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Biomedical subjects

M Thomas

Publications and source records attributed to M Thomas.

At least 271 records · Page 15Linked to original sources
PubMed1999

AP site structural determinants for Fpg specific recognition.

The binding of Escherichia coli and Lactococcus lactis Fapy-DNA glyosylase (Fpg) proteins to DNA containing either cyclic or non-cyclic abasic (AP) site analogs was investigated by electrophoretic mobility shift assay (EMSA) and by footprinting experiments. We showed that the reduced AP site is the best substrate analog for the E.coli and L.lactis enzymes ( K Dapp = 0.26 and 0.5 nM, respectively) as compared with the other analogs tested in this study ( K Dapp >2.8 nM). The 1,3-propanediol (Pr) residue-containing DNA seems to be the minimal AP site structure allowing a Fpg specific DNA binding, since the ethyleneglycol residue is not specifically bound by these enzymes. The newly described cyclopentanol residue is better recognized than tetrahydrofuran (for the E.coli Fpg, K Dapp = 2.9 and 25 nM, respectively). These results suggest that the hemiacetal form of the AP site is negatively discriminated by the Fpg protein suggesting a hydrogen bond between the C4'-hydroxyl group of the sugar and a Fpg residue. High-resolution hydroxyl radical footprinting using a duplex containing Pr shows that Fpg binds to six nucleotides on the strand containing the AP site and only the base opposite the lesion on the undamaged complementary strand. This comparative study provides new information about the molecular mechanism involved in the Fpg AP lyase activity.

Cyclopentanes↗
PubMed1999

Early events in the formation of a tissue structure from dispersed bovine adrenocortical cells following transplantation into scid mice.

The early events that follow the transplantation of dispersed bovine adrenocortical cells into scid mice were investigated. We introduced adrenocortical cells into a small cylinder inserted beneath the kidney capsule, where they form a tissue structure that becomes vascularized and secretes steroids that replace those from the animal's own adrenal glands, which are removed during the transplantation surgery. We studied cell proliferation, cell survival, apoptosis, and the role of p21WAF1/CIP1/SDI1 over the first 6 days following transplantation. Additionally we examined the invasion of the tissue by host macrophages and endothelial cells. The data show that there is healthy survival of most of the transplanted cells, and that this is related to their position in the cell transplantation cylinder. In the layer of cells that was adjacent to the kidney parenchyma there was a higher rate of cell proliferation and a lower rate of apoptosis than in cells that were located in the upper part of the cylinder. In the lower layer cells were more likely to have nuclear p21, and macrophages and endothelial cells were observed only in this region. Cells that incorporated bromodeoxyuridine administered to animals 2 or 4 days following transplantation were not more likely than other cells to be undergoing a second division when the animals were killed at 6 days, suggesting that proliferation in the lower layer is not confined to a small subpopulation of cells. Among different animals, the extent to which the spaces between the transplanted cells became lined by host endothelial cells was correlated with higher levels of proliferation and nuclear p21, suggesting that vascularization is the critical step for the continued survival and proliferation of the transplant. The present experiments show that bovine adrenocortical cells transplanted into scid mice form a useful model for the study of tissue formation from dispersed cells and the interaction of the transplanted cells with the host.

Adrenal Cortex↗
PubMed1999

Systemic adverse effect of antithyroid drugs.

Antithyroid drugs adverse effects are varied and rare. Autoimmune disorders (vasculitis, lupus erythematosus, polyarthritis...) are unusual and serious complications of antithyroid drugs. Since 1945, fewer than 100 cases of systemic manifestations related to antithyroid drugs have been reported in the literature, most frequently with propylthiouracil. The outcome is usually good after drug discontinuation, but some fatal cases have been reported. Because possible cross-sensitivity with other antithyroid drugs, the appropriate treatment for hyperthyroidism relapse if a patient has had an antithyroid drug adverse reaction, should be 131I-Iodine or surgery. We report four new cases of systemic manifestations during propylthiouracil therapy.

Adult↗
PubMed1999

Adsorption of low molecular weight proteins to hemodialysis membranes: experimental results and simulations.

