Publications by authors named "Takafumi Saito"

101 Publications

Vibrotactile Feedback System From the Fingertip to the Temples for Perceptual Enhancement of Contracture Palpation.

IEEE Trans Haptics 2021 Apr-Jun;14(2):285-290. Epub 2021 Jun 17.

Contractures are generally assessed by a physician or physical therapist through palpation. However, contracture palpation requires skill and experience. The frictional vibration, which has a pulse-like vibration due to sliding disturbances around the affected area during palpation, is important in assessing the degree of contracture progression. This paper aims to enhance the perceptual sensitivity of frictional vibration for contracture palpation using a vibrotactile feedback system. We previously proposed an evaluation system for palpation with a wearable skin vibration sensor that detects skin-propagated vibration, allowing touch with a bare fingertip. In this paper, we propose the vibrotactile feedback system that presents the tactile information of the fingertip detected by the wearable tactile sensor to the temples with a vibrotactile display. A stimulator that gives vibrations similar to those during the palpation, which include pulse-like vibration and small vibration, was assembled. Then, psychophysical experiments on the vibrotactile feedback system were conducted using this stimulator. The results showed that the detection sensitivity of the pulse-like vibration was significantly enhanced with the feedback.
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http://dx.doi.org/10.1109/TOH.2021.3076501DOI Listing
June 2021

Intrahepatic distribution of nerve fibers and alterations due to fibrosis in diseased liver.

PLoS One 2021 14;16(4):e0249556. Epub 2021 Apr 14.

Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan.

Autonomic nerve fibers in the liver are distributed along the portal tract, being involved in the regulation of blood flow, bile secretion and hepatic metabolism, thus contributing to systemic homeostasis. The present study investigated changes in hepatic nerve fibers in liver biopsy specimens from patients with normal liver, viral hepatitis and non-alcoholic steatohepatitis, in relation to clinical background. The areal ratio of nerve fibers to the total portal area was automatically calculated for each sample. The nerve fiber areal ratios (NFAR) for total nerve fibers and sympathetic nerve fibers were significantly lower in liver affected by chronic hepatitis, particularly viral hepatitis, and this was also the case for advanced liver fibrosis. However, the degree of inflammatory activity did not affect NFAR for either whole nerves or sympathetic nerves. Comparison of samples obtained before and after antiviral treatment for HCV demonstrated recovery of NFAR along with improvement of liver fibrosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249556PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046205PMC
April 2021

A machine learning-based treatment prediction model using whole genome variants of hepatitis C virus.

PLoS One 2020 5;15(11):e0242028. Epub 2020 Nov 5.

Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan.

In recent years, the development of diagnostics using artificial intelligence (AI) has been remarkable. AI algorithms can go beyond human reasoning and build diagnostic models from a number of complex combinations. Using next-generation sequencing technology, we identified hepatitis C virus (HCV) variants resistant to directing-acting antivirals (DAA) by whole genome sequencing of full-length HCV genomes, and applied these variants to various machine-learning algorithms to evaluate a preliminary predictive model. HCV genomic RNA was extracted from serum from 173 patients (109 with subsequent sustained virological response [SVR] and 64 without) before DAA treatment. HCV genomes from the 109 SVR and 64 non-SVR patients were randomly divided into a training data set (57 SVR and 29 non-SVR) and a validation-data set (52 SVR and 35 non-SVR). The training data set was subject to nine machine-learning algorithms selected to identify the optimized combination of functional variants in relation to SVR status following DAA therapy. Subsequently, the prediction model was tested by the validation-data set. The most accurate learning method was the support vector machine (SVM) algorithm (validation accuracy, 0.95; kappa statistic, 0.90; F-value, 0.94). The second-most accurate learning algorithm was Multi-layer perceptron. Unfortunately, Decision Tree, and Naive Bayes algorithms could not be fitted with our data set due to low accuracy (< 0.8). Conclusively, with an accuracy rate of 95.4% in the generalization performance evaluation, SVM was identified as the best algorithm. Analytical methods based on genomic analysis and the construction of a predictive model by machine-learning may be applicable to the selection of the optimal treatment for other viral infections and cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242028PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644079PMC
December 2020

Different patterns in age-related morphometric alteration of myelinated fibers and capillaries of the tibial nerve: a longitudinal study in normal rats.

J Anat 2020 06 12;236(6):1101-1111. Epub 2020 Feb 12.

Laboratory of Health and Exercise Epidemiology, Center for Health Science and Counseling, Kyushu University, Fukuoka, Japan.

Age-related regression of myelinated fibers in peripheral nerves of the lower limbs is strongly influenced by capillaries and results in balance dysfunction and falls. However, the temporal relationships between alteration patterns of myelinated fibers and capillaries have not yet been clarified. This study aimed to investigate age-related morphological and histological changes of both myelinated fibers and capillaries in peripheral nerves to clarify whether myelinated fibers or capillaries change earlier. Seven male Wistar rats each were randomly selected at 20 weeks (young group), 70 weeks (middle group), and 97 weeks (old group) for histological evaluations. The left and right tibial nerves were removed morphologically and histologically to examine myelinated fibers and capillaries. Axon diameter and myelin thickness were almost unaltered in the middle group compared with the young group but were significantly reduced in the old group when compared with the other two groups. However, the capillary diameter and number of microvascular branch points were substantially reduced in the middle group. The current study demonstrates that myelinated fibers of peripheral nerves show signs of regression in elderly rats, whereas capillaries start to reduce in middle-aged animals. In normal aging of the tibial nerve, capillaries may regress before myelinated fibers.
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http://dx.doi.org/10.1111/joa.13168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219619PMC
June 2020

Incidence of development of hepatocellular carcinoma in Japanese patients infected with hepatitis B virus is equivalent between genotype B and C in long term.

