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Biomedical subjects

B Fournier

Publications and source records attributed to B Fournier.

At least 55 records · Page 3Linked to original sources
PubMed1998

Human islet allotransplantation: world experience and current status.

Currently type-I diabetes mellitus is treated with exogenous insulin administration, but traditional insulin therapy does not prevent long-term systemic complications and therefore alternatives should be sought. Presently the only option is to substitute the insulin-producing beta cells in order to obtain a more physiological way to deliver insulin. Simultaneous kidney and pancreas transplantation is an established procedure. Pancreas transplantation, however, is a major surgical procedure with a high rate of complications. Transplantation of the isolated insulin-secreting islets of Langerhans is an alternative approach, which is easier and safer than whole organ transplantation. Since 1990, clinical trials of islet transplantation have begun in a few specialized centers worldwide and the International Islet Registry counting 305 human islet allografts at the end of 1995. Insulin independence at 1 year was achieved in 8% of the patients, but 20% of cases showed a graft function with a normal basal C peptide and improved glycemic regulation. We review here the different aspects of human islets of Langerhans allotransplatation, namely historical aspects, indications, isolation and purification procedures and the results obtained.

Cryopreservation↗
PubMed1998

Biological effects of eleven combined oral contraceptives on serum triglycerides, gamma-glutamyltransferase, alkaline phosphatase, bilirubin and other biochemical variables.

The objectives of this paper are to update and quantify the biological effects of the most commonly used oral contraceptives (OC) on 15 biochemical tests currently determined in clinical laboratories and to compare these effects between the different types of OC. The sample population was constituted by 1604 women using combined OCs and the control group comprised 3466 women in the same age range not taking medication. Women taking OC were divided into 11 groups according to the estrogen/progestogen combination. The effects of OCs were studied after adjustment for age, weight, height, body mass index and alcohol and tobacco consumption. The changes observed with the new progestogens were less important than in the past. In comparison with the controls, the mean serum triglyceride concentration was significantly increased by +8.5% to +36.0% (p<0.05 to p<0.001) in each group while those of total cholesterol and gamma-glutamyltransferase were increased only in 3 and 4 estrogen/progestogen combinations respectively. Conversely, the mean concentrations of alkaline phosphatase, total bilirubin, phosphate and albumin were significantly decreased. Using a discriminant analysis, three main groups according to the type of progestogen were defined: cyproterone acetate, DL-norgestrel and levonorgestrel, and all other progestogens. The changes in serum triglyceride concentration induced by OC intake must be considered by the clinician and are useful for taking a clinical and risk decision in an individual woman.

Adolescent↗
PubMed1998

Prolactin induces an inward current through voltage-independent Ca2+ channels in Chinese hamster ovary cells stably expressing prolactin receptor.

There is still only limited understanding of the early steps of prolactin (PRL) signal transduction in target cells. Recent studies have identified some of the essential first steps: these include the rapid association of the PRL receptor with JAK tyrosine kinases and tyrosine phosphorylation of a number of proteins, including members of the signal transducer and activator of transcription (Stats) family. On the other hand, binding of PRL to its receptor is rapidly followed by calcium influx. However, PRL-induced ionic events and the related ionic channels involved have not been clearly established. This work was undertaken to characterise the channels responsible for calcium influx and to obtain an insight into their activation processes. Using the patch-clamp technique in the cell-attached configuration, single Ca2+ channel currents were recorded following PRL application (10 nM) in Chinese hamster ovary (CHO) cells stably expressing PRL receptor (CHO-E32). Statistical analysis showed that the recorded currents were voltage-independent, with a slope conductance of 16 pS. Although these channels were present in excised patches, the fact that PRL was unable to activate them suggested that a soluble cytoplasmic component may be required. Application of the purified inositol phosphate, Ins(1,3,4,5)P4 (2 microM), to the inside of the excised patch membrane activated the voltage-independent 16 pS Ca2+ channel. The open probability (Popen) was enhanced. The inositol phosphates Ins(1,2,3,4,5)P5 and Ins(1,4,5)P3 did not affect channel activity while InsP6 (20 microM) had some effect, although less marked than that of Ins(1,3,4,5)P4. Using the anion-exchange HPLC technique, we then studied the effects of PRL (10 nM) on the turnover of inositol phosphates (InsPs) in CHO-E32. Our studies showed that PRL induces rapid increases in the production of Ins(1,3,4,5)P4 (207% at 30 s), InsP5 (171% at 30 s), and InsP6 (241% at 30 s). Conversely, Ins(1,4,5)P3 showed a transient decrease at 5 s, accompanied by a concomitant increase in Ins(1,3,4,5)P4, suggesting that the former could be transiently phosphorylated to produce the latter. Comparison of the production kinetics of Ins(1,4,5)P3, Ins(1,3,4,5)P4, InsP5, and InsP6 indicated the possibility of additional metabolic routes which have yet to be determined. This study suggests that PRL promotes Ca2+ entry through voltage-independent Ca2+ channels that may be activated by Ins(1,3,4,5)P4 and InsP6.

