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1.
Immunol Med ; : 1-7, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014981

RESUMO

Most children with acute hepatitis A virus (HAV) or hepatitis E virus (HEV) infection are asymptomatic. Bystander CD8+ T-cell activation has garnered attention owing to its possible pathophysiological role in adult hepatitis. However, no reports have studied it in pediatric hepatitis. Herein, we describe the case of a three-year-old girl with acute hepatitis by HEV genotype 1. She had a history of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections, and HEV hepatitis occurred shortly after asymptomatic HAV infection. Peripheral immunophenotyping revealed activation of non-HEV-specific CD8+ T cells which include EBV-specific and CMV-specific CD8+ T cells, during the acute phase. While alanine-aminotransferase levels declined after admission, the total number of activated CD8+ T cells increased for four days after admission and decreased thereafter. In contrast, activation of EBV-specific and CMV-specific CD8+ T cells was almost at the maximal level at the time of admission, which suggest development of activated bystander CD8+ T cells in the early stage. This case highlights the significance of the bystander CD8+ T-cell activation even in pediatric hepatitis and the size of the CD8+ T cell memory pool in the individuals for the development of hepatitis, given the patient's history of infections with EBV, CMV and HAV.

2.
Case Rep Psychiatry ; 2024: 7478666, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716398

RESUMO

Anorexia nervosa (AN) is a fatal condition associated with extreme underweight and undernutrition. It is more common in young females, with a female-to-male ratio of 10 : 1. Focal cortical dysplasia (FCD) is characterized by dysplasia of the cerebral cortex and is a common cause of pharmacoresistant epilepsy. However, FCD associated with AN has never been reported. We report the first case of AN in a 12-year-old male diagnosed with FCD-type 2 on head magnetic resonance imaging (MRI). He became concerned about lower abdominal distention and began reducing his food intake. He was admitted to our hospital after weight loss of 10 kg in a 1 year. Head MRI showed a localized high-signal area from the cortex to the white matter of the fusiform gyrus near the left hippocampus, with no associated decreased blood flow or electroencephalography (EEG) abnormalities. These findings were characteristic of FCD type II. In males with AN, the search for underlying disease is particularly important. The pathophysiology of the association between AN and FCD is unclear. However, both conditions are reportedly associated with autism spectrum disorder. Further cases are needed to clarify whether FCD is associated with eating disorders.

3.
Clin Exp Immunol ; 216(1): 104-111, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-37952216

RESUMO

The precise pathogenesis of Kawasaki disease remains unknown. In an attempt to elucidate the pathogenesis of KD through the analysis of acquired immunity, we comprehensively examined the immunophenotypic changes in immune cells such as lymphocytes and monocytes along with various cytokines, focusing on differences between pre- and post- treatment samples. We found high levels of CXCL9 and CXCL10 chemokines that decreased with treatment, which coincided with a post-treatment expansion of Th1 cells expressing CXCR3. Our results show that the CXCL10-CXCR3 axis plays an important role in the pathogenesis of KD.


Assuntos
Síndrome de Linfonodos Mucocutâneos , Humanos , Quimiocina CXCL10 , Quimiocina CXCL9 , Citocinas , Células Th1 , Monócitos , Receptores CXCR3
5.
Front Immunol ; 14: 1107808, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36875135

RESUMO

The pathological mechanisms of de novo inflammatory bowel disease (IBD) following SARS-CoV-2 infection are unknown. However, cases of coexisting IBD and multisystem inflammatory syndrome in children (MIS-C), which occurs 2-6 weeks after SARS-CoV-2 infection, have been reported, suggesting a shared underlying dysfunction of immune responses. Herein, we conducted the immunological analyses of a Japanese patient with de novo ulcerative colitis following SARS-CoV-2 infection based on the pathological hypothesis of MIS-C. Her serum level of lipopolysaccharide-binding protein, a microbial translocation marker, was elevated with T cell activation and skewed T cell receptor repertoire. The dynamics of activated CD8+ T cells, including T cells expressing the gut-homing marker α4ß7, and serum anti-SARS-CoV-2 spike IgG antibody titer reflected her clinical symptoms. These findings suggest that SARS-CoV-2 infection may trigger the de novo occurrence of ulcerative colitis by impairing intestinal barrier function, T cell activation with a skewed T cell receptor repertoire, and increasing levels of anti-SARS-CoV-2 spike IgG antibodies. Further research is needed to clarify the association between the functional role of the SARS-CoV-2 spike protein as a superantigen and ulcerative colitis.


