Publications by authors named "Masato Hayakawa"

22 Publications

  • Page 1 of 1

Successful Endovascular Repair of a Kommerell's Diverticulum and a Right-Sided Aortic Arch.

Heart Surg Forum 2020 Nov 23;23(6):E860-E862. Epub 2020 Nov 23.

Department of Cardiovascular Surgery, Nanbu Tokushukai Hospital, Yaese, Japan.

Background: A 57-year-old woman was diagnosed with Kommerell's diverticulum in the setting of a right aortic arch on computed tomography.

Case Report: Although asymptomatic, the maximum diameter of the aneurysm was 55 mm; thus, she underwent surgery to prevent rupture of the aneurysm. A bypass was constructed from the left common carotid artery to the left subclavian artery. A stent-graft was deployed from the distal right subclavian artery, and coil embolization of the diverticulum was performed via the left subclavian artery. She was discharged after 12 days of surgery. The postoperative four-month follow up showed a smaller aneurysm.

Conclusion: Thoracic endovascular aortic repair is feasible and effective for Kommerell's diverticulum.
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http://dx.doi.org/10.1532/hsf.3267DOI Listing
November 2020

Retrograde Type A Aortic Dissection after Thoracic Endovascular Aortic Repair for Type B Dissection.

Heart Surg Forum 2020 Jul 23;23(4):E524-E526. Epub 2020 Jul 23.

Department of Cardiovascular Surgery, Nanbu Tokushukai Hospital, Yaese, Japan.

Background: A 64-year-old woman presented with dilatation of the distal aortic arch secondary to chronic type B aortic dissection.

Case Report: The patient underwent fenestrated thoracic endovascular aortic repair (TEVAR) for closure of the entry site, and reconstruction of the left subclavian artery with a covered stent. On the 40th postoperative day, a retrograde type A aortic dissection (RTAD) was observed on computed tomography and she underwent emergency surgery. The entry tear, related to the proximal bare metal stent, was located in front of the aortic arch. A partial aortic arch replacement was performed.

Conclusion: Consideration of the risk factors of RTAD is important when performing TEVAR.
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http://dx.doi.org/10.1532/hsf.3009DOI Listing
July 2020

[Interlaboratory Study on Evaporation Residue Test for Food Contact Products (Report 2)].

Shokuhin Eiseigaku Zasshi 2018 ;59(1):64-71

National Institute of Health Sciences.

An interlaboratory study was performed to evaluate the equivalence between an official method and a modified method of evaporation residue test using heptane as a food-simulating solvent for oily or fatty foods, based on the Japanese Food Sanitation Law for food contact products. Twenty-three laboratories participated, and tested the evaporation residues of nine test solutions as blind duplicates. In the official method, heating for evaporation was done with a water bath. In the modified method, a hot plate was used for evaporation, and/or a vacuum concentration procedure was skipped. In most laboratories, the test solutions were heated until just prior to dryness, and then allowed to dry under residual heat. Statistical analysis revealed that there was no significant difference between the two methods. Accordingly, the modified method provides performance equal to the official method, and is available as an alternative method. Furthermore, an interlaboratory study was performed to evaluate and compare two leaching solutions (95% ethanol and isooctane) used as food-simulating solvents for oily or fatty foods in the EU. The results demonstrated that there was no significant difference between heptane and these two leaching solutions.
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http://dx.doi.org/10.3358/shokueishi.59.64DOI Listing
July 2018

[Interlaboratory Study on Evaporation Residue Test for Food Contact Products (Report 1)].

Shokuhin Eiseigaku Zasshi 2018 ;59(1):55-63

National Institute of Health Sciences.

