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Biomedical subjects

F Seillier-Moiseiwitsch

Publications and source records attributed to F Seillier-Moiseiwitsch.

8 recordsLinked to original sources
PubMed1999

Signature amino acid changes in latent membrane protein 1 distinguish Epstein-Barr virus strains.

Sequence variations in the Epstein-Barr virus (EBV) latent membrane protein 1 gene have been described in numerous EBV-associated tumors with some of these variations, most notably a 30-base pair deletion in the cytoplasmic carboxyl-terminal domain, suggested as associated with an increase in tumorigenicity. In this study, EBV DNA sequence was determined from 92 tissue specimens or cell lines, including nasopharyngeal carcinoma, oral hairy leukoplakia, post-transplant lymphoma, post-transplant without pathology, mononucleosis, Burkitt's lymphoma, parotid tumor, and normal from distinct geographical regions. The amino- and carboxyl-terminal sequences and, in some cases, the full-length sequences of latent membrane protein 1 were determined. Characteristic sequence patterns distinguished strains, with the carboxyl-terminal sequence being the most informative in distinguishing among the strains. Phylogenetic relationships between strains were determined, as were signature amino acid changes that discriminate between them. A correlation between strain and disease or strain and geographic location was not detected. The sequence variation and signature sequences identified at least seven distinct strains, as well as hybrid strains that apparently result from recombination.

Amino Acid Sequence↗
PubMed1999

Exploring the role of environmental factors in association and linkage studies.

We analyzed some simulated data to assess the success of statistical methodologies to establish the role of the environmental factors (EF) and to identify associated and linked markers. We considered five replicates for each of the four studies, and, with the knowledge of the generating model, concentrated our analyses on chromosomes (CH) 1, 3, and 5. To determine the influence of EF and associated markers on the affection status (AS), we utilized chi-square tests for independence and recursive partitioning (via the CART software). To identify linked markers, we scanned the relevant chromosomes with nonparametric multipoint linkage (NPL) and transmission/disequilibrium tests. These analyses were performed on the whole data set as well as on subsets of individuals and families defined by exposure to EF. CART correctly selected the associated marker (D1G024) and EF1 for Study (ST) 1 and did not generate trees for the other studies. NPL identified the relevant regions on CH3 and CH5 but failed to do so for CH1, except in ST4. Stratifying families by exposure to EF1 did not consistently increase sensitivity of NPL to the relevant CH3 markers, but did help characterize the genetic heterogeneity and identify linked families.

Chi-Square Distribution↗
PubMed1998

Resistance of HIV-1 to antiretroviral agents in blood and seminal plasma: implications for transmission.

OBJECTIVES: To evaluate blood and genital secretions from HIV-infected men for HIV-1 resistant to antiretroviral agents. DESIGN: A longitudinal study of 11 men with HIV infection and persistent detectable HIV RNA levels in blood and semen on antiretroviral therapy. METHODS: HIV-1 from the blood and seminal plasma, obtained before the initiation of a new therapeutic regimen and on therapy, were evaluated by population-based sequencing of reverse transcriptase (RT) and protease RNA for the development of resistance to antiretroviral therapy. The genetic relatedness of sequences over time was compared. RESULTS: RT genotypic resistance markers were present in seminal plasma at baseline in three out of six individuals with previous RT inhibitor experience. Eight out of 10 men, from whom the viral sequence was available on new therapy, demonstrated the evolution of new resistance mutations in the blood or seminal plasma, or both. The evolution of resistance mutations in blood and semen were frequently discordant, although over time similar patterns were seen. In two individuals, protease inhibitor resistance mutations evolved in the blood but not in the major variant in seminal plasma. Comparisons of the viral sequences between blood and seminal plasma from six men revealed two patterns. Three men showed a clustering of sequences from blood and semen. Three had sequences that appeared to evolve separately in the two compartments. CONCLUSIONS: HIV-1 variants with genotypic resistance markers are present in the male genital tract and evolve over time on incompletely suppressive antiretroviral therapy. The absence of genotypic changes consistent with protease inhibitor resistance in the semen, despite their presence in blood plasma, suggests the possibility of limited penetration of these agents into the male genital tract. Sexual transmission of resistant variants may have a negative impact on treatment outcome in newly infected individuals and on the spread of the diseases within a population. Therapeutic strategies that fully suppress HIV-1 in the genital tract should be a public health priority.

