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Norihiro Sakai,1,* Kenya Kamimura,1,* Yoko Shinagawa-Kobayashi,1 Takuro Nagoya,1 Yusuke Niwa,1 Masayoshi Ko,1 Toru Setsu,1 Akira Sakamaki,1 Takeshi Yokoo,1 Satoshi Abe,1 Hiroteru Kamimura,1 Soichi Sugitani,2 Masahiko Yanagi,3 Shuji Terai11Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan; 2Department of Gastroenterology, Murakami General Hospital, Murakami, Niigata, Japan; 3Department of Gastroenterology, Ojiya General Hospital, Ojiya, Niigata, Japan*These authors contributed equally to this workBackground: Sorafenib (SOR) is an anti-angiogenic chemotherapeutic that prolongs the survival rates of patients with hepatocellular carcinoma. However, SOR also damages normal vasculature and causes associated adverse events, including hand–foot syndrome and hypertension (HT). We previously reported in an animal study that vascular damage resulted in the narrowing of the normal vascular dimension area in medaka fish (Oryzias), and histidine (HIS), a major amino acid contained in dried bonito broth (DBB), prevented these changes. Therefore, in the study, we analyzed the effects of DBB and HIS on SOR-related vascular damages and associated adverse events in patients.Materials and methods: Three-dimensional (3D) vascular images of abdominal regions reconstituted from computed tomography were assessed to compare vascular diameter prior to and following SOR administration in groups receiving SOR monotherapy, DBB+SOR, and HIS+SOR. The clinical courses of hand–foot syndrome and HT and the toxicities of SOR in biochemical assays were monitored and compared between the groups. Correlations between hepatic function and SOR-related changes in the portal venous area dimension were also assessed.Results: SOR-related vascular damage revealed narrowing of the normal abdominal vasculature in the human body, which was monitored using 3D images. The damage was ameliorated by DBB and HIS, however, HIS had a more marked effect, particularly on the renal arteries and portal vein (PV). Maintenance of blood flow contributed to the maintenance of total cholesterol, prothrombin time, albumin (ALB), and renal functions. Changes in the 3D vascular area dimension of the PV and level of serum ALB were significantly correlated. The occurrences of the clinical symptoms of hand–foot syndrome and HT were lower in the DBB- and HIS-treated groups.Conclusion: Our results clearly demonstrate that DBB and HIS prevented SOR-related abdominal vascular damage and effectively maintained hepatic function, and prevented clinical symptoms and toxicity.Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000025937 and UMIN000026898).Keywords: sorafenib, histidine, dried bonito broth, vascular area dimension, albumin, hepatocellular carcinoma

Takamasa Kobayashi, Hirokazu Kawai, Oki Nakano, Satoshi Abe, Hiroteru Kamimura, Akira Sakamaki, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Satoshi Yamagiwa,† Shuji Terai Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan †Dr Satoshi Yamagiwa passed away on May 4, 2018 Background: Prognosis of patients with hepatocellular carcinoma (HCC) who undergo transcatheter intra-arterial therapies, including transcatheter arterial chemoembolization and transcatheter arterial infusion chemotherapy, is affected by many clinical factors including liver function and tumor progression. However, the effect of body composition such as skeletal muscle and visceral and subcutaneous adipose tissues (VAT and SAT, respectively) on the prognosis of these patients remains unclear. We investigated the prognostic value of body composition in HCC patients treated with transcatheter intra-arterial therapies. Patients and methods: This study retrospectively evaluated 100 HCC patients treated with transcatheter intra-arterial therapies between 2005 and 2015. Areas of skeletal muscle, VAT, and SAT were measured on computed tomography images at third lumbar vertebra level and normalized by the height squared to calculate the skeletal muscle index, VAT index, and SAT index (SATI). The visceral to subcutaneous adipose tissue area ratio was also calculated. Overall survival (OS) was compared between high- and low-index groups for each body composition. Furthermore, prognostic significance was assessed by univariate and multivariate analyses using Cox proportional hazards models. Results: Among the body composition indexes, only SATI could significantly differentiate OS (p=0.012). Multivariate analysis showed that SATI (low- vs. high-SATI: HR, 2.065; 95% CI, 1.187–3.593; p=0.010), serum albumin (

Kenya Kamimura,1 Yoko Shinagawa-Kobayashi,1 Ryo Goto,1 Kohei Ogawa,1 Takeshi Yokoo,1 Akira Sakamaki,1 Satoshi Abe,1 Hiroteru Kamimura,1 Takeshi Suda,2 Hiroshi Baba,3 Takayuki Tanaka,4 Yoshizu Nozawa,5 Naoto Koyama,6 Masaaki Takamura,1 Hirokazu Kawai,1 Satoshi Yamagiwa,1 Yutaka Aoyagi,1 Shuji Terai1 1Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan; 2Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata Medical and Dental Hospital, Minami-Uonuma, Niigata, Japan; 3Division of Anesthesiology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan; 4Uonuma Eye Clinic, Uonuma, Niigata, Japan; 5Institute of Food Sciences and Technologies, Ajinomoto Co., Inc., Kawasaki, Kanagawa, Japan; 6Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Kanagawa, Japan Background: Sorafenib (SOR) is a molecular medicine that prolongs the survival of patients with hepatocellular carcinoma (HCC). Therefore, the management of side effects is essential for the longer period of continuous medication. Among the various side effects, hand–foot syndrome (HFS) is the most common, occurring in 30%–50% of patients, and often results in discontinuation of the SOR medication. However, its mechanism has not been clarified, and no effective prevention method has been reported for the symptoms. Therefore, this study aimed to analyze its mechanism and to develop an effective prevention regimen for the symptoms. Materials and methods: To assess the mechanism of SOR-induced HFS, the peripheral blood flow in the hand and foot was carefully monitored by Doppler ultrasound, thermography, and laser speckle flowgraphy in the cases treated with SOR and its contribution was assessed. Then, the effect of dried-bonito broth (DBB), which was reported to improve peripheral blood flow, on the prevention of the symptom was examined by monitoring its occurrence and the peripheral blood flow. Results: A total of 25 patients were enrolled in this study. In all, eight patients developed HFS, and all cases showed a significant decrease in the peripheral blood flow. DBB contributed to an increase in the flow (p = 0.009) and significantly decreased occurrence of HFS (p = 0.005) than control. Multivariable analysis showed that the ingestion of DBB is a significant independent contributor to HFS-free survival period (p = 0.035). Conclusion: The mechanism of SOR-induced HFS involves a decrease in the peripheral blood flow, and the ingestion of DBB effectively prevents the development of the syndrome by maintaining the flow. Keywords: sorafenib, hepatocellular carcinoma, hand–foot syndrome, blood flow, bonito broth

