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Biomedical subjects

K Ohta

Publications and source records attributed to K Ohta.

At least 19 recordsLinked to original sources

An optical spectrum of the afterglow of a gamma-ray burst at a redshift of z = 6.295.

The prompt gamma-ray emission from gamma-ray bursts (GRBs) should be detectable out to distances of z > 10 (ref. 1), and should therefore provide an excellent probe of the evolution of cosmic star formation, reionization of the intergalactic medium, and the metal enrichment history of the Universe. Hitherto, the highest measured redshift for a GRB has been z = 4.50 (ref. 5). Here we report the optical spectrum of the afterglow of GRB 050904 obtained 3.4 days after the burst; the spectrum shows a clear continuum at the long-wavelength end of the spectrum with a sharp cut-off at around 9,000 A due to Lyman alpha absorption at z approximately 6.3 (with a damping wing). A system of absorption lines of heavy elements at z = 6.295 +/- 0.002 was also detected, yielding the precise measurement of the redshift. The Si ii fine-structure lines suggest a dense, metal-enriched environment around the progenitor of the GRB.

Journal Article↗

Pharmacologic and anti-IgE treatment of allergic rhinitis ARIA update (in collaboration with GA2LEN).

The pharmacologic treatment of allergic rhinitis proposed by ARIA is an evidence-based and step-wise approach based on the classification of the symptoms. The ARIA workshop, held in December 1999, published a report in 2001 and new information has subsequently been published. The initial ARIA document lacked some important information on several issues. This document updates the ARIA sections on the pharmacologic and anti-IgE treatments of allergic rhinitis. Literature published between January 2000 and December 2004 has been included. Only a few studies assessing nasal and non-nasal symptoms are presented as these will be discussed in a separate document.

Animals↗

Identification of a glucan-binding protein C gene homologue in Streptococcus macacae.

BACKGROUND/AIMS: The past few decades have seen the isolation of certain glucosyltransferases and a number of proteins from mutans streptococci. Some of these proteins have been shown to possess glucan-binding capabilities which confer an important virulence property on mutans streptococci for the role of these bacteria play in dental caries. Among these proteins is glucan-binding protein C, which is encoded by the gbpC gene, and which we have identified as being involved in the dextran-dependent aggregation of Streptococcus mutans. However, gbpC homologues have yet to be identified in other mutans streptococci. METHODS: We carried out polymerase chain reaction amplification of Streptococcus macacae using primers that were designed based on conserved sequences of S. mutans gbpC and identified a gbpC gene homologue. The gene of that homologue was then characterized. RESULTS: Nucleotide sequencing of the S. macacae gbpC homologue revealed a 1854 bp open reading frame encoding a protein with an N-terminal signal peptide. The molecular mass of the processed protein was calculated to be 67 kDa. We also found an LPxTG motif, the consensus sequence for gram-positive cocci cell wall-anchored surface proteins, which was followed by a characteristic sequence at the carboxal terminal region of the putative protein. This suggests that the S. macacae GbpC homologue protein was tethered to the cell wall. CONCLUSION: Based on these results, together with the demonstrated glucan-binding ability of the S. macacae GbpC homologue protein, we suggest that S. macacae cells are capable of binding dextran via the GbpC homologue protein, which is similar to the S. mutans GbpC protein. In addition, Southern hybridization analysis using the S. macacae gbpC homologue as a probe showed a distribution of gbpC homologues throughout the mutans streptococci.

Amino Acid Motifs↗

Selective expansion of CD16highCCR2- subpopulation of circulating monocytes with preferential production of haem oxygenase (HO)-1 in response to acute inflammation.

Monocytes are composed of two distinct subpopulations in the peripheral blood as determined by their surface antigen expressions, profiles of cytokine production and functional roles played in vivo. We attempted to delineate the unique functional roles played by a minor CD16(high)CCR2(-) subpopulation of circulating monocytes. They produced significant levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha, but very low levels of IL-10 upon in vitro stimulation. Characteristic profiles of cytokine production were confirmed by stimulating purified subpopulations of monocytes after cell sorting. It was noteworthy that freshly isolated CD16(high)CCR2(-) monocyte subpopulations produced significant levels of haem oxygenase (HO)-1, whereas the major CD16(low)CCR2(+) subpopulation produced little. These results were contrary to the generally accepted notion that the CD16(high)CCR2(-) monocyte subpopulation plays a predominantly proinflammatory role in vivo. The CD16(high)CCR2(-) subpopulation increased in Kawasaki disease and influenza virus infection. In accord with this, HO-1 mRNA expression by mononuclear cells was significantly increased in these illnesses. These results indicate that CD16(high)CCR2(-) subpopulations are of a distinct lineage from CD16(low)CCR2(+) monocytes. More importantly, they may represent a monocyte subpopulation with a unique functional role to regulate inflammation by producing HO-1 in steady state in vivo.

