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1.
J Org Chem ; 89(12): 8385-8396, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38684935

RESUMO

The iron-catalyzed Suzuki-Miyaura cross-coupling of secondary propargyl electrophiles with lithium organoborates has been established. A propyl-bridged bulky bisphosphine ligand, SciPROP-TB, cooperated with the bulky TIPS substituent at the alkyne terminal position to achieve the cross-coupling reaction with exclusive propargylic selectivity. The reaction features high functional group compatibility, regioselectivity, and yield with a broad substrate scope. The reaction of an optically active chiral propargyl bromide proceeds with complete racemization, supporting a mechanism involving propargyl radical formation.

2.
Artigo em Inglês | MEDLINE | ID: mdl-36913933

RESUMO

INTRODUCTION: Tau protein accumulation in the brain is thought to be one of the causes of progressive supranuclear palsy (PSP). The glymphatic system was discovered a decade ago as a waste drainage system in the brain that promotes the elimination of amyloid-beta and tau protein. We here evaluated the relationships between glymphatic system activity and regional brain volumes in PSP patients. METHOD: Subjects were 24 patients with PSP and 42 healthy participants who underwent diffusion tensor imaging (DTI). We computed the diffusion tensor image analysis along the perivascular space (DTI­ALPS) index as a proxy of glymphatic system activity, and estimated the relationships between the DTI­ALPS index and regional brain volume in PSP patients by whole-brain and region-of-interest analyses, including analyses of the midbrain and third and lateral ventricles. RESULTS: The DTI­ALPS index was significantly lower in patients with PSP, compared with healthy subjects. Further, there were significant correlations between the DTI­ALPS index and the regional brain volumes in the midbrain tegmentum, pons, right frontal lobe, and lateral ventricles in patients with PSP. CONCLUSIONS: Our data suggest that the DTI­ALPS index is a good biomarker for PSP and might be effective to distinguish PSP from other neurocognitive disorders.

3.
Mol Psychiatry ; 26(3): 825-834, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-31160692

RESUMO

Epilepsy is a diverse brain disorder, and the pathophysiology of its various forms and comorbidities is largely unknown. A recent machine learning method enables us to estimate an individual's "brain-age" from MRI; this brain-age prediction is expected as a novel individual biomarker of neuropsychiatric disorders. The aims of this study were to estimate the brain-age for various categories of epilepsy and to evaluate clinical discrimination by brain-age for (1) the effect of psychosis on temporal lobe epilepsy (TLE), (2) psychogenic nonepileptic seizures (PNESs) from MRI-negative epilepsies, and (3) progressive myoclonic epilepsy (PME) from juvenile myoclonic epilepsy (JME). In total, 1196 T1-weighted MRI scans from healthy controls (HCs) were used to build a brain-age prediction model with support vector regression. Using the model, we calculated the brain-predicted age difference (brain-PAD: predicted age-chronological age) of the HCs and 318 patients with epilepsy. We compared the brain-PAD values based on the research questions. As a result, all categories of patients except for extra-temporal lobe focal epilepsy showed a significant increase in brain-PAD. TLE with hippocampal sclerosis presented a significantly higher brain-PAD than several other categories. The mean brain-PAD in TLE with inter-ictal psychosis was 10.9 years, which was significantly higher than TLE without psychosis (5.3 years). PNES showed a comparable mean brain-PAD (10.6 years) to that of epilepsy patients. PME had a higher brain-PAD than JME (22.0 vs. 9.3 years). In conclusion, neuroimaging-based brain-age prediction can provide novel insight into or clinical usefulness for the diverse symptoms of epilepsy.


