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Biomedical subjects

A Martin

Publications and source records attributed to A Martin.

At least 433 records · Page 24Linked to original sources

Effect of alcohol on the activity and subcellular distribution of phosphatidate phosphohydrolase in rat liver.

The activity and subcellular distribution, before and after translocation with oleic acid, of hepatic phosphatidate phosphohydrolase (PAH: E.C.3.1.3.4) was measured following acute and chronic administration of ethanol with either 18% or 4.4% total calories as fat, to male Wistar rats. Acute injection produced a significant increase in PAH activity, without affecting the subcellular distribution or translocation of activity from the cytosol into the membraneous compartments induced by oleic acid. PAH activity, subcellular distribution and the translocation of activity by oleic acid was similar in all groups following chronic liquid feeding. Chronic ethanol feeding was associated with significantly increased plasma corticosterone in the ethanol-fed rats compared with controls, independent of the fat content of the diet. Plasma insulin was similar in chronic alcohol fed rats and controls. This suggests that enhanced PAH activity may contribute to triacylglycerol accumulation following acute alcohol injection, but activity normalises as hepatic lipid accumulation progresses and this effect is not due to attenuation of the hormonal effects of ethanol.

Animals↗

[Intracranial hypertension in severe diabetic ketoacidosis with coma. Two cases].

We observed two cases of severe diabetic ketoacidosis with coma and shock. In one case, coma was present at admission and in the second occurred within 15 hours. In both cases, intracranial hypertension was confirmed with an extradural captor. These findings are in agreement with observations of brain oedema in diabetic ketoacidosis with coma. Clinical data suggest that brain oedema may occur after a latency period but that clinical expression is much more rare, perhaps favoured by treatment (excessive rehydratation, alkalinization, too sharp drop in blood glucose level). In our cases, despite major fluid infusion, shock persisted requiring norepinephrine. This shock could have been the expression of the severe ketoacidosis or have resulted from an underlying infection. In case of sudden onset coma, a regularly encountered manifestation of brain oedema, respiratory assistance and mannitol infusion must be instituted rapidly. With this type of management, it should be possible to improve the severe prognosis of brain oedema in diabetic ketoacidosis.

Blood Glucose↗

A 1.7-Mb YAC contig around the human BDNF gene (11p13): integration of the physical, genetic, and cytogenetic maps in relation to WAGR syndrome.

WAGR (Wilms tumor, aniridia, genito-urinary abnormalities, mental retardation) syndrome in humans is associated with deletions of the 11p13 region. The brain-derived neurotrophic factor (BDNF) gene maps to this region, and its deletion seems to contribute to the severity of the patients' mental retardation. Yeast artificial chromosomes (YACs) carrying the BDNF gene have been isolated and characterized. Localization of two known exons of this gene leads to a minimal estimation of its size of about 40 kb. Chimerism of the BDNF YACs has been investigated by fluorescence in situ hybridization and chromosome assignment on somatic cell hybrids. Using the BDNF gene, YAC end sequence tagged sites (STS), and Généthon microsatellite markers, we constructed a 1.7-Mb contig and refined the cytogenetic map at 11p13. The resulting integrated physical, genetic, and cytogenetic map constitutes a resource for the characterization of genes that may be involved in the WAGR syndrome.

Base Sequence↗

Posttransplantation plasma cell dyscrasias.

BACKGROUND: Lymphoproliferative disorders that occur in patients receiving cyclosporine for immunosuppression after solid organ transplantation typically are B-cell neoplasms associated with Epstein-Barr virus (EBV), which may be polyclonal or monoclonal in origin. Although these tumors may have partial B-cell differentiation, (manifested as plasmacytoid features), terminal differentiation to plasma cells that secrete a monoclonal immunoglobulin is rare. The case of a patient who developed a posttransplantation lymphoproliferative disorder that was composed of multiple plasmacytomas located in the abdomen and urinary bladder after liver transplantation is presented. The patient also had high levels of an immunoglobulin-G kappa monoclonal paraprotein. METHODS: The plasmacytoma was examined for the presence of EBV by both polymerase chain reaction and in situ hybridization, and the possibility of a codon-12 mutation in the ras gene was investigated by digestion of DNA amplification products with the HpaII-restriction endonuclease. RESULTS: Epstein-Barr virus genomes were demonstrated by DNA amplification of sequences in the long, internal, direct repeat region, and in situ hybridization showed expression of EBV RNA transcripts that annealed to an EBER-1 probe. Immunohistochemistry showed clonally restricted expression of kappa light chains but failed to reveal evidence of expression of the latent membrane protein 1 encoded by EBV. Mutations of codon-12 in the H-ras gene were not detected. CONCLUSIONS: Resolution of the tumor and the paraprotein after radiation and reduction of immunosuppression indicates that terminal plasmacytic differentiation does not necessarily portend an unfavorable prognosis, even in a clonal lesion.

