bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exogenous protein Hsp70/Hsc70 can penetrate into brain structures and attenuate the severity of chemically‐induced seizures
Authors: Ekimova Irina V. , Nitsinskaya Larisa E. , Romanova Irina V. , Pastukhov Yuri F. , Margulis Boris A. , Guzhova Irina V. 
Published: September 2010

J. Neurochem.(2010)115, 1035–1044.AbstractHeat shock protein 70 kDa (Hsp70) possesses a remarkable neuroprotective activity and the results of recent studies demonstrated its efficacy in the attenuation of epileptic seizures. The aim of this study was to explore the effects of a pure Hsp70/Hsc70 preparation delivered to the brain regions involved in generalized seizures induced in rats by intracerebroventricular microinjections of NMDA or systemic injections of pentylenetetrazole. Purified Hsp70/Hsc70 was administered (intracerebroventricular) 2 h before the induction of seizures. Compared to the vehicle‐treated control animals, Hsp70/Hsc70‐pretreated rats demonstrated reduced severity of NMDA‐ and pentylenetetrazole‐induced seizures. To identify the brain structures potentially implicated in the Hsp70/Hsc70‐mediated anticonvulsant effect, we analysed the localization of a fluorescently‐labelled chaperone in the brain. Labelled Hsp70/Hsc70 was found in neurons and terminals of the limbic seizure complex of the brain and was co‐localized in these regions with NMDA receptors, synaptophysin and the GABA‐synthesizing enzyme,L‐glutamic acid decarboxylase 67. An immunoprecipitation assay confirmed interactions between Hsp70 and both synaptophysin andL‐glutamic acid decarboxylase 67 in brain tissue. We suggest that the anticonvulsant effect of exogenous Hsp70/Hsc70 is not only based on its protective capacity but is also related to its ability to modulate GABA neurotransmission, which in turn contributes to the maintenance of the excitatory‐inhibitory balance of the CNS.
Search for the acetylcholine and vesamicol binding sites in vesicular acetylcholine transporter: the region around the lumenal end of the transport channel
Authors: Khare Parul , Mulakaluri Anuprao , Parsons Stanley M. 
Published: September 2010

J. Neurochem.(2010)115, 984–993.AbstractVesicular acetylcholine transporter (VAChT; TC 2.A.1.2.13) mediates storage of acetylcholine (ACh) by synaptic vesicles. A three‐dimensional homology model of VAChT is available, but the binding sites for ACh and the allosteric inhibitor (−)‐trans‐2‐(4‐phenylpiperidino)cyclohexanol (vesamicol) are unknown. In previous work, mutations of invariant W331 in the lumenal beginning of transmembrane helix VIII (TM VIII) of rat VAChT led to as much as ninefold loss in equilibrium affinity for ACh and no loss in affinity for vesamicol. The current work investigates the effects of additional mutations in and around W331 and the nearby lumenal end of the substrate transport channel. Mutants of human VAChT were expressed in the PC12A123.7cell line and characterized using radiolabeled ligands and filtration assays for binding and transport. Properties of a new and a repeat mutation in W331 are consistent with the original observations. Of 16 additional mutations in 13 other residues (Y60 in the beginning of lumenal Loop I/II, F231 in the lumenal end of TM V, W315, M316, K317, in the lumenal end of TM VII, M320, A321, W325, A330 in lumenal Loop VII/VIII, A334 in the lumenal beginning of TM VIII, and C388, C391, F392 in the lumenal beginning of TM X), only A334F impairs binding. This mutation decreases ACh and vesamicol equilibrium binding affinities by 14‐ and 4‐fold, respectively. The current results, combined with previous results, demonstrate existence of a spatial cluster of residues close to vesicular lumen that decreases affinity for ACh and/or vesamicol when the cluster is mutated. The cluster is composed of invariant W331, highly conserved A334, and invariant F335 in TM VIII and invariant C391 in TM X. Different models for the locations of the ACh and vesamicol binding sites relative to this cluster are discussed.
Correlated changes in NMDA receptor phosphorylation, functional activity, and sedation by chronic ethanol consumption
Authors: Wu Peter H. , Coultrap Steven , Browning Michael D. , Proctor William R. 
Published: September 2010

