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This study aimed to investigate the effect of acidulated phosphate fluoride (APF) application on filler-free polymethyl methacrylate (PMMA)-based resin blocks for computer-aided design/computer-aided manufacturing (CAD-CAM), focusing on their use in pediatric crowns. Three types of PMMA-based blocks for CAD-CAM were evaluated, and a composite resin block for CAD-CAM was used as a control. Statistical analysis (p<0.05) of the data revealed that all PMMA-based blocks showed significantly higher gloss levels than the composite resin blocks. Two PMMA-based blocks also demonstrated significantly lower Ra and Sa values. SEM images showed no irregular changes in the surface properties of the PMMA-based blocks compared to those of the composite resin block. These results are significant in meeting the increasing demand for esthetic restorative treatments in pediatrics, where APF is commonly used for caries prevention. PMMA-based resin blocks for CAD-CAM are an effective alternative to prevent esthetic degradation from gloss reduction and plaque accumulation.

Droplet microfluidic-based technology is a powerful tool for biotechnology, and it is also expected that it will be applied to culturing and screening methods. Using this technology, a new high-throughput screening method for lactic acid bacteria was developed. In this study, the conventional culture of lactic acid bacteria that form clear zones on an agar medium was reproduced in water-in-oil droplets, and only the droplets in which lactic acid bacteria grew were collected one by one. Using this method, the specific recovery of Lactiplantibacillus plantarum from a mixture of L. plantarum and Escherichia coli and the acquirement of lactic acid bacteria from an environmental sample were successful. This method could be applied to various conventional screening methods using the clear zone as a microbial growth indicator. This has expanded the possibilities of applying droplet microfluidic-based technology to microbial cultivations., Competing Interests: YO and NH were employed by On-chip Biotechnologies Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mori, Watanabe, Nanri, Matsukura, Ota, Homma and Noda.)

A novel actinobacterium, designated HIs16-36 T , was isolated from the rhizosphere of a mangrove on Ishigaki Island, Okinawa, Japan, and its taxonomic position was investigated using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that strain HIs16-36 T was closely related to the members of the genus Arthrobacter . The highest 16S rRNA gene sequence similarity was observed with Arthrobacter crystallopoietes (98.5 %), followed by Arthrobacter globiformis (97.2 %). The peptidoglycan of strain HIs16-36 T was of the A4α type, with lysine as the diagnostic diamino acid. The predominant isoprenoid quinone was MK-9(H 2 ) and the major fatty acids were anteiso-C 15 : 0 and iso-C 15 : 0 . The polar lipids were identified as diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and two glycolipids. These chemotaxonomic features corresponded to those of the genus Arthrobacter . Meanwhile, the differences in some phenotypic characteristics, along with the results of average nucleotide identity and digital DNA-DNA hybridization analyses, indicated that strain HIs16-36 T should be distinguished from the recognized species of the genus Arthrobacter . Therefore, strain HIs16-36 T represents a novel species of the genus Arthrobacter , for which the name Arthrobacter mangrovi sp. nov. is proposed. The type strain is HIs16-36 T (=NBRC 112813 T =TBRC 15750 T ).

Background: Autoimmune cerebellar ataxia (AICA) is a general term for diseases in which the cerebellum is damaged by an autoimmune mechanism. For the diagnosis of the AICA, anti-thyroid antibodies (anti-thyroid peroxidase antibody and anti-thyroglobulin antibody), anti-glutamic acid decarboxylase (GAD) antibodies, and anti-gliadin antibodies are measured. Immunotherapy is known to be effective for AICA, but some patients with effective immunotherapy lack autoantibodies associated with cerebellar ataxia. The purpose of this study was to clarify whether the effectiveness of immunotherapy in patients with suspected AICA could be predicted by anti-mouse cerebellar tissue-derived antigen antibody tests., Methods: This study was conducted on 25 patients with idiopathic cerebellar ataxia (excluding multiple system atrophy, hereditary spinocerebellar degeneration, cancer-bearing patients, and patients taking phenytoin) who received immunotherapy from 2005 to 2016 at Tokyo Medical University Hachioji Medical Center. The patients were suspected of having AICA because they were positive for cerebellar ataxia-related autoantibodies (anti-thyroid antibody, anti-GAD antibody, anti-gliadin antibody, or anti-transglutaminase 6 antibody) or other autoantibodies. Antibodies that bind to mouse cerebellar tissue-derived antigens were defined as "anti-mouse cerebellar tissue-derived antigen antibodies" in this study, and their IgG-class antibodies were comprehensively measured using a slot blot., Results: Anti-mouse cerebellar tissue-derived antigen antibody test results were correlated with immunotherapy efficacy. Furthermore, the combination of anti-mouse cerebellar tissue-derived antigen and anti-GAD antibody tests could predict the effectiveness of immunotherapy with 83% sensitivity and 100% specificity, while the combination of the anti-mouse cerebellar tissue-derived antigen, anti-GAD, and anti-gliadin (IgA class) antibody tests could predict the effectiveness of immunotherapy with 94% sensitivity and 86% specificity., Conclusion: Anti-mouse cerebellar tissue-derived antigen antibody tests could help to provide useful information for immunotherapy administration to patients with idiopathic cerebellar ataxia suspected to be AICA.

The cerebellum is one of the main targets in the central nervous system for autoimmunity. Immune-mediated cerebellar ataxias include gluten ataxia, GAD antibody-associated cerebellar ataxia, Hashimoto's encephalopathy, and paraneoplastic cerebellar degeneration. Autoimmune cerebellar ataxia may be of either insidious or subacute onset, and vertigo or transient neurological symptoms occur in some patients before the onset of the disease, in contrast to spinocerebellar degeneration. If autoimmune cerebellar ataxia is suspected, early diagnosis and introduction of treatment are very important. For diagnosis, testing for gliadin antibody, TG6 antibody, GAD antibody, thyroid antibody, and anti-neuronal antibodies, including mGluR1, is useful. Magnetic resonance imaging voxel-based morphometry is also useful because it can detect cortical cerebellar atrophy of autoimmune cerebellar ataxia, different from spinocerebellar ataxia. As for treatment, it is important to remove autoimmune triggering factors (e.g.,dietary gluten or neoplasm). When the ataxia symptoms are causing hindrances in the daily life, it is worth considering immunotherapy including IVIg, steroid therapy and so on.

