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1.
Phys Rev Lett ; 130(1): 012501, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36669221

RESUMO

The atomic masses of ^{55}Sc, ^{56,58}Ti, and ^{56-59}V have been determined using the high-precision multireflection time-of-flight technique. The radioisotopes have been produced at RIKEN's Radioactive Isotope Beam Factory (RIBF) and delivered to the novel designed gas cell and multireflection system, which has been recently commissioned downstream of the ZeroDegree spectrometer following the BigRIPS separator. For ^{56,58}Ti and ^{56-59}V, the mass uncertainties have been reduced down to the order of 10 keV, shedding new light on the N=34 shell effect in Ti and V isotopes by the first high-precision mass measurements of the critical species ^{58}Ti and ^{59}V. With the new precision achieved, we reveal the nonexistence of the N=34 empirical two-neutron shell gaps for Ti and V, and the enhanced energy gap above the occupied νp_{3/2} orbit is identified as a feature unique to Ca. We perform new Monte Carlo shell model calculations including the νd_{5/2} and νg_{9/2} orbits and compare the results with conventional shell model calculations, which exclude the νg_{9/2} and the νd_{5/2} orbits. The comparison indicates that the shell gap reduction in Ti is related to a partial occupation of the higher orbitals for the outer two valence neutrons at N=34.


Assuntos
Nêutrons , Titânio
2.
Public Health ; 210: 34-40, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35870319

RESUMO

OBJECTIVES: Contact tracing for COVID-19 relies heavily on the cooperation of individuals with authorities to provide information of contact persons. However, few studies have clarified willingness to cooperate and motivation to provide information for contact tracing. This study sought to describe willingness to cooperate and motivation to report contact persons for COVID-19 contact tracing among citizens in Japan, and to assess any associated sociodemographic factors. STUDY DESIGN: Cross-sectional study. METHODS: This was an online-based survey using quota sampling. Participants were asked about their willingness to cooperate in reporting contacts for COVID-19 contact tracing if they tested positive. Participants also responded to questions regarding their reasons for cooperating or not cooperating and provided sociodemographic data. Multiple logistic regression analysis was performed to clarify associations between sociodemographic factors and willingness to cooperate. RESULTS: This study included 2844 participants. The proportion of participants who were not willing to cooperate in reporting contacts was 27.6%, with their main reasons being concerns about causing trouble for the other person and being criticised for revealing their names. Willingness to cooperate was lower among men, young adults and those with an educational level less than a university degree. CONCLUSIONS: To improve the effectiveness of contact tracing, educational campaigns, such as reducing the fear and stigma associated with COVID-19, may be important. Furthermore, it is essential to understand that individuals may have contacts whom they do not wish to disclose to others and to be considerate when handling such situations.


Assuntos
COVID-19 , Busca de Comunicante , COVID-19/epidemiologia , Estudos Transversais , Humanos , Japão/epidemiologia , Masculino , Inquéritos e Questionários , Adulto Jovem
3.
Cancer Immunol Immunother ; 69(11): 2247-2257, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32500232

RESUMO

Cancer vaccines induce cancer-specific T-cells capable of eradicating cancer cells. The impact of cancer peptide vaccines (CPV) on the tumor microenvironment (TME) remains unclear. S-588410 is a CPV comprising five human leukocyte antigen (HLA)-A*24:02-restricted peptides derived from five cancer testis antigens, DEPDC1, MPHOSPH1, URLC10, CDCA1 and KOC1, which are overexpressed in esophageal cancer. This exploratory study investigated the immunologic mechanism of action of subcutaneous S-588410 emulsified with MONTANIDE ISA51VG adjuvant (median: 5 doses) by analyzing the expression of immune-related molecules, cytotoxic T-lymphocyte (CTL) response and T-lymphocytes bearing peptide-specific T-cell receptor (TCR) sequencing in tumor tissue or blood samples from 15 participants with HLA-A*24:02-positive esophageal cancer. Densities of CD8+, CD8+ Granzyme B+, CD8+ programmed death-1-positive (PD-1+) and programmed death-ligand 1-positive (PD-L1+) cells were higher in post- versus pre-vaccination tumor tissue. CTL response was induced in all patients for at least one of five peptides. The same sequences of peptide-specific TCRs were identified in post-vaccination T-lymphocytes derived from both tumor tissue and blood, suggesting that functional peptide-specific CTLs infiltrate tumor tissue after vaccination. Twelve (80%) participants had treatment-related adverse events (AEs). Injection site reaction was the most frequently reported AE (grade 1, n = 1; grade 2, n = 11). In conclusion, S-588410 induces a tumor immune response in esophageal cancer. Induction of CD8+ PD-1+ tumor-infiltrating lymphocytes and PD-L1 expression in the TME by vaccination suggests S-588410 in combination with anti-PD-(L)1 antibodies may offer a clinically useful therapy.Trial registration UMIN-CTR registration identifier: UMIN000023324.


