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Background Colorectal cancer (CRC) is the most malignant complication in patients with Crohn’s disease (CD). We report 6 cases of CD-related CRC treated surgically at our hospital. Case presentation From 2010 to 2016, six CD patients were diagnosed with CRC. All patients were diagnosed with CD at 10 years (range, 15–42 years) in all patients. The histological type of cancer was mucinous carcinoma in two cases, well-differentiated tubular adenocarcinoma in two cases, and moderately differentiated tubular adenocarcinoma in two cases. CRC was detected by screening colonoscopy in three cases (50%), and from clinical symptoms in the remaining three cases (50%). Two cases underwent colonoscopy within 2 months after symptom onset, detecting CRC in the relatively early stage. However, one case was diagnosed with advanced-stage CRC by endoscopy 1 year after symptom onset, and experienced poor prognosis. Conclusions Regular surveillance colonoscopy is needed to detect early-stage CRC in CD patients. Clear surveillance methods need to be established based on evidence.

Transanal (Ta) pelvic exenteration is a promising, minimally invasive method for treating locally advanced colorectal cancer. However, since it is technically difficult to perform, Ta pelvic exenteration is rarely reported in locally advanced T4 rectal cancer cases. The aim of this study was to evaluate the feasibility of transabdominal laparoscopy-assisted Ta pelvic exenteration. Six patients (4 males and 2 females) had laparoscopy-assisted Ta total or posterior pelvic exenteration for locally advanced or recurrent colorectal cancer cases at the Nagasaki University Hospital between September 2018 and August 2019. Clinical and pathological outcomes were measured and analyzed. The median operation time and intraoperative blood loss were 481 (range 456–709) minutes and 352.5 (range 257–1660) ml, respectively. R0 resection was achieved in all cases, and no patient required open surgery. Two patients had grade 3 complications (Clavien-Dindo) or higher. There was no mortality, and no reoperation was required. The results suggest that laparoscopic-assisted Ta pelvic exenteration is an acceptable procedure, may help overcome the current technical difficulties, and may improve outcomes in patients with locally advanced rectal cancer.

The aim of the present study was to investigate the prognostic value of the C-reactive protein-to-albumin ratio (CAR) and compare it with other inflammation-based prognostic scores (Glasgow prognostic score, modified Glasgow prognostic score, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, prognostic nutritional index and prognostic index) in patients with esophageal squamous cell cancer (ESCC). A database of 116 patients with primary ESCC who underwent treatment at the Division of Surgical Oncology at Nagasaki University Hospital between January 2007 and August 2014 was retrospectively reviewed and the correlations between CAR and overall survival (OS) were investigated. Kaplan-Meier and Cox regression analyses were used to assess independent prognostic factors. The area under the curve (AUC) was used to compare the prognostic value of different scores. According to the receiver operator characteristics analysis, the recommended cut-off value for CAR was 0.042, with an AUC of 0.678 (sensitivity 31.1%, specificity 66.7%). Thus, patients were dichotomized into low (

Prognostic influences of hepatic transection by an anterior approach using the liver hanging maneuver (LHM) has not been fully clarified.We examined 233 patients who underwent major hepatectomy with the LHM (n = 75; hepatocellular carcinoma (HCC) in 35, colorectal liver metastasis (CLM) in 10, intrahepatic cholangiocarcinoma (ICC) in 14 and perihilar bile duct carcinoma (BDC) in 16) or without it (n = 158; HCC in 78, CLM in 21, ICC in 31 and BDC in 28).In HCC patients, cancer-positive margin rate, blood loss, transection time and prevalence of posthepatectomy ascites in the LHM group were significantly lower than those in the non-LHM group (p0.05). In CLM, transection time in the LHM group was significantly lower than that in the non-LHM group (p0.05). In BDC patients, amount of blood loss, transection time and prevalence of ascites in the LHM group were significantly lower than those in the non-LHM group (p0.05). In CLM patients, tumor recurrence rate in the non-LHM group was significantly higher than that in the LHM group and disease-free survival in the LHM group was significantly better than that in the non-LHM group in CLM patients and, however, this difference was not observed in a large CLM exceeding 5 cm. However, significant differences of posthepatectomy disease-free and overall survivals were not observed in HCC, ICC and BDC patients.Although advantages of LHM improving surgical records in major anatomical liver resections were clarified, oncological advantages in the long-term survival of LHM was still uncertain in the hepatobiliary malignancies.

AIM: Cancer death in the early period after hepatectomy still occurs in patients with colorectal liver metastasis (CLM). We examined the relationship between clinicopathological parameters and survival periods in 130 CLM patients who underwent hepatectomy. PATIENTS/METHODS: Patients were divided into four groups: Group 1 (5-year survivors without tumor relapse), Group 2 (survivors at 2-5years), Group 3 (cancer death at 2-5years), and Group 4 (cancer death within 2years). RESULTS: A short surgical margin was frequent in Group 4 compared to Group 1 (31 vs. 78%, P, European Journal of Surgical Oncology, 35(5), pp.504-509; 2009

