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P Loiseau

Publications and source records attributed to P Loiseau.

At least 19 recordsLinked to original sources
PubMed1995

HLA-Cw allele analysis by PCR-restriction fragment length polymorphism: study of known and additional alleles.

We describe a technique for HLA-Cw genotyping by digestion of PCR-amplified genes with restriction endonucleases. Locus-specific primers selectively amplified HLA-Cw sequences from exon 2 in a single PCR that avoided coamplification of other classical and nonclassical class I genes. Amplified DNAs were digested with selected enzymes. Sixty-three homozygous cell lines from International Histocompatibility Workshop X and 113 unrelated individual cells were genotypes for HLA-Cw and compared with serology. The present protocol can distinguish 23 alleles corresponding to the known HLA-Cw sequences. Genotyping of serologically undetectable alleles (HLA-Cw Blank) and of heterozygous cells was made possible by using this method. Six additional HLA-Cw alleles were identified by unusual restriction patterns and confirmed by sequencing; this observation suggests the presence of another family of allele-sharing clusters in the HLA-B locus. This PCR-restriction endonuclease method provides a simple and convenient approach for HLA-Cw DNA typing, allowing the definition of serologically undetectable alleles, and will contribute to the evaluation of the biological role of the HLA-C locus.

Alleles↗
PubMed1995

TAP2 gene polymorphism contributes to genetic susceptibility to multiple sclerosis.

MS is an autoimmune demyelinating disease that has been known to be associated with the HLA-DRB1*1501-DQA1*0102-DQB1*0602 haplotype. TAP1 and TAP2, two genes encoded within the MHC class II region between HLA-DP and -DQ loci, display genetic variability and are involved in the transport of antigenic peptides from the cytoplasm to the endoplasmic reticulum. Comparison of 116 MS patients with Caucasoid controls did not reveal any significant correlation between the previously described alleles of the TAP1 and TAP2 genes and MS. We report here an additional TAP2 dimorphism at codon 386, called I and J, corresponding to a silent mutation. An increased frequency of the J variant was observed in the patient population. The J mutation was not found in linkage disequilibrium with the HLA-DRB1*1501 allele and can be considered an additional genetic susceptibility marker of the disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Absence epilepsies.

Individuals fulfilling diagnostic criteria for childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE) were selected from a large group of patients who were born between 1945 and 1973 and had presented with absence seizures (AS). Updated data allowed an analysis of 52 patients with CAE and of 62 patients with JAE age > or = 20 years. In CAE, complete control was achieved in 90% of patients (95%, AS only; 77%, AS + generalized tonic-clonic seizures, GTCS). Only 16% of patients with an onset < 9 years had developed GTCS. In JAE, complete control was achieved in 37% of patients (47%, AS; 37%, GTCS). These figures support the validity of the International Classification of Epilepsy (ICE). Stricter diagnostic criteria are discussed.

Adult↗
PubMed1995

[Drug-resistant epilepsy in adults].

Various estimation of the proportion of difficult-to-treat epileptic patients is given in the literature. It varies from 5 percent to 25 percent, because of imprecise meaning of pharmacoresistancy and similar terms. There is no such thing as a unique pharmacoresistant epilepsy. Persisting seizures despite antiepileptic drug prescription does not necessarily mean refractory seizures. Seizures may be drug-resistant for a limited period only, or be intermittent, or be a long-lasting condition. Seizure frequency may remain unchanged, or decrease, more or less. Toxicity of AEDs must be considered. Unbearable side effects are a limiting factor for maintaining some active drugs. In practice, the term pharmacoresistancy may be used when seizures occur in spite of a convenient therapy, whatever their frequency, and whatever the resulting handicap. Predictive factors for intractibility may be considered under four headings, i.e. seizure types, patient, epileptic syndrome, and antiepileptic drugs. Most of the elements of the first three groups are available immediately after the first seizure and response to treatment may be estimated one or two years later. Outcome of an epilepsy may be evaluated, or guessed, rather early. This is crucial for management of epileptic patients.

Adult↗
PubMed1994

Indeterminate third-generation recombinant immunoblot assay in hepatitis C virus infection. Group d'Etudes Moléculaires des Hépatites (GEMHEP).

Third-generation recombinant immunoblot assay is widely used for the validation of the serological diagnosis of hepatitis C virus infection. To determine whether indeterminate recombinant immunoblot assay 3.0 patterns may be associated with viral replication and liver disease, 89 indeterminate patterns were studied (67 c22n 14 c33c, 5 c100p and 3 NS5); 35 (39%) had immunosuppression. Serum alanine aminotransferase activity was increased in 49 (55%); HCV RNA was evidenced through polymerase chain reaction in 52 (58%). The observation of indeterminate recombinant immunoblot assay 3.0 justifies investigation of liver disease and search for HCV RNA, since a large proportion of individuals with such patterns are hepatitis C virus-infected.

