Vav1 accelerates Ras-driven lung cancer and modulates its tumor microenvironment.

The potential impact of Vav1 on human cancer was only recently acknowledged, as it is detected as a mutant or an overexpressed gene in various cancers, including lung cancer. Vav1, which is normally and exclusively expressed in the hematopoietic system functions as a specific GDP/GTP nucleotide exchange factor (GEF), strictly regulated by tyrosine phosphorylation. To investigate whether Vav1 plays a causative or facilitating role in-vivo in lung cancer development and to examine whether it co-operates with other oncogenes, such as mutant K-Ras, we generated novel mouse strains that express: Vav1 or K-Ras in type II pneumocytes, as well as a transgenic mouse line that expresses both Vav1 and K-Ras in these cells.

Cholinergic transmission in C. elegans: Functions, diversity, and maturation of ACh-activated ion channels.

Acetylcholine is an abundant neurotransmitter in all animals. Effects of acetylcholine are excitatory, inhibitory, or modulatory depending on the receptor and cell type. Research using the nematode C.

Expression levels of selected genes can predict individual rheumatoid arthritis patient response to tumor necrosis factor alpha blocker treatment.

Objectives: Rheumatoid arthritis (RA) patients have many therapeutic options; however, tools to predict individual patient response are limited. The Genefron personal diagnostic kit, developed by analyzing large datasets, utilizes selected interferon stimulated gene expressions to predict treatment response. This study evaluates the kit's prediction accuracy of individual RA patients' response to tumor necrosis alpha (TNFα) blockers.

[AORTIC DISSECTION DIAGNOSED BY THE SUPRASTERNAL ECHOCARDIOGRAPHIC VIEW].

Patients with suspected dissection of the thoracic aorta require immediate diagnostic evaluation so that urgent therapeutic interventions can begin. We present a case of aortic dissection with an atypical initial presentation mimicking acute pericarditis, in which the correct diagnosis was made on the basis of the suprasternal view of transthoracic echocardiography.

Indomethacin sensitizes resistant transformed cells to macrophage cytotoxicity.

Activated macrophages are well known to exhibit anti-tumor properties. However, certain cell types show intrinsic resistance. Searching for a mechanism that could explain this phenomenon, we observed that the supernatant of resistant cells could confer resistance to otherwise sensitive tumor cells, suggesting the presence of a secreted suppressor factor.

A benchmark testing ground for integrating homology modeling and protein docking.

Protein docking procedures carry out the task of predicting the structure of a protein-protein complex starting from the known structures of the individual protein components. More often than not, however, the structure of one or both components is not known, but can be derived by homology modeling on the basis of known structures of related proteins deposited in the Protein Data Bank (PDB). Thus, the problem is to develop methods that optimally integrate homology modeling and docking with the goal of predicting the structure of a complex directly from the amino acid sequences of its component proteins.

Safety and efficacy of two dose levels of taliglucerase alfa in pediatric patients with Gaucher disease.

Taliglucerase alfa is a plant cell-expressed beta-glucocerebrosidase approved in the United States, Israel, Australia, Canada, and other countries for enzyme replacement therapy in adults with Type 1 Gaucher disease (GD), for treatment of pediatric patients in the United States, Australia, and Canada, and for the hematologic manifestations of Type 3 GD in pediatric patients in Canada. This multicenter, randomized, double-blind, parallel-dose, 12-month study assessed efficacy and safety of taliglucerase alfa in pediatric patients with GD. Eleven children were randomized to taliglucerase alfa 30U/kg (n=6) or 60U/kg (n=5) per infusion every other week.

Vav1 promotes lung cancer growth by instigating tumor-microenvironment cross-talk via growth factor secretion.

Vav1 is a signal transducer that functions as a scaffold protein and a regulator of cytoskeleton organization in the hematopoietic system, where it is exclusively expressed. Recently, Vav1 was shown to be involved in diverse human cancers, including lung cancer. We demonstrate that lung cancer cells that abnormally express Vav1 secrete growth factors in a Vav1-dependent manner.