BACKGROUND/PURPOSE: Large liver tumors often expand and severely compress intrahepatic vessels. In cases of the trisectionectomy for such tumors, however, it is difficult to adequately expose the transection planes. The liver hanging maneuver (LHM) is a useful technique for hemihepatectomy and an adequate transection plane might be also required in trisectionectomy. METHODS: LHM procedure is basically followed by the Belghiti's method. A nasogastric tube was used for hanging. At the hepatic hilum, the tube was placed between the liver and Glisson's pedicle. RESULTS: We report here the application of LHM for right and left trisectionectomy in patients with a large hepatoma in two cases. In case of a right trisectionectomy for a large tumor compressing the umbilical Glisson's pedicle, an adequate transection plane was obtained using the LHM because the resected and remnant livers rotated to the other side upon lifting the tube during transection. In case of a left trisectionectomy for a large hepatic tumor compressing the right hepatic vein, an adequate transection plane along the right hepatic vein was obtained using LHM as well. CONCLUSIONS: LHM is a useful surgical application for right and left trisectionectomy in patients with large liver tumors compressing the cut plane., European Journal of Surgical Oncology (EJSO), 35(3), pp.326-330; 2009

SummaryThe Kaposi's sarcoma-associated herpesvirus (KSHV), the infectious causative agent of Kaposi's sarcoma (KS), encodes a G protein-coupled receptor (vGPCR) implicated in the initiation of KS. Here we demonstrate that Kaposi's sarcomagenesis involves stimulation of tuberin (TSC2) phosphorylation by vGPCR, promoting the activation of mTOR through both direct and paracrine mechanisms. Pharmacologic inhibition of mTOR with rapamycin prevented vGPCR sarcomagenesis, while overactivation of this pathway was sufficient to render endothelial cells oncogenic. Moreover, mice haploinsufficient for TSC2 are predisposed to vascular sarcomas remarkably similar to KS. Collectively, these results implicate mTOR in KS initiation and suggest that the sarcomagenic potential of KSHV may be a direct consequence of the profound sensitivity of endothelial cells to vGPCR dysregulation of the TSC2/mTOR pathway.

Effects of tempering treatment on mechanical properties and microstructures have been studied for martensitic steel F82H doped with 60 ppm B and 200 ppm N (F82H þ B þ N). The tempering treatments were performed at 700–780 � C after the normalizing treatment at 1000 � C. Yield stress of the F82H þ B þ N steel tempered at 700, 750 and 780 � C was 740, 580 and 500 MPa, respectively, and ductile-brittle transition temperature (DBTT) of the specimens was � 55, � 85 and � 85 � C, respectively. The areal density of dislocations decreased from 1:1 � 10 14 to 2:5 � 10 13 m � 2 with increasing tempering temperature from 700 to 780 � C. The number density of precipitates decreased with increasing tempering temperature from 700 to 750 � C, while the number density was almost equivalent as increasing tempering temperature from 750 to 780 � C. The results indicate that the change of DBTT, depending on tempering temperature, is related with the change of yield strength, size and number density of carbides. Hardening behavior of the F82H þ B þ N steel irradiated by 10.5 MeV Fe 3þ to 10 dpa at 360 � C has been also studied by using a micro-indentator. The micro-hardness of the F82H þ B þ N steel tempered at 780 � C was changed from 3.6 to 4.8 GPa by the irradiation. Because hardening behavior of the F82H þ B þ N steel was found to be similar with that of F82H non-doped, doping effects of B on irradiation hardening were suppressed by co-doping of B and N.

The objectives of this work are to evaluate the effects of thermal history corresponding to a blanket fabrication process on Reduced Activation Ferritic/Martensitic steel (RAF/Ms) microstructure, and to establish appropriate Hot Isostatic Pressing (HIP) conditions without degradation in the microstructures. One of RAF/Ms F82H and its modified versions were investigated by metallurgical methods after isochronal heat treatments up to 1473 K simulating HIP thermal history. Although conventional F82H showed significant grain growth after conventional solid HIP conditions, F82H with 0.1 wt% tantalum maintained a fine grain structure after the same heat treatment. It is considered that the grain coarsening was caused by dissolution of tantalum-carbide which immobilizes grain boundaries. On the other hands, conventional RAF/Ms with coarse grains were recovered by post HIP normalizing at temperatures below the TaC solvus temperature. This process can refine the grain size of F82H to more than ASTM grain size number 7.

Feline immunodeficiency virus (FIV) gene orf-A, also designated orf-2, encodes a 77 amino acid accessory protein reported to be critical for efficient viral replication in vitro and in vivo and previously implicated to encode a Tat protein for FIV. However, recent studies have shown Orf-A to be important in the late steps of the FIV life cycle involved in virion formation and in early steps involved in virus infectivity (J. Virol. 77 (2003) 8819). The present study reports that expression of a GFP-Orf-A fusion protein in both primate and feline cell lines results in nuclear localization of this FIV accessory protein. Moreover, a nuclear localization signal (NLS) critical for nuclear import was mapped to amino acid residues 43 through 53 of Orf-A. Lastly, transient expression of GFP-Orf-A in cells induced an arrest at the second gap (G2) of the cell cycle. Our findings reveal that Orf-A is a nuclear protein that expresses properties similar to those reported for human immunodeficiency virus-1 (HIV-1)-encoded Vpr.

