Search

Donryu strain rats through two generations were fed semi-purified diets supplemented with safflower seed oil (rich in linoleic acid) or with perilla seed oil (rich in alpha-linolenic acid), or a conventional laboratory chow (normal control diet). Brightness-discrimination learning ability was determined to be the highest in the perilla oil-fed group, followed by the normal group, and then by the safflower group, extending our earlier observation in a different strain of rat that alpha-linolenic acid is a factor in maintaining high learning ability (Yamamoto, N., M. Saitoh, A. Moriuchi, M. Nomura, and H. Okuyama. 1987. J. Lipid Res. 28: 144-151). After the brightness-discrimination learning test was administered, extinction of learning was measured. The time required for extinction was significantly longer in the safflower group than in either the perilla group or the normal diet group. Thus, the dietary alpha-linolenate/linoleate balance affected both the learning and the extinction of learning. The glycolipids of the cerebrum, cerebellum, and olfactory lobe were analyzed. Although the fatty acid compositions of the sulfatide and gangliosides were significantly different in the three parts of the brain, relatively little difference was observed in the fatty acids of glycolipids between the safflower group and the perilla group, suggesting that gross changes in brain glycolipids are not responsible for the differences in learning abilities between these dietary groups.

Objectives: Although systemic chemotherapy for pancreatic ductal adenocarcinoma (PDAC) has made progress, ensuring long-term survival remains difficult. There are several reports on the usefulness of neutrophil-to-lymphocyte ratio (NLR) in predicting the prognosis of PDAC, but few reports in systemic chemotherapy. We hereby investigated the usefulness of NLR in systemic chemotherapy for PDAC., Materials and Methods: A retrospective study was conducted on patients with advanced PDAC treated with first-line systemic chemotherapy. Cox regression hazards models were performed to analyze the association between baseline patient characteristics and the initial treatment response, and overall survival (OS)., Results: A total of 60 patients with PDAC were enrolled. At baseline, there were significant differences in NLR and carbohydrate antigen 19-9 (CA19-9), as well as the selection rate of combination chemotherapy, between patients with partial response or stable disease and those with progressive disease. Univariate and multivariate analysis showed that NLR < 3.10, combination chemotherapy, and CA19-9 < 1011 U/mL were significant and independent predictive factors of the initial treatment response. Meanwhile, NLR < 3.10 and combination chemotherapy were independently associated with longer OS. Moreover, OS was significantly prolonged in patients with NLR < 3.10, regardless of whether combination chemotherapy or monotherapy. Patients with NLR < 3.10 at baseline had a significantly higher conversion rate to third-line chemotherapy and a longer duration of total chemotherapy., Conclusions: This study suggests that NLR may be a useful marker for predicting the initial treatment response to first-line chemotherapy and the prognosis for patients with advanced PDAC.

Background/objectives: Clinical responses to naldemedine vary between individuals with advanced cancer. This is a prospective, single-center, observational study aimed to evaluate the influence of genetic polymorphisms and cachexia status on plasma naldemedine and clinical responses., Methods: Forty-eight patients being treated with naldemedine for opioid-induced constipation under treatment of cancer pain were enrolled. Plasma naldemedine concentrations were determined on the fourth day or later after administration of naldemedine, and the associations with genotypes, cachexia status, and clinical responses were assessed., Results: Cancer patients exhibited a large variation in the plasma naldemedine concentrations, and it was correlated with serum total protein level. Patients who were homozygous CYP3A5*3 had a higher plasma concentration of naldemedine than those with the *1 allele. ABCB1 genotypes tested in this study were not associated with plasma naldemedine. A negative correlation was observed between the plasma naldemedine concentration and 4β-hydroxycholesterol level. The plasma naldemedine concentration was lower in patients with refractory cachexia than in those with precachexia and cachexia. While serum levels of interleukin-6 (IL-6) and acute-phase proteins were higher in patients with refractory cachexia, they were not associated with plasma naldemedine. A higher plasma concentration of naldemedine, CYP3A5*3/*3, and an earlier naldemedine administration after starting opioid analgesics were related to improvement of bowel movements., Conclusion: Plasma naldemedine increased under deficient activity of CYP3A5 in cancer patients. Cachectic patients with a higher serum IL-6 had a lower plasma naldemedine. Plasma naldemedine, related to CYP3A5 genotype, and the initiation timing of naldemedine were associated with improved bowel movements., (© 2024 The Authors. Fundamental & Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of Société Française de Pharmacologie et de Thérapeutique.)

Two units of highly stable luminescent triarylmethyl radical, (3,5-dichloro-4-pyridyl)bis(2,4,6-trichlorophenyl)methyl radical (PyBTM), were bridged by p-phenylene linker. The photoluminescence quantum yield (PLQY) of PyBTM-PhPyBTM was at most 0.4 % in various organic solvents. Adding two mesityl groups on the terminals did not improve the PLQY. In the MesPyBTM-PhPyBTM-Mes, the mesityl group did not worked as an electron donor unlike the previously reported monoradical MesPyBTM. However, adding two n-hexyl groups on the bridging p-phenylene did greatly improve it, and the PLQY of the PyBTM-(Hex 2 Ph)PyBTM was 7 % in dichloromethane and acetone, and 12 % in poly(methyl methacrylate) (PMMA) film. Twisting p-phenylene linker by hexyl groups hindered the π-conjugation and suppressed the non-radiative decay of the excited state., (© 2024 Wiley‐VCH GmbH.)

Background: Median arcuate ligament compression syndrome (MALS) causes upper abdominal pain and at times hemodynamic abnormalities in the pancreaticoduodenal region. Herein, we present a case of a 70 year-old man, initially diagnosed with splenic infarction and was successfully treated laparoscopically., Case Presentation: A 70-year-old man with abdominal pain admitted to our hospital. Abdominal-enhanced computed tomography revealed a poorly contrasted area in the spleen and stenosis at the root of the celiac artery. Arterial dilatation was observed around the pancreaticoduodenal arcade, however, no obvious aneurysm formation or arterial dissection was observed. Abdominal-enhanced magnetic resonance imaging indicated the disappearance of the flow void at the root of the celiac artery. The patient had no history of atrial fibrillation and was diagnosed with splenic infarction due to median arcuate ligament compression syndrome. We performed a laparoscopic median arcuate ligament section with five ports. Intraoperative ultrasonography showed a retrograde blood flow in the common hepatic artery and the celiac artery. After releasing the compression, the antegrade blood flow from the celiac artery to the splenic artery, and the common hepatic artery were visualized using intraoperative ultrasonography. The postoperative course of the patient was uneventful, and he was discharged on postoperative day 9. Postoperative computed tomography a month after surgery revealed no residual stenosis of the celiac artery or dilation of the pancreaticoduodenal arcade. Furthermore, the poorly contrasted area of the spleen improved., Conclusions: Reports indicate that hemodynamic changes in the abdominal visceral arteries due to median arcuate ligament compression are related to the formation of pancreaticoduodenal aneurysms. In this case, median arcuate ligament compression syndrome caused splenic infarction by reducing blood flow to the splenic artery., (© 2024. The Author(s).)

