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Background/Aims: Changes in estradiol that inhibits bone resorption were examined to investigate the in vivo defensive response to progression of bone disorder after gastric cancer surgery. Materials and Methods: Women who might show effects of menstruation were excluded because estradiol was examined. The subjects were 17 men with a mean age of 60.4 years who had undergone gastrectomy because of gastric cancer and were followed as outpatients. Microdensitometry was used to evaluate bone disorder. The duration after surgery until bone assessment was a mean of 3.5 years. The surgical procedure was total gastrectomy with Roux-Y reconstruction in 4 patients and subtotal gastrectomy with Billroth-I reconstruction in 9 patients and with Billroth-II reconstruction in 4 patients. Results: Bone disorder requiring treatment was observed in 6 out of the 17 patients (35.3%). Estradiol showed higher than normal values in 10 patients (58.8%). The incidence of bone disorder was high in patients with high estradiol levels, but the difference was not significant. Blood levels of estradiol in patients with bone disorder requiring treatment were high but again the difference was not significant (P = 0.119). Conclusions: Although the difference was not statistically significant, the increase in estradiol observed in patients with progressive bone disorder suggested to be caused by in vivo inhibition of enhanced bone metabolism after gastric cancer surgery.

Background Long noncoding RNAs (lncRNAs) have recently been known to play various important roles in maintaining molecular regulations. Significant amounts of lncRNAs HOTTIP, PVT1 and H19 are well known to be expressed in pancreatic cancer cells, however their association with efficacy of adjuvant chemotherapy for pancreatic cancer have not been fully investigated. The aim of this study was to evaluate expression of HOTTIP, PVT1 and H19 in the pancreatic cancer cells, and to clarify the predictive roles of those lncRNAs in pancreatic cancer patients who received adjuvant chemotherapy by S-1, an oral fluoropyrimidine or gemcitabine (GEM) after curative resection. Methods Pancreatic cancer patients who underwent curative resection followed by adjuvant chemotherapy by S-1 or GEM since 2005 to 2017 at Kanagawa Cancer Centre were enrolled in this study. In situ hybridization (RNA scope®) to detect each three lncRNAs was performed using tissue microarrays prepared from formalin-fixed and paraffin-embedded tissues of resected specimens. The relations between the expression of HOTTIP, PVT1 and H19 and clinicopathological characteristics were statistically analyzed. Results We analyzed 204 eligible pancreatic cancer patients. 114 patients received adjuvant chemotherapy by S-1, and 90 patients by GEM. The patients with higher expression of H19 were significantly associated with shorter relapse free survival (RFS) regardless of adjuvant chemotherapy regimens (p Conclusions The expression levels of PVT1 and HOTTIP in pancreatic cancer cells were associated with the efficacy of adjuvant chemotherapy for pancreatic cancer in the present study. The higher expression of H19 may serve as a significant predictive/prognostic marker for patients who received adjuvant chemotherapy by S-1 or GEM after curative resection. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Isolates of 24 enterococci, 5 Enterococcus casseliflavus and 19 Enterococcus gallinarum, possessing vanC genes and showing low-level resistance to vancomycin were obtained from mice from commercial mouse breeding companies. Since some of these isolates showed resistance to other antibiotics, the purpose of this study was to clarify the resistant profiles of these isolates. One E. casseliflavus isolate showed resistance to erythromycin with a minimal inhibitory concentration (MIC) of 8 μg/mL and also showed apparent resistance to fluoroquinolones with an MIC of 32 μg/mL for ciprofloxacin. The MICs of 2 other fluoroquinolone-resistant E. casseliflavus and E. gallinarum isolates were 3 and 6 μg/mL, respectively. These 3 resistant isolates showed an absence of macrolide- and fluoroquinolone-resistant genes, including amino acid substitutions in the quinolone resistance determining regions of DNA gyrase and topoisomerase IV. Resistance to tetracycline was detected in 2 E.gallinarum isolates that were highly resistant, exhibiting MICs of 48 and 64 μg/mL and possessing tet(O) genes.The results indicate that antibiotic-resistant enterococci are being maintained in some laboratory mouse strains that have never been treated with an antibiotic., Journal of veterinary science, 20(2), e13; 2019

Linalool has two enantiomers, (R)-linalool and (S)-linalool. Both are known to possess several biological activities in stressed animals. Our previous work revealed that inhalation of (R)-linalool altered hypothalamic gene expression in rats under stress. In the present study, we monitored hypothalamic gene expression in restrained rats with and without (S)-linalool inhalation by DNA microarray. The entire gene expression profile showed that inhalation of (S)-linalool significantly changed the expression levels of 316 hypothalamic genes in the restrained rats. The differentially expressed genes (e.g., App, Avp, Igf2, Igfbp2, Sst and Syt5) were found to relate to cell-to-cell signaling and nervous system development. These results indicate that (S)-linalool influences hypothalamic gene expression in restrained rats, and that inhalation of (S)-linalool under the stressed condition has some effects on stress-related biological responses.

