Splenocaval shunting for alleviation of portal hypertension in a dog: a case report

To demonstrate the usefulness of in vivo 31P nuclear magnetic resonance spectroscopy (MRS) in the diagnosis of ischemic heart disease, major findings from three clinical cardiac MRS investigations performed at our institute are summarized. The first study investigated whether 31P MRS with handgrip exercise testing could detect myocardial ischemia demonstrated by exercise 201Tl scintigraphy. Contrary to findings in normal subjects or patients with fixed thallium defects, the ratio of phosphocreatine (PCr) to ATP decreased significantly during exercise in patients with reversible thallium defects. In the second study, PCr and ATP content was measured by 31P MRS and compared in human myocardium with reversible ischemia or scar diagnosed by exercise thallium scintigraphy. Although the PCr content decreased in patients with either reversible or fixed thallium defects, the ATP content decreased only in the latter group. In the third study, postischemic myocardium with chronic mechanical dysfunction that exhibits recovery after revascularization in left ventriculography was metabolically characterized using quantitative cardiac 31P MRS. Postischemic myocardium with reversible mechanical dysfunction demonstrated reduced PCr but normal ATP content. These results suggest that 31P MRS is a clinically important method both for the detection of myocardial ischemia and in the evaluation of myocardial viability.     

Insulin stimulates pp120 endocytosis in cells co-expressing insulin receptors

pp120, a substrate of the insulin receptor tyrosine kinase, is a plasma membrane glycoprotein that is expressed in the hepatocyte as two spliced isoforms differing by the presence (full-length) or absence (truncated) of most of the intracellular domain including all phosphorylation sites. Co-expression of full-length pp120, but not its phosphorylation-defective isoforms, increased receptor-mediated insulin endocytosis and degradation in NIH 3T3 fibroblasts. We, herein, examined whether internalization of pp120 is required to mediate its effect on insulin endocytosis. The amount of full-length pp120 expressed at the cell surface membrane, as measured by biotin labeling, markedly decreased in response to insulin only when insulin receptors were co-expressed. In contrast, when phosphorylation-defective pp120 mutants were co-expressed, the amount of pp120 expressed at the cell surface did not decrease in response to insulin. Indirect immunofluorescence analysis revealed that upon insulin treatment of cells co-expressing insulin receptors, full-length, but not truncated, pp120 co-localized with alpha-adaptin in the adaptor protein complex that anchors endocytosed proteins to clathrin-coated pits. This suggests that full-length pp120 is part of a complex of proteins required for receptor-mediated insulin endocytosis and that formation of this complex is regulated by insulin-induced pp120 phosphorylation by the receptor tyrosine kinase. In vitro GST binding assays and co-immunoprecipitation experiments in intact cells further revealed that pp120 did not bind directly to the insulin receptor and that its association with the receptor may be mediated by other cellular proteins.     

Carboplatin liposomal nanoparticles: Preparation,characterization, and cytotoxicity effects on lung cancer in vitro environment

The study aimed to encapsulate anticancer drug carboplatin into liposomal nanoparticles by reverse-phase evaporation technique and evaluate its efficacy on lung cancer in vitro environment. Nanoparticles were characterized in terms of size, drug loading efficiency, drug retention capability, and cytotoxicity effects. Nanoscale particles with 67% drug encapsulation efficiency were prepared. Also, high retention capability (drug release equal to 25% after 72?h) of the nanodrug was confirmed. In addition, results of the nanodrug cytotoxicity indicated nanoparticles increased potency of the drug by approximately 90%. Findings of the study indicated liposome can be used for carboplatin delivery to lung cancer.     

Microarray studies on the genes responsive to the addition of spermidine or spermine to a Saccharomyces cerevisiae spermidine synthase mutant

The naturally occurring polyamines putrescine, spermidine or spermine are ubiquitous in all cells. Although polyamines have prominent regulatory roles in cell division and growth, precise molecular and cellular functions are not well‐established in vivo. In this work we have performed microarray experiments with a spermidine synthase, spermine oxidase mutant (Δspe3 Δfms1) strain to investigate the responsiveness of yeast genes to supplementation with spermidine or spermine. Expression analysis identified genes responsive to the addition of either excess spermidine (10^?5 M ) or spermine (10^?5 M ) compared to a control culture containing 10^?8 M spermidine. 247 genes were upregulated > two‐fold and 11 genes were upregulated >10‐fold after spermidine addition. Functional categorization of the genes showed induction of transport‐related genes and genes involved in methionine, arginine, lysine, NAD and biotin biosynthesis. 268 genes were downregulated more than two‐fold, and six genes were downregulated > eight‐fold after spermidine addition. A majority of the downregulated genes are involved in nucleic acid metabolism and various stress responses. In contrast, only a few genes (18) were significantly responsive to spermine. Thus, results from global gene expression profiling demonstrate a more major role for spermidine in modulating gene expression in yeast than spermine. Copyright © 2009 John Wiley & Sons, Ltd.     

Effect of pp120 on receptor-mediated insulin endocytosis is regulated by the juxtamembrane domain of the insulin receptor

pp120, a substrate of the insulin receptor tyrosine kinase, does not undergo ligand-stimulated phosphorylation by the insulin-like growth factor-1 (IGF-1) receptor. However, replacement of the C-terminal domain of the IGF-1 receptor beta-subunit with the corresponding segment of the insulin receptor restored pp120 phosphorylation by the chimeric receptor. Since pp120 stimulates receptor-mediated insulin endocytosis when it is phosphorylated, we examined whether pp120 regulates IGF-1 receptor endocytosis in transfected NIH 3T3 cells. pp120 failed to alter IGF-1 receptor endocytosis via either wild-type or chimeric IGF-1 receptors. Thus, the effect of pp120 on hormone endocytosis is specific to insulin, and the C-terminal domain of the beta-subunit of the insulin receptor does not regulate the effect of pp120 on insulin endocytosis. Mutation of Tyr960 in the juxtamembrane domain of the insulin receptor abolished the effect of pp120 to stimulate receptor endocytosis, without affecting pp120 phosphorylation by the insulin receptor. These findings suggest that pp120 interacts with two separate domains of the insulin receptor as follows: a C-terminal domain required for pp120 phosphorylation and a juxtamembrane domain required for internalization. We propose that the interaction of pp120 with the juxtamembrane domain is indirect and requires one or more substrates that bind to Tyr960 in the insulin receptor.     

Response perseveration in psychopaths: Interpersonal/affective or social deviance traits?

In order to clarify the role of the two broad components of psychopathy (interpersonal/affective and social deviance; R. D. Hare, 2003) in explaining maladaptive response perseveration in psychopaths, as well as the role of reflection after punished responses in this deficit, the authors administered a card perseveration task to 47 Spanish male inmates assessed using the Hare Psychopathy Checklist-Revised (PCL-R; R. D. Hare, 1991). Hierarchical regressions showed that psychopaths' maladaptive perseveration (more cards played and less money earned) was uniquely predicted by the social deviance features of psychopathy (PCL-R Factor 2)--particularly by its impulsive and irresponsible lifestyle facet (PCL-R Facet 3)--and not by its interpersonal/affective features (PCL-R Factor 1). Moreover, perseveration was related to a lack of reflection both after punishment and after reward feedback. The authors' results, in conjunction with previous evidence indicating perseverative deficits in several impulse control disorders, suggest that response perseveration may not be specific to psychopathy but rather is associated more generally with the externalizing dimension of psychopathology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)