Assuntos
COVID-19 , Colite Ulcerativa , Doenças Inflamatórias Intestinais , Humanos , Criança , Feminino , Linfócitos T CD8-Positivos , SARS-CoV-2 , Anticorpos Antivirais , Receptores de Antígenos de Linfócitos T
7.
Clin Immunol ; 245: 109138, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36184055

RESUMO

Recent studies have reported that pediatric acute liver failure of unknown origin is immune-mediated, with CD8+ T cells playing a key role. Moreover, investigation of superantigen-mediated T-cell activation by the SARS-CoV-2 spike protein in pediatric severe acute hepatitis is needed in the context of the proposed mechanism of multisystem inflammatory syndrome in children (MIS-C). We investigated the immunological characteristics of a Japanese pediatric patient with severe acute hepatitis post SARS-CoV-2 infection. The patient demonstrated autoimmune hepatitis-like liver histology with CD8+ lymphocyte-predominant infiltration. There was Th1-type immune skewing, including remarkable peripheral CD8+ T-cell activation and a skewed T cell receptor repertoire. We also found elevated plasma levels of the anti-SARS-CoV-2 spike-specific IgG antibody, and the titer peaked after treatment, as seen with MIS-C. These findings support that immunological activation involving SARS-CoV-2 spike protein plays a crucial role in a pediatric patient with acute severe hepatitis post SARS-CoV-2 infection.


Assuntos
COVID-19 , Hepatite , Criança , Humanos , Doença Aguda , Anticorpos Antivirais , Linfócitos T CD8-Positivos , SARS-CoV-2
9.
Clin Immunol ; 236: 108955, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35150919

RESUMO

The etiology of multiple inflammatory syndrome in children (MIS-C) remains poorly understood. As clues to elucidate the pathogenic condition, several characteristic peripheral immunophenotypes have been reported in MIS-C. However, no report has demonstrated the time course of the peripheral immunophenotype along with the clinical course in the same patient. Herein, we clarified the immunological characteristics of a Japanese patient with MIS-C. There was an initial cytokine storm followed by T-cell activation, especially of CD8+ T cells, with the expansion of T-cell receptor Vß 21.3-expressing cells, which suggests superantigen-mediated T-cell activation. In addition, we also found an increase in IgG-producing cells (plasmablasts and switched memory B cells), which were accompanied by elevated serum levels of anti-SARS-CoV-2 spike antigen-specific IgG antibodies. These time course of peripheral immunophenotypes support that immunological activation against SARS-CoV-2 spike protein plays a central role in the etiology of MIS-C.


Assuntos
Linfócitos T CD8-Positivos , COVID-19 , COVID-19/complicações , Criança , Humanos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Síndrome de Resposta Inflamatória Sistêmica
10.
Gastrointest Endosc ; 95(5): 969-974, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35065046

RESUMO

BACKGROUND AND AIMS: The best strategy to manage direct-acting oral anticoagulants (DOACs) for patients undergoing cold snare polypectomy remains unclear. This study compared the effect of continuing versus stopping DOACs only on the day of the procedure on bleeding after cold snare polypectomy. METHODS: This prospective, observational, single-center cohort study enrolled consecutive patients receiving antithrombotic agents and undergoing cold snare polypectomy of colorectal polyps ≤10 mm in diameter. During period 1 (2017 and 2018) antithrombotic agents including DOACs were not discontinued (DOAC continued group). In period 2 (2019 and 2020) DOACs were withheld only on the day of the procedure (DOAC withheld group) and restarted the next day after the procedure. The primary outcome was delayed bleeding requiring endoscopic treatment occurring within 2 weeks after cold snare polypectomy. Secondary outcomes were immediate bleeding and the number of hemostatic clips used. RESULTS: For the 2 groups, 204 (DOAC continued group; 34% women; mean age, 75 years) and 264 (DOAC withheld group; 36% women; mean age, 74 years) patients were enrolled. Clinical features were similar between the 2 groups. Delayed bleeding after cold snare polypectomy occurred in 4 of 47 patients (8.5%) in the DOAC continued group versus 0 of 66 (0%) in the DOAC withheld group (P < .001). Immediate postpolypectomy bleeding occurred in 12 of 47 patients (25.5%) in the DOAC continued group versus 4 of 66 (6.1%) in the DOAC withheld group (P < .008). CONCLUSIONS: Cold snare polypectomy may be safely preformed if DOACs are withheld only on the day of the procedure. (Clinical trial registration number: NCT02594813.).


