Publications by authors named "Hiroshi Matsumoto"

383 Publications

Mild metatropic dysplasia: emphasis on the magnetic resonance imaging of articular cartilage thickening.

BJR Case Rep 2021 Apr 4;7(2):20200155. Epub 2020 Nov 4.

Department of Radiology, National Defense Medical College, Saitama, Japan.

Metatropic dysplasia (MD) is a rare skeletal disorder characterized by short stature due to epiphyseal cartilage and growth plate abnormalities. The severity of MD varies from mild to lethal. This disorder is caused by mutations in the ) that encodes calcium-permeable, nonselective cation channels. A 33-year-old female presented at our hospital with a history of worsening knee pain diagnosed at the previous institution as a case of osteoarthritis. Radiographs of the knee showed epiphyseal irregularity without joint space narrowing. On MRI, fat-suppressed proton density-weighted imaging revealed thickened articular cartilage with a smooth surface and an abnormal signal intensity of the subchondral bone; weighted imaging demonstrated irregularity of the epiphysis. These findings and the familial history (both her children had mutations) led to the suspicion that her condition could be due to mosaicism for mutation. To the best of our knowledge, this is the first report of MRI findings focusing on articular cartilage thickening in a patient with mild MD. Bone dysplasia including MD should be considered in young patients with articular cartilage thickening and subchondral bone irregularities on MRI.
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http://dx.doi.org/10.1259/bjrcr.20200155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008457PMC
April 2021

Utility and safety of a new uneven double-lumen sphincterotome in cases of difficult biliary cannulation.

BMC Gastroenterol 2021 Mar 4;21(1):102. Epub 2021 Mar 4.

Department of Medicine, Shiga University of Medical Science, Seta Tsukinowa, Otsu, 520-2192, Japan.

Background: We investigated the utility and safety of a new uneven double-lumen sphincterotome in biliary cannulation in comparison with the conventional pancreatic guidewire (PGW) method.

Methods: We retrospectively evaluated 119 patients who required PGW placement because of difficult biliary cannulation. Endoscopic retrograde cholangiopancreatography (ERCP) was performed using a conventional ERCP catheter or a new uneven double-lumen sphincterotome. The success rate of bile duct cannulation, the operation time of bile duct cannulation, and the incidence of post-ERCP pancreatitis (PEP) were evaluated.

Results: Forty-four patients were treated with a new double-lumen sphincterotome (the new sphincterotome group) and 75 patients underwent conventional PGW placement (the conventional group). The success rate of bile duct cannulation was 39/44 (88.6%) in the new sphincterotome group and 63/75 (84.0%) in the conventional group (not significant). The total biliary cannulation time (from the reach to the papilla to the finish of biliary cannulation) was 16.0 (6.5-78) min in the new sphincterotome group and 26.0 (5-80) min in the conventional group (P < 0.01). The time from PGW placement to bile duct cannulation was 3.5 (0.3-57) min in the magictome group and 12.0 (1-65) min in the conventional group (P < 0.01). Hyperamylasemia was observed in 13/44 (29.5%) and 17/75 (22.7%), respectively (not significant). Five of 44 (11.3%) of the new sphincterotome group and 14/75 (18.7%) of the conventional group were diagnosed with PEP (not significant).

Conclusion: A new double-lumen sphincterotome allows selective bile duct cannulation to be performed in a shorter time than the conventional PGW method.
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http://dx.doi.org/10.1186/s12876-021-01689-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934518PMC
March 2021

A novel embryo quality scoring system to compare groups of embryos at different developmental stages.

J Assist Reprod Genet 2021 Mar 1. Epub 2021 Mar 1.

HORAC Grand Front Osaka Clinic, Osaka, 530-0011, Japan.

Purpose: To construct a new embryonic quality scoring system to compare groups of embryos at different developmental stages.

Methods: Based on a hypothesis that the implantation potential of any embryo in an ovum pickup (OPU) cycle remains the same at any stage of development, be it day 2, 3, or 5, a new embryo quality scoring (EQS) system was designed. It was based on the analysis of the clinical results of 1610 single embryo transfers. We validated this scoring system in the comparison of embryonic quality between groups by evaluating the mean scores calculated at day 2, day 3, and day 5 for 957 embryos (150 cycles) from 3 different groups. We then compared EQSs of patients with pregnancy favorable factors (group A) such as young age and high AMH levels, with the patients with contra features (group B).

Results: We confirmed that each mean EQS assessed at different stages of embryonic development within the same group was similar. The mean EQSs on day 3 and day 5 in group A were significantly higher than the mean EQSs on days 2, 3, and 5 in group B.

Conclusion: The novel EQS system proposed by us enables embryonic quality comparison between groups of embryos at different developmental stages.
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http://dx.doi.org/10.1007/s10815-021-02117-0DOI Listing
March 2021

A follow-up study of a randomized controlled study evaluating safety and efficacy of leuprorelin acetate every-3-month depot for 2 versus 3 or more years with tamoxifen for 5 years as adjuvant treatment in premenopausal patients with endocrine-responsive breast cancer.

Breast Cancer 2021 Feb 27. Epub 2021 Feb 27.

Department of Integrated Science and Technology, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, TokyoTokyo, 112-8551, Japan.

Background: Previously, we conducted the 5-year open-label, randomized controlled trial (RCT) of leuprorelin adjuvant therapy in post-operative premenopausal patients with endocrine-responsive breast cancer, which was a pilot study to investigate the optimal duration of leuprorelin treatment. Since, however, long-term outcomes became required for the adjuvant endocrine therapy, we performed this follow-up observation study.

Methods: Follow-up observation study was performed up to 10th year after randomization, continuing RCT to evaluate the efficacy and safety of leuprorelin every 3 months for ≥ 3 versus 2 years, with daily tamoxifen for 5 years. Primary endpoints were disease-free survival (DFS) and 2-year landmark DFS.

Results: Eligible patients (N = 222) were randomly assigned to receive leuprorelin for either 2 years (N = 112) or ≥ 3 years (N = 110) with tamoxifen. Leuprorelin treatment for ≥ 3 years versus 2 years provided no significant difference in DFS (HR 0.944, 95% CI 0.486-1.8392) or 2-year landmark DFS (N = 99 and 102 in 2-year and ≥ 3-year groups, HR 0.834, 0.397-1.753). In small, higher-risk subgroup (n = 17); however, 2-year landmark DFS in ≥ 3-year group was significantly longer (HR 0.095, 0.011-0.850) than that in 2-year group. The incidence of bone-related adverse events was around 5% in both groups.

