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Biomedical subjects

M Guerin

Publications and source records attributed to M Guerin.

At least 19 recordsLinked to original sources
PubMed2001

Tritium and 36Cl as constraints on fast fracture flow and percolation flux in the unsaturated zone at Yucca Mountain.

An analysis of tritium and 36Cl data collected at Yucca Mountain, Nevada suggests that fracture flow may occur at high velocities through the thick unsaturated zone. The mechanisms and extent of this "fast flow" in fractures at Yucca Mountain are investigated with data analysis, mixing models and several one-dimensional modeling scenarios. The model results and data analysis provide evidence substantiating the weeps model [Gauthier, J.H., Wilson, M.L., Lauffer, F.C., 1992. Proceedings of the Third Annual International High-level Radioactive Waste Management Conference, vol. 1, Las Vegas, NV. American Nuclear Society, La Grange Park, IL, pp. 891-989] and suggest that fast flow in fractures with minimal fracture-matrix interaction may comprise a substantial proportion of the total infiltration through Yucca Mountain. Mixing calculations suggest that bomb-pulse tritium measurements, in general, represent the tail end of travel times for thermonuclear-test-era (bomb-pulse) infiltration. The data analysis shows that bomb-pulse tritium and 36Cl measurements are correlated with discrete features such as horizontal fractures and areas where lateral flow may occur. The results presented here imply that fast flow in fractures may be ubiquitous at Yucca Mountain, occurring when transient infiltration (storms) generates flow in the connected fracture network.

Chlorine↗
PubMed2000

Treatment of acute disseminated encephalomyelitis with intravenous immunoglobulin.

Acute disseminated encephalomyelitis (ADEM) is a presumed immune-mediated, demyelinating disease of the CNS for which the standard treatment is high-dose steroids. We describe two patients with ADEM in whom treatment with IV methylprednisolone coincided with deterioration in their clinical status. They were subsequently treated with IV immunoglobulin and exhibited dramatic clinical improvement, with return to their previous level of functioning.

Acute Disease↗
PubMed2000

Action of atorvastatin in combined hyperlipidemia : preferential reduction of cholesteryl ester transfer from HDL to VLDL1 particles.

Combined hyperlipidemia (CHL) is characterized by a concomitant elevation of plasma levels of triglyceride-rich, very low density lipoproteins (VLDLs) and cholesterol-rich, low density lipoproteins (LDLs). The predominance of small, dense LDLs contributes significantly to the premature development of coronary artery disease in patients with this atherogenic dyslipoproteinemia. In the present study, we evaluated the impact of atorvastatin, a newly developed inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, on the cholesteryl ester transfer protein (CETP)-mediated remodeling of apolipoprotein (apo) B-containing lipoprotein subspecies, and more specifically, the particle subpopulations of VLDL and LDL in CHL. In parallel, we evaluated the atorvastatin-induced modulation of the quantitative and qualitative features of atherogenic apo B-containing and cardioprotective apo AI-containing lipoprotein subspecies. Atorvastatin therapy (10 mg/d for a 6-week period) in patients with a lipid phenotype typical of CHL (n=18) induced reductions of 31% (P<0.0001) and 36% (P<0.0001) in plasma total cholesterol and LDL cholesterol, respectively. In addition, atorvastatin significantly reduced VLDL cholesterol, triglycerides, and apo B levels by 43% (P<0.0001), 27% (P=0.0006), and 31% (P<0.0001), respectively. The plasma concentrations of triglyceride-rich lipoproteins (VLDL1, Sf 60 to 400; VLDL2, Sf 20 to 60; and intermediate density lipoproteins, Sf 12 to 20) and of LDL, as determined by chemical analysis, were markedly diminished after drug therapy (-30% and -28%, respectively; P<0.0007). Atorvastatin significantly reduced circulating levels of all major LDL subspecies, ie, light (-28%, P<0.0008), intermediate (-27%, P<0.0008), and dense (-32%, P<0.0008) LDL; moreover, in terms of absolute lipoprotein mass, the reduction in dense LDL levels (mean -62 mg/dL) was preponderant. In addition, the reduction in plasma dense LDL concentration after therapy was significantly correlated with a reduction in plasma VLDL1 levels (r=0.429, P=0.0218). Atorvastatin induced a significant reduction (-7%, P=0.0039) in total CETP-dependent CET activity, which accurately reflects a reduction in plasma CETP mass concentration. Total CETP-mediated CET from high density lipoproteins to apo B-containing lipoproteins was significantly reduced (-26%, P<0.0001) with drug therapy. Furthermore, CETP activity was significantly correlated with the atorvastatin-induced reduction in plasma VLDL1 levels (r=0.456, P=0. 0138). Indeed, atorvastatin significantly and preferentially decreased CET from HDL to the VLDL1 subfraction (-37%, P=0.0064), thereby reducing both the levels (-37%, P=0.0001) and the CE content (-20%, P<0.005) of VLDL1. We interpret our data to indicate that 2 independent but complementary mechanisms may be operative in the atorvastatin-induced reduction of atherogenic LDL levels in CHL: first, a significant degree of normalization of both the circulating levels and the quality of their key precursors, ie, VLDL1, and second, enhanced catabolism of the major LDL particle subclasses (ie, light, intermediate, and dense LDL) due to upregulation of hepatic LDL receptors.

