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R Suzuki

Publications and source records attributed to R Suzuki.

At least 217 records · Page 12Linked to original sources
PubMed1999

Molecular cloning of mXCR1, the murine SCM-1/lymphotactin receptor.

Single C motif-1 (SCM-1)/lymphotactin is a C-type member of the chemokine superfamily. Previously, we identified its specific receptor XCR1. Here we isolated the murine homologue of XCR1 (mXCR1). To demonstrate its biological activity, we produced recombinant mouse SCM-1 by the baculovirus expression system. B300-19 murine pre-B cells expressing mXCR1 responded to mSCM-1 in chemotactic and calcium-mobilization assays. mXCR1 mRNA was weakly expressed in spleen and lung of normal C57BL/6 mice. In spleen, CD8+ cells and NK1.1+ cells were found to express mXCR1. Identification of mXCR1 will now allow us to study the role of this unique cytokine system in the mouse models of inflammation and immunity.

Amino Acid Sequence↗
PubMed1999

Direct neurite-mast cell communication in vitro occurs via the neuropeptide substance P.

Communication between nerves and mast cells is a prototypic demonstration of neuroimmune interaction. However, whether mast cell activation occurs as a direct response to neuronal activation or requires an intermediary cell is unclear. Addressing this issue, we used an in vitro coculture approach comprising cultured murine superior cervical ganglia and rat leukemia basophilic cells (RBLs; possesses properties of mucosal-type mast cells). Following loading with the calcium fluorophore, Fluo-3, neurite-RBL units (separated by <50 nm) were examined by confocal laser scanning microscopy. Addition of bradykinin, or scorpion venom, dose-dependently elicited neurite activation (i.e., Ca2+ mobilization) and, after a lag period, RBL Ca2+ mobilization. Neither bradykinin nor scorpion venom had any direct effect on the RBLs in the absence of neurites. Addition of a neutralizing substance P Ab or a neurokinin (NK)-1 receptor antagonist, but not an NK-2 receptor antagonist, dose-dependently prevented the RBL activation that resulted as a consequence of neural activation by either bradykinin or scorpion venom. These data illustrate that nerve-mast cell cross-talk can occur in the absence of an intermediary transducing cell and that the neuropeptide substance P, operating via NK-1 receptors, is an important mediator of this communication. Our findings have implications for the neuroimmune signaling cascades that are likely to occur during airways inflammation, intestinal hypersensitivity, and other conditions in which mast cells feature.

Animals↗
PubMed1999

Involvement of distinct cellular compartments in the abnormal lymphoid organogenesis in lymphotoxin-alpha-deficient mice and alymphoplasia (aly) mice defined by the chimeric analysis.

Both lymphotoxin-alpha (LTalpha)-deficient mice and alymphoplasia (aly) mice, a natural mutant strain, manifest a quite similar phenotype: lack of lymph nodes (LN) and Peyer's patches (PP), with disturbed spleen architecture. The mechanisms underlying the defective lymphoid organogenesis in these mice were investigated by generating aggregation chimeras; ex vivo fused morulae were implanted into pseudo-pregnant host females and allowed to develop to term. Chimeric mice between LTalpha-deficient mice and wild-type mice restored LN and PP almost completely, suggesting that LTalpha expressed by circulating bone marrow-derived cells is essential for lymphoid organogenesis as well as for organization of spleen architecture. By contrast, chimeric mice between aly mice and wild-type mice showed only limited restoration of LN and PP. This suggests that the putative aly gene product does not act as a circulating ligand for lymphoid organogenesis, like LTalpha. Rather, abnormal development of lymphoid organs in aly mice seems most likely due to the defective development of the incipient stromal cells of the LN and PP. Supporting this hypothesis, up-regulation of VCAM-1 on aly mouse embryonic fibroblasts by signals through LTbetaR, which is exclusively expressed by nonlymphoid cells, was disturbed. These studies demonstrate that LTalpha and the putative aly gene product together control lymphoid organogenesis with a close mechanistic relationship in their biochemical pathways through governing the distinct cellular compartments, the former acting as a circulating ligand and the latter as a LTbetaR-signaling molecule expressed by the stroma of the lymphoid organs.

Animals↗
PubMed1999

Localization of mRNA for Dri 42, subtype 2b of phosphatidic acid phosphatase, in the rat brain during development.

The expression of a gene termed Dri 42, a differentiation-related gene originally identified from intestine and a gene encoding phosphatidic acid phosphatase 2b isoform, was localized in developing and matured rat brains by in situ hybridization histochemical analysis. The gene expression was dominant in the ventricular germinal zone without significant expression in the intermediate, mantle and marginal zones throughout embryonic brain and spinal cord. The dominant expression in the ventricular germinal zone was maintained at P0 and P7, but it markedly decreased at later postnatal stages, while persistently high expression was detected in Bergmann glial cells of the cerebellar Purkinje cell layer throughout the postnatal development.