Aims. We aim to clarify the long-term outcomes after an additional radical operation following gasless video endoscopic transanal rectal tumour excision (gasless VTEM) of ‘high-risk’ T1 and T2 rectal cancer. Methods. Gasless VTEM involves modification of transanal endoscopic microsurgery (TEM) by incorporating a standard laparoscopic video camera without a CO 2 insufflation system. This study between 1993 and 2003 included six men and five women with a median age of 64 years (range, 36–79). Specimens resected by gasless VTEM revealed (1) high-risk T1 carcinomas with one of the following histological types: poorly differentiated, lymphovascular invasion, and massive invasion of the submucosa (submucosal invasion greater than 200–300 μm from the muscularis mucosa) and (2) T2 carcinomas. Results. Eight patients had a high-risk T1 carcinoma and three patients had a T2 carcinoma. In two patients with a high-risk T1 carcinoma, a residual tumour was found in the specimen resected by the additional radical surgery. At a median follow-up of 86.5 months (range, 63.2–110.5), none of the patients developed tumour recurrence. Although one patient died with cancer at another organ site (hilar cholangiocarcinoma of the liver) 87 months after the additional radical surgery, the other 10 patients are alive and disease free. Conclusions. This study revealed favorable long-term outcomes after additional radical surgery following gasless VTEM in patients with high-risk T1 and T2 carcinomas.

Several retroviruses downmodulate the cell surface expression of envelope (Env) proteins through peptide sequences located in the cytoplasmic tail of the transmembrane (TM) subunit. We investigated whether cell surface expression of a chimeric protein containing the cytoplasmic domain of the TM protein (CTM) of bovine leukemia virus (BLV) was regulated by two membrane-proximal dileucine motifs or by tyrosine Y487 or Y498 in YXXL motifs. A chimeric protein composed of the extracellular and membrane-spanning portions of human CD8-α plus a wild-type (wt) BLV CTM was detectable on the surface of only 40% of the cells in which it was transiently expressed. Replacement of either dileucine pair with alanines increased the level of surface display of chimeric proteins. Nearly all cells became surface positive when both dileucine motifs were altered simultaneously and when either an N-terminal segment containing both dileucine motifs or a C-terminal segment containing all YXXL motifs was deleted. In contrast, replacement of Y487 or Y498 with alanine or phenylalanine enabled only small increases in surface display compared with wt levels. Chimeric proteins had similar stabilities but were downmodulated from the cell surface at three different rates. Point mutants segregated into each of the three groups of proteins categorized according to these different rates. Interestingly, Y487 mutants were downmodulated less efficiently than Y498 mutants, which behaved like wt. CD8-CTM chimeric proteins were phosphorylated on serine residues, but the native BLV Env protein was not phosphorylated either in transfected cells or in a lymphoid cell line constitutively producing BLV. Thus, both dileucine and YXXL motifs within the BLV CTM contribute to downmodulation of a protein containing this domain. Interactions with other proteins may influence surface exposure of Env protein complexes in virus-infected cells, assisting in viral evasion of adaptive immunity.

Micro-indentation hardness was measured for the irradiated F82H steels by single (10.5 MeV Fe 3+ ) beam or dual (10.5 MeV Fe 3+ and 1.05 MeV He + ions) beam at the TIARA facility in JAERI. The extra component of radiation hardening due to helium was slightly detected in the dual-beam (10 appmHe/dpa) irradiation at 633 K up to 33 dpa. As increased the ratio of He/dpa (100 appmHe/dpa), the extra component due to helium was increased. The microstructures in single/dual (10 appmHe/dpa) ion beam irradiated F82H steels consisted of interstitial loops and defect clusters at 50 dpa. However, at a higher ratio of He/dpa (100 appmHe/dpa), nano-voids were also observed in dual ion irradiated F82H.

We have recently engineered an in vivo endothelial cell-specific retroviral gene transfer system and found that a single Kaposi's sarcoma (KS)-associated herpesvirus/human herpesvirus 8 gene encoding a G protein-coupled receptor (vGPCR), is sufficient to induce KS-like tumors in mice. By using this system, we show here that the Akt signaling pathway plays a central role in vGPCR oncogenesis. Indeed, a constitutively active Akt was sufficient to induce benign hemangiomas in mice, whereas heterozyogosity for PTEN (the phosphatase and tension homologue deleted on chromosome 10), modestly enhancing basal Akt activity, dramatically enhanced vGPCR sarcomagenesis. Examination of KS biopsies from AIDS patients revealed active Akt as a prominent feature, supportive of a role for Akt in human Kaposi's sarcomagenesis. By using a vGPCR agonist-dependent mutant, we further establish constitutive activity as a requirement for vGPCR sarcomagenesis, validating targeted inhibition of key vGPCR signaling pathways as an approach for preventing its oncogenic potential. These observations prompted us to explore the efficacy of inhibiting Akt activation as a molecular approach to KS treatment. Pharmacological inhibition of the Akt pathway with the chemotherapeutic agent 7-hydroxystaurosporine prevented proliferation of vGPCR-expressing endothelial cells in vitro and inhibited their tumorigenic potential in vivo . Both were associated with a decrease in Akt activity. These results identify Akt as an essential player in vGPCR sarcomagenesis and demonstrate the therapeutic potential of drugs targeting this pathway in the treatment of KS.

Effect of heat treatment on mechanical properties and microstructures of Fe-8Cr-2W-0.1C-0.2V-0.04Ta martensitic steel F82H doped with about 60 mass ppm B or both of 60 mass ppm B and 200 mass ppm N has been examined. The normalization was heated at temperatures from 950 to 1250 °C for 1.8 ks, followed by air cooling or water quenching. After tempering treatment at 780 °C or 750 °C, the distributions of boron, boron nitride and oxygen were measured by a secondary ion mass spectrometry (SIMS). Optical microstructural observation and tensile and Charpy impact tests were performed also. In the boron doped F82H the tensile properties were similar to the non-doped F82H, but the ductile-brittle transition temperature (DBTT) shifted from -43 °C to 15 °C. SIMS images with high intensity of boron were observed in localized regions of the boron doped F82H. Water quenching reduced the DBTT shift, about 30°C, and the localized boron intensity was slightly decreased. In the boron and nitrogen doped tempered-F82H heat-treated by the water quenching from the normalizing temperature, the properties of tensile and Charpy impact were similar to the non doped F82H, and no pronounced localized boron image was observed in the SIMS image and no intensities of oxides and boron nitride were observed either.