Tenascin C (TNC) is an extracellular matrix glycoprotein that is highly expressed in cancer stroma and is associated with tumor progression in pancreatic adenocarcinoma (PAAD). In this study, we aimed to investigate the potential involvement of TNC in the response to immune checkpoint inhibitors (ICI) among PAAD patients. Transcriptomic profiles were obtained from public databases and analyzed to compare TNC mRNA levels between tumor and normal tissues. Bioinformatic programs were used to predict paracrine communications between cancer cells and cancer-associated fibroblasts (CAFs), and the Tumor Immune Dysfunction and Exclusion (TIDE) score was calculated to predict response to ICI treatment in PAAD patients. An independent immunotherapeutic cohort was used to validate the clinical impact of the signatures. Results showed that TNC mRNA levels were significantly upregulated in tumors compared to normal tissues in PAAD, and patients with high TNC expression had significantly shorter overall survival than those with low TNC expression (P = 0.0125). TNC was predominantly expressed in CAFs of PAAD patients and was found to potentially enhance the epithelial-mesenchymal transition (EMT) of cancer cells via integrin receptors, contributing to resistance to ICI treatment. Patients with high TNC expression and high ITGαV or ITGB3 expression were associated with poor response to ICI therapy. In conclusion, these findings suggest that TNC -high CAFs play a crucial role in tumor progression and resistance to ICI therapy in PAAD patients, and targeting TNC and its interactions with cancer cells may provide a potential strategy for improving the efficacy of ICI therapy in PAAD., Competing Interests: None., (AJCR Copyright © 2023.)

Background: The usefulness of static monitoring using central venous pressure has been reported for anesthetic management in hepatectomy. It is unclear whether intra-hepatectomy dynamic monitoring can predict the postoperative course. We aimed to investigate the association between intraoperative dynamic monitoring and post-hepatectomy complications. Furthermore, we propose a novel anesthetic management strategy to reduce postoperative complication., Methods: From 2018 to 2021, 93 patients underwent hepatectomy at our hospital. Fifty-three patients who underwent dynamic monitoring during hepatectomy were enrolled. Flo Trac system was used for dynamic monitoring. The baseline central venous oxygen saturation (ScvO 2 ) was defined as the average ScvO 2 for 30 min after anesthesia induction. ScvO 2 fluctuation (ΔScvO 2 ) was defined as the difference between the baseline and minimum ScvO 2 . Postoperative complications were evaluated using the comprehensive complication index (CCI)., Results: Patients with ΔScvO 2  ≥ 10% had significantly higher CCI scores (0 vs. 20.9: p = 0.043). In univariate analysis, patients with higher CCI scores demonstrated significantly higher preoperative C-reactive protein-to-lymphocyte ratio (7.51 vs. 24.49: p = 0.039), intraoperative bleeding (105 vs. 581 ml: p = 0.008), number of patients with major hepatectomy (4/45 vs. 3/8: p = 0.028), and number of patients with ΔScvO 2  ≥ 10% (11/45 vs. 6/8; p = 0.010). Multivariate logistic regression analysis revealed that ΔScvO 2  ≥ 10% (odds ratio: 9.53, p = 0.016) was the only independent predictor of elevated CCI., Conclusions: Central venous oxygen saturation fluctuation during hepatectomy is a predictor of postoperative complications. Anesthetic management based on intraoperative dynamic monitoring and minimizing the change in ScvO 2 is a potential strategy for decreasing the risk of post-hepatectomy complications., (© 2023. The Author(s).)

Background: Pseudoaneurysm (PA) rupture after pancreaticoduodenectomy (PD) is a life-threatening complication. Most PA cases originate from postoperative pancreatic fistulas (POPFs). Although several risk factors for POPF have been identified, specific risk factors for PA formation remain unclear. Therefore, we retrospectively analyzed PD cases with soft pancreas and proposed a novel strategy for early detection of PA formation., Methods: Overall, 120 patients underwent PD between 2010 and 2020 at our institution; of these, 65 patients with soft pancreas were enrolled. We evaluated the clinicopathological factors influencing PA formation and developed a risk score to predict PA formation., Results: In total, 11 of the 65 patients developed PAs (PA formation group: PAG), and 8 of these 11 PAs ruptured. The median time to PA formation was 15 days, with a minimum of 5 days. The PAG was significantly older than the non-PA formation group, were predominantly men, and had comorbid diabetes mellitus. Pre- and intra-operative findings were similar between the two groups. Importantly, no significant differences were found in postoperative drain amylase levels and total drain amylase content. Cholinesterase and C-reactive protein (CRP) levels on postoperative day (POD) 3 were significantly different between the two groups. Multivariate analysis showed that cholinesterase ≤ 112 U/L and CRP ≥ 16.0 mg/dl on POD 3 were independent predictors of PA formation., Conclusions: Decreased cholinesterase and elevated CRP on POD 3 (Cho-C score) are useful predictors of PA formation in cases with soft pancreas. In such cases, periodic computed tomography evaluations and strict drain management are necessary to prevent life-threatening hemorrhage., (© 2023. The Author(s).)

