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Biomedical subjects

E Gauthier

Publications and source records attributed to E Gauthier.

At least 19 recordsLinked to original sources
PubMed2006

Morphometric evidence for impairment of renal autoregulation in advanced essential hypertension.

A morphometric study was performed on 22 renal biopsies from hypertensive patients with proteinuria and/or azotemia, with no evidence of other renal disease. These results were compared with our earlier study of normotensive aging kidneys. Afferent arterioles in hypertensive kidneys showed a significant increase in lumen diameter (15.7+/-4.9 vs 13.4+/-4.7 microm, P=0.0007) and wall area (1234+/-769 vs 998+/-445 microm(2), P=0.037), due primarily to shift in the distribution of arteriolar types, from predominantly normal toward predominantly hyaline arterioles in hypertension. Glomeruli were divided into four basic types: normal, hypertrophic, focal segmental glomerulosclerosis (FSGS) type, and sclerosing. Overall, glomeruli in hypertensive kidneys were much larger than in normotensive aging kidneys, for example, total capillary area (16 247+/-10 681 vs 11 624+/-5702 microm(2), P<0.00001). This increase was due primarily to an increase in size of each type, for example, for hypertrophic glomeruli: total capillary area (22 205+/-10 426 vs 15 349+/-4577 microm(2), P=0.0038). There was an excellent correlation between arteriolar lumen diameter and mean glomerular capillary area for hypertrophic/FSGS-type glomeruli (r=0.4778, P=0.0013), such that as arteriolar diameter increases the mean glomerular capillary area increases, consistent with loss of autoregulation. The morphologic correlates of loss of autoregulation, with afferent arteriolar dilatation and increase in glomerular capillary size, glomerular hypertrophy, and subsequent FSGS, are present on a focal basis in aging kidneys and, much more extensively, although still focally, in hypertensive kidneys.

Adult↗
PubMed2005

Serum amyloid A: production by human white adipocyte and regulation by obesity and nutrition.

AIMS/HYPOTHESIS: The acute-phase proteins, serum amyloid As (SAA), are precursors of amyloid A, involved in the pathogenesis of AA amyloidosis. This work started with the characterisation of systemic AA amyloidosis concurrent with SAA overexpression in the subcutaneous white adipose tissue (sWAT) of an obese patient with a leptin receptor deficiency. In the present study a series of histopathological, cellular and gene expression studies was performed to assess the importance of SAA in common obesity and its possible production by mature adipocytes. MATERIALS AND METHODS: Gene expression profiling was performed in the sWAT of two extremely obese patients with a leptin receptor deficiency. Levels of the mRNAs of the different SAA isoforms were quantified in sWAT cellular fractions from lean subjects and from obese subjects before and after a very-low-calorie diet. These values were subsequently compared with serum levels of SAA in these individuals. In addition, histopathological analyses of sWAT were performed in lean and obese subjects. RESULTS: In sWAT, the expression of SAA is more than 20-fold higher in mature adipocytes than in the cells of the stroma vascular fraction (p<0.01). Levels of SAA mRNA expression and circulating levels of the protein are sixfold (p<0.001) and 3.5-fold (p<0.01) higher in obese subjects than in lean subjects, respectively. In lean subjects, 5% of adipocytes are immunoreactive for SAA, whereas the corresponding value is greater than 20% in obese subjects. Caloric restriction results in decreases of 45-75% in levels of the transcripts for the SAA isoforms and in circulating levels of the protein. CONCLUSIONS/INTERPRETATION: The results of the present study indicate that SAA is expressed by sWAT, and its production at this site is regulated by nutritional status. If amyloidosis is seen in the context of obesity, it is possible that production of SAA by adipocytes could be a contributory factor.

Adipocytes↗
PubMed2005

[A global intervention program for institutionalized demented patients].

