195 research outputs found

    PLD4 Is Involved in Phagocytosis of Microglia: Expression and Localization Changes of PLD4 Are Correlated with Activation State of Microglia

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    Phospholipase D4 (PLD4) is a recently identified protein that is mainly expressed in the ionized calcium binding adapter molecule 1 (Iba1)-positive microglia in the early postnatal mouse cerebellar white matter. Unlike PLD1 and PLD2, PLD4 exhibits no enzymatic activity for conversion of phosphatidylcholine into choline and phosphatidic acid, and its function is completely unknown. In the present study, we examined the distribution of PLD4 in mouse cerebellar white matter during development and under pathological conditions. Immunohistochemical analysis revealed that PLD4 expression was associated with microglial activation under such two different circumstances. A primary cultured microglia and microglial cell line (MG6) showed that PLD4 was mainly present in the nucleus, except the nucleolus, and expression of PLD4 was upregulated by lipopolysaccharide (LPS) stimulation. In the analysis of phagocytosis of LPS-stimulated microglia, PLD4 was co-localized with phagosomes that contained BioParticles. Inhibition of PLD4 expression using PLD4 specific small interfering RNA (siRNA) in MG6 cells significantly reduced the ratio of phagocytotic cell numbers. These results suggest that the increased PLD4 in the activation process is involved in phagocytosis of activated microglia in the developmental stages and pathological conditions of white matter

    Impact of Comorbid Hepatic Steatosis on Treatment of Chronic Hepatitis C in Japanese Patients and the Relationship with Genetic Polymorphism of IL28B, PNPLA3 and LDL Receptor

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    The impact of hepatic steatosis on interferon therapy for patients with chronic hepatitis C (CHC) has been associated with single-nucleotide polymorphisms (SNP) of IL28B, patatin-like phospholipase domain-containing protein 3 (PNPLA3), and low-density lipoprotein (LDL) receptor. Whether this holds true for Japanese patients, however, remains unresolved. The present study prospectively enrolled 226 Japanese patients with CHC, and investigated the impact of hepatic steatosis and its related SNPs, including rs8099917 of IL28B, rs738409 of PNPLA3, and rs14158 of LDL receptor, on outcomes of peg-interferon and ribavirin therapy. In multivariate logistic regression analysis, significant factors affecting the severity of hepatic steatosis were high body mass index and the minor alleles of IL28B SNP (p0.020 and 0.039, respectively). The risk alleles of PNPLA3 SNP also showed weak association (p0.059). Severe steatosis and the minor alleles of IL28B SNP were significantly associated with null or partial virological response in patients with HCV genotype 1, as were female gender, and low LDL cholesterol (p0.049, and 0.001, respectively). The SNP genotype of PNPLA3 and LDL receptor did not have a significant impact on therapeutic outcomes. With respect to the SNP sites examined, the SNP of PNPLA3 has a weak association with severe hepatic steatosis, but not with the outcome of interferon therapy

    Percutaneous Endoscopic Gastrostomy, Duodenostomy and Jejunostomy

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    Although enteral feeding by nasal gastric tube is popular for the patients who have a swallowing disability and require long-term nutritional support, but have intact gut, this tube sometimes causes aspiration pneumonia or esophageal ulcer. For these patients, conventional techniques for performance of a feeding gastrostomy made by surgical laparotomy have been used so far. However, these patients are frequently poor anesthetic and operative risks. Percutaneous endoscopic gastrostomy (PEG) which can be accomplished with local anesthesia and without the necessity for laparotomy has become popular in the clinical treatment for these patients. PEG was performed in 31 cases, percutaneous endoscopic duodenostomy (PED) in 1 case, and percutaneous endoscopic jejunostomy (PEJ) in 2 cases. All patients were successfully placed, and no major complication and few minor complications (9%) were experienced in this procedure. After this procedure, some patients could discharge their sputa easily and their pneumonia subsided. PED and PEJ for the patients who had previously received gastrostomy could also be done successfully with great care. Our experience suggests that PEG, PED, and PEJ are rapid, safe, and useful procedures for the patients who have poor anesthetic or poor operative risks

    Association between Hardness (Difficulty of Chewing) of the Habitual Diet and Premenstrual Symptoms in Young Japanese Women