Apolipoproteins B↗
PubMed1999

Evidence for a cholesteryl ester donor activity of LDL particles during alimentary lipemia in normolipidemic subjects.

Postprandial hypertriglyceridemia represents an independent risk factor for coronary artery disease. In the postprandial state, elevated levels of triglyceride-rich lipoproteins (TRL) are minor acceptors of HDL-cholesteryl ester (CE) transferred by CETP in normolipidemic subjects: indeed, LDL particles represent the major CE acceptors. In order to evaluate further the potential atherogenicity of lipoprotein particles characteristic of the postprandial phase in normolipidemic subjects, we determined the quantitative and qualitative features of apoB- and apoAI-containing lipoproteins over an 8-h period following consumption of a mixed meal. During postprandial lipemia, we observed a significant decrease (-12%) in plasma AI concentration (138+/-4 and 156+/-4 mg/dl, at 3 h and baseline, respectively, P<0.005). Concomitantly, a progressive increase (+13%) was detected in HDL2 concentrations (138+/-7 mg/dl at 4 h vs. 122+/-12 mg/dl at baseline, P<0.005), as well as a significant reduction (-9%) in HDL3 levels (137+/-6 mg/dl at 3 h vs. 150+/-4 mg/dl at baseline; P<0.05). Additionally, plasma LDL was reduced by 5% (247+/-12 mg/dl at 3 h vs. 260+/-15 mg/dl at baseline; P<0.05) 3 h following meal intake. Moreover, a significant reduction (-10%) occurred in the CE/TG ratio in LDL at 2 h postprandially (8+/-2 at 2 h vs. 9+/-3 at baseline; P<0.005). These changes reflected an increment (17+/-3 mg/dl at 3 h vs. 15+/-4 mg/dl at baseline; P<0.05) in LDL triglyceride concentrations. Despite the high CE acceptor capacity of LDL particles, no measurable increase in their CE content was detected during the postprandial phase. We demonstrated that CE accepted by LDL particles from HDL are secondarily transferred to chylomicrons by CETP. As chylomicrons displayed a 260-fold lower CE/TG ratio than LDL (0.03:1 and 7.8:1 in chylomicrons and LDL, respectively), CE-rich LDL may act to donate CE to chylomicrons. In conclusion, our data indicate that the presence of elevated levels of chylomicrons induces LDL to act as a secondary donor of CE during the postprandial phase.

Adult↗
PubMed1999

Isolated trigeminal neuropathy due to trigeminal nerve root hemorrhage.

BACKGROUND: Isolated trigeminal neuropathy is uncommon; causes include trauma, inflammation, or neoplasm. METHODS: We report a patient who fell and struck his head during a myocardial infarction, was treated with streptokinase, and developed symptoms and signs of an isolated trigeminal sensory neuropathy. RESULTS: Imaging showed hemorrhage in the trigeminal nerve root; follow-up imaging showed resolution of the hemorrhage, but no underlying structural lesion. CONCLUSION: A combination of head trauma plus thrombolysis resulted in an isolated trigeminal neuropathy.

