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1.
BMC Nephrol ; 24(1): 373, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102596

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with chronic kidney disease (CKD) and could be related to oxidative stress. Vascular calcification (VC) has been established as a critical risk factor for accelerated CVD. In CKD, phosphorus (Pi), iron (Fe) and Nrf2 are modulators of VC and important agonists and antagonists of oxidative stress. The aim of this study was to determine whether Fe administration, which is commonly used to treat renal anemia, affects aortic Fe overload and VC, and whether Nrf2 and its related genes, ferritin H and HIF-1α, are involved in the development of VC. METHODS: A CKD model was created in rats by administering adenine and simultaneously feeding a high-Pi diet. In addition to control and CKD rats without Fe administration (No-Fe group), Fe was administered orally (PO-Fe group) or intraperitoneally (IP-Fe group) to CKD animals to clarify the effects of Fe administration on the aortic Fe and calcium (Ca) contents and the involvement of Nrf2 and its induced antioxidative proteins, ferritin H and HIF-1α, in VC. RESULTS: The aortic Fe content increased significantly in the IP-Fe group, which was closely correlated with liver HAMP (hepcidin) expression in all animals. Fe administration had no significant effect on the aortic Ca and Pi contents regardless of the route of Fe administration. The aortic mRNA level of Nrf2 was significantly increased in the IP-Fe group and correlated with serum Pi levels and aortic Fe contents, which could respond to oxidative stress. Notably, the mRNA level of Nrf2 was also significantly correlated with the mRNA levels of ferritin H and HIF-1α. Since we could not measure Nrf2 protein levels in this study, we confirmed the upregulation of HMOX1 and NQO1 mRNA expression in parallel with Nrf2 mRNA. CONCLUSION: Parenteral Fe administration increased aortic Fe in parallel with the liver HAMP mRNA level but did not affect VC. Aortic Nrf2 mRNA levels correlated significantly with aortic Fe and serum Pi levels and with aortic mRNA levels of ferritin H and HIF-1α as well as HMOX1 and NQO1.


Assuntos
Doenças Cardiovasculares , Insuficiência Renal Crônica , Calcificação Vascular , Humanos , Ratos , Animais , Ferro/metabolismo , Fósforo , Fator 2 Relacionado a NF-E2/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Ferritinas , Cálcio/metabolismo , Calcificação Vascular/tratamento farmacológico , Calcificação Vascular/etiologia , Doenças Cardiovasculares/complicações , RNA Mensageiro
3.
Medicine (Baltimore) ; 102(8): e33055, 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36827025

RESUMO

RATIONALE: Ornithine transcarbamylase (OTC) deficiency, a urea cycle disorder, is a rare congenital metabolic error that leads to hyperammonemia. Psychiatric symptoms of hyperammonemia are nonspecific and can cause autism spectrum disorder (ASD)-like symptoms and attention-deficit/hyperactivity disorder (ADHD)-like symptoms. Some studies report that OTC deficiency is often initially diagnosed as ASD or ADHD. However, there are no reports of OTC deficiency comorbid with ASD and ADHD. PATIENT CONCERNS: The patient is 17-year-old girl diagnosed with OTC deficiency at 3 years of age. She had behavioral problems since childhood, including depressed mood, irritability, and impulsive behavior; however, they were considered OTC-mediated nonspecific psychiatric symptoms. Therefore, the patient had not been appropriately assessed for ASD and ADHD. She presented with depressed mood and self-harm at 17 years of age. DIAGNOSES: We diagnosed her with ASD and ADHD based on her medical history and semistructured interviews. INTERVENTIONS: We focused her ASD and ADHD traits and discussed strategies with her for better adaptive living. OUTCOMES: Our interventions resulted in her better social adjustment. LESSONS: Physicians should consider the possibility of comorbid ASD and ADHD in individuals with OTC, facilitating appropriate and intervention for better outcomes.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Hiperamonemia , Doença da Deficiência de Ornitina Carbomoiltransferase , Humanos , Feminino , Criança , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Espectro Autista/epidemiologia , Comorbidade
4.
Neuropsychiatr Dis Treat ; 18: 2421-2430, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36304993