The Japanese reduced activation ferritic steels (RAFSs) R&D road map towards DEMO is shown. The important steps include high-dose irradiation in fission reactors such as the high flux isotope reactor at Oak Ridge National Laboratory, irradiation tests with 14 MeV neutrons in the International Fusion Materials Irradiation Facility and application to ITER test blanket modules to provide an adequate database of RAFSs for the design of DEMO. The current status of RAFS development is also introduced. The major properties of concern are well-known, and process technologies are mostly ready for fusion application. RAFSs are now certainly ready to proceed to the next stage. A materials database is already in hand, and further progress is anticipated with the design of the ITER test blanket. Oxide dispersion strengthening steels are quite promising for high temperature operation of the blanket system, with potential improvements in radiation resistance and in corrosion resistance.

In a fusion reactor, a blanket made of a low activation material like F82H steel is fabricated by HIP (hot isostatic pressing) bonding method. In a previous study, grain coarsening has been found in specific HIP-bond region of a mock-up of blanket structures. To verify an effect of the coarsening on mechanical properties of the HIP-bond region, tensile and impact tests were done. In result of the tensile test, there was no significant influence of the coarsening on the tensile properties of the HIP-bond region up to 500 °C. In the impact test (RT ∼−50 °C), temperature at which the absorbed energy of the HIP-bond region changed markedly (−35 °C) was almost same to DBTT of the matrix region (−30 °C), but the absorbed energy at room temperature (RT) decreased by about 40% in comparison with that of the matrix region. The major factors were: (1) large inclusions in the HIP interface; and (2) brittle fracture in a part of the HIP-bond region due to grain coarsening. It is important to eliminate a contamination caused by the inclusions from the HIP bonding surfaces, and also it is necessary to suppress and/or refine the grain coarsening.

In order to determine the contributions of different microstructural features to strength and to deformation mode, microstructure of deformed flat tensile specimens of irradiated reduced activation F82H (IEA heat) base metal (BM) and its tungsten inert-gas (TIG) weldments (weld metal and weld joint) were investigated by transmission electron microscopy (TEM), following fracture surface examination by scanning electron microscopy (SEM). After irradiation, the fracture surfaces of F82H BM and TIG weldment showed a martensitic mixed quasi-cleavage and ductile-dimple fracture. The microstructure of the deformed region of irradiated F82H BM contained dislocation channels. This suggests that dislocation channeling could be the dominant deformation mechanism in this steel, resulting in the loss of strain-hardening capacity. While, the necked region of the irradiated F82H TIG, where showed less hardening than F82H BM, showed deformation bands only. From these results, it is suggested that the pre-irradiation microstructure, especially the dislocation density, could affect the post-irradiation deformation mode.

The orf-A ( orf-2 ) gene of feline immunodeficiency virus (FIV) is a small open reading frame predicted to encode a 77-amino-acid protein that contains putative domains similar to those of the ungulate lentiviral Tat protein. Orf-A is reported to be critical for efficient viral replication in vitro and in vivo. A series of FIV-pPPR-derived proviruses with in-frame deletions and point mutations within orf-A were constructed and tested for replication in feline lymphoid cells. Orf-A mutant proviruses were also tested for viral gene and protein expression, viral particle formation, and virion infectivity. Deletions within orf-A severely restricted FIV replication in feline peripheral blood mononuclear cells (PBMC) and interleukin-2-dependent T-cell lines. In addition, substitutions of alanines for leucines in the putative leucine-rich domain, for cysteines in the putative cysteine-rich domain, and for a tryptophan at position 43 in Orf-A restricted the replication of FIV mutants. Deletions and point mutations in orf-A imposed a small effect or no effect on FIV long-terminal-repeat-driven viral gene expression and had no effect on viral protein expression. However, release of cell-free, virion-associated viral RNA in supernatants from cells transfected with orf-A mutant proviruses was severely restricted but was rescued by cotransfection with a wild-type Orf-A expression vector. In addition, virions derived from orf-A mutant proviruses expressed reduced infectivity for feline PBMC. Our findings suggest that Orf-A functions involve multiple steps of the FIV life cycle including both virion formation and infectivity. Furthermore, these observations suggest that Orf-A represents an FIV-encoded analog more similar to the accessory gene vpr , vpu , or nef than to the regulatory gene tat encoded by the primate lentiviruses.

Previous work reported that a TIG weld joint of F82H exhibited low irradiation hardening in a tensile test, compared to the base metal. Microhardness tests and microstructure observation on the neutron-irradiated TIG weld joint of F82H revealed that the over-tempered zone in the heat-affected zone (HAZ) exhibited this good performance. The region in the HAZ where the prior austenite grain size became very fine during welding also exhibited lower irradiation hardening. Hypotheses for these low-hardening mechanisms were proposed based on the phase diagram and grain size.

An atomic-scale graded structure had been formed in an all-proportion miscible alloy in bismuth (Bi)-antimony (Sb) (70:30 in mol%) system by the sedimentation of substitutional solute atoms under a strong gravitational field of 1 million G level in maximum acceleration at 220–240□ (Mashimo et al. 1997, Mashimo et al. 2001). The large and long crystals whose grain sizes were several mm long and several hundreds of μm wide were oriented along the direction of gravity in the high gravity region larger than about 0.7×106 G, while those of the small crystals in the low gravity region smaller than it were several 10 Pin. It was found that the large strain existed in the large crystals by back-reflection Laue method. It was found that the c axis of hexagonal structure of a large crystal was roughly parallel to the direction of gravity by Transmission Electron Microscopy (TEM) observation.