Assuntos
Vacinas Anticâncer/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos T Citotóxicos/imunologia , Idoso , Antígenos de Neoplasias/imunologia , Feminino , Antígeno HLA-A24/imunologia , Humanos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Linfócitos T Citotóxicos/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Vacinas de Subunidades Antigênicas/uso terapêutico
4.
Nutr Metab Cardiovasc Dis ; 28(9): 922-928, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30057013

RESUMO

BACKGROUND AND AIMS: Recent studies identified that metabolically abnormal non-overweight phenotype is a risk factor for cardiovascular diseases. However, only little is known about risk factors for the progression from metabolically healthy non-overweight (MHNO) to metabolically abnormal phenotype. In this study, we investigated the impact of respiratory function on the progression from MHNO to metabolically abnormal phenotype. METHODS AND RESULTS: In this retrospective cohort study, 8949 (3872 men and 5077 women) individuals with MHNO, who participated in a health-checkup program from 2004 to 2015, were enrolled. Four metabolic factors (high-normal blood pressure or hypertension, impaired fasting glucose or diabetes, hypertriglyceridemia, and low HDL cholesterol concentration) were used to define metabolically healthy (less than two factors) or metabolically abnormal (two or more factors) phenotypes. Respiratory function was measured by spirometry. Over a median 4.0 years of follow-up, 927 participants progressed to metabolically abnormal phenotype. The percentage of FVC for predicted values (HR 0.98, 95% CI 0.93-1.03, p = 0.418) was not associated with the progression to metabolically abnormal phenotype after adjusting for covariates, including age, sex, alcohol consumption, exercise, smoking status, and body mass index, whereas the percentage of FEV1 for predicted values (%FEV1) (HR 0.87, 95% CI 0.84-0.91, p < 0.001) and the FEV1/FVC ratio (HR 0.86, 95% CI 0.78-0.95, p = 0.004) were associated with the progression to metabolically abnormal phenotype. CONCLUSION: Decrease in respiratory function in terms of %FEV1 and the FEV1/FVC ratio is associated with the progression to metabolically abnormal phenotype in individuals with MHNO.


Assuntos
Pulmão/fisiopatologia , Síndrome Metabólica/fisiopatologia , Obesidade Metabolicamente Benigna/fisiopatologia , Respiração , Adulto , Progressão da Doença , Feminino , Volume Expiratório Forçado , Humanos , Japão/epidemiologia , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Obesidade Metabolicamente Benigna/diagnóstico , Obesidade Metabolicamente Benigna/epidemiologia , Fenótipo , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Capacidade Vital
5.
Haemophilia ; 22(3): 433-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26686734

