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Biomedical subjects

M Yamada

Publications and source records attributed to M Yamada.

At least 19 recordsLinked to original sources

Possible association of beta-arrestin 2 gene with methamphetamine use disorder, but not schizophrenia.

Recent investigations suggest that the AKT/glycogen synthase kinase 3 (GSK3) signaling cascade may be associated with the pathophysiology of schizophrenia and methamphetamine (METH) use disorder. One important molecule related to this cascade is beta-arrestin 2 (ARRB2). We therefore conducted a genetic case-control association analysis of the gene for ARRB2 with schizophrenia and METH use disorder in a Japanese population (547 people with schizophrenia, 177 with METH use disorder and 546 controls). A possible association of 'tag single nucleotide polymorphisms (SNPs)' was found in METH use disorder (rs1045280: P(genotype) = 0.0118, P(allele) = 0.00351; rs2036657: P(allele) = 0.0431; rs4790694: P(genotype) = 0.0167, P(allele) = 0.0202), but no association was found with schizophrenia. We also evaluated the gene-gene interactions among ARRB2, AKT1, and GSK3B, which we previously reported for each of these diseases. However, no interaction was seen in our samples. This is the first association analysis of ARRB2, and our results indicate that ARRB2 may play a role in the pathophysiology of METH use disorder.

Adult↗

Roles of M2 and M3 muscarinic receptors in cholinergic nerve-induced contractions in mouse ileum studied with receptor knockout mice.

BACKGROUND AND PURPOSE: The functional roles of M(2) and M(3) muscarinic receptors in neurogenic cholinergic contractions in gastrointestinal tracts remain to be elucidated. To address this issue, we studied cholinergic nerve-induced contractions in the ileum using mutant mice lacking M(2) or M(3) receptor subtypes. EXPERIMENTAL APPROACH: Contractile responses to transmural electrical (TE) stimulation were isometrically recorded in ileal segments from M(2)-knockout (KO), M(3)-KO, M(2)/M(3)-double KO, and wild-type mice. KEY RESULTS: TE stimulation at 2-50 Hz frequency-dependently evoked a fast, brief contraction followed by a slower, longer one in wild-type, M(2)-KO or M(3)-KO mouse preparations. Tetrodotoxin blocked both the initial and later contractions, while atropine only inhibited the initial contractions. The initial cholinergic contractions were significantly greater in wild-type than M(2)-KO or M(3)-KO mice; the respective mean amplitudes at 50 Hz were 91, 74 and 68 % of 70mM K(+)-induced contraction. Pretreatment with pertussis toxin blocked the cholinergic contractions in M(3)-KO but not in M(2)-KO mice. Cholinergic contractions also remained in wild-type preparations, but their sizes were reduced by 20-30 % at 10-50 Hz. In M(2)/M(3)-double KO mice, TE stimulation evoked only slow, noncholinergic contractions, which were significantly greater in sizes than in any of the other three mouse strains. CONCLUSION AND IMPLICATIONS: These results demonstrate that M(2) and M(3) receptors participate in mediating cholinergic contractions in mouse ileum with the latter receptors assuming a greater role. Our data also suggest that the lack of both M(2) and M(3) receptors causes upregulation of noncholinergic excitatory innervation of the gut smooth muscle.

Anesthetics, Local↗

The MM2-cortical form of sporadic Creutzfeldt-Jakob disease presenting with visual disturbance.

A subclass of sporadic Creutzfeldt-Jakob disease (sCJD) characterized by onset with visual symptoms (Heidenhain variant) has been reported to belong to the MM1 or MV1 type according to Parchi's classification. The authors report a 65-year-old woman with MM2-cortical sCJD with slowly progressive visual disturbance as the initial symptom. Diffusion-weighted MRIs revealed hyperintensity in both occipital cortices at an early stage.

Aged↗

Pattern of dietary fiber intake among the Japanese general population.

OBJECTIVES: To evaluate the dietary fiber (DF) intake pattern among the Japanese general population. DESIGN: We performed a dietary survey among the general population in northern Japan to evaluate the intake patterns. DF intake was calculated by substituting the DF content of each food in the Dietary Fiber Table for the intake of each food from this dietary survey. SUBJECTS: Five hundred and seventy-seven subjects participated in the study, 198 men and 379 women. RESULTS: In subjects with higher DF intakes the origins of the DF that were from all food groups, but with the notable exception of rice. The contribution of the seaweed group was of particular interest. From multiple regression analysis, as for food group, seaweeds showed the highest positive correlation with DF intake in both genders, followed by vegetables, pulses, fruits. On the other hand, rice showed the negative correlation with DF intake in both genders. As for life factor, body mass index showed the negative correlation with DF intake in women. CONCLUSION: Seaweed, a typical Japanese food, was most related to the increase in DF intake for the Japanese general population, whereas rice, the Japanese staple, had a small influence on decreased DF intake.