INTRODUCTION: Over the last decades many approaches have been developed to manage cognitive and behavioral disturbances in dementia. The present work describes a global intervention program carried out with moderately to severely demented institutionalized patients. The aims of the intervention program are to stimulate and maintain the preserved abilities of demented patients in a supportive context, to decrease the behavioral disturbance and to avoid burnout of care-unit staff. METHODS: This intervention combines different means: psychosocial care (validation therapy, social interaction), cognitive stimulation (memory and verbal training), and motor and sensitive stimulation. The global intervention program requires a special trained team composed of a supervisor, six aid-nurses, an occupational therapist, a speech therapist, a psychomotor therapist and a psychologist. The team cared for the patients five days per week over a three-month period. Assessments were conducted before and after the intervention program to measure the benefit. RESULTS: Positive effects were shown for cognitive abilities, nutritional problems and staff burnout. However, due to the small sample size for this study, more research is needed to verify the effectiveness of this global intervention program, particularly the implications for nutrition. CONCLUSION: This global intervention combined with pharmacological treatment seems to be useful for managing psychological and behavioral disorders of institutionalized demented patients.

Activities of Daily Living↗
PubMed2004

Breast cancer risk associated with being treated for infertility: results from the French E3N cohort study.

BACKGROUND: The use of fertility drugs (FDs) is steadily increasing in Western countries and concern has been raised as to the possible impact of fertility treatments on breast cancer risk. METHODS: We analysed this association in the French E3N study. In this prospective cohort, data on treatment against infertility, duration and time of administration were collected at entry through self-administered questionnaires. Cox regression analysis was used to estimate adjusted relative risks (RRs). RESULTS: Among the 92 555 women from the study population, 6602 women were treated for infertility. During the 10 year follow-up period, 2571 cases of primary invasive breast cancer were diagnosed (183 in treated women). Our study showed no overall significant association between breast cancer risk and treatment for infertility (RR = 0.95, confidence interval 0.82-1.11), after surgery or FDs, and whatever the type, the duration of use and the age at first use of FDs. However, infertility treatment was associated with an increased risk, of borderline significance, of breast cancer among women with a family history of breast cancer. This last result had limited statistical power. CONCLUSIONS: Our study provides evidence that treatment for infertility does not influence breast cancer risk overall. An interaction with a familial history of breast cancer is possible but should be investigated further.

Adult↗
PubMed2003

Initial characterization of new bacteria degrading high-molecular weight polycyclic aromatic hydrocarbons isolated from a 2-year enrichment in a two-liquid-phase culture system.

AIMS: To characterize some polycyclic aromatic hydrocarbons (PAH)-degrading microorganisms isolated from an enriched consortium degrading high molecular weight (HMW) PAHs in a two-liquid-phase (TLP) soil slurry bioreactor, and to determine the effect of low molecular weight (LMW) PAH on their growth and HMW PAH-degrading activity. METHODS AND RESULTS: Several microorganisms were isolated from a HMW-PAH (pyrene, chrysene, benzo[a]pyrene and perylene) degrading consortium enriched in TLP cultures using silicone oil as the organic phase. From 16S rRNA analysis, four isolates were identified as Mycobacterium gilvum B1 (99% identity),Bacillus pumilus B44 (99% identity), Microbacterium esteraromaticum B21 (98% identity), and to the genus Porphyrobacter B51 (96% identity). The two latter isolates have not previously been associated with PAH degradation. Isolate B51 grew strongly in the interfacial fraction in the presence of naphthalene vapours and phenanthrene compared with cultures without LMW PAHs. Benzo[a]pyrene was degraded in cultures containing a HMW PAH mixture but pyrene had no effect on its degradation. The growth of isolates B1 and B21 was improved in the aqueous phase than in the interfacial fraction for cultures with naphthalene vapours. Pyrene was required for benzo[a]pyrene degradation by isolate B1. For isolate B21, pyrene and chrysene were degraded only in cultures without naphthalene vapours. CONCLUSION: Consortium enriched in a TLP culture is composed of microorganisms with different abilities to grow at the interface or in the aqueous phase according to the culture conditions and the PAH that are present. Naphthalene vapours increased the growth of the microorganisms in TLP cultures but did not stimulate the HMW PAH degradation. SIGNIFICANCE AND IMPACT OF THE STUDY: New HMW PAH-degrading microorganisms and a better understanding of the mechanisms involved in HMW PAH degradation in TLP cultures.

Bacteria↗
PubMed2001

Environmental pesticide exposure as a risk factor for Alzheimer's disease: a case-control study.