Adsorption of alpha-lactalbumin and Cytochrome C on different hollow-fiber hemodialysis modules, whose main membrane constituent was polyacrylonitrile (PAN), polymethylmethacrylate (PMMA) or polysulfone (PS), were compared under different pH and flow rate conditions. These proteins were chosen as models of small scarce proteins like beta2-microglobulin from which the patient's blood should be epurated. Influence of pH suggests the importance of electrostatic interactions on a charged membrane since adsorption greatly decreases at pH 10.9 for Cytochrome C (pI = 10.6) and at pH 7.4 for alpha-lactalbumin (pI = 5). The difference in adsorbance between different membranes is most probably due to their different microstructures. However, the chemical nature of the support plays a non-negligible role since PMMA membranes have smaller initial adsorption rates than PAN membranes. This is correlated with the density of membrane surface charge showing the importance of electrostatic interactions. The influence of the wall shear rate on adsorption kinetics is analyzed through numerical simulations, in terms of transport limitation in the liquid phase and interfacial reaction.

Acrylic Resins↗
PubMed1999

[Cranial pachymeningitis].

INTRODUCTION: Pachymeningitis is a fibrous inflammatory process with non-specific symptoms, involving the dura mater. Due to MRI development, diagnosis is both easier and earlier. CURRENT KNOWLEDGE AND KEY POINTS: We report seven cases and review current literature. Clinical features are headaches and cranial nerve palsies. CSF shows inflammatory changes, while MRI evidences thickening of the dura mater. Disease etiologies in the present study were tuberculosis in two cases, sarcoidosis, Lyme disease, lymphoma and dural puncture; in one case only the disease was of unknown origin. The condition of six patients improved with specific treatment. FUTURE PROSPECTS AND PROJECTS: Further MRI development should allow detection of new forms of pachymeningitis and standardization of patients' management through the study of more important series.

Adult↗
PubMed1999

Use of a state data bank to measure incidence and prevalence of a chronic disease: end-stage renal failure.

The Western Australian Health Services Research Linked Database was used to examine trends in the incidence rate and prevalence of end-stage renal failure and to describe treatment patterns in these patients. Linked hospital morbidity and mortality records from 1980 to 1994 were selected if a record had a principal diagnosis or procedure of chronic renal failure, dialysis, or renal transplantation. Patient records were grouped according to the stage of care (predialysis, dialysis, transplant, or death). A total of 1, 046 patients with a principal diagnosis or procedure that met our criteria for end-stage renal failure was admitted to the hospital from 1985 to 1994. Trends in the incidence rate and prevalence of end-stage renal failure by sex and race, patterns of care, indices of comorbidity, and waiting time to transplantation were calculated. Results showed that both the incidence rate and prevalence of end-stage renal failure increased from 1986 to 1994, most noticeably in the aboriginal population. Rates of renal failure in 1994 were 15 times greater in aborigines than in nonaborigines. Of the hospital patients, 73.5% received dialysis three times a week. Complications associated with dialysis treatment were the most common cause of comorbid hospitalization. The mean waiting time to transplantation was 503 days for those who had a transplant and 6.3 years for all patients. The escalating numbers of patients undergoing renal dialysis, the high cost of maintaining them on dialysis, and the additional use of hospital services for comorbid conditions highlight the need to develop programs to prevent the occurrence of renal failure, particularly in the aboriginal population.

Adult↗
PubMed1999

The prevalence of Chlamydia pneumoniae in atherosclerotic and nonatherosclerotic blood vessels of patients attending for redo and first time coronary artery bypass graft surgery.

