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1.
Heart Vessels ; 2024 May 08.
Article in English | MEDLINE | ID: mdl-38717698

ABSTRACT

MicroRNA(miR)-143 and miR-145 are mainly expressed in vascular smooth muscle cells. However, the relationship between plasma miR-143 or miR-145 levels and the left ventricular (LV) function in patients with heart diseases remains unclear. Blood samples were taken from the antecubital vein in patients with heart diseases (n = 52), such as coronary artery disease, old myocardial infarction, cardiomyopathy, and valvular heart disease, and controls without heart diseases (n = 22). We measured plasma miR-143 and -145 levels by quantitative RT-PCR using TaqMan MicroRNA Assays and THUNDERBIRD Probe qPCR Mix. Plasma BNP levels were also measured. Echocardiography was performed to measure the LV ejection fraction (LVEF) and LV dilation. Plasma miR-143 and miR-145 levels were significantly higher in patients with heart diseases than in controls, respectively. Plasma miR-143 and miR-145 levels were significantly higher in patients with LVEF < 50% than in those with LVEF ≧ 50%, respectively. Plasma miR-143 and miR-145 levels were inversely correlated with LVEF, respectively. Plasma miR-143 and miR-145 levels were positively correlated with LV end-systolic dimension, respectively. Plasma miR-143 and -145 levels were positively correlated with plasma BNP levels, respectively. Plasma BNP levels were inversely correlated with LVEF. Plasma miR-143 and miR-145 levels are elevated in patients with LV dysfunction and may counteract LV dysfunction.

2.
Lymphat Res Biol ; 22(2): 131-137, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38563976

ABSTRACT

Background: We aimed to determine the course of arm swelling caused by the use of taxanes and to identify valid predictors of persistent swelling. Methods and Results: A total of 15 patients with unilateral arm swelling that developed during the course, or within 3 months after termination, of postoperative taxane-based chemotherapy were included in the present study. The patients attended follow-up appointments every 3-6 months for 24 months after their initial visit. Their arm circumference was measured at each follow-up appointment, while ultrasonography of the skin and subcutaneous tissues was performed at the 0-, 6-, 12-, and 24-month follow-ups. Of the 15 patients, 12 (80%) saw their taxane-induced arm swelling resolved within a median of 12 months (range, 3-29 months) after their final taxane administration. Of the 12 patients whose swelling resolved, 9 did not use compression sleeves; however, their course of resolution did not differ from the other 3 patients who regularly used compression sleeves. In the three patients with persistent swelling, the excess subcutaneous thickness in the medial upper arm (median, 283%) was significantly greater than that in the patients whose swelling resolved (120%; p < 0.05) during their initial visits. Conclusions: Of the 15 patients included in the present study, 80% saw their taxane-induced arm swelling resolve within a median of 12 months after their final taxane administration, independent of the use of compression therapy. Persistent swelling may be predicted during the initial visit based on subcutaneous thickening of the medial upper arm.


Subject(s)
Lymphedema , Humans , Lymphedema/etiology , Taxoids , Bridged-Ring Compounds/adverse effects , Arm
3.
J Surg Res ; 296: 589-596, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38340493

ABSTRACT

INTRODUCTION: We previously demonstrated the usefulness of combining stitching with covering to seal alveolar air leaks in an animal model. This study aimed to clarify the effectiveness and feasibility of this sealing method in the clinical setting. METHODS: Data of 493 patients who underwent thoracoscopic anatomical resection between 2013 and 2020 for lung cancer were retrospectively reviewed. Prolonged air leak was defined as chest drain placement lasting 5 d or longer due to air leak. Until July 2017 (early study period), we covered air leaks using mesh. However, for sealing (late study period), we additionally stitched leaks with pledget in patients at high risk of prolonged air leak. The pneumostasis procedure, intraoperative confirmation test of pneumostasis, and chest tube management were uniform during both periods. RESULTS: The incidence of prolonged air leak was significantly lower in the late than in the early period (3.6% versus 12.5%), whereas pulmonary emphysema was more severe in the late period compared to the early period. Intraoperative failure of sealing air leaks was significantly reduced in the late period than in the early period. In both univariate and propensity score matching analysis, the study period was a significant predictor of prolonged air leak. CONCLUSIONS: The combination of stitching and covering with mesh may contribute to reducing prolonged air leak incidence in patients undergoing thoracoscopic anatomical lung resection for lung cancer.