The aim of this study was to evaluate the influence of pesticide exposure on the development of Alzheimer's disease (AD), taking into account the potentially confounding factors (genetic, occupational exposure, and sociodemographic). The 1924 study participants (>70 years old) were randomly selected in the Saguenay-Lac Saint-Jean region (Quebec, Canada). The AD diagnosis was established in three steps according to recognized criteria. Sixty-eight cases were paired with a nondemented control for age (+/-2 years) and sex. Structured questionnaires addressed to subjects and proxy respondents allowed a description of the sociodemographic characteristics, lifestyle characteristics, and residential, occupational, familial, and medical histories. Assessment of environmental exposure to pesticides was based on residential histories and the agriculture census histories of Statistics Canada (1971-1991) for herbicide and insecticide spraying in the area. Statistical analyses were performed with a logistic regression, adjusting for potential confounding factors. The results failed to show a significant risk of AD with an exposure to herbicides, insecticides, and pesticides. However, future investigations are needed to establish more precisely the identification, measurement, mobility, and bioavailability of neurotoxic pesticide residues in relation to AD.

Aged↗
PubMed2000

Aluminum forms in drinking water and risk of Alzheimer's disease.

The objective of this study was to assess the relation between long-term exposure to different aluminum (Al) forms in drinking water and Alzheimer's disease (AD). The study participants were selected from a random sample of the elderly population (> or = 70 years of age) of the Saguenay-Lac-Saint-Jean region (Quebec). Sixty-eight cases of Alzheimer's disease diagnosed according to recognized criteria were paired for age (+/-2 years) and sex with nondemented controls. Aluminum speciation was assessed using established standard analytical protocols along with quality control procedures. Exposure to Al forms (total Al, total dissolved Al, monomeric organic Al, monomeric inorganic Al, polymeric Al, Al(3+), AlOH, AlF, AlH(3)SiO(2+)(4), AlSO(4)) in drinking water was estimated by juxtaposing the subject's residential history with the physicochemical data of the municipalities. The markers of long-term exposures (1945 to onset) to Al forms in drinking water were not significantly associated with AD. On the other hand, after adjustment for education level, presence of family cases, and ApoE varepsilon4 allele, exposure to organic monomeric aluminum estimated at the onset of the disease was associated with AD (odds ratio 2.67; 95% CI 1.04-6.90). On average, the exposure estimated at the onset had been stable for 44 years. Our results confirm prime the importance of estimation of Al speciation and consideration of genetic characteristics in the assessment of the association between aluminum exposure and Alzheimer's disease.

Age of Onset↗
PubMed2000

Artificial and epigenetic regulation of the I factor, a nonviral retrotransposon of Drosophila melanogaster.

The I factor (IF) is a LINE-like transposable element from Drosophila melanogaster. IF is silenced in most strains, but under special circumstances its transposition can be induced and correlates with the appearance of a syndrome of female sterility called hybrid dysgenesis. To elucidate the relationship between IF expression and female sterility, different transgenic antisense and/or sense RNAs homologous to the IF ORF1 have been expressed. Increasing the transgene copy number decreases both the expression of an IF-lacZ fusion and the intensity of the female sterile phenotype, demonstrating that IF expression is correlated with sterility. Some transgenes, however, exert their repressive abilities not only through a copy number-dependent zygotic effect, but also through additional maternal and paternal effects that may be induced at the DNA and/or RNA level. Properties of the maternal effect have been detailed: (1) it represses hybrid dysgenesis more efficiently than does the paternal effect; (2) its efficacy increases with both the transgene copy number and the aging of sterile females; (3) it accumulates slowly over generations after the transgene has been established; and (4) it is maintained for at least two generations after transgene removal. Conversely, the paternal effect increases only with female aging. The last two properties of the maternal effect and the genuine existence of a paternal effect argue for the occurrence, in the IF regulation pathway, of a cellular memory transmitted through mitosis, as well as through male and female meiosis, and akin to epigenetic phenomena.

Aging↗
PubMed1998

Rapid evaluation in Escherichia coli of antisense RNAs and ribozymes.

The characterization of a simple bacterial system using commercially available plasmids and strains, developed to assess the effectiveness of trans-acting (antisense RNA and ribozymes) RNA in Escherichia coli, is reported. This system was used to test various trans-acting RNA molecules against the expression of the I factor, a functional transposable element from Drosophila melanogaster. For this target, results indicate that antisense RNA efficiency depends on the hybridization length between sense and antisense RNA. The introduction of a single hammerhead ribozyme within the antisense RNAs does not increase its inhibitory activity. These predictions were subsequently confirmed in Drosophila melanogaster.

