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Biomedical subjects

F Rey

Publications and source records attributed to F Rey.

At least 19 recordsLinked to original sources
PubMed2003

Sex reversal effects on Caiman latirostris exposed to environmentally relevant doses of the xenoestrogen bisphenol A.

Exposure to environmental contaminants known as endocrine disruptors (EDs) alters the development and function of reproductive organs in several species. Bisphenol A (BPA) is an estrogenic chemical that leaches from dental materials and plastic food and beverage containers. BPA has been found in sewage, surface and drinking water, and therefore poses a potentially significant risk for human and wildlife. Prenatal exposure of rodents to environmentally relevant doses of BPA alters the development of the reproductive organs of male and female offspring. Species with temperature dependent sex determination (TSD) could act as sentinels of ecosystem health by providing sensitive biomarkers of endocrine disruptor's effects. We selected Caiman latirostris as an animal model to study endocrine disruption caused by BPA. The aim of this study was to determine whether exposure in ovum to BPA could cause estrogen-like effects on the reproductive system of C. latirostris. Sex determination and gonadal histoarchitecture were the endpoints evaluated after in ovum exposure to different doses of BPA and 17beta-estradiol (E(2)). We confirmed that C. latirostris is a species with TSD and additionally demonstrated that BPA causes estrogen-like developmental effects by reversing gonadal sex and altering gonadal histoarchitecture. Differences in responses to BPA and E(2) in our in vivo system were on the order of 100-fold. In contrast published in vitro studies have reported differences on the order of 10,000x or more. These results support the utility of C. latirostris, a species in which sex determination is temperature dependent, as a tool in assessing estrogenic activity in vivo and as a sentinel to monitor EDs in aquatic environment.

Air Pollutants, Occupational↗
PubMed2003

Synthesis of ITQ-21 in OH- media.

ITQ-21 has been synthesized from F- free gels; aluminum can be incorporated and this does not affect the rate of nucleation. The introduction of stoichiometric amounts of NH4F with respect to the number of double four rings (D4R) present in the structure leads to an increase in the nucleation and crystallization rate with a quantitative incorporation of fluoride ions into the solid.

Journal Article↗
PubMed2002

Chrysotile and tremolite asbestos fibres in the lungs and parietal pleura of Corsican goats.

BACKGROUND AND AIMS: Environmental exposures to chrysotile and tremolite from the soil cause pleural plaques and mesothelioma in northeast Corsica. Goats grazing in the contaminated areas inhale asbestos fibres. We used this natural animal model to study whether these exposures actually result in increased fibre burdens in the lungs and parietal pleura. METHODS: Ten goats from areas with asbestos outcrops and two from other areas were slaughtered. Fibre content of lung and parietal pleural samples was determined by analytical transmission electron microscopy. RESULTS: Both chrysotile and tremolite fibres were detected. In the exposed goats, the geometric mean concentrations of asbestos fibres longer than 1 microm were 0.27 x 10(6) fibres/g dry lung tissue and 1.8 x 10(6) fibres/g dry pleural tissue. Asbestos fibres were not detected in the lungs of the two control goats. Chrysotile fibres shorter than 5 microm were predominant in the parietal pleura. Tremolite fibres accounted for 78% and 86% of the fibres longer than 5 microm in lung and parietal pleural samples, respectively. CONCLUSIONS: Environmental exposure in northeast Corsica results in detectable chrysotile and tremolite fibre loads in the lung and parietal pleura of adult goats. Tremolite fibres of dimensions with a high carcinogenic potency are detected in the parietal pleura.

Animals↗
PubMed2001

ITQ-16, a new zeolite family of the beta group with different proportions of polymorphs A, B and C.

ITQ-16 is a new zeolite family formed by polymorphs A, B and C of the beta intergrowth in which the proportion of polymorph C can be controlled by changing the organic structure directing agent and/or by changing the Ge content of the synthesis gel; ITQ-16 can be synthesised either in fluoride or fluoride-free medium and Al can be introduced in the framework giving a material with very strong Brönsted acidity.

