Effect of branched-chain amino acid supplementation on the oxidized/reduced state of plasma albumin in rats with chronic liver disease

We examined whether continuous supplementation with branched-chain amino acids phosphorylates ribosomal protein S6, a downstream effector of mammalian target of rapamycin, and improves hypoalbuminemia of rats with chronic liver disease. Sprague-Dawley rats were fed a casein diet (control group) or a branched-chain amino acid-supplemented casein diet (branched-chain amino acid group) for 11 weeks with repeated injections of carbon tetrachloride. Throughout this experimental period, no significant difference in plasma albumin concentration was seen between groups. The percentage of reduced albumin within total plasma albumin gradually decreased in both control and branched-chain amino acid groups. After 11 weeks with supplementation, phosphorylation of ribosomal protein S6 was significantly increased in the liver of rats in the branched-chain amino acid group compared with the control group. Furthermore, the percentage of reduced albumin within total albumin was significantly higher in the branched-chain amino acid group than in the control group. These results indicate that continuous supplementation with branched-chain amino acids in rats with chronic liver disease induces phosphorylation of hepatic ribosomal protein S6 and attenuates decreases in the percentage of reduced albumin, although levels of plasma albumin are not increased

Simultaneous ground and satellite observations of an isolated proton arc at subauroral latitudes

We observed an isolated proton arc at the Athabasca station MLAT: 62◦N) in Canada on 5 September, 2005, using a ground-based allsky imager at wavelengths of 557.7 nm, 630.0 nm, and 486.1 nm (Hβ). This arc is similar to the detached proton arc observed recently by the IMAGE satellite [Immel et al., 2002]. The arc appeared at 0500-0700 UT (2100-2300 MLT) coincident with strong Pc 1 geomagnetic pulsations in the frequency range of the electromagnetic ion cyclotron (EMIC) wave. A small substorm took place at 0550 UT, while the isolated arc did not change its structure and intensity before and after the substorm onset. From particle data obtained by the NOAA 17 satellite, we found that the isolated arc was located in the localized (L ∼4) enhancement of ion precipitation fluxes at an energy range of 30-80 keV. Trapped ion flux enhancements (ring current ions) were also observed at two latitudinally separated regions. The localized ion precipitation was located at the outer boundary of the inner ring current ions. The DMSP F13 satellite observed signatures of ionospheric plasma trough near the conjugate point of the arc in the southern hemisphere. The trough is considered to be connected to the plasmapause. These results indicate that the source region of the isolated arc was located near the plasmapause and in the ring current. We conclude that the observed isolated proton arc at subauroral latitudes were driven by the EMIC waves, which were generated near the plasmapause and scattered the ring current protons resonantly into the loss cone

Histological Study of the Left Atrial Wall: A Consideration of the Compound Myocardial Architecture and Potential Durability with Respect to Catheter Ablation in Pulmonary Vein Isolation Procedures

Pulmonary vein isolation using radiofrequency energy is performed extensively to treat symptomatic, drug-refractory atrial fibrillation. However, anatomical knowledge of the left atrial wall surrounding the pulmonary vein (PV) openings is insufficient to create an ablation line. Using autopsy hearts from 23 individuals (median age of 63 years), we studied the histological nature of anatomical obstacles or related isthmuses near the PV openings. None of the individuals had a history of tachyarrhythmia or other major cardiac abnormalities. After macroscopic measurement of the minimum width of each isthmus, the following areas were excised and histologically prepared: atrial roof-mitral valve annulus (MVA), left superior pulmonary vein (LSPV) -left atrial appendage (LAA), LAA-MVA, left inferior pulmonary vein (LIPV) -MVA, right superior pulmonary vein (RSPV) -fossa ovalis (FO), right inferior pulmonary vein (RIPV) -FO, and FO-MVA. Within the obstacles near the PV openings, the LSPV-LAA isthmus was found to be the narrowest, whereas the LIPV-MVA was the widest and thickest isthmus. Histological complexity of each isthmus was determined, and the compound architecture of the myocardium was revealed. The further presence of a variety of nerve endings as well as myocardial blood supply enhanced the tissue diversity. Such an insight into the diversity of myocardial architecture or histological complexity in each isthmus might be helpful in creating a reliable ablation line in pulmonary vein isolation procedures