Adult↗

Value of 123I-MIBG radioactivity in the differential diagnosis of DLB from AD.

OBJECTIVE: To evaluate the diagnostic reliability of cardiac iodine-123 metaiodobenzylguanidine ((123)I-MIBG) radioactivity in discriminating dementia with Lewy bodies (DLB) from Alzheimer disease (AD) regardless of parkinsonism. BACKGROUND: The diagnosis of DLB may be confounded by the absence of parkinsonism. This highlights the need to improve the accuracy of antemortem diagnosis of DLB without parkinsonism. METHODS: Cardiac sympathetic denervation was examined using myocardial (123)I-MIBG scintigraphy in 37 patients with DLB, 42 patients with AD, and 10 normal elderly controls. The DLB patients consisted of seven patients without parkinsonism (DLB/P-) and 30 patients with parkinsonism (DLB/P+) at the time of the study. RESULTS: The heart-to-mediastinum uptake ratio (H/M ratio) of myocardial MIBG uptake was decreased in both the DLB groups vs the AD group (p < 0.0001) and control group (p < 0.0001). The washout rate (WR) was higher in the DLB group than in the control group (p < 0.0001) and AD group (p < 0.0001). No differences were found between the AD and control groups or between the DLB/P+ and DLB/P- groups in either the early or delayed H/M ratio or WR. In discriminating between DLB and AD, regardless of parkinsonism, the delayed H/M ratio had a sensitivity of 100%, a specificity of 100%, and a positive predictive value of 100% at a cutoff value of 1.68. CONCLUSIONS: Our results indicate that dementia with Lewy bodies results in cardiac sympathetic denervation and that iodine-123 metaiodobenzylguanidine myocardial scintigraphy is a sensitive tool for discriminating dementia with Lewy bodies from Alzheimer disease even in patients without parkinsonism.

3-Iodobenzylguanidine↗

Carbocisteine inhibits rhinovirus infection in human tracheal epithelial cells.

The aim of the study was to examine the effects of a mucolytic drug, carbocisteine, on rhinovirus (RV) infection in the airways. Human tracheal epithelial cells were infected with a major-group RV, RV14. RV14 infection increased virus titres and the cytokine content of supernatants. Carbocisteine reduced supernatant virus titres, the amount of RV14 RNA in cells, cell susceptibility to RV infection and supernatant cytokine concentrations, including interleukin (IL)-6 and IL-8, after RV14 infection. Carbocisteine reduced the expression of mRNA encoding intercellular adhesion molecule (ICAM)-1, the receptor for the major group of RVs. It also reduced the supernatant concentration of a soluble form of ICAM-1, the number and fluorescence intensity of acidic endosomes in the cells before RV infection, and nuclear factor-kappaB activation by RV14. Carbocisteine also reduced the supernatant virus titres of the minor group RV, RV2, although carbocisteine did not reduce the expression of mRNA encoding a low density lipoprotein receptor, the receptor for RV2. These results suggest that carbocisteine inhibits rhinovirus 2 infection by blocking rhinovirus RNA entry into the endosomes, and inhibits rhinovirus 14 infection by the same mechanism as well as by reducing intercellular adhesion molecule-1 levels. Carbocisteine may modulate airway inflammation by reducing the production of cytokines in rhinovirus infection.

Aged↗

Portal systemic shunt through the renal vein.

BACKGROUND: Despite the semi-routine use of color Doppler sonography for evaluating portal circulation abnormalities, there is a relative paucity of detailed color Doppler findings of portal systemic (P-S) shunt through the renal vein (P-SR shunt). METHODS: We reviewed the color Doppler findings of 18 patients with P-SR shunt to determine its clinical significance and appropriate scanning techniques for diagnosing accurately P-SR shunt. RESULTS: The splenorenal shunt was imaged as a highly tortuous vessel at the splenic hilum, which then coursed backward behind the spleen. Splenic vein flow was reversed or very slow. The gastrorenal shunt originated from the splenic vein, coursed backward, and joined the left renal vein. Flow direction in the splenic vein was always hepatopetal. The P-S shunt through the right renal vein originated from duodenal or jejunal varices, coursed posterolaterally, and joined the right renal vein at the renal hilum. CONCLUSION: Familiarity with these color Doppler findings will help increase the diagnostic confidence of P-SR shunt by color Doppler sonography.

