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1.
Infect Dis (Lond) ; : 1-4, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32238024

RESUMO

A 35-year-old woman presented with fever and mild diarrhoea without any respiratory symptoms 9 days after travelling to Japan from Wuhan, China. Her computed tomography scan revealed pneumonia. The first polymerase chain reaction (PCR) test on throat swab for the novel corona virus upon admission was negative. Therefore, she was treated for community-acquired pneumonia, but fever persisted. On hospital day 5, PCR test on induced sputum was positive, but a second polymerase chain reaction test on throat swab remained negative. She was discharged, fully recovered, on hospital day 12. A lower respiratory tract specimen should be obtained for better diagnosis of corona virus disease 2019, even in the absence of respiratory symptoms for patients with significant travel or exposure history.

2.
Clin Exp Rheumatol ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32083551

RESUMO

OBJECTIVES: To clarify the efficacy and safety of calcineurin inhibitors (CNI) for treating adult-onset Still's disease (AOSD). METHODS: This multicentre historical cohort study enrolled the consecutive patients with AOSD according to Yamaguchi classification criteria. The endpoints were set as the time from the initiation of treatment to events, the persistency rate of CNI and safety. Based on the recurrent event data analysis, these endpoints were evaluated for each event. We divided the events into two groups according to the treatment that included CNI or conventional therapy without CNI. RESULTS: One hundred seventy-eight patients with 247 events were analysed. CNI were predominantly used in 72 events with a recurrent history, typical skin rash, high ferritin levels, and/or severe complications such as macrophage activation syndrome, disseminated intravascular coagulation, serositis, meningitis. CNI led to a significantly longer event-free survival (hazard ratio: 0.57, 95% confidential interval: 0.32-0.99) after adjustment of concomitant medications. Subgroup analysis showed that CNI were effective for AOSD patients with high ALT level (hazard ratio: 0.11, 95% confidential interval: 0.02-0.59) and severe complications (hazard ratio: 0.11, 95% confidential interval: 0.01-0.94). The persistency rate of CNI was 71% at 5th year. Adverse events occurred more frequently in the CNI group (18% versus 8%, p=0.02); however, CNI did not involve in increased risk of adverse events, including nephrotoxicity, after adjustment (p=0.23). CONCLUSIONS: Our retrospective analysis suggested that CNI could be an effective and safe option for treating AOSD.

3.
4.
Laryngoscope ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31693183

RESUMO

OBJECTIVES/HYPOTHESIS: Voice outcomes of cordectomy for early glottic cancer are often poor due to vocal fold scarring and tissue defects. Improvements in this aspect could make cordectomy a more acceptable treatment option than radiotherapy. We hypothesized that a polyglycolic acid (PGA) sheet could be used to cover vocal fold defects. The present study aimed to prevent vocal fold scarring after cordectomy using the PGA sheet. STUDY DESIGN: Animal experiment. METHODS: Nine male beagles were divided into three groups including a control group (n = 3). Following cordectomy, the vocal fold defect was covered with the PGA sheet plus fibrin glue (PGA group; n = 3) or with the PGA sheet plus fibrin glue containing basic fibroblast growth factor (bFGF; the PGA-bFGF group, n = 3). Vocal folds were chronologically observed, and larynges were removed 6 months after surgery. Mucosal amplitude was measured using a high-speed camera, and histological analysis was performed. RESULTS: The re-epithelialization process was delayed in the PGA and PGA-bFGF groups compared with the control group. The mucosal amplitude was significantly more normalized and the thickness ratio significantly higher in the PGA and PGA-bFGF groups compared with the control group. The PGA-bFGF group had the highest elastic fiber density, followed by the PGA group and then the control group, with a significant difference between the PGA-bFGF and control groups. CONCLUSIONS: The PGA sheet plus fibrin glue could serve as an effective regenerative scaffold for reconstructing vocal fold morphology and function after cordectomy, with the potential benefit of establishing an endoscopic sealing method for vocal fold defects. LEVEL OF EVIDENCE: NA Laryngoscope, 2019.

