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Proteinuria is a marker for cardiovascular diseases and all-cause mortality. In the Specific Health Checkups in Japan, when subjects show trace proteinuria (grade±) on dipstick assay, further examination is recommended to them. Although 150 mg/gCr is a threshold for diagnosing chronic kidney disease (CKD), little data on the relationship between dipstick grade± and the protein-creatinine ratio have been reported.A cross-sectional study using urine specimens obtained in a single institute, JCHO Saitama Northern Medical Center, was performed from October 2014 to March 2016. The level of proteinuria was measured in fresh morning urine samples from 819 volunteer participants of the Specific Health Checkups by two methods: Eiken Uropaper III to detect and qualitatively grade proteinuria, and total protein concentration by the pyrogallol red method.Sensitivity, specificity, and the positive likelihood ratio to detect proteinuria of 30 mg/dL by 1+ were 90.3%, 97.8%, and 41.9, whereas 150 mg/gCr by ± were 45.3%, 81.4%, and 2.4, respectively. Therefore, screening for 150 mg/gCr by dipstick grade± had a false-negative rate of 54.7% and false-negative rate was significantly higher in women (8.0%) than in men (1.7%) (p0.0001).Although the dipstick assay is useful to detect clinically significant proteinuria, substantial numbers of false-negative results occur in checkups for identifying subjects with a risk of CKD.

C–C chemokine receptor 1 (CCR1) and CCR5 are involved in various inflammation and immune responses, and regulate the progression of the autoimmune diseases differently. However, the number of residues identified at the binding interface was not sufficient to clarify the differences in the CCR1- and CCR5-binding modes to MIP-1α, because the NMR measurement time for CCR1 and CCR5 samples was limited to 24 h, due to their low stability. Here we applied a recently developed NMR spectra reconstruction method, Conservation of experimental data in ANAlysis of FOuRier, to the amide-directed transferred cross-saturation experiments of chemokine receptors, CCR1 and CCR5, embedded in lipid bilayers of the reconstituted high density lipoprotein, and MIP-1α. Our experiments revealed that the residues on the N-loop and β-sheets of MIP-1α are close to both CCR1 and CCR5, and those in the C-terminal helix region are close to CCR5. These results suggest that the genetic influence of the single nucleotide polymorphisms of MIP-1α that accompany substitution of residues in the C-terminal helix region, E57 and V63, would provide clues toward elucidating how the CCR5–MIP-1α interaction affects the progress of autoimmune diseases. Electronic supplementary material The online version of this article (doi:10.1007/s10858-015-9992-x) contains supplementary material, which is available to authorized users.

Summary Hepatocellular carcinoma (HCC) is a common cancer worldwide and represents the outcome of the natural history of chronic liver disease. The growing rates of HCC may be partially attributable to increased numbers of people with non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH). However, details of the liver‐specific molecular mechanisms responsible for the NAFLD–NASH–HCC progression remain unclear, and mouse models that can be used to explore the exact factors that influence the progression of NAFLD/NASH to the more chronic stages of liver disease and subsequent HCC are not yet fully established. We have previously reported a choline‐deficient, L‐amino acid‐defined, high‐fat diet (CDAHFD) as a dietary NASH model with rapidly progressive liver fibrosis in mice. The current study in C57BL/6J mice fed CDAHFD provided evidence for the chronic persistence of advanced hepatic fibrosis in NASH and disease progression towards HCC in a period of 36 weeks. When mice fed CDAHFD were switched back to a standard diet, hepatic steatosis was normalized and NAFLD activity score improved, but HCC incidence increased and the phenotype of fibrosis‐associated HCC development was observed. Moreover, when mice continued to be fed CDAHFD for 60 weeks, HCC further developed without severe body weight loss or carcinogenesis in other organs. The autochthonous tumours showed a variety of histological features and architectural patterns including trabecular, pseudoglandular and solid growth. The CDAHFD mouse model might be a useful tool for studying the development of HCC from NAFLD/NASH, and potentially useful for better understanding pathological changes during hepatocarcinogenesis.