Adult↗

Association of serum undercarboxylated osteocalcin with serum estradiol in pre-, peri- and early post-menopausal women.

OBJECTIVE: We investigated changes in serum concentration of undercarboxylated osteocalcin (ucOC), which is a sensitive marker of vitamin K status, and association of ucOC concentration with estradiol concentration in pre-, peri- and early post-menopausal women. METHODS: The study population consisted of 193 pre-, peri- and post-menopausal Japanese women aged 39-66 yr. Serum ucOC concentration was measured to assess vitamin K status; serum concentrations of intact osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) were measured as bone formation markers; and urine concentration of N-telopeptide was measured as a bone resorption marker. Serum estradiol and estrone concentrations were measured by a highly sensitive radioimmunoassay. Bone mineral density (BMD) was measured at the lumbar spine. RESULTS: Serum concentration of ucOC in peri-menopausal women was significantly (p=0.0005) higher than that in pre-menopausal women, while serum OC concentration in post-menopausal women for whom 1 yr had passed since menopause was significantly (p=0.0003, p=0.024, respectively) higher than the concentrations in pre-menopausal and peri-menopausal women. Serum ucOC concentration showed a significant negative correlation with estradiol concentration (r=-0.372, p<0.0001) and a significant positive correlation with serum FSH concentration (r=0.324, p<0.0001). Serum OC concentration was positively correlated with serum FSH concentration (r=0.317, p<0.001). CONCLUSIONS: The results showed that the change in ucOC concentration during the menopausal transition is different from that in OC concentration. In addition, serum ucOC concentration is closely associated not only with FSH concentration but also estradiol concentration.

Adult↗

Anti-amyloidogenic therapies: strategies for prevention and treatment of Alzheimer's disease.

Deposition of amyloid beta-protein (Abeta) in the brain is an early and invariant neuropathological feature of Alzheimer's disease (AD). The current search for anti-AD drugs is mainly focused on modification of the process of accumulation of Abeta in the brain. Here, we review four anti-amyloidogenic strategies: (i) reduction of Abeta production, which has mainly been approached with secretase inhibition, (ii) promotion of the Abeta degrading catabolic pathway, including an Abeta degrading enzyme, neprilysin, (iii) immunotherapy for Abeta and (iv) inhibition of Abeta aggregation. We have reported that AD patients have a favorable molecular environment for Abeta aggregation and that various compounds, such as polyphenols, interfere with Abeta aggregation and destabilize preformed Abeta fibrils.

Alzheimer Disease↗

Fluoride exposure inhibits protein expression and enzyme activity in the lung-stage larvae of Ascaris suum.

Sodium fluoride (NaF) is an anion that has been previously shown to block the moulting process of Ascaris suum larvae. This study describes moulting and development-specific protein expression profiles of A. suum lung-stage L3 (AsLL3) following NaF exposure. AsLL3s cultured in the presence or absence of NaF were prepared for protein analysis using two-dimensional (2D) electrophoresis. NaF exposure inhibited at least 22 proteins in AsLL3 compared with moulted larvae (i.e. AsLL4). A further comparison of AsLL4 with those of pre-cultured AsLL3 and NaF-exposed AsLL3 revealed 8 stage-specifically and 4 over-expressed proteins. Immunoblot analysis revealed an inhibition by NaF of 19 immunoreactive proteins. Enzyme assay and immunochemical data showed an inhibition of the moulting-specific inorganic pyrophosphatase activity by 41% and a decreased expression in NaF-treated larvae, indicating its significance in the moulting process. A protein spot associated with NaF inhibition was isolated and identified by peptide mass spectrometry and bioinformatics approaches to be a member of 3-hydroxyacyl-CoA dehydrogenase/short-chain dehydrogenase enzyme families. These results have implications for the identification of proteins specific to the moulting process as potential chemotherapeutic targets.

Amino Acid Sequence↗

Regulation of local and metastatic host-mediated anti-tumour mechanisms by L-selectin and intercellular adhesion molecule-1.