Subject(s)
Lung Neoplasms , Pneumonectomy , Animals , Humans , Pneumonectomy/adverse effects , Pneumonectomy/methods , Retrospective Studies , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Lung Neoplasms/surgery , Chest Tubes/adverse effects , Lung/surgery
4.
Sensors (Basel) ; 24(3)2024 Jan 28.
Article in English | MEDLINE | ID: mdl-38339561

ABSTRACT

This research proposes a novel approach to global path and resource planning for lunar rovers. The proposed method incorporates a range of constraints, including static, time-variant, and path-dependent factors related to environmental conditions and the rover's internal resource status. These constraints are integrated into a grid map as a penalty function, and a reinforcement learning-based framework is employed to address the resource constrained shortest path problem (RCSP). Compared to existing approaches referenced in the literature, our proposed method enables the simultaneous consideration of a broader spectrum of constraints. This enhanced flexibility leads to improved path search optimality. To evaluate the performance of our approach, this research applied the proposed learning architecture to lunar rover path search problems, generated based on real lunar digital elevation data. The simulation results demonstrate that our architecture successfully identifies a rover path while consistently adhering to user-defined environmental and rover resource safety criteria across all positions and time epochs. Furthermore, the simulation results indicate that our approach surpasses conventional methods that solely rely on environmental constraints.

6.
Asian J Endosc Surg ; 16(4): 800-803, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37586698

ABSTRACT

Surgical approaches for traumatic diaphragmatic hernia include transabdominal, transthoracic, and thoracoabdominal. Selection of the optimal approach depends on the timing and organ damage, often minimally invasive approaches with laparoscopy or thoracoscopy are performed. A 47-year-old man with blunt chest trauma was diagnosed with left traumatic diaphragmatic hernia 1 month after the trauma. The prolapsed omentum was detached from the chest wall and around the hernia orifice and returned to the abdominal cavity by coordinated thoracoscopic and laparoscopic manipulations. The 4 × 2 cm herniation in the diaphragm was sutured closed from the thoracic side while preventing re-prolapse of the omentum and abdominal organs from the abdominal side. A combined thoracoscopic and laparoscopic approach can be effective in confirming organ damage, repositioning of prolapsed organs, and safe repair of the diaphragm in latent traumatic diaphragmatic hernia.


Subject(s)
Hernia, Diaphragmatic, Traumatic , Hernia, Diaphragmatic , Laparoscopy , Thoracic Injuries , Wounds, Nonpenetrating , Male , Humans , Middle Aged , Hernia, Diaphragmatic, Traumatic/diagnostic imaging , Hernia, Diaphragmatic, Traumatic/etiology , Thoracic Injuries/complications , Wounds, Nonpenetrating/complications , Wounds, Nonpenetrating/surgery , Hernia, Diaphragmatic/surgery , Laparoscopy/adverse effects
7.
J Cardiothorac Surg ; 18(1): 249, 2023 Aug 21.
Article in English | MEDLINE | ID: mdl-37605209

ABSTRACT

BACKGROUND: Although thoracic surgeons occasionally encounter dense adhesions of interlobar lymph node anthracosilicosis with the pulmonary artery, adhesiolysis may be challenging. Besides, characteristic microscopic features of the adherent lesion remain limited. CASE PRESENTATION: During a thoracoscopic right upper lobectomy of a patient with stage IA3 primary lung adenocarcinoma, several interlobar lymph nodes adhered to the posterior ascending branch of the pulmonary artery to the right upper lobe were noted. After an unplanned conversion to a thoracotomy to avoid massive bleeding, the pulmonary artery branch was safely isolated. Microscopic examination revealed lymph node anthracosilicosis proximal to the peripheral pulmonary artery wall, with granulomatous inflammation. The adventitial stroma of the pulmonary artery developed into dense and borderless fibrous tissue with dust-laden macrophages. CONCLUSIONS: Our pathological findings on lymph node anthracosilicosis provide substantial evidence that adhesions between lymph nodes and the pulmonary artery walls may develop into dense and borderless fibrous tissue. This finding would remind thoracic surgeons that adhesiolysis could cause injury to the pulmonary artery.


