Support for the homeobox transcription factor gene ENGRAILED 2 as an autism spectrum disorder susceptibility locus.

Our previous research involving 167 nuclear families from the Autism Genetic Resource Exchange (AGRE) demonstrated that two intronic SNPs, rs1861972 and rs1861973, in the homeodomain transcription factor gene ENGRAILED 2 (EN2) are significantly associated with autism spectrum disorder (ASD). In this study, significant replication of association for rs1861972 and rs1861973 is reported for two additional data sets: an independent set of 222 AGRE families (rs1861972-rs1861973 haplotype, P=.0016) and a separate sample of 129 National Institutes of Mental Health families (rs1861972-rs1861973 haplotype, P=.

Adenovirus infection dramatically augments lipopolysaccharide-induced TNF production and sensitizes to lethal shock.

We observed a remarkable synergism of adenoviruses and LPS in triggering the production of TNF in intact animals. We found that in mice pre-exposed to adenoviruses, LPS injections generated extremely high levels of TNF with altered kinetics. The elevated TNF synthesis stemmed mostly from posttranscriptional up-regulation of TNF production, although transcription of the TNF gene was also induced.

Esophageal ATP synthase and keratinocyte growth factor gene expression changes after acid and bile-induced mucosal damage.

Objective And Design: Intramural gene expression changes may be critically involved in tissue damage, defense and repair after esophageal regurgitation. The aims were to characterize the consequences of short-term exposure to luminal bile, acid, or bile mixed with acid on the beta-ATPase, keratinocyte growth factor 1 (KGF-1) and KGF receptor (KGF-R) expressions within the mucosa and the muscle layer in a large animal model.

Materials And Subjects: Esophageal segments of anesthetized dogs were exposed to saline (n = 3), diluted canine bile (n = 6), hydrochloric acid (n = 5) or bile + hydrochloric acid (n = 5), and tissue biopsies were taken at the end of the 180-min observation period.

Specific genetic disorders and autism: clinical contribution towards their identification.

Autism is a heterogeneous disorder that can reveal a specific genetic disease. This paper describes several genetic diseases consistently associated with autism (fragile X, tuberous sclerosis, Angelman syndrome, duplication of 15q11-q13, Down syndrome, San Filippo syndrome, MECP2 related disorders, phenylketonuria, Smith-Magenis syndrome, 22q13 deletion, adenylosuccinate lyase deficiency, Cohen syndrome, and Smith-Lemli-Opitz syndrome) and proposes a consensual and economic diagnostic strategy to help practitioners to identify them. A rigorous initial clinical screening is presented to avoid unnecessary laboratory and imaging studies.

Immunohistochemical localization of cocaine- and amphetamine-regulated transcript peptide in the central nervous system of the frog Rana esculenta.

The distribution of cocaine- and amphetamine-regulated transcript peptide (CARTp)- like immunoreactivity was studied only in the rat central nervous system (CNS). In mammals, CART peptides occur among others in brain areas that control feeding behavior. We mapped CARTp-immunoreactive structures in the CNS of the frog Rana esculenta and assumed that differences may exist in the CARTp-containing neuronal populations between the frog, which does not feed in winter, and the rat.

Biochemical and structural studies of the interaction of Cdc37 with Hsp90.

The heat shock protein Hsp90 plays a key, but poorly understood role in the folding, assembly and activation of a large number of signal transduction molecules, in particular kinases and steroid hormone receptors. In carrying out these functions Hsp90 hydrolyses ATP as it cycles between ADP- and ATP-bound forms, and this ATPase activity is regulated by the transient association with a variety of co-chaperones. Cdc37 is one such co-chaperone protein that also has a role in client protein recognition, in that it is required for Hsp90-dependent folding and activation of a particular group of protein kinases.

[Endoscopic stapling diverticulostomy for Zenker diverticulum].

Introduction: The authors have successfully applied the endoscopic stapling diverticulostomy for three patients with symptomatic Zenker diverticulum.

