A New Disorder in UV-Induced Skin Cancer with Defective DNA Repair Distinct from Xeroderma Pigmentosum or Cockayne Syndrome

We report the characterization of a Japanese woman who exhibited many freckles and skin cancers in sun-exposed areas, but displayed no photosensitivity. Fibroblasts (KPSX7) derived from this patient showed similar UV sensitivity to that of normal human fibroblasts. The KPSX7 cells showed normal levels of unscheduled DNA synthesis, recovery of RNA synthesis, recovery of replicative DNA synthesis, protein-binding ability to UV-damaged DNA, and post-translational modification of xeroderma pigmentosum (XP) C. These results indicate that the patient had neither XP nor Cockayne syndrome. Although these results suggest that the KPSX7 cells were proficient in nucleotide excision repair activity, host-cell reactivation (HCR) activity of KPSX7 cells was reduced. Furthermore, introduction of UV damage endonuclease into the cells restored repair activity in the HCR assay to almost normal levels. These results indicate that KPSX7 cells are defective for some types of repair activity in UV-damaged DNA. In summary, the patient had a previously unknown disorder related to UV-induced carcinogenesis, with defective DNA repair

Regulatory Mechanism of Skeletal Muscle Glucose Transport by Phenolic Acids

Type 2 diabetes mellitus (T2DM) is one of the most severe public health problems in the world. In recent years, evidences show a commonness of utilization of alternative medicines such as phytomedicine for the treatment of T2DM. Phenolic acids are the most common compounds in non-flavonoid group of phenolic compounds and have been suggested to have a potential to lower the risk of T2DM. Skeletal muscle is the major organ that contributes to the pathophysiology of T2DM. Studies have shown that several phenolic acids (caffeic acid, chlorogenic acid, gallic acid, salicylic acid, p-coumaric acid, ferulic acid, sinapic acid) have antidiabetic effects, and these compounds have been implicated in the regulation of skeletal muscle glucose metabolism, especially glucose transport. Glucose transport is a major regulatory step for whole-body glucose disposal, and the glucose transport processes are regulated mainly through two different systems: insulin-dependent and insulin-independent mechanism. In this chapter, we reviewed recent experimental evidences linking phenolic acids to glucose metabolism focusing on insulin-dependent and insulin-independent glucose transport systems and the upstream signaling events in skeletal muscle

Laparoscopic Hepatectomy: Current State in Japan Based on the 4th Nationwide Questionnaire

Purpose. Since laparoscopic hepatectomy (LH) became covered by national health insurance in April 2010 in Japan, the numbers of applied cases and institutions performing it have increased and the indication has expanded. We surveyed the current state and safety of LH in Japan. Methods. A questionnaire survey was performed in 41 institutions related to the Japanese Endoscopic Liver Surgery Study Group and 747 institutions certified by the Japanese Society of Gastroenterological Surgery, and responses concerning all 2962 cases of LH performed by August 2011 were obtained. Results. The surgical procedure employed was hemihepatectomy in 234 (8%), segmentectomy in 88 (3%), left lateral segmentectomy in 434 (15%), segmentectomy in 156 (5%), and partial resection in 1504 (51%) cases. The approach was pure laparoscopy in 1835 (63%), hand-assisted laparoscopic surgery in 201 (7%), and laparoscopy-assisted surgery in 926 (31%). Regarding perioperative complications, surgery was switched to laparotomy in 59 (2.0%), reoperation was performed in 4 (0.1%), and surgery-related death occurred in 2 (0.07%). Intraoperative accidents occurred in 68 (2.3%), and postoperative complications developed in 94 (3.2%). Conclusions. When the selection of cases is appropriate, LH for liver diseases can be safely performed

Caffeine modulates phosphorylation of insulin receptor substrate-1 and impairs insulin signal transduction in rat skeletal muscle

Caffeine decreases insulin sensitivity and insulin-stimulated glucose transport in skeletal muscle; however, the precise mechanism responsible for this deleterious effect is not understood fully. We investigated the effects of incubation with caffeine on insulin signaling in rat epitrochlearis muscle. Caffeine (≥1 mM, ≥15 min) suppressed insulin-stimulated insulin receptor substrate (IRS)-1 Tyr[612] phosphorylation in a dose- and time-dependent manner. These responses were associated with inhibition of the insulin-stimulated phosphorylation of phosphatidylinositol 3-kinase (PI3K) Tyr[458], Akt Ser[473], and glycogen synthase kinase-3β Ser9 and with inhibition of insulin-stimulated 3-O-methyl-D-glucose (3MG) transport but not with inhibition of the phosphorylation of insulin receptor-β Tyr[1158/62/63]. Furthermore, caffeine enhanced phosphorylation of IRS-1 Ser[307] and an IRS-1 Ser307 kinase, inhibitor-κB kinase (IKK)-α/β Ser[176/180]. Blockade of IKK/IRS-1 Ser[307] by caffeic acid ameliorated the caffeine-induced downregulation of IRS-1 Tyr[612]phosphorylation and 3MG transport. Caffeine also increased the phosphorylation of IRS-1 Ser789 and an IRS-1 Ser[789] kinase, 5′-AMP-activated protein kinase (AMPK). However, inhibition of IRS-1 Ser[789] and AMPK phosphorylation by dantrolene did not rescue the caffeine-induced downregulation of IRS-1 Tyr612 phosphorylation or 3MG transport. In addition, caffeine suppressed the phosphorylation of insulin-stimulated IRS-1 Ser[636/639] and upstream kinases, including the mammalian target of rapamycin and p70S6 kinase. Intravenous injection of caffeine at a physiological dose (5 mg/kg) in rats inhibited the phosphorylation of insulin-stimulated IRS-1 Tyr[612] and Akt Ser[473] in epitrochlearis muscle. Our results indicate that caffeine inhibits insulin signaling partly through the IKK/IRS-1 Ser[307] pathway, via a Ca[2+]- and AMPK-independent mechanism in skeletal muscle