Acute Disease↗

Reduction of osteocalcin expression in aged human dental pulp.

AIM: To investigate the expression of osteocalcin mRNA in young and in aged human dental pulp tissue to determine the characteristics of osteocalcin expression. METHODOLOGY: Human dental pulp tissues of the third molars were obtained from healthy young (17-23 years) and aged (>50 years) subjects, and total RNA was extracted. Osteocalcin mRNA expression was determined by RT-PCR and by quantitative real-time RT-PCR (QRT-PCR). The threshold cycle (Ct) value, which reflects the amount of PCR, was calculated and the difference between the value in young and aged pulp was statistically analysed. RESULTS: Osteocalcin mRNA was detected in all samples of human dental pulp tissue homogenates by RT-PCR analysis. Osteocalcin mRNA was expressed in young adult dental pulp but was decreased in aged human dental pulp. QRT-PCR analysis also showed a reduced expression of osteocalcin mRNA in aged human pulp. Expression of osteocalcin in young human pulp was significantly higher (about sixfold) than in aged pulp (P<0.01, Mann-Whitney U-test). CONCLUSION: Reduction of osteocalcin expression may be associated with the loss of viability in human dental pulp tissue, and may be a characteristic of aged human dental pulps.

Adolescent↗

Epitope analysis of myeloperoxidase-specific antineutrophil cytoplasmic autoantibodies (MPO-ANCA) in childhood onset Graves' disease treated with propylthiouracil.

AIM: This study aimed to elucidate the relationship between epitope profiles and clinical manifestations of patients with myeloperoxidase antineutrophil cytoplasmic autoantibodies-(MPO-ANCA) positive childhood onset Graves' disease treated with propylthiouracil (PTU). METHODS: Sixteen patients were studied. The patients were grouped into ten without clinical vasculitis and nephritis (non-vasculitis group) and six with biopsy-proven pauci-immune necrotizing crescentic glomerulonephritis (vasculitis group). Epitope analysis was performed on serum samples by an enzyme-linked immunosorbent assay (ELISA) using a panel of recombinant deletion mutants of MPO. RESULTS: The high frequency sites were region upstream of Met341 (Ha region) near the N-terminus of the heavy chain, and regions downstream of Gly598 (Hf and Hg regions) near the C-terminus. Most patients in the non-vasculitis group had polyclonal MPO-ANCA recognizing both the above linear sites and other epitope sites of the heavy chain of MPO. Only one of ten patients in the non-vasculitis group, and four of six patients in the vasculitis group had MPO-ANCA recognizing only the linear sites of the heavy chain of the MPO molecule (Ha, Hf and/or Hg). Of the four patients in the vasculitis group, two had nephritis, like rapidly progressive glomerulonephritis and one had alveolar hemorrhage. CONCLUSION: These findings suggest that most patients with childhood onset Graves' disease treated with PTU who manifest no vasculitis have polyclonal MPO-ANCA recognizing both the linear and other epitope sites of the heavy chain of MPO. However, some patients who develop nephritis have MPO-ANCA recognizing only the linear sites of the heavy chain of MPO. This clonality of MPO-ANCA may be a risk factor that induces clinical vasculitis and nephritis in patients treated with PTU. Therefore, patients exposed to PTU should be monitored for MPO-ANCA level and epitopes.

Adolescent↗

Treatment with low-dose angiotensin-converting enzyme inhibitor (ACEI) plus angiotensin II receptor blocker (ARB) in pediatric patients with IgA nephropathy.