Adolescent↗
PubMed1992

Unexpected consistent involvement of V beta gene segments in inappropriate T-cell receptor beta gene rearrangements occurring in B-lineage acute lymphoblastic leukemias.

T-cell receptor beta (TCR beta) gene rearrangements occur in a third of early B-cell acute lymphoblastic leukemias (ALLs). V, D, and J segments involved in these inappropriate rearrangements remain unknown and are of interest, both because partial D beta J beta and complete V beta D beta J beta recombinations occur at distinct stages of thymic maturation and because these rearrangements are regulated differently. We have therefore studied in detail seven cases of B-lineage ALL that show inappropriate clonal TCR beta gene rearrangements. Analysis of genomic DNA by Southern hybridization with C beta, J beta 1, V beta 8, and V beta 11 probes suggested the involvement of V beta segment in tumor cell rearrangements. A complete genomic library constructed from one case was screened with a C beta probe, and the TCR beta gene rearrangement was cloned and fully sequenced to show an out of frame V beta 2.2-J beta 2.6 recombination. TCR beta gene rearrangements occurring in other cases were further analyzed by polymerase chain reaction (PCR) using J beta and V beta primers and the resulting specific PCR products were sequenced. Evidence of clonal V beta rearrangements was obtained in all cases. These unexpected findings represent the first definitive demonstration that complete V beta(D beta)J beta rearrangements can occur in B-lineage cells and contrast with the previously reported lack of V beta(D beta)J beta rearrangement in B cells from V beta-J beta-C beta-E mu transgenic mice. In the context of increasing evidence that rearrangements are linked to transcription of unrearranged gene segments, these data prompt a search in B-lineage ALL cells for the presence of germline V beta transcripts whose deregulated expression may be linked to early transforming events.

Animals↗
PubMed1992

Human absence epilepsies.

A historical review of the concept of absence seizures. Their clinical features are very suggestive but a diagnosis made solely on clinical grounds is not always safe. Comparable pitfalls exist in the interpretation of EEG patterns. Absence seizures belong to several epileptic syndromes. They are briefly described.

Electroencephalography↗
PubMed1992

Occurrence of polyglucosan bodies in temporal lobe epilepsy.

Massive occurrence of polyglucosan bodies (PBs) was found within the surgically removed temporal lobe of a 34 year old woman with complex partial seizures. This peculiar feature is very unusual in neuropathological examinations of epileptogenic foci. This patient could not be included in any of the classic diseases in which PBs are found. She exhibited a localised form of glycogen storage disease.

Adult↗
PubMed1992

A longitudinal assessment of seizure outcome and overall benefit from 100 cortectomies for epilepsy.

Results of 100 cortical resections for 76 temporal, 23 frontal and one parietal lobe epilepsies were studied in terms of seizure relief and overall benefit. A non-homogenous Markov chain model was used to take into account both the intravariability of post-surgical outcome and the differences in duration of follow-up in a group of patients consecutively operated. The seizure free (SF) state was defined as no seizure in the previous five months at first follow up visit and none in the preceding 12 months at subsequent annual visits. For the whole of the population the SF probability was 82%, 66%, 61%, and 62% at six months, one year, two and five years respectively. A better outcome was found for temporal lobe epilepsy (SF probability: 68% at the fifth postoperative year) than for frontal lobe epilepsy (SF probability: 42% at the fifth postoperative year) with a statistically significant difference. Pre- and postoperative interictal signs and symptoms were classified according to their clinical significance: (a) mild handicap--symptoms recognisable but no interference with usual life, and (b) moderate or severe handicap--interference with some or all daily activities. The interictal state was considered more impaired after surgery than before in two situations: (a) either symptoms, absent before surgery, appeared in the postoperative period involving a moderate or severe handicap, or (b) symptoms present before surgery and answerable for a mild or moderate handicap that increased to involve a moderate or severe handicap respectively in the postoperative period. Surgery was considered a major benefit when two conditions were fulfilled-namely, a SF state and no deterioration of the interictal stage when compared with the preoperative period. The probability of obtaining such a benefit was 58%, 51%, 48% and 56% at six months, one year, two and five years respectively. The results suggest that surgery is an effective treatment for more than 50% of long lasting medically intractable epilepsies.

Adolescent↗
PubMed1992

The prognosis of benign localized epilepsy in early childhood.

