Long-term Mercury Exposure Accelerates the Development of Hypertension in Prehypertensive Spontaneously Hypertensive Rats Inducing Endothelial Dysfunction: the Role of Oxidative Stress and Cyclooxygenase-2.

Mercury is a metal widely dispersed in nature that when in contact with human organism, it damages the cardiovascular system. Long-term mercury exposure for 30 days induces endothelial dysfunction without blood pressure changes in normotensive adult rats. However, it is not known whether exposure to mercury can exacerbate endothelial dysfunction and hypertension development in predisposed animals.

Chronic Mercury Exposure in Prehypertensive SHRs Accelerates Hypertension Development and Activates Vasoprotective Mechanisms by Increasing NO and HO Production.

Mercury is a heavy metal associated with cardiovascular diseases. Studies have reported increased vascular reactivity without changes in systolic blood pressure (SBP) after chronic mercury chloride (HgCl) exposure, an inorganic form of the metal, in normotensive rats. However, we do not know whether individuals in the prehypertensive phase, such as young spontaneously hypertensive rats (SHRs), are susceptible to increased arterial blood pressure.

STUDY OF THE ANTEROLATERAL LIGAMENT OF THE KNEE IN FORMALIN-EMBEDDED CADAVERS.

Objective: To verify the incidence and characterize morphologically the anterolateral ligament of the knee (ALL) in cadaveric samples of the collection of the Laboratory of Anatomy of the Department of Morphology of the Universidade Federal do Espírito Santo.

Methods: Dissections and cross sections were performed for mesoscopic analysis of the anterolateral region of 15 knees preserved in 4% formalin solution in order to identify the ALL.

Results: After dissection of the skin and subcutaneous tissue of the knee anterolateral region, it was possible to identify the iliotibial tract (ITT), the patellar ligament and the femoral biceps tendon.

Design of a multi-signature ensemble classifier predicting neuroblastoma patients' outcome.

Background: Neuroblastoma is the most common pediatric solid tumor of the sympathetic nervous system. Development of improved predictive tools for patients stratification is a crucial requirement for neuroblastoma therapy. Several studies utilized gene expression-based signatures to stratify neuroblastoma patients and demonstrated a clear advantage of adding genomic analysis to risk assessment.

Bone marrow-infiltrating human neuroblastoma cells express high levels of calprotectin and HLA-G proteins.

Metastases in the bone marrow (BM) are grim prognostic factors in patients with neuroblastoma (NB). In spite of extensive analysis of primary tumor cells from high- and low-risk NB patients, a characterization of freshly isolated BM-infiltrating metastatic NB cells is still lacking. Our aim was to identify proteins specifically expressed by metastatic NB cells, that may be relevant for prognostic and therapeutic purposes.

Bone marrow of neuroblastoma patients shows downregulation of CXCL12 expression and presence of IFN signature.

Background: At diagnosis, children with neuroblastoma (NB) present with either localized or metastatic disease. Since the mechanisms responsible for BM invasion are not well known, we investigated the transcriptome of resident BM cells from NB patients as compared to healthy children.

Procedure: Ninety-two and 88 children with localized and metastatic NB, respectively, and 15 healthy children were included in the study.

Identification of multiple hypoxia signatures in neuroblastoma cell lines by l1-l2 regularization and data reduction.

Hypoxia is a condition of low oxygen tension occurring in the tumor and negatively correlated with the progression of the disease. We studied the gene expression profiles of nine neuroblastoma cell lines grown under hypoxic conditions to define gene signatures that characterize hypoxic neuroblastoma. The l(1)-l(2) regularization applied to the entire transcriptome identified a single signature of 11 probesets discriminating the hypoxic state.

A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients.

Background: Hypoxia is a condition of low oxygen tension occurring in the tumor microenvironment and it is related to poor prognosis in human cancer. To examine the relationship between hypoxia and neuroblastoma, we generated and tested an in vitro derived hypoxia gene signature for its ability to predict patients' outcome.

Results: We obtained the gene expression profile of 11 hypoxic neuroblastoma cell lines and we derived a robust 62 probesets signature (NB-hypo) taking advantage of the strong discriminating power of the l1-l2 feature selection technique combined with the analysis of differential gene expression.

