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Biomedical subjects

K Agematsu

Publications and source records attributed to K Agematsu.

At least 19 recordsLinked to original sources
PubMed2006

Secretory IgA, salivary peroxidase, and catalase-mediated microbicidal activity during hydrogen peroxide catabolism in viridans streptococci: pathogen coaggregation.

Viridans streptococci can kill methicillin-resistant Staphylococcus aureus (MRSA) through the production of hydrogen peroxide (H2O2). However, several hundred viridans streptococci cells are necessary to kill 1 cfu of MRSA. We analyzed the potency of bactericidal and fungicidal effector molecules induced by catabolism of H2O2 in the oral cavity. Secretory IgA (SIgA) and an unidentified salivary component bound Streptococcus sanguinis, a viridans streprococcus, and MRSA into coaggregates. In these coaggregates, salivary peroxidase and the MRSA catalase produced singlet molecular oxygen (1O2) from H2O2 produced by viridans streptococci. SIgA converted 1O2 into ozone, which has potent bactericidal and fungicidal activity. We calculated that <10 cfu of Streptococcus sanguinis were necessary to kill 1 cfu of MRSA in the coaggregate. SIgA, Aspergillus niger catalase, and H2O2 in saliva killed Candida albicans, which is highly resistant to reagent H2O2. Together with indigenous bacteria and innate immunity, SIgA potentially constitutes a novel system that may sustain oral homeostasis.

Adult↗
PubMed2005

Polarization of Th1/Th2 in human CD4 T cells separated by CD62L: analysis by transcription factors.

BACKGROUND: T-cell surface antigens that differentiate clearly between Th1 and Th2 have not been identified. Discrimination of Th1/Th2 subpopulations by CD62L expression has been reported. We investigated the expression of transcription factors that regulate Th1/Th2 cytokine synthesis in human CD4+ T-cell subpopulations separated by CD45RO and CD62L, and compared the ratio of CD62L+ to CD62L- cells between healthy individuals and patients with allergic diseases. METHODS: Human peripheral blood samples were obtained from healthy volunteers and patients. CD4+ T cells were isolated by negative selection. Three CD4+ T-cell subpopulations separated by CD45RO and CD62L were isolated using three-color fluorescence. Sorted cells were stimulated with anti-CD3 monoclonal antibody, and the cytokine levels were measured using a Cytometric Bead Array Kit. Transcription factor expression was examined by reverse transcriptase polymerase chain reaction (RT-PCR) and real-time RT-PCR. RESULTS: Interleukin (IL)-4 and IL-5 production levels by CD45RO+CD62L+CD4+ T cells were higher than those of CD45RO+CD62L-CD4+ T cells (P < 0.05), whereas interferon-gamma and tumor necrosis factor-alpha production were lower levels (P < 0.05). T-cell immunoglobulin mucin-3 and T-bet expression were detected in CD45RO-CD62L+ and CD45RO+CD62L- cells following stimulation, but not in CD45RO+CD62L+ cells. However, the ratio of CD62L+ to CD62L- cells was the same in both healthy individuals and patients (P = 0.54). There was no difference in Th1/Th2 cytokine synthesis by CD4+ T cells. CONCLUSION: Analyses of cytokine syntheses and transcription factor expression demonstrated that CD62-negative and -positive subpopulations of human CD45RO+CD4+ T cells represent characteristics of Th1 and Th2, respectively.

CD4-Positive T-Lymphocytes↗
PubMed2005

[Critical hypertrophic obstructive cardiomyopathy patient with improved hemodynamics following mitral valve replacement: report of a case].

A 75-year-old man with dyspnea was admitted to our hospital in critical condition. Catheterization showed normal coronary arteries and good left ventricular function. Transesophageal echocardiography showed left ventricular hypertrophy and severe mitral regurgitation. We decided to perform mitral valve replacement because the patient was in critical condition and it was necessary to complete the operation smoothly. During the operation, we could see the dilated mitral valve annulus and hypertrophic mitral valve, which was restricted. The patient's hemodynamics showed improvement after mitral valve replacement with a mechanical prosthesis, and he was discharged on postoperative day 21. In conclusion, mitral valve replacement is a beneficial method for the treatment of patients with critical hypertrophic obstructive cardiomyopathy.