Liver Cirrhosis is the end stage of chronic liver disease which may happen due to alcoholism, viral infections due to Hepatitis B, Hepatitis C viruses and is difficult to treat. Liver transplantation is the only available definitive treatment which is marred by lack of donors, post operative complications such as rejection and high cost. Autologous bone marrow stem cells have shown a lot of promise in earlier reported animal studies and clinical trials. We have in this study administered in 22 patients with chronic liver disease, autologous bone marrow stem cell whose results are presented herewith.

We performed a whole genome QTL analysis to confirm the existence of QTL affecting fatty acid composition and to investigate the effects of additive, dominance, imprinting, and epistatic interactions between QTL in an [F.sub.2] resource population. The [F.sub.2] population, comprising 166 pigs, was obtained by crossing a Duroc boar and a Meishan sow. The [F.sub.2] population was measured for fatty acid composition and was used for whole genome QTL analysis, using a total of 180 microsatellite markers. The suggestive and significant thresholds were equivalent to likelihood ratio test statistics (LRT) of 13.7 and 20.5, respectively. For single QTL analysis, 2 suggestive QTL and 1 significant QTL were detected. Suggestive QTL for C14:0 and C16:1 were identified on chromosomes 12 and 7, respectively, and a significant QTL for C18:2 was detected on chromosome 5 with the greatest LRT of 22.9. For C14:0, a significant QTL with paternal imprinting effect was also detected on chromosome 12, where the locus was in the same region as an additive QTL effect, with a large LRT of 24.2. The suggestive QTL on chromosome 7 was not significant when correction for backfat thickness was included. For epistatic QTL analysis, a total of 5 epistatic pairs were located on chromosomes 4, 5, 9, and 16. The same epistatic pairs were significant when correction for backfat thickness was included. The individual QTL identified in the single QTL analysis and in the epistatic QTL analysis were not the same loci, except for C18:2. For C14:0, an epistatic QTL pair was detected on chromosome 16, with the least P-value of 4.9 x [10.sup.-12]. The present study constitutes one of the first reports on the mapping of imprinted QTL and epistatic pairs of QTL affecting fatty acid composition in a swine population. Key words: epistatic interaction, fatty acid composition, quantitative trait locus, swine doi: 10.2527/jas.2009-1917

We constructed a pig F2 resource population by crossing a Meishan sow and a Duroc boar to locate economically important trait loci. The F2 generation was composed of 865 animals (450 males and 415 females) from four F1 males and 24 F1 females and was genotyped for 180 informative microsatellite markers spanning 2,263.6 cM of the whole pig genome. Results of the genome scan showed evidence for significant quantitative trait loci ( Key Words: Growth, Linkage Analysis, Meat Quality, Pigs, Quantitative Trait Loci

The design, construction and characterization of a superconducting magnet built for superconducting magnetic energy storage are presented. The magnet, which consists of 18 double-pancake type coils, has a pulse-discharge speed of 10T/s and a transport current of 350 A. It has also undergone charge-discharge tests and forced-deenergizing tests to quantify its insulation, cooling, mechanical strenth and quench properties.

Background Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a commonly occurring condition related to systemic autoimmune disease. It is characterized histopathologically by a distinct pattern of granulomatous inflammation in the presence or absence of leukocytoclastic vasculitis. The properties of granulomatous cells in PNGD are still uncertain. Objective We sought further investigation on the phenotype of the infiltrated cells in PNGD from two patients with systemic lupus erythematosus (SLE) and reviewed the previous published reports in order to provide a comprehensive summary on the clinical features of PNGD in SLE. Methods The immunohistochemical features of granulomatous cells in PNGD associated with SLE were analyzed. Immunohistochemical studies were performed on sections from our two cases using antibodies against CD68, CD163, CD15, Factor XIIIa, myeloperoxidase and neutrophil elastase. The clinical characteristics of the SLE patients who developed PNGD were also evaluated. We included all cases retrieved through a PubMed search with the key words PNGD and SLE. Results Cutaneous lesions consisted of erythematous plaques distributed on the face and upper limbs in both cases. The infiltrated cells were mainly positive for CD68 and CD163, a phenotype suggestive of M2 macrophages. Some mature neutrophils and lymphocytes were also present. A review of the literature of PNGD associated with SLE revealed a predominance in females, high prevalence of lupus nephritis and a good response to systemic steroids, with frequent skin lesions relapses during tapering of the treatment. Limitations This study examined only two cases; the pathogenesis of the disease remains to be clarified. Conclusion PNGD lesions were abundantly infiltrated by M2 macrophages, suggesting that they may have a role in this condition. SLE accompanied by PNGD might be associated with lupus nephritis and frequent relapses of skin lesions. [ABSTRACT FROM AUTHOR]