An interlaboratory study was performed to evaluate the equivalence between an official method and a modified method of evaporation residue test using three food-simulating solvents (water, 4% acetic acid and 20% ethanol), based on the Japanese Food Sanitation Law for food contact products. Twenty-three laboratories participated, and tested the evaporation residues of nine test solutions as blind duplicates. For evaporation, a water bath was used in the official method, and a hot plate in the modified method. In most laboratories, the test solutions were heated until just prior to evaporation to dryness, and then allowed to dry under residual heat. Statistical analysis revealed that there was no significant difference between the two methods, regardless of the heating equipment used. Accordingly, the modified method provides performance equal to the official method, and is available as an alternative method.
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http://dx.doi.org/10.3358/shokueishi.59.55DOI Listing
July 2018

Duodenal diverticulitis accompanied by abscess formation treated successfully using an endoscopic nasobiliary drainage catheter: a case report.

Clin J Gastroenterol 2017 Jun 20;10(3):240-243. Epub 2017 Mar 20.

Department of Gastroenterology and Hepatology, JA Niigata Medical Center Hospital, 3-27-11 kobari, Nishiku, Niigata, 950-2022, Japan.

Diverticulitis and diverticular abscesses are rare and potentially serious complications of duodenal diverticulum. These conditions often lead to perforation of the diverticulum, necessitating surgical treatment. There have been few reported cases of duodenal diverticulitis with or without perforation treated by endoscopic drainage. Here, we present a case of duodenal diverticulitis accompanied by abscess formation that was treated successfully with an endoscopic nasobiliary drainage catheter. We suggest this treatment could be an acceptable option for selected patients with a localized abscess that is resistant to conservative treatment.
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http://dx.doi.org/10.1007/s12328-017-0736-1DOI Listing
June 2017

Re-evaluation of Phenotypic Expression in Differentiated-type Early Adenocarcinoma of the Stomach.

Pathol Int 2017 Mar 15;67(3):131-140. Epub 2017 Jan 15.

Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

A total of 313 cases of differentiated-type early gastric adenocarcinomas, including 113 cases of small-sized carcinoma (5< × ≤10 mm) and 121 cases of microcarcinoma (0< × ≤5 mm), were examined immunohistochemically to clarify the phenotypic expressions. They were classified into four categories (gastric phenotype (G-type), intestinal phenotype, gastrointestinal phenotype, and null phenotype) by a two-step process: the phenotype based on an immunoprofile of mucin core proteins (MUCs) with CDX2 (w/.CDX2-assessment); and the phenotype of MUCs only (w/o.CDX2-assessment). CDX2 expression was observed in 89.1% (279/313); it was highly expressed in 87.6% (106/121) of microcarcinomas. MUC2 expression increased as tumor size increased (P < 0.05). Compared with w/o.CDX2-assessment, w/.CDX2-assessment showed significantly fewer G-type carcinomas (P < 0.05). Each phenotype marker was less expressed in the submucosal part than in the mucosal part. In conclusion, CDX2 was a sensitive marker for assessing intestinal phenotype. A large portion of the early differentiated-type adenocarcinomas expressed CDX2 from the very early stage of carcinogenesis, and the proportion of G-type was unexpectedly low. Lower expression of each phenotype marker was considered the cause of phenotype alteration during submucosal invasion.
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http://dx.doi.org/10.1111/pin.12506DOI Listing
March 2017

Interlaboratory Study on Caprolactam Test for Food-Contact Nylon Products.

Shokuhin Eiseigaku Zasshi 2016 ;57(6):222-229

Tokyo Office, Japan Chemical Innovation and Inspection Institute.

The Japanese Food Sanitation Law sets a limit on the migration level of caprolactam for food-contacting nylon products. Here, we carried out an interlaboratory study in twenty laboratories to evaluate the performance of the official GC-FID test method and a GC-MS method as an alternative test method to the official method. Each laboratory quantified caprolactam in three test solutions in 20% ethanol as blind duplicates using GC-FID or GC-MS. The official method (GC-FID with absolute calibration) gave trueness, repeatability (RSDr) and reproducibility (RSDr) values of 96-97%, 3.3-5.4% and 4.0-6.7%, respectively. These values met the target criteria (trueness: 80-110%, RSDr: 10%, RSDr: 25%). The performance of the method was further improved by the introduction of heptalactam as an internal standard. As for GC-MS method, some values of the RSDr exceeded 10% when absolute calibration was used. However, when an internal standard was introduced, the trueness, RSDr and RSDr of GC-MS method were all acceptable at 94-96%, 2.0-4.4% and 7.0-9.4%, respectively. Therefore, GC-MS with an internal standard is available as an alternative test method to the official method.
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http://dx.doi.org/10.3358/shokueishi.57.222DOI Listing
March 2017