Method: Under light general anesthesia the hypopharynx was explored with a rigid, double lipped laryngoscope (Weerda, Storz). The common wall between the esophagus and and diverticulum was cut across and reunited with a endosurgical stapler.

The role of the glucocorticoid-dependent mechanism in the progression of sodium taurocholate-induced acute pancreatitis in the rat.

The effects of glucocorticoids on acute pancreatitis (AP) have remained contradictory. The aim of this study was to investigate the time courses of the effects of the exogenous glucocorticoid agonists dexamethasone (DEX) and hydrocortisone (HYD) and a glucocorticoid antagonist (RU-38486) and to characterize the local and systemic responses in AP in rats. The glucocorticoid antagonist and agonists were administered just before AP induction.

Alkali ingestion predisposes to developing giant mid-esophageal pulsion diverticulum - a report of a medical rarity.

Pulsion diverticulae of the mid-esophagus with unknown etiology are usually asymptomatic and therefore considered incidental findings on chest X-rays, barium swallows, or endoscopic procedures. Diagnosis is often delayed due to the rarity of clinical symptoms. The clinical, radiological, etiological and surgical features in a patient with extraordinary symptomatic giant mid-esophageal pulsion diverticulum with history of alkali ingestion are presented here.

Cocaine- and amphetamine-regulated transcript peptide (CART) is a selective marker of rat granule cells and of human mossy cells in the hippocampal dentate gyrus.

Cocaine- and amphetamine-regulated transcript (CART) peptide immunocytochemistry was used to reveal cellular localization in the dentate gyrus and in Ammon's horn of the rat and human hippocampal formations. In the rat dentate gyrus, only granule cells were labeled, whereas in humans, only mossy cells of the hilar region expressed CART peptide immunoreactivity. In the rat, CART-positive granule cells were located at the molecular layer border of the granule cell layer and had no features that would distinguish them from other granule cells.

[The role of glucocorticoid-dependent mechanisms in the progression of experimentally induced acute pancreatitis].

Background: The effects of glucocorticoids on acute pancreatitis (AP) have remained contradictory. To investigate the time courses of the effects of the exogenous glucocorticoid agonists dexamethasone (DEX) and hydrocortisone (HYD) and a glucocorticoid antagonist (RU-38486), and to characterize the local and systemic responses in experimental AP.

Methods: The glucocorticoid agonists and antagonist were administered just before AP induction.

Endoscopic intubation with conventional plastic stents: a safe and cost-effective palliation for inoperable esophageal cancer.

Access to expensive equipment and costly self-expanding metal endoprostheses is limited in some regions where unresectable esophageal cancer is not infrequent. The aim of this study was to review the long-term results of palliation of malignant esophageal obstruction using low-priced conventional plastic stents. One hundred sixty-nine patients with dysphagia due to inoperable esophageal cancer underwent esophageal intubation under endoscopic control alone, without general anesthesia, by the pulsion method.

[Palliation of inoperable esophageal tumor with endoscopic intubation].

Rationale: Access to expensive equipment and costly self-expanding metal endoprostheses is limited in some regions where unresectable esophageal cancer is not infrequent. The aim of this study was to review the long-term results of palliation of malignant esophageal obstruction using low-priced conventional plastic stents.

Patients And Methods: 103 patients with dysphagia due to inoperable esophageal cancer underwent esophageal intubation under endoscopic control alone, without general anesthesia, by the pulsion method.

Thoracic epidural anesthesia improves the gastric microcirculation during experimental gastric tube formation.

Background: Gastric tube formation is a surgical technique to reestablish the continuity of the gastrointestinal tract after esophagectomy. Our aims were to study the microcirculatory consequences of experimental gastric tube formation and characterize the effects of thoracic epidural anesthesia (TEA) during this condition.

Methods: The experiments were performed on mongrel dogs anesthetized with pentobarbital.

Microcirculatory changes in the canine oesophageal mucosa during experimental reflux oesophagitis: comparison of the effects of acid and bile.