Conclusions: Adjuvant leuprorelin treatment for ≥ 3 years with tamoxifen only showed similar efficacy and safety profiles to those for 2 years in analyses among all patients but suggested greater benefit in higher-risk patients. No new safety signal was identified for long-term leuprorelin treatment.

Trial Registration Number: Not applicable. This was an observational study.
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http://dx.doi.org/10.1007/s12282-020-01205-wDOI Listing
February 2021

PDZK1 induces resistance to apoptosis in esophageal adenocarcinoma cells.

Esophagus 2021 Feb 14. Epub 2021 Feb 14.

Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki-City, Okayama, 701-0192, Japan.

Background: Esophageal cancer is a lethal malignancy with a poor prognosis. The incidence of esophageal adenocarcinoma, which develops from Barrett's esophagus (BE), has recently been increasing. In a previous study, we found that PDZK1 expression is higher in long segment BE compared to that in short-segment BE. However, the function of PDZK1 in the mucosa of BE is unclear.

Aims: Clarify the role of PDZK1 in BE mucosa using PDZK1 overexpressed cells.

Methods: Human adenocarcinoma-derived OE33 cells were used as a parental cell line and transfected to generate PDZK1 overexpressed OE33 cells (PC cells) or transfected with empty vector as control cells (NC cells). Cell growth of NC and PC cells in 10% fetal bovine serum was evaluated by cell counting. The effect of PDZK1 on proteasome inhibitor (PSI)-induced apoptosis was qualified by fluorescence microscopy and quantified by flow cytometry. Expression of apoptosis-related proteins was evaluated by western blotting.

Results: There were no significant differences in cell growth between NC and PC cells. PSI significantly increased apoptosis in NC cells, but not in PC cells. In response to PSI, increased levels of cleaved-caspase3 and decreased pro-caspase3 levels were found in NC cells, but not in PC cells. In NC cells, PSI significantly decreased Bcl-2 expression without affecting Bax levels. In contrast, high expression of both Bcl-2 and Bax was observed in PC cells.

Conclusion: Overexpression of PDZK1 protein induces an apoptosis-resistant phenotype in BE cells, which may be a potential therapeutic target.
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http://dx.doi.org/10.1007/s10388-021-00819-zDOI Listing
February 2021

Investigation of clomazone-tolerance mechanism in a long-grain cultivar of rice.

Pest Manag Sci 2021 May 28;77(5):2454-2461. Epub 2021 Jan 28.

Graduate School of Agriculture, Kyoto University, Kitashirakawa-Oiwake-cho, Kyoto, Japan.

Background: Clomazone is a potent herbicide for controlling weeds that have evolved resistance to other herbicides due to its unique mode of action. Clomazone is used in rice cultivation, but is limited to long-grain cultivars because other cultivars are highly sensitive to it. In this study, we investigated the mechanism of clomazone tolerance in a long-grain cultivar.

Results: The long-grain cultivar Kasalath tolerated approximately five-fold higher doses of clomazone compared to two short-grain cultivars, Nipponbare and Koshihikari. While Arabidopsis thaliana transformed with a rice cytochrome P450, CYP81A6, showed resistance to clomazone, the cyp81a6 knockout Kasalath was unchanged in its clomazone sensitivity. The inheritance of clomazone sensitivity in the F1 and F2 of Kasalath and Nipponbare indicated the involvement of multiple loci for clomazone tolerance. Four chromosome segment substitution lines of Nipponbare/Kasalath and Koshihikari/Kasalath exhibited partial tolerance to clomazone. The overlapping DNA region among the four lines is on chromosome 5 within 11.5 Mb.

Conclusion: Multiple loci are involved in clomazone tolerance in Kasalath, one of which is located on chromosome 5. This information will help develop short-grain cultivars tolerant to clomazone. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.6274DOI Listing
May 2021

HPeV3-associated acute encephalitis/encephalopathy among Japanese infants.

Brain Dev 2021 Apr 8;43(4):528-537. Epub 2021 Jan 8.

Department of Pediatrics, Saitama Medical University, Saitama, Japan.

Objective: The current study aimed to identify and compare the clinical characteristics of human parechovirus type 3 (HPeV3)-associated acute encephalitis/encephalopathy (HPeV3E/E) between infants with abnormal brain magnetic resonance imaging (MRI) findings (typical, or MRI-positive HPeV3E/E) and those with MRI-negative findings (MRI-negative HPeV3E/E).

Methods: This is a retrospective study on patients with HPeV3 infection, and a two-step questionnaire survey performed on 837 hospitals in Japan between 2014 and 2016.

Results: We identified 240 infants with HPeV3 infection, of which 34 had been clinically-diagnosed HPeV3E/E (cHPeV3E/E). However, detailed clinical data were provided by 32 of the 34 patients. Among these 32, 23 had undergone MRI and were categorized into two groups, MRI-positive (n = 17) and -negative (n = 6). There were no significant intergroup differences in clinical lab results or symptoms, except for gastrointestinal symptoms that were only present in the MRI-negative patients. The MRI-positive group showed white matter involvement on brain MRI during the acute phase, and 8 patients presented with lesions on follow-up MRI. Furthermore, 4 (50%) of the 8 patients had neurological sequelae.

Conclusion: Clinical characteristics of cHPeV3E/E patients with and without lesions on brain MRI showed no significant differences. Therefore, considering the difficulty in distinguishing febrile infants with cHPeV3E/E from those with a sepsis-like illness, during an HPeV3 infection epidemic, it is imperative to frequently perform brain MRI in febrile infants presenting with severe disease for the early diagnosis of HPeV3E/E presenting with brain lesions.
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http://dx.doi.org/10.1016/j.braindev.2020.12.010DOI Listing
April 2021

Mucosa-Associated Microbiota in Patients with Irritable Bowel Syndrome: A Comparison of Subtypes.

Digestion 2021 3;102(1):49-56. Epub 2020 Dec 3.

Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Background: Most studies on gut microbiome of irritable bowel syndrome (IBS) have focused on fecal microbiota, instead of mucosa-associated microbiota (MAM).

Aims: The aim of this study wasto investigate the MAM in IBS patients including the difference in subtypes of IBS, namely, diarrhea-predominant IBS (IBS-D) and constipation-predominant IBS (IBS-C).

Methods: Endoscopic brush samples were taken from terminal ileum and sigmoid colon of patients with IBS (17 IBS-D patients and 7 IBS-C patients) and 10 healthy controls. The MAM of samples was profiled by 16S rRNA gene amplicon sequencing. Potential changes in the MAM at the functional level were evaluated using PICRUSt software and the KEGG database.

