A mammalian adaptor protein with conserved Src homology 2 and phosphotyrosine-binding domains is related to Shc and is specifically expressed in the brain

The Shc adaptor protein, hereafter referred to as ShcA, possesses two distinct phosphotyrosine-recognition modules, a C-terminal Src homology 2 (SH2) domain and an N-terminal phosphotyrosine-binding (PTB) domain, and is itself phosphorylated on tyrosine in response to many extracellular signals. Phosphorylation of human ShcA at Tyr-317 within its central (CH1) region induces binding to the Grb2 SH2 domain and is thereby implicated in activation of the Ras pathway. Two shc-related genes (shcB and shcC) have been identified in the mouse. shcB is closely related to human SCK, while shcC has not yet been found in other organisms. The ShcC protein is predicted to have a C-terminal SH2 domain, a CH1 region with a putative Grb2-binding site, and an N-terminal PTB domain. The ShcC and ShcB SH2 domains bind phosphotyrosine-containing peptides and receptors with a specificity related to, but distinct from, that of the ShcA SH2 domain. The ShcC PTB domain specifically associates in vitro with the autophosphorylated receptors for nerve growth factor and epidermal growth factor. These results indicate that ShcC has functional SH2 and PTB; domains. In contrast to shcA, which is widely expressed, shcC RNA and proteins are predominantly expressed in the adult brain. These results suggest that ShcC may mediate signaling from tyrosine kinases in the nervous system, such as receptors for neurotrophins.     

Impact of apolipoprotein E polymorphism on lipoproteins and risk of myocardial infarction. The ECTIM Study

Human apolipoprotein (apo) E, a polymorphic protein with three common alleles, epsilon 2, epsilon 3, and epsilon 4, plays an important role in lipoprotein metabolism. This article describes the association of this polymorphism with lipids, apolipoproteins, and lipoproteins with a particular regard to lipoprotein particles, as defined by their apolipoprotein content, as well as the risk of myocardial infarction in a multicenter population-based case-control study (ECTIM study). In the ECTIM study, 574 male patients aged 25 to 64 were examined 3 to 9 months after myocardial infarction in four regions participating in the World Health Organization MONICA project: Belfast (Northern Ireland) and Lille, Strasbourg, and Toulouse (France). Control subjects (n = 722) were randomly selected from the regional populations. The distribution of apoE phenotypes was significantly different across the four control samples (P = .04), with a higher frequency of the epsilon 4 allele in Belfast (14.3%) than in Toulouse (8.2%). The association of apoE polymorphism with biological measurements was studied in the control groups (n = 640) after men with coronary heart disease or those taking hypolipidemic drugs were omitted, with the apoE3/3 phenotype as a reference after adjustment for concomitant factors. Individuals carrying the epsilon 2 allele had lower levels of plasma cholesterol, low-density lipoprotein cholesterol (LDL-C), and apoB and higher levels of triglycerides, very-low-density lipoprotein cholesterol (VLDL-C), apoC-III, apoE, lipoprotein (Lp) C-III:B, and Lp E:B. However, the effect of the epsilon 2 allele on triglyceride, VLDL-C, apoE, and Lp E:B parameters was heterogeneous across the populations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Deep brain stimulation for essential tremor

We examined the effects and safety of deep brain stimulation (DBS) as a treatment for essential tremor (ET). Ten ET patients with disabling medication-refractory tremor underwent stereotactic implantation of a DBS lead in the left Vim thalamic nucleus and completed a 6-month follow-up. The Clinical Tremor Rating Scale and disability assessments were performed at baseline, 1-, 3-, and 6-month follow-up. There were significant improvements in dressing, drinking, eating, bathing, and handwriting as reported by the subjects. Tremor severity, writing, pouring, and spiral and line drawing were significantly improved as rated by the examiner. Improvements persisted through the 6-month follow-up period. Although global disability significantly lessened in the group as a whole, one subject with hand-finger tremor accentuated by writing had no change in disability status. In this 6-month open-label study, DBS was effective and safe in reducing tremor and functional disability in ET.     

