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1.
BMC Pulm Med ; 23(1): 88, 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36932380

RESUMO

BACKGROUND: Recently, deaths due to mucormycosis in immunocompromised hosts have increased; however, the clinical and pathological features of mucormycosis are not fully understood, especially in view of the associated high mortality and rare incidence in immunocompetent patients. CASE PRESENTATION: We have described a rare autopsy case of a 67-year-old Japanese man with chronic obstructive pulmonary disease who contracted mucormycosis. He had not been on any immunosuppressants, and his immune functions were intact. Since 3 days prior to admission to our hospital, he had experienced progressive dyspnea, productive cough, and fever. Chest computed tomography revealed pleural effusion in the left lower hemithorax and consolidation in the right lung field. Although he was administered with tazobactam-piperacillin hydrate (13.5 g/day), renal dysfunction occurred on the ninth disease day. Therefore, it was switched to cefepime (2 g/day). However, his general condition and lung-field abnormality worsened gradually. Cytological analysis of the sputum sample at admission mainly revealed sporangiophores and unicellular sporangioles, while repeated sputum culture yielded Cunninghamella species. Therefore, he was diagnosed with pulmonary mucormycosis. Liposomal amphotericin B (5 mg/kg/day) was initiated on the 28th disease day. However, chest radiography and electrocardiography detected cardiomegaly and atrial fibrillation, respectively, and he died on the 37th disease day. A postmortem examination revealed clusters of fungal hyphae within the arteries of the right pulmonary cavity wall, the subpericardial artery, intramyocardial capillary blood vessels, and the esophageal subserosa vein. Direct sequencing revealed that all fungal culture samples were positive for Cunninghamella bertholletiae. CONCLUSIONS: Cunninghamella bertholletiae could rapidly progress from colonizing the bronchi to infecting the surrounding organs via vascular invasion even in immunocompetent patients.


Assuntos
Pneumopatias Fúngicas , Mucormicose , Masculino , Humanos , Idoso , Mucormicose/diagnóstico , Autopsia , Pneumopatias Fúngicas/diagnóstico
2.
Nutr Cancer ; 74(5): 1606-1613, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34431441

RESUMO

We aimed to assess the prognostic and predictive significance of pretreatment Geriatric Nutritional Risk Index (GNRI) and Prognostic Nutritional Index (PNI) measurements on advanced non-small cell lung cancer (NSCLC) patients treated with first-line therapy. Patients with advanced NSCLC treated between February 2014 and August 2020 were retrospectively analyzed. The optimal cutoff points for GNRI and PNI were measured with receiver operating characteristic (ROC) curve analysis according to overall survival (OS). The predictive factors for progression-free survival (PFS) and OS were evaluated with univariate and multivariate analyses via the Cox hazards regression. A total of 160 patients were included in the study. Significant differences between the low and high-GNRI or PNI groups were found regarding ECOG-PS. The low-GNRI and low-PNI groups had significantly shorter PFS and OS than the high-GNRI and high-PNI groups. A multivariate analysis using a Cox regression model revealed that the high-GNRI group was an independent prognostic factor of OS and PFS, and the PNI group was an independent prognostic factor of OS. Pretreatment GNRI and PNI may therefore be a potential effective predictor of the survival of advanced NSCLC patients undergoing first-line treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Avaliação Nutricional , Prognóstico , Estudos Retrospectivos
3.
J Infect Chemother ; 27(2): 373-378, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33071037

RESUMO

One of the human natural defense systems protects against nontuberculous mycobacterial (NTM) infection by IFN-γ producing T lymphocyte cells. Most disseminated NTM infections usually occur in severe immune-compromised patients, such as HIV infection or after organ transplant patients. However, there have been several reports of non-compromised patients with disseminated NTM infection, including antibiotic resistance cases and the presence of a neutralizing antibody against IFN-γ. We elucidated the anti-IFN-γ neutralizing antibody in a 65 year-old Japanese man whose legs were paralyzed because of multiple abscesses in vertebral bodies. Although his vertebral bodies were released due to an operation and antibiotics were administered, this treatment efficacy was poor. Patient's plasma demanded not only IFN-γ expression in peripheral blood mononuclear cells (PBMC) obtained from healthy controls, but also recombinant human IFN-γ expression. Furthermore, IFN-γ receptor expression was increased, compared to the healthy control. Finally, anti-IFN-γ antibody was detected in his plasma. These results suggested that anti-IFN-γ antibody induced an incurable NTM infection. IFN-γ was subcutaneously administrated with antibiotics, and then the abscesses diminished and his general condition was successfully improved. This therapy might be useful against severe NTM infections.


