PubMed Health⌕ Search

Biomedical subjects

G Prevost

Publications and source records attributed to G Prevost.

At least 19 recordsLinked to original sources

Asobara, braconid parasitoids of Drosophila larvae: unusual strategies to avoid encapsulation without VLPs.

Ichneumonoidae parasitoids have been well described for their regulatory effects on host physiology which are usually associated with the activity of polydnaviruses (PDVs) or viruslike-particles (VLPs) injected by the female wasps at oviposition. Among them, parasitoids of the braconid families display specific characteristics like the required activity of secretions from the maternal venom glands or of teratocytes from embryological origin. However, none of these features were observed in two braconid species of the Asobara genus parasitizing Drosophila hosts. In the absence of PDVs and VLPs, the two species A. tabida and A. citri seem to have developed unique strategies to avoid immunity defenses and to succeed in their Drosophila larval hosts. The aim of this study is to report on the complex relationships of braconid parasitoids with their hosts and to present some of the insights from studying Drosophila parasitoids.

Animals↗

Polymorphisms of the receptor of advanced glycation endproducts (RAGE) and the development of nephropathy in type 1 diabetic patients.

OBJECTIVES: We investigated the association of the RAGE (Receptor for Advanced Glycation End products) exon3 gene polymorphisms with stages of nephropathy in type 1 diabetes. METHODS: The RAGE exon 3 genotype was assessed by Denaturing Gradient Gel Electrophoresis (DGGE) procedure in 487 type 1 diabetic patients with proliferative retinopathy subdivided into four groups according to their level of renal involvement and in 351 control subjects (GENEDIAB study). RESULTS: We reported here three main low frequency dimorphisms, previously submitted to data banks, Gly82Ser, Val89 CTC/CTG, and Arg77Cys. The genotype distribution of these polymorphisms was not statistically different in type 1 diabetic patients compared to healthy controls (p=0.37). Among the three described polymorphisms, only the RAGE Gly82Ser genotype frequency was significantly increased in the group with advanced nephropathy (11%) defined by a chronic renal failure compared to the three others groups: no nephropathy, 5%; incipient (microalbuminuria) 5%; established (macroalbuminuria), 2%) (P=0.04). The 82 Ser allele was identified as an independent risk marker for the stage of advanced nephropathy: adjusted odds ratio 3.17(95% CI 1,32-7,85, p=0.008). CONCLUSION: These data suggest that the 82 Ser allele of the RAGE gene is a risk allele for developing advanced nephropathy. This suggests that some RAGE gene polymorphisms may be associated with progression to diabetic advanced nephropathy in Caucasian type 1 diabetic patients.

Amino Acid Substitution↗

[Infective dermatitis and recurrent strongyloidiasis in a child].

INTRODUCTION: Infective dermatitis is a chronic childhood dermatosis, associated with HTLV-1 infection. We report the observation of a young Haitian girl in French Guyana. OBSERVATION: An 8 year-old girl presented recurring dermatosis on the scalp and armpits since she was 2 years old. The initial clinical examination showed the presence of centro-facial micro-papules, associated with a nasal pyodermatitis. A bacteriological culture isolated a Staphylococcus aureus. Phenotypic analysis did not indicate any production of exfoliatin or leucocidin. Serologic tests for HTLV1 were positive. In addition, the child presented recurring symptomatic anguillulosis, despite numerous antihelmintic treatments. A clinical and parasitological cure was obtained with a monthly treatment of ivermectin. COMMENTS: This is the first case of infective dermatitis reported in french Guyana. The clinical analysis that led to this diagnosis showed a minor form of this dermatosis. The phenotypic analysis of the Staphylococcus aureus isolated from the cutaneous lesions did not indicate any factors of virulence habitually associated with pyodermatitis in Guyana. This is the first case of chronic digestive anguillulosis (a parasitic complaint usually associated with an adult HTLV-1 infection) associated with an infective dermatitis.

Child↗

[Bilateral acute retinal necrosis syndrome associated with meningoencephalitis caused by herpes simplex virus 2. A case report].

