Publications by authors named "Yusuke Takahashi"

396 Publications

Significance of urinary liver-type fatty acid-binding protein in patients with normal renal function after undergoing intestinal urinary diversion: a preliminary study.

Clin Exp Nephrol 2021 Jun 7. Epub 2021 Jun 7.

Department of Urology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543, Japan.

Background: Liver-type fatty acid-binding protein (L-FABP) in urine is one of the early diagnostic biomarkers for acute and chronic kidney injuries. Although this protein is also identified in the intestine, there is no verified reference value for patients with intestinal urinary diversion (UD). The aim of the present study was to measure L-FABP values in such patients and compare them with the results for patients without UD.

Methods: Spot urine specimens were collected from 41 patients with UD and 50 subjects without UD with estimated glomerular filtration rates of over 60 ml/min/1.73 m, and the L-FABP values were measured. The normal upper cutoff value in healthy subjects without UD is considered to be 7.24 μg/g Cr. First, the median values of the two groups were compared. Next, the subjects with negative proteinuria and without comorbidities associated with renal function were further selected and the median values of the groups were compared.

Results: The mean age was significantly higher in the UD group. The types of UD were ileal conduit (38 patients) and ileal neobladder (three patients). The median L-FABP value in the UD group was significantly higher than that in the non-diversion group (89.1 μg/g Cr vs. 2.0 μg/g Cr, p < 0.0001). After adjustment for their backgrounds, the median value remained higher in the UD group.

Conclusions: L-FABP values in subjects with UD are higher than in those without UD. By this result, to develop a reference value in patients with intestinal UD population, further studies are required.
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http://dx.doi.org/10.1007/s10157-021-02088-7DOI Listing
June 2021

Clinical Guideline-Guided Outcome Consistency for Surgically Resected Stage III Non-Small Cell Lung Cancer: A Retrospective Study.

Cancers (Basel) 2021 May 21;13(11). Epub 2021 May 21.

Department of Thoracic Oncology, Aichi Cancer Center, Nagoya 464-8681, Japan.

Clinical guidelines can help reduce the use of inappropriate therapeutics due to localism and individual clinician perspectives. Nevertheless, despite the intention of clinical guidelines to achieve survival benefit or desirable outcomes, they cannot ensure a robust outcome. This retrospective study aimed to investigate whether guideline-consistency, including adjuvant treatments after surgical resection (ATSR) and guideline-matched first-line treatment for recurrence (GMT-R), according to the genomic profiles and immune status, could influence overall survival (OS). From 2006 to 2017, the clinical data of 308 patients with stage III non-small cell lung cancer (NSCLC) after surgical resection were evaluated. ATSR and GMT-R were allowed in 164 (53.2%) and 129 (62.3%) patients cases after surgical pulmonary resection, among which 207 (67.2%) recurrences were identified. The 5-year OS in guideline-consistent cases was significantly better than that in guideline-inconsistent cases ( < 0.01). Subgroup analyses further showed that the 5-year OS after propensity adjustment was significantly better in guideline-consistent than in guideline-inconsistent cases ( < 0.01), but not in either ATSR or GMT-R ( = 0.24). These data suggest that the guideline-consistent alternatives, which comprise ATSR or GMT-R, can contribute to survival benefits in pathological stage III NSCLC. However, only either ATSR or GMT-R has a potential survival benefit in these patients.
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http://dx.doi.org/10.3390/cancers13112531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196738PMC
May 2021

Visualization of Spatial Distribution of Spermatogenesis in Mouse Testes Using Creatine Chemical Exchange Saturation Transfer Imaging.

J Magn Reson Imaging 2021 May 30. Epub 2021 May 30.

Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Background: When determining treatment strategies for male infertility, it is important to evaluate spermatogenesis and its spatial distribution in the testes.

Purpose: To investigate the usefulness of creatine chemical exchange saturation transfer (CrCEST) imaging for evaluating spermatogenesis and its spatial distribution.

Study Type: Prospective.

Animal Model: C57BL/6 control mice (n = 5) and model mice of male infertility induced by whole testis X-ray irradiation (n = 11) or localized X-ray irradiation to lower regions of testes (n = 3).

Field Strength/sequence: A 11.7-T vertical-bore magnetic resonance imaging (MRI)/segmented fast low-angle shot acquisition for CEST.

Assessment: The magnetization transfer ratio for the CrCEST effect (MTR ) was calculated in each testis of the control mice and X-ray irradiation model mice at 10, 15, 20, and 30 days after irradiation. Correlation analysis was performed between MTR and Johnsen's score, a histological score for spermatogenesis. In the localized X-ray irradiation model, regional MTR and Johnsen's score were calculated for correlation analysis.

Statistical Tests: Unpaired t-test, one-way analysis of variance with Tukey's HSD test and Pearson's correlation analysis. A P value < 0.05 was considered statistically significant.

Results: In the irradiation model, CrCEST imaging revealed a significant linear decrease of MTR after irradiation (control, 8.7 ± 0.6; 10 days, 7.9 ± 0.8; 15 days, 6.5 ± 0.6; 20 days, 5.4 ± 1.0; 30 days, 4.4 ± 0.8). A significant linear correlation was found between MTR and Johnsen's score (Pearson's correlation coefficient (r) = 0.79). In the localized irradiation model, CrCEST imaging visualized a significant regional decrease of MTR in the unshielded region (shielded, 6.9 ± 0.7; unshielded, 4.9 ± 1.0), and a significant linear correlation was found between regional MTR and Johnsen's score (r = 0.78).

Data Conclusion: Testicular CrCEST effects correlated well with spermatogenesis. CrCEST imaging was useful for evaluating spermatogenesis and its spatial distribution.

Evidence Level: 2 TECHNICAL EFFICACY: Stage 2.
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http://dx.doi.org/10.1002/jmri.27734DOI Listing
May 2021

Quantification of Cellulose Pyrolyzates via a Tube Reactor and a Pyrolyzer-Gas Chromatograph/Flame Ionization Detector-Based System.

ACS Omega 2021 May 26;6(18):12022-12026. Epub 2021 Apr 26.

Graduate School of Environmental Studies, Tohoku University, 6-6-07 Aoba, Aramaki-aza, Aoba-ku, Sendai, Miyagi 980-8579, Japan.

