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論文

論文
Itabashi, Yukihiro ; Baba, Toshiaki ; Kato, Satoru ; Hakamada, Kenichi
出版情報: 弘前医学.  61  pp.1-7,  2010-03-25.  弘前大学出版会
URL: http://hdl.handle.net/10129/3274
概要:  Forty patients with an average age of 64.6 years (range: 45-83) with early gastric cancer of cT1 (M,SM) underwent a cur ative-intended laparoscopy-assisted distal gastrectomy (LADG) where laparoscopic D1+αnodal clearance and extra-abdominal Billroth-I stapled anastomosis were performed. There was no conversionto open gastrectomy. The operation time for the 40 cases ranged 150 - 482 min (median: 285), while that for thelatest 10 cases reduced to 154-278 min (median: 216). The length of hospital stay of the patients varied 10-85 days(median: 17). Postoperative complications encountered were anastomosis-related: 2 anastomotic bleeding and 2anastomotic passage disturbance( 1 stricture and 1 temporary stenosis) occurred but no dehiscence. Four inaccuratepreoperative diagnoses of tumor invasion depth were revealed by postoperative pathology of the resected specimens.Thereafter the accuracy in the preoperative diagnosis was highly enhanced with implementation of endoscopicultrasound. Recurrence occurred in one patient with pT2( SS) pN2, who died of pleural carcinomatosis 4 years and 3months after surgery.  As the reduced operation time in LADG came closer to that in open distal gastrectomy, we will continuethis procedure for early gastric cancer. For this, the importance of an accurate preoperative diagnosis can’t beoveremphasized. 続きを見る
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論文
Yoshida, Ikko ; Ishizaka, Hiroshi ; Hasegawa, Kazushi ; Satoh, Kiyohiko ; Osanai, Tomohiro ; Motomura, Shigeru ; Okumura, Ken
出版情報: 弘前医学.  61  pp.8-18,  2010-03-25.  弘前大学出版会
URL: http://hdl.handle.net/10129/3275
概要: Objectives The purpose of this study was to test the hypothesis that adenosine-induced coronarymicrovascular dilation is blunted in the animals with diabetes mellitus( DM) through the impairment of KATP channelfunction.  Background Adenosine-induced coronary vasodilation is demonstrated to be mediated by activation of ATPsensitivepotassium( KATP) channels and nitric oxide( NO). Methods The hearts of Otsuka Long-Evans Tokushima fatty rats (OLETF, type 2 DM rats), and control Long-Evans Tokushima fatty rats( LETO) at the ages of 32 and 8 weeks were perfused using a Langendorff system withconstant perfusion pressure (80 mmHg). Changes in coronary fl ow to adenosine, pinacidil and sodium nitroprusside(SNP) were examined before and after administration of glibenclamide( 10-7 M), or NG-nitro-L-arginine methyl ester(L-NAME, 10-4 M).  Results At the age of 32 weeks, adenosine- and pinacidil-induced increases in coronary fl ow were blunted in OLETFas compared with those in LETO (both p<0.05). Glibenclamide attenuated adenosine-induced increase in coronaryfl ow in LETO (p<0.05), but not in OLETF. In contrast, L-NAME attenuated adenosine-induced increase in coronaryflow in OLETF (p<0.05), but not in LETO. SNP-induced increases in coronary flow in LETO and OLETF werecomparable and were not aff ected by glibenclamide. In 8-week-old OLETF and LETO, no diff erence was observed inadenosine-, pinacidil- and SNP-induced increases in coronary fl ow between OLETF and LETO. Conclusions In this type 2 DM model, KATP channel function in coronary microcirculation is impaired. Adenosineinducedincrease in coronary fl ow is mediated mainly by NO mechanism. 続きを見る
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論文
Sutoh, Takemichi ; Fukuda, Ikuo ; Kimura, Daisuke ; Tsushima, Takao
出版情報: 弘前医学.  61  pp.19-25,  2010-03-25.  弘前大学出版会
URL: http://hdl.handle.net/10129/3276