Cerebral Hemorrhage↗
PubMed1997

Familial lecithin:cholesterol acyltransferase deficiency: molecular analysis of a compound heterozygote: LCAT (Arg147 --> Trp) and LCAT (Tyr171 --> Stop).

Lecithin:cholesterol acyltransferase (LCAT) is responsible for the formation of the majority of plasma cholesteryl esters. Familial LCAT deficiency is associated with corneal opacity, anemia and proteinurea and typically results in renal failure in the 4-5th decade; this syndrome is equally characterized by the quasi-absence of plasma LCAT activity with variable enzyme mass and very low levels of plasma cholesteryl esters. In this study, we report detailed analyses of plasma lipids and lipoprotein profile in two sisters (CM and ML) presenting classical homozygous LCAT-deficiency; the younger sibling (CM) had proteinurea from an early age whereas the older sister (ML) has never exhibited renal dysfunction. We investigated the molecular defect in the 45 year-old woman (proband CM) exhibiting all clinical and biochemical features of familial LCAT deficiency: a plasma cholesterol level of 105 mg/dl, of which 95% was unesterified, an HDL-cholesterol of 6.5 mg/dl and an apo A-I level of 52 mg/dl. The proband (CM) displayed a plasma cholesterol esterification rate which corresponded to 2% of normal LCAT activity; plasma LCAT protein concentration was 0.56 microg/ml and equivalent to approximately 10% of normal LCAT mass. Analysis by single strand conformation polymorphism (SSCP) of the PCR products corresponding to exons 4 and 5 of the LCAT gene revealed a visible band shift. Sequence analyses of exons 4 + 5 revealed two separate single point mutations: a C --> T transition replacing Arg147 by Trp and a T --> G transition converting Tyr171 to a stop codon. The presence of these two point mutations was confirmed by restriction enzyme analyses: the C --> T transition abolished a MwoI site whereas the T --> G transition created an AvrII site. The Arg147 mutation was associated with a non-secreted protein. The Tyr171 mutation resulted in formation of a truncated protein lacking the catalytic site. In summary, we have identified an LCAT deficient patient corresponding to a compound heterozygote for the Arg147 --> Trp mutation and a new molecular defect involving a Tyr171 --> Stop mutation in the LCAT gene.

Apolipoprotein A-I↗
PubMed1997

Immunogenicity of the recombinant SAPA protein of Trypanosoma cruzi for mice.

The humoral and cellular immune responses induced by the recombinant SAPA (shed acute phase antigen) of Trypanosoma cruzi were studied in mice and correlated with the immunologic control of parasitemia. The immunizing schedule used consisted of 2 weekly injections of 50 micrograms glutathione-S-transferase (GST)-SAPA in Freund's adjuvant. Specific alpha GST-SAPA antibodies were detected by enzyme-linked immunosorbent assay 1 wk after each antigen dose, the concentration of antibodies after the second injection being 30-fold higher than after the first. Immediate- (ITH) and delayed-type hypersensitivity (DTH) reactions were observed as footpad swelling after injecting 50 micrograms GST-SAPA in preimmunized mice as compared to naive controls. Adoptive transfer experiments indicated that these cutaneous reactions were mediated by lymphoid cells and not by serum. Both humoral and cellular responses were specific for the GST-SAPA antigen and did not cross-react with either the GST or the recombinant GST-1 T. cruzi antigen. Immunized mice that had developed high levels of antibody and DTH reaction to GST-SAPA were able to control the level of parasitemia after challenge with 10(3) blood trypomastigotes. The levels of parasitemia obtained were lowered to about 1/3 (P < 0.05) and mortality at day 60 was reduced from 67 to 25% (P = 0.085). Comparison of this immunizing method with other schedules involving more injections or higher antigen doses indicates that control of parasitemia can be obtained with low amounts of antigen and seems to be associated with the development of DTH.