Subject(s)
Anthracosilicosis , Lung Neoplasms , Humans , Pulmonary Artery/surgery , Tissue Adhesions , Lymph Nodes
8.
Biochem Biophys Rep ; 35: 101510, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37457362

ABSTRACT

In our previous study, we found that dry-preserved multilayered fibroblast cell sheets promoted angiogenesis and wound healing in a mouse ulcer model by releasing high levels of intracellular fibroblast growth factor 2 (FGF2), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF), from dried cells. In the present study, to identify which cell types are suitable for human dry-preserved cell sheets (dry sheets), we compared the intracellular FGF2 levels in seven types of cells reported as cell sheets for clinical use or preclinical studies. FGF2 levels were high in mesenchymal cells, including human oral fibroblasts (HOFs) and human dermal fibroblasts (HDFs), human dental pulp stem cells (DPSCs), and human mesenchymal stem cells (MSCs); in contrast, FGF2 levels in human umbilical vascular endothelial cells (HUVECs), human skeletal muscle myoblasts (SkMMs), and human epidermal keratinocytes (HEKs) were remarkably low, approximately 25% those in fibroblasts. In addition, we prepared dry sheets from HOFs, DPSCs, and MSCs, and analyzed the growth factors released from each dry sheet upon rehydration. High levels of FGF2, HGF, and VEGF were detected in the eluate prepared by immersing each dry sheet. In particular, FGF2 and HGF were the most abundant in HOFs. An in vitro cell proliferation assay showed that these eluates significantly enhanced HUVEC proliferation compared to control cells. Furthermore, cells incubated with HOF eluate showed significantly higher cell proliferation than cells incubated with DPSC and MSC eluates. However, this proliferative response was significantly blocked by FGF2-neutralizing antibodies. These results demonstrate that growth factors released from human dry sheets have physiological activity and that this activity is mainly mediated by the effect of FGF2. Fibroblasts are ideal for the clinical application of dry-preserved cell sheets in humans owing to their high intracellular FGF2 content, fast cell proliferation, ease of handling, availability, and low culture costs, making them the most suitable cell source for regenerative medicine, with FGF2 release as the mechanism of action.

9.
Am J Transl Res ; 15(5): 3217-3228, 2023.
Article in English | MEDLINE | ID: mdl-37303629

ABSTRACT

OBJECTIVE: Anastomotic leakage is a common and severe complication of esophageal reconstruction. Accordingly, there is a clinical need for novel methods to prevent it. We developed multilayered, growth factor-secreting fibroblast sheets that promote wound healing and angiogenesis. The present study aimed to assess the utility of allogenic multilayered fibroblast sheets in preventing esophageal anastomotic leakage in a rat model of esophageal reconstruction. METHODS: Allogenic multilayered fibroblast sheets prepared from oral mucosal tissues were implanted at esophageal anastomotic sites. RESULTS: The allogenic multilayered fibroblast sheet group had significantly higher burst pressure and collagen deposition compared to a control group five days postoperatively. The expression levels of collagen type I and III mRNAs around esophageal suture sites were higher in the allogenic multilayered fibroblast sheet group compared to the control group on postoperative days 0, 3, and 5. There was a trend toward lower anastomotic leakage and lower abscess scores in the allogenic multilayered fibroblast sheet group compared to the control group; however, these differences did not reach statistical significance. Allogenic multilayered fibroblast sheets completely disappeared at ten days after implantation. Further, no inflammation was observed at suture sites with implanted allogenic multilayered fibroblast sheets at five days after surgery. CONCLUSION: Allogenic multilayered fibroblast sheets may represent a promising method of preventing esophageal anastomotic leakage.

