Immunosuppressive effect of bactobolamine on in vitro lymphocyte alloactivation: synergism with cyclosporine.
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Benzopyrans↗
Biomedical subjects
Y Nishimura
Publications and source records attributed to Y Nishimura.
Structural genomics projects in Japan.
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Cell-Free System↗
Accelerated tissue regeneration through incorporation of basic fibroblast growth factor-impregnated gelatin microspheres into artificial dermis.
The objective of this study was to evaluate the effect of incorporation of basic fibroblast growth factor (bFGF)-impregnated gelatin microspheres into an artificial dermis on the regeneration of dermis-like tissues. When used in the free form in vivo, bFGF cannot induce sufficient wound healing activity, because of its short half-life. Therefore, sustained release of bFGF was achieved by impregnation into biodegradable gelatin microspheres. A radioisotope study revealed that incorporation of bFGF-impregnated gelatin microspheres significantly prolonged in vivo retention of bFGF in the artificial dermis. Artificial dermis with incorporated bFGF-impregnated gelatin microspheres or bFGF in solution was implanted into full-thickness skin defects on the back of guinea pigs (1.5 cm x 1.5 cm) (n = 4). Incorporation of bFGF into the artificial dermis accelerated fibroblast proliferation and capillary formation in a dose-dependent manner. However, the accelerated effects were more significant with the incorporation of bFGF-impregnated gelatin microspheres than with free bFGF at doses of 50 microg or higher. We conclude that the gelatin microsphere is a promising tool to accelerate bFGF-induced tissue regeneration in artificial dermis.
Animals↗
Efficient expression of the envelope protein of feline immunodeficiency virus in a recombinant feline herpesvirus type 1 (FHV-1) using the gC promoter of FHV-1.
We constructed two recombinant feline herpesvirus type 1 (FHV-1) expressing the envelope (Env) protein of feline immunodeficiency virus (FIV). One recombinant, designated dlTK-env, has the whole FIV env gene inserted at a thymidine kinase (TK) deletion site. The second recombinant, designated dlTK(gCp)-env, has a cassette containing a partial FIV env gene fused with the signal sequence of the gC protein of FHV-1 (under the control of the gC promoter) inserted at the same site. Growth kinetics of both the recombinants in Crandell feline kidney (CRFK) cells were similar to that of the parent strain of FHV-1. By indirect immunofluorescence assays and immunoblot analyses, we confirmed the expression of the FIV Env protein in CRFK cells infected with both recombinants. Enzyme-linked immunosorbent assays showed that the maximum Env expression level achieved by dlTK(gCp)-env was more than four times higher than that observed for dlTK-env. Flow cytometric analyses revealed that the Env protein produced by both recombinants was efficiently expressed on the cell surface. The dlTK(gCp)-env reported here may thus be a promising candidate for a live recombinant vaccine to protect against FIV infection.
Animals↗
Analysis of T cell responses to the beta 2-glycoprotein I-derived peptide library in patients with anti-beta 2-glycoprotein I antibody-associated autoimmunity.
Antiphospholipid syndrome (APS) is an autoimmune disease that accompanies anti-phospholipid antibodies measured as either anti-cardiolipin antibodies (aCL) or lupus anticoagulant. beta(2)-glycoprotein I (beta(2)GPI) is the most common and apparently the best-characterized antigenic target for aCL. To investigate T-cell responses to beta(2)GPI, we stimulated PBMC of 18 APS or systemic lupus erythematosus (SLE) patients carrying anti-beta(2)GPI and 10 healthy controls, using a peptide library covering the beta(2)GPI sequence. We established seven CD4(+) T cell lines reactive with beta(2)GPI peptide. Three of four epitopes for patient-derived T cell lines were p244-264, whereas one T cell line from a control subject also recognized p244-264. Furthermore, there was no tendency for particular HLA class II molecules to present beta(2)GPI peptides. However, cytokine producing patterns were significantly different between T cell lines from patients and those from healthy individuals (p =.028); patients' T cells tend to exhibit higher IL-4 and lower IFN-gamma responses. These T cell lines did not react to beta(2)GPI purified from human plasma. These results indicate that beta(2)GPI-reactive CD4(+) T cells of APS/SLE patients mainly recognize cryptic p244-264 in the context of various HLA class II molecules, and exhibit Th0-Th2-type responses. Our findings may provide a clue to the pathogenesis of APS.