Assuntos
Epilepsia do Lobo Temporal , Transtornos Psicóticos , Encéfalo/diagnóstico por imagem , Epilepsia do Lobo Temporal/diagnóstico por imagem , Humanos , Neuroimagem , Transtornos Psicóticos/diagnóstico por imagem , Convulsões
4.
J Immunol ; 205(11): 2959-2967, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33097573

RESUMO

Extensive activation of mast cells is the major switch that triggers systemic anaphylaxis, resulting in the subsequent release of anaphylactic mediators into circulation. We previously demonstrated that rapid changes in oxygen tension lead to mast cell degranulation, and the released tryptase triggers retinal angiogenesis in a murine oxygen-induced retinopathy model. However, whether a rapid shift from hyperoxia to normoxia (relative hypoxic stress) is a risk factor for systemic anaphylaxis remains unknown. In this study, we demonstrated that the relative hypoxia stress induces systemic mast cell activation via transient receptor potential ankyrin 1 (TRPA1) channels, which immediately leads to hypothermia and increased vascular permeability in adult mice. Although mast cell-deficient or TRPA1-deficient mice did not exhibit anaphylactic symptoms following a rapid sift to normoxia, preinjection with bone marrow-derived cultured mast cells (BMCMCs) derived from wild-type TRPA1-expressing mice restored anaphylactic responses. In addition, we found that the rapid reductions in oxygen tension in a culture atmosphere triggered the degranulation of BMCMCs derived from wild-type TRPA1-expressing mice but not that of BMCMCs derived from TRPA1-deficient mice. In human LAD2 mast cells, the relative hypoxic stress led to the degranulation, which was suppressed by the addition of a TRPA1 inhibitor. Gradual reductions from hyperoxia to normoxia led to no anaphylactic symptoms. Our results demonstrated that TRPA1-triggered mast cell degranulation is a novel pathway that induces anaphylactic shock without Ag-Ab reactions. These findings introduce a potential role for oxygen in inducing mast cell-dependent anaphylaxis and highlight the need to reconsider chronic pure oxygen therapy for anoxic diseases.


Assuntos
Anafilaxia/metabolismo , Hiperóxia/metabolismo , Mastócitos/metabolismo , Canal de Cátion TRPA1/metabolismo , Animais , Células da Medula Óssea/metabolismo , Células Cultivadas , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxigênio/metabolismo , Triptases/metabolismo
5.
J Allergy Clin Immunol ; 147(4): 1354-1368.e3, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33011245

RESUMO

BACKGROUND: Staphylococcus aureus is the dominant infective trigger of atopic dermatitis (AD). How this bacterium drives type 2 allergic pathology in the absence of infection in patients with AD is unclear. OBJECTIVE: We sought to identify the S aureus-derived virulence factor(s) that initiates the cutaneous type 2-promoting immune response responsible for AD. METHODS: In vitro human keratinocyte cell culture, ex vivo human skin organ explants, and the eczema-prone Nishiki-nezumi Cinnamon/Tokyo University of Agriculture and Technology strain mouse were used as model systems to assess type 2-promoting immune responses to S aureus. Identification of the bioactive factor was accomplished using fast protein liquid chromatography and mass spectrometry. Bioactivity was confirmed by cloning and expression in an Escherichia coli vector system, and S aureus second immunoglobulin-binding protein (Sbi) mutant strains confirming loss of activity. RESULTS: S aureus was unique among staphylococcal species in its ability to induce the rapid release of constitutive IL-33 from human keratinocytes independent of the Toll-like receptor pathway. Using the eczema-prone Nishiki-nezumi Cinnamon/Tokyo University of Agriculture and Technology strain mouse model, we showed that IL-33 was essential for inducing the immune response to S aureus in vivo. By fractionation and candidate testing, we identified Sbi as the predominant staphylococcus-derived virulence factor that directly drives IL-33 release from human keratinocytes. Immunohistology of skin demonstrated that corneodesmosin, a component of corneodesmosomes that form key intercellular adhesive structures in the stratum corneum, was disrupted, resulting in reduction of skin barrier function. CONCLUSIONS: S aureus-derived Sbi is a unique type 2-promoting virulence factor capable of initiating the type 2-promoting cytokine activity underlying AD.