Abdominal Neoplasms↗

bcl-2 expression in normal breast tissue during the menstrual cycle.

bcl-2 is a proto-oncogene discovered through the t(14;18) translocation occurring in most human follicular lymphomas. The function so far attributed to bcl-2 is to counteract the occurrence of apoptosis and to prolong cell survival without affecting the cycling cells. Apoptosis has been described in normal breast tissue epithelial cells, and it peaks at the end of the luteal phase. We have studied bcl-2 expression by an immunohistochemical method in 50 samples of normal breast tissue distributed throughout the menstrual cycle. bcl-2 staining predominated in the lobular epithelial cells. It displayed a striking cyclic variation, with maximal expression at the mid-cycle period and a sharp decrease at the end of the cycle. These results strongly suggest that the regulation of bcl-2 expression in breast tissue is hormone-dependent. This could be of significance in tumorigenesis.

Adolescent↗

Ontogenic and nutritional modifications in the intestinal fucosylation process at the weaning period. Influence of dietary fibers.

In the rat small intestine, the glycosylation changes which normally take place at the weaning period are characterized by a shift from sialylation to fucosylation. The introduction of dietary fibers at weaning is one of the more striking nutritional modification so that some authors have suggested that the presence of fibers and the development of colonic fermentation might be important for the development of the small intestine, as for the colon. In order to define the respective contribution of ontogenic and nutritional factors to the intestinal glycosylation changes at this period, some aspects of the intestinal glycosylation were studied in five groups of rats (16-day-old suckling rats, prolonged nursing 23-day-old rats, 23-day-old rats weaned at day 19 with either a fiber-free, a cellulose or a pectin diet). Intestinal glycoproteins of suckling rats are characterized by a low fucose content and a high proportion of mannose. The amounts of the neutral sugars (fucose, mannose and galactose), expressed either per gram of intestine or for one intestine, are always higher in the fiber-fed groups than in the prolonged-nursing group or the group fed the fiber-free diet. Activities which promote fucosylation process (GDP-fucose production and fucosyltransferase activities) and those which are opposed to fucosylation (endogenous inhibitor of fucosyltransferase and GDP-fucose pyrophosphatase) are strongly modified in opposite ways at day 23 as compared to day 16. These modifications depend on the age of the animal (ontogenic factors) with additional modifications induced by the dietary factors. In particular, similar sugar contents and patterns are obtained with cellulose and pectin diets though the enzymatic activities of the fucosylation pathway are very different. No correlation was found between the caecal content of short chain fatty acids and any of the parameters under study. Thus, dietary fibers induce metabolic changes in the small intestine glycosylation in short-term experiments independently of colonic fermentation. Besides, these results point out that the consideration of fucosyl-transferase activities alone are not sufficient to predict glycoprotein fucose content and that other regulatory sites are involved. Dietary manipulations at the weaning period could represent a good model for the study of glycosylation regulation.

Animals↗

Comparison of ribotyping, pulsed-field gel electrophoresis and random amplified polymorphic DNA for typing Clostridium difficile strains.

Clostridium difficile is a Gram-positive sporulating anaerobic bacillus which causes pseudomembranous colitis. Nosocomial acquisition of this bacteria has proved frequent, and epidemiological markers are needed to recognize and control common-source outbreaks. We therefore compared the results of pulsed-field gel electrophoresis (PFGE) after restriction with SmaI or NruI, random-amplified polymorphic DNA (RAPD) using 3 10-mer oligonucleotides, and ribotyping to differentiate between 30 unrelated strains of C. difficile belonging to 8 serotypes. The strains were separated into 26 different types by PFGE, 25 by RAPD, but into only 18 types by ribotyping. Median percentages of similarity between strains ranged from 27 in the PFGE assay to 90 in the ribotyping assay, but there was good agreement between the 3 methods for the clustering of strains. PFGE was more time-consuming than RAPD but its patterns were easier to analyze.

Bacterial Typing Techniques↗

Purification and partial amino acid sequence of fuctinin, an endogenous inhibitor of fucosyltransferase activities.