Background: The prevalence of deep venous thrombosis (DVT) in patients with gastric cancer before surgery is unknown. This study aimed to clarify the risk factors for DVT of the lower extremities in patients with gastric cancer before surgery and to evaluate the usefulness of ultrasonographic screening for prevention of postoperative pulmonary thromboembolism (PTE)., Methods: Patients who had undergone lower-extremity venous ultrasonography before surgery for gastric cancer were retrospectively analyzed. Univariate and multivariate logistic regression analyses were performed to identify the predictors of DVT before surgery. Perioperative management of patients with DVTs and the incidence of postoperative PTE were investigated., Results: Of the total 1140 patients, 86 had DVT preoperatively. On univariate analysis, the incidence of DVT was significantly higher with: female sex; age ≥80 years; PS ≥ 1 (vs. PS = 0); stage IV (vs. stages I-III); history of preoperative chemotherapy; and the presence of a central venous catheter (CVC). Multivariate logistic regression analysis demonstrated that sex, age ≥80 years, PS ≥ 1, history of preoperative chemotherapy, and the presence of CVC were significantly correlated with DVT before surgery. Postoperative PTE occurred in 2 patients with proximal DVT. No patients in whom DVT was not detected developed PTE., Conclusions: Female sex, older age, worse PS, the presence of CVC, and a history of preoperative chemotherapy were the independent risk factors for DVT. Routine lower-extremity venous ultrasonographic screening is useful for prevention of PTE because it can identify patients at high or low risk for PTE.

Gluten-related disorders (GRDs) are conditions that develop in response to the common trigger of gluten ingestion and manifest as a variety of clinical symptoms. GRDs have been considered rare in Asian countries, including Japan, because of lower consumption of wheat products than in Europe and the U.S.A. and differences in genetic background. Recently, however, GRDs, such as celiac disease and gluten ataxia, have been reported in Japan, albeit sporadically and their presence is now recognized in this country. Gluten ataxia is defined as an anti-gliadin antibody positive sporadic ataxia. Recently, it was reported that the presence of anti-transglutaminase-6 (TG6) antibody can be used to diagnose gluten ataxia. Herein, we will review evidence relating to gluten ataxia and report two cases of anti-TG6 antibody positive gluten ataxia. In patients with gluten ataxia, sensory disturbance is generally considered to be so mild that it contributes minimally to ataxia. However, our patients showed a positive Romberg sign. Deep sensory disturbance, in addition to cerebellar disturbance, may have been involved in the clinical symptoms of our cases.

An 81-year-old woman presented with a chief complaint of gait disturbance. Brain magnetic resonance imaging (MRI) showed mild cerebellar atrophy and cerebral blood flow scintigraphy revealed reduced blood flow in the cerebellum. The patient was diagnosed with cortical cerebellar atrophy, and was given taltirelin hydrate, but symptoms slowly progressed. Thirteen years after onset, a positive result for anti-transglutaminase 6 (TG6) IgA antibodies was identified, and gluten ataxia was diagnosed. Despite steroid therapy and gluten-free diet therapy, no improvements were seen, and independent walking became difficult for the patient. High-dose intravenous immunoglobulin therapy resulted in improvements in the Posture and Gait subscore of the International Cooperative Ataxia Rating Scale (ICARS) from 15 to 11 points, and the patient regained the ability to walk independently. Gluten ataxia are rarely reported in Japan and anti-TG6 antibodies were considered useful for its diagnosis.

In the last few years, a lot of publications suggested that disabling cerebellar ataxias may develop through immune-mediated mechanisms. In this consensus paper, we discuss the clinical features of the main described immune-mediated cerebellar ataxias and address their presumed pathogenesis. Immune-mediated cerebellar ataxias include cerebellar ataxia associated with anti-GAD antibodies, the cerebellar type of Hashimoto's encephalopathy, primary autoimmune cerebellar ataxia, gluten ataxia, Miller Fisher syndrome, ataxia associated with systemic lupus erythematosus, and paraneoplastic cerebellar degeneration. Humoral mechanisms, cell-mediated immunity, inflammation, and vascular injuries contribute to the cerebellar deficits in immune-mediated cerebellar ataxias.

Objective: Autoimmune cerebellar ataxias were recently reported to be treatable. However, the proportion of patients with cortical cerebellar atrophy of unknown etiology with autoimmune-associated cerebellar ataxia and the actual effectiveness of immunotherapy in these diseases remain unknown., Methods: We measured the level of autoantibodies (including anti-gliadin antibody, anti-glutamic acid decarboxylase (GAD) antibody, and anti-thyroid antibody) in 58 Japanese patients with cerebellar ataxia, excluding those with multiple system atrophy, hereditary spinocerebellar ataxia, cancer, or those who were receiving phenytoin, and the efficacy of immunotherapy was assessed., Results: Thirty-one of 58 (53%) patients were positive for anti-GAD antibody, anti-gliadin antibody, or anti-thyroid antibody. Seven of the 12 anti-gliadin antibody-positive patients, three of the four anti-GAD antibody-positive patients, and three of the six anti-thyroid antibody-positive patients responded well to immunotherapy, indicating that 59% of patients with ataxia-associated antibody-positive cerebellar ataxia undergoing immunotherapy responded well., Conclusion: Some patients with cerebellar ataxia have autoimmune conditions and diagnosing autoimmune cerebellar ataxia is therefore an important component in the care of patients with this disease entity.

Ipomoea trifida (H. B. K.) G. Don. is the most likely diploid ancestor of the hexaploid sweet potato, I. batatas (L.) Lam. To assist in analysis of the sweet potato genome, de novo whole-genome sequencing was performed with two lines of I. trifida, namely the selfed line Mx23Hm and the highly heterozygous line 0431-1, using the Illumina HiSeq platform. We classified the sequences thus obtained as either 'core candidates' (common to the two lines) or 'line specific'. The total lengths of the assembled sequences of Mx23Hm (ITR&#95;r1.0) was 513 Mb, while that of 0431-1 (ITRk&#95;r1.0) was 712 Mb. Of the assembled sequences, 240 Mb (Mx23Hm) and 353 Mb (0431-1) were classified into core candidate sequences. A total of 62,407 (62.4 Mb) and 109,449 (87.2 Mb) putative genes were identified, respectively, in the genomes of Mx23Hm and 0431-1, of which 11,823 were derived from core sequences of Mx23Hm, while 28,831 were from the core candidate sequence of 0431-1. There were a total of 1,464,173 single-nucleotide polymorphisms and 16,682 copy number variations (CNVs) in the two assembled genomic sequences (under the condition of log2 ratio of >1 and CNV size >1,000 bases). The results presented here are expected to contribute to the progress of genomic and genetic studies of I. trifida, as well as studies of the sweet potato and the genus Ipomoea in general., (© The Author 2015. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.)