Detection of cell-free RNA in children with neuroblastoma and comparison with that of whole blood cell RNA.

Background: Since there is no validated assay to monitor disease in children with neuroblastoma (NB), we tested whether NB specific cell-free RNA could be detected in their plasma samples. Moreover, with the aim of reducing patients' discomfort, we compared this assay to a recently standardized procedure that uses a larger amount of whole blood.

Procedures: Using conditions that excluded RNA recovery from contaminating tumor cells, the total amount of cell-free RNA present in healthy children and patients with NB was quantified.

The l1-l2 regularization framework unmasks the hypoxia signature hidden in the transcriptome of a set of heterogeneous neuroblastoma cell lines.

Background: Gene expression signatures are clusters of genes discriminating different statuses of the cells and their definition is critical for understanding the molecular bases of diseases. The identification of a gene signature is complicated by the high dimensional nature of the data and by the genetic heterogeneity of the responding cells. The l1-l2 regularization is an embedded feature selection technique that fulfills all the desirable properties of a variable selection algorithm and has the potential to generate a specific signature even in biologically complex settings.

Induction of epithelial mesenchimal transition and vasculogenesis in the lenses of Dbl oncogene transgenic mice.

Background: The Dbl family of proteins represents a large group of proto-oncogenes involved in cell growth regulation. The numerous domains that are present in many Dbl family proteins suggest that they act to integrate multiple inputs in complicated signaling networks involving the Rho GTPases. Alterations of the normal function of these proteins lead to pathological processes such as developmental disorders and neoplastic transformation.

Early response of gene clusters is associated with mouse lung resistance or sensitivity to cigarette smoke.

We have investigated the effects of cigarette smoke exposure in three different strains of mice. DBA/2 and C57BL/6J are susceptible to smoke and develop different lung changes in response to chronic exposure, whereas ICR mice are resistant to smoke and do not develop emphysema. The present study was carried out to determine early changes in the gene expression profile of mice exposed to cigarette smoke with either a susceptible or resistant phenotype.

Transcriptome of hypoxic immature dendritic cells: modulation of chemokine/receptor expression.

Hypoxia is a condition of low oxygen tension occurring in inflammatory tissues. Dendritic cells (DC) are professional antigen-presenting cells whose differentiation, migration, and activities are intrinsically linked to the microenvironment. DCs will home and migrate through pathologic tissues before reaching their final destination in the lymph node.

Induction of macrophage glutamine: fructose-6-phosphate amidotransferase expression by hypoxia and by picolinic acid.

We studied the expression of glutamine: fructose-6-phosphate amidotransferase (GFAT), the rate limiting enzyme in the hexosamine biosynthetic pathway controlling protein glycosylation. We obtained the first evidence that the GFAT mRNA and protein are constitutively expressed in murine mononuclear phagocytes (Mf) and inducible by picolinic acid (PA), a catabolite of tryptophan, hypoxia and desferrioxamine (DFX). These stimuli share the property to transactivate gene expression through the Hypoxia Responsive Element (HRE).

Normalization of low-density microarray using external spike-in controls: analysis of macrophage cell lines expression profile.

Background: The normalization of DNA microarrays allows comparison among samples by adjusting for individual hybridization intensities. The approaches most commonly used are global normalization methods that are based on the expression of all genes on the slide and on the modulation of a small proportion of genes. Alternative approaches must be developed for microarrays where the proportion of modulated genes and their distribution are unknown and they may be biased towards up- or down-modulated trends.

Growth arrest-inducing genes are activated in Dbl-transformed mouse fibroblasts.

The Dbl oncogene is a guanine nucleotide exchange factor for Rho GTPases and its activity has been linked to the regulation of gene transcription. Dbl oncogene expression in NIH3T3 cells leads to changes in morphological and proliferative properties of these cells, inducing a highly transformed phenotype. To gain insights into Dbl oncogene-induced transformation we compared gene expression profiles between Dbl oncogene-transformed and parental NIH3T3 cells by cDNA microarray.

Hypoxia modifies the transcriptome of primary human monocytes: modulation of novel immune-related genes and identification of CC-chemokine ligand 20 as a new hypoxia-inducible gene.