10.
Eur J Cardiothorac Surg ; 63(5)2023 05 02.
Article in English | MEDLINE | ID: mdl-37067497

ABSTRACT

OBJECTIVES: Covering the bronchial stump with free fat tissue has been used as minimally invasive prophylaxis against bronchial stump fistulas; however, postoperative changes in the bronchial stump have not been well validated. Our goal was to examine changes in the bronchial stump in response to covering with free fat tissue in a rat model. METHODS: A left pneumonectomy was performed on 16 Wistar/ST rats, 12 of which had a bronchial stump covered with free subcutaneous fat tissue. Four rats that underwent a left pneumonectomy alone were sacrificed on postoperative day 7, and the 12 rats whose bronchial stumps were additionally covered with fat tissue were sacrificed on postoperative days 7, 14 and 56. Macroscopic and histological changes and pressure resistance of the bronchial stumps due to coverage with free fat tissue were examined. RESULTS: None of the rats showed macroscopic infection or necrosis in the thoracic cavity at the time of the rethoracotomy. The normal bronchial stumps remained mostly exposed, whereas the bronchial stumps covered with fat tissue were well-coated with tissue mass. Histologically, fibrous connective tissue containing microvessels gradually formed around the bronchial stump covered with fat tissue, and some of the tissue masses still had normal fat structures 56 days postoperatively. Covering with fat tissue significantly increased the pressure resistance of the bronchial stump 7 days postoperatively and further increased with time. CONCLUSIONS: Covering the bronchial stump with free fat tissue formed fibrous connective tissue around the bronchial stump and reinforced its closure.


Subject(s)
Bronchi , Bronchial Fistula , Rats , Animals , Bronchi/surgery , Bronchi/pathology , Rats, Wistar , Bronchial Fistula/etiology , Bronchial Fistula/prevention & control , Bronchial Fistula/surgery , Pneumonectomy/adverse effects , Adipose Tissue
11.
Circ J ; 87(6): 824-833, 2023 05 25.
Article in English | MEDLINE | ID: mdl-36775328

ABSTRACT

BACKGROUND: MicroRNA (miR)-143 and miR-145 are non-coding RNAs present in smooth muscle cells and the heart. However, their behavior and physiological role in patients with acute myocardial infarction (AMI) have not been clarified.Methods and Results: Plasma miR-143 and miR-145 concentrations were measured on Day 0 (on admission) and on Day 7 in AMI patients who could be followed up for 6 months (n=25). The control group consisted of subjects without significant coronary stenosis (n=20). Blood samples were collected from the antecubital vein, and plasma miR-143 and miR-145 concentrations were measured by quantitative reverse transcription-polymerase chain reaction. In AMI patients (n=25), left ventricular ejection fraction (LVEF) was measured by echocardiography in the acute and chronic (6 months) phases. On Day 7, plasma miR-143 and miR-145 concentrations were significantly higher in AMI patients than in the control group and on Day 0 in AMI patients. Plasma miR-143 and miR-145 concentrations increased significantly from Day 0 to Day 7. The increase in plasma miR-143 concentrations (∆miR-143) in the acute phase was positively correlated with the increase in LVEF in the chronic phase. Among many factors, only ∆miR-143 was favorably correlated with left ventricle (LV) functional recovery in the chronic phase. CONCLUSIONS: An increase in plasma miR-143 concentrations in the acute phase may be a biomarker predicting recovery of LV function in the chronic phase in AMI patients.