Animals↗
PubMed1999

Establishment of an inducible expression system of chimeric MLL-LTG9 protein and inhibition of Hox a7, Hox b7 and Hox c9 expression by MLL-LTG9 in 32Dcl3 cells.

The MLL (HRX/ALL-1 gene is frequently disrupted in infantile leukemias and therapy-related leukemias and fused to various translocation partner genes. We previously showed that chimeric MLL proteins localize in the nuclei in a fashion similar to that of MLL protein even if the partner gene encodes a cytoplasmic protein and indicated the importance of the N-terminal portion of MLL common to various MLL translocations. This time we established an inducible expression system for chimeric MLL-LTG9 and truncated N-terminal MLL proteins (MLL-Zf(-)) in 32Dcl3 cells. By utilizing this system, we were able to show inhibition of Hox a7, Hox b7 and Hox c9 genes' expression by induced MLL-LTG9 and MLL-Zf(-). Up-regulation of Hox a7, Hox b7 and Hox c9 was observed when 32Dcl3 cells were cultured with granulocyte colony stimulating factor (G-CSF) in place of interleukin 3 and induction of MLL-LTG9 and MLL-Zf(-) was shown to suppress this upregulation. At the same time, expression of two mammalian Polycomb group genes, M33 and mel-18, which both reportedly affect Hox genes' expression, was not inhibited by MLL-LTG9 and MLL-Zf(-) induction. These results indicate that MLL has an important effect on the expression of at least some Hox genes in hematopoietic cells and suggest that inhibition of the proper expression of Hox genes by chimeric MLL proteins may dysregulate hematopoietic cell differentiation and proliferation, which then can lead to leukemogenesis.

Cell Differentiation↗
PubMed1999

Establishment and characterization of nurse cell-like stromal cell lines from synovial tissues of patients with rheumatoid arthritis.

OBJECTIVE: To investigate the features of synovial stromal cells established from patients with rheumatoid arthritis (RA), and to define these cells as nurse cells. METHODS: Synovial nurse-like stromal cell lines (RA-SNCs) were established from patients with RA. These cell lines were examined for morphology, pseudoemperipolesis activity, cell surface markers, and cytokine production. The interaction between these RA-SNCs and a synovial tissue B cell clone was also examined. RESULTS: RA-SNCs had nurse cell activity. They spontaneously produced interleukin-6 (IL-6), IL-8, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor. Furthermore, they produced IL-1beta and tumor necrosis factor alpha and expressed higher levels of the other cytokines after coculture with the B cell clone. Proliferation and Ig production by the B cell clone were dependent on direct contact with RA-SNCs. CONCLUSION: These results indicate that the RA-SNCs were nurse cells. The findings suggest that RA-SNCs may play an important role in the pathogenesis of RA by producing large amounts of cytokines and maintaining infiltrating lymphocytes.

Antibodies, Monoclonal↗
PubMed1999

Time course of activated coagulation time at various sites during continuous haemodiafiltration using nafamostat mesilate.

OBJECTIVE: To determine the adequate site of activated coagulation time (ACT) measurement during continuous haemodiafiltration (CHDF) using nafamostat mesilate. DESIGN: Prospective, consecutive, clinical study. SETTING: An intensive care unit of a general hospital. PATIENTS: Ten patients with acute organ failure including kidney, lung and liver, caused by sepsis after major surgery. INTERVENTIONS: A CHDF circuit with a haemofilter made of polymethylmethacrylate membrane was primed with 50 mg nafamostat in 500 ml saline, and was started at a circuit flow rate of 100 ml/min. Continuous injection of 0.5 mg/kg per h nafamostat, 700 ml/h of dialysis fluid and 1000 ml/h of filtrate fluid was set. MEASUREMENTS AND RESULTS: The circuit pressure at the inlet and outlet of the circuit were monitored, and ACT was measured every 2 h at the site of nafamostat injection, outlet, patient's artery and inlet until 24 h. A value of standard deviation of ACT at each site was regarded as the variation value of ACT. The circuit pressure did not change significantly. The ACT did not change significantly at any measurement site. The variation value of ACT at the inlet of the circuit was significantly lower than that at the site of nafamostat injection. CONCLUSIONS: The ACT value at the inlet of the circuit may be adequate to monitor anticoagulation during CHDF using nafamostat.