Assuntos
Infecções por HIV , Infecções por Mycobacterium não Tuberculosas , Idoso , Autoanticorpos , Humanos , Injeções Subcutâneas , Interferon gama , Leucócitos Mononucleares , Masculino , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico
4.
BMC Pulm Med ; 21(1): 6, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407304

RESUMO

BACKGROUND: Immune checkpoint inhibitors have potential applications in treating various cancers but are associated with immune-related adverse events, such as inflammation, in a wide range of organs; however, allergic inflammation caused by these agents has not been extensively studied. CASE PRESENTATION: A 65-year-old man was diagnosed with a kidney neuroendocrine carcinoma. Three months after kidney resection surgery, the tumor cells had metastasized to his liver and lymph nodes. Subsequently, the patient started chemotherapy; however, regardless of treatment, the tumor grew, and the patient experienced a series of adverse effects, such as taste disorder, anorexia, and general fatigue. Finally, he was administered a programmed cell death (PD)-1 inhibitor, nivolumab (biweekly, toal 200 mg/body), which was effective against kidney carcinoma. However, the patient had a bronchial asthma attack at 22 cycles of nivolumab treatment and chest computed tomography (CT) revealed an abnormal bilateral shadow after 37 cycles of nivolumab treatment. Bronchoscopy findings revealed eosinophil infiltration in the lungs along with severe alveolar hemorrhage. Paranasal sinus CT scanning indicated sinusitis and nerve conduction analysis indicated a decrease in his right ulnar nerve conduction velocity. Based on these findings, the patient was diagnosed with eosinophilic granulomatosis with polyangiitis; he was treated with prednisolone, which alleviated his bronchial asthma. To restart nivolumab treatment, the dose of prednisolone was gradually tapered, and the patient was administered a monthly dose of mepolizumab and biweekly dose of nivolumab. To date, there have been no bronchial attacks or CT scan abnormalities upon follow up. CONCLUSIONS: We present a rare case in which a patient with cancer was diagnosed with eosinophilic granulomatosis with polyangiitis following treatment with a PD-1 inhibitor. Blockade of PD-1 and the programmed cell death ligand (PD-L) 1/PD-1 and PD-L2/PD-1 signaling cascade may cause allergic inflammation. Further studies are needed to identify the specific mechanisms underlying allergic inflammation after PD-1 blockade.


Assuntos
Síndrome de Churg-Strauss/induzido quimicamente , Inibidores de Checkpoint Imunológico/efeitos adversos , Nivolumabe/efeitos adversos , Idoso , Carcinoma Neuroendócrino/tratamento farmacológico , Síndrome de Churg-Strauss/tratamento farmacológico , Humanos , Neoplasias Renais/tratamento farmacológico , Masculino , Prednisolona/uso terapêutico , Tomografia Computadorizada por Raios X
5.
BMC Health Serv Res ; 17(1): 438, 2017 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-28651532

RESUMO

BACKGROUND: For achieving equity of the accessibility to primary healthcare, measuring potential geographical accessibility is essential. The provider-to-population ratio is the most frequently used measure. However, it is difficult to be used in closer region because it does not take into consideration the people and health services beyond its boundary. In order to overcome this problem, we measured the potential access to hospital, using both distance measures and the enhanced two-step floating catchment area (E2SFCA) method. The aim of this study was to compare the number of hospitals in the neighborhood and the E2SFCA score with regard to the amount and equity for access to hospitals. METHODS: This descriptive study used publicly available data from 2010. The E2SFCA score and number of neighborhood hospitals were obtained from Tochigi province in Japan using a geographic information system. Dataset of four measures by each census tract was obtained. The measures were E2SFCA score, number of hospitals within the 5 km range, number of hospitals within the 10 km range, and number of hospitals within the 15 km range. Correlation and disparity analyses with the Lorenz curve and Gini coefficient were performed. RESULTS: The measures were obtained in a smaller area than municipality considering adjacent areas using a geographical approach. The E2SFCA score was 5.3 [3.2-7.3] hospitals/million (median [quantile range]), compared to 5.6 hospitals/million in total for the given district. The median number of hospitals within the 5 km, 10 km, and 15 km ranges were 1, 39, and 47, respectively. There was no hospital within the 5 km range in one third of the blocks. Both the number of hospitals within the 10 km range and those within the 15 km range were well correlated. Regional difference became smaller as the distance to count the number of hospitals increased. The gap between small number of hospitals and the high E2SFCA score indicated the location of community hospital in depopulated areas. CONCLUSIONS: The E2SFCA method is superior for analyzing spatial access to hospital, because it provides information in the closer sub-regions. Regional differences were hardly seen in access to hospital beyond the 10 km range. Further studies in other regions and countries are needed for precise assessment.


