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Introduction The emerging interdisciplinary field of cardio-oncology is of interest to clinicians because a history of cancer or cancer treatment is considered a severe risk factor for cardiovascular disease (CVD). Both cancer and CVD can reduce skeletal muscle mass; together, they can lead to a poorer prognosis. However, it is unclear whether a patient's cancer history can lower physical function and lead to a poor prognosis with the coexistence of cancer history and physical dysfunction in patients with CVD. This study aimed to identify the relationship between cancer history and physical function, as well as the prognostic value of their combination, in patients with CVD. Methods We reviewed 3,640 patients with CVD (mean age, 67.9±13.5 years) who underwent physical-function tests (gait speed and 6-min walking distance [6MWD]). We performed multivariate linear regression analysis to assess potential associations between cancer history and physical-function tests in patients with CVD. Additionally, we used the Kaplan–Meier curve and Cox regression analyses to assess survival and prognostic significance for patients divided into four groups according to the presence or absence of cancer history and high or low physical function. Results In multivariate linear regression analysis, cancer history was independently associated with lower gait speed and 6MWD (gait speed, P=0.048 and 6MWD, P=0.040). A total of 581 deaths occurred over a median follow-up period of 3.08 years (interquartile range: 1.36–5.27). For all-cause mortality, patients with a history of cancer and reduced physical function were found to have a significantly higher mortality risk even after adjusting for several covariates (gait speed, HR: 1.66, P=0.003 and 6MWD, HR: 1.71, P=0.003). Conclusion Cancer history was correlated with physical dysfunction in patients with CVD. Moreover, the coexistence of cancer history and physical dysfunction resulted in poorer prognosis in patients with CVD. Funding Acknowledgement Type of funding sources: None.

Study question Does prolactin (PRL) treatment during recovery culture affect human blastocyst outgrowth? Summary answer PRL treatment for 120 min promoted trophoblast outgrowth in cryopreserved human blastocysts by upregulating the expressions of epithelial-to-mesenchymal transition (EMT) and focal adhesion-related genes. What is known already Human embryos express the PRL receptor at the morula and the blastocyst stages. This expression correlates with the blastocyst diameter and the time required for the embryos to reach the blastocyst stage. Treatment with PRL from cleavage to the blastocyst stage improves blastocyst outgrowth to fibronectin. However, whether PRL treatment after warming cryopreserved blastocysts cultured to the blastocyst stage without PRL influences outgrowth competence remains unknown. Furthermore, the optimal time for post-warming PRL treatment remains to be ascertained. Study design, size, duration A total of 374 discarded human vitrified blastocysts donated for research by consenting couples were used. The study was approved by the Institutional Review Board. The blastocysts were randomly allocated to two groups, to be cultured in medium either with PRL (n = 208) or without PRL (control; n = 166). The gene expression level, blastocyst adhesion, outgrowth area, and distance of trophoblast migration were compared between the groups. Participants/materials, setting, methods Vitrified human blastocysts were cultured for 120 min after warming. Some blastocysts were treated with PRL for 15–120 min during the recovery period. The blastocysts were plated on fibronectin-coated dishes and cultured to assess blastocyst adhesion and outgrowth. The expressions of PRL-interacting genes were assessed by quantitative RT-PCR 12 h after outgrowth culture. The migration distance at the outer edge of the trophoblast cells was examined using time-lapse systems. Main results and the role of chance The mRNA expressions of ezrin, radixin, and moesin, which regulate cell adhesion and invasion by controlling actin reorganisation during EMT, was stimulated by PRL treatment for 120 min. The expressions of EMT-related genes, transforming growth factor β1, snail1, and twist1 were also promoted by treatment with PRL for 120 min. The blastocysts treated with PRL also exhibited augmented expression of cadherin2 and transcriptional repression of cadherin1. Higher mRNA expressions of integrin-based focal adhesion-related genes, ITGA5 and ITGB1, were observed after treatment with PRL for 120 min compared to that in the other groups. PRL treatment for 120 min did not alter the rate of blastocyst adhesion to fibronectin-coated dishes 96 h after the outgrowth culture assay. However, multiple linear regression analysis revealed that the outgrowth area was significantly increased in blastocysts treated with PRL. The migration distance of trophoblast cells was significantly increased after PRL treatment. Furthermore, a more beneficial effect of prolactin treatment on blastocyst outgrowth was observed when the blastocysts were vitrified on day 5 compared to that when the blastocysts were vitrified on day 6. Moreover, the outgrowth area was increased by PRL treatment when the blastocyst diameter was larger than 180 µm. Limitations, reasons for caution The results may vary between in vivo and in vitro conditions. Further clinical studies are required to explore the clinical efficacy of PRL treatment. Wider implications of the findings This study showed that PRL treatment for 120 min improved trophoblast migration in cryopreserved human blastocysts. Therefore, recovery culture with PRL treatment post-warming followed by blastocyst transfer could improve pregnancy outcomes. Trial registration number not applicable

