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1.
Surg Today ; 54(1): 31-40, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37129682

RESUMEN

PURPOSE: Latent lymph node metastasis is a clinical concern in the surgical treatment of non-small cell lung cancer (NSCLC). The present study identified a simple tool, including the volume-doubling time (VDT), for evaluating the risk of nodal metastasis. METHODS: We reviewed, retrospectively, 560 patients who underwent radical resection for cN0M0 NSCLC. The whole tumor VDT and solid component VDT (SVDT) for differentiating the histological type and adenocarcinoma subtype were analyzed and a nomogram was constructed using variables selected through a stepwise selection method. The model was assessed through a calibration curve and decision curve analysis (DCA). RESULTS: Lymph node metastases were detected in 89 patients (15.9%). The SVDT tended to be longer in patients with adenocarcinoma (294.5 days, p < 0.0001) than in those with other histological types of NSCLC, but was shorter when the solid/micropapillary component was predominant (127.0 days, p < 0.0001). The selected variables (tumor location, solid component diameter, consolidation tumor ratio, SVDT, and carcinoembryonic antigen) demonstrated significant differences and were used for the nomogram. The calibration curve indicated consistency, and the DCA showed validity across most threshold ranges from 0 to 68%. CONCLUSIONS: The established nomogram is a useful tool for the preoperative prediction of lymph node metastasis, and the SVDT was the most influential factor in the nomogram.


Asunto(s)
Adenocarcinoma , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/patología , Nomogramas , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Adenocarcinoma/patología , Tomografía Computarizada por Rayos X , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología
2.
Ann Thorac Cardiovasc Surg ; 30(1)2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-37518007

RESUMEN

PURPOSES: Secondary spontaneous pneumothorax (SSP) is occasionally observed in elderly patients suffering from diffuse lung diseases. The purpose of this study was to analyze the outcomes of surgical treatment of SSP patients with chronic lung diseases. METHODS: In total, 242 patients who underwent surgery for spontaneous pneumothorax at Chiba University Hospital from January 2006 to October 2016 were included in this study. The patients' records were reviewed retrospectively for data on their background, surgical treatment, morbidity, mortality, and recurrence. RESULTS: Of the spontaneous pneumothorax cohort, primary spontaneous pneumothorax (PSP) accounted for 144 patients. Among the 98 patients with SSP, 57 cases were caused by chronic obstructive pulmonary disease (COPD) and 21 were caused by interstitial pneumonia (IP). The postoperative complication rate was 19.3% in the COPD group, 42.9% in the IP group, and 11.1% in the PSP group. The recurrence rate was 5.3% in the COPD group, 28.6% in the IP group, and 21.5% in the PSP group. CONCLUSIONS: The morbidity and recurrence were comparable between PSP and SSP cases with COPD, whereas these values were unfavorable in SSP cases with IP compared with PSP ones. Surgical intervention should be carefully considered in SSP patients with IP.


Asunto(s)
Enfermedades Pulmonares Intersticiales , Neumotórax , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Anciano , Neumotórax/diagnóstico por imagen , Neumotórax/etiología , Estudios Retrospectivos , Resultado del Tratamiento , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/cirugía , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/cirugía , Recurrencia , Cirugía Torácica Asistida por Video/efectos adversos
3.
Surg Today ; 54(2): 162-167, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37340140

RESUMEN

PURPOSE: Preoperative investigations to detect invasion to neighboring organs are important for deciding on the most appropriate surgical approach for thymoma. We evaluated preoperative computed tomography (CT) findings in thymoma patients to identify the CT features associated with tumor invasion. METHODS: Clinicopathologic information on 193 patients who underwent surgical resection for thymoma at Chiba University Hospital between 2002 and 2016 was collected retrospectively. The surgical pathology identified invasion of thymoma in 35 patients: in the lung (n = 18), pericardium (n = 11), or both (n = 6). Contact lengths between the tumor contour and lung (CLTL) or pericardium (CLTP) were measured at the maximum section of the tumor on axial CT. Univariate and multivariate analyses were performed to analyze the relationship between pathological invasion of the lung or pericardium and the clinicopathologic features. RESULTS: The mean CLTL and CLTP were significantly longer in patients with invasion of the neighboring organs than in those without invasion. A lobulated tumor contour was identified in 95.6% of the patients with invasion of the neighboring organs. A multivariate analysis revealed that a lobulated tumor contour was significantly associated with both lung and pericardial invasion. CONCLUSIONS: A lobulated tumor contour was significantly associated with lung and/or pericardial invasion in thymoma patients.


