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In residential areas where liquefaction occurred during the 2011 Great East Japan Earthquake, houses, roads, water pipes, sewage pipes and gas pipes were damaged, interrupting daily life. Though settled and tilted houses were repaired by uplifting, the ground in the whole area, including around lifelines and roads, must be treated by special measures to prevent liquefaction-induced damage. A project to improve the liquefiable soil of an entire area by lowering the ground water table started in November 2011. Based on case studies at sites of damaged and undamaged houses, a water table of about GL-3m was judged to be appropriate to prevent damage due to liquefaction. In-situ tests clarified that the pore water pressure decreased due to dewatering only at shallow depths and that subsidence was small.

Objective We aim to clarify the clinico-radiological characteristics of cerebral amyloid angiopathy-related intracerebral hemorrhage and to investigate the efficacy of pathological diagnosis using biopsy specimens. Method We retrospectively reviewed 253 consecutive patients with cortico-subcortical hemorrhage who had been admitted to Aizawa Hospital between January 2006 and July 2013. We had performed craniotomy and hematoma evacuation in 48 patients, as well as biopsy of the evacuated hematoma, cerebral parenchyma adjacent to the hematoma, or both, and they were classified according to the histological results (positive or negative for vascular amyloid deposition) and to the Boston criteria. We compared the clinico-radiological characteristics of cerebral amyloid angiopathy-related intracerebral hemorrhage. We also investigated the detection rate of cerebral amyloid angiopathy with respect to the origins of the specimens. Results Pathological examination revealed that 22 subjects were positive for vascular amyloid. The number of the cerebral microbleeds located in the deep or infratentorial region was significantly larger in the negative group than in the positive group ( P .05). There was no significant difference in the distribution of lobar cerebral microbleeds and in the prevalence of hypertension. In the probable cerebral amyloid angiopathy-related intracerebral hemorrhage patients, the probability of having vascular amyloid detected by biopsy of both hematoma and parenchyma was 100%. Rebleeding in the postoperative periods was observed in 2 cases (9.1%) of the positive group. Conclusions Our results demonstrate the importance and safety of biopsy simultaneously performed with hematoma evacuation. Deep or infratentorial microbleeds are less correlated with cerebral amyloid angiopathy-related intracerebral hemorrhage than with noncerebral amyloid angiopathy-related intracerebral hemorrhage.

Background Cancer cell metabolism requires sustained pools of intracellular nicotinamide adenine dinucleotide (NAD+) which is maintained by a balance of NAD+ hydrolase activity and NAD+ salvage activity. We recently reported that human prostate cancer can be initiated following oncogene expression in progenitor-like luminal cells marked by low expression of the NAD+-consuming enzyme CD38. CD38 expression is reduced in prostate cancer compared to benign prostate, suggesting that tumor cells may reduce CD38 expression in order to enhance pools of NAD+. However, little is known about how CD38 expression is repressed in advanced prostate cancer and whether CD38 plays a role in regulating NAD+ levels in prostate epithelial cells. Methods CD38 expression, its association with recurrence after prostatectomy for clinically localized prostate cancer, and DNA methylation of the CD38 promoter were evaluated in human prostate tissues representing various stages of disease progression. CD38 was inducibly over-expressed in benign and malignant human prostate cell lines in order to determine the effects on cell proliferation and levels of NAD+ and NADH. NAD+ and NADH were also measured in urogenital tissues from wild-type and CD38 knockout mice. Results CD38 mRNA expression was reduced in metastatic castration-resistant prostate cancer compared to localized prostate cancer. In a large cohort of men undergoing radical prostatectomy, CD38 protein expression was inversely correlated with recurrence. We identified methylation of the CD38 promoter in primary and metastatic prostate cancer. Over-expression of wild-type CD38, but not an NAD+ hydrolase-deficient mutant, depleted extracellular NAD+ levels in benign and malignant prostate cell lines. However, expression of CD38 did not significantly alter intracellular NAD+ levels in human prostate cell lines grown in vitro and in urogenital tissues isolated from wild-type and CD38 knockout mice. Conclusions CD38 protein expression in prostate cancer is associated with risk of recurrence. Methylation results suggest that CD38 is epigenetically regulated in localized and metastatic prostate cancer tissues. Our study provides support for CD38 as a regulator of extracellular, but not intracellular, NAD+ in epithelial cells. These findings suggest that repression of CD38 by methylation may serve to increase the availability of extracellular NAD+ in prostate cancer tissues.