ObjectiveTriglyceride (TG) accumulation in arterial tissue is associated with the development of cardiovascular disease; however, the underlying mechanism remains unclear. Cilostazol (CLZ), a selective inhibitor of phosphodiesterase 3, has antiplatelet and vasodilating effects and may decrease serum TG levels. We examined the effect of CLZ on TG accumulation in the arterial tissue of a rat model of carotid artery ligation.MethodsRats were fed normal chow with 0.1% CLZ (CLZ group) or without CLZ (control group) for 4 weeks after unilateral carotid artery ligation near the carotid bifurcation.ResultsAt the end of this period, the control group showed 3.3-fold higher TG levels in the ligated carotid artery than in the contralateral artery; however, compared with the contralateral artery, the ligated artery in the CLZ group showed significantly lower levels of TG accumulation but similar serum levels of TG, total cholesterol, and high-density lipoprotein cholesterol. Furthermore, matrix-assisted laser desorption/ionization imaging mass spectrometry revealed that the ligated carotid artery in both groups had ubiquitous accumulation of TG in the intima, media, and adventitia, along with decreased heme B signals, which was indicative of ischemia. However, heme B signals were less reduced in the CLZ group than in the control group.ConclusionsOur results indicate that CLZ can inhibit the ubiquitous accumulation of TG in arterial tissues, possibly by ameliorating tissue ischemia. CLZ may be useful in improving arterial tissue hemodynamics and lipid metabolism.Clinical RelevanceTriglyceride (TG) accumulation in arterial tissue is associated with the development of cardiovascular disease; however, the underlying mechanism remains unclear. Cilostazol, an antiplatelet and vasodilating drug, has been widely used for patients with peripheral artery occlusive disease to improve intermittent claudication. This study examined the effect of cilostazol on TG accumulation in the arterial tissue of a rat model of carotid artery ligation. We identified a novel effect of cilostazol on inhibition of accumulating TG in the ligated carotid artery tissue. This effect may be expected in clinical use in humans

Purpose Secreted protein acidic and rich in cysteine (SPARC) is one of the first known matricellular proteins that modulates interactions between cells and extracellular matrix. Recent studies investigated the clinical significance of SPARC gene expression in the development, progression, and metastasis of cancer. The present study examined the relations of the relative expression of the SPARC gene to clinicopathological factors and overall survival in patients with gastric cancer. Methods We studied surgical specimens of cancer tissue and adjacent normal mucosa obtained from 227 patients with previously untreated gastric cancer. The relative expression levels of SPARC mRNA in cancer tissue and in adjacent normal mucosa were measured by quantitative real-time, reverse-transcription polymerase chain reaction. Results The relative expression level of the SPARC gene was higher in cancer tissue than in adjacent normal mucosa. High expression levels of the SPARC gene were related to serosal invasion (P = 0.046). Overall survival at 5 years differed significantly between patients with high SPARC gene expression and those with low expression (P = 0.006). Conclusions Overexpression of the SPARC gene may be a useful independent predictor of outcomes in patients with gastric cancer. J. Surg. Oncol. 2013; 108:364–368. © 2013 Wiley Periodicals, Inc.

The reactions of paddlewheel-type diruthenium(II, II) complexes, [Ru2(II,II)(x-FPhCO2)4(THF)2] (x-FPhCO2(-) = x-fluorobenzoate with x- = o-, m-, p-), with 2,6-diaminopyridine (dapy) and 7-azaindole (azain) afford axially capped discrete compounds, [Ru2(II,II)(x-FPhCO2)4(dapy)2] (x = o-, 1; m-, 2; p-, 3) and [Ru2(II,II)(o-FPhCO2)4(azain)2] (4), respectively. In these compounds, intramolecular hydrogen bonds are observed between NH2 groups for 1-3 or imine NH groups for 4 and oxygen atoms of carboxylate groups. In addition, hydrogen bonds of NH2···F are also observed for 1 and 4 with an o-positioned F atom on benzoate. This coordination mode, i.e., a dual bonding mode with σ-bonding and hydrogen bonding, should assist ligand coordination to the axial position of the [Ru2] unit. The Ru-N bond distance in 1-4 is shorter than that observed in related compounds reported previously. In a similar fashion, reactions with planar M(II) dithiobiuret (dtb) complexes, [M(II)(dtb)2] (M(II) = Pd(II) and Pt(II)), were carried out. One-dimensional alternating chains, [{Ru2(II,II)(o-FPhCO2)4}{M(II)(dtb)2}] (M(II) = Pd(II), 5; Pt(II), 6), were obtained, in which the hydrogen-bonding modes of NH2···O and NH2···F are present, as expected. DFT calculations for the [M(II)(dtb)2] unit revealed that the LUMO of [M(II)(dtb)2] lies at -2.159 and -1.781 eV for M = Pd and Pt, respectively, which is much higher than HOMO energy at -4.184 eV calculated for [Ru2(II,II)(o-FPhCO2)(THF)2], proving that the respective units are essentially electronically isolated in the chains.

