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Biomedical subjects

L Mallet

Publications and source records attributed to L Mallet.

At least 37 records · Page 2Linked to original sources

[Cirrhosis with non alcoholic steatohepatitis: role of tamoxifen].

We report a case of non-alcoholic steatohepatitis with cirrhosis in a woman receiving tamoxifen as adjuvant treatment for breast cancer. Despite the presence of other risk factors for non-alcoholic steatohepatitis (such as diabetes, obesity and hyperlipidemia), the patient developed non-alcoholic steatohepatitis and cirrhosis only after tamoxifen was started. We suggest that patients receiving tamoxifen, especially patients with predisposing metabolic disorders, should be evaluated for non-alcoholic steatohepatitis, because progression to cirrhosis may occur.

Aged↗

Abnormal psychosocial situations among inpatients from a child and adolescent psychiatric department in a teaching hospital in France.

In order to examine the relationships between Associated Abnormal PsychoSocial Situations and psychiatric disorders in children and adolescents, an exploratory analysis using Axis V of the ICD-10 was performed on 1050 child and adolescent psychiatric inpatients. A logistic regression analysis was completed with respect to four groups of DSM-III-R diagnostic categories (Emotional Disorders, Disruptive Behavior Disorders, Specific Developmental Disorders, Non Specific Developmental Disorders). AAPSS were more frequently found in children and adolescents with Emotional Disorders or Disruptive Behavior Disorders than in those with Developmental Disorders but there was no diagnostic specificity in the distribution of AAPSS.

Adolescent↗

Functional connectivity in depressive, obsessive-compulsive, and schizophrenic disorders: an explorative correlational analysis of regional cerebral metabolism.

In order to investigate the changes in functional relationships between brain regions in three psychiatric disorders, an exploratory statistical analysis of the regional cerebral metabolic rates for glucose (rCMRglu) obtained with positron emission tomography (PET) was performed. Correlations between various rCMRglu were computed in control, depressive, obsessive-compulsive, and schizophrenic groups to determine whether alterations of the correlation pattern were found in the psychiatric groups. The absence of correlation between left and right frontal lobes was common to the three psychiatric groups studied. Depressive patients recovered a better frontal interhemispheric coupling after successful treatment and the alterations in the depressed state also involved the relation between the right temporal cortex and the right thalamus. Obsessive-compulsive patients had not only lateral frontal dysfunction but also alterations in the functional relationships between cortex and thalami. In schizophrenic patients, the modifications of regional cerebral metabolic correlations involved both anterior and posterior cortical regions. Thus, although the relationship between left and right frontal lobes was altered in three psychiatric disorders, the pattern of functional connectivity between frontal regions, posterior cortical and subcortical regions differed depending on the diagnostic group.

Adult↗

Indomethacin-induced behavioral changes in an elderly patient with dementia.

OBJECTIVE: To describe a case of behavioral changes induced by indomethacin in an elderly man with a history of senile dementia of the Alzheimer type. CASE SUMMARY: A 92-year-old white man with a history of senile dementia of the Alzheimer type, glaucoma, and constipation was treated with indomethacin for an episode of pseudogout. After six doses of indomethacin 25 mg, the patient became very agitated, confused, and was physically and verbally aggressive to the nurses. Indomethacin was discontinued and the patient recovered after receiving haloperidol 0.5 mg/d p.o. over a period of 10 days. DISCUSSION: Only a few cases of psychosis have been reported in the literature concerning the use of indomethacin in patients over the age of 60 years. The mechanism by which indomethacin causes psychosis is not well understood, but it is postulated that the acute psychosis may be related to the similarity between the molecular structure of indomethacin and serotonin. Both indomethacin and serotonin have an indolic moiety, which may explain the development of acute psychosis in this patient. CONCLUSIONS: Healthcare providers should be aware that patients with a history of dementia who are receiving indomethacin may be at risk of developing severe behavior problems along with gastrointestinal and renal adverse effects.

Aged↗

The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its evolutionary implications.

In 1992 we started assembling an ordered library of cosmid clones from chromosome XIV of the yeast Saccharomyces cerevisiae. At that time, only 49 genes were known to be located on this chromosome and we estimated that 80% to 90% of its genes were yet to be discovered. In 1993, a team of 20 European laboratories began the systematic sequence analysis of chromosome XIV. The completed and intensively checked final sequence of 784,328 base pairs was released in April, 1996. Substantial parts had been published before or had previously been made available on request. The sequence contained 419 known or presumptive protein-coding genes, including two pseudogenes and three retrotransposons, 14 tRNA genes, and three small nuclear RNA genes. For 116 (30%) protein-coding sequences, one or more structural homologues were identified elsewhere in the yeast genome. Half of them belong to duplicated groups of 6-14 loosely linked genes, in most cases with conserved gene order and orientation (relaxed interchromosomal synteny). We have considered the possible evolutionary origins of this unexpected feature of yeast genome organization.

