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Biomedical subjects

B Fournier

Publications and source records attributed to B Fournier.

At least 73 records · Page 4Linked to original sources
PubMed1996

Effects of apo B and apo E gene polymorphisms on lipid and apolipoprotein concentrations after a test meal.

The role of apo B signal peptide and apo E polymorphisms, and individual factors (age, sex, etc.) have been investigated on the interindividual variability of the postprandial response of 274 subjects ingesting a 1.260-KJ milkshake. The mean postprandial response, observed during 4 h, is significantly positive for total cholesterol (P < 0.005), LDL-cholesterol (P < 0.0001), triglycerides (P < 0.001), apo E (P < 0.0001) and glucose (P < 0.0001), whereas HDL-cholesterol, apo A-I and apo B do not present mean postprandial variation. Independently of the mean response, some parameters present a large interindividual variability of response, which is significantly influenced by cofactors, such as weight or BMI, for total and LDL-cholesterol, apo B and apo E or tobacco use for HDL-cholesterol. Sex has no effect on any lipid levels. Total, LDL-cholesterol and apo E responses are correlated with their corresponding fasting values. ApoB signal peptide polymorphism is not involved in the postprandial responses, whereas apo E polymorphism explains a significant part of the variability of HDL-cholesterol and apo A-I responses.

Adult↗
PubMed1996

Broadband ultrasound attenuation imaging: a new imaging method in osteoporosis.

The purpose of this study was to evaluate the usefulness in osteoporosis of a new ultrasound imaging device able to create a parametric image of broadband ultrasound attenuation (BUA) at the os calcis. Three regions of interest were located in the great tuberosity of the os calcis. Precision was evaluated in 37 patients. Calcaneal bone mineral density (BMD) and BUA were compared in 33 patients. In 236 patients (including 77 with osteoporotic fractures), BUA and lumbar and femoral BMD measurements were performed. The measurements were compared using correlation coefficients. Their clinical value was estimated by comparisons of the results between patients with fractures and age-matched controls, using comparisons of the means, areas under the ROC curves, and logistic regression. Precision was in a 1.4-3.3% range. Local BUA and BMD were highly correlated (r = 0.88). Significant correlations were found between BUA and lumbar (r = 0.56) and femur (r = 0.66) BMD. In multiple regression, years since menopause and weight were significant predictors of BUA. Patients with fractures had lower BUA and BMD than age-matched controls. BUA showed the largest difference between the two populations (13-16%). Areas under the ROC curves were similar for BUA and BMD. Logistic regression after adjustment for confounding factors showed that BUA discriminated between fracture and nonfracture subjects. Broadband ultrasound attenuation imaging improves the reproducibility of ultrasound measurements. It may be useful in osteoporosis, due to its good discriminating value.

Adult↗
PubMed1996

Ultrasound parametric imaging of the calcaneus: in vivo results with a new device.

An ultrasound transmission scanning system was constructed to make in vivo parametric images of the acoustic properties of the heel. Broadband ultrasonic attenuation (BUA) images were obtained in transmit mode by using a pair of broadband focused transducers (center frequency 0.5 MHz, diameter 29 mm, focus 50 mm) immersed in a water bath at room temperature. With these characteristics, the theoretical beam width at the focus was approximately 5 mm. The total duration of the acquisition period was 3 minutes. Comparison of the BUA image and the radiograph of the calcaneus was possible in one case and showed that all the anatomical details could be identified. The images reported here demonstrate the wide range of BUA found in both the whole bone and within a ROI centered in the posterior part of the bone thus reinforcing the idea of tremendous heterogeneity of the acoustic properties of bone. This suggests that the accurate control of the position of the measurement site is of the utmost importance for between-subject comparison and for repetitive measurements. We proposed a new method, the likelihood image, as an efficient way of highlighting the regions of the image suspected to be subject to waveform distortion. It could be used to guide the selection of the optimal measurement site. Our results suggest that ultrasound parametric imaging has the potential for enhancing the current ultrasound technique by (1) allowing reproducible, repetitive measurements, (2) permitting the selection of similar optimal measurement sites in all subjects, and (3) avoiding accuracy errors due to waveform distortion.

Adult↗
PubMed1996

In-vitro susceptibility of Klebsiella oxytoca strains to 13 beta-lactams in the presence and absence of beta-lactamase inhibitors.