Assuntos
Proteínas de Bactérias/imunologia , Proteínas de Transporte/imunologia , Dermatite Atópica/imunologia , Interleucina-33/imunologia , Queratinócitos/imunologia , Staphylococcus aureus/imunologia , Fatores de Virulência/imunologia , Adulto , Alérgenos/imunologia , Ambrosia/imunologia , Animais , Células Cultivadas , Humanos , Camundongos , Pyroglyphidae/imunologia , Staphylococcus aureus/patogenicidade
6.
Int Arch Allergy Immunol ; 182(4): 292-300, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33176320

RESUMO

BACKGROUND: Recently, the relationship between antigen contact via skin (skin sensitization) and the development of food allergies has gained increasing attention. However, few studies have examined the effects of skin sensitization on healthy skin. OBJECTIVE: To examine the effect of sensitization in healthy skin on IgE and cytokine production during food allergy development. METHODS: The effect of skin sensitization on food allergy was evaluated using DO11.10 mice whose T cells express ovalbumin (OVA)-specific T-cell receptors. OVA was applied to the back skin of mice dehaired by various methods, and then food allergy was induced by providing them with an OVA-containing diet. OVA-specific IgE production in the sera and decreases in body temperature due to anaphylactic reaction were measured as indicators of food allergy. In addition, IL-4 production and proliferation of splenocytes were measured in mice with food allergy after skin sensitization. RESULTS: Skin sensitization in healthy skin increased IgE production and exacerbated anaphylactic symptoms induced by ingesting the antigen. Moreover, skin sensitization enhanced IL-4 production from splenocytes during the onset of food allergy. In contrast, oral tolerance was induced even after establishing skin sensitization. CONCLUSION: Skin sensitization temporarily exacerbated food allergy by enhancing systemic Th2 responses. These findings will help identify the mechanisms involved in food allergy and help develop treatments.


Assuntos
Alérgenos/imunologia , Hipersensibilidade Alimentar/imunologia , Pele/imunologia , Células Th2/imunologia , Administração Cutânea , Alérgenos/administração & dosagem , Anafilaxia/imunologia , Anafilaxia/metabolismo , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Hipersensibilidade Alimentar/metabolismo , Hipersensibilidade Alimentar/patologia , Hipersensibilidade Alimentar/terapia , Tolerância Imunológica , Imunização , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunoterapia , Camundongos , Pele/metabolismo , Células Th2/metabolismo
7.
Biosci Biotechnol Biochem ; 85(12): 2442-2449, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34617563

RESUMO

The high-temperature water treatment is one of the methods used to reduce the molecular weight of proteins. In this study, in order to establish a practical method for preparing hypoallergenic materials using the high-temperature water treatment, we investigated the effects of processing temperature on the antigenicity and allergenicity of a food allergen. Additionally, the foaming ability of the samples was also evaluated as a function desired in the food industry. We used ovalbumin as a model allergen. As a result, although there was no significant difference among the samples treated with different processing temperatures, all the antigens treated with high-temperature water showed a decrease in antigenicity and allergenicity. In addition, when ovalbumin was treated at a temperature of 130 °C or higher, there was a significant improvement in foaming properties. These findings indicate that high-temperature water treatment is a potential strategy for preparing practical hypoallergenic materials.


Assuntos
Ovalbumina
8.
J Neuroradiol ; 48(2): 88-93, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32335071

