Biochemical characterization of highly active Trypanosoma brucei gambiense glycerol kinase, a promising drug target.

Human African trypanosomes are blood parasites that cause sleeping sickness, a debilitating disease in sub-Saharan Africa. Glycerol kinase (GK) of these parasites additionally possesses a novel property of reverse catalysis. GK is essential to blood stream form trypanosome, and therefore a promising drug target.

Histidine augments the suppression of hepatic glucose production by central insulin action.

Glucose intolerance in type 2 diabetes is related to enhanced hepatic glucose production (HGP) due to the increased expression of hepatic gluconeogenic enzymes. Previously, we revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses HGP. Here, we show that increased plasma histidine results in hepatic STAT3 activation.

Usefulness of examining hepatic functional volume using technetium-99m galactosyl serum albumin scintigraphy in hepatocellular carcinoma.

Objectives: The aim of the study was to clarify the clinical significance of single-photon emission computed tomography/computed tomography (SPECT/CT) imaging in terms of technetium-99m galactosyl human serum albumin (99mTc-GSA) scintigraphy. To this end, we examined the relationship using data from surgical records of 67 patients with hepatocellular carcinoma who underwent hepatectomy.

Materials And Methods: Liver functional parameters or functional volume was estimated by 99mTc-GSA scintigraphy and computed tomography volumetry was used to estimate morphological volume.

XRCC3 gene polymorphism is associated with survival in Japanese lung cancer patients.

We focused on OGG1 Ser326Cys, MUTYH Gln324His, APEX1 Asp148Glu, XRCC1 Arg399Gln, and XRCC3 Thr241Met and examined the relationship between the different genotypes and survival of Japanese lung cancer patients. A total of 99 Japanese lung cancer patients were recruited into our study. Clinical data were collected, and genotypes of the target genes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Sociodemographic determinants of attitudinal barriers in the use of mental health services in Japan: findings from the World Mental Health Japan Survey 2002-2006.

Aim: Sociodemographic correlates of Japanese attitudinal barriers to mental health services might be different from previous studies in Western countries, reflecting a different culture. We investigated sociodemographic correlates of attitudinal barriers to mental health services in a community population in Japan, based on data collected in the World Mental Health Survey Japan surveys.

Methods: An interview survey was conducted of a random sample of residents living in 11 communities across Japan during 2002-2006.

Ras-related C3 botulinum toxin substrate 1 (RAC1) regulates glucose-stimulated insulin secretion via modulation of F-actin.

Aims/hypothesis: The small G-protein ras-related C3 botulinum toxin substrate 1 (RAC1) plays various roles in mammalian cells, such as in the regulation of cytoskeletal organisation, cell adhesion, migration and morphological changes. The present study examines the effects of RAC1 ablation on pancreatic beta cell function.

Methods: Isolated islets from pancreatic beta cell-specific Rac1-knockout (betaRac1(-/-)) mice and RAC1 knockdown INS-1 insulinoma cells treated with small interfering RNA were used to investigate insulin secretion and cytoskeletal organisation in pancreatic beta cells.

Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling.

The human multidrug and toxin extrusion (MATE) transporter 1 contributes to the tissue distribution and excretion of many drugs. Inhibition of MATE1 may result in potential drug-drug interactions (DDIs) and alterations in drug exposure and accumulation in various tissues. The primary goals of this project were to identify MATE1 inhibitors with clinical importance or in vitro utility and to elucidate the physicochemical properties that differ between MATE1 and OCT2 inhibitors.

Preservation of wild isolates of human malaria parasites in wet ice and adaptation efficacy to in vitro culture.

Wild isolates of malaria parasites were preserved in wet ice for 2-12 days and cultivated by a candle jar method. In four isolates of Plasmodium falciparum collected from Myanmar and preserved for 12 days, all failed to grow. In 31 isolates preserved for 5-10 days, nine were transformed to young gametocytes, but 22 isolates grew well.

Social capital and stigma toward people with mental illness in Tokyo, Japan.

Living in a community with high social capital might lead to lower stigma towards people with mental illness. We examined the association between social capital and stigma toward people with mental illness in the community of Tokyo, Japan. A random sample of 2,000 community residents was selected and surveyed.

Significance of ELF3 mRNA expression for detection of lymph node metastases of colorectal cancer.

Background: Lymph node (LN) evaluation is an important factor for the prognosis of colorectal cancer (CRC). The purpose of our study was to investigate the effectiveness of E74-like factor 3 (ELF3) and carcinoembryonic antigen (CEA) as useful markers to detect LN metastases in CRC.

Materials And Methods: We examined the mRNA expression of ELF3 and CEA in LNs and tissues from 22 patients with CRC and in controls with ulcerative colitis (UC) by real-time quantitative reverse transcription polymerase chain reaction, as well as by hematoxylin-eosin staining.

