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C Roche

Publications and source records attributed to C Roche.

At least 37 records · Page 2Linked to original sources

Dengue: an evaluation of dengue severity in French Polynesia based on an analysis of 403 laboratory-confirmed cases.

We conducted a retrospective study of 403 laboratory-confirmed dengue cases hospitalized in Tahiti between August 1989 and March 1997. According to standard WHO criteria, 337 of these cases were dengue fever (DF) and 64 were dengue haemorrhagic fever (DHF). Of the 10 fatal cases, 6 were DF and 4 were DHF. As an alternative, we used a correspondence analysis procedure to define dengue severity based on basic clinical and biological criteria for which we assigned a severity score, and then selected the 50 most severe cases from this analysis. Of the latter, 17 patients had been classified as DF and 33 as DHF by the WHO criteria. From this analysis, haemorrhages and decreased platelets counts associated with hepatic disorders are the main criteria associated with the severe dengue cases. Thus in our study population, the WHO classification does not account for the overall severity of dengue; hepatic failure should be considered as a specific severe form of dengue since plasma leakage, which is the pathophysiological hallmark of DHF, is only one of the pathogenic mechanisms leading to severity.

Adolescent↗

[Angiogenesis and endocrine tumors].

Endocrine tumors are characteristically hypervascularized. This property recalls that of normal endocrine tissues, which possess a dense and specialized capillary network. The cellular and molecular mechanisms of the angiogenesis process associated with endocrine tumorigenesis are poorly known. Most normal endocrine cells constituvely express high levels of angiogenic factors, such as VEGF, which likely play an important role in the development of the characteristic vascular architecture of normal endocrine tissues. Clinical and experimental data suggest that a surexpression of such angiogenic factors is unlikely to be involved in the induction of the angiogenic process associated with endocrine tumorigenesis. In contrast, according to some experimental observations, the loss of endocrine-specific anti-angiogenic factors may be required for the initiation of the angiogenic process and the transition from endocrine hyperplasia to endocrine neoplasia. Such inhibitory factors remain to be identified and characterized. A better understanding of the mechanisms of angiogenesis in endocrine tumors is important for the delineation of novel therapeutic strategies.

Animals↗

Mutations in the cationic trypsinogen gene and evidence for genetic heterogeneity in hereditary pancreatitis.

Hereditary pancreatitis (HP) is a rare inherited disorder, characterised by recurrent episodes of pancreatitis often beginning in early childhood. The mode of inheritance suggests an autosomal dominant trait with incomplete penetrance. The gene, or at least one of the genes, responsible for hereditary pancreatitis has been mapped to the long arm of chromosome 7 and a missense mutation, an arginine to histidine substitution at residue 117 in the trypsinogen cationic gene (try4) has been shown to segregate with the HP phenotype. The aim of this work was to investigate the molecular basis of hereditary pancreatitis. This study was performed on 14 HP families. The five exons of the trypsinogen cationic gene were studied using a specific gene amplification assay combined with denaturing gradient gel electrophoresis (DGGE). The present paper describes three novel mutations, namely K23R and N29I and a deletion -28delTCC in the promoter region. We also found a polymorphism in exon 4, D162D. In eight of these families we found a mutation which segregates with the disease. A segregation analysis using microsatellite markers carried out on the other families suggests genetic heterogeneity in at least one of them. Our findings confirm the implication of the cationic trypsinogen gene in HP and highlight allelic diversity associated with this phenotype. We also show that the pattern of inheritance of HP is probably complex and that other genes may be involved in this genetic disease.

Cations↗

Hypomelanosis of ITO. A study of 76 infantile cases.