RESUMO

BACKGROUND AND PURPOSE: Beta-propeller protein-associated neurodegeneration (BPAN) is one subtype of neurodegeneration with brain iron accumulation. It is difficult to diagnose BPAN due to the non-specificity of their clinical findings and neuroimaging in early childhood. We experienced four pediatric patients with serial brain MRI and evaluated the alteration of the findings through their course. METHODS: We retrospectively reviewed the clinical findings and 21 MRI findings of the four patients with genetically confirmed pediatric BPAN. We also performed a quantitative MR assessment using the quantitative susceptibility mapping (QSM) values of the globus pallidus (GP), substantia nigra (SN), and deep cerebellar nuclei (DCN) compared to 10 age-matched disease controls. RESULTS: Only one patient was suspected of BPAN based on imaging findings before the genetic diagnosis was made. The other three patients could not be suspected until their Whole-exome sequencings (WES) done. In all four cases, no abnormal signals were noted in the GP and SN at the initial brain MRI, but hypointensities were observed after the ages of 4-7 years on T2-weighted images and after the ages of 2-7 years on susceptibility-weighted images. In three patients, T2 hyperintensity in the bilateral DCN was persistently observed throughout the observational period. Three patients showed transient T2 hyperintensity and swelling in the GP, SN and/or DCN during the episodes of pyrexia and seizures. The other findings included cerebral and cerebellar atrophy, thinning of the corpus callosum, and delayed myelination. The QSM values of the GP and SN were significantly higher in the patients compared to the controls (P=0.005, respectively), but that of the DCN did not differ significantly (P=0.16). CONCLUSION: Brain MRI is a useful method to establish the early diagnosis of BPAN.


Assuntos
Proteínas de Transporte , Doenças Neurodegenerativas , Criança , Pré-Escolar , Humanos , Imageamento por Ressonância Magnética , Doenças Neurodegenerativas/diagnóstico por imagem , Neuroimagem , Estudos Retrospectivos
9.
J Neuroradiol ; 48(6): 419-424, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31889551

RESUMO

BACKGROUND AND PURPOSE: Chorea-acanthocytosis, a rare neurodegenerative disease, affects both the striatum and the medial temporal lobe which may cause involuntary movements and epilepsy, respectively. We examined the imaging changes of the hippocampus/amygdala and the striatum as well as clinical symptoms. MATERIALS AND METHODS: We retrospectively reviewed 29 MRI and 13 SPECT studies and the clinical findings of seven genetically confirmed chorea-acanthocytosis patients. We evaluated the time-dependent imaging changes of the hippocampus/amygdala and striatum and examined the relationships among these images and symptoms. RESULTS: The initial symptom was epilepsy in four patients and involuntary movements in three patients. These symptoms were eventually noted in five and all seven patients, respectively. On MRI, most patients showed striatum atrophy before a hippocampus/amygdala abnormality emerged, but one patient showed a hippocampus/amygdala abnormality before striatum atrophy. Abnormal MRI findings of hippocampus/amygdala were noted in five patients and atrophy of striatum in all seven patients. SPECT demonstrated hypoperfusion of hippocampus/amygdala in three patients and that of striatum in all five available patients. Four patients demonstrated hypoperfusion of striatum earlier than that of hippocampus/amygdala and one patient showed hypoperfusion of both simultaneously. Many imaging abnormal lesions were accompanied by their corresponding symptoms, but not always so. CONCLUSION: Striatum abnormalities were the initial imaging findings in many chorea-acanthocytosis patients, but epilepsy or hippocampus/amygdala imaging abnormalities may be the only findings at the early stage. It is important to understand the detailed clinical and imaging time courses for the diagnosis of chorea-acanthocytosis.


Assuntos
Epilepsia do Lobo Temporal , Neuroacantocitose , Doenças Neurodegenerativas , Atrofia , Hipocampo , Humanos , Imageamento por Ressonância Magnética , Neuroacantocitose/diagnóstico por imagem , Estudos Retrospectivos
10.
Acta Neuropsychiatr ; 33(3): 121-125, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33349287

RESUMO

Objective: Previous studies have shown differences in the regional brain structure and function between patients with bipolar disorder (BD) and healthy subjects, but little is known about the structural connectivity between BD patients and healthy subjects. In this study, we evaluated the disease-related changes in regional structural connectivity derived from gray matter magnetic resonance imaging (MRI) scans. Methods: The subjects were 73 patients with BD and 80 healthy volunteers who underwent 3-Tesla MRI. Network metrics, such as the small world properties, were computed. We also performed rendering of the network metric images such as the degree, betweenness centrality, and clustering coefficient, on individual brain image. Then, we estimated the differences between them, and evaluate the relationships between the clinical symptoms and the network metrics in the patients with BD. Results: BD patients showed a lower clustering coefficient in the right parietal region and left occipital region, compared with healthy subjects. A weak negative correlation between Young mania rating scale and clustering coefficient was found in left anterior cingulate cortex. Conclusions: We found differences in gray matter structural connectivity between BD patients and healthy subjects by a similarity-based approach. These points may provide objective biological information as an adjunct to the clinical diagnosis of BD.