Assuntos
Pólipos do Colo , Idoso , Anticoagulantes/efeitos adversos , Estudos de Coortes , Pólipos do Colo/cirurgia , Colonoscopia/métodos , Inibidores do Fator Xa , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Masculino , Hemorragia Pós-Operatória/tratamento farmacológico , Hemorragia Pós-Operatória/epidemiologia , Estudos Prospectivos
11.
J Clin Gastroenterol ; 56(2): e109-e113, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33471491

RESUMO

BACKGROUND AND AIMS: We evaluated the effectiveness of water jelly ingestion for both rehabilitation and the prevention of aspiration pneumonia in a retrospective analysis of elderly patients with moderate to severe dysphagia. PATIENTS AND METHODS: Study 1: consecutive patients with borderline ingestion in an endoscopic swallowing evaluation were enrolled (n=36, 18 men and 18 women: mean age 82±9 y) and categorized into a group with water jelly (50 to 100 mL) ingestion training 3×/day or an untrained control group. Their food intake levels were then compared using a Food Intake Level Scale. Study 2: consecutive patients who were hospitalized because of aspiration pneumonia were enrolled (n=64, 35 men and 29 women: mean age 81±9 y) and categorized into a group with cyclic ingestion of water jelly immediately after each meal or a control group. The incidence of aspiration pneumonia that was newly developed during hospitalization was compared between the groups. RESULTS: In study 1, 36 patients with a Hyodo-Komagane score of 8 were enrolled. Three of the 12 (25%) patients who underwent water jelly ingestion training were able to eat a pureed diet (level 5, 2 patients; level 6, 1 patient) while none of the 24 patients (0%) who did not undergo this training were able to eat any form of diet (levels 5 and 6, no patients) (P=0.011). In study 2, 64 patients were enrolled. No newly developed aspiration pneumonia was observed in the 34 patients (0%) who received cyclic water jelly ingestion, whereas 17% (5/30) of patients not receiving water jelly after meals newly developed aspiration pneumonia during hospitalization (P=0.031). CONCLUSIONS: Water jelly ingestion was effective for both rehabilitation and the prevention of aspiration pneumonia in elderly patients with moderate to severe dysphagia.


Assuntos
Transtornos de Deglutição , Pneumonia Aspirativa , Idoso , Idoso de 80 Anos ou mais , Deglutição , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/prevenção & controle , Ingestão de Alimentos , Feminino , Humanos , Masculino , Pneumonia Aspirativa/etiologia , Pneumonia Aspirativa/prevenção & controle , Estudos Retrospectivos , Água
12.
Pediatr Int ; 64(1): e14721, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33813788

RESUMO

BACKGROUND: In Japan there are limited opportunities for pediatric gastrointestinal (GI) trainees to learn GI endoscopy. This study investigated whether a short-term intensive training for 3 months in an adult GI unit enabled pediatric GI trainees to acquire the required number of cases and the technical competence to perform pediatric GI endoscopic procedures. METHODS: This was a retrospective case series of pediatric GI trainees who underwent 3 months of intensive endoscopy training, which also included direct observation and a questionnaire. The numbers of esophagogastroduodenoscopies (EGD), ileocolonoscopies, and snare polypectomies each trainee performed as well as cecal intubation rates were collected with the goal of meeting the standards of overseas educational guidelines. The trainees were also asked about continuing experience with pediatric endoscopic procedures after the intensive training. RESULTS: There were 10 enrolled trainees, 9 men, average age, 34 (range, 29-41). The average number (range) of EGD and ileocolonoscopies that the 10 trainees had done before this training period was 52 (0-200) and 15 (0-20), respectively. The average number (range) of EGD, ileocolonoscopies and snare polypectomies per each trainee was 651.7 (485-814), 159.2 (130-195) and 25.8 (10-55), respectively, over 3 months: all trainees thus fulfilled all of the criteria of the minimal training requirements. All trainees also reached the required threshold in the cecal intubation rate (>90%). In addition, all trainees were able to perform pediatric endoscopic procedures alone after the intensive training period. CONCLUSIONS: Short-term intensive training for 3 months in an adult GI setting enabled pediatric GI trainees to acquire technical competence for pediatric endoscopic procedures.


