aged↗
PubMed1997

Interactions between leptin and hypothalamic neuropeptide Y neurons in the control of food intake and energy homeostasis in the rat.

Leptin acts on the brain to inhibit feeding, increase thermogenesis, and decrease body weight. Neuropeptide Y (NPY)-ergic neurons of the hypothalamic arcuate nucleus (ARC) that project to the paraventricular nuclei (PVN) and dorsomedial nuclei (DMH) are postulated to control energy balance by stimulating feeding and inhibiting thermogenesis, especially under conditions of energy deficit. We investigated whether leptin's short-term effects on energy balance are mediated by inhibition of the NPY neurons. Recombinant murine leptin (11 microg) injected into the lateral ventricle of fasted adult Wistar rats inhibited food intake by 20-25% between 2 and 6 h after administration, compared with saline-treated controls (P < 0.05). Uncoupling protein mRNA levels in brown adipose tissue (BAT) rose by 70% (P < 0.01). Leptin treatment significantly reduced NPY concentrations by 20-50% (P < 0.05) in the ARC, PVN, and DMH and significantly decreased hypothalamic NPY mRNA levels (0.61 +/- 0.02 vs. 0.78 +/- 0.03 arbitrary units; P < 0.01). A second study examined changes in leptin during 5 days' intracerebroventricular NPY administration (10 microg/day), which induced sustained hyperphagia and excessive weight gain. In NPY-treated rats, leptin mRNA levels in epididymal fat were comparable to those in saline-treated controls (0.94 +/- 0.17 vs. 1.0 +/- 0.28 arbitrary units; P > 0.1), but plasma leptin levels were significantly higher (4.88 +/- 0.66 vs. 2.85 +/- 0.20 ng/ml; P < 0.01). Leptin therefore acts centrally to decrease NPY synthesis and NPY levels in the ARC-PVN projection; reduced NPY release in the PVN may mediate leptin's hypophagic and thermogenic actions. Conversely, NPY-induced obesity results in raised circulating leptin concentrations. Leptin and the NPY-ergic ARC-PVN neurons may interact in a homeostatic loop to regulate body fat mass and energy balance.

Adipose Tissue, Brown↗
PubMed1995

Effects of fasting and refeeding on ob gene expression in white adipose tissue of lean and obese (oblob) mice.

A 33-mer antisense oligonucleotide has been utilized as a probe for the rapid chemiluminescence-based detection of ob (obese) mRNA. Expression of the ob gene was evident in several white adipose tissue depots of mice (epididymal, highest; subcutaneous and omental, lowest), but not in other organs. Fasting (24 h) induced a substantial fall in ob mRNA in the epididymal fat of lean mice, which was rapidly reversed on refeeding, responses consistent with the putative role of ob in energy balance. Fasting had no effect, however, on ob mRNA levels in obese (oblob) mice.

Adipose Tissue↗
PubMed1995

Rapid chemiluminescent detection of mRNAs on northern blots with digoxigenin end-labelled oligonucleotides.

A simplified, nonradioactive procedure for the detection of specific mRNAs on Northern blots has been developed, utilizing digoxigenin-labelled oligonucleotides and chemiluminescence. Antisense oligonucleotide (30-35 mer) probes were designed and synthesised based on published cDNA and gene sequences. These probes were end-labelled (5') with digoxigenin. Total RNA was fractionated by agarose gel electrophoresis and capillary blotted onto positively charged nylon membranes. After hybridization, the mRNA/digoxigenin-labelled oligonucleotide complex was detected by a chemiluminescence-based method using disodium 3-(4-methoxyspiro-[1,2-dioxetane-3-2'(5'chloro)- tricyclo[3.3.1.13.7]decane]-4-yl)phenyl phosphate (CSPD) as substrate. The advantages of this simplified technique for detecting mRNAs in physiological and nutritional studies are described.

Animals↗
PubMed1995

Metabolic effects of fatty acid-bearing albumin on a proximal tubule cell line.

