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Biomedical subjects

V David

Publications and source records attributed to V David.

At least 91 records · Page 5Linked to original sources
PubMed1998

Rewarding effects elicited by the microinjection of either AMPA or NMDA glutamatergic antagonists into the ventral tegmental area revealed by an intracranial self-administration paradigm in mice.

In order to study the functional role of the trans-synaptic neuronal interaction between glutamatergic afferents and mesolimbic dopaminergic neurons in internal reward processes, BALB/c male mice were unilaterally implanted with a guide-cannula, the tip of which was positioned 1.5 mm above the ventral tegmental area (VTA). On each day of the following experimental period, a stainless steel injection cannula was inserted into the VTA in order to study the eventual self-administration behaviour of either the competitive N-methyl-D-aspartate antagonist, D(-)-2-amino-7-phosphonoheptanoic acid (AP-7) or the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX) (3 ng/50 nL) using a spatial discrimination task in a Y maze. Mice rapidly discriminated between the arm enabling a microinjection of either of these glutamatergic antagonists and the neutral arm of the maze, and a robust self-administration of either of these compounds was observed from the first session of acquisition. These data provide strong evidence that the intra-VTA microinjection of either of these subclasses of glutamatergic antagonist produces an effect which is interpreted centrally by the experimental subjects as being highly rewarding. Once the self-administration response had been fully acquired by the experimental subjects, preinjection of the dopaminergic D2 antagonist, sulpiride (50 mg/kg i.p.), 30 min before the test, produced a rapid extinction of the self-administration response. This latter result demonstrates the dopaminergic D2 receptor dependence of this intra-VTA self-administration of both of these subclasses of glutamatergic antagonist. We conclude that the different glutamatergic afferent neuronal inputs to the VTA globally exert, in vivo, via the mediation of interposed endogenous GABAergic interneurons, a tonic trans-synaptic inhibitory regulation of neuronal activity in the mesolimbic dopaminergic pathway and that this complex neuronal interaction in the VTA plays a significant functional part in the modulation of internal reward processes.

2-Amino-5-phosphonovalerate↗
PubMed1998

Low-level vancomycin resistance in Clostridium innocuum.

Low-level vancomycin resistance was observed for 28 clinical Clostridium innocuum isolates and C. innocuum NCIB 10674, whereas teicoplanin was active. DNA from three clinical isolates and the type strain could not be amplified by PCR with primers specific for the genes vanA, vanB, and vanC, suggesting that C. innocuum is intrinsically resistant to vancomycin.

Anti-Bacterial Agents↗
PubMed1998

Identification of cofilin, coronin, Rac and capZ in actin tails using a Listeria affinity approach.

Actin assembly is involved in cell motility and intracellular movement of Listeria monocytogenes. Induction of Listeria actin tails is mediated by the surface protein ActA. The N-terminal domain of ActA is sufficient for this function. Cell components known to play a role in the actin-based motility of Listeria are VASP (vasodilatator-stimulated phosphoprotein), the multiprotein Arp2/3 complex and cofilin. VASP interacts with the central domain of ActA. Proteins interacting with the N-terminal domain of ActA have not been identified. To identify novel host cell components of ActA-induced actin tails, we used bovine brain extracts and an affinity approach with Listeria as matrix. Several known components of Listeria tails were isolated including VASP, Arp3 and cofilin. Cofilin was identified by peptide sequencing, and cofilin recruitment and Listeria tail length were found to be pH-dependent, in agreement with its recently reported role in enhancing actin filament turnover. In addition, three proteins not previously known to be associated with Listeria tails, coronin, Rac and capZ, were identified in our affinity approach. In infected cells, the localization of the identified proteins was studied by immunofluorescence. Our findings suggest that these latter proteins, which are known to play critical roles in cellular actin rearrangements, may also be involved in the dynamics of Listeria-induced actin assembly.

Actin Depolymerizing Factors↗
PubMed1998

99mTc MIBI prone scintimammography in patients with suspicious breast cancer: relationship with mammography and tumor size.