Animals↗
PubMed1998

[Perceived health and pregnancy: study of several behavioral and environmental determinants among a population of pregnant women].

The aim of this study, based on data of the Centre for Preventive Medicine, is to compare the perceptions women have of their health within a population of pregnant women that was divided into two categories: one group of women who feel they are in a poor health, the others feel they are in good health. The study results seem to differentiate between both the psychological and physical profiles of the two groups of pregnant women. The women who are not followed by a doctor don't seem to have a more negative perception of their health status. It seems, in addition, that the negative perception of health status has not only psychological roots, but also behavioural and environmental ones.

Adolescent↗
PubMed1997

The human peroxisomal multifunctional protein involved in bile acid synthesis: activity measurement, deficiency in Zellweger syndrome and chromosome mapping.

The dehydrogenation of 24R,25R-varanoyl-CoA, the physiological intermediate formed during the peroxisomal breakdown of the bile acid intermediate trihydroxycoprostanic acid, was studied in human liver. The reaction appeared to be catalyzed by two different enzymes. A first one, present in the cytosol, did not discriminate between the four possible varanoyl-CoA isomers and did not require the CoA moiety. The second enzymic activity was associated with peroxisomes and acted only on the 24R,25R-isomer, in which the 24-hydroxy group possesses the D-configuration. The D-specific dehydrogenase is part of a 79 kDa protein which represents the human counterpart of a recently discovered second multifunctional protein in rat liver peroxisomes, named multifunctional protein 2 (MFP-2). Human MFP-2, like its rat counterpart, is also responsible for the formation (by hydratation) of 24R,25R-varanoyl-CoA. A deficiency of MFP-2 in Zellweger liver could be demonstrated immunologically by using antibodies against the rat enzyme and enzymically -- after removal of the cytosol -- by using 24R,25R-varanoyl-CoA. The gene coding for MFP-2 was mapped to chromosome 5q2.3.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1997

Expression of neuroparsin cDNA in insect cells using baculovirus vectors.

The cDNA encoding neuroparsin A, a polytropic neurohormone of the locust, Locusta migratoria, was inserted into the genome of Autographa californica nuclear polyhedrosis virus such that transcription was under control of the p10 promoter. A polypeptide having the same charge and the same apparent molecular weight as the authentic neuroparsin A and that was reactive against neuroparsin immune serum was produced in recombinant virus-infected lepidopteran cell lines but not in control virus-infected cells. The baculovirus-expressed polypeptide was purified by two steps of liquid chromatography (anion exchange and reversed phase) which were previously used to purify the natural neuroparsin. The purified baculovirus-expressed polypeptide enhanced fluid reabsorption of everted rectum preparations, as did the natural neuroparsin. Thus, this gene expression system produced a polypeptide identical to authentic neuroparsin.

Animals↗
PubMed1997

Assessment of the relationship between broadband ultrasound attenuation and bone mineral density at the calcaneus using BUA imaging and DXA.

The purposes of this study was to determine the relationship between broadband ultrasound attenuation (BUA) and bone mineral density (BMD) measured at different regions of the calcaneus with identical site-matched regions of interest (ROIs). Dual-energy X-ray absorptiometry (DXA) measurements of the calcaneus and BUA imaging were performed in 30 women (15 premenopausal and 15 postmenopausal). Four square ROIs were located in the great tuberosity and one square ROI in the foramen calcaneus. A ROI adapted to the shape and size of the whole calcaneus was also considered. All ROIs were analyzed three times with both techniques to minimize intra-observer variability. The correlation coefficient between attenuation and frequency was used as an index of BUA measurement error. Before accepting a measurement of BUA in inhomogeneous material, it could be useful to map the spatial variations of the measurement error. In all ROIs we found the BUA and BMD were strongly related (r = 0.78-0.91, p < 0.001). The correlation between BUA and BMD was slightly higher in the inferior part of the posterior tuberosity than in the superior part and in the foramen calcaneus. The very high correlation between attenuation and frequency found in all ROIs (r = 0.99) suggests that measurement errors of propagation were probably not significant. Ultrasound imaging yields the opportunity for studying the spatial acoustic properties in the calcaneus and their relation to bone mass or structural parameters provided by independent imaging techniques. BUA measured with current transmission techniques reflects mainly bone mass, and microarchitecture to a smaller extent.

