シコク チュウオウブ セイブ カミドイ チイキ ト オダ チイキ ニオケル ミカブ リョクショク ガンルイ ノ チシツ コウゾウ

Geological structures of the Mikabu greenstones and northern margin of the Chichibu Terrain were studied in the Kamidoi and Oda Areas in Central to West Shikoku. It has been thought that the Mikabu greenstones did not occur in the Kamidoi and Nishi-ishihara Areas in Central Shikoku, because of the existence of the Nishi-ishihara and Ikegawa thrusts. This study, however, clarified that the Mikabu greenstones composed of tuff and tuff breccia occur in a narrow zone there. The Mikabu greenstones are intercalated in the Jurassic accretionary complex as a layered unit, and are folded by the Kamiyakawa-Ikegawa antiform. The Mikabu greenstones of the Oda Area are also intercalated in the Jurassic complex and form the Odagawa antiform, which is the same as the Kamiyakawa-Ikegawa antiform. There is no large thrusts along the southern margin of the Mikabu greenstones. The Jurassic complexes under the Mikabu greenstones of the Kamidoi and Oda Areas have undergone the pumpellyite-actinolite facies metamorphism, like as the Mikabu greenstones and the overlying Jurassic complex. The Kiyomizu Tectonic Line, which runs along the northern margin of the Mikabu greenstones, is probably a large fault, dividing the Sanbagawa Terrain from the Mikabu greenstones and the Nortner Chichibu Terrain

Cathepsin B-inhibitor promotes the development of Th1 type protective T cells in mice infected with Leishmania major

BALB/c mice are genetically susceptible to infection with Leishmania major (L. major). When such mice infected with L. major were treated with specific inhibitors of cathepsin B, a lysosomal cysteine protease that digests exogenous antigenic proteins, the mice acquired resistance against L. major infection. T cells from these mice produced large amounts of IFN-γ and low amounts of IL-4 as compared with those of untreated BALB/c mice. In addition, the mice treated with cathepsin B inhibitor produced a high titer of IgG2a specific antibodies and only low titers of IgG1 and IgE antibodies. This type of response is in contrast with the high specific IgG1 or IgE antibody responses which are the usual antibody responses in BALB/c mice infected with L. major. These findings indicate that cathepsin B may be critically involved in processing antigens of L. major to promote exclusively the development of Th2 type CD4+T cell responses

Molecular cloning of a cystatin from parasitic intestinal nematode, Nippostrongylus brasiliensis

A novel member of the cystatin family, nippocystatin (NbCys), was identified from excretory-secretory (ES)-products of a nematode Nippostrongylus brasiliensis, and the cDNA was cloned and sequenced. The mRNA of NbCys was confirmed to be expressed in both larvae and adults of the parasite. NbCys was translated as a proform with a single domain for secretion and was detected as a 14-kDa mature form in ES-products of the adult worm. Recombinant protein of NbCys profoundly inhibited the activity of cysteine proteases such as cathepsin L and B, but not that of cathepsin D, an aspartic protease. Furthermore, the ES-products had also been confirmed to inhibit cysteine proteases. Taken together, NbCys may play a role in evasion of N. brasiliensis from host defense systems, since cysteine proteases are known to participate in immune systems of infected hosts

シコク チュウオウブ イノ チイキ ニオケル チチブタイ ホクタイ ノ ナノカワ ショウジョウ ダンソウ シュウヘン ノ チシツ コウゾウ

The Nanokawa thrust occurs in the Jurassic accretionary complexes of the Northern Chichibu Terrain in the Ino Area， Central Shikoku. Along the thrust，greenstones and pelitic semi-schists are thrust over chaotic formations，sandstones and greenstones. The strata of the hanging wall of the thrust dip gently and are slightly folded，whereas those of the footwall dip steeply to the north. Metamorphic minerals of the greenstones of the hanging wall and footwall of the Nanokawa thrust are examined. The greenstones of the hanging wall contain alkali amphibole， alkali pyroxene， stilpnomelane and pumpellyite， and have undergone the pumpellyite-actinolite facies metamorphism. On the other hand， those of the footwall contain prehnite and pumpellyite， and have undergone the prehnite-pumpellyite facies metamorphism. The Nanokawa thrust is a large overthrust， which has a different metamorphic grade between the hanging wall and footwall. The Nanokawa thrust， which runs to the north of Shirakidani limestone body in Central Shikoku， and to the north of the Torigatayama limestone body in Middle West Shikoku， is probably a southern boundary of the Jurassic accretionary deposits which have undergone the Sambagawa Metamorphism

Notch controls the number of intraepithelial TCRαβ+CD8αα+ T cells

Intestinal intraepithelial lymphocytes (IELs) expressing CD8αα on αβ T cells (TCRαβ+CD8αα+ IELs) have suppressive capabilities in enterocolitis, but the mechanism that maintains homeostasis and cell number is not fully understood. Here, we demonstrated that the number of TCRαβ+CD8αα+ IELs was severely reduced in mice lacking recombination signal binding protein for immunoglobulin kappa J region (Rbpj) or Notch1 and Notch2 in T cells. Rbpj-deficient TCRαβ+CD8αα+ IELs expressed low levels of Atp8a2, which encodes a protein with flippase activity that regulates phospholipid asymmetry of plasma membrane such as flipping phosphatidylserine in the inner leaflet of plasma membrane. Rbpj-deficient TCRαβ+CD8αα+ IELs cannot maintain phosphatidylserine in the inner leaflet of the plasma membrane. Furthermore, depletion of intestinal macrophages restored TCRαβ+CD8αα+ IELs in Rbpj-deficient mice, suggesting that exposure of phosphatidylserine on the plasma membrane in Rbpj-deficient TCRαβ+CD8αα+ IELs acts as an “eat-me” signal. Together, these results revealed that Notch–Atp8a2 is a fundamental regulator for IELs and highlighted that membrane phospholipid asymmetry controlled by Notch-mediated flippase expression is a critical determinant in setting or balancing the number of TCRαβ+CD8αα+ IELs