J. Neurochem.(2010)115, 1112–1122.AbstractAlcohol abuse leads to tolerance, dependence, and memory impairments that involve excitatory glutamatergic NMDA synaptic transmission. The NMDA receptor (NMDAR) is known to undergo activity‐dependent adaptive functional changes. Since we observed that acute ethanol inhibition of the NMDAR was regulated by protein tyrosine phosphorylation, we investigated the role of protein tyrosine kinases and phosphatases on the NMDAR functions by chronic ethanol treatment. We carried out whole‐cell recording, western blotting, and behavioral righting reflex measurements to assess the impact of chronic ethanol treatment on NMDAR function. Our results indicated that these receptors became resistant to the acute ethanol inhibition following chronic ethanol consumption. This resistance occurred without an increase in the NMDAR subunit expression but was associated with decreases in the levels of phospho‐Y‐1472 NR2B, increases in the levels of STEP33, increases in phospho‐p38 mitogen‐activated protein kinase (pp38 MAPK), and acquisition of tolerance to the sedative effects of ethanol. These data suggested that altered protein tyrosine phosphorylation of the NMDAR subunits significantly contributes to functional changes of this receptor by chronic ethanol ingestion. Therefore, preservation of the integrity of tyrosine phosphorylation mechanisms of the NMDAR may be important in controlling the progression of alcohol tolerance and dependence.
Effect of age on proliferation‐regulating factors in human adult neurogenic regions
Authors: Werry Eryn L. , Enjeti Shilpa , Halliday Glenda M. , Sachdev Perminder S. , Double Kay L. 
Published: September 2010

J. Neurochem. (2010) 115, 956–964.AbstractNeurogenesis, the birth of new neurons, continues throughout adulthood in the human subventricular zone (SVZ) and hippocampus. It is not known how levels of putative proliferation‐regulating factors change with age in human adult neurogenic areas. The current project employed ELISAs to investigate changes in levels of putative proliferation‐regulating factors in the healthy human SVZ and dentate gyrus throughout the adult lifespan (18–104 years). Levels of brain‐derived neurotrophic factor, basic fibroblast growth factor and interleukin (IL)‐1β were significantly higher in the hippocampus than in the SVZ and levels of glial‐derived neurotrophic factor and transforming growth factor‐α were significantly higher in the SVZ (p < 0.005), suggesting that factors with predominant influences on neurogenesis differ between the two human adult neurogenic areas. Hippocampal levels of transforming growth factor‐β1 strongly increased with age (n = 9, p < 0.01), whereas hippocampal and SVZ levels of brain‐derived neurotrophic factor, epidermal growth factor, basic fibroblast growth factor, glial‐derived neurotrophic factor, heparin‐binding epidermal growth factor, insulin‐like growth factor‐1, IL‐1β, IL‐6 and transforming growth factor‐α did not change significantly with age in the SVZ or hippocampus. These findings suggest regulation of the adult neurogenic environment in the human brain may differ over time from that in other species.
Benefits of histone deacetylase inhibitors for acute brain injury: a systematic review of animal studies
Authors: Gibson Claire L. , Murphy Sean P. 
Published: September 2010