The production of vertebrate retinal projection neurons, retinal ganglion cells (RGCs), is regulated by cell-intrinsic determinants and cell-to-cell signaling events. The basic-helix-loop-helix (bHLH) protein Atoh7 is a key neurogenic transcription factor required for RGC development. Here, we investigate whether manipulating human ATOH7 expression among uncommitted progenitors can promote RGC fate specification and thus be used as a strategy to enhance RGC genesis. Using the chicken retina as a model, we show that cell autonomous expression of ATOH7 is sufficient to induce precocious RGC formation and expansion of the neurogenic territory. ATOH7 overexpression among neurogenic progenitors significantly enhances RGC production at the expense of reducing the progenitor pool. Furthermore, forced expression of ATOH7 leads to a minor increase of cone photoreceptors. We provide evidence that elevating ATOH7 levels accelerates cell cycle progression from S to M phase and promotes cell cycle exit. We also show that ATOH7-induced ectopic RGCs often exhibit aberrant axonal projection patterns and are correlated with increased cell death during the period of retinotectal connections. These results demonstrate the high potency of human ATOH7 in promoting early retinogenesis and specifying the RGC differentiation program, thus providing insight for manipulating RGC production from stem cell-derived retinal organoids.

A large number of houses suffered from liquefaction-induced damages in recent large earthquakes due to lack of economical countermeasures. In this study, the shallow ground improvement, up to several meters deep, was proposed as an economical liquefaction countermeasure for houses. Based on the case studies, the design criteria of allowable tilt angles and penetration settlements of houses were proposed for the required level of serviceability against moderate and large earthquakes. The results of questionnaire survey, airborne LiDAR survey and centrifuge model tests demonstrated that even a few meters of non-liquefiable layers in shallow ground could greatly reduce settlements and tilting of houses. A series of numerical analyses indicated that non-liquefiable layer of three meters thick below ground water table improved by solidification methods can prevent significant damages of houses. Furthermore, cost analyses were carried out for different ground improvement methods for both new and existing houses.

Objectives To clarify clinical picture of transient myoclonic state in elderly patients. Methods The Aizawa Hospital database was searched to identify all patients with transient myoclonic state with or without asterixis between April 2006 and June 2013. Medical records, brain images and laboratory data including electroencephalograms and electromyograms were reviewed. Results We found 26 patients: 10 women and 16 men, and their ages ranged from 56 to 96 years (79.7 ± 9.9 years, mean ± standard deviation). The affected sites of the myoclonic jerks were predominantly the lower face, neck and upper extremities. The myoclonus appeared at conscious resting condition, slightly exaggerated by posturing or action. Asterixis was observed in eight patients. Single myoclonic bursts were 1.70 ± 0.94 s long. The interval of myoclonic bursts was 4.47 ± 2.44 s. Single myoclonic bursts were composed of 9.5 ± 2.5 Hz myoclonic contractions, and single myoclonic contractions were 44.4 ± 12.3 ms in duration. Most of the patients suffered from chronic diseases, but they were basically independent in activity of daily living. Oral administration of clonazepam was effective. Conclusions Transient myoclonic state has relatively stereotyped features. The pathophysiology may include some metabolic abnormality on a background of age-related arteriosclerotic changes. Its prognosis is benign, and prompt oral administration of clonazepam abolishes it. Further investigations will be needed to clarify its cause and pathophysiology.

Objective To describe hypocalcaemia due to vitamin D deficiency in ‘hikikomori’ syndrome. Materials and methods A 37-year-old man with ‘hikikomori’ syndrome for a year was admitted with hypocalcaemia (serum ionic calcium 1.17 mmol/l). Serum 1,25(OH)2-vitamin D3 determined by liquid chromatography–tandem mass spectrometry was depressed at 12.1 pg/ml (29.0 pmol/l) and plasma intact PTH elevated at 324 ng/l. Administration of 1 μg/day 1α(OH)-vitamin D3 and 1 g/day calcium lactate for 1 week normalized calcium and PTH, and raised 1,25(OH)2-vitamin D3 to low normal levels. Conclusion This is the first report of hypocalcaemia due to vitamin D deficiency in a patient with ‘hikikomori’ syndrome. LEARNING POINTS A patient with psychiatric disorders can develop endocrine/metabolic abnormality. Hikikomori syndrome should be listed as a possible cause of hypocalcaemia in adults. Early diagnosis of hypocalcaemia in hikikomori syndrome prevents bone damage.

