The cellular mechanism of thalamic ponto-geniculo-occipital waves

The cellular mechanisms underlying the genesis of thalamic ponto-geniculo-occipital waves were studied in reserpinized cats under urethane anaesthesia. Simultaneous field potential and intracellular recordings were performed in the lateral geniculate nucleus after acute lesions of retinal and visual cortical inputs. In most relay cells, reserpine-induced ponto-geniculo-occipital waves were associated with a transient depolarization that was often interrupted by a unitary inhibitory postsynaptic potential. The depolarization grew in size with membrane hyperpolarization and was accompanied by an increase in membrane conductance. The inhibitory postsynaptic potential is likely to have resulted from the activation of intrageniculate interneurons since perigeniculate cells were always inhibited during the occurrence of ponto-geniculo-occipital waves. Under reserpine, thalamic ponto-geniculo-occipital waves could also be triggered by peribrachial or auditory stimulation. These evoked ponto-geniculo-occipital waves were associated with intracellular events identical to those occurring spontaneously after reserpine administration. In addition, thalamic spindle oscillations were readily blocked by the occurrence of spontaneous or evoked ponto-geniculo-occipital waves. On the basis of the present results and those already published in the literature, the conclusion is reached that lateral geniculate ponto-geniculo-occipital waves result from a nicotinic activation of relay cells and from a parallel muscarinic inhibition of perigeniculate cells by peribrachial afferents. The functional significance of the ponto-geniculo-occipital activity is discussed on the basis of the antagonistic action of these signals on thalamic oscillations. It is proposed that these signals are the central correlates of orienting reactions elicited by sensory stimuli during waking (the so-called eye movement potentials) and by internally generated drives during paradoxical sleep.     

Serous papillary carcinoma of the endometrium arising from endometrial polyps: a clinical, histological, and immunohistochemical study of 13 cases

Serous papillary carcinoma is an aggressive tumor. Point mutations in the p53 suppressor gene might explain in part the rapid growth of this malignant tumor and its unfavorable outcome. The aims of this study were to evaluate the behavior of serous papillary carcinoma developing in endometrial polyps and to assess the p53 protein overexpression. Patients included in this study were treated in our institution between 1982 and 2003. All clinical and pathological materials were examined. A p53 protein immunohistochemical analysis was performed on paraffin-embedded tissues. Thirteen serous papillary carcinomas arising from benign polyps of the endometrium were identified. The patients' age averaged 73 years. All patients were treated surgically. After an average follow-up of 22 months, 54% of the patients were dead or alive with disease. Of 10 serous papillary carcinomas, 8 (80%) for which paraffin blocks were available overexpressed the p53 protein. A serous papillary carcinoma arising from benign polyps of the endometrium remains a malignant neoplasia with an unfavorable outcome even if the primary tumor is limited to the polyp. The high rate of protein p53 overexpression suggests that a p53 gene mutation occurs early in the disease and might explain the rapid growth of the tumor.     

Variation at the ADAM10 gene locus is not associated with Creutzfeldt-Jakob disease

Prion diseases are characterized by the accumulation in the brain of a misfolded and protease-resistant form of the prion protein (PrP(c)). PrP(c) contains an amyloidogenic, neurotoxic sequence that is essential for conversion into PrP(Sc), the pathological isoform. During normal processing, PrP(c) is cleaved at a site within this sequence, and this cleavage is thought to destroy the amyloidogenic potential of the protein. ADAM10, a disintegrin and metalloprotease that plays a key role in the pathogenesis of Alzheimer's disease, was recently shown to use PrP(c) as a substrate. We investigated whether variability in the ADAM10 gene could contribute to the pathogenesis of Creutzfeldt-Jakob disease (CJD), by analyzing a single nucleotide polymorphism (SNP) within ADAM10, as a genetic marker potentially in linkage disequilibrium with a functional polymorphism, in patients with sporadic or variant CJD. We observed no significant differences in ADAM10 genotype or allele frequencies between CJD patients and healthy individuals. Moreover, the distribution of ADAM10 SNP genotypes and alleles did not differ between groups of patients based on genotype at the polymorphic codon 129 of the prion protein gene--the sole major genetic risk factor for CJD identified to date. Our data indicate that ADAM10 is unlikely to confer genetic susceptibility to CJD.     

Copolymers of trimethylene carbonate and epsilon-caprolactone for porous nerve guides: synthesis and properties

Copolymers of trimethylene carbonate and epsilon-caprolactone were synthesized and characterized with the aim of assessing their potential in the development of a flexible and slowly degrading artificial nerve guide for the bridging of large nerve defects. The effect of the monomer ratio on the physical properties of the polymers and its influence on the processability of the materials was investigated. Under the applied polymerization conditions (130 degrees C, 3 days using stannous octoate as a catalyst) high molecular weight polymers (Mn above 93 000) were obtained. All copolymers had glass transition temperatures below room temperature. At trimethylene carbonate contents higher than 25 mol% no crystallinity was detected. A decrease in crystallinity resulted in the loss of strength and decrease in toughness, as well as in an increased polymer wettability. Amorphous poly(trimethylene carbonate), however, showed excellent ultimate mechanical properties due to strain-induced crystallization (Tm = 36 degrees C). Low crystallinity copolymers could be processed into dimensionally stable porous structures by means of immersion precipitation and by combination of this technique with the use of porosifying agents. Porous membranes of poly(trimethylene carbonate) could be prepared when blended with small amounts of high molecular weight poly(ethylene oxide). Poly(trimethylene carbonate) and poly(trimethylene carbonate-co-epsilon-caprolactone) copolymers with high epsilon-caprolactone content possess good physical properties and are processable into porous structures. These materials are most suitable for the preparation of porous artificial nerve guides.     