5.
Auris Nasus Larynx ; 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31575450

RESUMO

Cells in the maculae flavae (MFe) are inferred to be involved in the metabolism of extracellular matrices of the human vocal fold mucosa. The latest research has supported the hypothesis that the tension caused by phonation (vocal fold vibration) regulates the behavior of these cells in the MFe of the human vocal fold. Tensile and compressive strains have direct effects on cell morphology and structure including changes in cytoskeletal structure and organization. Cytoskeletons are one of the structures which play a role as mechanoreceptors for the cells. The microstructure of the intermediate filaments and the expression of their proteins were investigated regarding the cells in the MFe of the human vocal fold unphonated over a decade. The adult vocal fold mucosa of a 64-year-old male with cerebral hemorrhage unphonated for 11 years was investigated by immunohistochemistry and electron microscopy. The intermediate filaments in the cytoplasm of the cells had become fewer in number. And the expression of their characteristic proteins (vimentin, desmin, GFAP) was also reduced. The results of this study are consistent with the hypothesis that mechanotransduction caused by vocal fold vibration could possibly be a factor in regulating the function and fate of the cells in the MFe.

6.
J Cardiovasc Electrophysiol ; 30(12): 2877-2884, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31646695

RESUMO

BACKGROUND: Contemporary implantable cardioverter-defibrillator (ICD) programming involving delayed high-rate detection and use of supraventricular tachycardia (SVT) discriminators has significantly reduced the rate of inappropriate shocks. The extent to which SVT algorithms alone reduce inappropriate therapies is poorly understood. METHODS AND RESULTS: PainFree SST enrolled 2770 patients with a single- or dual-chamber ICD or cardiac resynchronization defibrillator. Patients were followed for 22 ± 9 months with SVT discriminators on in 96% of patients. Sustained ventricular tachyarrhythmias and SVT episodes were adjudicated by an independent physician committee. For this analysis, all episodes were subjected to postprocessing computer simulation with SVT discriminators off with and without delayed high-rate detection criteria (ventricular fibrillation zone only, 30/40 at 320 ms). There were 3282 adjudicated SVT episodes of which 115 resulted in an ICD shock and 113 received only ATP (2-year inappropriate shock and therapy rates of 3.1% and 4.1%). Therapy was appropriately withheld for the remaining 3054 SVT episodes. With both SVT discriminators and delayed high-rate detection simulated off, the 2-year inappropriate therapy rate would have been 22.9% (hazard ratio [HR] = 6.24; 95% confidence interval [CI]: 5.20-7.49). With SVT discriminators simulated off and delayed high-rate detection simulated on in all patients, the 2-year rate would have been 6.4% (HR = 1.63; CI: 1.44-1.85). CONCLUSIONS: The use of SVT discriminators has a significant role in reducing the rate of inappropriate ICD therapy even in the setting of delayed high-rate detection settings. Deactivating SVT discriminators would have resulted in an overall increase in the inappropriate ICD therapy rate by 63% and 524% with and without delayed high-rate detection programming, respectively.

7.
Auris Nasus Larynx ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31471098

RESUMO

OBJECTIVES: Conventional pharyngeal flap surgery, which closes the median portion of the velopharynx, has been performed for dysarthria patients with velopharyngeal insufficiency (VPI). However, for VPI due to unilateral pharyngeal paralysis, median closing disrupts pharyngeal contraction of the unaffected side and allows pharyngeal pressure to escape through the nose at the lateral portion of the affected side during speech and swallowing. The purpose of this study was to evaluate the effectiveness of lateral pharyngeal flap (LPF) surgery for unilateral VPI. METHODS: Seven patients with unilateral VPI (five males and two females with an average age of 54 years) underwent LPF surgery combined with other transoral surgeries for dysphagia. The LPF surgical technique was as follows: after the laterocaudal-based pedicle flap of the soft palate and cranial-based pedicle flap of the posterior pharyngeal wall on the affected side were transorally elevated, each mucosal pedicle flap was sutured together. Functional oral intake scale (FOIS) scores and swallowing pressure before and after surgery were compared. RESULTS: Unilateral velopharyngeal closure preserved nasal breathing after LPF surgery in all patients. Rhinolalia aperta improved postoperatively in all patients except one. The mean FOIS scores were 2.3 preoperatively and 3.7, 5.3, and 5.9 at 2 weeks, 1 month, and 6 months postoperatively, respectively. The mean pressures significantly increased at the velopharynx (from 49±30mmHg to 92±45mmHg) and oropharynx (from 48±18mmHg to 66±15mmHg) six months after the surgery. CONCLUSION: LPF surgery leaving the unaffected side intact can be an effective surgical procedure for patients with unilateral VPI.