Results: There were no differences in MAM composition between terminal ileum and sigmoid colon according to β-diversity based on the UniFrac distance. In view of α-diversity, Shannon (evenness) but not Chao1 (richness) or observed operational taxonomic units tended to be lower in sigmoid colon MAM of IBS-C and IBS-D than the control group. The abundance of 4 genera in the sigmoid colon and 7 genera in the terminal ileum was significantly different among the 3 groups. Linear discriminant analysis effect size (LEfSe) showed that the genera of Ruminococcus, Akkermansia, Butyrivibrio, Methylobacterium, and Microbacterium and the family Erysipelotrichaceae were significantly higher in the IBS-C group, and the abundance of the genera Streptococcus, Acidaminococcus, Butyricicoccus, and Parvimonas was significantly higher in the IBS-D group. In addition, the proportion of genes responsible for the secretion system and LPS biosynthesis was significantly higher and that for methane metabolism, lysine biosynthesis, and enzyme families was significantly lower in the IBS-D group than in the IBS-C group.

Conclusion: Dysbiosis pattern and the function of the microbiome seem to be different among subtypes of IBS, and MAM may play a crucial role in IBS symptom generation.
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http://dx.doi.org/10.1159/000512167DOI Listing
December 2020

Long-Term Effect of Honeycomb β-Tricalcium Phosphate on Zygomatic Bone Regeneration in Rats.

Materials (Basel) 2020 Nov 26;13(23). Epub 2020 Nov 26.

Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan.

In recent years, artificial bones with high biocompatibility have been developed for hard tissue reconstruction. However, current bone replacement methods are inadequate for large defects, causing infection, exposure, and damage. We have developed a new honeycomb β-tricalcium phosphate (TCP) material, which achieved good bone regeneration after implantation in a rat complete zygomatic bone defect. In this study, we further investigated the ability of honeycomb β- TCP for remodeling after bone regeneration as a long-term result. Bone morphogenic protein (BMP)-2-free honeycomb β-TCP (TCP group) and honeycomb β-TCP with BMP-2 (BMP group) were implanted in the zygomatic bone of rats. Micro-computed tomography was performed to track the zygomatic bone morphology, and specimens were histologically examined for osteogenesis and remodeling. In the TCP group, no bone formation was observed at 1 month, but it was observed at 6 months. Bone formation was observed in the BMP group at 1 month, and β-TCP absorption reproducing the zygomatic bone morphology was observed at 6 months. This honeycomb β-TCP with BMP-2 may provide appropriate remodeling that reproduces good bone formation in the early stage and good morphology in the long term, offering an alternative bone reconstruction material to vascularized bone grafts.
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http://dx.doi.org/10.3390/ma13235374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731290PMC
November 2020

Efficient detection of copy-number variations using exome data: Batch- and sex-based analyses.

Hum Mutat 2021 Jan 11;42(1):50-65. Epub 2020 Nov 11.

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Many algorithms to detect copy number variations (CNVs) using exome sequencing (ES) data have been reported and evaluated on their sensitivity and specificity, reproducibility, and precision. However, operational optimization of such algorithms for a better performance has not been fully addressed. ES of 1199 samples including 763 patients with different disease profiles was performed. ES data were analyzed to detect CNVs by both the eXome Hidden Markov Model (XHMM) and modified Nord's method. To efficiently detect rare CNVs, we aimed to decrease sequencing biases by analyzing, at the same time, the data of all unrelated samples sequenced in the same flow cell as a batch, and to eliminate sex effects of X-linked CNVs by analyzing female and male sequences separately. We also applied several filtering steps for more efficient CNV selection. The average number of CNVs detected in one sample was <5. This optimization together with targeted CNV analysis by Nord's method identified pathogenic/likely pathogenic CNVs in 34 patients (4.5%, 34/763). In particular, among 142 patients with epilepsy, the current protocol detected clinically relevant CNVs in 19 (13.4%) patients, whereas the previous protocol identified them in only 14 (9.9%) patients. Thus, this batch-based XHMM analysis efficiently selected rare pathogenic CNVs in genetic diseases.
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http://dx.doi.org/10.1002/humu.24129DOI Listing
January 2021

Preference and Experience of Colonic Examination for Participants Presenting to Hospitals with a Positive Fecal Immunochemical Test Result.

Patient Prefer Adherence 2020 22;14:2017-2025. Epub 2020 Oct 22.

Department of Internal Medicine, Hokkaido Gastroenterological Hospital, Sapporo, Japan.

Purpose: Patients who test positive on the fecal immunochemical test (FIT) for colorectal cancer (CRC) are referred for colonoscopy for further diagnostic evaluation. Colonoscopy is not a perfect method and may be a challenge for some FIT-positive patients. Computed tomographic colonography (CTC) is an alternative method that is less invasive and allows examination of the whole colon. The study objective was to evaluate the preference of FIT-positive patients for either colonoscopy or CTC for CRC examination.

Patients And Methods: Individuals older than 40 years with a positive FIT test at eight Japanese hospitals between December 2012 and July 2015 were invited to participate. Participants were given detailed information regarding colonoscopy and CTC before deciding on either examination. They completed questionnaires before the procedure regarding their preference and after the procedure regarding their experience.

Results: The pre- and post-questionnaires of 846 and 834 participants, respectively, were analyzed. Participants preferred colonoscopy over CTC (colonoscopy, 72%; CTC, 28%). The possibility of obtaining biopsy samples and removing colorectal polyps during the procedure was the main reason for colonoscopy selection. Patients selected CTC to reduce discomfort but reported that CTC bowel preparation was more burdensome than colonoscopy bowel preparation. The overall experience of the examination did not differ between the groups.

Conclusion: Colonoscopy is the standard examination for FIT-positive patients. However, when given a choice, almost one-third of participants chose CTC because they thought it would be a more "comfortable" examination. Clinicians should therefore be aware of patients' potential preference for noninvasive colorectal examinations.
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http://dx.doi.org/10.2147/PPA.S267354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588835PMC
October 2020

Immunodeficiency in a patient with microcephalic osteodysplastic primordial dwarfism type I as compared to Roifman syndrome.

Brain Dev 2021 Feb 12;43(2):337-342. Epub 2020 Oct 12.

Department of Pediatrics, National Defense Medical College Hospital, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.

