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Background Epstein–Barr virus-positive mucocutaneous ulcer (EBV-MCU) is a new category of mature B-cell neoplasms. Ulcers occur in the oropharyngeal mucosa, skin, and gastrointestinal tract. The onset of EBV-MCU is suggested to be related to the decreased immunity of the patient, the causes of which include the use of immunosuppressive agents and aging. EBV-MCU may regress spontaneously and it often has a benign course after the dose reduction or discontinuation of immunosuppressive agents or during follow-up. Here, we report the case of a patient who required surgical resection for the intestinal obstruction arising from EBV-MCU. Case presentation A Japanese elderly male visited our hospital with chief complaints of a palpable mass and dull pain in the left upper quadrant, loss of appetite, and weight loss. Although abdominal computed tomography and total colonoscopy (TCS) revealed a tumor with circumferential ulcer in the transverse colon, histopathological analysis of a biopsy specimen of this lesion showed only nonspecific inflammation. Because the tumor spontaneously regressed during the time he underwent tests to obtain a second opinion from another hospital, TCS was reperformed on the patient. TCS revealed that the tumor decreased in size and the inflammatory changes in the surrounding mucosa tended to improve; however, tightening of the surrounding mucosa due to scarring was observed. Another histopathological analysis of a biopsy specimen showed widespread erosion of the mucosa and the formation of granulation tissue with marked infiltration of various inflammatory cells into the mucosal tissue of the large intestine. Moreover, some of the B-lymphocyte antigen CD20-positive B cells were also positive for EBV-encoded small RNA-1, suggesting the possibility of EBV-MCU. Later, the tumor developed into an intestinal obstruction; thus, the transverse colon was resected. Histopathological analysis of the resected specimen demonstrated scattered Hodgkin and Reed–Sternberg-like multinucleated large B cells in addition to EBER-1-positive cells. The patient was finally diagnosed as having EBV-MCU. Conclusions This is the first report of a case of EBV-MCU that developed into an intestinal obstruction requiring surgical resection. It is necessary to consider the possibility of EBV-MCU when examining an ulcerative or tumorous lesion in the gastrointestinal tract.

We report our experience of two cases of refractory cellulitis caused by peripheral micro-arteriovenous fistulas (AVFs) in the lower extremity. The micro-AVFs were so small that they could not be located accurately; further, the patients’ symptoms differed markedly from those previously reported for AVF. AVF is known to cause ischemic symptoms. In contrast, micro-AVF causes congestive symptoms and remains undetected in the majority of patients. Identification of this pathology is crucial to enable effective treatment by the ligation of the incompetent perforator vein that increases venous hypertension, leading to congestive symptoms.

Herein we aimed to investigate the degradation of surgical instruments in our hospital and how water quality affects the rate of metal corrosion.We observed 279 stainless steel instruments, and determined the presence of damage like metal corrosion or scale formation. We also measured the concentrations of chloride(Clsup-/sup)and silicate(SiOsub4/subsup4-/sup)ions in the water used for cleaning in our operating rooms, including tap water from the city water supply and reverse-osmosis(RO)filtered water.Pitting corrosion was observed on 71% of the instruments we investigated. The concentration of Clsup-/supwas 0.7mg/L in tap water and 0.1mg/L in RO water, while the concentration of SiOsub4/subsup4-/supwas 0.3mg/L in both the tap and RO water.Of the dissolved ions Clsup-/supand SiOsub4/subsup4-/sup, Clsup-/supis more of a concern, as it causes pitting corrosion over time, while SiOsub4/subsup4-/supcauses scale formation. Considering the typical water quality in the operating-room environment, degradation must be monitored for the general maintenance of metal surgical instruments.

Background and Aim: Surgical site infection (SSI) remains an important concern in Japan. The Japanese Soci‐ ety for Infection and Prevention Control disclosed that the incidence of SSIs has been lowered only by a fraction over the past 10 years. The importance of taking steps to reduce the occurrence of SSIs is recognized by many hospitals, but to date, no truly effective countermeasures have been reported. We executed a plan to better un‐ derstand the spec fic surveillance needs at St. Marianna University School of Medicine Hospital and then de‐ velop and institute procedures that would reduce the incidence of SSIs. Methods and Results: In 2005, we began development of an enhanced SSI surveillance system. With our basic CDC-based surveillance system in place, we assembled a team of doctors and nurses to oversee surveillance. We practiced strict record keeping and data analysis, gleaned information from staff, and enlisted the coopera‐ tion of other departments. New procedures were established accordingly and implemented in three phases. Be‐ tween 2005 and 2013, we witnessed informative fluctuat ons in the incidence of SSIs. Key components of our new system were standardized postoperative wound cleansing, use of buried absorbable sutures to close surgical wounds, consistent provision of 6 antibacterial agents, each one active against a common organ spec fic patho‐ gen, and establishment of a prophylactic protocol. New methods of information sharing were also instituted. We lowered the incidence of SSIs from 8% in 2006 to approximately 6.9% in 2012. We continue to monitor the number of SSIs occurring and are encouraged by a steady decline. Conclusion: Establishment of the SSI team at our hospital has proven to be a useful multidisciplinary approach to nosocomial infection awareness and control. Gradual introduction of the system to the various departments and step-by-step implementation have decreased the occurrence of SSIs and the nosocomial spread of infectious agents.