AIM: IgA nephropathy associated with heavy proteinuria is considered a more progressive form of this disease. In this report, we describe the favorable clinical effect of combination therapy with low doses of an angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) in the chronic stage of pediatric IgA nephropathy associated with heavy proteinuria. PATIENTS: We initially used ACEI for seven children with IgA nephropathy and heavy proteinuria who did not achieve remission with the routine treatment including steroids. RESULTS: With ACEI therapy alone, only three patients showed an antiproteinuric response. In one of the three patients, the proteinuria decreased by half, but was still over 1 g/day. In the other four patients, the proteinuria did not decrease. In these five patients, of whom one partial was a responder and four were non-responders for ACEI, ARB was added, and in marked contrast to ACEI therapy alone, the antiproteinuric effect was significantly augmented (p < 0.01). The antiproteinuric response induced by combination therapy was not accompanied by blood pressure changes. Urinary low-molecular protein and N-acetyl-beta-D-glucosaminidase (NAG) levels tended to decrease after both ACEI alone and combination therapy. CONCLUSION: These data indicate that inhibition therapy of the angiotensin system not only decreases proteinuria levels but also protects renal tubular cells. Moreover, there were no obvious side effects associated with this therapy during the follow-up period of our clinical trial. In conclusion, this report shows that the combination of low doses of ACEI and ARB might provide marked antiproteinuric and long-term renoprotective effects in pediatric IgA nephropathy, with this approach appearing to be both well-tolerated and safe.

Angiotensin II Type 1 Receptor Blockers↗

The role of climate variability in the inter-annual variation of terrestrial net primary production (NPP).

Eleven years data set of global net primary production (NPP) and long-term climatic and land use data were used to explore the patterns of inter-annual variability of terrestrial NPP in relation to potential causal factors. Global anomalies in temperature, precipitation and cloud cover were found to significantly contribute in different ways and magnitudes to the variability of NPP of global ecosystems particularly forests and grasslands. El Niño/La Niña events represented an important factor affecting forests, woodlands and grasslands while deforestation was found to largely contribute to the NPP variability of tropical forests. Regionally, NPP variability is related to variation of precipitation in the tropics but is related to both variation and annual mean of temperature and cloud cover in the mid-northern latitudes. We hypothesized that the increase in variability of potential causal factor(s) will provoke more declines of NPP in the tropics but will yield more pulses or at least maintain a mean NPP in the mid-northern latitudes.

Carbon Dioxide↗

Synthetic sulfonolipids deduced from sulfonoquinovosyl diacylglycerols of sea urchin reduces hepatic ischemia-reperfusion injury in rats.

BACKGROUND: In hepatic surgery and liver transplantation, ischemia-reperfusion (I/R) is an unavoidable process, and protection against hepatic I/R injury is a major unresolved problem. In this study, we investigated whether 3-O-(6-deoxy-6-sulfono-beta-D-glucopyranosyl)-1,2-di-O-acylglycerol bound to saturated C18 fatty acids (beta-SQAG9), which was derived from sea urchin intestines, could reduce this injury. This agent was recently reported to have immunosuppressive effects in allogeneic rat skin grafts. MATERIALS & METHODS: Male Lewis rats were divided into two experimental groups. Group 1 rats were injected with SQAG9 (50 mg/kg) into the penile vein 15 minutes before the induction of ischemia and into the portal vein just reperfusion. The same amounts of normal saline were injected into rats in the control group (group 2). Each experimental groups included six rats. Seventy percent hepatic ischemia (20 minutes) was induced by occluding the blood vessels and bile duct with a vascular clamp. For examination of hepatic function, serum levels of aspartate aminotransferase, (AST) alanine transaminase (ALT), and lactic dehydrogenase (LDH) were measured. In addition, histological examination was also assessed. RESULTS: Three hours after reperfusion, the mean plasma concentration of AST, ALT, LDH in group 1 was suppressed compared with group 2. Six hours after reperfusion, the hepatic damage in group 1 was mild in comparison with that in group 2. CONCLUSIONS: Our data demonstrated that SQAG-9 reduced the warm hepatic I/R injury.

Animals↗

Acute myelogenous leukemia in a donor after granulocyte colony-stimulating factor-primed peripheral blood stem cell harvest.