概要: Nafamostat mesilate( FUT-175), a synthetic serine protease inhibitor, has been reported to have antitumouractivities tow ard solid tumours. The objective of this study was to characterize the biological activities of FUT-175 ina malignant mesothelioma cell line. We used MSTO-211H, a biphasic-type human malignant pleural mesothelioma cellline. The effect on cell growth was evaluated by 3(- 4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Secretion of urokinase-type plasminogen activator( u-PA) and plasminogen activator inhibitor-1( PAI-1) was analysedby enzyme-linked immunosorbent assay. The eff ects on relative mRNA expression levels were measured by reversetranscription polymerase chain reaction. The eff ect on cell invasiveness was evaluated by cell invasion assay. FUT-175at 10-5 M signifi cantly inhibited cell growth and cell invasiveness. Cell growth reduced to 47.0 ± 2.1% compared withthe control. The number of invasive cells also reduced to 16.0 ± 0.7 cells/hpf, while that of control cells was 41.4 ± 8.0cells /hpf. U-PA and PAI-1 secreted from the cells were also reduced by FUT-175 in a dose-dependent manner. Theseresults suggest that FUT-175 has the potential to act as a therapeutic agent against local growth and invasion, andfunctions by reducing PAI-1 and u-PA production of the human malignant mesothelioma(195 words) 続きを見る
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論文
Nodagashira, Tatsuya ; Odagiri, Hiroki ; Ikenaga, Shojiro-Kazunori ; Maruyama, Masateru ; Sato, Toshiyuki ; Hakamada, Kenichi
出版情報: 弘前医学.  61  pp.26-34,  2010-03-25.  弘前大学出版会
URL: http://hdl.handle.net/10129/3277
概要:  Tissue-specifi c promoter has been used for cancer-specifi c suicide gene therapy, but its transcriptionalactivity is r elatively low. For more effi cient gene therapy of HER2-expressing tumor, a double adenovirus infectionsystem was established, in which a ‘regulator’ vector carried Cre gene under the control of HER2 promoter and ‘target’vectors carried target genes activated by Cre. We constructed a Cre recombinase expression vector, AxHER2Cre, forthe ‘regulator’ vector. By the combination of this vector and AxCALNLZ, β-D-galactosidase was induced in 90% and70% of MKN7 and MDA-MB-453, HER2‒overexpressing cell lines, but only about 20% and 10% of MKN28 and MCF7,low HER2-expressing cell lines. By the quantifi cation analysis, the β-galactosidase activities induced by this systemwere comparable to those by the combination of AxCANCre and AxCALNLZ. These results indicated that Cre/loxP system under the regulation of HER2 promoter could induce effi cient gene expression, maintaining the HER2-expression specifi city. Breast cancer with HER2 overexpression is treated with trastuzumab. However, refractoryor resitance of HER2 positive breast cancer against trastuzumab becomes a severe clinical problem, recently. Thissystem seemed to be another therapeutic option. 続きを見る
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論文
Sato, Hideaki ; Sato, Masashi ; Chiba, Makie ; Ito, Kyoko ; Ito, Koichi
出版情報: 弘前医学.  61  pp.35-45,  2010-03-25.  弘前大学出版会
URL: http://hdl.handle.net/10129/3278
概要: The ability of murine allogeneic umbilical cord blood cells (UCBCs) to reconstitute the immune systemwas investigated. U CBCs obtained from fetuses of C57BL/6 (B6; H-2b) mice, which were transgenic for greenfluorescent protein (GFP), were transplanted into RAG2 (-/-) BALB/c mice (H-2d). After transplantation, flowcytometric analysis revealed successful reconstitution of phenotypically mature GFP-positive immune cells of donororigin, including T cells, B cells, monocytes, and granulocytes in the peripheral blood of the recipient mice. Analysisof functional maturation of lymphocytes revealed that 2,4,6-trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH)-immunized UCBC-transplanted recipients produced both TNP-specific IgM and IgG antibodies. These resultsindicated that the recipient mice were capable