内側視索前野を中心とした養育行動の神経内分泌学的基盤に関わる研究の動向

Maternal behaviors are defined as adult behavior directed to offspring to provide necessary conditions, such as nutrition, thermoregulation, and cleanness, for their survival. Since postpartum females in mice and rats show higher frequency and duration of maternal behaviors compared to virgin females, it is hypothesized that changes in neuronal circuitry induced by the fluctuation of gonadal steroid hormones during gestation and parturition may be involved in the induction of the behavior. The medial preoptic area (MPOA) of the hypothalamus plays a central role in the regulation of maternal behavior. Gonadal steroid hormones facilitate the expression of maternal behavior by binding to their receptors expressed in the MPOA. In this review, we will first overview recent findings, with the use of recently developed techniques, on properties of the MPOA neurons activated during maternal behavior. We then discuss possible interaction of the MPOA with other brain systems, such as dopaminergic and oxytocinergic, in the regulation of maternal behavior

Detailed analyses of the crucial functions of Zn transporter proteins in alkaline phosphatase activation

Numerous zinc ectoenzymes are metalated by zinc and activated in the compartments of the early secretory pathway before reaching their destination. Zn transporter (ZNT) proteins located in these compartments are essential for ectoenzyme activation. We have previously reported that ZNT proteins, specifically ZNT5-ZNT6 heterodimers and ZNT7 homodimers, play critical roles in the activation of zinc ectoenzymes, such as alkaline phosphatases (ALPs), by mobilizing cytosolic zinc into these compartments. However, this process remains incompletely understood. Here, using genetically-engineered chicken DT40 cells, we first determined that Zrt/Irt-like protein (ZIP) transporters that are localized to the compartments of the early secretory pathway play only a minor role in the ALP activation process. These transporters included ZIP7, ZIP9, and ZIP13, performing pivotal functions in maintaining cellular homeostasis by effluxing zinc out of the compartments. Next, using purified ALP proteins, we showed that zinc metalation on ALP produced in DT40 cells lacking ZNT5-ZNT6 heterodimers and ZNT7 homodimers is impaired. Finally, by genetically disrupting both ZNT5 and ZNT7 in human HAP1 cells, we directly demonstrated that the tissue-nonspecific ALP-activating functions of both ZNT complexes are conserved in human cells. Furthermore, using mutant HAP1 cells, we uncovered a previously-unrecognized and unique spatial regulation of ZNT5-ZNT6 heterodimer formation, wherein ZNT5 recruits ZNT6 to the Golgi apparatus to form the heterodimeric complex. These findings fill in major gaps in our understanding of the molecular mechanisms underlying zinc ectoenzyme activation in the compartments of the early secretory pathway

Fish oil-enriched nutrition combined with systemic chemotherapy for gastrointestinal cancer patients with cancer cachexia

Despite recent advances in chemotherapy for gastrointestinal cancer, a crucial factor related to poor prognosis is reduced tolerance to chemotherapy induced by cancer cachexia. Fish oil (FO)-derived eicosapentaenoic acid (EPA) modulates inflammation in patients with various malignancies; however, the impact of FO-enriched nutrition as a combined modality therapy on clinical outcomes remains controversial. We systemically analysed chronological changes in biochemical and physiological status using bioelectrical impedance analysis in 128 gastrointestinal cancer patients provided with or without FO-enriched nutrition during chemotherapy. Furthermore, we evaluated the clinical significance of FO-enriched nutrition and clarified appropriate patient groups that receive prognostic benefits from FO-enriched nutrition during treatment of gastrointestinal cancer. The control group showed significant up-regulation of serum CRP) levels and no significant difference in both skeletal muscle mass and lean body mass. In contrast, the FO-enriched nutrition group showed no changes in serum CRP concentration and significantly increased skeletal muscle mass and lean body mass over time. Furthermore, high CRP levels significantly correlated with reduced tolerance to chemotherapy, and FO-enriched nutrition improved chemotherapy tolerance and prognosis, particularly in gastrointestinal cancer patients with a modified Glasgow prognostic score (mGPS) of 1 or 2. We conclude that FO-enriched nutrition may improve the prognosis of patients with cancer cachexia and systemic inflammation (i.e., those with a mGPS of 1 or 2)

Earthquakes: from chemical alteration to mechanical rupture

In the standard rebound theory of earthquakes, elastic deformation energy is progressively stored in the crust until a threshold is reached at which it is suddenly released in an earthquake. We review three important paradoxes, the strain paradox, the stress paradox and the heat flow paradox, that are difficult to account for in this picture, either individually or when taken together. Resolutions of these paradoxes usually call for additional assumptions on the nature of the rupture process (such as novel modes of deformations and ruptures) prior to and/or during an earthquake, on the nature of the fault and on the effect of trapped fluids within the crust at seismogenic depths. We review the evidence for the essential importance of water and its interaction with the modes of deformations. Water is usually seen to have mainly the mechanical effect of decreasing the normal lithostatic stress in the fault core on one hand and to weaken rock materials via hydrolytic weakening and stress corrosion on the other hand. We also review the evidences that water plays a major role in the alteration of minerals subjected to finite strains into other structures in out-of-equilibrium conditions. This suggests novel exciting routes to understand what is an earthquake, that requires to develop a truly multidisciplinary approach involving mineral chemistry, geology, rupture mechanics and statistical physics.Comment: 44 pages, 1 figures, submitted to Physics Report

