Search PubMed⌕ Search

Biomedical subjects

D Thomas

Publications and source records attributed to D Thomas.

At least 487 records · Page 27Linked to original sources
PubMed1993

Grading of soft tissue sarcomas: experience of the EORTC Soft Tissue and Bone Sarcoma Group.

A practical grading system for soft tissue sarcomas was developed, based on 282 eligible patients entered in an EORTC adjuvant clinical trial. The primary tumours in this trial had to be adequately treated. Histopathological parameters, which appeared significant in two preceding studies, were tested. These parameters were differentiation of the tumour, presence and amount of necrosis, the presence and amount of myxoid areas and the number of mitoses. In addition, the size of the tumour was also analysed. The quantitative data (mitotic count and size of the tumour) were not a priori grouped, but were divided into categories based on the results of the statistical analysis. Based on a multivariate analysis only mitotic count, the presence or absence of necrosis and the size of the tumour were significantly correlated with the duration of survival or the time to distant metastases. Of these parameters, the mitotic count was the most important.

Adolescent↗
PubMed1993

Long-term adjuvant immunotherapy in stage I high risk malignant melanoma, comparing two BCG preparations versus non-treatment in a randomised multicentre study (EORTC Protocol 18781).

The present study reports the results of a multicentre adjuvant trial with BCG (Bacillus Calmette-Guérin) in high risk patients (Breslow thickness > or = 1.5 mm, Clark level > or = III) with malignant melanoma, after surgical removal of their primary tumour. The trial was specifically designed in order to resolve the controversy and to provide some definite answers regarding the value of adjuvant BCG treatment in stage I malignant melanoma. Patients were randomised to either BCG RIV (108 patients) or BCG Pasteur (109 patients) for 3 years or to follow-up only (110 patients). The two vaccines used had greatly divergent properties regarding their mode of preparation, their composition and their immunomodulating activities. Of the 353 randomised patients, 23 were ineligible, 3 refused participation after randomisation and 327 were evaluable for final analysis. Median follow-up time was 6 years (range 0-10 years). The log-rank test comparison showed no statistical difference between the three arms regarding time to progression (P = 0.55) and duration of survival (P = 0.82). Treatment was generally well tolerated, with no major adverse events in either treatment arm. These findings confirm data with different BCG preparations and with stage II melanoma which also demonstrated no benefit regarding patient survival and time to relapse.

Adolescent↗
PubMed1993

Nucleation and growth phases in the polymerization of coat and scaffolding subunits into icosahedral procapsid shells.

The polymerization of protein subunits into precursor shells empty of DNA is a critical process in the assembly of double-stranded DNA viruses. For the well-characterized icosahedral procapsid of phage P22, coat and scaffolding protein subunits do not assemble separately but, upon mixing, copolymerize into double-shelled procapsids in vitro. The polymerization reaction displays the characteristics of a nucleation limited reaction: a paucity of intermediate assembly states, a critical concentration, and kinetics displaying a lag phase. Partially formed shell intermediates were directly visualized during the growth phase by electron microscopy of the reaction mixture. The morphology of these intermediates suggests that assembly is a highly directed process. The initial rate of this reaction depends on the fifth power of the coat subunit concentration and the second or third power of the scaffolding concentration, suggesting that pentamer of coat protein and dimers or trimers of scaffolding protein, respectively, participate in the rate-limiting step.

Bacteriophage P22↗
PubMed1993

Chemotherapy administration and data collection in an EORTC collaborative group--can we trust the results?

As part of a phase II study of the EORTC Soft Tissue and Bone Sarcoma Group, 15 centres took part in a programme to evaluate the quality of treatment delivered and data collected. The centres were visited and facilities for treatment and data management were reviewed. Source data in randomly selected patient hospital records were compared with information which had previously been completed on case record forms and returned to the EORTC Data Centre. The review included 71% of the patients entered into the study and 76% of the treatment cycles. Chemotherapy was prepared by nurses or clinicians in 58% and by pharmacists in 42% of the centres and was administered by specialist nurses in 67% of the hospitals. 8776 items were checked with source data. 3.4% were incorrect, 0.2% were missing and 30% could not be verified as correct (mainly related to the lack of recording of toxicity data in hospital records). The mean doses of chemotherapy delivered and treatment intervals were those stipulated in the protocol but 21% of the cycles were delayed for avoidable reasons. Several modifications to the procedures for running chemotherapy trials were suggested by this survey including the use of a systematic checklist for recording toxicity and chemotherapy administration and the development of quality assurance programmes in other collaborative groups and single centres to ensure that published results are credible.