Assuntos
Ceco , Gastroenterologia , Adulto , Criança , Competência Clínica , Colonoscopia , Endoscopia Gastrointestinal , Gastroenterologia/educação , Humanos , Masculino , Estudos Retrospectivos
13.
Pediatr Int ; 64(1): e15041, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34699658

RESUMO

BACKGROUND: Juvenile polyposis syndrome (JPS) is one of the hereditary polyposis syndromes caused by abnormal regulation of transforming growth factor ß signaling because of mutations in BMPR1A and SMAD4. Juvenile polyposis syndrome patients with SMAD4 mutations develop cardiovascular events, whereas those with BMPR1A usually do not. Analysis of genetic mutations in JPS patients can be helpful in devising suitable strategies for medical management. In this study, we demonstrate the pathogenicity of a novel intronic mutation in BMPR1A using mRNA extracted from colonic mucosa of a boy with JPS. METHODS: Genomic DNA extracted from peripheral blood and total RNA isolated from the colonic mucosa were used for DNA sequencing and reverse transcription polymerase chain reaction (RT-PCR) analyses, respectively. RESULTS: A 13-year-old boy, with no previous medical history, presented to the hospital complaining of bloody stools. Colonoscopy revealed multiple polyps in the colon, and the resected polyps were compatible with juvenile polyps. Sequencing analysis revealed a novel intronic mutation (c.778+5G>C) in BMPR1A. Reverse transcription polymerase chain reaction analysis of RNA extracted from the colonic mucosa showed an aberrant splicing form of BMPR1A. Trio analysis showed that his mother also had the same BMPR1A mutation. She was diagnosed with cancer of the cecum and polyposis of the colon at the age of 41. CONCLUSION: We demonstrate the presence of a novel BMPR1A intronic mutation that exhibits splicing abnormality in a family with JPS. Further research and development will help elucidate the genotype-phenotype relationship in JPS.


Assuntos
Mutação em Linhagem Germinativa , RNA , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Feminino , Humanos , Polipose Intestinal/congênito , Mutação , Síndromes Neoplásicas Hereditárias , RNA Mensageiro/genética
14.
Int J Rheum Dis ; 24(10): 1325-1330, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34424609

RESUMO

BACKGROUND: Kawasaki disease (KD) is a syndrome that results in acute systemic vasculitis and is a major cause of acquired heart disease in developed countries. KD is diagnosed based on certain characteristic symptoms and echocardiogram results. It has been reported that abdominal ultrasound is of value in supporting the diagnosis of KD. Nevertheless, abdominal ultrasound is not a routine procedure in KD. Moreover, dilatation of the common bile duct (CBD) has been rarely reported in previous cases. CASE PRESENTATION: A 4-year-old boy presented with fever and markedly high transaminase level (aspartate aminotransferase, 5323 U/L; alanine aminotransferase, 1554 U/L). The patient was diagnosed as having KD based on characteristic symptoms and echocardiogram findings. Ultrasound revealed dilatation of the CBD as well as cervical lymphadenopathy resembling a cluster of grapes, thickening of the gallbladder wall, and increased periportal echogenicity throughout the liver parenchyma. The patient received initial treatment with intravenous immunoglobulin at day 4 of fever and second-line treatment with intravenous immunoglobulin and prednisolone because of recurrent fever on day 6. Dilatation of the CBD was improved from 6.6 mm on day 4 to 3.1 mm on day 8. Although re-dilatation was observed, it gradually diminished and normalized (4.3 mm on day 28, 4.0 mm on day 63, 3.3 mm on day 105, and 2.8 mm on day 182). CONCLUSION: This case highlights the usefulness of abdominal ultrasound and the importance of considering dilatation of the CBD as one of the complications of KD.


Assuntos
Ducto Colédoco/diagnóstico por imagem , Síndrome de Linfonodos Mucocutâneos/diagnóstico por imagem , Ultrassonografia , Pré-Escolar , Ducto Colédoco/efeitos dos fármacos , Dilatação Patológica , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Valor Preditivo dos Testes , Prednisolona/uso terapêutico , Resultado do Tratamento
15.
Dig Endosc ; 33(7): 1045-1058, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33423305

RESUMO

Gastrointestinal endoscopy is fundamental to diagnostic and therapeutic procedures in pediatric gastroenterology. In the decades since endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) for hepatobiliary and pancreatic disease were introduced into clinical practice, there has been increasing interest in these procedures, and practice guidelines and position papers that clearly define the role of ERCP and EUS in children have been published. Based on the distinction of endoscopy between children and adults, this review focuses on the current state of ERCP and EUS procedures in children, including the types of endoscopes used in children, general anesthesia and radiation exposure, biliary and pancreatic indications, considerations of education and training for ERCP and EUS procedures in children, and expectations for development of endoscopes for children.


