Objective-To determine whether a renal diet modified in protein, phosphorus, sodium, and lipid content was superior to an adult maintenance diet in minimizing uremic episodes and mortality rate in cats with stage 2 or 3 chronic kidney disease (CKD). Design-Double-masked, randomized, controlled clinical trial. Animals-45 client-owned cats with spontaneous stage 2 or 3 CKD. Procedures-Cats were randomly assigned to an adult maintenance diet (n = 23 cats) or a renal diet (22) and evaluated trimonthly for up to 24 months. Efficacy of the renal diet, compared with the maintenance diet, in minimizing uremia, renal-related deaths, and all causes of death was evaluated. Results-Serum urea nitrogen concentrations were significantly lower and blood bicarbonate concentrations were significantly higher in the renal diet group at baseline and during the 12- and 24-month intervals. Significant differences were not detected in body weight; Hct; urine protein-to-creatinine ratio; and serum creatinine, potassium, calcium, and parathyroid hormone concentrations. A significantly greater percentage of cats fed the maintenance diet had uremic episodes (26%), compared with cats fed the renal diet (0%). A significant reduction in renal-related deaths but not all causes of death was detected in cats fed the renal diet. Conclusions and Clinical Relevance-The renal diet evaluated in this study was superior to an adult maintenance diet in minimizing uremic episodes and renalrelated deaths in cats with spontaneous stage 2 or 3 CKD.

In this study, we investigated the Five-factor model in the concurrent prediction of positive symptom schizotypy as measured by the Magical Ideation (Eckblad & Chapman, 1983) and Perceptual Aberration (Chapman, Chapman, & Raulin, 1978) scales and negative symptom schizotypy as measured by the Physical Anhedonia (Chapman, Chapman, & Raulin, 1976) and Revised Social Anhedonia (Eckblad, Chapman, Chapman, & Mishlove, 1982; Mishlove & Chapman, 1985) scales. Previous studies suggest that these measures reflect the core symptoms found in schizotypal and schizoid personality disorder (Bailey, West, Widiger, & Freiman, 1993). Negative symptoms were significantly predicted by Neuroticism (+), Extraversion (-), Openness (-), and Agreeableness (-) domains of the Revised NEO Personality Inventory (NEO-PI-R; Costa & McCrae, 1992). Additionally, positive symptoms were significantly predicted by Neuroticism (+), Openness (+), and Agreeableness (-). In addition, we examined the validity of lower order traits in de- scribing these symptoms of character pathology. These findings lend further support for the use of domain and facet scales of the NEO-PI-R in the identification of personality pathology.

SummaryRecently we described the molecular cloning of SLP-76, a hematopoietic cell-specific 76-kD protein that was first identified through its association with GST/Grb2 fusion proteins. The primary sequence of SLP-76 predicts a protein of 533 amino acids comprising an amino-terminal region with numerous potential tyrosine phosphorylation sites, a central region rich in proline residues, and a single carboxy-terminal SH2 domain. Here we demonstrate formally that Grb2 associates with unphosphorylated SLP-76 and map the Grb2 binding site on SLP-76 to amino acids 224-244. We also demonstrate that upon T cell receptor (TCR) stimulation, SLP-76 undergoes rapid tyrosine phosphorylation and associates with tyrosine phosphoproteins of 36, 62, and 130 kD. In vitro experiments show that the SH2 domain of SLP-76 associates with the 62-and 130-kD proteins and additionally with a serine/threonine kinase. Finally, we demonstrate that transient overexpression of SLP-76 results in dramatically enhanced TCR-mediated induction of nuclear factor of activated T cells (NFAT) and interleukin (IL) 2 promoter activity; and we provide evidence that a functional SLP-76 SH2 domain is required for this effect. Our data document the in vivo associations of SLP-76 with several proteins that potentially participate in T cell activation and implicate SLP-76 itself as an important molecule in TCR-mediated IL-2 production. L igation of the TCR results in the rapid activation of several protein tyrosine kinases (PTKs) with the subsequent phosphorylation of numerous cellular proteins (1-3), including components of the TCR itself (2, 3), Src and Syk family PTKs (Lck, Fyn, and ZAP-70 [for review see reference 4]), phospholipase C~/1 (5-7), GAP (8), ezrin (9), CD5 (10, 11), Shc (12), Vav (13,14), Cbl (15), and several cytoskeletal proteins (16). However, many substrates of the TCR-activated PTKs remain unidentified. Our laboratory has been interested in characterizing some of these molecules. As one strategy, we chose to investigate tyrosine phosphoproteins that associate with Grb2, an adapter molecule that has been shown to play a central role in coupling fignaling pathways in other systems.Using this approach, we and others have demonstrated that tyrosine phosphoproteins of 36, 76, and 116 kD associate with Grb2 in T cells (17)(18)(19)(20). The 116-kD protein has been identified recently as the product of the c-Cbl protooncogene (15); however, its function remains unclear. The molecular identity of the 36-kD protein remains uncertain, but recent data from our laboratory suggest that tyrosine phosphorylation of this molecule is required for coupling the TCK with the phosphatidylinositol second messenger pathway (Motto, D., M. Musci, S. Ross, and G. Koretzky, manuscript submitted for publication). Recently, in a collaborative effort (Paul Findell, Palo Alto, CA), we purified the 76-kD Grb2-associated phosphoprotein and cloned its cDNA, which encodes a novel hematopoietic cell-specific protein we have termed SLP-76, for S_H2 domain leukocyte Erotein o...

The Hedgehog family of secreted intercellular signaling molecules are regulators of patterning and organogenesis during animal development. In this study we provide genetic evidence that Sonic Hedgehog (Shh) has a role in the control of murine T cell development. Analysis of Shh−/− mouse embryos revealed that Shh regulates fetal thymus cellularity and thymocyte differentiation. Shh is necessary for expansion of CD4−CD8− double-negative (DN) thymocytes and for efficient transition from the earliest CD44+CD25− DN population to the subsequent CD44+CD25+ DN population and from DN to CD4+CD8+ double-positive cells.

DSM-5 includes a dimensional model of personality pathology, operationalized in the Personality Inventory for DSM-5 (PID-5), with 25 facets grouped into five higher-order factors resembling the Big Five personality dimensions. The present study tested how well these 25 facets could be integrated with the 10-factor structure of traits within the Big Five that is operationalized by the Big Five Aspect Scales (BFAS). In two healthy adult samples, 10-factor solutions largely confirmed our hypothesis that each of the 10 BFAS scales would be the highest loading BFAS scale on one and only one factor. Varying numbers of PID-5 scales were additional markers of each factor, and the overall factor structure in the first sample was well replicated in the second. Our results allow Cybernetic Big Five Theory (CB5T) to be brought to bear on manifestations of personality disorder, because CB5T offers mechanistic explanations of the 10 factors measured by the BFAS. Future research, therefore, may begin to test hypotheses derived from CB5T regarding the mechanisms that are dysfunctional in specific personality disorders.