We investigated MOVPE growth conditions to grow large-area and thick single crystal CdTe layers with uniform material properties directly on (211) Si substrates to develop nuclear radiation detectors. We found that group VI/II precursor flow-ratio as well as rapid thermal annealing performed by interrupting the growth at the initial stage has marked influence on the crystal quality. By using a VI/II precursor ratio of 3.0, and a 900 °C anneal performed in flowing hydrogen, we were able to achieve 1-sq inch sized thick single crystal CdTe that showed uniform material properties and high crystal quality throughout the wafer. We further demonstrated that the grown crystals were suitable for fabricating nuclear radiation detector. (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Implantable cardioverter defibrillators (ICDs) are now being used in children. ICDs can be used to prevent sudden cardiac death caused by not only congenital heart defects, but also various non-structural diseases, such as long QT syndrome. However, a standard implantation technique for children, especially infants, has not yet been established. As the surgical implantation in infants is not amenable to transvenous lead placement, it was necessary to choose from epicardial, subcutaneous and pericardial ICD systems. However, many of these systems are associated with high rates of late complications. Lead fracture, insulation breakage, migration, buckling or crinkling of the patch lead and constrictive pericarditis have been reported as the most common lead-related complications. An increase in the defibrillation threshold is another issue that must be considered when using an ICD in a child or infant. Further studies on the outcomes, psychosomatic impact and other specific complications in the pediatric population need to be considered. The clinical use of ICDs in infants is still limited. Therefore, it is important to have many surgical options available so that the treatment can be custom-tailored to suit individual patients.

Non-alcoholic steatohepatitis (NASH) is a progressive fibrotic disease, the pathogenesis of which has not been fully elucidated. One of the most common models used in NASH research is a nutritional model where NASH is induced by feeding a diet deficient in both methionine and choline. However, the dietary methionine-/choline-deficient model in mice can cause severe weight loss and liver atrophy, which are not characteristics of NASH seen in human patients. Exclusive, long-term feeding with a high-fat diet (HFD) produced fatty liver and obesity in mice, but the HFD for several months did not affect fibrosis. We aimed to establish a mouse model of NASH with fibrosis by optimizing the methionine content in the HFD. Male mice were fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) consisting of 60 kcal% fat and 0.1% methionine by weight. After 1-14 weeks of being fed CDAHFD, the mice were killed. C57BL/6J mice maintained or gained weight when fed CDAHFD, while A/J mice showed a steady decline in body weight (of up to 20% of initial weight). In both strains of mice, plasma levels of alanine aminotransferase increased from week 1, when hepatic steatosis was also observed. By week 6, C57BL/6J mice had developed enlarged fatty liver with fibrosis as assessed by Masson's trichrome staining and by hydroxyproline assay. Therefore, this improved CDAHFD model may be a mouse model of rapidly progressive liver fibrosis and be potentially useful for better understanding human NASH disease and in the development of efficient therapies for this condition.

In the photosynthetic light reactions of plants and cyanobacteria, plastocyanin (Pc) plays a crucial role as an electron carrier and shuttle protein between two membrane protein complexes: cytochrome b 6 f (cyt b 6 f ) and photosystem I (PSI). The rapid turnover of Pc between cyt b 6 f and PSI enables the efficient use of light energy. In the Pc-cyt b 6 f and Pc-PSI electron transfer complexes, the electron transfer reactions are accomplished within −4 s. However, the mechanisms enabling the rapid association and dissociation of Pc are still unclear because of the lack of an appropriate method to study huge complexes with short lifetimes. Here, using the transferred cross-saturation method, we investigated the residues of spinach ( Spinacia oleracea ) Pc in close proximity to spinach PSI and cyt b 6 f , in both the thylakoid vesicle–embedded and solubilized states. We demonstrated that the hydrophobic patch residues of Pc are in close proximity to PSI and cyt b 6 f , whereas the acidic patch residues of Pc do not form stable salt bridges with either PSI or cyt b 6 f , in the electron transfer complexes. The transient characteristics of the interactions on the acidic patch facilitate the rapid association and dissociation of Pc.

The Phox homology (PX) domain is a functional module that targets membranes through specific interactions with phosphoinositides. The p47(phox) PX domain preferably binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P(2)) and plays a pivotal role in the assembly of phagocyte NADPH oxidase. We describe the PI(3,4)P(2) binding mode of the p47(phox) PX domain as identified by a transferred cross-saturation experiment. The identified PI(3,4)P(2)-binding site, which includes the residues of helices α1 and α1' and the following loop up to the distorted left-handed PP(II) helix, is located at a unique position, as compared with the phosphoinositide-binding sites of all other PX domains characterized thus far. Mutational analyses corroborated the results of the transferred cross-saturation experiments. Moreover, experiments with intact cells demonstrated the importance of this unique binding site for the function of the NADPH oxidase. The low affinity and selectivity of the atypical phosphoinositide-binding site on the p47(phox) PX domain suggest that different types of phosphoinositides sequentially bind to the p47(phox) PX domain, allowing the regulation of the multiple events that characterize the assembly and activation of phagocyte NADPH oxidase.