Objectives: To compare the effect of treatment with silodosin 4 mg once daily versus that of silodosin 4 mg twice daily on storage symptoms in Japanese patients with benign prostatic hyperplasia., Methods: A prospective, multicenter, 12-week, open-labeled study randomized a total of 268 men aged 50 years or older with benign prostatic hyperplasia and overactive bladder to silodosin 4 mg/day or 8 mg/day. Changes in the end-points of the average value of International Prostate Symptom Score, quality of life index in the International Prostate Symptom Score, Overactive Bladder Symptom Score and urodynamic parameters were evaluated. The change in the storage symptom subtotal score of the International Prostate Symptom Score was considered as the primary end-point., Results: Silodosin 4 mg/day was not inferior to silodosin 8 mg/day in regard to the primary end-point. In contrast, the efficacy of treatment with silodosin 4 mg twice daily was greater than that of 4 mg once daily, based on both the quality of life index and the Overactive Bladder Symptom Score total score. There was a discrepancy between the scores evaluated using the International Prostate Symptom Score and Overactive Bladder Symptom Score questionnaires., Conclusions: Silodosin 4 mg once daily is not inferior to silodosin 4 mg twice daily in regard to storage symptoms score evaluated by the International Prostate Symptom Score. In contrast, silodosin 4 mg twice daily is more effective on storage symptoms evaluated by the Overactive Bladder Symptom Score than silodosin 4 mg once daily., (© 2015 The Japanese Urological Association.)

Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease with exacerbations involving recurrent or bilateral optic neuritis and longitudinally extensive transverse myelitis. Pulse steroid therapy is recommended as the initial, acute-phase treatment for NMO. If ineffective, treatment with plasma exchange (PE) should commence. However, no evidence exists to support the effectiveness of PE long after the acute phase. Immunoadsorption therapy (IA) eliminates pathogenic antibodies while sparing other plasma proteins. With IA, side effects of PE resulting from protein substitution can be avoided. However, whether IA is effective for NMO remains unclear. We describe a patient with anti-aquaporin-4-positive myelitis who responded to IA using a tryptophan polyvinyl alcohol gel column that was begun 52 days after disease onset following the acute phase. Even long after the acute phase when symptoms appear to be stable, IA may be effective and should not be excluded as a treatment choice., (© 2014 Wiley Periodicals, Inc.)

Recently, the Department of Clinical Examination has been extensively subdivided. When we perform examinations, we often require wide knowledge of other specialized fields. This symposium was planned to consider the procedure for examinations in the kidney urology field. Seven professionals gave lectures on the interpretation and adequacy of examinations involving the kidney urology field. Knowledge of not only specialized fields but also wide, basic, routine fields is required to perform more precise examinations. Therefore, we became aware that cooperation between examination departments is essential to improve our overall judgments.

Purpose: We examined the complications in the diagnosis and treatment of interstitial cystitis in daily clinical practice., Materials and Methods: The study included 82 patients who were suspected of having interstitial cystitis at our hospital from March 2002 to April 2013. All hydrodistention procedures were performed with the aid of an anesthesiologist, as recommended by the Ministry of Health, Labour, and Welfare since April 2010., Results: Of the 82, 20 patients were male and 62 were female, (mean age at diagnosis 53 years.) Six of the suspected cases did not have interstitial cystitis. Of the 67 patients diagnosed with interstitial cystitis during hydrodistention, 29 (43%) did not experience pain. The time taken to diagnose these asymptomatic patients was longer than that taken for those who experienced pain. Twenty-eight patients (42%) discontinued treatment because it was ineffective., Conclusion: Interstitial cystitis has been widely recognized, but general physicians are unable to provide a diagnosis and suggest aggressive treatment because of difficulty associated in the treatment and diagnosis. To resolve these issues, physicians should be keep in mind that interstitial cystitis involves a hypersensitive bladder, and that some patients may not experience pain. Further, knowledge about Hunner's ulcer is essential. We believe that the most important points are improving health insurance about facility criteria of hydrodistention, and evaluating behavioral modification and dietary manipulation.

Gluten ataxia, a type of cerebellar ataxia caused by exposure to gluten in sensitive patients, has been considered common in the USA and Europe, and rare in Asia. We measured anti-deamidated gliadin peptide (DGP) antibody levels in 49 patients with cerebellar ataxia, excluding those with multiple system atrophy, hereditary spinocerebellar ataxia, or cancer, as well as those who were receiving oral administration of phenytoin. Anti-DGP antibody was positive in eight (16.3 %) patients, five of these patients were positive only for IgA, one was positive for both IgG and IgA, and two were positive only for IgG antibody. Intravenous immunoglobulin was administered to five of the eight patients, and was markedly effective in one, moderately effective in two, and ineffective in two. Steroid therapy was administered to four patients, but none had an apparent response. Ataxia symptoms improved in one patient treated with a gluten-free diet only. Although it had been thought to be extremely rare in Asia, we speculate that more than 10 % of cerebellar ataxia patients in Japan currently have gluten ataxia; therefore, measuring anti-DGP antibody or anti-gliadin antibody in cerebellar ataxia patients in Asia is important.

To develop a high density linkage map in faba bean, a total of 1,363 FBES (Faba bean expressed sequence tag [EST]-derived simple sequence repeat [SSR]) markers were designed based on 5,090 non-redundant ESTs developed in this study. A total of 109 plants of a 'Nubaria 2' × 'Misr 3' F2 mapping population were used for map construction. Because the parents were not pure homozygous lines, the 109 F2 plants were divided into three subpopulations according to the original F1 plants. Linkage groups (LGs) generated in each subpopulation were integrated by commonly mapped markers. The integrated 'Nubaria 2' × 'Misr 3' map consisted of six LGs, representing a total length of 684.7 cM, with 552 loci. Of the mapped loci, 47% were generated from multi-loci diagnostic (MLD) markers. Alignment of homologous sequence pairs along each linkage group revealed obvious syntenic relationships between LGs in faba bean and the genomes of two model legumes, Lotus japonicus and Medicago truncatula. In a polymorphic analysis with ten Egyptian faba bean varieties, 78.9% (384/487) of the FBES markers showed polymorphisms. Along with the EST-SSR markers, the dense map developed in this study is expected to accelerate marker assisted breeding in faba bean.

We evaluated atrophic sites in the brainstem and cerebellum in the patients with spinocerebellar degeneration by using voxel-based morphometry (VBM). Gray matter atrophy was found extensively in both the cerebellar hemispheres and vermis of subjects presenting the cerebellar variant of multiple system atrophy (MSA-C; n=9). In addition, remarkable white matter atrophy was observed in the middle cerebellar peduncle, brainstem, and cerebellar hemispheres. In contrast, gray matter atrophy was not apparent in the cerebellar hemispheres or vermis of subjects in the SCA3 group (n=6), whereas intense white matter atrophy was visible in the middle cerebellar peduncle, brainstem, and cerebellar hemispheres. White matter atrophy was also observed in the brainstem and surrounding the dentate nucleus in both cases of dentatorubral-pallidoluysian atrophy (DRPLA) (n=2), whereas gray matter atrophy of the cerebellum was not remarkable. In both the SCA6 group (n=3) and the SCA31 group (n=2), gray matter atrophy was prominent in the cerebellar hemispheres and vermis; however, white matter atrophy was not found in the middle cerebellar peduncle and brainstem, whereas symmetric atrophy of white matter was found in the vicinity of the dentate nucleus. In each of these diseases, VBM findings were consistent with the pathological findings; therefore, VBM can be considered a useful tool for the diagnosis of spinocerebellar degeneration.