Background: Owing to the lack of definite diagnostic modalities, it is challenging to distinguish malignant cases of cholangiocarcinoma (CCA), which often causes biliary tract obstruction, from benign ones. Here, we investigated a novel lipid biomarker of CCA in bile-derived small extracellular vesicles (sEVs) and developed a simple detection method for clinical application., Methods: Bile samples from seven patients with malignant diseases (hilar CCA = 4, distal CCA = 3) and eight patients with benign diseases (gallstones = 6, primary sclerosing cholangitis = 1, autoimmune pancreatitis = 1) were collected through a nasal biliary drainage tube. sEVs were isolated via serial ultracentrifugation and characterized using nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting (with CD9, CD63, CD81, and TSG101). Comprehensive lipidomic analysis was performed using liquid chromatography-tandem mass spectrometry. Using a measurement kit, we further confirmed whether lipid concentrations could be used as a potential CCA marker., Results: Lipidomic analysis of bile sEVs in the two groups identified 209 significantly increased lipid species in the malignant group. When focusing on lipid class, phosphatidylcholine (PC) level was 4.98-fold higher in the malignant group than in the benign group (P = 0.037). The receiver operating characteristic (ROC) curve showed a sensitivity of 71.4%, a specificity of 100%, and an area under the curve (AUC) of 0.857 (95% confidence interval [CI]:0.643-1.000). Using a PC assay kit, the ROC curve showed a cutoff value of 16.1 μg/mL, a sensitivity of 71.4%, a specificity of 100%, and an AUC of 0.839 (95% CI: 0.620-1.000)., Conclusion: PC level in sEVs from human bile is a potential diagnostic marker for CCA and can be assessed by a commercially available assay kit., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Donor-radical acceptor systems have recently attracted much attention as efficient doublet emitters that offer significant advantages for applications such as OLEDs. We employed an alkylbenzene (mesityl group) as the simplest donor to date and added it to a diphenylpyridylmethyl radical acceptor. The (3,5-difluoro-4-pyridyl)bis[2,6-dichloro-4-(2,4,6-trimethylphenyl)phenyl]methyl radical (Mes 2 F 2 PyBTM) was prepared in only three steps from commercially available reagents. A stable radical composed of only one pyridine ring, four benzene rings, methyl groups, halogens, and hydrogens showed fluorescence of over 60% photoluminescence quantum yield (PLQY) in chloroform, dichloromethane, and PMMA. The key to high fluorescence efficiency was benzene rings perpendicular to the diphenylpyridylmethyl radical in the doublet ground (D 0 ) state. The relatively low energy of the β -HOMO and the electron-accepting character of the radical enabled the use of benzenes as electron donors. Furthermore, the structural relaxation of the doublet lowest excited (D 1 ) state was minimized by steric hindrance of the methyl groups. The reasons for this high efficiency include the relatively fast fluorescence transition and the slow internal conversion, both of which were explained by the overlap density between the D 1 and D 0 states., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The western conifer seed bug (WCSB, Leptoglossus occidentalis) is a pest of many pine species and is invasive worldwide. WCSB directly and indirectly deteriorates pine nut production by sucking seeds from cones. Currently, researchers think that WCSBs search for food by a combination of cues from visible light, infrared radiation, and chemicals such as monoterpenes. Some research revealed that WCSBs prefer larger cones, and it was thought that WCSBs suck seeds from and obtain more heat on larger cones. However, in early spring, we observed that most WCSBs gathered on male cones rather than on female cones and young cones. We hypothesized that male pine cones were warmer than female cones and needles, and WCSBs sucking male cones may receive more heat. To test these hypotheses, we measured spectral reflectance with a hyperspectral sensor and temperature of pine organs with tiny thermocouples, and the data were analyzed by a heat budget model. Our results revealed that male cones were significantly warmer and more reflective than female cones and needles, which may attract WCSBs. These results supported our hypothesis that WCSBs on male cones were warmer than those on other organs. This study will help further understanding of WCSBs and the adaptive value of pine cone colors., Competing Interests: The authors have declared that no competing interests exist.

Background: Staphylococcus hominis (S. hominis) is an opportunistic pathogen that is often highly resistant to antibiotics and is difficult to treat. In patients diagnosed with an adrenocorticotropic hormone (ACTH)-producing tumor that compromises the immune system due to hypercortisolemia, cancer treatment and infection control should be considered simultaneously. This report presents a case of refractory postoperative S. hominis bacteremia requiring the prolonged administration of several antibiotics in a patient with an ACTH-producing pancreatic neuroendocrine neoplasm (pNEN)., Case Presentation: A 35-year-old man visited a neighboring hospital for a thorough examination after experiencing weight gain and lower limb weakness for several months. Enhanced computed tomography revealed a pancreatic tail tumor and bilateral adrenal enlargement. Elevated plasma ACTH and serum cortisol were noted. Biopsy under endoscopic ultrasonography revealed the tumor as an ACTH-producing pNEN. The patient was transferred to our hospital for further treatment. Pneumocystis pneumonia was noted and treated with sulfamethoxazole and adjunctive glucocorticoids. Hypercortisolism was controlled with metyrapone and trilostane. Somatostatin receptor scintigraphy and ethoxybenzyl magnetic resonance imaging detected other lesions in the pancreatic head. A total pancreatectomy was performed given that the lesions were found in both the pancreatic head and tail. Plasma ACTH and serum cortisol levels decreased immediately after the resection. Pathological examination revealed that the pancreatic tail tumor was NEN G2 and T3N1aM0 Stage IIB and the pancreatic head lesions were SSTR-positive hyperplasia of the islet of Langerhans cells. On postoperative day 11, catheter-associated bacteremia occurred. Initially, meropenem hydrate and vancomycin hydrochloride were administered empirically. S. hominis was identified and appeared sensitive to these antibiotics according to susceptibility testing. However, S. hominis was repeatedly positive in blood cultures for more than one month, despite treatment with several antibiotics. Eventually, with the combined use of three antibiotics (meropenem hydrate, vancomycin hydrochloride, and clindamycin phosphate) for more than 3 weeks, the S. hominis-associated bacteremia improved. He was discharged 79 days after surgery., Conclusions: Our patient with an ACTH-producing pNEN was immunocompromised and needed meticulous attention for infectious complications even after successful tumor removal. Specifically, S. hominis bacteremia in such patients demands intensive treatments, such as with combinational antibiotics., (© 2022. The Author(s).)

Background: Various hemostatic devices have been utilized to reduce blood loss during hepatectomy. Nonetheless, a comparison between monopolar and bipolar coagulation, particularly their usefulness or inferiority, has been poorly documented. The aim of this study is to reveal the characteristics of these hemostatic devices., Methods: A total of 264 patients who underwent open hepatectomy at our institution from January 2009 to December 2018 were included. Monopolar and bipolar hemostatic devices were used in 160 (monopolar group) and 104 (bipolar group) cases, respectively. Operative outcomes and thermal damage to the resected specimens were compared between these groups using propensity score matching according to background factors. Multivariate logistic regression analysis was performed to identify predictive factors for postoperative complications., Results: After propensity score matching, 73 patients per group were enrolled. The monopolar group had significantly lower total operative time (239 vs. 275 min; P = 0.013) and intraoperative blood loss (487 vs. 790 mL; P < 0.001). However, the incidence rates of ascites (27.4% vs. 8.2%; P = 0.002) and grade ≥ 3 intra-abdominal infection (12.3% vs. 2.7%; P = 0.028) were significantly higher in the monopolar group. Thermal damage to the resected specimens was significantly longer in the monopolar group (4.6 vs. 1.2 mm; P < 0.001). Use of monopolar hemostatic device was an independent risk factor for ascites (odds ratio, 5.626, 95% confidence interval 1.881-16.827; P = 0.002) and severe intra-abdominal infection (odds ratio, 5.905, 95% confidence interval 1.096-31.825; P = 0.039)., Conclusions: Although monopolar devices have an excellent hemostatic ability, they might damage the remnant liver. The use of monopolar devices can be one of the factors that increase the frequency of complications., (© 2022. The Author(s).)

The luminescence of stable radicals can be enhanced by coordination to metal complexes. The 4% fluorescence quantum yield of (3,5-difluoro-4-pyridyl)bis(2,4,6-trichlorophenyl)methyl radical (F 2 PyBTM) in dichloromethane was enhanced up to 36% by coordination to Au I with N -heterocyclic carbene ligand, which is a record for metal-radical complexes.

