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Biomedical subjects

P Loiseau

Publications and source records attributed to P Loiseau.

At least 109 records · Page 6Linked to original sources

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↗

[Facio-linguo-masticatory diplegia and epilepsy. Cortical dysplasia].

Neuronal migration anomalies are caused by insults occurring during the third to fifth gestational months when neuroblasts migrate from the germinal zone to the cortical plate. They lead to several cerebral malformations such as macrogyria, identified nowadays by MRI. We describe a case of bilateral parieto-rolandic macrogyria responsible for a bi-opercular syndrome resulting in a facio-linguo-masticatory diplegia associated with mental retardation and severe epilepsy.

Adult↗

[Research and surgical treatment of epilepsy].

The currently available surgical procedures for the treatment of epilepsy, from fundamental data to therapeutic results, including various means of investigation are reported. The work is based on a review of the literature and on the cases studied by the two teams from the Universities of Montreal and Bordeaux who share the same concept of epilepsy surgery. The patient groups of the two teams include 316 S.E.E.G., 214 cortectomies, 39 callosotomies and 2 multiple sub-pial transsections. In the first part, the authors attempt to demonstrate that the epileptic focus corresponds to the region where the seizures arise, that this focus is not directly comparable to the region where inter-ictal spikes are recorded and sometimes becomes autonomous from the causal lesion. The epileptic phenomenon has a definite harmful effect on cerebral functions and a probable self-aggravating potential. The second chapter summarizes the clinical data on which the indications and contraindications are based. These obviously depend on whether the intervention is intended to be curative or palliative. Various non-invasive and invasive investigations are then reviewed, according to their relative importance and the experience of each team. The main points developed are: the electroclinical correlations during seizures, the symptomatological data for differentiating between temporal and frontal lobe seizures, the contribution of M.R.I. in demonstrating the epileptogenic and epileptic lesions, the electrophysiological information suggesting that S.E.E.G. remains the most informative mean of investigation. The various methods of investigation of assessing electrical, functional (cerebral blood flow, metabolism) and morphological aspects of epilepsy, supply non-redondant findings about the localisation of the epileptic focus. The chapter on surgical techniques mainly discusses the various modes of implantation of subdural and intracerebral electrodes and reports the same rate of morbidity in both cases. Orthogonal teleradiography is still perfectly suited to the implantation of intracerebral electrodes. S.E.E.G. is still the most anatomically precise technique. However, in certain conditions, extraoperative E.Co.G. is more adequate. New surgical modalities have recently appeared such as the multiple subpial transsections which allow treatment of epileptic foci unapproachable by cortectomy and such as modified techniques of hemispherectomy, which by decreasing morbidity, renew interest in them. In the chapter on surgical results, the authors emphasize the methodological problems of evaluation that partly account for their wide variability. The results obtained with the various surgical modalities are reviewed. The outcome in cortectomies is discussed at length in terms of the data from the literature as well as the results reported by both teams.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Expression of human recombination activating genes (RAG1 and RAG2) in neoplastic lymphoid cells: correlation with cell differentiation and antigen receptor expression.

Regulation of V-(D)-J recombinations that occur in antigen receptor encoding genes remains poorly understood. Recently, two genes, RAG1 and RAG2, that are able to activate rearrangement of synthetic recombination substrates were cloned in mouse and a human gene homologous to RAG1 was described. To define the differentiation stages corresponding to RAG1 and RAG2 RNA expression, we have studied a large number of B- and T-lymphoid neoplasias. First, we show that a human gene homologous to the murine RAG2 is transcribed in humans. Moreover, using a polymerase chain reaction approach, we have shown that RAG are expressed not only in T-cell receptor (TCR)-negative T-cell acute lymphoblastic leukemias (T-ALLs), but also in some cases in which a significant percentage of cells expressed surface TCR. Absence of RAG expression was shown in certain T-ALLs at variable stages of thymic differentiation. Data obtained in B-lineage ALLs show that RAG RNAs are expressed in almost all slg- B-lineage ALLs but are not transcribed in the slg+ B-cell proliferations tested, including Burkitt's ALLs, follicular center cell lymphomas, and chronic leukemias. These findings are consistent with the involvement of RAG in the control of in vivo V-(D)-J recombinations. These findings are also of interest in the delineation of potential regulatory factors acting on RAG transcription and in the understanding of the mechanisms of specific chromosomal abnormalities occurring in immature lymphoid cells.