Interlaboratory Study on Volatiles Test for Food-Contacting Polystyrene Products.

Shokuhin Eiseigaku Zasshi 2016 ;57(5):169-178

Japan Recreation and Miscellaneous Goods Safety Laboratory.

Using polystyrene, acrylonitrile-styrene resin and acrylonitrile-butadiene-styrene resin pellets as samples, an interlaboratory study was performed to evaluate the volatiles test method, based on the specifications described in the Japanese Food Sanitation Law for food-contacting polystyrene products. The study was conducted with the participation of twenty-one laboratories. Each laboratory quantified the contents of styrene, toluene, ethylbenzene, isopropylbenzene and propylbenzene in three test pellets using GC-FID, GC-MS or headspace-GC-FID. Statistical analysis revealed that the repeatability (RSDr) and reproducibility (RSDr) were 1.0-2.6 and 2.5-5.5% for the GC-FID method. The values of the performance parameters fulfilled the requirements (RSDr: 10%, RSDr: 25%), and the performance is sufficient for specifications testing. The RSDr and RSDr of results obtained using the GC-MS and HS-GC methods were 1.4-7.8 and 4.9-13%(GC-MS), and 2.0-2.6 and 3.3-6.9%(HS-GC-FID), respectively. The quantified levels were similar to those obtained with GC-FID. The study suggests that the GC-MS and HS-GC methods can be employed as alternative methods to the GC-FID method.
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http://dx.doi.org/10.3358/shokueishi.57.169DOI Listing
March 2017

Magnified endoscopic findings with a barnacle-like appearance in enterocolitis associated with sepsis.

Gastrointest Endosc 2015 Feb 22;81(2):472-3; discussion 473. Epub 2014 Nov 22.

Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

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http://dx.doi.org/10.1016/j.gie.2014.09.026DOI Listing
February 2015

Combined total arch replacement and bypass from the ascending aorta to the bilateral profunda femoris arteries.

Ann Vasc Dis 2014 16;7(2):183-6. Epub 2014 May 16.

Division of Cardiovascular Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan.

A 72-year-old woman who had aortic arch aneurysm was admitted. The patient was unable to walk without assistance because of aortoiliac occlusive disease. Total arch replacement and the ascending aorta to the bilateral profunda femoris artery bypass were performed during the same operation. On outpatient visits, the patient was able to walk with a cane and the ankle-brachial pressure index was markedly improved. This combined procedure is an option for patients with aortoiliac occlusive disease who are not candidates for alternate inflow procedures, especially when the patient has another indication for median sternotomy.
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http://dx.doi.org/10.3400/avd.cr.13-00121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072872PMC
July 2014

Quadricuspid aortic valve: a report on a 10-year case series and literature review.

Ann Thorac Cardiovasc Surg 2014 15;20 Suppl:941-4. Epub 2014 Mar 15.

Division of Cardiovascular Surgery, Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan.