Adult↗
Persistent hypoglossal artery associated with arteriovenous malformation: a case report.
A rare case of persistent hypoglossal artery in conjunction with arteriovenous malformation was presented. MRA could delineate persistent hypoglossal artery and arteriovenous malformation very clearly. The patient suffered from intracranial hemorrhage from in the 37th week of pregnancy. MRI, MRA, angiography, and CT of this rare condition are reported.
Adult↗
A case of Marchiafava-Bignami disease: MRI findings on spin-echo and fluid attenuated inversion recovery (FLAIR) images.
Marchiafava-Bignami disease (MBD) was diagnosed in a 56-year-old man. Spin-echo (SE) magnetic resonance imaging (MRI) at the acute phase showed normal signal areas in the central layer of the corpus callosum (CC), although the intensity of these areas revealed abnormal hyperintensity on fluid attenuated inversion recovery (FLAIR). On follow-up SE MRI at the late phase, the central layer of the CC showed fluid-like intensity. On FLAIR MRI, the lesions of the CC turned into hypointense cores surrounded by hyperintense rims indicating central necrosis and peripheral demyelination. Degenerative changes of the CC in MBD were clearly demonstrated by FLAIR MRI.
Alcoholism↗
gem-diamine 1-N-iminosugars of L-fucose-type, the extremely potent L-fucosidase inhibitors.
An efficient route from D-ribono-gamma-lactone to gem-diamine 1-N-iminosugars of L-fucose-type, a new family of glycosidase inhibitor, has been developed in a formation of a gem-diamine 1-N-iminopyranose ring by the Mitsunobu reaction of an aminal as a key step. The analogues were proved to be the extremely potent inhibitors against alpha-L-fucosidase (IC50 approximately 3 ng mL(-1), Ki approximately 5 x 10(-9) M). The present study has shown that a cyclic methanediamine generated in media affects glycosidases as a real active-form of the gem-diamine 1-N-iminosugars of L-fucose-type.
Carbohydrate Sequence↗
Both the HLA-CPB1 and -DRB1 alleles correlate with risk for multiple sclerosis in Japanese: clinical phenotypes and gender as important factors.
The purpose of this study was to clarify the association of HLA-DRB1 and -DPB1 alleles with multiple sclerosis (MS) in Japanese, to determine whether optico-spinal MS (OS-MS) and conventional MS are immunogenetically distinct, and to verify the role of gender difference in HLA associations of MS. We studied HLA-DRB1 and -DPB1 polymorphisms in 166 Japanese patients with MS. Forty-seven patients were classified as having the optico-spinal MS (OS-MS) and 119 as having conventional MS. A lack of DPB1*0301 and a higher frequency of DPB1*0501 compared with controls (corrected P<0.0074; odds ratio=9.48) were found in OS-MS. By contrast, we found for the first time an association of DPB1*0301 with conventional MS in Japanese (corrected P=0.0444; odds ratio=3.28). Logistic analysis, adjusted for sex and age, revealed independent associations of DPB1*0301 (P=0.0004, adjusted odds ratio (aOR)=4.70), DPB1*0501 (P=0.0081, aOR= 2.50) and DRB1*1501 (P=0.0252, aOR=2.21) with conventional MS. However, the frequencies of DRB1*1501 and DPB1*0501 in male patients with conventional MS were equal to those in male controls while the DPB1*0301 frequency was increased in both male and female patients. We did not find any association of these HLA alleles with disease course and severity. In conclusion, OS-MS is a DPB1*0501-associated distinct subtype of MS, and DPB1*0301 is the most strongly associated allele with conventional MS in Japanese. In addition, gender plays an important role in HLA association with MS.