Pyrolysis of cellulose primarily produces 1,6-anhydro-β-d-glucopyranose (levoglucosan), which easily repolymerizes to form coke precursors in the heating zone of a pyrolysis reactor. This hinders the investigation of primary pyrolysis products as well as the elucidation of cellulose pyrolysis mechanisms, particularly because of the significant buildup of coke during slow pyrolysis. The present study discusses the applicability of a pyrolysis-gas chromatography/flame ionization detection (Py-GC/FID) system using naphthalene as the internal standard, with the aim of substantially improving the quantification of pyrolyzates during the slow pyrolysis of cellulose. This method achieved quantification of levoglucosan with a yield that was 14 times higher than that obtained from offline pyrolysis in a simple tube reactor. The high yield recovery of levoglucosan was attributed to the suppression of levoglucosan repolymerization in the Py-GC/FID system, owing to the rapid escape of levoglucosan from the heating zone, low concentration of levoglucosan in the gas phase, and rapid quenching of levoglucosan. Therefore, this method facilitated the improved quantification of primary pyrolysis products during the slow pyrolysis of cellulose, which can be beneficial for understanding the primary pyrolysis reaction mechanisms. This method can potentially be applied to other polymeric materials that produce reactive pyrolyzates.
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http://dx.doi.org/10.1021/acsomega.1c00622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154023PMC
May 2021

Etiological pathways of depressive and anxiety symptoms linked to personality traits: A genetically-informative longitudinal study.

J Affect Disord 2021 May 15;291:261-269. Epub 2021 May 15.

Faculty of Letters, Keio University, Japan.

Background: The comorbidity of depression and anxiety is associated with an increased risk of prolonged adverse mental health status. However, little is currently known about their genetic and environmental influences that help to explain both the comorbidity and distinctiveness. Using longitudinal twin data, the present study investigated both the overlapping and distinct relationships between depression and anxiety viewed from the perspective of Gray's Reinforcement Sensitivity Theory (RST): two personality traits of the Behavioral Inhibition and Activation Systems (BIS and BAS).

Methods: A total of 422 twin pairs (298 monozygotic and 124 dizygotic pairs) participated by completing a personality questionnaire at wave 1, and mood symptoms questionnaires at wave 2. The waves were on average 2.23 years apart.

Results: Multivariate Cholesky decomposition indicated that the genetic variance of the personality traits (BIS and BAS) explained all of the genetic variance in depressive and anxiety symptoms. Additionally, genetic factors related to the BIS positively explained depressive and anxiety symptoms, whereas genetic factors related to the BAS negatively explained only depressive symptoms.

Limitations: Limitations include shorter time interval and the reliance on self-reported data.

Conclusions: The present study provided evidence explaining the overlap and differentiation of depressive and anxiety symptoms by using data on personality traits in a longitudinal, genetically-informative design. The findings suggested the personality traits from Gray's RST model played an important role in the prediction, and clarified the description, of both depressive and anxiety symptoms.
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http://dx.doi.org/10.1016/j.jad.2021.05.004DOI Listing
May 2021

Sporadic foveolar-type gastric adenoma with a raspberry-like appearance in Helicobacter pylori-naïve patients.

Virchows Arch 2021 May 27. Epub 2021 May 27.

Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan.

Sporadic foveolar-type gastric adenoma (FGA) has been described as an extremely rare polyp that is whitish and flatly elevated. However, we recently found that sporadic FGA with a raspberry-like appearance (FGA-RA) is not rare in Helicobacter pylori (H. pylori)-naïve gastric mucosa. We endoscopically or surgically treated 647 patients with gastric epithelial neoplasms in the last 5 years, with 7.7% (50/647) being H. pylori-naïve. Among these, 43 FGA-RAs were diagnosed based on histologic and endoscopic features in 34 patients, who were all enrolled in this retrospective study. All lesions were observed by white-light endoscopy (WLE) and narrow-band imaging with magnification endoscopy (NBIME). We subsequently analyzed their endoscopic and microscopic features and patient characteristics. The patients were 22 males and 12 females aged 57±23 years (mean±2SD). WLE showed raspberry-like small polyps mimicking gastric hyperplastic polyps in the oxyntic gastric compartment (body/fundus). Multiple growths were confirmed in 20.6% (7/34) of the patients. NBIME revealed irregularly shaped papillary/gyrus-like microstructures with abnormal capillaries. Histologically, all lesions were intraepithelial neoplasms, and most of lesions (62.8%, 27/43) exhibited low-grade dysplasia. Immunohistochemically, neoplastic cells featured strong and diffuse MUC5AC expression, negative or very low MUC6 expression, and negative MUC2/CD10 expression. They also showed Ki-67 hyperexpression with a mean labeling index of 59.4±48.7%. The coexistence of fundic gland polyps in the background mucosa was significantly higher in multiple FGA-RA cases than in solitary cases (100% vs. 55.5%, P< 0.05). FGA-RA is a newly suggested histologic variant of sporadic FGA whose occurrence is not rare in daily endoscopic practice.
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http://dx.doi.org/10.1007/s00428-021-03124-3DOI Listing
May 2021

Regioselective C-H Azidation of Anilines and Application to Synthesis of Key Intermediate for Pharmaceutical.

J Org Chem 2021 Jun 26;86(11):7842-7848. Epub 2021 May 26.

MA Group, Tokuyama Corporation 40, Wadai, Tsukuba, Ibaraki 300-4247, Japan.

A catalytic system for regioselective C-H azidation of inactive anilines was developed. In the presence of CuSO·5HO, simultaneous addition of NaN and NaSO to aq. CHCN solution of free anilines under weakly acidic conditions (pH 4.5) smoothly underwent C-H azidation to provide corresponding α-azidated products in high yields. Methyl α-azidoanthranilate obtained by this method was readily transformed via simple reduction followed by cyclization to methyl 2-ethoxybenzimidazol-7-carboxylate, a key intermediate for antihypertensive Candesartan Cilexetil.
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http://dx.doi.org/10.1021/acs.joc.1c00734DOI Listing
June 2021

Micropapillary Predominance Is a Risk Factor for Brain Metastasis in Resected Lung Adenocarcinoma.