Cytokine-Based Log-Scale Expansion of Functional Murine Dendritic Cells

BACKGROUND: Limitations of the clinical efficacy of dendritic cell (DC)-based immunotherapy, as well as difficulties in their industrial production, are largely related to the limited number of autologous DCs from each patient. We here established a possible breakthrough, a simple and cytokine-based culture method to realize a log-scale order of functional murine DCs (>1,000-fold), which cells were used as a model before moving to human studies. METHODOLOGY/PRINCIPAL FINDINGS: Floating cultivation of lineage-negative hematopoietic progenitors from bone marrow in an optimized cytokine cocktail (FLT3-L, IL-3, IL-6, and SCF) led to a stable log-scale proliferation of these cells, and a subsequent differentiation study using IL-4/GM-CSF revealed that 3-weeks of expansion was optimal to produce CD11b+/CD11c+ DC-like cells. The expanded DCs had typical features of conventional myeloid DCs in vitro and in vivo, including identical efficacy as tumor vaccines. CONCLUSIONS/SIGNIFICANCE: The concept of DC expansion should make a significant contribution to the progress of DC-based immunotherapy

Anticancer drug clustering in lung cancer based on gene expression profiles and sensitivity database

BACKGROUND: The effect of current therapies in improving the survival of lung cancer patients remains far from satisfactory. It is consequently desirable to find more appropriate therapeutic opportunities based on informed insights. A molecular pharmacological analysis was undertaken to design an improved chemotherapeutic strategy for advanced lung cancer. METHODS: We related the cytotoxic activity of each of commonly used anti-cancer agents (docetaxel, paclitaxel, gemcitabine, vinorelbine, 5-FU, SN38, cisplatin (CDDP), and carboplatin (CBDCA)) to corresponding expression pattern in each of the cell lines using a modified NCI program. RESULTS: We performed gene expression analysis in lung cancer cell lines using cDNA filter and high-density oligonucleotide arrays. We also examined the sensitivity of these cell lines to these drugs via MTT assay. To obtain our reproducible gene-drug sensitivity correlation data, we separately analyzed two sets of lung cancer cell lines, namely 10 and 19. In our gene-drug correlation analyses, gemcitabine consistently belonged to an isolated cluster in a reproducible fashion. On the other hand, docetaxel, paclitaxel, 5-FU, SN-38, CBDCA and CDDP were gathered together into one large cluster. CONCLUSION: These results suggest that chemotherapy regimens including gemcitabine should be evaluated in second-line chemotherapy in cases where the first-line chemotherapy did not include this drug. Gene expression-drug sensitivity correlations, as provided by the NCI program, may yield improved therapeutic options for treatment of specific tumor types

Genetic Mapping of Social Interaction Behavior in B6/MSM Consomic Mouse Strains

Genetic studies are indispensable for understanding the mechanisms by which individuals develop differences in social behavior. We report genetic mapping of social interaction behavior using inter-subspecific consomic strains established from MSM/Ms (MSM) and C57BL/6J (B6) mice. Two animals of the same strain and sex, aged 10 weeks, were introduced into a novel open-field for 10 min. Social contact was detected by an automated system when the distance between the centers of the two animals became less than ~12 cm. In addition, detailed behavioral observations were made of the males. The wild-derived mouse strain MSM showed significantly longer social contact as compared to B6. Analysis of the consomic panel identified two chromosomes (Chr 6 and Chr 17) with quantitative trait loci (QTL) responsible for lengthened social contact in MSM mice and two chromosomes (Chr 9 and Chr X) with QTL that inhibited social contact. Detailed behavioral analysis of males identified four additional chromosomes associated with social interaction behavior. B6 mice that contained Chr 13 from MSM showed more genital grooming and following than the parental B6 strain, whereas the presence of Chr 8 and Chr 12 from MSM resulted in a reduction of those behaviors. Longer social sniffing was observed in Chr 4 consomic strain than in B6 mice. Although the frequency was low, aggressive behavior was observed in a few pairs from consomic strains for Chrs 4, 13, 15 and 17, as well as from MSM. The social interaction test has been used as a model to measure anxiety, but genetic correlation analysis suggested that social interaction involves different aspects of anxiety than are measured by open-field test