of mounting antibody responses to T-dependent antigens; further, Igclass switching from IgM to IgG confi rmed that both B cells and CD4+ helper T cells derived from allogeneic UCBCswere immunologically competent. Furthermore, mice transplanted with allogeneic UCBCs accepted skin grafts fromboth B6 and BALB/c mice. However, these chimeric mice completely rejected skin grafts from third party C3H/HeJ (H-2k) mice, indicating the presence of functional CD8+ killer T cells as well as CD4+ helper T cells. In termsof potential clinical application, our results indicate that allogeneic UCBC transplantation can enable recovery of thenormal immune system in recipients. 続きを見る
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Ito, Kyoko ; Masuko, Kazutaka ; Ito, Koichi
出版情報: 弘前医学.  61  pp.46-57,  2010-03-25.  弘前大学出版会
URL: http://hdl.handle.net/10129/3279
概要: Contact between dendritic cells( DCs) and resting T cells is essential for initiation of the primary immuneresponse. In this study, we examined whether neuronal leucine-rich repeat protein 3 (NLRR3), a receptor involvedin nerve system development, participates in DC-T cell binding and T-cell activation. We confirmed that NLRR3is expressed on naive T cells. NLRR3 contains an Arg-Gly-Asp (RGD) motif in its amino acid sequence, for whichseveral integrins can be considered as potential ligands. Indeed, monocyte-derived DCs expressed several integrinsthat can bind to the RGD motif. Functionally, DC-induced resting allogeneic T-cell proliferation was partially inhibitedby addition of integrin-specific antibodies and synthetic RGD peptides, indicating that RGD-containing molecules,including NLRR3 and several integrins, at least participate in the events of the initial primary immune responseinvolving naive T cells and DCs. Furthermore, DCs were shown to bind directly to NLRR3-transfected Chinesehamster ovary cells in a NLRR3-dependent manner, and the binding was removed in the presence of integrin-specifi cantibodies. These data suggest that NLRR3 plays an important role in initiation of the primary immune response. 続きを見る
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Yokoyama, Hiroaki ; Saito, Shin ; Higuma, Takumi ; Hanada, Hiroyuki ; Osanai, Tomohiro ; Daitoku, Kazuyuki ; Fukuda, Ikuo ; Okumura, Ken
出版情報: 弘前医学.  61  pp.58-64,  2010-03-25.  弘前大学出版会
URL: http://hdl.handle.net/10129/3280
概要: Adipose tissue secretes various bioactive molecules (adipokines), and apelin is one kind of adipokines.Recently, it was shown that plasma apelin level is decreased in patients with chronic heart failure, and apelin mightplay an important role in the pathogenesis of cardiovascular disease. However, plasma apelin level in coronary arterydisease( CAD) or other heart disease such as valvular heart disease( VHD) has not been elucidated. We enrolled 31patients with CAD and 14 patients with VHD who underwent elective cardiac surgery. We also examined plasmaapelin level in 20 healthy subjects (Control). Blood samples were obtained before the surgery. Paired samples ofvisceral and subcutaneous adipose tissues were harvested during surgery. Plasma apelin level was lower in both CADand VHD than in Control. When compared between CAD and VHD, it was lower in CAD than in VHD, and was notaff ected by treatment with HMG-CoA reductase inhibitors (statins) which was shown to increase adiponectin level.Left ventricular ejection fraction( LVEF) was lower in CAD than in VHD. There was no correlation between plasmaapelin level and LVEF. Gene expression of apelin in visceral adipose tissue was higher than that in subcutaneousadipose tissue, but it was similar between two groups. These suggest that plasma apelin level was decreased inpatients with cardiac diseases, especially in those with CAD. Its role in the pathophysiology of CAD remains to beelucidated. 続きを見る