A powerful endogenous protein inhibitor of fucosyltransferase activities, called fuctinin, was purified to homogeneity from rat small-intestinal mucosa. The purification scheme involved DEAE-cellulose ion-exchange chromatography, ammonium sulfate fractionation, hexyl-agarose hydrophobic chromatography and size-exclusion HPLC. Active native fuctinin has an isoelectric point of 4.55 and apparent molecular mass approximately 66 kDa, whereas a single protein band with a molecular mass of approximately 24 kDa was obtained by denaturing polyacrylamide gel electrophoresis, suggesting that fuctinin is an oligomeric protein. Two-dimensional polyacrylamide gel electrophoresis displayed eight spots in this single band. Comparisons of the N-terminal amino acid sequences of each spot support the idea of the existence of three related polypeptides and suggest a proteolytic N-terminal cleavage despite the use of an efficient protease inhibitor throughout the purification. In spite of the presence of an N-glycosylation site, fuctinin is not glycosylated. One of the three polypeptides, peptide 3, possesses two consensus sequences for phosphorylation and a consensus sequence for myristoylation. The sequences of functinin-related peptides, especially peptide 3, exhibit high similarity to the N-terminal domain of the Set protein and a putative human leukocyte antigen-associated protein. The possible implications of these results are discussed.

Amino Acid Sequence↗

Cell-permeable ceramides inhibit the stimulation of DNA synthesis and phospholipase D activity by phosphatidate and lysophosphatidate in rat fibroblasts.

The interactions of ceramides with phosphatidate and lysophosphatidate in the regulation of signal transduction in rat fibroblasts were examined. C2- and C6-ceramides (N-acetylsphingosine and N-hexanoylsphingosine, respectively) at 10 microM inhibited the stimulation of DNA synthesis that was produced by 50-100 microM phosphatidate, or lysophosphatidate, or by exogenous phospholipase D. Sphingosine (10 microM) had the opposite effect to the ceramides on DNA synthesis. C2- or C6-ceramides failed to inhibit the stimulation of DNA synthesis by insulin or serum. The ceramides did not modify the actions of phosphatidate, or lysophosphatidate, in decreasing the forskolin-induced increase in cAMP. C2- and C6-ceramides inhibited the stimulation of phospholipase D activity by: (a) phosphatidate, lysophosphatidate, phorbol ester, thrombin, or serum in intact fibroblasts and (b) phorbol ester or guanosine 5'-3-O-(thio)triphosphate in permeabilized fibroblasts. The ceramides can therefore modify cell signaling via phospholipase D, but this effect alone could not explain the decreased DNA synthesis. Incubation of fibroblasts with C2- or C6-ceramides or sphingomyelinase inhibited the interaction of exogenous phosphatidate or lysophosphatidate with the fibroblasts by 42 and 53%, respectively. Furthermore, a greater proportion of the phosphatidate, or lysophosphatidate, that was associated with the fibroblasts was metabolized further when the cells were pretreated with ceramides or sphingomyelinase. This effect was accompanied by an increased activity of N-ethylmaleimide-insensitive phosphatidate phosphohydrolase. Ceramides may therefore produce part of their growth inhibitory effects by blocking some of the signal transducing effects of phosphatidate and lysophosphatidate.

Animals↗

13C-NMR relaxation in three DNA oligonucleotide duplexes: model-free analysis of internal and overall motion.

Natural-abundance 13C-NMR spectra of [d(TCGCG)] (1), [d(CGCGCG)]2 (2), and [d(GGTATACC)]2 (3) were measured at 90.6 MHz to obtain 13C-1H NOEs and T1 relaxation times; relaxation data were also measured at 125.7 MHz for 1 and 2 and at 62.9 MHz for 1. Analysis of the relaxation data was performed in the context of the "model-free" approach of Lipari and Szabo [Lipari, G., & Szabo, A. (1982) J. Am. Chem. Soc. 104, 4546-4559], leading to the following conclusions: (i) Optimized values for the overall correlation times of 0.9 ns for 1 and 1.4 ns for 2 are close to those predicted by light-scattering results on similar molecules [Eimer et al. (1990) Biochemistry 29, 799-811]. (ii) For the nonterminal residues, the "order parameter", S2, is around 0.8 for the protonated base carbons and 0.6 for the sugar carbons, indicating less spatial restriction on the sugar carbons (in the model-free approach, the order parameter is 1 for a rigid body and 0 for a system with completely unrestricted internal motion). (iii) The order parameters for the terminal residues vary over a wide range with the smallest values around 0.2-0.3 for the HO-13C5' and the 13C3'-OH; rational trends are seen in the variation of S2 with chain position in the terminal residues. (iv) The analysis shows that the order parameters are accurate within 15%. (v) The "effective internal correlation time", tau e, is very short for the sugar carbons (30-300 ps) and less well-defined, but probably also short, for the bases. (vi) The analysis indicates that most of the relaxation in DNA is accounted for by S2 and the tau e is so short that a good approximation to any relaxation property, P (e.g., T1, T2, 13C-1H NOE, 1H-1H cross-relaxation rate), is P = S2Prigid, where Prigid is the value for the property in a system without internal motion (the analysis assumes the same isotropic overall motion for both the rigid and flexible bodies).