Background: Microcephalic osteodysplastic primordial dwarfism type I (MOPD I, also known as Taybi-Linder syndrome) is a rare genetic disorder associated with severe intrauterine growth retardation, short stature, microcephaly, brain anomalies, stunted limbs, and early mortality. RNU4ATAC, the gene responsible for this disorder, does not encode a protein but instead the U4atac small nuclear RNA (snRNA), a crucial component of the minor spliceosome. Roifman syndrome is an allelic disorder of MOPD I that is characterized by immunodeficiency complications.

Case Report: The patient described herein is an 18-year-old woman exhibiting congenital dwarfism and microcephaly with structural brain anomaly. She suffered human herpesvirus 6 (HHV-6)-associated acute necrotizing encephalopathy at the age of one, thereafter resulting in severe psychomotor disabilities. Genetic analysis using gene microarray and whole-exome sequencing could not identify the cause of her congenital anomalies. However, Sanger sequencing revealed a compound heterozygous mutation within RNU4ATAC (NR_023343.1:n.[50G > A];[55G > A]). Immunological findings showed decreases in total lymphocytes, CD4 T cells, and T cell regenerative activity. Furthermore, antibodies against varicella-zoster, rubella, measles, mumps, and influenza were very low or negative despite having received vaccinations for these viruses. HHV-6 IgG antibodies were also undetected.

Discussion: The patient here exhibited a marked MOPD I phenotype complicated by various immunodeficiencies. Previous studies have not demonstrated immunodeficiency comorbidities within MOPD I subjects, but this report suggests an evident immunodeficiency in MOPD I. Patients with MOPD I should be treated with one of the immunodeficiency syndromes.
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http://dx.doi.org/10.1016/j.braindev.2020.09.007DOI Listing
February 2021

Protocol of a randomised controlled trial on the efficacy of medication optimisation in elderly inpatients: medication optimisation protocol efficacy for geriatric inpatients (MPEG) trial.

BMJ Open 2020 10 12;10(10):e041125. Epub 2020 Oct 12.

Division of General Internal Medicine, Department of Internal Medicine, St Marianna University School of Medicine, Kawasaki-shi, Kanagawa, Japan.

Introduction: Whether medication optimisation improves clinical outcomes in elderly individuals remains unclear. The current study aims to evaluate the effect of multidisciplinary team-based medication optimisation on survival, rehospitalisation and unscheduled hospital visits in elderly patients.

Methods And Analysis: We report the protocol of a single-centre, open-label, randomised controlled trial. The enrolled subjects will be medical inpatients, aged 65 years or older, admitted to a community hospital and receiving five or more regular medications. The participants will be randomly assigned to receive either an intervention for medication optimisation or the usual care. The intervention will consist of a multidisciplinary team-based medication review, followed by a medication optimisation proposal based on the Screening Tool of Older Persons' potentially inappropriate Prescriptions/Screening Tool to Alert doctors to the Right Treatment criteria and an implicit medication optimisation protocol. Medication optimisation summaries will be sent to primary care physicians and community pharmacists on discharge. The primary outcome will be a composite of death, unscheduled hospital visits and rehospitalisation until 48 weeks after randomisation. Secondary outcomes will include each of the primary endpoints, the number of prescribed medications, quality of life score, level of long-term care required, drug-related adverse events, death during hospitalisation and falls. Participants will be followed up for 48 weeks with bimonthly telephone interviews to assess the primary and secondary outcomes. A log-rank test stratified by randomisation factors will be used to compare the incidence of the composite endpoint. The study was initiated in 2019 and a minimum of 500 patients will be enrolled.

Ethics And Dissemination: The study protocol has been approved by the Institutional Ethical Committee of St. Marianna University School of Medicine (No. 4129). The results of the current study will be submitted to a peer-reviewed journal.

Trial Registration Number: UMIN000035265.
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http://dx.doi.org/10.1136/bmjopen-2020-041125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552871PMC
October 2020

Erratum: Relationship between the Incidence of Postoperative Fistula or Dysphagia and Resection Style, Gastric Tube Formation, and Irradiation following Free Jejunum Transfer: Erratum.

Plast Reconstr Surg Glob Open 2020 Aug 10;8(8):e3094. Epub 2020 Aug 10.

Department of Plastic and Reconstructive Surgery, Japanese Red Cross Okayama Hospital, Okayama, Japan.

[This corrects the article DOI: 10.1097/GOX.0000000000002663.].
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http://dx.doi.org/10.1097/GOX.0000000000003094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489679PMC
August 2020

Prognostic Value of Psoas Muscle Mass Index in Patients With Non‒ST-Segment‒Elevation Myocardial Infarction: A Prospective Observational Study.

J Am Heart Assoc 2020 10 25;9(19):e017315. Epub 2020 Sep 25.

Department of Cardiology Kansai Medical University Osaka Japan.

Background Muscle wasting is an important predictor of long-term outcome in patients with cardiovascular disease, but the prognostic value of muscle wasting in patients with non‒ST-segment‒elevation myocardial infarction is not established. The aim of this study is to investigate the prognostic value of muscle wasting, defined by psoas muscle mass index (PMI), in patients with non‒ST-segment‒elevation myocardial infarction. Methods and Results A total of 132 consecutive patients with non‒ST-segment‒elevation myocardial infarction were prospectively enrolled between 2015 and 2018. Primary end point was incidence of cardiovascular events including cardiovascular deaths, non-fatal myocardial infarction, or non-fatal stroke. Cross-sectional area of the psoas muscle at the L3 vertebral level was obtained by computed tomography and PMI was calculated. The median follow-up period was 2.4 years (interquartile range, 1.1-4.0 years). There were 45 cardiovascular events (34%) during the study periods. The optimal cutoff value of PMI to predict cardiovascular events was 772 mm/m, as assessed by receiver operating curve analysis. Patients with reduced PMI (PMI<772 mm/m) had significantly higher cardiovascular events than those with preserved PMI (PMI≥772 mm/m) (48% versus 21%; log-rank test <0.001). Multivariate Cox proportional hazards model revealed that reduced PMI was a statistically significant predictor of cardiovascular events (hazard ratio, 3.30; 95% CI, 1.70-6.40; <0.001). Conclusions Muscle wasting defined as PMI is a simple and useful objective marker to predict future cardiovascular outcome in patients with non‒ST-segment‒elevation myocardial infarction. Registration Information URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000013445.
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http://dx.doi.org/10.1161/JAHA.120.017315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792369PMC
October 2020

Loss of skeletal muscle mass predicts cardiac death in heart failure with a preserved ejection fraction but not heart failure with a reduced ejection fraction.