The evolution of crystal structure, spin structure, and macroscopic magnetization of manganese-substituted BiFeO3 (BiFe1−xMnxO3), a candidate for multiferroic materials, were investigated on bulk and epitaxial thin-film. Mn substitution for Fe induced collinear antiferromagnetic spin structure around room temperature by destabilizing the cycloidal spin modulation which prohibited the appearance of net magnetization generated by Dzyaloshinskii-Moriya interaction. For the bulk samples, however, no significant signal of ferromagnetism was observed because the direction of the ordered spins was close to parallel to the electric polarization so that spin-canting did not occur. On the contrary, BiFe1−xMnxO3 thin film on SrTiO3 (001) had a collinear spin structure with the spin direction perpendicular to the electric polarization at room temperature, where the appearance of spontaneous magnetization was expected. Indeed, ferromagnetic hysteresis behavior was observed for BiFe0.9Mn0.1O3 thin film.

胆嚢癌の組織型は腺癌が主であり，小細胞癌の報告は稀である．今回，われわれは胆嚢原発小細胞癌の1例を経験したので報告する．患者は66歳，男性．腹痛で他院受診，当初は胆嚢炎と診断され胆嚢ドレナージを施行された．しかし，その後胆嚢癌が疑われたため，当院に紹介受診となった．来院時血液検査では炎症反応は認めず，CA125が40.2U/mlと上昇していた．CTで胆嚢底部に45×39mmの充実性腫瘍を認め，一部漿膜側に突出していたが周囲リンパ節の腫大は認めなかった．多臓器転移も認めなかったので手術を施行した．腹腔鏡で明らかな腹膜播種のないことを確認した後，開腹した．腫瘍の明らかな漿膜面への露出はなく，周囲リンパ節腫大も認めなかった．胆嚢床切除術を施行した．病理診断はSmall cell carcinoma，SS，INFβ，ly1，v1，pn0，pHinf0，pBM0，pEM0であった．経過は良好で術後2年6カ月現在も外来通院中である．

症例は60歳，女性．検診で腫瘍マーカーの高値を指摘されて紹介，CEAが8.7ng/ml，CA19-9が51U/mlであった．膵尾部に30mm大の多房性嚢胞性腫瘍を認めた．同腫瘍は主膵管と連続しており，主膵管が拡張していたことから混合型IPMNと診断した．また，臍から腹腔内に突出するように70mm大の嚢胞性腫瘍を認めた．IPMNの転移性腫瘍である可能性も考えたが，IPMNがinvasive carcinomaとは考えにくいことから同時重複腫瘍と判断し膵体尾部切除術と臍腫瘍摘出術を施行した．病理所見でも両腫瘍は共に1層の高円柱上皮で被われた嚢胞性腫瘍で，IPMN（IPMC）と尿膜管癌と診断された．IPMNに合併した尿膜管癌の報告はわれわれが検索した限りではみられなかった．両者は形態的にも病理組織学的にも類似しており，興味深い症例と思われた．

症例68歳・男性．14年前肝機能障害，6年前右腎盂尿管癌．経過観察時に，腹部USで肝腫瘍指摘され入院．腹部画像検査で，肝S8に径3cm強の境界明瞭な腫瘍を認め，さらに膵鉤部には分葉状の3cm大の嚢胞性病変が描出した．肝腫瘍は，肝細胞癌・単発3cm以上．膵嚢胞性腫瘍は，膵管内乳頭粘液腫瘍（IPMN）分枝型・3cm以上・MPD軽度拡張があることより両病変とも手術適応と判断．肝障害度A，ICG15分補正値11％，背景肝が慢性肝炎状態であり，同時手術は避け肝前区域切除先行し，7カ月後に幽門輪温存膵頭十二指腸切除術施行．肝組織は，肝細胞癌単結節周囲増殖型．膵組織は，膵管内乳頭粘液性腺癌（IPMC）微小浸潤の混合型病変であった．IPMNは多臓器悪性腫瘍の合併が多く報告されている．今回，3重複癌である腎盂尿管癌術後の同時性肝細胞癌合併IPMCを報告する．

