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| 1 | A novel negative regulatory mechanism of Smurf2 in BMP/Smad signaling in bone显示文摘Transforming growth factor-β(TGF-β)and bone morphogenetic protein(BMP)play important roles in bone metabolism.Smad ubiquitination regulatory factors(Smurfs)regulate TGF-β/BMP signaling via ubiquitination,resulting in degradation of signaling molecules to prevent excessive activation of TGF-β/BMP signaling.Though Smurf2 has been shown to negatively regulate TGF-β/Smad signaling,its involvement in BMP/Smad signaling in bone metabolism has not been thoroughly investigated.In the present study,we sought to evaluate the role of Smurf2 in BMP/Smad signaling in bone metabolism.Absorbable collagen sponges containing 3μg of recombinant human BMP2(rhBMP2)were implanted in the dorsal muscle pouches of wild type(WT)and Smurf2−/−mice.The rhBMP2-induced ectopic bone in Smurf2−/−mice showed greater bone mass,higher mineral apposition and bone formation rates,and greater osteoblast numbers than the ectopic bone in WT mice.In WT mice,the ectopic bone consisted of a thin discontinuous outer cortical shell and scant inner trabecular bone.In contrast,in Smurf2−/−mice,the induced bone consisted of a thick,continuous outer cortical shell and abundant inner trabecular bone.Additionally,rhBMP2-stimulated bone marrow stromal cells(BMSCs)from Smurf2−/−mice showed increased osteogenic differentiation.Smurf2 induced the ubiquitination of Smad1/5.BMP/Smad signaling was enhanced in Smurf2−/−BMSCs stimulated with rhBMP2,and the inhibition of BMP/Smad signaling suppressed osteogenic differentiation of these BMSCs.These findings demonstrate that Smurf2 negatively regulates BMP/Smad signaling,thereby identifying a new regulatory mechanism in bone metabolism. | Junichi Kushioka Takashi Kaito Rintaro Okada Hiroyuki Ishiguro Zeynep Bal Joe Kodama Ryota Chijimatsu Melanie Pye Masahiro Narimatsu Jeffrey LWrana Yasumichi Inoue Hiroko Ninomiya Shin Yamamoto Takashi Saitou Hideki Yoshikawa Takeshi Imamura | 2020 | Bone Research2020，8，4： | 6 |
| 2 | HER2 heterogeneity is a poor prognosticator for HER2-positive gastric cancer显示文摘BACKGROUND The clinical significance of intratumoral human epidermal growth factor receptor 2(HER2)heterogeneity is unclear for HER2-positive gastric cancer,although it has been reported to be a significant prognosticator for HER2-positive breast cancer,which has received trastuzumab-based chemotherapy.AIM To clarify the clinical significance of intratumoral HER2 heterogeneity for HER2-positive gastric cancer,which has received trastuzumab-based chemotherapy.METHODS Patients with HER2-positive unresectable or metastatic gastric cancer who received trastuzumab-based chemotherapy as a first line treatment were included.The patients were classified into two groups according to their intratumoral HER2 heterogeneity status examined by immunohistochemistry(IHC)on endoscopic biopsy specimens before treatment,and their clinical response to chemotherapy and survival were compared.RESULTS A total of 88 patients were included in this study,and HER2 heterogeneity was observed in 23(26%)patients(Hetero group).The overall response rate was significantly better in patients without HER2 heterogeneity(Homo group)(Homo vs Hetero:79.5%vs 35.7%,P=0.002).Progression-free survival of trastuzumab-based chemotherapy was significantly better in the Homo group(median,7.9 vs 2.5 mo,HR:1.905,95%CI:1.109-3.268).Overall survival was also significantly better in the Homo group(median survival time,25.7 vs 12.5 mo,HR:2.430,95%CI:1.389-4.273).Multivariate analysis revealed IHC HER2 heterogeneity as one of the independent poor prognostic factors(HR:3.115,95%CI:1.610-6.024).CONCLUSION IHC of HER2 heterogeneity is the pivotal predictor for trastuzumab-based chemotherapy.Thus,HER2 heterogeneity should be considered during the assessment of HER2 expression. | Akio Kaito Takeshi Kuwata Masanori Tokunaga Kohei Shitara Reo Sato Tetsuo Akimoto Takahiro Kinoshita | 2019 | World Journal of Clinical Cases2019，7，15： | 5 |