8.
Laryngoscope Investig Otolaryngol ; 4(4): 405-409, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31453349

RESUMO

Objectives: There is growing evidence to suggest that the cells in the maculae flavae of the vocal fold mucosa are tissue stem cells of the human vocal fold. This study investigated the metabolic activity of the cells in the maculae flavae of the human vocal fold from the aspect of mitochondrial microstructure. Study Design: Histologic analysis of the human vocal folds. Methods: Five normal human adult vocal folds obtained from autopsy cases were investigated under transmission electron microscopy. Results: Mitochondria were randomly distributed in the cytoplasm of the cells. The morphological features of the mitochondria consisted of a double-membrane-bounded body containing matrices and a system of cristae. In each mitochondria, the lamellar cristae were sparse. The intercristal space was occupied by a mitochondrial matrix which contained electron-dense matrix granules, mitochondrial DNA, and ribonucleoprotein granules. Some mitochondria spread out over or fused to the surface of a lipid droplet in the cytoplasm. In addition, both the mitochondrial outer and inner membranes and the membranes of the lipid droplets had disappeared. Some close association between mitochondria and rough endoplasmic reticulum was present. Conclusions: The features of the mitochondria of the cells in the maculae flavae of the human vocal fold suggested that their metabolic activity and oxidative phosphorylation were low and that they may have shifted to the utilization of lipids to some extent for their metabolic needs. Level of Evidence: NA.

9.
J Cardiol Cases ; 19(2): 66-69, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31193704

RESUMO

Catheter ablation (CA) targeting premature ventricular contraction (PVC) from Purkinje fibers can be an effective therapy for refractory ventricular fibrillation (VF) after myocardial infarction (MI). We experienced two cases in which catheter ablation targeting PVC initiating VF after percutaneous coronary intervention (PCI) in post-MI patients was effective despite transient early recurrences of VF. The first patient (a 68-year-old woman with MI) developed drug-refractory VF 3 days after PCI to the left anterior descending artery (LAD) and left circumflex artery. CA targeting Purkinje potential preceding PVC at the infarcted area eliminated both the PVCs and VF. Three days after the procedure, the VF attacks relapsed by a different type of PVC. However, the VF responded to conventional treatments and disappeared thereafter. In the second patient (an 83-year-old woman with old MI), refractory VF attacks occurred after PCI to the LAD. CA targeting Purkinje potential preceding two distinct types of PVC successfully suppressed the VF. Although the VF relapsed 2 days after CA, it was suppressed by conventional treatment and disappeared the next day. .

10.
Intern Med ; 58(14): 2041-2044, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30918200

RESUMO

An 84-year-old man presented with syncope. Prior to admission, ambulatory electrocardiogram had demonstrated non-sustained ventricular tachycardia. Echocardiography showed severe aortic stenosis. He was also diagnosed with hypertrophic cardiomyopathy (HCM) by cardiac magnetic resonance (CMR) showing remarkable inhomogeneous left ventricular hypertrophy and extensive late gadolinium enhancement (LGE) in the lesions at the upper border and right-ventricular side of the basal-mid septal wall. Finally, he showed complete atrioventricular (AV) block followed by a long pause and syncope several times after admission. In this case with several possible causes of syncope, the CMR findings suggested a clue concerning the etiology of his syncope: complete AV block in HCM.


Assuntos
Bloqueio Atrioventricular/complicações , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Fibrose/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/complicações , Imagem Cinética por Ressonância Magnética/métodos , Marca-Passo Artificial , Síncope/complicações , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica , Bloqueio Atrioventricular/cirurgia , Meios de Contraste , Eletrocardiografia Ambulatorial/métodos , Fibrose/cirurgia , Gadolínio DTPA , Ventrículos do Coração/fisiopatologia , Humanos , Hipertrofia Ventricular Esquerda/cirurgia , Masculino , Miocárdio/patologia , Síncope/cirurgia , Resultado do Tratamento
11.
Ann Otol Rhinol Laryngol ; 128(7): 585-594, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30832485