Adult↗
PubMed1993

Aneurysm of the interventricular membranous septum with thrombo-embolism--an indication for surgical repair?

A 40-year-old woman with a significant neurological history presented with right hemiparesia, paraesthesia of the right upper member and of the hemiface. Computer tomography scanning revealed hypodensity along the right lateral ventricle which corresponded to the left hemiplegia which had developed when she was 20 years old. Arteriography of the four cervical axes was normal. Echocardiography visualized an aneurysm of the membraneous septum free of thrombosis without ventricular septal defect. The embolism was thought to be of cardiac origin and a decision was taken to correct it by surgery. Ten years after surgical repair no other neurological event has occurred.

Adult↗
PubMed1993

Predicting recovery of motor complete quadriplegic patients. 24 hour v 72 hour motor index scores.

This paper reports motor index scores on motor complete (Frankel A, B), C4-T1, quadriplegic patients at admission, 72 h to 1 week and 6 months after spinal cord injury. This study is designed to test the hypothesis that the 72-h to 1-week motor index score (referred to as 72-h motor score) is superior to motor scores recorded within the first 24 h in predicting 6 month motor scores. Twenty-seven quadriplegic subjects, ages 15-70 years, were followed prospectively using manual muscle test to document motor recovery. Biceps, wrist extensors, triceps, flexor digitorum profoundus and first dorsal interossei were tested within 24 h, 72 h-1 week and 6 months after injury to comprise the motor index score. Average total motor scores for both upper extremities at admission were 14.0, at 72 h 13.9, and at 6 months 19.3 (ANOVA, P < 0.01). Total bilateral motor scores changed by 5.3 from admission to 6 months and by 5.4 from 72 h to 6 months. No significant difference existed between the admission and post 72-h motor score in predicting the 6-month motor score (Newmann-Keuls P > 0.05). Thus, despite significant change in motor score after spinal cord injury, both admission and 72-h motor scores equally predicted 6 month motor recovery of C4-T1 motor complete quadriplegic patients.

Adolescent↗
PubMed1993

Neutrophils, differentiated macrophages, and monocyte/macrophage antigen presenting cells infiltrate murine epidermis after UV injury.

We asked whether, as in humans, a population of antigen-presenting macrophages infiltrates the epidermis of ultraviolet (UV)-exposed BALB/c mice. Using three-color flow cytometry on cell suspensions plus in situ immunofluorescence microscopy, the phenotype of normal Langerhans cells was class II major histocompatibility complex (MHC+), CD11b+, NLDC-145+, BM8+ CD45+ and homogeneous. By contrast, in epidermal cells harvested 3 d following UV (UV-EC), there were two subsets of class II MHC+ cells: 1) class II MHChi CD11b+, and 2) class II MHClo CD11b-. Neither expressed the Langerhans cell markers BM8 and NLDC-145. In addition, there were two major populations of class II MHC- CD11b+ cells; half of these expressed the GR-1 neutrophil marker. Langerhans and dendritic epidermal T cells were markedly reduced after UV injury. By electron microscopy, immunomagnetic bead-purified CD11b+ cells in UV-EC were comprised of neutrophils, differentiated macrophages, and mononuclear cells with prominent lysosomes, but no Birbeck granules; the class II MHC+ subset resembled a monocytic cell in between differentiated macrophages and indeterminate dendritic cells. Functionally, immediately following in vivo UV exposure, the allogeneic antigen-presenting cell capacity of UV-EC was reduced to 21 +/- 6% of control epidermal cells (C-EC); by 3 d, antigen-presenting cell activity of UV-EC had recovered to 59 +/- 11% of C-EC, although at this time NLDC-145+ Langerhans cells had reached their lowest number. The recovered antigen-presenting cell activity was critically dependent upon the class II MHChiCD11b+ cells. Sensitization of BALB/c mice through skin that contained these antigen-presenting cells (3 d after UV) resulted in tolerance to dinitrofluorobenzene. By contrast, sensitization through UV-exposed skin immediately after the exposure resulted in unresponsiveness without tolerance, demonstrating temporal association of tolerance with leukocytic infiltration. In summary, murine epidermis responds to an acute UV injury in vivo with an initial abrogation of antigen-presenting activity followed by epidermal infiltration with neutrophils, differentiated macrophages, and monocytic antigen-presenting cells that are distinct from Langerhans cells with regard to expression of Langerhans cell markers and ultrastructure.