The perceived intensity of the taste of a food is enhanced only if the odor of the food is perceptually similar to the taste. For example, a caramel-like odor enhances the perceived intensity of sweetness. The way gustatory and olfactory signals are integrated in the brain depends largely on one’s previous experiences with taste and odor pairings. To elucidate the effects of a sweet, sugary odor, ethylmaltol, on sucrose taste, as perceived by the central integration of flavor, we recorded salivary hemodynamic responses to the odor and taste pairings using near-infrared spectroscopy (NIRS) of seven panelists. First, we observed concentration-dependent increases in the amplitude of the responses to 0 to 6 % sucrose solutions. Second, when ethylmaltol odor was added to a 4 % sucrose solution, we observed a significant increase in the amplitude of the responses from all panelists. The addition of ethylmaltol to a tasteless solution caused no significant change in the amplitude of the salivary hemodynamic response. These results indicate that the sweet odor of ethylmaltol enhances the salivary hemodynamic response when combined with a sweet taste. Therefore, a congruent combination of sweet odor and taste greatly enhances salivary responses, which are dependent on the central integration of odor and taste.

An unidentified Helicobacter species, strain MIT 01-6451, was frequently detected in mice obtained from domestic commercial and academic institutions in Japan. To partially characterize this strain, its distributions in the gastrointestinal tract and hepatobiliary system of mice were investigated. In gastrointestinal tissues, this strain was detected in all cecum, colon, and feces samples tested, whereas fewer mice were positive in the ileum, jejunum, and duodenum. Interestingly, strain MIT 01-6451 was also detected in most stomach samples and in 33% of gallbladder samples. One mouse was found to be infected with multiple Helicobacter species. Fourteen copies of 16S rRNA genes were cloned from the tissues of this mouse. One had the highest level of sequence homology with H. canadensis, while 13 had the highest level of homology with the H. ganmani type strain or strain MIT 01-6451. Twelve of these 13 16S rRNA genes were mosaic sequences, being partially derived from H. ganmani and strain MIT 01-6451. These results suggest that H. ganmani and Helicobacter sp. MIT 01-6451 are prevalent in specific-pathogen-free mouse colonies in Japan and that lateral gene transfer probably occurs among Helicobacter species during coinfection., Experimental Animals, 62(2), pp.109-116; 2013

Fenestrated endovascular abdominal aneurysm repair (FEVAR) using branched arteries devices for visceral arteries is increasingly being used for the repair of juxtarenal aortic aneurysms (JAAs) in Europe, United States, Australia, New Zealand, and Asia. This study aimed to evaluate the technical feasibility and short-term results of FEVAR in treating JAAs in Japanese patients.FEVAR with Cook fenestrated stent-graft (Cook Medical Inc., Bloomington, Indiana, USA) was performed for 5 patients at high risk for open repair of JAA. Seventeen visceral vessels were successfully accommodated with 12 fenestrations, and five visceral arteries with four scallops with a loss of renal artery. In one case, a type III endoleak occurred at a renal artery fenestration, and this had disappeared in the 1-month postoperative computed tomography (CT). The mean follow-up duration was 8 months. Iliac leg occlusion occurred in 1 case, which was treated with thrombectomy and additional leg device deployment. All patients had survived at the end of the follow-up period and continued their outpatient visits.Implantation of a Cook fenestrated stent-graft incorporating the visceral arteries is technically feasible in high-risk Japanese patients with JAA and may be a viable alternative to current methods.

A high-speed YBa2Cu3O7-δ direct detection system was developed to monitor terahertz picosecond pulses in the time domain. High-TC superconducting thin-film YBa2Cu3O7-δ microbridges with critical temperatures of TC = 85 K were embedded into a planar log-spiral antenna to couple the broadband terahertz radiation (0.1 -2 THz) of several picosecond pulsed sources. The YBa2Cu3O7-δ detectors were installed in a liquid nitrogen cryostat equipped with 18 GHz effective bandwidth readout electronics. THz pulses generated at the electron storage rings ANKA and UVSOR-II have been resolved with a temporal resolution of 30 ps (full width at half maximum) limited by the readout electronics bandwidth. Beam dynamic effects of bursting coherent synchrotron radiation were successfully monitored.

Objective: Previously, we analyzed human varicose veins (VV) using imaging mass spectrometry (IMS) and detected the abnormal accumulation of lipid molecules in the walls of VV, possibly due to insufficient lipid drainage by the lymphatic vessels. In this study, we created an animal model of lymphatic insufficiency to investigate the effects of insufficient lymph drainage on vein walls. Methods: In rats, the lymphatic collecting vessels surrounding the femoral vein were ligated on one side (the model tissue), which caused the local retention of lymphatic fluid in the perivascular tissue. The equivalent contralateral tissue was used as a control. A histological study of the femoral vein and the surrounding perivascular tissue was conducted. IMS was used to analyze the distribution of lipid molecules in the perivascular tissue. Results: Fourteen days after the procedure, the lymphatic vessels in the model tissue were significantly dilated. Furthermore, IMS revealed that the composition of the lipid molecules in the perivascular regions of the model tissue had altered. Compared with the control tissue, the model tissue exhibited marked perivascular accumulation of lysophosphatidylcholine (1-acyl 16:0), phosphatidylcholine (16:0/20:4), and triglycerides (52:2). Interestingly, the walls of the femoral veins running through the model tissue were 3.4-fold thicker than those of the femoral veins running through the control tissue. The number of tumor necrosis factor α-positive adipocytes was increased in the perivascular regions of the model tissue. Conclusion: The findings of this study indicated that the accumulation of lymphatic fluid due to insufficient lymph drainage changes the structure of vein walls, and such changes might be associated with chronic venous insufficiency. (This is a translation of Jpn J Phlebol 2015; 26: 227-235.).