RESUMO

OBJECTIVES: In tracheal regeneration, the slow process of epithelialization is often a barrier to the stability and safety of the transplanted trachea. The aim of this study was to examine a new tracheal regeneration technique using organotypically cultured tissue composed of autologous cells. METHODS: Nine beagles were prepared. Chondrocytes from auricular cartilage and epithelial cells from buccal mucosa were isolated and cultured. Tissue-engineered cartilages were fabricated with chondrocytes at a density of 1 × 107 cells/mL (high-density group) and 1 × 106 cells/mL (low-density group). A fabricated epithelial cell sheet was laid on a poly(lactic-co-glycolic acid) block in atelocollagen gel containing the chondrocytes, and the organotypically cultured tissues were transplanted into a partially resected trachea. The control group had only the block transplanted. RESULTS: The tissue-engineered cartilages in the high-density group contained many viable chondrocytes and many cartilage matrices. The low-density group had abundant collagen fibers and no chondrocytes. Tracheal endoscopy revealed no deformation or atrophy at the transplant site in the high-density group. Histologically, partially hyaline cartilages covered with epithelium and lamina propria were found in the high-density group but not in the low-density and control groups. CONCLUSIONS: Stable tracheal regeneration was achieved using organotypically cultured tissue fabricated with autologous high-density chondrocytes and epithelial cells.


Assuntos
Condrócitos/citologia , Células Epiteliais/citologia , Técnicas de Cultura de Tecidos/métodos , Engenharia Tecidual/métodos , Traqueia/citologia , Animais , Materiais Biocompatíveis , Condrócitos/transplante , Colágeno , Cães , Cartilagem da Orelha/citologia , Células Epiteliais/transplante , Mucosa Bucal/citologia , Técnicas de Cultura de Órgãos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Regeneração , Tecidos Suporte , Traqueia/transplante , Transplante Autólogo
12.
Laryngoscope Investig Otolaryngol ; 4(1): 76-82, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30828622

RESUMO

Objective: The latest research suggests cells in the maculae flavae (MFe) are putative stem cells of the vocal fold mucosa and the MFe are a candidate for a stem cell niche. Distribution and properties of label-retaining cells (LRCs) in the vocal fold mucosa were investigated. Study Design: Histologic analysis of the rat vocal folds. Methods: Oral administration of bromodeoxyuridine (BrdU) was given to rats and the LRCs in the vocal fold mucosa were observed by immunohistochemistry. Immunoreactivity to antibodies directed to BrdU, Ki67, cytokeratin, vimentin, glial fibrillary acidic protein, desmin, Sox17, CD34, CD45, Type I collagen, and CD44 was studied. Extracellular matrices around LRCs were observed by Alcian blue staining and hyaluronidase digestion study. Results: LRCs were present in the MFe and were resting cells (G0-phase). They expressed epithelium, muscle, neural, and mesenchymal cell-associated intermediate filament proteins, and an endodermal marker, indicating cells in the MFe are undifferentiated and express proteins of all three germ layers. They expressed hematopoietic markers (CD34, CD45) and Type I collagen, which are the major markers of bone marrow derived circulating fibrocytes. The hyaluronan concentration in the MFe was high and the cells in the MFe expressed the surface hyaluronan receptor CD44, indicating that the MFe were a hyaluronan-rich matrix. Conclusion: LRCs reside in the MFe and MFe had a hyaluronan-rich matrix. The results of this study are consistent with the hypothesis that the cells in the MFe are putative stem cells and the MFe are a candidate for a stem cell niche. Level of Evidence: N/A.

13.
Laryngoscope Investig Otolaryngol ; 4(1): 89-94, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30828624

RESUMO

Objectives: Human papillomavirus (HPV) infects basal cells of the stratified squamous epithelium through micro epithelial trauma. However, laryngeal papillomatosis commonly appears in any site on the laryngeal mucosa not covered by stratified squamous epithelium. The purpose of this study is to clarify pathological mechanisms of laryngeal papillomatosis based on the characteristics of the laryngeal epithelium. Study Design: Morphological and immunohistochemical study. Methods: Larynges from one newborn and two adults were used. Morphological differences in the laryngeal squamo-ciliary junction (lSCJ) were compared to those in the cervical squamo-columnar junction (cSCJ) in a resected cervix uterus. Morphological characteristics of laryngeal epithelial distribution were also compared between the newborn and adult larynges. Immunohistochemical evaluations were performed using p63 (an epithelial stem-cell marker) and integrin-α6 (a cellular HPV receptor). Results: Morphological differences were noted between the lSCJ and the cSCJ. The lSCJ was present in the adult, but not the newborn supraglottis. Goblet cells in the pseudostratified ciliated columnar epithelium were also found in the adult but not the newborn larynx. In addition, basal cells of the stratified squamous epithelium as well as the pseudostratified ciliated columnar epithelium expressed p63 and integrin-α6 in both newborn and adult larynges. Conclusions: HPV can infect any immature laryngeal epithelium with or without the lSCJ. Squamous metaplasia of pseudostratified ciliated columnar epithelium with a latent HPV infection can also cause tumorigenesis. Level of Evidence: N/A.