J Viral Hepat 2019 07 23;26(7):866-872. Epub 2019 Apr 23.

Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan.

Hepatitis B virus (HBV) genotypes B (HBV/B) and C (HBV/C) are the most prevalent genotypes among Japanese patients with hepatitis. Reportedly, HBV/C infection has been associated with more severe disease progression, manifesting as developing cirrhosis and hepatocellular carcinoma (HCC), than HBV/B infection. However, no long-term studies have examined the development of HCC in HBV/B-infected patients in Japan. The aims of our study were to compare the incidence of HCC in HBV/B- or HBV/C-infected patients. A total of 241 patients were followed up among 295 hepatitis B surface antigen (HBsAg)-positive carriers. Genotypes of HBV were A in 1% (4/295), B in 61% (179/295), C in 37% (110/295) and D in 1% (2/295) patients, and 96% of HBV/B were infected with subgenotype Bj. The mean age at HCC diagnosis was significantly higher in HBV/B than in HBV/C (67.0 ± 10.0 vs 57.7 ± 8.0 years, P < 0.001). The value of FIB-4 index was significantly higher in HBV/B than in HBV/C (P < 0.01). The rate of HCC was higher in HBV/C than in HBV/B, and a significant difference was observed until the 20-year observation period (P = 0.048). However, thereafter, HCC associated with HBV/B increased, and no significant difference was observed between HBV/B and HBV/C. HCC development was consistently observed even in HBV/B infection, especially among elderly patients with advanced fibrosis compared with HBV/C. HBV/B-infected patients developed HCC later in life, and in the long term, we found no differences in incidence of HCC development rates between these two genotypes.
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http://dx.doi.org/10.1111/jvh.13099DOI Listing
July 2019

Feasibility and reliability of supermicrosurgical vasa recta anastomosis for double-pedicled free jejunum transfer.

JPRAS Open 2019 Mar 12;19:125-134. Epub 2019 Jan 12.

Department of Plastic and Reconstructive Surgery, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Background: Although free jejunal transfer is an established and reliable procedure for reconstruction after total pharyngolaryngectomy (TPL), vascular thrombosis remains a surgical challenge. To reduce the risk, a double-pedicled free jejunal flap transfer has been attempted using a root jejunal artery and an arcade artery, although several drawbacks exist. The vasa recta are terminal straight vessels that arborize from an arcade artery without branching. We present a novel double-pedicled free jejunum transfer using vasa recta anastomosis.

Methods: Between 2011 and 2015, we performed 14 double-pedicled free jejunal flap transfers for reconstruction after TPL. Vasa recta were used for second arterial anastomosis in 5 out of 14 patients. Others include a root artery in three patients and an arcade artery in six patients. Indocyanine green (ICG) angiography was performed to confirm the patency and perfusion of the entire flap by the second artery alone.

Results: The flaps survived completely in all cases. The vasa recta (average diameter; 0.8 mm) were anastomosed to the superior thyroid artery and transverse cervical artery in four and one cases, respectively. Supramicrosurgical end-to-side anastomosis was performed in two cases. ICG angiography showed sufficient perfusion of the entire flap with the second artery alone in all cases.

Conclusion: As vasa recta were confirmed as being capable of perfusing the entire flap up to 25 cm, the double-pedicle method using vasa recta might be an option to reduce the risk of flap necrosis, particularly in high-risk patients.
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http://dx.doi.org/10.1016/j.jpra.2019.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061654PMC
March 2019

Remodeling of myelinated fibers and internal capillaries in distal peripheral nerves following aerobic exercise in aged rats.

J Appl Physiol (1985) 2018 10 19;125(4):1051-1061. Epub 2018 Jul 19.

Laboratory of Health and Exercise Epidemiology, Center for Health Science and Counseling, Kyushu University, Kasuga City, Fukuoka , Japan.

The aim of this study was to determine whether aerobic exercise (AE) in old age contributes to improving the morphologies of myelinated fibers (MFs) in peripheral nerves as well as capillaries. Furthermore, we investigated whether such processes are associated with complementary activity of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in the circulating blood and peripheral nerve tissue. Fourteen male Wistar rats (age: 95 wk) were randomly divided into moderate AE ( n = 8) and sedentary (SED; n = 6) groups. Rats in the AE group performed treadmill running for 1 h per day for 2 wk, following which the bilateral tibial nerves of the two groups were removed to examine MF and capillary structure. Levels of BDNF and VEGF in the serum and peripheral nerves were analyzed via enzyme-linked immunosorbent assay. Myelin thickness, axon diameter, and capillary luminal diameter were significantly larger in the AE group than in the SED group ( P < 0.0001). Levels of serum BDNF and VEGF were significantly lower and higher, respectively, in the AE group than in the SED group ( P < 0.001). Conversely, BDNF and VEGF levels in tibial nerve tissue were significantly higher, respectively, and lower in the AE group than in the SED group ( P < 0.001). In conclusion, our study indicates that regular AE induces enlargement of the capillaries and thickens the myelin in aged peripheral nerves, likely via a complementary process involving BDNF and VEGF. NEW & NOTEWORTHY Accumulating evidence indicates that age-related sarcopenia is accompanied by the degeneration of myelinated fibers (MFs) in peripheral nerves. Our study indicates that regular aerobic exercise contributes to increased thickness of the myelin surrounding MFs and enlargement of the capillaries, likely via a complementary process involving brain-derived neurotrophic factor and vascular endothelial growth factor. Our findings demonstrate that regular, moderate-intensity aerobic exercise may help to prevent and reverse peripheral nerve regression in older adults.
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http://dx.doi.org/10.1152/japplphysiol.00257.2018DOI Listing
October 2018