Base Sequence↗

Sensory assessment of fat content: effect of emulsion and subject characteristics.

This work examines some of the fundamental stimulus properties contributing to the perception and discrimination of fat content in foods. In an initial experiment, oil-in-water (O/W) emulsions were prepared with 0, 5, 10, ..., 40, 45, and 50% sunflower oil (SUN) and homogenized at pressures of 100 and 300 bar. These were rated for "fat content" and "smoothness" on 9-point category scales. There were significant effects of fat concentration and processing pressure. Higher pressures, associated with a decreased fat particle size/number ratio, generated a slightly enhanced perception of fat content. In a second experiment, O/W emulsions were prepared with 0, 12, 24, 36, and 48% fat at 100 and 300 bar, from two oils differing in fat saturation: SUN and Hycoa 5 (HY5, a highly saturated commercial cocoa butter substitute). The results indicate significant main and interactive effects of fat type and concentration, but no significant effect of processing pressure were seen in this experiment. HY5 emulsions had a substantially greater measured viscosity and were judged higher in fat content than those prepared from SUN, particularly at higher fat levels. Analyses indicate a significant independent contribution of fat concentration to perceived fat content, beyond increased viscosity. There were no consistent main or interactive effects of subject age or body composition on judgments of fat content.

Adolescent↗

Theoretical and experimental behaviour of the muscle viscosity coefficient during maximal concentric actions.

The aim of this study was to calculate the theoretical variation of the nonlinear damping factor (B) as a function of the muscle shortening velocity, and then to compare the theoretical values with the experimental data obtained on both the elbow flexor and the ankle extensor muscles. The theoretical variation of the B factor was determined from a muscle model consisting of a contractile component in parallel with a viscous damper both in series with an elastic component, and by using, the characteristic equation of the force velocity curve. In this muscle model, the viscous element modelled the inability of the muscle to generate as big a contracting force (while shortening) as possible under isometric conditions. Eight volunteer subjects performed maximal concentric elbow flexions and ankle extensions on an isokinetic ergometer at angular velocities of 60, 120, 180, 240, 300 and 360 degrees.s-1, and held two maximal isometric actions at an elbow angle of 90 degrees (0 degrees corresponds to the full extension) and at an ankle angle of 0 degree (0 degree corresponds to the foot flexion of 90 degrees relative to the leg axis). From these measurements, the force and the shortening velocity values of each muscle were determined by using a musculo-skeletal model of the joint. The results showed that the theoretical behaviour of the B factor would seem to be dependent on the shortening velocity and on the parameter which varies according to the muscle fibre type composition and affects the curvature of the force-velocity curve (af).(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Word retrieval to letter and semantic cues: a double dissociation in normal subjects using interference tasks.

Recent evidence suggests that letter and semantic category verbal fluency tasks may use different component processes of a distributed word retrieval system. We hypothesized that the retrieval of words that begin with the same letter places greater demands on frontal lobe mediated strategic search processes than on temporal lobe mediated semantic knowledge. Conversely, generation of words from the same semantic category places greater demands on semantic knowledge than on strategic search. This hypothesis was tested by requiring subjects to generate lists of words to letter and semantic cues alone and while performing an interference task. A motor sequencing task (developed by Moscovitch, Neuropsychology of Memory, pp. 5-22, 1992) was used to activate frontal regions and an object decision task was used to activate posterior temporal cortex. In support of the hypothesis, letter fluency was reduced to a greater extent by concurrent performance of the motor sequencing task than by the object decision task. The opposite interference pattern was found for semantic category fluency.

Adult↗

No effect of oral or sample temperature on sensory assessment of fat content.

This work examined the possible influences of oral and sample temperature on the perception of fat content of a model food system. Melting or related phenomena may contribute to the greater sensation of fat content and the highly acceptable textural characteristics associated with certain fats. Thirty-one adults assessed the fat content of 0%, 12%, 24%, 36%, and 48% oil-in-water emulsions prepared with a commercial cocoa butter substitute having a melting range of 17-41 degrees C. Samples were evaluated at combinations of sample and mouth temperatures of 20 and 36 degrees C, with oral temperatures manipulated by repeated cold- and warm-water rinses prior to assessments. There were no significant differences amongst these treatments on perceived fat content of the samples, nor were subject characteristics of age or body composition related to judgments of fat content in these stimuli. Although previous studies had shown that degree of fat saturation is associated with enhanced perception of fat content (11), that does not appear to be related to the degree or occurrence of melting in the mouth over the ranges studies here.

Adolescent↗