The present study was undertaken to evaluate p53 gene mutation as a prognostic factor in patients with colorectal cancer. Nonisotopic RNase cleavage assay (NIRCA), recently used for detecting gene mutations, was employed to detect p53 gene mutations in this study. In 15 samples of colorectal tumors, NIRCA was confirmed to be simple, accurate, and thus useful for clinical use, compared with polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP). In another group of 79 cases of colorectal cancer analyzed for p53 gene mutation by using NIRCA, mutations were detected in 58 of 79 (73.4%) cases. Multivariate Cox proportional-hazards analysis showed that p53 gene mutation was a significant prognostic factor in patients with colorectal cancer. Our results showed that NIRCA is a simple and sensitive method, and thus useful for genetic screening of colorectal cancer. Furthermore, our results showed that p53 gene mutation is an independent predictor of poor prognosis in colorectal cancers.

Under some conditions, p21(Waf1/Cip1) plays an assembly factor role for the cyclins and cyclin-dependent kinases, and recent reports demonstrate that p21 can act as an anti-apoptotic protein. Thus, it is logical to exploit this function of p21 as an anti-cancer target. We have performed a pilot study showing that daily subcutaneous injection of a phosphorothioate antisense p21 oligodeoxynucleotide, which we have previously shown to attenuate p21 levels in vitro, into nude mice who have been implanted with highly metastatic breast cancer cells results in inhibition of tumor growth and angiogenesis. Inhibition of in vitro endothelial capillary formation confirms that these oligodeoxynucleotides have a direct effect upon tumor angiogenesis. The attractiveness of our novel approach to breast cancer therapy, which capitalizes on the anti-apoptotic function of p21, derives from the ease of transfection of antisense oligodeoxynucleotides as well as the observations that p21(-/-) mice do not develop spontaneous tumors, making techniques exploiting the assembly factor and anti-apoptotic role of p21 worthy of further study against breast cancer.

The evaluation of the temperature dependence of irradiation hardening in a reduced activation ferritic/martensitic steel (RAFs), F82H (Fe–8Cr–2W–V–Ta) and Ni-doped (1%, 2%) F82H, was performed using single/dual-beam ion irradiation and ultra-micro-indentation technique. In analyzing the load–displacement curve, it was assumed that the elastic modulus did not exceed the original value due to irradiation-induced damage because micro-hardness was defined as a function of composite elastic modulus. Secondly, micro-structural evolution was characterized for irradiation conditions where significant changes in micro-hardness in RAFs were found. Finally, based on these results, the plastic deformation behavior of F82H steels with the irradiation hardening was investigated.

A Ti–35Al–10V intermetallic compound manufactured by powder metallurgy contains α2, β and γ phases. It has a better strength and ductility than the Ti–Al binary alloy containing α2 and γ phases. A typical 0.2% yield strength and total elongation of Ti–35Al–10V at 500 °C are 700 MPa and 15%, respectively. At 600 °C, the strength is still above 600 MPa and total elongation increases up to 60%. Transmission electron microscope (TEM) observation of the deformed microstructure suggests a transformation induced ductility in the β phase. After neutron irradiation of 3.5×1025 n/cm2 at 400 and 600 °C, the total elongation is only 10% at the 600 °C test, and almost no plastic elongation was observed at the 400 °C test. The TEM observation of irradiated Ti–35Al–10V did not show the formation of the ω phase.

Metallurgical examinations and hardness measurements were performed at hot isostatic pressing (HIP)-bonded regions in blanket structures made from F82H alloy in order to investigate the HIP-bondability and the influence on the microstructure due to the HIP and heat treatments which would correspond to the fabrication of an actual blanket. The metallurgical examination showed that the HIP-bonded interfaces were sufficiently diffusion-bonded without significant defects, i.e. voids and/or exfoliations, although grain coarsening was observed at a part of the HIP interfaces. Hardness was nearly equal in the coarsening region and a region without coarsening, but about a 10 Hv increase was found in a boundary in between the regions with and without coarsening. Microcrystallized grains were observed in a region about ∼6 μm from HIP interfaces, and the hardness increased by about 0.2 GPa in the region.

The effects of cold working and impurities on swelling behavior in austenitic stainless steels irradiated at 400 °C to 17.3 dpa under spectrally tailored conditions in the Oak Ridge research reactor and high flux isotope reactor were investigated. The specimens were 20% cold-worked JPCA, 316R, K (low carbon (0.02%)) and C (low carbon (0.02%) and doped with 0.08% niobium). The helium generation rate was about 15 appm He/dpa. Cavities, dislocation loops and carbides were formed by irradiation in these steels. The swelling in the JPCA-CW and 316-CW was 0.003% and 0.004%, respectively and in the C-CW and K-CW was 0.02% and 0.01%, respectively. Swelling in K and C steels was strongly reduced by 20% cold-work, and the swelling in JPCA-CW and 316R-CW steels was comparable to JPCA-SA and 316R-SA steels. The synergistic treatments of addition of some impurities and cold working are very effective for the suppression of swelling at 400 °C in austenitic stainless steels.