Assuntos
Acessibilidade aos Serviços de Saúde , Hospitais/provisão & distribuição , Área Programática de Saúde , Sistemas de Informação Geográfica , Hospitais/estatística & dados numéricos , Japão , Atenção Primária à Saúde , Análise Espacial
6.
Genes Cells ; 19(6): 504-16, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24774443

RESUMO

Cyclin D1, an oncogenic G1 cyclin, and YB-1, a transcription factor involved in cell growth, are both over-expressed in several human cancers. In human lung cancer, the functional association between YB-1 and cyclin D1 has never been elucidated. In this study, we show YB-1 is involved in the transcription of cyclin D1 in human lung cancer. Depletion of endogenous YB-1 by siRNA inhibited progression of G1 phase and down-regulated both the protein and mRNA levels of cyclin D1 in human lung cancer cells. Forced over-expression of YB-1 with a cyclin D1 reporter plasmid increased luciferase activity, and ChIP assay results showed YB-1 bound to the cyclin D1 promoter. Moreover, the amount of YB-1 mRNA positively correlated with cyclin D1 mRNA levels in clinical non-small-cell lung cancer (NSCLC) specimens. Immunohistochemical analysis also indicated YB-1 expression correlated with cyclin D1 expression in NSCLC specimens. In addition, most of the cases expressing both cyclin D1 and CDC6, another molecule controlled by YB-1, had co-existing YB-1 over-expression. Together, our results suggest that aberrant expression of both cyclin D1 and CDC6 by YB-1 over-expression may collaboratively participate in lung carcinogenesis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Ciclina D1/genética , Neoplasias Pulmonares/metabolismo , Proteína 1 de Ligação a Y-Box/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Grandes/metabolismo , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D1/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Proteína 1 de Ligação a Y-Box/genética
7.
Genes Cells ; 18(11): 999-1006, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24165022

RESUMO

Y box binding protein 1 (YB1) has multiple functions associated with drug resistance, cell proliferation and metastasis through transcriptional and translational regulation. Increased expression of YB1 is closely related to tumor growth and aggressiveness. We showed that YB1 protein levels were decreased through replicative and premature senescence and were correlated with increased expression levels of p16(INK) (4A) tumor suppressor gene. Depletion of YB1 was associated with increased levels of p16 in human and murine primary cells. Forced expression of YB1 in mouse embryonic fibroblasts resulted in decreased expression of p16 and increased cell proliferation. Senescence-associated expression of ß-galactosidase was repressed in YB1-over-expressing cells. Chromatin immunoprecipitation assays showed that YB1 directly associates with the p16 promoter. Taken together, all our findings indicate that YB1 directly binds to and represses p16 transcription, subsequently resulting in the promotion of cell growth and prevention of cellular senescence.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Fatores de Transcrição/genética , Proteína 1 de Ligação a Y-Box/metabolismo , Animais , Senescência Celular , Inibidor p16 de Quinase Dependente de Ciclina/genética , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Genes Supressores de Tumor , Humanos , Camundongos , Regiões Promotoras Genéticas , Fatores de Transcrição/metabolismo , Proteína 1 de Ligação a Y-Box/genética
8.
Sci Rep ; 14(1): 891, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195761

RESUMO

We propose an augmented reality (AR)-based training system for basketball free-throws. The optimal shot trajectory for free-throws is projected by a head-mounted display according to the shooter's release point. The efficacy of the training system was assessed in novice shooters by comparing changes in success rates and eye-gaze behavior (quiet eye [QE]) between AR-training and control-training groups. The success rate during the AR training with the optimal trajectory did not differ from the pre-training rate; however, in post-AR training, i.e., after removal of the optimal trajectory, the success rate increased. Additionally, AR training increased the QE duration (QED) compared with that recorded during pre- and post-training blocks. In contrast, the control group showed no change in the success rate or QED. These findings imply that our AR training system affected QE behavior and improved free-throwing shooting performance after training. Thus, our system is expected to enhance basketball free-throw shooting performance.