Purpose : There is no clear consensus on how to treat patients undergoing coronary artery bypass grafting (CABG) who have severe concomitant carotidcerebral artery stenosis. The aim of this study was to evaluate our surgical results in patients with severe carotid and/or cerebrovascular disease undergoing CABG. Methods :Between October 2003 and April 2009, a total of 47 such patients were treated at our institution with the following strategies: (1) protective carotid artery stenting for severe carotid stenosis performed either before (n = 20) or after (n = 5) CABG or (2) a superficial temporal artery-middle cerebral artery anastomosis procedure followed by CABG if indicated (n = 4). Off-pump CABG was performed in 75% of the patients. Results. There were no major perioperative strokes or in-hospital deaths; however, three patients had transient ischemic attacks and two had minor strokes during the early post-CABG period. All of the patients with postoperative cerebrovascular events had had unilateral carotid artery occlusion. There were no late deaths during the follow-up period (up to 6 years, with a mean of 27 months). However, major adverse cardiocerebrovascular events (MACCE) occurred in seven patients (14.9%). The rates of freedom from MACCE at 1 and 3 years were 92% and 74%, respectively. Conclusion :It appears that our two-staged approach is safe and may reduce the risk of postoperative cerebrovascular events.

It has been reported that surgical treatment for prosthetic valve endocarditis complicated by destruction of the aortic annulus is associated with high mortality and morbidity. The aim of this study was to evaluate the efficacy of our surgical strategy for this situation.Between October 2003 and April 2009, eight patients (mean age 68.6 years) with prosthetic valve endocarditis complicated by destruction of the aortic annulus were surgically treated at our hospital. We use a relatively simple procedure consisting of a patch plasty of the abscess cavity in addition to complete removal of the infected tissue of the abscess cavity followed by standard aortic valve replacement. All patients had active endocarditis and were in New York Heart Association functional class III or IV. Preoperative echocardiography revealed that four patients had moderate or severe aortic regurgitation, and two had mitral valve endocarditis as well.There were no operative deaths (≤30 days). Cardiac complications included paroxysmal atrial fibrillation in three patients and transient atrioventricular block in one. One patient died of multiple organ failure 66 days after the surgery. The overall in-hospital mortality was 12.5%. Patients were followed-up for 6-49 months (mean 31 months). There was no recurrent prosthetic valve endocarditis. One patient required reoperation (mitral annuloplasty and redo aortic valve replacement). There were two late deaths: lung cancer in one and multiple organ failure related to pneumonia after the aforementioned redo operation in the other.Our simple procedure for complicated prosthetic valve endocarditis yielded excellent early and midterm outcomes.

患児は9歳，男児．上気道炎で近医経過観察中，39度台の発熱が遷延し，左側胸水貯留を認めるようになり紹介された．多房性の膿胸を呈しており胸腔ドレーンを留置したが症状の改善は得られず，小開胸を用いた胸腔鏡補助下胸腔内掻爬ドレナージ術を施行した．胸腔内は胸膜の癒着が著しく，癒着の間に多房性の胸水が少量づつ貯留していた．肺は胼胝で覆われ拡張できなくなっていた．鈍的に癒着を剥離したのち，可及的に胼胝を切除した．胸腔内を充分洗浄しドレーンを留置した．小児においては，膿胸の進行が急速であること，体格上，充分な太さの胸腔ドレーンを留置できないことから，早期にドレナージ不良となることが予想され，ドレナージが効かなくなった段階ですみやかに手術療法を考慮すべきである．手術においては，小開胸を用いた，胸腔鏡補助下胸腔内掻爬ドレナージ術が有用であった．

Video-assisted thoracoscopic surgery is a type of minimal-access surgery. The nature of the surgery means that there are limitations on the size of a tumor that can be removed through an access incision. Herein, we report our experience removing a giant teratoma (16 × 14 × 13 cm in size) from the anterior mediastinum of a young girl. We employed video-assisted thoracoscopic surgery to remove the teratoma through a mini-thoracotomy following the extraction of the cystic components.

Large molecules, such as membrane proteins, play crucial roles in various biologically important events. We have developed the transferred cross-saturation (TCS) method, which enables the identification of the contact residues of protein ligands in large complexes. However, rational optimization of the experimental conditions for the TCS method has been hampered by the lack of information about the influence of each experimental parameter on the observed TCS effects. Here, we established the theoretical description of the TCS method, which explicitly incorporated the isotopomers in the sample solution, and developed the computer software to perform numerical simulations. Using them, we analyzed the effects of each experimental parameter on the observed TCS effects by the simulations. The simulation studies indicated that: (i) the proton concentration in the solvent should be 10–30%, (ii) a larger p b , which is the bound fraction of the ligand, is preferred for higher saturation efficiency, (iii) the TCS method is applicable to systems where k off > 0.1 s −1 , (iv) for k off ≥ 10 s −1 , p b ≥ 0.1 is preferred, (v) for k off ∼ 1 s −1 , p b ≥ 0.5 is preferred, and (vi) the TCS method is applicable to systems with large τ c (∼1 μs), where p b is ∼0.01. The assumptions in the model spin simulation were experimentally verified, using the ubiquitin–YUH1 interaction. The established method will be useful for estimating and optimizing the TCS experimental conditions.