Tungsten-inert-gas weld joints prepared from the IEA heat of F82H were irradiated with 10.5 MeV Fe ions and 1.05 MeV He ions at 450 °C. Transmission electron microscopy observation revealed a marked cavity growth up to 30 nm at 50 dpa in the over-tempered portion of the heat-affected zone (HAZ), while cavities in the quenched portion of HAZ remained smaller (up to 10 nm). Base metal results also showed that a specimen tempered at 780 °C contained larger cavities than those tempered at 750 °C. Cavities in cold-worked specimens were the smallest. Initial dislocation densities in F82H, which are affected by heat treatment and/or mechanical treatment, dominate the cavity growth.

The synergistic effects of displacement damage and atomic hydrogen and helium on swelling of the ferritic/martensitic steel, F82H, has been investigated. The irradiation was performed at temperatures between 470 and 600 °C to 50 dpa (displacement per atoms) under conditions of simultaneous ion beams consisting of Fe3+, He+ and H+ ions or Fe3+ and He+ ions. The swelling of F82H steel under triple beams with 18 appm He/dpa and 70 appm H/dpa was larger than that under dual beams with 18 appm He/dpa. The swelling in F82H under triple beams increased with decreasing irradiation temperature from 0.1% to 3.2%, while swelling under dual beams was between 0.04% and 0.08%. On the other hand, in the case of triple beam irradiation with a high ratio of gas/dpa, the swelling tended to increase with irradiation temperature. The swelling in ferritic/martensitic steels is significantly enhanced by the synergistic effect of displacement damage, hydrogen and helium atoms.

Background Transanal endoscopic microsurgery (TEM) is unpopular because of its high cost and most surgeons' unfamiliarity with microscopic surgery. This report describes an experience with a modification of TEM, gasless video endoscopic transanal rectal tumour excision (gasless VTEM), which incorporates a standard laparoscopic video camera and requires no carbon dioxide insufflation system. Methods One hundred and one patients with 105 rectal tumours underwent gasless VTEM between 1993 and 2000. Results Histological examination revealed 18 adenomas, 75 carcinomas (Tis, 47; T1, 23; T2, five), 11 carcinoid tumours and one lymphoma. The median height above the dentate line and maximum tumour diameter was 5·0 (range 2–14) cm and 2·0 (range 0·4–8·0) cm respectively. The peritoneal cavity was opened intraoperatively in two patients. The median operating time was 53 (range 15–202) min. Bleeding, suture dehiscence and transient incontinence developed after operation in four patients. There was no operative death. Median hospital stay was 5 (range 1–21) days. Eleven patients with T1/T2 staging underwent subsequent radical resection. The median duration of follow-up was 52·3 months. One patient with a carcinoma developed a recurrence. Conclusion Gasless VTEM is a feasible, safe and minimally invasive procedure for the treatment of selected rectal adenomas and early carcinomas. The suggested modifications may make the procedure more widely available.

Objective. In order to elucidate which cytokine preferentially stimulates the synovium in patients with rheumatoid arthritis (RA), we investigated the roles of tumour necrosis factor a (TNF-a) and interleukin 6 (IL-6) using SCID mice engrafted with human RA tissue (SCID-HuRAg). Methods. The SCID-HuRAg mice were prepared according to our previously described method. First, SCID-HuRAg mice were treated with chimeric anti-TNF-a monoclonal antibody (mAb, 100 mgumouse) and histological changes were examined 4 weeks after the initial treatment. Secondly, a total of 100 mg of recombinant TNF-a or IL-6 (0.6 mguh) was administered daily to mice using an osmium pump. The histological changes and serum cytokine levels were examined 4 weeks after the initial administration. Human immunoglobulin G (IgG) was administered to mice as a control. Results. Synovial inflammatory cells were significantly decreased after the anti-TNF-a mAb treatment; conversely, the degree of synovial inflammation was significantly exacerbated by TNF-a administration. The levels of both IL-6 and TNF-a in sera were significantly increased by recombinant TNF-a administration, while TNF-a levels were unchanged by IL-6 administration. This suggests that TNF-a controls IL-6 production. Despite the profound changes in inflammation, we found no effects on bone and no articular cartilage damage was produced by TNF-a. Conclusion. This study provides strong evidence that TNF-a is a key molecule in the control of the inflammatory changes that occur in the RA synovium. In addition, TNF-a regulates IL-6 production. However, other inflammatory pathways independent of TNF-a may contribute to the bone and cartilage damage seen in RA. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by hyperplasia of the synovium and an excess of inflammatory cells, leading to progressive destruction of the joints. In RA, several cytokines, e.g. interleukin (IL)-1, IL-6, IL-8, IL-12, IL-17, tumour necrosis factor-a (TNF-a), interferon-c (IFN-c) and granulocyte‐macrophage colony-stimulating factor (GM-CSF), are involved in almost all aspects of articular inflammation and destruction w1x. TNF-a has been considered a pivotal cytokine in the pathogenesis of RA, as significant clinical and laboratory evidence has been obtained by TNF-a blockade w1‐3x. Moreover, it has been verified that neutralized monoclonal antibodies (mAb) against TNF-a can reduce the production of other proinflammatory cytokines, such as IL-1 and GM-CSF, in cultured RA synovia w4x .I n the clinical trials performed to date, anti-TNF-a mAb has been effective in the majority of treated RA patients. Moreover, anti-TNF-a mAb may reduce tissue perfusion in the inflamed synovium, according to the results