症例は62歳の男性で，肝右葉に腫瘤を指摘され紹介となった．HBs Ag，HBc Ab，HCV Abは陰性で，腹部超音波検査では辺縁低エコー帯を有する径40 mmの高エコーな腫瘤であった．造影CTでは腫瘍は低吸収で，辺縁の一部に造影効果を認めたが同部のwash outは乏しかった．MRIでは腫瘍の大部分は脂肪成分であった．確定診断には至らなかったが，脂肪成分を多く含む高分化型肝細胞癌を疑い手術を施行した．摘出した腫瘍は弾性軟で被膜を有し，病理組織学的にwell to moderately differentiated hepatocellular carcinomaと診断された．高分化型肝癌には脂肪成分に富むものがあるが本症例のように4 cmと大型になることは少ない．肝細胞癌としては非典型的な発育機序を呈したと考えられ，興味深い症例と思われたので報告する．

症例は69歳，女性．C型慢性肝炎に対してペグインターフェロン（Peg-IFN）・リバビリン併用療法を施行．Peg-IFN開始前，肝S5領域に腹部超音波にて径10 mm大の低エコー結節を認め，Dynamic CTで周囲から中央へ濃染する腫瘍であり，肝血管腫として経過観察されていた．Peg-IFN終了後，肝S5領域の腫瘍が径15 mm大に増大を認めたために精査入院となった．Dynamic CTでは腫瘍辺縁が動脈相で濃染し，平衡相でwash outを認めるようになり，腫瘍中心部に非濃染部を持つ腫瘍へと変化していた．肝細胞癌（Hepatocellular carcinoma：HCC），あるいは胆管細胞癌（Cholangiocellular carcinoma：CCC）との混合型肝癌を強く疑い，肝右葉切除術を施行した．腫瘍は組織学的に小型細胞がスリット状の腺腔を形成し，間質には豊富な結合織を認め，免疫染色でCK7, CK19, CK19-9, EMAが陽性，HepPar-1が陰性，c-kitが一部陽性を示し，細胆管細胞癌（Cholangiolocellular carcinoma：CoCC）と診断した．近年，CoCCの報告は増加を認めるも，その臨床像，画像的特徴，組織学的特徴などは必ずしも明らかとは言えない．今回，小腫瘍として発見され，画像上造影所見の変化を認めたCoCCの一切除例を経験したので報告する．

Background/Aim: Ischemic preconditioning (IPC) may reduce hepatic ischemia-reperfusion (IR) injury, but efficacy of IPC on mitochondrial proteome is not demonstrated. We investigated how IPC modifies the mitochondrial proteome after IR injury. Methods: Rats were subjected to 25 min of portal triad crossclamping (IR group, n = 8). In the IPC group (n = 8), 10 min of temporal portal triad clamping was performed before 25 min of portal clamping. Samples were obtained after 24 h. The mitochondrial inner-membrane potential was measured by the uptake of a lipophilic cationic carbocyanine probe and mitochondrial proteome was also investigated using 2-dimensional differential in-gel electrophoresis and liquid chromatography-tandem mass spectrometry. Results: Mitochondrial inner-membrane potential and glutathione were lower and serum transaminase was higher in the IPC group than in the IR group. The mitochondrial precursor of aldehyde dehydrogenase 2 and α-methylacyl-CoA-racemase were upregulated in the IPC group in comparison to the IR group. In contrast, protein disulfide-isomerase A3 precursor, 60S acid ribosomal protein P0, carbonic anhydrase 3 and superoxide dismutase were significantly more downregulated in the IPC group than in the IR group. Conclusions: A hepatoprotective effect by IPC was not shown; however, IPC caused significant up- or downregulation of several mitochondrial proteins.

症例は59歳の男性. 健診で指摘された肝機能異常を契機に発見された肝腫瘤の精査の結果, S8局在, 径25mm・単発の肝細胞癌と診断し手術施行. 術後診断は中分化型肝細胞癌であった. 術後3カ月目に突然の下肢筋力低下と痺れが出現. 第8胸椎の転移性腫瘍による脊髄圧迫と診断され緊急入院. 保存的治療により症状改善みられず緊急手術施行. 術後病理診断で肝細胞癌の骨転移と診断. 術後放射線治療が行われた後, 目立った後遺症なく退院された. 肝細胞癌の骨転移は約3%と稀で, その多くは原病巣の径が大きい場合や肝内病巣が多発している場合である. 今回比較的径の小さい肝細胞癌であり, しかも術後早期に残肝内に再発病巣がなかったにも関わらず術後早期に骨転移をきたした稀な症例を経験した. 非癌部はNASHによる肝硬変と診断された. NASHに生じた肝細胞癌の転移・再発形式に関し示唆的な症例であった.