Background/objective: Pancreaticoduodenectomy (PD) is highly invasive with unsatisfactory postoperative complication rates. Nutritional and fluid management after major surgery attracts much attention with regard to the reduction in severe postoperative complications. We retrospectively analyzed PD cases and proposed a novel strategy for perioperative fluid and nutritional therapy according to the risk stratification by pancreatic fistula (PF) and delayed gastric emptying (DGE)., Methods: Between 2003 and 2018, 140 patients underwent PD at our institute of which 134 patients were enrolled. We evaluated the clinicopathological factors affecting severe (≥10%) body weight loss (BWL), factors affecting the incidence of PF and intraabdominal complications (IAC), and factors related to DGE., Results: Multivariate analysis indicated that male sex, severe PF, and DGE are significant risk factors for BWL ≥10%. PF and IAC were predominantly observed in male patients and those with non-pancreatic cancer. A fluid balance ≥6000 ml on postoperative day 2 was the sole risk factor for primary DGE. Secondary DGE significantly correlated with stomach preserving PD. Importantly, the average BWL was around 15% in grade B or C secondary DGE., Conclusion: Severe postoperative complications resulted in significant BWL. Enteral feeding is unnecessary in cases with a hard pancreas and dilated pancreatic duct if appropriate perioperative fluid management is performed. Secondary DGE followed by PF or IAC is unavoidable to some extent, especially in the case of soft pancreas with a fine pancreatic duct. In such cases, enteral feeding with tube ileostomy should be considered, and stomach preserving PD is likely to be harmful., Competing Interests: Declaration of competing interest None., (Copyright © 2021. Published by Elsevier Taiwan LLC.)

Objective: In the diabetes treatment policy after the Kumamoto Declaration 2013, it is difficult to accurately predict the incidence of complications in patients using the JJ risk engine. This study was conducted to develop a prediction equation suitable for the current diabetes treatment policy using patient data from Kitasato University Kitasato Institute Hospital (Hospital A) and to externally validate the developed equation using patient data from Kitasato University Hospital (Hospital B). Outlier tests were performed on the patient data from Hospital A to exclude the outliers. Prediction equation was developed using the patient data excluding the outliers and was subjected to external validation., Results: By excluding outlier data, we could develop a new prediction equation for the incidence of coronary heart disease (CHD) as a complication of type 2 diabetes, incorporating the use of antidiabetic drugs with a high risk of hypoglycemia. This is the first prediction equation in Japan that incorporates the use of antidiabetic drugs. We believe that it will be useful in preventive medicine for treatment for people at high risk of CHD as a complication of diabetes or other diseases. In the future, we would like to confirm the accuracy of this equation at other facilities., (© 2021. The Author(s).)

Background: Pancreatic juice is constantly activated by contaminated bile in patients with pancreaticobiliary maljunction (PBM). Here, we report a case of laparoscopic distal pancreatectomy for a patient with PBM and sphincterotomized papilla, resulting in fatal pancreatic fistula., Case Presentation: A 79-year-old man was diagnosed with pancreatic intraductal papillary mucinous neoplasm and common bile duct stones. Endoscopic sphincterotomy was performed prior to surgery. The pancreatic duct was simultaneously visualized when the contrast agent was injected into the common bile duct. Sudden bleeding was observed from the abdominal drain on postoperative day (POD) 6. Emergent stent graft placement and coil embolization were performed for bleeding from the splenic artery. On POD 9, the drainage fluid changed to yellowish in color with bile contamination. For internal drainage of the digestive fluid, endoscopic retrograde biliary tube and pancreatic drainage tube were placed. On POD 24, second emergent coil embolization was performed for bleeding from the left gastric artery. On POD 25, open abdominal drainage was performed. On POD 32, third emergent coil embolization was performed for bleeding from the gastroduodenal artery. Subsequently, remnant pancreatic resection was performed. On POD 39, massive bleeding was again observed from the abdominal drain. Emergency arterial portography revealed bleeding in the right wall of the superior mesenteric vein. The patient died of hemorrhagic shock on the same day., Conclusions: The extreme risk of severe pancreatic fistula after distal pancreatectomy should be considered in patients with PBM and sphincterotomized papilla. In this extraordinary situation, surgeons should promptly decide whether to resect the remnant pancreas to prevent losing the patient., (© 2021. The Author(s).)

Background/aim: We sought to identify the mechanisms of perineural invasion in pancreatic ductal adenocarcinoma (PDAC)., Materials and Methods: We utilized in vitro cancer cell-nerve co-culture models comprising human PDAC cell lines (MIA Paca2 and PANC-1) and a dorsal root ganglion (DRG) isolated from neonatal mice. We compared gene expression profiles between cell lines with/without DRG conditioned medium (DRG-CM) using RNA-sequencing (RNA-seq)., Results: Migration, invasion, and neurotropism were significantly enhanced in MIA Paca2 but not in PANC-1 cells co-cultured with DRGs. Among 285 genes which showed significant differences in expression levels between cell lines in RNA-seq, we focused on Ephrin receptor A4 (EPHA4), which was upregulated in MIA Paca2 cells treated with DRG-CM. The abilities of migration, invasion, and neurotropism enhanced by DRG co-culture were abolished when EPHA4 was knocked down by siRNA in MIA Paca2 cells., Conclusion: EPHA4 can be a potential target gene to regulate perineural invasion in PDAC cells.

Objective: In 2018, we conducted a retrospective survey using the medical records of 484 patients with type 2 diabetes. The observed value of coronary heart disease (CHD) incidence after 5 years and the predicted value by the JJ risk engine as of 2013 were compared and verified using the discrimination and calibration values., Results: Among the total cases analyzed, the C-statistic was 0.588, and the calibration was p < 0.05; thus, the JJ risk engine could not correctly predict the risk of CHD. However, in the group expected to have a low frequency of hypoglycemia, the C-statistic was 0.646; the predictability of the JJ risk engine was relatively accurate. Therefore, it is difficult to accurately predict the complication rate of patients using the JJ risk engine based on the diabetes treatment policy after the Kumamoto Declaration 2013. The JJ risk engine has several input items (variables), and it is difficult to satisfy them all unless the environment is well-equipped with testing facilities, such as a university hospital. Therefore, it is necessary to create a new risk engine that requires fewer input items than the JJ risk engine and is applicable to several patients.