The susceptibility of Klebsiella oxytoca isolates was tested by an agar diffusion method (167 strains collected in six countries) and an agar dilution method (38 strains). Multivariate analysis of inhibition zone diameters by principal component analysis clearly individualised four susceptibility patterns, including the phenotype of strains overproducing beta-lactamase and resistant to penicillins, first-generation cephalosporins, cefuroxime and aztreonam, but susceptible to ceftazidime. This phenotype was different from that conferred by plasmid-mediated extended-spectrum beta-lactamases; strains expressing these enzymes were also resistant to ceftazidime and cefotaxime. The bla(oxy) gene from K. oxytoca was introduced into Escherichia coli and K. oxytoca recipients and conferred increased resistance to beta-lactams in the recipient cells. Clavulanic acid was effective in association with piperacillin (MIC decreased 36-fold), ceftriaxone (35-fold) and aztreonam (19-fold) against overproducing strains, in spite of a relatively high IC50 (0.3 microM). Sulbactam (IC50, 400 microM) was ineffective in this context when combined with piperacillin (MIC decreased 1.5-fold), ceftriaxone (1.6-fold) and aztreonam (1.6-fold). The inhibitory activity of tazobactam (IC50, 8.2 microM) was heterogeneous depending on the strain and the beta-lactam with which it was combined. When combined with piperacillin or ceftriaxone little potentiation in antibiotic activity occurred (MIC decreased 3.9-fold and 4.5-fold, respectively); however, tazobactam plus aztreonam resulted in a 50-fold decrease in MIC of antibiotic.

Enzyme Inhibitors↗
PubMed1996

Chromosomal beta-lactamase genes of Klebsiella oxytoca are divided into two main groups, blaOXY-1 and blaOXY-2.

The chromosomally encoded beta-lactamase gene (blaOXY-2) of the wild-type Klebsiella oxytoca SL911 was cloned and sequenced. Its nucleotide sequence similarity with the previously sequenced K. oxytoca beta-lactamase gene (blaOXY-1) (Y. Arakawa, M. Ohta, N. Kido, M. Mori, H. Ito, T. Komatsu, Y. Fujii, and N. Kato, Antimicrob. Agents Chemother. 33:63-70, 1989) is 87.3%, and its amino acid similarity is 89.7%. This group of K. oxytoca beta-lactamases is related to chromosomal beta-lactamases of Citrobacter diversus, Proteus vulgaris, and Yersinia enterocolitica and to the plasmid-mediated extended-spectrum beta-lactamases MEN-1 and Toho-1. By colony hybridization with 86 strains susceptible and resistant to aztreonam, isolated in six countries, K. oxytoca beta-lactamase genes hybridized with either a specific blaOXY-1 DNA probe (668 bp) or a blaOXY-2 DNA probe (723 bp). Thus, beta-lactamase genes could be divided into two groups: blaOXY-1 (47% of the strains) and blaOXY-2 (53% of the strains). A study of isoelectric points confirmed the great variability reported in the literature. However, the two beta-lactamase groups were each represented by four different pIs: for OXY-2, 5.2, 5.7, 6.4, and 6.8, with the 5.2 form representing 59% of all OXY-2 enzymes, and for OXY-1, 7.1, 7.5, 8.2, and 8.8, with the 7.5 form representing 88% of all OXY-1 enzymes.

Amino Acid Sequence↗
PubMed1996

beta-lactamase gene promoters of 71 clinical strains of Klebsiella oxytoca.

beta-Lactamase gene promoters of 45 clinical Klebsiella oxytoca isolates resistant to beta-lactams and exhibiting beta-lactamase hyperproduction differed from those in 26 susceptible strains. Direct sequencing revealed one mutation in either the -10 or -35 conserved sequences: a G-to-A transition of the fifth base (67%) or a G-to-T transversion of the first base of the -10 sequence (27%) or a T-to-A transversion in the fourth base in the -35 sequence (4%). One strain carried both the -10 transition and the -35 transversion.

Base Sequence↗
PubMed1996

Stimulation of creatine kinase specific activity in human osteoblast and endometrial cells by estrogens and anti-estrogens and its modulation by calciotropic hormones.