Background: Volar melanotic macules are asymptomatic light-brown or tannish-grey macules usually found on the palms and/or soles of blacks, although they have also been reported on the volar surfaces of whites. Similar lesions have not been reported before in Japanese people. Since the cause is as yet unknown, it remains to be discussed whether they are a distinct entity. Methods: In this report, a 52-year-old Japanese man with volar melanotic macules is reported with the clinical and histopathological findings. Results: A 52-year-old Japanese man presented with many light-brown macules on his bilateral soles. He had a 20-year history of tinea pedis. Histopathological examination revealed melanophages and inflammatory infiltrates in the superficial dermis. There was a slight increase in melanin granules around the acrosyringium. Fontana-Masson stain revealed a slight increase in melanin granules in the basal layer including the acrosyringium and superficial dermis. These changes corresponded with postinflammatory pigmentation. Conclusions: This is the first report of volar melanotic macules in Japanese people. We suggest that volar melanotic macules is not an independent entity but a clinicopathological one that includes postinflammatory pigmentation, and that the condition is the volar counterpart of mucosal melanotic macules.

F82H(8Cr–2WVTa steel) IEA heat was used to prepare tungsten-inert-gas (TIG) and electron-beam (EB) weld joints, followed by heat treatment at 720°C for 1 h. Hardening in the weld metal and softening in the heat-affected zone (HAZ) were detected in TIG weld joints. In EB weld joints, hardening in the weld metal was more clearly observed but HAZ softening was hardly observed. Hardness of TIG weld metal was reduced after 550°C thermal-aging, but softening of the base metal was only observed after 650°C thermal-aging. M 23 C 6 phase was the major precipitate in aged base metal and weld joints. The amount of precipitates in aged weld metal was lower than that of normalized and tempered base metal. W-rich Laves phase was also detected in aged weld metal, HAZ and base metal.

Four kinds of Ti–Al intermetallic compounds were made from powder metallurgical processing using mechanical alloying or plasma rotating electrode processing. One consisted of α2-Ti3Al single phase, and the others consisted of α2-Ti3Al and γ-TiAl duplex phases. These intermetallic compounds were irradiated at 673 K to the fluence of 5.16 × 1025 n/m2 (E > 1 MeV) in the high flux isotope reactor. After irradiation, transmission electron microscopy was carried out. Cavities were observed in both the α2-Ti3Al- and γ-TiAl-phases. The nucleation behavior of cavities in the α2-Ti3Al- and γ-TiAl-phases was influenced by chemical composition and fabrication processes.

The synergistic effect of displacement damage and helium generation under neutron irradiation on tensile behavior and microstructures of austenitic stainless steels was investigated. The steels were irradiated at 400°C in the spectrally-tailored (ST) Oak Ridge research reactor/high flux isotope reactor (ORR/HFIR) capsule to 17 dpa with a helium production of about 200 appm and in the HFIR target capsule to 21 and 34 dpa with 1590 and 2500 appm He, respectively. The increase of yield strength in the target irradiation was larger than that in the ST irradiation because of the high-number density of Frank loops, bubbles, voids, and carbides. Based on the theory of dispersed barrier hardening, the strengths evaluated from these clusters coincide with the measured increase of yield strengths. This analysis suggests that the main factors of radiation hardening in the ST and the target irradiation at 400°C are Frank-type loops and cavities, respectively.

Microstructural evolution in solution-annealed Japanese-PCA (JPCA-SA) and four other austenitic stainless steels, irradiated at 400°C to 17.3 dpa in the ORR and the high flux isotope reactor (HFIR) spectrally tailored experiment, were investigated by transmission electron microscopy (TEM). The mean He/dpa ratio throughout the irradiation fell between 12 and 16 appm He/dpa , which is close to the He/dpa values expected for fusion. In all the specimens, a bi-modal size distribution of cavities was observed and the number densities were about 1.0×10 22 m −3 . There was no significant difference between the number densities in the different alloys, although the root mean cubes of the cavity radius are quite different for each alloy. Precipitates of the MC type were also observed in the matrix and on grain boundaries in all alloys except a high-purity (HP) ternary alloy. The JPCA-SA (including 0.06% carbon and 0.027% phosphorus) and standard type 316 steel (including 0.06% carbon and 0.028% phosphorus) showed quite low-swelling values of about 0.016 and 0.015%, respectively, while a HP ternary austenitic alloy showed the highest swelling value of 2.9%. This suggests that the existence of impurities affects the cavity growth in austenitic stainless steels even at 400°C.

An open reading frame (ORF) with homology to interleukin-10 (IL-10) has been identified in rhesus cytomegalovirus (RhCMV). The IL-10-like protein is generated from a multispliced, polyadenylated early gene transcript encompassing part of the corresponding UL111A ORF of human CMV (HCMV). Immunological analyses confirm expression of the IL-10-like protein both in tissue culture and in RhCMV-infected rhesus macaques. Conserved ORFs were subsequently identified in human, baboon, and African green monkey CMV, and a fully processed transcript has been mapped in fibroblasts infected with the Towne strain of HCMV. The conservation of this previously unrecognized ORF suggests that the protein may play an essential role in primate CMV persistence and pathogenesis.

Rhesus macaques infected with simian immunodeficiency virus (SIV) containing either a large nef deletion (SIVmac239Δ 152 nef) or interleukin-2 in place of nef developed high virus loads and progressed to simian AIDS. Viruses recovered from both juvenile and neonatal macaques with disease produced a novel truncated Nef protein, tNef. Viruses recovered from juvenile macaques infected with serially passaged virus expressing tNef exhibited a pathogenic phenotype. These findings demonstrated strong selective pressure to restore expression of a truncated Nef protein, and this reversion was linked to increased pathogenic potential in live attenuated SIV vaccines.