J. Neurochem. (2010) 115, 806–813.AbstractDrugs that inhibit histone deacetylase (HDAC) activities have enormous potential as neuroprotective agents. We performed a systematic review of controlled animal studies that administered known inhibitors of the zinc‐dependent HDACs before and/or after acute cerebral injury and assessed anatomic/functional outcomes. Relevant studies were found by searching PubMed, Embase and Web of Science. From more than 100 identified publications, those data meeting specific criteria were analyzed using the Cochrane Review Manager software. A beneficial effect of administering HDAC inhibitors was seen in studies involving cerebral ischemia or non‐ischemic models of acute cerebral injury. Specific studies assessed efficacy when drug was administered up to 14 days prior to, and 14 days following, the onset of cerebral injury. This systematic review provides objective evidence of a neuroprotective role for drugs that inhibit HDACs and highlights particular areas that require further experimental investigation.
N‐Methyl‐d‐aspartate receptor subunit‐ and neuronal‐type dependence of excitotoxic signaling through post‐synaptic density 95
Authors: Fan Jing , Vasuta Oana Cristina , Zhang Lily Y. J. , Wang Liang , George Ashley , Raymond Lynn A. 
Published: September 2010

J. Neurochem.(2010)115, 1045–1056.AbstractNMDA receptors (NMDARs) mediate excitatory synaptic transmission during repetitive or prolonged glutamate release, playing a critical role in synaptic plasticity or cell death, respectively. Evidence indicates that a major pathway of NMDAR signaling to cell death in cortical and hippocampal neurons requires the scaffolding protein post‐synaptic density 95 (PSD‐95) and activation of neuronal nitric oxide synthase. However, it is not known if this PSD‐95‐dependent pathway contributes to excitotoxicity in other brain regions. It is also unclear whether the neuroprotective effects of Tat‐NR2B9c, a membrane‐permeant peptide that disrupts PSD‐95/NMDAR binding, correlate with uncoupling NR2B‐ and/or NR2A‐type NMDARs from PSD‐95. In this study, we used cultured hippocampal and striatal neurons to test the potency of Tat‐NR2B9c on uncoupling NR2 subunits from PSD‐95 and protecting against NMDA‐induced excitotoxicity. We found that the concentration of Tat‐NR2B9c required to dissociate 50% of PSD‐95 was fourfold lower for NR2B than NR2A in cultured hippocampal and striatal neurons, and that this concentration correlated tightly with protection against NMDA‐induced toxicity in hippocampal neurons without altering NMDAR current. In contrast, NMDAR signaling to cell death in cultured striatal neurons occurred independently of the NR2B/PSD‐95 interaction or neuronal nitric oxide synthase activation. These results will facilitate development of neuronal type‐specific protective therapies.
Individual variation in organ histogenesis as a causative factor in the developmental origins of health and disease: Unnoticed congenital anomalies?
Authors: Otani Hiroki , Udagawa Jun , Hatta Toshihisa , Kagohashi Yukiko , Hashimoto Ryuju , Matsumoto Akihiro , Satow Fumio , Nimura Masayuki 
Published: September 2010

ABSTRACTMorphological studies of congenital anomalies have mainly focused on abnormal shape (i.e. malformation) and thus on disturbed organogenesis. However, in regard to postnatal functions of organs that develop through branching mechanisms, organ size is another important morphological feature. These organs consist of a large number of structural and functional units, such as nephrons in the kidney, and the total number of these units, that is approximately proportional to the organ size, has been shown to vary widely among individuals. Organ‐specific cells are differentiated and organized to form structural units and realize organ‐specific functions during the histogenetic period (i.e. from mid‐gestation to the early postnatal period). The total number of units is attained at the end of histogenesis and determines the total functional capacity, including the functional reserve of the organ, and thus may be related to predispositions to postnatal organ‐based diseases, because the functional reserve decreases during the course of life and eventually become short of the minimum requirement of each organ. Therefore, it may be hypothesized that a smaller number of units of organs at the end of histogenesis is one of the predisposing factors for postnatal diseases (i.e. a form of unnoticed but late‐manifested congenital anomalies), in this era of extended longevity. However, the mechanisms that control the total number of units in each organ during histogenesis and the possible relationship among the numbers of units in different organs remain unknown. Here, we review our trials based on the above hypothesis in order to (1) mathematically analyze the morphometric data of the different organs in fetuses to elucidate relationship among developing organs, (2) analyze the developing neuro‐immuno‐endocrine network as a series of mechanisms to systemically correlate the histogenesis of multiple organs, and (3) examine the maternal environment, including dietary fat, as a factor to influence histogenesis and thus the predisposition to type 1 diabetes.
Impact of splenectomy in patients with liver cirrhosis: Results from 18 patients in a single center experience
Authors: Imura Satoru , Shimada Mitsuo , Utsunomiya Tohru , Morine Yuji , Ikemoto Tetsuya , Mori Hiroki , Hanaoka Jun , Iwahashi Shuichi , Saito Yu , Yamanaka‐Okumura Hisami , Takeda Eiji 
Published: September 2010