Asunto(s)
Timoma , Neoplasias del Timo , Humanos , Timoma/diagnóstico por imagen , Timoma/cirugía , Estudios Retrospectivos , Neoplasias del Timo/diagnóstico por imagen , Neoplasias del Timo/cirugía , Pericardio/diagnóstico por imagen , Pericardio/cirugía , Pulmón/patología
4.
Surg Today ; 54(4): 325-330, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37555929

RESUMEN

PURPOSE: Coccidioidomycosis, caused by the Coccidioides species, is a well-known disease in the Southwestern United States and North Mexico, with scattered reports in Latin America countries. While this disease is still rare in Japan and other Asian countries, its incidence has been increasing over the last two decades. Coccidioides species are highly infectious and require caution when encountered. This study presents a case series of chronic pulmonary coccidioidomycosis surgically treated at a single institution. METHODS: We conducted a retrospective chart review of six patients who underwent lung resection for pulmonary coccidioidomycosis at Chiba University Hospital between January 2007 and December 2021. RESULTS: All six patients had travelled to the Southwestern United States. Preoperative serology was negative for the anti-Coccidioides antibody in four patients and positive in two. Chest computed tomography revealed a single, well-defined round nodule in all patients. Preoperative biopsy taken from three patients failed to obtain a definitive diagnosis. Histopathological examination of the resected pulmonary nodules revealed granulomas that contained numerous spherules with many endospores, thereby confirming the diagnosis of pulmonary coccidioidomycosis. CONCLUSIONS: Pulmonary coccidioidomycosis should be suspected based on travel history and radiological findings. Meticulous care should be taken during specimen processing to prevent cross infection.


Asunto(s)
Coccidioidomicosis , Humanos , Coccidioidomicosis/diagnóstico , Coccidioidomicosis/cirugía , Coccidioidomicosis/epidemiología , Estudios Retrospectivos , Coccidioides , Biopsia , Tomografía Computarizada por Rayos X
6.
Life (Basel) ; 13(10)2023 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-37895424

RESUMEN

Antibody-mediated rejection (AMR) is a risk factor for chronic lung allograft dysfunction, which impedes long-term survival after lung transplantation. There are no reports evaluating the efficacy of the single use of anti-CD20 antibodies (aCD20s) in addition to calcineurin inhibitors in preventing AMR. Thus, this study aimed to evaluate the efficacy of aCD20 treatment in a murine orthotopic lung transplantation model. Murine left lung transplantation was performed using a major alloantigen strain mismatch model (BALBc (H-2d) → C57BL/6 (BL/6) (H-2b)). There were four groups: isograft (BL/6→BL/6) (Iso control), no-medication (Allo control), cyclosporine A (CyA) treated, and CyA plus murine aCD20 (CyA+aCD20) treated groups. Severe neutrophil capillaritis, arteritis, and positive lung C4d staining were observed in the allograft model and CyA-only-treated groups. These findings were significantly improved in the CyA+aCD20 group compared with those in the Allo control and CyA groups. The B cell population in the spleen, lymph node, and graft lung as well as the levels of serum donor-specific IgM and interferon γ were significantly lower in the CyA+aCD20 group than in the CyA group. Calcineurin inhibitor-mediated immunosuppression combined with aCD20 therapy effectively suppressed AMR in lung transplantation by reducing donor-specific antibodies and complement activation.