[Bilateral Internal Carotid Artery Dissection Caused by Elongated Styloid Processes:A Case Report].

No Shinkei Geka 2018 Jan;46(1):53-59

Department of Neurosurgery, Nagano Red Cross Hospital.

We report a case of bilateral internal carotid artery(ICA)dissection associated with bilateral elongated styloid processes(ESPs). A 46-year-old man presented with transient aphasia and left visual disturbance at a business meeting. He complained of a foreign body sensation in his throat during swallowing for two years. Magnetic resonance imaging(MRI)demonstrated fresh small infarcts in the left corona radiata. Magnetic resonance angiography(MRA)revealed string signs bilaterally in the cervical ICAs. The patient was diagnosed with bilateral idiopathic ICA dissection and was treated with ozagrel and clopidogrel. Three-dimensional computed tomographic angiogram(3DCTA)indicated bilateral ESPs and bilateral ICA stenosis. 3DCTA with the patient's head tilting and neck extension revealed that each ICA was compressed by the ipsilateral ESP. A follow-up MRA showed complete normalization of bilateral ICAs after neck rest and anti-platelet therapy, following which, clopidogrel was stopped. The patient wore a soft cervical collar until the operation, to avoid contact between the ESPs and ICAs due to changes in head position. Bilateral ESP resection was performed to prevent recurrence of cerebral ischemic events caused by ICA dissection. The patient was discharged one week after the surgery without any neurological deficit. There was no recurrence of symptoms during the next eight months after the operation.
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http://dx.doi.org/10.11477/mf.1436203675DOI Listing
January 2018

Free Lateral Digital Flap for Reconstruction of the Fingers.

Ann Plast Surg 2017 Nov;79(5):477-481

From the Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Background: The region between the proximal interphalangeal (PIP) and the metacarpophalangeal (MP) creases has greater laxity than other regions in the fingers, allowing for primary closure of the donor site. We postulated if we could consistently locate perforators from the region between the PIP and the MP crease on the radial side of the middle and ring fingers, on which a scar would be less conspicuous than one on the radial side of the index finger, these regions would be ideal donor sites for digital reconstruction using very small flaps.

Methods: In 20 fingers (10 middle fingers and 10 ring fingers) from 5 volunteers, perforators from the radial proper digital artery were visualized between the PIP and the MP creases using ultrasonography. Based on this information, and to evaluate its feasibility, a free lateral digital flap was used for reconstruction of small digital defects in 3 cases.

Results: Of the 20 fingers, 19 had at least 1 digital artery perforator (DAP) arising from the radial proper digital artery between the PIP and MP creases. The average distance from the PIP crease to the DAP was 9.0 mm. The average diameter of the DAP was 0.37 mm. In all clinical cases, flaps survived completely with pleasing cosmesis. There were no donor site complications.

Conclusions: With their consistent anatomy and relatively low donor site morbidity, free lateral digital flaps from the radial side of the middle or ring fingers may be a reliable option for reconstruction of the volar surface of the digits.
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http://dx.doi.org/10.1097/SAP.0000000000001090DOI Listing
November 2017

Pancreatic hyperechogenicity associated with hypoadiponectinemia and insulin resistance: A Japanese population study.

World J Hepatol 2016 Nov;8(33):1452-1458

Naohiko Makino, Nakao Shirahata, Teiichiro Honda, Yoshiaki Ando, Akiko Matsuda, Yushi Ikeda, Miho Ito, Yuko Nishise, Takafumi Saito, Yoshiyuki Ueno, Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, Japan.

Aim: To examine the relationship between pancreatic hyperechogenicity and risk factors for metabolic syndrome.

Methods: A general population-based survey of lifestyle-related diseases was conducted from 2005 to 2006 in Japan. The study involved 551 participants older than 40 year of age. Data for 472 non-diabetic adults were included in the analysis. The measures included the demographic factors, blood parameters, results of a 75 g oral glucose tolerance test, and abdominal ultrasonography. The echogenicity of the pancreas and liver was compared, and then the subjects were separated into two groups: cases with pancreatic hyperechogenicity ( = 208) and cases without (controls, = 264). The differences between both groups were compared using an unpaired -test or Fisher's exact test. Multiple logistic regression analysis was used to determine the relationship between the pancreatic hyperechogenicity and clinical and biochemical parameters.