An explosive subsoiler was envisaged and designed to achieve greater soil rupture volume and longer sustainability of drainage for the improvement of meadow soil. In this paper, the results are presented from soil bin experiments with the explosive subsoiler, that were conducted in Japan prior to field experiments in China, to investigate soil rupture volume. The results showed that the sand and pseudogley soil were broken down by a moving subsoiler with gas injection. With a gas flow rate of 10 g/s, a pressure of about 6 kPa was produced at the nozzle port, a cavity was formed underground, and the subsoil was disturbed. Both forward and lateral rupture distances were constant, regardless of the differences in the soil and the gas flow rate. Hence, the average forward rupture distance was 0·75 m and the average lateral rupture distance was 0·25 m. Both values were influenced by the shape of the subsoiler body. Only 13% of the power required for gas injection was used in cavity formation, while the remaining 87% induced soil disturbance.

The objective of this work was to develop a special subsoiler which would break down the impermeable horizons of meadow soil by using gas pressure explosions produced by injecting a fuel and air mixture. A major part of the soil volume would fail to withstand the gas pressure, and longer sustainability would be obtained. In this paper, an explosive subsoiler was envisaged and designed, and the gas pressure and temperature produced in an explosive gas producer were theoretically analysed. The results showed that the maximum temperature and pressure predicted in the combustion chamber was 3307 K and 16 MPa, respectively. These values decreased to 2607 K and 5·5 MPa when the engine crank angle was +25° where the explosive gas could be taken from the combustion chamber and be utilized. These values also decreased steeply at larger dead volumes of the subsoiler body. The predicted temperature and pressure varied from 498 to 1780 K and from 0·4 to 1·5 MPa, respectively, with the range of the fuel injection.

The simian immunodeficiency virus (SIV) nef gene is an important determinant of viral load and acquired immunodeficiency syndrome (AIDS) in macaques. A role(s) for the HIV-1 nef gene in infection and pathogenesis was investigated by constructing recombinant viruses in which the nef gene of the pathogenic molecular clone SIVmac239 nef was replaced with either HIV-1sf2nef or HIV-1sf33nef. These chimeras, designated SHIV-2nef and SHIV-33nef, expressed HIV-1 Nef protein and replicated efficiently in cultures of rhesus macaque lymphoid cells. In two SHIV-2nef-infected juvenile rhesus macaques and in one of two SHIV-33nef-infected juvenile macaques, virus loads remained at low levels in both peripheral blood and lymph nodes in acute and chronic phases of infection (for >83 weeks). In striking contrast, the second SHIV-33nef-infected macaque showed high virus loads during the chronic stage of infection (after 24 weeks). CD4+ T-cell numbers declined dramatically in this latter animal, which developed simian AIDS (SAIDS) at 47–53 weeks after inoculation; virus was recovered at necropsy at 53 weeks and designated SHIV-33Anef. Sequence analysis of the HIV-1sf33nef gene in SHIV-33Anef revealed four consistent amino acid changes acquired during passage in vivo. Interestingly, one of these consensus mutations generated a tyr-x-x-leu (Y-X-X-L) motif in the HIV-1sf33 Nef protein. This motif is characteristic of certain endocytic targeting sequences and also resembles a src-homology region-2 (SH-2) motif found in many cellular signaling proteins. Four additional macaques infected with SHIV-33Anef contained high virus loads, and three of these animals progressed to fatal SAIDS. Several of the consensus amino acid changes in Nef, including Y-X-X-L motif, were retained in these recipient animals exhibiting high virus load and disease. In summary, these findings indicate that the SHIV-33Anef chimera is pathogenic in rhesus macaques and that this approach, i.e., construction of chimeric viruses, will be important for analyzing the function(s) of HIV-1 nef genes in immunodeficiency in vivo, testing antiviral therapies aimed at inhibiting AIDS, and investigating adaptation of this HIV-1 accessory gene to the macaque host.

Human immunodeficiency virus type 1 (HIV-1) Nef enhances virus replication in both primary T lymphocytes and monocyte-derived macrophages. This enhancement phenotype has been linked to the ability of Nef to modulate the activity of cellular kinases. We find that despite the reported high-affinity interaction between Nef and the Src kinase Hck in vitro, a Nef-Hck interaction in the context of HIV-1-infected primary macrophages is not detectable. However, Nef binding and activation of the PAK-related kinase and phosphorylation of its substrate could be readily detected in both infected primary T lymphocytes and macrophages. Furthermore, we show that this substrate is a complex composed of the recently characterized PAK interacting partner PIX (PAK-interacting guanine nucleotide exchange factor) and its tightly associated p95 protein. PAK and PIX-p95 appear to be differentially activated and phosphorylated depending on the intracellular environment in which nef is expressed. These results identify the PIX-p95 complex as a novel effector of Nef in primary cells and suggest that the regulation of the PAK signaling pathway may differ in T cells and macrophages.

A Ti–40Al–10V (at%) intermetallic compound has been developed using vacuum arc remelting and hot-isostatic pressing (HIP), followed by isothermal hot-forging (IHF). The alloy, composed mainly of B2 and γ phases with equiaxial grains of several μ m in average diameter and a small amount of α 2 phase with equiaxial grains of smaller size, shows excellent tensile properties; it has an elongation larger than 6% on average and yield strength larger than 700 MPa at low (ambient temperature) to intermediate temperatures, although the strength decreases rapidly at temperatures higher than 600°C.