The Most General and Renormalizable Maximal Abelian Gauge

We construct the most general gauge fixing and the associated Faddeev-Popov ghost term for the SU(2) Yang-Mills theory, which leaves the global U(1) gauge symmetry intact (i.e., the most general Maximal Abelian gauge). We show that the most general form involves eleven independent gauge parameters. Then we require various symmetries which help to reduce the number of independent parameters for obtaining the simpler form. In the simplest case, the off-diagonal part of the gauge fixing term obtained in this way is identical to the modified maximal Abelian gauge term with two gauge parameters which was proposed in the previous paper from the viewpoint of renormalizability. In this case, moreover, we calculate the beta function, anomalous dimensions of all fields and renormalization group functions of all gauge parameters in perturbation theory to one-loop order. We also discuss the implication of these results to obtain information on low-energy physics of QCD.Comment: 24 pages, 3 figure

Hormonal Regulation of Glycogen Synthase and Phosphorylase Activities in Human Polymorphonuclear Leukocytes

Peer Reviewe

The Determinants and Effect of the Incentive Intensity: Empirical Evidence from Japan

This study examines various determinants of incentive intensity and the moderating effect of risk aversion on the relationship between incentive intensity and organisational performance. Prior studies have reported mixed results concerning the determinants of incentive intensity, and few studies have examined the moderation effect. We analysed empirical data from a cross-sectional survey of 600 Japanese organisations that manage foreign subsidiaries. The principal and agency structure can be seen in both participants (HQ and a foreign subsidiary) with the agency problem. The first determinant is environmental uncertainty, which is investigated in two types of uncertainties: market and general business environmental uncertainties. The findings suggest that general business environmental uncertainty is negatively associated with incentive intensity, but the negative effect of market environmental uncertainty on it depends on the prospect of incremental profits. The rest of the determinants are derived from the incentive intensity principle, including some features of management accounting systems. In this study, the effects of the determinants are supported as expected in principle. In particular, the incentive intensity is influenced by the prospect of incremental profits, an agent’s risk preference, and their responsiveness to incentives. As for the moderation effect, the positive effect of the incentive intensity on the performance is decreased by an agent’s risk aversion. Our empirical results explain mixed evidence in previous studies and are consistent with the agency theory

A successful rechallenge with cetuximab for a case with metastatic rectal cancer

　A 55-year-old man who had been diagnosed with rectal cancer with multiple liver metastases and lymph node metastases on colonoscopy and computed tomography (CT) was referred to Okayama University Hospital for treatment. Based on the diagnosis of non-curative rectal cancer, we planned to perform systematic chemotherapy after surgical resection. We performed a low anterior resection of a 36×35 mm upper rectal moderately differentiated adenocarcinoma with wil-type KRAS. After the resection, a FOLFIRI regimen with cetuximab was given as the first-line chemotherapy. Although metastatic lesions in the liver showed shrinkage, we decided to switch regimens because of intolerable adverse events. A modified FOLFOX6 regimen with bevacizumab was administered as the second-line treatment. There were no signs of disease progression until eight months later, when positron emission tomography (PET)/CT scans revealed that the new metastatic lesions appeared. As the third-line treatment, an irinotecan with cetuximab regimen was administered, leading to a good response for over 12 months. 　We experienced a successful rechallenge with cetuximab for a case with metastatic rectal cancer. For patients with wild-type KRAS colorectal cancer, rechallenge with cetuximab-based chemotherapy can be an effective therapeutic option