Base Sequence↗

Comparative study of poliovirus excretion after vaccination of infants with two oral polio vaccines prepared on Vero cells or on primary monkey kidney cells.

A comparative study was designed to assess the bioequivalence of 2 oral poliovaccines (OPV) produced on 2 different cell systems: primary monkey kidney (PMK) cells and the Vero cell line. The Vero cell line has been used to overcome the problem of obtaining a regular supply of high quality monkeys that are devoid of latent viruses. For this study, 9 children were vaccinated with PMK-OPV and 12 children with Vero-OPV. The comparison covered poliovirus excretion, reversion of polioviruses in the 5'-noncoding region, and immunogenicity. Major molecular markers in the 5'-noncoding region related to neurovirulence already had been identified at position 480 for type 1, position 481 for type 2, and position 472 for type 3 poliovirus. Two nucleic-acid based methods were designed for studying these positions: a RT-PCR followed by sequencing, which required preliminary culture and cloning; and a type-specific nested PCR followed by sequencing, which enabled direct detection and genotyping of polioviruses. Twenty-eight stool specimens were analyzed by this second method with no PCR inhibition problem. The use of Vero cell line did not modify the global pattern of poliovirus excretion, reversion frequency, or seroconversion. These results provide additional support for the use of the well-characterized Vero cell line in OPV manufacturing.

Animals↗

Intergenic Flip Flop, a method for systematic gene disruption and cloning in yeast.

We have developed a strategy named Intergenic Flip Flop which, for each gene, allows us to produce in one experiment both a disrupting cassette and a plasmid for gap repair. The same method can also be used to insert a reporter gene downstream from the promoter. This approach extends the polymerase chain reaction (PCR)-based strategy proposed by Maftahi et al. 1996. Our method consists of PCR amplification of the two flanking intergenic regions of the open reading frame (ORF) of interest, using two sets of oligonucleotides. Each PCR product is flanked by two short defined nucleotidic sequences with a unique restriction site, allowing subsequent hybridization between them. The association of the two amplimers by the complementary sequences either in the same orientation as in genomic DNA or in the opposite orientation, allows the generation, after PCR, of two distinct cassettes which can be cloned into suitable vectors. When the amplimer in the head-to-tail orientation is cloned in a vector containing a selective marker for yeast such as G418 resistance, it provides a disrupting cassette after cleavage at the unique restriction site introduced by the PCR between the two intergenic amplimers. The amplimer with a direct orientation cloned into a yeast vector, after cleavage at the unique restriction site between the intergenic regions, permits cloning by gap repair of the gene of interest in yeast. Finally, a reporter gene can be inserted in the same plasmid. We report here the successful application of this strategy to an ORF of chromosome XIV of Saccharomyces cerevisiae: N1216.

Cloning, Molecular↗

Positional cloning of a gene involved in hereditary multiple exostoses.

Hereditary multiple exostosis (EXT) is an autosomal dominant condition mainly characterized by the presence of multiple exostoses on the long bones. These exostoses are benign cartilaginous tumors (enchondromata). Three different EXT loci on chromosomes 8q (EXT1), 11p (EXT2) and 19p (EXT3) have been reported, and recently the EXT1 gene was identified by positional cloning. To isolate the EXT2 gene, we constructed a contig of yeast artificial chromosomes (YAC) and P1 clones covering the complete EXT2 candidate region on chromosome 11p11-p12. One of the transcribed sequences isolated from this region corresponds to a novel gene with homology to the EXT1 gene, and harbours inactivating mutations in different patients with hereditary multiple exostoses. This indicates that this gene is the EXT2 gene. EXT2 has an open reading frame encoding 718 amino acids with an overall homology of 30.9% with EXT1, suggesting that a family of related genes might be responsible for the development of EXT.

Amino Acid Sequence↗

A 43.5 kb segment of yeast chromosome XIV, which contains MFA2, MEP2, CAP/SRV2, NAM9, FKB1/FPR1/RBP1, MOM22 and CPT1, predicts an adenosine deaminase gene and 14 new open reading frames.

