Biomedical subjects

R Suzuki

Publications and source records attributed to R Suzuki.

At least 37 records · Page 2Linked to original sources

PubMed2004

Comparison of the activities of multinucleated bone-resorbing giant cells derived from CD14-positive cells in the synovial fluids of rheumatoid arthritis and osteoarthritis patients.

OBJECTIVE: To investigate the morphology and function of multinucleated bone-resorbing giant cells derived from CD14-positive cells in the synovial fluids (SF) of patients with rheumatoid arthritis (RA) or osteoarthritis (OA). METHODS: CD14-positive cells were obtained by magnetic-activated cell sorting of primary cultures of mononuclear cells from the SF. Multinucleated bone-resorbing giant cells were induced from the CD14-positive cells in the presence or absence of cytokines. We examined various characteristics, including osteoclast markers, fusion index and bone-resorption activities of the multinucleated giant cells. RESULTS: Multinucleated giant cells were induced from the CD14-positive cells in the SF of the RA and OA patients by the addition of interleukin (IL)-3, IL-5 and IL-7, or granulocyte-macrophage colony-stimulating factor (GM-CSF), respectively. These multinucleated giant cells were positive for tartrate-resistant acid phosphatase (TRAP), carbonic anhydrase II, actin, vitronectin receptor and the calcitonin receptor. However, the average values for the number of nuclei, fusion index and bone-resorption functions of the SF cells from the RA patients were significantly higher than those derived from the OA patients. CONCLUSION: These results suggest that the induction and activities of multinucleated bone-resorbing giant cells may play a pivotal role in bone destruction, and that these processes may be enhanced significantly in RA patients.

Adult↗

PubMed2004

Epidermal growth factor and insulin inhibit cell death in pancreatic beta cells by activation of PI3-kinase/AKT signaling pathway under oxidative stress.

Production of reactive oxygen species (ROS) during islet purification by enzymatic digestion as well as during warm and cold ischemia causes islet cell damage. Recent reports have shown that activated Akt, the downstream protein after phosphatidylinositol (PI) 3-kinase, is involved in cell survival by phosphorylating several proteins that mediate apoptosis. We analyzed the role of PI3-kinase/Akt pathway activation using insulin or epidermal growth factor (EGF) on islet beta cell survival during oxidative stress. Canine islets and murine beta cell line (BTC) were cultured in the presence of hydrogen peroxide (H(2)O(2)) for 12 to 20 hours. Viability and cell death were measured by MTT assay. Maximum cell damage was observed with as little as 100 micromol/L of H(2)O(2). Pretreatment with 100 ng/mL of insulin significantly decreased cell damage. Meanwhile, the protective effect of insulin was partially blocked with an inhibitor of PI3-kinase, LY294002, suggesting the utilization of PI3-kinase/Akt signaling pathway for the observed cytoprotective effect. Similar to insulin, EGF also protected beta cells from oxidative stress. Our results suggest that PI3-kinase/Akt activation by insulin or EGF is beneficial for islet beta cell protection.

Adult↗

PubMed2004

Surveillance of severe invasive group-G streptococcal infections and molecular typing of the isolates in Japan.

The number of patients with severe invasive group-G streptococcal (Streptococcus dysgalactiae subsp. equisimilis) infections has been increasing in Japan. The emm genotypes and SmaI-digested pulsed-field gel electrophoresis DNA profiles were variable among the strains isolated, suggesting there has not been clonal expansion of a specific subpopulation of strains. However, all strains carried scpA, ska, slo and sag genes, some of which may be involved in the pathogenesis of the disease.

Adhesins, Bacterial↗

PubMed2004

Intestinal thrombotic microangiopathy after allogeneic bone marrow transplantation: a clinical imitator of acute enteric graft-versus-host disease.