99mTc MIBI prone scintimammography (PSM) is reported to be a specific examination in order to assess the nature of breast lesions. Fifty-three patients whose mammography was stratified according to the breast imaging reporting and data system (BI-RADS), the five category classification of mammography approved by the American college of radiology, were studied with prone scintimammography, with the aim of assessing the accuracy of this exam and its usefulness in clinical practice. Thirty-five out of forty-one patients with BI-RADS category V (high probability of cancer) showed cancer at histology. Thirty-one of them had positive PSM. Three out of the six patients with mammo-graphic features of category IV indicated malignancy. PSM was positive in all of them and negative in the three benign lesions. One of the five patients with category III mammography showed cancer and positive PSM. The PSM was negative in 12/13 patients with benign patology (specificity 92.3%). When the cancers were stratified for T-category significant differences were found between the sensitivity for tumors larger or smaller than 1 cm. The sensitivity was 50% for the cancers smaller than 1 cm and 96.9% for those larger than 1 cm. PSM is a very specific method to determine the nature of breast lesions. Its sensitivity is also high but has to be improved when tumors smaller than 1 cm have to be detected. From a clinical point of view PSM can at the moment be considered as an accurate method for the study of borderline lesions of IV and also of III BI-RADS category. In this case a positive PSM indicates an impact in clinical decision making.

Breast Diseases↗
PubMed1998

Effect of aspirin on the contractility of aortic smooth muscle and the course of blood pressure development in male spontaneously hypertensive rats.

The effects of acetylsalicylic acid (ASA) on aortic smooth muscle contractility were studied in aortic rings of male SHR and WKY rats. The rats were administered two intraperitoneal injections of 10 mg/kg of ASA per week for ten weeks. Blood pressure of each rat was monitored twice weekly prior to the i.p. injections. Twenty four hours after the last injection the aortic smooth muscles were evaluated for generation of active tension in response to KCl, Phenylephrine (PE), Clonidine and Norepinephrine (NE). In another set of experiments calcium conductance was evaluated in the presence or absence of endothelium both in ASA treated and non treated animals. We report that aortic rings from ASA-treated SHR animals were more responsive to contractile agents than rings from non-treated SHR male rats. Also, the Ca2+ conductance in vitro was enhanced appreciably in SHR aortic rings denuded of their monolayer of endothelium in response to ASA treatment. No decrease in systolic blood pressure was observed in response to ASA treatment in SHR male rats. These results suggest that acetylsalicylic acid not only may modulate aortic smooth muscle contractility through the metabolites of arachidonic acid but may repair to a great extent the hypertension associated plasma membrane permeability defect of vascular myocytes.

Animals↗
PubMed1998

[A mammographic evaluation of the morphostructural variations of the breast during hormone-replacement therapy in the postmenopause].

INTRODUCTION: Exogenous hormones may cause breast tissue changes, generally increasing its density. We used mammography to detect the to early effects of hormone replacement therapy in postmenopausal women. MATERIAL AND METHODS: We examined 300 postmenopausal women (group A: 70 women in surgical menopause treated with estrogen replacement therapy; group B: 230 women in spontaneous menopause receiving estrogen and progestin replacement therapy). The mammographic patterns, according to Wolfe's classification, were compared with those of group C (case control group of 300 women) and group X after 1 year of therapy. The modification were classified as total and partial changes in mammographic density. The results were analyzed with Pearson's chi 2 test. RESULTS: The evidence of a change in parenchymal pattern was found in 103/300 women (34.3%). Twenty-one women in group A and 82 in group B showed increased mammographic density (the DY breast by Wolfe). Partial changes were observed in 64 cases (21.3%). Comparing groups A and B to groups C and X (before therapy), the changes were statistically significant (p < .001), while comparing groups A and B the difference was not significant (p = 1.000). CONCLUSIONS: The likely widespread use of hormone replacement therapy in the future will require an increase in the number of mammograms and a possible re-evaluation of sensitivity. To improve follow-up timing and to avoid a decrease in sensitivity, radiologists will have to consider both general and specific factors and to pay attention to the patterns of global increase in breast tissue density, the DY pattern of Wolfe's classification.