Prenatal diagnosis of genetic disease in Japan today, as of the end of 1978, and results of a follow-up study of infants born after genetic amniocentesis are reported. Of the 585 amniocentesis in 523 women, 568 cases contributed data for the results of their analysis. A previous history of pregnancy with Down's syndrome was a major indication in these 585 cases (59.5%); other indications included advanced maternal age 69 cases (11.8%), and metabolic disorder 56 cases (9.6%). Fetal loss occurred in a total 12 out of 542 cases (2.2%). Ten of these fetal losses occurred during the mid-trimester. No increase in perinatal mortality, perinatal morbidity or retardation of physical and mental development as a consequence of amniocentesis was observed. Erroneous diagnosis was attested in 7 out of 568 cases (1.2%). Test accuracy was thus demonstrated at 98.8%.

To study effect of amniotic fluid volume on umbilical cord length, 939 pregnant women at 24-41 weeks of gestation, including 10 twin cases, 51 preterm premature rupture of the membranes (PROM) and 70 premature delivery cases, were examined for their amniotic fluid volume within a week of delivery by the ultrasound procedure and these 949 newborns were also examined for umbilical cord length and incidence of fetal distress. In the polyhydramnios group (pocket size of more than 8 cm), 8 of 20 infants (40%) had longer cords and 6 infants (30%) had shorter cords, while only one of 49 infants (2%) with oligohydramnios (pocket size of less than 2 cm) had a longer cord and 36 infants (73.5%) had shorter cords than the mean cord length (+/- SD) of the normal group. The 20 twins had significantly shorter cords than those of the normal group (P less than 0.05) and the polyhydramnios group (P less than 0.01). The PROM group showed significantly higher incidence of oligohydramnios (P less than 0.05) and fetal distress (P less than 0.01), which suggests that intrauterine space availability is important for assuring fetal well-being.

75歳，男性．検診の胸部レントゲンで異常陰影を指摘され，精査にて右第3肋骨を主座とした最大径7cmの肋骨腫瘍と診断され当科紹介受診となった．画像上，軟骨肉腫や血管腫などが疑われ，FDG-PETで集積を認めたため，悪性の肋骨腫瘍を疑い切除を施行した．手術は後側方切開で行い，腫瘍および第3/4肋骨後方を含めて胸壁切除を施行した．病理診断は海綿状血管腫で，悪性所見は認められなかった．原発性骨腫瘍のうち約3割は悪性腫瘍であり，骨血管腫は約0.7％と比較的少なく，さらに肋骨原発の海綿状血管腫の報告はまれである．本症例では悪性所見の有無を確認するためFDG-PETを施行し集積を認めたが，結果的に良性腫瘍との診断を得た．海綿状血管腫では内部に出血と炎症を繰り返すとされ，そのために集積を認めたと考えられた．画像的に悪性疾患，特に肉腫が否定できない場合，術前の生検には慎重にならざるを得ない場合がある．

4本の異常動脈を有し奇静脈に還流する肺葉内肺分画症に対して胸腔鏡下分画肺切除を施行した症例を報告する．【症例】17歳，男性．胸部異常陰影を契機に左肺下葉の肺葉内肺分画症と診断され，胸腔鏡下に分画肺切除術を施行した．術後3年現在，合併症なく経過している．【考察】肺分画症に対しては，MDCTで分画肺の局在とともに流入動脈と流出静脈を確認して，分画肺を含む肺葉切除や区域切除が施行されることが多い．本症例では術前に確認できなかった異常血管を含めて安全に血管処理を行え，さらに正常肺のほとんどが温存できた．肺分画症治療においては，MDCTで描出されない脈管の可能性を意識して治療に臨む必要がある．

Paroxysmal nocturnal hemoglobinuria is a rare acquired autoimmune disease, and is frequently associated with venous thrombosis. A patient who developed thrombotic occlusion of the inferior vena cava is described. Treatment with heparin and urokinase, followed by oral anticoagulant, was effective in resolving abdominal symptoms. The venous thrombosis resolved completely, but the patient died during treatment of aplastic anemia.