Irinotecan, a DNA topoisomerase I inhibitor, is widely used in cancer chemotherapy. However, little is known of the mechanisms of its antitumor effects and the development of drug resistance in human hepatocellular carcinoma (HCC). In this study, we investigated the effects of short-term culture with SN-38, the active metabolite of irinotecan, on apoptosis in Huh7 cells. The cells were cultured with SN-38 for 24, 72, and 120 h, and apoptosis was determined using the terminal dUTP nick-end labeling (TUNEL) assay. The expressions of p53, apoptosis-related proteins, and P-glycoprotein (P-gp), a protein conferring the multidrug-resistant phenotype, were analyzed using Western blotting. Induced expression of P-gp was detected using fluorescence microscopy. SN-38 significantly induced apoptosis in Huh7 cells at 24 h. SN-38 also increased the expression of p53, Bax, and caspase-9 and decreased Bcl-xL expression in Huh7 cells. SN-38 decreased p53 expression and increased P-gp expression after 120 h, resulting in inhibition of apoptosis. This inhibition was reversed by the addition of verapamil to the culture medium during 120 h incubation. SN-38-induced P-gp expression was additionally enhanced by p53 decoy oligodeoxynucleotide. The changes in P-gp expression were directly moderated by p53 gene downregulation, suggesting that it plays a role in the mechanism of drug resistance. These results suggest that the accumulation of irinotecan in HCC leads to the development of drug resistance.

X-ray photoelectron spectroscopy and first-principles density-functional calculations were used to study the interaction of thiophene, H(2)S, and S(2) with Ni(2)P(001), alpha-Mo(2)C(001), and polycrystalline MoC. In general, the reactivity of the surfaces increases following the sequence MoCNi(2)P(001)alpha-Mo(2)C(001). At 300 K, thiophene does not adsorb on MoC. In contrast, Ni(2)P(001) and alpha-Mo(2)C(001) can dissociate the molecule easily. The key to establish a catalytic cycle for desulfurization is in the removal of the decomposition products of thiophene (C(x)H(y) fragments and S) from these surfaces. Our experimental and theoretical studies indicate that the rate-determining step in a hydrodesulfurization (HDS) process is the transformation of adsorbed sulfur into gaseous H(2)S. Ni(2)P is a better catalyst for HDS than Mo(2)C or MoC. The P sites in the phosphide play a complex and important role. First, the formation of Ni-P bonds produces a weak "ligand effect" (minor stabilization of the Ni 3d levels and a small Ni --P charge transfer) that allows a high activity for the dissociation of thiophene and molecular hydrogen. Second, the number of active Ni sites present in the surface decreases due to an "ensemble effect" of P, which prevents the system from deactivation induced by high coverages of strongly bound S. Third, the P sites are not simple spectators and provide moderate bonding to the products of the decomposition of thiophene and the H adatoms necessary for hydrogenation.

抗癌治療を施行した切除不能膵癌44例〔化学 (C) 療法29例, 放射線化学 (C+R) 療法12例, 放射線 (R) 療法3例〕において, 各治療法別に治療成績について検討した.50%生存期間 (MST) はC療法4.5カ月, C+R療法8.1カ月, R療法が4.0カ月であり, 有意差はみられなかったが, C+R療法では, 若干の生存期間の延長傾向が認められた. 各治療法別の奏効率, performance status (PS) 改善率およびCA 19-9値の低下率に有意差は認めなかった.診断確定後, 初回よりgemcitabine (GEM) を投与した36例中, 単独投与例は27例で, MSTは5.3カ月であった. 奏効率は7.4%, PSの改善は14.8%で, CA 19-9値低下は22.7%であった. 完遂例は38.2%で, 91.2%に骨髄抑制を認め, 1例の死亡例を認めた.GEMの総投与量および投与回数の増加と予後延長との間に有意な相関を認め, GEM単独投与例においては, 1回投与量を減量してでも継続投与することが有効と考えられた.

Since the importance of human tissue in the research for therapeutics and drug development has been widely recognized, the frequency of human tissue use for research has increased. The Human Science Research Resources Bank (HSRRB) has been established by the Japan Health Sciences Foundation as the first bank of human tissue for research in Japan. This public bank supplies human tissues for medical research to the scientists in Japan. To collect the human tissue for this bank, St. Marianna University School of Medicine has established an in-house institutional bank system as the human tissue supplier. The job clinical research coordinator, and a newly formatted informed consent and masking system of personal information by a special security manager have all been introduced, and high-quality tissue storage was installed for this system. The details of our system is described in the present paper; the problems encountered and countermeasures for such problems are also discussed.