Results: Subjects with pancreatic hyperechogenicity had decreased serum adiponectin concentration compared to control subjects [8.9 (6.5, 12.8) 11.1 (7.8, 15.9), < 0.001] and more frequently exhibited features of metabolic syndrome. Logistic regression analysis showed that the following variables were significantly and independently associated with pancreatic hyperechogenicity: Presence of hypoadiponectinemia, increased body mass index (BMI), higher homeostasis model assessment of insulin resistance (HOMA-IR) score, and presence of fatty liver. Similar associations were also observed in subjects with pancreatic hyperechogenicity without fatty liver. Multivariate association analysis of data from participants without fatty liver showed that hypoadiponectinemia was significantly associated with pancreatic hyperechogenicity (OR = 0.93, 95%CI: 0.90 - 0.97, < 0.001). This association was independent of other confounding variables. Additionally, an increased BMI and higher HOMA-IR score were significantly associated with pancreatic hyperechogenicity.

Conclusion: Pancreatic hyperechogenicity is independently associated with increased BMI, insulin resistance, and hypoadiponectinemia in the general population.
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http://dx.doi.org/10.4254/wjh.v8.i33.1452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5124716PMC
November 2016

MiR-139-5p is associated with inflammatory regulation through c-FOS suppression, and contributes to the progression of primary biliary cholangitis.

Lab Invest 2016 11 26;96(11):1165-1177. Epub 2016 Sep 26.

Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan.

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized pathologically by destruction of intrahepatic bile ducts. PBC is largely classified into three subtypes based on clinical course: (i) gradually progressive, (ii) portal hypertension, and (iii) hepatic failure. Previous studies have indicated that serum levels of the pro-inflammatory cytokine TNF-α, is elevated in PBC patients with fibrosis. Although the severity of cholangitis might also be related to the PBC subtype, its etiology has been unclear. Several studies have shown that microRNAs (miRNAs) demonstrate specific expression patterns in various diseases. In the present study, we evaluated miRNA expression patterns among the PBC subtypes using comprehensive deep sequencing. We also carried out histologic examination by laser capture microdissection and investigated how the identified miRNAs were involved in PBC clinical progression using the miRNA transfection method. On average, ~11 million 32-mer short RNA reads per sample were obtained, and we found that the expression levels of 97 miRNAs differed significantly among the four groups. Heat mapping demonstrated that the miRNA profiles from hepatic failure and portal hypertension type were clustered differently from those of the gradually progressive type and controls. Furthermore, we focused on miR-139-5p, which has an adequate number of total short reads. Quantitative reverse transcription PCR showed that miR-139-5p was significantly downregulated in clinically advanced PBC. Also, examination of liver tissues demonstrated that the expression of lymphocyte-derived miR-139-5p was significantly higher in hepatocytes. In vitro, the level of TNF-α was significantly elevated in supernatant of cells with upregulation of miR-139-5p. Furthermore, c-FOS gene transcription was repressed. Thus, we have demonstrated a novel inflammation-regulatory mechanism involving TNF-α and c-FOS transcription through miR-139-5p in the NF-κB signaling pathway. We conclude that the specific miRNA miR-139-5p might be involved in the pathogenesis of PBC, especially during clinical progression.
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http://dx.doi.org/10.1038/labinvest.2016.95DOI Listing
November 2016

Serum metabolome profiles characterized by patients with hepatocellular carcinoma associated with hepatitis B and C.

World J Gastroenterol 2016 Jul;22(27):6224-34

Takafumi Saito, Kazuo Okumoto, Hiroaki Haga, Tomohiro Katsumi, Kei Mizuno, Taketo Nishina, Sonoko Sato, Yoshiyuki Ueno, Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Yamagata 990-9585, Japan.

Aim: To clarify the characteristics of metabolite profiles in virus-related hepatocellular carcinoma (HCC) patients using serum metabolome analysis.

Methods: The serum levels of low-molecular-weight metabolites in 68 patients with HCC were quantified using capillary electrophoresis chromatography and mass spectrometry. Thirty and 38 of the patients suffered from hepatitis B virus-related HCC (HCC-B) and hepatitis C virus-related HCC (HCC-C), respectively.

Results: The main metabolites characteristic of HCC were those associated with glutathione metabolism, notably 13 γ-glutamyl peptides, which are by-products of glutathione induction. Two major profiles, i.e., concentration patterns, of metabolites were identified in HCC patients, and these were classified into two groups: an HCC-B group and an HCC-C group including some of the HCC-B cases. The receiver operating characteristic curve for the multiple logistic regression model discriminating HCC-B from HCC-C incorporating the concentrations of glutamic acid, methionine and γ-glutamyl-glycine-glycine showed a highly significant area under the curve value of 0.94 (95%CI: 0.89-1.0, P < 0.0001).

Conclusion: The serum levels of γ-glutamyl peptides, as well as their concentration patterns, contribute to the development of potential biomarkers for virus-related HCC. The difference in metabolite profiles between HCC-B and HCC-C may reflect the respective metabolic reactions that underlie the different pathogeneses of these two types of HCC.
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http://dx.doi.org/10.3748/wjg.v22.i27.6224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945981PMC
July 2016

Quadruple-component superficial circumflex iliac artery perforator (SCIP) flap: A chimeric SCIP flap for complex ankle reconstruction of an exposed artificial joint after total ankle arthroplasty.

J Plast Reconstr Aesthet Surg 2016 Sep 23;69(9):1260-5. Epub 2016 Jun 23.

