MicroRNA profiling as a tool for pathway analysis in a human in vitro model for neural development.

MicroRNAs (miRNA) are a recently recognised class of small, non-coding RNAs involved in the post-transcriptional regulation of gene expression and with crucial implication for mammalian development. In particular, they play key roles in neuronal development, from early neurogenesis to neuronal differentiation and synaptic development, and also in in vitro systems. The detection of embryotoxic hazards in the preclinical phase is still a challenge, often due to species-species variations. In this study we analysed whether miRNA expression profiles in a human pluripotent cell model can be a helpful tool for a more mechanistic approach to pharmacology and toxicology. Differentiating human pluripotent cells were repeatedly treated with non-cytotoxic doses of methylmercury chloride (MeHgCl), a well known brain developmental toxicant. The expression of proteins, mRNA and miRNAs were used to monitor successful neural differentiation. Significant changes in the expression of 12 miRNAs were detected. By using available bioinformatics tools, we obtained validated and predicted targets for the identified miRNAs, on which we performed functional clustering analysis. Through this approach, we identified several terms and functional clusters associated with neural development, together with indicators of general toxic effect, such as apoptosis or stress response-related genes. Interestingly, our results also suggest a previously undiscovered association between MeHgCl and the ubiquitin-proteasome protein degradation pathway. Although further investigations are needed, our results suggest that miRNA expression analysis is a powerful tool in pathway-oriented toxicity and could improve early-phase hazard assessments.

DeltaNp63 expression is associated with poor survival in ovarian cancer.

BACKGROUND: P63 belongs to the 'p53 family' whose role in cancer progression has been recently revisited in light of the plethora of splicing variants that are generated. We analyzed the expression of the full-length TAp63 gene and its dominant-negative form deltaNp63 in ovarian cancer biopsies to correlate their expression with clinical outcome. MATERIALS AND METHODS: Real-time RT-PCR analysis was used to determine the levels of TAp63 and deltaNp63 in 83 stage I and in 86 stage III ovarian cancer biopsies and in seven human ovarian cancer cell. RESULTS: TAp63 levels were comparable in stage I and stage III, but deltaNp63 levels increased 77-fold in stage III, independently of the p53 status. Patients with high deltaNp63 expression had the worst overall survival (OS); patients with a deltaNp63/TAp63 ratio >2 had a poor OS. Patients with a high deltaNp63/TAp63 ratio were those with a poor response to platinum-based therapy. CONCLUSIONS: Data indicate a role for deltaNp63 as a potential biomarker to predict patient's outcome and tumor progression in ovarian cancer. This would have particularly clinical relevance in ovarian cancer where the high rate of mortality reflects our lack of knowledge of molecular mechanisms underlying cell progression toward malignancy.

Central pontine myelinolysis induced by hypophosphatemia following Wernicke's encephalopathy.

A 62-year-old woman, after a resection and ileostomy for multiple perforations of the terminal ileum and prolonged postoperative parenteral nutrition, developed thiamine deficiency with clinical and magnetic resonance imaging features of Wernicke's disease. Later on the patient developed central pontine myelinolysis. For this condition, a pathogenetic role of a transient hypophosphatemia was suggested by both laboratory data and course of the disease.

High prevalence of hepatitis C virus infection in a small central Italian town: lack of evidence of parenteral exposure.

In the spring of 1994, anti-HCV prevalence and associated risk factors were evaluated in 681 subjects representing all age-groups in the general population of a small central Italian town. The overall anti-HCV prevalence was 8.4%, ranging from 3.7% in the 30-39 age-group to 18.2% (p < 0.01) in the 60-70 age-group; no subject below 30 years of age was positive. Multiple logistic regression analysis showed that the only variables independently associated with anti-HCV positivity were awareness of unspecified liver disease (O.R. 3.58), age > 45 years (O.R. 2.72), and lowest number of years of schooling (O.R. 11.0) while no association was found with any parenteral exposure such as blood transfusion, intravenous drug use, major or minor surgical intervention, use of glass syringes or dental therapy. The HBsAg prevalence in this population was 1.3%, which corresponds to the rate reported in central Italy. These findings show a high level of HCV endemicity, with no evidence of parenteral exposure.

[The scimitar syndrome. A clinical contribution and review of the literature (author's transl)]. / La "sindrome della scimitarra." Contributo clinico e revisione della letteratura.

The scimitar syndrome groups a combination of several congenital anomalies in the right lung with an abnormal right pulmonary venous drainage in the inferior vena cava or the right atrium. After a survey of 130 cases in the literature, clinical, angiografic and hemodynimac features of the syndrome are defined. The Authors report two new cases diagnosed in adults, characterised by a clean discordance between the clinical features and the angiographic ones. The former case is completely asymptomatic and the radiographic feature is typical, while the latter shows a characteristic symptomatology but there isn't a clean "scimitar image". But notwithstanding the absence of this "scimitar image", the Authors think that the anomalous pulmonary drainage in the right atrium and the several anomalies in the right lung can be attributed to the scimitar syndrome, physiopatologically.

[Acute myeloid leukemia with megakaryocytic predominance and malignant megakaryocyte proliferation. Apropos of 3 cases]. / Leucémie myéloïde aiguë à prédominance mégacaryocytaire et proliférations mégacaryocytaires malignes. A propos de trois observations.

Three cases of acute myeloid leukemia with megakaryocyte predominance are reported. In the first case megakaryocytosis was particularly evident in bone marrow, liver and spleen. In the second case high content of megakaryocytes was observed in the bone marrow and spleen, during the preleukemic phase only. Third case exhibited a strong predominance of megakaryocytes exclusively within the bone marrow. The characteristics of such observations and their nosologic position within myeloproliferative disorders group are discussed, with special reference to modern views concerning myeloid leukemia.