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Biomedical subjects

G Thomas

Publications and source records attributed to G Thomas.

At least 433 records · Page 24Linked to original sources
PubMed1994

Asbestos fibers and interferon-gamma up-regulate nitric oxide production in rat alveolar macrophages.

The present study was undertaken to determine whether asbestos exposure induces the formation of nitric oxide (NO.) radical by rat alveolar macrophages (AM). For this purpose, AM from Sprague-Dawley rats were cultured for 48 h in the presence or absence of either chrysotile (serpentine) or crocidolite (amphibole) asbestos fibers. The effects of asbestos fibers were compared with those of nonfibrogenic carbonyl iron particles. Nitrite (NO2-), the stable oxidation product of NO. in macrophage conditioned medium, was assayed by the Griess reaction. Production of NO2- by AM was significantly increased by both chrysotile (P < 0.01) and crocidolite (P < 0.05) asbestos fibers (10 micrograms/ml). Since interferon-gamma (IFN-gamma) is known to induce NO. synthase within macrophages, and since elevated levels of intrapulmonary IFN-gamma have been noted in asbestos workers, the combined effects of asbestos and IFN-gamma also were studied in the context of NO. formation. Addition of IFN-gamma (250 to 500 IU/ml) synergistically enhanced the formation of NO2- induced by chrysotile and crocidolite. Notably, carbonyl iron had no significant effect on NO. production by AM. NO2- production was significantly attenuated by the NO. synthase inhibitor, NG-monomethyl-L-arginine (0.5 to 1 mg/ml). By contrast, superoxide dismutase (150 U/ml) significantly enhanced asbestos-induced NO2- production by AM (P < 0.001). Since superoxide anion can interact with NO. to generate the toxic hydroxyl radical, and since superoxide dismutase is known to protect against asbestos-induced injury, the induction of NO. radical by asbestos fibers may represent a novel form of asbestos-related injury.

Amino Acid Oxidoreductases↗
PubMed1994

Function of the Dräger Oxylog ventilator at high altitude.

We have assessed the performance of the Dräger Oxylog ventilator at high altitude using a decompression chamber and a lung simulator set to mimic the normal and non-compliant lung. In the normal lung, tidal volume increased by 28% at 2040 metres and by 106% at 9120 metres. A lesser change, but in the opposite direction, occurred in respiratory rate. The net effect was a linear increase in minute volume with altitude. At 2040 and 9144 metres minute volume increased by 13% and by 45%, and rate decreased by 10% and 30% respectively. In the abnormal lung stimulation, similar, but slightly less marked, changes occurred in all variables. These changes are of sufficient magnitude to require frequent observation of tidal volume and respiratory rate during aircraft ascent and descent.

Adult↗
PubMed1994

Serum dehydroepiandrosterone sulfate levels as an individual marker.

To assess the significance of the serum dehydroepiandrosterone sulfate (DHEAS) concentration as a parameter of the individual hormonal milieu, two different groups of subjects were studied: DHEAS levels were determined 3 times at 6-month intervals in 47 elderly hospitalized women, aged 71-94 yr (group 1), and 6 times over 2 consecutive weeks in 10 healthy male volunteers, aged 24-30 yr (group 2). For reference, serum cortisol (F) levels were determined concomitantly. In each group and on each sampling occasion, the subjects were ranked according to their DHEAS or F values. The stability over time of the ranking was much higher for DHEAS than for F; estimated concordance coefficients were 92% (group 1) and 88% (group 2) for DHEAS vs. 51% (group 1) and 49% (group 2) for F. We conclude that due to a comparatively low within- to between-subject variability ratio, DHEAS is a highly specific individual marker.

Adult↗
PubMed1994

Non-biting Muscidae and control methods.

Many non-biting muscids (filth flies) are characterised by the habit of visiting manure or rotting organic material to feed and/or oviposit. As these flies also often have close associations with human beings, as well as human habitations and domestic animals, they are potentially both a nuisance and a contributory factor in the transmission of diseases. The authors examine the biology, economic importance and control of four of the most important non-biting muscids: housefly, Musca domestica; face fly, Musca autumnalis; Australian bush fly, Musca vetustissima; sheep head fly, Hydrotaea irritans.

Animals↗
PubMed1994

S6 phosphorylation and the p70s6k/p85s6k.