Assuntos
Transtorno Bipolar/diagnóstico , Mapeamento Encefálico/instrumentação , Encéfalo/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adulto , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/patologia , Encéfalo/patologia , Estudos de Casos e Controles , Análise por Conglomerados , Feminino , Substância Cinzenta/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Escalas de Graduação Psiquiátrica/normas
11.
J Clin Psychopharmacol ; 40(1): 14-17, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31834097

RESUMO

BACKGROUND: Hyperprolactinemia is a troublesome adverse effect of antipsychotics. Aripiprazole (ARP), which is one of second-generation antipsychotics, has been reported to lower serum prolactin (PRL) levels. However, few studies have compared the effect of ARP on plasma PRL levels between monopharmacy and polypharmacy with antipsychotics. METHODS: We conducted a large-scale investigation of the physical risk for inpatients with schizophrenia using a questionnaire covering demographic data, the number, dose and type of antipsychotics, and serum PRL levels. RESULTS: Sufficient data to conduct an assessment of the effect on PRL levels between antipsychotic monopharmacy and polypharmacy were obtained from 316 of the inpatients. Serum PRL levels in ARP combination group were lower than non-ARP combination group, regardless of antipsychotic monopharmacy or polypharmacy. CONCLUSIONS: The present study suggests that ARP lowers serum PRL levels regardless of monopharamacy or polypharmacy with antipsychotics.


Assuntos
Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Prolactina/sangue , Esquizofrenia/tratamento farmacológico , Adulto , Idoso , Antipsicóticos/efeitos adversos , Aripiprazol/efeitos adversos , Estudos Transversais , Regulação para Baixo , Quimioterapia Combinada , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Polimedicação , Esquizofrenia/sangue , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Resultado do Tratamento
12.
Org Biomol Chem ; 18(16): 3022-3026, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32239018

RESUMO

The first iron-catalysed cross coupling of propargyl electrophiles with lithium alkenylborates has been developed. Various propargyl electrophiles can be cross-coupled with lithium (E)- or (Z)-alkenylborates in a stereospecific manner to afford the corresponding 1,4-enynes in good to excellent yields. The reaction features high SN2-type regioselectivity and functional group compatibility.

13.
J Magn Reson Imaging ; 49(3): 818-824, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30430664

RESUMO

BACKGROUND: Diffusional kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) metrics provide more specific information regarding pathological changes than diffusion tensor imaging (DTI). PURPOSE: To detect microstructural abnormalities in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS) patients by using DKI and NODDI metrics. STUDY TYPE: Prospective. POPULATION: Twenty ME/CFS patients and 23 healthy controls were recruited. FIELD STRENGTH/SEQUENCE: Three-b value DWI (b-values = 0, 1000, and 2000 sec/mm2 ) and 3D T1 -weighted images were at 3.0T. ASSESSMENT: Mean kurtosis (MK), neurite density index (NDI), orientation dispersion index (ODI), fractional anisotropy (FA), and mean diffusivity (MD) were calculated. STATISTICAL TESTING: The two-sample t-test analysis in SPM12 software was used to compare the differences between ME/CFS and control groups. RESULTS: In the ME/CFS patients, we observed significant FA decreases in the genu of the corpus callosum and the anterior limb of the right internal capsule (P < 0.05), but no significant difference in MD (P = 0.164); there were also significant MK decreases in the right frontal area, anterior cingulate gyrus, superior longitudinal fasciculus (SLF), and left parietal area (P < 0.05). Significant NDI decreases were observed in the right posterior cingulate gyrus, SLF, and left frontal area of the ME/CFS patients (P < 0.05). Significant ODI decreases were seen in the bilateral occipital areas, right superior temporal gyrus, the anterior limb of internal capsule, and the posterior cingulate gyrus (P < 0.05), and significant ODI increases were revealed in the bilateral occipital and right temporal areas (P < 0.05). DATA CONCLUSION: Right SLF abnormalities may be a diagnostic marker for ME/CFS. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:818-824.