7.
Sci Immunol ; 8(88): eadg2979, 2023 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-37862432

RESUMEN

Loss of RNA homeostasis underlies numerous neurodegenerative and neuroinflammatory diseases. However, the molecular mechanisms that trigger neuroinflammation are poorly understood. Viral double-stranded RNA (dsRNA) triggers innate immune responses when sensed by host pattern recognition receptors (PRRs) present in all cell types. Here, we report that human neurons intrinsically carry exceptionally high levels of immunostimulatory dsRNAs and identify long 3'UTRs as giving rise to neuronal dsRNA structures. We found that the neuron-enriched ELAVL family of genes (ELAVL2, ELAVL3, and ELAVL4) can increase (i) 3'UTR length, (ii) dsRNA load, and (iii) activation of dsRNA-sensing PRRs such as MDA5, PKR, and TLR3. In wild-type neurons, neuronal dsRNAs signaled through PRRs to induce tonic production of the antiviral type I interferon. Depleting ELAVL2 in WT neurons led to global shortening of 3'UTR length, reduced immunostimulatory dsRNA levels, and rendered WT neurons susceptible to herpes simplex virus and Zika virus infection. Neurons deficient in ADAR1, a dsRNA-editing enzyme mutated in the neuroinflammatory disorder Aicardi-Goutières syndrome, exhibited intolerably high levels of dsRNA that triggered PRR-mediated toxic inflammation and neuronal death. Depleting ELAVL2 in ADAR1 knockout neurons led to prolonged neuron survival by reducing immunostimulatory dsRNA levels. In summary, neurons are specialized cells where PRRs constantly sense "self" dsRNAs to preemptively induce protective antiviral immunity, but maintaining RNA homeostasis is paramount to prevent pathological neuroinflammation.


Asunto(s)
Infección por el Virus Zika , Virus Zika , Humanos , Regiones no Traducidas 3'/genética , ARN Bicatenario , Enfermedades Neuroinflamatorias , Inflamación , Receptores de Reconocimiento de Patrones/genética , Neuronas
8.
J Thorac Dis ; 15(7): 3840-3848, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37559661

RESUMEN

Background: Robot-assisted thoracic surgery (RATS) has become widely used for mediastinal procedures since 2018 when it was included in insurance coverage in Japan. Few studies have compared the surgical outcomes of RATS with the more established video-assisted thoracic surgery (VATS) approach to mediastinal surgery. We aimed to compare the perioperative outcomes of VATS and RATS to examine the advantages of the RATS approach in a single institutional cohort. Methods: A total of 144 patients who underwent VATS and 46 who underwent RATS mediastinal surgery between 2014 and 2022 were enrolled. We compared clinicopathological features such as age, sex, smoking history, respiratory function, surgical field, laterality, surgical procedure, board certification of the surgeon, and histology between the two groups. Perioperative outcomes including operation time, volume of blood lost, number of conversion cases to open surgery, duration of chest drainage, postoperative hospital stay, and postoperative complications were also reviewed. Results: The comparison of patient characteristics between the groups showed significant differences in median age (VATS, 52.5 years; RATS, 67.0 years; P=0.001), combined resection of surrounding tissues of the tumor (VATS, 2.1%; RATS, 10.9%; P=0.02), board certification of the surgeon (VATS, 53.5%; RATS, 100.0%; P<0.001), and histology (RATS group had a higher percentage of thymic epithelial tumors, P=0.01). Regarding perioperative outcomes, the median operation time was 120 min in the VATS group and 88 min in the RATS group, showing a significant difference (P=0.03). There were no significant differences in the volume of blood lost, incidence of conversion to open chest surgery, duration of chest drainage, postoperative length of stay in hospital, and incidence of perioperative complications. In the perioperative outcomes of cases operated on by board-certified surgeons, the median operation time (VATS, 117 min; RATS, 88 min; P=0.02) and median postoperative length of stay in hospital (VATS, 7 days; RATS, 6 days; P=0.001) showed significant differences, while other postoperative outcomes were not significantly different. Conclusions: RATS for mediastinal surgery is as safe as the VATS approach and may result in a shorter operative time and postoperative hospital stay. Further analysis of RATS for mediastinal surgery in a larger cohort is warranted.