Animals↗
PubMed1993

Preservation of renal haemodynamic response to an oral protein load in non-insulin-dependent diabetes mellitus.

Glomerular Filtration Rate (GFR) and Effective Renal Plasma Flow (ERPF) were determined, for 2 h prior to and 3 h following the ingestion of a 1.2 g kg-1 meat meal, in seven normotensive normoalbuminuric Type 2 diabetic patients exhibiting good glycaemic control (fasting plasma glucose (mean +/- SD): 7.2 +/- 2.0 mmol l-1; glycosylated haemoglobin: 8.1 +/- 1.7%) and in nine normal subjects selected for similar basal GFR values. Baseline GFR and ERPF (corrected to 1.73 m2 surface area) were 83 +/- 10 and 410 +/- 76 ml min-1 for the Type 2 diabetic patients and 86 +/- 11 and 405 +/- 113 ml min-1 for the normals. GFR increased by 38 +/- 8 and 32 +/- 15% in the diabetic patients and normals, to 108 +/- 25 and 105 +/- 26 ml min-1 (p < 0.01 vs baseline). Peak ERPF was 501 +/- 127 and 476 +/- 119 ml min-1 for the two respective groups (p < 0.01 vs baseline). Filtration fractions at peak GFR and EPRF values were unchanged from baseline for either groups. Fractional clearance of albumin for the Type 2 diabetic patients was unaltered by protein ingestion. Therefore, protein ingestion in Type 2 diabetes, as in normals, results in an acute elevation of GFR. Absolute and incremental changes in GFR were identical for the two groups. These data demonstrate a preserved capacity for renal vasodilatation in Type 2 diabetic patients despite their greater chronological age.

Adult↗
PubMed1993

Effects of ultrasound energy on total peripheral artery occlusions: initial angiographic and angioscopic results.

Ultrasonic energy has been shown to ablate atherosclerotic plaques and arterial and venous thrombi. We used an ultrasonic angioplasty device developed by our group in ten patients with totally occluded femoral artery during surgical bypass. Ultrasonic angioplasty was performed with a 130-cm long and 0.8-cm diameter titanium probe with a 2- or 2.5-mm titanium ball-tip. In one patient, angioplasty could not be performed. Angiographic and angioscopic examination were performed before and after angioplasty in nine patients. Before ultrasound recanalization, angioscopic examination showed that the proximal end of the occlusion was formed by atheromatous material in 3 cases, red thrombus in 3 cases, amd white thrombus in 3 cases. After ultrasound recanalization, angioscopy showed residual stenosis at the site of entry in only one case. In three other cases, the artery was free of residual stenosis without persistent clot. In the five other patients, a residual stenosis was present beyond the proximal occlusion point with some fibrin mesh and small clots. At angiography, flow was restored in 4 cases; in 4 patients flow rate of entry was slow in the distal segment; and in 1 patient, the distal arterial bed could not be opacified. Altogether, ultrasonic angioplasty was able to recanalize a complete occlusion in nine out of ten patients, with partial or complete dissolution of clots and with no complication. At its present stage of development, adjunctive balloon angioplasty would be needed in most cases to obtain unrestricted flow and unsignificant residual stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Purification and characterization of protein H, the major porin of Pasteurella multocida.