Assuntos
Imagem de Difusão por Ressonância Magnética , Encefalomielite/diagnóstico por imagem , Síndrome de Fadiga Crônica/diagnóstico por imagem , Neuritos/patologia , Adulto , Anisotropia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Estudos de Casos e Controles , Imagem de Tensor de Difusão , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
14.
Alzheimer Dis Assoc Disord ; 33(3): 206-211, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31135455

RESUMO

PURPOSE: Hippocampal subfield volumetry should be more useful than whole hippocampal (WH) volumetry for diagnosing Alzheimer disease (AD). This study sought to confirm this. METHODS: We investigated cognitively normal (CN) participants and patients with mild cognitive impairment (MCI) or AD using high-resolution T2-weighted and 3-dimensional T1-weighted magnetic resonance imaging. Using medial temporal subregion volumetry, we investigated discriminative power for MCI and AD versus CN. PATIENTS: We recruited 30 CN participants, 30 amnestic MCI patients, and 49 AD patients between April 2015 and October 2016. RESULTS: For AD, discriminative power of the combined volumes of the subiculum, entorhinal cortex, and cornu ammonis 1 was highest [area under the curve (AUC)=0.915; 85.7% sensitivity, 86.7% specificity, 86.1% accuracy], and was significantly higher than that of the WH volume (AUC=0.887; 90.0% sensitivity, 75.5% specificity, 84.5% accuracy) (P=0.019). For MCI, discriminative power of the subiculum volume was highest (AUC=0.747; 80.0% sensitivity, 73.3% specificity, 76.7% accuracy), but was only slightly higher than that of the WH volume (AUC=0.730; 56.7% sensitivity, 90.0% specificity, 73.3% accuracy). CONCLUSIONS: Using the combined volumes of the subiculum, entorhinal cortex, and cornu ammonis 1 may enable greater diagnostic accuracy compared with the WH volume or any single subfield in AD patients.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Córtex Entorrinal/patologia , Hipocampo/patologia , Processamento de Imagem Assistida por Computador/estatística & dados numéricos , Imageamento por Ressonância Magnética , Idoso , Feminino , Humanos , Masculino , Sensibilidade e Especificidade , Substância Branca/patologia
15.
Int J Geriatr Psychiatry ; 34(1): 186-192, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30328161

RESUMO

OBJECTIVES: The present study investigated the usefulness of evaluating the existence of volume reduction in brain regions using voxel-based morphometry (VBM) to dissociate major depressive disorder (MDD) from bipolar disorder (BD). METHODS/DESIGN: This study enrolled 92 individuals with MDD, 32 individuals with BD, and 43 healthy controls (HCs). We focused on gray matter volume (GMV) of the subgenual anterior cingulate cortex (sgACC), subcallosal area (SCA), and hippocampus. The degree of volume reduction in these brain regions was calculated as the z score, and the differences of z scores in these regions were investigated among the MDD, BD, and HC groups. We then performed a receiver operating characteristic curve analysis to dissociate the individuals with MDD and BD from the HCs based on the z scores in the GMV of these brain regions. RESULTS: While there were no significant differences in the z scores of the hippocampus among the three groups, the z score of the sgACC was significantly higher in the MDD group than in the BD and HC groups, and the SCA z score was significantly higher in the MDD and BD groups than in the HC group. CONCLUSIONS: Our findings suggest that VBM evaluation of GMV reduction in the sgACC may be useful as an objective adjunctive tool to distinguish between MDD and BD.