Activation of cell growth leads to the multiple phosphorylation of 40S ribosomal protein S6. The kinase responsible for controling this event is termed p70s6k/p85s6k. Both isoforms of the kinase are derived from a common gene activated by a complex set of phosphorylation events; each resides in a unique cellular compartment: the p70s6k in the cytoplasm and the p85s6k in the nucleus. Although p70s6k/p85s6k represent the first mitogen-activated serine/threonine kinase described, the signaling pathway leading to activation of both isoforms remains obscure. Recent studies have shown that this pathway is distinct from that of p21ras and the p42mapk/p44mapk, and that bifurcation of these pathways takes place at the level of the receptor. Experiments with point mutants of the PDGF receptor and inhibitors of phosphatidyl-inositol-3-OH kinase have implicated the latter molecule in this signaling event, but more recent findings suggest an alternative route may be employed. The p70s6k signaling pathway can also be ablated by the immunosuppressant rapamycin, which blocks p70s6k activation and S6 phosphorylation without affecting the other kinases whose activation is triggered by mitogen treatment. In parallel, rapamycin suppresses the translation of a family of mRNAs that contain a polypyrimidine tract at their 5' transcriptional start site. The implication is that this event is mediated by the phosphorylated form of S6 that may either (1) directly interact with the polypyrimidine tract or (2) alter the affinity of the 40S ribosome mRNA binding site for polypyrimidine tract mRNAs, or (3) recognize proteins that directly bind to the polypyrimidine tract.

Animals↗
PubMed1994

p70s6k/p85s6k: mechanism of activation and role in mitogenesis.

The p70s6k/p85s6k represent two isoforms of the same kinase which are derived by differential splicing from a common gene. The p85s6k isoform is identical to p70s6k except for a 23 amino acid extension at its N-terminus, which constitutively targets it to the nucleus. Both isoforms are activated by multisite phosphorylation in response to mitogens and reside on the same signaling pathway, a pathway which is distinct from that of p42mapk/p44mapk pathway. Inhibitory p70s6k/p85s6k antibodies or the immunosuppressant rapamycin selectively inhibit kinase activity and repress or abolish cell growth depending on the inhibitory agent employed and the cell type examined. Recent studies imply that these effects are exerted through inhibition of 40S ribosomal protein S6 phosphorylation, the kinase target, which in turn suppresses the translation of a family of transcripts essential for cell growth.

Amino Acid Sequence↗
PubMed1994

[Genetic anomalies of colorectal cancers].

The prognosis of colorectal cancer has been based essentially on pathological data for many years. The analysis of genetic anomalies has led to fundamental progress and clinical advances. Genetic anomalies are routinely studied. 1--Flowcytometry evaluates the quantity of DNA in the nucleus during the cell cycle. 2--Cytogentics is the study of karyotype anomalies by loss or gain of chromosome material and structural changes. 3--Molecular biology gives a means of recognizing chromosome losses and especially to study oncogenic or antioncogenic mutations. These analyses allow: 1--an evaluation of their value as a prognosis factor and thus their use for indicating adjuvant medical and/or surgical treatments. 2--an understanding of cancerogenic processes. 3--the development of future therapeutic techniques based on a better understanding of the mechanisms involved. 4--familial counselling in high risk families and an examination of responsible or favouring genes in certain familial cancers. Research into familial forms has recently led led to the demonstration of genetic alterations located on chromosomes 1 and 2. These anomalies called RER correspond to alterations found on tumors. Studying these alterations will allow better prediction of high risk subjects in cancer families without polyposis.

Colorectal Neoplasms↗
PubMed1994

5-Fluorouracil related toxic myocarditis: case reports and pathological confirmation.

This report describes two cases of cardiotoxicity associated with the use of 5-fluorouracil (5-FU) in the treatment of neoplastic disease, and reviews the literature to date. The manifestations of cardiac toxicity were significant ventricular dysfunction during continuous infusion of 5-FU, accompanied by symptoms resembling cardiac ischemia in one case and irreversible cardiogenic shock in another. Detailed cardiac investigations and pathological findings provide convincing evidence that the development of acute myocarditis is the likely mechanism of 5-FU cardiotoxicity, rather than coronary insufficiency as has commonly been postulated. Although cardiotoxicity as a complication of 5-FU therapy remains rare, recognition of this entity is important as it may lead to serious hemodynamic compromise and may recur with drug rechallenge.

Acute Disease↗
PubMed1994

Molecular cytogenetic analysis of a series of 23 DiGeorge syndrome patients by fluorescence in situ hybridization.

The authors have studied a series of 23 DiGeorge syndrome patients by prometaphase chromosome analysis and/or by FISH with a set of 6 cosmid probes spanning the previously described commonly deleted region. Four patients display a cytogenetically visible interstitial deletion in band 22q11.2, whereas the other 18 patients exhibit a molecular deletion evidenced only by FISH analysis. For 21 of the patients studied, the deletion encompasses the 6 loci tested, while for one, only the most telomeric of these loci is conserved. The last patient does not show any deletion with the probes used.