In glomerular disease, fatty acids carried on albumin are taken up by the proximal tubule with filtered albumin. We postulate that the fatty acids carried on filtered albumin could contribute to the deleterious effects of proteinuria. The effects of fatty acid-albumin complexes on lipid metabolism have been studied in opossum kidney (OK) cells, a proximal tubule cell line. OK cells transported two-thirds of [14C]palmitate-albumin (5 mg/ml) intracellularly within 16 h. [14C]palmitate-albumin was distributed into phosphatidylcholines, phosphatidylinositols, and tri- and diglycerides. 14C-labeled unsaturated fatty acid albumins (oleate, linoleate, and arachidonate) showed preferential incorporation into triglycerides, with lesser incorporation into phospholipids. Studies of total lipid pools showed that fatty acid-albumin uptake produced a particularly marked increase in total triglyceride levels (approximately 10-fold). Oil red O staining of OK cells cultured with oleate-albumin showed a marked increase in intracellular lipid droplets, compared with cells cultured with delipidated albumin, consistent with triglyceride accumulation. Less than 1% of [14C]palmitate taken up was isolated as intracellular free fatty acid. Less than 5% of [14C]palmitate internalized was oxidized to 14CO2. Different fatty acids, when taken up by the OK cell, have distinct metabolic fates. Each fatty acid is incorporated in a characteristic fashion into certain complex lipids, possibly dependent on the presence or absence of double bonds. We propose that this may have functional consequences for the proximal tubule in the human nephrotic syndrome.

Animals↗
PubMed1995

Rural-urban differences in black family structure: an analysis of the 1990 census.

This article examines the relationship between family structure and persisting disadvantage among U.S. blacks. The "article employs data from the 1990 Public Use Microdata Samples to compare the rural African American family to its urban counterpart. Results from the logistic regression analysis reveal that for rural Blacks, family structure is less important than community type and race relative to poverty status. These findings suggest a need for a refinement of the underclass debate."

Black or African American↗
PubMed1995

Modulation by progesterone of interleukin-6 production by gingival fibroblasts.

The gingivitis associated with pregnancy has been attributed to increased concentrations of circulating estrogen and/or progesterone. However, the mechanism by which these steroids increase gingival inflammation is not known. Interleukin-6 (IL-6), a pleiotropic cytokine produced by many cell types including human gingival fibroblasts (hGF), is secreted in response to inflammatory challenges such as bacterial lipopolysaccharide and interleukin-1 (IL-1). This study tested the hypothesis that progesterone could modulate the local production of IL-6 by hGF. The effects of progesterone on IL-6 production were measured in vitro in serum-free, phenol red-free medium to eliminate possible effects of such medium additives. The concentration of IL-6 secreted into supernatant medium after a 24 hour challenge with IL-1 beta was estimated by radioimmunoassay. Total RNA from steroid-treated hGF was probed for IL-6 mRNA. In serum-free medium, progesterone dose-dependently and significantly (P < 0.05) inhibited IL-6 production by hGF, as did the glucocorticoids hydrocortisone (HC) and dexamethasone. At progesterone concentrations common in late pregnancy, IL-6 production was reduced to levels 40 to 50% of control. In addition, mRNA was significantly down-regulated by progesterone and HC, at both basal levels and after IL-1 beta challenge. These results suggest that high levels of progesterone during pregnancy affect the development of localized inflammation by down-regulation of IL-6 production, rendering the gingiva less efficient at resisting the inflammatory challenges produced by bacteria.

Analysis of Variance↗
PubMed1994

Chemiluminescent detection of mRNAs on northern blots with digoxigenin end-labeled oligonucleotides.