Cultivated strawberry (Fragaria x ananassa) is octoploid and shows allogamous behaviour. The present study aims at dissecting this octoploid genome through comparison with its wild relatives, F. iinumae, F. nipponica, F. nubicola, and F. orientalis by de novo whole-genome sequencing on an Illumina and Roche 454 platforms. The total length of the assembled Illumina genome sequences obtained was 698 Mb for F. x ananassa, and ∼200 Mb each for the four wild species. Subsequently, a virtual reference genome termed FANhybrid&#95;r1.2 was constructed by integrating the sequences of the four homoeologous subgenomes of F. x ananassa, from which heterozygous regions in the Roche 454 and Illumina genome sequences were eliminated. The total length of FANhybrid&#95;r1.2 thus created was 173.2 Mb with the N50 length of 5137 bp. The Illumina-assembled genome sequences of F. x ananassa and the four wild species were then mapped onto the reference genome, along with the previously published F. vesca genome sequence to establish the subgenomic structure of F. x ananassa. The strategy adopted in this study has turned out to be successful in dissecting the genome of octoploid F. x ananassa and appears promising when applied to the analysis of other polyploid plant species.

Background: Abdominal ultrasound is the most convenient modality for examining the morphology of the pancreas without physical stress. Steroid response is one of the key features of autoimmune pancreatitis; however, visualizing this response has not been evaluated using ultrasonography., Methods: Thirty-three consecutive autoimmune pancreatitis cases were retrospectively investigated for pancreatic and extrapancreatic lesions by ultrasonography before steroid therapy (n=33) and at two weeks (n=28) and one month (n=19) after starting oral steroid treatment., Results: Steroid treatment resulted in obvious shrinkage of the pancreatic lesion in 86% of the cases at two weeks and in 97% until one month. The maximum thickness of the pancreatic lesion was reduced from 28 to 22 mm in two weeks (P<0.0001), and pancreatic echographic findings improved in one month. Swelling of the peripancreatic lymph node was recognized in 48% and the aortic wall thickness in 12%, mostly reduced in two weeks (P=0.005). One case of definitive autoimmune pancreatitis revealed a steroid response only by following endoscopic retrograde cholangiopancreatography but not by ultrasonography or computed tomography., Conclusions: Abdominal ultrasound revealed a steroid response in most cases of autoimmune pancreatitis within two weeks. Ultrasonography is suitable for initial confirmation of a steroid response; however, atypical cases showing insufficient response or not fulfilling criteria should undergo further examination., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Control of sound in phononic band-gap structures promises novel control and guiding mechanisms. Designs in photonic systems were quickly matched in phononics, and rows of defects in phononic crystals were shown to guide sound waves effectively. The vast majority of work in such phononic guiding has been in the frequency domain, because of the importance of the phononic dispersion relation in governing acoustic confinement in waveguides. However, frequency-domain studies miss vital information concerning the phase of the acoustic field and eigenstate coupling. Using a wide range of wavevectors k, we implement an ultrafast technique to probe the wave field evolution in straight and L-shaped phononic crystal surface-phonon waveguides in real- and k-space in two spatial dimensions, thus revealing the eigenstate-energy redistribution processes and the coupling between different frequency-degenerate eigenstates. Such use of k-t space is a first in acoustics, and should have other interesting applications such as acoustic-metamaterial characterization.

The majority of cases of anti-glutamic acid decarboxylase (GAD)-antibody-positive cerebellar ataxia are reported to have high levels of anti-GAD antibody, and the diagnostic value of low titers of anti-GAD antibody in a patient with cerebellar ataxia is still unknown. The purpose of this study was to verify the characteristics of low-titer-anti-GAD-antibody-positive cerebellar ataxia patients and the diagnostic value of low titers of anti-GAD antibody in patients with cerebellar ataxia. The subjects were six patients positive for low-titer GAD antibody (<100 U/mL). We examined them with MRI, including voxel-based morphometry, and with single-photon emission computed tomography and monitored the GAD antibody index in the cerebrospinal fluid. The levels of antineuronal, antigliadin, anti-SS-A, antithyroid antibodies, and of vitamins E, B1, and B12 were determined. Thoracic and abdominal CT scans were performed to exclude a paraneoplastic origin. We treated three patients with immunotherapy. All cases showed cortical cerebellar atrophy. The GAD antibody index in three of the five patients reviewed was >1.0. Two of the six patients were thyroid antibody-positive, and one was both antinuclear- and anti-SS-A antibody-positive. After the administration of immunotherapy to three patients, two showed clear effectiveness, and one, transient effectiveness. Effectiveness was greatest in the two patients with familial occurrence of the disease. In cerebellar ataxia, regardless of family history or isolated illness, it is critical to measure the GAD antibody level, and, even with a low titer level, if the result is positive, immunotherapy should be considered.

Various autoantibodies are associated with autoimmune-mediated cerebellar ataxia. Anti-Yo, -Zic, -CARPVIII, -Tr, -Ri, -Hu, -Ma, -CRMP-5, -ANNA-3, -PCA-2, -VGCC, and -mGluR antibodies (Abs) are found in paraneoplastic cerebellar ataxia, whereas anti-GAD, -thyroid, and -gliadin Abs are found in non-paraneoplastic cerebellar ataxia. Most of these antibodies are not pathogenic but are diagnostic markers. However, anti-VGCC, anti-mGluR, and anti-GAD Abs have been shown to cause cerebellar ataxia, because administration of these Abs mimics cerebellar ataxia in vivo. Experiments using in vitro preparations show that anti-VGCC Ab depresses excitatory synaptic transmissions, and anti-GAD Ab suppresses inhibitory synaptic transmissions. Anti-mGluR Ab interferes with the induction of synaptic plasticity. These results suggest that pathogenic Abs elicit cerebellar synaptic dysfunction, and thereby cause ataxia in patients.