ObjectiveIntervention therapy has been recently performed on the left internal thoracic artery graft stenosis. The purpose of this study was to evaluate the natural course of the left internal thoracic artery graft stenosis at the anastomotic site and clarify whether intervention therapy should be performed early after surgery.MethodsWe investigated early angiographic results of the left internal thoracic artery graft in 343 consecutive patients who underwent coronary bypass surgery. In 100 of 343 patients who underwent follow-up angiography, the graft diameter and percentage diameter stenosis at the anastomotic site were compared between early postoperative and follow-up angiography. None of these patients underwent intervention therapy on the left internal thoracic artery graft.ResultsOf 343 patients, 46 showed 50% or greater diameter stenosis, and 20 showed 70% or greater diameter stenosis at the anastomotic site. In the 100 patients with follow-up angiography, the graft diameter significantly increased (1.8 ± 0.4 vs 2.1 ± 0.5 mm, P < .0001) at follow-up angiography. The percentage diameter stenosis significantly decreased (69% ± 13% vs 35% ± 20%, P < .0001) at follow-up angiography in the patients with 50% or greater diameter stenosis at early postoperative angiography. Regression of left internal thoracic artery graft stenosis was detected in most patients with 70% or greater diameter stenosis.ConclusionsOur study demonstrated that left internal thoracic artery graft stenosis at the anastomotic site at early postoperative angiography might improve without intervention therapy. We should consider the natural course of the left internal thoracic artery graft stenosis in determining the indication of intervention therapy early after surgery.

目的. 上葉発生肺癌におけるリンパ節転移様式を評価し, 選択的縦隔リンパ節郭清の妥当性につき検討した. 方法. 1986年から2003年までに当院にて切除された原発性肺癌症例中, 肺門・縦隔リンパ節郭清 (ND2a) が施行された上葉発生肺癌で縦隔リンパ節転移陽性であった44症例を対象とし, リンパ節転移様式を調査した. 結果. 右上葉発生14症例のうち上縦隔領域リンパ節転移は12例に認められ, 下縦隔領域への転移は4例に認められた. スキップ転移は1例で, 上縦隔領域リンパ節への転移であり, 下縦隔領域へのスキップ転移はなかった. 左上葉に関して, 上区発生肺癌 (22症例) では上縦隔・大動脈領域リンパ節転移は21例に認められ, 下縦隔領域リンパ節転移は2例に認められた. スキップ転移は9例に認められ, いずれも大動脈領域への転移であった. 舌区発生肺癌 (8症例) では上縦隔・大動脈領域リンパ節転移は5例に認められ, 下縦隔領域へは7例に認められた. スキップ転移は1例に認められ, multiple stationとして上縦隔・下縦隔領域へ転移を認めていた. 結論. 右上葉および左上葉上区発生肺癌はそのリンパ節転移様式から, 肺門および上縦隔領域リンパ節が術中迅速病理診断にて転移陰性であれば, 下縦隔領域リンパ節郭清を省略できる可能性が示唆された.

Background Bronchioloalveolar carcinoma (BAC) of the lung is a subtype of adenocarcinoma for which the incidence is actually rising, but the histologic definition of BAC has been recently changed by the revised World Health Organization (WHO) classification in 1999. The clinical features of patients with BAC diagnosed according to the recently revised WHO classification have not yet been clarified. In this retrospective study, we investigated the pattern of recurrence and survival outcome for patients with resected BAC by pathology review, compared with those in patients who had adenocarcinoma other than BAC. Methods From 1985 through 2002, 108 patients underwent surgical resection for pulmonary adenocarcinoma 3 cm or less in diameter at the University of Yamanashi, Japan. All of the resected specimens of these 108 patients were pathologically reviewed again to confirm the diagnosis as BAC or adenocarcinoma other than BAC. The tumor was defined as BAC when the adenocarcinoma lesion had a pure bronchioloalveolar growth pattern and no evidence of stromal, vascular, or pleural invasion according to the WHO classification (third edition). Results Twenty-five patients (23%) had a diagnosis of BAC, and 83 (77%) had a diagnosis of other adenocarcinoma. There was a female predominance among both patients with BAC and those with other adenocarcinoma. Lymph node involvement was seen for 30 lesions (36%) of adenocarcinoma other than BAC, but not for any BAC lesions. The median duration of follow-up after surgery was 5.1 years. There was no recurrence in the postoperative course in patients with BAC for a 5-year disease-free survival rate of 100%, whereas the 5-year disease-free survival rate for other adenocarcinoma was 63.5%. Conclusions The patients with resected BAC, which is defined as a noninvasive adenocarcinoma by the revised WHO classification, had an excellent prognosis. However, these results may depend on a strictly accurate pathology diagnosis as BAC. Limited resection might be curative in patients with focal BAC based on evidence of pathologic noninvasive features.