Aged↗
PubMed2005

[Mitral valve repair of valve insuffficiency with broad and complex lesions due to infective endocarditis; report of a case].

Surgical intervention is necessary for the treatment of infective endocarditis, although antibiotic therapy has been shown to be effective for treatment of this disorder. Mitral valve infective endocarditis frequently presents with broad and complex lesions, and thus a variety of valve repair is needed. A 40-year-old woman with mitral valve insufficiency due to infective endocarditis underwent mitral valve repair. During the operation, torn chordae, aneurysm with perforation of the anterior leaflet, and torn chordae of the posterior leaflet were found. The chordae of the anterior leaflet were reconstructed and the aneurysm was excised, and autopericardial patch repair was performed. Then, resection and suturing of the prolapsing lesion of posterior leaflet were performed. Mitral valve repair preserves the left ventricular apparatus and function. Therefore, mitral repair results in better prognosis than valve replacement. The repair of the mitral valve should be attempted for the treatment of valve insufficiency due to infective endocarditis.

Adult↗
PubMed2004

[An anastomosis assist mirror; a new device for off-pump coronary artery bypass].

An anastomosis assist mirror for off-pump coronary artery bypass (OPCAB) is described. This new device is designed to make a view of the circumflex coronary artery which is often troublesome to access during OPCAB. It is composed of 3 parts: a small circular mirror, a paper clip and a flexible arm between the mirror and the clip. The paper clip is situated at an edge of a sternal retractor. The mirror is positioned beside the sheer surface of the lateral wall of the heart by regulating the flexible arm. It shows a flat, reflective view of the anastomotic site and makes an anastomosis easy. The device enables us to avoid excessive manipulation on the heart and hemodynamic instability, thereby reducing unnecessary volume overload, inotropic drugs or mechanical cardiac assistance.

Anastomosis, Surgical↗
PubMed2003

[Clinical outcome of emergency off-pump coronary artery bypass grafting].

From January 2001 to January 2003, we performed 25 emergency off-pump coronary artery bypass grafting (CABG) procedures for patients with acute myocardial infarction (AMI) or unstable angina pectoris. During the same period, we also performed 2 emergency on-pump beating CABG procedures for patients with left main coronary trunk (LMT) shock syndrome. For the present study, we evaluated the operative results of the 25 cases of emergency or urgent off-pump CABG. The patients were divided into 3 groups, those with acute AMI with cardiogenic shock (group 1; n = 8), acute myocardial infarction without shock (group 2; n = 8), and unstable angina (group 3; n = 9). There were no differences between groups 1 and 2 with regard to age, number of diseased vessels, and preoperative use of an intraaortic balloon pump, however, patients in group 1 had a higher number of completely obstructed coronary arteries. Patients in groups 1 and 2 underwent off-pump CABG within 3.5 hours after a coronary angiography or coronary intervention procedure, while those in group 3 underwent off-pump CABG within 2 days of coronary angiography. The mean number of grafts per patient was 1.8, 2.1, and 2.3 in groups 1, 2, and 3, respectively. One group 1 patient with an LMT lesion was transferred to on-pump beating CABG because of hemodynamic instability. The 30-day mortality rate was 38% (3 of 8) in group 1, whereas it was 0% in groups 2 and 3. Intubation time, ICU stay, and postoperative stay were similar among the 3 groups. An early angiographic study was undertaken in all surviving patients and the results demonstrated patency in all of the examined grafts. Although our results are limited, emergency off-pump CABG was found to be safe and feasible for AMI without cardiogenic shock or unstable myocardial ischemia. However, the outcome of this procedure for patients with preoperative cardiogenic shock was not satisfactory, therefore, a combination therapy of appropriate mechanical circulatory support, prior revascularization by catheter intervention, and emergency surgical revascularization are considered to improve survival of those patients.