Journal Article↗
PubMed2001

Antibody inhibition of the transcriptase activity of the rotavirus DLP: a structural view.

On entering the host cell the rotavirus virion loses its outer shell to become a double-layered particle (DLP). The DLP then transcribes the 11 segments of its dsRNA genome using its own transcriptase complex, and the mature mRNA emerges along the 5-fold axis. In order to better understand the transcription mechanism and the role of VP6 in transcription we have studied three monoclonal antibodies against VP6: RV-238 which inhibits the transcriptase activity of the DLP; and RV-133 and RV-138 which have no effect on transcription. The structures obtained by cryo-electron microscopy of the DLP/Fab complexes and by X-ray crystallography of the VP6 trimer and the VP6/Fab-238 complex have been combined to give pseudo-atomic structures. Steric hindrance between the Fabs results in limited Fab occupancy. In particular, there are on average only three of a possible five Fabs-238 which point towards the 5-fold axis. Thus, Fabs-238 are not in a position to block the exiting mRNA, nor is there any visible conformational change in VP6 on antibody binding at a resolution of 23 A. However, the epitope of the inhibiting antibody involves two VP6 monomers, whereas, those of the non-inhibiting antibodies have an epitope on only one VP6. Thus, the inhibition of transcription may be a result of inhibition of a possible change in the VP6 conformation associated with the transcription of mRNA.

Antibodies, Viral↗
PubMed2001

Influence of selenium supplements on the post-traumatic alterations of the thyroid axis: a placebo-controlled trial.

OBJECTIVE: To investigate whether early selenium (Se) supplementation can modify the post-traumatic alterations of thyroid hormone metabolism, since the first week after trauma is characterised by low plasma Se and negative Se balances. DESIGN: Prospective, placebo-controlled randomised supplementation trial. SETTING: Surgical ICU in a tertiary university hospital. PATIENTS: Thirty-one critically ill trauma patients aged 42 +/- 16 years (mean +/- SD), with severe multiple injury (Injury Severity Score 30 +/- 7). INTERVENTION: Supplementation during the first 5 days after injury with either Se or placebo. The selenium group was further randomised to receive daily 500 microg Se, with or without 150 mg alpha-tocopherol (AT) and 13 mg zinc supplements. The placebo group received the vehicle. Circulating Se, AT, zinc, and thyroid hormones were determined on D0 (= day 0, admission), D1, D2, D5, D10, and D20. RESULTS: Plasma Se, low on D0, normalised from D1 in the selenium group; total T4 and T3 increased more and faster after D2 (P = 0.04 and 0.08), reverse T3 rising less between D0 and D2 (P = 0.05). CONCLUSIONS: Selenium supplements increased the circulating Se levels. Supplementation was associated with modest changes in thyroid hormones, with an earlier normalisation of T4 and reverse T3 plasma levels. The addition of AT and zinc did not produce any additional change.

Adult↗
PubMed2001

Apparent digestibility of crude fibre in ponies fed either a low or high-protein diet.

The question addressed was whether apparent crude fibre digestibility in ponies would change after lowering protein intake from adequate to borderline deficient. Four adult ponies were fed a low- and high-protein diet according to a cross-over design. The diets consisted of grass hay and concentrates and provided either 1.5 or 3.6 g digestible crude protein/kg(0.75) per day. The two whole rations provided 2.4 g crude fibre/kg body weight per day. Apparent crude fibre digestibility was not affected by protein intake (low-protein diet: 42.9 +/- 4.03%; high-protein diet: 38.1 +/- 1.14%, means +/- SE, n=4). The low-protein diet caused a significant increase in the ratio of faecal: urinary nitrogen. It is suggested that, when the low-protein diet was fed, sufficient urea flew from the blood into the intestine and ammonia released in the hindgut was conserved so that microbial growth, and thus fibre fermentation, was maintained.