We report a case of advanced esophageal and gastric cancer that was successfully treated via multimodal therapy. A 65- year-old man with hoarseness was referred to our hospital. He was diagnosed with clinical T4aN2M0, Stage IV esophageal squamous cell carcinoma and clinical T3N1M0, Stage II B gastric adenocarcinoma. He was treated with 3 courses of chemotherapy, administered over 4weeks, with S-1(80mg/m / / 2: day 1-14), cisplatin(60mg/m2: day 1), and docetaxel(40mg/m2: day 1). Computed tomography(CT)revealed shrinkage of the primary esophageal tumor, gastric tumor, and lymph node metastases. Next, we selected definitive radiation chemotherapy(CRT), because lymph node metastases remained around the bilateral recurrent laryngeal nerves. After CRT with a total 60 Gy plus administration of 5-fluorouracil and cisplatin, CT showed that the primary esophageal tumor and lymph node metastases had disappeared. Then, distal gastrectomy was performed for the remaining gastric cancer, as part of the multimodal therapy. After gastrectomy, no systemic chemotherapy was performed. At a follow-up examination 5 years and 6 months after the start of chemotherapy, the patient is alive without recurrence.

A30 -year-old woman underwent total gastrectomy with D2 lymph node dissection after being diagnosed with clinical T3, N2, M0, Stage III B gastric cancer. The postoperative pathological findings revealed a T3(SE), N2, M0, Stage III B tumor. Headache, dizziness, and vomiting occurred during chemotherapy for peritoneal recurrence, using weekly paclitaxel on days 1, 8, and 15. Head CT showed a solitary tumor with a diameter of 28mm in the cerebellum, as well as cerebellar swelling and hydrocephalus. She underwent an emergency craniotomy and tumor enucleation. Pathological examination revealed a metastatic brain tumor from the gastric cancer. She received 12 courses of CPT-11 plus cisplatin until discontinuation because of an adverse event. The patient is alive 6 years after the diagnosis of the cerebellar metastasis without recurrence.

Most microsurgeons believe that smoking and severity of injury adversely affect the outcome of digital replantation surgery. As countermeasures, several pharmacologic agents have been used for the perioperative period. The purpose of this retrospective study was to examine whether the rate of necrosis is appreciably different across smokers versus nonsmokers with prostaglandin E1 therapy.The authors' study subjects included 144 patients (184 digits) who underwent replantation or revascularization between August of 2013 and August of 2015.The primary outcome was the incidence of total necrosis after replantation surgery, and the secondary outcomes were the rate of overall necrosis, proportion of total necrosis to overall necrosis, and total success. Intravenous administration of prostaglandin E1 was performed at the rate of 120 μg/day for 7 days after surgery in all patients. These outcomes of each injury type were compared between smoking and nonsmoking groups.Among the 184 injured digits, the incidence of total necrosis in smokers (23 percent) was higher than that in nonsmokers (17 percent), although no significant difference was shown (p = 0.36). The adjusted odds ratio was 1.17 (95 percent CI, 0.51 to 2.69). Similarly, there was no significant difference in the secondary outcomes between the two groups.The authors' retrospective study found no significant difference in the formation or extent of necrosis after replantation or revascularization between smoking and nonsmoking groups when all patients were treated with prostaglandin E1.Risk, II.

Background: The use of cultured epithelial autografts for the treatment of extensive burn wounds has become popular in recent years. We examined extensive burn wounds in 14 patients by using a combination of autograft and cultured epithelial autografts developed in Japan (JACE). Methods: We undertook a skin biopsy at 2, 4, and 6 weeks after transplantation with JACE. By using electron microscopy we observed the engraftment process. Results: In transmission electron microscope findings, we recognized the engraftment process of JACE. Keratinocytes matured gradually. Collagen fibers formed thick bundles in the dermis layer. In scanning electron microscope findings, we observed papillary dermis development on the artificial dermis. Conclusions: After managing wound bed preparation by using artificial dermis, we were able to recognize the good result of grafting JACE on meshed 6:1 split thickness autografts. This is because the auto dermis from autograft extended under the JACE, binding between JACE, and the dermis became strong.

In this paper, we present a case of undifferentiated carcinoma of the gallbladder, which is a rare disease with poor prognosis. A 77-year-old woman presented with right hypochondralgia. An abdominal CT scan showed a tumor more than 80 mm in diameter invading the liver parenchyma and transverse colon, and showed liver and lymph node metastases. We diagnosed the patient with stage Ⅳ carcinoma of the gallbladder. We resected the gallbladder, S4a plus S5 of the liver, part of the transverse colon, the lymph nodes, the greater omentum, and the extra hepatic bile duct; biliary reconstruction was then performed. Histological examination showed that most areas consisted of undifferentiated cells. The diagnosis of undifferentiated carcinoma was made according to the WHO classification of tumors of the digestive system. No recurrence has been detected for 1 year.