RESUMO

Purpose: Internet addiction (IA) has become a global problem and is one of the most common reasons for children to be referred for intervention because IA results in social and educational dysfunction and conflict with parents. IA is associated with various comorbid psychiatric disorders, with notable association between IA and family factors. However, little is known about parental psychopathology. This study aimed to examine the prevalence of IA and association between IA and maternal depression and anxiety in clinical samples after adjusting for comorbidities. Patients and Methods: A cross-sectional study was conducted between April 2020 and August 2021 at the Department of Neuropsychiatry of Osaka Metropolitan University Hospital in Japan. A total of 218 clinically referred children and adolescents (aged 8 to 15 years) were assessed using the Internet Addiction Test, which is one of the most popular questionnaires to evaluate IA, the Child Behavior Checklist (CBCL), and The Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. IA was defined as a total score on the Internet Addiction Test ≥ 50. Of those, for the evaluation of maternal depression and anxiety, the 132 mothers of the children who were referred after January 2021 completed K6 as well. Results: A total of 68 participants (31.2%) presented with IA and had higher total and externalizing scores of CBCL, social anxiety disorder, and oppositional defiant disorder compared to those without IA. IA was associated with the six-item Kessler scale scores of mothers, being raised by single parents, and anxiety disorders after adjusting for age, sex, and family income (95% CI: 1.023-1.215). Conclusion: Maternal depression and anxiety may be one of the risk factors for children and adolescents to develop IA. Care for maternal depression and anxiety may contribute to intervention for children and adolescents with IA.

5.
Front Psychiatry ; 13: 860278, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573381

RESUMO

Irritability is one of the most common reasons for which children and adolescents are referred for psychiatric evaluation and care. However, clinical irritability is difficult to define; thus, its prevalence varies widely. Chronic irritability may be associated with sensory processing difficulties (SPD), but little is known about the relationship between these two factors in clinical populations. In this study, we examined the prevalence of chronic irritability and its association with SPD in 166 children aged 5-16 years who were referred to the psychiatric outpatient clinic of the Osaka City University Hospital. Chronic irritability and parent-reported scores for the Short Sensory Profile, Infant Behavior Checklist-Revised, Child Behavior Checklist, and Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children (Present and Lifetime version) questionnaires were used for assessment. A total of 22 children (13.2%) presented with chronic irritability (i.e., the irritability group) and were more likely to have oppositional defiant disorder, externalizing problems, and attention issues than those without chronic irritability (i.e., the control group). SPD were reported in eight (36%) patients in the irritability group and in 21 (15%) in the control group (p = 0.029). Moreover, compared to the control group, the irritability group showed a significant difference in almost all items of the Short Sensory Profile. Chronic irritability was associated with more severe overall SPD, even after adjusting for possible confounding factors (internalizing and externalizing problems, age, sex, and low income). We provide evidence to support our hypothesis that chronic irritability is associated with SPD in children and adolescents. Therefore, SPD should be assessed to provide appropriate interventions in children and adolescents with chronic irritability.

6.
Medicine (Baltimore) ; 100(22): e26233, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087907

RESUMO

RATIONALE: Coronavirus disease 2019 (COVID-19) is affecting mental health profoundly. Previous studies have reported pandemic-related anxiety. Anxiety disorder and autism spectrum disorder (ASD) are common comorbidities. However, there has been no report of any patient with undiagnosed ASD who developed anxiety disorders caused by the COVID-19 pandemic. In this case report, we describe an 8-year-old Japanese boy with undiagnosed ASD who developed COVID-19 phobia, resulting in avoidant restrictive food intake disorder (ARFID). PATIENT CONCERNS: As COVID-19 was highly publicized in the mass media and the risk of droplet infection was emphasized upon, the patient began to fear viral contamination from food, culminating in a refusal to eat or even swallow his saliva. He was admitted to a pediatric medical center in Osaka with life-threatening dehydration and was then referred to our child psychiatry department. DIAGNOSIS: We diagnosed the patient with COVID-19 phobia resulting in ARFID. We identified ASD traits from his present social communication skills and developmental history. INTERVENTIONS: We provided psychoeducation of ASD for the parents and administered supportive psychotherapy. OUTCOMES: Shortly after our intervention to relieve his ASD-related anxiety, his dysphagia improved. LESSONS: Our findings suggest that children with undiagnosed ASD may develop COVID-19 phobia. In these cases, intervention for ASD may be more appropriate than starting treatment for anxiety disorders as the first-line option. COVID-19 is the biggest pandemic in the recent past, and more undiagnosed ASD patients who develop COVID-19 phobia may seek treatment. Clinicians should consider the underlying ASD in these patients and assess their developmental history and present social communication skills.