RESUMO

INTRODUCTION: Haemophilia B is an X-linked bleeding disorder caused by a coagulation factor IX gene (F9) abnormality. Numerous F9 defects have been identified to date; however, only a few with an entire F9 deletion have been reported in detail. AIM: To elucidate the cause of severe haemophilia B, we investigated the precise X chromosome abnormalities in four Japanese patients who did not show all amplifications in F9-specific PCR. METHODS: We analysed the patient's genomic DNA using Multiplex ligation-dependent probe amplification (MLPA). To assess the extent of any deletions, we further performed mapping PCRs, inverse PCRs or long-range PCRs and direct sequencing analyses of the X chromosome. RESULTS: We detected entire F9 deletions in four haemophilia B patients and identified the precise deleted regions of the X chromosome including F9. Patient 1 had a 149-kb deletion with breakpoints 90-kb upstream and 30-kb downstream from F9. Patients 2 and 3 showed 273-kb and 1.19-Mb deletions respectively. Patient 4 had two deleted regions: a 1663-bp deletion 1.34-Mb upstream from F9 and a 7.2-Mb deletion including F9. These distinct breakpoints found in four different patients suggest that the mechanism of X chromosome deletion may be different between individuals. Non-allelic homologous recombination (NAHR), microhomology-mediated break-induced replication (MMBIR) or fork stalling and template switching (FoSTeS) may occur in respective X chromosomes of the four haemophilia B patients analysed. CONCLUSIONS: We identified diverse X chromosomal rearrangements in four haemophilia B patients, which might be caused by distinct mechanisms of genomic rearrangement.


Assuntos
Cromossomos Humanos X , Fator IX/genética , Hemofilia B/genética , Adolescente , Adulto , Sequência de Bases , Criança , DNA/química , DNA/genética , DNA/metabolismo , Análise Mutacional de DNA , Rearranjo Gênico , Humanos , Japão , Masculino , Reação em Cadeia da Polimerase Multiplex , Deleção de Sequência , Adulto Jovem
6.
J Obstet Gynaecol Res ; 42(6): 632-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26935605

RESUMO

AIM: Women with pre-eclampsia (PE), placenta previa (PP), placental abruption (PA), and placental mesenchymal dysplasia (PMD) have been described as having placental permeability dysfunction. This study was performed to determine whether occult fetomaternal hemorrhage (FMH) is common in women with such complications and in women with non-reassuring fetal status. METHODS: Forty-one antenatal and 39 postnatal blood samples were obtained from 46 women, including 11 with placental permeability dysfunction (5, 3, 2, and 1 with PE, PP, PA, and PMD, respectively) and 35 controls without such complications. To estimate the amount of fetal red blood cells, flow cytometry was performed using the fetal cell count system with two antibodies against fetal hemoglobin and carbonic anhydrase and the ß-γ system with two monoclonal antibodies against hemoglobin ß-chain and hemoglobin γ-chain. A diagnosis of FMH was made when the fraction size of the isolated cell population on scatter plots expressing fetal hemoglobin alone or hemoglobin γ-chain alone accounted for ≥0.02% of the total cell population on scatter plots. RESULTS: FMH was identified in five women, including one each with PE, PA, PP, PMD, and no complications. Thus, the prevalence rate of FMH was significantly higher in women with complications than in controls (36% [4/11] vs 2.9% [1/35], respectively, P =  0.009). The FMH occurrence rate did not differ between women with and without non-reassuring fetal status (7.7% [1/13] vs 12% [4/33], respectively, P =  1.000). CONCLUSION: The risk of fetal red blood cells trafficking into the maternal circulation may be increased in women complicated with PE, PA, PP, and PMD.


Assuntos
Transfusão Feto-Materna/epidemiologia , Doenças Placentárias/sangue , Doenças Placentárias/epidemiologia , Descolamento Prematuro da Placenta/sangue , Descolamento Prematuro da Placenta/epidemiologia , Adulto , Feminino , Sangue Fetal , Transfusão Feto-Materna/complicações , Humanos , Permeabilidade , Placenta Prévia/sangue , Placenta Prévia/epidemiologia , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/epidemiologia , Gravidez , Resultado da Gravidez
7.
Skin Res Technol ; 21(3): 295-301, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25323334

RESUMO

BACKGROUND/PURPOSE: In oxidative coloring, the hair cuticle layers are not only the penetration pathway for active ingredients but also one of the most important dyeing regions. The dyeing mechanism of oxidative dyes in fine structures of the cuticle remains unclear. To investigate the dyeing behavior of oxidative dyes in fine structures of the cuticle, hair cross-sections were analyzed by nanoscale secondary ion mass spectrometry (NanoSIMS). METHODS: The preparation method of hair cross-section for NanoSIMS measurement was improved. Improved hair cross-sections were analyzed using NanoSIMS. RESULTS: The cuticle layer thickness of the hair cross-section could be widened. It was confirmed that (12) C(-) ions were more strongly detected from endocuticle than from other fine structures of cuticle. The NanoSIMS (12) C(-) image and hue saturation intensity (HSI) D(-) /(1) H(-) ratio image of the hair, dyed with deuterium-labeled oxidative dye, indicated that the endocuticle had a higher D(-) /(1) H(-) ratio than the other fine structures of the cuticle. It was substantiated that more colored chromophores were fixated in the endocuticle than in other fine structures of the cuticle. CONCLUSION: The dyeing behavior of oxidative dyes in fine structures of hair cuticle was substantiated by NanoSIMS analysis using the improved hair cross-section preparation method.