The patient was an 82-year-old man, who contracted chronic hepatitis C in 1977. In 1997, he was diagnosed with intraductal papillary-mucinous neoplasm (IPMN), and was treated with surgery. In August 2005, cholangiocellular carcinoma (CCC) and hepatocellular carcinoma (HCC) were detected, and he underwent a subsegmentectomy of the liver. In February 2007, he had a supradiaphragmatic lymph node recurrence of CCC. It was a solitary lesion; therefore, we resected the recurrent tumor by thoracoscopic surgery. In January 2012, squamous cell lung cancer was detected and he had a thoracoscopic operation. Furthermore, in February 2015, 2HCCs were detected in S5 and S5/8 of the liver. He underwent radiofrequency ablation. Over the course of 18 years, this patient developed cancers in his pancreas, intrahepatic bile duct, liver, and lung. However, the patient has survived without recurrence because of aggressive therapy and diligent surveillance after surgery.

The aim of this study was to evaluate the safety and feasibility of the bioabsorbable staple line reinforcement in distal pancreatic resection.Thirteen patients underwent distal pancreatic resection using the bioabsorbable staple line reinforcement between May 2014 and December 2014. Surgical complications were evaluated by Clavien-Dindo classification.Median age was 64 years. Median operation time was 219 minutes and median blood loss was 490 mL. ComplicationsGrade 2 were observed in 3 patients. Among them, pancreatic fistula (Grade 2) was found in 2 patients and ileus (Grade 2) in 1. No surgical mortality was observed.Our results may suggest that the bioabsorbable staple line reinforcement is safe and feasible in distal pancreatic resection.

By remarkable progress of chemotherapy for pancreatic cancer, we sometimes achieve resection of initially unresectable pancreatic cancer after chemotherapy. Otherwise, the safety and feasibility of radical pancreatic resection after chemotherapy is not still clear. In this report, we evaluated the safety and feasibility of conversion surgery for initially unresectable pancreatic cancer in our center.Between 2009 and 2014, approximately 500 patients were diagnosed with unresectable pancreatic cancer and received chemotherapy, and after chemotherapy, 10 patients were found to have resectable tumors on computed tomography. We evaluated surgical complications using the Clavien-Dindo classification. Clinicopathological data were reviewed by using UICC, seventh edition, and the chemotherapeutic effect was measured by using Evans classification.The mean age of patients was 68 years, with 4 men and 6 women. The preoperative chemotherapy regimens were S-1 chemotherapy in 2 patients, gemcitabine in 5 patients, and gemcitabine plus S-1 chemotherapy in 3 patients. Nine patients underwent pancreatoduodenectomy, and 1 underwent distal pancreatosplenectomy. The mean operative time was 527.5 minutes, and the mean estimated blood loss was 875 mL. Surgery-related morbidity more than Grade 2 based on Clavien-Dindo classification occurred in 6 patients. Mortality was 0%.Our study suggests that conversion surgery for initially unresectable pancreatic cancer is safe and feasible.

We report the rare case of a 54-year-old man with uncontrolled renovascular hypertension, who was found to have an abdominal aortic aneurysm with congenital solitary pelvic kidney and superior mesenteric artery stenosis. A single renal artery branched from aneurysmal aortic bifurcation, and both the renal artery and the superior mesenteric artery (SMA) had severe stenosis at their origins. The aneurysm was repaired with a bifurcated Dacron graft, to which the renal artery was anastomosed. SMA bypass was created between the graft's left limb and the SMA using another Dacron graft. The operation was successful, with improvement in renal functions and control of hypertension.

Occlusive dressing is widely accepted and used to manage skin ulcers. However, with respect to its application to incisional wounds, most studies have been conducted about the clinical effects on incisional healing of surgical sites. Studies of the histological effects of occlusive dressing for incisional wounds have been few. The aim of this study was to clarify the histological effects of occlusive dressings on healing of incisional skin wounds. Rat dorsal skin was incised down to the panniculus and sutured immediately. Dressing types included 2-octyl cyanoacrylate and hydrocolloid materials as occlusive dressings and no-dressing as the open therapy. Histological examination and dermoscopic observation were performed 1, 2, 4 and 7 days after surgery. The findings from each dressing type were compared. In the open therapy group, the upper portion of the edge of incision was necrosed minimally and finally healed with wide scar formation. However, in the occlusive dressing groups, micronecrosis of the incision edge seen in the no-dressing group was not observed, healing was more rapid and the remaining scar was finer. Occlusive dressing can prevent micronecrosis of the incision edge, resulting in rapid and excellent healing. This study shows that the efficacy of and supports the use of occlusive dressing in incisional wound management.