Aged↗
PubMed1999

Graphic analysis of microscopic tumor cell infiltration, proliferative potential, and vascular endothelial growth factor expression in an autopsy brain with glioblastoma.

BACKGROUND: Growth of brain tumors requires tumor-cell attachment to adjacent structures, degradation of surrounding matrixes, migration of tumor cells, proliferation of vasculature, and tumor cell proliferation. Comparison of the findings on neuroimaging, degrees and patterns of tumor invasion, regional tumor cell viability detected by Ki-67 immunohistochemistry, and regional vascular endothelial growth factor (VEGF) expression in whole-brain specimen of glioblastoma therefore is of great interest, and will facilitate study of the host reaction against the glioblastoma. METHODS: We graphically analyzed microscopic tumor-cell infiltration, regional differences in Ki-67 labeling indices (LI), and immunohistochemical expression of VEGF in an autopsy brain with glioblastoma. RESULTS: Glioblastoma cells infiltrated the brain far beyond the gross limits of the tumor and the areas with high signal intensity on T2-weighted magnetic resonance images. A wide range of histologic malignancy was apparent from hematoxylin-eosin staining and the Ki-67 labeling indices. VEGF was highly expressed in normal astrocytes located outside the tumor. CONCLUSION: Graphic analysis of histologic and immunohistochemical patterns is a useful method of investigating the mechanisms of glioma growth, tumor cell infiltration in the brain, and the host reaction of the brain against neoplasms.

Aged↗
PubMed1999

Malignancies of natural killer (NK) cell precursor: myeloid/NK cell precursor acute leukemia and blastic NK cell lymphoma/leukemia.

Malignant hematolymphoid disorders arising from natural killer (NK) cells have become widely recognized in the past decade. Recently, we as well as others have drawn attention to some neoplasms of conceivable NK cell precursor origin that might represent two distinct entities, i.e. myeloid/NK cell precursor acute leukemia and blastic NK cell lymphoma/leukemia. Both of these diseases were characterized by remarkable extramedullary involvement and lymphoblastoid morphology, although the sites of involvement differed. Myeloid/NK cell precursor acute leukemia exhibited more frequent involvement of bone marrow (BM) and lymph nodes, whereas blastic NK cell lymphoma/leukemia affected extranodal sites, mainly the skin/subcutis. Tumor cells of these two diseases shared the CD16-, CD56+ and CD57- phenotype, but differed in other phenotypic profiles. Indeed, myeloid/NK cell precursor acute leukemia was immunophenotypically characterized by the expression of CD34 and blastic NK cell lymphoma/leukemia by that of CD4. On the theoretical level in the NK cell differentiation pathway, myeloid/NK cell precursor acute leukemia might be derived from a myeloid antigen-positive precursor preceding a NK cell committed precursor as a conceivable counterpart of blastic NK cell lymphoma/leukemia. Most cases with either disease lacked cytotoxic activities or molecules, a finding which seems to support their precursor origin. Notably, Epstein Barr virus (EBV) was negative in all cases, which contrasted with its high level associated with mature NK cell malignancies. Chemotherapy for acute myeloid leukemia was generally effective for myeloid/NK cell precursor acute leukemia, while the regimen for lymphoid malignancy was effective for blastic NK cell lymphoma/leukemia. These data suggests that each of these two diseases constitutes a distinct entity, which is also different from mature NK cell malignancies.

Acute Disease↗
PubMed1999

Specific interaction of fused H protein of bacteriophage phiX174 with receptor lipopolysaccharides.

The DNA fragment encoding the spike H protein of bacteriophage phiX174 was amplified by polymerase chain reaction. The fragment was sub-cloned into pQE-30 to yield pQE-H. The histidine-tagged H protein (HisH) was obtained from the cell extract of Escherichia coli M15 (pREP4) harboring pQE-H and purified by nickel chelating and anion-exchange chromatographies. HisH was shown to bind dose-dependently to the lipopolysaccharides (LPSs) isolated from phiX174-sensitive strains, E. coli C or Salmonella typhimurium TV119 (Ra mutant). In sharp contrast, HisH did not bind to the LPSs from insensitive strains, E. coli F583 (Rd2 mutant) or E. coli O111:B4 (smooth strain). Since the same selectivity was observed in the plaque counting assay for in vitro inactivation of phiX174, the spike H protein was shown to recognize receptor LPS.

Bacteriophage phi X 174↗
PubMed1999

Fluorescence automatic cell sorter and immunohistochemical investigation of CD68-positive cells in meningioma.