14.
Acta Histochem ; 121(2): 164-170, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30558911

RESUMO

The latest research suggests cells in the maculae flavae located at both ends of the lamina propria of the human vocal fold mucosa have stemness. This study investigated the differentiation potential of the cells in the maculae flavae of the human vocal fold mucosa. Four normal human adult vocal folds from surgical specimens were used. After extraction of the anterior maculae flavae located at the anterior end of the lamina propria of the human vocal fold mucosa under microscope, the maculae flavae were minced, cultured and proliferated in mesenchymal stem cell growth medium and morphological features were assessed. Cell surface markers were detected using flow cytometry. Cell differentiation into adipogenic, chondrogenic and osteogenic lineages was performed. Cell's differentiation potential was assessed using a human pluripotent stem cell functional identification kit and immunohistochemistry. Subcultured cells formed a colony-forming unit. Subcultured cells expressed CD90, CD105 and CD73 and lacked expression of CD45, CD34, CD11b, CD19 and HLA-DR. They differentiated into adipogenic, chondrogenic and osteogenic lineages. Consequently, the cell features in the maculae flavae meet the minimal criteria defining mesenchymal stromal cells. In addition, subcultured cells differentiated into ectoderm, mesoderm and endoderm and expressed stage-specific embryonic antigen 3 (SSEA-3). The results of this study are consistent with the hypothesis that the cells in the maculae flavae in the lamina propria of the human vocal fold mucosa are putative stem cells.


Assuntos
Antígenos Glicosídicos Associados a Tumores/metabolismo , Diferenciação Celular/fisiologia , Antígenos Embrionários Estágio-Específicos/metabolismo , Células-Tronco/citologia , Prega Vocal/citologia , Condrogênese/fisiologia , Humanos , Células-Tronco Mesenquimais/citologia , Nicho de Células-Tronco/fisiologia
15.
Pacing Clin Electrophysiol ; 42(2): 132-138, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30478983

RESUMO

BACKGROUND: Atrial arrhythmias are associated with major adverse cardiovascular events. Recent reports among implantable cardioverter defibrillator (ICD) patients have demonstrated a high prevalence of atrial fibrillation (AF), predominantly in dual-chamber recipients. AF incidence among patients with single-chamber systems (approximately 50% of all ICDs) is currently unknown. The objective was to estimate the prevalence of new-onset AF among single-chamber ICD patients by observing the rates of new atrial tachycardia (AT)/AF among a propensity scoring matched cohort of dual-chamber ICD patients from the PainFree SmartShock technology study, to better inform screening initiatives. METHODS: Among 2770 patients enrolled, 1862 single-chamber, dual-chamber, and cardiac resynchronization therapy subjects with no prior history of atrial tachyarrhythmias were included. Daily AT/AF burden was estimated using a propensity score weighted model against data from dual-chamber ICDs. RESULTS: Over 22 ± 9 months of follow-up, the estimated incidence of AT/AF-lasting at least 6 min, 6 h, and 24 h per day -in the single-chamber cohort was 22.0, 9.8, and 6.3%, whereas among dual-chamber patients, the prevalence was 26.6, 13.1, and 7.1%, respectively. Initiation of oral anticoagulation was estimated to occur in 9.8% of the propensity matched single-chamber cohort, which was higher than the actual observed rate of 6.0%. Stroke and transient ischemic attack occurred at low rates in all device subgroups. CONCLUSIONS: Atrial arrhythmias occur frequently, and significant underutilization of anticoagulation is suggested in single-chamber ICD recipients. Routine screening for AF should be considered among single-chamber ICD recipients.