Protein H (B. Lugtenberg, R. van Boxtel, D. Evenberg, M. de Jong, P. Storm, and J. Frik, Infect. Immun. 52:175-182, 1986) is the major polypeptide of the outer membrane of Pasteurella multocida, a bacterium pathogenic for humans and animals. We have purified this protein to homogeneity by size exclusion chromatography after selective extraction with surfactants and demonstrated its pore-forming ability after reincorporation into planar lipid bilayers. In these experiments, the current through the pores was a linear function of the applied voltage in the range of -50 to +50 mV. Voltages beyond +/- 50 mV tended to partially close the channels, giving rise to apparent negative resistances. These observations suggest that protein H channels are probably not voltage regulated in vivo. With the patch clamp technique, single-channel conductance fluctuations of 0.33 nS were recorded in 1 M KCl. Electrophoretic and circular dichroism analyses showed that protein H forms homotrimers stable in sodium dodecyl sulfate at room temperature, with a high content of beta-sheet secondary structure. Upon boiling, the trimers were fully dissociated into monomers with an increase of alpha helix and irregular structure, at the expense of beta sheets. The apparent molecular mass of fully denatured monomers ranged between 37 and 41.8 kDa, depending on the electrophoretic system used for analysis. The trimeric arrangement of protein H was confirmed by image analysis of negatively stained, two-dimensional crystal arrays. This morphological study revealed, in agreement with electrophoretical data, a trimeric structure with an overall diameter of 7.7 nm. Each monomer appeared to contain a pore with an average diameter of 1 nm. Quantitative comparisons revealed that the amino acid composition (hydropathy index of -0.40) and the N-terminal sequence (determined over 36 residues) of protein H are similar to those of bacterial general porins, notably porin P2 of Haemophilus influenzae. We conclude from this set of structural and functional data that protein H of P. multocida is a pore-forming protein related to the superfamily of the nonspecific bacterial porins.

Amino Acid Sequence↗
PubMed1993

Cysteine biosynthesis in Saccharomyces cerevisiae occurs through the transsulfuration pathway which has been built up by enzyme recruitment.

The transsulfuration pathways allow the interconversion of homocysteine and cysteine with the intermediary formation of cystathionine. The various organisms studied up to now incorporate reduced sulfur into a three- or a four-carbon chain and use differently the transsulfuration pathways to synthesize sulfur amino acids. In enteric bacteria, the synthesis of cysteine is the first step of organic sulfur metabolism and homocysteine is derived from cysteine. Fungi are capable of incorporating reduced sulfur into a four-carbon chain, and they possess two operating transsulfuration pathways. By contrast, synthesis of cysteine from homocysteine is the only existing transsulfuration pathway in mammals. In Saccharomyces cerevisiae, genetic, phenotypic, and enzymatic study of mutants has allowed us to demonstrate that homocysteine is the first sulfur amino acid to be synthesized and cysteine is derived only from homocysteine (H. Cherest and Y. Surdin-Kerjan, Genetics 130:51-58, 1992). We report here the cloning of genes STR4 and STR1, encoding cystathionine beta-synthase and cystathionine gamma-lyase, respectively. The only phenotypic consequence of the inactivation of STR1 or STR4 is cysteine auxotrophy. The sequencing of gene STR4 has allowed us to compare all of the known sequences of transsulfuration enzymes and enzymes catalyzing the incorporation of reduced sulfur in carbon chains. These comparisons reveal a partition into two families based on sequence motifs. This partition mainly correlates with similarities in the catalytic mechanisms of these enzymes.

Alleles↗
PubMed1993

Phosphatidylcholine hydrolysis activates NF-kappa B and increases human immunodeficiency virus replication in human monocytes and T lymphocytes.