We show the complications observed in a large series of children with hypomelanosis of Ito (HI) or incontinentia pigmenti achromians, studied in a neurology service over 30 years. Of the 76 patients, 35 were male (46%) and 41 female (54%) with ages ranging from newborn to 10 years at the time of the first visit. They were thoroughly studied from the clinical, genetic, psychological, neuroradiological, with computed tomography (CT) and/or magnetic resonance imaging (MRI), and electroencephalographic (EEG) points of view. Mental retardation was observed in 43 cases (57%) of whom eight (10%) showed autistic behavior; 16 (21%) were borderline and only 17 (22%) had a normal mental level (IQ > 85). Thirty-seven patients (49%) had seizures, consisting of infantile spasms in six cases (8%). Twelve cases showed macrocephaly and coarse facies, six had microcephaly, and 14 showed hypotonia with pes valgus and genu valgus. Three cases of cerebellar hypoplasia, another of intracranial arteriovenous malformation and another of distal spinal muscular atrophy were observed as well. Some other anomalies, such as syndactyly, clinodactyly, abnormalities of the skeleton, asymmetry of the facies, ears, body and/or extremities, gynecomastia and asymmetrical breasts, short stature, oral alterations, congenital cardiopathies and genital anomalies, were also occasionally found. Three children died, but necropsy was performed only in one. Anatomical and histological studies did not disclose specific findings.

Alopecia↗

[The specific epidemiological surveillance of dengue: the method and its importance since the dengue-2 epidemic in French Polynesia in 1996].

Dengue fever is present in tropical and subtropical regions and its geographical extension and the simultaneous increase of its mortality are worrisome. In endemic or epidemic countries, the aim of dengue-specific epidemiological surveillance is to confirm as soon as possible the circulation of a new viral dengue serotype, i.e. the beginning of an epidemic. The efficiency of the control strategy is improved by an earlier epidemic alert. In French Polynesia, dengue-3 virus circulated since 1989 at low level and, in May 1996, a specific epidemiological surveillance was undertaken because of the threat of a dengue-4 epidemic. From each suspected dengue case reported by 18 Polynesian physicians located in the Société Islands, a blood sample was taken for virological assay and clinical data were reported. Between May and November 1996, the virology unit of the Institut Malardé isolated 21 viruses (2 dengue-3 and 19 dengue-2) from 302 suspected cases. The dengue-specific epidemiological surveillance confirmed that dengue-2 virus was circulating and reduced the time of the epidemiological alert by 2 or 3 months compared to previous epidemics. Taking into account the day of illness, a logistic regression undertaken on the clinical data showed that the absence of cough was the only predictive sign of dengue diagnosis. The performance of this dengue-specific epidemiological surveillance system led us to consider its implementation in all concerned countries. A collaboration with international reference laboratories could be a solution for the developing countries.

Adolescent↗

Changing clinical and biological manifestations of dengue during the dengue-2 epidemic in French Polynesia in 1996/97--description and analysis in a prospective study.

In August 1996 dengue-2 virus was detected in French Polynesia for the first time since 1976. A prospective study was conducted from November 1996 to April 1997. Each time one of 7 physicians suspected dengue, the patient was enrolled and epidemiological, clinical and biological data were recorded. Dengue diagnosis was confirmed by virus isolation and IgM detection. The aims of this study were to find clinical and biological predictive factors constituting a specific profile of dengue (DF) and dengue haemorrhagic fever (DHF/DSS) and to assess the possibility of diagnosing dengue at primary health care level using clinical criteria and basic laboratory parameters. Of 298 clinically suspect cases, 196 (66%) were confirmed as dengue. The association of macular rash, pruritus, low platelet count and leukopenia was statistically predictive of dengue but not clinically, since these four signs occur in many other viral infections. As the prevalence of clinical and biological manifestations varied over time in our study, a specific profile useful for dengue diagnosis cannot be defined. With six cases of DHF, the morbidity of this dengue-2 outbreak was very low despite the sequential infection scheme DEN-3/DEN-2. The clinical expression of dengue could depend on a specific virus strain circulating in a specific population in a particular place, with varying virulence over time.

Adolescent↗

Possible dengue sequential infection: dengue spread in a neighbourhood during the 1996/97 dengue-2 epidemic in French Polynesia.