Aim:  With the recent advances in medical or surgical treatments in chronic hepatic disorders, the indications for splenectomy in hepatic disorders have greatly expanded. We performed splenectomy for cirrhotic patients and investigated the effects of splenectomy on hepatic functional reserve and nutrition metabolism.Methods:  Eighteen patients (Child–Pugh B/C: 12/6; Child–Pugh A: excluded) who underwent splenectomy at our institute between 2005 and 2008 were enrolled. Twelve patients (67%) had hepatocellular carcinoma (HCC), eight of whom met the Milan criteria.Results:  Overall survival rate was 83.3% at 1 year and 62.7% at 2 years. The survival rate of six patients with liver cirrhosis classified a Child–Pugh C was 80.0% at 1 year and 60.0% at 2 years. Three patients underwent hepatic resection and nine patients received ablation therapy against hepatocelluar carcinoma. Portal pressure decreased after splenectomy in most patients (mean decrease, 4.7 mmHg). Four weeks after the operation, the markers of hepatic functional reserve, indocyanine green retention rate at 15 min (ICGR15) and Technetium‐99m‐galactosyl human serum albumin value (99mTc‐GSA), improved from 38.5% to 35.1% and from 0.773 to 0.788 (LHL15), respectively. The non‐protein respiratory quotient (npRQ) did not change in short period after the operation. Other outcomes, including liver function test in cirrhotic patients with long‐term (1 year) follow‐up after splenectomy (n = 7), did not improve significantly. Post‐operative complications included portal thrombus (n = 2), ascites (n = 2) were observed in six patients (33%).Conclusion:  Splenectomy improved hepatic functional reserve and nutritional metabolism in some cases. However, the long‐term outcomes should still be evaluated.
Effects of late evening snack on diurnal plasma glucose profile in patients with chronic viral liver disease
Authors: Suzuki Kazutomo , Kagawa Kagemasa , Koizumi Kazuhito , Suzuki Kazuyoshi , Katayama Hiromi , Sugawara Miwa 
Published: September 2010

Aim:  Glycemic control is important to improve the prognosis in cirrhotic patients with complications from diabetes. A late evening snack (LES) has been recommended for cirrhotic patients. We investigated the effects of LES on diurnal plasma glucose levels.Methods:  Subjects comprised 47 patients with chronic viral liver disease (chronic hepatitis, n = 11; cirrhosis, n = 36) treated in the Department of Gastroenterology & Hepatology, Dokkyo Medical University Koshigaya Hospital. Diurnal variations in plasma glucose were first investigated with three meals/day, in accordance with the European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines. Starting the next day, patients were given four meals including a LES, without changing meal content. Diurnal variations in plasma glucose were examined on day 7, and urine C‐peptide immunoreactivity (CPR), and homeostasis model assessment insulin resistance (HOMA‐IR) were investigated.Results:  With a LES, plasma glucose levels in patients with chronic hepatitis were significantly lower 2 hours before and 2 hours after dinner. In cirrhotic patients, significant decreases in plasma glucose levels were seen 2 hours after breakfast, before lunch, and before dinner. Significant decreases were noted in average plasma glucose levels and highest plasma glucose levels with four meals including a LES in patients with liver cirrhosis. This decrease was greater when maximum plasma glucose levels were higher on the three‐meal regimen.Conclusions:  Improvements in plasma glucose levels were seen with four meals per day, including a LES, in viral chronic liver disease, particularly cirrhosis.
Hepatic steatosis in chronic hepatitis C is a significant risk factor for developing hepatocellular carcinoma independent of age, sex, obesity, fibrosis stage and response to interferon therapy
Authors: Kurosaki Masayuki , Hosokawa Takanori , Matsunaga Kotaro , Hirayama Itsuko , Tanaka Tomohiro , Sato Mitsuaki , Yasui Yutaka , Tamaki Nobuharu , Ueda Ken , Tsuchiya Kaoru , Kuzuya Teiji , Nakanishi Hiroyuki , Itakura June , Takahashi Yuka , Asahina Yasuhiro , Enomoto Nobuyuki , Izumi Namiki 
Published: September 2010