Study question What are the similarities and differences between the morphokinetics of abnormal, one- (1PN) and three-pronuclear (3PN) and normal bi-pronuclear (2PN) fertilisation? Summary answer The morphokinetic analysis of 1PN/3PN fertilisation reveals novel aspects of abnormal early development. What is known already Assisted reproduction technology has allowed the observation of early human development. Initially assessed statically at a single time point, fertilization has revealed its complexity once observed by Time-Lapse Microscopy (TLM). Detailed morphokinetic analysis of fertilisation has been reported in the last few years, unveiling previously unknown cytoplasmic phenomena (e.g. the cytoplasmic wave and halo) and the importance of cell symmetry for embryo development. At present, abnormal fertilization remains neglected, despite potential for understanding the physiology and pathology of early human development. Study design, size, duration This retrospective study involved TLM observation of normally (2PN, n = 2,685) and abnormally (1PN, n = 41; 3PN, n = 127) fertilised oocytes generated in ICSI cycles. Oocyte retrievals were carried out after the clomiphene citrate-based minimal ovarian stimulation, between October 2019 and December 2020. Oocytes of patients with different diagnoses of infertility were included in the analysis, while cases involving cryopreserved gametes or surgically retrieved sperm were excluded. Participants/materials, setting, methods Microinjected oocytes were assessed by a combined TLM-culture system (Embryoscope). Oocytes not suitable for TLM assessment, due to excess of residual corona cells or inadequate orientation for correct observation, were not analysed. Phenomena, relevant to meiotic resumption, pronuclear dynamics, cytoplasmic/cortical modifications, cleavage pattern, and embryo quality, were annotated and compared between groups. Main results and the role of chance Second polar body (PBII) extrusion was observed in all 1PN- and in a majority of 3PN-zygotes (92.1%). A 0.3-hour delay in PBII extrusion was confirmed in 3PN-zygotes (P = 0.0439). In a significant proportion of 3PN-zygotes, a third (female) PN formed from reabsorption of the PBII. The cytoplasmic wave was observed not only in 2PN- and 3PN-, but also in 1PN-zygotes. The presence and position of cytoplasmic halo were comparable among the three classes of zygotes. However, the duration of the cytoplasmic halo was prolonged in 1PN-zygotes (P < 0.0001). PN juxtaposition immediately before PN breakdown was less frequent in 3PN- compared with 2PN-zygotes (P = 0.0159). Furthermore, asynchronous PN breakdown was increased in 3PN- compared with 2PN-zygotes (P = 0.0026). The PN area of 1PN- was larger than that of 2PN-zygotes; however, the PN area of 3PN-zygotes was smaller than that of 2PN-zygotes. In 1PN-zygotes, a developmental delay was observed starting from the disappearance of the cytoplasmic halo, reaching 9 hours at the time of cleavage (P < 0.0001). A higher incidence of abnormal cleavage (P = 0.0019) and blastomere fragmentation (P < 0.0001) was observed in 1PN-zygotes. Cleavage progression was increasingly affected especially in 1PN-zygotes, resulting in blastocyst formation rates of 70.2%, 12.2% and 53.5% in 2PN-, 1PN- and 3PN-zygotes, respectively (P < 0.0001). Limitations, reasons for caution The study data derive from treatments carried out in a single centre. The study findings therefore require independent verification from other research groups. Wider implications of the findings These observations suggest that 1PN and 3PN fertilisation follow the general pattern of normal fertilization. Crucially, they also shed light on diverse and previously undescribed phenomena - e.g. reabsorption of the PBII in 3PN zygotes - underpinning the origins of abnormal fertilization and potentially clinically relevant. Trial registration number not applicable