Subject(s)
MicroRNAs , Myocardial Infarction , Humans , Stroke Volume , Ventricular Function, Left , Myocardial Infarction/genetics , Heart , MicroRNAs/genetics
12.
Hepatol Res ; 53(7): 681-686, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36826420

ABSTRACT

AIM: Primary hepatic angiosarcoma (PHA) is extremely rare, and its imaging findings are similar to those of other liver tumors including hepatocellular carcinoma (HCC). Here, we report a case of hepatitis C virus (HCV)-related HCC followed by PHA that showed remarkable clinical response to atezolizumab plus bevacizumab (Atezo/Bev) therapy. CASE PRESENTATION: A 78-year-old man with recurrent HCC had a liver tumor with lymphadenopathy. Although considered as HCC recurrence, microscopic examination of the resected liver and lymph node showed PHA. Three months later, a solitary lung nodule was newly detected and subsequently resected. The pathological diagnosis was poorly differentiated HCC. Therefore, the patient was finally diagnosed with double cancer of PHA and HCC. Thereafter, he developed a new liver tumor with lymphadenopathy and received Atezo/Bev therapy. Liver tumor biopsy was carried out before the treatment. The pathological diagnosis was angiosarcoma. The patient showed a partial response after two courses of Atezo/Bev therapy. CONCLUSION: To our best knowledge, this report is the first case to present HCV-related HCC followed by PHA and to show that Atezo/Bev therapy is beneficial for PHA.

13.
Heart Vessels ; 37(10): 1689-1700, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35524780

ABSTRACT

The purpose of the present study was to develop a 60 MHz integrated backscatter intravascular ultrasound (IB-IVUS) and to evaluate its usefulness for the detection of lipid area with backward attenuation of ultrasound signal (AT) that for the prediction of post-procedural myocardial injury (PMI) after percutaneous coronary intervention (PCI). In a pathological study, images were acquired from 221 cross-sections of 18 coronary arteries from 13 cadavers obtained at autopsy. In the clinical training study, we compared non-targeted plaques in 38 patients by a previous IB-IVUS system (38 MHz) and a new IB-IVUS system (60 MHz). In the clinical testing study, we included 70 consecutive patients who underwent PCI. Serum troponin-I was measured just before and 24 h after PCI to evaluate PMI. As the % microcalcification + % cholesterol cleft area increased, the attenuation of IB values increased (r = 0.56, p < 0.001). The slopes of regression lines of the area of each tissue component between 38 and 60 MHz IB-IVUS were excellent. The lipid pool area with AT tended to be more useful than that of the conventional lipid pool area for the prediction of PMI (p = 0.11). We developed a 60 MHz IB-IVUS imaging system for tissue characterization of coronary plaques. Cutoff value of purple color was the most reliable value for the prediction of PMI.


Subject(s)
Coronary Artery Disease , Heart Injuries , Percutaneous Coronary Intervention , Plaque, Atherosclerotic , Coronary Artery Disease/diagnosis , Coronary Artery Disease/surgery , Coronary Vessels/diagnostic imaging , Coronary Vessels/pathology , Heart Injuries/diagnostic imaging , Heart Injuries/etiology , Humans , Lipids , Percutaneous Coronary Intervention/adverse effects , Plaque, Atherosclerotic/diagnosis , Plaque, Atherosclerotic/pathology , Ultrasonography, Interventional/methods
14.
J Am Coll Cardiol ; 79(8): 789-801, 2022 03 01.
Article in English | MEDLINE | ID: mdl-35210034

ABSTRACT

BACKGROUND: Autophagy is a cellular process that degrades a cell's own cytoplasmic components for energy provision and to maintain a proper intracellular environment. Left ventricular reverse remodeling (LVRR) promises a better prognosis for patients with dilated cardiomyopathy (DCM). OBJECTIVES: The authors tested the hypothesis that autophagy is involved in LVRR and has prognostic value in the human failing heart. METHODS: Using left ventricular endomyocardial biopsy specimens from 42 patients with DCM (21 LVRR-positive and 21 LVRR-negative) and 7 patients with normal cardiac function (control), the authors performed immunohistochemistry and immunofluorescent labeling of LC3 and cathepsin D and electron microscopic observation in addition to general morphometry under light microscopy. RESULTS: The clinical characteristics of LVRR-positive patients were similar to those of the LVRR-negative patients, except for pulmonary artery pressure and left atrial dimension. Morphometry under light microscopy did not differ among specimens from DCM patients, regardless of their LVRR status. Electron microscopy revealed that autophagic vacuoles (autophagosomes and autolysosomes) and lysosomes were abundant within cardiomyocytes from DCM patients. Moreover, cardiomyocytes from LVRR-positive patients contained significantly more autophagic vacuoles with higher autolysosome ratios and cathepsin D expression levels than cardiomyocytes from LVRR-negative patients. Logistic regression analysis adjusted for age showed that increases in autophagic vacuole number and cathepsin D expression were predictive of LVRR. DCM patients who achieved LVRR experienced fewer cardiovascular events during the follow-up period. CONCLUSIONS: The authors show that autophagy is a useful marker predictive of LVRR in DCM patients. This provides novel pathologic insight into a strategy for treating the failing DCM heart.