The cultivated strawberry (Fragaria × ananassa) is an octoploid (2n = 8x = 56) of the Rosaceae family whose genomic architecture is still controversial. Several recent studies support the AAA'A'BBB'B' model, but its complexity has hindered genetic and genomic analysis of this important crop. To overcome this difficulty and to assist genome-wide analysis of F. × ananassa, we constructed an integrated linkage map by organizing a total of 4474 of simple sequence repeat (SSR) markers collected from published Fragaria sequences, including 3746 SSR markers [Fragaria vesca expressed sequence tag (EST)-derived SSR markers] derived from F. vesca ESTs, 603 markers (F. × ananassa EST-derived SSR markers) from F. × ananassa ESTs, and 125 markers (F. × ananassa transcriptome-derived SSR markers) from F. × ananassa transcripts. Along with the previously published SSR markers, these markers were mapped onto five parent-specific linkage maps derived from three mapping populations, which were then assembled into an integrated linkage map. The constructed map consists of 1856 loci in 28 linkage groups (LGs) that total 2364.1 cM in length. Macrosynteny at the chromosome level was observed between the LGs of F. × ananassa and the genome of F. vesca. Variety distinction on 129 F. × ananassa lines was demonstrated using 45 selected SSR markers.

Objective: The long-term use of levodopa to treat Parkinson's disease (PD) is often limited by the development of motor complications (e.g., levodopa-induced dyskinesia, LID). We hypothesized that a non-ergot dopamine agonist with strong affinity for D3) dopamine receptors (pramipexole) may improve LID in patients taking an ergot D1/D2 dopamine agonist., Methods: Patients with PD and LID being treated with levodopa in addition to an ergot dopamine agonist were randomized to either a group in which pramipexole was added to current medications or a group in which the ergot dopamine agonist was switched to pramipexole. Dyskinesia was evaluated using Core Assessment Program for Surgical Interventional Therapies scores. The unified Parkinson's disease rating scale scores, modified Hoehn and Yahr stages (at 'on' time), Parkinson's disease questionnaire-39 scores and clinical global impression-improvement scores were also used for evaluation., Results: At 24 weeks, pramipexole alleviated LID with more efficiency in the switch group., Conclusion: Pramipexole may be a therapeutic option for treating LID because its effects on D3 dopamine receptors may balance the D1 dopamine receptor supersensitivity associated with LID.

We present a case of slowly progressive gait ataxia with a 16-year history in an 87-year-old woman. In 1994 she became aware of a slight unsteadiness while walking and cortical cerebellar atrophy was diagnosed. She had no familial history of neurological disorders. In 2007, idiopathic thrombocytopenic purpura (ITP) was diagnosed. The symptoms gradually worsened, and she was admitted in 2010 because she could not walk without support. MRI voxel-based morphometry (VBM) imaging showed atrophy of the entire cerebellum, and SPECT using eZIS showed reduced perfusion in the same regions. Her blood was positive for both anti-TPO antibody (42 IU/ml) and anti-gliadin antibody (20.2 EU). We therefore diagnosed autoimmune cerebellar atrophy. The patient showed a positive response to intravenous immunoglobulins (IVIg) and regained the ability to walk unassisted. Her posture and gait disturbance scores on the International Cooperative Ataxia Rating Scale had improved from 20 to 9. Even 16 years after onset, intravenous immunoglobulins were effective. In cases of prolonged disease, immunotherapy can be effective in autoimmune cerebellar atrophy and should not be excluded from the treatment choices.

The patient was an 84-year-old woman who had the onset of truncal ataxia at age 77 and a history of Basedow's disease. Her ataxic gait gradually deteriorated. She could not walk without support at age 81 and she was admitted to our hospital at age 83. Gaze-evoked nystagmus and dysarthria were observed. Mild ataxia was observed in all limbs. Her deep tendon reflex and sense of position were normal. IgA anti-gliadin antibody, IgG anti-gliadin antibody, anti-SS-A/Ro antibody, anti-SS-B/La antibody and anti-TPO antibody were positive. A conventional brain MRI did not show obvious cerebellar atrophy. However, MRI voxel based morphometry (VBM) and SPECT-eZIS revealed cortical cerebellar atrophy and reduced cerebellar blood flow. IVIg treatment was performed and was moderately effective. After her death at age 85, the patient was autopsied. Neuropathological findings were as follows: selective loss of Purkinje cells; no apparent degenerative change in the efferent pathways, such as the dentate nuclei or vestibular nuclei; no prominent inflammatory reaction. From these findings, we diagnosed this case as autoimmune cerebellar atrophy associated with gluten ataxia. All 3 autopsies previously reported on gluten ataxia have noted infiltration of inflammatory cells in the cerebellum.In this case, we postulated that the infiltration of inflammatory cells was not found because the patient's condition was based on humoral immunity. The clinical conditions of gluten ataxia have not yet been properly elucidated, but are expected to be revealed as the number of autopsied cases increases.

A 76-year-old woman experienced unsteadiness in walking in 1996. On the basis of clinical and imaging findings, the patient was diagnosed multiple system atrophy. During follow-up, her gait disturbance became aggravated leaving her unable to walk unaided. She was referred to our department in 2003. T2-weighted images on brain magnetic resonance imaging (MRI) revealed low signal intensity in both putamina and a linear high-signal-intensity area on their outsides. Single photon emission computed tomography (SPECT) disclosed a reduced blood flow in both corpora striata. These findings were consistent with the diagnosis of Parkinsonian-type multiple system atrophy. The patient had anti-glutamic acid decarboxylase (GAD) antibody-positive type 1 diabetes mellitus and a normal thyroid function, and was positive for antithyroid antibodies. She was not found to have anemia on blood tests, but was positive for intrinsic factor antibodies. Vitamin B12 was markedly reduced to below the detection limit. The findings suggested that the patient's condition was autoimmune polyglandular syndrome type 3. In 2004, treatment with intramuscular injection of vitamin B12 was initiated, after which the patient's gait disturbance was improved and she was able to walk unaided. In 2009, her unsteady gait returned and was again unable to walk unaided. Autoimmune encephalopathy was suspected, and thus high-dose intravenous immunoglobulin therapy was performed. Following treatment she was able to walk steadily. This case suggests the importance of detailed tests for autoantibodies, including endocrine autoantibodies, and the measurement of vitamin B12 and total homocysteine levels in view of the possibility of autoimmune polyglandular syndrome-related neurological disorders in diabetic patients with intractable neurological disorders that are difficult to diagnose.

The patient, a 63-year-old man, experienced the subacute onset of chorea, for which his family doctor prescribed oral haloperidol. However, the involuntary movements gradually worsened, and the patient was referred and admitted. High-signal lesions were seen in the caudate nucleus, putamen and globus pallidus bilaterally on MRI T2-weighted and FLAIR images. Chest CT, FDG-PET and tissue biopsies also revealed that the patient had lung adenocarcinoma with multiple lymph node metastases. The patient was diagnosed as having paraneoplastic chorea associated with primary lung adenocarcinoma. Antineuronal antibodies, such as anti-CRMP-5 and anti-Yo antibodies, were absent. The patient received steroid pulse therapy, oral prednisolone therapy, and concurrent radiochemotherapy. Chorea and high-signal lesions in the corpus striatum bilaterally on MRI improved quickly, and the mediastinal lymph node swelling also improved. The patient has been stable for 3 years since the onset of his symptoms. As the prognosis of paraneoplastic chorea is relatively favorable in some patients, it should be considered in the differential diagnosis of patients with chorea.