ESC Heart Fail 2020 Sep 23. Epub 2020 Sep 23.

Department of Cardiology, Kansai Medical University, 10-15, Fumizono-cho, Moriguchi, Osaka, 5708507, Japan.

Aims: Loss of skeletal muscle mass is an important determinant associated with poor long-term prognosis in patients with acute decompensated heart failure (ADHF). However, limited evidence is available. This study investigated the prognostic value of the psoas muscle mass index (PMI) in patients with ADHF.

Methods And Results: A total of 210 consecutive patients aged ≥60 years with ADHF were enrolled using a prospective database between 2015 and 2017. Primary endpoint was incidence of cardiac death. Cross-sectional psoas muscle area at the L3 vertebral level was obtained by computed tomography, and PMI was calculated by height. Reduced PMI was defined as a PMI below the 25th sex-specific percentile. Patients were also classified by their left ventricular ejection fraction (EF) as having either heart failure with a reduced ejection fraction (HFrEF, EF < 50%) or heart failure with a preserved ejection fraction (HFpEF, EF ≥ 50%). The median follow-up period was 1.8 years. There were 44 cardiac deaths (21%) during the study period. Patients with reduced PMI had significantly higher cardiac death rates than those with preserved PMI (33% vs. 17%, log-rank test P = 0.006). In subgroup analysis, HFpEF patients with reduced PMI had significantly higher cardiac death rates than those with preserved PMI (38% vs. 16%, log-rank test P = 0.006); conversely, HFrEF patients had comparable cardiac death rates regardless of their PMI group (27% for reduced PMI vs. 18% for preserved PMI, log-rank test P = 0.24). Multivariate Cox proportional hazards model revealed that patients with reduced PMI had a 2.3-fold higher risk of cardiac death compared with patients with preserved PMI (95% confidence interval 1.23-4.42, P = 0.01).

Conclusions: Reduced PMI helps to predict long-term outcome in patients with HFpEF but not HFrEF.
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http://dx.doi.org/10.1002/ehf2.13021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754999PMC
September 2020

Activated microglia-derived macrophage-like cells exacerbate brain edema after ischemic stroke correlate with astrocytic expression of aquaporin-4 and interleukin-1 alpha release.

Neurochem Int 2020 11 11;140:104848. Epub 2020 Sep 11.

Department of Legal Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan. Electronic address:

Brain edema following brain infarction affects mobility and mortality. The mechanisms underlying this process remain to be elucidated. Animal studies have shown that aquaporin-4 (AQP4) expression in astrocytes increases after stroke, and its deletion significantly reduces brain swelling. Recently, two kinds of cells, resident microglia-derived macrophage-like cells (MG-MΦ) and bone marrow-derived macrophages (BM-MΦ), have been reported to accumulate in the ischemic core and stimulate adjacent astrocytes. Therefore, we hypothesized that these cells play crucial roles in the expression of AQP4 and ultimately lead to exacerbated brain edema. To verify this hypothesis, we investigated the role of MG- or BM-MΦ in brain edema using a rat model of transient middle cerebral artery occlusion and rat astrocyte primary cultures. AQP4 expression significantly increased in the peri-infarct tissue at 3-7 days post-reperfusion (dpr) and in the core tissue at 5 and 7 dpr, which synchronized with the expression of Iba1, Il1a, Tnf, and C1qa mRNA. Interleukin (IL)-1α treatment or coculture with MG- and BM-MΦ increased AQP4 expression in astrocytes, while an IL-1 receptor type I antagonist reduced these effects. Furthermore, aggravated animals exhibited high expression of Aqp4 and Il1a mRNA in the ischemic core at 7 dpr, which led to the exacerbation of brain edema. MG-MΦ signature genes were highly expressed in the ischemic core in aggravated rats, while BM-MΦ signature genes were weakly expressed. These findings suggest that IL-1α produced by MG-MΦ induces astrocytic AQP4 expression in the peri-infarct and ischemic core tissues, thereby exacerbating brain edema. Therefore, the regulation of MG-MΦ may prevent the exacerbation of brain edema.
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http://dx.doi.org/10.1016/j.neuint.2020.104848DOI Listing
November 2020

Hokuriku-plus familial hypercholesterolaemia registry study: rationale and study design.

BMJ Open 2020 09 10;10(9):e038623. Epub 2020 Sep 10.

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.

Introduction: Familial hypercholesterolaemia (FH) is an autosomal-dominant inherited genetic disease. It carries an extremely high cardiovascular risk associated with significantly elevated low-density lipoprotein (LDL) cholesterol. The diagnostic rate of this disease in some European nations is quite high, due to the presence of multiple prospective registries. On the other hand, few data-and in particular multicentre data-exist regarding this issue among Japanese subjects. Therefore, this study intends to assemble a multicentre registry that aims to comprehensively assess cardiovascular risk among Japanese FH patients while taking into account their genetic backgrounds.

Methods And Analysis: The Hokuriku-plus FH registry is a prospective, observational, multicentre cohort study, enrolling consecutive FH patients who fulfil the clinical criteria of FH in Japan from 37 participating hospitals mostly in Hokuriku region of Japan from April 2020 to March 2024. A total of 1000 patients will be enrolled into the study, and we plan to follow-up participants over 5 years. We will collect clinical parameters, including lipids, physical findings, genetic backgrounds and clinical events covering atherosclerotic and other important events, such as malignancies. The primary endpoint of this study is new atherosclerotic cardiovascular disease (ASCVD) events. The secondary endpoints are as follows: LDL cholesterol, secondary ASCVD events and the occurrence of other diseases including hypertension, diabetes and malignancies.

Ethics And Dissemination: This study is being conducted in compliance with the Declaration of Helsinki, the Ethical Guidelines for Medical and Health Research Involving Human Subjects, and all other applicable laws and guidelines in Japan. This study protocol has been approved by the Institutional Review Board at Kanazawa University. We will disseminate the final results at international conferences and in a peer-reviewed journal.

Trial Registration Number: UMIN000038210.
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http://dx.doi.org/10.1136/bmjopen-2020-038623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485236PMC
September 2020

Nutrients and probiotics: current trends in their use to eradicate .

J Clin Biochem Nutr 2020 Jul 5;67(1):26-28. Epub 2020 Jun 5.