Subject(s)
Autophagy , Cardiomyopathy, Dilated/pathology , Heart Failure/pathology , Ventricular Remodeling , Adult , Aged , Female , Humans , Male , Middle Aged , Prognosis
15.
Semin Thorac Cardiovasc Surg ; 34(1): 349-358, 2022.
Article in English | MEDLINE | ID: mdl-33711463

ABSTRACT

Bronchopleural fistula is one of the most serious postoperative complications caused by the incomplete healing of a bronchial stump. Fibroblasts play an important role in wound healing by facilitating connective tissue formation and inducing angiogenesis. We developed a method for production of multilayered fibroblast sheets that secreted some growth factors and promoted wound healing. The present study aimed to assess the treatment effect of multilayered fibroblast sheets on bronchial stump healing. In this rat model, left pneumonectomy was performed, and multilayered fibroblast sheets derived from autologous oral mucosal tissues were transplanted to the bronchial stump. The changes in the bronchial stump were examined macroscopically, histologically, and mechanically. The fibroblast sheets promoted the formation of thick connective tissues around the bronchial stump. The formed connective tissues were accompanied by new blood vessels, and fibrosis was observed over time. Then, 7 days after the transplantation of the fibroblast sheets, the bronchial wall became significantly thicker, and the area of the blood vessels for the bronchial wall tissues was significantly larger in the experimental group than in the control group. In addition, the burst pressure in the bronchial stump was significantly higher in the experimental group than in the control group. Bronchial stumps were reinforced by the transplantation of multilayered fibroblast sheets derived from autologous oral mucosal tissues.


Subject(s)
Bronchial Fistula , Animals , Bronchi/surgery , Bronchial Fistula/etiology , Fibroblasts , Humans , Pneumonectomy/adverse effects , Rats , Treatment Outcome
16.
Clin Exp Nephrol ; 25(11): 1231-1239, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34228250

ABSTRACT

BACKGROUND: Tolvaptan is a vasopressin type 2 receptor antagonist and has been used to treat autosomal dominant polycystic kidney disease (ADPKD) since 2014. There has been limited real-world data on the safety and efficacy of tolvaptan. METHODS: This post-marketing surveillance was conducted to evaluate the long-term safety and the efficacy of tolvaptan in Japanese patients with ADPKD in real-world clinical settings. The baseline characteristics of 1630 patients treated with tolvaptan are reported. Safety analysis comprises evaluation of adverse drug reactions (ADRs). The efficacy evaluation includes percent change in total kidney volume (TKV) and change in estimated glomerular filtration rate (eGFR) before and after tolvaptan treatment. RESULTS: Mean age was 49.7 ± 11.2 years and 843 (51.7%) patients were male. Baseline TKV was 2158 ± 1346 mL and eGFR was 44.4 ± 21.7 mL/min/1.73 m2. The majority of CKD patients were stage G3b (27.0%) and G4 (30.1%). Frequently reported ADRs were hepatic function abnormal (8.3%), thirst (8.2%), and hyperuricaemia (6.9%). The frequency of ALT elevation (> 30 and > 90 IU/L) was slightly high (32.9 and 8.3%) to previous studies. After tolvaptan treatment, the annual rate of percentage change in TKV reduced from 11.68%/year to 2.73%/year (P < 0.0001). Similar results were also obtained for the effect on change in eGFR from - 3.31 to - 2.28 mL/min/1.73 m2/year after initiation of tolvaptan treatment (P = 0.0403). CONCLUSION: There were no major problems with safety of tolvaptan treatment and comparable efficacy for TKV and eGFR was observed in relation to the previous pivotal two randomized control trials in this post-marketing surveillance.