High phosphate diet reduces atherosclerosis formation in apolipoprotein E-deficient mice

Although higher serum phosphate level is a risk factor for cardiovascular diseases in general population as well as chronic kidney disease patients, it has not been clarified whether higher phosphate can affect atherosclerotic plaque formation. In this study, we investigated the effect of prolonged-intake of different concentrations of phosphate on atherosclerosis formation using apolipoprotein E-deficient mice. Apolipoprotein E-deficient mice were fed with high fat diet including 0.6%, 1.2% or 1.8% phosphate. After 20-week treatment, atherosclerotic plaque formation in aorta in 1.8% phosphate diet group was unexpectedly less than that in the other groups. To elucidate mechanisms of suppression of plaque formation by high phosphate diet, we hypothesized that high phosphate diet may modify a profile of monocytes/macrophages suppressing plaque formation. We confirmed that elevated peripheral monocytes (CD11b+, F4/80+ cell numbers) in apolipoprotein E-deficient mice were decreased by feeding with 1.8% P diet. In addition, ex vivo study indicated that high dose of phosphate induced macrophage apoptosis. These observations suggest that excess phosphate intake decreased atherosclerosis formation, at least in part, by changing the profile of peripheral monocytes or inducing apoptosis of macrophages in apolipoprotein E-deficient mice

CD98 and T Cell Activation

Upon their recognition of antigens presented by the MHC, T cell proliferation is vital for clonal expansion and the acquisition of effector functions, which are essential for mounting adaptive immune responses. The CD98 heavy chain (CD98hc, Slc3a2) plays a crucial role in the proliferation of both CD4+ and CD8+ T cells, although it is unclear if CD98hc directly regulates the T cell effector functions that are not linked with T cell proliferation in vivo. Here, we demonstrate that CD98hc is required for both CD4+ T cell proliferation and Th1 functional differentiation. T cell-specific deletion of CD98hc did not affect T cell development in the thymus. CD98hc-deficient CD4+ T cells proliferated in vivo more slowly as compared with control T cells. C57BL/6 mice lacking CD98hc in their CD4+ T cells could not control Leishmania major infections due to lowered IFN-γ production, even with massive CD4+ T cell proliferation. CD98hc-deficient CD4+ T cells exhibited lower IFN-γ production compared with wild-type T cells, even when comparing IFN-γ expression in cells that underwent the same number of cell divisions. Therefore, these data indicate that CD98hc is required for CD4+ T cell expansion and functional Th1 differentiation in vivo, and suggest that CD98hc might be a good target for treating Th1-mediated immune disorders

Role of innate immune cells in protection against Toxoplasma gondii at inflamed site

The intraperitoneal infection with Toxoplasma gondii (T. gondii) caused accumulation of γδ T, NK, NK1.1+T-like (NKT) cells at inflamed sites. To clarify the roles of these cells in protection against T. gondii at the inflamed sites, BALB/c mice were depleted of γδ T, NK, NK and NKT cells by treatment with antibody against TCR-γδ, asialoGM1 or Interleukin-2 receptor β-chain (IL-2Rβ), respectively, prior to infection. Mice treated with anti-TCR-γδ monoclonal antibody (mAb) became more susceptible to infection, whereas mice treated with anti-IL-2Rβ mAb acquired resistance. Treatment with anti-asialoGM1 Ab showed no effect. We previously reported that heat shock protein 65 (HSP65) in macrophages induced by γδ T cells plays an essential role in protective immunity against T. gondii infection, by preventing apoptotic death of infected macrophages. In the present study, we showed that treatment with anti-IL-2Rβ mAb, but not with anti-asialoGM1 Ab, enhanced the HSP65 induction in macrophages, and inhibited Interleukin-4 (IL-4) expression in nonadherent peritoneal exudate cells. Furthermore, neutralization of endogenous IL-4 by anti-IL-4 mAb enhanced the HSP65 induction in macrophages. These findings suggest that NKT cells, but not NK cells, negatively regulate the protective immunity against T. gondii infection possibly by producing IL-4and suppressing HSP65 induction

Tumour blood vessel normalisation by prolyl hydroxylase inhibitor repaired sensitivity to chemotherapy in a tumour mouse model

Blood vessels are important tissue structures that deliver oxygen and nutrition. In tumour tissue, abnormal blood vessels, which are hyperpermeable and immature, are often formed; these tissues also have irregular vascularisation and intravasation. This situation leads to hypoperfusion in tumour tissue along with low oxygen and nutrition depletion; this is also called the tumour microenvironment and is characterised by hypoxia, depleted nutrition, low pH and high interstitial pressure. This environment induces resistance to anticancer drugs, which causes an increase in anticancer drug doses, leading to increased side effects. We hypothesised that normalised tumour blood vessels would improve tumour tissue perfusion, resupply nutrition and re-oxygenate the tumour tissue. Chemotherapy would then be more effective and cause a decrease in anticancer drug doses. Here we report a neovascularisation-inducing drug that improved tumour vascular abnormalities, such as low blood flow, blood leakage and abnormal vessel structure. These results could lead to not only an increased chemo-sensitivity and tissue-drug distribution but also an up-regulated efficiency for cancer chemotherapy. This suggests that tumour blood vessel normalisation therapy accompanied by angiogenesis may be a novel strategy for cancer therapy