Assuntos
Tinturas para Cabelo/química , Cabelo/química , Cabelo/ultraestrutura , Oxidantes/química , Fenilenodiaminas/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Absorção Fisico-Química , Humanos , Japão , Nanotecnologia/métodos , Distribuição Tecidual
8.
Biochim Biophys Acta ; 1833(5): 1006-16, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23328083

RESUMO

Sphingosine kinase 1 (SPHK1) overexpression in malignant cells has been reported. Mouse Friend cells showed higher SPHK1 but not SPHK2 expression compared with other mouse cell lines. A Sphk1 promoter analysis demonstrated the region between -53bp and the first exon as the minimal promoter. Further promoter truncation revealed the importance of a MYB-binding site. EMSA using this region as the probe demonstrated one band containing c-MYB protein, and its intensity decreased during erythroid differentiation with hexamethylane bisacetamide (HMBA), a potent inducer of erythroid differentiation of Friend cells. ChIP assay also revealed in vivo binding of c-MYB. c-MYB overexpression and siRNA for c-Myb affected SPHK1 expression, confirming the important regulatory role of c-MYB in SPHK1 expression. HMBA reduced c-MYB expression rapidly. Induced differentiation by HMBA caused a marked and rapid reduction of SPHK1 mRNA, protein and enzyme activity leading to the rapid decrease of cellular sphingosine 1-phosphate level. Moreover, terminally differentiated cells did not resume SPHK1 expression. Compared with original Friend cells, stable overexpression of wild-type SPHK1 showed higher cell proliferation, resistance to cell death by serum depletion. Interestingly, HMBA-induced differentiation of these cells was delayed but not completely suppressed. In contrast, SPHK inhibitor and its siRNA inhibited cell growth and enhanced HMBA-induced differentiation significantly, suggesting that SPHK1 delayed HMBA-induced differentiation by its cell proliferation-promoting activity. Effects of pertussis toxin, a G-protein-coupled receptor inhibitor, and S1P receptor antagonist on Friend cell growth and differentiation were negligible, suggesting the importance of the intracellular SPHK1/S1P signaling in Friend cells.


Assuntos
Diferenciação Celular/genética , Fosfotransferases (Aceptor do Grupo Álcool) , Proteínas Proto-Oncogênicas c-myb , Receptores de Lisoesfingolipídeo , Animais , Linhagem Celular , Regulação para Baixo , Humanos , Camundongos , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-myb/genética , Proteínas Proto-Oncogênicas c-myb/metabolismo , RNA Mensageiro/genética , RNA Interferente Pequeno , Receptores de Lisoesfingolipídeo/antagonistas & inibidores , Receptores de Lisoesfingolipídeo/genética , Receptores de Lisoesfingolipídeo/metabolismo , Transdução de Sinais
9.
Neurocase ; 20(2): 133-43, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23173635

RESUMO

A 42-year-old man suffered damage to the left supra-sylvian areas due to a stroke and presented with verbal short-term memory (STM) deficits. He occasionally could not recall even a single syllable that he had heard one second before. A study of mismatch negativity using magnetoencephalography suggested that the duration of auditory sensory (echoic) memory traces was reduced on the affected side of the brain. His maximum digit span was four with auditory presentation (equivalent to the 1st percentile for normal subjects), whereas it was up to six with visual presentation (almost within the normal range). He simply showed partial recall in the digit span task, and there was no self correction or incorrect reproduction. From these findings, reduced echoic memory was thought to have affected his verbal short-term retention. Thus, the impairment of verbal short-term memory observed in this patient was "pure auditory" unlike previously reported patients with deficits of the phonological short-term store (STS), which is the next higher-order memory system. We report this case to present physiological and behavioral data suggesting impaired short-term storage of verbal information, and to demonstrate the influence of deterioration of echoic memory on verbal STM.