Alleles↗
Structural genomics projects in Japan.
Two major structural genomics projects exist in Japan. The oldest, the RIKEN Structural Genomics Initiative, has two major goals: to determine bacterial, mammalian, and plant protein structures by X-ray crystallography and NMR spectroscopy and to perform functional analyses with the target proteins. The newest, the structural genomics project at the Biological Information Research Center, focuses on human membrane proteins.
Animals↗
Ordering of ceramide formation, caspase activation, and Bax/Bcl-2 expression during etoposide-induced apoptosis in C6 glioma cells.
Etoposide (VP-16) a topoisomerase II inhibitor induces apoptosis of tumor cells. The present study was designed to elucidate the mechanisms of etoposide-induced apoptosis in C6 glioma cells. Etoposide induced increased formation of ceramide from sphingomyelin and release of mitochondrial cytochrome c followed by activation of caspase-9 and caspase-3, but not caspase-1. In addition, exposure of cells to etoposide resulted in decreased expression of Bcl-2 with reciprocal increase in Bax protein. z-VAD.FMK, a broad spectrum caspase inhibitor, failed to suppress the etoposide-induced ceramide formation and change of the Bax/Bcl-2 ratio, although it did inhibit etoposide-induced death of C6 cells. Reduced glutathione or N-acetylcysteine, which could reduce ceramide formation by inhibiting sphingomyelinase activity, prevented C6 cells from etoposide-induced apoptosis through blockage of caspase-3 activation and change of the Bax/Bcl-2 ratio. In contrast, the increase in ceramide level by an inhibitor of ceramide glucosyltransferase-1, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol caused elevation of the Bax/Bcl-2 ratio and potentiation of caspase-3 activation, thereby resulting in enhancement of etoposide-induced apoptosis. Furthermore, cell-permeable exogenous ceramides (C2- and C6-ceramide) induced downregulation of Bcl-2, leading to an increase in the Bax/Bcl-2 ratio and subsequent activation of caspases-9 and -3. Taken together, these results suggest that ceramide may function as a mediator of etoposide-induced apoptosis of C6 glioma cells, which induces increase in the Bax/Bcl-2 ratio followed by release of cytochrome c leading to caspases-9 and -3 activation.
Animals↗
Molecular cloning and sequencing of a cDNA encoding the feline cytotoxic T-lymphocyte-associated protein 4 (CTLA4) homologue.
The feline CTLA4 cDNA encodes a transmembrane protein which shares 87.9% sequence identity with the human CTLA4 molecule. The cytoplasmic region of the feline CTLA4 is identical to that of humans and mice, which suggests conserved function(s) such as the regulation of cell-surface expression of this molecule.
Abatacept↗
Transcriptional and post-transcriptional regulation of monocyte chemoattractant protein-3 gene expression in human endothelial cells by phorbol ester and cAMP signalling.
Monocyte chemoattractant protein-3 (MCP-3) is one of the most broadly active chemokines, potentially inducing chemotaxis of all leucocytic cells. In the present study, we examined the regulation of MCP-3 mRNA and protein production in endothelial cells by protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA) and cAMP signalling. On stimulation of endothelial cells with 10 nM PMA, MCP-3 mRNA increased to 300-fold the basal level at 3 hr and rapidly declined to 0.2-fold the basal level at 24 hr. PMA-induced MCP-3 mRNA and protein production of human endothelial cells were partially inhibited by pretreatment with the adenylate cyclase activator, forskolin, or membrane-permeable cAMP derivative. The PMA-induced MCP-3 mRNA increase was almost abrogated when cells were pretreated with cycloheximide (CHX). Forskolin inhibited the transcription of PMA-induced MCP-3 gene expression. Following PMA stimulation for 3 hr, subsequent addition of actinomycin D suppressed the rapid decay of PMA-induced MCP-3 mRNA. These results suggest that PMA induces the transcriptional activation of the MCP-3 gene through de novo protein synthesis and the rapid decay of PMA-induced MCP-3 mRNA through de novo synthesis of adenosine/uridine (AU)-rich element binding proteins and cAMP signalling inhibits the PMA-induced transcriptional activation of the MCP-3 gene expression.