Ultra-short gamma ray pulses of the picosecond and femtosecond ranges can be generated using laser Compton scattering with 90° collisions at the UVSOR-II electron storage ring. Measurement techniques for a gamma ray pulse width in the femtosecond range are being developed. As the first stage of pulse width measurement, we tested a pulse width measuring method for the gamma rays with pulse width of 4.8 ps (FWHM) consisted of a multi-pixel photon counter (MPPC) and a digital oscilloscope. The time resolution of the MPPC was measured as 477 ps (FWHM) by using a single photon counting technique. The results indicated that the shortest pulse width that an MPPC can evaluate is 82 ps under ideal conditions. However, the experimental data were affected by a time jitter. The measured gamma ray pulse width including time jitter was 540 ps. The main reason for the large discrepancy was considered to be the noise of the trigger signal. We successfully reduced the time jitter to 77 ps after an improvement. As the next stage, we will develop a pulse width measurement technique in the femtosecond range by using a pump-probe technique with a femtosecond laser and ultra-short gamma ray pulses.

Background To search for biomarkers identifying pancreatic cancer patients likely to benefit from adjuvant gemcitabine chemotherapy, we investigated the status of several histone modifications in pancreatic tumors and their relationship to clinicopathological features and outcomes. Methods Sixty one pancreatic cancer patients, primarily treated by surgical removal of tumors, were involved in the study. Thirty patients completed postoperative adjuvant gemcitabine, and in 31 it was discontinued. Tumor specimens were examined using immunohistochemistry for di- and tri-methylation of histone H3 lysine 4 (H3K4me2 and H3K4me3), dimethylation and acetylation of histone H3 lysine 9 (H3K9me2 and H3K9ac), and acetylation of histone H3 lysine 18 (H3K18ac). Positive tumor staining for each histone modification was used to classify patients into low- and high-staining groups, which were examined for relationships to clinicopathological features and clinical outcomes. Results High expression of H3K4me3 was related to the well and moderately differentiated tumor histological type ( p = 0.012) and low expression of H3K4me2 was related to the presence of perineural invasion ( p = 0.007). No cellular histone modifications were associated with overall or disease-free survival of patients as a whole. In the subgroup analyses, a low level of H3K4me2 was significantly associated with worse disease free survival in patients that completed adjuvant gemcitabine ( p = 0.0239). Univariate and multivariate hazard models also indicated that a low level of H3K4me2 was a significant independent predictor of disease-free survival ( p = 0.007). Conclusion H3K4me2 was found to be a predictor of response to adjuvant gemcitabine in Asian patients with pancreatic cancer.

Chromatin remodeling factors have been the subject of great interest in oncology. However, little is known about their role in pancreatic cancer. The objective of this study was to clarify the clinical significance of the SWItch/sucrose non-fermentable (SWI/SNF) complex in patients with pancreatic cancer. A total of 68 patients with pancreatic cancer who underwent R0, 1 resection were enrolled. Cancer tissues were processed to tissue microarray, then stained immunohistochemically by using antibody of SWI/SNF components; BRM, BRG1, BAF250a, BAF180 and BAF47. The correlation of expression levels and clinicopathological outcomes were analyzed, followed by the multivariate analysis of prognostic factors for overall survival. The expression levels of the SWI/SNF components were categorized as low or high according to the median value of Histoscore. Statistical analysis revealed that BRM expression was related to tumor size, T factor, M factor, lymphatic invasion and stage BRG1 expression to histology and stage BAF180 expression to tumor size and BAF47 expression to lymphatic invasion, respectively. Multivariate Cox proportional hazard analysis showed that high BRM and low BAF180 expression levels were independent predictors of worse survival in patients with pancreatic cancer. High BRM, and low BAF180 were also independent prognostic factors for poor survival in the subgroup with adjuvant gemcitabine. These results suggest that the specific cofactors of SWI/SNF chromatin remodeling complex certainly have roles in pancreatic cancer. High BRM, and low BAF180 are useful biomarkers for poor prognosis in pancreatic cancer.

The dry weight of tendon tissue is accounted for mainly by collagen fibers. Accordingly, the tendon-healing process primarily involves repair of collagen fibers. During the remodeling phase of tendon healing, newly proliferating collagen fibers are transformed into a mature repaired tendon. Despite the importance of this phenomenon, the details of fibrous rebuilding have not been reported previously. The aim of this study was to visualize the ultrastructural changes and to obtain a clear understanding of the reorganization of the collagen fibers in the tendon repair site, using rat Achilles tendons. We used scanning electron microscopy (SEM) with cell maceration as the main method of analysis. Pretreatment with cell maceration removed the cellular components successfully. This allowed precise visualization of each collagen fiber and the three-dimensional network of the fibers. This study was the first to apply the cell-maceration/SEM method to observe tendon tissue. Seven days after surgery, new collagen fibers grew extensively in the repair site in a random arrangement. Fourteen days after surgery, the collagen fibers began to form an axial arrangement. Near the tendon stump, this change progressed from the outer layer to the core region. On the other hand, in the middle of the repair site, it progressed from the core to the outer layer. Change in the axial arrangement of collagen fibers contributes to the connection between the repair site and the tendon stump and to the separation of the repair site from the paratenon.