Assuntos
Transtorno Bipolar/patologia , Transtorno Depressivo Maior/patologia , Substância Cinzenta/patologia , Giro do Cíngulo/patologia , Hipocampo/patologia , Córtex Pré-Frontal/patologia , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Estudos de Casos e Controles , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Lobo Temporal
16.
Neurol Sci ; 40(6): 1191-1198, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30852697

RESUMO

In this retrospective study, we analyzed the effects of age on brain volumes in healthy brains across adulthood. We investigated the correlations between brain volumes and age in the brains of 563 healthy individuals (age range: 20-86, 55% female) whose MRI scans and related information were drawn from the IXI database ( brain-development.org/ixi-dataset /). We conducted a regression analysis to assess the effect of age on whole-brain volumes as well as selected regional volumetric measures. The whole-brain analysis revealed a negative linear relationship between gray matter (GM) and age as well as nonlinear patterns of the relationship between age and the white matter (WM), cerebrospinal fluid (CSF), and the GM/WM ratio across adulthood. The regional volumetric analysis showed linear and non-linear age-related regional volumetric changes with aging. Our present findings contribute to the understanding of how structures in the human brain change over the adult years and will help address the pathological age-related neural changes in age-related neural disorders such as Parkinson disease and Alzheimer disease.


Assuntos
Envelhecimento/fisiologia , Encéfalo/anatomia & histologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Feminino , Substância Cinzenta/anatomia & histologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Substância Branca/anatomia & histologia , Adulto Jovem
17.
Psychogeriatrics ; 19(6): 591-600, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30891900

RESUMO

BACKGROUND: Neuropsychiatric symptoms (NPS) have been recognized as risk factors for conversion to dementia in patients with mild cognitive impairment (MCI). Early detection of NPS may allow for possible interventions in such patients. The present study used mild behavioural impairment to explore the role of NPS in a wide range of patients, from those who are cognitively intact to those with dementia. METHODS: A total of 234 patients with mild cognitive impairment were followed up for up to 3 years in a Japanese cohort study. Longitudinal data from patients who developed dementia during the study and those who did not were statistically analyzed. RESULTS: Cox regression analysis revealed that only abnormal perception and thought was significant in terms of dementia conversion. Moreover, mixed-effects models indicated that baseline mild behavioural impairment symptoms did not affect cognitive trajectories such as changes in Mini-Mental State Examination or Alzheimer's Disease Assessment Scale-cognitive subscale scores. CONCLUSION: We conclude that only abnormal perception and thought content were risk factors for dementia and that NPS may not lead to deterioration of cognitive function in patients with mild cognitive impairment.


Assuntos
Cognição/fisiologia , Disfunção Cognitiva/diagnóstico , Demência/diagnóstico , Transtornos Mentais/etiologia , Idoso , Idoso de 80 Anos ou mais , Sintomas Comportamentais , Disfunção Cognitiva/complicações , Disfunção Cognitiva/psicologia , Demência/complicações , Demência/psicologia , Progressão da Doença , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Testes Neuropsicológicos , Avaliação de Sintomas
18.
Biochem Biophys Res Commun ; 496(1): 231-237, 2018 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-29317205

RESUMO

The Foxe3rct mutation, which causes early-onset cataracts, is a recessive mutation found in SJL/J mice. A previous study reported that cataract phenotypes are modified by the genetic background of mouse inbred strains and that the Pde6brd1 mutation, which induced degeneration of the photoreceptor cells, is a strong candidate genetic modifier to accelerate the severity of cataractogenesis of Foxe3rct mice. We created congenic mice by transferring a genomic region including the Foxe3rct mutation to the B6 genetic background, which does not carry the Pde6brd1 mutation. In the congenic mice, the cataract phenotypes became remarkably mild, and the development of cataracts was suppressed for a long time. Moreover, we created transgenic mice by injecting BAC clones including the wild-type Pde6b gene into the eggs of SJL-Foxe3rct mice. Although the resistant effect for cataract phenotypes in transgenic mice was less than that in congenic mice, the severity and onset time of cataract phenotypes were clearly improved and delayed, respectively, compared with the phenotypes of the original SJL-Foxe3rct mice. These results clearly show that the development of early-onset cataracts requires at least two mutant alleles of Foxe3rct and Pde6brd1, and another modifier associated with the severity of cataract phenotypes in Foxe3rct mice underlies the genetic backgrounds in mice.