Assuntos
Fibrilação Atrial/epidemiologia , Desfibriladores Implantáveis , Complicações Pós-Operatórias/epidemiologia , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Desenho de Prótese
16.
Pacing Clin Electrophysiol ; 41(9): 1185-1191, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29928759

RESUMO

BACKGROUND: The PainFree Smart Shock Technology (SST) study showed a low implantable cardioverter-defibrillator (ICD) inappropriate shock rate. However, the majority of patients were from Western countries with patient characteristics different from those in Japan. ICD shock rates using the novel SST algorithms in Japanese patients are still unknown. METHODS: All 2,770 patients in the PainFree SST study (Japan [JPN]: N = 181, other geographies [OJPN]: N = 2,589) were included in this analysis. RESULTS: Japanese patients had higher average left ventricular ejection fraction (P < 0.0001), higher prevalence of secondary prevention indications (P < 0.0001), nonischemic cardiomyopathy (P < 0.0001), and permanent atrial fibrillation (P < 0.0001). The appropriate shock rate at 12 months was not different between JPN and OJPN: 6.4% and 6.3%, respectively (P = 0.95). The inappropriate shock rate at 12 months was significantly higher in Japanese patients (2.9% vs 1.7%, P = 0.017). However, after propensity score matching to adjust for the difference in baseline characteristics, the difference in inappropriate shock rate was not statistically significant (P = 0.51). CONCLUSIONS: There was no difference in the appropriate shock rate between Japan and other geographies. The inappropriate shock rate in Japan was low, although it was slightly higher compared to other geographies due to baseline characteristics, including a higher prevalence of permanent AF. There was not a statistically significant difference after adjusting for baseline characteristics.


Assuntos
Morte Súbita Cardíaca/prevenção & controle , Cardioversão Elétrica , Idoso , Algoritmos , Desfibriladores Implantáveis , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Medição da Dor , Pontuação de Propensão , Estudos Prospectivos
17.
Arthritis Rheumatol ; 70(12): 2046-2056, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29905030

RESUMO

OBJECTIVE: T cells from systemic lupus erythematosus (SLE) patients have reduced protein levels of RasGRP1, a guanine nucleotide exchange factor for Ras, and increased transcript of alternatively spliced (AS) forms lacking exon 11. Serine/arginine-rich splicing factor 1 (SRSF1) binds pre-messenger RNA (pre-mRNA) to regulate AS forms of several genes, including CD3ζ in SLE T cells. This study was undertaken to assess whether SRSF1 controls the expression of RasGRP1 in T cells from patients with SLE. METHODS: We studied T cells from 45 SLE patients and 18 healthy subjects. Expression levels of SRSF1, wild-type (WT) RasGRP1, and DNA methyltransferase 1 (DNMT1) were assessed by quantitative polymerase chain reaction. Direct binding of SRSF1 to exon 11 of RasGRP1 mRNA was evaluated with an oligonucleotide-protein pulldown assay. Healthy T cells and SLE T cells were treated with SRSF1-specific small interfering RNA or SRSF1 expression vector, respectively, and then evaluated for mRNA/protein expression. RESULTS: SRSF1 expression levels were significantly lower in T cells from SLE patients compared to those from healthy subjects, and correlated inversely with disease activity and positively with levels of RasGRP1-WT and DNMT1. SRSF1 bound directly to exon 11 of RasGRP1 mRNA. Silencing of SRSF1 in human T cells led to increased ratios of RasGRP1-AS to RasGRP1-WT and decreased levels of RasGRP1 protein, whereas overexpression of SRSF1 in SLE T cells caused recovery of RasGRP1, which in turn induced DNMT1/interleukin-2 expression. CONCLUSION: SRSF1 controls the alternative splicing of RasGRP1 and subsequent protein expression. Our findings extend evidence that alternative splicing plays a central role in the aberrant T cell function in patients with SLE by controlling the expression of multiple genes.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Lúpus Eritematoso Sistêmico/genética , Proteínas Repressoras/metabolismo , Fatores de Processamento de Serina-Arginina/metabolismo , Linfócitos T/metabolismo , Adulto , Estudos de Casos e Controles , Éxons , Feminino , Inativação Gênica , Humanos , Interleucina-2/metabolismo , Masculino , Pessoa de Meia-Idade
18.
Oncol Lett ; 15(5): 8062-8066, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29731914