Clin Lung Cancer 2021 Apr 18. Epub 2021 Apr 18.

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Background: Histologic subtyping offers some prognostic value in lung adenocarcinoma. We thus hypothesized that histologic subtypes may be useful for risk stratification of brain metastasis (BM). In this study, we aimed to investigate the impact of histologic subtypes on the risk for BM in patients with resected lung adenocarcinoma.

Patients And Methods: Of 1099 consecutive patients who had undergone curative-intent surgery (2000-2014), 448 patients who had undergone complete resection for lung adenocarcinoma were included in this study. Correlated clinical variables and BM-free survival were analyzed.

Results: Micropapillary predominance was significantly associated with higher risk of BM after complete resection in univariate analyses (P < .001). In addition, multivariate analyses showed that micropapillary predominance was an independent risk factor for BM (hazard ratio = 2.727; 95% confidence interval, 1.260-5.900; P = .011), along with younger age and advanced pathologic stage. Unlike the other subtypes, an increase in the percentage of the micropapillary subtype was positively correlated with an increase in BM frequency. Patients with micropapillary adenocarcinoma showed significantly poorer brain metastasis-free survival compared with those with non-micropapillary adenocarcinoma (3 years, 78.2% vs. 95.6%; 5 years, 67.3% vs. 94.3%; P < .001).

Conclusion: The current study demonstrated a significant correlation between micropapillary subtype and higher risk of BM in patients with resected lung adenocarcinoma. This routine histologic evaluation of resected adenocarcinoma may provide useful information for the clinician when considering postoperative management in patients with lung adenocarcinoma. Histologic subtyping offer some prognostic value in lung adenocarcinoma. Because brain metastasis is critical and often refractory to systemic chemotherapy, early detection is clinically important to achieve effective local treatment. We retrospectively analyzed the association between histologic subtypes and occurrence of brain metastasis and found a significant association between micropapillary predominance and higher risk for brain metastasis. Our findings may be relevant when considering postoperative management.
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http://dx.doi.org/10.1016/j.cllc.2021.04.001DOI Listing
April 2021

Robotic open-thoracotomy-view approach using vertical port placement and confronting monitor setting.

Interact Cardiovasc Thorac Surg 2021 May 11. Epub 2021 May 11.

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Objectives: Robotic lung resections (RLRs) are conventionally performed using look-up views of the thorax from the caudal side. To conduct RLR with views similar to those in open thoracotomy, we adopted a vertical port placement and confronting upside-down monitor setting, which we called robotic 'open-thoracotomy-view approach'. We herein present our experience of this procedure.

Methods: We retrospectively reviewed 58 patients who underwent RLR (43 with lobectomy; 15 with segmentectomy) with 3-arm open-thoracotomy-view approach using the da Vinci Surgical System between February 2019 and October 2020. The patient cart was rolled in from the left cranial side of the patient regardless of the side to be operated on. Robotic ports were vertically placed along the axillary line, and 2 confronting monitors and 2 assistants were positioned on each side of the patient. The right-side monitor, which was set up for the left-side assistant to view, projected the upside-down image of the console surgeon's view.

Results: All procedures were safely performed. The median duration of surgery and console operation was 215 and 164 min, respectively. Emergency conversion into thoracotomy and severe morbidities did not occur, and the median postoperative hospitalization duration was 3 days. In all procedures, the console surgeon and 2 assistants had direct 'bird-eye' views of the cranially located intrathoracic structures and instrument tips, which are sometimes undetectable with the conventional look-up view.

Conclusions: The open-thoracotomy-view approach setting is a possible option for RLR. It offers natural thoracotomy views and can circumvent some of the known limitations of the conventional procedure.
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http://dx.doi.org/10.1093/icvts/ivab033DOI Listing
May 2021

A multicenter retrospective study of the esophageal triamcinolone acetonide-filling method in patients with extensive esophageal endoscopic submucosal dissection.

Scand J Gastroenterol 2021 Jun 15;56(6):647-655. Epub 2021 Apr 15.

Department of Gastroenterology, Faculty of Medicine, Shimane University, Izumo, Japan.

Objective: Endoscopic submucosal dissection (ESD) for extensive esophageal cancer is sometimes associated with post-ESD stenosis, despite preventative steroid therapy. In this retrospective multicenter analysis, we evaluated the factors associated with therapy resistance.

Materials And Methods: We enrolled 73 patients with 75 extensive esophageal cancers treated with ESD. Stenosis prevention was performed using two esophageal triamcinolone acetonide (TA)-fillings, and repeated if stenosis was found on follow-up. Therapy-resistance factors associated with incidence of severe stenosis requiring endoscopic balloon dilation (EBD) were evaluated, including age, gender, previous treatment history, tumor location, morphology, resection size, histologic type, invasion depth, and horizontal resection grade (HR-grade 1, ≥ 9/12 and <10/12 of the circumference; grade 2, ≥ 10/12 and <11/12; grade 3, ≥ 11/12 but not circumferential; and grade 4, entirely circumferential).

Results: Severe stenosis occurred in 17.3%(13/75) of cases, with a median of two EBDs (range, 1-6 times). Severe stenosis was significantly associated with HR-grade elevation and previous treatment history ( < .05); multivariate analysis showed both as independent therapy-resistance factors ( < .05). Patients without previous treatment history demonstrated severe stenosis at 12.9%(9/70): 0%(0/26) HR-grade 1, 18.8%(3/16) grade 2, 17.6%(3/17) grade 3, and 27.3%(3/11) grade 4, showing a risk of HR-grade 2 or more resection but an acceptable stenosis prevention even after entirely circumferential resection. Conversely, patients with previous treatment history demonstrated severe stenosis at a high frequency of 80%(4/5).

Conclusions: Esophageal TA-filling is a promising stenosis-preventive steroid therapy, even in entirely circumferential ESD cases. However, HR-grade 2 or more elevation and previous treatment history were independently associated with therapy resistance.
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http://dx.doi.org/10.1080/00365521.2021.1910998DOI Listing
June 2021

Successful Treatment of Protein-Losing Enteropathy After Superior Mesenteric Artery Occlusion without Surgery.