INTRODUCTION: Acute retinal necrosis syndrome (ARN syndrome) is a rare viral disease with a poor prognosis in most cases. It is characterized by substantial ocular inflammation with progressive retinal necrosis, occlusive vasculitis and sometimes extraocular features. CASE REPORT: We report the case of a 62-year-old woman who was referred for a suspicion of a stroke. Ophthalmological examination revealed a profound bilateral visual loss due to extensive retinal necrosis. The patient was immediately treated with antiherpetic drugs. ARN syndrome with meningoencephalitis caused by herpes simplex virus type 2 was confirmed by PCR studies performed on aqueous humor and cerebrospinal fluid. Herpes simplex virus 2 (IgG+ , IgM-) was probably reactivated after intrathecal injection of steroids because of pain associated with narrowing of the lumbar vertebral canal. The patient was treated with intravenous Acyclovir for 3 weeks. After 4 months, both retinas were detached. DISCUSSION AND CONCLUSION: ARN syndrome caused by herpes simplex virus 2 most often occurs after reactivation of the latent virus in patients with a neurological medical history or congenital infection. Antiviral treatment must begin early to decrease risks of bilateralization and complications.

Acyclovir↗

Induction of apoptosis in prostate carcinoma cells by BH3 peptides which inhibit Bak/Bcl-2 interactions.

Interactions between proteins of the Bcl-2 family play an important role in the regulation of apoptosis. Anti-apoptotic family members can heterodimerize with pro-apoptotic family members and antagonize their function, thus protecting against death. In cells protected from death by overexpression of Bcl-2 much of the Bax is present in Bax/Bcl-2 hetero-multimers and its death signal is blocked as it cannot homodimerize. This led us to use the Bcl-2/Bax heterodimer as a target for new compounds which may provide a therapy particularly suited to tumour cells for which resistance to conventional therapy is associated with elevated expression of Bcl-2. We assessed whether apoptosis could be induced in prostate tumour cells by blocking this heterodimerization with synthetic peptide sequences derived from the BH3 domain of pro-apoptotic Bcl-2 family members. Prostate cells were found to undergo up to 40% apoptosis 48 h following the introduction of synthetic peptides from the BH3 domains of Bax and Bak. The caspase inhibitor z-VAD.fmk provided protection against apoptosis mediated by these peptides. Immunoprecipitation studies revealed that introduction of peptides derived from the BH3 regions of Bak and Bax into cells blocked Bak/Bcl-2 heterodimerization. These data suggest that by blocking the dimerization through which Bcl-2 would normally inhibit apoptosis the apoptotic pathway driven by Bak was re-opened.

Amino Acid Chloromethyl Ketones↗

Results of a phase III prospective, randomised trial, comparing mitoxantrone and vinorelbine (MV) in combination with standard FAC/FEC in front-line therapy of metastatic breast cancer.

This comparative phase III trial of mitoxantrone+vinorelbine (MV) versus 5-fluorouracil+cyclophosphamide+either doxorubicin or epirubicin (FAC/FEC) in the treatment of metastatic breast cancer was conducted to determine whether MV would produce equivalent efficacy, while resulting in an improved tolerance in relation to alopecia and nausea/vomiting. This multicentre study recruited and randomised 281 patients with metastatic breast cancer; 280 were evaluable for response survival and toxicity (138 received FAC/FEC, 142 received MV). Patient characteristics were matched in each arm and stratification for prior exposure to adjuvant therapy was made prospectively. The overall response rate (ORR) was equivalent in the two arms (33.3% for FAC/FEC versus 34.5% for MV), but MV was more effective in patients who had received prior adjuvant therapy (13% (95% confidence interval (CI) 3-23) for FAC/FEC versus 33% (95% CI 20-47) for MV P=0.025) with a better progression-free survival (PFS) (5 months (range 1-18 months) versus 8 months (range 1-27 months); P=0.0007 for FAC/FEC versus MV, respectively) while FAC/FEC was more effective in previously untreated patients (ORR 43% (95% CI 33-53) versus 35% (95% CI 25-45), P=0.26; PFS 9 months (range 0-29 months) versus 6 months (range 0-26 months) P=0.014). Toxicity was monitored through the initial six cycles of therapy; febrile neutropenia and delayed haematological recovery was more frequent for MV (P=0.001), while nausea/vomiting of grades 3-4 was greater for FAC/FEC (P=0.031), as was alopecia (P=0.0001), cardiotoxicity was the same for the two regimens. MV represents a chemotherapy combination with equivalent efficacy to standard FAC/FEC and improved results for patients who have previously received adjuvant chemotherapy. Toxicity must be balanced to allow for increased haematological suppression and risk of febrile neutropenia with MV compared with a higher risk of subjectively unpleasant side-effects such as nausea/vomiting and alopecia with FAC/FEC.

