Nakano Y

References (10)

Title : Analyzing schizophrenia-related phenotypes in mice caused by autoantibodies against NRXN1alpha in schizophrenia - Shiwaku_2023_Brain.Behav.Immun__
Author(s) : Shiwaku H , Katayama S , Gao M , Kondo K , Nakano Y , Motokawa Y , Toyoda S , Yoshida F , Hori H , Kubota T , Ishikawa K , Kunugi H , Ikegaya Y , Okazawa H , Takahashi H
Ref : Brain Behavior & Immunity , : , 2023
Abstract : The molecular pathological mechanisms underlying schizophrenia remain unclear; however, genomic analysis has identified genes encoding important risk molecules. One such molecule is neurexin 1alpha (NRXN1alpha), a presynaptic cell adhesion molecule. In addition, novel autoantibodies that target the nervous system have been found in patients with encephalitis and neurological disorders. Some of these autoantibodies inhibit synaptic antigen molecules. Studies have examined the association between schizophrenia and autoimmunity; however, the pathological data remain unclear. Here, we identified a novel autoantibody against NRXN1alpha in patients with schizophrenia (n=2.1%) in a Japanese cohort (n=387). None of the healthy control participants (n=362) were positive for anti-NRXN1alpha autoantibodies. Anti-NRXN1alpha autoantibodies isolated from patients with schizophrenia inhibited the molecular interaction between NRXN1alpha and Neuroligin 1 (NLGN1) and between NRXN1alpha and Neuroligin 2 (NLGN2). Additionally, these autoantibodies reduced the frequency of the miniature excitatory postsynaptic current in the frontal cortex of mice. Administration of anti-NRXN1alpha autoantibodies from patients with schizophrenia into the cerebrospinal fluid of mice reduced the number of spines/synapses in the frontal cortex and induced schizophrenia-related behaviors such as reduced cognition, impaired pre-pulse inhibition, and reduced social novelty preference. These changes were improved through the removal of anti-NRXN1alpha autoantibodies from the IgG fraction of patients with schizophrenia. These findings demonstrate that anti-NRXN1alpha autoantibodies transferred from patients with schizophrenia cause schizophrenia-related pathology in mice. Removal of anti-NRXN1alpha autoantibodies may be a therapeutic target for a subgroup of patients who are positive for these autoantibodies.
ESTHER : Shiwaku_2023_Brain.Behav.Immun__
PubMedSearch : Shiwaku_2023_Brain.Behav.Immun__
PubMedID: 37004758

Title : Distribution, fine structure, and three-dimensional innervation of lamellar corpuscles in rat plantar skin - Koike_2021_Cell.Tissue.Res__
Author(s) : Koike T , Ebara S , Tanaka S , Kase M , Hirahara Y , Hayashi S , Oe S , Nakano Y , Kitada M , Kumamoto K
Ref : Cell Tissue Research , : , 2021
Abstract : Lamellar corpuscles function as mechanoreceptors in the skin, composed of axon terminals and lamellae constructed by terminal Schwann cells. They are classified into Pacinian, Meissner, and simple corpuscles based on histological criteria. Lamellar corpuscles in rat dermal papilla cells have been reported; however, the morphological aspects have yet to be thoroughly investigated. In the present study, we analyzed the enzyme activity, distribution, fine structure, and three-dimensional innervation of lamellar corpuscles in rat plantar skin. The lamellar corpuscles exhibiting non-specific cholinesterase were densely distributed in rat footpads, evident as notable skin elevations, especially at the apex, the highest portion of the ridges in each footpad. In contrast, only a few lamellar corpuscles were found in other plantar skin areas. Lamellar corpuscle was considered composed of a flat axon terminal Schwann cell lamellae, which were roughly concentrically arranged in the dermal papilla. These histological characteristics correspond to those of the simple corpuscle. Moreover, the axon tracing method revealed that one trunk axon innervated several simple corpuscles. The territory of the trunk axons overlapped with each other. Finally, the animals' footprints were analyzed. During the pausing and walking phases, footpads are often in contact with the floor. These results demonstrate that the type of lamellar corpuscles in the dermal papillae of rat plantar skin is a simple corpuscle and implies that their distribution pattern in the plantar skin is convenient for efficient sensing and transmission of mechanical stimuli from the ground.
ESTHER : Koike_2021_Cell.Tissue.Res__
PubMedSearch : Koike_2021_Cell.Tissue.Res__
PubMedID: 34562148