Quadricuspid aortic valve is rare, with an estimated incidence of 0.008% to 1.46%. Most cases are encountered incidentally during aortic valve surgery or autopsy. The condition frequently progresses to aortic regurgitation, which can manifest in adulthood and may require surgical treatment. This anomaly may sometimes be associated with other malformations, the most common being coronary artery anomalies. We performed a retrospective chart review of patients diagnosed with quadricuspid aortic valve between January 2002 and July 2012 and report here on cases treated surgically. We encountered three cases of quadricuspid aortic valve among 627 patients undergoing aortic valve surgery at our institution (an incidence of 0.48%). All three had aortic regurgitation and two were free of cardiac anomaly; the other had ascending aortic aneurysm and coronary malformation. According to Hurwitz's classification, two of the valves were of type b and one of type d. Under Nakamura's classification, meanwhile, two of the valves were type II and the other type III. All patients underwent successful aortic valve replacement and had uneventful postoperative courses.
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http://dx.doi.org/10.5761/atcs.cr.13-00125DOI Listing
November 2015

Target vessel detection by epicardial ultrasound in off-pump coronary bypass surgery.

Innovations (Phila) 2013 Jul-Aug;8(4):249-52

From the *Division of Cardiovascular Surgery, Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa, Otsu, Shiga, Japan; and †Division of Cardiovascular Surgery, Oumikusatsu Tokusyukai Hospital, Kusatsu, Shiga, Japan.

Objective: The detection of embedded coronary arteries is difficult especially in off-pump coronary bypass surgery. From June 2010, we introduced high-frequency epicardial ultrasound (ECUS) to assess and evaluate embedded arteries during off-pump coronary bypass surgery.

Methods: Between June 2010 and June 2011, a total of 89 consecutive patients underwent isolated coronary bypass surgery at our institution. The patients consisted of 72 men and 17 women with a mean age of 67.9 years. We routinely use the VeriQC system (MediStim, Oslo, Norway) to detect the target vessels in the operation. The patients were assigned to one of two groups, depending on whether ECUS was used in the operation (n = 10, ECUS group) or not (n = 79, non-ECUS group). We analyzed the impact of introducing the ECUS in terms of operative outcome.

Results: All patients underwent revascularization using the off-pump technique without emergent conversion to cardiopulmonary bypass during surgery. The total number of distal anastomoses was 299, and 12 target vessels could not be identified either visually or on palpation. Thus, the frequency of the embedded coronary arteries was 4.01% (12/299 cases). The preoperative profiles of the two groups were not significantly different. Operation time was significantly longer in the ECUS group (P = 0.02). There were no significant differences in postoperative outcome between the two groups.

Conclusions: In the present study, in which the target coronary arteries could not be detected either visually or on palpation in 12 (4.01%) of 299 cases, the use of high-frequency ECUS allowed all patients to undergo off-pump coronary bypass surgery without conversion to cardiopulmonary bypass during the operation. High-frequency ECUS is therefore useful in off-pump coronary bypass surgery.
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http://dx.doi.org/10.1097/IMI.0b013e3182a75e95DOI Listing
June 2014

Off-pump coronary artery bypass grafting using skeletonized in situ arterial grafts.

Ann Cardiothorac Surg 2013 Jul;2(4):552-6

Division of Cardiovascular Surgery, Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa, Otsu, Shiga, Japan.

Skeletonization is an advanced technique of graft harvesting for coronary artery bypass grafting (CABG), and while it requires meticulous attention, it has many advantages. For example, skeletonization of internal thoracic artery (ITA) can minimize sternal ischemia and lower the risk of mediastinitis, and is longer and larger than pedicled ITA. In this article we describe the surgical techniques demonstrated in our video, which details our techniques of skeletonization of arterial grafts and off-pump coronary artery bypass (OPCAB) exclusively using these in situ grafts. Our method of right gastroepiploic artery (GEA) skeletonization has only three technical steps. The first step is to pass thin vessel loops under the GEA. The second step is to unroof the tissue surrounding the GEA. The last step is to seal and sever all the branches. Skeletonization of the GEA not only prevents vasospasm but also leads to GEA dilatation, and facilitates inspection and makes sequential anastomosis easier. Bilateral use of the skeletonized ITA and use of the skeletonized GEA can cover most coronary artery target sites without any manipulation of the ascending aorta. In our consecutive series of over 1,000 patients, the stroke rate was 0.5%. Our method helps to make the technique simple and secure in this technically demanding operation, and we believe that OPCAB with these grafts provides the best possible coronary revascularization.
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http://dx.doi.org/10.3978/j.issn.2225-319X.2013.07.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741885PMC
July 2013

Total arch replacement with selective antegrade cerebral perfusion and mild hypothermic circulatory arrest.