High mobility group box 1 protein (HMGB1) has multiple functions, including the maintenance of nucleosomes and the regulation of gene transcription. HMGB1 is released from activated macrophages, resulting in the induction of inflammatory cytokines. Recently, much research about the role of HMGB1 in cerebrovascular disease (CVD) has been reported. In an animal model, HMGB1 neutralization ameliorates brain infarction, there is an early release of HMGB1 from neurons, and HMGB1 antibody attenuates delayed cerebral vasospasm in experimental subarachnoid hemorrhage. It was also reported that elevation of HMGB1 in serum correlates with severity of acute intracerebral hemorrhage. However, the evidence of HMGB1 localization in brains of patients with CVD is very limited. Therefore, we investigated at autopsy the immunolocalization of HMGB1 in brains of patients with CVD (acute and chronic cerebral infarction, acute cerebral hemorrhage, subarachnoid hemorrhage). In 3 out of 10 acute cerebral infarction cases, the cytoplasm of neurons located around the ischemic core (i.e., penumbra) was positive for HMGB1. In the chronic stage of cerebral infarction, macrophages located in some ischemic regions were positive for HMGB1. Around the hematoma in the basal ganglia, HMGB1-like immunoreactivity (IR) was intense in macrophages. However, around the subarachnoid hematoma, HMGB1-like IR was not seen in the cortex. In arteries surrounded by subarachnoid hematoma, HMGB1-like IR was located in the cytoplasm of vascular smooth muscle cells. These findings, which partially differ from animal model results, may provide translational research and a basis for understanding the role of HMGB1 in brains of patients with CVD.

Aims Choline-deficient diet is extensively used as a model of nonalcoholic fatty liver disease (NAFLD). In this study, we explored genes in the liver for which the expression changed in response to the choline-deficient (CD) diet. Main methods Male CD-1 mice were divided into two groups and fed a CD diet with or without 0.2% choline bitartrate for one or three weeks. Hepatic levels of choline metabolites were analyzed by using liquid chromatography mass spectrometry and hepatic gene expression profiles were examined by DNA microarray analysis. Key findings The CD diet lowered liver choline metabolites after one week and exacerbated fatty liver between one and three weeks. We identified > 300 genes whose expression was significantly altered in the livers of mice after consumption of this CD diet for one week and showed that liver gene expression profiles could be classified into six distinct groups. This study showed that STAT1 and interferon-regulated genes was up-regulated after the CD diet consumption and that the Stat1 mRNA level was negatively correlated with liver phosphatidylcholine level. Stat1 mRNA expression was actually up-regulated in isolated hepatocytes from the mouse liver with the CD diet. Significance This study provides insight into the genomic effects of the CD diet through the Stat1 expression, which might be involved in NAFLD development.

Dopamine has a significant role in retinal processing, and it has been demonstrated that retinal dopamine content is decreased in parkinsonian patients. We measured the latency of the evoked discharges in the optic tract (OT) to flash stimuli during stereotactic pallidal neurosurgery in 25 patients with Parkinson's disease (PD) (13 women and 12 men, age 38-78 years, unified Parkinson's disease rating scale (UPDRS) Motor Score in the Off state 11-54, Hoehn and Yahr stage in the Off state 1.5-5) and investigated the effects of age at surgery, disease duration, levodopa dose, and severity of parkinsonian symptoms on the latency. OT discharges were evoked by monocular flash stimuli delivered from a flashlight with a krypton bulb with a tungsten filament. The luminance at the eye measured ∼4 × 10(4) cd/m(2). The light wavelength of the stimulus was composed of a wide spectrum with its peak at around 800 nm or longer. The latency of OT discharges ranged 49-79 msec, and there was a significant positive correlation between the latencies of evoked activities in the OT to a flashlight and age (r = 0.59, P < 0.001, by Pearson correlation), but no correlation between the latency and the severity of parkinsonian symptoms and between the latency and duration of illness. These results indicate that the delay in visual processing and conduction at the level of the retina and the OT are substantially derived from age-related degenerative changes in the retina and visual pathway which are apparently unrelated to the striatal dopamine deficiency in PD.

Isolated bilateral internal ophthalmoplegia is a rare and problematic condition affecting activities of daily living. Herein, we describe the cases of 2 patients with postinfectious isolated bilateral internal ophthalmoplegia, i.e., mydriasis without external ophthalmoplegia. One patient demonstrated no other neurological symptom, while the other patient showed mild gait ataxia. Magnetic resonance imaging revealed no abnormal findings in the brain or brainstem. Light-near dissociation of the pupils was not recognized in either patient, and supersensitivity to dilute pilocarpine was observed in 1 of the 2 patients. An increased titer of the anti-GQ1b IgG antibody was noted in 1 patient. A review of the literature revealed five similar cases; the symptomatic characteristics, ratio of positive anti-GQ1b IgG antibody, and effective treatment are discussed.