Adenylyl Cyclases↗
Fine specificity of T cells reactive to human PDC-E2 163-176 peptide, the immunodominant autoantigen in primary biliary cirrhosis: implications for molecular mimicry and cross-recognition among mitochondrial autoantigens.
The anti-mitochondrial antibody response in primary biliary cirrhosis (PBC) is primarily directed at E2 components of PDC, OGDC, and BCOADC, and E3BP. Previous work has shown that the immunodominant autoreactive T- cell epitope is the PDC-E2 163-176 peptide, restricted by HLA DR53. To address molecular mimicry and cross-recognition among mitochondrial autoantigens, we analyzed reactivity, including agonism and antagonism assays, to a series of single amino acid-substituted peptides using cloned T-cell lines in PBC and controls. Interestingly, fine specificities were unique for every single T-cell clone, but the clones could be categorized into two distinct groups based on recognition motifs of the T-cell receptor (TCR) ligand: group A (170)ExDK(173) and group B (168)EIExD(172). (170)E is the most critical TCR contact residue for both groups of cloned T-cell lines, whereas (173)K and (168)E are the critical TCR contact residues for group A and group B cloned T-cell lines, respectively. More importantly, some group A-cloned T-cell lines cross-reacted to human E3BP 34-47, human OGDC-E2 100-113, and several peptides derived from various microbial proteins carrying an ExDK motif, whereas group B-cloned T-cell lines reacted only to E3BP 34-47 carrying an EIExD motif. Furthermore, an RGxG motif was exclusively found in the complementarity-determining region (CDR3) of the TCR Vbeta in the group B-cloned T-cell lines, while G, S, and/or R were frequently found in the CDR3 of the TCR Vbeta in the group A-cloned T-cell lines. These data provide a framework for understanding molecular mimicry among mitochondrial antigens.
Amino Acid Sequence↗
Long-term follow-up study of artificial dermis composed of outer silicone layer and inner collagen sponge.
In the oriental population including the Japanese, donor-site hypertrophy is more pronounced than in Caucasians. To solve the problem of donor-site morbidity and to ensure graft 'take', we started the second-stage procedure of a thin split thickness skin graft (STSG) onto acellular 'bilayer artificial skin', or 'artificial dermis'. Since reporting the original version of the material (OV), a revised version (RV) and the present version (PV, Pelnac) have been developed in stages to eliminate inconveniences associated with its use and to reduce the primary cost of manufacture. We have now used our materials, consisting of OV, RV and PV, on 52 skin defects in 41 patients. STSG took almost perfectly in all patients. The long-term results of these three materials were investigated in 20 patients who had been followed up for more than 2 years, excluding three patients whose donor sites had been directly closed. The longest and the mean follow-up periods of these patients were 12 years 5 months and 6 years 10 months, respectively. At the grafted sites, wrinkles caused by shrinkage, partial depigmentation and hypertrophy were observed in five (25%), one (5%) and one (5%) of the 20 patients, respectively. At the donor sites, slight unsightliness was observed in five (25%) of the 20 patients. Excellent or good results were obtained in 18 (90%) of the 20 patients in comprehensive evaluation. There were no significant differences in the long-term follow-up evaluations among these materials. In conclusion, the long-term postoperative appearance of the STSG site was good though a very thin (approximately 0.2mm) STSG is used; scarring of the donor site was minimal and it was possible to take repeated skin grafts from the same donor site.
Adolescent↗
Expression of cyclooxygenase-2 and nitrotyrosine in human gastric mucosa before and after Helicobacter pylori eradication.