Background Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular (CV) events, therefore there is a need to identify T2DM patients at higher risk. A novel imaging biomarker, the peri-coronary adipose tissue (PCAT) attenuation on coronary CT angiography (CTA), reflects peri-coronary inflammation. We hypothesized that the assessment of PCAT attenuation is useful for risk stratification in T2DM patients. Purpose We aimed to investigate whether high PCAT attenuation is related to increased risk of CV events in T2DM patients. Methods This study is a post-hoc analysis of the prospective cohort study consist of T2DM patients who underwent clinically indicated coronary CTA at a Japanese University Hospital. As CT findings, coronary artery calcium score, epicardial adipose tissue volume, high-risk plaque features (positive remodeling, low density plaque, spotty calcification), significant stenosis (>50% luminal narrowing), and PCAT attenuation were examined. PCAT attenuation was assessed in Hounsfield units (HU) of proximal 40-mm segments of the left anterior descending artery. CV events was defined as CV death, acute coronary syndrome, and hospitalization for heart failure. Results In a total of 333 T2DM patients (63% male, age 66±11 years), the mean PCAT attenuation was −70.6±6.1 HU. During the follow-up period of 4.2 years, 20 CV events (2 cases of CV death, 14 of acute coronary syndrome, 4 of heart failure) were confirmed. Patients with CV events had higher PCAT attenuation than those without CV events (−67.4 vs −70.8 HU, p=0.013). Multivariate linear regression analysis revealed that the independent determinants of PCAT attenuation were male (p Conclusion High PCAT attenuation was a strong predictor of CV events in T2DM patients independent of coronary CTA findings and traditional risk factors. Our study suggested that assessment of PCAT attenuation could be a valuable tool for risk stratification in T2DM patients. Funding Acknowledgement Type of funding sources: None. Figure 1. Representative casesFigure 2. Kaplan-Meier curves

Recent advances in the field of natural computing have boosted the hope that complicated problems can be solved efficiently on the heuristics applying natural phenomena. In particular, it is expected that Ising spin model implemented with CMOS circuits solves combinatorial optimization problems more effectively and conveniently at room temperature, and thus, it is potentially achievable for practical use. So far, we have developed Ising machine that can be implemented with simple logic circuits consisting of XNOR gate utilized as spin decision logics for finding the ground state. In this study, we propose the hybrid-type spin decision logic (HDL), a combination of two conventional methods. HDL can find the global optimal solution of combinatorial optimization problems, that is impossible to solve with conventional spin decision logics.

Study question Does fatty acid (FA) supplementation into vitrification and warming solutions influence the developmental competence of oocyte and embryo after vitrification and warming? Summary answer FA supplementation during the warming process improves the developmental competence of vitrified-warmed mouse oocytes and embryonic-morphologies after vitrification at the cleavage-stage in bovines and humans. What is known already Vitrified metaphase II stage oocytes exhibit a diminished ability to develop into blastocysts and live births. Previous studies have shown reduction in intracellular lipid content as one of the factors associated with reduced developmental competence of oocytes after vitrification as the intracellular lipid content of oocytes is affected by vitrification. FAs derived from break down of lipids are primarily transferred to the mitochondria, where it plays a crucial role in cellular metabolism. However, the effects of FA supplementation in warming solutions on the cytoplasmic lipid content and subsequent embryo development are unknown. Study design, size, duration A chemically defined FA mixture was added to the vitrification and/or warming solutions. Oocytes collected from C57BL6/N (n = 80) were randomly divided into three groups (fresh, n = 634; non-FA (control), n = 961; FA, n = 1,686), and were vitrified-warmed with/without FA. Lipid composition, developmental competence, and gene expression levels were compared among the groups. Bovine embryos (fresh, n = 420; control, n = 524; FA, n = 492) and discarded human day-2 embryos (control, n = 87; FA, n = 92) were used to examine the developmental competence of embryos. Participants/materials, setting, methods Lipids in the ooplasm were stained with Nile red and the fluorescence intensity was analysed. The developmental competence of mouse oocytes was examined by performing intracytoplasmic sperm injection. Expressions of FA metabolism-related genes were measured. The bovine embryos were vitrified at the four-cell stage and cultured to the blastocyst stage after warming. Cryopreserved discarded human embryos were warmed and cultured. The obtained blastocysts were then placed on fibronectin-coated dishes to examine the outgrowth formation. Main results and the role of chance Lipid content of mouse oocytes was significantly lower in the control group compared to that in the fresh group (P Limitations, reasons for caution Since the experiments of the current study on human embryos were performed in vitro using discarded embryos, in vivo developmental ability was not evaluated. Therefore, to validate the application of our findings in human assisted reproductive technologies, further clinical trials (ART) are warranted. Wider implications of the findings FA supplementation into the warming solutions improved the developmental competence of vitrified–warmed oocytes and cleaved embryos by activating the β-oxidation pathway. These results indicate that FA supplementation into warming solutions is a potential strategy to improve clinical outcomes in human ART. Trial registration number not applicable

Combinatorial optimization problems often arise naturally in various fields of research. However, finding the global optimum solution of these problems remains computationally difficult. Ising spin model is considered to be an effective method to solve combinatorial optimization problems because these problems can be mapped and embedded into the Ising spin model. In general, Ising spin model requires to adjust and tune the spin connection parameters, for example, topology of spin connection and resolution of exchange interaction coefficient values between spins, according to the problems. In this paper, we focus on the number of spin connection, which is one of the spin connection parameters, and perform the calculation experiments through solving max-cut problems with Ising spin computing. As a result, all-to-all connectivity makes Ising spin computing well suited for searching the ground states of complex combinatorial optimization problems.