Animals↗
PubMed1999

The HIV-1 Vpr co-activator induces a conformational change in TFIIB.

Vpr is a HIV-1 virion-associated protein which plays a role in viral replication and in transcription and cell proliferation. We have previously reported that Vpr stimulates transcription of genes lacking a common DNA target sequence likely through its ability to interact with TFIIB. However, the molecular mechanism of the Vpr-mediated transcription remains to be precisely defined. In this in vitro study, we show that the binding site of Vpr in TFIIB overlaps the domain of TFIIB which is engaged in the intramolecular bridge between the N- and C-terminus of TFIIB, highly suggesting that binding of Vpr may induce a change in the conformation of TFIIB. Indeed, with a partial proteolysis assay using V8 protease, we demonstrate that Vpr has the ability to change the conformation of TFIIB. We investigated in this partial proteolysis assay a series of Vpr-mutated proteins previously defined for their transactivation properties. Our data show a correlation between the ability of Vpr-mutated proteins to stimulate transcription and their ability to induce a conformational change in TFIIB, indicating a functional relevance of the Vpr-TFIIB interaction.

Binding Sites↗
PubMed1999

The mutant genotype is the main determinant of the metabolic phenotype in phenylalanine hydroxylase deficiency.

Phenylketonuria and mild hyperphenylalaninemias are allelic disorders caused by mutations in the phenylalanine hydroxylase (PAH) gene. Following identification of the disease-causing mutation in 11 PAH-deficient patients, we tested the activity of the mutant gene products in an eukaryotic expression system. Two mutations markedly reduced PAH activity (A259V and L333F), one mutation mildly altered the enzyme activity (E390G), while the majority of mutant genotypes reduced the in vitro expression of PAH activity to 15-30% of controls. Comparing the predicted residual activity derived from expression studies to the clinical phenotypes of our PAH-deficient patients, we found that homozygosity for the L333F and E390G mutations resulted in severe and mild PAH deficiencies, respectively, both in vivo and in vitro, while compound heterozygosity (L333F/E390G) resulted in an intermediate dietary tolerance. Similarly, in vitro expression studies largely predicted dietary tolerance in compound heterozygotes for the A259V/IVS12nt1 (typical PKU), A259V/A403V, G218V/I65T, and G218V/R158Q mutations (mild variants). Taken together, these results support the view that expression studies are useful in predicting residual enzyme activity and that the mutant genotype at the PAH locus is the major determinant of metabolic phenotype in hyperphenylalaninemias.

Alleles↗
PubMed1999

Diagnosis, treatment, and outcome of pituitary tumors and other abnormal intrasellar masses. Retrospective analysis of 353 patients.