OBJECTIVES: To determine if Chlamydia pneumoniae (C. pneumoniae) is more prevalent in atherosclerotic compared with normal blood vessels of patients requiring redo and first time coronary artery bypass graft surgery (CABG). BACKGROUND: Serological and pathological studies have associated atherosclerosis with C. pneumoniae infection. As atherosclerosis is one of the causes of graft failure following CABG, then it may be expected that the prevalence of the organism in failed grafts and diseased native vessels should be greater than in the new grafts. METHODS: Endarterectomy specimens and failed and new grafts were collected from 49 patients with late graft failure. Endarterectomy specimens and new grafts were also collected from nine patients having first time CABG. The presence of C. pneumoniae DNA was then checked for using a nested polymerase chain reaction. RESULTS: The prevalence of C. pneumoniae DNA in failed venous grafts (38.2%) was similar to that in endarterectomy specimens from native coronary arteries (38.5%) and greater than that in new saphenous vein grafts (11.8%). However, it was similar to that in new internal mammary artery grafts (30.0%). Also, the interval between surgery in redo patients was the same regardless of whether C. pneumoniae was present or not. CONCLUSIONS: Cross sectional studies cannot determine whether C. pneumoniae is a cause of atherosclerosis since they do not show whether infection precedes or follows its development. However, our results suggest that the organism is not an important factor in graft failure or atherosclerosis.

Aged↗
PubMed1999

Acute fatigue in chronic fatigue syndrome patients.

BACKGROUND: Chronic fatigue syndrome (CFS) patients often complain that they are more susceptible to acute mental fatigue. It is important to determine whether this is observed using objective tests of sustained attention and responding. METHODS: Sixty-seven patients who fulfilled the criteria for CFS proposed by Sharpe et al. (1991) were compared with 126 matched healthy controls. Acute fatigue was assessed by comparing performance at the start and end of a lengthy test session and by examining changes over the course of individual tasks. RESULTS: CFS patients showed impaired performance compared to the controls and these differences increased as the volunteers developed acute fatigue. In addition, differences between the two groups were larger at the end of the test session. CONCLUSIONS: The present results show that CFS patients are more susceptible to acute fatigue than healthy controls. This could reflect motor fatigue or an inability to compensate for fatigue with increased effort. This profile is consistent with previous research on fatigue and suggests that interpretation of certain aspects of CFS may be helped by considering it as the end point of a continuum of fatigue rather than a distinct disease.

Acute Disease↗
PubMed1999

Identification of HLA-A*0224: implications for PCR-SSP HLA typing.

We describe a novel HLA-A*02 allele, A*0224, that was identified after a comparison of DNA and serological typing revealed a discrepancy in the HLA-A types: HLA-A2 was defined by serology but was not detected by the polymerase chain reaction using sequence-specific primers (PCR-SSP). DNA sequencing indicated the presence of a variant HLA-A*02 allele that differed from A*0201 by a single base (C/A) at position 453. This base substitution corresponded to the annealing site of a primer common to the two A*02-amplifying PCR-SSP mixtures used in the method. This provides an explanation for the results and highlights a limitation of PCR-SSP methods even where two PCR mixtures are used to detect alleles. Serological titration studies suggested that A*0201, A*0205 and A*0224 are unlikely to be differentiated during routine serological typing.

Base Sequence↗
PubMed1999

HLA-B*4703: sequence confirmation, serology and distribution.

This study has confirmed the nucleotide sequence of exons 2 and 3 of the B*4703 allele, discovered by an unusual HLA-B47 and Bw6 serological pattern, in two subjects of Black/Japanese and Caribbean Black descent. Titration studies on 25 HLA-B47 cross-reactive sera, stimulated by B13, B27, B44 and B60, and nine Bw6 antisera/monoclonal antibodies, showed that the B*4703 product can be distinguished from the established HLA-B47 specificity. The phenotypes of these donors and an International Cell Exchange donor suggests an association between B*4703 and Cw*0701/ 06 in Black subjects. No examples of B*4703 (or B*4702) were found in 10,194 PCR-SSP HLA-A,B typed Welsh Bone Marrow Donor Registry panel members indicating a phenotype frequency of <0.0098% in this primarily Northern European Caucasoid population.

Alleles↗
PubMed1999

Dietary and lifestyle factors affecting plasma vitamin D levels in Asian children living in England.