Adolescent↗
PubMed1994

[Contribution of genetic typing for the diagnosis of familial adenomatous polyposis in pediatrics].

BACKGROUND: The gene responsible for familial adenomatous polyposis, (APC), has been recently cloned and genetic map with several polymorphic markers has been established. POPULATION AND METHODS: Blood samples (20 ml) were taken from 34 subjects belonging to four families at risk for familial adenomatous polyposis. Nineteen of these 34, less than 20 years old, had one parent having polyposis or dead because of it. Polyposis was diagnosed, in ten of these 19 by endoscopy. Genomic DNA was extracted from peripheral leukocytes and Southern blot analyses were performed in each family, using RFLPs on both sides of the APC locus. RESULTS: DNA analysis identified normal and mutant haplotypes at the APC locus in each family. It was thus possible to follow the segregation of mutant alleles. These results were compared with the anamnestic and endoscopic data. Bearing in mind the risk of recombination when using extragenic markers, RFLPs allowed early diagnosis of APC in pre and/or asymptomatic patients. CONCLUSIONS: Genetic analysis can be used to diagnose APC in affected families, provided the risk of recombination is taken into account. Intragenic microsatellites markers will soon be available. These will provide more information on the APC gene, and hence direct molecular diagnosis of APC.

Adenomatous Polyposis Coli↗
PubMed1994

[Pathology of the human apolipoprotein E gene].

Apolipoprotein E (apo E) is a polymorphic glycoprotein that plays an essential part in the binding to receptors for the uptake of chylomicrons and VLDL remnants and of LDL. The three major isoforms are E3 (Cys112/Arg158), E4 (Arg112/Arg158) and E2 (Cys112/Cys158). The apo E genetic variation has a great impact. In most of type III familial hyperlipoproteinemias (HLP), E2 is implicated at the homozygote status. In other cases, rare alleles are directly responsible for dominant type III HLP. Apo E polymorphism is an essential determinant in the interindividual variations of lipids in healthy subjects in various populations. Its influence can be significant on the efficacy of nutritional or therapeutic interventions. The allele epsilon 4 appears to be associated with an increased risk of premature atherosclerosis. Recently, epsilon 4 was demonstrated to be associated with an early Alzheimer's disease onset. Apo E polymorphism contributes to the lipid disorders in diabetes and obesity. The analysis of apo E polymorphism can be carried out with two conceptually different approaches. The first one is based on the separation of plasma isoforms of the protein by isoelectric focusing or bidimensional electrophoresis. The other one consists in the application of molecular biology techniques (PCR and endonuclease restriction profiles) for a detection of the common alleles and of several rare alleles, avoiding the possible errors of the phenotyping technique of the apo E protein. The application of genetic engineering allows a better understanding of the role played by apo E towards its receptors and in other molecular interactions which are not well known up to now.

Amino Acid Sequence↗
PubMed1994

Relative efficiency of denaturing gradient gel electrophoresis and single strand conformation polymorphism in the detection of mutations in exons 5 to 8 of the p53 gene.

p53 is the most commonly mutated gene in a large variety of human tumors including familial cancers. Because p53 mutations have in a number of human cancer types, been related to a negative outcome of the disease and the importance of pre-symptomatic diagnosis in cancer-prone families, screening for p53 mutations is becoming more and more widely used. In order to avoid sequencing of the complete coding sequence, several pre-screening methods have been developed and applied to the p53 gene. Among them, Single Strand Conformation Polymorphism (SSCP) and Denaturing Gradient Gel Electrophoresis (DGGE) appear to be highly sensitive. In this work, we used 52 different p53 variants to compare the two methods. In our conditions, DGGE is more sensitive than SSCP since 100% of the variants were detected. SSCP detected 90% of the variants, but efficiency of the method can still be improved by additional optimization experiments.

Base Sequence↗
PubMed1994

Common and rare genotypes of human apolipoprotein E determined by specific restriction profiles of polymerase chain reaction-amplified DNA.

The three common isoforms of human apolipoprotein E (apo E) differ at positions 112 and 158 and are named E3, E4, and E2 according to phenotyping by isoelectric focusing (IEF). The polymerase chain reaction (PCR) method allows the detection of common and several rare allelic apo E variants not detected by IEF. We propose a genotyping procedure for apo E that characterizes a given allele on the basis of amplification of specific sequences of the gene followed by the action of restriction endonucleases. When the nucleotide change does not lead to a restriction site, PCR-directed mutagenesis creates the discriminant site, and the differentiation of the three common alleles and five rare variants is possible. We present here profiles of common alleles and of three rare alleles, Weisgraber [Cys112/Asp127/Cys158], Christchurch [Cys112/Ser136/Arg158], and a new rare variant [Cys112/Leu142/Cys158].

Alleles↗