A concise and efficient synthetic approach to 2 alpha-(omega-hydroxyalkoxy)-1 alpha,25-dihydroxyvitamin D(3) (4a-c), including 2-epi-ED-71, was developed starting from D-glucose as a chiral template for the construction of the 2 alpha-modified A-ring precursors (11a-c). It was found that the best ligand for the bovine thymus vitamin D receptor (VDR) in this series is 4b, which has 1.8 times greater binding affinity for the bovine thymus VDR than that of the natural hormone 1. Interestingly, potency in the induction of HL-60 cell differentiation for 4a-c was almost the same or weaker than that of 1 despite the strong binding affinity for the VDR. Next, we were interested in the "double modification"of 1 based on 4a-c with C20-epimerization, affording 2 alpha-(omega-hydroxyalkoxy)-20-epi-1 alpha,25-dihydroxyvitamin D(3) (20-epi-4a-c). All three 2 alpha-substituted 20-epi analogues of 1 (20-epi-4a-c) exhibited stronger binding affinities for the VDR, and their conformations in the ligand binding domain of VDR were analyzed by molecular modeling. Double-modified analogues of 20-epi-4a-c showed marked HL-60 cell differentiation activity, and 20-epi-4a possesses an activity 58-fold higher than that of the natural hormone 1.

In the Western World ischemic coronary disease is the leading cause of morbidity and mortality. Therapeutic approaches mostly aim to restore flow to a localized segment by angioplasty or bypass surgery. Therapeutic angiogenesis and or arteriogenesis describes a strategy where blood vessel formation is induced for the purposes of treating and/or preventing ischemic disease. At present, at least 17 clinical trials of myocardial angiogenesis have been presented involving over 900 patients. Therapeutic angiogenesis makes use of the administration of angiogenic growth factor protein or gene to promote the development of endogenous collateral vessels in ischemic myocardium. Most recently, interest has grown in the potential angiogenesis effects of cell therapy--such as autologous bone marrow cells or cultured stem cells--and there are now several groups initiating phase I/II trials in this area.

症例は73歳男性.AFP産生胃癌と大腸癌の重複癌術後に, 肝転移と両側肺転移を来たした.肝部分切除後, 全身状態良好で肺以外に転移を認めなかったため, 2回にわたり, 肺部分切除術を施行した.切除肺の病理標本でAFP染色が陽性であり, 胃癌の肺転移が証明された.肺転移切除後, 高値であったAFP, CEAは低下した.胃癌の肺転移は一般に癌性リンパ管症の形が多く, 腫瘤影を認めるものは稀であり, また肺転移を病理学的に証明することは比較的困難であるが, 本症例においてはAFP産生胃癌であったためにそれを証明することができた.

動注化学療法は一般的となり成績も良好となっているが,致死率の高い合併症もみられる.今回われわれは,動注用ポート感染に対して血行再建を先行した後にポートを摘除し救命できた1例を経験したので報告する.症例は60歳,男性,直腸癌術後肝転移に対して右総大腿動脈より肝動脈にカテーテルを挿入,ポートを右鼠径部に留置した.最近1年間は使用していなかったが,発熱および右鼠径部の発赤・疼痛などを認めるようになったため当科に紹介となった.ポート感染の診断で緊急手術を行った.左大伏在静脈を用いて感染巣を避けるルートで右外腸骨一浅大腿動脈バイパスを行い,創を閉鎖してから感染ポートを摘除した.総大腿動脈は2重結紮の後に切離し,さらに右外腸骨動脈をバイパスの中枢側吻合部末梢で結紮した.その後肝・脾膿瘍,肝動脈瘤を合併したが,保存的治療にて改善し術後40病日に退院となった.

目的.肺癌診療における予後予想因子として, リンパ節への転移状況は大きなウエートを占める. リンパ行性転移に対する研究及び転移リンパ節に対する治療の研究に焦点を合わせたより有用な実験動物モデルの開発を試みた. 方法. 雄ヌードラットを使用し, 放射線照射後にヒト肺扁平上皮癌細胞RERF-LC-AIを足背部に皮下注射した. 鼠径部に腫瘤が触知出来た時点で転移有りと判断した. その2週間後にラットを屠殺し, 膝窩部及び鼠径部リンパ節への転移について組織学的に検討した. 結果. 触診にて転移と判断するまでに要した日数は, 41.1±4.1日 (n: 20) であった. 膝窩部リンパ節への転移は100%(n=20) であった. 全例で, 膝窩部リンパ節においては腫瘍細胞が皮質・髄質を侵し, リンパ節の1/2以上を占めていた. 鼠径部リンパ節転移は95.0%(n=20) に確認出来, 早期に採取した1例を除いて腫瘍細胞がリンパ節の1/2以上を占めていた. 結論. 我々は, ヒト肺癌細胞をヌードラット足背部へ移植し, 膝窩部及び鼠径部への転移一次・二次リンパ節モデルを作製した. 腫瘍の生着・転移は高率に起こり, その触診による転移の予測も簡便・正確であった.