Assuntos
Córtex Auditivo/fisiopatologia , Percepção Auditiva/fisiologia , Transtornos da Memória/diagnóstico , Acidente Vascular Cerebral/complicações , Afasia de Broca/complicações , Córtex Auditivo/patologia , Humanos , Magnetoencefalografia , Masculino , Transtornos da Memória/etiologia , Pessoa de Meia-Idade , Percepção da Fala/fisiologia , Acidente Vascular Cerebral/patologia
10.
Osteoarthritis Cartilage ; 21(6): 831-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23523852

RESUMO

OBJECTIVE: To determine whether differences in synovial fluid (SF) biomarkers of collagen and proteoglycan turnover are associated with pre-radiographic damage to articular cartilage and menisci following anterior cruciate ligament (ACL) injury and are of clinical value. METHOD: SF samples from ACL injured knees of 108 patients were obtained when damage to cartilages and menisci was evaluated arthroscopically. Concentrations of SF collagenase-generated cleavage neoepitope of type II collagen (C2C) were determined using ELISA and aggrecan-derived disaccharides of chondroitin-4-sulfate (Δdi-C4S), chondroitin-6-sulfate (Δdi-C6S), and keratan sulfate (KS), were measured in SF by High performance liquid chromatography (HPLC). RESULTS: Radiographic examination failed to detect any intra-articular degenerative changes. The number of high-grade cartilage lesions was positively associated with age, duration after injury and the level of C2C, and negatively with the level of KS. There was no association between the number of high-grade cartilage and meniscal lesions. Multivariable logistic regression revealed significant associations of increased C2C (adjusted Odds ratio (OR) of the upper quartile to remainder of 2.49, 95% Confidence interval (CI) = 0.85-7.27) and decreased KS (adjusted OR of the lower quartile to the remainder of 3.32, 95% CI = 1.19-9.24) with the presence of three or more high-grade cartilage lesions, independent of age and duration after injury. The combined impact of increased C2C and decreased KS was 22.8 (95% CI = 1.95-265.9), far exceeding the impact of each independent biomarker. CONCLUSION: Combinations of the C2C and KS as described here may offer greater ability to identify patients with early pre-radiographic high-grade cartilage damage compared to single clinical or biomarker parameters.


Assuntos
Ligamento Cruzado Anterior/metabolismo , Cartilagem Articular/metabolismo , Meniscos Tibiais/metabolismo , Líquido Sinovial/química , Adolescente , Adulto , Agrecanas/análise , Lesões do Ligamento Cruzado Anterior , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/lesões , Cromatografia Líquida de Alta Pressão , Colágeno Tipo II/análise , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Sulfato de Queratano/análise , Modelos Logísticos , Masculino , Meniscos Tibiais/diagnóstico por imagem , Proteoglicanas/análise , Radiografia , Lesões do Menisco Tibial , Adulto Jovem
12.
Endoscopy ; 45(4): 316-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23345110

RESUMO

Strictures remaining after nonsurgical treatment for esophageal cancer are generally more refractory to endoscopic balloon dilation (EBD) when compared with anastomotic strictures. The aim of the present study was to evaluate the efficacy and safety of a radial incision and cutting (RIC) method for the treatment of refractory strictures after nonsurgical treatment of esophageal cancer. All subjects complained of grade 2 or worse dysphagia, even after at least 10 sessions of EBD. Between August 2009 and May 2012, eight consecutive patients with refractory esophageal stricture after nonsurgical treatments, including chemoradiotherapy (CRT) alone (n = 3), CRT followed by salvage endoscopic treatment (n = 3), or endoscopic submucosal dissection (ESD; n = 2), underwent the RIC procedure. After the RIC procedure, dysphagia in all the patients dramatically improved to grade 1 or 0 without any major complications; however, the long-term efficacy was unfavorable as only 37.5 % (3 /8) demonstrated adequate lumen patency at 3 months, and re-intervention was necessary in six patients (75 %).