Assuntos
Gastroenterologia , Pancreatopatias , Adulto , Criança , Colangiopancreatografia Retrógrada Endoscópica , Endossonografia , Humanos , Pâncreas , Pancreatopatias/diagnóstico por imagem
16.
Brain Dev ; 43(3): 475-481, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33234382

RESUMO

Peroxisomal acyl-CoA oxidase (ACOX1) deficiency is a rare autosomal recessive single enzyme deficiency characterized by hypotonia, seizures, failure to thrive, developmental delay, and neurological regression starting from approximately 3 years of age. Here, we report two siblings with ACOX1 deficiency born to non-consanguineous Japanese parents. They showed mild global developmental delay from infancy and began to regress at 5 years 10 months and 5 years 6 months of age respectively. They gradually manifested with cerebellar ataxia, dysarthria, pyramidal signs, and dysphasia. Brain MRI revealed T2 high-intensity areas in the cerebellar white matter, bilateral middle cerebellar peduncle, and transverse tracts of the pons, followed by progressive atrophy of these areas. Intriguingly, the ratios of C24:0, C25:0, and C26:0 to C22:0 in plasma, which usually increase in ACOX1 deficiency were within normal ranges in both patients. On the other hand, whole exome sequencing revealed novel compound heterozygous variants in ACOX1: a frameshift variant (c.160delC:p.Leu54Serfs*18) and a missense variant (c.1259 T > C:p.Phe420Ser). The plasma concentration of individual very long chain fatty acids (C24:0, C25:0, and C26:0) was elevated, and we found that peroxisomes in fibroblasts of the patients were larger in size and fewer in number as previously reported in patients with ACOX1 deficiency. Furthermore, the C24:0 ß-oxidation activity was dramatically reduced. Our findings suggest that the elevation of individual plasma very long chain fatty acids concentration, genetic analysis including whole exome analysis, and biochemical studies on the patient's fibroblasts should be considered for the correct diagnosis of ACOX1 deficiency.


Assuntos
Acil-CoA Oxidase/deficiência , Acil-CoA Oxidase/genética , Adrenoleucodistrofia/genética , Erros Inatos do Metabolismo Lipídico/genética , Feminino , Humanos , Masculino , Mutação , Irmãos
17.
JGH Open ; 4(5): 898-902, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33102761

RESUMO

BACKGROUND AND AIM: As the significance of the quantitative fecal immunochemical test (FIT) in patients who previously underwent a colonoscopy is unknown, this study aimed at investigating the association between fecal hemoglobin concentration and the risk of colorectal cancer (CRC). METHODS AND RESULTS: We retrospectively analyzed FIT-positive patients who underwent a colonoscopy through our opportunistic annual screening program from April 2010 to March 2017 at the Kyoto Second Red Cross Hospital. We stratified them into no colonoscopy and past colonoscopy (>5 years or ≤5 years) groups based on whether they had a history of undergoing a colonoscopy and analyzed the correlation between fecal hemoglobin concentration and advanced neoplasia or invasive cancer detection in each group. We analyzed 1248 patients with positive FIT results. There were 748 (59.9%), 198 (15.9%), and 302 (24.2%) patients in the no colonoscopy, past colonoscopy (>5 years), and past colonoscopy (≤5 years) groups, respectively. In the no colonoscopy group, the advanced neoplasia detection rate significantly increased with the fecal hemoglobin concentration (P < 0.001). However, no significant trend was observed in the past colonoscopy (both >5 years and ≤5 years) group (P = 0.982). No invasive cancer was detected in the past colonoscopy (≤5 years) group. CONCLUSION: The risk of CRC might be low even if fecal hemoglobin concentration was high, especially in those who underwent colonoscopy within 5 years.

