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Background Dietary salt restriction is believed to be a mainstay in the management of patients with heart failure. However, the effect of salt intake on heart failure has not been well evaluated in outpatient medical practice. Aims The aim of the present study was to assess the hypothesis that B-type natriuretic peptide ( BNP) level, as an objective marker of heart failure, is associated with salt intake in patients with heart failure. Methods One hundred and thirteen consecutive patients with mild compensated heart failure (77 ± 10 years old, 51 female) were included. We estimated dietary salt intake by the concentration of sodium and creatinine in spot urine. We measured BNP at the time of urine sampling and assessed the relationship between the % changes in BNP levels (%Δ BNP) and the changes in the estimated daily salt excretion (Δ NaCl) during the follow-up period. Results The baseline median BNP level was 150 (interquartile range: 83-263) pg/ mL and the estimated daily salt excretion was 162 ± 45 mmol/day. There was a positive correlation between %Δ BNP and Δ NaCl (r = 0.61, P < 0.01). Multiple regression analysis revealed that %Δ BNP was associated with Δ NaCl ( P < 0.01), but not with changes in systolic blood pressure and bodyweight. Conclusions Changes in BNP levels were associated with changes in the estimated daily salt excretion in outpatients with compensated heart failure. Salt restriction may be beneficial for the management of patients with heart failure. [ABSTRACT FROM AUTHOR]

Objective: Approximately 25% of patients who undergo percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) have diabetes, and the diagnosis of diabetes roughly doubles the mortality risk associated with coronary artery disease. However, the impact of diabetes may differ according to ethnicity. Our objective was to examine the impact of diabetes on long-term survival among U.S. and Japanese patients who underwent PCI or CABG.Research Design and Methods: For the current analysis, we included 8,871 patients from a Japanese multicenter registry (Coronary Revascularization Demonstrating Outcome database in Kyoto; median follow-up 3.5 years; interquartile range [IQR] 2.6-4.3) and 7,229 patients from a U.S. multipractice registry (Texas Heart Institute Research Database; median follow-up 5.2 years; IQR 3.8-6.5).Results: Diabetes was more prevalent among Japanese than U.S. patients (39.2 vs. 31.0%; P < 0.001). However, after revascularization, long-term all-cause mortality was lower in diabetic Japanese patients than in diabetic U.S. patients (85.4 vs. 82.2%; log-rank test P = 0.009), whereas it was similar in nondiabetic Japanese and U.S. patients (89.1 vs. 89.5%; P = 0.50). The national difference in crude mortality was also significant among insulin-using patients with diabetes (80.8 vs. 74.9%; P = 0.023). When long-term mortality was adjusted for known predictors, U.S. location was associated with greater long-term mortality risk than Japanese location among nondiabetic patients (hazard ratio 1.58 [95% CI 1.32-1.88]; P < 0.001) and, especially, diabetic patients (1.88 [1.54-2.30]; P < 0.001).Conclusions: Although diabetes was less prevalent in U.S. patients than in Japanese patients, U.S. patients had higher overall long-term mortality risk. This difference was more pronounced in diabetic patients. [ABSTRACT FROM AUTHOR]

The presentation of human leukocyte antigens (HLA) class I requires the coordinated expression of numerous components involved in antigen presentation. Tumor cells may alter the antigen presentation by HLA class I, allowing them to evade antitumor immunity. In many cases, the lack of antigen presentation can be attributed to the downregulation of genes needed for antigen processing, such as the transporters associated with antigen processing (TAP) 1, and the proteasomal component, low molecular weight proteins (LMP) 2. The TAP1 and LMP2 genes are transcribed from a shared bidirectional promoter containing an interferon (IFN)-γ-response factor element; thus, the IFN-γ-signal strongly induces both TAP1 and LMP2 expression. Low molecular weight proteins2-deficient mice exhibited the development of uterine leiomyosarcomas. Here, the differential responsiveness to IFN-γ of the SKN human uterine leiomyosarcomas cell line was investigated. We now identify the G871E mutation in the ATP-binding region of Janus kinases 1, suggesting that the loss of TAP1 and LMP2 induction is a defect in the earliest steps of the IFN-γ-signal pathway, resulting in the inability of SKN cells to upregulate the antigen-processing pathway. Understanding the mechanisms by which these tumors circumvent cytokine signalling, thereby evading antitumor-specific immunity, would greatly aid the efficacy of immunotherapy for treating uterine leiomyosarcomas.Oncogene (2006) 25, 4016–4026. doi:10.1038/sj.onc.1209434; published online 13 February 2006 [ABSTRACT FROM AUTHOR]

In analyzing the regulation of neurotrophin production/secretion from microglia, C8-ceramide (d-erythro-sphingosine, N-octanoyl-) was found to induce secretion of brain-derived neurotrophic factor (BDNF) from microglia in vitro. In the present study, the action of C8-ceramide in secreting neurotrophic and harmful factors was investigated and compared with the effects of lipopolysaccharide (LPS). C8-ceramide as well as LPS enhanced the production/secretion of BDNF but, different from LPS, did not induce tumor necrosis factor α, interleukin-1β, or nitric oxide. The C8-ceramide-induced BDNF release was significantly suppressed by protein kinase C (PKC) inhibitor, bisindolylmaleimide, which targets PKC isoforms, α, β, γ, δ and ε. However, it was not suppressed by a specific inhibitor of PKCα. Furthermore, PKCβ and γ were undetected in the microglia. Therefore, PKCδ and/or ε appear to be functioning PKC isoforms. In contrast, none of the mitogen-activated protein kinases (MAPKs) and none of the transcription factors, including the cAMP response element-binding transcription factor (CREB) and nuclear factor κB (NFκB) were activated in the microglia in response to C8-ceramide. These results indicate that ceramide-induced BDNF release in microglia is mediated by a signaling pathway associated with PKCδ and/or ε, but not with activation of MAPKs, CREB and NFκB. [ABSTRACT FROM AUTHOR]

