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Prognostic impact of the number of involved lymph node stations in patients with completely resected non-small cell lung cancer: a proposal for future revisions of the N classification
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
Influenza A virus enhances ciliary activity and mucociliary clearance via TLR3 in airway epithelium
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
GATA2 mediates the negative regulation of the prepro-thyrotropin-releasing hormone gene by liganded T3 receptor β2 in the rat hypothalamic paraventricular nucleus
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
IGF2 mutations: report of five cases, review of the literature, and comparison with H19/IGF2:IG-DMR epimutations
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
GATA2 mediates the negative regulation of the prepro-thyrotropin-releasing hormone gene by liganded T3 receptor β2 in the rat hypothalamic paraventricular nucleus
Get PDF浜松医科大学博士（医学）doctoral医学系研究科Thyroid hormone (T3) inhibits thyrotropin-releasing hormone (TRH) synthesis in the hypothalamic paraventricular nucleus (PVN). Although the T3 receptor (TR) β2 is known to mediate the negative regulation of the prepro-TRH gene, its molecular mechanism remains unknown. Our previous studies on the T3-dependent negative regulation of the thyrotropin β subunit (TSHβ) gene suggest that there is a tethering mechanism, whereby liganded TRβ2 interferes with the function of the transcription factor, GATA2, a critical activator of the TSHβ gene. Interestingly, the transcription factors Sim1 and Arnt2, the determinants of PVN differentiation in the hypothalamus, are reported to induce expression of TRβ2 and GATA2 in cultured neuronal cells. Here, we confirmed the expression of the GATA2 protein in the TRH neuron of the rat PVN using immunohistochemistry with an anti-GATA2 antibody. According to an experimental study from transgenic mice, a region of the rat prepro-TRH promoter from nt. -547 to nt. +84 was able to mediate its expression in the PVN. We constructed a chloramphenicol acetyltransferase (CAT) reporter gene containing this promoter sequence (rTRH(547)-CAT) and showed that GATA2 activated the promoter in monkey kidneyderived CV1 cells. Deletion and mutation analyses identified a functional GATA-responsive element (GATA-RE) between nt. -357 and nt. -352. When TRβ2 was co-expressed, T3 reduced GATA2-dependent promoter activity to approximately 30%. Unexpectedly, T3-dependent negative regulation was maintained after mutation of the reported negative T3-responsive element, site 4. T3 also inhibited the GATA2-dependent transcription enhanced by cAMP agonist, 8-bromo-cAMP. A rat thyroid medullary carcinoma cell line, CA77, is known to express the preproTRH mRNA. Using a chromatin immunoprecipitation assay with this cell line where GATA2 expression plasmid was transfected, we observed the recognition of the GATA-RE by GATA2. We also confirmed GATA2 binding using gel shift assay with the probe for the GATA-RE. In CA77 cells, the activity of rTRH(547)-CAT was potentiated by overexpression of GATA2, and it was inhibited in a T3-dependent manner.
These results suggest that GATA2 transactivates the rat prepro-TRH gene and that liganded TRβ2 interferes with this activation via a tethering mechanism as in the case of the TSHβ gene.doctoral thesi
Multidisciplinary team management for prevention of pneumonia and long-term weight loss after esophagectomy: a single-center retrospective study
Get PDF浜松医科大学博士（医学）doctoral医学系研究科Background In April 2017, we launched the multidisciplinary Hamamatsu Perioperative Care Team (HOPE) for all surgical patients. We developed a reinforced intervention strategy, particularly for esophagectomy. We herein report the outcomes of the HOPE at 2 years after commencement.
Methods A total 125 patients underwent esophagectomy and gastric conduit reconstruction for esophageal or esophagogastric junction cancer between January 2014 and December 2018 at the Department of Surgery in Hamamatsu University School of Medicine. The patients were divided into the pre-HOPE group including 62 patients who underwent esophagectomy before the introduction of the HOPE and the HOPE group including 63 patients who underwent esophagectomy after the introduction of the HOPE. The outcomes of surgery were compared between the two groups.
Results There were no significant differences in the clinicopathological characteristics between the two groups. The incidence rates of atrial fibrillation and pneumonia were significantly lower in the HOPE group than in the pre-HOPE group (6% vs. 19%, p=0.027 and 14% vs. 29%, p=0.037, respectively). The estimated calorie doses at the time of discharge were approximately 750 and 1500 kcal/day in the pre-HOPE group and the HOPE group, respectively. The body weight loss was significantly less in the HOPE group than the pre-HOPE group at 1, 3, 6, and 12 months postoperatively than that before the surgery (p<0.001).
Conclusions The introduction of the multidisciplinary HOPE was associated with a significant reduction in the incidence of postoperative pneumonia and significantly less weight loss.doctoral thesi
Factors associated with improved quality of life outcomes in patients undergoing surgery for adult spinal deformity
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• Patients with poor preoperative health-related quality of life were more likely to achieve improvement in SRS-22r parameters after extensive corrective fusion surgery for adult spinal deformity.
• Postoperative improvement to sagittal vertical axis increased the likelihood of MCID for the SRS-22r Subtotal domain.
• Revision surgery negatively affected the likelihood of meaningful functional improvements; therefore, minimizing the risk of revision surgery is important.Mini abstract
Patients with poor preoperative health-related quality of life were more likely to achieve functional improvement after extensive corrective fusion surgery for adult spinal deformity. Postoperative improvement to sagittal vertical axis increased the likelihood of MCID for the SRS-22r Subtotal domain.Structured abstract
Study design: Retrospective longitudinal cohort study.
Objective: This study aimed to elucidate factors affecting the likelihood of achieving minimum clinically important difference (MCID) to patient-reported outcomes defined by the Scoliosis Research Society-22r (SRS-22r) among patients with adult spinal deformity (ASD) who underwent extensive corrective fusion surgery from the thoracic spine to the pelvis.
Summary of background data: Achieving MCID for SRS-22r parameters was a measure of surgical efficacy. Patient characteristics and surgical and radiographic factors that affect the likelihood of achieving MCID for SRS-22r parameters are unknown.
Methods: Data from patients with ASD who underwent extensive corrective fusion surgery from the thoracic spine to the pelvis during 2010-2016 were retrospectively reviewed. Data from a total of 167 patients with ≥2 years of follow-up were included. Multivariate analysis was used to investigate factors associated with the likelihood of achieving MCID for each of the SRS-22r domains (Function, Pain, Subtotal) 2 years after surgery. The following MCID values were used: 0.90 for Function, 0.85 for Pain, and 1.05 for the Subtotal.
Results: MCID achievement rate was 36.5% for Function, 46.1% for Pain, and 44.3% for the Subtotal domain. In multivariate analysis, preoperative SRS-22r Function (OR=0.204, 95% CI, 0.105-0.396) increased the likelihood of achieving MCID for SRS-22r Function. Preoperative SRS-22r Subtotal (OR=0.211, 95% CI, 0.107-0.413), preoperative pelvic tilt (OR=1.072, 95% CI, 1.012-1.136), preoperative pelvic incidence minus lumbar lordosis (OR=0.965, 95% CI, 0.934-0.997), and postoperative sagittal vertical axis (OR=0.985, 95% CI, 0.974-0.995) affected the likelihood of achieving MCID for the SRS-22r Subtotal.
Conclusions: Patients with poor preoperative health-related quality of life were more likely to achieve improvement in SRS-22r parameters after extensive corrective fusion surgery for ASD. Achieving postoperative sagittal alignment increased the likelihood of achieving MCID for the SRS-22r Subtotal domain.journal articl