Aged↗
PubMed2002

IL-10 enhances B-cell IgE synthesis by promoting differentiation into plasma cells, a process that is inhibited by CD27/CD70 interaction.

Interleukin-10 (IL-10) is a major regulatory cytokine of inflammatory responses that is considered to play an important role in specific immunotherapy. However, whether IL-10 enhances or inhibits B-cell IgE production has remained a matter of contention. To clarify the effect of IL-10 on IgE synthesis in the presence of IL-4 and CD40 signalling, we examined B-cell proliferation, germline epsilon transcripts and plasma cell differentiation. In addition, the effect of CD27 signalling on IgE synthesis in the presence of IL-10, IL-4 and CD40 signalling was investigated. IL-10 facilitated the production of IgE in mononuclear cells and highly purified B-cells, enhanced B-cell proliferation and, most importantly, promoted the generation of plasma cells. However, IL-10 did not enhance expression of germline epsilon transcripts. The addition of CD27 signalling through the use of CD32-CD27 ligand (CD70) double transfectants significantly diminished the B-cell proliferation, IgE synthesis and plasma cell differentiation enhanced by IL-10. IL-10 enhances B-cell IgE production by promoting differentiation into plasma cells. CD27/CD70 interactions under IL-10 and sufficient CD40 cosignalling exert the opposite effect on IgE synthesis. The results of this study indicate that precautions are critical when planning immunotherapy using IL-10 in IgE-related allergic diseases.

Adult↗
PubMed2002

Involvement of CD27/CD70 interactions in antigen-specific cytotoxic T-lymphocyte (CTL) activity by perforin-mediated cytotoxicity.

CD27 molecules are shown to be essential in the regulation of the death, activation and differentiation of T and B cells. However, the influence of CD27 on cytotoxic T-cell function remains obscure. Autologous EBV transformed B-cell lines (LCL), which highly express CD27 ligand CD70, here stimulated T cells and induced the cytotoxic T-lymphocyte (CTL) activity via T-cell antigen receptors (TCR). The cytotoxicity against LCL was diminished when anti-CD70 blocking MoAb was added initially in the culture. Resting T cells killed more CD70-transfected P815 cells than wild type P815 cells in the presence of anti-CD3 MoAb as measured by a 4-h 51Cr release assay, and the cytotoxicity of both of the cell populations completely disappeared in the presence of concanamycin A (CMA). The expression of the perforin by the LCL-induced CTL in the presence of anti-CD70 blocking MoAb was diminished as compared with that without the blockage of CD27/CD70 interactions. The CTL induced by LCL did not kill Fas-transfected WR cells. CD27 signalling in the T cells did not affect Fas ligand (FasL) mRNA expression, LAK activity and IFN-gamma synthesis in humans. Our data demonstrate that CD27/CD70 interactions enhance the cytotoxicity of CTL in the induction phase through enhancement of killing activity induced via the perforin-dependent mechanism, but not via the Fas/FasL system.

Antigens, CD↗
PubMed2001

Neutrophil-specific granule deficiency: homozygous recessive inheritance of a frameshift mutation in the gene encoding transcription factor CCAAT/enhancer binding protein--epsilon.

