Immunohistochemical characterization of the lymphocyte and the immunoglobulin-containing cell in the epithelium and the lamina propria of normal human intestines.

In order to clarify difference of the mucosal immunity in various sites of normal large and small intestines, we studied the population of lymphocyte subsets and immunoglobulin (Ig)-containing cells in situ in biopsy specimens taken from various sites (ascending colon, sigmoid colon and rectum) of the large intestine and from the duodenum using an immunohistochemical method. Monoclonal antibodies against pan-T (Leu 1), cytotoxic/suppressor T (Leu2a), helper/inducer T (Leu3a), suppressor T (Leu15) and natural killer/K (Leu7) cells, and polyclonal antibodies to human IgG, IgA and IgM were used. In the duodenum, intraepithelial lymphocytes (IELs) were more prominent than in the large intestine. Immunoelectron microscopic observation revealed that some Leu2a+ IELs possessed pseudopods extending into intestinal epithelial cells, indicating that some IELs belong to the cytotoxic T cell subset. Leu7+ IELs were scarcely observed and Leu7+/Leu1+ ratio was higher in the large intestine than in the duodenum. Furthermore, the number of Leu7+ cells were more in the distal than the proximal colon. In the lamina propria Ig-containing cells tended to be fewer in the rectum than in the duodenum and the proximal colon. Our findings may suggest the variation of local immune responses and the difference of assigned immunological functions among the various sites of the intestines.</p

Improvement of resistance against hydrogen embrittlement by increasing carbon segregationat prior austenite grain boundary in low-carbon martensitic steels

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Improvement of resistance against hydrogen embrittlement by controlling carbon segregation at prior austenite grain boundary in 3Mn-0.2C martensitic steels

This study challenged to improve the resistance against hydrogen embrittlement by increasing the concentration of carbon segregated at prior austenite grain boundary (PAGB), XPAGB, in low-carbon martensitic steels. The specimens with/without carbon segregation treatment (Non-seg and Seg specimens, respectively) had almost the same microstructure, other than higher XPAGB in the Seg specimen. While the uncharged Non-seg and Seg specimens exhibited similar mechanical properties, the maximum stress of the hydrogen-charged specimen was much higher in the Seg specimen than that in the Non-seg specimen even when diffusible hydrogen contents were almost the same. In addition, the fraction of intergranular fracture surface was much smaller in the Seg specimen. Based on these results, we conclude that the segregated carbon suppressed the accumulation of hydrogen around PAGB by site competition and increased cohesive energy of PAGB, leading to the significantly improved resistance against hydrogen-related intergranular fracture

Change of Deformation Mechanisms Leading to High Strength and Large Ductility in Mg-Zn-Zr-Ca Alloy with Fully Recrystallized Ultrafine Grained Microstructures

Recently, we have found that fully recrystallized ultrafine-grained (UFG) microstructures could be realized in a commercial precipitation-hardened Magnesium (Mg) alloy. The UFG specimens exhibited high strength and large ductility under tensile test, but underlying mechanisms for good mechanical properties remained unclear. In this study, we have carried out systematic observations of deformation microstructures for revealing the influence of grain size on the change of dominant deformation modes. We found that plastic deformation of conventionally coarse-grained specimen was predominated by {0001} slip and {10–12} twinning, and the quick decrease of work-hardening rate was mainly due to the early saturation of deformation twins. For the UFG specimens, {10–12} twinning was dramatically suppressed, while non-basal slip systems containing component of Burgers vector were activated, which contributed significantly to the enhanced work-hardening rate leading to high strength and large ductility. It was clarified by this study that limited ductility of hexagonal Mg alloys could be overcome by activating unusual slip systems ( dislocations) in fully recrystallized UFG microstructures

Regulation of Id2 expression by CCAAT/enhancer binding protein β

Mice deficient for Id2, a negative regulator of basic helix–loop–helix (bHLH) transcription factors, exhibit a defect in lactation due to impaired lobuloalveolar development during pregnancy, similar to the mice lacking the CCAAT enhancer binding protein (C/EBP) β. Here, we show that Id2 is a direct target of C/EBPβ. Translocation of C/EBPβ into the nucleus, which was achieved by using a system utilizing the fusion protein between C/EBPβ and the ligand-binding domain of the human estrogen receptor (C/EBPβ-ERT), demonstrated the rapid induction of endogenous Id2 expression. In reporter assays, transactivation of the Id2 promoter by C/EBPβ was observed and, among three potential C/EBPβ binding sites found in the 2.3 kb Id2 promoter region, the most proximal element was responsible for the transactivation. Electrophoretic mobility shift assay (EMSA) identified this element as a core sequence to which C/EBPβ binds. Chromatin immunoprecipitation (ChIP) furthermore confirmed the presence of C/EBPβ in the Id2 promoter region. Northern blotting showed that Id2 expression in C/EBPβ-deficient mammary glands was reduced at 10 days post coitus (d.p.c.), compared with that in wild-type mammary glands. Thus, our data demonstrate that Id2 is a direct target of C/EBPβ and provide insight into molecular mechanisms underlying mammary gland development during pregnancy