Subject(s)
Antidiuretic Hormone Receptor Antagonists/therapeutic use , Polycystic Kidney, Autosomal Dominant/drug therapy , Tolvaptan/therapeutic use , Adult , Alanine Transaminase/blood , Antidiuretic Hormone Receptor Antagonists/adverse effects , Chemical and Drug Induced Liver Injury/blood , Chemical and Drug Induced Liver Injury/etiology , Female , Glomerular Filtration Rate/drug effects , Humans , Hyperuricemia/chemically induced , Japan , Kidney/pathology , Male , Middle Aged , Organ Size/drug effects , Polycystic Kidney, Autosomal Dominant/complications , Product Surveillance, Postmarketing , Prospective Studies , Renal Insufficiency, Chronic/etiology , Renal Insufficiency, Chronic/physiopathology , Thirst/drug effects , Tolvaptan/adverse effects
17.
J Cardiol ; 77(1): 30-40, 2021 01.
Article in English | MEDLINE | ID: mdl-32907780

ABSTRACT

Diabetic cardiomyopathy, clinically diagnosed as ventricular dysfunction in the absence of coronary atherosclerosis or hypertension in diabetic patients, is a cardiac muscle-specific disease that increases the risk of heart failure and mortality. Its clinical course is characterized initially by diastolic dysfunction, later by systolic dysfunction, and eventually by clinical heart failure from an uncertain mechanism. Light microscopic features such as interstitial fibrosis, inflammation, and cardiomyocyte hypertrophy are observed in diabetic cardiomyopathy, but are common to failing hearts generally and are not specific to diabetic cardiomyopathy. Electron microscopic studies of biopsy samples from diabetic patients with heart failure have revealed that the essential mechanism underlying diabetic cardiomyopathy involves thickening of the capillary basement membrane, accumulation of lipid droplets, and glycogen as well as increased numbers of autophagic vacuoles within cardiomyocytes. Autophagy is a conserved mechanism that contributes to maintaining intracellular homeostasis by degrading long-lived proteins and damaged organelles and is observed more often in cardiomyocytes within failing hearts. Diabetes mellitus (DM) impairs cardiac metabolism and leads to dysregulation of energy substrates that contribute to cardiac autophagy. However, a "snapshot" showing greater numbers of autophagic vacuoles within cardiomyocytes may indicate that autophagy is activated into phagophore formation or is suppressed due to impairment of the lysosomal degradation step. Recent in vivo studies have shed light on the underlying molecular mechanism governing autophagy and its essential meaning in the diabetic heart. Autophagic responses to diabetic cardiomyopathy differ between diabetic types: they are enhanced in type 1 DM, but are suppressed in type 2 DM. This difference provides important insight into the pathophysiology of diabetic cardiomyopathy. Here, we review recent advances in our understanding of the pathophysiology of diabetic cardiomyopathy, paying particular attention to autophagy in the heart, and discuss the therapeutic potential of interventions modulating autophagy in diabetic cardiomyopathy.


Subject(s)
Autophagy/physiology , Diabetes Mellitus, Type 2/complications , Diabetic Cardiomyopathies/physiopathology , Heart Failure/etiology , Myocytes, Cardiac/metabolism , Animals , Diabetic Cardiomyopathies/complications , Humans , Myocytes, Cardiac/ultrastructure
18.
Biochem Biophys Res Commun ; 533(3): 548-552, 2020 12 10.
Article in English | MEDLINE | ID: mdl-32977947