Animals↗
PubMed1995

ATP opens an electrophoretic potassium transport pathway in respiring yeast mitochondria.

In the presence of KCl and only at low phosphate concentrations, ATP stimulated state 4 of the respiration of isolated yeast mitochondria. This effect could be related to a partial collapse of the transmembrane potential which was created by the respiratory chain or the F0F1-ATPase. Sodium and lithium could not replace potassium ion. Atractyloside prevented the opening of this K+ pathway, suggesting that only matricial ATP operated. All these effects were inhibited by increasing phosphate concentration, or by adding propranolol, quinine, Zn2+ or Mg2+.

Adenosine Triphosphate↗
PubMed1995

A Bcl-2-related gene is activated in avian cells transformed by the Rous sarcoma virus.

The oncoprotein p60v-src encoded by the Rous sarcoma virus (RSV) genome is the prototype of non-receptor tyrosine kinases. More than 50 targets of p60v-src have been described to date. However, the precise mechanisms of RSV transformation remain to be elucidated. Here, we present the study of a new v-src-activated gene, NR-13, which encodes a protein identified as a new member of the Bcl-2 family. This protein is localized in the membrane with a pattern already observed with Bcl-2. In quail embryos, this gene is mainly expressed in neural and muscular tissues. Its expression is dramatically down-regulated after embryonic day 7 (E7) in the optic tectum. To evaluate a possible role for NR-13 in the control of apoptotic processes in this particular brain area, in situ hybridization and DNA ladder fractionation studies were performed to correlate NR-13 expression with typical situations of apoptosis during brain development. Our results support the idea that RSV could activate anti-apoptotic functions of the host cell resulting in an increase of their lifespan, which could be particularly relevant to tumour formation.

Amino Acid Sequence↗
PubMed1993

Isolation, characterization and function of the two cytochromes c of the yeast Candida parapsilosis.

Candida parapsilosis is a strictly aerobic yeast which possesses two respiratory chains with a peculiar organisation, different from that of plant mitochondria. Besides the classical electron transport pathway, mitochondria of C. parapsilosis develops an alternative pathway, which does not branch off at the ubiquinone level, but merges at the complex IV level. Two pools of cytochromes c were distinguished by their spectrometric and potentiometric properties: (i) sequential cytochrome c reduction was promoted by two substrates, PMS (Em = 70 mV) and TMPD (Em = 280 mV). TMPD promoted the reduction of a cytochrome c with maxima at 551.9 and 417.3 nm for the alpha and the Soret bands, respectively, whereas cytochrome c reducible by PMS exhibited maxima at 549.7 and 419.9 nm; (ii) two midpoint redox potentials were resolved at 180 mV and 280 mV, respectively. The two cytochromes c were copurified by ion-exchange chromatography on Amberlite; after this step, the two cytochromes c can always be differentiated by TMPD and PMS, these reductants promoting different absorption bands. The two cytochromes c were separated by reverse-phase HPLC; this last purification step resolved two proteins with the same relative molecular mass of 13600 but a different amino-acid composition. Comparison of N-terminal sequences revealed differences between the two proteins. It was hypothesized that one cytochrome c is implicated in the functioning of the main chain and the other in that of the secondary pathway.

Amino Acid Sequence↗
PubMed1991

Biochemical studies carried out on different groups of Candida parapsilosis and Candida rhagii strains by comparing some cellular and mitochondrial activities.

A comparative biochemical study was performed on some strains of Candida rhagii and on strains belonging to different subgroups of Candida parapsilosis. Measurements of alcohol dehydrogenase activity, resistance to drugs and occurrence of an alternative pathway enabled us to confirm the classification between several subgroups within the C. parapsilosis species.

1-Propanol↗
PubMed1989

Modifications of the relative proteolipid composition in the ATP synthase of a respiratory competent mutant of Saccharomyces cerevisiae.