A DEN-2 epidemic occurred in French Polynesia from August 1996 to April 1997 after 7 years of DEN-3 circulation. The susceptible population constituted all expatriates and Polynesians under 21. In August 1996, two successive DEN-2 cases occurred in Teroma, a Tahitian neighbourhood close to the international airport of Tahiti. A serological prospective study of persons < 21 years living in Teroma was conducted. The study population was bled in September 1996, October 1996 and June 1997. Analysis of dengue spread in Teroma confirmed that dengue transmission occurs primarily in the house, thus vector control campaigns should incorporate focal insecticide spraying and systematic daily use of insecticide in houses. The evolution in time of the disease demonstrated that among a susceptible population, prevalence and incidence rates are related to the time of exposure, and consequently to age. Comparison of dengue incidence or dengue prevalence between populations therefore requires adjusted age rates. Most studies did not adjust for age, leading to the conclusion that DHF is more frequent during secondary than during primary dengue infection. Prospective studies taking into account the time of dengue exposure are necessary to confirm the sequential infection hypothesis.

Adolescent↗

A proline-rich motif downstream of the receptor binding domain modulates conformation and fusogenicity of murine retroviral envelopes.

The entry of retroviruses into cells depends on receptor recognition by the viral envelope surface subunit SU followed by membrane fusion, which is thought to be mediated by a fusion peptide located at the amino terminus of the envelope transmembrane subunit TM. Several fusion determinants have been previously identified in murine leukemia virus (MLV) envelopes, but their functional interrelationships as well as the processes involved in fusion activation upon retroviral receptor recognition remain unelucidated. Despite both structural and functional similarities of their envelope glycoproteins, ecotropic and amphotropic MLVs display two different postbinding properties: (i) while amphotropic MLVs fuse the cells at neutral pH, penetration of ecotropic MLVs is relatively acid pH dependent and (ii) ecotropic envelopes are more efficient than amphotropic envelopes in inducing cell-to-cell fusion and syncytium formation. By exploiting the latter characteristic in the analysis of chimeras of ecotropic and amphotropic MLV envelopes, we show here that substitution of the ecotropic MLV proline-rich region (PRR), located in the SU between the amino-terminal receptor binding domain and the TM-interacting SU carboxy-terminal domains, is sufficient to revert the amphotropic low-fusogenic phenotype into a high-fusogenic one. Furthermore, we have identified potential beta-turns in the PRR that control the stability of SU-TM associations as well as the thresholds required to trigger either cell-to-cell or virus-to-cell fusion. These data, demonstrating that the PRR functions as a signal which induces envelope conformational changes leading to fusion, have enabled us to derive envelopes which can infect cells harboring low levels of available amphotropic receptors.

Amino Acid Sequence↗

[The value of images in diagnosis of neuron migration disorders].

OBJECTIVE: To present the fitest classification and the imaging peculiarities of the malformations of cortical development, most of which have been related with the epilepsy origin. METHODS: The study is based on an anatomical-histological classification scheme that shows three great groups of malformations of cortical development: 1. Malformations due to abnormal neuronal and glial proliferation. 2. Malformations due to abnormal neuronal migration. 3. Malformations due to abnormal cortical organization. RESULTS: The result of these abnormalities of the cortical development is the presence of several anatomical histological entities, actually perfectly identified by the magnetic resonance (MR), especially with the new high resolution methods. The most frequent entities, such as polymicrogyria, lissencephaly, pachygyria, schizencephaly, cerebral heterotopia (cortical, subcortical or subependymal), and other rarer types are reviewed according with the numerous references of the literature and the findings observed in the cases of our series of about one hundred patients which includes cases of every type of malformation. CONCLUSION: MR is a conclusive study in order to identify and classify the malformations of cortical development, most of which are associated with neurological disturbances: epilepsy, mental retardation, language and/or behavioral problems or motor dysfunction.

Brain↗

Accuracy of an automatic and patient-triggered long-term solid memory ambulatory cardiac event recorder.