Objective: Gemcitabine has been widely used, and cisplatin plus gemcitabine is considered as standard first-line chemotherapy for patients with advanced biliary tract cancer. However, no standard therapy was established following the progression to gemcitabine-containing first-line therapy. As S-1 monotherapy as second-line chemotherapy is still not well known in a practical setting this study aimed to clarify its efficacy and safety. Methods: We retrospectively reviewed 55 consecutive patients who received S-1 monotherapy as second-line chemotherapy after failure of a gemcitabine-containing regimen at our institution from September 2007 to March 2011. The inclusion criteria were preserved organ function and an Eastern Cooperative Oncology Group performance status of 0‐2 and without massive ascites or pleural effusion. S-1 was administered orally twice a day at a dose of 40 mg/m 2 for 28 days, followed by 14 days of rest. Results: Fifty-one patients were selected for this analysis. The overall response rate was 4.0% and the disease control rate was 38.0%. The median survival time was 6.0 months and the median progression-free survival was 2.3 months. Adverse events were generally mild, and treatment-related death did not occur. In the subgroup analysis, overall survival was significantly shorter in the patients with peritoneal dissemination and those who had shown no response to the first-line chemotherapy (P ¼ 0.033 and 0.023, respectively). Conclusions: S-1 monotherapy as the second-line chemotherapy for patients with gemcitabine-refractory advanced biliary tract cancer is also feasible in a practical setting and its efficacy is almost the same as in the previous prospective study.

ObjectiveRecent studies suggest that biologic changes in the vein wall associated with varicose veins (VVs) occur not only in valvular tissue but also in nonvalvular regions. We previously used imaging mass spectrometry (IMS) to determine the distribution of lipid molecules in incompetent valve tissue. In this study, we used IMS to analyze incompetent great saphenous veins (GSVs) in patients with varicose vein (VV) to assess the distribution of lipid molecules.MethodsWe obtained GSV tissue from 38 VV patients (50 limbs) who underwent GSV stripping. For the control veins (CV), we obtained GSV samples from 10 patients undergoing infrainguinal bypass with reversed GSV grafting for peripheral artery occlusive disease (10 limbs). Conventional and immunofluorescence staining were performed for histopathologic examination. The total lipid content in the homogenized vein tissue was determined. The localization of each lipid molecule in the vein wall was assessed by IMS.ResultsThe histologic examination showed the VV walls were significantly thicker than the CV walls, and only the VV adventitia was positive for lipid staining. The VV wall had higher concentrations of phospholipids and triglycerides than the CV wall. IMS revealed an abnormal accumulation of lysophosphatidylcholine (LPC; 1-acyl 16:0) and phosphatidylcholine (diacyl 16:0/20:4) in the VV intima and media. Triglyceride was found only in VV adventitia. The number of lymphatic vessels, as measured by staining with D2-40, a lymphatic vessel-specific marker, was significantly lower in the VV adventitia than in the CV adventitia. Lymphatic vessel reduction may be associated with insufficient lymphatic drainage in the VV adventitia causing histologic changes in VV tissue.ConclusionsThe accumulation of LPC (1-acyl 16:0) and PC (diacyl 16:0/20:4) in the VV intima and media may be associated with chronic inflammation, leading to VV tissue degeneration. Furthermore, insufficient lipid drainage by lymphatic vessel may be responsible for accumulation of lipid molecules and subsequent vein wall degeneration.Clinical RelevanceAbnormal distribution of lipid molecules in varicose vein (VV) tissue in patients at CEAP class C2-3 and C4-5 suggests that VV-associated accumulation of lipid molecules begins in the early clinical stages of the disease and continues through the advanced stages. In particular, the accumulation of both lysophosphatidylcholine (1-acyl 16:0) and phosphatidylcholine (diacyl 16:0/20:4) in the media was significantly higher in VV tissue from patients in advanced clinical stages, suggesting an association between lipid accumulation and chronic inflammation of skin and subcutaneous tissues. Further study is needed to clarify the effect of lymph stasis on VVs and chronic inflammation. The mechanism whereby adventitial lymphatic vessels are damaged is also unknown. Consistent venous hypertension and subsequent overload to the lymphatics may account for the lymphatic damage. In addition, accumulation of possible proinflammatory lipid molecules in VV walls may further damage the adventitial lymphatic vessels.

Aim: Obesity and visceral obesity are closely related to the development of colorectal cancer, as well as other metabolic complications. We investigated the prognostic significance of body mass index (BMI) and visceral obesity in 273 patients with resectable colorectal cancer. Methods: Visceral fat area (VFA) and subcutaneous fat area were measured on digital images of patients’ computed tomograms obtained before surgery. The patients were divided into two groups according to the cut-off levels of VFA proposed by Oka et al. Men with a VFA of ≥130 cm2 and women with a VFA of ≥90 cm2 were classified as obese (VFA-obese) and the others were classified as non-obese (VFA-non-obese). The patients were also divided into an overweight group and a normal range group, according to their preoperative BMI. Results: There was no significant difference in cumulative recurrence-free survival (RFS) or overall survival (OS) between the VFA-obese group and the VFA-non-obese group. In the subgroup of patients with Dukes’ C disease (n = 100) there was no statistically significant difference in RFS and OS between the VFA-obese group and the VFA-non-obese group. The results were similar when the patients were classified according to their BMI. Conclusion: Neither obesity nor increased visceral adiposity has any influence on outcomes in patients with resectable colorectal cancer.