Ann Cardiothorac Surg 2013 Mar;2(2):235-8

Division of Cardiovascular Surgery, Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa, Otsu, Shiga, 520-2192, Japan.

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http://dx.doi.org/10.3978/j.issn.2225-319X.2013.03.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741831PMC
March 2013

Early and long-term patency of in situ skeletonized gastroepiploic artery after off-pump coronary artery bypass graft surgery.

Ann Thorac Surg 2013 Jul 31;96(1):90-5. Epub 2013 May 31.

Department of Cardiovascular Surgery, Shiga University of Medical Science, Setatsukinowa, Otsu, Shiga, Japan.

Background: There is at present no accurate figure for the long-term patency rate of the skeletonized gastroepiploic artery (GEA).

Methods: From January 2002 to July 2012, 956 consecutive patients underwent isolated off-pump coronary artery bypass graft (OPCABG) surgery at our institution. Of these, the 424 who underwent GEA grafting and postoperative GEA graft evaluation were the subjects of the present study. Of these 424 subjects, 155 (36.6%) underwent long-term outpatient evaluation using multidetector computed tomography angiography.

Results: No patient was converted from off pump to on pump surgery. Overall 30-day mortality was 0.5% (2 of 424). The overall early (4 to 21 days after surgery) patency rate of the skeletonized GEA was 98.2% (599 of 610 anastomoses). A total of 215 GEA anastomoses, including 55 sequential bypasses, were followed for long-term evaluation, of which 12, including three sequential bypasses, were found to be occluded. The overall patency rate in skeletonized GEA grafting over a mean follow-up period of 73 months was 94.4% (203 of 215). The cumulative patency rate of the skeletonized GEA was 97.8% at 30 days, 96.7% at 1 year, 96.0% at 3 years, 94.7% at 5 years, and 90.2% at 8 years after surgery. Multivariate Cox proportional hazard regression analysis showed that target vessel stenosis (p = 0.008, hazard ratio 0.086, 95% confidence interval: 0.014 to 0.53) was the only independent predictor of late graft occlusion.

Conclusions: We demonstrated an accurate long-term patency rate for the skeletonized GEA superior to that for pedicled GEA or saphenous vein graft. A low-grade degree of target vessel stenosis was the only risk factor for late GEA occlusion.
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http://dx.doi.org/10.1016/j.athoracsur.2013.04.018DOI Listing
July 2013

Surgical repair of Kommerell's diverticulum and an aberrant subclavian artery.

Surg Today 2014 Feb 27;44(2):247-51. Epub 2013 Apr 27.

Division of Cardiovascular Surgery, Department of Surgery, Shiga University of Medical Science, Setatsukinowacho, Otsu, Shiga, 520-2192, Japan,

Purpose: The coexistence of Kommerell's diverticulum and an aberrant subclavian artery (ASCA) is a rare congenital variation of the vascular structure. We report our experience of treating aneurysms associated with these anomalies.

Methods: Between June 2007 and November 2011, five consecutive patients underwent repair of an aneurysm associated with Kommerell's diverticulum and an ASCA at Shiga University Hospital. Four of the five patients had a right-sided aortic arch associated with the ASCA. One patient underwent emergency surgery for a ruptured thoracic aneurysm. The operations performed were descending aorta replacement through right thoracotomy in one patient and total arch replacement through a median thoracotomy, under deep hypothermic circulatory arrest and selective cerebral perfusion, in four patients. No staged operation was required.