Purpose Endoscope-assisted surgery has widely been adopted as a basic surgical procedure, with various training systems using virtual reality developed for this procedure. In the present study, a basic training system comprising virtual reality for the removal of submandibular glands under endoscope assistance was developed. The efficacy of the training system was verified in novice oral surgeons. Material and methods A virtual reality training system was developed using existing haptic devices. Virtual reality models were constructed from computed tomography data to ensure anatomical accuracy. Novice oral surgeons were trained using the developed virtual reality training system. Results The developed virtual reality training system included models of the submandibular gland and surrounding connective tissues and blood vessels entering the submandibular gland. Cutting or abrasion of the connective tissue and manipulations, such as elevation of blood vessels, were reproduced by the virtual reality system. A training program using the developed system was devised. Novice oral surgeons were trained in accordance with the devised training program. Conclusions Our virtual reality training system for endoscope-assisted removal of the submandibular gland is effective in the training of novice oral surgeons in endoscope-assisted surgery.

We proposed "prompt decision logic", which has the advantage for accelerating the ground-state searches of Ising spin model. The Ising spin model describes the behavior of magnetic spins. It consists of each spin having four-nearest-neighbor (adjacent) spins. Escaping local minimum is a key for solving combinatorial optimization problems. Actually, many of the combinatorial optimization problems can be mapped onto the Ising spin model. In this report, we observed convergence properties of Ising spin computing with prompt decision logic, without any scheduling during energy convergence. Furthermore, the prompt decision logic showed better success probability than that of majority voting logic, as the problem size grows. Therefore, the prompt decision logic is useful for Ising spin computing and able to solve the combinatorial optimization problems.

In this paper, I present the impact of environmental regulation on technological innovation and competitive advantage. Previous research has verified that several aspects of environmental regulation, such as economic incentive, anticipation, stringency and certainty drive new technologies. However, such research merely pays attention to the technological innovation within each firm. How does some technological innovation diffuse within the industry and how does the firm get competitive advantage confronted with the environmental regulation? To answer this question, I use the case study strategy. The case describes the process of developing sulphur-free gasoline that reduces the CO2 emission volume developed by a major Japanese oil company. Through the case analysis, I show that technological innovation before regulation have a possibility to provide the firm high quality finished technological innovation and also provide the firm a chance of creating competitive advantage.

For the excavation of soil with a high ground water level within a cofferdam, seepage water flows through soil under a hydraulic head difference, H, between up- and downstream sides of a sheet pile wall, and seepage failure is often a problem. Seepage failure sometimes occurs even when a cofferdam has been expertly constructed based on a current design method. There still remain various shortfalls in the theory of the seepage failure of soil. In this paper, the prismatic failure concept 2D (pfc-2D) is first presented, which is one of the conventional methods for designing against seepage failure. Next, the non-dimensional formulization of the critical hydraulic head difference against seepage failure, Hc, is discussed especially in two dimensions. When the prototype (real) and model (test) soils are geometrically similar, we discuss whether or not the non-dimensional formulization for the Hc value is possible. The possibilities of the non-dimensional formulizations of the Hc values in the case of the other flow conditions of 2DC, 3D, and AXS flows are also discussed.

We compared the effects of the Airway Scope(®) on haemodynamic responses during tracheal intubation with those of direct laryngoscopy in normotensive and hypertensive patients. The systolic blood pressure, diastolic blood pressures and heart rate were recorded: (a) before anaesthesia; (b) immediately before intubation; (c) at intubation; and (d) 1, 2, 3, 4 and 5 min after intubation. In normotensive patients, the increase in blood pressure and heart rate over time were significantly lower with the Airway Scope than with the Macintosh laryngoscope (p 0.05). We conclude that the Airway Scope attenuates haemodynamic responses to tracheal intubation in comparison with the laryngoscope in normotensive but not in hypertensive patients. You can respond to this article at http://www.anaesthesiacorrespondence.com.