Department of Plastic and Reconstructive Surgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Total ankle arthroplasty (TAA) is becoming popular in patients with rheumatoid arthritis (RA)-associated ankle joint degeneration. However, ankle wound complications can occur after TAA, which sometimes requires challenging reconstruction due to anatomical complexity of the ankle. Superficial circumflex iliac artery (SCIA) perforator (SCIP) flap has been reported to be useful for various reconstructions, but no case has been reported regarding a chimeric SCIP flap for complex ankle reconstruction. We report a case of complex ankle defect successfully reconstructed with a free quadruple-component chimeric SCIP flap. A 73-year-old female patient with RA underwent TAA, and suffered from an extensive ankle soft tissue defect (13 × 5 cm) with exposure of the implanted artificial joint and the extensor tendons. A chimeric SCIP flap was raised based on the deep branch and the superficial branch of the SCIA, which included chimeric portions of the sartorius muscle, the deep fascia, the inguinal lymph node (ILN), and the skin/fat. The flap was transferred to the recipient ankle. The sartorius muscle was used to cover the artificial joint, the deep fascia to reconstruct the extensor retinaculum, the ILN to prevent postoperative lymphedema, and the adiposal tissue to put around the extensor tendons for prevention of postoperative adhesion. Postoperatively, the patient could walk by herself without persistent leg edema or bowstringing of the extensor tendons, and was satisfied with the concealable donor scar. Although further studies are required to confirm efficacy, multicomponent chimeric SCIP has a potential to be a useful option for complex defects of the ankle.
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http://dx.doi.org/10.1016/j.bjps.2016.06.010DOI Listing
September 2016

Primitive red alga Cyanidioschyzon merolae accumulates storage glucan and triacylglycerol under nitrogen depletion.

J Gen Appl Microbiol 2016 Jul 16;62(3):111-7. Epub 2016 May 16.

Department of Functional Molecular Biology, Graduate School of Medicine, Yamaguchi University.

Most microalgae accumulate neutral lipids, including triacylglycerol (TAG), into spherical structures called lipid bodies (LBs) under environmental stress conditions such as nutrient depletion. In green algae, starch accumulation precedes TAG accumulation, and the starch is thought to be a substrate for TAG synthesis. However, the relationship between TAG synthesis and the starch content in red algae, as well as how TAG accumulation is regulated, is unclear. In this study, we cultured the primitive red alga Cyanidioschyzon merolae under nitrogen-depleted conditions, and monitored the formation of starch granules (SGs) and LBs using microscopy. SGs stained with potassium iodide were observed at 24 h; however, LBs stained specifically with BODIPY 493/503 were observed after 48 h. Quantitative analysis of neutral sugar and cytomorphological semi-quantitative analysis of TAG accumulation also supported these results. Thus, the accumulation of starch occurred and preceded the accumulation of TAG in cells of C. merolae. However, TAG accumulation was not accompanied by a decrease in the starch content, suggesting that the starch is a major carbon storage sink, at least under nitrogen-depleted conditions. Quantitative real-time PCR revealed that the mRNA levels of genes involved in starch and TAG synthesis rarely changed during the culture period, suggesting that starch and TAG synthesis in C. merolae are not controlled through gene transcription but at other stages, such as translation and/or enzymatic activity.
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http://dx.doi.org/10.2323/jgam.2015.12.001DOI Listing
July 2016

Proximal and distal patterns: Different spreading patterns of indocyanine green lymphography in secondary lower extremity lymphedema.

J Plast Reconstr Aesthet Surg 2016 Mar 5;69(3):368-75. Epub 2015 Nov 5.

Department of Plastic and Reconstructive Surgery, University of Tokyo, Tokyo, Japan.

Background: As a clinical evaluation of secondary lymphedema of the leg, indocyanine green (ICG) lymphographic assessment has established its usefulness. In this study, we analyzed the ICG findings of patients with secondary lymphedema of the leg, focusing on the location and spreading pattern of dermal backflow (DBF).

Methods: Between April 2013 and June 2015, we investigated ICG findings performed on 90 patients with secondary lymphedema of the leg following malignant cancer resection. The patients comprised 88 women and two men; ICG lymphography was performed 12-24 h after the injection.

Results: Of the 90 patients, ICG lymphographic DBF was evident in 64 from the proximal region of the leg, termed as the proximal pattern. Of the 90 patients, DBF was found to appear in 18 patients mainly in the distal part of the leg, termed as the distal pattern.

Conclusions: In the proximal pattern, the ICG injected into the distal part of the leg propelled to the proximal part, but an obstruction after lymphadenectomy caused ICG pooling to appear first on the proximal side. In the distal pattern, the lymphatic system hypoplasia of the leg may have already been present, and lymph node dissection might be the only trigger for the development of lymphedema. This classification may reflect the pumping function and preexisting hypoplasty of the lymphatic vessels, and provides a novel approach for the pathological evaluation of lymphedema. Patients with proximal pattern on ICG lymphography may well indicate lymphaticovenous anastomosis.
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http://dx.doi.org/10.1016/j.bjps.2015.10.042DOI Listing
March 2016

Near-infrared fluorescent swallow test for detection of the alimentary tract anastomotic leakage.

J Plast Reconstr Aesthet Surg 2016 Jan 9;69(1):141. Epub 2015 Oct 9.