Results: One patient died of mediastinitis, subsequent to a ruptured Kommerell's diverticulum, 45 days postoperatively. There were no other deaths in the early or late (6-58 months) postoperative period. One patient required re-exploration for bleeding, but none of the patients suffered neurologic complications.

Conclusions: Aortic disease with an ASCA and Kommerell's diverticulum can be repaired safely under elective conditions.
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http://dx.doi.org/10.1007/s00595-013-0602-9DOI Listing
February 2014

Mid-term results for the use of the extended sandwich patch technique through right ventriculotomy for postinfarction ventricular septal defects.

Eur J Cardiothorac Surg 2013 May 19;43(5):e116-20. Epub 2013 Feb 19.

Division of Cardiovascular Surgery, Department of Surgery, Shiga University of Medical Science, Otsu, Japan.

Objectives: Postinfarction ventricular septal defect (VSD) is a rare, but feared, complication after acute myocardial infarction. Although numerous techniques and materials have been used, the best technique has not yet been settled upon. We present a novel technique of VSD closure through the VSD via right ventricular (RV) incision and assess short- and mid-term outcomes.

Methods: Between April 2008 and March 2012, 15 consecutive patients presenting with postinfarction VSD underwent surgical repair using this technique in our department.

Results: Thirty-day mortality was 20% (3 patients). Two patients died from low cardiac output. No early complications related to the VSD repair were observed, such as shunt recurrence, severe septal dyskinesia or pseudoaneurysmal change in the left ventricular myocardium. The left ventricle was contracted well without mitral regurgitation. The mean follow-up period was 17 ± 15 months. The Kaplan-Meier estimate of 3-year cumulative survival is 76%. At the mid-term stage, one trivial residual leak was noted, but no patient required reoperation. RV function was within the normal range after the operation.

Conclusions: This method of VSD repair using right ventricle incision and trans-VSD approach is safe and simple and reduces the postoperative recurrence of VSD.
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http://dx.doi.org/10.1093/ejcts/ezt027DOI Listing
May 2013

Selective cerebral perfusion with mild hypothermic lower body circulatory arrest is safe for aortic arch surgery.

Eur J Cardiothorac Surg 2013 Apr 11;43(4):e94-8. Epub 2013 Jan 11.

Department of Cardiovascular Surgery, Shiga University of Medical Science, Setatsukinowa, Otsu, Shiga, Japan.

Objectives: The antegrade selective cerebral perfusion (SCP) technique, which extends the safe time limit for arch surgery, has now gained acceptance. However, neither the optimal hypothermic temperature nor the optimal SCP flow rate has been clearly determined.

Methods: From January 2008 to February 2012, a total of 105 patients underwent total arch replacement under a single surgeon (A.T.) at Shiga Medical University Hospital. The patients were 85 males and 20 females with a mean age of 73 years (range 41-88). The cause of the aneurysm was atherosclerosis in 90 patients and dissection in 15. Eighty-one patients with chronic lesion underwent elective surgery and 24 underwent emergent surgery. Univariate analysis of postoperative neurological dysfunction and early mortality was performed.

Results: The mean operation time, cardiopulmonary bypass (CPB) time, coronary ischaemic time, lower body circulatory arrest (CA) time and SCP time were 277 ± 83 min, 164 ± 40 min, 92 ± 33 min, 58 ± 22 min and 95 ± 28 min, respectively. Thirty-day mortality occurred in 1 ruptured emergent case (1%). Hospital mortality (>30 days) occurred in 3 cases (3%), 2 due to multisystem organ failure following emergent rupture and the other to cerebrovascular accident in an elective surgery case. Permanent neurological dysfunction (PND) occurred in 3 patients (3%) and temporary neurological dysfunction (TND) also in 3 patients (3%).

Conclusions: SCP under mild hypothermia can be safely applied to aortic arch surgery and is associated with a low rate of hospital mortality and morbidity. However, prolonged SCP time is associated with incidences of postoperative neurological deficit.
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http://dx.doi.org/10.1093/ejcts/ezs690DOI Listing
April 2013

Specific interactions between lactose repressor protein and DNA affected by ligand binding: ab initio molecular orbital calculations.