A comparative study of the proteolipid composition of the F0-sector of the ATP synthase of wild-type strain of Saccharomyces cerevisiae and of nuclear mutants, modified at the level of the oxidative phosphorylation due to an enhanced proton permeability of the inner membrane, was carried out. Analysis of the crude proteolipid extract by electrophoresis and high liquid performance chromatography showed some differences at the level of mitochondrial DNA encoded proteolipids. Subunit 6 and in particular subunit 8 were present in reduced amounts, whereas subunit 9 was present in equal amounts in both types of strain. However, the phosphate binding affinity of subunit 8 was the same in wild-type and mutant strains. The fact that subunit 6 and subunit 8 are cotranscripted on a single mRNA led to the problem of the regulation of the mitochondrial synthesis of these two proteins by a nuclear gene.

Chromatography, High Pressure Liquid↗
PubMed1989

Inhibition of the phosphate-stimulated cytochrome c oxidase activity by thiophosphate.

Yeast and mammalian cytochrome c oxidase activity is inhibited by thiophosphate. This inhibition was observed when using either whole mitochondria or the isolated or reconstituted enzyme. The kinetics of the reduction reaction enabled us to demonstrate that thiophosphate acted on the electron transfer between hemes a and a3. With whole mitochondria, phosphate alone stimulated respiration. The inhibition induced by thiophosphate was suppressed by phosphate only in mitochondria, but not when the isolated enzyme was used. The possibility of a kinetic regulation is discussed.

Animals↗
PubMed1989

The second respiratory chain of Candida parapsilosis: a comprehensive study.

The yeast C. parapsilosis CBS7157 is strictly dependent on oxidative metabolism for growth since it lacks a fermentative pathway. It is nevertheless able to grow on high glucose concentrations and also on a glycerol medium supplemented with antimycin A or drugs acting at the level of mitochondrial protein synthesis. Besides its normal respiratory chain C. parapsilosis develops a second electron transfer chain antimycin A-insensitive which allows the oxidation of cytoplasmic NAD(P)H resulting from glycolytic and hexose monophosphate pathways functioning through a route different from the NADH-coenzyme Q oxidoreductase described in S. cerevisiae or from the alternative pathways described in numerous plants and microorganisms. The second respiratory chain of C. parapsilosis involves 2 dehydrogenases specific for NADH and NADPH respectively, which are amytal and mersalyl sensitive and located on the outer face of the inner membrane. Since this antimycin A-insensitive pathway is fully inhibited by myxothiazol, it was hypothesized that electrons are transferred to a quinone pool that is different from the classical coenzyme Q-cytochrome b cycle. Two inhibitory sites were evidenced with myxothiazol, one related to the classical pathway, the other to the second pathway and thus, the second quinone pool could bind to a Q-binding protein at a specific site. Elimination of this second pool leads to a fully antimycin A-sensitive NADH oxidation, whereas its reincorporation in mitochondria allows recovery of an antimycin A-insensitive, myxothiazol sensitive NADH oxidation. The third step in this second respiratory chain involves a specific pool of cytochrome c which can deliver electrons either to a third phosphorylation site or to an alternative oxidase, cytochrome 590. This cytochrome is inhibited by high cyanide concentrations and salicylhydroxamates.

Candida↗
PubMed1989

Exercise tolerance in the heat on low and normal salt intakes.

1. Salt restriction is recommended in the treatment of hypertension and is included in national dietary guidelines, but its effect on exercise in hot conditions has not been extensively studied. 2. The effects of 2 weeks on two levels of salt intake (50 and 150 mmol/day) on the ability to exercise (60% of maximal oxygen uptake) in a hot environment (35 degrees C) were studied in eight healthy normotensive subjects. 3. All subjects were able to complete the exercise load on the two levels of salt intake. No differences in mean oxygen uptake, heart rate or rectal temperature during exercise were observed between the two salt intakes. 4. Plasma sodium, potassium and osmolality were similar on the two salt intakes both before and during exercise. Plasma renin activity and aldosterone concentration were elevated after 2 weeks on the reduced salt intake and remained so during exercise. 5. The estimated sweat rate during exercise was similar on the two salt intakes but the loss of sodium was less on the low salt intake. 6. On the basis of these results it is concluded that moderate salt restriction does not impair the ability to exercise in a hot environment.

Adult↗