Background: The response of the oesophageal microcirculation to luminal damaging agents may play an important role in reflux-induced mucosal injury. We characterized the microcirculatory consequences of exposure to bile with or without hydrochloric acid, and determined the changes in the constitutive nitric oxide synthase and inducible nitric oxide synthase activities in a canine model of acute reflux oesophagitis.

Methods: Group 1 served as a saline-treated control, while groups 2-4 were exposed for 3 h to bile alone, to hydrochloric acid, or to bile + hydrochloric acid, respectively.

Designing proteins for therapeutic applications.

Protein design is becoming an increasingly useful tool for optimizing protein drugs and creating novel biotherapeutics. Recent progress includes the engineering of monoclonal antibodies, cytokines, enzymes and viral fusion inhibitors.

The influence of omega-3 polyunsaturated fatty acids (omega-3 pufa) on lactobacilli adhesion to the intestinal mucosa and on immunity in gnotobiotic piglets.

The effect of application of omega-3 polyunsaturated fatty acids (omega-3 PUFA) on intestinal colonization by Lactobacillus paracasei and on cellular immunity has been investigated in gnotobiotic pigs. The administration of polyunsaturated fatty acids positively affected the adhesion of Lactobacillus paracasei to the jejunal mucosa of gnotobiotic piglets. When compared to the control group, the number of Lactobacillus paracasei adhering to the jejunal mucosa was by 12% higher in piglets of the experimental group (5.

[Changes in microcirculation of esophageal mucosa during acute experimental reflux. Pathogenic role of the biliary component].

Unlabelled: Our aims were to examine microcirculation during experimental reflux esophagitis in dogs. We compared the effects of microcirculation of the mucosa to 3-hr exposure with acid, mixed acid and bile, we measured the changes in constitutive and inducible nitric oxide synthase activity (cNOS and iNOS).

Methods: The microcirculation of the upper esophagus was investigated by intravital videomicroscopy.

[Thoracic epidural anesthesia improves the gastric microcirculation during experimental gastric tube formation].

We studied the effects of gastric tube formation and thoracic epidural anaesthesia (TEA) on gastric microcirculation, hemodynamic and bowel motility changes. The experiments were performed on pentobarbital-anesthetized, mongrel dogs. Mean arterial pressure (MAP), gastric and mesenteric blood flow (Transonic Systems Inc.

Potassium channel blockers tetraethylammonium and 4-aminopyridine fail to prevent microglial activation induced by elevated potassium concentration.

The effect of potassium channel blocker tetraethylammonium and 4-aminopyridine was examined on the elevated K+ concentration-induced microglial activation on rat hippocampal slice preparations. Microglial cells were detected by immunohistochemisty with a monoclonal antibody (OX 42) raised against a type 3 complement receptor. During activation the morphology of the microglial cells changes and the staining intensity increases.

Rational design and engineering of therapeutic proteins.

An increasing number of engineered protein therapeutics are currently being developed, tested in clinical trials and marketed for use. Many of these proteins arose out of hit-and-miss efforts to discover specific mutations, fusion partners or chemical modifications that confer desired properties. Through these efforts, several useful strategies have emerged for rational optimization of therapeutic candidates.

Kupffer cell phagocytosis blockade decreases morbidity in endotoxemic rats with obstructive jaundice.

Objective And Design: The consequences of Kupffer cell phagocytosis blockade were studied in endotoxemic rats with obstructive jaundice.

Material Or Subjects: 159 male Wistar rats.

Treatment: Obstructive jaundice was induced by bile duct ligation (BDL).

Distribution of urocortin-like immunoreactivity in the central nervous system of the frog Rana esculenta.

Corticotropin-releasing factor (CRF), sauvagine, and urotensin I are all members of the so-called CRF neuropeptide family. Urocortin (Ucn), a 40-amino-acid neuropeptide recently isolated from the rat brain, is the newest member of this family. Until now, the distribution of Ucn in the central nervous system (CNS) has been studied only in placental mammals.