Assuntos
Transtornos de Deglutição/cirurgia , Neoplasias Esofágicas/terapia , Estenose Esofágica/etiologia , Estenose Esofágica/cirurgia , Idoso , Quimiorradioterapia/efeitos adversos , Transtornos de Deglutição/etiologia , Dilatação , Estenose Esofágica/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Fotoquimioterapia/efeitos adversos
13.
J Chem Phys ; 139(8): 084317, 2013 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-24007007

RESUMO

Mobilities of Li(+)-attached butanol isomers, (n-BuOH)Li(+), (s-BuOH)Li(+), (i-BuOH)Li(+), and (t-BuOH)Li(+), in helium gas were measured over a range of reduced electric fields (E/N = 25-96 Td) at room temperature. Arrival time measurements accurately identified small differences in the measured mobilities of the isomer ions. At low E/N (≤30 Td, corresponding to a mean collision energy ε≤0.05 eV), (n-BuOH)Li(+) showed a mobility about 1.5% greater than that of the other ions, but at high E/N (≥75 Td, ε≥0.1 eV) its mobility was about 1.1% less.

14.
Anaesth Rep ; 11(2): e12244, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37700794

RESUMO

The influence of general anaesthetic agents on intra-operative neurophysiological monitoring in neonates and infants has rarely been reported. Propofol-based anaesthesia is recommended to avoid suppression of neurophysiological monitoring. However, the administration of propofol in children undergoing prolonged procedures, especially those younger than six months, should be carefully controlled due to the potential risk of propofol infusion syndrome. Adding a small dose of inhalational anaesthetic can be an option to reduce propofol requirements. Recent guidelines in Japan suggest limiting inhalational anaesthetics to less than 0.5 minimum alveolar concentrations when co-administered with low-dose propofol during intra-operative neuromonitoring. However, there is still insufficient evidence regarding the impact of sevoflurane on neurophysiological monitoring when co-administered with propofol in infants. This report describes a case of a three-month-old infant undergoing spinal lipoma resection in which there was a dramatic suppression of neurophysiological monitoring with the addition of 0.35-0.45% sevoflurane to propofol-based anaesthesia.

15.
ESMO Open ; 8(1): 100762, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36610262

RESUMO

BACKGROUND: We conducted comprehensive clinical and molecular characterization of claudin 18.2 expression (CLDN18.2) in advanced gastric or gastroesophageal junction cancer (GC/GEJC). PATIENTS AND METHODS: Patients with advanced GC/GEJC who received systemic chemotherapy from October 2015 to December 2019 with available tumor specimens were analyzed. We evaluated clinicopathological features of CLDN18.2 expression with four molecular subtypes: mismatch repair deficient, Epstein-Barr virus-positive, human epidermal growth factor receptor 2-positive, and others. In addition, programmed death-ligand 1 (PD-L1) combined positive score (CPS), genomic alterations, and the expression of immune cell markers were assessed. Clinical outcomes of standard first- or second-line chemotherapy and subsequent anti-programmed cell death protein 1 (anti-PD-1) therapy were also investigated according to CLDN18.2 expression. RESULTS: Among 408 patients, CLDN18.2-positive (moderate-to-strong expression in ≥75%) was identified in 98 patients (24.0%) with almost equal distribution in the four molecular subtypes or CPS subgroups. CLDN18.2-positive was associated with Borrmann type 4, KRAS amplification, low CD16, and high CD68 expression. Overall survival with first-line chemotherapy was not significantly different between CLDN18.2-positive and -negative groups [median 18.4 versus 20.1 months; hazard ratio 1.26 (95% confidence interval 0.89-1.78); P = 0.191] regardless of stratification by PD-L1 CPS ≥5. Progression-free survival and objective response rates of first- and second-line chemotherapy, and anti-PD-1 therapy also showed no significant differences according to CLDN18.2 status. CONCLUSIONS: CLDN18.2 expression in advanced GC/GEJC was associated with some clinical and molecular features but had no impact on treatment outcomes with chemotherapy or checkpoint inhibition. CLDN18.2-positive also had no impact on overall survival. This information could be useful to interpret the results from currently ongoing clinical trials of CLDN18.2-targeted therapies for advanced GC/GEJC and to consider a treatment strategy for CLDN18.2-positive GC/GEJC.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Humanos , Antígeno B7-H1 , Infecções por Vírus Epstein-Barr/patologia , Herpesvirus Humano 4/metabolismo , Neoplasias Gástricas/patologia , Junção Esofagogástrica/metabolismo , Junção Esofagogástrica/patologia , Claudinas/genética , Claudinas/uso terapêutico
16.
Radiography (Lond) ; 29(3): 557-563, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36965243