This article describes the first case of acute myeloid leukemia (AML) in a healthy donor at 14 months after granulocyte colony-stimulating factor (G-CSF)-primed peripheral blood stem cell (PBSC) harvest. In September 2001, a healthy 61-year-old female was given G-CSF prior to PBSC harvest for her brother with multiple myeloma. In spite of successful engraftment, the recipient died from a disease relapse. In November 2002, the donor, admitted with high fever and leukocytosis with 98.5% blastoid cells, was diagnosed as having AML (M1). Her leukemia cells were positive for CD13, CD33, and G-CSF receptor without chromosomal abnormality and responded to G-CSF in vitro. During chemotherapy, she died of progressive pneumonia. If our case is truly the first, the incidence of leukemia in donors may not be higher than that of naturally occurring leukemia. However, efforts towards an international long-term study, or at least to report every case similar to ours, would be required to be conclusive.

Female↗

Oligoclonal expansion of circulating and tissue-infiltrating CD8+ T cells with killer/effector phenotypes in juvenile dermatomyositis syndrome.

Although triggering by infectious agents and abnormal immune responses may play some role in the pathogenesis of juvenile dermatomyositis syndrome (JDMS), the precise mechanism of muscle destruction and vascular damage is largely unknown. In this study, we tried to elucidate the role of cytotoxic T cells in two patients with JDMS, who were diagnosed based on the characteristic symptoms, laboratory data, MRI findings and electromyographic patterns. Peripheral blood T cell phenotypes were determined by flow cytometry, using mAbs against specific T cell receptor (TCR) Vbetas. Complementarity-determining region3 (CDR3) size analysis was performed by gene scanning of CDR3 polymerase chain reaction (PCR) amplification products specific for each Vbeta. Subsequently, CDR3 nucleotide sequences were obtained after cloning of the predominant products. The distribution of lymphocytes infiltrating the muscle tissue was analysed by immunohistochemistry. In both patients examined, a unique combination of TCR Vbeta repertoires was increased within the CD8+ T cells. These subpopulations expressed a characteristic phenotype, indicating that they are memory/effector T cells with killer functions. At the same time, immunohistological and molecular biological examinations of the biopsied muscle samples revealed that identical CD8+ T cell clones with identical phenotypes/TCR Vbeta infiltrated within the inflammatory tissue, in particular around vessels. These findings indicate that oligoclonal expansion of CD8+ T cells plays a central role in the pathogenesis of muscle injury in the juvenile form of dermatomyositis syndrome and may provide a useful clinical parameter of disease activity and responsiveness to anti-inflammatory therapy.

Antigens, CD↗

Reduction of connexin 43 expression in aged human dental pulp.

AIM: To investigate the expression of connexin 43 (CX43) mRNA in young and old human dental pulp tissues to determine the characteristics of CX43 expression. METHODOLOGY: Samples were obtained from human dental pulp of healthy young (17-23 years) and aged (>50 years) subjects. CX43 expression was determined by RT-PCR and by quantitative real-time RT-PCR (QRT-PCR). The threshold cycle (Ct) value, which reflects the amount of PCR, was calculated and the difference between value in the young pulp and that in the aged pulp was statistically analysed. RESULTS: RT-PCR analysis of human dental pulp tissue detected CX43 mRNA in all the samples. CX43 was abundantly expressed in young adult dental pulp, but expression of CX43 mRNA was dramatically decreased in aged human dental pulp. QRT-PCR analysis also showed the reduced expression of CX43 in aged pulp, and expression of CX43 in young pulp was significantly higher (about 10-fold, P < 0.01, Mann-Whitney U-test). CONCLUSION: Reduction of CX43 expression may be associated with the loss of viability in human dental pulp, and is considered as one characteristic of aged pulp.

Adolescent↗

Locoregional immunotherapy of malignant effusion from colorectal cancer using the streptococcal preparation OK-432 plus interleukin-2: induction of autologous tumor-reactive CD4+ Th1 killer lymphocytes.