Background Reoperative (redo) mitral valve surgery is still a continuing challenge to surgeons. The aim of this study was to detect the factors that affect late mortality or morbidity after redo mitral valve surgery in patients with rheumatic disease. Methods Between May 1983 and February 2003, 92 patients who underwent redo mitral valve surgery for rheumatic disease were enrolled. Risk factors influencing survival or cardiac events were investigated with univariate analysis and a Cox model. Results Operative mortality rate was 4.2%. Kaplan-Meier actuarial analysis demonstrated an 84.7% 5-year, a 69.5% 10-year, and a 65.9% 15-year survival. Multivariate analysis demonstrated that age at surgery and preoperative New York Heart Association (NYHA) class were found to be independent predictors of late deaths, and that higher age, advanced NYHA class, and previous mitral valve replacement were independent predictors of cardiac events. Conclusions Redo mitral valve surgery can be achieved with low early mortality. However, long-term results of redo mitral surgery are not necessarily satisfactory in patients with preoperative advanced NYHA class or with a previous mechanical heart valve, and especially in 60 years or older age.

Background: There is little information available concerning plasma concentrations of B-type natriuretic peptide (BNP) in children with a ventricular septal defect. The aim of the present study was to determine hemodynamic factors that control plasma concentrations of BNP and the clinical implications of BNP compared with atrial natriuretic peptide (ANP) in children with ventricular septal defect. Methods: Fifty-nine patients with ventricular septal defect (28 boys and 31 girls) without pulmonary vascular disease were enrolled. The patients’ ages ranged from 3 months to 13 years (mean 3.1 years). Plasma BNP and ANP were determined by immunoradiometric assay. Hemodynamic variables derived from cardiac catheterization were analyzed in terms of correlation with BNP and ANP. Results: It was found that plasma BNP significantly positively correlated with ANP (ANP = 2.1 × BNP + 25 pg/mL; r= 0.81, P

Stable transformants of Saos-2 cells that contain the luciferase reporter gene under the control of the human p16INK4a transcriptional regulatory region were established, and were used to identify growth-inhibiting substances from culture broths of actinomycetes and extracts of plants. Among the active substances so far identified were an aclacinomycin-derivative, cenerubin B, and a cardiac glycoside, periplocin. These substances inhibited growth of normal human fibroblasts, and induced senescent phenotypes including a flattened morphology and increased acidic beta-galactosidase activity, although the activities of their derivatives to induce p16CDKN2 and beta-galactosidase did not coincided with each other. These results suggest that the reporter system using the p16CDKN2 transcriptional regulatory region is a useful means for screening growth inhibiting substances that are potential anti-tumor agents.

NMR is a unique methodology for obtaining information about the conformational dynamics of proteins in heterogeneous biomolecular systems. In various NMR methods, such as transferred cross-saturation, relaxation dispersion, and paramagnetic relaxation enhancement experiments, fast determination of the signal intensity ratios in the NMR spectra with high accuracy is required for analyses of targets with low yields and stabilities. However, conventional methods for the reconstruction of spectra from undersampled time-domain data, such as linear prediction, spectroscopy with integration of frequency and time domain, and analysis of Fourier, and compressed sensing were not effective for the accurate determination of the signal intensity ratios of the crowded two-dimensional spectra of proteins. Here, we developed an NMR spectra reconstruction method, “conservation of experimental data in analysis of Fourier” (Co-ANAFOR), to reconstruct the crowded spectra from the undersampled time-domain data. The number of sampling points required for the transferred cross-saturation experiments between membrane proteins, photosystem I and cytochrome b6f, and their ligand, plastocyanin, with Co-ANAFOR was half of that needed for linear prediction, and the peak height reduction ratios of the spectra reconstructed from truncated time-domain data by Co-ANAFOR were more accurate than those reconstructed from non-uniformly sampled data by compressed sensing. Electronic supplementary material The online version of this article (doi:10.1007/s10858-015-9908-9) contains supplementary material, which is available to authorized users.

