High prevalence and low E6 genetic variability of human papillomavirus 58 in women with cervical cancer and precursor lesions in Southeast Mexico

Infection with some genotypes of human papillomavirus (HPV) is the most important risk factor associated with cervical cancer (CC). Throughout the world, HPV type 58 prevalence varies from one region to another; it is higher in women from certain countries in Asia and Latin America, such as China and Mexico. Although intratypic variants have been reported on a few occasions, our knowledge about HPV 58 genetic variation remains limited. Therefore, this work aims to (i) determine the prevalence of HPV type 58 amongst Mexican women with invasive CC or precursor lesions and (ii) identify HPV 58 sequence variants. One hundred and forty five colposcopy clinic patients were studied. Genotyping of HPV 16, 18 and 58 was determined by specific nested PCR and HPV 58 variants were detected by direct sequencing. The general prevalence of HPV was 51.7% (75/145). HPV 16 was found in 30.6% (23/75) and HPV 58 in 24% (18/75) of the patients. HPV 18 was not identified in patients with cervical intraepithelial neoplasia (CIN) grade I; it was only found in those with CIN II, with a prevalence of 6.8% (3/44). In patients with CC, the prevalence of HPV 16 and 58 was 78.9%. Regarding HPV 58 variants, 94.4% of the HPV 58 sequences were identical to the prototype strain, whereas one sample showed changes at a single nucleotide. This study demonstrates a high prevalence of HPV 58 and a low genetic variability of E6 sequences amongst Mexican colposcopy patients.

Comparative randomised trial of high and conventional doses of praziquantel in the treatment of schistosomiasis mansoni

The efficacy of oral praziquantel in the treatment of schistosomiasis has been considered low by most public health institutions. In this paper, we compared the efficacy of two dosages of praziquantel (80 mg/kg vs. 50 mg/kg) in patients with chronic schistosomiasis mansoni. Two hundred eighty-eight patients with schistosomiasis from a community in Brazil were randomly divided into two groups: 145 patients (Group 1) received 80 mg/kg body weight of oral praziquantel divided in two equal doses with 1 h interval and 143 patients (Group 2) received 50 mg/kg body weight of oral praziquantel. To keep the study masked, patients in Group 2 received placebo 1 h after the first dose. All patients were subjected to clinical and ultrasonographic examination. Cure assessment was performed by repeating two stool examinations, by a quantitative method, at 30, 90 and 180 days after treatment. The morbidity of schistosomiasis was low, with a few cases of light periportal thickening and 16 cases of mild splenomegaly. The cure rates were 89.7% for Group 1 and 83.9% for Group 2. There was no difference in the efficacy of both therapeutic dosages of praziquantel assayed. The adverse reactions were more frequent with higher dosage.

Methylation alterations are not a major cause of PTTG1 misregulation.

BACKGROUND On its physiological cellular context, PTTG1 controls sister chromatid segregation during mitosis. Within its crosstalk to the cellular arrest machinery, relies a checkpoint of integrity for which gained the over name of securin. PTTG1 was found to promote malignant transformation in 3T3 fibroblasts, and further found to be overexpressed in different tumor types. More recently, PTTG1 has been also related to different processes such as DNA repair and found to trans-activate different cellular pathways involving c-myc, bax or p53, among others. PTTG1 over-expression has been correlated to a worse prognosis in thyroid, lung, colorectal cancer patients, and it can not be excluded that this effect may also occur in other tumor types. Despite the clinical relevance and the increasing molecular characterization of PTTG1, the reason for its up-regulation remains unclear. METHOD We analysed PTTG1 differential expression in PC-3, DU-145 and LNCaP tumor cell lines, cultured in the presence of the methyl-transferase inhibitor 5-Aza-2'-deoxycytidine. We also tested whether the CpG island mapping PTTG1 proximal promoter evidenced a differential methylation pattern in differentiated thyroid cancer biopsies concordant to their PTTG1 immunohistochemistry status. Finally, we performed whole-genome LOH studies using Affymetix 50 K microarray technology and FRET analysis to search for allelic imbalances comprising the PTTG1 locus. CONCLUSION Our data suggest that neither methylation alterations nor LOH are involved in PTTG1 over-expression. These data, together with those previously reported, point towards a post-transcriptional level of misregulation associated to PTTG1 over-expression.