Patients with idiopathic Parkinson’s disease (PD) appear to have reduced capacity for detoxification of certain environmental compounds. The glutathione S-transferases (GSTs) are candidate genes for PD because they are involved in the metabolism of pesticides and cigarette smoke. We investigated the relationship of the seven GST polymorphisms ( GSTM1 deletion, GSTT1 deletion, GSTP1 rs1695, GSTO1 rs4925, GSTO1 rs11191972, GSTO2 rs156697 and GSTO2 rs2297235) and PD risk with special reference to the interaction with pesticide use or cigarette smoking among 238 patients with PD cases and 370 controls in a Japanese population. None of the GST polymorphisms were associated with PD. GSTO1 rs4925 and GSTO2 rs2297235 were found to be in strong linkage disequilibrium ( D ′ = 0.98). Cigarette smoking was significantly associated with decreased risk of PD. However, no interaction of smoking with any of the GST polymorphisms was observed. Self-reported pesticide use was not associated with increased risk of PD. There was no evidence of interaction between self-reported pesticide use and either GST polymorphism. Our results suggest that the tested GST polymorphisms did not play an important role in PD susceptibility in our Japanese population. Our study does not give evidence of interaction between the GST polymorphisms and smoking may although this study provided sufficient statistical power to detect modest interaction. As for interaction between GSTP polymorphisms and pesticide use, the power of this study to detect an interactive effect was low due to a small number of pesticide users. Future studies involving larger control and case populations and better pesticide exposure histories will undoubtedly lead to a more thorough understanding of the role of the GST polymorphisms in PD development.

長野県波田町にある有機水稲栽培歴30年以上の水田で，2003∼05年に耕耘方法の違いが水稲および雑草の生育に与える影響を検討した。稲ワラをすき込む秋耕起の有・無，有機施肥後の春耕の時期（入水0・40日前）および春耕の深度（5・15cm）の3要因について，秋耕起を一次因子とする分割区法で実験した結果，秋耕起有り・入水40日前の春耕処理で雑草重量が低下し，オモダカ（Sagittaria trifolia L.），イヌホタルイ（Scirpus hotarui Roxb. var. ohwianus T. Koyama Ohwi）およびキカシグサ（Rotala indica（Willd.）Koehne）などの小型広葉雑草が抑制傾向にあった。秋耕起で作土中の移植直後の可給態窒素含量（Av-N）が減少し，無除草条件では水稲収量が増加して，雑草の根量とクログワイ（Eleocharis kuroguwai Ohwi）の新規塊茎重量が低下した。また，入水40日前の春耕および入水前の深耕もクログワイの新規塊茎重量を減少させた。入水直前の有機施肥ではAv-Nが増大するとともに雑草と水稲の生育量がともに増加した。乾田条件の秋耕起と入水直前の有機施肥浅耕の組み合わせで，養分供給と根系発達に影響を与え，初期除草との体系で有機水田の雑草害と繁殖を抑制する可能性が認められた。

Background – Recent studies suggest that angiotensin II, a major substrate in the renin–angiotensin system, protects neurons through stimulation of its type 2 receptors. However, quite a few clinical studies of angiotensin II levels have shown their relation to disease severity in neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Aims of the study – To clarify the significance of angiotensin II in ALS. Methods – We assayed angiotensin II concentrations in cerebrospinal fluid (CSF) samples from 23 patients with ALS, nine patients with spinocerebellar degeneration (SCD) and 24 control individuals. We evaluated the disability levels of patients with ALS using the Revised ALS Functional Rating Scale (ALSFRS-R) and calculated the disease progression rate (DPR). Results – CSF angiotensin II levels were significantly lower in the ALS group compared with that in the control group (P = 0.00864), and showed a significant positive correlation with scores on the ALSFRS-R, and a significant negative correlation with the DPR. Conclusions – In the present study, we reveal for the first time that angiotensin II levels in the CSF from patients with ALS are significantly reduced and significantly associated with disease severity and progression rate. These findings suggest that reduced levels of intrathecal angiotensin II may play a role in ALS.

Proton knockout reactions on carbon isotopes p( 9–16 C,2p) 8–15 B at 250 MeV/A were performed for systematic information on weakly- to strongly-bound 1p valence protons and deeply-bound 1s inner-shell protons. Various information such as the s-hole distributions, excitation energy of the s-hole states, momentum widths for 1s and 1p orbits, and relative (p,2p) yields are obtained.