Infiltration of brain neoplasms by mononuclear cells including monocytes/macrophages has attracted little attention since they have marked morphological heterogeneity. Twenty-seven meningiomas were studied by anti-CD68 antibody-gated flow cytometry and by immunohistochemical analysis using the anti-CD68 antibodies. Flow cytometric analysis divided cells contained within tumor tissues into CD68-positive and -negative cells. In addition, eight gliomas, eight metastatic brain tumor, and 12 pituitary adenomas were investigated in the same way to compare meningiomas. The mean contents of CD68-positive cells were 24.0 +/- 3.7% in meningiomas, 4.4 +/- 1.4% in gliomas, 9.5 +/- 3.9% in metastatic brain tumors, and 4.5 +/- 1.8% in pituitary adenomas. Immunohistochemically, CD68-positive cells showed significant heterogeneity and were detected as round, rod-shaped, ameboid and ramified cells in meningiomas. Although the infiltrated mononuclear cells in gliomas have been investigated to some degree and showed that they express cytokines and/or growth factors, these infiltrated cells in meningioma have barely been studied. The CD68-positive cells detected in this study are likely to be monocytes, macrophages and microglias, and are presumed to be in various functional stages and to play important roles in growth regulation in meningioma.

Adenoma↗
PubMed1999

The effectiveness of spinal and systemic morphine on rat dorsal horn neuronal responses in the spinal nerve ligation model of neuropathic pain.

The treatment of pain arising from nerve injury can be difficult and the opioid sensitivity of neuropathic pain remains debatable. Clinical and animal studies report a wide range in the effectiveness of morphine, ranging from inadequate to potent analgesia. In this electrophysiological study we compare the effectiveness of spinal versus systemic administration of morphine on the natural and electrically evoked responses of spinal neurones of rats with a selective spinal nerve (L5/6) ligation. Recordings were made 1 week and/or 2 weeks after ligation. We have also compared the effects of morphine, by the two routes, on normal and sham operated animals. In spinal nerve ligated rats, morphine (0.1-5 microg) administered via the intrathecal route produced greater dose-dependent inhibitions of the neuronal responses compared with those produced by the systemic route (1-6 mg/kg). The dose response curves for intrathecal morphine on the C-fibre evoked and noxious natural stimuli evoked neuronal responses (mechanical and thermal) of spinal nerve ligated rats were to the left of those of sham operated and normal rats, suggesting an enhanced potency of intrathecal morphine after nerve injury. This was clearest for the lower doses of the opioid. The effects of spinal morphine on the responses to low intensity stimuli were similar in all groups of rats. In contrast to the spinal route, systemic morphine was less effective in inhibiting the evoked neuronal responses of spinal nerve ligated rats. This was especially clear for the C-fibre evoked and noxious natural stimuli evoked responses (mechanical and thermal) of spine nerve ligated rats. Our results suggest that the effectiveness of morphine may be partly related to the timing of the treatment relative to the duration of the neuropathy, the route of administration and also the neuropathic symptom. Spinal opioids may be a useful approach to pain control in neuropathic pain states where systemic routes produce inadequate analgesia.

Analgesics, Opioid↗
PubMed1999

Experimental metastasis is suppressed in MMP-9-deficient mice.

Matrix metalloproteinases (MMPs) are thought to play a key role in tumor invasion and metastasis. The role of MMP-9 (gelatinase B) in tumor metastasis was examined in MMP-9-deficient mice produced by gene targeting using embryonic stem cells. MMP-9-deficient mice develop normally and are fertile. In these mice, the number of metastatic colonies of B16-BL6 melanoma cells or Lewis lung carcinoma cells that were implanted intravenously fell by 45% for B16-BL6 melanoma and 59% for Lewis lung carcinoma (p = 0.03 and p = 0.0043, respectively). Gelatin zymography showed that both tumor cell lines did not secrete MMP-9 by themselves but the host cells surrounding the tumor cells secrete MMP-9 in vivo. These results indicated that host-derived MMP-9 plays an important role in the process of tumor metastasis.

Animals↗
PubMed1999

Theophylline induces apoptosis of the IL-3 activated eosinophils of patients with bronchial asthma.

In bronchial asthma, eosinophils are upregulated and their survival is suggested to be prolonged by the action of some cytokines such as Interleukin (IL)-3, IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF). We find here that the survival of eosinophils in the peripheral blood of patients with asthma is correlated with the serum levels of IL-3 but not of IL-5 and GM-CSF. Interestingly, theophylline is revealed to induce apoptosis of the prolonged survival eosinophils by IL-3, as judged by morphological changes and nucleosomal DNA fragmentation. During the apoptosis, caspase-3 in eosinophils stimulated by IL-3 is activated by theophylline. The substrate of caspase-3, poly (ADP-ribose) polymerase (PARP), is cleaved in the eosinophils after theophylline treatment. These results suggest that theophylline is able to induce apoptosis of the IL-3 activated eosinophils in patients with bronchial asthma, and that its clinical effectiveness may be due to the reduction of inflammatory cells in the airway.