Alternative methods to analyse the impact of HIV mutations on virological response to antiviral therapy

Background  

Principal component analysis (PCA) and partial least square (PLS) regression may be useful to summarize the HIV genotypic information. Without pre-selection each mutation presented in at least one patient is considered with a different weight. We compared these two strategies with the construction of a usual genotypic score.     

Endothelin receptor expression in human decidua

The endothelins are signalling peptides that act via two receptors, ET(A) and ET(B). In the human endometrium, endothelin receptors have been demonstrated in glands and stroma and have been shown to vary during the course of the menstrual cycle. The present study was undertaken to determine whether or not expression of endothelin receptors changes during pregnancy or after administration of exogenous progestagens. The expression of the receptors was correlated with the appearance of basement membrane components during decidualization of the endometrial stroma. Decidual specimens (n = 15) were obtained during the first trimester of pregnancy and 10 at term. Sixteen pairs of endometrial biopsies were obtained from women with menorrhagia before and after exposure to exogenous progestagens. A total of 15 hysterectomy specimens were used as controls for the expression of stromal basement membrane proteins in the absence of decidualization. Autoradiography was carried out with selective ligands for ET(A) ([125I]-PD 151242) and ET(B) ([125I]-BQ3020). The distribution of ligand binding was then compared with the distribution of laminin alpha2 light chain and collagen IV. ET(A), ET(B), laminin alpha2 light chain, and collagen IV were expressed in stromal decidual cells in the first trimester of pregnancy. ET(B) was also found on endometrial glandular epithelium. Quantitative macro-autoradiography and multiple regression analysis demonstrated a highly significant positive correlation (P < 0.001) between expression of ET(B) and laminin alpha2 light chain. In the third trimester qualitative examination suggested a reduction of ET(A) in the stroma. Progestagen-induced decidua exhibited a similar pattern to that found in first trimester decidua. This study has demonstrated up-regulation of ET(B) during the progesterone- dependent process of decidualization and suggests a paracrine or autocrine role for endothelins in the decidua.      

Correlations of Soluble Interleukin-2 and Tumor Necrosis Factor Type II Receptors with Immunologic and Virologic Responses Under HAART

We assessed the correlations between some plasma markers of immune activation (soluble receptors of interleukin 2 (sIL2-R) and TNFp75 (sTNFII-R) and usual markers of HIV infection in patients treated with protease-inhibitors (PI). Forty-six PI-naive HIV-1-infected adults were included in a 1-year prospective cohort from the initiation of a PI-containing regimen (M0). Measurements of CD4+cell count, plasma HIV-RNA, sIL2-R and sTNFII-R were performed at M0, M6, and M12. The evolution of sIL2-R from baseline to M12 was significantly different between immunological responders (IR) (CD4+count above 200/mm³ for subject having less than 200 CD4 +/mm³ at inclusion, or increase of at least 50 CD4+/mm³ for others) (58 UI/ml) and non-IR (+28 UI/ml) (P =0.01). The evolution of sTNFII-R between M0 and M12 was significantly different between virological responders (VR) (plasma HIV-1 RNA less than 500 copies/ml at M12) (–2.5 ng/ml) and non-VR (+0.2 ng/ml) (P =0.02). Our study shows significative correlations between the evolutions of soluble interleukin-2 and TNFR-II receptors and those of CD4+T-lymphocytes or HIV-RNA responses in patients under HAART.     

Influence of ionic disturbances produced by gastric washing on cortical spreading depression

Summary The ionic composition of the internal environment was altered in rabbits by means of gastric washing, combined with intramuscular administration of 3-Beta-aminoethylpyrazole. The effects of this treatment on cortical spreading depression (SD) were studied. C1^- and Na⁺ concentrations decreased significantly in serum and in cerebrospinal fluid after the treatment. This made the animals much more susceptible to SD, as established by the high incidence of spontaneous SD, increased SD velocity of propagation and facilitated its interhemispheric transfer. An intensification of the epileptiform activity associated with SD was also observed. Intravenous replacement of NaCl abolished the above effects on SD. When the intravenous replacement was done with Na-Isethionate, those effects were enhanced. It is concluded that chloride deficiency was the main factor responsible for the observed facilitating effects.This work was supported by grants from the BNDE (FUNTEC-74 e 143), CNP_q and CAPES