Thrombotic microangiopathy after bone marrow transplantation (post-BMT TMA) is a serious transplant-related complication. We identified 16 patients with TMA after allogeneic BMT who showed histopathological evidence of intestinal TMA in their gut specimens (six autopsies, 10 biopsies). In all, 14 patients had grade II-IV acute graft-versus-host disease (GVHD). The first seven patients were retrospectively diagnosed with TMA. Since six of them were diagnosed with progressive GVHD at that time because there was no awareness of the existence of intestinal TMA, they received more intensive treatment for GVHD, but all died between days +49 and +253. In contrast, the remaining nine patients were recently diagnosed with intestinal TMA on the basis of colonoscopic biopsies. For eight of these patients, the immunosuppressants were reduced, and the patients' intestinal symptoms improved gradually. Six of the nine patients were still alive 12 months after the diagnosis of TMA. Our findings suggest that the gut may be a site involved in post-BMT TMA, presenting as ischemic enterocolitis. Differentiating intestinal TMA from acute GVHD is important in patients suffering from severe and refractory diarrhea after BMT.

Acute Disease↗

PubMed2004

Aggressive natural killer-cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells.

Aggressive natural killer-cell leukemia (ANKL) is a rare form of large granular lymphocyte leukemia, which is characterized by a systemic proliferation of NK cells. The clinical features of 22 ANKL cases were analyzed. Hepatomegaly (64%), splenomegaly (55%) and lymphadenopathy (41%) were also frequently observed. Leukemic cells were identified as CD1-, CD2+, surface CD3-, CD4-, CD5-, CD7+, CD8+/-, CD10-, CD11b+/-, CD13-, CD16+, CD19-, CD20-, CD25-, CD33(-), CD34-, CD38+, CD56+, CD122+, HLA-DR+ and TCR-. Two of the 16 cases examined for CD57 were positive and three of the seven cases examined for cytoplasmic CD3. Epstein-Barr virus was detected in the tumor cells of 11 of the 13 cases examined. No common cytogenetic abnormalities were identified and 6q anomaly was detected in only one. Three of 13 patients treated with chemotherapy containing anthracycline/anthraquinone attained complete remission, in contrast to none of the eight who were treated with regimens without anthracycline. Although the overall prognosis was poor with a median survival of 58 days, those who attained remission showed better prognosis (P=0.005). These findings suggest that ANKL is an entity of mature cytotoxic NK-cell neoplasms with distinct phenotype and disease presentations. Intensive treatment for ANKL may result in a better prognosis.

Adult↗

PubMed2003

Tissue reconstruction process in the area of peri-tumoural oedema caused by glioblastoma--immunohistochemical and graphical analysis using brain obtained at autopsy.

BACKGROUND: In the area of peri-tumoural oedema, proteolytic agents derived from the tumour cause tissue degradation, which promotes tumour cell invasion. METHOD: We investigated the biological processes in the area of peri-tumoural oedema, using a brain obtained at autopsy from a patient who died from glioblastoma. Immunohistochemistry was performed to detect vascular endothelial growth factor (VEGF), c-myc, p53, paternally expressed gene-3 (PEG-3), transforming growth factor beta (TGFB), and tumour necrosis factor alpha (TNFA). The data were translated into colour graphics and the localization of these proteins was analyzed. FINDINGS: In the area of peri-tumoural oedema, Ki-67 and p53 positive cells were observed with TGFB expression. Moreover, c-myc, PEG-3, VEGF, and TNFA were also expressed strongly in the glial cells or extra-cellular spaces in the area of peri-tumoural oedema. INTERPRETATION: These data suggest that in the area of peri-tumoural oedema, tissue reconstruction processes take place with concomitant anti-tumour activities. The expression of c-myc, VEGF, and TNFA in the area of peri-tumoural oedema may indicate that these proteins are not utilized for tumour growth, but may be used to guard the brain against tumour invasion. Peri-tumoural oedema does not only indicate the tissue damage caused by tumour, but many tissue reconstruction processes take place in these areas against tumour cell invasion.