Department of Internal Medicine, Division of Gastroenterology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.

is a well-known bacterium that infects the human gastric mucosa and causes gastric inflammation, ultimately resulting in gastric cancer. To reduce the incidence of gastric cancer, eradication therapy is important. However, the rate of successful eradication gradually decreases due to increased antibiotic resistance to . In order to increase the eradication rate and reduce gastric cancer incidence, food factors or probiotics are expected to play a beneficial role. Although several foods have been reported to inhibit bacterial load and gastric inflammation, further assessment on large population prospective studies in this field is warranted. Several food compounds, including phytochemicals, are reported to suppress the incidence of gastric cancer. Future evaluations should consider differences in geographic factors. Probiotics are effective and safe for use in eradication therapy.
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http://dx.doi.org/10.3164/jcbn.20-51DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417805PMC
July 2020

Molecular biomarker identification for esophageal adenocarcinoma using endoscopic brushing and magnified endoscopy.

Esophagus 2021 Apr 29;18(2):306-314. Epub 2020 Jul 29.

Division of Gastroenterology Department of Internal Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki City, Okayama Prefecture, 701-0192, Japan.

Background: Barrett's esophagus (BE) is a predisposing factor for esophageal adenocarcinoma (EAC); however, the precise mechanism underlying this association remains unclear. The identification of biomarkers that are associated with an increased risk of BE progression to EAC would facilitate diagnosis and early treatment. Toward this goal, we aimed to identify biomarkers associated with BE and EAC in patients.

Methods: In conjunction with high-resolution magnified endoscopy with narrow-band imaging (ME-NBI), we obtained brushing samples from the long-segment BE (LSBE) or short-segment BE (SSBE) of patients with EAC or without EAC (control). To identify candidate biomarker genes, microarray analysis was performed for a training set of 28 American samples. To confirm the microarray results, expression levels of the 16 candidate biomarkers were evaluated by real-time polymerase chain reaction analysis, using samples collected from an additional 53 American patients. In addition, we also performed a functional analysis for these genes using Gene Ontology (GO) enrichment analysis.

Results: Among the 16 genes identified as differentially expressed by microarray analysis, the GO analysis indicated matrix metalloproteinase (MMP) family associated with 'collagen metabolic process' and 'multicellular organismal macromolecule metabolic process' as the two top biological processes. Brushing samples of patients with EAC showed up-regulated expression of decay-accelerating factors (DAF and CD55) and topoisomerase type Iiα (TOP2A), and down-regulated expression of the sodium channel epithelial 1 beta subunit (SCNN1B).

Conclusions: The up-regulation of CD55 and TOP2A, and the down-regulation of SCNN1B were common to the brushing samples and might serve as molecular biomarkers for identifying EAC in patients with SSBE.

Trial Registration: University Hospital Medical Information Network (UMIN) (000004004).
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http://dx.doi.org/10.1007/s10388-020-00762-5DOI Listing
April 2021

Inflammatory cytokines, appetite-regulating hormones, and energy metabolism in patients with gastrointestinal cancer.

Oncol Lett 2020 Aug 21;20(2):1469-1479. Epub 2020 May 21.

Division of Clinical Nutrition, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.

This study investigated energy metabolism and its association with inflammatory cytokines and appetite- regulating hormones in patients with gastrointestinal cancer. Subjects were inpatients scheduled to undergo therapeutic intervention for diagnosed gastrointestinal cancer. Nutritional status on admission was assessed based on anthropometric measurements, nutrition screening results, food intake rate (energy intake/energy provided in hospital food), and biochemical test results. Fat-free mass (FFM) was measured using the bioelectrical impedance analysis. Resting energy expenditure (REE) and respiratory quotient were measured with indirect calorimetry, and basal energy expenditure (BEE) was calculated using the Harris-Benedict equation. A total 51 patients with gastrointestinal cancer were enrolled (17 with esophageal cancer, 15 with gastric cancer, and 19 with colorectal cancer); 16 had stage I disease, 11 had stage II, 13 had stage III, and 11 had stage IV. The levels of inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α increased significantly with cancer stage progression (P<0.001; Jonckheere-Terpstra trend test). The REE/body weight and the REE/FFM tended to increase with cancer stage progression (P=0.064 and P=0.053, respectively; Jonckheere-Terpstra trend test). FFM showed a significant negative correlation with the level of TNF-α (P=0.008; Spearman's correlation coefficient). Also, food intake rate showed a significant negative correlation with levels of IL-6 and TNF-α (P<0.001). The level of active ghrelin was positively correlated with that of IL-6 and energy metabolism (P=0.004 and 0.016, respectively) and negatively correlated with food intake rate (P=0.035), which suggests a state of ghrelin resistance. In conclusion, this study confirmed increases in the levels of inflammatory cytokines with the progression of gastrointestinal cancer and suggested the possible association of such increases with decreased FFM and the increased energy metabolism. However, the increased levels of active ghrelin failed to compensate for cachexia in cancer patients.
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http://dx.doi.org/10.3892/ol.2020.11662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377097PMC
August 2020

Oral Mucosa Reconstruction With a Free Muscle Flap.

J Craniofac Surg 2020 Oct;31(7):1995-1997

Department of Plastic and Reconstruction Surgery, Okayama University Hospital, Okayama City, Japan.

The use of cutaneous flaps for oral cavity reconstruction is common. However, physiologic reconstruction is not possible because of the presence of hair, and the thickness of cutaneous flaps causes difficulty when performing alveolar ridge augmentation. The authors found few published studies regarding the usefullness of oral reconstruction with free muscle flaps and no studies of histologic examination of reconstructed mucosa. Therefore, they performed a primary reconstruction of oral cavity defects with muscle flaps and allowed the raw surface to epithelialize in 5 patients who underwent oral cavity reconstruction. All flaps were successfully engrafted, and no complications occurred. Epithelialization occurred within approximately 3 months. The authors performed oral mucosal biopsy with the patient's consent and confirmed that the reconstructed oral mucosa appeared histologically normal. This method is more effective than the use of a cutaneous flap, and the physiologic reconstruction of the oral mucosa and alveolar ridge augmentation can be performed in a single operation. However, it is difficult to use in patients who require radiation therapy after the operation because of the requirement of 3 months for full epithelialization. Additionally, muscle contracture could lead to functional disabilities; thus, this procedure should be performed carefully in patients who exhibit large soft tissue defects or who have hard tissue intervention.
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http://dx.doi.org/10.1097/SCS.0000000000006703DOI Listing
October 2020

Clinical and endoscopic characteristics of eosinophilic esophagitis in Japan: a case-control study.