Microglia play various important roles in the CNS via the synthesis of cytokines. The ATP-evoked production of interleukin-6 (IL-6) and its intracellular signals were examined using a mouse microglial cell line, MG-5. ATP, but not its metabolites, produced IL-6 in a concentration-dependent manner. Although ATP activated two mitogen-activated protein kinases, i.e. p38 and extracellular signal-regulated protein kinase, only p38 was involved in the IL-6 induction. However, the activation of p38 was not sufficient for the IL-6 induction because 2′- and 3′-O-(4-benzoylbenzoyl) ATP, an agonist to P2X7 receptors, failed to produce IL-6 despite the fact that it activated p38. Unlike in other cytokines in microglial cells, P2Y rather than P2X7 receptors seem to have a major role in the IL-6 production by the cells. The ATP-evoked IL-6 production was attenuated by Gö6976, an inhibitor of Ca[sup 2+]-dependent protein kinase C (PKC). The P2Y receptor responsible for these responses was insensitive to pertussis toxin (PTX) and was linked to phospholipase C. Taken together, ATP acting on PTX-insensitive P2Y receptors activates p38 and Ca[sup 2+]-dependent PKC, thereby resulting in the mRNA expression and release of IL-6 in MG-5. This is a novel pathway for the induction of cytokines in microglia. [ABSTRACT FROM AUTHOR]

Genetic studies have implicated amyloid precursor protein (APP) in the pathogenesis of Alzheimer's disease. While accumulating lines of evidence indicate that APP has various functions in cells, little is known about the proteins that modulate its biological activity. Toward this end, we employed a two-hybrid system to identify potential interacting factors. We now report that fibulin-1, which contains repetitive Ca[sup 2+]-binding EGF-like elements, binds to APP at its amino-terminal growth factor-like domain, the region that is responsible for its neurotrophic activities. Fibulin-1 expression in the brain is confined to neurons, and is not expressed significantly by astrocytes or microglia. Direct binding of fibulin-1 to the secreted form of APP (sAPP) was demonstrated with a pull-down assay using fragments of both fibulin-1 fused with glutathione-S transferase and sAPP, produced in bacteria and yeast, respectively. The fibulin-1/sAPP heteromer was shown to form in the conditioned medium of transfected COS-7 cells. Furthermore, fibulin-1 blocks sAPP-mediated proliferation of primary cultured rat neural stem cells. These results suggest that fibulin-1 may play a significant role in modulating the neurotrophic activities of APP. [ABSTRACT FROM AUTHOR]

The brain concentration of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) increased in rats maintained on restricted volume of low-protein or normal-protein diet, whereas these two agents decreased in rats fed low-protein diet ad libitum. In these two food-restricted groups brain 5-HT and 5-HIAA concentrations were not correlated with brain tryptophan hydroxylase activity, but the concentrations correlated closely with cerebral tryptophan concentrations. The cerebral tryptophan concentration in the two food-restricted groups was not consistent with the total or free tryptophan concentration in plasma. In these restricted rats cerebral tryptophan concentration was elevated, and, unlike the plasma tryptophan, it showed no diurnal variation. These results suggested that tryptophan uptake into the brain from plasma was enhanced by limiting food volume intake. Tryptophan uptake was increased by glucagon injection without changing the plasma tryptophan level, but injection of hydrocortisone or insulin had little or no effect on tryptophan concentration in either the plasma or brain. d-Glucose injection elevated plasma tryptophan concentration but decreased brain tryptophan concentration. [ABSTRACT FROM AUTHOR]

Offers eleven abstracts from published research. "Effects of Antidepressant Medication on Morbidity and Mortality in Depressed Patients After Myocardial Infarction"; "Abdominal Aortic Aneurysms and Concomitant Diseases Requiring Surgical Intervention: Simultaneous Operations vs Staged Treatment Using Endoluminal Stent Grafting"; "Immunological Effects of Laparoscopic vs Open Colorectal Surgery: A Prospective Clinical Study"; "Nonsteroidal Anti-inflammatory Drugs and Increased Risk of Acute Urinary Retention"; "Management of Cervical Metastases in Advanced Squamous Cell Carcinoma of the Tonsillar Fossa Following Radiotherapy"; "Statin Use and the Risk of Incident Dementia: The Cardiovascular Health Study"; "Development of Sarcoidosis in Cosmetic Tattoos".

The article presents an abstract of the research paper "Microglia Express the Glutamate Transporter EAAT2/GLT-1." In the model of facial nerve axotomy, the expression of glutamate transporter-1 has not been fully investigated. The expression was studied by using confocal and immunofluorescence techniques.

The article presents an abstract of the study "Application of Temperature-Responsive Polymer, Poly (n-isopropyl-acrylamide) - Grafted Dish on the Detachment of Cultured Microglia." The study will be presented at a joint meeting of the International Society for Neurochemistry and the European Society for Neurochemistry which will be organized in Berlin, Germany, from August 8-14, 1999. The result suggests that poly N-isopropylacrylamide-grafted dish could provide an excellent way to recover intact microglia.

The article presents an abstract of the study "Selective Activation of PI 3-Kinase in Primary Astrocytes by Hepatocyte Growth Factor (HGF)." The study will be presented at a joint meeting of the International Society for Neurochemistry and the European Society for Neurochemistry which will be organized in Berlin, Germany between August 8-14, 1999. The study found that phospholipase C ϒ l and P13-kinase are down-regualted by SHP-1 in the non-stimulated astrocytes.