Onset of seizures during early childhood is a not infrequent possibility in benign partial (localization-related) epilepsy (BPEC) when all these syndromes and not only benign partial epilepsy with centrotemporal spikes are considered. In patients followed up for long periods of time, temporal changes in the EEG often make impossible a distribution into discrete syndromes. The electroclinical patterns overlap and the determining factor is not the location but the morphology of the sharp waves. A complete remission is observed in all patients, with rolandic and/or extrarolandic foci. In rare patients, seizures occur during adolescence or later and an early onset is a possible risk factor for such an outcome. It is not a relapse of BPEC but another epileptic syndrome, usually a generalized idiopathic epilepsy. BPEC may be considered as a risk factor for late epilepsy. Patients with an early onset of BPEC tend to have a longer active period of epilepsy and a higher total number of seizures, whatever is the EEG pattern. But neither frequent seizures nor a long seizure period impair the children's abilities. Nonetheless, when BPEC begins in early childhood, the patient is prone to experience frequent seizures during several years. Drug therapy is advisable more often than in BPEC with a later onset.

Adolescent↗
PubMed1992

[Pilot study of Ginkgolide B, a PAF-acether specific inhibitor in the treatment of acute outbreaks of multiple sclerosis].

Ten patients with relapsing-remitting multiple sclerosis in acute relapse were treated with a five-day course of intravenous ginkgolide B, a specific inhibitor of PAF-acether. Eight patients had improvement of their neurological score, beginning 2 to 6 days after the initiation of therapy. This improvement was sustained in 5 patients and only transient in 3. Two out of these 3 patients with secondary failure and the other 2 who did not respond to ginkgolide therapy, received i.v. methylprednisolone. Three patients experienced mild side effects under ginkgolide therapy but none of the patients had any serious adverse effect. A controlled randomized study is underway, in order to confirm these results and test higher dosages and more prolonged administration.

Adult↗
PubMed1992

Synthesis of the orally macrofilaricidal and stable glycerolipidic prodrug of melphalan, 1,3-dipalmitoyl-2-(4'(bis(2''-chloroethyl)amino)phenylalaninoyl)gl ycerol.

A new strategy is presented to develop macrofilaricidal compounds orally administered and able to concentrate in the lymphatic system. A diglyceride derivative of melphalan, 1,3-dipalmitoyl-2-(4'(bis(2''-chloroethyl)amino)phenylalaninoyl)gl y cerol, was synthesized. The esterification of melphalan by 1,3-dipalmitin allowed chemical stabilization of the alkylating agent in aqueous dispersion. No degradation of this prodrug was observed after a 3-month storage of an aqueous dispersion at 4 degrees C. The filaricidal activity of the prodrug was compared with those of melphalan in vitro against adults, infective larvae and microfilariae of Molinema dessetae, and evaluated in vivo on Molinema dessetae infected Proechimy oris. In vitro, melphalan and the glycerolipidic prodrug were inactive against microfilariae but active at 1 mmol/l against infective larvae and adults. In vivo studies were performed with rodents subcutaneously inoculated with infective larvae from Aedes aegypti. The number of macrofilariae was significantly reduced following treatment with a single oral dose of the alkylating agent prodrug (0.082 mmol/kg).

Aedes↗
PubMed1992

In vitro and in vivo evaluation of macrofilaricidal activity of GABA and 1,3-dipalmitoyl-2-(4-aminobutyryl)glycerol HCl: a diglyceride prodrug.

A new therapeutic target has been identified from the filaria Molinema dessetae: the gabaergic system. gamma-aminobutyric acid (GABA) itself showed antifilarial effect in vitro and a macrofilaricidal action in vivo at high dose by intraperitoneal route (10(-2) M). Nevertheless, no action was observed by oral route. The study we report here consists to obtain an antifilarial effect by oral route using a diglyceride prodrug. Such a strategy is based on the triglycerides metabolism. A diglyceride prodrug of gamma-aminobutyric acid has been synthesized and its filaricidal activity compared with that of GABA, in vitro on adults of Molinema dessetae and in vivo on Molinema dessetae infected Proechimys oris. In vitro, GABA at 2.5 x 10(-3) M induced a temporary paralysis and the ester drug at the same concentration was fully active on adults. In vivo, no significant activity was observed by oral administration of a daily dose of GABA (10(-2) M). A five day course of GABA at 10(-2) M via the intraperitoneal route induced a significant reduction of male and female worms. We did not find any activity of the prodrug in vivo, either by the oral route (10(-2) M) or after an intraperitoneal administration (10(-3) M). The interest of GABA and GABA derivatives as potential filaricidal drugs was discussed.

Animals↗