Malignant melanoma is often accompanied by a host response of inflammatory cell infiltration that is highly regulated by multiple adhesion molecules. To assess the role of adhesion molecules, including L-selectin and intercellular adhesion molecule-1 (ICAM-1), in this process, subcutaneous primary growth and metastasis to the lung of B16 melanoma cells not expressing L-selectin, ICAM-1 or their ligands were examined in mice lacking L-selectin, ICAM-1 or both. Primary subcutaneous growth of B16 melanoma was augmented by loss of L-selectin, ICAM-1 or both, while pulmonary metastasis was enhanced by the loss of L-selectin or combined loss of L-selectin and ICAM-1. In both situations, the combined loss of L-selectin and ICAM-1 exhibited the greatest effect. This enhancement was associated generally with a reduced accumulation of natural killer (NK) cells, CD4+ T cells and CD8+ T cells and also with a diminished release of interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha but not interleukin (IL)-6. Cytotoxicity against melanoma was not defective by the absence of ICAM-1, L-selectin or both, suggesting that the enhancement of tumour growth and metastasis caused by the loss of adhesion molecules results from an impaired migration of effector cells into the tissue rather than from a suppression of the cytotoxic response. The results indicate that L-selectin and ICAM-1 contribute co-operatively to the anti-tumour reaction by regulating lymphocyte infiltration to the tumour.

Animals↗

Propofol acts at the sigma-1 receptor and inhibits pentazocine-induced c-Fos expression in the mouse posterior cingulate and retrosplenial cortices.

BACKGROUND: The sigma-1 receptor is functionally linked with psychotomimetic effects of various drugs. A sigma-1 receptor agonist enhances bradykinin-induced intracellular Ca(2+) concentration ([Ca(2+)]i) increase and induces c-Fos expression in a part of the brain. The aim of this study was to investigate the effects of several intravenous anaesthetics on the sigma-1 receptor. METHODS: First, using Wistar rat brains, (+)[(3)H]SKF-10,047, a selective sigma-1 receptor agonist was displaced by propofol, dexmedetomidine, droperidol, and thiopental. Second, Fura-2 loaded NG-108 cells were incubated with (+)pentazocine, a selective sigma-1 receptor agonist, and propofol and then its fluorescence was observed after stimulation with bradykinin. Third, male ICR mice received Intrafat or propofol intraperitoneally (i.p.), followed by pentazocine i.p. Brain slices were prepared and Fos-like immunoreactivity was detected using an immunohistochemical method. results: Propofol, droperidol, and dexmedetomidine displaced (+)[(3)H]SKF-10,047 binding in a concentration-dependent manner with Ki50s of 10.2 +/- 0.6, 0.17 +/- 0.03, 5.73 +/- 1.2 microM, respectively. Thiopental sodium was practically ineffective. Propofol produced a statistically significant reduction in the maximal binding capacity (Bmax) but did not affect the dissociation constant (K(d)). (+)Pentazocine significantly enhanced bradykinin-induced [Ca(2+)]i increases, but propofol did not affect it. Pentazocine induced marked Fos-LI positive cells in the posterior cingulate and retrosplenial cortices (PC/RS), which was significantly reduced by propofol. CONCLUSIONS: These results suggest that propofol may be a sigma-1 receptor antagonist, and that various effects of propofol on the brain may be mediated, at least partly, by the sigma-1 receptor.

Analgesics, Opioid↗

Neuromyelitis optica associated with myasthenia gravis: characteristic phenotype in Japanese population.

We report two female patients with neuromyelitis optica (NMO, Devic's syndrome) following or coincidental with myasthenia gravis (MG). Their illnesses were characterized by subacute myelitis with optic neuritis, high serum levels of muscle acetylcholine receptor antibody, and autoimmune thyroid disease. Both patients fulfilled the clinical criteria of NMO, however, NMO-IgG, autoantibody against aquaporin-4 water channel, was absent from their sera. Both NMO and MG are relatively rare diseases. The considerable coincidence of these two disorders suggests that there is a subgroup of patients with NMO having a common immunological pathogenesis with MG.

Adult↗

Optic nerve and spinal cord manifestations of malignant atrophic papulosis (Degos disease).