Adult↗

PubMed2003

Very early expression of vascular endothelial growth factor in brain oedema tissue associated with brain contusion.

BACKGROUND: Brain oedema associated with cerebral contusion can be life-threatening. Mechanisms of the development of brain oedema are still unclear. METHOD: We investigated the expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (KDR/Flk-1) in the contusional brain tissue obtained during neurosurgery from 5 patients. FINDINGS: VEGF is expressed in some but not all the astrocytes, and KDR/Flk-1 is expressed in vascular endothelial cells in the con-tusional tissue as early as 3 hours after onset. CONCLUSION: The results suggested that the VEGF is induced in the contusional tissue in the very early period after onset, and that it increases capillary permeability via KDR/Flk-1 resulting in vasogenic type brain oedema.

Adolescent↗

PubMed2003

Chronological changes of perihematomal edema of human intracerebral hematoma.

Recent investigations have indicated the importance of secondary brain damage in the pathophysiology of intracerebral hemorrhage (ICH), which includes ischemic brain damage and edema formation around a hematoma. The purpose of the current study is to investigate chronological changes of perihematomal edema in patients with human ICH and also the correlation between volume of perihematomal edema and neurological status. Fourteen patients with medium-sized putaminal hemorrhage (29.4 +/- 13.2 ml) without hematoma enlargement were included in this study. To investigate chronological changes of perihematomal edema, we performed CT scans prospectively on the day of hemorrhage and repeated them on days 1, 3, 7, 14, and 28. We evaluated the patients neurologically using the NIH stroke scale on the day a CT scan was performed. The volume of perihematomal edema in human ICH increased rapidly three days after hemorrhage and the score on the NIH stroke scale showed a deterioration. The volume of perihematomal edema then increased slowly until day 14 after hemorrhage, and decreased thereafter. Despite progression of perihematomal edema, the score on the NIH stroke scale improved gradually after day 3.

Aged↗

PubMed2003

The reaction of osteoclasts when releasing osteocytes from osteocytic lacunae in the bone during bone modeling.

Osteocytes are released from the osteocytic lacunae when osteoclasts resorb the bone matrix during bone modeling and remodeling. It remains unknown how osteoclasts react when releasing osteocytes during bone modeling, and the fate of these released osteocytes is also unclear. Femoral mid-shafts of 2-day-old kittens were sectioned into serial 0.5 microm-thick semithin or 0.1 microm-thick ultrathin sections, and examined by light microscopy (LM) and transmission electron microscopy (TEM). The sections showed many osteoclasts at the endosteum but there were no osteoblasts. There were many half-released, fully released, half-exposed, and fully exposed osteocytes on the bone surfaces. Many cell-like structures were seen in the cell bodies of osteoclasts by LM, and some semithin sections were re-sectioned into ultrathin sections for re-observation by TEM. By TEM, these were determinated to be mononuclear cells. The serial ultrathin sections showed that the mononuclear cells appeared to be engulfed in osteoclasts on one section but that the cell was connected with the bone surface of the osteocytic lacuna on another section. These results show that the mononuclear cells in the osteoclasts were osteocytes. The present study suggests that osteoclasts engulf some osteocytes but do not engulf others when releasing osteocytes during bone modeling.

Animals↗

PubMed2003

Cytomegalovirus antigenemia and outcome of patients treated with pre-emptive ganciclovir: retrospective analysis of 241 consecutive patients undergoing allogeneic hematopoietic stem cell transplantation.