Aim Eicosanoids play various pathogenic roles in aortic valve calcification. Eicosanoids are derived from the arachidonic acid generated by phospholipase A2 (PLA2). We therefore sought to determine whether PLA2s are expressed in human aortic valves and, if so, whether the expression of PLA2s is related to the expression of osteogenic molecules in these tissues. Methods Histological and gene expression analyses of 38 non-rheumatic aortic valves obtained at the time of cardiac valve replacement surgery were conducted. Moreover, gene expression analyses were performed using valve interstitial cells (VICs) obtained from human aortic valves. Results Among the PLA2s examined, the degree of immunoreactivity for PLA2s-IIE and -V was found to significantly correlate with the grade of calcification in the aortic valves. The degree of immunoreactivity and gene expression levels of PLA2s-IIE and -V significantly correlated with those of bone morphogenetic protein (BMP)-2, osteopontin and alkaline phosphatase (ALP). In addition, immunoreactivity for cyclooxygenase (COX)-1, COX-2 and 5-lipoxygenase, downstream enzymes of PLA2 in the arachidonic acid cascade, was co-localized with that for PLA2s-IIE and -V in cells expressing α-smooth muscle actin and macrophages expressing CD68. Furthermore, in the in vitro experiments using cultured VICs, the mRNA expression levels of BMP-2, osteopontin and ALP were suppressed by the inhibition of the expression of PLA2s-IIE or -V with specific siRNAs. Conclusions The expression of PLA2s-IIE and -V correlates with the development of calcification as well as the expression of pro-osteogenic molecules in human aortic valves, and inhibiting the expression of PLA2s-IIE and -V suppresses the induction of osteogenic molecules in cultured cells. Therefore, PLA2s-IIE and -V may play a role in the pathogenesis of valve calcification.

Although the immediate results of radical operation for tetralogy of Fallot are excellent, long-term follow-up has shown that the number of repeated procedures has increased in many institutions. We describe patients who underwent a second or third procedure after radical operation for tetralogy of Fallot.Between April 1981 and August 1996, we operated on 44 patients for the second time and on 4 for the third time after radical operation for tetralogy of Fallot. Indications for a second and third procedure included right ventricular outflow tract obstruction in 38 patients, infective endocarditis in 4, and isolated residual ventricular septal defect in 3.One patient died after concomitant replacement of the pulmonary and tricuspid valves. Three patients who underwent sternotomy more than twice (before the second or third operation) underwent accidental cardiovascular trauma during this procedure (30%). Moreover, when patients underwent more than two sternotomy procedures before the repeated operation for tetralogy of Fallot, the total bypass time, interval between cessation of the cardiopulmonary pump to completion of the operation, amount of blood transfusion, and length of intensive care unit stay were significantly higher compared with those who underwent less than two sternotomy procedures (p0.05). Right ventricular outflow tract obstruction was the main indication for a second operation. After the second operation for right ventricular outflow tract obstruction in 35 patients, the preoperative right ventricle to left ventricle pressure ratio decreased significantly (from 0.75 +/- 0.13 to 0.51 +/- 0.12; p0.0001). However, the right ventricle to left ventricle pressure ratio did not significantly decrease in patients who underwent a third procedure to treat right ventricular outflow tract obstruction.The surgical results of a second procedure after radical operation for tetralogy of Fallot were acceptable. However, the risk of accidental cardiovascular trauma during dissection was high among patients who underwent sternotomy more than twice before repeat operation.

Background: Non-mosaic Klinefelter patients are generally azoospermic and there is no therapy to improve the spermatogenesis. Some patients have a few spermatozoa in their ejaculates, which can be used for intracytoplasmic sperm injection (ICSI), but only a few cases resulting in a successful birth have been reported. Methods: Out of 52 non-mosaic 47,XXY Klinefelter patients, four cases having spermatozoa in their ejaculates were retrospectively studied. Results: Intracytoplasmic sperm injection was performed in three cases using their ejaculates and resulted in one chemical abortion and one death in utero (8 weeks). Using testicular sperm, one patient had a healthy baby with a normal karyotype. Conclusion: Some non-mosaic Klinefelter patients have ejaculated sperm that can result in a successful birth following ICSI. However, the birth rate is very low compared with the fertilization rate, suggesting increased risk of chromosomal abnormalities.

We encountered a surgical case of aortic valve prolapse caused by a fissure formed in the commissural region and coronary cusp, and we achieved a favorable outcome. On pathologic examination, the fissured valve was found to be myxoid degeneration with ruptured elastic fibers and clustering of foamy macrophages, and it was diagnosed as an atherosclerotic change not associated with rheumatic change. The fissure appeared to develop because of hypertensive stress in a region rendered vulnerable by atherosclerosis. Although this mechanism is atypical, it should be recognized that poorly controlled hypertension can cause aortic valve prolapse and induce acute heart failure.