Adolescent↗

Autoimmune markers in slow type 1 diabetes: confrontation to type 1 diabetes.

UNLABELLED: Slow onset type 1 diabetes is an heterogeneous entity. Its clinical features may mimick type 2 diabetes but its pathophysiological mechanisms are close to type 1 diabetes. AIM OF THE STUDY: To find out the frequencies, levels and associations of ICA, GADab and IA-2ab in type 2 diabetic patients with atypical phenotype. To compare it to type 1 diabetes. PATIENTS AND METHODS: ICA, GADab and IA-2ab were determined in: - 61 patients (age at diagnosis 48.2 +/- 10, range 36-73 years) with an initial diagnosis of type 2 diabetes but having at least one symptom suggesting a slow type 1 diabetes (loss of weight, absence of obesity at diagnosis or secondary failure of oral hypoglycaemic agents). - 70 patients with type 1 diabetes (age 18 +/- 8.9, range 2-35 years). Clinical data evaluated in slow type 1 were maximal BMI, BMI and loss of weight at diagnosis and autoimmune disease. Fasting C-peptide and insulinemia were also assessed. RESULTS: (Slow type 1 diabetes versus type 1 diabetes). ICA (43% vs 70%; p <0.01) and IA-2ab (16% vs 75%; p <0.01) were more frequent in type 1. GADab were as frequent (62% vs 74%). Association of the three antibodies (15.7% vs 58.5%; p <0.05) were more frequent in type 1. Prevalence of GADab alone (27.5% vs 7.5%; p <0.05) was higher in slow type 1 diabetes and with higher levels (median 55.5 UI/ml vs 17 UI/ml; p <0.01). There was no difference for levels of ICA (25.5 UJDF/ml vs 28 UJDF/ml) or IA-2ab (11.5 UI/ml vs 38.5 UI/ml). BMI of GADab positive patients was lower. Delay of insulinotherapy was shorter in GADab or ICA positive patients. We did not find any relationship between antibodies presence and fasting C-peptide or insulinemia. CONCLUSION: Slow type 1 diabetes should be evoked in atypical type 2 diabetes. Slow onset type 1 diabetic patients have different autoimmune patterns suggesting a different pathophysiological process. GADab and ICA are useful markers to predict future insulinopenia.

Adult↗

Human RAGE GLY82SER dimorphism and HLA class II DRB1-DQA1-DQB1 haplotypes in type 1 diabetes.

Advanced glycation end products (AGEs) are believed to play an important role in the development of diabetic complications. AGEs increase in diabetes and modulate cellular functions through binding to a specific cell surface receptor (RAGE). The RAGE gene maps to chromosome 6p in the HLA class III area and is telomeric to the class II region at 250 kb from DRA. A recent report described the characterization of a major RAGE gene variant as a biallelic single base polymorphism (G/A 557) in the exon 3 sequence leading to a change of a glycine to a serine at position 82. Using DGGE and PCR-RFLP, we have investigated the distribution of this dimorphism in conjunction with HLA class II genes in large populations of type 1 diabetic patients and healthy subjects. Although no association of this RAGE gene polymorphism with disease susceptibility was found, we report a strong linkage disequilibrium between the variant carrying the serine amino acid at position 82 and two HLA-DR2 and HLA-DR4 specificities. In particular, we describe two major extensive HLA class II haplotypes associated with this serine variant and identified as DRB1*0401-DQA1*0301-DQB1*0301 in the diabetic group and DRB1*1501-DQA1*0102-DQB1*0602 in control individuals. These data were partially confirmed by family transmission analysis.