Assuntos
Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/psicologia , COVID-19/psicologia , Transtornos Fóbicos/complicações , Transtorno Alimentar Restritivo Evitativo , Criança , Humanos , Masculino , SARS-CoV-2
7.
J Hum Genet ; 66(6): 569-578, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33262389

RESUMO

Missense and truncating variants in protocadherin 19 (PCDH19) cause PCDH19-related epilepsy. In this study, we aimed to investigate variations in distributional characteristics and the clinical implications of variant type in PCDH19-related epilepsy. We comprehensively collected PCDH19 missense and truncating variants from the literature and by sequencing six exons and intron-exon boundaries of PCDH19 in our cohort. We investigated the distribution of each type of variant using the cumulative distribution function and tested for associations between variant types and phenotypes. The distribution of missense variants in patients was clearly different from that of healthy individuals and was uniform throughout the extracellular cadherin (EC) domain, which consisted of six highly conserved domains. Truncating variants showed two types of distributions: (1) located from EC domain 1 to EC domain 4, and (2) located from EC domain 5 to the cytoplasmic domain. Furthermore, we also found that later onset seizures and milder intellectual disability occurred in patients with truncating variants located from EC domain 5 to the cytoplasmic domain compared with those of patients with other variants. Our findings provide the first evidence of two types of truncating variants in the PCDH19 gene with regard to distribution and the resulting clinical phenotype.


Assuntos
Caderinas/genética , Epilepsia/genética , Estudos de Associação Genética , Convulsões/genética , Idade de Início , Pré-Escolar , Estudos de Coortes , Epilepsia/patologia , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Masculino , Mutação de Sentido Incorreto/genética , Fenótipo , Protocaderinas , Convulsões/patologia
8.
BMC Microbiol ; 20(1): 217, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32689952

RESUMO

BACKGROUND: Lactobacillus gasseri OLL2809 can highly induce interleukin (IL)-12 production in immune cells. Even though beneficial properties of this strain for both humans and animals have been reported, the mechanism by which the bacteria induces the production of IL-12 in immune cells remains elusive. In this study, we investigated the mechanism of induction of IL-12 using a mouse macrophage cell line J774.1. RESULTS: Inhibition of phagocytosis of L. gasseri OLL2809, and myeloid differentiation factor 88 and Toll-like receptors (TLRs) 7 and 9 signalling attenuated IL-12 production in J774.1 cells. Total RNA and genomic DNA of L. gasseri OLL2809, when transferred to the J774.1 cells, also induced IL-12 production. The difference in the IL-12-inducing activity of Lactobacilli is attributed to the susceptibility to phagocytosis, but not to a difference in the total RNA and genomic DNA of each strain. CONCLUSION: We concluded that total RNA and genomic DNA of phagocytosed L. gasseri OLL2809 induce IL-12 production in J774.1 cell via TLRs 7 and 9, and the high IL-12-inducing activity of L. gasseri OLL2809 is due to its greater susceptibility to phagocytosis.


Assuntos
DNA Bacteriano/imunologia , Interleucina-12/metabolismo , Lactobacillus gasseri/genética , Macrófagos/imunologia , Glicoproteínas de Membrana/metabolismo , RNA Bacteriano/imunologia , Receptor 7 Toll-Like/metabolismo , Receptor Toll-Like 9/metabolismo , Animais , Técnicas de Cultura de Células , Linhagem Celular , Genoma Bacteriano , Lactobacillus gasseri/imunologia , Macrófagos/citologia , Macrófagos/microbiologia , Camundongos , Fator 88 de Diferenciação Mieloide/metabolismo , Fagocitose , Transdução de Sinais , Regulação para Cima
9.
Epilepsia ; 60(9): 1870-1880, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31418850

RESUMO

OBJECTIVE: Pathogenic variants of KCNQ2, which encode a potassium channel subunit, cause either benign (familial) neonatal epilepsy-B(F)NE)-or KCNQ2 encephalopathy (KCNQ2 DEE). We examined the characteristics of KCNQ2 variants. METHODS: KCNQ2 pathogenic variants were collected from in-house data and two large disease databases with their clinical phenotypes. Nonpathogenic KCNQ2 variants were collected from the Genome Aggregation Database (gnomAD). Pathogenicity of all variants was reevaluated with clinical information to exclude irrelevant variants. The cumulative distribution plots of B(F)NE, KCNQ2 DEE, and gnomAD KCNQ2 variants were compared. Several algorithms predicting genetic variant pathogenicity were evaluated. RESULTS: A total of 259 individuals or pedigrees with 216 different pathogenic KCNQ2 variants and 2967 individuals with 247 different nonpathogenic variants were deemed eligible for the study. Compared to the distribution of nonpathogenic variants, B(F)NE and KCNQ2 DEE missense variants occurred in five and three specific KCNQ2 regions, respectively. Comparison between B(F)NE and KCNQ2 DEE sets showed that B(F)NE missense variants frequently localized to the intracellular domain between S2 and S3, whereas those of KCNQ2 DEE were more frequent in S6, and its adjacent pore domain, as well as in the intracellular domain between S6 and helix A. The scores of Protein Variation Effect Analyzer (PROVEAN) and Percent Accepted Mutation (PAM) 30 prediction algorithms were associated with phenotypes of the variant loci. SIGNIFICANCE: Missense variants in the intracellular domain between S2 and S3 are likely to cause B(F)NE, whereas those in S6 and its adjacent regions are more likely to cause KCNQ2 DEE. With such regional specificities of variants, PAM30 is a helpful tool to examine the possibility that a novel KCNQ2 variant is a B(F)NE or KCNQ2 DEE variant in genetic analysis.