A 43,481 bp fragment from the left arm of chromosome XIV of Saccharomyces cerevisiae was sequenced. A gene for tRNA(phe) and 23 non-overlapping open reading frames (ORFs) were identified, seven of which correspond to known yeast genes: MFA2, MEP2, CAP/SRV2, NAM9, FKB1/FPR1/RBP1, MOM22 and CPT1. One ORF may correspond to the yet unidentified yeast adenosine deaminase gene. Among the 15 other ORFs, four exhibit known signatures, which include a protein tyrosine phosphatase, a cytoskeleton-associated protein and two ATP-binding proteins, four have similarities with putative proteins of yeast or proteins from other organisms and seven exibit no significant similarity with amino acid sequences described in data banks. One ORF is identical to yeast expressed sequence tags (EST) and therefore corresponds to an expressed gene. Six ORFs present similarities to human dbESTs, thus identifying motifs conserved during evolution. Nine ORFs are putative transmembrane proteins. In addition, one overlapping and three antisense ORFs, which are not likely to be functional, were detected.

Adenosine Deaminase↗

The mitochondrial receptor complex: Mom22 is essential for cell viability and directly interacts with preproteins.

A multisubunit complex in the mitochondrial outer membrane is responsible for targeting and membrane translocation of nuclear-encoded preproteins. This receptor complex contains two import receptors, a general insertion pore and the protein Mom22. It was unknown if Mom22 directly interacts with preproteins, and two views existed about the possible functions of Mom22: a central role in transfer of preproteins from both receptors to the general insertion pore or a more limited function dependent on the presence of the receptor Mom19. For this report, we identified and cloned Saccharomyces cerevisiae MOM22 and investigated whether it plays a direct role in targeting of preproteins. A preprotein accumulated at the mitochondrial outer membrane was cross-linked to Mom22. The cross-linking depended on the import stage of the preprotein. Overexpression of Mom22 suppressed the respiratory defect of yeast cells lacking Mom19 and increased preprotein import into mom19 delta mitochondria, demonstrating that Mom22 can function independently of Mom19. Overexpression of Mom22 even suppressed the lethal phenotype of a double deletion of the two import receptors known so far (mom19 delta mom72 delta). Deletion of the MOM22 gene was lethal for yeast cells, identifying Mom22 as one of the few mitochondrial membrane proteins essential for fermentative growth. These results suggest that Mom22 plays an essential role in the mitochondrial receptor complex. It directly interacts with preproteins in transit and can perform receptor-like activities.

Amino Acid Sequence↗

Improved strategy for large-scale DNA sequencing using DNaseI cleavage for generating random subclones.

Large-scale DNA sequencing projects require the use of specific and reliable strategies. Here, we describe an improved strategy using DNaseI cleavage and sequencing strategy using DNaseI cleavage and sequencing from both ends of the plasmid inserts. This strategy yields better results than those obtained using partial digestion with restriction enzymes and cloning in single-stranded vectors.

Bacteriophage M13↗

Complete DNA sequence of yeast chromosome II.

In the framework of the EU genome-sequencing programmes, the complete DNA sequence of the yeast Saccharomyces cerevisiae chromosome II (807 188 bp) has been determined. At present, this is the largest eukaryotic chromosome entirely sequenced. A total of 410 open reading frames (ORFs) were identified, covering 72% of the sequence. Similarity searches revealed that 124 ORFs (30%) correspond to genes of known function, 51 ORFs (12.5%) appear to be homologues of genes whose functions are known, 52 others (12.5%) have homologues the functions of which are not well defined and another 33 of the novel putative genes (8%) exhibit a degree of similarity which is insufficient to confidently assign function. Of the genes on chromosome II, 37-45% are thus of unpredicted function. Among the novel putative genes, we found several that are related to genes that perform differentiated functions in multicellular organisms of are involved in malignancy. In addition to a compact arrangement of potential protein coding sequences, the analysis of this chromosome confirmed general chromosome patterns but also revealed particular novel features of chromosomal organization. Alternating regional variations in average base composition correlate with variations in local gene density along chromosome II, as observed in chromosomes XI and III. We propose that functional ARS elements are preferably located in the AT-rich regions that have a spacing of approximately 110 kb. Similarly, the 13 tRNA genes and the three Ty elements of chromosome II are found in AT-rich regions. In chromosome II, the distribution of coding sequences between the two strands is biased, with a ratio of 1.3:1. An interesting aspect regarding the evolution of the eukaryotic genome is the finding that chromosome II has a high degree of internal genetic redundancy, amounting to 16% of the coding capacity.

Base Composition↗