9.
Nat Immunol ; 24(8): 1256-1264, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37400674

RESUMEN

Innate lymphoid cells (ILCs) can quickly switch from a quiescent state to an active state and rapidly produce effector molecules that provide critical early immune protection. How the post-transcriptional machinery processes different stimuli and initiates robust gene expression in ILCs is poorly understood. Here, we show that deletion of the N6-methyladenosine (m6A) writer protein METTL3 has little impact on ILC homeostasis or cytokine-induced ILC1 or ILC3 responses but significantly diminishes ILC2 proliferation, migration and effector cytokine production and results in impaired antihelminth immunity. m6A RNA modification supports an increase in cell size and transcriptional activity in activated ILC2s but not in ILC1s or ILC3s. Among other transcripts, the gene encoding the transcription factor GATA3 is highly m6A methylated in ILC2s. Targeted m6A demethylation destabilizes nascent Gata3 mRNA and abolishes the upregulation of GATA3 and ILC2 activation. Our study suggests a lineage-specific requirement of m6A for ILC2 responses.


Asunto(s)
Inmunidad Innata , Linfocitos , Citocinas/metabolismo , Homeostasis , Inmunidad Innata/genética , Inmunidad Innata/inmunología , Linfocitos/inmunología , ARN/metabolismo , Animales , Ratones
10.
Kyobu Geka ; 76(7): 512-517, 2023 Jul.
Artículo en Japonés | MEDLINE | ID: mdl-37475093

RESUMEN

In Japan, robot-assisted thoracic surgery (RATS) was introduced in thoracic surgery in 2001, but it did not become widespread. However, surgery for mediastinal tumors and lobectomy for lung cancer with RATS were covered by insurance in 2018 and are currently becoming popular as a general practice, following video-assisted thoracic surgery(VATS). Forty-six patients with mediastinal tumors were treated by RATS from February 2014 to November 2022 in our institution. Theoretically, the RATS approach is performed from one side in a semi-supine position under CO2 insufflation as with the VATS approach of our institution. In the case of extended thymectomy, a bilateral approach is performed by changing the patient's position. The median surgery time was 88 min, and the median surgery time in unilateral and bilateral approaches were 79 and 208 min, respectively. Blood loss during surgery was quite minimum, and no patients required conversion to VATS or thoracotomy. Regarding adverse events, postoperative bleeding was observed in one patient (2.2%). RATS has been successfully introduced and expanded safely for mediastinal tumors. Considering further expansion of RATS indications while conducting verification by comparison with VATS in the future is necessary.


Asunto(s)
Neoplasias Pulmonares , Neoplasias del Mediastino , Robótica , Cirugía Torácica , Humanos , Neoplasias del Mediastino/cirugía , Neoplasias Pulmonares/cirugía , Cirugía Torácica Asistida por Video , Estudios Retrospectivos
11.
J Thorac Dis ; 15(4): 1640-1647, 2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37197533

RESUMEN

Background: In the surgical treatment of chest wall tumors requiring large chest wall resection, reconstruction of the chest wall defect is required using various autologous tissues or artificial materials. However, no appropriate method has been reported to evaluate whether each reconstruction is successful or not. Therefore, we performed lung volumetry before and after surgery to evaluate the negative effects of chest wall surgery on lung expansion. Methods: Twenty-three patients with chest wall tumors who underwent surgery were included in this study. Lung volume (LV) before and after surgery was measured using SYNAPSE VINSENT (FUJIFILM, Tokyo, Japan). The rate of change in LV was calculated as the postoperative and preoperative LV of the operative side × preoperative/postoperative LV of the opposite side. The excised chest wall area was calculated as vertical diameter × horizontal diameter of the tissue specimen. Results: Reconstruction methods included rigid reconstruction (a combination of titanium mesh and extended polytetrafluoroethylene sheet) in four patients, non-rigid reconstruction (extended polytetrafluoroethylene sheet only) in 11, no reconstruction in five, and no chest wall resection in three. Changes in LV were generally well preserved, regardless of the resected area. In addition, LVs were well maintained in most patients who underwent chest wall reconstruction. However, in some cases, decreased lung expansion was observed with migration and deflection of the reconstructive material into the thorax due to postoperative lung inflammation and shrinking. Conclusions: Lung volumetry can be used to evaluate the effectiveness of chest wall surgery.