SUMMARY Aging is associated with loss of tissue mass and a decline in adult stem cell function in many tissues. In contrast, aging in the prostate is associated with growth-related diseases including benign prostatic hyperplasia (BPH). Surprisingly, the effects of aging on prostate epithelial cells have not been established. Here we find that organoid-forming progenitor activity of mouse prostate basal and luminal cells is maintained with age. This is caused by an age-related expansion of progenitor-like luminal cells that share features with human prostate luminal progenitor cells. The increase in luminal progenitor cells may contribute to greater risk for growth-related disease in the aging prostate. Importantly, we demonstrate expansion of human luminal progenitor cells in BPH. In summary, we define a Trop2+ luminal progenitor subset and identify an age-related shift in the luminal compartment of the mouse and human prostate epithelium., In Brief Aging is a significant risk factor for BPH and prostate cancer, but how aging increases disease risk in the prostate remains poorly defined. Crowell et al. show that progenitor-enriched luminal cells are expanded with aging in the mouse and human prostate, and may contribute to BPH., Graphical Abstract

We report on a patient with sporadic Creutzfeldt–Jakob disease (CJD) who showed dystonia, periodic myoclonus, and periodic sharp wave complexes (PSWCs) on EEG. The EEG–EMG polygraphic study revealed that dystonia appeared without relation to periodic myoclonus and PSWCs and that dystonia EMGs were strongly suppressed after periodic myoclonus EMGs. These findings suggest that dystonia has a pathogenesis different from that of periodic myoclonus and PSWCs, but dystonia and periodic myoclonus may be generated through the sensorimotor cortex in CJD.

SUMMARY Inflammation is a risk factor for prostate cancer, but the mechanisms by which inflammation increases that risk are poorly understood. Here, we demonstrate that low expression of CD38 identifies a progenitor-like subset of luminal cells in the human prostate. CD38lo luminal cells are enriched in glands adjacent to inflammatory cells and exhibit epithelial nuclear factor κB (NF-κB) signaling. In response to oncogenic transformation, CD38lo luminal cells can initiate human prostate cancer in an in vivo tissue-regeneration assay. Finally, the CD38lo luminal phenotype and gene signature are associated with disease progression and poor outcome in prostate cancer. Our results suggest that prostate inflammation expands the pool of progenitor-like target cells susceptible to tumorigenesis., In Brief Chronic inflammation of the prostate is a risk factor for cancer, but how inflammation increases disease risk remains poorly defined. Liu et al. show that luminal progenitor cells expressing low levels of CD38 are expanded around inflammation, and these progenitors are target cells that can initiate human prostate cancer.

Aim Assessment of plaque characteristics is important for the optimal treatment of carotid stenosis, particularly in elderly patients. Macrophage infiltration is reported to be involved in carotid plaque instability. However, immunohistochemical assessment of the detailed localization of macrophage infiltration in carotid plaques remains limited. We attempted to elucidate this using 3-D ultrasonography (3D-US). We compared findings of the detailed localization of macrophage infiltration with findings from the newly developed tomographic ultrasound imaging (TUI). Methods We obtained specimens of carotid arteries from 18 patients undergoing carotid endarterectomy (CEA), and investigated the localization of macrophages and vascular smooth muscle cells. Their localization obtained from 11 patients was compared with their preoperative TUI findings. Results We classified the localization of macrophage infiltration into four types: (i) focal infiltration in the thick fibrous cap (12 cases); (ii) subendothelial zonal infiltration (2 cases); (iii) peripheral infiltration around the lipid core (8 cases); and (iv) local infiltration near the shoulder of the fibrous cap (2 cases). Among them, preoperative TUI was available in 11 CEA cases for histological comparison. We identified two sites of focal macrophage infiltration that corresponded to local echogenic lesions without an acoustic shadow on TUI. The proliferation of smooth muscle cells failed to show an apparent echogenicity. Conclusions TUI could not only evaluate the morphological features, but also showed the two types of focal macrophage infiltration relevant to plaque instability as an echogenic focus. TUI carried out by 3D-US is an easily applicable and non-invasive method that is considered useful for evaluating carotid plaques in elderly patients. Geriatr Gerontol Int 2013; 13: 834–841.

