Prognostic significance of WNT signaling in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies and is associated with a variety of molecular abnormalities. Although WNT signaling through its canonical/non-canonical pathways is one of the major factors involved in oncogenesis or progression of PDA, the prognostic significance of WNT signaling still remains poorly investigated. In this study, the status of the WNT signaling pathways was immunohistochemically analyzed in 101 PDAs, and its potential association with patient postoperative survival was assessed. Nuclear expression of beta-catenin, a hallmark of the activated canonical pathway, was identified in 59 cases, and was associated with reduced survival compared to the patients lacking nuclear beta-catenin expression (P?=?0.002). In contrast, activation of the non-canonical pathway (25 cases), as indicated by co-expression of WNT2/5a and nuclear NFATc1, was not correlated with reduced survival (P?=?0.268). Co-activation of both pathways (16 cases) was associated with worse prognosis in comparison with cases with an activated non-canonical pathway (P?=?0.034). In addition, nuclear beta-catenin expression was an independent unfavorable prognostic factor (P?=?0.006). Our data indicate that activated WNT signaling through its canonical pathway has a significantly negative effect on the clinical course of PDA, and the canonical WNT pathway should be considered as a future therapeutic target for PDA.     

Synthesis of a Multiblock Copolymer of cis‐1,4‐Polybutadiene and Poly(3‐buten‐1‐ol)

Synthesis of a multiblock copolymer composed of cis‐1,4‐polybutadiene (PBd) segments and poly(3‐buten‐1‐ol) segments is performed via successive hydroboration and oxidation of cis‐1,4/syn‐1,2‐multiblock PBd. The ratio of functionalization can be controlled by changing the amount of the borane reagent. The obtained polymer shows two distinctive glass‐transition temperatures, which correspond to the cis‐1,4‐PBd block and the poly(3‐buten‐1‐ol) block. These thermal properties clearly show that the functionalization of the PBd proceeds keeping the elastic property derived from cis‐1,4 segment.

     

Icteric acute hepatitis E with no response of immunoglobulin M class anti‐hepatitis E virus antibody

A 68‐year‐old Japanese man developed icteric acute hepatitis during periodic care after undergoing gastrectomy due to early gastric cancer. The routine serological markers for hepatitis A, B and C viruses were all negative. Although the liver enzymes spontaneously recovered without any specific therapy, cholestasis was relatively prolonged and successfully treated with prednisolone. Determination of serum hepatitis E virus (HEV) RNA revealed the transient infection of HEV, and both immunoglobulin (Ig)A and IgG class anti‐HEV antibodies were detected after the disease onset, whereas those were negative when measured 3 weeks prior to the onset. In addition, the titer of serum IgA class antibody was associated with the clinical signs of hepatitis. In contrast, no IgM class antibody was detected throughout the course. This case suggests that screening only with IgM class antibody is not sufficient to detect acute HEV infection.     

Insecticide resistance in potential vector mosquitoes for West Nile virus in Japan

Culex pipiens complex is the significant vector mosquito of West Nile virus. To take stock of the current situation of insecticide susceptibilities and design an ideal mosquito control strategy, we collected Culex pipiens pallens Coquillet, Culex pipiens form molestus Forskal, and Culex quinquefasciatus Say from fields in Japan and conducted bioassays for five larvicides (fenitrothion, temephos, etofenprox, diflubenzuron, and pyriproxyfen) by using a larval dipping method. Among five insecticides tested, obvious reduced susceptibilities were observed for etofenprox, which is the only pyrethroid compound registered as a larvicide in Japan. Twenty-two of 56 colonies exhibited a >10% survival rate at the etofenprox concentration of 5.7 microg/ml, which is a 10 times higher concentration of the working solution. The LC50 of a colony collected from Fukuoka prefecture for etofenprox exceeded 60 microg/ml (resistance ratio >2,307), and this colony also exhibited cross-resistance to other pyrethroids, permethrin (299-fold) and phenothrin (1,200-fold). The insect growth regulators diflubenzuron and pyriproxyfen were found to be sufficiently effective enough to control Culex larvae present, but decreased sensitivities to these insecticides were slightly detected in some colonies of Cx. p. form molestus collected from urban areas. Several etofenprox-resistant colonies of Cx. p. form molestus exhibited simultaneously decreased susceptibilities to other insecticides, including temephos, diflubenzuron, and pyriproxyfen.     

Selective pulmonary vasodilatory effect of ZSY-27 in dogs with pulmonary hypertension due to pulmonary embolism

The pulmonary vasodilator effect of ZSY-27, a newly synthesized phosphodiesterase inhibitor, was studied in dogs with pulmonary hypertension resulting from autologous muscle-induced pulmonary embolism (PE). A bolus injection of ZSY-27 (1 mg/kg) significantly decreased mean pulmonary arterial pressure from 32 +/- 4 to 24 +/- 5 mm Hg and pulmonary vascular resistance index from 415 +/- 60 to 316 +/- 94 dyne.sec/cm5.m2. ZSY-27 did not change mean arterial pressure. The cardiac index was slightly increased and the systemic vascular resistance index was slightly decreased after ZSY-27 injection, but these changes were not statistically significant. This study suggests that ZSY-27 is a possible therapeutic agent for pulmonary hypertension secondary to PE.     