Department of Plastic and Reconstructive Surgery, The University of Tokyo, Japan.

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http://dx.doi.org/10.1016/j.bjps.2015.09.019DOI Listing
January 2016

Inguinal seroma prevention by reverse mapping using inodocyanine green lymphography.

Microsurgery 2016 Sep 25;36(6):525-6. Epub 2015 Aug 25.

Department of Plastic and Reconstructive Surgery, the University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.

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http://dx.doi.org/10.1002/micr.22468DOI Listing
September 2016

Diagnosis of trauma-induced lymphedema using indocyanine green lymphography.

J Plast Reconstr Aesthet Surg 2015 Nov 26;68(11):e177-8. Epub 2015 Jul 26.

Department of Plastic and Reconstructive Surgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.bjps.2015.07.013DOI Listing
November 2015

Inguinal seroma prevention after superficial circumflex iliac artery perforator flap harvest using non-microsurgical lympho-venous shunt.

J Plast Reconstr Aesthet Surg 2015 Oct 12;68(10):1479-81. Epub 2015 Jun 12.

Department of Plastic and Reconstructive Surgery, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

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http://dx.doi.org/10.1016/j.bjps.2015.06.007DOI Listing
October 2015

Geographic distribution and characteristics of genotype A hepatitis B virus infection in acute and chronic hepatitis B patients in Japan.

J Gastroenterol Hepatol 2016 Jan;31(1):180-9

The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa.

Background And Aims: The prevalence of sexually transmitted acute infections of the genotype A hepatitis B virus (HBV) has been increasing in Japan. Genotype A HBV is associated with an increased risk of HBV progression to chronic infection after acute hepatitis B (AHB) in adults. A nationwide survey was conducted to evaluate the geographic distribution, clinical, and virologic characteristics of genotype A AHB and chronic hepatitis B (CHB) in Japan.

Methods: Five hundred seventy AHB patients were recruited between 2005 and 2010, and 3682 CHB patients were recruited between 2010 and 2011. HBV genotypes were determined for 552 and 3619 AHB and CHB patients, respectively. Clinical characteristics were compared among different genotypes in AHB and CHB patients. Genomic characteristics of HBV genotype A were examined by molecular evolutionary analysis.

Results: Hepatitis B virus genotype A was the predominant genotype for AHB between 2005 and 2010. Phylogenetic analysis showed that all strains in the AHB patients with genotype A were classified into subtype Ae. Among CHB patients, the occurrence of genotype A was 4.1%, and genotype A was spreading in young adults. In genotype A CHB patients, early stage liver diseases were predominant, although liver diseases progressed to cirrhosis or hepatocellular carcinoma in some patients.

Conclusions: The distribution of HBV genotypes is quite different between AHB and CHB in Japanese patients. Genotype A infection is spreading in young adults of Japanese CHB patients. Sequences derived from Japanese AHB patients were identical to or closely resembled the sequences derived from other Japanese AHB patients.
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http://dx.doi.org/10.1111/jgh.13030DOI Listing
January 2016

Precise measurement using a new background sheet with crack scales for super microsurgical anastomosis.

J Plast Reconstr Aesthet Surg 2015 Oct 30;68(10):1476-7. Epub 2015 May 30.

Department of Plastic and Reconstructive Surgery, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

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http://dx.doi.org/10.1016/j.bjps.2015.05.030DOI Listing
October 2015

Algae sense exact temperatures: small heat shock proteins are expressed at the survival threshold temperature in Cyanidioschyzon merolae and Chlamydomonas reinhardtii.

Genome Biol Evol 2014 Sep 29;6(10):2731-40. Epub 2014 Sep 29.

Department of Biological Science and Chemistry, Faculty of Science, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan Core Research for Evolutional Science and Technology (CREST, JST), Japan Science and Technology Agency, Kawaguchi, Japan

The primitive red alga Cyanidioschyzon merolae inhabits acidic hot springs and shows robust resistance to heat shock treatments up to 63 °C. Microarray analysis was performed to identify the key genes underlying the high temperature tolerance of this organism. Among the upregulated genes that were identified, we focused on two small heat shock proteins (sHSPs) that belong to a unique class of HSP families. These two genes are located side by side in an inverted repeat orientation on the same chromosome and share a promoter. These two genes were simultaneously and rapidly upregulated in response to heat shock treatment (>1,000-fold more than the control). Interestingly, upregulation appeared to be triggered not by a difference in temperatures, but rather by the absolute temperature. Similar sHSP structural genes have been reported in the green alga Chlamydomonas reinhardtii, but the threshold temperature for the expression of these sHSP-encoding genes in Ch. reinhardtii was different from the threshold temperature for the expression of the sHSP genes from Cy. merolae. These results indicate the possible importance of an absolute temperature sensing system in the evolution and tolerance of high-temperature conditions among unicellular microalgae.
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http://dx.doi.org/10.1093/gbe/evu216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224343PMC
September 2014

Bone marrow cell-based regenerative therapy for liver cirrhosis.

World J Methodol 2013 Dec 26;3(4):65-9. Epub 2013 Dec 26.

Takafumi Saito, Kyoko Tomita, Hiroaki Haga, Kazuo Okumoto, Yoshiyuki Ueno, Department of Gastroenterology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.