Neutrophil-specific granule deficiency (SGD) is a rare congenital disorder. The neutrophils of individuals with SGD display atypical bi-lobed nuclei, lack expression of all secondary and tertiary granule proteins, and possess defects in chemotaxis, disaggregation, receptor up-regulation, and bactericidal activity, resulting in frequent and severe bacterial infections. Previously, a homozygous mutation in the CCAAT/enhancer binding protein-epsilon (C/EBPepsilon) gene was reported for one case of SGD. To substantiate the role of C/EBPepsilon in the development of SGD and elucidate its mechanism of inheritance, the mutational status of the gene was determined in a second individual. An A-nucleotide insertion in the coding region of the C/EBPepsilon gene was detected. This mutation completely abolished the predicted translation of all C/EBPepsilon isoforms. Microsatellite and nucleotide sequence analyses of the C/EBPepsilon locus in the parents of the proband indicated that the disorder may have resulted from homozygous recessive inheritance of the mutant allele from an ancestor shared by both parents. The mutant C/EBPepsilon(32) protein localized in the cytoplasm rather than the nucleus and was unable to activate transcription. Consistent with this, a significant decrease in the levels of the messenger RNAs (mRNAs) encoding the secondary granule protein human 18-kd cationic antimicrobial protein (hCAP-18)/LL-37 and the primary granule protein bactericidal/permeability-increasing protein were observed in the patient. The hCAP-18 mRNA was induced by overexpression of C/EBPepsilon(32) in the human myeloid leukemia cell line, U937, supporting the hypothesis that C/EBPepsilon is a key regulator of granule gene synthesis. This study strongly implicates mutation of the C/EBPepsilon gene as the primary genetic defect involved in the development of neutrophil SGD and defines its mechanism of inheritance.

Adult↗
PubMed2001

Inhibition of methicillin-resistant Staphylococcus aureus colonization of oral cavities in newborns by viridans group streptococci.

We investigated the role of viridans group streptococci in the prevention of colonization with methicillin-resistant Staphylococcus aureus (MRSA) in neonatal intensive care units. During a 26-month period at a children's hospital, 207 (49.9%) of 415 newborns were colonized with MRSA by the time of discharge. Two groups of newborns with matching durations of hospitalization were compared with regard to the prevalence of future colonization with MRSA: group 1 (103 patients) did not acquire colonization with viridans group streptococci and group 2 (63 patients) did acquire colonization with viridans group streptococci at birth or by 1 to 2 weeks (age, < or =11 days). The rate of colonization among patients in group 2 (9.5%) was significantly lower than that among patients in group 1 (44.7%; P<.001). No significant difference in patient characteristics (e.g., birth weight, diseases) was observed. These results indicate that viridans group streptococci, as bacteria that formerly occupied the oral cavities in newborns, may inhibit later colonization with MRSA.

Antibiosis↗
PubMed2001

H(2)O(2) produced by viridans group streptococci may contribute to inhibition of methicillin-resistant Staphylococcus aureus colonization of oral cavities in newborns.

In an accompanying report, we showed that viridans group streptococci may prevent methicillin-resistant Staphylococcus aureus (MRSA) colonization of the oral cavities of newborns. In the present study, we investigated the mechanism of prevention in vitro. Most viridans group streptococci had bacteriocin-like activity and killed MRSA, Burkholderia cepacia, Enterobacter aerogenes, and Pseudomonas aeruginosa; however, Escherichia coli, Enterobacter cloacae, and Candida albicans were resistant. The activity was induced only by H(2)O(2)-secreting strains and was inhibited by horseradish peroxidase or catalase in a dose-dependent manner. The mean concentration of H(2)O(2) produced by 18 strains of viridans group streptococci (1 x 10(8) cfu in 200 microL of culture medium+/-standard deviation was 1.24+/-0.60 mmol. Viridans group streptococci inhibited MRSA growth in saliva as well as in culture media. These results indicate that H(2)O(2) produced by viridans group streptococci may inhibit MRSA colonization of oral cavities in newborns.

Antibiosis↗
PubMed2001

Mechanism of hypergammaglobulinemia by HIV infection: circulating memory B-cell reduction with plasmacytosis.

The mechanism of hypergammaglobulinemia in patients infected with HIV has remained unclear in spite of the identification of a reduction of CD4+ T cells. The amounts of CD27+ memory B cells were remarkably reduced in the peripheral blood and immunoglobulin (Ig) production was diminished in HIV-infected patients. Some of the freshly isolated patients' T cells expressed the CD70 (CD27 ligand) on the surface and the CD70 expression on both of the CD4+ and CD8+ T cells was greatly enhanced by various stimuli. It was also striking that plasmacytosis was observed in patients' bone marrow. Thus, our findings suggest that CD70 expressed spontaneously or by activation on T cells of HIV-infected patients stimulates memory B cells via CD27 and promotes their differentiation into plasma cells, resulting in the elevation of serum Ig levels and the elimination of circulating memory B cells in HIV-infected patients.