CMV disease remains a major infectious complication after allogeneic hematopoietic stem cell transplantation (HSCT). To investigate the relationship between CMV antigenemia, treatment with ganciclovir (GCV), and outcome, we retrospectively analyzed 241 consecutive patients at risk for CMV infection who underwent allogeneic HSCT. Antigenemia-guided pre-emptive strategy with GCV was used for all patients. CMV antigenemia developed in 169 patients (70.1%), and CMV disease in 18 patients (7.5%). Multivariate analysis showed that acute GVHD (grades II-IV) was the only risk factor for developing antigenemia, and acute GVHD and advanced age for CMV disease. GCV use, as well as acute GVHD and advanced age, significantly increased the risk for bacterial and fungal infection after engraftment. Those who developed CMV antigenemia had a poorer outcome than those who did not (log-rank, P=0.0269), although the development of CMV disease worsened the outcome with only borderline significance (log-rank, P=0.0526). In conclusion, detection of antigenemia proved to be a poor prognostic factor for HSCT patients, which may be attributed to a combination of factors, including CMV disease itself, the effect of treatment, and a host status that allows for reactivation of CMV. Optimal pre-emptive strategy needs to be determined.

Adolescent↗

PubMed2003

The presence and longevity of peripherally expanded donor-derived TCRalphabeta+ mature T lymphocyte clones after allogeneic bone marrow transplantation for adult myeloid leukemias.

There are two major pathways for T-cell regeneration after allogeneic bone marrow transplantation; thymus-dependent T-cell differentiation of T-cell progenitors, and peripheral expansion of mature T cells in the graft. In order to learn to what extent the peripheral expansion of donor-derived mature T lymphocytes contributes to reconstitution of the TCRalphabeta+ T-cell repertoire after allogeneic bone marrow transplantation for adult myeloid leukemias, we pursued the fate of donor-derived T-cell clones using the amino-acid sequences of the complementarity-determining region 3 (CDR3) of the TCR-beta chain as a clonal marker. Clonal expansion of TCRalphabeta+ T lymphocytes with specific TCRBV subfamilies was identified in donor blood. Identical T-cell clones were not found in blood from recipients before transplantation. The donor-derived T-cell clones were identified in the circulating blood from recipients a few months after allogeneic bone marrow transplantation, and they remained in the blood for 18 months after transplant in two recipients, and for 56 months in one. These results suggest that the peripheral expansion of mature T lymphocytes in the graft makes a significant contribution to post-transplant T-cell regeneration during the early period of transplantation in humans, and that mature T cells can survive in recipients for several years. Further investigation will be required to explore which antigens drive the expansion of T-cell clones in donors and recipients, and the mechanisms of maintaining homeostatic balance between the thymus-dependent pathway and the peripheral expansion of mature T cells in post-transplant T-cell regeneration.

Adult↗

PubMed2003

Dual mutations in the AML1 and FLT3 genes are associated with leukemogenesis in acute myeloblastic leukemia of the M0 subtype.

Point mutations of the transcription factor AML1 are associated with leukemogenesis in acute myeloblastic leukemia (AML). Internal tandem duplications (ITDs) in the juxtamembrane domain and mutations in the second tyrosine kinase domain of the Fms-like tyrosine kinase 3 (FLT3) gene represent the most frequent genetic alterations in AML. However, such mutations per se appear to be insufficient for leukemic transformation. To evaluate whether both AML1 and FLT3 mutations contribute to leukemogenesis, we analyzed mutations of these genes in AML M0 subtype in whom AML1 mutations were predominantly observed. Of 51 patients, eight showed a mutation in the Runt domain of the AML1 gene: one heterozygous missense mutation with normal function, five heterozygous frameshift mutations and two biallelic nonsense or frameshift mutations, resulting in haploinsufficiency or complete loss of the AML1 activities. On the other hand, a total of 10 of 49 patients examined had the FLT3 mutation. We detected the FLT3 mutation in five of eight (63%) patients with AML1 mutation, whereas five of 41 (12%) without AML1 mutation showed the FLT3 mutation (P=0.0055). These observations suggest that reduced AML1 activities predispose cells to the acquisition of the activating FLT3 mutation as a secondary event leading to full transformation in AML M0.