This study evaluated the R-Test Evolution, a new type of cardiac event recorder bearing both patient-triggered and automatic capabilities. Its 7-day automatic arrhythmia analysis showed promising clinical advantages, especially when investigating patients with unexplained rare events such as syncope, feeling of weakness or faintness, palpitations, stroke, or in patients inconsistent in their use of patient-triggered recordings.

Arrhythmias, Cardiac↗

Genetic studies of neuropeptide Y and neuropeptide Y receptors Y1 and Y5 regions in morbid obesity.

Synthesis and release of neuropeptide Y (NPY) are both regulated by leptin binding to its hypothalamic receptor mediating some of the effects of leptin on food intake. Moreover, NPY administration is a powerful stimulant of feeding behaviour. Thus, we investigated the potential implication of NPY, NPY-Y1 and -Y5 subtype receptors [rNPY-Y1/-Y5] in the development of human obesity. Two complementary genetic approaches were used: 1) linkage analyses between obesity and polymorphic markers located nearby NPY and rNPY-Y1/-Y5 genes (respectively on chromosomes 7p15.1 and 4q[31.3-32]) in 93 French Caucasian morbidly obese families; 2) single strand conformation polymorphism (SSCP) scanning of the coding region of the NPY and rNPY-Y1 genes performed in 50 unrelated obese patients ascertained on the basis of a body mass index of 27 kg/m2 or more and a family history of obesity. No evidence of linkage between morbid obesity or obesity-related quantitative traits and NPY and rNPY-Y1/ Y5 regions was found in this population. Moreover, SSCP scanning revealed no mutation in the coding region of NPY and rNPY-Y1 genes among obese subjects. These results suggest that NPY and NPY-Y1/ Y5 receptors are unlikely to be implicated in the development of human morbid obesity, at least in the French Caucasian population.

Alleles↗

Intestinal-type fibroblasts selectively influence proliferation rate and peptide synthesis in the murine entero-endocrine cell line STC-1.

The intestinal epithelium consists of enterocytes, endocrine cells, goblet cells and Paneth cells, which differentiate from pluripotent stem cells located at the crypt bases. The role of the epithelial-mesenchymal inter-actions has been well documented for the differentiation of enterocytes, but the mechanisms that control endocrine cell differentiation are poorly understood. We have cultured the intestinal endocrine cell line STC-1, which synthesizes most of the intestinal peptide hormones, in media conditioned by several subepithelial fibroblast cell lines from three distinct sites of intestine. The fibroblast Swiss 3T3 cell line was used as a non-intestinal control. Our results show that culture media from intestinal fibroblasts inhibit the proliferation rate of STC-1 cells, while those from Swiss 3T3 fibroblasts do not. As regards peptide hormone gene expression, Swiss 3T3-conditioned media have no effect, whereas media from intestinal fibroblasts variably affect cholecystokinin, glucagon, secretin and somatostatin mRNA levels. In particular, clonal subepithelial myofibroblasts do not exert the same effects as mixed subepithelial fibroblasts from homologous intestinal segment. Taken together, these results suggest that cultured fibroblasts of intestinal origin release soluble factors that inhibit STC-1 cell proliferation and modulate, in a region-specific manner, the expression of hormonal peptide genes in this nonspecialized endocrine cell line.

Animals↗

Benign mucous membrane pemphigoid presenting as desquamative gingivitis in a 14-year-old child.

A 14-year-old girl presented with painful, erythematous gingivae, which occasionally developed blisters. There were no other mucosal or skin lesions. Clinical, histopathological and immunofluorescence studies suggested a diagnosis of benign mucous membrane (cicatricial) pemphigoid, presenting as desquamative gingivitis. Benign mucous membrane pemphigoid in childhood is rare and only a few cases with exclusive oral mucosal involvement have been reported in the literature. The desquamative gingivitis responded well to a topical steroid regimen.