Peripheral blood monocytes migrate to and accumulate in hypoxic areas of inflammatory and tumor lesions. To characterize the molecular bases underlying monocyte functions within a hypoxic microenvironment, we investigated the transcriptional profile induced by hypoxia in primary human monocytes using high-density oligonucleotide microarrays. Profound changes in the gene expression pattern were detected following 16 h exposure to 1% O(2), with 536 and 677 sequences showing at least a 1.

Analysis of HLA-G expression in breast cancer tissues.

Among the different mechanisms by which cancer can elude the immune system, alterations in the expression of human leukocyte antigen (HLA) class I molecules on tumor cells may play a crucial role by impairing the HLA molecules interaction with T and natural killer (NK) cells specific receptors. More recently, aberrant expression of HLA-G has been described in different tumor tissues in addition to HLA class I downregulation. The HLA-G molecule is a nonclassical HLA class I antigen selectively expressed by trophoblast and thymic epithelial cells.

Supplemental therapy in isolated vitamin E deficiency improves the peripheral neuropathy and prevents the progression of ataxia.

A 24-year-old male, who suffered since childhood from a progressive form of ataxia associated with peripheral neuropathy, was found severely deficient in serum vitamin E. He walked with bilateral aid and presented severe dysmetria of the limbs and dysarthric speech; muscular strength and trophism were slightly diminished in the distal muscles of four limbs and there was hypotonia of the arms; he presented absent deep tendon reflexes, bilateral Babinski's sign, reduced proprioception at four limbs, pes cavus and fasciculations of the tongue. Intestinal fat malabsorption and other gastrointestinal or haematological conditions associated with deficiency of this vitamin were ruled out.

Femoral nerve damage after abdominal rectopexy.

Iatrogenic femoral nerve damage has already been described after hysterectomy, but never after abdominal rectopexy. We report the occurrence of femoral nerve injury in six of twenty-four patients operated on for complete rectal prolapse (n = 21) or rectorectal intussusception (n = 3). Four patients had unilateral and two bilateral lesions.

Posterior interosseous nerve neuropathy. Clinical and electromyographical aspects.

A clinical-EMGraphic examination was carried out in 37 patients with posterior interosseous nerve neuropathy: 5 cases had a traumatic origin, 4 iatrogenic, and 28 non-traumatic. One of the non-traumatic cases had a lipoma, and another had chondroma. In the other cases, nerve entrapment at the level of the arcade of Frohse could be presumed.

Genetic epidemiology of hereditary motor sensory neuropathies (type I).

Patients affected with hereditary motor sensory neuropathy (HMNS) type I were traced through hospital records. Each case was re-examined, a family history was drawn, and EMG examination was performed in those members of the family who could have inherited the trait. In the prevalence year 1987, in a population of 1,067,130 inhabitants of 2 contiguous provinces of northeast Italy, 100 living cases were recorded in 30 families, giving a minimal prevalence rate estimate of 9.

X-linked Charcot-Marie-Tooth disease. A linkage study in a large family by using 12 probes of the pericentromeric region.

Linkage analysis was performed on 41 subjects belonging to a large family with a recurrence of X-linked Charcot-Marie-Tooth disease (CMTX), by using 12 restriction fragment length polymorphism markers mapping in p11-q13. The results are in agreement with previous linkage data. Three new markers that are potentially useful for genetic analysis of CMTX families are described.

Contribution of electromyography to the diagnosis, treatment and prognosis of cervical disc disease: a study of 114 patients.

The aim of this study is to verify whether EMG has the same diagnostic and prognostic capacity in cervical root syndrome as it does in lumbo-sacral syndromes. Our population includes 114 patients affected by a cervico-brachialgia with EMG denervation provoked by cervical disc disease. 26 patients were submitted to a myelography confirming the discal origin of the syndrome: there were 3 cases of disc protrusion and 23 cases of cervical spondylosis.

Radiation-induced brachial plexopathy: clinical and electromyographical (EMG) considerations in 13 cases.

The purpose of this study was to determine the clinical and electromyographical characteristics of the initial picture, and the subsequent course of the radiation-induced brachial plexopathy. The AA. studied 13 females affected by infiltrating carcinoma of the breast, who underwent a radical mastectomy with removal of the axillary cavity, followed by radiotherapy (total dose was 50 Gy per cycle).