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Itabashi, Yukihiro ; Baba, Toshiaki ; Kato, Satoru ; Hakamada, Kenichi
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
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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.
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| 2.
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Yoshida, Ikko ; Ishizaka, Hiroshi ; Hasegawa, Kazushi ; Satoh, Kiyohiko ; Osanai, Tomohiro ; Motomura, Shigeru ; Okumura, Ken
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Objectives The purpose of this study was to test the hypothesis that adenosine-induced coronarymicrovascular dilation is
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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.
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| 3.
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Sutoh, Takemichi ; Fukuda, Ikuo ; Kimura, Daisuke ; Tsushima, Takao
概要:
Nafamostat mesilate（ FUT-175）, a synthetic serine protease inhibitor, has been reported to have antitumouractivities tow
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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）
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Nodagashira, Tatsuya ; Odagiri, Hiroki ; Ikenaga, Shojiro-Kazunori ; Maruyama, Masateru ; Sato, Toshiyuki ; Hakamada, Kenichi
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Tissue-specifi c promoter has been used for cancer-specifi c suicide gene therapy, but its transcriptionalactivity is r
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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.
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Ito, Kyoko ; Masuko, Kazutaka ; Ito, Koichi
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Contact between dendritic cells（ DCs） and resting T cells is essential for initiation of the primary immuneresponse. In
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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.
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| 6.
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Yokoyama, Hiroaki ; Saito, Shin ; Higuma, Takumi ; Hanada, Hiroyuki ; Osanai, Tomohiro ; Daitoku, Kazuyuki ; Fukuda, Ikuo ; Okumura, Ken
概要:
Adipose tissue secretes various bioactive molecules （adipokines）, and apelin is one kind of adipokines.Recently, it was
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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.
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| 7.
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Lee, Sangun ; Umeda, Takashi ; Takahashi, Ippei ; Matsuzaka, Masashi ; Danjo, Kazuma ; Iwane, Kaori ; Iwasaki, Hiroki ; Nakaji, Shigeyuki
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The changes in the anthropometric and blood biochemical parameters, neutrophil functions such asreactive oxygen species
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（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.
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| 8.
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Zheng, Zhongxi ; Miura, Tomisato ; Nozaka, Hiroyuki ; Takamatsu, Terumasa ; Sato, Tatsusuke
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To date, digital pathology is based on single focal plane images, and with its rapid development, image quality and information are becoming critical concern in the field. This paper presents a new multiple focal-plane based focus image
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fusion algorithm to enhance the image quality. First of all, we will introduce a new focus image fusion lgorithm; next, we will demonstrate some experimental data and results on cytopathology slide images; and finally, we will verify the effectiveness of this algorithm using computer vision techniques and cytopathology diagnosis, and draw the conclusions.
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| 9.
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Oomura, Yutaka ; Aou, Shuji ; Fukunaga, Kouji ; Moriguchi, Sigeki ; Sasaki, Kazuo
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Leptin is well known to be involved in the inhibition of feeding, thermogenesis, reproduction and neuroendocrine functio
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ns through its actions on the rodent hypothalamic receptors. Leptin facilitated the presynaptic transmitter release and postsynaptic sensitivity to the transmitters in the hippocampal CA1 neurons. Thus longterm potentiation （LTP） and the phosphorylation of Ca2+/calmodulin protein kinase II （CaMK II） were facilitated in the CA1 neurons. Therefore behavioral performance related to spatial learning and memory was improved by leptin in vivo applications. Orexin-A produced by glucose-sensitive neurons in the lateral hypothalamic area （LHA）and released during food intake facilitates feeding. Orexin-A suppressed LTP and CaMK II phosphorylation without affecting the presynaptic transmitter release. Therefore behavioral performance on learning and memory was impaired. The present studies suggest that leptin and orexin signalings in the brain may have important implications for cognitive function.
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Herman, Peter ; Sanganahalli, Basavaraju G. ; Coman, Daniel ; Blumenfeld, Hal ; Hyder, Fahmeed
概要:
Neuronal activity mapping of cerebral functions using oxidative energetics has become an accepted functional magnetic re
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sonance imaging （fMRI） technique, termed calibrated fMRI. It requires calculation of oxygen consumption （CMRO2） from blood oxygenation level dependent （BOLD） signal using multi-modal measurements of blood flow （CBF） and volume （CBV）. This approach is based on a biophysical model which describes tissue oxygen extraction at steady-state, therefore it is unclear if this conventional steady-state BOLD model can be applied transiently for calculating dynamic CMRO2 changes. In particular, it is unknown whether calculation of CMRO2 from calibrated fMRI differs between brief and long stimuli. In this study linearity was experimentally demonstrated between BOLD-related components and neural activity. We used multi-modal fMRI （at 11.7T） and neuronal signal measurements of local fi eld potential （LFP） and multi-unit activity （MUA） in α-chloralose anesthetized rats during forepaw stimulation to show that respective transfer functions （of BOLD, CBV, CBF） generated by deconvolution with LFP（ or MUA） are time invariant, for events in the millisecond to minute range. Since the transfer functions are time invariant for event-related and steady-state stimuli, it is possible to use calibrated fMRI in a dynamic manner. The multi-modal results allowed assignment of a significant component of the BOLD signal that can be ascribed to CMRO2 transients. Here we discuss the importance of minimizing residual signal, represented by the diff erence between modeled and raw signals, in convolution analysis using multi-modal fMRI and neural signals.
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