Am J Case Rep 2021 Apr 12;22:e931114. Epub 2021 Apr 12.

Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.

BACKGROUND Protein-losing enteropathy as a complication of superior mesenteric artery occlusion is extremely rare and severe, and sometimes requires intestinal resection. However, the ideal treatment strategy has not yet been determined. CASE REPORT A 77-year-old man with underlying hypertension and diabetes was admitted to the Emergency Department with acute abdominal pain after eating. Contrast-enhanced computed tomography revealed complete occlusion of the superior mesenteric artery with thrombosis, and superior mesenteric artery occlusion was diagnosed. It was successfully treated with interventional therapy, followed by continuous intra-arterial prostaglandin E1 infusion and continuous intravenous heparin infusion. However, the patient developed hypoproteinemia and diarrhea about 10 days after the interventional therapy. Colonoscopy and X-ray studies did not reveal any abnormal findings; however, technetium-99m-labeled human serum albumin scintigraphy indicated protein-losing enteropathy. With total parenteral nutrition and protein-rich oral nutrition, with protein intake at twice the amount in a standard diet, serum albumin improved from 15 g/L to 32 g/L after treatment. Additionally, we administered diuretics to avoiding edema related to the hypoproteinemia. The patient recovered from the hypoproteinemia and diarrhea without complications. CONCLUSIONS Protein-losing enteropathy is an extremely rare but critical complication of superior mesenteric artery occlusion. Treating the underlying pathology is the mainstay of protein-losing enteropathy and dietary modifications also play a critical role. Our patient was successfully treated with strict nutritional therapy, combined oral protein-rich nutrition and total parenteral nutrition, which avoided surgery.
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http://dx.doi.org/10.12659/AJCR.931114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053643PMC
April 2021

Absolute quantitative analysis of cardiac amyloidosis using SPECT/CT with Tc-pyrophosphate.

Amyloid 2021 Apr 7:1-2. Epub 2021 Apr 7.

Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan.

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http://dx.doi.org/10.1080/13506129.2021.1903418DOI Listing
April 2021

Luteinizing hormone (LH) formed a complex with an immunoglobulin G caused abnormally high levels of LH: A case report.

Clin Biochem 2021 Mar 24. Epub 2021 Mar 24.

Division of Laboratory Medicine, Sapporo Medical University Hospital, Japan; Department of Infection Control and Laboratory Medicine, Sapporo Medical University School of Medicine, Japan. Electronic address:

We encountered a 30-year-old woman with remarkably elevated luteinizing hormone (LH) levels, as measured by electrochemiluminescent immunoassay (ECLIA), and no specific symptoms. We performed the following investigations: dilution linearity test, polyethylene glycol (PEG) precipitation test, immunoprecipitation test, protein G addition test, and high-performance liquid chromatography (HPLC) analysis. The linearity of patient's serum was similar to that of a standard LH preparation, and non-specific reactions were not observed. The recovery rate of LH shown by the PEG precipitation test, immunoprecipitation test, and protein G addition test was low. Moreover, an abnormal peak in HPLC was located at a slightly larger molecular weight position than that of IgG. These results showed the presence of macro-LH, LH, and anti-LH-IgG autoantibody complex and suggested that the clearance of LH from the blood was delayed due to IgG binding, and therefore, the LH value was falsely high. We should keep the possibility of macro-LH in mind in cases of unexpectedly high LH values.
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http://dx.doi.org/10.1016/j.clinbiochem.2021.03.010DOI Listing
March 2021

One-Pot γ-Lactonization of Homopropargyl Alcohols via Intramolecular Ketene Trapping.

Org Lett 2021 04 22;23(7):2831-2835. Epub 2021 Mar 22.

Laboratory of Synthetic Natural Products Chemistry and Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.

A one-pot γ-lactonization of homopropargyl alcohols via an alkyne deprotonation/boronation/oxidation sequence has been developed. Oxidation of the generated alkynyl boronate affords the corresponding ketene intermediate, which is trapped by the adjacent hydroxy group to furnish the γ-lactone. We have optimized the conditions as well as examined the substrate scope and synthetic applications of this efficient one-pot lactonization.
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http://dx.doi.org/10.1021/acs.orglett.1c00840DOI Listing
April 2021

Changes in Smad1/5/9 expression and phosphorylation in astrocytes of the rat hippocampus after transient global cerebral ischemia.

J Chem Neuroanat 2021 Apr 9;113:101941. Epub 2021 Mar 9.

Department of Clinical Nutrition, Graduate School of Comprehensive Rehabilitation, Osaka Prefecture University, 7-30 Habikino, Osaka, 583-8555, Japan.

Smad proteins are known to transduce the actions of the transforming growth factor-β (TGF-β) family including TGF-βs, activins, and bone morphogenetic proteins (BMPs). We previously reported that Smad1/5/9 immunoreactivity was observed in astrocytes of various rat brain regions including the hippocampus, suggesting that Smad1/5/9 may be associated with the physiology of astrocytes. However, the Smad1/5/9 expression and activation in the hippocampal astrocytes after global cerebral ischemia has not been yet elucidated. In this study, we examined temporal changes in the expression and phosphorylation of Smad1/5/9 in the hippocampus using a rat model of global cerebral ischemia. Furthermore, we examined the candidate ligand involved in the phosphorylation of Smad1/5/9 in the hippocampus after ischemia. Pyramidal neuronal cell death in the CA1 regions was visible at 3 days, and maximum death occurred within 7 days after ischemia. At 7 days after ischemia, astrocytes that showed strong immunoreactivity for Smad1/5/9 were frequently observed in the CA1 region. Additionally, there was an increase in phosphorylated Smad1/5/9 (phospho-Smad1/5/9) -immunopositive astrocytes in the CA1 region 7 days after ischemia. Real-time PCR analysis showed an increase in the expression level of TGF-β1 mRNA in the hippocampus after ischemia. Intracerebroventricular injection of SB525334, an inhibitor of TGF-β/Smad signaling, reduced immunoreactivity for phospho-Smad1/5/9 in astrocytes. These results suggest that TGF-β1 may be a key molecule for ischemia-induced Smad1/5/9 phosphorylation in astrocytes, and TGF-β1-Smad1/5/9 signaling may play a role in post-ischemic events, including brain inflammation or tissue repair rather than neuroprotection of the hippocampus.
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http://dx.doi.org/10.1016/j.jchemneu.2021.101941DOI Listing
April 2021

Sarcopenia is poor risk for unfavorable short- and long-term outcomes in stage I non-small cell lung cancer.