We have tested whether breakdown of phosphatidylcholine (PC) initiated by exogenous addition of a PC-specific phospholipase C (PC-PLC) from Bacillus cereus or by endogenous overexpression of PC-PLC induces functional activation of NF-kappa B and increases human immunodeficiency virus (HIV) enhancer activity. PC-PLC-activated hydrolysis of PC was found to induce bona fide p50/p65 NF-kappa B binding activity in three different cell lines of human or murine origin. No significant changes in the turnover of other cellular phospholipids were detected in PC-PLC-treated cells. Induction of NF-kappa B by PC-PLC did not depend on de novo synthesis of proteins or autocrine secretion of either tumor necrosis factor or interleukin 1. In human monocytic and lymphoblastoid T-cell lines, induction of NF-kappa B by PC-PLC resulted in clear induction of luciferase expression vectors placed under the control of synthetic kappa B enhancers or wild type, but not kappa B-mutated, HIV long terminal repeat constructs. HIV replication was increased by PC-PLC in chronically infected monocytes and T lymphocytes. NF-kappa B activation promoted by addition of exogenous PC-PLC correlated with an intense production of diacylglycerol. However, addition of a phosphatidylinositol-specific PLC from B. cereus also induced diacylglycerol but did not activate kappa B enhancer-directed vectors. PC-PLC-induced NF-kappa B activation could not be blocked by a specific inhibitor of phorbol ester-inducible protein kinases C. These results indicate that a cellular transduction pathway, dependent on specific PC breakdown, is functional in T lymphocytes and monocytes and may be used by various transmembrane receptors to activate HIV transcription through NF-kappa B-dependent induction of the HIV enhancer.

Cell Line↗
PubMed1993

Organic osmolytes in acute hyponatremia.

The defense of brain volume during hyponatremia cannot be explained by the losses of brain sodium and potassium. We have examined the brain losses of organic osmolytes in rats after 24 h of severe hyponatremia induced by the administration of vasopressin and 5% dextrose in water. Normonatremic controls and animals with intermediate plasma sodium concentration ([Na]) were produced in vasopressin-treated animals by the administration of isocaloric gavages containing varying amounts of NaCl and free water. The animals were killed at 24 h by decapitation, and one brain hemisphere was quickly frozen in liquid nitrogen for organic osmolyte determinations. When compared with controls (plasma [Na] = 139 +/- 1.5 mM), hyponatremic animals (plasma [Na] = 96 +/- 1 mM) had significantly reduced brain contents for sodium, potassium, chloride, glutamate, myo-inositol, N-acetylaspartate, aspartate, creatine, taurine, gamma-aminobutyric acid, and phosphoethanolamine. Plasma [Na] was highly correlated (P < 0.001) with the brain contents for sodium, potassium, and organic osmolytes. Whereas the observed increase in brain water during hyponatremia was only 4.8%, by calculation, brain swelling without brain organic osmolyte losses would have been 11%, an amount that jeopardizes survival.

Acute Disease↗
PubMed1993

Principles of study design in environmental epidemiology.

This paper discusses the principles of study design and related methodologic issues in environmental epidemiology. Emphasis is given to studies aimed at evaluating causal hypotheses regarding exposures to suspected health hazards. Following background sections on the quantitative objectives and methods of population-based research, we present the major types of observational designs used in environmental epidemiology: first, the three basic designs involving the individual as the unit of analysis (i.e., cohort, cross-sectional, and case-control studies) and a brief discussion of genetic studies for assessing gene-environment interactions; second, various ecologic designs involving the group or region as the unit of analysis. Ecologic designs are given special emphasis in this paper because of our lack of resources or inability to accurately measure environmental exposures in large numbers of individuals. The paper concludes with a section highlighting current design issues in environmental epidemiology and several recommendations for future work.

Bias↗
PubMed1993

Methodologic research needs in environmental epidemiology: data analysis.

A brief review is given of data analysis methods for the identification and quantification of associations between environmental exposures and health events of interest. Data analysis methods are outlined for each of the study designs mentioned, with an emphasis on topics in need of further research. Particularly noted are the need for improved methods for accommodating exposure assessment measurement errors in analytic epidemiologic studies and for improved methods for the conduct and analysis of aggregate data (ecologic) studies.

Data Interpretation, Statistical↗