In partial-liver transplantation, the use of small grafts sometimes results in graft failure, usually caused by portal hypertension after transplantation (Tx). Portal hypertension after Tx can be decreased with a porto-caval shunt (PCS). The purpose of this study is to clarify the effect of the PCS on extremely reduced-size liver Tx. In a pig model, the posterior segment of 25% of a whole liver was transplanted orthotopically. The pigs were divided two groups: group A, graft with PCS ( n=7), and group B, graft without PCS ( n=7). The PCS was made by means of side-to-side anastomosis of the portal vein and the inferior vena cava. We examined the portal vein pressure, survival rate, regeneration rate of the graft, Ki-67 as an index of cell proliferation, and histological findings, and carried out liver-function tests. In group A, five pigs survived for more than 4 days and the remaining two died of a perforated gastric ulcer on post-operative day (POD) 2. In group B, all pigs except one died of graft failure within 24 h. Portal vein pressure after reperfusion in group A and group B was of statistically significant difference ( P0.05), 14.2+/-3.2 and 18.9+/-4.7 cmH(2)O, respectively. In group A, the regeneration rate of the graft was 94%, 4 days after Tx, and Ki-67 stained remarkably in the parenchymal hepatocytes. In TEM finding, structure of the sinusoid was also well maintained after Tx. From these results we can conclude that the key to success in liver Tx with extremely small grafts lies in the control of the portal vein pressure.

腰部には上腰三角・下腰三角と2つの解剖学的抵抗減弱部位が存在するが,特に下腰三角部にヘルニアが発症することは極めて稀である.今回われわれは,特発性下腰ヘルニアの1例を経験したので若干の文献的考察を加え報告する.症例は73歳,男性.左側腹部膨隆を主訴に来院.左下腰三角に14×9cmの膨隆を認め, CTにて左側腹部に腸管と腹膜脂肪組織の脱出認め,腰ヘルニアと診断.手術はヘルニア嚢を解放せず広背筋・腹斜筋群を寄せ,その上方をメッシュにて補強した.術後,現在まで再発を認めていない.

われわれは高齢者にみられた稀な下部直腸(Rb)穿孔の1例を経験したので報告する.症例81歳,女性.腹痛を自覚し,腹部CTで直腸周囲に浸出液およびair fluid levelを認めた.緊急注腸造影にて下部直腸から造影剤の腸管外流出を認め,直腸穿孔と診断し,同日緊急開腹術を施行し,下部直腸の穿孔とその周囲の膿瘍形成を認めた.穿孔部に明らかな腫瘍性病変,潰瘍性病変は認めなかった. Hartmann手術を施行し,術後経過は良好であった.病理組織学的検査でも特徴的所見は認めず,特発性直腸穿孔と診断した.

IN CLINICAL orthotopic liver transplantation, the graft frequently deteriorates due to various mechanisms, including preservation injury, warm ischemia during implantation, and reperfusion injury. After hepatocyte damage, some cytokines stimulate hepatocytes and play key roles in the regulation of hepatic regeneration. In livingrelated liver transplantation (LRLT), we often must use partial livers, which are smaller than the standard liver volume of recipients. After transplantation, the size of the partial liver graft increases rapidly in a short period of time. During graft enlargement, it is believed that changes of serum cytokines reflect the status of the regeneration process of the liver graft. In this study, we measured serum cytokines that play a the role in the regulation of liver regeneration, (ie, hepatocyte growth factor [HGF], interleukin-6 [IL-6], and transforming growth factor-b1 [TGFb1]. The purpose of this study was to investigate the relationship between changes of serum cytokine levels and growth of the graft, as well as recovery from graft damage.

Background We have recently identified a novel cell-cell adhesion system, named NAP system, which is localized at cadherin-based cell-cell adherens junctions (AJs). The NAP system is composed of at least nectin, afadin and ponsin. Nectin is an immunoglobulin-like cell adhesion molecule. Afadin is an actin filament-binding protein which associates nectin with the actin cytoskeleton. Ponsin is an afadin-binding protein which furthermore binds to vinculin and provides a possible linkage of nectin-afadin to cadherin-catenin through vinculin. We compared here the behaviour of the NAP and cadherin-catenin systems during the formation and disruption of the polarized junctional alignment in epithelial cells. Results At the early stage of the formation of the polarized junctional alignment in MTD-1 A cells, primordial spot-like junctions were formed at the tips of thin cellular protrusions radiating from adjacent cells. Nectin, afadin, ponsin, cadherin and catenin were simultaneously recruited to these junctions. As the cell polarization proceeded, the spot-like junctions were gradually fused to form belt-like AJs where all these proteins were concentrated. The disruption of cell-cell AJs in MDCK cells by culturing at a low Ca2+ concentration caused rapid endocytosis of cadherin, but not that of nectin or afadin. Addition of 12-O-tetradecanoylphorbol-13-acetate to the cells formed a tight junction-like structure where nectin and afadin, but not cadherin, accumulated. Conclusion These results indicate that the NAP and cadherin-catenin systems show similar and differential behaviour during the formation and disruption of the polarized junctional alignment in epithelial cells.