Aim:  Hepatic steatosis is linked to development of hepatocellular carcinoma (HCC) in non‐viral liver disease such as non‐alcoholic steatohepatitis. The present study aimed to assess whether hepatic steatosis is associated with the development of HCC in chronic hepatitis C.Methods:  We studied a retrospective cohort of 1279 patients with chronic hepatitis C who received interferon (IFN) therapy between 1994 and 2005 at a single regional hospital in Japan. Of these patients, 393 had a sustained virological response (SVR) and 886 had non‐SVR to IFN therapy. After IFN therapy, these patients were screened for development of HCC every 6 months. The average period of observation was 4.5 years.Results:  HCC developed in 68 patients. The annual incidence of HCC was 2.73% for patients with a steatosis grade of 10% or greater and 0.69% for patients with a steatosis grade of 0–9%. On multivariate analysis, higher grade of steatosis was a significant risk factor for HCC independent of older age, male sex, higher body mass index (BMI), advanced fibrosis stage and non‐SVR to IFN therapy. The adjusted risk ratio of hepatic steatosis was 3.04 (confidence interval 1.82–5.06, P < 0.0001), which was higher than that of older age (1.09), male sex (2.12), non‐SVR to IFN (2.43) and higher BMI (1.69).Conclusion:  Hepatic steatosis is a significant risk factor for development of HCC in chronic hepatitis C independent of other known risk factors, which suggest the possibility that amelioration of hepatic steatosis may prevent hepatocarcinogenesis.
Significance of interferon‐β for the treatment of hepatitis C virus infection in hemodialyzed patients
Authors: Zeniya Mikio , Yokoyama Keitaro , Imamura Noritsugu , Murai Seizo , Ishikawa Tomohisa , Hokari Atsushi , Koike Kazuhiko , Takahashi Hiroki , Sadaoka Syunichi 
Published: September 2010

Aim:  We evaluated the adverse effects and efficacy associated with interferon‐β (IFN‐β) for the treatment of hepatitis C virus (HCV) infection in 20 hemodialyzed (HD) patients.Methods:  IFN‐β was administrated at a dose of 3 MIU three times a week for 24 weeks simultaneously at the time of HD for the patients of genotype 2a whose viral loads were less than 150 KIU/mL and considered to respond well to IFN therapy.Results:  There was a sustained virological response (SVR) rate of this treatment in 90% of the patients, and sex, age and HD duration had no affect. Slight adverse effects such as fever, malaise and itching were observed during the treatment periods but none serious in any of the patients. Also, no significant difference in adverse effect was observed between 3 MIU and higher dose (6 MIU) groups.Conclusion:  Because IFN‐β can be administrated easily into the circuit of HD, adverse effects can be monitored earlier and taken measures against quickly. Taken together, IFN‐β‐based therapy has a potential for HCV treatment in HD patients but further studies for the patients who have higher viral loads will be required to confirm this.
Epidemiological survey of Japanese children infected with hepatitis B and C viruses
Authors: Iitsuka Toshiyuki , Murakami Jun , Nagata Ikuo , Kanzaki Susumu , Shiraki Kazuo 
Published: September 2010