We reviewed the clinical features, essential laboratory data, pituitary imaging findings (computerized tomography and magnetic resonance imaging), management, and outcome of 353 consecutive patients with the presumptive diagnosis of pituitary tumor investigated from January 1984 through December 1997 at University Hospital, Lausanne, Switzerland. In 18 cases primary empty sella turcica was diagnosed, and in 13 cases of pseudacromegaly there were no endocrine abnormalities. The remaining 322 patients disclosed abnormal pituitary masses, including 275 pituitary adenomas, 18 craniopharyngiomas, 6 cases of primary pituitary hyperplasia, 6 intrasellar meningiomas, 6 cases of distant metastases, 4 intrasellar cysts, 2 chordomas, 1 primary lymphoma, and 1 astrocytoma. Biologic data and immunohistochemical analysis of the excised tissues demonstrated that prolactinomas and nonsecreting adenomas (NSAs) were the most frequent pituitary tumors (40% and 39%, respectively), followed by somatotropic adenomas with acromegaly (11%) and Cushing disease (6%). In contrast with the vast majority of NSAs, which significantly expressed glycoprotein hormones in tissue without secreting them, there was a small group of glycoprotein hormone-secreting adenomas (2%), which had a more severe clinical course after surgery. Thirty-eight pituitary masses were incidentally discovered, most of them NSAs. The expansion of pituitary adenomas into the right cavernous sinus was twice as frequent as to the left cavernous sinus. For the differential diagnosis of hyperprolactinemia, basal prolactin (PRL) levels above 85 micrograms/L, in the absence of renal failure and PRL-enhancing drugs, and a PRL increment of less than 30% after thyrotropin-releasing hormone (TRH) accurately ruled out functional hyperprolactinemia due to NSA, and were typical of prolactinomas. For screening and follow-up of acromegaly, basal growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, as well as the paradoxical GH response to TRH (present in 2/3 acromegalic patients), could be used as convenient tools, but the most accurate test for diagnosis and prediction of outcome after therapy was GH (lack of) suppression during oral glucose tolerance test. In Cushing disease, single evening plasma cortisol was as good as the overnight dexamethasone suppression test for screening, and a combined dexamethasoneovine corticotropin-releasing hormone (oCRH) test was as accurate as the long dexamethasone suppression test to confirm the diagnosis. Bilateral inferior petrosal sinus catheterization coupled with oCRH test confirmed the pituitary origin of excess adrenocorticotropic hormone (ACTH) in all patients, including those with normal pituitary on magnetic resonance imaging (50% of the cases). However, this procedure failed to predict tumor localization correctly within the pituitary in 21% of patients. Pituitary cysts, meningiomas, and craniopharyngiomas with an intrasellar component were correctly diagnosed based on pituitary imaging in 75%, 67%, and 44% of cases, respectively. The remainder, as well as the cases of pituitary hyperplasia, metastases, and other less frequent pathologies, were initially diagnosed as NSAs or as masses of unknown nature. When surgery was indicated, pituitary adenomas and other intrasellar masses were operated on by the transsphenoidal route, with the exception of 100% of meningiomas, 83% of craniopharyngiomas, and 10% of NSAs, which were operated on by the transcranial route. Favorable late surgical outcome of prolactinomas could be predicted by a restored PRL response to TRH. However, dopamine agonist (DA) therapy, usually resulting in satisfactory control of PRL levels and in tumor shrinkage, progressively displaced surgery as primary treatment for prolactinomas throughout the study period. After full-term pregnancy, the size of prolactinoma decreased in 7 of 9 patients, and PRL was normal in 2. Surgery was the first treatment for NSAs, with a tumor rela

Acromegaly↗
PubMed1999

DNA repair enzyme uracil DNA glycosylase is specifically incorporated into human immunodeficiency virus type 1 viral particles through a Vpr-independent mechanism.

The Vpr protein, encoded by the human immunodeficiency virus type 1 (HIV-1) genome, is one of the nonstructural proteins packaged in large amounts into viral particles. We have previously reported that Vpr associates with the DNA repair enzyme uracil DNA glycosylase (UDG). In this study, we extended these observations by investigating whether UDG is incorporated into virions and whether this incorporation requires the presence of Vpr. Our results, with highly purified viruses, show that UDG is efficiently incorporated either into wild-type virions or into Vpr-deficient HIV-1 virions, indicating that Vpr is not involved in UDG packaging. Using an in vitro protein-protein binding assay, we reveal a direct interaction between the precursor form of UDG and the viral integrase (IN). Finally, we demonstrate that IN-defective viruses fail to incorporate UDG, indicating that IN is required for packaging of UDG into virions.

Cell Line↗
PubMed1998

Secretion of extracellular factor(s) induced by X-irradiation activates the HIV type 1 long terminal repeat through its kappaB motif.