9.
BMC Fam Pract ; 14: 149, 2013 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-24103405

RESUMO

BACKGROUND: The current research into single nucleotide polymorphisms has extended the role of genetic testing to the identification of increased risk for common medical conditions. Advances in genetic research may soon necessitate preparation for the role of genetic testing in primary care medicine. This study attempts to determine what proportion of patients would be willing to undergo genetic testing for salt-sensitive hypertension in a primary care setting, and what factors are related to this willingness. METHODS: A cross-sectional study using a self-report questionnaire was conducted among outpatients in primary care clinics and hospitals in Japan. The main characteristics measured were education level, family medical history, personal medical history, concern about hypertension, salt preference, reducing salt intake, and willingness to undergo genetic testing for salt-sensitive hypertension. RESULTS: Of 1,932 potential participants, 1,457 (75%) responded to the survey. Of the respondents, 726 (50%) indicated a willingness to undergo genetic testing. Factors related to this willingness were being over 50 years old (adjusted odds ratio [ad-OR] = 1.42, 95% Confidence interval = 1.09 - 1.85), having a high level of education (ad-OR: 1.83, 1.38 - 2.42), having a family history of hypertension (ad-OR: 1.36, 1.09 - 1.71), and worrying about hypertension (ad-OR: 2.06, 1.59 - 2.68). CONCLUSIONS: Half of the primary care outpatients surveyed in this study wanted to know their genetic risk for salt-sensitive hypertension. Those who were worried about hypertension or had a family history of hypertension were more likely to be interested in getting tested. These findings suggest that primary care physicians should provide patients with advice on genetic testing, as well as address their anxieties and concerns related to developing hypertension.


Assuntos
Atitude Frente a Saúde , Testes Genéticos/estatística & dados numéricos , Hipertensão/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Atenção Primária à Saúde , Adulto , Fatores Etários , Idoso , Estudos Transversais , Escolaridade , Feminino , Predisposição Genética para Doença/psicologia , Humanos , Hipertensão/genética , Japão , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Inquéritos e Questionários
10.
Seishin Shinkeigaku Zasshi ; 115(2): 160-7, 2013.
Artigo em Japonês | MEDLINE | ID: mdl-23691805

RESUMO

Mie Prefectural Mental Care Center is a public psychiatric hospital that has 400 beds and 250 outpatients a day. The main catchment area is Tsu City (population: 290,000). Our hospital started early intervention in Aug 2008, and opened the Youth Mental Support Center MIE (YMSC MIE) in Oct 2008. This article reports an early intervention trial in a regional area of Japan. The mission of YMSC MIE is the education, consultation, staff training, and intervention for mental health problems and early psychosis of youths. In Jul 2009, we set up the Youth Assist Clinic (YAC) to support youths with mental health problems and early psychoses. Our activities consist of school-based, community-based, and hospital-based approaches. Specific programs are as follows: 1) School-based approaches: Outreach consultation to school. Mental health lessens. Creating mental health textbooks. Education for parents and teachers. 2) Community-based approaches: To enlighten primary physicians and mental clinic psychiatrists about the importance of early psychosis. To survey their concerns regarding early psychosis. Promoting awareness of community staff and the general public. 3) Hospital-based approaches: YAC. Case manager system. Family meetings for the family including the young with mental disorders. Peer group. Looking back over our 3-year trials, especially in school and the community, we find several problems, as follows: 1) Lack of consultation skills of medical staff outside the hospital. 2) Limiting number of schools which have mental support system. 3) Support for school attendance and learning. 4) Lack of concern about early psychosis of primary physicians and mental clinic psychiatrists. 5) Staff training for early intervention. We are now getting close to improving these issues.