Animals↗
PubMed1993

Effect of combination treatment with zanoterone (WIN 49596), a steroidal androgen receptor antagonist, and finasteride (MK-906), a steroidal 5 alpha-reductase inhibitor, on the prostate and testes of beagle dogs.

The effects of the steroidal androgen receptor antagonist zanoterone (WIN 49596) and the steroidal 5 alpha-reductase inhibitor finasteride (MK-906) either alone or in combination on prostatic size, histomorphology, and biochemistry were determined in the intact male dog. Additionally, the effects of treatment with zanoterone and/or finasteride on testicular size, serum testosterone and LH levels, and spermatogenesis were determined in the same dogs. Daily oral treatment for 16 weeks with either zanoterone alone at 10 mg/kg.day or finasteride alone at 1.0 mg/kg.day reduced (P < 0.05) the size of the prostate, resulted in mild to moderate diffuse glandular atrophy of the prostate, and decreased prostatic DNA and prostatic arginine esterase (the primary canine prostatic protein) levels compared to those in intact controls. These changes occurred with no effect on testicular weight, testicular histomorphology, daily sperm production, or serum LH levels. Serum testosterone concentrations were increased (P < 0.05) approximately 3-fold in the 10 mg/kg.day zanoterone treatment group compared to those in intact controls. Combination treatment of male dogs for 16 weeks with zanoterone (10 mg/kg.day) plus finasteride (1.0 mg/kg.day) orally also reduced (P < 0.05) prostate size, resulted in moderate to marked diffuse prostatic glandular atrophy, and decreased prostatic DNA and arginine esterase levels more than either drug alone, without affecting testicular size, testicular histomorphology, serum LH concentrations, or serum testosterone concentrations compared to those in intact controls. The effects of combination treatment with zanoterone and finasteride on prostatic size; histomorphology; and DNA, arginine esterase protein, and arginine esterase mRNA levels were similar to those observed in castrate controls. In addition, in situ estimates of prostatic size using transrectal ultrasonography indicated that the median time to 70% prostatic regression in dogs administered combination zanoterone plus finasteride was similar to that in castrate controls (9.6 and 9.3 weeks, respectively), indicating that the combination was more effective in causing prostatic regression than either drug alone. Finally, at the dosages used, no adverse effects of combination treatment with zanoterone plus finasteride on testicular or other major body organ weights were observed. Based on these results, combination therapy using zanoterone and finasteride for the treatment of human androgen-dependent disorders such as benign prostatic hyperplasia and prostate cancer has potential utility.

Androstenes↗
PubMed1988

Effects of the detergent sucrose monolaurate on binding of amphotericin B to sterols and its toxicity for cells.

Amphotericin B (AmB) is a potent antifungal agent used to treat patients with systemic mycoses. The cytotoxicity of AmB is related to its binding to membrane sterols and its clinical usefulness is based on its greater affinity to ergosterol, the fungal sterol, compared to the mammalian cell sterol, cholesterol (1-3). Here we report that sucrose monolaurate (L.S.) decreased the binding of AmB to cholesterol without interfering with its binding to ergosterol. Furthermore, the toxicity of AmB for mouse erythrocytes (RBC) and cultured mouse fibroblasts, L-929, cells was significantly decreased by low concentrations of L.S., whereas under the same conditions, its toxicity for Candida albicans was unaffected. We observed a very good correlation between the spectroscopic and cell studies. The results reported here on the effects of L.S. on the selectivity of AmB toxicity for fungal cells compared to animal cells and the relative nontoxic nature of sugar esters suggest a potential for compounds of this type to enhance the therapeutic index of AmB.

Amphotericin B↗
PubMed1986

Time course of long-term placebo therapy effects in angina pectoris.

A cohort of thirty-five patients with angina pectoris were followed-up for six months with placebo as the only anti-anginal treatment apart from short-acting nitroglycerin. Only patients with at least five attacks per week were entered into the study. Prior to the study, their average number of attacks per week was 10.3(+/- 0.9) and their average nitroglycerin tablet consumption per week was 10.6(+/- 1.2). After admission into the study, the individual dosage of placebo could be blindly titrated during the first eight weeks. Once an adequate dosage was found, it was continued for 6 months. The primary end-point was predefined success or failure of the placebo treatment. Failure was assessed on the lack of improvement, occurrence of 'side-effects', or need for other anti-anginal treatment. In 27 patients, the placebo treatment was said to be a success (95% confidence limits of the percentage of success: 60-90%). No severe cardiac event occurred (confidence limits: 0-10%). Six patients developed 'side-effects'. The number of attacks per week decreased by 48% (P less than 0.0001) during the titration period (8 weeks) and by 77% during the whole 6 months. Exercise test improved, however, less markedly.