Diabetes Mellitus, Type 1↗

Analysis with a combination of macrorestriction endonucleases reveals a high degree of polymorphism among Bordetella pertussis isolates in eastern France.

From 1990 to 1996, routine screening for whooping cough identified 399 patients with a calmodulin-dependent adenylate cyclase-positive test result and yielded 69 Bordetella pertussis isolates. None of the patients were fully vaccinated, and most were less than 6 months old. Analysis of total DNA by pulsed-field gel electrophoresis (PFGE) after XbaI, SpeI, or DraI macrorestriction yielded 19, 15, and 5 different patterns, respectively, whereas ribotyping failed to demonstrate any strain polymorphism. Discrimination among the isolates was improved by combining the PFGE profiles. Some patterns were more frequent, but the corresponding patients were not clearly epidemiologically related. The patterns for two strains obtained during a 3-month period from patients who were neighbors differed by the length of a single DNA fragment. These data strongly suggest that one type of isolate is widely spread throughout the world and is carried by individuals other than patients who develop a true illness.

Bacterial Typing Techniques↗

Corynebacterium singulare sp. nov., a new species for urease-positive strains related to Corynebacterium minutissimum.

We studied two coryneform strains from clinical specimens. These strains had type IV and corynemycolic acids in their cell walls and also had phenotypic characteristics, such as urease activity and fermentation of glucose and sucrose but not trehalose, which did not permit assignment to any previously recognized taxon. According to DNA-DNA hybridization data, these two strains are members of the same species (level of DNA similarity, 86%). Phylogenetic analysis based on comparisons of almost complete small-subunit ribosomal DNA sequences revealed that these strains are closely related to Corynebacterium minutissimum, but DNA relatedness experiments clearly showed that they constitute a distinct new species with a level of DNA relatedness to the C. minutissimum type strain of less than 40%. This new species can be differentiated from C. minutissimum strains by its enzymatic activities and carbon source utilization, and the name Corynebacterium singulare is proposed for it. The type strain is strain IBS B52218 (= CCUG 37330), which was isolated from a semen specimen.

Base Composition↗

Corynebacterium durum sp. nov., from human clinical specimens.

A new Corynebacterium species, Corynebacterium durum, was isolated from respiratory tract specimens of five human patients. The strains of this species exhibited similar morphologic and biochemical features that differentiated them from all recognized species. Notably, all of these strains developed irregular and strongly adherent colonies under aerobic conditions and produced acid from mannitol and galactose. The cells are long pleomorphic rods with some filaments. This species has characteristics of the genus Corynebacterium, such as 55 mol% guanine plus cytosine in the DNA and the presence of corynomycolic acids, meso-diaminopimelic acid, arabinose, and galactose in the cell wall. These isolates formed a homogeneous group in which the DNA-DNA similarity values (as determined by an S1 nuclease procedure) compared with reference strain IBS G15036T (T = type strain) ranged from 71 to 100%. The analysis of the nearly complete 16S rRNA gene sequence of IBS G15036T indicated that this new species represents a distinct taxon within the genus Corynebacterium. This new species can be identified on the basis of its colony morphology, fermentation of sugars, and enzymatic activities. Strain IBS G15036 (= CCUG 37331) is the type strain of C. durum.

Base Composition↗

Frequency of isolation of Staphylococcus intermedius from humans.

We collected 3,397 consecutive isolates of coagulase-positive staphylococci from various specimens of hospitalized patients. All were retrospectively classified as Staphylococcus aureus, except two which were identified as S. intermedius: one isolated from the nasal flora of a healthy carrier and the other isolated from pleural fluid, probably as a sample contaminant.

Aged↗

[Value of scintigraphy using meta-iodo-benzyl-guanidine (MIBG) in the investigation of cardiac autonomic neuropathy in diabetic patients. Comparison with Ewing tests].