| 3 | Effect of branched-chain amino acids in patients receiving intervention for hepatocellular carcinoma显示文摘AIM:To investigate the usefulness of branched-chain amino acids(BCAA)before transarterial chemoembolization(TACE)or radiofrequency ablation(RFA).METHODS:We investigated the usefulness of preintervention with BCAAs by comparing patients treated with BCAAs at 12.45 g/d orally for at least 2 wk before TACE or RFA and those not receiving such pretreatment.A total of 270 patients with hepatocellular carcinoma complicated by cirrhosis were included in the study.Mean changes from baseline(Δ)in serum albumin(Alb),C-reactive protein(CRP),and transaminase levels,as well as peak body temperature were also determined and compared at days 2,5,and 10 after the start of TACE or RFA.RESULTS:In patients who underwent TACE or RFA,BCAA pre-intervention significantly suppressed the development of post-intervention hypoalbuminemia and reduced inflammatory reactions during the subsequent clinical course.After TACE,theΔAlb peaked on day 2,remained constantly lower in BCAA-treated patients,compared to the control group,and was-0.13±0.42g/dL in BCAA-treated patients and-0.33±0.51 g/dL in untreated patients on day 10.TheΔCRP was also significantly lower in BCAA-treated patients on days2,5 and 10 after TACE.Like the trends noted after TACE,a similar tendency was noted as to theΔAlb andΔCRP after RFA.The changes in serum Alb level were inversely correlated with CRP changes;therefore,a possible involvement of the anti-inflammatory effect of BCAAs was inferred as a factor contributory to the suppression of decrease in serum Alb level.CONCLUSION:Pre-intervention with BCAAs may hasten the recovery of serum Alb level and mitigate postoperative complications in patients undergoing TACE or RFA. | Tomoaki Ishihara Motoh Iwasa Hideaki Tanaka Masahiko Kaito Jiro Ikoma Toshiya Shibata Yoshiyuki Takei | 2014 | World Journal of Gastroenterology2014，20，10： | 2 |
| 4 | High-temperature strength characterization of advanced 9Cr-ODS ferritic steels显示文摘 | S. Ukai S. Ohtsuka T. Kaito H. Sakasegawa N. Chikata S. Hayashi S. Ohnuki | 2009 | Materials Science & Engineering A2009，，： | 2 |
| 5 | Positional occlusion of the vertebral artery in a case of rheumatoid atlantoaxial subluxation presenting with multiple cerebral and cerebellar infarction显示文摘 | Hiroyasu Fujiwara Takashi Kaito Takahiro Makino Kazuo Yonenobu | 2012 | Modern Rheumatology2012，，4： | 2 |
| 6 | Potentiation of the activity of bone morphogenetic protein-2 in bone regeneration by a PLA-PEG/hydroxyapatite composite显示文摘 | Kaito T Myoui A Takaoka K | 2005 | Biomaterials2005，26，1： | 1 |
| 7 | Coalescence growth mechanism of smoke particles显示文摘 | Kaito C | 1985 | Jpn J Appl Phys1985，24，3： | 1 |
| 8 | CD2+tetraploid acute promyelocytic leukemia variant with double(15;17)translocations显示文摘 | Kaito K Otsubo H Dobashi N | 2005 | Int J Hematol2005，81，1： | 1 |
| 9 | Coalescence growth mechanism of smoke particles显示文摘 | KAITO C | 1985 | Jpn J Appl Phys1985，24，3： | 1 |
| 10 | Hepatitis C virus core particle detected by immunoelectron microscopy and optical rotation technique显示文摘 | Ishida S Kaito M Kohara M | 2001 | Hepatol Res2001，20，3： | 1 |
| 11 | A new method for the quantitative analysis of the scale and composition of nanosized oxide in 9Cr-ODS steel显示文摘 | M. Ohnuma J. Suzuki S. Ohtsuka S.-W. Kim T. Kaito M. Inoue H. Kitazawa | 2009 | Acta Materialia2009，，18： | 1 |
| 12 | LC-MS/MS method for the quantitation of serum tocilizumab in rheumatoid arthritis patients using rapid tryptic digestion without IgG purification显示文摘The quantitation of serum tocilizumab using liquid chromatography tandem-mass spectrometry(LC-MS/MS)method has not been widely applied in clinical settings because of its time-consuming and costly sample pretreatments.The present study aimed to develop a validated LC-MS/MS method for detecting serum tocilizumab by utilizing immobilized trypsin without an immunoglobulin G purification step and evaluate its applicability in the treatment of rheumatoid arthritis(RA)patients administered intravenously