Assuntos
Intervenção Educacional Precoce , Transtornos Mentais/terapia , Intervenção Educacional Precoce/métodos , Educação em Saúde/estatística & dados numéricos , Promoção da Saúde , Humanos , Japão , Transtornos Mentais/diagnóstico , Encaminhamento e Consulta , Instituições Acadêmicas
11.
Respir Med Case Rep ; 42: 101823, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36915472

RESUMO

Severe immune thrombocytopenia is a rare side-effect of rifampicin (RFP) and can be life-threatening. Here, we report the case of a 74-year-old male with tuberculous pleurisy who developed severe thrombocytopenia after first exposure to RFP. Platelet count decreased to 1 × 103/µL after 7 days of treatment with RFP, isoniazid, ethambutol, and pyrazinamide. After all the drugs were discontinued, the platelet count recovered. As thrombocytopenia did not occur after re-administration of drugs other than RFP, the patient was diagnosed with RFP-induced thrombocytopenia. Clinicians should be aware that RFP can induce acute and severe thrombocytopenia even without previous exposure to this drug.

12.
Respir Med Case Rep ; 46: 101918, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37822764

RESUMO

We report a 68-year-old woman with tracheobronchitis and laryngitis associated with Crohn's disease (CD), which was discovered during the evaluation of suspected lung cancer. She had no symptoms induced by these upper airway diseases (UADs). Bronchoscopy revealed swelling of the epiglottis with edematous change and a mass like epiglottis fold. There were nodular and edematous changes in the trachea and bilateral main bronchus. Histological findings demonstrated infiltration by numerous lymphocytes and plasma cells. Dexamethasone as the premedication for chemotherapy against lung cancer was efficacious for these extraintestinal manifestations of CD. Our case was rare in that bronchial lesion and UADs appeared concomitantly.

13.
Bioorg Med Chem ; 20(9): 2796-802, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22483840

RESUMO

Voltage-gated sodium channels (VGSCs) are responsible for generating action potentials in nervous systems. Veratridine (VTD), a lipid soluble alkaloid isolated from sabadilla lily seed, is believed to bind to segment 6 of VGSCs and act as a partial agonist. However, high resolution structural interaction mechanism between VGSCs and VTD is difficult to elucidate because of the large size and membrane localization of VGSCs. Here, the authors designed model peptides corresponding to domain IV segment 6 (DIVS6) of rat skeletal muscle Na(v)1.4 and analyzed the complex of the model peptides and VTD by solution NMR analysis to obtain structural information of the interaction. The model peptides successfully formed an α-helices, which is the suspected native conformation of DIVS6, in aqueous 2,2,2-trifluoroethanol, a membrane-mimicking solvent. The VTD binding residues of the model peptide were identified using the NMR titration experiments with VTD, including a newly discovered VTD binding residue Leu14 (µ1-L1580 in Na(v)1.4), which has not been reported by point mutation studies. Mapping of VTD binding residues on the model peptide revealed the hydrophobic interaction surface. NMR titration experiments with a non-toxic analog of VTD, veracevine, also indicated that the steroidal backbone of VTD interacts with the hydrophobic interaction surface of DIVS6 and that the 3-acyl group of VTD possibly causes neurotoxicity by interacting with domain I segment 6 and/or domain IV segment 4.


Assuntos
Espectroscopia de Ressonância Magnética , Peptídeos/metabolismo , Canais de Sódio/metabolismo , Veratridina/metabolismo , Sequência de Aminoácidos , Animais , Interações Hidrofóbicas e Hidrofílicas , Cinética , Modelos Moleculares , Dados de Sequência Molecular , Peptídeos/síntese química , Peptídeos/química , Ligação Proteica , Estrutura Terciária de Proteína , Ratos , Canais de Sódio/química , Veratridina/química
14.
Respir Med Case Rep ; 36: 101606, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242519

RESUMO

Anti-melanoma differentiation-associated gene 5 (MDA5) and anti-aminoacyl-tRNA synthetase (ARS) antibodies are two major myositis-specific autoantibodies with distinct clinical features. However, the clinical course remains unclear in patients with clinically amyopathic dermatomyositis (CADM)-interstitial lung disease (ILD) who have co-existing anti-MDA5 and anti-ARS antibodies. Here, we describe the case of a 32-year-old woman with CADM-ILD who had anti-MDA5 and anti-PL12 antibodies. Her serum ferritin level was within the normal range. However, chest computed tomography revealed bilateral lower-lobe consolidation and ground-glass opacities. Treatment with prednisolone and immunosuppressants was successful in improving the skin lesion and ILD, but relapse occurred on reducing the dose of prednisolone. These clinical features match those of anti-ARS antibody-positive dermatomyositis-ILD. Because these two conditions show significantly different clinical features and require different intensities of treatment, clinicians should carefully follow-up these patients throughout the course of the disease.