Objective: With conventional MRI and single-photon emission computed tomography (SPECT), accurate diagnosis and precise classification of cerebellar atrophy are often difficult. The objective was to verify the utility of MRI voxel-based morphometry (VBM) in combination with SPECT using easy Z-score imaging (eZIS) for diagnosing and classifying cerebellar atrophy., Patients and Methods: We assessed gray matter atrophy using VBM and blood perfusion using SPECT with eZIS in fifteen patients with different types of cerebellar atrophy, such as the cerebellar variant of multiple system atrophy (MSA-C), spinocerebellar ataxia type 3 (SCA3), SCA6, and autoimmune cerebellar ataxia (AICA)., Results: In all five MSA-C patients, VBM imaging showed atrophy of the brainstem, the entire cerebellar vermis, and the cerebellar hemispheres, while SPECT using eZIS showed reduced perfusion in the same regions. Regarding SCA3, brainstem atrophy and reduced perfusion were recognized in two of the four patients, but none exhibited abnormal findings in the posterior lobe of the cerebellar vermis. SPECT showed that all four patients had obviously reduced perfusion in the anterior lobe of the vermis, but VBM demonstrated that there was no obvious atrophy of gray matter in any patient, meaning that the results of SPECT and VBM contradicted each other completely. All SCA6 and AICA patients exhibited atrophy and reduced perfusion in the cerebellar hemispheres but not in the brainstem. Only one AICA patient exhibited atrophy and reduced perfusion of the entire cerebellar vermis., Conclusion: VBM clearly showed characteristic gray matter atrophy in the cerebellum and brainstem in different pathological conditions, thus indicating its high degree of utility in diagnosing and classifying cerebellar atrophy in combination with SPECT using eZIS.

A 52-year-old woman was admitted to the hospital because of appetite loss, unsteadiness, psychogenic symptoms, ataxia, and consciousness disturbance as a result of the ingestion of a diet restricted to only carbohydrates for a long term. Laboratory examination indicated the presence of pancytopenia with macrocytic anemia; further, decreased vitamin B1 and B12 levels were detected in her serum. Magnetic resonance imaging fluid attenuated inversion recovery (FLAIR), revealed high-signal intensity in the bilateral corpus striatum, third ventricle circumference, and cerebellar cortex. Thereafter, she received drip infusion that did not include vitamin B1 or B12 and subsequently suffered a cardiac arrest due to the aggravation of cardiac insufficiency; consequently, she was transferred to our hospital. Upon admission the patient was diagnosed to have obvious cardiomegaly with pleural effusion; further, a negative T-wave was obtained on the electrocardiogram. A diagnosis of beriberi heart disease was made because of thiamine deficiency. She was treated by thiamine administration, following which the cardiac symptoms improved immediately. Various neurological symptoms caused by encephalopathy, peripheral neuropathy and subacute combined spinal cord degeneration improved by treatment with thiamine and cyanocobalamine administration; however, some of these symptoms still remained. General awareness of the fact that neurological symptoms can be caused by vitamin deficiency is essential.

We present the case of a 51-year-old man with a 5-year history of slowly progressive gait ataxia and dysarthria who showed a wide-based gait requiring assistance. The patient's score on the Revised Hasegawa Dementia Scale (HDS-R) was 22/30 and constructional apraxia was also evident. Cerebrospinal fluid analysis showed 3 cells/microl, and the protein concentration was 58 mg/dl. Brain MRI showed no evidence of cerebellar atrophy, and SPECT-eZIS showed no decrease in cerebellar blood flow. However, voxel based morphometry (VBM) and FineSRT revealed cortical cerebellar atrophy and reduced cerebellar blood flow. In addition, the patient tested positive for anti-gliadin (IgA) and anti-SS-A/Ro antibodies, and was thus diagnosed as having autoimmune cerebellar ataxia. The patient showed positive response to intravenous immunoglobulins (IVIg) and regained the ability to walk unassisted. The HDS-R score also improved to 27/30. If cortical cerebellar atrophy can be diagnosed in the early stages in patients with progressive cerebellar ataxia by imaging techniques such as MRI-VBM and FineSRT, and if such patients test positive for anti-gliadin, anti-GAD or anti-thyroid antibodies, it is possible that they have autoimmune cerebellar ataxia. The commencement of immunotherapy including IVIg should be considered in such

Objective: It has been reported that autoimmune cerebellar ataxias, such as anti-glutamic acid decarboxylase (GAD)-antibody-positive cerebellar ataxia and gluten ataxia, are treatable. Here, we examined the therapeutic efficacy of intravenous immunoglobulin (IVIg) on autoantibody-positive cerebellar ataxia., Patients and Methods: IVIg therapy was administered in seven autoantibody-positive cerebellar ataxia patients. Therapeutic efficacy was examined in terms of its effects on clinical symptoms and changes in brain perfusion using single photon emission computed tomography (SPECT)., Results: Treatment was effective in four cerebellar cortical atrophy patients (two anti-GAD antibody-positive and two anti-gliadin antibody-positive) and in one anti-thyroid antibody-positive spinocerebellar ataxia type 3 (SCA3) patient, but not in two multiple system atrophy (MSA) patients. All four IVIg effective patients who underwent SPECT showed apparent increases in cerebellar perfusion., Conclusion: If cerebellar ataxia with an autoimmune mechanism is suspected and radiological findings do not reveal MSA, it is worth considering immunotherapy including IVIg.

Hemiballism is most commonly caused by ischemic stroke and most cases have a favorable prognosis. Lesions directly involving the subthalamic nucleus (STN) are the cause of a minority of cases but are usually associated with poor prognosis. We report two patients with a small STN lesion who presented with transient hemiballism. A small lesion confined to and only focally affecting the STN may cause hemiballism yet may have excellent outcome. Precise evaluation of the affected region with MRI is useful in predicting the prognosis.