Adult↗
PubMed1986

Failure of a pure anti-platelet drug to decrease the number of attacks more than placebo in patients with Raynaud's phenomenon.

Fifty-eight patients with Raynaud's phenomenon were randomly allocated in a six week double-blind clinical trial in parallel groups to compare the efficacy of a pure antiplatelet agent, ticlopidine (250 mg b.i.d.) with that of a placebo. There was no significant difference between the two treatments in percent reduction of weekly number of attacks and in subjective improvement assessed by both patient and investigator. It is unlikely that platelets are involved in the mechanisms of Raynaud's crisis.

Adult↗
PubMedDate not supplied

Congenital erythropoietic porphyria: prenatal diagnosis and autopsy findings in two sibling fetuses.

Congenital erythropoietic porphyria is an autosomal recessive disease characterized by a deficiency of uroporphyrinogen III cosynthetase activity, with diffuse tissue accumulation of specific type I porphyrins. The diagnosis of this disease was made in two fetuses, who were siblings, and from a Caucasian nonconsanguinous family. The first fetus died in utero with hydrops fetalis and anemia, but without an etiopathogenic diagnosis. In the second case, the diagnosis was based on pink fluorescence of the amniotic fluid examined fortuitously in sunlight. DNA analysis showed that the fetus was heteroallelic for the mutation C73R. The autopsy showed brown skin, and at histological examination, porphyrin pigment was deposited in many tissues. Retrospectively, similar deposits were found in the tissues of the first fetus.

Adult↗
PubMedDate not supplied

Two-liquid-phase slurry bioreactors to enhance the degradation of high-molecular-weight polycyclic aromatic hydrocarbons in soil.

High-molecular-weight (HMW) polycyclic aromatic hydrocarbons (PAHs) are pollutants that persist in the environment due to their low solubility in water and their sequestration by soil and sediments. The addition of a water-immiscible, nonbiodegradable, and biocompatible liquid, silicone oil, to a soil slurry was studied to promote the desorption of PAHs from soil and to increase their bioavailability. First, the transfer into silicone oil of phenanthrene, pyrene, chrysene, and benzo[a]pyrene added to a sterilized soil (sandy soil with 0.65% total volatile solids) was measured for 4 days in three two-liquid-phase (TLP) slurry systems each containing 30% (w/v) soil but different volumes of silicone oil (2.5%, 7.5%, and 15% [v/v]). Except for chrysene, a high percentage of these PAHs was transferred from soil to silicone oil in the TLP slurry system containing 15% silicone oil. Rapid PAH transfer occurred during the first 8 h, probably resulting from the extraction of nonsolubilized and of poorly sorbed PAHs. This was followed by a period in which a slower but constant transfer occurred, suggesting extraction of more tightly bound PAHs. Second, a HMW PAH-degrading consortium was enriched in a TLP slurry system with a microbial population isolated from a creosote-contaminated soil. This consortium was then added to three other TLP slurry systems each containing 30% (w/v) sterilized soil that had been artificially contaminated with pyrene, chrysene, and benzo[a]pyrene, but different volumes of silicone oil (10%, 20%, and 30% [v/v]). The resulting TLP slurry bioreactors were much more efficient than the control slurry bioreactor containing the same contaminated soil but no oil phase. In the TLP slurry bioreactor containing 30% silicone oil, the rate of pyrene degradation was 19 mg L(-)(1) day(-)(1) and no pyrene was detected after 4 days. The degradation rates of chrysene and benzo[a]pyrene in the 30% TLP slurry bioreactor were, respectively, 3.5 and 0.94 mg L(-)(1) day(-)(1). Low degradation of pyrene and no significant degradation of chrysene and benzo[a]pyrene occurred in the slurry bioreactor. This is the first report in which a TLP system was combined with a slurry system to improve the biodegradation of PAHs in soil.

Biodegradation, Environmental↗