MicroRNA Profile of Circulating CD4-positive Regulatory T Cells in Human Adults and Impact of Differentially Expressed MicroRNAs on Expression of Two Genes Essential to Their Function.

Regulatory T cells (Tregs) are characterized by a high expression of IL-2 receptor α chain (CD25) and of forkhead box P3 (FOXP3), the latter being essential for their development and function. Another major player in the regulatory function is the cytotoxic T-lymphocyte associated molecule-4 (CTLA-4) that inhibits cytotoxic responses. However, the regulation of CTLA-4 expression remains less well explored. We therefore studied the microRNA signature of circulating CD4(+) Tregs isolated from adult healthy donors and identified a signature composed of 15 differentially expressed microRNAs. Among those, miR-24, miR-145, and miR-210 were down-regulated in Tregs compared with controls and were found to have potential target sites in the 3'-UTR of FOXP3 and CTLA-4; miR-24 and miR-210 negatively regulated FOXP3 expression by directly binding to their two target sites in its 3'-UTR. On the other hand, miR-95, which is highly expressed in adult peripheral blood Tregs, positively regulated FOXP3 expression via an indirect mechanism yet to be identified. Finally, we showed that miR-145 negatively regulated CTLA-4 expression in human CD4(+) adult peripheral blood Tregs by binding to its target site in CTLA-4 transcript 3'-UTR. To our knowledge, this is the first identification of a human adult peripheral blood CD4(+) Treg microRNA signature. Moreover, unveiling one mechanism regulating CTLA-4 expression is novel and may lead to a better understanding of the regulation of this crucial gene.

Four years with FALCON - an ESTRO educational project: achievements and perspectives.

Variability in anatomical contouring is one of the important uncertainties in radiotherapy. FALCON (Fellowship in Anatomic deLineation and CONtouring) is an educational ESTRO (European SocieTy for Radiation and Oncology) project devoted to improve interactive teaching, the homogeneity in contouring and to compare individual contours with endorsed guidelines or expert opinions. This report summarizes the experience from the first 4 years using FALCON for educational activities within ESTRO School and presents the perspectives for the future.

Biblia sacra, pars. I

Genesis (7v) ; Exodus (36) ; Levit. (59) ; Numeri (75v) ; Deuteron. (97) ; Josue (116) ; Judices (129) ; Ruth (141v) ; Job (145) ; Reg. I, I, 1-XXV, 6, et II, VII, 13-IV, XXV, 21 (159v).

Graduale Albiense.

F. 1v Labyrinthe contenant des vers latins commençant par les lettres O et T. F. 2 Prosa s. Salvii : « Alleluia regi... » F. 2v Prosa in Penthecosten : « Sancti Spiritus adsit nobis gratia... » F. 3 Antiennes diverses. F. 4v-146v Graduel, avec plusieurs versets alléluiatiques à chaque messe, proses et pièces gallicanes et wisigothiques : — Litanies d'Albi (67) ; — ste Cécile (121) ; — Messes diverses (135v) ; — Preces mortuorum (138) ; — Antiennes diverses (139-145v) ; — s. Sauve (145) ; — Toussaint (145v). F. 147 Versi de tonis : « Pange, Camena, tuis... » ; — Tonaire : « Diximus enim octo... » F. 148-153v et 155 : « Nonenoe ane » et formules complètes des huit tons.

Missale romanum.

F. 1 Séquence et messe de la Fête-Dieu. F. 2 Calendrier romain, avec additions des Chartreux de Sainte-Croix de Jérusalem à Rome. F. 8-134 et 151v-197v Temporal : « Ordo missalis romane curie » : — Exultet (122v). F. 134v « Ordo missae. » F. 199-255v Sanctoral : Vig. s. André (199) ; — ste Catherine (255) ; — ste Claire (255v). F. 255v Commun des saints. F. 277v Messes votives. F. 290 Bénédiction de l'eau (incompl. de la fin).