Ann Transl Med 2021 Feb;9(4):325

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.

Background: Sarcopenia characterized by skeletal muscle loss may influence postoperative outcomes through physical decline and weakened immunity. We aimed to investigate clinical significance of sarcopenia in resected early-stage non-small cell lung cancer (NSCLC).

Methods: We retrospectively reviewed 315 consecutive patients with pathologic stage I NSCLC who had undergone lobectomy with systematic nodal dissection. Sarcopenia was defined as the lowest quartile of psoas muscle area on the 3rd vertebra on the high-resolution computed tomography (HRCT) image. Clinicopathological variables were used to investigate the correlation to postoperative complications as well as overall and recurrence-free survival.

Results: Upon multivariable analysis, male sex [odds ratio (OR) =5.780, 95% confidence interval (CI): 2.681-12.500, P<0.001], and sarcopenia (OR =21.00, 95% CI: 10.30-42.80, P<0.001) were independently associated with postoperative complications. The sarcopenia group showed significantly lower 5-over all survival (84.4% 69.1%, P<0.001) and recurrence-free survival (77.2% 62.0%, P<0.001) comparing with the non-sarcopenia group. In a multivariable analysis, sarcopenia was an independent prognostic factor [hazard ratio (HR) =1.978, 95% CI: 1.177-3.326, P=0.010] together with age ≥70 years (HR =1.956, 95% CI: 1.141-3.351, P=0.015) and non-adenocarcinoma histology (HR =1.958, 95% CI: 1.159-3.301, P=0.016).

Conclusions: This is the first study which demonstrates that preoperative sarcopenia is significantly associated with unfavorable postoperative complications as well as long-term survival in pathologic stage I NSCLC. This readily available factor on HRCT may provide valuable information to consider possible choice of surgical procedure and perioperative management.
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http://dx.doi.org/10.21037/atm-20-4380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944314PMC
February 2021

Effect of heel lifts in elderly individuals with spinal kyphosis.

Clin Biomech (Bristol, Avon) 2021 Mar 23;83:105307. Epub 2021 Feb 23.

Department of Rehabilitation, Akita City Hospital, 4-30, Kawamoto Matsuoka Town, Akita City, Akita, Japan.

Background: The present study aimed to elucidate the effects of heel lifts on spinal alignment, walking, and foot pressure pattern in elderly individuals with spinal kyphosis.

Methods: The spinal alignment, walking speed, step length and foot pressure of 33 community-dwelling elderly individuals with spinal kyphosis (3 men, 30 women; mean age 77.3 years) were examined before and after the application of 10-mm moderately elastic heel lifts.

Findings: Spinal alignment of total inclination (mean value 6.9°vs 4.5°) and thoracic angle (43.6°vs 36.2°) were significantly lower after the application of heel lifts than before the application. The lumbar angle (7.3°vs 10.0°) was significantly higher after the application than before the application. Walking speed (0.78 vs 0.88 m/s) and step length (0.42 m vs 0.45 m) were significantly higher after the application. The partial foot pressure as a percentage of body weight of the hallux (6.7% vs 9.0%) and lateral toes (6.5% vs 9.0%) was significantly higher after the application of heel lifts than before the application. The partial foot pressure as a percentage of body weight of the heel (68.9% vs 57.5%) was significantly lower after the application than before the application.

Interpretation: In conclusion, heel lifts influenced the sagittal spinal alignment of elderly individuals. Walking speed and step length increased after the application of these devices. Increase in foot pressure in the hallux and lateral toe areas was probably related to these improvements in walking parameters.
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http://dx.doi.org/10.1016/j.clinbiomech.2021.105307DOI Listing
March 2021

Hybrid approach with laparoscopic wall-inversion surgery and single-incision intragastric surgery for intraluminal gastrointestinal stromal tumor: A case report.

Asian J Endosc Surg 2021 Feb 16. Epub 2021 Feb 16.

Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan.

Laparoscopic wedge resection (LWR) for intraluminal gastrointestinal stromal tumor (GIST) leads to excessive resection of normal gastric wall. We report a case of GIST around the cardia successfully treated with full-thickness partial resection using a hybrid approach of laparoscopic surgery and single-incision intragastric surgery (SIIGS). A 69-year-old woman had a 5 cm intraluminal GIST at the posterior wall around the cardia. Submucosal injection of glycerin and indigo carmine was performed with transoral endoscopy. Circumferential seromuscular incision followed by placement of seromuscular sutures to invert the lesion into the stomach was performed under laparoscopy. By SIIGS, resection of the inverted mucosa and retrieval of the tumor were completed. A hybrid approach consisting of laparoscopic wall-inversion surgery and SIIGS was useful for intraluminal GIST and may expand the indications for laparoscopic wall-inversion surgery by removing size limitations.
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http://dx.doi.org/10.1111/ases.12927DOI Listing
February 2021

Subsegmental resection preserves regional pulmonary function: A focus on thoracoscopy.

Thorac Cancer 2021 04 14;12(7):1033-1040. Epub 2021 Feb 14.

Department of Surgery, Division of Thoracic Surgery, The Teikyo University, Tokyo, Japan.

Background: The aim of this study was to evaluate regional postoperative preserved pulmonary function (PPPF) and three-dimensional (3D) volumetric changes according to the number of resected subsegments and investigate the factors that most affected pre-/post PPPF.

Methods: Patients who underwent thoracoscopic lobectomy (n = 73), and segmentectomy (n = 87) were eligible for inclusion in the study. They were classified according to the number of resected subsegments which ranged from 1 to 10. The percentage of pre-/postoperative forced expiratory volume in 1 s (FEV1) was used for comparison. Furthermore, lung volumetric changes were calculated using 3D computed tomography (CT) volumetry.