Reduced Frontal Glutamate + Glutamine and N-Acetylaspartate Levels in Patients With Chronic Schizophrenia but not in Those at Clinical High Risk for Psychosis or With First-Episode Schizophrenia

Changes in brain pathology as schizophrenia progresses have been repeatedly suggested by previous studies. Meta-analyses of previous proton magnetic resonance spectroscopy (¹H MRS) studies at each clinical stage of schizophrenia indicate that the abnormalities of N-acetylaspartate (NAA) and glutamatergic metabolites change progressively. However, to our knowledge, no single study has addressed the possible differences in ¹H MRS abnormalities in subjects at 3 different stages of disease, including those at ultrahigh risk for psychosis (UHR), with first-episode schizophrenia (FES), and with chronic schizophrenia (ChSz). In the current study, 24 patients with UHR, 19 FES, 25 ChSz, and their demographically matched 3 independent control groups (n = 26/19/28 for the UHR, FES, and ChSz control groups, respectively) underwent ¹H MRS in a 3-Tesla scanner to examine metabolites in medial prefrontal cortex. The analysis revealed significant decreases in the medial prefrontal NAA and glutamate + glutamine (Glx) levels, specifically in the ChSz group as indexed by a significant interaction between stage (UHR/FES/ChSz) and clinical status (patients/controls) (P = .008). Furthermore, the specificity of NAA and Glx reductions compared with the other metabolites in the patients with ChSz was also supported by a significant interaction between the clinical status and types of metabolites that only occurred at the ChSz stage (P = .001 for NAA, P = .004 for Glx). The present study demonstrates significant differences in ¹H MRS abnormalities at different stages of schizophrenia, which potentially correspond to changes in glutamatergic neurotransmission, plasticity, and/or excitotoxicity and regional neuronal integrity with relevance for the progression of schizophrenia.Key words: anterior cingulate cortex, at-risk mental state, biomarkers, frontal lobe, magnetic resonance imaging, neurochemical abnormality     

Comparative effects of topiroxostat and febuxostat on arterial properties in hypertensive patients with hyperuricemia

Elevated serum uric acid is a cardiovascular risk factor in patients with hypertension, even when blood pressure (BP) is well controlled. Xanthine oxidoreductase inhibitors (XORi) reduce serum uric acid levels and have several other potential effects. This multicenter, randomized, open‐label study compared the effects of two XORi, topiroxostat and febuxostat, on arterial stiffness, uric acid levels, and BP in hypertensive patients with hyperuricemia. Patients received topiroxostat 40–160 mg/day or febuxostat 10–60 mg/day, titrated to maintain serum uric acid <6 mg/dl, for 24 weeks. The primary endpoint was change in the cardio‐ankle vascular index (CAVI) from baseline to 24 weeks. There were no significant changes in CAVI from baseline to 24 weeks (from 9.13 to 9.16 [feboxustat] and 8.98 to 9.01 [topiroxostat]). Compared with baseline, there were significant reductions in serum uric acid (–2.9 and –2.5 mg/dl; both p < 0.001) and morning home systolic BP (–3.6 and –5.1 mm Hg; both p < 0.01) after 24 weeks'' treatment with febuxostat and topiroxostat. BP decreased to the greatest extent in the subgroup of patients with uncontrolled blood pressure at baseline. Topiroxostat, but not febuxostat, significantly decreased plasma xanthine oxidoreductase activity versus baseline. The urinary albumin‐creatinine ratio (UACR) decreased significantly from baseline to 24 weeks with topiroxostat (–20.8%; p = 0.021), but not febuxostat (–8.8%; p = 0.362). In conclusion, neither topiroxostat nor febuxostat had any significant effects on arterial stiffness over 24 weeks'' treatment.     

Amino acid metabolism in parenteral nutrition: With special reference to the calorie: Nitrogen ratio and the blood urea nitrogen level

A clinical and experimental study was made on amino acid metabolism during parenteral nutrition with glucose and a synthetic amino acid solution. Good correlation was noted between the calorie: nitrogen ratio of the infusate and the blood urea nitrogen level, as well as between the calorie: nitrogen ratio and the amount of urinary excretion of urea nitrogen, nonprotein nitrogen, and amino nitrogen. Final results revealed that the extent to which amino acid is utilized for protein synthesis is directly proportional to the caloric supply, and for complete utilization of 1 g of nitrogen the required caloric intake is in the neighborhood of 450 total calories or 425 nonprotein calories. Blood urea nitrogen level can be used as a parameter of amino acid utilization during parenteral nutrition. Its level is influenced not only by renal function but also by calorie: nitrogen ratio of infusate.