Background: We sought to identify the risk factors of totally implantable central venous access port (TICVAP)-related infections in patients with malignant disease., Patients and Methods: Overall, 324 consecutive patients who received a TICVAP at our institution were retrospectively analysed. We further analysed cases of TICVAP-related complications. The risk factors for TICVAP-related infection were investigated using Cox regression hazard models., Results: With a median TICVAP duration of 268 days (range=1-1,859 days), TICVAP-related complications were observed in 36 cases and infectious complications in late phase were the most common, seen in 19 cases (9.26%). A multivariate analysis showed that patients with head and neck malignancy (p<0.001) and patients who received TICVAP insertion in the upper arm (p<0.001) were independently at a higher risk for TICVAP-related infections., Conclusion: Patients with head and neck malignancy or TICVAP insertion in the upper arm have potentially increased risk for late-phase TICVAP-related infections., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Choroidal malignant melanoma is the most common primary malignant tumor of the eye in adults. Prognosis after recurrence of this disease has been dismal because of the absence of an effective therapy. However, resection of recurrent foci and a subsequent treatment with immune-checkpoint inhibitor may improve the prognosis after recurrence of this disease. This study presents a case of late-onset liver metastases of choroidal malignant melanoma, successfully treated with hepatectomy and postoperative adjuvant nivolumab., Case Presentation: A 53-year-old woman had undergone left ocular enucleation because of choroidal malignant melanoma 13 years prior to admission. She visited a nearby clinic with complaints of epigastric pain. She was referred to our hospital because a giant liver tumor was observed on abdominal ultrasonography. Enhanced computed tomography revealed multiple liver tumors in the right lobe, 49 mm in diameter with ring enhancement in subsegment (S) 5/6, and 14 and 8 mm without any enhancement in S7 and S5, respectively. On magnetic resonance imaging, the main tumor showed high intensity on T1-weighted with fat suppression, suggesting melanin deposition. Based on the diagnosis of multiple liver metastases of choroidal malignant melanoma, right hepatectomy and regional lymphadenectomy were performed. She was discharged without postoperative complications. Histological examination revealed that all tumors were metastatic malignant melanoma. She was treated with nivolumab postoperatively, and no recurrences were observed during 22 months of follow-up., Conclusions: Aggressive surgery plus adjuvant nivolumab appears to be a promising treatment for choroidal malignant melanoma with late-onset liver metastases.

Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein which stimulates the proliferation, differentiation, and functional activation of myeloid hematopoietic cells. G-CSF-producing pancreatic cancer is rare and its prognosis is strikingly poor. A 69-year-old woman with well-to-moderately differentiated ductal adenocarcinoma (pT3N0M0, stage IIA) underwent distal pancreatectomy and splenectomy. Postoperative adjuvant chemotherapy with S-1 was administered for 6 months. Eleven months after surgery, periodic blood examination revealed remarkable leukocytosis (19,120/µL) without fever, which worsened 3 weeks later (36,160/µL). Furthermore, laboratory data showed elevation of the fibrin degradation product-D dimer and that the G-CSF level was high (406 pg/mL), as well as thrombopenia. Multiple liver and lung metastases were detected by contrast-enhanced computed tomography (CT). The patient was treated with gemcitabine plus nab-paclitaxel, and heparin, thrombomodulin alfa, and platelet transfusion were administered concurrently. Leukocytosis and thrombopenia were alleviated after 1 course of chemotherapy. However, remarkable leukocytosis (53,480/µL) recurred on day 1 of the third course of chemotherapy. Contrast-enhanced CT showed a significantly increased number of liver metastases and lung metastases. The patient chose not to receive second-line chemotherapy and died 1 month later at the affiliated hospital. Pancreatic cancer producing G-CSF shows very aggressive behavior. Leukocytosis without infection during routine observation should be considered as a warning of a rapidly growing recurrence., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 by S. Karger AG, Basel.)

Commercially available powdered activated carbon (PAC) with a median diameter of 12-42 μm was ground into 1 μm sized superfine PAC (SPAC) and 200 nm sized submicron SPAC (SSPAC) and investigated as a pretreatment material for the prevention of hydraulically irreversible membrane fouling during a submerged microfiltration (MF) process. Compared with PAC and SPAC, SSPAC has a high capacity for selective biopolymer adsorption, which is a characteristic found in natural organic matter and is commonly considered to be a major contributor to membrane fouling. Precoating the membrane surface with SSPAC during batch filtration further removes the biopolymers by straining them out. In lab-scale membrane filtration experiments, an increase in the transmembrane pressure (TMP) was almost completely prevented through a precoating with SSPAC based on its pulse dose after coagulation pretreatment. The precoated SSPAC formed a dense layer on the membrane preventing biopolymers from attaching to the membrane. Coagulation pretreatment enabled the precoated activated carbon to be rinsed off during hydraulic backwashing. The functionality of the membrane was thereby retained for a long-term operation. Precoating the membranes with SSPAC after coagulation is a promising way to control membrane fouling, and efficiently prevents an increase in the TMP because of the straining effect of the SSPAC and the high capacity of the SSPAC to adsorb any existing biopolymers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Evolutionary developmental biology of our closest living relative, the chimpanzee (Pan troglodytes), is essential for understanding the origin of human traits. However, it is difficult to access developmental events in the chimpanzee in vivo because of technical and ethical restrictions. Induced pluripotent stem cells (iPSCs) offer an alternative in vitro model system to investigate developmental events by overcoming the limitations of in vivo study. Here, we generated chimpanzee iPSCs from adult skin fibroblasts and reconstructed early neural development using in vitro differentiation culture conditions. Chimpanzee iPSCs were established using straightforward methods, namely, lipofection of plasmid vectors carrying human reprogramming factors, combined with maintenance in a comprehensive feeder-free culture. Ultimately, direct neurosphere formation culture induced rapid and efficient differentiation of neural stem cells from chimpanzee iPSCs. Time course analysis of neurosphere formation demonstrated ontogenetic changes in gene expression profiles and developmental potency along an early neural development path from epiblasts to radial glia. Our iPSC culture system is a potent tool for investigating the molecular and cellular foundation underlying chimpanzee early neural development and better understanding of human brain evolution., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

To induce and maintain naïve pluripotency in mouse embryonic and induced pluripotent stem cells (ESCs/iPSCs), chemically defined N2B27 medium with PD0325901, CHIR99021, and leukemia inhibitory factor (2i/LIF) is a classic and simple condition. However, this method cannot be simply extrapolated to human ESCs/iPSCs that are principally stabilized in primed pluripotency and become primitive neuroepithelium-like cells in N2B27+2i/LIF culture. Here, we assessed iPSC reprogramming of fibroblasts from chimpanzee, our closest living relative, in N2B27+2i/LIF culture. Under this condition, chimpanzee cells formed alkaline phosphatase-positive dome-shaped colonies. The colony-forming cells could be stably expanded by serial passaging without a ROCK inhibitor. However, their gene expression was distinct from iPSCs and neuroepithelium. They expressed the OCT3/4 transgene and a subset of transcripts associated with pluripotency, mesenchymal-epithelial transition, and neural crest formation. These cells exhibited a differentiation potential into the three germ layers in vivo and in vitro. The current study demonstrated that iPSC reprogramming in N2B27+2i/LIF culture converted chimpanzee fibroblasts into a multipotent cancerous state with unique gene expression, but not fully pluripotent stem cells., Competing Interests: Declaration of competing interest H.O. is a Scientific Advisory Board Member of San Bio Co. Ltd. The other authors have no competing interests., (Copyright © 2020 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)