Assuntos
Encefalopatias/genética , Epilepsia Neonatal Benigna/genética , Canal de Potássio KCNQ2/genética , Espasmos Infantis/genética , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Mutação de Sentido Incorreto , Linhagem , Fenótipo
10.
Dig Endosc ; 31(4): 413-421, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30723945

RESUMO

OBJECTIVES: This study aimed to compare the diagnostic yield of mucosal incision-assisted biopsy (MIAB) and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with a rapid on-site evaluation (ROSE) for gastric subepithelial lesions (SEL) suspected of being gastrointestinal stromal tumors (GIST) with an intraluminal growth pattern. METHODS: This was a prospective randomized, cross-over multicenter study. The primary outcome was the diagnostic yield of EUS-FNA and MIAB. The secondary outcomes were the technical success rate, complication rate, procedure time and biopsy frequency. RESULTS: A total of 47 patients were randomized to the MIAB group (n = 23) and EUS-FNA group (n = 24). There was no significant difference in the diagnostic yield of MIAB and EUS-FNA (91.3% vs 70.8%, P = 0.0746). The complication rates of MIAB and EUS-FNA did not differ to a statistically significant extent. The mean procedure time in the MIAB group was significantly longer than that in the EUS-FNA group (34 vs 26 min, P = 0.0011). CONCLUSIONS: The diagnostic yield of MIAB was satisfactorily as high as EUS-FNA with ROSE for gastric SEL with an intraluminal growth pattern.


Assuntos
Ressecção Endoscópica de Mucosa/métodos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Neoplasias Gástricas/patologia , Idoso , Estudos Cross-Over , Detecção Precoce de Câncer , Ressecção Endoscópica de Mucosa/instrumentação , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/instrumentação , Endoscopia do Sistema Digestório , Feminino , Gastroscopia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
11.
Inflamm Bowel Dis ; 25(6): 1019-1027, 2019 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-30668727

RESUMO

BACKGROUND: T helper (Th)- and regulatory T (Treg) cell-related immune molecules are implicated in ulcerative colitis (UC). However, the association between their mucosal expression during remission and the subsequent clinical course of UC is unknown. METHODS: The expression of cytokines and transcription factors related to Th1, Th2, Th17, and Treg in endoscopic mucosal biopsy specimens from 40 UC patients in clinical remission and 9 controls was measured by quantitative polymerase chain reaction. The relationship between their expression patterns, as stratified by Mayo Endoscopic Subscore (MES), and any future relapse was evaluated by univariate and multivariate analyses. RESULTS: Six of 40 patients (baseline MES 0/1/2, 22/14/4) experienced a relapse during the study period (median, 37 months). At baseline, even in the MES0 patients, the interleukin (IL)-17A of the patients was significantly upregulated in comparison with controls (P = 0.0351). Future relapse was associated with a higher baseline expression of IL-17A, IL-17F, and IL-21 in MES0/1, and the upregulation of IL-17F and IL-21 remained statistically significant when limited to MES0 patients. Kaplan-Meier analysis revealed that as a single marker, a higher IL-21 level best grouped patients with an increased risk of relapse (P = 0.0042). Furthermore, a multivariate model that consisted of IL-21 and T-bet showed an even greater value (P = 0.0001). CONCLUSIONS: The profiles of Th/Treg-related gene expression in the colonic mucosa are altered, even during clinical and endoscopic remission of UC, with a detectable Th17-predominant profile predicting future relapse. This association might represent latent immune dysregulation during disease quiescence and has the potential to be utilized to improve patient care.