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論文
Lee, Sangun ; Umeda, Takashi ; Takahashi, Ippei ; Matsuzaka, Masashi ; Danjo, Kazuma ; Iwane, Kaori ; Iwasaki, Hiroki ; Nakaji, Shigeyuki
出版情報: 弘前医学.  61  pp.87-96,  2011-01-17.  弘前大学大学院医学研究科・弘前医学会
URL: http://hdl.handle.net/10129/4345
概要: The changes in the anthropometric and blood biochemical parameters, neutrophil functions such asreactive oxygen species (ROS) production capability, phagocytic activity (PA) and the profile of mood state (POMS)were measured after 2-hours of judo training session for 24 male university freshmen judoists who had not done anytraining for a long period. As for neutrophil function, PA significantly decreased after the training compared with thepre-value, though ROS production capability did not change. The Depression, Tension and total mood disturbance (TMD) decreased significantly after the training. Furthermore, the change in blood sugar correlated positively withthe changes in the Depression, Fatigue and TMD. The change in creatine kinase was positively associated with thechange in the Confusion. The training negatively acted on the appearance of physiological fatigue, and positivelyacted on the appearance of mental fatigue, and some relationship between both. Furthermore, the typical responseof the neutrophil function (PA decrease and no change in ROS) does not coincide with the typical neutrophilcompensation pattern e.g. PA decrease and ROS increase may be due to the lack of training on the part of the subjects for the last 6 months. 続きを見る
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論文
Abe, Kazuhiro ; Higuchi, Tsuyoshi ; Mizunuma, Hideki ; Kakizaki, Ikuko ; Endo, Masahiko ; Suto, Shinichiro
出版情報: 弘前医学.  61  pp.97-103,  2011-01-17.  弘前大学大学院医学研究科・弘前医学会
URL: http://hdl.handle.net/10129/4346
概要: The aim of study is to analyze functional sugar chains, glycosaminoglycans (GAGs) in urine frompostmenopausal women with osteoporosis. A 24-hour urine was collected from 15 osteoporotic women and normalwomen. All women were postmenopausal and aged at 60 to 70 years old. Diagnosis of osteoporosis was based onthe diagnosis criteria proposed by the Japan Osteoporosis Society after measurement of lumbar spine bone mineraldensity by dual energy X-ray absorptiometry. The urine was concentrated by dialysis and evaporation, thenprecipitated with ethanol. The precipitate was then reconstituted into NaCl solution, precipitated again by adding 10% cetylpyridinium chloride and the precipitation was used as complex GAGs fraction. The yield of complex fractionwas significantly higher in osteoporotic subjects than that in normal control. Then, the complex GAGs fraction wasanalyzed by cellulose acetate membrane electrophoresis and high performance liquid chromatography (HPLC),respectively. Cellulose acetate membrane electrophoresis has revealed that GAGs in urine contained partiallydesulfated chondroitin sulfate. However, further analysis by HPLC has shown that the excretion of desulfated GAGswas rather less in osteoporotic women, indicating that urinary GAGs fraction from osteoporotic women containsunknown acidic polysaccharides as well as GAGs. 続きを見る
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論文
大久保, 愉一 ; 松坂, 方士 ; 高橋, 一平 ; 檀上, 和真 ; 中路, 重之 ; 梅田, 孝
出版情報: 弘前医学.  61  pp.104-113,  2011-01-17.  弘前大学大学院医学研究科・弘前医学会
URL: http://hdl.handle.net/10129/4347
概要: 労働者のメンタルヘルスと社会環境学的要因を調査し,メンタルヘルスに及ぼすこれらの影響を調査した.東北,北海道の労働者6310名に家族構成,生活習慣,健康度,職場環境,抑うつ度(CES-D)をアンケートで聞き取り,CES-D と他の項目の関係 を検討した.その結果,「仕事・職業満足度」「仕事裁量度」「仕事士気度」「上司関係満足度」「自己評価点」「健康度」「生活習慣点」「家族・友人満足度」で,低得点群に比較し高得点群でオッズ比が小さく,「悪対処数(問題となるストレス解消行動の数)」ではその逆であった.一方,「勤務時間」「時間外勤務」「仕事量質負担度」では有意な結果は得られなかった.以上より,わが国の労働者は地域社会・家庭のストレスを職場に持ち込み,さらにうつに対する感受性がうつ度に大きく影響していることが示唆された.また,仕事量質の影響は大きくなく,労働者のメンタルヘルス改善を考えた場合,社会精神文化を考慮した職場環境を構築することが重要と考えられた. 続きを見る