Results: The percentage of pre-/postoperative EFV1 between 4 and 5-7 and between 5-7 and 10 were significant (p = 0.03 and p < 0.01, respectively), but not between 1-2 to 4 (p = 0.99). The difference between volumetric changes in the left lower lobe of patients with a number of resected subsegments was significant (p < 0.01). On univariate and multivariate analyses, chronic inflammation was significant for decrease in recovery percentages. When the PPPF was compared among resected subsegments, it gradually decreased with an increase in the number of patients without a postoperative procrastination of inflammation (p < 0.01).

Conclusions: Segmentectomy is feasible and useful for PPPF. Even a relatively large-volume resection procedure where 5-7 subsegments are resected can preserve pulmonary function. Chronic inflammation was statistically identified as a risk factor for postoperative preserved pulmonary function.

Key Points: .
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http://dx.doi.org/10.1111/1759-7714.13841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017248PMC
April 2021

Genetic and environmental architecture of conscientiousness in adolescence.

Sci Rep 2021 Feb 5;11(1):3205. Epub 2021 Feb 5.

Faculty of Letters, Keio University, Tokyo, Japan.

Using a genetically informative design (about 2000 twin pairs), we investigated the phenotypic and genetic and environmental architecture of a broad construct of conscientiousness (including conscientiousness per se, effortful control, self-control, and grit). These four different measures were substantially correlated; the coefficients ranged from 0.74 (0.72-0.76) to 0.79 (0.76-0.80). Univariate genetic analyses revealed that individual differences in conscientiousness measures were moderately attributable to additive genetic factors, to an extent ranging from 62 (58-65) to 64% (61-67%); we obtained no evidence that shared environmental influences were observed. Multivariate genetic analyses showed that for the four measures used to assess conscientiousness, genetic correlations were stronger than the corresponding non-shared environmental correlations, and that a latent common factor accounted for over 84% of the genetic variance. Our findings suggest that individual differences in the four measures of conscientiousness are not distinguishable at both the phenotypic and behavioural genetic levels, and that the overlap was substantially attributable to genetic factors.
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http://dx.doi.org/10.1038/s41598-021-82781-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864923PMC
February 2021

Distinct roles of LRP5 and LRP6 in Wnt signaling regulation in the retina.

Biochem Biophys Res Commun 2021 03 3;545:8-13. Epub 2021 Feb 3.

Department of Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Harold Hamm Diabetes Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Electronic address:

Dysregulation of Wnt signaling is implicated in multiple ocular disorders. The roles of Wnt co-receptors LRP5 and LRP6 in Wnt signaling regulation remain elusive, as most retinal cells express both of the co-receptors. To address this question, LRP5 and LRP6 were individually knocked-out in a human retinal pigment epithelium cell line using the CRISPR-Cas9 technology. Wnt signaling activity induced by various Wnt ligands was measured using wild-type and the KO cell lines. The results identified three groups of Wnt ligands based on their co-receptor specificity: 1) activation of Wnt signaling only through LRP6, 2) through both LRP5 and LRP6 and 3) predominantly through LRP5. These results indicate that LRP5 and LRP6 have differential roles in Wnt signaling regulation.
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http://dx.doi.org/10.1016/j.bbrc.2021.01.068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919854PMC
March 2021

Recombinant canine basic fibroblast growth factor-induced differentiation of canine bone marrow mesenchymal stem cells into voltage- and glutamate-responsive neuron-like cells.

Regen Ther 2020 Dec 1;15:121-128. Epub 2020 Aug 1.

Laboratory of Veterinary Surgery, Department of Veterinary Medicine, College of Bioresource and Sciences, Nihon University, Fujisawa, Kanagawa, 252-0880, Japan.

Introduction: Basic fibroblast growth factor (bFGF) is a promising cytokine in regenerative therapy for spinal cord injury. In this study, recombinant canine bFGF (rc-bFGF) was synthesized for clinical use in dogs, and the ability of rc-bFGF to differentiate canine bone marrow mesenchymal stem cells (BMSCs) into functional neurons was investigated.

Methods: The rc-bFGF was synthesized using a wheat germ cell-free protein synthesis system. The expression of rc-bFGF mRNA in the purification process was confirmed using a reverse transcription-polymerase chain reaction (RT-PCR). Western blotting was performed to confirm the antigenic property of the purified protein. To verify function of the purified protein, phosphorylation of extracellular signal-regulated kinase (ERK) was examined by assay using HEK293 cells. To compare the neuronal differentiation capacity of canine BMSCs in response to treatment with rc-bFGF, the cells were divided into the following four groups: control, undifferentiated, rh-bFGF, and rc-bFGF groups. After neuronal induction, the percentage of cells that had changed to a neuron-like morphology and the mRNA expression of neuronal markers were evaluated. Furthermore, to assess the function of the canine BMSCs after neuronal induction, changes in the intracellular Ca concentrations after stimulation with KCl and l-glutamate were examined.

Results: The protein synthesized in this study was rc-bFGF and functioned as bFGF, from the results of RT-PCR, western blotting, and the expression of pERK in HEK293 cells. Canine BMSCs acquired a neuron-like morphology and expressed mRNAs of neuronal markers after neuronal induction in the rh-bFGF and the rc-bFGF groups. These results were more marked in the rc-bFGF group than in the other groups. Furthermore, an increase in intracellular Ca concentrations was observed after the stimulation of KCl and l-glutamate in the rc-bFGF group, same as in the rh-bFGF group.

Conclusions: A functional rc-bFGF was successfully synthesized, and rc-bFGF induced the differentiation of canine BMSCs into voltage- and glutamate-responsive neuron-like cells. Our purified rc-bFGF may contribute, on its own, or in combination with canine BMSCs, to regenerative therapy for spinal cord injury in dogs.
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http://dx.doi.org/10.1016/j.reth.2020.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770349PMC
December 2020

LSR promotes epithelial ovarian cancer cell survival under energy stress through the LKB1-AMPK pathway.

Biochem Biophys Res Commun 2021 01 31;537:93-99. Epub 2020 Dec 31.

Center for Intractable Immune Disease, Kochi Medical School, Kochi University, Kochi, Japan.