12.
Artículo en Inglés | MEDLINE | ID: mdl-36102798

RESUMEN

OBJECTIVES: This study aimed to evaluate the efficacy and safety of intraoperative cone-beam computed tomography-guided video-assisted thoracoscopic surgery wedge resection of impalpable small pulmonary nodules. METHODS: This was a single-centre phase 2 trial conducted between April 2018 and March 2019. Peripheral small pulmonary nodules, defined as either ground-glass opacity-dominant (>50%) nodules measuring ≤3 cm in diameter (ground-glass opacity-dominant type) or nodules measuring ≤2 cm in diameter located deeper than the nodule diameter from the visceral pleura (deep solid type), were eligible for resection using a cone-beam computed tomography-guided thoracoscopic manner. The primary end-point was macroscopic complete resection, and secondary end-points were: nodule extraction rate, operation time, localization time, marking accuracy, microscopic complete resection and safety. RESULTS: Twenty-two nodules, in 9 men and 11 women with a mean age of 64.3 years, were visualized and resected. The nodules were located in the right upper, middle and lower lobes in 3, 1 and 5 patients, respectively, and in the left upper and lower lobes in 5 and 8 patients, respectively. Seven nodules were ground-glass opacity-dominant types, and 15 were deep solid types. Cone-beam computed tomography could clearly image all nodules. The mean time for localization was 17.4 min. The mean operation time was 110.7 min. Macroscopic complete resection was accomplished in 21 nodules (95.5%). Microscopic complete resection was achieved in all nodules (100%). Postoperative air leakage and bleeding were observed in 1 patient (5%). CONCLUSIONS: Cone-beam computed tomography might be a safe and useful guide for video-assisted thoracoscopic surgery wedge resection of impalpable peripheral pulmonary nodules. DATE AND NUMBER OF IRB APPROVAL: 15 November 2017, 381. CLINICAL TRIAL REGISTRATION NUMBER: UMIN 000030388.


Asunto(s)
Neoplasias Pulmonares , Nódulos Pulmonares Múltiples , Nódulo Pulmonar Solitario , Tomografía Computarizada de Haz Cónico , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Nódulos Pulmonares Múltiples/cirugía , Estudios Retrospectivos , Nódulo Pulmonar Solitario/diagnóstico por imagen , Nódulo Pulmonar Solitario/cirugía , Cirugía Torácica Asistida por Video/efectos adversos , Cirugía Torácica Asistida por Video/métodos , Tomografía Computarizada por Rayos X/métodos
13.
Intern Med ; 61(12): 1823-1833, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35705311

RESUMEN

Objective Evaluating the rate of decline in the estimated glomerular filtration rate (eGFR) may help identify patients with occult chronic kidney disease (CKD). We herein report that eGFR fluctuation complicates the assessment of the rate of decline and propose a long-term eGFR plot analysis as a solution. Methods In 142 patients with persistent eGFR decline in a single hospital, we evaluated the factors influencing the rate of eGFR decline, calculated over the long term (≥3 years) and short term (<3 years) using eGFR plots, taking into account eGFR fluctuation between visits. Results The difference between the rate of eGFR decline calculated using short- and long-term plots increased as the time period considered in the short-term plots became shorter. A regression analysis revealed that eGFR fluctuation was the only factor that explained the difference and that the fluctuation exceeded the annual eGFR decline in all participants. Furthermore, the larger the eGFR fluctuation, the more difficult it became to detect eGFR decline using a short-term eGFR analysis. Obesity, a high eGFR at baseline, and faster eGFR decline were associated with larger eGFR fluctuations. To circumvent the issue of eGFR fluctuation in the assessment of the rate of eGFR decline, we developed a system that generates a long-term eGFR plot using all eGFR values for a participant, which enabled the detection of occult CKD, facilitating early therapeutic intervention. Conclusion The construction of long-term eGFR plots is useful for identifying patients with progressive eGFR decline, as it minimizes the effect of eGFR fluctuation.