Hepatic angiomyolipoma (AML) is a rare stromal tumor composed of variable admixtures of thick-walled vessels, smooth muscles and adipose tissue. One of the specific radiological findings of hepatic AML is an early drainage vein noted via enhanced computed tomography (CT). We report a case of hepatic AML showing early drainage veins into both the hepatic and portal vein. The case involved a 46-year-old woman who was referred to our hospital because of a giant hepatic tumor. CT revealed well-enhanced 14 cm and 1 cm tumors in the left and right lobes, respectively. Magnetic resonance imaging demonstrated the existence of adipose tissues in the larger tumor. Hepatic arteriography revealed early drainage veins draining into both the hepatic and portal vein. Based on a diagnosis of hepatic AML, left hepatectomy and partial hepatectomy were performed. Pathology revealed both tumors as hepatic AML based on human melanoma black-45 immuno-positivity. Hepatic AML with early drainage veins into both the hepatic and portal vein is rare. The dilated and retrogressive vein drains the abundant arterial blood flow of the tumor. The finding of early drainage veins into not only the hepatic vein but also the portal vein should be helpful for diagnosing hepatic AMLs.

Background: Postoperative chemotherapy is beneficial for many pancreatic cancer patients. However, some patients require dose reduction or the discontinuation of adjuvant chemotherapy because of adverse treatment-related effects. In this study, we aimed to evaluate two main outcomes. First, we evaluated the clinicopathological factors affecting patient disease-free survival (DFS) and overall survival (OS) following upfront surgery. Second, we evaluated the factors that influence the continuity of adjuvant chemotherapy., Methods: Fifty-four patients with resected pancreatic cancer were enrolled. First, we evaluated the clinicopathological factors affecting postoperative survival using the Kaplan-Meier method and Cox regression method. Next, factors affecting the continuity of adjuvant chemotherapy were analyzed using multiple logistic regression analysis., Results: Univariate and multivariate analyses revealed that positive LN metastasis (HR (95% CI) 6.329 (2.381-16.95); p < 0.001) and relative dose intensity (RDI) < 80% for adjuvant chemotherapy (HR (95% CI) 5.154 (1.761-15.15); p = 0.003) were independent predictive factors for DFS. Regarding OS, extended dissection of the nerve plexus around the superior mesenteric artery (SMA) (HR (95% CI) 4.504 (1.721-11.76); p = 0.002), positive microscopic surgical margin (HR (95% CI) 5.565 (1.724-17.96); p = 0.004), and adjuvant chemotherapy of RDI < 80% (HR (95% CI) 3.534 (1.135-2.667); p = 0.029) were also independent predictive factors. Moreover, the level of RDI significantly correlated with DFS and OS. Multiple logistic regression analysis revealed that low RDI was significantly associated with postoperative body weight loss (BWL) ≥ 10%., Conclusions: The following factors were significantly associated with poor survival: extended dissection of the nerve plexus around the SMA, lymph node metastasis, residual tumor, and RDI of the adjuvant chemotherapy. Patient's prognosis with adjuvant chemotherapy of RDI < 80% was worse. BWL ≥10% was the most important factor affecting the continuity of adjuvant chemotherapy. Perioperative nutritional intervention is necessary for patients who receive adjuvant chemotherapy for advanced pancreatic cancer.

A 60-year-old female visited our hospital because of the identification of two duodenal tumors on upper gastrointestinal endoscopy performed for the investigation of anemia. The oral ampullary tumor was proven to be a neuroendocrine tumor (NET) on endoscopic biopsy. However, biopsy was not performed for the anal submucosal tumor (SMT) in the third duodenal portion because the tumor was included in the planned resection area. Multiple dermal soft tumors and café-au-lait spots were noted;her mother and daughter showed the same symptoms. The patient was diagnosed with neurofibromatosis type 1 (NF1). Laparotomy revealed more than 10 nodules at the serosal surface of the duodenum and proximal jejunum. Pancreaticoduodenectomy was performed with an additional 30-cm length of the jejunum that included most of the protruding tumors. Pathologically, the ampullary tumor and the other duodenal/jejunal SMTs were NET G2 and gastrointestinal stromal tumors (GISTs), respectively. Here, we report the rare case of simultaneous occurrence of an ampullary NET and multiple duodenal/jejunal GISTs in a patient with NF1.

Pancreatic cancer often invades the duodenum and causes obstruction, but rarely causes massive duodenal bleeding. A 68-year-old male was admitted to our hospital because of vomiting. Enhanced abdominal CT showed a hypovascular tumor with air bubbles in the uncinate process of the pancreas. The tumor invaded the duodenum and metastasized to the liver and peritoneum. The main trunk of the superior mesenteric artery (SMA) was circumferentially involved. After admission, he had hematemesis and melena. Emergency gastroduodenoscopy revealed pulsating vessels in the third portion of the duodenum and he eventually experienced hemorrhagic shock. Severe bleeding occurred from his mouth and anus like a catastrophic flood. It was difficult to sustain blood pressure even with massive blood transfusion with pumping. After insertion of an intra-aortic balloon occlusion catheter, the massive bleeding was eventually stopped. Although we attempted interventional radiography, aortography revealed direct communication between the main SMA trunk and the duodenal lumen. The tumor was considered anatomically and oncologically unresectable. Thus, we did not perform further intervention. The patient died 2 h after angiography. Herein, we report the case of pancreatic head cancer causing lethal bleeding associated with tumor-involved SMA. Duodenal bleeding associated with pancreatic cancer invasion should be considered as an oncogenic emergency.

Non-human primates are our closest relatives and are of special interest for ecological, evolutionary and biomedical research. The Japanese macaque (Macaca fuscata) has contributed to the progress of primatology and neurosciences over 60 years. Despite this importance, the molecular and cellular basis of the Japanese macaque remains unexplored since useful cellular tools are lacking. Here we generated induced pluripotent stem cells (iPSCs) from skin fibroblasts of the Japanese macaque with Sendai virus or plasmid vectors. The Japanese macaque iPSCs (jm-iPSCs) were established under feeder-free culture conditions, but feeder cells turned out to be essential for their maintenance. The jm-iPSCs formed human iPSC-like flat colonies which were positive for pluripotent antigens including alkaline phosphatase, SSEA4, and TRA-1-81. They also expressed endogenous OCT3/4, SOX2, L-MYC, and KLF4 and other pluripotent marker genes. The potential to differentiate into all three germ layers and neural stem cells was confirmed by embryoid body and neurosphere formation, respectively. The jm-iPSCs will provide a robust in vitro tool for investigating the underlying mechanisms of development and physiology studies with the Japanese macaque.