Occult lung infarction may induce false interpretation of 18F-FDG PET in primary staging of pulmonary malignancies.

PURPOSE: The aim of the present report is to describe abnormal (18)F-fluorodeoxyglucose (FDG) accumulation patterns in the pleura and lung parenchyma in a group of lung cancer patients in whom lung infarction was present at the time of positron emission tomography (PET). METHODS: Between November 2002 and December 2003, a total of 145 patients (102 males, 43 females; age range 38-85 years) were subjected to whole-body FDG PET for initial staging (n=117) or restaging (n=11) of lung cancer or for evaluation of solitary pulmonary nodules (n=17). Of these patients, 24 displayed abnormal FDG accumulation in the lung parenchyma that was not consistent with the primary lesion under investigation (ipsilateral n=12, contralateral n=9 or bilateral n=3). Without correlative imaging, this additional FDG uptake would have been considered indeterminate in differential diagnosis. RESULTS: Of the 24 patients who were identified as having such lesions, six harboured secondary tumour nodules diagnosed as metastases, while in three the diagnosis of a synchronous second primary lung tumour was established. Additionally, nine patients were identified as having post-stenotic pneumonia and/or atelectasis (n=6) or granulomatous lung disease (n=3). In the remaining six (4% of all patients), a diagnosis of recent pulmonary embolism that topographically matched the additional FDG accumulation (SUV(max) range 1.4-8.6, mean 3.9) was made. Four of these six patients were known to have pulmonary embolism, and hence false positive interpretation was avoided by correlating the PET findings with those of the pre-existing diagnostic work-up. The remaining two patients were harbouring small occult infarctions that mimicked satellite nodules in the lung periphery. Based on histopathological results, the abnormal FDG accumulation in these two patients was attributed to the inflammatory reaction and tissue repair associated with the pathological cascade of pulmonary embolism. CONCLUSION: In patients with pulmonary malignancies, synchronous lung infarction may induce pathological FDG accumulation that can mimic active tumour manifestations. Identifying this potential pitfall may allow avoidance of false positive FDG PET interpretation.

Comienza el decenio de acción para la seguridad vial 2011-2020

Boletín semanal para profesionales sanitarios de la Secretaría General de Salud Pública y Participación Social de la Consejería de Salud

« Les Armories et enseignes du souverene et compagnions du tresnoble ordre de la Jarretiere, en nombre de xxv, come ilz sont par ordre au chasteau de Wyndsor, l'an 1572 ».

Blasons peints, à pleine page.

Major, minor, trace element, Sm-Nd and Sr isotope compositions of mafic rocks from the earliest oceanic crust of the Alpine Tethys

Recent isotopic and biochronologic dating has demonstrated that the Gets nappe contains remnants of the oldest part of the oceanic crust of the Alpine Tethys. The ophiolites are associated with deep sea sediments, platform carbonates and continental crustal elements suggesting a transitional environment between continental and oceanic crust. Therefore, the ophiolites from the Gets nappe provide the opportunity to assess the nature of mantle source and the magma evolution during the final rifting stage of the European lithosphere. Trace clement analyses of mafic rocks can he divided into two sets: (1) P, Zr and Y contents are consistent with those of mid-ocean ridge basalts and REE patterns have a P-MORB affinity. (2) P,Zr Ti and Y contents are compatible with within-plate basalts and are characterized by REE spectra similar to that of T-MORB. Both have Nd isotopic compositions similar to those of synrift magma of the Red Sea and to the Rhine Graben. The model ages are in agreement with an LREE-enriched subcontinental mantle source derived from depleted mantle 800 to 900 Ma ago. Minor, trace element and Sm-Nd compositions suggest that these rocks are basaltic relies of an earliest stage of oceanic spreading i.e. an embryonic ocean. Comparison between REE patterns, Nd and Sr isotope compositions, isotopic and biochronologic ages from different Alpine Tethys ophiolites shows that samples with enriched LREE are from the older ophiolitic suites and are relies of the embryonic ocean floor. Later phases of ocean spreading are characterized by basalts that are depleted in LREE.