[The general internist--an endangered species?].

The status of general internal medicine is in a state of decay, and along with it, the position of general internists is declining. Nowadays, most internists depart from general internal medicine to the sub-specialties. The expected future shortage of general internists threatens the medical profession, endangers the future care of hospitalized medical patients and calls for a change in policy.

Vav1 fine tunes p53 control of apoptosis versus proliferation in breast cancer.

Vav1 functions as a signal transducer protein in the hematopoietic system, where it is exclusively expressed. Vav1 was recently implicated in several human cancers, including lung, pancreatic and neuroblasoma. In this study, we analyzed the expression and function of Vav1 in human breast tumors and breast cancer cell lines.

Single cell transfection in chick embryos.

A central theme in developmental biology is the diversification of lineages and the elucidation of underlying molecular mechanisms. This entails a thorough analysis of the fates of single cells under normal and experimental conditions. To this end, transfection methods that target single progenitors are a prerequisite.

High-dose glycine added to olanzapine and risperidone for the treatment of schizophrenia.

Background: Clinical trials indicate that glycine site agonists of the N-methyl-D-aspartate (NMDA) receptors may reduce negative and cognitive symptoms in treatment-resistant schizophrenia when used as adjuvants to conventional antipsychotics but possibly not to clozapine. In this study, we assessed whether high-dose glycine may also be therapeutically beneficial when added to olanzapine and risperidone treatment.

Methods: Seventeen olanzapine- or risperidone-treated schizophrenia patients participated in a double-blind, placebo-controlled, 6-week crossover treatment trial with.

Pilot-controlled trial of D-cycloserine for the treatment of post-traumatic stress disorder.

Dysfunction of glutamatergic neurotransmission may be relevant to the pathogenesis of post-traumatic stress disorder (PTSD). Preclinical and clinical evidence suggests that PTSD symptoms could be alleviated following enhancement of neurotransmission mediated at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. Eleven patients with chronic PTSD participated in a double-blind, placebo-controlled, cross-over trial with 50 mg/d D-cycloserine which acts as a partial agonist at the glycine regulatory site on the NMDA receptor.

Vascular trauma in high-velocity gunshot wounds and shrapnel-blast injuries in Israel.

High-velocity gunshot and shrapnel-blast vascular injuries pose a great challenge and need to be approached in a systematic, multidisciplinary fashion. Early revascularization with temporary shunts, the use of autologous tissue, major venous reconstruction, a low threshold for fasciotomy, and reliable tissue coverage are the mainstays of management.

Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia.

Background: Disturbances of N-methyl-D-aspartate (NMDA) receptor-mediated glutamatergic neurotransmission may play an important role in the pathophysiology of negative symptoms of schizophrenia. Glycine, a small nonessential amino acid, functions as an obligatory coagonist at NMDA receptors through its action at a strychnine-insensitive binding site on the NMDA receptor complex. Glycine-induced augmentation of NMDA receptor-mediated neurotransmission may thus offer a potentially safe and feasible approach for ameliorating persistent negative symptoms of schizophrenia.

Double-blind, placebo-controlled, crossover trial of glycine adjuvant therapy for treatment-resistant schizophrenia.

Background: It has been proposed that schizophrenia is associated with underactivity of brain glutamatergic neurotransmission, especially at the level of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Glycine potentiates NMDA receptor-mediated neurotransmission, indicating that it may serve as an effective therapeutic agent in the treatment of schizophrenia.

Method: Eleven treatment-resistant patients with chronic schizophrenia completed a double-blind, placebo-controlled, six-week, randomly assigned, crossover treatment trial of 0.

Trophoblasts protect the inner cell mass from macrophage destruction.

Several mechanisms have been suggested to account for the survival of the semiallogeneic fetus in the maternal uterus. However, no data are available to explain how the blastocyst resists the high number of macrophages in the uterus at the time of implantation. The present study examines the in vitro development of murine 3.