Background. We hypothesized that microcirculatory disturbance was an obstacle to liver transplantation (LTx) from non-heart-beating donors (NHBDs) and that it was attributed mainly to a deterioration of sinusoidal endothelial cells (SECs) and sinusoidal narrowing. This study was designed to examine porcine orthotopic LTx using livers obtained from pretreated agonal NHBDs, and to determine whether the maintenance of the liver microcirculation would result in successful LTx from agonal NHBDs. Methods. Pigs were allocated to five groups: (i) control group; (ii) NM group, in which grafts were rinsed with nafamostat mesilate (NM) rinse; (iii) LD group, in which Kupffer cells in grafts were eliminated by liposome-encapsulated dichloromethylene diphosphonate (L-DMDP); (iv) LDNM group, in which grafts pretreated with L-DMDP were rinsed with NM rinse; (v) heart-beating donor (HBD) group. In all groups, but the HBD group, the livers were pretreated with FK506 and prostaglandin I 2 analogue, and were preserved in University of Wisconsin solution after cardiac arrest. Thereafter orthotopic LTx was performed. Results. After reperfusion, it was histologically demonstrated that elimination of Kupffer cells prevented SECs deterioration and NM rinse prevented sinusoidal narrowing. The hepatic energy charge recovered in all groups except the control group. In the LDNM group, three of four recipients survived more than 7 days. Conclusions. For a successful LTx from agonal NHBDs, it is important to prevent microcirculatory disturbance caused by SEC deterioration and sinusoidal narrowing after reperfusion. Combination therapy consisting in the elimination of Kupffer cells and NM rinse prevented primary graft non-function in liver grafts from agonal NHBDs.

We recently purified and characterized from rat brain a GTPase-activating protein (GAP) specific for the Rab3 small G protein subfamily implicated in Ca2+-dependent exocytosis. Rab3 GAP showed two bands with M r of about 130,000 (p130) and 150,000 (p150) on SDS-polyacrylamide gel electrophoresis. p130, but not p150, showed the catalytic activity. Because p150 was likely the subunit of Rab3 GAP, here we cloned the cDNA of p150, determined its primary structure, and characterized it. The tissue and subcellular distribution patterns of p150 and p130 were similar, and both the proteins were enriched in the synaptic soluble fraction. p150 was co-immunoprecipitated with p130 from this fraction. Recombinant p150 formed a heterodimer with recombinant p130 as estimated by sucrose density gradient ultracentrifugation. Recombinant p150 neither showed the Rab3A GAP activity nor affected the activity of recombinant p130. When p150 and p130 were co-expressed in the cells, the subcellular localization of each protein did not change. These results indicate that p150 is the noncatalytic subunit of Rab3 GAP.

We purified a novel actin filament (F-actin)-binding protein from the soluble fraction of Saccharomyces cerevisiae by successive column chromatographies by use of the 125I-labeled F-actin blot overlay method. The purified protein showed a minimum Mr of about 140 kDa on SDS-polyacrylamide gel electrophoresis and we named it ABP140. A search with the partial amino acid sequences of ABP140 against the Saccharomyces Genome Database revealed that the open reading frame of the ABP140 gene (ABP140) corresponded to YOR239W fused with YOR240W by the +1 translational frame shift. The encoded protein consisted of 628 amino acids with a calculated Mr of 71,484. The recombinant protein interacted with F-actin and showed the activity to crosslink F-actin into a bundle. Indirect immunofluorescence study demonstrated that ABP140 was colocalized with both cortical actin patches and cytoplasmic actin cables in intact cells. However, elimination of ABP140 by gene disruption did not show a deleterious effect on cell growth or affect the organization of F-actin. These results indicate that ABP140 is not required for cell growth but may be involved in the reorganization of F-actin in the budding yeast.

A 62-year-old man was admitted with dyspnea. Computed tomography (CT) revealed left massive pleural effusion and a cystic lesion in the posterior mediastinal compartment extending to the pancreatic head via the esophageal hiatus. The pleural effusion had a high amylase content. Based on these findings, we diagnosed mediastinal pancreatic pseudocyst accompanied by pancreatic pleural effusion. We treated him with CT-guided puncture and endoscopic pancreatic drainage. Endoscopic pancreatic treatment is possible for pancreatic pseudocysts.

Rho kinase is an important factor in tumor progression. We demonstrated that Rho kinase-associated coil-containing protein kinase (ROCK) is expressed in hepatic tissues in hepatocellular carcinoma (HCC) and confirmed its roles in cell survival in HCC cells using the ROCK inhibitor, fasudil. ROCK protein levels were estimated in hepatic tissues with HCC compared with healthy liver tissues or hepatic hemangioma tissues using immunohistochemistry. Furthermore, HepG2 and Huh7 cells were cultured with ROCK inhibitor, fasudil for 24 h in vitro. Cell proliferation was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay, and apoptotic cells were detected by cell death ELISA. The expression apoptosis-related proteins were analyzed using Western blotting. Fasudil significantly decreased cell proliferation and induced apoptosis mediated by increases in p53, Bax, caspase-9, and caspase-3 in HepG2 and Huh7 cells. The induction of apoptosis was inhibited in HCC cells precultured with p53 decoy oligodeoxynucleotide. These results suggest that ROCK inhibits the p53-mediated apoptosis pathway in HCC. Fasudil may thus be a beneficial approach to HCC therapy.