18.
Pain ; 159(5): 939-947, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29438227

RESUMO

Transient receptor potential vanilloid 4 (TRPV4) receptor modulates pain, and this has been noted in several animal models. However, the involvement of TRPV4 in osteoarthritic (OA) pain remains poorly understood. This study assessed the functional changes in TRPV4 and the expression of its endogenous ligand 5,6-epoxyeicosatrienoic acid (5,6-EET) in a rat monoiodoacetate (MIA)-induced OA pain model (MIA rats). Monoiodoacetate-treated rats showed reduced grip strength as compared to sham-treated rats, and this loss in function could be recovered by the intraarticular administration of a TRPV4 antagonist (HC067047 or GSK2193874). By contrast, the intraarticular administration of the TRPV4 agonist, GSK1016790A, increased the pain-related behaviors in MIA rats but not in sham rats. TRPV4 expression was not increased in knee joints of MIA rats; however, the levels of phosphorylated TRPV4 at Ser824 were increased in dorsal root ganglion neurons. In addition, 5,6-EET was increased in lavage fluids from the knee joints of MIA rats and in meniscectomy-induced OA pain model rats. 5,6-EET and its metabolite were also detected in synovial fluids from patients with OA. In conclusion, TRPV4 was sensitized in the knee joints of MIA rats through phosphorylation in dorsal root ganglion neurons, along with an increase in the levels of its endogenous ligand 5,6-EET. The analgesic effects of the TRPV4 antagonist in the OA pain model rats suggest that TRPV4 may be a potent target for OA pain relief.


Assuntos
Artrite Experimental/metabolismo , Osteoartrite/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Artrite Experimental/induzido quimicamente , Modelos Animais de Doenças , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Força da Mão , Ácido Iodoacético , Leucina/análogos & derivados , Leucina/farmacologia , Masculino , Morfolinas/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Osteoartrite/induzido quimicamente , Dor , Medição da Dor , Fosforilação , Pirróis/farmacologia , Ratos , Ratos Sprague-Dawley , Sulfonamidas/farmacologia , Canais de Cátion TRPV/antagonistas & inibidores
19.
Sci Rep ; 7(1): 11137, 2017 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-28894200

RESUMO

Partner of sld five 1 (PSF1) is an evolutionary conserved DNA replication factor involved in DNA replication in lower species, which is strongly expressed in normal stem cell populations and progenitor cell populations. Recently, we have investigated PSF1 functions in cancer cells and found that PSF1 plays a significant role in tumour growth. These findings provide initial evidence for the potential of PSF1 as a therapeutic target. Here, we reveal that PSF1 contains an immunogenic epitope suitable for an antitumour vaccine. We analysed PSF1 peptides eluted from affinity-purified human leukocyte antigen (HLA) by mass spectrometry and identified PSF179-87 peptide (YLYDRLLRI) that has the highest prediction score using an in silico algorithm. PSF179-87 peptide induced PSF1-specific cytotoxic T lymphocyte responses such as the production of interferon-γ and cytotoxicity. Because PSF1 is expressed in cancer cell populations and highly expressed in cancer stem cell populations, these data suggest that vaccination with PSF179-87 peptide may be a novel therapeutic strategy for cancer treatment.


Assuntos
Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/imunologia , Vacinas Anticâncer/imunologia , Antígenos HLA/imunologia , Peptídeos/imunologia , Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/química , Animais , Apresentação de Antígeno , Linhagem Celular Tumoral , Cromatografia Líquida , Citotoxicidade Imunológica , Modelos Animais de Doenças , Epitopos de Linfócito T/química , Epitopos de Linfócito T/imunologia , Feminino , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Imunogenicidade da Vacina , Camundongos , Neoplasias/imunologia , Peptídeos/sangue , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Espectrometria de Massas em Tandem
20.
Biochem Biophys Res Commun ; 478(4): 1746-50, 2016 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-27608598

RESUMO

We demonstrated that castration enhanced the expression of uncoupling protein 1 (Ucp1), a thermogenic protein, in brown adipose tissue (BAT) and subcutaneous (sc) white adipose tissue (WAT) in male mice. Castration of male mice increased body temperature and reduced body weight gain compared with those of sham-operated mice. BAT Ucp1 mRNA expression in castrated male mice was significantly higher than that in sham-operated mice. Histologically, cells with multilocular fat droplets were observed in the castrated inguinal scWAT. Immunohistochemical staining revealed that these cells positively reacted with the anti-Ucp1 antibody. The Ucp1-positive area near the inguinal lymph node in the castrated WAT was extensive compared with that of the sham-operated WAT. Castration-induced Ucp1 up-regulation in scWAT was suppressed by high-fat diet feeding. These findings suggest that thermogenesis by BAT activation and scWAT browning contribute to castration-induced inhibition of body weight gain. However, considering that the effect of castration was blunted by high-fat diet consumption, thermogenesis stimulation in response to castration is inhibited by chronic over-nutrition.


Assuntos
Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Orquiectomia , Gordura Subcutânea/metabolismo , Adipócitos/metabolismo , Animais , Temperatura Corporal , Peso Corporal , Dieta Hiperlipídica , Expressão Gênica , Imuno-Histoquímica , Masculino , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Termogênese , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
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