We have previously demonstrated sex-specific stimulation of creatine kinase specific activity (CK) in bone cells both in vivo and in vitro, in primary culture cells derived from rat and human bone and in established human bone-derived cell lines. We found that the female-derived cell line, SaOS-2, responded to 17 beta-estradiol (E2) by increased CK specific activity. The effects of E2 on the CK activity in SaOS-2 cells was inhibited by 100-fold excess of 4-hydroxytamoxifen (Tam) as well as by the other antiestrogen, ICI 164,384. Tam by itself had some stimulatory effect whereas ICI 164,384 showed no estrogenic activity. We also demonstrated the estrogenic-like effect of another anti-estrogen, raloxifene (Ral), which is agonist only in the SaOS-2 osteoblast-like cells but not in the human endometrial, Ishikawa cell line. Ishikawa cells respond to E2 and to Tam by increased CK activity. In both osteoblasts and endometrial cell lines, Ral and Tam were inhibitory in the presence of E2. The effects of E2 on SaOS-2 cells are at least partially mediated by the estrogen receptor (ER) at the level of transcription as demonstrated by transient transfection experiments using the human creatine kinase promoter chloramphenicol acetyltransferase in these cells. Pretreatment of SaOS-2 with calcitropic hormones, either 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) or human parathyroid hormone (1-34) (hPTH(1-34)) increased the stimulation of CK by E2 by 40-60% relative to E2 alone and significantly increased the sensitivity of the cells to E2 by lowering the effective hormonal dose needed for stimulation of CK by E2 by 100-fold. This stimulatory effect of pretreatment of the cells with 1,25(OH)2D3 was due to a 2.5-fold increase in the level of ER expression as measured directly by enzyme immunoassay in the SaOS-2/1 subline. The increase in the responsiveness to E2 by hPTH(1-34) was not due to an increase in ER level in the cells. We can conclude that in cell cultures as in vivo, Ral shows different effects depending on the cell type, namely estrogenic-like activity in skeletal cells but not in uterine cells. We can also conclude that as with rat-derived cells, in bone cells derived from human bone 1,25(OH)2D3 increased the sensitivity to E2 due to an increase in the number of ER in the cells, whereas PTH(1-34) augmented the response to E2 without increasing ER, by another, as yet unknown, mechanism. These studies suggest that the treatment of pathological bone disorders may be improved by combined hormone therapy.

Calcitriol↗
PubMed1996

[Isolation and cryopreservation of human islets of Langerhans].

Islet transplantation represents an alternative to whole pancreas transplantation for the treatment of patients suffering from diabetes type I. The transplantation of a sufficient number of islets is an essential condition for successful allograft. Islet cryopreservation allows the storage of islet preparations for subsequent pooling, at the time of transplantation, of cryopreserved islets with a fresh preparation in order to increase the mass of transplanted pancreatic endocrine tissue. From May 1994 to April 1995, islets were isolated from 22 human pancreases using a modified automated method, and 19 preparations were cryopreserved. The function of cryopreserved islets was tested in vitro (static incubation and perifusion). The results of static incubation experiments confirmed that the insulin secretion of cryopreserved human islets in response to glucose stimulation was comparable to the response of islets that have not been frozen. In static incubation experiments, the mean (+/- SEM) insulin secretion of islets, prior to cryopreservation, was 239.3 (+/- 58.9) and 479.5 (+/- 59.5) pg/islet/15 min at 2.8 mM glucose and 16.7 mM glucose respectively. The mean (+/- SEM) insulin secretion of cryopreserved islets was 274 (+/- 103.2) and 468.5 (+/- 191.9) pg/islet/15 min at 2.8 mM and 16.7 mM glucose respectively. The perifusion experiments also demonstrated a significant increase of insulin secretion from cryopreserved islets perifused with a stimulating glucose concentration. Our experiments allow us to envisage the use of cryopreserved islet preparations for allotransplantation in diabetic patients.

Adult↗
PubMed1996

Combined islet-lung transplantation in a cystic fibrosis patient.