X-irradiation has been used in the treatment of several human diseases, including AIDS-related-malignancies. X-irradiation might induce the transcription and the replication of human immunodeficiency virus type 1 (HIV-1) and enhance nuclear factor kappa B (NF-kappaB). In the present article we show that the activation of the HIV-1 long terminal repeat (LTR) by direct X-irradiation can be mimicked by coculture of transfected cells with X-irradiated nontransfected (HIV-1-negative) cells. In the human colonic carcinoma cell line HT29, the activation seems to depend on an extracellular factor(s) released by a cell line treated with X-rays. The HIV-1 LTR cis-acting element conferring X-indirect responsiveness was identified as the kappaB tandem motif. The two main nuclear HIV-1 kappaB-binding complexes activated by X-direct and -indirect irradiation were the NF-kappaB p50/p65 and c-Rel/p65 heterodimers. Nuclear NF-kappaB activation was dependent on protein neosynthesis. It was partially inhibited by 100 microM pyrrolidine dithiocarbamate, a potent antioxidant drug, but was not correlated with a significant decrease in cellular IkappaBalpha. Furthermore, X-irradiation induces the expression of several cytokine genes generally associated with stress response and antibodies against interleukin 6 and TNF-alpha partially inhibited the X-indirect activation of the HIV-1 LTR. The use of protein kinase C (PKC)-specific inhibitor and of forskolin, an adenylate cyclase activator, suggests that a PKC-dependent pathway and the cAMP intracellular concentration could play a role in the X-indirect enhancement of HIV-1 LTR transcription in the HT29 cell line. In addition, supernatants of an X-irradiated HT29 cell culture activated the HIV-1 stimulation in infected peripheral blood monocytes.

Antioxidants↗
PubMed1998

A European multicenter study of phenylalanine hydroxylase deficiency: classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype.

Phenylketonuria (PKU) and mild hyperphenylalaninemia (MHP) are allelic disorders caused by mutations in the gene encoding phenylalanine hydroxylase (PAH). Previous studies have suggested that the highly variable metabolic phenotypes of PAH deficiency correlate with PAH genotypes. We identified both causative mutations in 686 patients from seven European centers. On the basis of the phenotypic characteristics of 297 functionally hemizygous patients, 105 of the mutations were assigned to one of four arbitrary phenotype categories. We proposed and tested a simple model for correlation between genotype and phenotypic outcome. The observed phenotype matched the predicted phenotype in 79% of the cases, and in only 5 of 184 patients was the observed phenotype more than one category away from that expected. Among the seven contributing centers, the proportion of patients for whom the observed phenotype did not match the predicted phenotype was 4%-23% (P<.0001), suggesting that differences in methods used for mutation detection or phenotype classification may account for a considerable proportion of genotype-phenotype inconsistencies. Our data indicate that the PAH-mutation genotype is the main determinant of metabolic phenotype in most patients with PAH deficiency. In the present study, the classification of 105 PAH mutations may allow the prediction of the biochemical phenotype in >10,000 genotypes, which may be useful for the management of hyperphenylalaninemia in newborns.

Alleles↗
PubMed1998

Cisplatin, ifosfamide, and vinorelbine combination chemotherapy in stage III-IV non-small-cell lung cancer: a phase II study.

The authors evaluate the combination of three drugs, vinorelbine, ifosfamide, and cisplatin, which have been shown to produce good response rates and a significant gain in survival when any two of them are given together. Seventy-seven untreated patients with inoperable stage III-IV non-small-cell lung cancer from three centers were included. The combination consisted of cisplatin 30 mg/m2 daily, ifosfamide 1,500 mg/m2 daily, mesna 1,500 mg/m2 daily on days 1-3, and vinorelbine 25 mg/m2 daily on days 1 and 8. Four cycles were administered every 4 weeks for a total of 267 cycles, before an assessment for toxicity, effective dose intensity, response rate, and survival was made. Toxicity was mainly hematologic (grade 3-4 neutropenia (15.7%), anemia (8.2%), and thrombopenia (2.6%)) but did not require granulocyte colony-stimulating factors. Objective response rate was 41.1% (95% confidence interval, 29.5-52.9%) in 68 patients suitable for assessment. The mean time to progression and median survival were 7.7 +/- 1.3 months and 11.6 months, respectively. One-year survival was 47.1%. The effective dose intensity of cisplatin and ifosfamide correlated strongly with survival, whereas stage and performance status did not. This study confirms previously reported favorable results for response and survival rates obtained in stage III-IV non-small-cell lung cancer with the vinorelbine, ifosfamide, and cisplatin combination. Respect of a scheduled dose intensity has a clear-cut influence on survival and should be evaluated routinely in future polychemotherapy trials.