Assuntos
Colite Ulcerativa/diagnóstico , Colite Ulcerativa/imunologia , Imunidade nas Mucosas/imunologia , Mucosa Intestinal/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Colite Ulcerativa/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recidiva , Indução de Remissão , Índice de Gravidade de Doença
12.
Eat Weight Disord ; 23(6): 761-768, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30221324

RESUMO

PURPOSE: Shoplifting, prevalent in patients diagnosed with bulimia nervosa (BN), is a serious behavioral problem in eating disorder (ED) patients. However, little is known about its overall presence, etiology, and consequences. This study aimed to determine whether shoplifting occurs before or after the onset of ED and to investigate the prevalence and correlates of shoplifting in ED patients. METHODS: This was a cross-sectional study of 284 treatment-seeking female patients aged 13-45 with EDs [171 anorexia nervosa (AN); 113 BN]. Shoplifting, impulsive behaviors (self-injury, suicide attempt, sexual promiscuity, alcohol, and illicit drug use), depression, self-esteem, and clinical features of EDs were assessed with an interview. RESULTS: Lifetime shoplifting prevalence was 28.5% (81/284) with 70.4% (57/81) occurring before ED onset. Multivariate logistic regression analysis revealed that depression [odds ratio (OR), 2.63; 95% confidence interval (CI), 1.24-5.60], alcohol abuse (OR, 3.91; 95% CI 1.34-11.38), illicit substance use (OR, 14.42; 95% CI, 1.65-125.86), and self-esteem (OR, 0.90; 95% CI; 0.82-0.99) were associated with lifetime shoplifting, while illness duration, BN, and ED symptom severity were not. CONCLUSIONS: Shoplifting is common in ED patients and precedes ED onset in most patients with a shoplifting history, although the causal relationship between shoplifting and EDs remains inconclusive. Shoplifting may be associated with impulsive behaviors (e.g., alcohol and illicit drug use), depression, and low self-esteem, but not with ED severity. Future research should focus on the unrecognized role of shoplifting as a marker to identify patients at risk of impulsive behaviors and consider treatment options. LEVEL OF EVIDENCE: Level V, observational cross-sectional descriptive study.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Comportamento Impulsivo/fisiologia , Autoimagem , Roubo/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Depressão/psicologia , Feminino , Humanos , Japão , Pessoa de Meia-Idade , Tentativa de Suicídio/psicologia , Roubo/psicologia , Adulto Jovem
13.
Neuropsychiatr Dis Treat ; 14: 1747-1753, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30013347

RESUMO

Early-onset obsessive-compulsive disorder (OCD) is more severe than later-onset OCD. There are no reports of any early-onset OCD patients being cured, especially with respect to preschoolers. In this case report, we describe the successful treatment and cure of a 6-year-old preschool girl with severe OCD since the age of 3. At the age of 3, the patient began to fear contamination and danger to herself and her family, leading to excessive hand-washing, and several months later, ritualized checking. The OCD symptoms waxed and waned for about 3 years and thereafter worsened gradually over a few weeks, culminating in a refusal to eat and dress. At the age of 6, after a week of inpatient pediatric treatment with no improvement, the patient was transferred to Osaka City University Hospital to seek psychiatric treatment. The patient fully recovered from OCD following family-based cognitive-behavioral therapy (CBT) and short-term use of low-dose fluvoxamine in an inpatient setting. After treatment, the OCD symptoms disappeared with complete remission for over 3 years. Now, aged 9, the patient has good global functioning and is well adjusted in her daily life with no need for any treatment. To the best of our knowledge, this is the first report of preschool-onset OCD with long-term complete remission with inpatient treatment in a preschooler with severe OCD. Some preschoolers with very early-onset OCD may have good prognosis without continuous pharmacotherapy, although the symptoms with the onset are severe enough to require hospitalization. Preschool-onset OCD is likely to be misdiagnosed as separation anxiety disorder. Our findings suggest that family-based CBT, which is the treatment of choice for preschool-onset OCD, can be applicable to inpatient treatment. Early detection and intensive intervention of OCD in preschoolers may improve the chance of remission.