Adult↗
PubMed2001

Direct B/B-cell interactions in immunoglobulin synthesis.

The principal roles of B/B-cell interactions in immune response have not yet been established. We therefore investigated B/B-cell interactions in immunoglobulin synthesis via direct cell-to-cell contact, particularly in the tumour necrosis factor receptor (TNFR)/tumour necrosis factor (TNF) family. We prepared highly purified peripheral blood B cells and stimulated them with Epstein--Barr virus (EBV)-transformed B lymphoblastoid cell lines (LCLs) as activated human B cells. The IgG production by B cells was increased by the addition of fixed LCLs in a dose-dependent manner in the presence of IL-10 plus IL-2. LCLs strongly expressed CD40 and CD70 on their surface, but marginal or no CD154, CD27, OX40 (CD134) and CD134 ligand. The enhancement of immunoglobulin production by LCLs was completely blocked by the initial addition of anti-CD70 blocking MoAb, but not by anti-CD154 or anti-CD134 ligand MoAb. The addition of LCLs also caused a reduction in CD27 expression on B cells, and this effect was completely blocked by anti-CD70 MoAb, indicating a direct B cell--LCL contact via CD27/CD70. LCLs markedly promoted B-cell differentiation into plasma cells in the presence of IL-10 plus IL-2. These findings demonstrate that direct interactions between B and B cells via CD27/CD70 induce immunoglobulin production by promoting the generation of plasma cells.

Antigens, CD↗
PubMed2001

Complete arrest from pro- to pre-B cells in a case of B cell-negative severe combined immunodeficiency (SCID) without recombinase activating gene (RAG) mutations.

The B-cell lineage in a patient with B-cell-negative severe combined immunodeficiency (SCID) was analysed by using antisurrogate light chain (SL) MoAbs. Peripheral CD3(+) T cells and CD19(+) B cells were absent in the patient. The common gamma (gamma c) chain was expressed normally on the patient's peripheral NK cells and his peripheral mononuclear cells did not possess any mutations in recombinase activating gene (RAG)-1, 2. Normal levels of expression of Ku70 and Ku80 protein were found by Western blot analysis. The patient did, however, display an increase in fibroblast sensitivity to irradiation. Furthermore, flow cytometric analyses of bone marrow cells showed that surface IgM and cytoplasmic mu positive cells were absent and that CD19(+) B cells were composed of only CD34(+) terminal deoxynucleotidyl transferase (TdT)(+) SL(+) pro-B cells. The complete arrest of pro- to pre-B cell development in the SCID patient's bone marrow suggests that some genes involved in V(D)J recombination, excepting the RAG gene, may play a causative role in the immunodeficiency.

Antigens, CD↗
PubMed2001

A thiol proteinase inhibitor, E-64-d, corrects the abnormalities in concanavalin A cap formation and the lysosomal enzyme activity in leucocytes from patients with Chediak-Higashi syndrome by reversing the down-regulated protein kinase C activity.

We have reported previously that the abnormally down-regulated protein kinase C (PKC) causes cellular dysfunction observed in natural killer (NK) cells, polymorphonuclear leucocytes (PMNs) and fibroblasts from beige mouse, an animal model of Chediak-Higashi syndrome (CHS). Here we show that the abnormal down-regulation of PKC activity also occurs in Epstein-Barr (EB) virus-transformed cell lines from CHS patients. When CHS cell lines were stimulated with concanavalin A (Con A) for 20 min, the membrane-bound PKC activity declined markedly, whereas that in control cell lines increased. We found that E-64-d, which protects PKC from calpain-mediated proteolysis, reversed the declined PKC activity and corrected the increased Con A cap formation to almost normal levels in CHS cell lines. We confirmed that the dysregulation of PKC activity also occurred in peripheral blood mononuclear leucocytes (PBMC) from CHS patients and that E-64-d corrected both the declined PKC activity and increased Con A cap formation. E-64-d also corrected the reduced lysosomal elastase and cathepsin G activity in CHS cell lines. In contrast, chelerythrin, a specific inhibitor of PKC, and C2-ceramide, which promotes PKC breakdown induced by calpain, increased Con A cap formation and inhibited both elastase and cathepsin G activity in normal cell lines. Moreover, we found that ceramide production in CHS cell lines increased significantly after Con A stimulation, which coincides with our previous observation in fibroblasts from CHS mice. These results suggest an association between ceramide-induced PKC down-regulation and the cellular dysfunctions in CHS.