Absorptiometry, Photon↗
PubMed1997

Quantitative ultrasound imaging at the calcaneus using an automatic region of interest.

A new approach to measuring bone properties at the calcaneus using ultrasound parametric imaging has recently emerged. However, an additional source of observer-related error is the substantial regional variations in the pattern of ultrasound parameters. The contribution of intra-observer and inter-observer variability to the coefficient of variation can be eliminated using an algorithm which selects the region of interest (ROI) completely automatically. The objective of the present study was the clinical assessment of an automatic ROI for both broadband ultrasonic attenuation (BUA) and speed of sound (SOS) measurement using ultrasound parametric imaging. The automatic ROI was defined as the circular region of lowest attenuation in the posterior tuberosity of the calcaneus. We have tested this algorithm using clinical images of the calcaneus from 265 women. Mean coefficients of variation were 1.6% (95% confidence interval 1.4%-1.9%) and 0.26% (95% confidence interval 0.23%-0.32%) for BUA and SOS respectively (standardized CV was 2.1% for BUA and 2.6% for SOS). Z-scores in an osteoporotic group were -0.61 and -0.52 for BUA and SOS respectively. In healthy women, the age-related decline was -0.50 dB/ MHz per year (0.7%/year) for BUA and -1.2 m/s per year (0.08%/year) for SOS. In the subgroup of healthy postmenopausal women, using stepwise multiple regression, we found that BUA was predicted best by years since menopause (YSM) and weight, with overall model r2 = 0.28; SOS was predicted best by YSM only (r2 = 0.21). Neither the range of biological variation of ultrasound parameters nor the clinical value were affected by the choice of the region of lowest attenuation for measurement. The automatic procedure was totally independent of operator interaction, therefore excluding loss of precision due to intra- or inter-observer variability. The results showed the high precision and robustness of the procedure. These factors make this approach viable for routine clinical use.

Aged↗
PubMed1997

Expression of the estrogen-related receptor 1 (ERR-1) orphan receptor during mouse development.

We studied the expression of the estrogen-related receptor 1 (ERR-1) during mouse embryonic development. ERR-1 is expressed at very early stages in ES cells and at E8.5 in the mesodermal cells of the visceral yolk sac. ERR-1 continues to be expressed later in mesodermal tissues and particularly in heart and in skeletal muscles. This expression persists during all the embryonic development and in adult stage. ERR-1 transcripts level increases during muscle differentiation. Accordingly, we show that ERR-1 expression increases during the myoblast to myotube transition in differentiating C2 myoblastic cells. ERR-1 has also been detected in the nervous system during embryonic development. At E10.5, a high level of ERR-1 transcripts can be observed in differentiated cells of the intermediate zone of the spinal cord which also suggests a role of ERR-1 in the differentiation of the nervous system. The same is observed in the telencephalon vesicules at E13.5. Later, at E15.5 and E17.5, expression persists in the spinal cord but decreases dramatically in the central nervous system. Moreover, ERR-1 expression increases during skin formation and is detected in the stratum spinosum which contains differentiated Malpighian cells. Finally, we also observed ERR-1 in endodermal derivatives such as the epithelium of intestine and urogenital system. The DNA target of ERR-1 has been identified to be the SF-1/FTZ-F1 responsive element (SFRE) and we show in this paper that SF-1/FTZ-F1 and ERR-1 bind to and activate transcription independently through the SFRE element. Our study suggests that ERR-1 may be implicated in numerous physiological or developmental functions, particularly in the muscle, the central and peripheral nervous system and the epidermis. Interestingly, in these various systems ERR-1 expression is correlated with post-mitotic cells stage, suggesting that ERR-1 may play a role in the differentiation process.

Animals↗
PubMed1997

Effects of clonidine and flesinoxan on blood pressure variability in conscious spontaneously hypertensive rats.

The effects of two centrally acting antihypertensive agents, clonidine (0.1 mg/kg/day s.c.) and flesinoxan (1 mg/kg/day s.c.), on short-term blood pressure variability (BPV) were investigated in conscious spontaneously hypertensive rats (SHRs). The drugs were infused subcutaneously during 24 h and 4 weeks by osmotic minipumps. BPV was characterized by spectral analysis. In conscious SHRs, clonidine significantly and preferentially reduced the low frequency (LF; 0.25-0.75 Hz) oscillations of mean arterial pressure (MAP) in short-term (24 h) and long-term (4 weeks) treatments but significantly decreased MAP level only in short-term treatments. In contrast, flesinoxan significantly reduced MAP level whatever the duration of infusion but decreased LF-MAP only in short-term treatments. These results show that centrally mediated inhibition of sympathetic tone by stimulation of either alpha2-adrenoceptors or 5-HT1A (serotonin) receptors can reduce BPV. This effect is independent of the modifications in BP level. The effects of the drugs on baroreceptors may also contribute to the decrease in BPV. The dual properties of clonidine (alpha2-adrenoceptors and imidazoline receptors) may account for its differential effects on BP level and BPV.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1997

Variability of chromosomally encoded beta-lactamases from Klebsiella oxytoca.