In total, 16 patients with cytologically proven malignant effusion from colorectal cancer were treated by locoregional administration of the streptococcal preparation OK-432 alone or OK-432 plus the T-cell growth factor interleukin (IL)-2, and the action mechanism of the treatment was studied. A positive clinical response, showing a cytologic disappearance of cancer cells and decrease of effusion, was observed in nine of 11 (82%) patients treated with OK-432 alone and in all five patients treated with OK-432 plus IL-2. Flow cytometric analysis revealed that OK-432 plus IL-2 locally induced acute inflammation-like responses, including serial cellular infiltrations of granulocyte migration within a matter of hours, and activation of macrophages and T lymphocyte involvement within the following days, and that a predominant expansion of CD3+CD4+ lymphocytes (CD: cluster of differentiation) was induced by in vitro stimulation with IL-2 of locoregional cells after the OK-432 administration (OK/IL-2AK cells). The OK/IL-2AK cells produced tumour necrosis factor-alpha and interferon-gamma, but these cells did not produce IL-4 and IL-6. The OK/IL-2AK cells expressed potent killing activity against autologous tumour cells. This activity was abrogated by treatment of the lymphocytes with anti-CD3, -CD4, -TCRalphabeta antibody, and by the treatment of target cells with anti-human leukocyte antigen (HLA)-DR antibody. The OK/IL-2AK cells expressed Fas-L gene, and flow cytometric analysis demonstrated HLA-DR expression in approximately 75% of CEA+ or cytokeratin+ effusion cells. TCRVbeta gene analysis of the OK/IL-2AK cells showed an oligoclonal usage of TCRbeta20, which was also involved in the cytotoxic mechanism of the OK/IL-2AK cells. Single-strand conformational polymorphism analysis demonstrated the clonotypes for the TCRVbeta20 gene, and the CDR3s of the gene were sequenced. The clonotypic PCR using the TCRVbeta20-CDR3 sequences could detect the CDR3-identical TCRs in effusion lymphocytes from the other patients. Taken together, it is suggested that locoregional administration of OK-432 plus IL-2 is highly effective for the management of malignant effusion from colorectal cancer. OK-432 plus IL-2 induces autologous tumour-reactive CD4+ Th1 killer lymphocytes, which recognise tumour antigen(s) presented with HLA class II molecules on effusion tumour cells by means of preferential usage of TCRVbeta20. The clonotypic PCR using the TCRVbeta20-CDR3 sequences may be informative for treating malignant effusion from colorectal cancer using OK-432 plus IL-2.

Adult↗

Thrombopoietin stimulates ex vivo expansion of mature neutrophils in the early stages of differentiation.

We examined the effects of thrombopoietin (TPO) in combination with stem cell factor (SCF), interleukin-3 (IL-3), and granulocyte colony-stimulating factor (G-CSF) on the proliferation and differentiation of human neutrophils. Purified CD34(+) hematopoietic progenitor cells were cultivated with SCF, IL-3, and G-CSF for 7 days (early phase), and thereafter nonadherent cells were further cultivated for 9 days with G-CSF alone (late phase). A large number of highly selected neutrophils (>95%) was obtained on day 16. We compared the expansion capacity in the presence or absence of TPO in each culture phase. The significantly larger number of neutrophils was obtained in the presence of TPO in the early culture phase. The number of expanded cells plateaued at day 16. Ultimately, a 550-fold increase in the number of neutrophils was achieved. These neutrophils gained the ability to respond effectively with chemotaxis and superoxide release, and were appropriately primed by G-CSF, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and IL-1beta for enhanced release of O(2)(-). The responsiveness of these cells was identical to that of peripheral blood neutrophils. However, TPO did not accelerate the maturation of neutrophils supported by G-CSF in the late phase of culture. Furthermore, priming effects and triggering effects of TPO on the production of superoxide metabolites from peripheral blood neutrophils were not observed. These results suggest that TPO regulates the proliferation and differentiation of neutrophils in the early stages, but not the late stages, of differentiation.

Antigens, CD34↗

Successful treatment with reduced-intensity stem cell transplantation in a case of relapsed refractory central nervous system lymphoma.

A 33-year-old male with refractory relapsed central nervous system lymphoma underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an HLA-identical sibling after reduced-intensity conditioning chemotherapy. The preparative regimen for allo-HSCT consisted of fludarabine and busulfan. Cyclosporine (CsA) and short-term methotrexate were used as prophylaxis for acute graft-versus-host disease (GVHD). Although CsA was quickly reduced to induce a graft-versus-lymphoma (GVL) effect, no symptoms of GVHD and GVL effect were evident. Donor lymphocyte infusion (DLI) was performed on day +40 following transplantation. The patient developed acute GVHD (grade III) after DLI, and lymphoma regression was observed after the occurrence of GVHD. Four months after transplantation, complete remission was achieved with extensive chronic GVHD, and the patient continues to be disease free at 15 months after transplantation.

Adult↗