Asunto(s)
Insuficiencia Renal Crónica , Tasa de Filtración Glomerular , Humanos , Riñón/fisiología , Obesidad , Análisis de Regresión , Factores de Riesgo
14.
Kyobu Geka ; 75(4): 244-251, 2022 Apr.
Artículo en Japonés | MEDLINE | ID: mdl-35342153

RESUMEN

Lung transplantation has become popular in Japan, showing better survival rate than other countries. However, the results are still not satisfactory compared with other solid organ transplantation. One of the reasons for this might be that knowledge on donor-specific antibodies or antibody-related rejection, which has been attracting attention these days, is less than that of kidney or liver transplantation. Our laboratory has continued basic research in this field using rodent lung transplantation model. We have previously shown that type V collagen is associated in chronic rejection as an autoimmune, and that oral administration of type V collagen induces tolerance. The murine chronic rejection model of the minor antigen mismatch was developed, and involvement of the humoral immunity and role of the complement activation were shown. We are now studying the effects of immune checkpoint molecules, which play a central role in the field of cancer therapy, on rejection after lung transplantation. We are also working to verify the effects of anti-complement drugs and molecular targeted drugs in the future treatment on rejection.


Asunto(s)
Rechazo de Injerto , Trasplante de Pulmón , Animales , Anticuerpos , Reacciones Antígeno-Anticuerpo , Rechazo de Injerto/prevención & control , Humanos , Japón , Ratones
15.
PLoS One ; 17(1): e0262277, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34986190

RESUMEN

DNA methylation (DNAme; 5-methylcytosine, 5mC) plays an essential role in mammalian development, and the 5mC profile is regulated by a balance of opposing enzymatic activities: DNA methyltransferases (DNMTs) and Ten-eleven translocation dioxygenases (TETs). In mouse embryonic stem cells (ESCs), de novo DNAme by DNMT3 family enzymes, demethylation by the TET-mediated conversion of 5mC to 5-hydroxymethylation (5hmC), and maintenance of the remaining DNAme by DNMT1 are actively repeated throughout cell cycles, dynamically forming a constant 5mC profile. Nevertheless, the detailed mechanism and physiological significance of this active cyclic DNA modification in mouse ESCs remain unclear. Here by visualizing the localization of DNA modifications on metaphase chromosomes and comparing whole-genome methylation profiles before and after the mid-S phase in ESCs lacking Dnmt1 (1KO ESCs), we demonstrated that in 1KO ESCs, DNMT3-mediated remethylation was interrupted during and after DNA replication. This results in a marked asymmetry in the distribution of 5hmC between sister chromatids at mitosis, with one chromatid being almost no 5hmC. When introduced in 1KO ESCs, the catalytically inactive form of DNMT1 (DNMT1CI) induced an increase in DNAme in pericentric heterochromatin and the DNAme-independent repression of IAPEz, a retrotransposon family, in 1KO ESCs. However, DNMT1CI could not restore the ability of DNMT3 to methylate unmodified dsDNA de novo in S phase in 1KO ESCs. Furthermore, during in vitro differentiation into epiblasts, 1KO ESCs expressing DNMT1CI showed an even stronger tendency to differentiate into the primitive endoderm than 1KO ESCs and were readily reprogrammed into the primitive streak via an epiblast-like cell state, reconfirming the importance of DNMT1 enzymatic activity at the onset of epiblast differentiation. These results indicate a novel function of DNMT1, in which DNMT1 actively regulates the timing and genomic targets of de novo methylation by DNMT3 in an enzymatic activity-dependent and independent manner, respectively.