To establish a simplified, nonradioactive approach for identifying mRNAs on Northern blots, antisense oligonucleotides have been used as probes in combination with chemiluminescence-based detection. Oligonucleotides (approximately 32-mer) were end-labeled with digoxigenin (DIG) and used in conjunction with adamantyl 1,2-dioxetane aryl phosphate substrates (Lumigen PPD and CSPD). Oligonucleotides were designed as probes for several mRNAs in tissues of rats and mice, including the mitochondrial uncoupling protein, lipoprotein lipase, GLUT1, GLUT4, and beta-actin. Uncoupling protein mRNA was detected in total RNA from brown adipose tissue with a 32-mer DIG-labeled oligonucleotide, within 2 min of exposure to film. This mRNA could also be detected when as little as 250 ng of total RNA was applied to the gel, following 4 h exposure to film, and was present only in brown fat. The mRNA for lipoprotein lipase was detectable with a 30-mer DIG-labeled oligonucleotide in 1 micrograms of total RNA from mouse heart, within 2 h of exposure. The mRNA for the GLUT1 glucose transporter was detected in total RNA from rat midbrain using a 32-mer DIG-labeled oligonucleotide, while beta-actin mRNA was detected with a 30-mer oligonucleotide. The mRNA for the insulin-sensitive glucose transporter GLUT4 was detected with a 32-mer DIG-labeled oligonucleotide and found only in those tissues in which glucose uptake is stimulated by insulin. The speed of detection was greater with CSPD and was augmented by exposure of membranes to film at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1994

Glucose transporters (GLUTs 1-4) and their mRNAs in regions of the rat brain: insulin-sensitive transporter expression in the cerebellum.

Major regions of the rat brain have been examined for the presence of glucose transporters (GLUTs 1-4) and their mRNAs. Both the mRNA and immunoreactive protein for GLUT1 and GLUT3 were found in each brain region (medulla, pons, cerebellum, midbrain, hypothalamus, thalamus, hippocampus, parietal cortex). The mRNA and protein for GLUT4 were identified in the cerebellum, but not elsewhere in the brain. GLUT2 protein and mRNA were not detected in any region of the brain. Although GLUT1 and GLUT3 are the major brain glucose transporters, the presence of GLUT4 in the cerebellum suggests that insulin-sensitive glucose uptake may occur in a specific part of the brain.

Animals↗
PubMed1993

Presence of the brown fat-specific mitochondrial uncoupling protein and iodothyronine 5'-deiodinase activity in subcutaneous adipose tissue of neonatal lambs.

Subcutaneous adipose tissue of neonatal lambs has been examined for the presence of markers diagnostic of thermogenic brown fat. Uncoupling protein, uncoupling protein mRNA, and iodothyronine 5'-deiodinase activity were each detected in subcutaneous adipose tissue, as well as in the major internal fat depot (perirenal), of newborn lambs. These brown fat markers were not present, however, in adipose tissue of adult sheep. It is concluded that subcutaneous fat in newborn lambs is functionally 'brown', and similar to the internal fat; subcutaneous and internal adipose tissues follow a similar developmental path--from 'brown' to 'white'.

Adipose Tissue↗
PubMed1993

Simvastatin therapy for hypercholesterolemic patients with nephrotic syndrome or significant proteinuria.

Experimental evidence suggests that lipid lowering therapy could slow the progression of renal disease in humans. We have conducted a double-blind, placebo controlled trial of the HMG CoA reductase inhibitor simvastatin in patients with the nephrotic syndrome or significant proteinuria (> 1 g/day) and hypercholesterolemia (> or = 6.5 mmol/liter). Patients were placed on a lipid lowering diet for at least 10 weeks before randomization. After a four-week placebo run-in, 30 adults were randomized to simvastatin or placebo therapy (10 mg/day, increasing to 20 to 40 mg/day as required) for 24 weeks. There were seven dropouts, none of whom were "definitely" related to drug therapy. Total and LDL cholesterol levels fell by a mean of 33 and 31%, respectively, in simvastatin treated patients, compared with only 5 and 1% in patients on placebo (P < 0.001, P = 0.002, respectively). Apolipoprotein B100 levels fell by a mean of 31% in the simvastatin group but rose 0.3% in the placebo group (P = 0.014). There were no significant changes in HDL levels. There were no significant differences between the groups in their urine protein levels, their rise in plasma creatinine, or decline in plasma inulin clearance. Simvastatin is a safe, effective therapy for hypercholesterolemia in proteinuric states. A much larger trial is needed to show if potent lipid-lowering therapy slows progression of hypercholesterolemic proteinuric diseases.

Adolescent↗