Title : Generation of a Nearly Monocycle Optical Pulse in the Near-Infrared Region and Its Use as an Ionization Source in Mass Spectrometry - Nakano_2020_Anal.Chem_92_7130
Author(s) : Nakano Y , Imasaka T
Ref : Analytical Chemistry , 92 :7130 , 2020
Abstract : We report on the generation of an octave-spanning (600-1400 nm) nearly monocycle (1.1 cycle) ultrashort optical pulse (3.2 fs) in the near-infrared region by the Fourier synthesis of two pulses at 800 and 1200 nm, both of which were spectrally broadened by self-phase modulation and were compressed by chirp mirrors. The 3.2 fs pulse was converted into the ultraviolet by third harmonic generation, the pulse width being evaluated to 1.9 fs. The near-infrared pulse (3.2 fs) was employed as an ionization source in mass spectrometry, and the signal intensity was significantly increased for pentachlorobenzene, an environmental pollutant listed in the Stockholm Convention. The present data and the spectral properties obtained by quantum chemical calculations suggest that the method offers a potential advantage for the detection of Novichok, a chemical warfare agent that is thought to have been used in a terrorist attack.
ESTHER : Nakano_2020_Anal.Chem_92_7130
PubMedSearch : Nakano_2020_Anal.Chem_92_7130
PubMedID: 32233421

Title : Chronic Cerebral Hypoperfusion Accelerates Alzheimer's Disease Pathology with Cerebrovascular Remodeling in a Novel Mouse Model - Zhai_2016_J.Alzheimers.Dis_53_893
Author(s) : Zhai Y , Yamashita T , Nakano Y , Sun Z , Shang J , Feng T , Morihara R , Fukui Y , Ohta Y , Hishikawa N , Abe K
Ref : J Alzheimers Dis , 53 :893 , 2016
Abstract : Recently, aging societies have been showing an increasingly strong relationship between Alzheimer's disease (AD) and chronic cerebral hypoperfusion (HP). In the present study, we created a new mouse model for AD with HP, and investigated its clinical and pathological characteristics. Alzheimer's disease transgenic mice (APP23) were subjected to bilateral common carotid arteries stenosis with ameroid constrictors for slowly progressive cerebral HP. In contrast to simple APP23 mice, cerebral HP exacerbated motor and cognitive dysfunctions with white matter lesions and meningo-parenchymal amyloid-beta (Abeta) burdens. Strong cerebrovascular inflammation and severe amyloid angiopathy with cerebrovascular remodeling were also observed in APP23 + HP mouse brains. An acetylcholinesterase inhibitor galantamine improved such clinical dysfunctions, retrieved above neuropathological characteristics, and enhanced nicotinic acetylcholine receptor (nAChR)-binding activity. The present study demonstrates that chronic cerebral HP enhanced cognitive/motor dysfunctions with parenchymal/cerebrovascular Abeta accumulation and cerebrovascular remodeling. These neuropathological abnormalities were greatly ameliorated by galantamine treatment associated with nAChR-mediated neuroprotection by allosterically potentiating ligand action.
ESTHER : Zhai_2016_J.Alzheimers.Dis_53_893
PubMedSearch : Zhai_2016_J.Alzheimers.Dis_53_893
PubMedID: 27314529

Title : [Clinical Analysis of Esophageal Bypass Surgery with Nutritional Assessment in Patients with Unresectable Esophageal Cancer] - Funaki_2015_Gan.To.Kagaku.Ryoho_42_1543
Author(s) : Funaki H , Fujii Y , Fujita J , Morioka E , Kaida D , Ohonishi T , Tomita Y , Noguchi M , Fujita H , Kinami S , Nakano Y , Ueda N , Kosaka T
Ref : Japanese Journal of Cancer & Chemotherapy , 42 :1543 , 2015
Abstract : BACKGROUND: Esophageal bypass surgery is palliative surgery for unresectable esophageal cancer with esophageal stenosis, which often leads to poor nutrition. We investigated the clinical characteristics, nutritional status, and outcomes of patients who underwent esophageal bypass surgery. PATIENTS AND
METHODS: We reviewed 11 cases of esophageal bypass surgery for unresectable esophageal cancer performed in our hospital between 1992 and 2015, and we examined the surgical outcome along with preoperative nutritional assessment.
RESULTS: There were 1, 9, and 1 cases of cStage, a, and b, respectively. For the bypass, a gastric tube was used in 8 cases and colon reconstruction in 3. Postoperative complications were 1 case of recurrent laryngeal nerve palsy(9%), 4 cases of anastomotic leakage(36%), and 4 cases of pneumonia(36%). The preoperative nutritional status(total protein, albumin, and cholinesterase levels)in the esophageal bypass group(n=11)was significantly worse than that in the esophagectomy group(n=40). The median survival of all patients(n=11)was 5.7 months. Patients receiving induction chemoradiotherapy followed by bypass surgery(n=7)had a median survival of 15.2 months. CONCLUSION: Since patients undergoing esophageal bypass surgery often present with malnutrition, attention to anastomotic leakage and infectious complications is necessary.
ESTHER : Funaki_2015_Gan.To.Kagaku.Ryoho_42_1543
PubMedSearch : Funaki_2015_Gan.To.Kagaku.Ryoho_42_1543
PubMedID: 26805090