ABSTRACT

Wnt/ß-catenin signaling is important for development and progression of colorectal cancer (CRC). The degradation complex for ß-catenin is functionally impaired in CRC cells, thereby resulting in the accumulation of ß-catenin and its translocation into the nucleus. Nuclear ß-catenin interacts with and co-activates T cell factor4 (TCF4), resulting in ß-catenin/TCF4-dependent transcription. Therefore, nuclear ß-catenin has been categorized as the main driving force in the tumorigenesis of CRC. Recent studies reveal that Jun activation domain-binding protein 1 (JAB1) enhances the degradation of seven in absentia homolog-1 (SIAH-1), a putative E3 ubiquitin ligase of ß-catenin, and positively regulates the expression of total ß-catenin in human CRC cells. An another recent study also shows that nuclear ß-catenin is ubiquitinated and degraded by an E3 ubiquitin ligase, tripartite motif-containing protein 33 (TRIM33). However, the regulatory mechanism for the expression of nuclear ß-catenin remains to be fully understood. In this study, we have demonstrated that JAB1 positively regulates the expression of nuclear ß-catenin, c-MYC as a ß-catenin/TCF4 target, and cell cycle regulators, such as Ki-67 and topoisomerase IIα, in human CRC cells. Taken together, these results suggest that JAB1 is considered as a promising target for novel CRC therapy.


Subject(s)
COP9 Signalosome Complex/physiology , Colorectal Neoplasms/metabolism , Intracellular Signaling Peptides and Proteins/physiology , Peptide Hydrolases/physiology , beta Catenin/metabolism , Cell Line, Tumor , Cell Nucleus/metabolism , DNA Topoisomerases, Type II/metabolism , Humans , Ki-67 Antigen/metabolism , Poly-ADP-Ribose Binding Proteins/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Transcription Factor 7-Like 2 Protein/metabolism
19.
J Med Ultrasound ; 28(2): 120-122, 2020.
Article in English | MEDLINE | ID: mdl-32874873

ABSTRACT

A 47-year-old woman consulted a doctor due to a persistent cough. Computed tomography revealed a 30 mm × 60 mm intracardiac mass in the right atrium. Because of lung metastasis, her respiratory status did not allow a more invasive procedure, such as general anesthesia. Although intracardiac echocardiography (ICE) during percutaneous transcatheter biopsy (PTB) is not covered by medical insurance, we performed PTB under ICE guidance. Pathology and immunohistochemistry revealed primary cardiac angiosarcoma. Primary cardiac angiosarcoma is a rare tumor with a poor prognosis. After seven cycles of chemotherapy, the pulmonary metastasis was clearly improved. The patient is alive 18 months after the first consult, even though the mortality of angiosarcoma is high. ICE during PTB allowed us to choose appropriate chemotherapy and improve her pulmonary metastasis. ICE during PTB reduces the need for a diagnostic open-chest procedure that requires a more invasive approach.

20.
J Neurol Surg B Skull Base ; 81(2): 193-197, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32206539

ABSTRACT

Background Surgery for petroclival tumors is very challenging for neurosurgeons because the position of the tumor in relation to the brainstem, cranial nerves, and posterior fossa vessels greatly restricts the surgical field. Some papers have described using sigmoid sinus ligation to open the surgical field; however, pre- and intraoperative evaluations of the safety of ligation have been limited, despite the risk of complications from venous insufficiency. Here, we describe our method of preoperatively evaluating the potential safety of a retrolabyrinthine transsigmoid approach with nondominant ipsilateral sigmoid sinus ligation (RLTSwSSL). Methods A retrospective review was conducted on petroclival tumors treated over a 5-year period with RLTSwSSL after evaluation with both an endovascular balloon occlusion test (BOT) and an open-field sinus clipping occlusion test (COT). Changes in pressure of < 10 mm Hg and the absence of neurodegeneration during the tests indicated that it would be safe to proceed with permanent ligation. Results Four patients with large petroclival tumors underwent surgery via RLTSwSSL after detailed preoperative evaluations with both BOT and COT. All patients had uneventful courses of recovery without developing any complications derived from venous insufficiency. Conclusion In our case series, we have described a protocol for using both BOT and COT to evaluate the likely outcomes after sigmoid sinus ligation and thereby to improve safety. Further studies are needed to establish definite criteria for both occlusion tests that will ensure good outcomes.

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