The beta-lactamase genes of Klebsiella oxytoca were previously divided into two main groups: bla(OXY-1) and bla(OXY-2). The two beta-lactamase groups were each represented by beta-lactamases with four different pIs. In each group, one form of beta-lactamase is more frequent than the others combined. The beta-lactamase gene of each representative beta-lactamase with a different pI that was not yet sequenced (pIs 5.7, 6.8 [OXY-2], 7.1, 8.2, and 8.8 [OXY-1]) was cloned and sequenced. The susceptibility patterns as well as relative rates and kinetic parameters for beta-lactam hydrolysis revealed that OXY-2 enzymes hydrolyzed several of the beta-lactams that were examined (carbenicillin, cephalothin, cefamandole, ceftriaxone, and aztreonam) at a greater rate than the OXY-1 enzymes did. Comparison of K. oxytoca beta-lactamases with plasmid-mediated extended-spectrum beta-lactamases MEN-1 and TOHO-1 implied that the threonine at position 168 present in OXY-2 beta-lactamase instead of the alanine in OXY-1 could be responsible for its modified substrate hydrolysis. In each group, the beta-lactamase with a variant pI differs from the main form of beta-lactamase by one to five amino acid substitutions. The substrate profile and the 50% inhibitory concentrations revealed that all substitutions differing from the main form of beta-lactamase were neutral except one difference in the OXY-1 group. This substitution of an Ala to a Gly at position 237 increases the hydrolysis of some beta-lactams, particularly aztreonam; decreases the hydrolysis of benzylpenicillin, cephaloridine, and cefamandole, and decreases the susceptibility to clavulanic acid (fivefold increase in the 50% inhibitory concentration).

Amino Acid Sequence↗
PubMed1997

The ERR-1 orphan receptor is a transcriptional activator expressed during bone development.

We studied the expression of estrogen-related receptor ERR-1 during mouse embryonic development. ERR-1 mRNA is present in bones formed by both the endochondral and intramembranous routes, and the onset of its expression coincides with bone formation. By RT-PCR experiments, we found that ERR-1, but not the related receptor ERR-2, is expressed in osteoblastic osteosarcoma cell lines as well as in primary osteoblastic cell populations derived from normal human bone. By gel shift analysis we found that ERR-1 binds as a monomer specifically to the SFRE sequence (SF-1-responsive-element; TCAAGGTCA). Mutation analysis revealed that both the core AGGTCA motif and the TCA 5'-extension are required for efficient ERR-1 binding. In transient transfection assays, ERR-1 acts as a potent transactivator through the SFRE sequence. This effect is cell-specific since ERR-1 activates transcription in the rat osteosarcoma cell line ROS 17.2/8 as well as in HeLa, NB-E, and FREJ4 cells but not in COS1 and HepG2 cells. Notably, the osteopontin (a protein expressed by osteoblasts and released in the bone matrix) gene promoter is a target for ERR-1 transcriptional regulation. Our findings suggest a role for ERR-1 in bone development and metabolism.

Animals↗
PubMed1997

1,25-Dihydroxyvitamin D3 induces the expression of vascular endothelial growth factor in osteoblastic cells.

Angiogenesis is a fundamental process in skeletal development and repair, and previous studies indicate that vascular endothelial growth factor (VEGF), an endothelial cell-specific angiogenic factor, may be involved in bone formation and repair. Therefore, we studied the hormonal regulation of VEGF expression in SaOS-2 osteoblast-like cells, both at the protein level, and at the transcriptional level by transient transfection experiments. 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], increased VEGF expression by approximately 3-fold, and the increase was dose dependent, with maximum stimulation between 1.0 and 10 nM of 1,25-(OH)2D3. Up-regulation of VEGF protein was detected already after 6 h of treatment. VEGF up-regulation was also observed in ROS-17/2.8 and OHS-4 osteoblast-like cells but not in MCF-7 and MDA-MB231 breast carcinoma cells. Dexamethasone (Dex) decreased VEGF expression to 40% of the control, but when added together with 1,25-(OH)2D3, had no effects on the up-regulation of VEGF by 1,25-(OH)2D3. PTH1-34 stimulated weakly VEGF expression, but combined with 1,25-(OH)2D3, resulted in a close to 5-fold stimulation. A 4-day pretreatment of the cells with Dex increased the vitamin D3 receptor expression and resulted in a stronger stimulation of VEGF by 1,25-(OH)2D3, alone or in combination with PTH1-34. The results show that the VEGF promoter is a target of 1,25-(OH)2D3 regulation in osteoblasts, despite the lack of classical vitamin D3 responsive elements. The up-regulation of VEGF in osteoblast-like cells by calciotropic hormones provides additional evidence of the involvement of VEGF in bone metabolism.