To determine whether cure of Helicobacter pylori infection influences the expression of COX-2 and nitrotyrosine in the distal stomach of humans, biopsy specimens were examined immunohistochemically. H. pylori infection was determined using a rapid urease test, culture and histology. Positive staining of COX-2/nitrotyrosine in the epithelium was expressed as the percentage of stained cells to the total epithelial cells. There was a significant increase in COX-2/nitrotyrosine staining in H. pylori -positive subjects compared with H. pylori -negative subjects. Cure of the infection resulted in a significant decrease in both COX-2/nitrotyrosine staining in all patients (52.1+/-12.1% vs 15. 4+/-7.2%, P<0.001; and 57.3+/-13.6% vs 36.1+/-18.0%, P<0.01, respectively). However, immunoreactivity of COX-2/nitrotyrosine was observed in all cases with intestinal metaplasia even after the cure of H. pylori infection.Thus, cure of H. pylori infection may decrease the risk of gastric carcinogenesis due to COX-2 and NO-related compounds in gastric mucosa but not in those patients with intestinal metaplasia.
Adult↗
Diagnostic utility of CSF soluble CD27 for primary central nervous system lymphoma in immunocompetent patients.
The aim of this study is to determine the diagnostic utility of cerebrospinal fluid (CSF) soluble CD27 (sCD27) as a tumor marker for primary central nervous system lymphoma (PCNSL) in immunocompetent patients. A total of 93 CSF samples were collected from the following four patient groups: the PCNSL group, 13 patients (26 samples) with PCNSL, 12 samples obtained at initial diagnosis, 10 during therapy, four at complete remission; the other brain tumors (OBT) group, 30 patients (30 samples) with other brain tumors; the other neurological diseases (OND) group, 25 (25 samples) with other neurological diseases; the inflammatory neurological diseases (IND) group, 12 patients (12 samples) with inflammatory neurological diseases. sCD27 levels were determined by sandwich enzyme-linked immunosorbent assay. The optimal cut-off value was found to be 15 U ml-1. The CSF sCD27 levels were over 15 U ml-1 in 23 of the 26 PCNSL samples and were significantly higher than those in the OBT and OND groups in which all samples were below 15 U ml-1. Elevated CSF sCD27 levels were also observed in 11 of 12 IND samples. In the two PCNSL patients whose CSF sCD27 levels were studied longitudinally, the sCD27 levels correlated very well with remission and relapse of the disease. CSF sCD27 is useful as a tumor marker for PCNSL in immunocompetent patients, and is also useful to evaluate the effect of various types of treatment. Although there was a large cross-reactivity in the CSF sCD27 levels between PCNSL and IND group, white blood cell count in the CSF is helpful to distinguish these two diseases.
Adult↗
Activation of caspase-9 and -3 during H2O2-induced apoptosis of PC12 cells independent of ceramide formation.
The treatment of PC12 cells with H2O2 (100-500 microM) resulted in typical apoptotic changes including fragmentation and condensation of nuclei, and DNA fragmentation observed as DNA ladder. H2O2-induced apoptosis was associated with activation of caspase-3 as assessed by cleavage of specific fluorogenic substrate peptide and processing of procaspase-3 and poly(ADP-ribose) polymerase. However, formation of ceramide, which often locates upstream of caspase-3, was not observed. The inhibitory peptide relatively specific for caspase-3, z-DEVD-FMK and non-selective caspase inhibitor z-VAD-FMK inhibited activation of caspase-3 and apoptotic cell death. However, the relatively specific inhibitors, Ac-YVKD for caspase-1 and Ac-IETD for caspase-8/6, did not affect the occurrence of apoptotic cell death. As an upstream activation of caspase-3, induction of cytochrome c release followed by processing of procaspase-9 was observed by Western blotting, although the formation of intracellular ceramide was not observed. On the other hand, in PC12 cells overexpressing Bcl-2, the number of apoptotic cells was markedly decreased and activation of both caspases-9 and -3 was prevented. These results suggest that cytochrome c and caspase-9 initiate the activation of executor caspase-3 in H2O2-treated PC12 cells, and that Bcl-2 inhibits H2O2-induced release of cytochrome c from mitochondria and then proteolytic processing of procaspase-9.
Animals↗