イチゴ育苗時における雨滴や頭上灌水はイチゴ炭疽病蔓延の主要因である．そこで点滴チューブによりセルトレイ上に敷いた親水性不織布に給水させ，切り口からイチゴ株元へ灌水する方法について検討した結果，本灌水法は本病に対する伝染抑制効果を認め，さらに雨よけを併用することで本病の伝染抑制効果は極めて高くなった． また，全供試株の複葉1枚に本病原菌を接種した感染株における効果を検討した結果，本灌水法と雨よけを併用すると各株の発病進展を顕著に抑制した．イチゴ株元付近の温湿度変化を調査した結果，本灌水法では温度は高い傾向であったが，湿度は明らかに低く，湿度上昇を抑制させる効果があると考えられた．

症例は51歳，男性．直腸癌で，1996年8月低位前方切除，D3郭清を行った．病理組織学的検査では，RaRb, 3型，43×42mm，中分化腺癌，SE, ly2, v1, N1, P0, H0, M0, Stage IIIaであった．術後は5'-DFURを内服していたが，1998年9月胸部CTで多発肺転移を認め，FP, UFTとPSKの内服，低用量CPT-11, 5'DFURとPSKの内服，IFL療法などを続けた．肺転移は著変なく経過した．2002年8月，脳MRIで小脳転移を認め，ガンマナイフ治療を行った．その後，小脳，大脳に新たな転移が出現し，2006年1月まで合計11回，20カ所(小脳5カ所，大脳15カ所）のガンマナイフ治療を施行したが，脳転移出現後も，明らかな神経学的異常を認めず，通常通り就労していた．しかし2006年5月，術後9年9カ月(肺転移後7年8カ月，脳転移後3年9カ月）で死亡した．多発脳転移，肺転移をともなった直腸癌に対して，ガンマナイフと化学療法により長期生存をえることができた．

We compared the Airway Scope with a gum elastic bougie and fibreoptic bronchoscope in a manikin with a simulated Cormack and Lehane Grade 3 laryngoscopic view. Twenty-seven anaesthetists intubated the trachea of the manikin with these devices and the time required for intubation was measured. They were then asked to rate the subjective difficulty of intubation (1 = very easy; 5 = very difficult). Mean (SD) intubation times were 16.6 (11.2) s with the Airway Scope, 29.4 (10.9) s with the gum elastic bougie (p < 0.0001), and 30.6 (20.0) s with the fibreoptic bronchoscope (p < 0.0001). The median (range) difficulty was 2 (1-4) with the Airway Scope, 3 (2-4) with the gum elastic bougie (p < 0.001), and 2 (1-5) with the fibreoptic bronchoscope (p = 0.014). In Cormack and Lehane grade 3 laryngoscopic views, the Airway Scope may enable faster and easier tracheal intubation than does a Macintosh laryngoscope with a gum elastic bougie or a fibreoptic bronchoscope.

症例は63歳の女性. 左鎖骨上窩の腫瘤を自覚して来院した. 生検で腺癌のリンパ節転移であった. さらに全身を検索するとS状結腸に2型の癌を認め, Virchowリンパ節転移と判明した. さらに肝転移も認めた. 手術はS状結腸切除, D3郭清を行った. 病理組織学的所見は, 中分化腺癌, SS, N2, P0, H1, M1 (Virchowリンパ節No. 216), Stage IVであった. 術後5'-DFUR 600mg/dayの経口投与と週1回のCPT-11 60mgの点滴静注を開始した. 2カ月後にVirchowリンパ節転移とともにCTで肝転移の消失も確認した. しかし, その後, 術後3年11カ月目に左腋窩リンパ節を触知した. 全身精査で他に転移を認めなかったため, 左腋窩腫瘍摘出術を行った. 病理組織学的所見はS状結腸癌のリンパ節転移であった. 現在, 初回手術後5年4カ月経過し再発なく健存中である. 遠隔転移, 肝転移をともなった大腸癌に対して, 積極的な手術と化学療法により長期生存を得ている稀な症例を経験した.

Alanine:glyoxylate aminotransferase 2 (AGXT2; EC 2.6.1.44) degrades asymmetric dimethylarginine (ADMA), a competitive inhibitor of nitric oxide (NO) synthase. Increased ADMA, reduced NO, and hypertension are shown in Agxt2 knockout mice. There are four single nucleotide polymorphisms (rs37370, rs37369, rs180749, and rs16899974) with which AGXT2 activity changes in humans and may be related to vulnerability of vascular sclerosis. To examine the relationship between them, we studied the functional haplotypes of the AGXT2 gene and decided their relationship with arteriosclerotic changes via carotid intima-media thickness (carotid IMT) in Japanese subjects. Genotyping of those polymorphisms and the carotid IMT in 1,426 Japanese subjects were then evaluated. Subjects with C-A-A-A haplotype (rs37370, rs37369, rs180749, rs16899974) showed low AGXT2 activity (P0.0001; Pearson’s correlation coefficients: 0.497). The C-A-A-A haplotype was significantly associated with mean carotid IMT (P=0.049) and max carotid IMT (P=0.004). Subjects with two C-A-A-A haplotypes exhibited thicker mean carotid IMT (P=0.022) and maximum carotid IMT (P=0.001). In multiple regression analysis, subjects with two C-A-A-A haplotypes were independently and positively associated with mean carotid IMT (P=0.02) and maximum IMT (P=0.005) after correction. There was a significant correlation between the functional variants in the AGXT2 gene and carotid IMT in Japanese. The AGXT2 genotype may be an important factor underlying atherosclerosis.