Breast Neoplasms↗
PubMed1997

Islet autotransplantation in a cirrhotic liver.

Chronic pancreatitis resulting from alcohol abuse might in some rare cases require a total surgical resection of the pancreas to treat severe local complications. We have learned from the new techniques developed for islet isolation that it is now possible to obtain a sufficient number of good quality islets from one single pancreas to be transplanted into one recipient. We present a case of total surgical pancreatectomy for chronic pancreatitis in a previously non-diabetic patient with immediate islet isolation and autotransplantation. At operation, a cirrhotic liver was found, but no portal hypertension. We still decided to embolize a non purified preparation of endocrine tissue into the liver without alteration of liver function or durable modification of the portal pressure. One year after this procedure, the patient remains insulin-independent with a close to normal glycemic regulation as demonstrated by stimulation tests. Islet autotransplantation does not appear to be generally contra-indicated in the presence of a cirrhotic liver; provided the portal pressure is within normal limits. Under these circumstances, satisfactory glycemic control is achieved.

Blood Glucose↗
PubMed1997

[Orthotopic liver transplantation for familial Portuguese amyloidosis].

Type I familial amyloid polyneuropathy (FAP), or Andrade's disease, is an inherited autosomal dominant disease, always fatal, involving mixed progressive polyneuropathy associated with systemic amyloid deposits. The disease is secondary to mutations of a gene (located on chromosome 18) which encodes for a serum protein, transthyretin. This variant protein is essentially (> 90%) produced in the liver and constitutes the biological marker of the disease. Many surgical teams have established a liver transplantation program for this non-cirrhotic pathology. Between January and August 1994, we performed three orthotopic liver transplantations (OLT) in patients with FAP. The patients were men aged between 30 and 33 years and the mean duration of symptoms was 3 years. The diagnosis of FAP was confirmed by rectal biopsy and detection of the genetic mutation (PCR analysis). All patients presented a severe sensory, motor and autonomic neuropathy with major digestive and urologic dysfunction. Two other patients were not accepted for OLT because of advanced disease with ulcerous lesions of the inferior limbs and cardiopathy. All patients survived with excellent post-operative hepatic function. One month after OLT, one patient had hepatocellular rejection which responded favorably to steroids. Another patient developed post-transfusional B hepatitis 10 months after the graft, but without major hepatic lesions. In the three cases, we observed stabilization of the peripheral neuropathy and an objective improvement of the autonomic affection (neurogenic bladder, diarrhea). The patients who did not undergo transplantation died within a year. Thus, in patients suffering from familial amyloid polyneuropathy OLT must be performed, especially in the early stage of the disease and especially in young patients before serious neurological complications set in.

Amyloid Neuropathies↗
PubMed1997

[Islands of Langerhans autotransplantation after pancreatic resection for benign pathology].

One way to prevent the occurrence of insulin-dependent diabetes after major pancreatic resection is to perform islet of Langerhans autotransplantation. Thus far, we have performed nine autotransplantations. The last three autotransplantations were performed in patients with benign tumoral pathology (one corporeal mucinous cyst, one isthmic insulinoma and one corporeal cystadenoma). In these three cases, we performed a distal 40%, 75% and 80% pancreatectomy respectively, since enucleation was not indicated or not feasible. After resection and removal of the tumoral lesion, pancreatic segments were injected intraductally with collagenase and digested according to a modified semi-automated Ricordi's technique. We obtained 105,000, 415,000 and 144,300 non-purified islets which were then embolized into the liver by intraportal injection during the same operative procedure. After surgery, all patients were insulin-independent. There was no morbidity or mortality. In a patient who presented acute pancreatitis of the residual pancreas five months after transplantation, insulin therapy was introduced. More than one year after the graft, the two other patients remain insulin-independent. In conclusion, we propose islet autotransplantation after pancreatic resection for benign focal pathology, to prevent or delay the occurrence of insulin-dependent diabetes.

Adult↗