Cell Transformation, Neoplastic↗

PubMed2003

Heterogeneous copy numbers of API2-MALT1 chimeric transcripts in mucosa-associated lymphoid tissue lymphoma.

T(11;18)(q21;q21) results in a chimeric transcript between API2 at 11q21 and MALT1 at 18q21 and is a characteristic chromosomal aberration of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). API2-MALT1 chimeric transcripts are present in approximately one-third of all cases of MALT lymphoma. MALT lymphoma is also known to have variations in histological features and tumor cell proportions. Real-time polymerase chain reaction (PCR) was used to examine number of API2-MALT1 copies in clinical samples for further investigation of the pathophysiology of MALT lymphoma. A total of 13 samples of MALT lymphoma contained API2-MALT1 transcripts from 1.7 x 10(-2) to 1.0 copies/beta-actin copy. These findings were compared to the proportions of tumor cells in genomic VDJ PCR products determined by Southern blotting. Tumor cell ratios varied widely among the patients' samples, and no significant correlation was found between transcript copy number and tumor cell ratio. These results suggest that copy numbers of API2-MALT1 do not reflect tumor cell proportions, and that the number of copies of API2-MALT1 in a tumor cell is different for each clinical sample.

Adult↗

PubMed2003

DS-Nh as an experimental model of atopic dermatitis induced by Staphylococcus aureus producing staphylococcal enterotoxin C.

DS-Nh mice raised under conventional conditions spontaneously develop dermatitis similar to human atopic dermatitis (AD), which is associated with staphylococcal infection. In the present study, we show that Staphylococcus aureus producing staphylococcus exotoxin C (SEC) was recovered from the culture of the skin lesions of DS-Nh mice with AD-like dermatitis and that the serum levels of anti-SEC antibodies from these mice were elevated. We describe here how to promote experimental AD by epicutaneous injection with SEC-producing S. aureus to DS-Nh mice. In order to assess the role of SEC in the pathogenesis of AD, the mitogenic activity, TCRBV repertoire analysis and the production of IL-4 and IFN-gamma from spleen mononuclear cells (MNC) from DS-Nh stimulated by SEC were compared with those due to SEA, SEB and TSST. The weakest was the mitogenic activity of SEC, and higher IL-4 responses and lower IFN-gamma responses to SEC showed correlation with TCRBV8S2-positive T cells, which were selectively stimulated by SEC. We also demonstrate that SEC-producing S. aureus was able to survive in DS-Nh after intradermal injection. These results suggest a possible role for SEC in the pathogenesis of AD through host-S. aureus relationships.

Animals↗

PubMed2003

Tartrate resistant acid phosphatase (TRAP) positive cells in rheumatoid synovium may induce the destruction of articular cartilage.

OBJECTIVE: To examine the role of tartrate resistant acid phosphatase (TRAP) positive mononuclear and multinucleated cells in the destruction of articular cartilage in patients with rheumatoid arthritis (RA). METHODS: The presence of TRAP positive cells in the synovial tissue of patients with RA was examined by enzyme histochemistry and immunohistochemistry. Expression of mRNAs for matrix metalloproteinases (MMPs) was assessed by the reverse transcriptase-polymerase chain reaction (RT-PCR) and northern blot analysis. Production of MMPs by mononuclear and multinucleated TRAP positive cells was examined by immunocytochemistry, enzyme linked immunosorbent assay (ELISA) of conditioned medium, and immunohistochemistry of human RA synovial tissue. In addition, a cartilage degradation assay was performed by incubation of (35)S prelabelled cartilage discs with TRAP positive cells. RESULTS: TRAP positive mononuclear cells and multinucleated cells were found in proliferating synovial tissue adjacent to the bone-cartilage interface in patients with RA. Expression of MMP-2 (gelatinase A), MMP-9 (gelatinase B), MMP-12 (macrophage metalloelastase), and MMP-14 (MT1-MMP) mRNA was detected in TRAP positive mononuclear and multinucleated cells by both RT-PCR and northern blot analysis. Immunocytochemistry for these MMPs showed that MMP-2 and MMP-9 were produced by both TRAP positive mononuclear and multinucleated cells, whereas MMP-12 and MMP-14 were produced by TRAP positive multinucleated cells. MMP-2 and MMP-9 were detected in the conditioned medium of TRAP positive mononuclear cells. TRAP positive mononuclear cells also induced the release of (35)S from prelabelled cartilage discs. CONCLUSION: This study suggests that TRAP positive mononuclear and multinucleated cells located in the synovium at the cartilage-synovial interface produce MMP-2 and MMP-9, and may have an important role in articular cartilage destruction in patients with RA.