The aim of the present study was to evaluate the relationship between motorcycling and erectile dysfunction (ED). We investigated the relationship between motorcycling and erectile function using the 5-items version of the International Index of Erectile Function (IIEF5) in 234 motorcyclists (response rate 75%) and 752 healthy controls (response rate 66%). In all, 161 (69%) of 234 motorcyclists were diagnosed as ED based on IIEF5. The prevalence of ED in the motorcycle group increased by age as: 58, 63, 76 and 93%, for motorcyclists in 20-29, 30-39, 40-49 and 50-59 years, respectively. There was a significant difference in the prevalence of ED between the motorcycle group and the control group in all age groups. On stepwise logistic regression analysis, motorcycling was the strongest risk factor for ED. Although the severity of ED in motorcyclists was not so severe, motorcycling may be one of risk factors for ED.

Sildenafil is most effective in men with mild-to-moderate ED, but not severe ED in Japan. In order to evaluate the efficacy of sildenafil, we conducted the present study using the AVSS test by the RigiScan Plus. The subjects were 56 patients (age: 34-82 years, mean: 60.5 years) with ED. The IIEF5 questionnaire and the AVSS test were conducted before and after administration of sildenafil. The penile rigidity could not be measured in 19 patients. Of these 19, sildenafil was effective in 7 and not effective in 12. The 7 cases in whom sildenafil was effective were all false-negatives. The sensitivity of sildenafil was 84%, and its specificity was 100%. This study suggests that the AVSS test by RigiScan Plus can objectively evaluate the efficacy of sildenafil, and shows potential for predicting that efficacy.

A 52-year-old woman with diabetes mellitus (DM) complained of weakness of the arms and legs. She was referred to our hospital in November 2002 because of anemia, thyroid tumor and meningioma including DM. She was short in stature, juvenile bilateral cataract, intractable skin ulcers, clavus on the sole of her foot, a bird-like face and high-pitched voice. Typical physical features led to the final diagnosis of Werner's syndrome. Although the myelogram revealed no abnormal findings except erythroid hypoplasia, cytogenetic analysis of bone marrow cells showed deletion of chromosome 20 in 10% of the analyzed cells, which suggested the possibility of that myelodysplastic syndrome (MDS) or acute myeloblastic leukemia (AML) could occur. She had a thyroidectomy because both lobes of the thyroid gland were enlarged and caused hoarseness, In addition, it is common knowledge that the goiter could become malignant. We need to follow her carefully because she might be vulnerable to malignant disease, including leukemia and malignant meningioma.

The Rho activator ECT2 functions as a key regulator in cytokinesis. ECT2 is phosphorylated during G2/M phase, but the physiological significance of this event is not well known. In this study, we show that phosphorylation of ECT2 at threonine-341 (T341) affects the autoregulatory mechanism of ECT2. In G2/M phase, ECT2 was phosphorylated at T341 most likely by Cyclin B/Cyclin-dependent kinase 1 (Cdk1), and then dephosphorylated before cytokinesis. Depletion of ECT2 by RNA interference (RNAi) efficiently induced multinucleate cells. Expression of the phospho-deficient mutant of ECT2 at T341 suppressed the multinucleation induced by RNAi to ECT2, indicating that ECT2 is biologically active even when it is not phosphorylated at T341. However, the phospho-mimic mutation at T341 weakly stimulates the catalytic activity of ECT2 as detected by serum response element reporter gene assays. As T341 is located at the hinge region of the N-terminal regulatory domain and C-terminal catalytic domain, phosphorylation of T341 may help accessing downstream signaling molecules to further activate ECT2. We found that the phospho-mimic mutation T341D increases binding with itself or the N-terminal half of ECT2. These results suggest a conformational change of ECT2 upon phosphorylation at T341. Therefore, ECT2 activity might be regulated by the phosphorylation status of T341. We propose that T341 phosphorylation by Cyclin B/Cdk1 could be a trigger for further activation of ECT2.

We report a 34-year-old man with the complication of chylous ascites after retroperitoneal lymphadenectomy that was refractory to various conservative therapies. Because surgical treatment for chylous ascites was considered, lymphangiography was performed to identify the area of leakage of chyle, after which the chylous ascites spontaneously healed.