Urinary stone proteins: an update

The discovery of an organic component in kidney stones dates back to 1684. More than 150 years elapsed before the incrustation of this organic component, which is now called the matrix, was proposed as the mechanism of stone formation. The composition of the matrix remained largely unknown until the development of electron microscopy and the advances in biochemistry combined in the 1950's to usher in the modern era of renal stone matrix investigation. Composed mainly of selectively incorporated proteins generally characterized by high glutamic and aspartic acid content and the frequent occurrence of gamma-carboxyglutamic acid, the matrix displays a variable and complex composition and shares a few proteins in many stones. The embryonic stone may first appear in the renal tubules where it can acquire the blood and cell membrane proteins recently found by analysis of stone protein extracts. The combination of supersaturation, an appropriate environment, the availability of calcium binding proteins which may be abnormal, and the incorporation of proteins extracted from leukocytes and cell wall membranes may induce stone formation.     

Estimation and hypothesis testing of treatment effects in animal reproductive toxicology studies

Healy (1) and Dempster et al. (8) proposed statistical methods to evaluate the treatment effects in animal reproductive toxicology research. Both methods assume homogeneous variance for the dams and the pups, respectively, in all the treatment groups. In this paper, via mixed effect modeling, we propose a method to estimate the treatment effects allowing heterogeneous variances for the dams and the pups, respectively, in different treatment groups. Covariates will also be included in the model. A procedure to test the fixed effects is also discussed. An example from an animal reproductive toxicological study is used to illustrate the procedures.     

Tongue flicking in agamid lizards: morphology, kinematics, and muscle activity patterns

We wanted to examine whether a relation between foraging strategy, morphology, the mechanics of tongue protrusion, and prey chemical detection and discrimination exists in agamid lizards. Tongue-flick behavior was observed in two species of this family: Uromastix acanthinurus and Plocederma stellio. Potential prey chemical discrimination by means of tongue flicking was examined by using applicator tests. Tongue flicks were subsequently recorded by high-speed video in combination with the electrical activity of a number of jaw and hyolingual muscles. The kinematics of jaws and tongue and the muscle activity patterns were quantified. To investigate if the observed differences in tongue-flick behavior (mainly in the frequency of use) are translated into corresponding differences in tongue morphology, the tongues of both species were examined by light and scanning electron microscopy. The species differed mainly in the surface morphology of the foretongue and in the abundance and distribution of taste buds on the tongue and oral cavity. These differences can be related to behavioural observations; whereas U. acanthinurus readily uses tongue flicks to detect and discriminate between food items, P. stellio does not. However, differences in tongue-flick mechanics (kinematics, electromyograms) between both species were minor. Based on the data gathered in this study and from previously published data, an evolutionary transformation series leading to the complex tongue-flick cycles as observed in snakes is proposed. The required morphological and mechanical changes that accompany such an evolutionary sequence are discussed.     

Purification of a tumoral marker recognized by monoclonal antibody Po66 and associated with human lung squamous cell carcinoma

This paper reports on the production of tumor necrosis factor (TNF) and granulocyte macrophage colony-stimulating factor (GM-CSF) by cultured mononuclear adherent cells derived from bone marrow of 25 patients affected by myelodysplastic syndrome (MDS) of different FAB subtypes. Mean production of GM-CSF was much lower than in controls, without significant differences among different subtypes. Mean production of TNF was similar in MDS patients and in controls, but noteworthy differences were observed between patients with RA, RAEB and RAEB-t and patients with RARS and CMML. Growth of bone marrow granulocyte macrophage and erythroid progenitors did not correlate with TNF and GM-CSF production, although in MDS subtypes with higher GM-CSF levels, colony growth was slightly higher than in subtypes with lower GM-CSF production.