Alleles↗

Gene polymorphism of HLA-DPB1 and DPA1 loci in caucasoid population: frequencies and DPB1-DPA1 associations.

The genetic polymorphism of the HLA-DPB1 and DPA1 loci was studied in 60 unrelated caucasoid individuals by PCR-RFLP. The polymorphic second exon of DPB1, the third exon of DPA1, and the transmembrane DPA1 exon were specifically amplified in vitro by polymerase chain reaction (PCR). Amplified DNAs were digested with selected enzymes. Twenty patterns were obtained with DPB1 defining 20 DPB1 alleles. Thirty-nine homozygous cell lines were used as HLA-DP reference cells. The results obtained with these cell lines were compared to those obtained by PLT, RFLP, and SSO. Although three subdivisions of the allele DPA1*01 were reported, DPA1*0103 was the only represented one in the caucasoid population. In the studied population, it was the most frequent DPA1 allele (76.6%), whereas DPA1*0201 frequency is 23.3%. DPB1*0401 and DPB1*0402 are the most frequent among the DPB1 alleles (40.0% and 13.3%, respectively). This may lead to a lower HLA-DPB1 diversity among caucasoids. Certain HLA-DPB1 alleles associate exclusively with one DPA1 allele (DPB1*0401, 0402, and 0301 with DPA1*01 and DPB1*0101, 0501, and 1701 with DPA1*0201) whereas the others can associate with both DPA1 alleles. This by itself can create another kind of polymorphism, indicating the importance of HLA-DPA1 typing. Thus, PCR-RFLP seems to be one of the best DNA typing methods: it represents direct, accurate, fast, and nonradioactive typing for both HLA-DPA1 and HLA-DPB1 alleles.

Alleles↗

Antiparasitic activity of Annona muricata and Annona cherimolia seeds.

Methanolic extracts of Annona muricata and A. cherimolia (Annonaceae) seeds were tested for antiparasitic activity against E. histolytica, N. brasiliensis, M. dessetae and A. salina. The acetogenins isolated from these extracts are found to be responsible for the important activity on infective larvae of Molinema desetae.

Animals↗

Glucose, K+, and albumin concentrations in the alveolar milieu of normal humans and pulmonary sarcoidosis patients.

Some properties of the alveolar epithelial barrier during transalveolar transport of water and solutes were studied in normal humans and patients with sarcoidosis by means of the transalveolar capillary concentration gradients of various solutes. A total of 9 normal control subjects (Group A) and 60 sarcoidosis patients, 52 with an evolving disease (Group B) and 8 recovered (Group C), underwent bronchoalveolar lavage (BAL). The second aliquot of fluid was used to measure urea, glucose, potassium, and albumin, which were also investigated in plasma. Urea was used to determine the volume of alveolar epithelial lining fluid (AELF volume). Results are expressed as the ratio of solute concentration in AELF over that in plasma (A/P ratio). In Group A there were clear concentration gradients of glucose, potassium, and albumin between the AELF and plasma, as the A/P ratios of glucose, potassium, and albumin were 0.02 +/- 0.006 (mean +/- SEM), 3.2 +/- 0.34, and 0.04 +/- 0.008, respectively. In Group B the A/P ratios of glucose (0.21 +/- 0.02, p less than 0.001) and albumin (0.17 +/- 0.02, p less than 0.001) were significantly increased but that of potassium remained unchanged (2.9 +/- 0.2). The A/P ratios of these various solutes were independent of chest x-ray typing. The albumin but not the glucose A/P ratio was correlated with the percentage of lymphocytes recovered from BAL (p less than 0.02); however, there was no correlation between the albumin A/P ratio and the CD4+/CD8+ T lymphocyte ratio. In group C there was a striking contrast between the albumin A/P ratio, which was normal, and the glucose A/P ratio, which was clearly elevated despite a normal lymphocyte count.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Molecular HLA-class II typing: advantages and clinical application.