Asia Pac Allergy 2020 Apr 23;10(2):e16. Epub 2020 Apr 23.

Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan.

Background: Eosinophilic esophagitis (EoE) is an allergy-associated clinicopathologic condition gaining an increasing amount of recognition in various areas of the world. While the clinical definition and characteristics may differ depending on country and region, sufficient studies have not yet been performed in Japan.

Objective: To assess the prevalence of EoE among the Japanese population and the clinical features associated with the disease.

Methods: Endoscopic data from January 2012 to October 2018 was gathered from 9 Japanese clinical institutes. EoE, defined as esophageal mucosal eosinophilia of at least 15 eosinophils per high-power field, was determined based on esophageal biopsies. Clinical and endoscopic patterns in the cases with EoE were investigated and compared with 186 age- and sex-matched controls.

Results: From 130,013 upper endoscopic examinations, 66 cases of EoE were identified (0.051%; mean age, 45.2 years [range, 7-79 years]; 45 males). Twenty-five patients (37.9%) with EoE were diagnosed by endoscopy during a medical check-up. Patients with EoE had more symptoms (69.7% vs. 10.8%, < 0.01) such as dysphagia and food impaction, and more allergies (65.2% vs. 23.7%, < 0.01) compared with the controls. The prevalence of atrophic gastritis was lower in EoE patients than in the controls (20.0% vs. 33.3%, < 0.05).

Conclusion: The prevalence of EoE in the Japanese population was 0.051% which was comparable with previous reports in Japan. History of allergies and the absence of atrophic gastritis were associated with EoE.
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http://dx.doi.org/10.5415/apallergy.2020.10.e16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203441PMC
April 2020

Case-control association study of rare nonsynonymous variants of SCN1A and KCNQ2 in acute encephalopathy with biphasic seizures and late reduced diffusion.

J Neurol Sci 2020 Jul 2;414:116808. Epub 2020 Apr 2.

Department of Developmental Medical Sciences, School of International Health, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Purpose: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is characterized by prolonged febrile seizures at onset and subsequent damage to the cerebral cortex of infants and children. The pathogenesis is suspected to be excitotoxicity leading to neuronal death. SCN1A and KCNQ2 are causative genes of genetic epilepsy including Dravet syndrome and Ohtahara syndrome. Here we conducted a case-control rare-variant association study of the two genes in AESD.

Methods: The coding regions of SCN1A and KCNQ2 were sequenced by the Sanger method for 175 and 111 patients, respectively, with AESD. As control subjects, we used genetic data from 3554 subjects provided by the Integrative Japanese Genome Variation Database (iJGVD). Then we performed a case-control association study of rare missense and splice region variants (minor allele frequency < 0.005) of each gene with AESD using Weighted Sum Statistics (WSS) and Sequence Kernel Association Test (SKAT).

Results: SCN1A rare variants had a significant association with AESD after correction for multiple tests (WSS, permutated p value 4.00 × 10: SKAT, p value 2.51 × 10). The association was more significant when we focused on deleterious variants (WSS, permutated p = 9.00 × 10; SKAT, p = 4.99 × 10). Although KCNQ2 rare nonsynonymous variants tended to be more frequent in patients than in controls, there was no significant difference.

Conclusion: Our study provided statistical evidence of an association between SCN1A and AESD for the first time, and established SCN1A as one of the susceptibility genes for AESD.
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http://dx.doi.org/10.1016/j.jns.2020.116808DOI Listing
July 2020

[Factors Affecting Nutrient Intake of Students after High School Graduation: Focusing on Changes in Diet and the Period of Solitary Living].

Nihon Eiseigaku Zasshi 2020 ;75(0)

Faculty of Culture and Sport Policy, Toin University of Yokohama.

Objectives: In this study, we aim to establish supportive measures for sustaining a healthy diet in students and young adults after graduating from high school by examining possible factors leading to changes in their daily nutrient consumption.

Methods: A questionnaire survey was conducted among university, college, and vocational school students throughout the main island of Japan (total numbers of respondents with valid responses, 1,256) to evaluate their diets using a five-point scale. Two groups were selected based on the status of daily nutrient consumption. One group comprised 258 students who had maintained high nutrition scores (scored ≥ 4 points in all six primary food groups) since their third year in high school (maintained high-score group) and the other group comprised 250 students whose nutrition scores declined after high school (decreased-score group: scored high in the third year of high school but the scores decreased after admission to universities, colleges, and other institutes). By comparing these two groups, we investigated the possible factors affecting the decrease in nutrition scores.

Results: As the number of students in "the period of solitary living" and with the behavior of "skipping breakfast" increased, the proportion of students in the decreased-score group was found to increase. The eating behaviors that significantly differed between the students in the third year and those after graduating from high school were "skipping breakfast", "eating out", and "instant food intake" in the decreased-score group in both genders.

Conclusion: Results of this study indicate that we must promote measures that address the factors affecting nutrition intake after high school graduation.
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http://dx.doi.org/10.1265/jjh.19012DOI Listing
August 2020

Molecular mechanisms of Wischnewski spot development on gastric mucosa in fatal hypothermia: an experimental study in rats.

Sci Rep 2020 02 5;10(1):1877. Epub 2020 Feb 5.

Department of Legal Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.

Numerous dark-brown-coloured small spots called "Wischnewski spots" are often observed in the gastric mucosa in the patients dying of hypothermia, but the molecular mechanisms through which they develop remain unclear. We hypothesised that hypothermia may activate the secretion of gastric acid and pepsin, leading to the development of the spots. To investigate this, we performed experiments using organotypic rat gastric tissue slices cultured at 37 °C (control) or 32 °C (cold). Cold loading for 6 h lowered the extracellular pH in the culture medium. The mRNA expression of gastrin, which regulates gastric acid secretion, increased after cold loading for 3 h. Cold loading increased the expression of gastric H,K-ATPase pump protein in the apical canalicular membrane and resulted in dynamic morphological changes in parietal cells. Cold loading resulted in an increased abundance of pepsin C protein and an elevated mRNA expression of its precursor progastricsin. Collectively, our findings clarified that cold stress induces acidification by activating gastric H,K-ATPase pumps and promoting pepsin C release through inducing progastricsin expression on the gastric mucosa, leading to tiny haemorrhages or erosions of the gastric mucosa that manifest as Wischnewski spots in fatal hypothermia.
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http://dx.doi.org/10.1038/s41598-020-58894-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002760PMC
February 2020

Development and evaluation of a simultaneous and efficient quantification strategy for final prostanoid metabolites in urine.