UNLABELLED: Cardiac autonomic neuropathy is a frequent complication of diabetes leading to resting tachycardia, postural hypotension, painless myocardial ischaemia, rhythm disturbances and sudden cardiac death. The aim of the study was to evaluate in a diabetic population the sensitivity of two exploration modes of autonomic neuropathy in diabetics: the Ewing tests which are, at present time, the reference method and the (123-I) meta-iodo-benzyl-guanidine (MIBG) single photon emission computed tomography (SPECT) which evaluates the cardiac sympathetic innervation. PATIENTS AND METHODS: 9 male insulin-dependent diabetes mellitus patients were studied. Mean age was 40.7 +/- 15 years and diabetes duration was 10.8 +/- 6 years. None had hypertension or macroangiography as demonstrated by patient's history, clinical examination, rest and exercise electrocardiography and ambulatory blood pressure monitoring. The complications observed were background retinopathy in 2 patients, incipient nephropathy in 3 and a peripheral neuropathy in 1 patient. Ewing tests, i.e. Valsalva maneuver, beat to beat heart rate variation during deep breathing and standing, blood pressure response to standing and to sustained handgrip, were performed. The results were considered as pathologic when the score was over 2. After injection of 10 mCi (123-I) MIBG, planar images were realized at times 1, 2 and 4 hours and SPECT images after 2 hours. The heart/mediastinum uptake ratio was calculated. RESULTS: We noted abnormalities of planar images in 3 patients, SPECT images in 1, and both in 1 patient. None was positive for Ewing tests. CONCLUSION: Although MIBG SPECT will explore only the sympathetic innervation, these preliminary findings suggest that this technique could be more sensitive for the evaluation of cardiac autonomic neuropathy. Nevertheless cost and lack of disponibility of this technique should limit its use.

3-Iodobenzylguanidine↗

Enterotoxin production by coagulase-negative staphylococci isolated from goats' milk and cheese.

An antigen related to the Enterotoxin E from Staphylococcus aureus was produced by ten of 187 coagulase-negative staphylococci (CNS) isolated from goats' milk, whey and cheese in quantities ranging from 10 to 90 ng/ml supernatant. The enterotoxin-producing strains were identified at the species level as S. simulans, S. xylosus, S. equorum, S. lentus and S. capitis. Detection of the enterotoxins was done by the VIDAS SET test (bioMérieux) and by an indirect double-sandwich ELISA technique using anti-enterotoxin monoclonal antibodies. The results obtained were further confirmed by Southern blotting, using two radioactive oligonucleotide probes that hybridized specifically with the gene of S. aureus coding for the enterotoxin E.

Animals↗

5-Fluorouracil versus 5-fluorouracil plus alpha-interferon as treatment of metastatic colorectal carcinoma. A randomized study.

BACKGROUND: In 1989, S. Wadler reported very promising results (76% response rate) with a combination of 5-fluorouracil (5-FU) plus alpha-2a interferon (IFN) in the treatment of metastatic colorectal carcinoma (MCRC). In vitro, there are several potential explanations for synergism between the two agents. We therefore decided in 1989 to start a randomized study comparing 5-FU alone with 5-FU plus IFN. PATIENTS AND METHODS: 105 non-pretreated patients with measurable metastatic colorectal carcinoma entered into this study. The patients were randomly allocated either in arm A (n = 49) with 5-FU: 750 mg/m2 i.v. CI d1-d5 followed by 750 mg/m2 i.v. bolus once a week, or in arm B (n = 56) with 5-FU as in arm A plus IFN 9 x 10(6) IU sub-cutaneously three times a week. RESULTS: After two months of treatment we observed 1 CR and 2 PR in arm A (response rate 6.1%), 3 CR and 8 PR in arm B (response rate 19.6%), i.e., a significant difference (P = 0.05). Event-free survival was significantly higher in arm B (6 months) than in arm A (2 months) (P < 0.01), while median survival was slightly higher in arm B (12 months) than in arm A (10 months) (P < 0.05). For overall survival the difference was not significant after adjustment on center treatment and baseline Karnofsky status (P = 0.13). Toxicity was also greater in arm B. Sixteen percent of patients in arm A and 36% in arm B experienced certain grade 3-4 side effects (P < 0.05). CONCLUSION: 5-FU plus IFN is more effective than 5-FU alone in terms of response rate, event free survival but not of overall survival. 5-FU plus IFN is more toxic. As IFN has no demonstrated efficacy in MCRC as a single agent, this study suggests that IFN is acting as a 5-FU modulatory agent. The response rate observed (19.6%) is similar to the results obtained elsewhere with 5-FU plus leucovorin.