Bone marrow cells are capable of differentiation into liver cells. Therefore, transplantation of bone marrow cells has considerable potential as a future therapy for regeneration of damaged liver tissue. Autologous bone marrow infusion therapy has been applied to patients with liver cirrhosis, and improvement of liver function parameters has been demonstrated. In this review, we summarize clinical trials of regenerative therapy using bone marrow cells for advanced liver diseases including cirrhosis, as well as topics pertaining to basic in vitro or in vivo approaches in order to outline the essentials of this novel treatment modality.
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http://dx.doi.org/10.5662/wjm.v3.i4.65DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145572PMC
December 2013

Epiregulin promotes the emergence and proliferation of adult liver progenitor cells.

Am J Physiol Gastrointest Liver Physiol 2014 Jul 8;307(1):G50-7. Epub 2014 May 8.

Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan; CREST, Yamagata University Faculty of Medicine, Yamagata, Japan.

We have previously reported that epiregulin is a growth factor that seems to act on liver progenitor cells (LPCs) during liver regeneration. However, the relationship between epiregulin and LPCs has remained unclear. The aim of the present study was to clarify the role of epiregulin during liver regeneration. The serum levels of epiregulin in patients with acute liver failure were examined. A liver injury model was developed using mice fed a diet containing 0.1% 3.5-diethoxycarbonyl-1.4-dihydrocollidine (DDC) to induce LPCs. We then evaluated the expression of epiregulin and LPCs in these mice. The proliferation of epithelial cell adhesion molecule + LPCs cultured with epiregulin was examined in vitro, and finally epiregulin was overexpressed in mouse liver. In patients with acute liver failure, serum epiregulin levels were elevated significantly. In DDC mice, LPCs emerged around the portal area. Epiregulin was also detected around the portal area during the course of DDC-induced liver injury and was partially coexpressed with Thy1. Serum epiregulin levels in DDC mice were also significantly elevated. Recombinant epiregulin augmented the proliferative capacity of the LPCs in a dose-dependent manner. In mice showing overexpression of epiregulin, the expression of PCNA on hepatocytes was increased significantly. Finally, LPCs emerged around the portal area after epiregulin gene delivery. We concluded that epiregulin promotes the proliferation of LPCs and DNA synthesis by hepatocytes and is upregulated in the serum of patients with liver injury. Furthermore, induction of epiregulin leads to the appearance of LPCs. Epiregulin would be a useful biomarker of liver regeneration.
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http://dx.doi.org/10.1152/ajpgi.00434.2013DOI Listing
July 2014

Possible autoimmune hepatitis induced after chronic active Epstein-Barr virus infection.

Clin J Gastroenterol 2014 Feb 23;7(1):58-61. Epub 2013 Nov 23.

Department of Gastroenterology, Yamagata University Faculty of Medicine, 2-2-2 Iidanishi, Yamagata, 990-9585, Japan.

Chronic active Epstein-Barr virus infection (CAEBV) can be manifested in a variety of systemic conditions, including interstitial pneumonia, malignant lymphoma, and coronary aneurysm. Sometimes it may be associated with hepatic failure, although the mechanism underlying CAEBV-related hepatotoxicity remains unclear. We encountered a case of autoimmune hepatitis (AIH) associated with CAEBV. A 61-year-old male was referred to our hospital because of abnormal liver enzyme levels after initial diagnosis of CAEBV had been made by laboratory tests and liver biopsy. On admission, positivity for anti-nuclear antibody was evident, and examination of the liver biopsy specimen showed findings compatible with AIH. Steroid administration was initiated, and the liver function parameters subsequently improved. Although phenotypic changes in liver biopsy specimens are rare in this condition, the present case could provide clues to the possible pathogenesis of AIH.
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http://dx.doi.org/10.1007/s12328-013-0438-2DOI Listing
February 2014

Transmission of hepatitis C virus: self-limiting hepatitis or chronic hepatitis?

World J Gastroenterol 2013 Nov;19(41):6957-61

Takafumi Saito, Yoshiyuki Ueno, Department of Gastroenterology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.

It has been suggested that hepatitis C virus (HCV) is selectively transmitted to a new host as an infectious clone from multiple HCV variants (quasispecies) in the donor. Most individuals with HCV infection develop chronic hepatitis, but approximately 15%-40% of them clear the virus spontaneously and the hepatitis is resolved in a self-limiting manner in the acute phase of infection. This difference in the outcome of acute hepatitis C is attributable to both viral characteristics and genetic regulation of infection. In particular, the evolutionary dynamics of the infecting virus and host genetic polymorphisms pertaining mainly to the immune system, including polymorphisms in the region of the Interleukin 28B gene encoding interferon-λ-3, are associated with susceptibility to HCV infection.
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http://dx.doi.org/10.3748/wjg.v19.i41.6957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819531PMC
November 2013

Metabolome analysis of erythrocytes from patients with chronic hepatitis C reveals the etiology of ribavirin-induced hemolysis.

Int J Med Sci 2013 9;10(11):1575-7. Epub 2013 Sep 9.

1. Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Yamagata 990-9585;

Ribavirin is one of the major agents used in combination therapy with interferon for chronic hepatitis C, but is often associated with hemolytic anemia as a serious adverse event. Employing metabolome analysis, we demonstrated that the concentrations of intermediate metabolites produced by glycolysis and the pentose phosphate cycle in patients' erythrocytes were significantly decreased after administration of ribavirin. Our findings suggest that hemolysis associated with ribavirin is triggered by an energy crisis and consequent oxidative stress, thus having implications for the prevention of such hemolysis.
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http://dx.doi.org/10.7150/ijms.6436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775117PMC
April 2014

A case of adult type 1 Gaucher disease complicated by temporal intestinal hemorrhage.

Case Rep Gastroenterol 2013 16;7(2):340-6. Epub 2013 Aug 16.

Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata ; Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Yamagata.

A 21-year-old man with a history of sudden rectal hemorrhage was referred to our hospital. Examination disclosed thrombocytopenia and hepatosplenomegaly. A liver biopsy specimen demonstrated Gaucher cells in Glisson's capsule. Additional investigations revealed a low level of leukocyte β-glucosidase activity and common mutations of the glucocerebrosidase gene, L444P/D409H. We diagnosed the patient with Gaucher disease type 1. He underwent enzyme replacement therapy. Thrombocytopenia and hepatosplenomegaly improved at a rate of approximately 50 and 20%, respectively, within 6 months. This case suggests that we must pay attention to adult Gaucher disease as a differential diagnosis for cryptogenic thrombocytopenia.
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http://dx.doi.org/10.1159/000354725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764967PMC
September 2013

Dynamics of serum metabolites in patients with chronic hepatitis C receiving pegylated interferon plus ribavirin: a metabolomics analysis.

Metabolism 2013 Nov 15;62(11):1577-86. Epub 2013 Aug 15.

Department of Gastroenterology, Yamagata University School of Medicine, Yamagata 990-9585, Japan. Electronic address:

Objectives: Serum samples from patients with chronic hepatitis C were subjected to metabolomics analysis to clarify the pretreatment characteristics of their metabolites and also changes in specific metabolites resulting from antiviral therapy with pegylated interferon plus ribavirin (PegIFN/RBV).

Materials/methods: The serum levels of low-molecular-weight metabolites in the twenty patients before and 24weeks after completion of PegIFN/RBV therapy were analyzed using capillary electrophoresis and liquid chromatography-mass spectrometry.

Results: Ten patients showed a non-virological response (NVR) and 10 achieved a sustained virological response (SVR) with eradication of viremia. The pretreatment levels of tryptophan were significantly higher in the patients of SVR than in those of NVR (p=0.010). The area under the curve (AUC) value of tryptophan calculated from the receiver operating characteristic (ROC) curve for discriminating SVR from NVR was 0.84 (95% confidential interval, 0.66-1.02, p=0.010). The ROC curve of multiple logistic regression model incorporating the pretreatment levels of tryptophan and γ-glutamate-arginine showed that the AUC value was highly significant (AUC=0.92, 95% confidential interval, 0.79-1.05, p=0.002). Twenty four weeks after completion of treatment, the levels of γ-glutamyl dipeptides, glutamic acid, 5-oxoproline, glucosamine and methionine sulfoxide were decreased, whereas those of 5-methoxy-3-indoleacetate, glutamine, kynurenine and lysine were increased significantly (p<0.05) in both the NVR and SVR patients.

Conclusions: The pretreatment serum levels of certain metabolites including tryptophan are associated with the response to PegIFN/RBV therapy. PegIFN/RBV therapy can ameliorate the oxidative stress responsible for glutathione metabolism.
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http://dx.doi.org/10.1016/j.metabol.2013.07.002DOI Listing
November 2013

Serum prolactin levels and prolactin mRNA expression in peripheral blood mononuclear cells in hepatitis C virus infection.

J Med Virol 2013 Jul;85(7):1199-205

Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Japan.

Prolactin is not only a pituitary hormone but an immunoregulatory hormone secreted from lymphocytes. Prolactin induction in relation to hepatitis C virus (HCV) infection has not been elucidated. The serum levels of prolactin were examined in 232 HCV-infected subjects positive for anti-HCV antibody and 65 healthy controls negative for it, who were recruited in the cohort study. The prolactin mRNAs were measured in peripheral blood mononuclear cells (PBMCs) of eleven healthy volunteers including five men and six women before and after stimulation by HCV in vitro. The serum level of prolactin and prolactin mRNA in PBMCs were measured by chemiluminescence immunoassay and real-time PCR, respectively. The serum levels of prolactin were significantly higher in the HCV-infected subjects (median: 7.5, IQR: 5.7-10.9 ng/ml) than in the controls (median: 5.6, IQR: 4.4-8.3 ng/ml) (P < 0.01). They were significantly higher in HCV-infected males (median: 8.0, IQR: 5.9-11.8 ng/ml) than in the controls (median: 4.8, IQR: 4.2-5.9 ng/ml) (P < 0.001), however, the difference was not significant between HCV-infected females (median: 7.3, IQR: 5.6-10.5 ng/ml) and the controls (median: 6.4, IQR: 5.3-9.8 ng/ml). The mRNA expression of prolactin was induced in PBMCs of all males, but it was induced in PBMCs of the two of six females examined in vitro. These results suggest that the serum level of prolactin is higher in HCV-infected males than in healthy males, and that HCV infection induces the mRNA expression of prolactin in PBMCs that is more apparent in male than in females.
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http://dx.doi.org/10.1002/jmv.23599DOI Listing
July 2013
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