J Comput Chem 2011 Jun 15;32(8):1661-70. Epub 2011 Feb 15.

Department of Computer Science and Engineering, Toyohashi University of Technology, Toyohashi, Aichi 441-8580, Japan.

Transcription mechanisms of gene information from DNA to mRNA are essentially controlled by regulatory proteins such as a lactose repressor (LacR) protein and ligand molecules. Biochemical experiments elucidated that a ligand binding to LacR drastically changes the mechanism controlled by LacR, although the effect of ligand binding has not been clarified at atomic and electronic levels. We here investigated the effect of ligand binding on the specific interactions between LacR and operator DNA by the molecular simulations combined with classical molecular mechanics and ab initio fragment molecular orbital methods. The results indicate that the binding of anti-inducer ligand strengthens the interaction between LacR and DNA, which is consistent with the fact that the binding of anti-inducer enhances the repression of gene transcription by LacR. It was also elucidated that hydrating water molecules existing between LacR and DNA contribute to the specific interactions between LacR and DNA.
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http://dx.doi.org/10.1002/jcc.21744DOI Listing
June 2011

Translocation of lysosomal cathepsin D caused by oxidative stress or proteasome inhibition in primary cultured neurons and astrocytes.

Biol Pharm Bull 2010 ;33(1):22-8

Research Team for Functional Genomics, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.

We reported previously that N-linked glycoproteins were accumulated in the cytosol of the normal aging rat brain, and that one protein had been identified as cathepsin D (Mech. Ageing Dev., 127, 771-778 (2006)). In this study, to elucidate the mechanism of cathepsin D accumulation in the cytosol, we examined the effects of oxidative stress and proteasome inhibition on the apoptosis and subcellular localization of cathepsin D in primary cultured neurons and astrocytes. Using 4'-6-diamidino-2-phenylindole (DAPI)- or Hoechst 33342-staining and annexin V detection, we found that oxidative stress caused by tert-butyl hydroperoxide and proteasome inhibition by lactacystin induced apoptosis in neurons and astrocytes. Furthermore, after cell fractionation, it was demonstrated that cathepsin D was translocated from lysosomes to cytosol under apoptosis-inducing conditions in both cells. These results suggested that oxidative stress and the suppression of proteasome activity triggered the translocation of cathepsin D from lysosomes to cytosol. The possible mechanism of age-related accumulation of cathepsin D in the cytosol of the normal rat brain will be discussed.
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http://dx.doi.org/10.1248/bpb.33.22DOI Listing
June 2010

Molecular mechanics and molecular orbital simulations on specific interactions between peroxisome proliferator-activated receptor PPARalpha and plasticizer.

J Mol Graph Model 2008 Aug 23;27(1):45-58. Epub 2008 Feb 23.

Department of Occupational Environmental Health, Nagoya University, Graduate School of Medicine, Nagoya, Japan.

Peroxisome proliferator-activated receptor alpha (PPARalpha) has various physiological functions such as lipid and glucose metabolism, inflammation and fibrosis in living organisms. Many types of ligand molecules such as phthalate and adipate esters control these physiological functions. In the present study, to elucidate the dependence of PPARalpha properties on ligand binding, we investigated stable structures and electronic properties for the complexes of PPARalpha and phthalate as well as adipate esters, which are used as a plasticizer, by molecular simulations based on molecular mechanics and molecular orbital methods. Furthermore, to elucidate the influence of these esters in vivo, we injected them into male mice and observed the change in the expression of PPARalpha-related enzymes. The comparison between the calculated and observed results indicates that the change in the expression has a correlation with the size of energy gaps between highest occupied and lowest unoccupied molecular orbitals of the complexes with mouse PPARalpha and esters.
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http://dx.doi.org/10.1016/j.jmgm.2008.02.003DOI Listing
August 2008
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