Acid Phosphatase↗

PubMed2003

Changing prevalent T serotypes and emm genotypes of Streptococcus pyogenes isolates from streptococcal toxic shock-like syndrome (TSLS) patients in Japan.

We surveyed T serotypes and emm genotypes of Streptococcus pyogenes isolates from streptococcal toxic shock-like syndrome (TSLS) patients. T1 (emm1) remained dominant through 1992 to 2000, but the dominant T3 (emm3.1) strains from 1992 to 1995 disappeared during 1996-2000. Strains of several emm genotypes emerged during 1996-2000, indicating alterations in the prevalent strains causing TSLS.

Antigens, Bacterial↗

PubMed2002

Nerve-mast cell (RBL) interaction: RBL membrane ruffling occurs at the contact site with an activated neurite.

Mast cell-neurite interaction serves as a model for neuroimmune interaction. We have shown that neurite-mast cell communication can occur via substance P interacting with neurokinin (NK)-1 receptors on the mucosal mast cell-like cell, the rat basophilic leukemia (RBL) cell. Neurite (murine superior cervical ganglia) and RBL cell [expressing the granule-associated antigen CD63-green fluorescent protein (GFP) conjugate] cocultures were established and stimulated with bradykinin (BK; 10 nM) or scorpion venom (SV; 10 pg/ml), both of which activate only neurites. Cell activation was assessed by confocal imaging of Ca2+ (cells preloaded with fluo 3), and analyses of RBL CD63-GFP+ granule movement were conducted. Neurite activation by BK or SV was followed by RBL Ca2+ mobilization, which was inhibited by an NK-1 receptor antagonist (NK-1 RA). Moreover, membrane ruffling was observed on RBL pseudopodial extensions in contact with the activated neurite, but not on noncontacting pseudopodia. RBL membrane ruffling was inhibited by NK-1 RA, but not NK-2 RA, and was accompanied by a significant increase in granule movement (0.13 +/- 0.04 vs. 0.05 +/- 0.01 microm/s) that was most evident at the point of neurite contact: many of the granules moved toward the plasmalemma. This is the first documentation of such precise (restricted to the membrane's contact site) transfer of information between nerves and mast cells that could allow for very subtle in vivo communication between these two cell types.

Animals↗

PubMed2002

The acceleration of cosmic-ray protons in the supernova remnant RX J1713.7-3946.

Protons with energies up to approximately 10(15) eV are the main component of cosmic rays, but evidence for the specific locations where they could have been accelerated to these energies has been lacking. Electrons are known to be accelerated to cosmic-ray energies in supernova remnants, and the shock waves associated with such remnants, when they hit the surrounding interstellar medium, could also provide the energy to accelerate protons. The signature of such a process would be the decay of pions (pi(0)), which are generated when the protons collide with atoms and molecules in an interstellar cloud: pion decay results in gamma-rays with a particular spectral-energy distribution. Here we report the observation of cascade showers of optical photons resulting from gamma-rays at energies of approximately 10(12) eV hitting Earth's upper atmosphere, in the direction of the supernova remnant RX J1713.7-3946. The spectrum is a good match to that predicted by pion decay, and cannot be explained by other mechanisms.

Journal Article↗