14.
Neuropsychiatr Dis Treat ; 12: 185-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26848267

RESUMO

Psychogenic nonepileptic seizures (PNES) are observable changes in behavior or consciousness that are similar to epileptic seizures but are not associated with electrophysiologic changes. PNES occur in children with underlying psychological distress and are especially frequent in those with epilepsy. Because PNES are heterogeneous, comprehensive treatment tailored to each patient is required to reduce psychosocial stress. Currently, reports regarding children with PNES concomitant with autism spectrum disorder (ASD) do not exist, and effective treatment strategies for these children are lacking. In this case report, we describe a 10-year-old Japanese girl with undiagnosed ASD who developed PNES while undergoing treatment for benign childhood epilepsy with centrotemporal spikes. She exhibited hypersensitivity to sound and interpersonal conflicts caused by social communication deficits. The PNES symptoms improved shortly after our intervention, which was designed to reduce her distress caused by auditory hypersensitivity and impaired social communication, both characteristics of ASD. To the best of our knowledge, this is the first report describing PNES in a child with ASD. Our findings suggest that PNES can result from psychological distress in children with undiagnosed ASD and highlight the importance of examining ASD traits in patients with PNES.

15.
J Cell Biol ; 212(3): 297-306, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26833786

RESUMO

The highly conserved Rab guanosine triphosphatase (GTPase) Rab8 plays a role in exocytosis toward the polarized plasma membrane in eukaryotic cells. In murine Rab8-deficient small intestine cells, apical proteins are missorted into lysosomes. In this study, we identified a novel Rab8-interacting protein complex containing an EH domain-binding protein 1-like 1 (EHBP1L1), Bin1/amphiphysin II, and dynamin. Biochemical analyses showed that EHBP1L1 directly bound to GTP-loaded Rab8 and Bin1. The spatial dependency of these complexes at the endocytic recycling compartment (ERC) was demonstrated through overexpression and knockdown experiments. EHBP1L1- or Bin1-depleted or dynamin-inhibited small intestine organoids significantly accumulated apical membrane proteins but not basolateral membrane proteins in lysosomes. Furthermore, in EHBP1L1-deficient mice, small intestine cells displayed truncated and sparse microvilli, suggesting that EHBP1L1 maintains the apical plasma membrane by regulating apical transport. In summary, our data demonstrate that EHBP1L1 links Rab8 and the Bin1-dynamin complex, which generates membrane curvature and excises the vesicle at the ERC for apical transport.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Transporte/metabolismo , Polaridade Celular , Células Epiteliais/enzimologia , Mucosa Intestinal/enzimologia , Intestino Delgado/enzimologia , Proteínas do Tecido Nervoso/metabolismo , Proteínas Nucleares/metabolismo , Vesículas Transportadoras/enzimologia , Proteínas Supressoras de Tumor/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Transporte Biológico , Proteínas de Transporte/genética , Dinaminas/metabolismo , Células Epiteliais/ultraestrutura , Células HEK293 , Células HeLa , Humanos , Mucosa Intestinal/ultraestrutura , Intestino Delgado/ultraestrutura , Lisossomos/enzimologia , Camundongos , Camundongos Knockout , Microvilosidades/enzimologia , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Organoides , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Transporte Proteico , Interferência de RNA , Transdução de Sinais , Transfecção , Proteínas Supressoras de Tumor/genética , Proteínas rab de Ligação ao GTP/genética
16.
J Dairy Sci ; 99(2): 915-923, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26686726

RESUMO

Yogurt is generally recognized as a beneficial food for our health, but research into its physiological effects has focused mainly on intestinal dysfunctions such as constipation and diarrhea. We previously found yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (hereafter OLL1073R-1) could reduce risks of catching the common cold and flu in human trials. It was assumed that immunostimulatory exopolysaccharide (EPS) produced from OLL1073R-1 play an important role in this context. However, few studies have examined the immunostimulatory effects of traditional Bulgarian yogurts fermented with different strains of lactobacilli and their metabolites. Therefore, we screened 139 L. delbrueckii ssp. bulgaricus strains and identified OLL1073R-1 as the most robust producer of EPS. This strain was also the only strain that induced the production of IFN-γ in vitro. Oral administration of the EPS or yogurt fermented with OLL1073R-1 and Streptococcus thermophilus OLS3059 (OLL1073R-1 yogurt) augmented natural killer (NK) cell activity and induced IFN-γ production in spleen cells in mice, whereas 2 other yogurts fermented with other strains had no effect on NK cell activity. Cellular preparations of the OLL1073R-1 strain also slightly augmented NK cell activity, but were less effective than EPS itself. The EPS-dependent stimulation of NK cell activity was abrogated in IFN-γ knockout mice and in myeloid differentiation factor 88 knockout mice. Furthermore, IFN-γ production from spleen cells stimulated with EPS was completely blocked with both anti-IL-12 and anti-IL-18 antibodies in vitro. These findings suggest that NK cell activation by OLL1073R-1 yogurt is EPS-dependent, occurs via IL-12- and IL-18-mediated IFN-γ production, and requires myeloid differentiation factor 88. We showed that traditional Bulgarian yogurt could exert immunostimulatory effects by selecting starter strains and part of the mechanisms depend on IFN-γ inducible EPS produced from L. delbrueckii ssp. bulgaricus. Further investigations on processes of fermentation to increase of the EPS may lead to the development of new functional foods that keep our immune functions stable.