RESUMO

INTRODUCTION: Dual-energy computed tomography (DECT) can generate virtual non-contrast (VNC) images. Herein, we sought to improve the accuracy of VNC images by identifying the optimal slope of contrast media (SCM) for VNC-image generation based on the iodine concentration and subject's body size. METHODS: We used DECT to scan a multi-energy phantom including four iodine concentration rods (15, 10, 5, and 2 mg/mL), and 240 VNC images (eight SCM ranging from 0.49 to 0.56 × three body sizes × ten scans) that were generated by three-material decomposition. The CT number of each iodine and solid water rod part was measured in each VNC image. The difference in the CT number between the iodine and the solid water rod part was calculated and compared using paired t-test or repeated measures ANOVA. RESULTS: The SCM that achieved an absolute value of the difference in CT number of <5.0 Hounsfield units (HU) for all body sizes simultaneously was greater at lower iodine concentration (SCM of 0.5, 0.51, and 0.53 at 10, 5, and 2 mg/mL iodine, respectively). At an iodine concentration of 15 mg/mL, no SCM achieved an absolute difference of <5.0 HU in CT number for all body sizes simultaneously. At all iodine concentrations, the SCM achieving the minimal difference in the CT number increased with the increase in body size. CONCLUSION: By adjusting the SCM according to the iodine concentration and body size, it is possible to generate VNC images with an accuracy of <5.0 HU. IMPLICATIONS FOR PRACTICE: Improving the accuracy of VNC images minimizing incomplete iodine subtraction would make it possible to replace true non-contrast (TNC) images with VNC images and reduce the radiation dose.


Assuntos
Iodo , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/métodos , Reprodutibilidade dos Testes , Imagens de Fantasmas
17.
Clin Exp Allergy ; 42(2): 218-28, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22233535

RESUMO

BACKGROUND: Interleukin (IL)-33 is a novel member of the IL-1 cytokine family and a ligand for the orphan IL-1 family receptor ST2. The IL-33 induces T helper 2-type inflammatory responses and is considered to play a crucial rule in allergic inflammations, such as asthma and atopic dermatitis. However, the role of IL-33 and its receptor ST2 in allergic rhinitis remains unknown. OBJECTIVE: We investigated expression of IL-33 and ST2 in the nasal epithelium of patients with allergic rhinitis and the mechanisms of the production of cytokines/chemokines induced by treatment with IL-33 using normal human nasal epithelial cells (HNECs) in vitro. METHODS: Expression of IL-33 and ST2 in normal and allergic rhinitis nasal mucosa was evaluated by reverse transcription- and real-time polymerase chain reactions and immunohistochemical methods. The IL-33 in serum, and IL-8 and GM-CSF were measured by ELISA. For in vitro experiments, HNECs in primary culture were used. RESULTS: The IL-33 levels in the sera of patients with allergic rhinitis were significantly higher than that in normal controls. Expression of IL-33 and ST2 was significantly elevated in the epithelium from patients with allergic rhinitis. The IL-33 mRNA in HNECs in vitro was significantly induced by treatment with IFN-γ and the toll-like receptor 9 ligand ODN2006. The IL-33-induced production of IL-8 and GM-CSF from HNECs in vitro was significantly suppressed by corticosteroid treatment and distinct signal transduction inhibitors of ERK, p38 MAPK, JNK, NF-κB and epidermal growth factor receptor. CONCLUSIONS AND CLINICAL RELEVANCE: The IL-33 and its receptor ST2 play important roles in allergic rhinitis. The IL-33-mediated inflammatory responses via ST2 are regulated by distinct signalling pathways in HNECs and the IL-33/ST2 pathway may provide new therapeutic targets for allergic rhinitis.