15.
Medicine (Baltimore) ; 101(39): e30806, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36181091

RESUMO

RATIONALE: The relationship between rheumatoid arthritis (RA) and eosinophilic inflammation is unclear. According to recent studies, it has been suggested that T helper 2 cell responses play a role in the inhibition of RA. It is unclear how the immunological response after coronavirus disease-2019 (COVID-19) vaccination affects T cell immune reactions. PATIENT CONCERNS AND DIAGNOSES: Here, we report the case of an 88-year-old woman diagnosed with RA and chronic eosinophilic pneumonia (CEP). She was diagnosed with CEP about 20 years ago, and, through steroid treatment, she improved and had no relapse for 16 years. At the time of diagnosis of CEP, the rheumatoid factor (RF) was increased; however, there were no joint symptoms. After receiving the COVID-19 vaccine, joint and respiratory symptoms gradually worsened. Laboratory examinations showed increased RF, anti-cyclin citrullinated peptide antibody, and peripheral absolute eosinophil count. Musculoskeletal ultrasonography showed synovitis. INTERVENTION AND OUTCOME: Methylprednisolone pulse therapy improved respiratory and joint symptoms immediately; RA and CEP stabilized with no relapses. LESSONS: Eosinophilic and rheumatoid reactions following COVID-19 vaccination were an-reported adverse events. Eosinophilic inflammation might be reflected on an anti-inflammatory reaction in initial phase of RA.


Assuntos
Artrite Reumatoide , Vacinas contra COVID-19 , COVID-19 , Eosinofilia Pulmonar , Idoso de 80 Anos ou mais , Anti-Inflamatórios , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Feminino , Humanos , Inflamação , Metilprednisolona/uso terapêutico , Eosinofilia Pulmonar/etiologia , Fator Reumatoide , Vacinação
16.
Aging (Albany NY) ; 13(13): 16957-16973, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253690

RESUMO

Many aging related diseases such as cancer implicate the myofibroblast in disease progression. Furthermore genesis of the myofibroblast is associated with manifestation of cellular senescence of unclear significance. In this study we investigated the role of a common regulator, namely telomerase reverse transcriptase (TERT), in order to evaluate the potential significance of this association between both processes. We analyzed the effects of TERT overexpression or deficiency on expression of CDKN2A and ACTA2 as indicators of senescence and differentiation, respectively. We assess binding of TERT or YB-1, a repressor of both genes, to their promoters. TERT repressed both CDKN2A and ACTA2 expression, and abolished stress-induced expression of both genes. Conversely, TERT deficiency enhanced their expression. Altering CDKN2A expression had no effect on ACTA2 expression. Both TERT and YB-1 were shown to bind the CDKN2A promoter but only YB-1 was shown to bind the ACTA2 promoter. TERT overexpression inhibited CDKN2A promoter activity while stimulating YB-1 expression and activation to repress ACTA2 gene. TERT repressed myofibroblast differentiation and senescence via distinct mechanisms. The latter was associated with TERT binding to the CDKN2A promoter, but not to the ACTA2 promoter, which may require interaction with co-factors such as YB-1.


Assuntos
Diferenciação Celular/fisiologia , Senescência Celular/fisiologia , Miofibroblastos/fisiologia , Telomerase/fisiologia , Actinas/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Humanos , Masculino , Regiões Promotoras Genéticas , RNA Interferente Pequeno , Telomerase/biossíntese , Telomerase/genética
17.
Medicine (Baltimore) ; 100(21): e26149, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032770