The ON and OFF channels are basic functional elements in parallel processing in the visual system in vertebrates including primates. We analysed the responses of the optic tract fibre activity in response to switching a flashlight on or off in 25 awake patients with Parkinson's disease who underwent stereotactic surgery targeting the internal globus pallidus. The responses were evoked in a darkened room by a light with a luminance of approximately 4 × 10(4) cd m(-2) at the eye and a wide-spectrum wavelength. Most of the responses at the light on event were excitatory (38 out of 41 sites, 93%). Thirty-five sites with increase in activity at the light on event showed reciprocal responses or no responses to light off, and these sites were classified as containing ON fibres. In single-fibre analysis, all of 14 ON fibres were recorded at the sites of multi-fibre excitatory responses. Six sites showed multi-fibre excitatory responses at the light off event; three sites showed sustained reduction in activity at the light on event, and these three sites were classified as containing OFF fibres. In single-fibre analysis, two OFF fibres were recorded at the sites of multi-fibre suppressive responses at the light on event, and the other two OFF fibres were recorded at the sites of multi-fibre excitatory responses at the light on event. We found that all excitatory responses to light on were transient, while all but one excitatory responses to light off were sustained. Reduction in activity tended to be smaller than increase in activity at the light on event. These results demonstrate that the ON and OFF channels, and their transient and sustained features function in visual processing in humans.

14-3-3 proteins are now recognized to have a wide range of potential functions and pathological relevance, such as regulating the intercellular signal processes of differentiation, the development and growth of cells, or preventing or mediating cell apoptosis and survival by controlling the localization of potential signaling molecules. We investigated the immunolocalization of 14-3-3 proteins in atherosclerotic lesions of human cerebral and carotid arteries using 14-3-3 isoform-specific antibodies to distinguish 7 isoforms, and confirmed the cell type localization using double immunofluorolabeling. 14-3-3 common (COM)-like immunoreactivity (IR) was intense, mainly in the foam cells and multinucleated giant cells of the carotid artery. The beta, gamma, epsilon, tau, eta, and zeta (6/7) isoform-specific antibodies showed similar results to those with anti-14-3-3 COM antibody. However, among these isoform-specific antibodies, the anti-eta isoform antibody most intensely immunolabeled multinucleated giant cells and foam cells, and the anti-zeta isoform antibody most intensely immunolabeled infiltrating vascular smooth muscle cells (VSMCs), in carotid plaques. Zeta IR was also observed in one part of the mural thrombus and in the nuclei of foam cells. Gamma isoform-like IR was relatively limited in cell components, but extracellular lesions were partly positive for this isoform. In the main cerebral arteries, the anti-epsilon isoform antibody most intensely immunolabeled infiltrating VSMCs in the intima of thickened fibrous cap plaques. Endothelial cells were also positive for the epsilon isoform. These findings may provide a basis for understanding the isoform-specific role associated with atherosclerotic lesions of the cerebral and carotid arteries.

Blue-Multi-Laser-Diode Annealing (BLDA) was performed in the continuous wave (CW) mode on Si films as thick as 0.5 μm and 1 μm deposited by rf sputtering. As a result of controlling the laser power from 4.0 to 4.8 W, a whole Si layer of 0.5 μm in thickness was completely crystallized and consisted of a columnar structure of fine grains beneath a partially melted Si surface owing to the high temperature gradient along the depth in the Si layer. After additional hydrogenation in a furnace ambient, the ratio of the photo/dark current under AM1.5 illumination distinctly improved to 6 times higher than that of as-deposited condition. The BLDA is expected to be applied to thin-film solar cells and/or to thin film transistor (TFT) photo-sensor systems on panels as a new low-temperature poly-silicon (LTPS) fabrication technique.

BACKGROUND: No prospective study of gamma knife thalamotomy for intractable tremor has previously been reported. Objective: To clarify the safety and optimally effective conditions for performing unilateral gamma knife (GK) thalamotomy for tremors of Parkinson disease (PD) and essential tremor (ET), a systematic postirradiation 24-month follow-up study was conducted at 6 institutions. We present the results of this multicenter collaborative trial. Methods: In total, 72 patients (PD characterized by tremor, n = 59; ET, n = 13) were registered at 6 Japanese institutions. Following our selective thalamotomy procedure, the lateral part of the ventralis intermedius nucleus, 45% of the thalamic length from the anterior tip, was selected as the GK isocenter. A single 130-Gy shot was applied using a 4-mm collimator. Evaluation included neurological examination, magnetic resonance imaging and/or computerized tomography, the unified Parkinson's disease rating scale (UPDRS), electromyography, medication change, and video observations. Results: Final clinical effects were favorable. Of 53 patients who completed 24 months of follow-up, 43 were evaluated as having excellent or good results (81.1%). UPDRS scores showed tremor improvement (parts II and III). Thalamic lesion size fluctuated but converged to either an almost spherical shape (65.6%), a sphere with streaking (23.4%), or an extended high-signal zone (10.9%). No permanent clinical complications were observed. Conclusion: GK thalamotomy is an alternative treatment for intractable tremors of PD as well as for ET. Less invasive intervention may be beneficial to patients.