A fatal case of malignant atrophic papulosis (Degos disease) with optic nerve and spinal cord involvement is described. Magnetic resonance imaging (MRI) of the optic nerve showed abnormal signal enhancement on fat suppressed T1 weighted images after intravenous meglumine gadopentetate infusion. On T2 weighted sagittal images, a sawtooth pattern was observed over seven vertebral segments of the spinal cord. On necropsy, a severe loss of myelinated nerve fibres in the left optic nerve was seen, with thrombotic obstruction of the central retinal artery. Spongy degeneration was observed in all levels of the spinal cord, with patchy and motheaten patterns caused by thromboses and endothelial proliferation in subarachnoid vessels. Findings on MRI were consistent with findings on pathological examination.

Atrophy↗

Association study of the dihydropyrimidinase-related protein 2 gene and methamphetamine psychosis.

Dihydropyrimidinase-related protein 2 (DRP-2 or DPYSL-2)mediates the intracellular response to collapsin, a repulsive extracellular guidance cue or axonal outgrowth. DRP-2 is also referred to as collapsin response mediator protein 2 (CRMP-2). We have previously demonstrated that the DRP-2 gene is associated with susceptibility to schizophrenia, but not to bipolar disorders. In addition, a genetic association was observed with paranoid-type schizophrenia, but not with hebephrenic-type schizophrenia. It has been well documented that repeated abuse of methamphetamine (METH) for a long period frequently produces psychotic symptoms, such as auditory hallucinations and delusions that are hardly distinguishable from those of paranoid-type schizophrenia. Therefore, we hypothesized that a certain genetic variant of the DRP-2 gene may affect individual vulnerability to the development of METH-induced psychosis. We examined the genetic association by a case-control method. The polymorphism *2236T>C in the 3' untranslated region of the DRP-2 gene, which has been shown to be a negative genetic risk factor for paranoid-type schizophrenia, was analyzed in 198 patients with METH psychosis and 221 corresponding healthy controls in a Japanese population. No significant association of the DRP-2 gene with METH psychosis was found. Neither did we find an association with the clinical phenotype of METH psychosis, such as the age of first consumption of METH, latency to development of psychosis after METH abuse, prognosis of psychosis after detoxification from METH use, complication of spontaneous relapse of psychosis without reconsumption of the drug, or multisubstance abuse status. These findings indicate that a genetic variant of the DRP-2 gene may not affect the risk of METH psychosis or any clinical phenotype of the disorder.

Adult↗

Association study of the tumor necrosis factor-alpha gene and its 1A receptor gene with methamphetamine dependence.

Recent preclinical findings that repeated treatment with methamphetamine (METH) induced an increase in tumor necrosis factor-alpha (TNF-alpha) mRNA in some brain regions and that TNF-alpha blocked METH neurotoxicity and rewarding effects suggest TNF-alpha, a multifunctional pro-inflammatory cytokine, may be involved in METH dependence. We hypothesized that genetic polymorphisms of the TNF-alpha gene and its receptor genes may be associated with vulnerability to METH dependence. Genetic association of -308G>A and -857C>T in the promotor region of the TNF-alpha gene, and 36A>G in exon 1 of the TNF receptor 1A gene (TNFR-SF1A), were analyzed in patients with METH dependence (n = 185) and healthy controls (n = 221) in a Japanese population. No significant association of alleles or haplotypes of the TNF-alpha or TNFR-SF1A genes with METH dependence was found. Neither was any significant association of clinical phenotype with METH dependence found. These results suggest that genetic variations in the TNF-alpha gene and its receptor genes may not be involved in individual vulnerability to METH dependence.

Adult↗

No association between CART (cocaine- and amphetamine-regulated transcript) gene and methamphetamine dependence.

Cocaine- and amphetamine-regulated transcript (CART) was originally discovered as a peptide that increased in the rat striatum after injection of a psychostimulant drug, such as cocaine or amphetamine, and is suggested to play potential roles in drug dependence. We tested the genetic association between the CART gene and methamphetamine (METH) dependence and/or psychosis. The subjects were 203 patients with METH dependence and 239 age- and gender-matched healthy controls. Two single nucleotide polymorphisms (SNPs) of the CART gene, -156A>G and IVS1 + 224G>A, were examined . There were no significant differences in genotype and allele distributions of the polymorphisms between patients with METH dependence and/or psychosis and controls. Neither were significant differences in subgroups of clinical phenotypes, for example, age at first consumption of METH, latency to onset of psychotic symptoms after the first consumption of METH, prognosis of psychosis after therapy, complication of spontaneous relapse to a psychotic state, or multisubstance abuse status, observed. The present findings suggest that the CART gene may not play a pivotal role in the development of METH dependence and psychosis, at least in a Japanese population.

Adult↗