The major histocompatibility complex (HLA system in Man) is characterized by its extensive degree of allelic polymorphism. After the serological and cellular methods, the molecular biological methods appeared to be a powerful tool in detecting HLA-class II polymorphism. Restriction fragment length polymorphism (RFLP), using restriction endonucleases, represented an efficient method of HLA-DR, DQ, and DP genotyping. Recently, the polymerase chain reaction (PCR) permitted the development of two major class II genotyping techniques: the PCR allele specific oligonucleotide typing and the PCR-RFLP typing. By these new methods, a refined and accurate determination of DRB, DQB, DQA, and DPB alleles is possible. The major application of a refined HLA class II typing is in transplantation especially for unrelated bone marrow grafts. Moreover, it permits the identification of the amino acids implicated in the cellular response which by itself is important for the fundamental immunological studies.

Genotype↗

Effect of gamma interferon on HLA class-I and -II transcription and protein expression in human breast adenocarcinoma cell lines.

The spontaneous expression of HLA class-I and class-II molecules in 5 human breast carcinoma cell lines, MCF-7, T47D, ZR75-1, HSL-53, MDA-MB 231, and their modulation during IFN-gamma treatment, are reported. The expression of cell-surface determinants was examined by indirect immunofluorescence using monoclonal antibodies (MAbs) specific for HLA class-I and class-II (DR, DQ and DP) antigens. The biosynthesis and maturation of these molecules were analyzed by 2-dimensional gel electrophoresis analysis (2D-PAGE) of class I, DR alpha, beta and invariant immunoprecipitates. Transcription was analyzed by Northern blot hybridization with HLA class-I and -II cDNA-specific probes. In all cell lines, more than 80% of cells expressed HLA class-I antigens at their surface. 2D-PAGE and mRNA studies showed a variable basal level of HLA class-I biosynthesis and transcription with a constant increase after 1,000 U/ml IFN-gamma treatment. HLA class-II determinants were totally absent from the surface of MCF-7, MDA MB231, ZR75-1 and T47D but they were detected in a small subpopulation of HSL-53 cells (DR 6%, DQ 6%, DP 20%). Spontaneous biosynthesis of HLA-DR molecules in immunoprecipitates analyzed by 2D-PAGE or transcripts in Northern blot were not detected in the 5 cell lines. Treatment with 1000 U/ml IFN-gamma induced or increased the expression of HLA class-II molecules in all cell lines but DQ expression was variable. While T47D, ZR75-1 and HSL-53 increased their transcripts and antigen expression, MDA, MB231 and MCF-7 showed no DQ mRNA transcript. Biochemical analysis of the DR products revealed a classical alpha, beta and invariant (li) chain pattern, but indicated a constant glycosylation defect in the invariant chain in all cell lines, associated with weak expression of the beta chain and the presence of an extra spot of low molecular weight in the acidic part of the gel. Thus, post-transcriptional events did not appear to be totally controlled by IFN-gamma in the different cell lines. These differences in DQ expression and glycosylation process in different breast cancer cells may be important in the activation of the immune response among different individuals.

Adenocarcinoma↗

[Classification and definition of epileptic syndromes].

Epileptic syndromes are classified in order to supply the clinician with a useful terminology. A description of individual types of seizure is not relevant in practice since identical seizures occur in patients with very different outcomes. An epileptic syndrome is an epileptic disorder characterized by a cluster of signs and symptoms. It has therapeutic and prognostic implications. Our proposal for classification of epileptic syndromes is a compromise between scientific classification and practical arrangement.

Epilepsies, Myoclonic↗

Regulation of transcription of the human T cell antigen receptor delta chain gene. A T lineage-specific enhancer element is located in the J delta 3-C delta intron.