D-Serine is a co-agonist of the N-methyl-D-aspartate receptor in glutamate neurotransmission and has been proposed as a potential therapeutic agent for schizophrenia. However, D-serine also acts as a nephrotoxic substance in rats at high doses. To investigate the pharmacokinetics and toxicokinetics of D-serine, a method for the stereoselective determination of serine enantiomers in rat plasma was developed using GC-MS with selected ion monitoring (GC-MS-SIM). DL-[2H3]Serine was used as an internal standard to account for losses associated with the extraction, derivatization and chromatography. Serine enantiomers were purified by cation-exchange chromatography using BondElut SCX cartridge and derivatized with HCl in methanol to form methyl ester followed by subsequent N,O-diacylation with optically active (+)-α-methoxy-α-trifluoromethylphenylacetyl chloride to form epimeric amide. Quantitation was performed by SIM of the molecular-related ions of the epimers in the chemical ionization mode. The intra- and inter-day reproducibility of the assay was less than 5% for D-serine and 3% for L-serine. The method was successively applied to study the pharmacokinetics of D-serine in rats. Copyright © 2011 John Wiley & Sons, Ltd.

D: -Amino acids are now recognized to be widely present in mammals. In rats, exogenously administered D: -methionine is almost converted into the L: -enantiomer via 2-oxo-4-methylthiobutylic acid as an intermediate. D: -Amino acid oxidase is associated with conversion of D: -methionine into the 2-oxo acid. Since D: -amino acid oxidase is present at the highest activity in the kidney compared to other organ, kidney injury is suggested to cause accumulation of D: -methionine. The purpose of the present study is to assess the role of kidney in the elimination of D: -methionine and metabolic conversion into L: -methionine in rats using a stable isotope methodology. After a bolus i.v. administration of D: -[²H₃)]methionine to 5/6-nephrectomized rats, plasma concentrations of D: -[²H₃]methionine, L: -[²H₃]methionine, and endogenous L: -methionine were determined by a stereoselective GC-MS method. Renal mass reduction slowed down the elimination of D: -[²H₃]methionine. The clearance values of conversion of D: -[²H₃]methionine into the L: -enantiomer in 5/6-nephrectomized rats were one-sixth of those in sham-operated rats. The elimination behavior of D: -[²H₃]methionine observed in rats demonstrated that kidney was the principal organ responsible for chiral inversion of D: -methionine.

Optically pure (R)- and (S)-3-aminotetradeutero-2-thiophenone (D- and L-[2H4]homocysteine thiolactone) for use as substrates for metabolic and pharmacokinetic studies has been prepared. The racemic [2H4]homocysteine thiolactone hydrochloride was prepared from commercially available and highly enriched DL-[3,3,4,4-2H4]methionine by intramolecular condensation with hydriodic acid. The racemate was derivatized with (S)-(+)-2-methoxyphenylacetic acid to form the diastereomeric amides. The diastereomers were separated by silica gel column chromatography. Hydrolysis of the D- and L-isomer amide in 4 M HCl–ethanol (1:2 v/v) afforded the optically pure D- and L-[2H4]homocysteine thiolactone, respectively. Copyright © 2010 John Wiley & Sons, Ltd.

2007年3月25日に発生した能登半島地震（MJMA=6.9）は，能登半島の先端に位置する輪島市をはじめとして多くの家屋に被害を与えた．石川県によれば，建物被害は全壊682棟，半壊1,719棟，一部損壊26, 907棟，非住家被害4,439棟，合計33,747棟となり，震度6強を記録した震源に近い輪島市門前町の全壊率が高い．現地調査によれば，門前町の宅地では液状化による噴砂も見られることから，大きな地震動だけではなく，液状化による地盤変状も建物被害に影響を及ぼしているのではないかと考えられた．そこで，井戸による地下水位調査，ボーリング調査，スウェーデン式サウンディングなどを行い，宅地地盤特性を調査し，地盤特性と建物被害との関係を考察した．その結果，液状化等の宅地地盤の変状が全体的な基礎の被害を生じ，この基礎の被害が上部構造物に影響を及ぼしたことが明らかとなった．