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    Recent evidence suggests that voluntary rhythmic movements such as chewing may increase blood serotonin and subsequently brain serotonin, which in turn acts to alleviate premenstrual symptoms. In this observational cross-sectional study, we tested the hypothesis that hardness (difficulty of chewing) of the habitual diet (i.e. dietary hardness) is associated with decreased premenstrual symptoms. Subjects were 640 female Japanese dietetic students aged 18–22 years. Dietary hardness was assessed as an estimate of masticatory muscle activity for the habitual diet (i.e. the difficulty of chewing the food). The consumption of a total of 107 foods was estimated by means of a self-administered, comprehensive diet history questionnaire, and masticatory muscle activity during the ingestion of these foods was estimated according to published equations. Menstrual cycle symptoms were assessed using the retrospective version of the Moos Menstrual Distress Questionnaire, from which total score and subscale scores (i.e. pain, concentration, behavioral change, autonomic reactions, water retention, and negative affect) in the premenstrual phase were calculated and expressed as percentages relative to those in the intermenstrual phase. Dietary hardness was not associated with total score in the premenstrual phase (P for trend = 0.48). Further, no association was seen for any subscale score in the premenstrual phase (P for trend = 0.18–0.91). In conclusion, this preliminary study failed to substantiate a hypothesized inverse relationship between hardness of the habitual diet and premenstrual symptoms. Considering the plausibility of the putative mechanism, however, further investigation using more relevant measures of chewing and premenstrual symptoms is warranted

    Late-onset spastic ataxia phenotype in a patient with a homozygous DDHD2 mutation

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    Autosomal recessive cerebellar ataxias and autosomal recessive hereditary spastic paraplegias (ARHSPs) are clinically and genetically heterogeneous neurological disorders. Herein we describe Japanese siblings with a midlife-onset, slowly progressive type of cerebellar ataxia and spastic paraplegia, without intellectual disability. Using whole exome sequencing, we identified a homozygous missense mutation in DDHD2, whose mutations were recently identified as the cause of early-onset ARHSP with intellectual disability. Brain MRI of the patient showed a thin corpus callosum. Cerebral proton magnetic resonance spectroscopy revealed an abnormal lipid peak in the basal ganglia, which has been reported as the hallmark of DDHD2-related ARHSP (SPG 54). The mutation caused a marked reduction of phospholipase A(1) activity, supporting that this mutation is the cause of SPG54. Our cases indicate that the possibility of SPG54 should also be considered when patients show a combination of adult-onset spastic ataxia and a thin corpus callosum. Magnetic resonance spectroscopy may be helpful in the differential diagnosis of patients with spastic ataxia phenotype.ArticleSCIENTIFIC REPORTS. 4:7132 (2014)journal articl

    A Myelin Galactolipid, Sulfatide, Is Essential for Maintenance of Ion Channels on Myelinated Axon But Not Essential for Initial Cluster Formation

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    Myelinated axons are divided into four distinct regions: the node of Ranvier, paranode, juxtaparanode, and internode, each of which is characterized by a specific set of axonal proteins. Voltage-gated N

    Psychiatric-disorder-related behavioral phenotypes and cortical hyperactivity in a mouse model of 3q29 deletion syndrome

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    3q29 microdeletion, a rare recurrent copy number variant (CNV), greatly confers an increased risk of psychiatric disorders, such as schizophrenia and autism spectrum disorder (ASD), as well as intellectual disability. However, disease-relevant cellular phenotypes of 3q29 deletion syndrome remain to be identified. To reveal the molecular and cellular etiology of 3q29 deletion syndrome, we generated a mouse model of human 3q29 deletion syndrome by chromosome engineering, which achieved construct validity. 3q29 deletion (Df/+) mice showed reduced body weight and brain volume and, more importantly, impaired social interaction and prepulse inhibition. Importantly, the schizophrenia-related impaired prepulse inhibition was reversed by administration of antipsychotics. These findings are reminiscent of the growth defects and neuropsychiatric behavioral phenotypes in patients with 3q29 deletion syndrome and exemplify that the mouse model achieves some part of face validity and predictive validity. Unbiased whole-brain imaging revealed that neuronal hyperactivation after a behavioral task was strikingly exaggerated in a restricted region of the cortex of Df/+ mice. We further elucidated the cellular phenotypes of neuronal hyperactivation and the reduction of parvalbumin expression in the cortex of Df/+ mice. Thus, the 3q29 mouse model provides invaluable insight into the disease-causative molecular and cellular pathology of psychiatric disorders
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