The prevalence of insulin-dependent diabetes mellitus (IDDM) in cystic fibrosis patients ranges from 2 to 8% and glucose intolerance up to 15%. In recent years, lung transplantation has helped to prolong life expectancy of cystic fibrosis patients and represents 10 to 30% of all indications for lung transplantation. The postoperative need for immunosuppressive therapy using diabetogenic agents has decompensatory effects on glucose regulation and will probably increase the number of insulin-dependent cystic fibrosis patients. We report the case of an insulin-dependent cystic fibrosis patient transplanted with a combined islet-lung allograft. The pre-transplantation C-peptide level was below 0.04 nmol/l and preoperative insulin requirement was some 100 U per day. A sequential bipulmonary lung transplantation was performed and, using the pancreas of the same donor, we isolated and purified the islets of Langerhans by a modified automated method. We obtained 232,200 islets equivalent, which were injected into the liver by portal embolization. The postoperative course was uncomplicated, the insulin requirement decreased to 50% of the preoperative need and the C-peptide value increased to normal values and remained with the normal range during a follow-up period of 15 months. In conclusion, we believe that, besides type I diabetic patients, insulin-dependent cystic fibrosis patients with a negative C-peptide value could also be good candidates for combined islet-lung allotransplantation.

Adult↗
PubMed1996

[Paraneoplastic pemphigus in chronic lymphocytic leukemia].

INTRODUCTION: Paraneoplastic pemphigus is an autoimmune bullous disease described by precise clinical, histological and immunological features presented by Anhalt in 1990. Prognosis is very severe and depends on the associated neoplasia and the gravity of the mucosal damage. CASE REPORT: Paraneoplastic pemphigus was diagnosed in a 62-year-old man with chronic lymphoid leukemia. The course was favorable up to one-year follow-up after general corticosteroid therapy. DISCUSSION: This case illustrates that paraneoplastic pemphigus can be controlled by general corticosteroids and would suggest the severe prognosis may be improved.

Glucocorticoids↗
PubMed1996

Reticulocytes: reference limits.

Healthy reference ranges for the total peripheral reticulocyte count and its three subpopulations, LFR (low fluorescence ratio), MFR (middle fluorescence ratio) and HFR (high fluorescence ratio) were established on 1219 healthy subjects. Samples were taken from subjects of both sexes with ages ranging from 4 to over 60 years. The observed ranges were found to be different between males and females for the group over 20 years old, while there was no difference between sexes found at the age between 4 and 19 years.

Adolescent↗
PubMed1995

The bone-specific estrogen centchroman inhibits osteoclastic bone resorption in vitro.

There is considerable interest in identifying bone-specific estrogen-like compounds with beneficial activities on bone and the cardiovascular system, but lacking side effects on the reproductive system. Two such compounds are currently under clinical investigation -raloxifene (Lilly) and centchroman (Novo-Nordisk). There is evidence suggesting that 17 beta-estradiol can inhibit osteoclastic bone resorption although this is somewhat controversial. Therefore, we examined the effect of centchroman and raloxifene, as well as 17 beta-estradiol, in the in vitro bone slice assay, where the direct effect of compounds on osteoclast activity can be assessed. Centchroman (0.001 - 1 microM) dose-dependently inhibited osteoclastic bone resorption up to 70% at 1 microM (p = 0.007) with an IC50 = 0.1 microM, while in contrast, raloxifene had no significant effect on bone resorption over the same dose range. 17 beta-estradiol (0.0001 - 1 microM) had a modest but significant inhibitory effect on resorption (40%, p < 0.05) at 1 microM, but no effect at lower physiological/therapeutic concentrations. Centchroman (1 microM) inhibited osteoclast cytoplasmic spreading by 32%, while raloxifene and 17 beta-estradiol were without effect. These results show that centchroman at therapeutic concentrations (ED50 approximately 1 mg/kg in animal models) is a potent inhibitor of osteoclastic bone resorption in vitro, suggesting that bone-specific estrogen-like molecules may have different mechanisms of action.

Animals↗
PubMed1995

Clinical approach to inherited peroxisomal disorders.