SNP- and haplotype-based genome-wide association studies for growth, carcass, and meat quality traits in a Duroc multigenerational population

Average linkage disequilibrium coefficient (r2) values plotted against intermarker distance for all autosomal chromosomes. (PDF 407 kb

Indication for mild therapeutic hypothermia based on an initial Glasgow Coma Scale motor score

Although neurological evaluation using the Glasgow Coma Scale motor score is mandatory for post-cardiac arrest patients, further study is required to determine if this score can be used as an indicator for mild therapeutic hypothermia. Although the current study conducted by Natsukawa et al. presents interesting data, there are some critical issues regarding study design, selection bias, and interpretation of study results that should be pointed out

Reconstructive Surgery of Poliomyelitic Disabled Hand and Arm with particular Reference to Opponens Plasty

The purpose of this report is to give light on problems concerning surgical reconstruction of the hand and arm disabled by poliomyelitis. Before any surgical intervention, too much attention cannot be placed to the over-all gain sought for the patient. With regard to opponens plasty, it must be emphasized that there are inherent obstacles against the complete reconstruction of poliomyelitic thumb. Authors have come to conclude that no stereotyped measure can be made for any weak thumb

Serial Assessment of Immune Status by Circulating CD8+ Effector T Cell Frequencies for Posttransplant Infectious Complications

To clarify the role of CD8+ effector T cells for infectious complications, 92 recipients were classified according to the hierarchical clustering of preoperative CD8+CD45 isoforms: Group I was naive, Group II was effector memory, and Group III was effector (E) T cell-dominant. The posttransplant infection rates progressively increased from 29% in Group I to 64.3% in Group III recipients. The posttransplant immune status was compared with the pretransplant status, based on the measure (% difference) and its graphical form (scatter plot). In Groups I and II, both approaches showed a strong upward deviation from pretransplant status upon posttransplant infection, indicating an enhanced clearance of pathogens. In Group III, in contrast, both approaches showed a clear downward deviation from preoperative status, indicating deficient cytotoxicity. The % E difference and scatter plot can be used as a useful indicator of a posttransplant infectious complication

Changes on the Physiological Lactonase Activity of Serum Paraoxonase 1 by a Diet Intervention for Weight Loss in Healthy Overweight and Obese Women

Low caloric diet (LCD) is used for weight loss. Paraoxonase 1 (PON-1) is associated with the antioxidant functions of high-density lipoprotein (HDL). Among limited data on the relationships between obesity and PON-1, there has been no study on the effects of a stand-alone LCD on the physiological lactonase activity of PON-1. We investigated the prospective effects of LCD intervention (2 months) for weight loss on serum PON-1 activities (lactonase, arylesterase [mono-esterase] and tri-esterase) and HDL cholesterol (HDL-C), and their association with low-density lipoprotein cholesterol (LDL-C) in overweight and non-morbidly obese but otherwise healthy women (n = 30; mean age, 50.3 years; mean body mass index [BMI], 28.5 kg/m2). In addition to the data such as BMI, blood pressure, blood glucose and lipids, PON-1 activities were examined between pre- and post-intervention. The intervention reduced all metabolic outcomes, and PON-1 lactonase activity (determined with 5-[thiobutyl]butyrolactone) significantly decreased by 6.1%, paralleled by arylesterase (by 7.3%) and tri-esterase (by 7.8%). In multiple regression analysis, the percent change of PON-1 lactonase was significantly, positively and independently correlated to that of LDL-C (β = 0.51), HDL-C (β = 0.40), and BMI (β = 0.37). Our results showed that the solo diet treatment on weight loss might reduce serum PON-1 lactonase activity with reduced HDL-C and LDL-C. The relationship between the lactonase and LDL-C may be adaptive, plausibly hypothesizing less need for PON-1 activity as an antioxidant property to protect lipoproteins. Further research is needed to confirm this prediction