Assuntos
Interleucinas/imunologia , Sistema de Sinalização das MAP Quinases/imunologia , Mucosa Nasal/imunologia , Receptores de Superfície Celular/imunologia , Rinite Alérgica Sazonal/sangue , Adolescente , Adulto , Idoso , Antivirais/farmacologia , Células Cultivadas , Receptores ErbB/genética , Receptores ErbB/imunologia , Receptores ErbB/metabolismo , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Humanos , Interferon gama/farmacologia , Proteína 1 Semelhante a Receptor de Interleucina-1 , Interleucina-33 , Interleucina-8/sangue , Interleucina-8/genética , Interleucina-8/imunologia , Interleucinas/biossíntese , Interleucinas/genética , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/imunologia , MAP Quinase Quinase 4/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Masculino , Pessoa de Meia-Idade , NF-kappa B/genética , NF-kappa B/imunologia , NF-kappa B/metabolismo , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Mensageiro/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rinite Alérgica Sazonal/genética , Rinite Alérgica Sazonal/patologia , Receptor Toll-Like 9/agonistas , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/imunologia , Receptor Toll-Like 9/metabolismo , Adulto Jovem , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
18.
J Fish Biol ; 80(6): 2345-56, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22551186

RESUMO

Miniaturized acceleration data loggers were attached to the lower mandible of common carp Cyprinus carpio to remotely identify feeding behaviour. Whether the acceleration signal could distinguish the quantity and quality of food was also investigated. The frequency and amplitude of the lower mandible stroke, calculated from surging acceleration determined by continuous wavelet transformation, significantly increased during the feeding period compared to that during the non-feeding period. These characteristic movement patterns were maintained for mean ±s.e. 187·3 ± 38·2 s when the fish were fed a single item of food and for mean ±s.e. 419·3 ± 28·6 s when they consumed multiple items. The dominant cycle and amplitude calculated according to feeding event duration, however, did not differ significantly between the two types of diets the fish consumed. Surging acceleration could detect mean ±s.e. 89·8 ± 13·5% of feeding events, although the false detection rate was mean ±s.e. 25·9 ± 10·9%. The results indicate that the mandible acceleration measurement method could be utilized to detect and record the feeding events in fishes that use a suction feeding mode similar to C. carpio.


Assuntos
Aceleração , Carpas/fisiologia , Coleta de Dados/instrumentação , Comportamento Alimentar , Pesqueiros/instrumentação , Animais , Dieta , Mandíbula/fisiologia
19.
Anaesth Rep ; 10(2): e12179, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35874323

RESUMO

There is a lack of evidence regarding the optimal intra-operative glycaemic level of patients with ornithine transcarbamylase deficiency to prevent cerebral oedema due to protein catabolism and hyperammonemia. We describe a case of a two-year-old girl with ornithine transcarbamylase deficiency who underwent cardiac surgery requiring cardiopulmonary bypass. A high-dose dextrose infusion to prevent protein catabolism was given throughout surgery, which caused uncontrollable hyperglycaemia unresponsive to high-dose insulin administration. Factors contributing to the hyperglycaemia may have included surgical stress, steroid administration and hypothermia. During invasive surgery, anaesthetists should carefully adjust the rates of dextrose and insulin infusions, guided by close monitoring of blood ammonia, glucose and lactate.

20.
Phys Rev E ; 106(5-2): 055207, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36559487

RESUMO

Magnetic reconnection in laser-produced magnetized plasma is investigated by using optical diagnostics. The magnetic field is generated via the Biermann battery effect, and the inversely directed magnetic field lines interact with each other. It is shown by self-emission measurement that two colliding plasmas stagnate on a midplane, forming two planar dense regions, and that they interact later in time. Laser Thomson scattering spectra are distorted in the direction of the self-generated magnetic field, indicating asymmetric ion velocity distribution and plasma acceleration. In addition, the spectra perpendicular to the magnetic field show different peak intensity, suggesting an electron current formation. These results are interpreted as magnetic field dissipation, reconnection, and outflow acceleration. Two-directional laser Thomson scattering is, as discussed here, a powerful tool for the investigation of microphysics in the reconnection region.

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