Adolescent↗

Peptones stimulate cholecystokinin secretion and gene transcription in the intestinal cell line STC-1.

In rats, protein hydrolysates (peptones) stimulate cholecystokinin (CCK) release both in vivo and in a model of isolated vascularly perfused duodeno-jejunum. However, the mechanisms involved in peptone-induced stimulation of CCK cells are not well understood. In particular, the possibility that peptones may directly interact with CCK-producing cells to stimulate CCK release and gene transcription has not yet been examined. To test this hypothesis, we used the enteroendocrine cell line STC-1. Incubation of STC-1 cells for 2 h with albumin egg hydrolysate over the concentration range 0.01-1% (wt/ vol) caused a dose-dependent release of CCK, with a maximal increase at 1420% of the control value. In contrast, BSA (1%, wt/vol) or a mixture of amino acids (1%, wt/vol) induced a modest rise in CCK secretion. A dose-dependent, hydrolysate-specific, increase in the CCK steady state RNA level was also observed. It was detectable by 2-4 h of peptone treatment and sustained until 24-48 h. Peptones did not increase the CCK RNA level in the colonic CCK-producing cell line GLUTag or in nonintestinal CCK-expressing cell lines, namely the pancreatic cell line RINm5F and the medullar thyroid carcinoma cell line CA77. The peptone-induced increase in the CCK RNA level resulted from enhanced gene transcription, because labeled CCK transcripts from nuclear run-on incubations increased 3-fold when cells were incubated with peptones, whereas the level of beta-actin transcripts was not modified. Finally, peptones dose-dependently stimulated the transcriptional activity of an 800-bp fragment of CCK gene promoter transfected in STC-1 cells. These studies indicate that peptones specifically stimulate CCK secretion and gene transcription in the intestinal cell line STC-1, and that cis-acting elements conferring peptone inducibility are located in the first 800 bp of the 5'-flanking region of the CCK gene.

Animals↗

Low-dose clozapine improves dyskinesias in Parkinson's disease.

The severity of parkinsonian motor disability and dyskinesias was evaluated in seven levodopa-responsive patients with Parkinson's disease after an acute challenge with the mixed dopamine agonist apomorphine, before and after low-dose clozapine (50 mg) for 18 +/- 2 days. There was a significant 59% improvement (p < 0.05) of apomorphine-induced dyskinesias without aggravation of parkinsonian motor disability following clozapine treatment. The results suggest that low-dose clozapine, already shown to improve psychotic symptoms, may help to reduce severe levodopa-induced dyskinesias in parkinsonian patients.

Aged↗

[Clinical significance of episodes of apnea in babies].

INTRODUCTION: The presence of episodes of apnea (EA) in infants is very alarming and requires rapid, precise determination of the etiology in view of the relationship with the syndrome of sudden death of infants. MATERIAL AND METHODS: We therefore studied 16 patients, aged between 1 and 12 months, admitted to to hospital after having episodes where they stopped breathing for more than 15 seconds, with or without associated bradycardia. Patients with previous or associated convulsions, premature birth or low birth weight for gestational age were excluded from the study. In all cases a prolonged EEG was recorded. RESULTS: The commonest age of presentation of EA was 3-4 months. In one case there was a history of a sudden infant death occurring in a brother. The etiology was determined in 12 cases: gastroesophageal reflex in 5, epilepsy in 3, hyponatremia in 2, drug reaction in 1, bronchiolitis in 1 and hypoglycemia in another. In three cases where no cause was found the EA was not repeated, although apnea monitorization was necessary for several months because of the anxiety of the family. CONCLUSIONS: Of the 3 cases in which EA was a critical epileptic sign, only 2 could be demonstrated on a Holter recording. In one of these, progress was poor and resistant crises of different morphology later occurred. We consider that EA in infants requires a thorough etiological study. Cases of unknown etiology require prolonged EEG recording to determine whether the apnea is cerebral in origin, followed by prolonged monitorization of apneas to avoid possible sudden death.

Apnea↗