Glutathione Related Enzyme Activities in Spontaneous Hypertensive Rat Heart

It has been reported that oxygen radicals are involved in the development of tissue injury in hypertension. To prevent o xidative stress, there are antioxidant systems inside the cells such as superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reducatase (GR), catalase (CAT) and glutathione S-transferase (GST). In this study changes in these antioxidant activities were estimated in the outer wall of the left ventricles from spontaneously hypertensive rats (SHR), stroke prone SHR (SHRSP) and normal Wister Kyoto rats (WKY). The activities of manganese-superoxide dismutase (Mn-SOD), which localizes in mitochondria and GST were lower in the left ventricles of SHR and SHRSP compared to those in WKY. Slight decrease in the GPX activity was observed in the left ventricles from SHR and SHRSP. On the other hand, the activity of GR and catalase was not different in them. The effect of Nicardipine, a calcium channel blocker, on these antioxidant activities was also esimated. Treatment of these rats with nicardipine (150 mg/kg/day) for 4 weeks improved blood pressure, from 176ﾂｱ10 mmHg to 140ﾂｱ8 mmHg in SHR (n = 5), from 201ﾂｱ11 mmHg to 167ﾂｱ5 in SHRSP (n = 5), respectively, and restored the activities of Mn-SOD, GST and GPX. Collectively, these results suggest that oxidative stress in hypertensive rat heart causes supression of antioxidant activities, which may contribute to myocardical injury, and nicardipine plays a cardioprotective role to reduce the oxidative stress in hypertensive heart

DHEA attenuates PDGF-induced phenotypic proliferation of vascular smooth muscle A7r5 cells through redox regulation.

It is known that dehydroepiandrosterone (DHEA) inhibits a phenotypic switch in vascular smooth muscle cells (VSMC) induced by platelet-derived growth factor (PDGF)-BB. However, the mechanism behind the effect of DHEA on VSMC is not clear. Previously we reported that low molecular weight-protein tyrosine phosphatase (LMW-PTP) dephosphorylates PDGF receptor (PDGFR)-beta via a redox-dependent mechanism involving glutathione (GSH)/glutaredoxin (GRX)1. Here we demonstrate that the redox regulation of PDGFR-beta is involved in the effect of DHEA on VSMC. DHEA suppressed the PDGF-BB-dependent phosphorylation of PDGFR-beta. As expected, DHEA increased the levels of GSH and GRX1, and the GSH/GRX1 system maintained the redox state of LMW-PTP. Down-regulation of the expression of LMW-PTP using siRNA restored the suppression of PDGFR-beta-phosphorylation by DHEA. A promoter analysis of GRX1 and gamma-glutamylcysteine synthetase (gamma-GCS), a rate-limiting enzyme of GSH synthesis, showed that DHEA up-regulated the transcriptional activity at the peroxisome proliferator-activated receptor (PPAR) response element, suggesting PPARalpha plays a role in the induction of GRX1 and gamma-GCS expression by DHEA. In conclusion, the redox regulation of PDGFR-beta is involved in the suppressive effect of DHEA on VSMC proliferation through the up-regulation of GSH/GRX system

A case of metastatic cecal cancer with mutation in the BRAF oncogene and poor survival

　A 79-year-old woman visited a previous hospital with a complaint of general fatigue. The patient was diagnosed with cecal cancer with multiple liver metastases and lymph node metastases on colonoscopy, abdominal ultrasonography and CT scan, and was referred to our division for treatment. Based on the diagnosis of non-curative colonic cancer, we planned to perform systematic chemotherapy after local surgical treatment. We performed an ileocecal resection, and the specimen showed poorly differentiated adenocarcinoma with mutation in the BRAF oncogene. After the surgical treatment, the tumor grew rapidly and the patient died from cancer on the 19th postoperative day without having the opportunity to undergo chemotherapy. 　Multiple genetic and epigenetic alterations in oncogenes and tumor suppressor genes are involved in the process of colorectal carcinogenesis. Some of the alterations have been identified as predictive and prognostic biomarkers. A mutation in the BRAF oncogene was reported to be associated with a very unfavorable prognosis in colorectal cancers. Some of the cases with rapid progression are suggested to have the BRAF oncogene mutation. According to our experience, chemotherapy before surgical treatment might improve the prognosis of cases with the BRAF mutation