Amino Acid Sequence↗
PubMed1998

Epstein-Barr virus strain variation in nasopharyngeal carcinoma from the endemic and non-endemic regions of China.

Nasopharyngeal carcinoma (NPC) occurs with a striking geographic incidence and is endemic in parts of southern China, where it is the major cause of cancer death. Epstein-Barr virus (EBV) is detected in all cells of the majority of NPC cases regardless of geographic origin. A small subset of EBV genes is expressed in NPC, including the latent membrane protein (LMP-1). LMP-1 is essential for transformation of B lymphocytes and is considered to be the EBV oncogene. This analysis of the DNA sequence variation within the LMP-1 gene reveals a consensus sequence for a strain, denoted China1, which predominates in East Asia where NPC is endemic. The China1 strain is characterized by nucleotide changes at 13 loci in the amino terminal portion of the LMP-1 gene when compared with the B95-8 prototype, including a point mutation resulting in the loss of an Xho1 restriction site. This strain was present in 9 of 15 NPC biopsy specimens from the endemic region and in 7 of 13 from northern China, where NPC is non-endemic. A second strain, China2, was detected in 4 of 15 endemic isolates and in 2 of 13 non-endemic isolates; this strain was characterized by a cluster of 5 nucleotide changes in the amino terminal portion of LMP-1 in addition to those seen in China1. It was also marked by distinct changes in the carboxy terminal region of LMP-1 including the retention of amino acids 343-352. All China1 isolates were EBV type 1, whereas the China2 isolates did not correlate with EBV type. Phylogenetic relationships between these 2 strains were determined, as were signature amino acid alterations that discriminate between them.

Base Sequence↗
PubMed1997

Identifying genetic markers to assess the presence of gene-environment interactions.

We analyzed a randomly chosen replicate with the goals of locating the closest markers to the genes involved in the discrete trait and utilizing these as surrogates for the genes in assessing the presence of gene-environment interactions. We screened the markers with an association test prior to using the transmission-disequilibrium test. We performed a segregation analysis, with regressive models and including the selected markers, to understand the underlying genetic mechanism and the role of the environmental factor. We were unsuccessful in locating the relevant markers due to the absence of linkage disequilibrium. Nevertheless, some insights were gained from the methods used.

Chromosome Mapping↗
PubMed1996

Predictive diagnostics for logistic models.

Novel methodology is implemented to assess the predictive power of covariate information associated with sequential binary events. Logistic models are first fitted on the basis of a subset of the observations and then evaluated sequentially on the rest. The probabilistic forecasts are compared to the outcomes via a scoring function, but as most validation samples are small, the usual reference distribution for the test statistics is inadequate. However, bootstrap-based distributions can easily be constructed. The first example pertains to the evaluation of screening tests for major depression. It illustrates that goodness-of-fit and predictive assessments lead to the selection of very different models. The second example deals with the prediction of a major event in the natural history of HIV-induced disease. It shows that this type of analysis can reveal features missed by other approaches.

Calibration↗
PubMed1993

Analysis of human immunodeficiency virus type 1 nef gene sequences present in vivo.

The nef genes of the human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2) and the related simian immunodeficiency viruses (SIVs) encode a protein (Nef) whose role in virus replication and cytopathicity remains uncertain. As an attempt to elucidate the function of nef, we characterized the nucleotide and corresponding protein sequences of naturally occurring nef genes obtained from several HIV-1-infected individuals. A consensus Nef sequence was derived and used to identify several features that were highly conserved among the Nef sequences. These features included a nearly invariant myristylation signal, regions of sequence polymorphism and variable duplication, a region with an acidic charge, a (Pxx)4 repeat sequence, and a potential protein kinase C phosphorylation site. Clustering of premature stop codons at position 124 was noted in 6 of the 54 Nef sequences. Further analysis revealed four stretches of residues that were highly conserved not only among the patient-derived HIV-1 Nef sequences, but also among the Nef sequences of HIV-2 and the SIVs, suggesting that Nef proteins expressed by these retroviruses are functionally equivalent. The "Nef-defining" sequences were used to evaluate the sequence alignments of known proteins reported to share sequence similarity with Nef sequences and to conduct additional computer-based searches for similar protein sequences. A gene encoding the consensus Nef sequence was also generated. This gene encodes a full-length Nef protein that should be a valuable tool in further studies of Nef function.

Acquired Immunodeficiency Syndrome↗