The patient was a 75-year-old asymptomatic man, in whom a tumor mass in the pancreatic tail had been found 6 months earlier. Computed tomography revealed a mass 7 cm in diameter, and an enhancement with contrast medium was observed at the periphery and partially inside the mass, but not in most parts of the tumor. Endoscopic retrograde cholangiopancreatography showed a filling defect in the main pancreatic duct. A distal pancreatectomy was performed because of the possibility of a malignant tumor. The tumor consisted of a lobular invasive growth component and a component with intraductal growth into the main pancreatic duct, and histologically the tumor cells had solid acinar to partially trabecular/tubular patterns. Trypsin (an acinic cell marker) expression was widely observed, followed by the expression of chromogranin A (an endocrine cell marker) in about 30% of the tumor cells. The tumor was diagnosed as mixed acinar-endocrine carcinoma according to the WHO classification.

We examined mortality from adult T-cell leukemia/lymphoma (ATL/ATLL) and other diseases alleged to be associated with human T-lymphotropic virus type I (HTLV-I) among anti-HTLV-I antibody-positive blood donors in Kyushu, Japan. During 1984-87, a total of 3,991 blood donors aged 40 years or over were followed from the date of donation to the date of death or the end of the study. Crude mortality rates from ATL (with 95 percent confidence intervals) were 68 per 100,000 (13-202) for males and 36 per 100,000 (3-132) for females. The rates were underestimated by approximately 50 percent because of self-selection and short observation periods. Neither death rates from other cancers nor death rates from all cancers were elevated.

Few case reports have previously documented a second surgery after pancreaticoduodenectomy due to recurrence or other reasons in patients with periampullary malignancies. The present report summarized the experience of this clinic with secondary surgery after Pancreaticoduodenectomy (PD).During the past 7 years, 7 out of 95 patients with periampullary malignancies underwent a second surgery after pancreaticoduodenectomy at this institution. The clinical courses of these patients are presented and 2 interesting cases are shown in the present study.One patient with lower bile duct adenocarcinoma underwent a remnant splenopancreatectomy due to pancreatic recurrence 36 months after pancreaticoduodenectomy. The other patient with lower bile duct adenocarcinoma underwent a hepatectomy due to a solitary liver metastasis 47 months after a pancreaticoduodenectomy. These 2 patients have survived 4 and 13 months after the second surgery. In the 7 patients requiring secondary surgery, 5 underwent the procedure due to recurrent disease, and 4 of the 5 received the second surgery to remove the lesion. The mean interval between pancreaticoduodenectomy and the second operation was 32 months in the 5 patients with recurrent disease and 27 months in the all 7 patients. One of the 5 patients died of recurrent disease only 5 months after the second procedure because the surgery was a palliative bypass. However, the other 3 survived more than 1 year after the resection of the lesion at the recurrent site.The present study reports 2 rare cases with lower bile duct adenocarcinoma in which a recurrent tumor was removed after pancreaticoduodenectomy. In this study, 4 patients undergoing a curative re-operation survived more than 1 year after the surgery. The present study was small, but the findings are significant because of the scarcity of reports of patients undergoing secondary surgery after PD.

Postoperative morbidity after a pancreaticoduodenectomy remains high mainly due to pancreatic fistula, but effective methods to prevent the development of pancreatic fistula have yet to be established. The present study prospectively investigated whether postoperative prophylactic irrigation around the pancreaticojejunostomy might be able to prevent eventual pancreatic fistula and infectious complications after a pancreaticoduodenectomy.Among 75 patients undergoing a pancreaticoduodenectomy between 2003 and 2005, 50 patients in whom the drain amylase level on postoperative day 1 were 1,500 IU/L or more were selected for the present study. Twenty-six of the 50 patients underwent postoperative prophylactic 72-hour continuous irrigation around the pancreaticojejunostomy starting from postoperative day 1 (Irrigation group). On the other hand, 24 of them did not undergo such irrigation (Non-irrigation group). The incidence of pancreatic fistula, infectious complications, delayed gastric emptying, and the length of hospital stay were then compared between the 2 groups.The incidences of pancreatic fistula, wound infection, drain infection, sepsis, delayed gastric emptying, overall morbidity, and length of hospital stay were found to be significantly less in the irrigation group than in the non-irrigation group.Prophylactic irrigation may possibly be able to prevent the occurrence of pancreatic fistula and infectious complications after a pancreaticoduodenectomy in patients with a risky pancreatic remnant.