Aim: The disc assay system for prostate-specific antigen (PSA) is a novel technique using a small amount of whole blood on filter paper. The accuracy of this assay system and its feasibility for use in prostate cancer mass screening were evaluated., Methods: In the first arm of the study, to evaluate the accuracy of the disc assay system, PSA values were determined by both a disc assay system and a standard serum assay system using the same blood samples obtained from 420 outpatients. In the second arm of the study, the feasibility and reliability of the disc assay system were examined in prostate cancer mass screening. A total of 2475 men were screened by the disc assay (disc group) and 3348 men were screened by the standard serum assay (serum group) in the first step of mass screening. In the second step of the screening in the disc group, 101 men underwent PSA tests by a standard serum assay, then the first PSA values determined by the disc assay were compared with the second PSA values determined by the standard serum assay. In the second step of the screening in the serum group, 94 men underwent additional PSA tests by a serum assay, and then the first PSA values were compared with the second PSA values. Two men in each group were excluded from analysis because the true PSA values of the first step were not available (more than 50 ng/mL)., Results: The PSA values determined by the disc assay closely correlated with those obtained by the standard assay (r = 0.987) in 295 outpatients with PSA levels between 1.0 and 20 ng/mL. In the PSA mass screening, the PSA values determined in the first step closely correlated with those in the second step both in the disc group (r = 0.916) and in the serum group (r = 0.845). A significant dissociation of the two PSA values was observed in seven of 99 men in the disc group and in three of 92 men in the serum group. However, there was no statistical significance in the incidence of dissociation in the two PSA values between the disc group and the serum group., Conclusions: The disc assay system seems to be a sensitive and accurate assay system. The feasibility and reliability of the disc assay system were well demonstrated in the field during prostate cancer mass screening.

In slowly progressive cerebellar atrophy, it has been difficult to suppress the progression of cerebellar symptoms because no effective therapeutic agents are available when the diagnosis of secondary cerebellar atrophy, such as drug-induced cerebellar atrophy or paraneoplastic syndrome, is denied. However, amongst the different forms of slowly progressive cerebellar atrophy, some may be associated with treatable immune abnormalities. Therefore, we investigated the therapeutic efficacy of intravenous immunoglobulin (IVIg) in 9 patients with slowly progressive cerebellar atrophy (4 sporadic atrophy; 5 hereditary atrophy). The results were as follows. With regard to the 4 cases of sporadic atrophy, gait ataxia and imbalance were markedly improved in 1 patient who had positive anti-GAD antibody. Moderate improvement was seen in 1 patient and slight improvement in 2. With regard to the 5 cases of hereditary atrophy, gait ataxia and imbalance were moderately improved in 2 patients with SCA3, although there were 3 non-responders. In conclusion, our study results suggested that not only patients with sporadic atrophy but also some with hereditary atrophy may respond to therapy. In cases of slowly progressive cerebellar atrophy in which the cause may be due to immune abnormality, we should consider instituting active immunotherapy when a pathological state caused by immune abnormality is suspected after extensive evaluations of autoantibodies, including anti-GAD, anti-thyroid and anti-gliadin antibody, malignancy, and so on.

Purpose: We studied the sonographic appearance of the anterior liver surface using an ultrasound scanner equipped with a 7.5-MHz annular-array transducer to determine the accuracy of this imaging modality in monitoring the course of chronic liver diseases., Methods: We prospectively evaluated patterns of the liver surface in the sonograms of 77 consecutive patients with chronic liver diseases who had undergone sonographic examination with a 7.5-MHz annular-array transducer and a 3.75-MHz convex-array transducer over a 2-year period and compared these findings with those of laparoscopy (using previously described categories) and histopathology., Results: Histopathologically confirmed disease prevalences for inactive chronic hepatitis, active chronic hepatitis, liver cirrhosis, and others were 10% (8/77), 56% (43/77), 29% (22/77), and 5% (4/77), respectively. The sonographic appearance of the liver surface with the 3.75-MHz transducer was classified as either a regular or an irregular pattern. The regular pattern corresponded to 69% (34/50) of the cases in laparoscopic category 200 or 300 and the irregular pattern with 85% (23/27) of the cases in category 400 or 500. The sonographic appearance of the liver surface with the 7.5-MHz transducer was classified as regular, unevenly irregular, diffusely irregular, or nodular. These 4 patterns detected 75% (24/32), 78% (14/18), 52% (12/23), and 75% (3/4) of the cases of laparoscopic categories 200, 300, 400, and 500, respectively. In a comparison of the sonographic patterns of the liver surface with the differential histopathologic findings, the regular sonographic pattern corresponded to 88% (7/8) of the cases of inactive chronic hepatitis, the unevenly irregular pattern with 35% (15/43) of the cases of active chronic hepatitis, and the diffusely irregular and nodular patterns (considered as 1 group) with 68% (15/22) of the cases of liver cirrhosis., Conclusions: Our results suggest that sonographic evaluation of the liver surface with a 7.5-MHz annular-array transducer using this classification provides detailed information on the evolution of chronic liver diseases that correlates with the laparoscopic and histopathologic findings and thus is a useful noninvasive method for monitoring the disease course to cirrhosis., (Copyright 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31: 393-400, 2003)

A high-power, narrow-linewidth Yb fiber laser with a fiber Bragg grating (FBG) pumped difference frequency generation (DFG) in a periodically poled lithium niobate (PPLN) crystal was investigated in detail. A mid-IR power of approximately 2.3 microW at 3.3 micrometers with a slope efficiency of 0.85 mW/W2 was achieved. A Doppler-broadened absorption spectrum of CH4 at 3038.497 cm-1 (3.2911 micrometers) was obtained with a 0.1-m long-gas cell at a pressure of 133 Pa. The linewidth of the DFG source was evaluated to be less than 96 MHz from the observed spectral linewidth. Real-time monitoring of CH4 (approximately 1.78 ppm) in ambient air in a multipass cell which has an optical path length of 10 m was also demonstrated.

We reported a 31 year-old man with repeated episodes of migraine at a frequency of about once a week on and after January, 2000. In January 2001, scintillating scotoma and pulsating headache appeared followed by left hemianopsia. His platelet count decreased to 80,000/microliter and high intensity areas were observed in the right occipital lobe and hippocampal gyrus on the FLAIR image of brain MRI. Subsequently performed brain MRA and vertebral angiography revealed segmental stenosis and obstruction in the right posterior cerebral artery. Under the diagnosis of migrainous infarction, sodium ozagrel and lomerizine hydrochloride were administered. Idiopathic thrombocytopenic purpura was additionally diagnosed based on the decreased platelet count which was then treated with predonisolone. After these treatment, his migraine attack disappeared. In this patient, platelet destruction due to idiopathic thrombocytopinic purpura and subsequent release of serotonin seemed to have involved in the occurrence of migrainous infarction.