Calpain↗
PubMed2000

Genetic defect in human X-linked agammaglobulinemia impedes a maturational evolution of pro-B cells into a later stage of pre-B cells in the B-cell differentiation pathway.

Surrogate light chains (lambda 5/VpreB) are selectively expressed in early precursors of B cells. B-cell defects in X-linked agammaglobulinemia (XLA) are caused by mutations in the gene for Bruton's tyrosine kinase. To elucidate the nature of early B-lineage cells in bone marrow (BM), samples from 13 XLA patients and 24 healthy controls of different ages were comparatively analyzed using an antihuman VpreB monoclonal antibody. Expression of surrogate light (SL) and mu-heavy chains were examined after cell membrane permeabilization because they are mainly expressed in the cytoplasm of early B-lineage cells. A flow cytometric analysis of normal BM identified 5 discrete cell types of B cells: mu(-)SL(++) (pro-B [B-cell progenitor]), mu(low)SL(++) (pre-B1a), mu(low)SL(+) (pre-B1b), mu(low)SL(- )(pre-B2), and mu(high)SL(- )(B). The large cells, presumably in cycling states, were enriched in pre-B1a cells. The frequencies of B-lineage cells in BM were higher in young children, and declined with advancing age. In contrast, XLA showed a profound reduction in BM B-lineage cells. In XLA BM, an expansion of pro-B cells with some small pre-B1a cells was marked, but other cells were negligible. These observations illustrate a B-cell maturation defect in XLA as well as a normal human B-cell differentiation pathway. The results suggest that the genetic defect in XLA may impede the evolution of pro-B cells beyond the earlier pre-B stage into the later stage of pre-B cells in B-cell development. (Blood. 2000;96:610-617)

Adolescent↗
PubMed2000

Theophylline induces neutrophil apoptosis through adenosine A2A receptor antagonism.

This study was designed to determine whether theophylline would augment granulocyte apoptosis via a mechanism of adenosine A2A receptor antagonism. A selective adenosine A2 receptor agonist (CGS-21680, 1 microM) exhibited the most efficient potency for decreasing neutrophil apoptosis for 16 h from 63+/-5 to 19+/-4% (P < 0.001); it exerted poor and adverse effects on eosinophil survival. A selective protein kinase A inhibitor KT-5720 (10 microM) reversed the capacity of dibutyryl cAMP but not CGS-21680 to induce an inhibitory effect on neutrophil apoptosis, suggesting that occupancy of adenosine A2 receptors inhibit neutrophil apoptosis by a cAMP-independent mechanism. Theophylline derivatives show the following pattern of potency for inducing neutrophil apoptosis competing with CGS-21680: 8-phenyltheophylline = 8-p-sulfophenyltheophylline > theophylline >> enprofylline. This pattern is consistent with the affinity established for A2A receptors. Theophylline demonstrated an additive effect to that of anti-Fas antibody (CH11, 1 microg/mL) in inducing neutrophil apoptosis, but not to that of adenosine deaminase or KF-17837 (a selective A2 receptor antagonist; 1 microM), suggesting conflicting effects on the receptor antagonism. These findings suggest that theophylline has an immunomodulatory action on neutrophil apoptosis via a mechanism of A2A antagonism.

Adenosine↗