Assuntos
Fermentação , Células Matadoras Naturais/imunologia , Lactobacillus delbrueckii/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Polissacarídeos Bacterianos/farmacologia , Iogurte/análise , Animais , Reatores Biológicos , Humanos , Interferon gama/biossíntese , Lactobacillus/metabolismo , Camundongos , Camundongos Knockout , Baço/efeitos dos fármacos , Baço/metabolismo , Streptococcus thermophilus/metabolismo , Iogurte/microbiologia
17.
Scand J Gastroenterol ; 51(4): 448-55, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26540372

RESUMO

OBJECTIVE: Although the World Health Organisation (WHO) defined a novel classification of gastroenteropancreatic neuroendocrine tumours (NETs) in 2010, indications for endoscopic resection of rectal NETs in the guidelines were based on evidence accumulated for carcinoid tumours defined by a previous classification. This study was designed to clarify indications for endoscopic resection of rectal NETs corresponding to the new WHO classifications. MATERIAL AND METHODS: One hundred-seventy rectal NETs resected endoscopically from April 2001 to March 2012 were histologically re-classified according to the WHO 2010 criteria. The clinicopathological features of these lesions were analysed, and the short- and long-term outcomes of endoscopic resection were evaluated. RESULTS: Of the 170 rectal NETs, 166 were histopathologically diagnosed as NET G1 and four as NET G2. Thirty-eight tumours (22.4%) were positive for lymphovascular invasion, a percentage higher than expected. Although the curative resection rate was low (65.3%), en bloc (98.8%) and complete (85.9%) resection rates were high. Modified endoscopic mucosal resection (88.0%) and endoscopic submucosal dissection (92.2%) resulted in significantly higher complete resection rates than conventional endoscopic mucosal resection (36.4%). No patient experienced tumour recurrence, despite the low curative resection rate. CONCLUSION: Despite the low curative resection rate, prognosis after endoscopic resection of rectal NETs was excellent. Prospective large-scale, long-term studies are required to determine whether NET G2 and tumours >1 cm should be included in the indication for endoscopic resection and whether tumours with lymphovascular invasion can be followed up without additional surgery.


Assuntos
Tumores Neuroendócrinos/cirurgia , Proctoscopia , Neoplasias Retais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/classificação , Neoplasias Retais/classificação , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Organização Mundial da Saúde , Adulto Jovem
18.
Osaka City Med J ; 61(2): 73-80, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26995851

RESUMO

BACKGROUND: Non-psychotic delusions are reported to be associated with depression and anxiety. When these delusions occur in high-functioning pervasive developmental disorder (HFPDD) children, they are often misdiagnosed as schizophrenia and have consequently been studied less. This study has three goals: to investigate the prevalence of non-psychotic delusions in HFPDD children, to test the hypothesis that HFPDD children are more likely to have non-psychotic delusions than non-HFPDD children, and to test the hypothesis that non-psychotic delusions are associated with depression and anxiety. METHODS: This is a cross-sectional and case-control study. The participants were 45 HFPDD children (cases) and 51 children without HFPDD (controls). Semi-structured interviews were conducted to assess the presence of non-psychotic delusions. We used the Child Behavior Checklist (CBCL) to assess levels of anxiety and depression. RESULTS: Of the cases, 62.2% had non-psychotic delusions, which was significantly higher than controls (25.5%, p<0.001, OR: 4.81, 95% CI: 2.01-11.51). Cases tended to score higher for internalizing problems (including anxiety and depression) on the CBCL than controls (69.8±9.4 vs 65.9±10.4, t= 1.9, p=0.062). Cases with non-psychotic delusions scored significantly higher for internalizing problems in CBCL than children without non-psychotic delusions (72.2±7.7 vs 65.7±10.7, t=2.4, p= 0.022). CONCLUSIONS: More than half of the HFPDD children were suffering from non-psychotic delusions, and these delusions were associated with anxiety and depression. Therefore, accurate diagnoses of non-psychotic delusions should be conducted for appropriate treatments to be prescribed.