Aim:  The lack of a nationwide survey on hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in Japan led us to investigate the epidemiological profiles of these infections among Japanese children.Methods:  We conducted a questionnaire survey of children (<20 years of age) infected with either HBV (n = 136) or HCV (n = 114), who visited 636 pediatric institutions in Japan from 2003 through 2005. Most HBV‐infected subjects (94%) were born in 1986 or after when a nationwide immunization program for infants born to HBe antigen‐positive carriers was initiated. The transmission routes were divided into five groups: maternal, horizontal (subdivided into intrafamilial, iatrogenic and other horizontal), and unknown transmission.Results:  Comparison of subjects born in 1990 or after and those born in 1989 or before, when anti‐HBc and anti‐HCV (c100‐3) screening tests of blood donors began, showed a shift in the relative proportions of maternal, intrafamilial, iatrogenic, other horizontal, and unknown transmission from 52%, 19%, 4%, 7% and 19% to 70%, 14%, 6%, 1% and 9%, respectively, for HBV, which was statistically insignificant (P = 0.120), and from 14%, 0%, 76%, 4% and 7% to 89%, 2%, 4%, 0% and 5%, respectively, for HCV, which was statistically significant (P < 0.001). HBV horizontal transmission did not decrease in proportion. No transfusion‐acquired HCV infection was reported in subjects born in 1993 or after.Conclusion:  Maternal transmission is a prominent source of HCV infection among Japanese children. The implementation of measures to prevent HBV horizontal infection is also essential, and the present system of selective vaccination should be expanded to universal vaccination.
Improved diagnosis of well‐differentiated hepatocellular carcinoma with gadolinium ethoxybenzyl diethylene triamine pentaacetic acid‐enhanced magnetic resonance imaging and Sonazoid contrast‐enhanced ultrasonography
Authors: Kawada Natsuko , Ohkawa Kazuyoshi , Tanaka Sachiko , Matsunaga Takashi , Uehara Hiroyuki , Ioka Tatsuya , Takano Yasuna , Takakura Rena , Imanaka Kazuho , Tamai Chie , Kawaguchi Tsukasa , Tomita Yasuhiko , Nakanishi Katsuyuki , Katayama Kazuhiro 
Published: September 2010

Aim:  Two new imaging modalities have been developed recently that are directed at the focal liver lesions: gadolinium ethoxybenzyl diethylene triamine pentaacetic acid (Gd‐EOB‐DTPA)‐enhanced magnetic resonance imaging (MRI) and Sonazoid contrast‐enhanced ultrasonography (CEUS). We investigated the usefulness of these modalities for the diagnosis of small (<2 cm), well‐differentiated hepatocellular carcinoma (HCC).Methods:  A total of 15 nodules from 13 patients, which were histologically diagnosed as well‐differentiated HCC, were subjected to this study. Lesions that showed hypervascularity in the arterial phase and washout in the portal or late non‐hemodynamic phase were regarded as HCC in the dynamic studies of all imaging modalities.Results:  By multidetector computed tomography (MDCT), six of 15 (40%) nodules were diagnosed as HCC. Gd‐EOB‐DTPA‐enhanced MRI diagnosed HCC in nine of the 15 (60%) nodules. Of the nine nodules that were not diagnosed by MDCT, four could be diagnosed by Gd‐EOB‐DTPA‐enhanced MRI. In Sonazoid CEUS, 10 of 15 nodules (67%) were diagnosed as HCC. Four of nine nodules that could not be diagnosed as HCC by MDCT, were diagnosed by Sonazoid CEUS. A total of 11 of the 15 (73%) nodules were diagnosed as HCC by Gd‐EOB‐DTPA‐enhanced MRI and Sonazoid CEUS in addition to MDCT.Conclusion:  Gd‐EOB‐DTPA‐enhanced MRI and Sonazoid CEUS had greater diagnostic value for small, well‐differentiated HCC than did conventional MDCT.