Association between polymorphisms in UDP-glucuronosyltransferase 1A6 and 1A7 and colorectal cancer risk.

Genetic polymorphisms of uridine diphosphate-glucuronosyltransferases 1A6 (UGT1A6) and 1A7 (UGT1A7) may lead to genetic instability and colorectal cancer carcinogenesis. Our objective was to measure the interaction between polymorphisms of these repair genes and tobacco smoking in colorectal cancer (CRC). A total of 68 individuals with CRC and 112 non-cancer controls were divided into non-smoker and smoker groups according to pack-years of smoking.

A calculation model for serum ionized calcium based on an equilibrium equation for complexation.

Measurement of ionized calcium is more important than measurement of total calcium in serum samples. In the present study, equations were derived from complexation and acid dissociation equilibrium equations, and were used to determine the concentration of ionized calcium from the observed serum concentrations of total calcium, albumin, total protein, and inorganic phosphate. The ionized calcium concentration was calculated in 67 serum samples from healthy subjects and 34 outpatients previously identified as having abnormal serum calcium levels.

DPP4 inhibitor vildagliptin preserves β-cell mass through amelioration of endoplasmic reticulum stress in C/EBPB transgenic mice.

The development of type 2 diabetes is accompanied by a progressive decline in β-cell mass and function. Vildagliptin, a dipeptidyl peptidase 4 inhibitor, is representative of a new class of antidiabetic agents that act through increasing the expression of glucagon-like peptide-1. The protective effect of this agent on β cells was studied in diabetic mice.

Diaminopyridine-based potent and selective mps1 kinase inhibitors binding to an unusual flipped-Peptide conformation.

Monopolar spindle 1 (Mps1) is an attractive cancer drug target due to the important role that it plays in centrosome duplication, the spindle assembly checkpoint, and the maintenance of chromosomal stability. A design based on JNK inhibitors with an aminopyridine scaffold and subsequent modifications identified diaminopyridine 9 with an IC50 of 37 nM. The X-ray structure of 9 revealed that the Cys604 carbonyl group of the hinge region flips to form a hydrogen bond with the aniline NH group in 9.

Scoliosis in Prader-Willi syndrome: effect of growth hormone therapy and value of paravertebral muscle volume by CT in predicting scoliosis progression.

Growth hormone (GH) therapy is now widely given to Prader-Willi syndrome (PWS) patients to encourage growth in body height and to prevent obesity. Scoliosis, one of the complications in this syndrome, is thought to be accelerated in parallel with a rapid increase in body height, especially during adolescence. To determine whether GH therapy aggravates scoliosis and to identify any factor which might predict the progression of scoliosis, we studied 35 (22 males and 13 female) PWS patients between the ages of 2-16 years on GH therapy whose scoliosis was followed with spinal X-rays every 6 months.

A case of an elderly patient with slowly progressive type 1 diabetes who developed severe nonocclusive mesenteric ischemia without predisposing events.

A 72-year-old woman with slowly progressive type 1 diabetes (SPIDDM) was admitted to our hospital because of increasing abdominal pain and diarrhea. The patient was diagnosed with nonocclusive mesenteric ischemia (NOMI), and a subtotal colonectomy was performed successfully. The resected sample revealed transmural gangrenous necrosis of the colon and rectum.

Phenotypic change of macrophages in the progression of diabetic nephropathy; sialoadhesin-positive activated macrophages are increased in diabetic kidney.

Background: Inflammatory process is involved in pathogenesis of diabetic nephropathy, although the activation and phenotypic change of macrophages in diabetic kidney has remained unclear. Sialoadhesin is a macrophage adhesion molecule containing 17 extracellular immunoglobulin-like domains, and is an I-type lectin which binds to sialic acid ligands expressed on hematopoietic cells. The aim of this study is to clarify the activation and phenotypic change of macrophages in the progression of diabetic nephropathy.

The source of the Ti 3d defect state in the band gap of rutile titania (110) surfaces.

The origin of the Ti 3d defect state seen in the band gap for reduced rutile TiO(2)(110) surfaces has been excitingly debated. The probable candidates are bridging O vacancies (V(O)) and Ti interstitials (Ti-int) condensed near the surfaces. The aim of this study is to give insights into the source of the gap state via photoelectron spectroscopy combined with ion scattering and elastic recoil detection analyses.

The mechanism of emerging catalytic activity of gold nano-clusters on rutile TiO2(110) in CO oxidation reaction.

This paper reveals the fact that the O adatoms (O(ad)) adsorbed on the 5-fold Ti rows of rutile TiO(2)(110) react with CO to form CO(2) at room temperature and the oxidation reaction is pronouncedly enhanced by Au nano-clusters deposited on the above O-rich TiO(2)(110) surfaces. The optimum activity is obtained for 2D clusters with a lateral size of ∼1.5 nm and two-atomic layer height corresponding to ∼50 Au atoms∕cluster.