We examined the effects of prostaglandin E₁ (PGE₁) on radiation-induced proliferation inhibition and apoptosis in keratinocytes and healing of radiation-induced skin injury in a rat model. PGE₁ had a protective effect on radiation-induced growth inhibition in keratinocytes in vitro, but not in fibroblasts. Varying concentrations of PGE₁ were subcutaneously administered into the posterior neck region. X-irradiation at a dose of 20 Gy was administrated to the lower part of the back using a lead sheet with two holes 30 min to 1 h before or after the administration of PGE₁. Although X-irradiation induced epilation, minor erosions, or skin ulcers in almost all rats, PGE₁ administration prior to irradiation reduced these irradiation injuries. Staining with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling showed that proportions of apoptotic keratinocytes in the X-irradiated skin of PGE₁-administered rats were significantly lower than for those in the skin of rats which did not receive PGE₁. Cutaneous full-thickness defective wounds were then formed in X-irradiated areas to examine the time course of wound healing. Wound healing was significantly delayed because of X-irradiation, but PGE₁ administration prior to irradiation led to a significantly shorter delay in wound healing compared with controls. Decreasing delay in wound healing was correlated with concentration of PGE₁ administrated. Thus, PGE₁-administration may potentially alleviate the radiation-induced skin injury.

Inverse Compton-scattered gamma rays of tunable energy were generated by changing the collision angle between a laser and an electron beam of fixed energy at the electron storage ring, UVSOR-II. Analytic expressions were derived for energy and intensity of the gamma rays. The measured energy and intensity of the gamma rays agreed with the theoretical values, and the pulse width was calculated to be a few ps, under experimental conditions. It was shown that ultra-short gamma ray pulses with a pulse width of 150 fs can be generated by optimizing the size of the laser spot.

Background Skin flap necrosis is a problem encountered postoperatively. The purpose of this study was to evaluate the effects of platelet-rich plasma containing fragmin/protamine microparticles (PRP&F/P MPs) on viability in a rat dorsal paired pedicle skin (DPPS) flap. Materials and Methods Two symmetrical adjoining rectangular flaps (8 × 2 cm each) were drawn on the rat dorsum. Two days after PRP&F/P MPs-, PRP-, F/P MPs-, and saline (control)-injections ( n = 8 each), flaps were elevated as a random pattern flap without the lateral thoracic, posterior intercostal, and deep circumflex iliac vessels. The flaps were immediately sutured back and the flap survival area was measured 7 d after flap elevation. Results The flap survival rate in PRP&F/P MPs-injected groups (73.1% ± 4.2%) was significantly higher than those in PRP (64.9% ± 4.0%), F/P MPs (59.4 ± 4.5%), and control (61.2% ± 4.2%) groups. Histologic observation of the flaps showed survived thick granulation tissue and neovascularization in PRP&F/P MPs-injected groups. Conclusions When PRP&F/P MPs are administered 2 d before the flap elevation, the improved flap survivals are observed. The pre-injection of PRP&F/P MPs may thus represent a promising treatment to prevent skin flap necrosis in reconstructive surgery.

Dynamics of radical cations and electrons in an admixture of a linear saturated hydrocarbon (n-dodecane) and halocarbon (carbon tetrachloride, CCl(4)) were investigated by picosecond electron beam pulse radiolysis. The decay of thermalized electrons (e(th)(-)) observed in infrared transient photoabsorption were simply accelerated by the addition of CCl(4), giving a high rate constant of 2.3 × 10(11) mol(-1) dm(3) s(-1). The decrease of the initial yield of e(th)(-) was quantified by C(37) (50 mmol), which is linked to the reaction of epithermal electrons (e(-)) with CCl(4). In contrast, the n-dodecane radical cation (RH(2)(•+)) monitored in the near-infrared indicated a convex-type dependence of the decay rate on CCl(4) concentration, although the initial yield of RH(2)(•+) remained almost constant up to a much higher CCl(4) concentration. The decay of RH(2)(•+) was analyzed by Monte Carlo simulations of geminate ion recombination with e(th)(-), chlorine anion (Cl(-)) formed via dissociative electron attachment, and CCl(4) radical anion. The results showed a good agreement with the experiments by considering two assumptions: (1) CCl(4) radical anion formed via e(th)(-) attachment and (2) narrowing of the initial distribution of Cl(-). The decrease in the initial yield of RH(2)(•+) at high CCl(4) concentration was well explained by immediate decomposition of CCl(4)(•+) to CCl(3)(+) and hole transfer from CCl(4)(•+) to adjacent RH(2) without diffusive motion of the reactants. Time-dependent density functional theory supported the spectroscopic assignment of intermediate species in the n-dodecane/CCl(4) system. The present results would be of help in understanding the electron capture reaction in multicomponent systems such as a chemically amplified resist in lithography.