We have defined transcriptional enhancing sequences inside the TCR-delta gene locus, using transient transfections with constructs containing DNA fragments cloned upstream to a reporter gene fused to a heterologous promoter. A 14-kb DNA region extending from the J delta 3 segment to 6 kb 3' to C delta was analyzed. We show the presence of positive regulatory sequences inside the J delta 3-C delta intron and have localized these sequences to two DNA fragments of approximately 300 and 258 bp. Analysis of cell specificity of the activation of such sequences demonstrates a T cell pattern for one of the two fragments. The nucleotide sequence of the T cell-specific element shows motifs sharing homology with previously described core enhancers.

Base Sequence↗

A survey of epileptic disorders in southwest France: seizures in elderly patients.

An underestimation of epileptic seizures occurring in aged patients is likely. In an epidemiological survey undertaken in Southwest France, the annual incidence rate per 100,000 persons 60 years or older was 127.2 for all seizures (101.3 in persons aged 60 to 69, 150.4 in those aged 70 to 79, and 139.9 in persons 80 years or older). It was 34.1 for symptomatic localization-related and undetermined epilepsies, 16.1 for isolated seizures, and 77.0 for seizures related to an acute situation, such as metabolic derangements, stroke, or head trauma. In this survey, seizures with an onset age of 60 or older represented 28.0% of the confirmed epilepsies, 17.5% of the isolated seizures, and 52.6% of the acute symptomatic seizures. These figures differ dramatically from those in most previous reports concluding that age-specific incidence declined through adult life. They are closer to the data from more recent reports. The main reason for such a high incidence of epileptic seizures in elderly patients is the number of acute symptomatic (or situation-related) seizures. However, even chronic epilepsies increase in frequency in aging persons. Cerebrovascular disease was the most frequently recognized origin (53.9% of the patients with confirmed epilepsies) and brain tumor was found in 32.9% of the patients.

Age Factors↗

Evaluation of HLA-class II identity between unrelated individuals by serological typing, DNA-RFLP method, and mixed lymphocyte reaction.

Seven groups, each consisting of two to nine unrelated HLA-A, -B, and -DR serologically identical individuals, were analyzed by DNA-restriction fragment length polymorphism (RFLP) and mixed lymphocyte reactions (MLR) in order to evaluate HLA-class II identity between unrelated individuals and to assess the importance of HLA-class II incompatibilities detected by DNA-RFLP in the allogeneic reactions. It is clear that DNA-RFLP represents a powerful typing method for HLA-DR, -DQ, and -DP since the combinations of the RFLP band patterns define all the serological specificities and most of the cellular specificities to give a highly accurate typing. This report shows that an HLA-DP incompatibility induces proliferation in primary mixed lymphocyte culture (MLC) between unrelated HLA-A, -B, -DR, -DQ, and -DW identical individuals, which may suggest the importance of this molecule as a transplantation antigen, especially for unrelated bone marrow transplantations. Still, an isolated HLA-DPw4/HLA-DP a disparity did not induce any proliferation in MLC. Moreover, our results show that DQw7 (w3)/DQw8 (w3) disparity associated with HLA-DR4 represents a nonfunctional incompatibility in MLR. The HLA-Dw subtypes of HLA-DR specificities can induce a high proliferative response in MLC. The HLA-Dw subtypes of HLA-DR specificities can induce a high proliferative response in MLC. Finally, DNA-RFLP typing represents a reliable method for the selection of histocompatible donor-recipient pairs and could potentially reduce many logistic problems and delays in live-donor transplantation, especially for unrelated bone marrow transplantation.

Base Sequence↗

A randomised double-blind placebo-controlled crossover add-on trial of lamotrigine in patients with treatment-resistant partial seizures.

Efficacy and safety of lamotrigine (LTG) as add-on therapy was assessed in a randomised double-blind placebo-controlled trial of this drug in 23 adult patients with refractory partial seizures. Fifteen patients showed an improvement on LTG treatment, with a greater than 50% decrease in total seizure count in 7 patients. Fourteen patients experienced fewer simple and complex partial seizures, with 8 patients benefitting by more than a 50% decrease in seizure frequency. The drug was well tolerated over the 2 month treatment period. The plasma concentration of concomitant antiepileptic drugs remained unchanged. No haematological or chemical abnormalities were noted.

Adolescent↗