1995年兵庫県南部地震，2004 年新潟県中越地震では，大規模盛土造成地の宅地地盤が液状化等による流動化現象で多くの建物に甚大な被害を生じた．その後，2006 年9 月から改正宅地造成等規制法が施行1)され，宅地耐震化促進事業2)を活用して，全国の地方公共団体で取組みが行われている．国土交通省では，大規模盛土造成地の変動予測調査ガイドライン3)を策定し，緩勾配の谷埋め型大規模盛土造成地について第一次スクリーニング段階での簡易変動予測評価手法を参考として記載している．しかし，腹付け型大規模盛土造成地の同様の簡易変動予測評価手法の記載がなく，早急な評価手法の確立が望まれている．本論文では，腹付け型大規模盛土造成地の過去の災害事例についての土質状況を含んだデータが少ないために，3タイプの安定解析を行い，1995年兵庫県南部地震の災害事例と合わせた最適な変動予測評価手法を提案する．

Two male patients aged 72 and 77 were found to have transthyretin (TTR) immunoreactive amyloid deposits in their gastrointestinal tracts when they underwent surgery for gastric and sigmoid colon cancer, respectively. They had no cardiac symptoms and there was no mutation in their TTR gene. Amyloid deposits were seen mainly on vascular walls in submucosal layers of the stomach and colon, while the muscularis mucosae, which is invariably affected in familial amyloid polyneuropathy (FAP), was completely free of amyloid deposition. The pattern of TTR-derived amyloid deposition in the gastrointestinal tract in SSA and in FAP are quite different.

Spontaneously hypertensive rats (SHR) and their substrains are a useful model for studying essential hypertension which is a complex, polygenic, and multifactorial disorder. Their genetic and metabolic features are of great interest because they may provide insights into the mechanism of blood pressure regulation. We have compared urinary metabolic profiles of young SHR with those of their age-matched normotensive controls, Wistar Kyoto rats, using (1)H NMR-based metabonomics. Principal components analysis was applied to the NMR spectral data after data-reduced and normalized by the total integral or the creatinine integral. Consequently, a clear separation of urine samples between the two strains was observed in the principal components scores plot. The loadings plot from the data normalized by the creatinine integral showed that many metabolites such as citrate, alpha-ketoglutarate, and hippurate contributed to the separation, and the urinary levels of most metabolites used in this study, including these three, were lower in SHR than in Wistar Kyoto rats. These metabolic changes may be concerned with blood pressure regulation in SHR, although a relation to other strain differences cannot be ruled out. The present study suggests the usefulness of a (1)H NMR-based metabonomic approach using SHR in the field of hypertension research.

金沢大学理工研究域地球社会基盤学系, Damage done to civil structures by the 2000 Tottori-ken Seibu Earthquake was investigated. Field surveys were made from October 8-10 by eight members dispatched by the JSCE in cooperation with other researchers. Descriptions are given of the earthquake, seismic ground motion; the damage done to such civil structures as roads, road bridges, lifelines, dams, port facilities; slope failures; and public risk management. Although peak ground accelerations were extremely intensive, structural damage was not as severe as compared with the average damage caused by past earthquakes in Japan. Such disaster responses as search and rescue activities, emergency responses, disaster information communication, and victim supports are discussed.

Objective: This study examines ABHD12 mutation analysis in 2 PHARC patients, originally thought to be Usher syndrome. Methods: The ABHD12 gene of 2 patients, who suffered from deaf-blindness and dysfunctional central and peripheral nervous systems, were sequenced. Results: We identified that both cases carried the same novel splice site mutation in the ABHD12 gene. However, 1 had epilepsy and the other had peripheral neuropathy. Based on haplotype analysis, the mutation is likely not a hot spot, but rather could be attributable to a common ancestor. Conclusion: This study shows that PHARC has phenotypic variability, even within a family, which is consistent with previous reports. Differential diagnosis of “deaf-blindness” diseases is crucial. Confirming the presence of associated symptoms is necessary for differentiating some deaf-blindness syndromes. In addition, mutation analysis is a useful tool for confirming the diagnosis.

An equation is theoretically derived which describes the relative standard deviation (RSD) of the amount ratios of analyte to its isotope-labeled variant in gas chromatography/mass spectrometry (GC/MS) using the stable isotope dilution method. The determination of methyltestosterone is taken as an example. The uncertainty equation proposed is justified by comparing the theoretical RSD values with the experimental RSD values obtained by replication over a wide range of analyte amount. The detection limit and quantitation limit are estimated from the continuous plot (precision profile) of the theoretical RSD against analyte amount.