Expression of Superoxide Dismutase in Basal Cell Carcinoma

There have been no studies of the expression of superoxide dismutase(SOD) at the mRNA and protein level in skin cancers. Northern blot analysis and enzyme-linked immunosorbent assay (ELISA) were performed in order to analyze the expression of Cu, Zn-SOD and Mn-SOD in basal cell carcinomas (BCC) and normal skin (NS). The expression of Mn-SOD mRNA and protein was significantly higher in BCC than in NS. The expression of Cu,Zn-SOD, however, was high in BCC at the mRNA level, but not at the protein level. These results suggest that an increase in the expression of Mn-SOD relates to the development of BCCs

Glutathione S-transferase pi localizes in mitochondria and protects against oxidative stress.

Glutathione S-transferases (GSTs) are multifunctional enzymes involved in the protection of cellular components against anti-cancer drugs or peroxidative stress. Previously we found that GST pi, an isoform of the GSTs, is transported into the nucleus. In the present study, we found that GST pi is present in mitochondria as well as in the cytosol and nucleus in mammalian cell lines. A construct comprising the 84 amino acid residues in the amino-terminal region of GST pi and green fluorescent protein was detected in the mitochondria. The mutation of arginine to alanine at positions 12, 14, 19, 71, and 75 in full-length GST pi completely abrogated the ability to distribute in the mitochondria, suggesting that arginine, a positively charged residue, is required for the mitochondrial transport of GST pi. Chemicals generating reactive oxygen species, such as rotenone and antimycin A, decreased cell viability and reduced mitochondrial membrane potential. The overexpression of GST pi diminished these changes. GST pi-targeting siRNA abolished the protective effect of GST pi on the mitochondria under oxidative stress. The findings indicate that the peptide signal is conducive to the mitochondrial localization of GST pi under steady-state conditions without alternative splicing or posttranslational modifications such as proteolysis, suggesting that GST pi protects mitochondria against oxidative stress

Significance of Impairment of Antioxidants in Colonic Epithelial Cells Isolated From TNBS-Iuduced Colitis Rats

The functional status of glutathione (GSH), its related enzymes and Cu, Zn-superoxide dismutase (SOD) in colonocytes isolated from trinitrobenzene sulphonic (TNBS)-induced colitis rats was studied. Colitis (T group) was induced in Wistar rats with 42 mg TNBS dissolved in 0.35 ml of 40% (v/v) ethanol instilled into the colon. The animals were sacrificed on day 14 and compared with saline-instilled rats (S group). The GSH concentration and the enzymatic activities of glutathione peroxidase (GPx), glutathione S-transferase (GST), and SOD were spectrophotometrically estimated. The severity of colitis was assessed histologically and by myeloperoxidase activity (MPO) in whole colonic tissue. The body weight loss of the rats in the T group was marked. In colonocytes isolated from rats in the T group, the concentration of GSH (7.9 ±1.4 vs.11.3 ± 0.4 nmol/mg protein, p < 0.05) and the activities of GST (104.4 ± 10.3 vs. 146.2 ± 18.5 mU/mg protein, p < 0.05) and SOD (74.4 ± 8.9 vs. 99.8 ± 7.5U/mg protein, p < 0.05) were lower, but the activity of GPx (430.0 -±14.1 vs. 283.9 ± 10.0 mU/mg protein, p < 0.05) was higher than in the S group. As expected, the activity of MPO in the T group was higher than in the S group (371.2 ± 14.7 vs. 158.9 ± 8.4 mU/mg tissue, p<0.05) and histologically, colitis was only observed in rats in the T group. In conclusion, the functional status of antioxidants in the colonic epithelial cells of rats challenged with TNBS solution is impaired. This impariment may make them more susceptible to oxidative damage that may contribute to the development of the lesions observed in this model. Further studies at the molecular level are necessary to investigate these novel findings in this model and their potential application for testing new therapeutic approaches in inflammatory diseases of the intestinal tract