Background We report an extremely rare case of concomitant huge exophytic GIST of the stomach and Kasabach-Merritt phenomenon (KMP). Case presentation The patient was a 67-year-old man experiencing abdominal distension since September 2006. A physical examination revealed a 25 × 30 cm hard mass that was palpable in the middle and lower left abdomen minimal intrinsic mobility and massive ascites. Since the admitted patient was diagnosed with DIC, surgery could not be performed. The patient received a platelet transfusion and the DIC was treated. Due to this treatment, the platelet count recovered to 7.0 × 104; tumor resection was performed at 16 days after admission. Laparotomy revealed a huge extraluminal tumor arising from the greater curvature of the stomach that measured 25 × 30 cm and had not ruptured into the peritoneal cavity or infiltrated other organs. Partial gastric resection was performed. The resected mass measured 25 × 25 × 20 cm. In cross section, the tumor appeared hard and homogenous with a small polycystic area. Histopathology of the resected specimen showed large spindle cell GIST with >5/50 HPF (high-power field) mitotic activity. The postoperative course was uneventful, and the coagulopathy improved rapidly. Conclusion Since the characteristic of tumor in this case was hypervascularity with bleeding and necrotic lesions, coagulopathy was thought to be caused by the trapping of platelets within a large vasculized tumor mass.

We investigated the organ-reducing ability of 1,2-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid methyl 6-(5-phenyl-3-pyrazolyloxy) hexyl ester (CV159) that exhibits selective blocking of Ca(2+)/calmodulin and inhibition of Ca(2+) overloading in living organisms (Sprague Dawley rats) using an in vivo and an ex vivo electron paramagnetic imaging technique. Decay rates in CV159-treated rats were significantly higher than those in untreated rats and were almost equal to those in the sham group. Both cytosol and mitochondrial superoxide scavenging activity in CV159-treated rats were significantly higher than those in untreated rats, and cytosol superoxide scavenging activity only was slightly higher than that in the sham group. Faint staining for anti-superoxide dismutase antibody was markedly observed in necrotic lesions in the liver of control group. Alanine aminotransferase level in CV-treated rats were significantly decreased as compared with the levels in untreated rats. Electron microscopy showed a decreased number of damaged mitochondria, whereas mitochondrial damage was significantly reduced in CV-treated animals. We conclude that CV159 retains the organ-reducing activity against radicals in hepatic I/R injury that is mediated by the inhibition of Ca(2+) overloading.

Background Reperfusion of ischemic tissues results in the formation of toxic reactive oxygen species (ROS), such as superoxide anion, hydroxyl radicals, hydroperoxide, and peroxynitrite. ROS are potent oxidizing agents, capable of damaging cellular membranes by lipid peroxidation. In the present study, we applied an in vivo electron paramagnetic resonance (EPR)/spin probe and an ex vivo EPR technique to provide direct evidence of ROS following experimentally induced small bowel ischemia/reperfusion (I/R) injury. Materials and Methods We used a rat model of small bowel I/R injury to explore the possibility that MnM2Py4P or Mn-salen can prevent the accumulation of ROS species following experimentally induced I/R injury. We examined the ability of MnM2Py4P and Mn-salen to scavenge radicals in living Sprague-Dawley (SD) rats using an in vivo and an ex vivo EPR technique with a spin probe. Results The CP decay rates in the MnM2Py4P- and Mn-salen-treated rats were significantly higher than those in the untreated rats and almost equal to those in sham group rats. There were no significant differences between the MnM2Py4P-treated group and the Mn-salen-treated group. Superoxide scavenging activities (SSA) in the MnM2Py4P- and EUK-8-treated group were higher than those in the untreated group and almost equal to the sham group. Conclusion The present study suggested that the protective effects of MnM2Py4P and Mn-salen against small bowel IR injury were mediated by the inhibition of O 2 , H 2 O 2 , and NO production.

Reperfusion of ischemic tissues results in the formation of toxic reactive oxygen species (ROS), such as superoxide anion, hydroxyl radicals, hydroperoxide, and peroxynitrite. ROS are potent oxidizing agents, fully capable of damaging cellular membranes by lipid peroxidation. In this study, we applied for the first time the in vivo electron paramagnetic resonance (EPR)/spin probe and ex vivo EPR technique to provide direct evidence of ROS following experimentally induced small bowel ischemia/reperfusion (I/R) injury. The decay rate (spin clearance rate) was determined over the first 3 minutes at 6 hours after reperfusion. Decay rates in rats subjected to I/R injury were lower than those in the sham group. Superoxide scavenging activity (SSA) in rats subjected to I/R injury was significantly lower than that in the sham group. In conclusion, this study demonstrated that it is possible to detect the accumulation of ROS following experimentally induced small intestine I/R injury using an in vivo and an ex vivo EPR technique with a spin probe.