Asunto(s)
ADN (Citosina-5-)-Metiltransferasa 1/genética , Metilación de ADN/genética , ADN Metiltransferasa 3A/genética , Células Madre Embrionarias de Ratones/metabolismo , 5-Metilcitosina/metabolismo , Animales , Diferenciación Celular/genética , Metilasas de Modificación del ADN/genética , Proteínas de Unión al ADN/genética , Impresión Genómica/genética , Heterocromatina/genética , Ratones , Ratones Noqueados , Retroelementos/genética
16.
J Cardiothorac Surg ; 16(1): 258, 2021 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-34496897

RESUMEN

BACKGROUND: A pulmonary arteriovenous malformation is an abnormal dilated blood vessel that makes direct communication between a pulmonary artery and pulmonary vein and can be associated with hypoxemia or neurological complications, including brain abscess and cerebral infarction. Treatment of pulmonary arteriovenous malformation includes surgical resection and transcatheter embolotherapy, however the adaptation of therapies should be considered when a patient is in bad condition. CASE PRESENTATION: A 51-year-old man was admitted after developing fever, consciousness disorder, and hypoxemia. Magnetic resonance imaging of the brain showed a brain abscess. Bilateral pulmonary arteriovenous malformations were found by contrast computed tomography. Because of a family history of pulmonary arteriovenous malformation, a history of epistaxis, and the existence of oral mucosa telangiectasia, he was diagnosed with hereditary hemorrhagic telangiectasia and brain abscess caused by intrapulmonary right-to-left shunt. The brain abscess improved with antibiotic treatment; however, the administration of oxygen did not ameliorate his hypoxemia. His hypoxemia was exacerbated by positive pressure ventilation. Considering his systemic and respiratory condition, we considered surgery to involve a high degree of risk. After controlling his brain abscess and pneumonia, transcatheter embolotherapy was performed. This improved his systemic condition, enabling surgical treatment. CONCLUSIONS: This middle-aged patient suffering from brain abscess and severe hypoxemia with multiple pulmonary arteriovenous malformations was successfully treated by a combination of transcatheter embolotherapy and surgery. The adaptation and combination of therapies, as well as the sequence of treatments, should be considered depending on the patient status and lesions.


Asunto(s)
Malformaciones Arteriovenosas , Absceso Encefálico , Embolización Terapéutica , Venas Pulmonares , Malformaciones Arteriovenosas/complicaciones , Malformaciones Arteriovenosas/diagnóstico por imagen , Malformaciones Arteriovenosas/terapia , Absceso Encefálico/diagnóstico por imagen , Absceso Encefálico/cirugía , Humanos , Hipoxia/etiología , Hipoxia/terapia , Masculino , Persona de Mediana Edad , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/cirugía , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/cirugía
17.
J Infect Chemother ; 27(7): 1072-1075, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33814353

RESUMEN

The coronavirus disease of 2019 (COVID-19), which began in Wuhan, China, at the end of 2019, is spreading around the world and causing many deaths, mainly from pneumonia. Currently, there are no specific drugs to treat COVID-19, and existing antiviral drugs are being used as an alternative. One of these is favipiravir, a new type of influenza drug. However, its efficacy, dosage, and duration of administration are still under study. In this case study, we administered favipiravir to patients with COVID-19 and determined the viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the COVID-19 pathogen, using semi-quantitative real-time reverse transcription PCR in sputum samples. We report on two patients in whom the viral load increased again after completion of 10 days of favipiravir treatment and a transient relapse of symptoms was observed.


Asunto(s)
COVID-19 , Transcripción Reversa , Amidas , China , Humanos , Pirazinas , Reacción en Cadena en Tiempo Real de la Polimerasa , Recurrencia , SARS-CoV-2
18.
Genes Genomics ; 43(3): 269-280, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33555502