Title : Combination Therapy of Cholinesterase Inhibitor (Donepezil or Galantamine) plus Memantine in the Okayama Memantine Study - Matsuzono_2015_J.Alzheimers.Dis_45_771
Author(s) : Matsuzono K , Hishikawa N , Ohta Y , Yamashita T , Deguchi K , Nakano Y , Abe K
Ref : J Alzheimers Dis , 45 :771 , 2015
Abstract : BACKGROUND/OBJECTIVE: To compare the effectiveness of combination therapy with cholinesterase inhibitors (ChEI) plus memantine in all AD patients and in older AD patients (age >75 years).
METHODS: The Okayama Memantine Study was used to compare the clinical effects of combination therapy of donepezil plus memantine (n = 61) or galantamine plus memantine (n = 53) in all AD patients, and in older AD patients separately, with six batteries at baseline, at 6 months with ChEI only monotherapy, and at 3, 6, and 12 months after addition of memantine to the treatment schedule (18 months total).
RESULTS: The addition of memantine resulted in stabilization of the Mini-Mental State Examination scores and Hasegawa dementia rating for 6 months, and then significantly declined at 12 months in both subgroups. Frontal assessment battery (FAB) declined significantly at 12 months after memantine addition in the donepezil subgroup, while the galantamine subgroup significantly improved at 6 months. Affective functions were well preserved after memantine addition until 12 months, except for the apathy scale at 12 months after memantine addition in the galantamine subgroup. The combination therapy of donepezil plus memantine was better for apathy in older AD patients, and galantamine plus memantine was better for cognitive functions.
CONCLUSIONS: The addition of memantine stabilized cognitive scores for 6 months and affective scores for 12 months in the donepezil subgroup. Additionally, memantine significantly improved FAB at 6 months in the galantamine subgroup although apathy scale became significantly worse at 12 months.
ESTHER : Matsuzono_2015_J.Alzheimers.Dis_45_771
PubMedSearch : Matsuzono_2015_J.Alzheimers.Dis_45_771
PubMedID: 25624417

Title : Redesign of enzyme for improving catalytic activity and enantioselectivity toward poor substrates: manipulation of the transition state - Ema_2012_Org.Biomol.Chem_10_6299
Author(s) : Ema T , Nakano Y , Yoshida D , Kamata S , Sakai T
Ref : Org Biomol Chem , 10 :6299 , 2012
Abstract : Secondary alcohols having bulky substituents on both sides of the hydroxy group are inherently poor substrates for most lipases. In view of this weakness, we redesigned a Burkholderia cepacia lipase to create a variant with improved enzymatic characteristics. The I287F/I290A double mutant showed a high conversion and a high E value (>200) for a poor substrate for which the wild-type enzyme showed a low conversion and a low E value (5). This enhancement of catalytic activity and enantioselectivity of the variant resulted from the cooperative action of two mutations: Phe287 contributed to both enhancement of the (R)-enantiomer reactivity and suppression of the (S)-enantiomer reactivity, while Ala290 created a space to facilitate the acylation of the (R)-enantiomer. The kinetic constants indicated that the mutations effectively altered the transition state. Substrate mapping analysis strongly suggested that the CH/pi interaction partly enhanced the (R)-enantiomer reactivity, the estimated energy of the CH/pi interaction being -0.4 kcal mol(-1). The substrate scope of the I287F/I290A double mutant was broad. This biocatalyst was useful for the dynamic kinetic resolution of a variety of bulky secondary alcohols for which the wild-type enzyme shows little or no activity.
ESTHER : Ema_2012_Org.Biomol.Chem_10_6299
PubMedSearch : Ema_2012_Org.Biomol.Chem_10_6299
PubMedID: 22710791
Gene_locus related to this paper: burce-lipaa , burce-q75nt4