Pancreaticoduodenal artery (PDA) aneurysm associated with celiac axis compression by the median arcuate ligament (MAL) is a rare disorder, but may be lethal if ruptured. Therefore, prophylactic surgical treatments need to be considered when MAL compresses the celiac axis. We herein report the usefulness of an arterial flow analysis for objectively evaluating this pathophysiology under four-dimensional flow-sensitive magnetic resonance imaging (4D-flow MRI). Celiac artery stenosis was incidentally found under contrast-enhanced CT in a 50-year-old woman with symptomatic solitary pancreatic insulinoma. Under 4D-flow MRI, retrograde blood flow and aberrant wall shear stress were detected in the pancreaticoduodenal artery arcade. After obtaining informed consent, enucleation for insulinoma concomitant with MAL dissection was performed. Hypoglycemic attack completely resolved immediately after surgery. One month after surgery, 4D-flow MRI revealed normalized vectorial flow and wall shear stress in the PDA arcade without hypoglycemic attack. 4D-flow MRI is a very useful and non-invasive modality for objectively evaluating visceral artery hemodynamics.

A 76-year-old man who had been diagnosed with long-QT syndrome type 2 had frequent syncopal attacks. The electrocardiogram was monitored, and frequent torsades de pointes (TdP) was detected despite administration of conventional medications: oral propranolol, verapamil, intravenous magnesium sulfate, verapamil, and lidocaine. In contrast, 2 μg/kg/min landiolol could completely suppress TdP. Subsequently, an implantable cardioverter defibrillator was placed, and he was diagnosed with silent myocardial ischemia using myocardial perfusion scintigraphy and coronary angiography. This is the first case report wherein landiolol effectively suppressed TdP due to long-QT syndrome with silent myocardial ischemia.

The above article from Human Psychopharmacology, first published on 25 January 2012 in Wiley OnlineLibrary (onlinelibrary.wiley.com), and in Volume 90, pp. 90-100, has been retracted by agreement between the authors, the journal Editor in Chief, David Baldwin, and John Wiley & Sons Ltd. The retraction has been agreed following an investigation by the St Marianna University Ethics Committee which determined that the paper was not as originally designed and approved., References: Tenjin, T., Miyamoto, S., Miyake, N., Ogino, S., Kitajima, R., Ojima, K., … Yamaguchi, N. (2012). Effect of blonanserin on cognitive function in antipsychotic-naïve first-episode schizophrenia. Hum. Psychopharmacol Clin Exp, 27, 90-100. https://doi.org/10.1002/hup.1276., (Copyright © 2017 John Wiley & Sons, Ltd.)

Recurrent congestive heart failure related to renal artery disease is an important clinical entity that is typically observed in bilateral renal artery stenosis or solitary functioning kidney. However, the relationship between heart failure and unilateral renal artery disease, especially that with total occlusion, remains unclear. We report a successful management by unilateral renal artery total occlusion stenting with an evidence of improvement of left ventricular filling and pulmonary artery pressure in case of a patient suffering from medical therapy resistant recurrent congestive heart failure with preserved ejection fraction.

Mammalian spermatogenesis has been investigated extensively in rodents and a strictly controlled developmental process has been defined at cellular and molecular levels. In comparison, primate spermatogenesis has been far less well characterized. However, important differences between primate and rodent spermatogenesis are emerging so it is not always accurate to extrapolate findings in rodents to primate systems. Here, we performed an extensive immunofluorescence study of spermatogenesis in neonatal, juvenile, and adult testes in the common marmoset (Callithrix jacchus) to determine primate-specific patterns of gene expression that underpin primate germ cell development. Initially we characterized adult spermatogonia into two main classes; mitotically active C-KIT(+)Ki67(+) cells and mitotically quiescent SALL4(+)PLZF(+)LIN28(+)DPPA4(+) cells. We then explored the expression of a set of markers, including PIWIL1/MARWI, VASA, DAZL, CLGN, RanBPM, SYCP1 and HAPRIN, during germ cell differentiation from early spermatocytes through round and elongating spermatids, and a clear program of gene expression changes was determined as development proceeded. We then examined the juvenile marmoset testis. Markers of gonocytes demonstrated two populations; one that migrates to the basal membrane where they form the SALL4(+) or C-KIT(+) spermatogonia, and another that remains in the lumen of the seminiferous tubule. This later population, historically identified as pre-spermatogonia, expressed meiotic and apoptotic markers and were eliminated because they appear to have failed to correctly migrate. Our findings provide the first platform of gene expression dynamics in adult and developing germ cells of the common marmoset. Although we have characterized a limited number of genes, these results will facilitate primate spermatogenesis research and understanding of human reproduction., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Thioredoxin (TRX) is a redox regulating protein which has protective effects against oxidative stress-induced damage to cells and tissues. In this study, we investigated the effects of orally administered TRX derived from edible yeast, Saccharomyces cerevisiae, on gastric mucosa. First, we examined the digestibility of orally administered yeast TRX in mice, and detected yeast TRX in the stomach for 4 h after administration. Next, we investigated the mitigation of gastric mucosal injury after the oral administration of yeast TRX in water-immersion restraint stress and HCl/ethanol-induced gastric ulcer models. Furthermore, we conducted DNA microarray analysis, using the HCl/ethanol-induced model, which revealed that several groups of genes related to tissue repair were upregulated in ulcer regions in the stomachs of rats administered with yeast TRX. These results demonstrated the viability of the use of oral administrations of yeast TRX to protect the gastric mucosa.

Blonanserin was developed as an antipsychotic drug in Japan and approved for the treatment of schizophrenia. It belongs to a series of 4-phenyl-2-(1-piperazinyl)pyridines and acts as an antagonist at dopamine D2, D3, and serotonin 5-HT2A receptors. Blonanserin has low affinity for 5-HT2C, adrenergic α1, histamine H1, and muscarinic M1 receptors, but displays relatively high affinity for 5-HT6 receptors. In several short-term double-blind clinical trials, blonanserin had equal efficacy as haloperidol and risperidone for positive symptoms in patients with chronic schizophrenia and was also superior to haloperidol for improving negative symptoms. Blonanserin is generally well tolerated and has a low propensity to cause metabolic side effects and prolactin elevation. We recently reported that blonanserin can improve some types of cognitive function associated with prefrontal cortical function in patients with first-episode and chronic schizophrenia. Taken together, these results suggest that blonanserin may be a promising candidate for a first-line antipsychotic for acute and maintenance therapy for schizophrenia. Further comparative studies are warranted to clarify the benefit/risk profile of blonanserin and its role in the treatment of schizophrenia.