Adult↗

Somatostatin-14 mainly binds the somatostatin receptor subtype 2 in human neuroblastoma tumors.

Neuroblastoma is a pediatric cancer for which a cure is elusive for most children with disseminated disease. Neuroblastomas possess receptors for somatostatin (SS). Some SS analogues can inhibit their proliferation. In addition, when SS analogues were used as agents for scintigraphy, neuroblastoma tumor sites can be localized with high efficiency. In this study, to better characterize the SS receptor subtype(s) (sst1-5) present in primary tumors and metastases of neuroblastoma, we show that: (1) The ligand 125I-Tyr11-SS-14 binding on membrane proteins from primary tumors and metastases of neuroblastoma cell line IGR-N-91 developed in nude mice shows similar values of Kd (in order of 0.1 nM) and Bmax (in order of fmol/mg) by filter-retention assay. These data are close to those measured on two other neuroblastoma cell lines: SK-N-SH and IGR-N-835 or to that measured on the rat cerebral cortex. (2) The IGR-N-91 sublines derived from primary tumor and metastases show one major complex of 57 kD by the chemical cross-linking assay using the ligands: 125I-SS-14 and 125I-BIM23014. One similar major complex of 57 kD was also detected in SK-N-SH and IGR-N-835 or in the cerebral cortex. (3) Addition of excess nonlabeled peptides selective for sst2 (BIM23014, BIM23060, BIM23068) suppressed the formation of the complex 57 kD whereas addition of BIM23052 or BIM23056 (sst5 and sst3 selective respectively) does not. This pharmacological profile corresponds to sst2. (4) Only RNA message of sst2 gene is detected in IGR-N-91 cells and its metastases derived sublines by reverse-transcription-polymerase chain reaction and Northern hybridization in keeping with the presence of sst2. (5) In human biopsies, the complex of 57 kD corresponding to sst2 is consistently detected in three samples of the histological subset of the disease: benign ganglioneuroma, ganglioneuroblastoma and immature neuroblastoma. Therefore, the sst2 should be considered as the primary target to develop more potent SS analogues for neuroblastoma therapy or/and scintigraphy.

Base Sequence↗

Fentanyl therapy controls autonomic hyperactivity in tetanus.

This report describes the use of fentanyl in severe tetanus after failure of established therapeutic modalities (heavy sedation, neuromuscular blockade and ventilation). Cardiovascular instability accompanying severe tetanus secondary to sympathetic overactivity and raised catecholamine levels is associated with a mortality of over 50%. In this clinical situation, a variety of drugs with a primary or secondary action on the cardiovascular system has been used with varying success. The following case of severe generalised tetanus in the adult associated with autonomic hyperactivity, was successfully managed with large doses of intravenous fentanyl.

Aged↗

Characterisation of a synergohymenotropic toxin produced by Staphylococcus intermedius.

Staphylococcal synergohymenotropic (SHT) toxins damage membranes of host defence cells and erythrocytes by the synergy of two secreted and non-associated proteins: class S and class F components. Whereas Panton-Valentine leucocidin (PVL), gamma-hemolysin and Luk-M from Staphylococcus aureus are members of this toxin family, a new bi-component toxin (LukS-I + LukF-I) from Staphylococcus intermedius, a pathogen for small animals, was characterised and sequenced. It is encoded as a luk-I operon by two cotranscribed genes, like PVL, LukS-I + LukF-I shares a strong leukotoxicity of various PMNs, but only slight haemolytic properties on rabbit erythrocytes. When intradermally injected into rabbit skin, a 100 ng dose caused acute inflammatory reaction leading to tissue necrosis. The new SHT seemed to be largely distributed among various Staphylococcus intermedius strains.

Amino Acid Sequence↗