Title : Structure and allele-specific expression variation of novel alpha\/beta hydrolase fold proteins in gentian plants - Hikage_2007_Mol.Genet.Genomics_278_95
Author(s) : Hikage T , Saitoh Y , Tanaka-Saito C , Hagami H , Satou F , Shimotai Y , Nakano Y , Takahashi M , Takahata Y , Tsutsumi K
Ref : Mol Genet Genomics , 278 :95 , 2007
Abstract : Previously, we identified two closely related proteins termed W14 and W15 that were enriched in the overwinter buds of the gentian plant Gentiana triflora. Expression of the latter protein W15 has been implicated in its association with cold hardiness, because of its absence in a cold-sensitive mutant. Here, we characterized these two proteins and the genes encoding them. Amino acid sequences of the W14 and W15 proteins showed difference at only three amino acid positions, and both of them showed homologies to alpha/beta hydrolase fold superfamily. Consistently, GST-fused W14 and W15 proteins expressed in bacteria showed hydrolase activity toward 1-naphtyl acetate. Structural analysis of these two genes in seven different gentian strains/cultivars including an anther culture-derived homozygous diploid revealed that W14 and W15 genes are allelic. Three genotypes were found; two strains carried both alleles (W14/W15), one carried the W15 genes in both alleles (W15/W15), and others were homozygous of W14 (W14/W14). Interestingly, expression of the two proteins exhibited allele-specificity. In one W14/W15 strain, expression of the W15 allele was almost repressed. In addition, organ specific expression of the alleles was observed in different cultivars. These observations were discussed in relation to winter hardiness of the gentian plants.
ESTHER : Hikage_2007_Mol.Genet.Genomics_278_95
PubMedSearch : Hikage_2007_Mol.Genet.Genomics_278_95
PubMedID: 17429693
Gene_locus related to this paper: gentr-a5a7n5

Title : Does donepezil treatment slow the progression of hippocampal atrophy in patients with Alzheimer's disease? - Hashimoto_2005_Am.J.Psychiatry_162_676
Author(s) : Hashimoto M , Kazui H , Matsumoto K , Nakano Y , Yasuda M , Mori E
Ref : Am J Psychiatry , 162 :676 , 2005
Abstract : OBJECTIVE: The only approved pharmacological approach for the symptomatic treatment of Alzheimer's disease in Japan is the use of a cholinesterase inhibitor, donepezil hydrochloride. Recent in vivo and in vitro studies raise the possibility that cholinesterase inhibitors can slow the progression of Alzheimer's disease. The purpose of the present study was to determine whether donepezil has a neuroprotective effect in Alzheimer's disease by using the rate of hippocampal atrophy as a surrogate marker of disease progression. METHOD: In a prospective cohort study, 54 patients with Alzheimer's disease who received donepezil treatment and 93 control patients with Alzheimer's disease who never received anti-Alzheimer drugs underwent magnetic resonance imaging (MRI) twice at a 1-year interval. The annual rate of hippocampal atrophy of each subject was determined by using an MRI-based volumetric technique. Background characteristics, age, sex, disease duration, education, MRI interval, apolipoprotein E (APOE) genotype, and baseline Alzheimer's Disease Assessment Scale score were comparable between the treated and control groups.
RESULTS: The mean annual rate of hippocampal volume loss among the treated patients (mean=3.82%, SD=2.84%) was significantly smaller than that among the control patients (mean=5.04%, SD=2.54%). Upon analysis of covariance, where those confounding variables (age, sex, disease duration, education, MRI interval, APOE genotype, and baseline Alzheimer's Disease Assessment Scale score) were entered into the model as covariates, the effect of donepezil treatment on hippocampal atrophy remained significant.
CONCLUSIONS: Donepezil treatment slows the progression of hippocampal atrophy, suggesting a neuroprotective effect of donepezil in Alzheimer's disease.
ESTHER : Hashimoto_2005_Am.J.Psychiatry_162_676
PubMedSearch : Hashimoto_2005_Am.J.Psychiatry_162_676
PubMedID: 15800138

Title : Cloning, expression and characterization of plasma platelet-activating factor-acetylhydrolase from guinea pig - Karasawa_1996_J.Biochem_120_838
Author(s) : Karasawa K , Kuge O , Kawasaki K , Nishijima M , Nakano Y
Ref : Journal of Biochemistry , 120 :838 , 1996
Abstract : In a previous study, we purified PAF-acetylhydrolase, which converts PAF to an inactive metabolite, lysoPAF, from peritoneal fluid of guinea pigs subjected to experimental endotoxin shock and found that this purified enzyme had similar biochemical properties to the plasma enzyme [Karasawa, K., Yato, M., Setaka, M., and Nojima, S. (1994) J. Biochem. 116, 374-379]. In this study, we isolated a homogeneous enzyme preparation from guinea pig plasma using a similar procedure. The molecular mass of this purified enzyme, as determined by SDS-PAGE was 58-63 kDa, larger than that (43 kDa) of the human enzyme. To elucidate the molecular structure of this enzyme and clarify its relationships with PAF-acetylhydrolases of other species, we isolated and sequenced a cDNA encoding this enzyme. Its cDNA contains an open reading frame encoding 436 amino acids and its predicted molecular mass (49 kDa) is lower than that of the native enzyme, suggesting that guinea pig plasma PAF-acetylhydrolase, unlike the human enzyme, is modified post-translationally, perhaps by glycosylation.
ESTHER : Karasawa_1996_J.Biochem_120_838
PubMedSearch : Karasawa_1996_J.Biochem_120_838
PubMedID: 8947850
Gene_locus related to this paper: cavpo-cxest , cavpo-pafa