During vertebrate neurogenesis, multiple extracellular signals influence progenitor cell fate choices. The process by which uncommitted progenitor cells interpret and integrate signals is not well understood. We demonstrate here that in the avascular chicken retina, vascular endothelial growth factor(VEGF) secreted by postmitotic neurons acts through the FLK1 receptor present on progenitor cells to influence cell proliferation and commitment. Augmenting VEGF signals increases progenitor cell proliferation and decreases retinal ganglion cell genesis. Conversely, absorbing endogenous VEGF ligand or disrupting FLK1 activity attenuates cell proliferation and enhances retinal ganglion cell production. In addition, we provide evidence that VEGF signals transmitted by the FLK1 receptor activate divergent intracellular signaling components, which regulate different responses of progenitor cells. VEGF-induced proliferation is influenced by the MEK-ERK pathway, as well as by the basic helix-loop-helix factor HES1. By contrast, VEGF-dependent ganglion cell suppression does not require MEK-ERK activation, but instead relies on VEGF-stimulated HES1 activity, which is independent of NOTCH signaling. Moreover, elevated HES1 expression promotes progenitor cell proliferation and prevents overproduction of retinal ganglion cells owing to the loss of VEGF or sonic hedgehog (SHH), another signal that suppresses ganglion cell development. Based on previous and current findings, we propose that HES1 serves as a convergent signaling node within early retinal progenitor cells to integrate various cell-extrinsic cues, including VEGF and SHH, in order to control cell proliferation and neuronal specification.

Objective: To evaluate presurgical factors affecting patient satisfaction with pallidal surgery. Methods: Forty-one parkinsonian patients who underwent unilateral pallidal surgery replied to a questionnaire on general satisfaction with the outcome of surgery graded on a five-point scale. The contribution of age, disease duration, required activity level, Unified Parkinson’s Disease Rating Scale Part II activity of daily living (ADL) score and presurgical to postsurgical ADL score change to the level of satisfaction was tested. The required activity level was defined as the physical activity level which the patients required to support their families. Results: Multiple regression analysis revealed that age at surgery (p = 0.02), required activity level (p = 0.005), ADL score in the on phase at surgery (p = 0.001), and ADL score in the off phase at surgery (p = 0.0001) were significant contributors to satisfaction. Conclusions: The patients who were relatively young and required higher activity levels tended to have a higher degree of satisfaction with the outcome, while patients with advanced age tended to be less satisfied, independent of symptomatic improvement after the surgery.

Recent studies suggest that advanced glycation end products (AGEs) can promote the development of atherosclerotic lesions in a similar manner to oxidatively modified low density lipoproteins. As oxidative stress accelerates the formation of AGEs, antioxidant drugs may exert atheroprotective effects via suppression of AGE formation. Although amlodipine, a calcium channel blocker, and fluvastatin, a 3-hydroxy-3-methylglutaryl CoA reductase inhibitor, show antioxidant and atheroprotective effects, the relation of AGEs to their effects is unknown. We immunohistochemically investigated the inhibitory effects of chronic treatment with amlodipine (5 mg/kg per day) or fluvastatin at a dose insufficient to reduce plasma cholesterol levels (2 mg/kg per day) on the accumulation of AGEs in atherosclerotic aortas of rabbits fed 1% cholesterol diet and 10% fructose containing water. After eight weeks of treatment, AGEs, namely argpyrimidine, carboxymethyllysine and pyrraline, markedly accumulated with intimal thickening in cholesterol and fructose-fed control rabbits, while the drugs inhibited those changes other than the pyrraline deposition without plasma lipid-lowering effects. Enhanced lipid peroxidation was observed in plasma from cholesterol and fructose-fed rabbits only, and lipid peroxidation was not suppressed by the drugs. These results suggest that the atheroprotective effects of the drugs are at least partly due to the suppression of AGE accumulation although the exact mechanism of AGE suppression is ambiguous.

Hot coke oven gas (COG) with a temperature of about 1050 K was produced from a test unit for coke production, the capacity of which was 80 kg of coal. The COG was introduced into an experimental unit with a tar converter where oxygen and steam were injected. Over 98% of the total carbon in the hot COG was partially oxidized, reformed with steam and converted to hydrogen and CO. About 1 Nm 3 /h of hydrogen was continuously produced for 5 h in this experiment. The experimental results suggest that three to five times the amount of hydrogen and CO that were present in the original COG could be recovered by this technology, utilizing the heat of the hot COG for the reaction. The feasibility study showed that hydrogen can be produced by this technology at a lower cost and higher efficiency than by the separation of cold COG.