Lipolysis-stimulated lipoprotein receptor (LSR), also known as a component of tricellular tight junctions, is highly expressing in epithelial ovarian cancer (EOC). However, the biological role of LSR in EOC cells remains unclear. In this study, we evaluated liver kinase B1 (LKB1) mediated AMP-activated protein kinase (AMPK) activity and investigated the effect of LSR on EOC cell survival under energy stress. LSR increased the levels of phospho-AMPKα at Thr172 and phospho-acetyl-CoA carboxylase (ACC) at Ser79 via LKB1-AMPK pathway in glucose deprivation in vitro. The increase of P-AMPKα (Thr172) and P-ACC (Ser79) was also detected in tumor microenvironment in vivo. Meanwhile, LSR promoted LKB1 localization at the cell membrane of EOC cells. By cell survival analysis, LSR attenuated glucose deprivation-induced cell death in EOC cells in vitro. Our results suggest that LSR promotes EOC cell survival and tumor growth through the LKB1-AMPK pathway.
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http://dx.doi.org/10.1016/j.bbrc.2020.12.079DOI Listing
January 2021

Comparison of surgical outcomes between thoracoscopic anatomical sublobar resection including and excluding subsegmentectomy.

Gen Thorac Cardiovasc Surg 2021 May 2;69(5):850-858. Epub 2021 Jan 2.

Department of Thoracic Surgery, Aichi Cancer Center, 1-1 Kanokoden Chikusa-ku, Nagoya, 464-8681, Japan.

Objectives: Despite the ubiquitous utilization of anatomical sublobar resection for malignant lung tumors, the effectiveness and feasibility of subsegmentectomy remains unclear. This study therefore compared the perioperative outcomes between anatomical sublobar resection including (IS) and excluding (ES) subsegmentectomy.

Methods: Patients who had undergone anatomical sublobar resection at our institution from January 2013 to March 2019 were retrospectively reviewed. Clinicopathologic characteristics and perioperative outcomes of the IS group (n = 58) were then analyzed the compared to those of the ES group (n = 203).

Results: No statistically significant differences in age, sex, comorbidities, tumor location, preoperative pulmonary function, or tumor size on imaging were found between both groups. The IS group had significantly higher preoperative computed tomography-guided marking rates (40% vs. 18%; p < 0.01) and used significantly more staplers for intersegmental dissection than the ES group [4, interquartile range (IQR): 3-4 vs. 3, IQR: 3-4; p = 0.03]. Both groups had comparable 30-day mortality (0% vs. 0%; p > 0.99), intraoperative complications (7% vs. 10%; p = 0.61), and postoperative complications (5% vs. 8%; p = 0.58). After propensity score matching, the IS group experienced significantly lesser blood loss than the ES group (5 mL, IQR: 1-10 vs. 5 mL, IQR: 5-20; p = 0.03). Both groups experienced no local recurrence and demonstrated similar postoperative pulmonary functions after surgery.

Conclusions: IS may be a feasible and acceptable therapeutic option for malignant lung tumors. Nonetheless, future investigations are required to further validate the current findings.
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http://dx.doi.org/10.1007/s11748-020-01556-3DOI Listing
May 2021

Accurate Estimation of the Duration of Testicular Ischemia Using Creatine Chemical Exchange Saturation Transfer (CrCEST) Imaging.

J Magn Reson Imaging 2021 05 17;53(5):1559-1567. Epub 2020 Dec 17.

Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.

Background: In the management of testicular torsion, estimating the duration of testicular ischemia is essential for deciding on an appropriate surgical treatment, but there are currently limited evaluation methods.

Purpose: To perform testicular creatine chemical exchange saturation transfer (CrCEST) imaging and to evaluate its ability to accurately estimate the duration of testicular ischemia.

Study Type: Prospective.

Animal Model: C57BL/6 control mice (n = 6) and testicular ischemia models induced by clamping the spermatic cord (n = 14). Eight of testicular ischemia models were serially imaged at two or three timepoints and a total of 26 images of ischemic testis were obtained. The ischemic duration ranged from 6-42 hours.

Field Strength/sequence: 11.7T vertical-bore MRI/segment fast low-angle shot acquisition for CEST.

Assessment: CrCEST imaging was performed and the magnetization transfer ratio for the CrCEST effect (MTR ) was calculated in control mice and testicular ischemia models. Correlation analysis between the duration of testicular ischemia and MTR decline was performed.

Statistical Tests: Paired t-test, and Pearson's correlation analysis.

Results: In control mice, the CrCEST effect in testes was significantly more than five times higher than that in skeletal muscle. MTR did not differ significantly between the right and left testes (8.6 ± 0.8 vs. 8.3 ± 0.6, P = 0.96). In testicular ischemia models, MTR of ischemic testes was significantly lower than that of controls (4 ± 2 vs. 8.9 ± 0.6, P < 0.001). Correlation analysis revealed a strong linear correlation between MTR decline and the duration of ischemia (r = 0.96, P < 0.001).

Data Conclusion: A decreased CrCEST effect in ischemic testes correlated well with ischemic duration. Testicular CrCEST imaging was useful for accurately estimating the duration of testicular ischemia.

Level Of Evidence: 2 TECHNICAL EFFICACY STAGE: 2.
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http://dx.doi.org/10.1002/jmri.27456DOI Listing
May 2021

Short-term and long-term outcomes of laparoscopic colectomy with multivisceral resection for surgical T4b colon cancer: Comparison with open colectomy.

Ann Gastroenterol Surg 2020 Nov 20;4(6):676-683. Epub 2020 Jul 20.

National Hospital Organization Osaka National Hospital Osaka Japan.

Aim: In response to the rising use of laparoscopic surgery, recent studies have shown that laparoscopic multivisceral resections for locally advanced colon cancer are safe, feasible, and provide acceptable oncological outcomes. However, the usefulness of laparoscopic multivisceral resection remains controversial. Here, we aimed to compare short-term and long-term outcomes between laparoscopic and open multivisceral resection approaches for treating locally advanced colon cancer.

Methods: We retrospectively collected data on 1315 consecutive patients admitted to the National Hospital Organization, Osaka National Hospital, for surgical treatment of colorectal cancer between 2010 and 2017. We assessed invasiveness in terms of operating times, blood loss, and complications. Oncological outcomes included 5-year survival rates and recurrences.