A 70-year-old Japanese man with amyloid polyneuropathy associated with a Val 107 transthyretin (TTR) mutation is reported. The patient presented with carpal tunnel syndrome, cardiomyopathy, bulbar palsy, dysphonia and polyneuropathy. DNA analysis of the TTR gene revealed a point mutation responsible for substitution of valine for isoleucine at position 107 of the TTR molecule. Taken together with reports of patients with the same TTR variant, Val 107 TTR mutation is probably associated with a clinical phenotype characterized by carpal tunnel syndrome, cardiomyopathy, bulbar palsy and dysphonia. This case implies a worldwide distribution of the Val 107 TTR mutation with a common clinical phenotype, despite different ethnic background.

A Yb fiber laser pumped cw narrow-linewidth tunable mid-IR source based on a difference frequency generation (DFG) in a periodically poled LiNbO3 (PPLN) crystal for trace gas detection was demonstrated. A high power Yb fiber laser and a distributed feedback (DFB) laser diode were used as DFG pump sources. This source generated mid-IR at 3 microns with a powers of ~2.5 microW and a spectral linewidth of less than 30 MHz. A frequency tuning range of 300 GHz (10 cm-1) was obtained by varying the current and temperature of the DFB laser diode. A high-resolution NH3 absorption Doppler-broadened spectrum at 3295.4 cm-1 (3.0345 microns) was obtained at a cell pressure of 27 Pa from which a detection sensitivity of 24 ppm m was estimated.

A new method for studying brain microcirculation is described. Both fluorescently labeled erythrocytes and plasma were visualized on-line through a closed cranial window in anesthetized rats, using laser-scanning two-dimension confocal microscopy. Video images of capillaries, arterioles, and venules were digitized off-line to measure microvessel diameter and labeled erythrocyte flow and velocity in parenchymal capillaries up to 200 microm beneath the brain surface. The method was used to analyze the rapid adaptation of microcirculation to a brief decrease in perfusion pressure. Twenty-second periods of forebrain ischemia were induced using the tour-vessel occlusion model in eight rats. EEG, arterial blood pressure, and body temperature were continuously controlled. In all conditions, labeled erythrocyte flow and velocity were both very heterogeneous in capillaries. During ischemia, capillary perfusion was close to 0, but a low blood flow persisted in arterioles and venules, while EEG was flattening. The arteriole and venule diameter did not significantly change. At the unclamping of carotid arteries, there was an instantaneous increase (by about 150%) of arteriole diameter. Capillary erythrocyte flow and velocity increased within 5 seconds, up to, respectively, 346 +/- 229% and 233 +/- 156% of their basal value. No capillary recruitment of erythrocytes was detected. All variables returned to their basal levels within less than 100 seconds after declamping. The data are discussed in terms of a possible involvement of shear stress in the reperfusion period.

An optical resonator simulation code based on the idea of a partially coherent optical field has been developed and used to optimize the design parameters of an unstable resonator with a stable core. The resonator was intended for use with low-gain, large-bore lasers, such as the chemical oxygen-iodine laser (COIL). First the design parameters of the resonator were optimized by the simulation code; then a set of mirrors was fabricated for a small-scale COIL. A 14-W output with M(2) = 29 was obtained. The experimentally obtained results were in good agreement with calculations.

Background and Purpose: The present study was designed to investigate whether neuronally derived nitric oxide (NO) plays a toxic role in the cascade of cellular events triggered by global cerebral ischemia in rats., Methods: 7-Nitroindazole (7-NI) was used as a selective inhibitor of neuronal NO synthase. Global ischemia was induced for 20 minutes in anesthetized rats following the four-vessel occlusion model. Electroencephalogram and brain and body temperatures were continuously monitored. All rats were thermoregulated for the entire duration of anesthesia. 7-NI (25 mg/kg) or its vehicle was given intraperitoneally just after the carotid clamping and again 1 hour later. Rats were randomly divided into four groups: (1) vehicle (n = 7); (2) 7-NI (n = 7); (3) L-arginine (300 mg/kg IP) +7-NI (n = 7); and (4) 7-NI associated with warming to 37 degrees C for 7 hours after disruption of anesthesia to compensate for the decrease in temperature induced by 7-NI (n = 9). Seven days after ischemia, hippocampal CA1 damage was evaluated by classic histology. The lesion was scored with the use of a point scale, and the surviving neurons were counted., Results: Lesion scores were significantly lower and neuron counts higher in the two (warmed and unwarmed) groups of rats in which 7-NI was given alone than in vehicle- and L-arginine +7-NI-treated rats., Conclusions: The results indicate that 7-NI was neuroprotective in 20-minute global ischemia in rats and that the neuroprotective effect of 7-NI was mostly due to the blockade of NO synthesis, suggesting that NO released from neurons in ischemic conditions has a deleterious influence on hippocampal pyramidal neurons.

The vasodilatory action of potassium channel openers through a membrane hyperpolarizing action is well known, but little is known about the effect of these drugs on ischemia-induced glutamate release in the brain. We evaluated the effects of a potassium channel opener (Y-26763), given intravenously at 0.03 mg/kg/h from 50 min prior to occlusion until 3 h postocclusion, on cerebral blood flow, extracellular glutamate concentration, and infarct volume in rats with focal ischemia. Y-26763 significantly inhibited the increase in extracellular glutamate concentration at 50 and 60 min of ischemia with a significant reduction of mean arterial blood pressure. However, there was no significant difference in blood flow in the core of infarcted cortex or in infarct volume between Y-26763- and vehicle-treated groups. These results suggest that Y-26763 inhibited presynaptic glutamate release through hyperpolarizing the membrane, but infarct volume was not reduced because of insufficient perfusion owing to its hypotensive effect.

The purpose of the present study was to clarify the effect of topical administration of a nitric oxide synthase inhibitor on extracellular glutamate concentration in transient forebrain ischemia. Two microdialysis probes were inserted into the bilateral striata of Wistar rats. NG-Nitro-L-arginine (L-NNA) with or without L-arginine was topically administered into the unilateral striatum through one of the microdialysis probes, while Ringer's solution was perfused into the contralateral striatum as the control, and 14 minutes of forebrain ischemia was applied. The extracellular glutamate concentration during ischemia and subsequent reperfusion was statistically significantly higher on the 100 microM L-NNA-perfused side than on the control side, but 1 mM L-NNA was ineffective. When 100 microM L-NNA was perfused together with 500 microM L-arginine, the glutamate concentration did not differ from that on the control side. Moreover, administration of 500 microM L-arginine significantly suppressed the glutamate elevation after reperfusion. The fact that the lower dose of L-NNA increased the accumulation of glutamate during ischemia and reperfusion without altering blood flow may indicate that nitric oxide affords protection against ischemia neuronal damage. However, since the higher dose of L-NNA did not affect the glutamate concentration, it appears that the effect of nitric oxide on extracellular glutamate concentration in forebrain ischemia differs, depending on the degree of the inhibition of NOS activity.