or subcutaneously with tocilizumab.The tocilizumab-derived signature peptide was deciphered using a nano-LC system coupled to a hybrid quadrupole-orbitrap mass spectrometer.The serum tocilizumab was rapidly digested by immobilized trypsin for 30 min.The chromatographic peak of the signature peptide and that of the internal standard were separated from the serum digests for a total run time of 15 min.The calibration curve of serum tocilizumab concentration was linear with a range of 2-200 μg/mL.The intra-and inter-day accuracy and relative standard deviation(RSD)were 90.7%-109.4%and<10%,respectively.The serum tocilizumab concentrations in the RA patients receiving intravenous and subcutaneous injections were 5.8-28.9 and 2.4-63.5 μg/mL,respectively.The serum tocilizumab concentrations using the current method positively correlated with those using the enzyme-linked immunosorbent assay,although a systematic error was observed between these methods.In conclusion,a validated LC-MS/MS method with minimal sample pretreatments for monitoring serum tocilizumab concentrations in RA patients was developed. | Takashi Mochizuki Kaito Shibata Takafumi Naito Kumiko Shimoyama Noriyoshi Ogawa Masato Maekawa Junichi Kawakami | 2022 | Journal of Pharmaceutical Analysis2022，12，6： | 1 |
| 13 | Improvement of regional cerebral blood flow after oral intake of ranched-chain amino acids in patients with cirrhosis显示文摘AIM: To evaluate the effect of oral intake of branchedchain amino acids (BCAA) on brain perfusion in patients with liver cirrhosis.METHODS: Single photon emission computed tomography scans were performed in 43 patients with cirrhosis and in 15 age-matched healthy subjects.Twenty-nine out of forty-three patients were randomly treated with either BCAA granules or placebo, and single photon emission computed tomography was performed before and after the treatment. We measured the regional cerebral blood flow values using a threedimensional stereotaxic region of interest template.RESULTS: Cirrhotic patients had regions of significant hypoperfusion in the bilateral central (right P=0.039,P<0.05; left P = 0.006 P<0.01), parietal (right P=0.018, P<0.05;left P=0.009, P<0.01), angular (right P=0.039, P<0.05;left P = 0.008, P<0.01), and left pericallosal segments (P= 0.038 P<0.05) as compared with healthy subjects. A significant increase in cerebral perfusion was observed 70 min after the oral intake of BCAA in the angular (right P=0.012,P<0.05;left P=0.049, P<0.05), temporal (right P=0.012, P<0.05; left P=0.038, P<0.05), pericallosal segments (right P = 0.025,P<0.05; left P = 0.049, P<0.05) and left precentral (P=0.044, P<0.05), parietal (P=0.040, P<0.05) and thalamus (P=0.033, P<0.05). No significant change in perfusion was observed in the placebo group.CONCLUSION: Administration of BCAA rapidly improves cerebral perfusion. | Mika Yamamoto Motoh Iwasa Kaname Matsumura Yuri Nakagawa Naoki Fujita Yoshinao Kobayashi Masahiko Kaito Kan Takeda Yukihiko Adachi | 2005 | World Journal of Gastroenterology2005，11，43： | 1 |
| 14 | Current situation of the malaria inspection in Jikei University Hospital显示文摘 | Tanno J Kaito K Kurihara E | 2004 | Rinsho Byori2004，52，3： | 1 |
| 15 | 显示文摘 | Hirata A Igarashi M Kaito T | 2004 | Tribol Int2004，37，1112： | 1 |
| 16 | Prognostic factors of hemophagncytic syndrome in adults:analysis of 34 cases显示文摘 | Kaito K Kobayashi M Katayashi T | 1997 | Eur J Haematol1997，59，： | 1 |
| 17 | Thl/Th2 lymphocyte balance in pa- tients with aplastic anemia显示文摘 | Kaito K Otsubo H Usui N | 2004 | Rinsho Byori2004，52，7： | 1 |
| 18 | A novel microcontroller for grid connected photovoltaic systems显示文摘 | Koizumi H Mizuno T Kaito T | | 0，，06： | 1 |
| 19 | Cytokine production in cerebrospinal fluid after subarachnoid haemorrhage显示文摘 | Kikuchi T Okuda Y Kaito N | 1995 | Neurol Res1995，17，： | 1 |
| 20 | Treatment strategies for Henoch - Schonlein purpura nephritis by histological and clinical severity 显示文摘 | Ninchoji T Kaito H Nozu K | 2011 | Pediatr Nephrol2011，26，4： | 1 |
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