Destruction of mesoscopic chemically modulated domains in single phase high entropy alloy via plastic deformation

Chemically modulated mesoscopic domains in a fcc single phase CrMnFeCoNi equi-atomic high entropy alloy (HEA) are detected by small angle diffraction performed at a synchrotron radiation facility, whereas the mesoscopic domains cannot be detected by conventional X-ray diffraction and 2D mappings of energy dispersive X-ray spectroscopy by scanning electron microscopy and scanning transmission electron microscopy. The mesoscopic domains are deformed and shrieked, and finally destructed by plastic deformation, which is supported by the comprehensive observations/measurements, such as electrical resistivity, Vickers hardness, electron backscattering diffraction, and hard X-ray photoemission spectroscopy. The destruction of the mesoscopic domains causes the decrease in electrical resistivity via plastic deformation, so called K-effect, which is completely opposite to the normal trend of metals. We confirmed that the presence and the size of local chemical ordering or short-range order domains in the single phased HEA, and furthermore, Cr and Mn are related to form the domains

Immunohistochemical studies of PIVKA-II in hepatocellular carcinoma by indirect immunofluorescence

Tissue PIVKA-II was examined in 32 hepatocellular carcinomas and 2 metastatic liver tumors using indirect immunofluorescence, and the results were compared with the size, histological grading and serum PIVKA-II level. The specificity of this method was confirmed by the disappearance of reactivity in PLC/PRF/5 cells after the addition of vitamin K to the culture medium. Positive PIVKA-II staining was observed as a clustered or a single cell pattern only in the HCC nodules, but not in the surrounding cirrhotic tissue. PIVKA-II staining was observed in all HCC groups regardless of histological grade. There was no relationship between PIVKA-II staining and the size of HCC. PIVKA-II was detected immunohistochemically even in small HCC of patients whose plasma PIVKA-II levels were below the detection limit. These results suggest that PIVKA-II production is a specific phenotype of HCC regardless of its histological grading and demonstrate that this immunofluorescent PIVKA-II staining is more sensitive and useful than plasma PIVKA-II assay for the diagnosis of HCC.</p

Recombinant mouse cytochromes P1-450 and P3-450: enzymatic characterization of the hemoprotein expressed in human cells infected with recombinant vaccinia virus.

We expressed mouse cytochrome P1-450 and P3-450 using recombinant vaccinia virus gene expression system in HeLa cells that were devoid of significant basal levels of P-450. HeLa cells were infected with the recombinant vaccinia virus containing either mouse cytochrome P1-450 or P3-450 cDNA, and the cell lysates were analyzed for the kinetics of P-450 enzyme activity and protein expression at the same time. 7-Ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase activities were measured as an expression of the cytochrome P-450 enzyme activities. Both cell lines began to express these enzyme activities as early as 12h after infection. The activities increased linearly up to the 24 h time point, and were kept for 36 h. Western immunoblot analysis showed that these cytochrome P-450 proteins were detected at 16 h and reached maximum quantity at 24 h after infection. These data showed a good correlation between cytochrome P-450 enzyme activity and protein concentration throughout the process of P-450 gene expression by vaccinia virus vector, suggesting a complete formation of cytochrome P-450 holoenzyme from the early stage of the protein expression.</p

Influences of ventricular pacing on hemodynamics, myocardial metabolism, and cardiac work efficiency: potential risks of rate-responsive ventricular pacing.

The influences of ventricular pacing at a rate of 70 beats/min (bpm) on the systemic and coronary hemodynamics, myocardial metabolism, and cardiac work efficiency were evaluated in five patients with bradycardia. The results were compared to those obtained in six normal subjects at rest. In order to elucidate the effects of a relatively high rate of ventricular pacing, cardiovascular and metabolic variables were also obtained at 120 bpm in the normal subjects. It was observed that the patients eventually benefited from ventricular pacing at a rate of 70 bpm and improved in systemic hemodynamics. Although coronary hemodynamics and myocardial metabolism were accelerated, the cardiac work efficiency was not improved. A pacing rate of 120 bpm in the normal subjects did not appear to accelerate systemic hemodynamics, but adverse accelerations of coronary hemodynamics and myocardial metabolism were observed, and the cardiac work efficiency was remarkably reduced as a result. Our observations indicated that the coronary reserve capacity was very important for ventricular pacing, and suggested that an undue increment of the pacing rate not only might be meaningless but also might induce ischemic angina. Therefore, we should be cautious in using a rate-responsive pacing mode, particularly in determination of the upper limit of pacing rates, although many benefits with this pacing mode have recently been advocated.</p