RESUMEN

BACKGROUND: DNA methylation is a significant epigenetic modification that is evolutionarily conserved in various species and often serves as a repressive mark for transcription. DNA methylation levels and patterns are regulated by a balance of opposing enzyme functions, DNA methyltransferases, DNMT1/3A/3B and methylcytosine dioxygenases, TET1/2/3. In mice, the TET enzyme converts DNA cytosine methylation (5mC) to 5-hydroxymethylcytosine (5hmC) at the beginning of fertilisation and gastrulation and initiates a global loss of 5mC, while the 5mC level is increased on the onset of cell differentiation during early embryonic development. OBJECTIVE: Global loss and gain of DNA methylation may be differently regulated in diverged species. METHODS: Chicken B-cell lymphoma DT40 cells were used as an avian model to compare differences in the overall regulation of DNA modification with mammals. RESULTS: We found that DNA methylation is maintained at high levels in DT40 cells through compact chromatin formation, which inhibits TET-mediated demethylation. Human and mouse chromosomes introduced into DT40 cells by cell fusion lost the majority of 5mC, except for human subtelomeric repeats. CONCLUSION: Our attempt to elucidate the differences in the epigenetic regulatory mechanisms between birds and mammals explored the evidence that they share a common chromatin-based regulation of TET-DNA access, while chicken DNMT1 is involved in different target sequence recognition systems, suggesting that factors inducing DNMT-DNA association have already diverged.


Asunto(s)
Desmetilación del ADN , Metilación de ADN , Animales , Línea Celular Tumoral , Células Cultivadas , Pollos/genética , Cromatina , Metilasas de Modificación del ADN/metabolismo , Dioxigenasas/metabolismo , Femenino , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Ratones , Células Madre Embrionarias de Ratones/metabolismo
19.
ACS Omega ; 6(1): 649-655, 2021 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-33458517

RESUMEN

We synthesized silica-coated barium titanate (BaTiO3) particles with different silica shell thicknesses and evaluated the effect of silica coating on the relative dielectric properties of silica-coated BaTiO3 particles. Furthermore, composite elastomers were prepared using hydrogenated carboxylated acrylonitrile-butadiene rubber (HXNBR) with a high relative dielectric constant (εr) and silica-coated BaTiO3 particles, and their performance as an actuator was evaluated. Both εr and relative dielectric loss of non-coated BaTiO3 particles increased at low frequencies (<200 Hz) associated with ionic conduction. However, εr and relative dielectric loss were reduced for the silica-coated BaTiO3 particles with thick silica shells, indicating that silica coating reduced ion migration. The dielectric breakdown strength increased with the thickness of the silica shell; it increased up to 80 V/µm for HXNBR/silica-coated BaTiO3 particles with 20 nm-thick silica shells. The maximum generated stress, strain, and output energy density of the composite elastomer with HXNBR (with a high relative constant) and silica-coated BaTiO3 were 1.0 MPa, 7.7%, and 19.4 kJ/m3, respectively. In contrast, the values of the same parameters for a reference elastomer (acrylic/BaTiO3; with low εr) were 0.4 MPa, 6.7%, and 6.8 kJ/m3 at the dielectric breakdown strength of 70 V/µm. The results indicated that the elastomers composed of HXNBR and silica-coated BaTiO3 exhibited higher generated stress, strain, and output energy density than elastomers for conventional dielectric actuators.

20.
Diabetes Technol Ther ; 23(1): 78-80, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32639844

RESUMEN

Diabetes is associated with mortality and severity of coronavirus disease (COVID-19). Protecting against infection in health care workers at high risk of COVID-19 is critical. This report investigates the usefulness and safety of remote continuous glucose monitoring (CGM) in a patient with diabetes and severe interstitial pneumonia caused by the coronavirus disease. The Dexcom G4 Platinum CGM system® was used to monitor blood glucose (BG) levels from outside the patient's isolation room. Continuous insulin infusion rates and boluses were determined based on the patient's BG levels. Real-time CGM made it possible to track BG trends and prevent dramatic variations in BG, although the rate of insulin infusion changed dynamic. Furthermore, the need for health care workers to enter the isolation room was minimized because the Dexcom G4 Platinum CGM system can evaluate from a distance of up to 6.0 m.


Asunto(s)
Automonitorización de la Glucosa Sanguínea/métodos , COVID-19/epidemiología , COVID-19/terapia , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/terapia , SARS-CoV-2 , Anciano , Glucemia/análisis , Comorbilidad , Diabetes Mellitus Tipo 2/sangre , Oxigenación por Membrana Extracorpórea , Humanos , Insulina/administración & dosificación , Masculino , Diálisis Renal
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