A one-transistor one-capacitor (1T1C) SBT-based embedded nonvolatile FeRAM, which operates at a low voltage of 0.9 V even after 10 years of imprint degradation, was fabricated using a 0.18-/spl mu/m process. The low voltage operation and high reliability characteristics have been achieved using a novel reference voltage scheme and a multilayer shielded bit-line structure.

With the rapid aging of Japan's population, medical professionals who specialize in geriatric medicine are in unprecedented demand. At Ehime University School of Medicine, the Department of Geriatric Medicine was established on April 1,1997. To assess the status of geriatric medicine in undergraduate education, we surveyed the opinions of medical students on geriatric medicine. A questionnaire was sent to both fourth-year medical students before their classes on internal medicine and geriatric medicine had ended and to sixth-year medical students after their classes had already ended. Medical students of Ehime University School of Medicine had significantly more interest in geriatric medicine than students at other medical schools. From a clinical viewpoint of problems in old age, they considered that cerebrovascular disease, cardiovascular disorders, neurocognitive disorders and pulmonary disease were important. A total of 60% agreed that all medical schools should have classes in geriatric medicine, which is a higher rate than that of previous reports. To study the opinions of medical students on textbooks on geriatrics, we also conducted a questionnaire among medical students. Although 90% of students had their own textbooks of internal medicine and almost half (42%) had textbooks on physical examination, none had their own textbook of geriatric medicine. The most frequent reason was "hard to choose the best textbook". The present study indicates that to develop education in geriatric medicine, it is important to make a recommendable text book for medical students, which is easily understood with high quality and originality.

A 68-year-old male, married, retired public official was admitted to hospital for thorough examination and appropriate treatment of gait disturbance and dizziness. He had been diagnosed with diabetes mellitus and hypertension for at least 28 years, and had been treated with insulin and antihypertensive medications intermittently at another hospital. We identified the major cause of his complaints as orthostatic hypotension, and controlled his casual systolic blood pressure (BP) to within the range of 140–160 mmHg in a sitting position. After a few weeks, on ophthalmic study, right papilledema was diagnosed. There was no progression of visual disturbance nor circulatory impairment in the optic fundi. Based on the results of 24-h ambulatory BP monitoring, we assumed that his supine systolic hypertension triggered the papilledema, so we controlled his supine systolic BP to within the range of approximately 140–160 mmHg. After 2 weeks of controlled BP the papilledema improved. Visual disturbance was not reported during 1 year of follow up. In case of severe autonomic disorder such as orthostatic hypotension, attention should be paid to changes in the optic fundi, and ophthalmoscopic examination should be performed regularly.

Erectile dysfunction (ED) is a common complication of diabetes mellitus. Erythrocyte aldose reductase (AR) has been implicated in a variety of diabetic complications. The subjects were 62 diabetic patients, of whom 25 were treated with hemodialysis (chronic renal failure CRF group) and the remaining 37 did not have chronic renal failure (DM group). The controls were 20 healthy volunteers age-matched to the patients. The level of AR was measured by the quantitative determination kit for AR in all patients and controls. In this study, ED was diagnosed by 5-item version of the International Index of Erectile Function (IIEF-5). The average level of AR in the CRF group was significantly higher than that in the DM group and controls (P

There has been considerable interest in using safeguarded needles to reduce needlestick injury. In a randomised design, we studied the efficacy and safety of two such needles (the Insyte AutoGuard and the Protective Acuvance), by comparing them with a conventional catheter needle (Insyte), for intravenous cannulation (18 G) in 150 patients and for intra-arterial cannulation in another 150 patients (20 G). For intravenous cannulation, the success rates were similar in the three groups but insertion of the AutoGuard or Acuvance catheter was significantly more difficult than the conventional catheter. For the Acuvance, the back-flow of blood into the chamber was sometimes too slow. For intra-arterial cannulation, insertion of the AutoGuard was significantly more difficult than the other two devices, mainly because the backflow chamber of the AutoGuard was too short so that the chamber often filled with blood before cannulation. Insertion of the Acuvance was significantly more difficult than the conventional catheter. For both intravenous and intra-arterial insertion, handling of the withdrawn needle was judged significantly safer in the AutoGuard group than the other two groups, whereas there was no significant difference in the safety between the Acuvance and conventional groups. In five subjects from the AutoGuard group, blood splashed on retraction of the needle. Blood contamination during needle withdrawal occurred frequently in the control and Acuvance groups, but rarely occurred in the AutoGuard group. Therefore, the AutoGuard needle is more suitable for intravenous cannulation, and the Acuvance is more suitable for intra-arterial cannulation.