Adult↗
PubMed1998

Persistence of parvovirus B19 DNA in testis of patients with testicular germ cell tumours.

Germ cell tumours (GCT) of the testis are the most common malignant tumours occurring in young adults. In view of the young age of patients, the increasing incidence of GCT and the overexpression of wild-type p53 observed in a majority of tumours, the possibility of the involvement of a virus in the development of this cancer was considered. Testicular GCT were analysed for the presence of cytomegalovirus and Epstein-Barr virus (EBV), which are known to cause overexpression of wild-type p53 protein, and parvovirus B19. The testicular tissue of 39 patients with testicular GCT and 12 patients with healthy testicular tissues was tested for presence of viral DNA by PCR. Neither cytomegalovirus nor EBV DNAs were detected in the 39 tumours analysed, but parvovirus B19 DNA sequences were demonstrated in the testicular tissue of 85% (33/39 cases) of patients with GCT. The sera of 16 of the 39 patients with GCT were tested for the presence of parvovirus B19 IgM and IgG. B19-specific IgG was detected in the sera of 11 patients (69%). Only one case was positive for parvovirus B19 IgM, which was also shown to have B19 genome sequences in the serum by PCR, indicating that in a majority of cases an acute B19 infection can be excluded as being the source of the B19 DNA sequences in the testis. B19 DNA could not be detected in normal testicular tissue and thus parvovirus B19 could play a role, direct or indirect, in the development of testicular GCT or have tropism for the tumour cells.

Adolescent↗
PubMed1998

A role for human immunodeficiency virus type 1 Vpr during infection of peripheral blood mononuclear cells.

Studies analysing human immunodeficiency virus type 1 replication in primary cells have demonstrated that Vpr, although dispensable, plays a role along with the matrix (MA) protein in allowing nuclear localization of viral preintegration complexes in non-dividing monocyte-derived macrophages (MDMs). In the current study, experimental infection conditions to analyse the role of Vpr, independently of MA, during infection of PHA/IL-2-stimulated peripheral blood mononuclear cells (PBMC) were designed. It was shown that the absence of Vpr results in a subtle effect on virus production in long-term infection. PCR analysis of the steps of virus retrotranscription during a single cycle of replication in stimulated PBMC revealed that the absence of Vpr alone correlates with an impairment in the nuclear localization of viral DNA. Our data indicate that Vpr is involved in the virus life-cycle during infection of dividing PBMC, presumably as it is during infection of MDMs.

Cells, Cultured↗
PubMed1998

The replicative impairment of Vif- mutants of human immunodeficiency virus type 1 correlates with an overall defect in viral DNA synthesis.

The Vif protein of human immunodeficiency virus type 1 (HIV-1) is essential for the infectivity of virions produced by non-permissive cells. The primary replicative defect of Vif particles involves either synthesis or stability of viral DNA, but the mechanism of this defect is unknown. Here, we report the results of a detailed analysis of HIV-1 DNA synthesis by isogenic Vif- mutants produced by different chronically infected H9 clones, which exhibit different degrees of impairment in their replicative capacity. We found that the degree of impairment of DNA synthesis by the mutant particles always correlated with the degree of their loss of infectivity. This impairment appears to be global, with a defect increasing along with synthesis of longer viral DNA species. We conclude that the primary replicative defect of Vif- virus involves the capacity of the reverse transcription complex of HIV-1 to efficiently elongate viral DNA, resulting in an inability to produce full-length viral DNA genomes.

Cell Line, Transformed↗