Journal Article↗
PubMed1999

Polymorphisms in the 5'-flanking region of tumor necrosis factor-alpha gene in patients with rheumatoid arthritis.

Polymorphisms in the 5'-flanking promoter/enhancer region of the tumor necrosis factor (TNF)-a gene were examined to study the genetic background of rheumatoid arthritis (RA). Four variant alleles, -1,031C/ -863A, -1,031C/-238A, -857T and -308A, were identified and examined in 387 RA patients and 575 healthy Japanese controls. The frequency of the -857T allele in RA patients was significantly higher than that in the controls. However, the HLA-DRB1 analysis in the same subjects showed that the DRB1*0405 allele, which is in linkage disequilibrium with the -857T, was more strongly associated with the disease susceptibility than the -857T allele. These results suggest that the susceptible gene to RA is more closely linked to the HLA-DRB1 locus than to the TNF-alpha locus.

5' Untranslated Regions↗
PubMed1999

Selective usage of D-type cyclins in lymphoid malignancies.

Three D-type cyclins, cyclin D1, D2 and D3, belong to the G1 cyclin, which regulates the G1/S transition of the cell cycle, and feature highly homologous amino acid sequences. The cyclin D1 gene was found to be transcriptionally activated in B-lymphoid malignancies with t(11;14), but available information is limited regarding expression of cyclin D2 and D3 in hematopoietic malignancies. We examined the expressions of three D-type cyclins to investigate how these homologous genes are differentially used. Northern blot hybridization with densitometric analyses was performed to examine 64 cell lines and 159 patients with various hematopoietic malignancies. Among lymphoid malignancies, cyclin D1 overexpression was exclusively detected in B cell malignancies accompanied by a genetic event consisting of 11q13 chromosomal translocation, consisting of 13 of 19 (68%) patients with mantle cell lymphoma, two of 11 (18%) with B-chronic lymphocytic leukemia, and one of six (17%) with multiple myeloma. The cyclin D2 expression was significantly higher in T cell malignancies than in B cell malignancies (P = 0.003 for cell lines and P < 0.0001 for patient samples, respectively). In the T cell malignancies, cyclin D2 overexpression was predominantly recognized in those with mature phenotype. Furthermore, cyclin D2 expression was upregulated by phytohemagglutinin (PHA) stimulation of normal T-lymphocytes, suggesting that this simply represents the proliferation status of mature T cells. Although cyclin D3 was ubiquitously expressed, its expression was reduced in lymphoid malignancies with cyclin D1 or D2 overexpression. In myeloid leukemias, although three D-type type cyclins were differentially expressed, no preference for particular D-type cyclins was found. This selective usage of D-type cyclins in lymphoid malignancies suggests an existence of a regulatory mechanism among three D-type cyclins.

Cell Lineage↗
PubMed1999

Molecular and immunological dissection of diffuse large B cell lymphoma: CD5+, and CD5- with CD10+ groups may constitute clinically relevant subtypes.

Diffuse large B cell lymphoma (DLBL) constitutes the greatest percentage of adult non-Hodgkin's lymphomas and represents a diverse spectrum of lymphoid neoplasms. Clinicopathologic, phenotypic and genotypic findings were correlated and compared for 63 DLBL cases to investigate whether they represent clinically relevant subtypes. They were all cyclin D1 negative and were phenotypically divided into three groups, ie group I (CD5+ type, n=11), group II (CD5- CD10+ type, n=19), and group III (CD5- CD10- type, n=33). Data were correlated by observing the respective gene rearrangement and expression of BCL2 and BCL6. In clinical aspects, the group I cases demonstrated a significantly inferior survival than those of the other two groups (log-rank test, P = 0.016). Although rearrangement of BCL2 and BCL6 did not show any inclination to a specific subgroup, the immunohistochemical detection of BCL2 was less frequent, at a statistically significant level (P=0.011), in group II (50%) than in group I (82%) and III (82%) cases. This appears to confirm the unique aspect of the CD5- CD10+ type DLBL, indicating a certain relationship with the normal germinal center cells which usually lack BCL2 expression. The BCL6 protein expression was detected in most of the present DLBL cases (92%) irrespective of this grouping. These data suggest that the phenotypic delineation by the detection of CD5 and CD10 will improve our understanding of DLBL and be helpful in a future subgrouping of DLBL.

Adult↗