RESUMO

Primary carcinoid tumors of the middle ear are uncommon. Cytodiagnosis of the middle ear is not usually performed as a preoperative examination because of the anatomical structure of the middle ear. To the best of our knowledge, the present study reports for the first time a case of a carcinoid tumor of the middle ear, which was preoperatively diagnosed using cytodiagnosis, and also review current literature. A 22-year-old woman complained of left-sided otalgia. A subcutaneous tumor in the left middle ear was observed. Magnetic resonance imaging revealed that the tumor was primarily present in the tympanic cavity of the middle ear and extended to the mastoid antrum and mastoid cells of the middle ear and to the external acoustic meatus. Fine needle aspiration cytology was performed from the tumor protruding into the external acoustic meatus. Cytologically, the tumor was composed of small uniform cells with small round nuclei and granular eosinophilic cytoplasm, arranged in a nested pattern. Tumor cells were immunocytochemically positive for synaptophysin and cytokeratin CAM5.2. These results indicated that this was a neuroendocrine tumor. No other tumor lesions were identified on computed tomography scans, and the tumor was considered to be the primary lesion. Tympanoplasty and mastidectomy were then performed and carcinoid tumor was diagnosed in the postoperative pathological diagnosis. To the best of our knowledge, the present study is the first to report on preoperative cytodiagnosis for carcinoid tumors of the middle ear.

19.
Circ J ; 82(6): 1481-1486, 2018 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-29445060

RESUMO

Prevention of sudden cardiac death (SCD) has become an important issue in today's cardiovascular field, together with various developments in secondary prevention of basic cardiac diseases. The importance of the implantable cardioverter defibrillator (ICD) is now widely accepted because it has exhibited significant improvement in patients' prognoses in ischemic and non-ischemic cardiovascular diseases. However, there is an unignorable gap between the ICD indication in the guidelines and real-world high-risk patients for SCD, especially in the acute recovery phase of cardiac injury. Although various studies have demonstrated a clinical benefit of defibrillation devices, the studies of immediate ICD use in the acute recovery phase have failed to exhibit a benefit in patients from the point of the view of a decrease in total deaths. To bridge this gap, the wearable cardioverter defibrillator (WCD) provides a safer observation period in the acute phase and eliminates inappropriate overuse of ICD in the subacute phase. Here, we discuss the usefulness of the WCD and current understanding of its indications based on various clinical data. In conclusion, WCD is a feasible bridge to therapy and/or safe observation for patients at high risk of SCD, especially in the acute recovery phase of cardiac diseases.


Assuntos
Morte Súbita Cardíaca/prevenção & controle , Desfibriladores/normas , Dispositivos Eletrônicos Vestíveis , Doenças Cardiovasculares/terapia , Desfibriladores/tendências , Humanos , Japão
20.
Int J Cardiol ; 255: 85-91, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29425569

RESUMO

BACKGROUND: Electrical storm (E-Storm), defined as multiple episodes of ventricular arrhythmias within a short period of time, is an important clinical problem in patients with an implantable cardiac defibrillator (ICD) including cardiac resynchronization therapy devices capable of defibrillation. The detailed clinical aspects of E-Storm in large populations especially for non-ischemic dilated cardiomyopathy (DCM), however, remain unclear. OBJECTIVE: This study was performed to elucidate the detailed clinical aspects of E-Storm, such as its predictors and prevalence among patients with structural heart disease including DCM. METHODS: We analyzed the data of the Nippon Storm Study, which was a prospective observational study involving 1570 patients enrolled from 48 ICD centers. For the purpose of this study, we evaluated 1274 patients with structural heart disease, including 482 (38%) patients with ischemic heart disease (IHD) and 342 (27%) patients with DCM. RESULTS: During a median follow-up of 28months (interquartile range: 23 to 33months), E-Storm occurred in 84 (6.6%) patients. The incidence of E-Storm was not significantly different between patients with IHD and patients with DCM (log-rank p=0.52). Proportional hazard regression analyses showed that ICD implantation for secondary prevention of sudden cardiac death (p=0.0001) and QRS width (p=0.015) were the independent risk factors for E-storm. In a comparison between patients with and without E-Storm, survival curves after adjustment for clinical characteristics showed a significant difference in mortality. CONCLUSION: E-Storm was associated with subsequent mortality in patients with structural heart disease including DCM.


Assuntos
Terapia de Ressincronização Cardíaca/mortalidade , Cardiomiopatias/mortalidade , Cardiomiopatias/terapia , Desfibriladores Implantáveis , Fibrilação Ventricular/mortalidade , Fibrilação Ventricular/terapia , Idoso , Terapia de Ressincronização Cardíaca/tendências , Cardiomiopatias/fisiopatologia , Desfibriladores Implantáveis/tendências , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Estudos Prospectivos , Sistema de Registros , Fibrilação Ventricular/fisiopatologia
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