Assuntos
Catarata/genética , Catarata/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 6/genética , Nucleotídeo Cíclico Fosfodiesterase do Tipo 6/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Predisposição Genética para Doença/genética , Animais , Progressão da Doença , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Relação Estrutura-Atividade
19.
Eur J Nucl Med Mol Imaging ; 45(8): 1405-1416, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29478082

RESUMO

PURPOSE: The aim of this multicenter trial was to generate a [123I]FP-CIT SPECT database of healthy controls from the common SPECT systems available in Japan. METHODS: This study included 510 sets of SPECT data from 256 healthy controls (116 men and 140 women; age range, 30-83 years) acquired from eight different centers. Images were reconstructed without attenuation or scatter correction (NOACNOSC), with only attenuation correction using the Chang method (ChangACNOSC) or X-ray CT (CTACNOSC), and with both scatter and attenuation correction using the Chang method (ChangACSC) or X-ray CT (CTACSC). These SPECT images were analyzed using the Southampton method. The outcome measure was the specific binding ratio (SBR) in the striatum. These striatal SBRs were calibrated from prior experiments using a striatal phantom. RESULTS: The original SBRs gradually decreased in the order of ChangACSC, CTACSC, ChangACNOSC, CTACNOSC, and NOACNOSC. The SBRs for NOACNOSC were 46% lower than those for ChangACSC. In contrast, the calibrated SBRs were almost equal under no scatter correction (NOSC) conditions. A significant effect of age was found, with an SBR decline rate of 6.3% per decade. In the 30-39 age group, SBRs were 12.2% higher in women than in men, but this increase declined with age and was absent in the 70-79 age group. CONCLUSIONS: This study provided a large-scale quantitative database of [123I]FP-CIT SPECT scans from different scanners in healthy controls across a wide age range and with balanced sex representation. The phantom calibration effectively harmonizes SPECT data from different SPECT systems under NOSC conditions. The data collected in this study may serve as a reference database.


Assuntos
Tomografia Computadorizada de Emissão de Fóton Único , Tropanos , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Bases de Dados Factuais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Imagens de Fantasmas
20.
Neuroradiology ; 60(6): 635-641, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29654334

RESUMO

PURPOSE: Although epilepsy in the elderly has attracted attention recently, there are few systematic studies of neuroimaging in such patients. In this study, we used structural MRI and diffusion tensor imaging (DTI) to investigate the morphological and microstructural features of the brain in late-onset temporal lobe epilepsy (TLE). METHODS: We recruited patients with TLE and an age of onset > 50 years (late-TLE group) and age- and sex-matched healthy volunteers (control group). 3-Tesla MRI scans, including 3D T1-weighted images and 15-direction DTI, showed normal findings on visual assessment in both groups. We used Statistical Parametric Mapping 12 (SPM12) for gray and white matter structural normalization and comparison and used Tract-Based Spatial Statistics (TBSS) for fractional anisotropy and mean diffusivity comparisons of DTI. In both methods, p < 0.05 (family-wise error) was considered statistically significant. RESULTS: In total, 30 patients with late-onset TLE (mean ± SD age, 66.8 ± 8.4; mean ± SD age of onset, 63.0 ± 7.6 years) and 40 healthy controls (mean ± SD age, 66.6 ± 8.5 years) were enrolled. The late-onset TLE group showed significant gray matter volume increases in the bilateral amygdala and anterior hippocampus and significantly reduced mean diffusivity in the left temporofrontal lobe, internal capsule, and brainstem. No significant changes were evident in white matter volume or fractional anisotropy. CONCLUSIONS: Our findings may reflect some characteristics or mechanisms of cryptogenic TLE in the elderly, such as inflammatory processes.


Assuntos
Imagem de Tensor de Difusão/métodos , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/patologia , Idade de Início , Idoso , Anisotropia , Mapeamento Encefálico , Estudos de Casos e Controles , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade
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