Results: We included 85 patients that underwent a colectomy with a multivisceral resection for locally advanced colon cancer; of these, 38 were treated with a laparoscopic approach and 47 were treated with an open approach. Compared to the open surgery group, the laparoscopic group had significantly less blood loss (median volume: 25 vs 140 mL,  <0.001), a lower complication rate (10.5% vs 29.8%,  = 0.036), and shorter hospital stays (12 vs 15 days,  = 0.028). After excluding patients with stage Ⅳ colon cancer, the groups showed similar pathologic outcomes and no significant differences in 5-year disease-free survival (73.9% vs 67.4%;  = 0.664) or 5-year overall survival (75.8% vs 67.7%;  = 0.695).

Conclusion: A laparoscopic approach for locally advanced colon cancer could be less invasive than an open approach without affecting oncological outcomes in selected patients.
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http://dx.doi.org/10.1002/ags3.12372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726680PMC
November 2020

Clinical adjustability of radiological tools in patients with surgically resected cT1N0-staged non-small-cell lung cancer from the long-term survival evaluation.

J Thorac Dis 2020 Nov;12(11):6655-6662

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Background: Various radiological tools have been introduced to determine the malignancy or prognosis of lung carcinomas. We retrospectively summarized the clinical outcomes to evaluate whether radiological tools such as consolidation-to-tumor ratio (CTR), tumor disappearance ratio (TDR), and mediastinal diameter (MD) are suitable for surgically resected non-small-cell lung cancer (NSCLC).

Methods: This retrospective study included 260 patients (128 men and 132 women; median age, 64 years) with cT1N0-staged NSCLC who underwent thoracotomy. Disease-free survival (DFS) and overall survival (OS) outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazards model.

Results: When the adjusted hazard ratios (HRs) with reference to cT1a/1 mi were calculated, significant differences were observed in cT1b and cT1c for DFS (P=0.04 and P<0.01, respectively) and in cT1c for OS (P=0.01). For HRs with reference to CTR (≤0.5), a significant difference was only observed in CTR (>0.5) for DFS (P=0.01). For HRs with reference to TDR (≤25%), significant differences were observed in TDR (>75%) for DFS (P=0.02) and OS (P=0.02). For HRs with reference to MD (≤5 mm), significant differences were observed in 6-20 mm (P=0.04) and >20 mm (P=0.02) for DFS and in >20 mm (P=0.02) for OS.

Conclusions: All radiological tools revealed significant correlations with prognosis in the patients with cT1N0-staged NSCLCs. We recommend the use of MD in a clinical context. However, further investigation of this issue is needed.
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http://dx.doi.org/10.21037/jtd-20-1610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711385PMC
November 2020

Efficacy of Xenon Light With Indocyanine Green for Intersegmental Visibility in Thoracoscopic Segmentectomy.

J Surg Res 2021 03 3;259:39-46. Epub 2020 Dec 3.

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan. Electronic address:

Background: We previously reported useful methods that can be implemented to identify intersegmental boundary lines (IBLs) by using an intravenous indocyanine green (ICG) fluorescence imaging system (ICG-FS) during a thoracoscopic anatomical segmentectomy (TAS). The aim of this study was to evaluate the recently released third-generation ICG-FS that features an emphasizing xenon-light source for IBL identification.

Methods: We prospectively studied cases involving 106 consecutive patients who underwent TAS. Intraoperatively, we used the third-generation ICG-FS, the conventional ICG methods (CIM) emphasizing xenon-light (CIM-X), and the spectra-A method (SAM) emphasizing xenon-light (SAM-X), for IBL identification. Furthermore, 16 of the 106 patients (15%) could be simultaneously evaluated using old-generation ICG-FSs, CIM, and SAM. All images were completely quantified for illuminance and for three colors, red, green, and blue.

Results: IBLs were successfully identified in all the patients (100%) with no adverse events. The SAM-X significantly increased the illuminance, especially in the resecting segments, compared to the CIM (39.0 versus 22.2, P < 0.01) and SAM (39.0 versus 29.3, P < 0.01), with enhanced red color compared to the CIM (33.1 versus 21.9, P < 0.01) and SAM (33.1 versus 14.0, P < 0.01). Furthermore, the SAM-X significantly increased the illuminance contrast compared to the CIM-X (34.1 versus 15.3, P < 0.01).

Conclusions: The present study suggests that the SAM-X potentially provided images with the highest visibility and colorfulness compared to the older generation ICG-FSs or CIM-X. Secure IBL identification can be more easily and safely performed using the SAM-X.
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http://dx.doi.org/10.1016/j.jss.2020.11.028DOI Listing
March 2021

AMPK regulates cell shape of cardiomyocytes by modulating turnover of microtubules through CLIP-170.

EMBO Rep 2021 01 29;22(1):e50949. Epub 2020 Nov 29.

Department of Medical Biochemistry, Osaka University Graduate School of Frontier Biological Science, Suita, Osaka, Japan.

AMP-activated protein kinase (AMPK) is a multifunctional kinase that regulates microtubule (MT) dynamic instability through CLIP-170 phosphorylation; however, its physiological relevance in vivo remains to be elucidated. In this study, we identified an active form of AMPK localized at the intercalated disks in the heart, a specific cell-cell junction present between cardiomyocytes. A contractile inhibitor, MYK-461, prevented the localization of AMPK at the intercalated disks, and the effect was reversed by the removal of MYK-461, suggesting that the localization of AMPK is regulated by mechanical stress. Time-lapse imaging analysis revealed that the inhibition of CLIP-170 Ser-311 phosphorylation by AMPK leads to the accumulation of MTs at the intercalated disks. Interestingly, MYK-461 increased the individual cell area of cardiomyocytes in CLIP-170 phosphorylation-dependent manner. Moreover, heart-specific CLIP-170 S311A transgenic mice demonstrated elongation of cardiomyocytes along with accumulated MTs, leading to progressive decline in cardiac contraction. In conclusion, these findings suggest that AMPK regulates the cell shape and aspect ratio of cardiomyocytes by modulating the turnover of MTs through homeostatic phosphorylation of CLIP-170 at the intercalated disks.
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http://dx.doi.org/10.15252/embr.202050949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788454PMC
January 2021