Assuntos
Ansiedade , Transtornos Globais do Desenvolvimento Infantil , Delusões , Depressão , Adolescente , Ansiedade/diagnóstico , Ansiedade/etiologia , Estudos de Casos e Controles , Criança , Transtornos Globais do Desenvolvimento Infantil/complicações , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Transtornos Globais do Desenvolvimento Infantil/psicologia , Cognição , Estudos Transversais , Delusões/diagnóstico , Delusões/epidemiologia , Delusões/etiologia , Depressão/diagnóstico , Depressão/etiologia , Feminino , Humanos , Relações Interpessoais , Japão/epidemiologia , Masculino , Competência Mental , Prevalência , Escalas de Graduação Psiquiátrica , Testes Psicológicos
19.
Osaka City Med J ; 60(1): 1-10, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25272562

RESUMO

BACKGROUND: In previous studies for children with pervasive developmental disorder (PDD), the prevalence for psychiatric comorbidities has varied because of their methodological differences. In this research, our PDD subjects were strictly limited by age and IQ scores, and we utilized a semi-structured interview to diagnose their coexisting disorders. The purpose of this study is to identify reliable prevalence and types of psychiatric comorbidities in children with high-functioning PDD (HFPDD). METHODS: The subjects were 49 children aged 6-15 years with HFPDD. In order to diagnose the comorbidities among them, we used the Japanese version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version. RESULTS: Forty-eight cases (98%) met the criteria for at least one comorbidity. The median number of the present comorbidities per child was 2, and the mode was 2. Depression (37%), attention deficit hyperactivity disorder (49%), and oppositional defiant disorder (45%) were frequently observed. CONCLUSIONS: Our finding indicates the high prevalence of comorbidities and the variety of the comorbid disorders in children with HFPDD. It is important to be aware of those comorbid disorders to provide the children with effective treatments.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/epidemiologia , Adolescente , Fatores Etários , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/diagnóstico , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/epidemiologia , Criança , Comportamento Infantil , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Transtornos Globais do Desenvolvimento Infantil/psicologia , Comorbidade , Depressão/diagnóstico , Depressão/epidemiologia , Feminino , Humanos , Inteligência , Testes de Inteligência , Entrevistas como Assunto , Japão/epidemiologia , Masculino , Valor Preditivo dos Testes , Prevalência , Escalas de Graduação Psiquiátrica
20.
Osaka City Med J ; 60(2): 63-71, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25803881

RESUMO

BACKGROUND: Studies have shown that children with pervasive developmental disorder (PDD) have high rates of sensory hypersensitivity. In addition, a few recent studies suggested that sensory hypersensitivity was related to anxiety or depression. However, most studies had methodological limitations because they included children with mental retardation and did not examine broadband psychopathology. Therefore, the purpose of this study was to examine the prevalence of sensory hypersensitivity in children with high-functioning PDD (HFPDD) and the correlation among sensory hypersensitivity, various characteristics, and broadband psychopathology. METHODS: We assessed 132 children with HFPDD (aged 6-15 years, 75% male) that were divided into sensory hypersensitivity (HS) and sensory non-hypersensitivity (non-HS) groups. A logistic regression model was used to examine correlations among sensory hypersensitivity, age, gender, PDD subtypes, socioeconomic status, and broadband psychopathology, including symptoms of anxiety and depression. RESULTS: Of the 132 children with HFPDD, 65.9% (n = 87) were categorized as HS and 34.1% (n = 45) as non-HS. The most common sensory hypersensitivity was auditory. Logistic regression analyses revealed that sensory hypersensitivity in HFPDD was significantly associated with autistic disorder and symptoms of anxiety and depression. CONCLUSIONS: Majority of children with HFPDD exhibited sensory hypersensitivity. Our findings suggested that sensory hypersensitivity may be a core feature of HFPDD and is possibly correlated to symptoms of anxiety and depression. We propose that sensory hypersensitivity in children with PDD should be aggressively assessed.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/epidemiologia , Transtornos de Sensação/epidemiologia , Limiar Sensorial , Estimulação Acústica , Adolescente , Fatores Etários , Ansiedade/epidemiologia , Ansiedade/psicologia , Limiar Auditivo , Estudos de Casos e Controles , Criança , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Transtornos Globais do Desenvolvimento Infantil/psicologia , Depressão/epidemiologia , Depressão/psicologia , Feminino , Humanos , Japão/epidemiologia , Modelos Logísticos , Masculino , Percepção Olfatória , Estimulação Luminosa , Prevalência , Fatores de Risco , Transtornos de Sensação/diagnóstico , Transtornos de Sensação/psicologia , Olfato , Paladar , Percepção Gustatória , Tato , Percepção do Tato , Percepção Visual
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