At least 21 genetic disorders have now been found that are linked to peroxisomal dysfunction. Whatever the genetic defect might be, peroxisomal disorders should be considered in various clinical conditions, dependent on the age of onset. The prototype of peroxisomal disorders is represented by 'classical' Zellweger syndrome (ZS) which is the most severe disorder combining all the characteristic symptoms. ZS is characterized by the association of errors of morphogenesis, severe neurological dysfunction, neurosensory defects, regressive changes, hepatodigestive involvement with failure to thrive, usually early death, and absence of recognizable liver peroxisomes. Other peroxisomal disorders (pseudo-Zellweger syndrome, neonatal adrenoleukodystrophy (NALD), pseudo-neonatal adrenoleukodystrophy, rhizomelic chondrodysplasia punctata (RCDP), and hyperpipecolic acidaemia) share some of these symptoms, but with varying organ involvement, severity of dysfunction, and duration of survival. The diagnosis should not cause difficulty when all the characteristic manifestations are present. Depending on the main presenting sign, peroxisomal disorders in neonates should be suspected in two categories of circumstances: polymalformative syndrome with craniofacial dysmorphism, and severe neurological dysfunction. During the first 6 months of life, the predominant symptoms may be hepatomegaly, prolonged jaundice, liver failure, anorexia, vomiting and diarrhoea leading to failure to thrive resembling a malabsorption syndrome; severe psychomotor retardation, hearing loss and ocular abnormalities become evident. Beyond 4 years of age, behavioural changes, intellectual deterioration, visual impairment and gait abnormalities may be the presenting symptoms. Independently of the clinical symptoms and age of onset, most peroxisomal disorders described so far can be clinically screened by recordings of electroretinogram, visual-evoked responses, and brain auditory-evoked responses, which are almost always abnormal. Nine of the 17 peroxisomal disorders with neurological involvement are associated with an accumulation of very long-chain fatty acids (VLCFA), which suggests that assay of plasma VLCFA should be used as a primary test. However, assays of plasma phytanic acid and plasma/urine bile acid intermediates should also be performed in view of the recent reports of atypical chondrodysplasia variants (without rhizomelic shortening) and isolated trihydroxycholestanoic aciduria. The differential diagnoses in various clinical conditions and age periods are discussed.

Child↗
PubMed1995

Apo B signal peptide insertion/deletion polymorphism is involved in postprandial lipoparticles' responses.

The changes in postprandial concentrations of five lipoparticles (LpC-III, LpC-III:B, LpC-IIInoB, LpA-I and LpA-I:A-II) were studied on 144 apparently healthy (71 male and 73 female) subjects during the 4 h following the ingestion of a 1.260 kJ milkshake. The influence of apo B signal peptide polymorphisms, apo E polymorphism, and other factors including age, gender, BMI, tobacco and alcohol consumption on the postprandial responses of lipoparticles was investigated. Apo-A-I-containing lipoparticles were not influenced during the 4 h following the test meal except for LpA-I:A-II, which decreased in women. LpA-I:A-II is the only particle that showed a gender-dependent change in postprandial concentration. Apo-CIII-containing lipoparticles showed significant postprandial variations. Particles containing both apo B and apo C-III (total LpC-III and LpC-III:B), mainly present in VLDL fraction, had significantly different postprandial responses among the genotypes of the apo B signal peptide polymorphism. Homozygotes for Del allele showed a decrease of LpC-III:B concentrations over the 4 h, whereas Ins/Ins homozygotes and Ins/Del heterozygotes had a peak in concentration at 2 h. The apo B signal peptide polymorphism explained 2.3% of the variance of LpCIII:B, whereas apo E polymorphism did not influence the postprandial concentrations of any lipoparticles.

Adult↗
PubMed1995

Action of linoleic acid on phospholipase C activity at the rectal level of the African locust under the control of protein kinase C.

Linoleic acid (18:2n-6), linolenic acid and eicosatrienoic acid stimulated fluid reabsorption in locust rectum. Only 18:2n-6 was able to enhance phospholipase C activity, inositol(1,4,5) trisphosphate production and to increase cytosolic free Ca2+ concentrations in epithelial cells via the opening of L-type Ca2+ channels. These effects resemble those exerted by neuroparsin, an antidiuretic neuronal hormone extracted from the storage lobes of the locust corpora cardiaca. As for neuroparsin, the effects of 18:2n-6 were abolished after pre-treatment with the protein kinase C inhibitor, polymyxin B. The results were consistent with a regulation of neuroparsin-sensitive phospholipase C activity by 18:2n-6 under control of protein kinase C, possibly by increasing membrane fluidity. Cyclooxygenase inhibitors attenuated the effects of 18:2n-6. This demonstrated that the results should be produced via the metabolites of 18:2n-6 HODEs rather than the PUFA itself.

8,11,14-Eicosatrienoic Acid↗