Background: The high use of long-term benzodiazepines (BZDs) with second-generation antipsychotics (SGAs) has been identified as an important issue in the treatment of schizophrenia in Japan. The aim of this study was to evaluate the effects of gradual reduction or discontinuation of daytime BZD use on cognitive function and quality of life (QOL) in patients with chronic schizophrenia receiving an SGA., Methods: Thirty schizophrenic patients who had received an SGA with concomitant BZDs for at least 3 months were enrolled. Before and 4 weeks after tapering of daytime BZDs, the Brief Assessment of Cognition in Schizophrenia Japanese-language version (BACS-J) and the Schizophrenia Quality of Life Scale Japanese-language version (SQLS-J) were administered. Clinical evaluation also included the Positive and Negative Syndrome Scale (PANSS). To compare for practice effects on the BACS-J, 10 patients with chronic schizophrenia were assessed without tapering BZDs., Results: BZDs were reduced or discontinued safely in most patients, and no emergent withdrawal symptoms were observed. Significant improvements were shown in verbal memory, working memory, and composite score, as measured by the BACS-J without practice effects. In addition, the motivation/energy score on the SQLS-J, the negative symptoms and total scores on the PANSS significantly improved after tapering BZDs., Conclusion: Reduction or discontinuation of long-term daytime use of BZDs may be warranted in patients with schizophrenia treated with SGAs, as it may improve cognitive function, subjective QOL, and psychiatric symptoms with no significant adverse effects., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to evaluate the effects of blonanserin, a novel antipsychotic, on cognitive function in first-episode schizophrenia., Methods: Twenty-four antipsychotic-naïve patients with first-episode schizophrenia participated in the study. Blonanserin was given in an open-label design for 8 weeks. The Brief Assessment of Cognition in Schizophrenia-Japanese language version (BACS-J) was administered as the primary outcome measure at baseline and 8 weeks. Clinical evaluation included the Positive and Negative Syndrome Scale (PANSS), the Schizophrenia Quality of Life Scale-Japanese language version (SQLS-J), and the Clinical Global Impression-Severity of Illness Scale (CGI-S). To exclude the possibility of retest effects on the BACS-J, 10 age-matched patients with chronic schizophrenia treated with blonanserin were tested at baseline and after an 8-week interval., Results: Twenty first-episode patients completed the study. Repeated measures analysis of covariance revealed a significant group-by-time interaction effect on the letter fluency task due to better performance in the first-episode group, but not in the control group. Main effect of time or group-by-time interaction effect on the Tower of London task was not significant; however, the first-episode group, but not the control group, showed substantial improvement with a moderate effect size. All items on the PANSS, SQLS-J, and CGI-S significantly improved after 8 weeks of treatment., Conclusions: These results suggest that blonanserin improves some types of cognitive function associated with prefrontal cortical function., (Copyright © 2012 John Wiley & Sons, Ltd.)

Background: The high use of long-term antiparkinsonian anticholinergic drugs with antipsychotics has been identified as an important issue in the treatment of schizophrenia in Japan. The aim of this study was to evaluate the effects of gradual discontinuation of biperiden, an anticholinergic drug, on cognitive function and quality of life (QOL) in schizophrenia., Methods: Thirty-four schizophrenic patients who had received a second-generation antipsychotic (SGA) with concomitant biperiden for at least 3 months were enrolled. Before and 4 weeks after discontinuation of biperiden, the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS-J) and the Schizophrenia Quality of Life Scale (SQLS-J) were administered. Clinical evaluation also included the Positive and Negative Syndrome Scale (PANSS). To compare the practice effect on BACS-J, 10 chronic patients with schizophrenia were assessed without tapering biperiden., Results: Biperiden was discontinued safely in most patients, and no emergent extrapyramidal symptoms were observed. Significant improvements were shown in attention, processing speed, and composite score, as measured by the BACS-J without practice effect. In addition, the psychosocial condition score on the SQLS-J and the general psychopathology score on the PANSS significantly improved after biperiden discontinuation., Conclusion: Discontinuation of long-term biperiden use may be warranted in patients with schizophrenia treated with SGAs, as it may improve cognitive function, subjective QOL, and psychiatric symptoms with no significant adverse effects., (Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.)

A cytochrome P-450 from adult pig testicular microsomes was purified to a specific content of 12 nmol P-450/mg protein. P-450 has a minimum molecular weight of 46000 +/- 1000, as judged on sodium dodecyl sulfate polyacrylamide gel electrophoresis. Adult testicular P-450 is prepared in the low-spin form with an absorbance maximum at 417 nm. The substrate-induced difference spectrum with progesterone is a typical I difference spectrum. P-450 was incorporated into liposomal membranes composed of phosphatidylcholine, and 17 alpha-hydroxylase activity was shown to amount to 15.5 nmol product/min/nmol of P-450. Furthermore, testicular cytochrome b 5 did not increase the 17 alpha-hydroxylase activity, and the activity was largely inhibited by the addition of sodium cholate, Emulgen 913 and testicular lipid.

The metamorphic changes in levels of glycolipids and myelin proteins and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) in the brains of bullfrog tadpoles, adult frogs, and axolotls were investigated, with particular emphasis on myelin maturation. The concentrations of cerebroside, sulfatide, and galactosyldiacylglycerol gradually increased from the onset of prometamorphosis throughout the active metamorphic period and then greatly increased after metamorphosis was completed. The ratio of glucocerebroside to galactocerebroside increased greatly in the prometamorphic period and then rapidly decreased to the frog level during the climax period. The fatty acid compositions of cerebroside and sulfatide showed a developmental change, with 24:1 being more predominant in the later metamorphic stage. The proportion of hydroxy fatty acids increased up to the onset of the prometamorphic stage and thereafter remained constant at approximately 50% of the total. The CNP activity remained unchanged throughout metamorphosis at 60% that in frog myelin and increased in the adult frog. The composition of tadpole myelin proteins remained constant during metamorphosis, with large basic protein being the most abundant, and in the frog, proteolipid protein and large basic protein were present in comparable amounts. The two adult forms of axolotl, i.e., the neotenous and metamorphosed forms, exhibited almost identical myelin constituents, and CNP activity in the neotenous form amounted to one-fifth that in the bullfrog. These results indicate that active biosynthesis of myelin marker components occurs as metamorphosis proceeds, but more pronounced changes of myelin components occur after metamorphosis is completed.

Cytochrome P-450 was purified from pig testis mitochondria to a specific content of 13.1 n mol/mg of protein. The purified preparation was found to contain a single species of P-450, on sodium dodecyl sulfate polyacrylamide gel electrophoresis, with an apparent molecular weight of about 53000 +/- 2000. The cholesterol side chain-cleavage system could be reconstituted by mixing the purified cytochrome P-450, adrenodoxin reductase, adrenodoxin, cholesterol and NADPH. The rate of conversion of cholesterol to pregnenolone was 6.2 n mol/min/n mol of P-450 under the conditions employed. The absorption spectrum of the oxidized cytochrome P-450 had maxima at 416, 530 and 568 nm. The reduced CO-complex of the cytochrome P-450 exhibited an absorption maximum at 448 nm. The purified P-450 was subjected to microsequence analysis and its NH2-terminal amino acid sequence was found to show considerable homology with that of bovine adrenal P-450 (SCC).