RESUMO

RATIONALE: Lung pleomorphic carcinoma (LPC) is generally resistant to chemotherapy or radiotherapy. However, a combination of immune checkpoint inhibitors and radiotherapy has a remarkable efficacy against LPC. PATIENT CONCERNS AND DIAGNOSES: Here, we report the case of a 50-year old man diagnosed with progressive LPC. The tumor invaded the carina and predominantly obstructed the right main bronchus; therefore, a combination of palliative chemoradiotherapy and atezolizumab was initiated. However the trachea was gradually obstructed. INTERVENTION AND OUTCOME: Argon plasma coagulation (APC) was performed to prevent tumor invasion. After three APC sessions, the tumor showed a necrotic change and was easily excised using biopsy forceps. LESSONS: A combination of chemoradiotherapy, atezolizumab, and APC showed a good efficacy, and the patient had a good response to atezolizumab maintenance therapy. Multidisciplinary treatments, such as a combination of immune checkpoint inhibitors and APC, could have synergistic efficacy in lung cancer.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Inibidores de Checkpoint Imunológico/uso terapêutico , Fotocoagulação a Laser , Lasers de Gás/uso terapêutico , Neoplasias Pulmonares/terapia , Brônquios/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Necrose , Traqueia/patologia , Resultado do Tratamento
18.
Respir Med Case Rep ; 31: 101196, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32913702

RESUMO

Immunoglobulin type G4 -related disease (IgG4-RD) is known as a chronic systemic inflammatory disease, which is sometimes associated with lung cancer. However, the detailed association between IgG4-RD and lung cancer in clinical settings is still poorly understood. An 80-year-old man was diagnosed with progressive lung adenocarcinoma carrying an EGFR point mutation at L858R, and osimertinib treatment was administered. Two months later, although osimertinib treatment showed good response to the primary tumor, fever and anorexia appeared, and multiple lymph nodes, in particular in the left axillary, became swollen. Ultrasonography-guided biopsy of the axillary lymph node revealed infiltration of lymphocytes with IgG4-positive plasma cells and fibrosis. Serum IgG4 levels were also increased. These results suggested that the multiple swollen lymph nodes were not metastasis, but IgG4-related disease. Based on these results, therapy using prednisolone was initiated. Multiple lymphadenopathy gradually decreased, and his symptoms improved. Currently, his good responses to osimertinib treatment have been maintained. Like in our case, multiple lymphadenopathy with IgG4-positive plasma cell infiltration during successful anti-cancer treatment is quite rare. In this case, it was hypothesized that anti-cancer treatment with osimertinib induced IgG4-positive plasma cell infiltration in multiple lymph nodes. When lymphadenopathy occurs during lung cancer treatment, IgG4-RD has to be considered other than lung cancer metastasis.

19.
Int J Chron Obstruct Pulmon Dis ; 15: 3013-3023, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33244227

RESUMO

Background: The validity of four-dimensional dynamic-ventilation CT scan for distinguishing COPD from asthma has not been established. Purpose: To assess whether four-dimensional dynamic-ventilation CT scan can aid in the diagnosis of COPD by comparing local lung movement during tidal breathing between COPD and asthma. Patients and Methods: Thirty-three COPD patients (30 males and three females; median age 74; range 44-89 years) and 11 asthma patients (five males and six females; median age 55; range: 32-75 years) underwent whole-lung dynamic-ventilation CT scan. CT data were reconstructed, one respiratory cycle to 10 phases, and in addtion we reconstructed threefold new phase data sets. We then analyzed local lung movement during tidal breathing using unpaired t-tests and chi-squared tests. Results: The local lung movement in COPD patients was significantly smaller than in asthma patients, especially in the ventral part of the lung. This was so even in patients who had mild emphysema (Goddard score <8). Conclusion: Quantitative evaluation using four-dimensional dynamic-ventilation CT scan demonstrated that local lung movement during tidal breathing, particularly in the ventral lung, was smaller in COPD than in asthma patients, which may help distinguish COPD from asthma.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/diagnóstico por imagem , Feminino , Tomografia Computadorizada Quadridimensional , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Respiração
20.
Respir Med Case Rep ; 31: 101236, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33083220

RESUMO

Epidermal growth factor receptor (EGFR) exon 20 insertion is not associated with sensitivity to EGFR tyrosine kinase inhibitors and chemotherapy. Here, we report the case of a 41-year-old man who presented a right lower lobe nodule and mediastinal lymph node enlargement diagnosed as EGFR exon 20 insertion adenocarcinoma with high-expression programmed cell death ligand 1 (PD-L1). He showed stable disease to chemoradiation treatment at the primary tumor site. However, durvalumab treatment has good response. Non-small cell lung cancer with EGFR exon 20 insertion and high PD-L1 expression may be treated with immunotherapy exposure.

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