Breast↗
PubMed1998

Prevalence of the C282Y mutation in Brittany: penetrance of genetic hemochromatosis?

Hemochromatosis (GH) is an inborn error of iron metabolism, characterized by progressive iron loading that, if untreated, causes high morbidity and death. The gene responsible for the disease (HFE), located 4.5 megabases telomeric to the HLA-A locus, encodes a protein homologous to class I MHC molecules. A main mutation, C282Y, has been identified within the gene. Although hemochromatosis is considered as the most frequent inherited disease in the populations of Northern European origin, its prevalence in Brittany had not been evaluated yet. In this issue we report the C282Y mutation frequency in a cohort of 1000 newborns from maternity hospitals of the four breton départements. The homozygote frequency was 5/1000 and heterozygote frequency was 12%; such high frequencies raise the question of the penetrance of the disease and the relevance of systematic genotypic screening for hemochromatosis.

Alleles↗
PubMed1997

A 1200-kilobase transcription map encompassing the D6S105 locus at 6p21.3.

The gene content of the MHC class I telomerically adjacent region, in linkage disequilibrium with hereditary hemochromatosis, has not been well characterized yet. In the present work, we established three bacterial clone contigs, including mainly P1-derived artificial chromosomes. These contigs cover 89% of the 1.2-Mb 6p-subtelomeric region encompassing locus D6S105. Terminal exon trapping was applied to selected clones from these contigs. Forty-six independent terminal exons were identified and mapped within the region, 2 of which matched perfectly to expressed sequence tags. These 3' exons are all expressed in human fetal brain but differentially expressed in four tissues and two cell lines. The high number of exons identified indicates that the high gene density observed in the MHC class I region extends to this telomerically adjacent region.

Animals↗
PubMed1997

Identification of two regions in the N-terminal domain of ActA involved in the actin comet tail formation by Listeria monocytogenes.

The ActA protein of Listeria monocytogenes induces actin nucleation on the bacterial surface. The continuous process of actin filament elongation provides the driving force for bacterial propulsion in infected cells or cytoplasmic extracts. Here, by fusing the N-terminus of ActA (residues 1-234) to the omega fragment of beta-galactosidase, we present the first evidence that this domain contains all the necessary elements for actin tail formation. A detailed analysis of ActA variants, in which small fragments of the N-terminal region were deleted, allowed the identification of two critical regions. Both are required to initiate the actin polymerization process, but each has in addition a specific role to maintain the dynamics of the process. The first region (region T, amino acids 117-121) is critical for filament elongation, as shown by the absence of actin tail in a 117-121 deletion mutant or when motility assays are performed in the presence of anti-region T antibodies. The second region (region C, amino acids 21-97), is more specifically involved in maintenance of the continuity of the process, probably by F-actin binding or prevention of barbed end capping, as strongly suggested by both a deletion (21-97) leading to 'discontinuous' actin tail formation and in vitro experiments showing that a synthetic peptide covering residues 33-74 can interact with F-actin. Our results provide the first insights in the molecular dissection of the actin polymerization process induced by the N-terminal domain of ActA.

Actins↗
PubMed1997

Clinical and family studies in genetic hemochromatosis: microsatellite and HFE studies in five atypical families.

A candidate gene (HFE) has been described for hereditary hemochromatosis on chromosome 6. The study of well-defined atypical hemochromatosis families using genetic markers may increase our understanding of the sensitivity and the specificity of genotyping in hemochromatosis. One hundred and thirteen Canadian families with genetic hemochromatosis were surveyed to find atypical families as possible examples of people with genetic recombinations. All families underwent clinical investigations including iron studies and HLA typing. Each individual was typed at three polymorphic microsatellite loci (D6S105, D6S1260, and D6S299) on chromosome 6. Sixteen subjects were studied for the two missense mutations described for the candidate gene for hemochromatosis (C282Y, H63D). There were eight HLA-identical siblings found in four different families (five men, three women; age range 30-72) with normal transferrin saturation and ferritin levels. There were two patients identified who were homozygous for the C282Y mutation without biochemical evidence of iron overload, and two patients with no evidence of the mutation with significant iron overload. Our conclusions are as follows: 1) finding HLA-identical siblings without iron overload does not confirm a genetic recombination, 2) difficulties in phenotypic definition of disease and the description of new iron overload syndromes that may differ from classical genetic HC cause complicated genetic studies, and 3) finding iron-loaded patients without a C282Y mutation and patients that are homozygous for the C282Y mutation without evidence of iron overload may limit the use of genotyping in population screening for hemochromatosis.