Prostaglandins Leukot Essent Fatty Acids 2020 06 6;157:102032. Epub 2019 Nov 6.

Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan; Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan; Global Center for Medical Engineering and Informatics, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan. Electronic address:

Prostanoids (PNs) play critical roles in various physiological and pathological processes. Therefore, it is important to understand the alternation of PN expression profiles. However, a simultaneous and efficient quantification system for final PN metabolites in urine has not yet been established. Here, we developed and evaluated a novel method to quantify all final PN metabolites. By purification using a reverse phase solid phase extraction (SPE) column, the matrix effects against the final PGD, PGE, and PGF metabolites were low, and their accuracies were nearly 100%. The matrix effects against the final PGI and TXA metabolites were high using reverse phase SPE column purification alone. By applying a tandem SPE method that combined reverse phase and ion exchange SPE columns, the matrix effects decreased so that the accuracy was nearly 100%. To validate the reliability of the method, each final metabolite was quantified from mouse urine to which the PNs (PGD, PGE, and PGI) were intravenously administered. As a result, the amounts of PN metabolites were correlated with those of the PNs administered to the blood in a dose-dependent manner. To validate the method using human samples, the urinary metabolites of Crohn's disease (CD, a PN-related disease) patients and healthy individuals were quantified. All five metabolites were successfully quantified. Only final PGE metabolite levels were significantly higher in CD patients than those in healthy individuals, so that the urinary metabolite profiles of CD patients is determined. In conclusion, we developed a novel method to quantify all final PN metabolites simultaneously and efficiently and demonstrated the practicality of the method using human CD patient samples.
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http://dx.doi.org/10.1016/j.plefa.2019.102032DOI Listing
June 2020

Clinicopathological values of PD-L1 expression in HER2-positive breast cancer.

Sci Rep 2019 11 13;9(1):16662. Epub 2019 Nov 13.

Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan.

Several ongoing clinical trials are investigating the use of immuno-targeting therapy with programmed cell death protein-1 and programmed death-ligand 1 (PD-L1) inhibitors for triple-negative breast cancer. However, the role of PD-L1 expression in HER2-positive breast cancer remains unclear. We investigated the clinicopathological utility of PD-L1 expression in HER2-positive breast cancer. Cohort A included 248 patients with invasive breast cancer (all subtypes). Cohort B included 126 HER2-positive patients who received neoadjuvant chemotherapy (NAC) concomitant with trastuzumab. The relationship of PD-L1 expression on the cancer cells with clinicopathological factors including pathological complete response (pCR) and prognosis was investigated. In cohort A, 8.1% patients were PD-L1-positive; PD-L1 positivity showed a correlation with high degree of tumor-infiltrating lymphocytes (TILs), estrogen receptor negativity, progesterone receptor negativity, and high histological grade. In cohort B, 17.5% patients were PD-L1-positive; PD-L1 positivity showed a significant correlation with high degree of TILs and high abundance of CD8-positive TILs. The pCR rates were related to TILs and PD-L1 expression. Among PD-L1-negative patients, high CD8-positive TILs were associated with significantly better prognosis. In conclusion, 17.5% of HER2-positive type patients were PD-L1-positive. PD-L1 expression was associated with response to NAC with trastuzumab in patients with HER2-positive breast cancer.
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http://dx.doi.org/10.1038/s41598-019-52944-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853939PMC
November 2019

Quinclorac resistance in Echinochloa phyllopogon is associated with reduced ethylene synthesis rather than enhanced cyanide detoxification by β-cyanoalanine synthase.

Pest Manag Sci 2020 Apr 27;76(4):1195-1204. Epub 2019 Nov 27.

Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

Background: Multiple herbicide resistant Echinochloa phyllopogon exhibits resistance to the auxin herbicide quinclorac. Previous research observed enhanced activity of the cyanide-detoxifying enzyme β-cyanoalanine synthase (β-CAS) and reduced ethylene production in the resistant line, suggesting β-CAS-mediated cyanide detoxification and insensitivity to quinclorac stimulation as the resistance mechanisms. To investigate the molecular mechanisms of quinclorac resistance, we characterized the β-CAS genes alongside plant transformation studies. The association of β-CAS activity and ethylene production to quinclorac resistance was assayed in the F6 progeny of susceptible and resistant lines of E. phyllopogon.

Results: A single nucleotide polymorphism in a β-CAS1 intron deleted aberrantly spliced mRNAs and enhanced β-CAS activity in the resistant line. The enhanced activity, however, was not associated with quinclorac resistance in F6 lines. The results were supported by lack of quinclorac resistance in Arabidopsis thaliana expressing E. phyllopogon β-CAS1 and no difference in quinclorac sensitivity between β-CAS knockout and wild-type rice. Reduced ethylene production co-segregated with quinclorac resistance in F6 lines which were previously characterized to be resistant to other herbicides by an enhanced metabolism.

Conclusion: β-CAS does not participate in quinclorac sensitivity in E. phyllopogon. Our results suggest that a mechanism(s) leading to reduced ethylene production is behind the resistance. © 2019 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.5660DOI Listing
April 2020

Developing Microsurgery through Experience in Yangon General Hospital, Myanmar.

Acta Med Okayama 2019 Oct;73(5):393-401

Department of Plastic and Reconstructive Surgery, Monash Health, Clayton, Vic, Australia.

Although many surgical centers perform microsurgery routinely in developed countries, performing microsurgery is challenging in resource-poor developing countries, such as Myanmar. With the establishment of educational training programs and the assistance of volunteer plastic surgical teams, local plastic surgeons can learn the techniques of microsurgery and apply them clinically. The purpose of this study was to establish baseline data and define the challenges of performing microsurgery in Yangon General Hospital, Myanmar. Sixty-four patients underwent reconstruction with free flaps from January 2015 to January 2018. All clinical records of these cases were assessed. The number of free flap reconstructions performed increased from 11 in the first year to 24 in the third year. The anterolateral thigh flap was the most commonly used (42%). The most common sites of reconstruction were mandible and intraoral defects. Total flap survival occurred in 58 of 64 patients (89%). The total salvageable flap rate for revision surgery was 66.6%; the successful revision rate was highest in 2017, with fewer complications. The flap salvage rates increased and the operative duration decreased as clinical experience improved. Establishing a microsurgical center requires a strong multidisciplinary team, clinical experience, continuous learning, sensible clinical application, and effective interdepartmental and intradepartmental cooperation.
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http://dx.doi.org/10.18926/AMO/57369DOI Listing
October 2019