OBJECTIVE: To determine the vitamin D status of a sample of young Asian children living in England by measurement of plasma 25-hydroxycholecalciferol levels; to relate biochemical measurements with parameters of diet, lifestyle and iron status in this population. DESIGN: The 'Infant Feeding in Asian Families' survey covered infants born to mothers of Bangladeshi, Indian or Pakistani origin, plus a sample of children born to White mothers in 41 local authority areas. The current study describes vitamin D values in a sub sample of Asian children from that survey. SETTING: Forty-one local authority areas which covered 95% of the Asian population at the time of the 1991 Census and include areas with the highest and lowest density of Asians. SUBJECTS: Seventy-one percent (2382) of mothers who were originally eligible were interviewed on four occasions up to the time their infant was 15 months. One thousand, seven hundred and thirty-eight of these children were followed up for this current study. Of these 618 had a blood sample analysed for vitamin D. OUTCOME MEASURES: Previous day's food intake, normal dietary intake, indicators of iron status and plasma vitamin D levels. RESULTS: Plasma vitamin D values are lower in the three groups of Asian children than values reported for children of a similar age in the National Diet and Nutrition Survey. Between one third and a half of children with a low haemoglobin also had low plasma vitamin D values; there was a significant association between failure to take a vitamin supplement, chapati consumption and low vitamin D values. CONCLUSIONS: It is particularly important that pre-school Asian children receive a vitamin D supplement. Children with low haemoglobin values should be screened for vitamin D deficiency.

Asia, Western↗
PubMed1999

Lack of interaction between thioctic acid, glibenclamide and acarbose.

AIMS: Thioctic acid (TA), glibenclamide and acarbose are widely used to either alone or concomitantly treat patients suffering from noninsulin-dependent diabetes (NIDDM). This study systematically investigated drug-drug interactions between TA and glibenclamide and TA and acarbose. METHODS: Fourteen male and 10 female healthy volunteers participated a randomized, open three period cross over trial (treatments A-C) followed by a fourth period (treatment D). A baseline profile for plasma insulin and glucose concentrations, variables which served as pharmacodynamic measures, was assessed before entering the trial. Treatments were A=600 mg TA orally, B=3.5 mg glibenclamide orally, C=600 mg TA+3.5 mg glibenclamide, D=600 mg TA+50 mg acarbose. Time courses of R(+)-TA and S(-)-TA as well as glibenclamide concentrations were measured with specific analytical methods. RESULTS: There was no clinically relevant change of TA enantiomer pharmacokinetics by glibenclamide or acarbose. Also, glibenclamide pharmacokinetics were not altered by TA to a clinically meaningful extent. Plasma insulin and glucose concentrations did not indicate an interaction between TA and glibenclamide or TA and acarbose. Glibenclamide had the expected effect on insulin and glucose levels independent of comedication. There were only minor and short lasting adverse events with the majority being (expected) hypoglycaemic symptoms occurring during the treatments with glibenclamide. CONCLUSIONS: Coadministration of single doses of TA and glibenclamide or TA and acarbose does not appear to cause drug-drug interactions.

Acarbose↗
PubMed1999

Arabidopsis thaliana proteins related to the yeast SIP and SNF4 interact with AKINalpha1, an SNF1-like protein kinase.

AKINalpha1, a Ser/Thr kinase from Arabidopsis thaliana belongs to the highly conserved SNF1 family of protein kinases in eukaryotes. Recent data suggest that the plant SNF1-related kinases (SnRK1 family) are key enzymes implicated in the regulation of carbohydrate and lipid metabolism. In Saccharomyces cerevisiae and mammals, the SNF1 and AMPKalpha protein kinases interact with two other families of proteins, namely SNF4/AMPKgamma and SIP1/SIP2/GAL83/AMPKbeta, to form active heterotrimeric complexes. In this paper, we describe the characterisation of three novel cDNAs. AKINbeta1 and AKINbeta2 encode proteins similar to SIP1, SIP2 and GAL83 and AKINgamma codes for a protein showing similarity with SNF4. Using the two-hybrid system, specific interactions have been shown between A. thaliana AKINbeta1/beta2, AKINgamma and AKINgamma as well as between the A. thaliana and S. cerevisiae subunits. Interestingly, AKINbeta1, AKINbeta2 and AKINgamma mRNAs accumulate differentially in A. thaliana tissues and are modulated during development and under different growth conditions. These data suggest the presence in higher plants of a conserved heterotrimeric complex. Moreover, the differential transcription of different non-catalytic subunits can constitute a first level of regulation of the SNF1-like complex in plants.

Amino Acid Sequence↗