Adult↗
PubMed1997

Self-administration of the GABAA antagonist bicuculline into the ventral tegmental area in mice: dependence on D2 dopaminergic mechanisms.

BALB/c mice were unilaterally implanted with a guide cannula, the tip of which was positioned 1.5 mm above the ventral tegmental area (VTA). On each day of the experimental period, a stainless steel injection cannula was inserted into the VTA in order to study the eventual self-administration of a low dose (1.5 ng/50 nl) of bicuculline, a GABAA-antagonist, using a spatial discrimination task in a Y maze. Mice rapidly discriminated between the arm enabling a micro-injection of bicuculline and the neutral arm of the maze, and robust self-administration of this GABAergic antagonist was observed. Once this self-administration response for bicuculline had been fully acquired, the systemic injection of the dopaminergic D2 antagonist sulpiride (50 mg/kg), 30 min before the test, produced a rapid extinction of the self-administration response. Moreover, if this same sulpiride pretreatment was given during the initial acquisition period mice did not discriminate between the two arms of the Y-maze. These data demonstrate the dopamine D2 dependence of this bicuculline self-administration behavior, and confirm that GABAergic interneurons and/or inputs normally transynaptically inhibit neuronal activity in the mesocorticolimbic dopamine system.

Animals↗
PubMed1997

A candidate gene for hemochromatosis: frequency of the C282Y and H63D mutations.

The gene whose alteration causes hereditary hemochromatosis (HFE according to the international nomenclature) was, more than 20 years ago, shown to map to 6p21.3. It has since escaped all efforts to identify it by positional cloning strategies. Quite recently, a gene named HLA-H was reported as being responsible for the disease. Two missense mutations, Cys282Tyr (C282Y) and His63Asp (H63D), were observed, but no proof was produced that the gene described is the hemochromatosis gene. To validate this gene as the actual site of the alteration causing hemochromatosis, we decided to look for the two mutations in 132 unrelated patients from Brittany. Our results indicate that more than 92% of these patients are homozygous for the C282Y mutation, and that all 264 chromosomes but 5 carry either mutation. These findings confirm the direct implication of HLA-H in hemochromatosis.

Chromosomes, Human, Pair 6↗
PubMed1997

Early singleton pregnancy outcome: effects of maternal age and mode of conception.

PURPOSE: To assess the effect of prognostic factors on the outcome of singleton pregnancies. MATERIALS AND METHODS: First-trimester ultrasonographic (US) scans that demonstrated a living fetus in 4,156 consecutive singleton pregnancies were studied. The relationship between outcome and maternal age, mode of conception, maternal symptoms, and US findings was evaluated. RESULTS: Spontaneous abortion occurred in 371 of 4,156 (8.9%) cases. Higher pregnancy-loss rates were associated with older maternal age (P < 10(-5)), assisted mode of conception (P < 10(-8)), maternal symptoms of pain and/or bleeding (P < .001), and abnormal US findings (P < 10(-8)). US abnormalities were more frequent in older women than in younger women (P < 10(-5)) and in assisted conceptions than in natural conceptions (P < 10(-8)). At stepwise logistic regression, with gestational age as a covariate, US abnormalities and maternal symptoms independently affected pregnancy outcome. Maternal age and mode of conception had no further statistically significant effect on pregnancy outcome. CONCLUSION: The prognosis for older mothers and for those with assisted conception is not statistically significantly different from that for younger mothers and for those with natural conception if maternal symptoms, US findings, and gestational age are the same.

Abortion, Spontaneous↗