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Biomedical subjects

T Kawamura

Publications and source records attributed to T Kawamura.

At least 235 records · Page 13Linked to original sources
PubMed1998

Design and fabrication of highly heat-resistant Mo/Si multilayer soft X-ray mirrors with interleaved barrier layers.

Introducing interleaved carbon barrier layers improves the heat-resistance of Mo/Si multilayers. The soft X-ray reflectivities of the multilayers were calculated, and the effects of heating on both the reflectivities and layer structures of Mo/Si multilayers with and without barrier layers were investigated using X-ray diffraction and transmission electron microscopy. The results show that, for applications using intense soft X-ray beams, Mo/Si multilayers with interleaved carbon barrier layers are better mirrors than Mo/Si multilayers because they have much better heat resistance and almost the same soft X-ray reflectivity as the Mo/Si multilayers.

Journal Article↗
PubMed1998

Differentiation of forbidden T cell clones and granulocytes in the parenchymal space of the liver in mice treated with estrogen.

Estrogen was administered to B6 (NK1.1+ strain), BALB/c (Mls-1b2a, V beta 3+ cells being forbidden clone), or (B6 x BALB/c) F1 mice (1 mg/mouse). On days 3 and 10, the number of cells yielded by the liver doubled, whereas that yielded by the thymus decreased prominently. The numbers of cells in the spleen, bone marrow, and blood were unchanged. c-kit+ stem cells, which give rise to multilineage cells, were present in the liver and bone marrow. The proportion of such c-kit+ cells in the liver increased while that in the bone marrow decreased on day 3. Therefore, the absolute number of c-kit+ stem cells increased severalfold in the liver and clusters of lymphoid cells became visible in the parenchymal space. At that time, the expression of recombination activating gene-1 and -2 mRNAs became prominent. Reflecting these phenomena, the number and proportion of IL-2R beta+ CD3int cells (i.e., primordial T cells) increased in the liver on days 3 and 10. An increase in the number of proportion of such CD3int cells was seen even in the thymus and uterus. In parallel with the increase of CD3int cells, the proportion of granulocytes also increased in various organs on day 3. Forbidden clones were present in either the NK1.1+ or the NK1.1- subset of CD3int cells in (B6 x BALB/c) F1 mice treated with estrogen and liver mononuclear cells in such mice acquired potent cytotoxicity against syngeneic thymocytes. These results reveal that estrogen has the ability to potentiate the generation of self-reactive T cells and granulocytes in the liver and other organs.

Animals↗
PubMed1998

Intermediate TCR cells can induce graft-versus-host disease after allogeneic bone marrow transplantation.

Mice fall victim to GVHD when subjected to immunosuppressive treatment and injected with allogeneic bone marrow cells. A major population of cells associated with GVHD is known to be T cells. However, whether such T cells are of thymic or extrathymic origin is obscure. We applied two immunosuppressive conditions, 9 and 6.5 Gy irradiation, to C3H/He mice (H-2k). Bone marrow cells for injection were obtained from C57BL/6 (B6) mice (H-2b). The 9-Gy mice were reconstituted by lymphocytes of donor origin and showed GVHD, whereas 6.5-Gy mice were reconstituted by lymphocytes of recipient origin and showed mild GVHD. The liver was the organ where the reconstitution of lymphocytes occurred efficiently, and a major lymphocyte subset was intermediate (int) CD3 cells (i.e., CD3int cells) in both mice. CD3int cells had the properties of extrathymic T cells, showing the phenotype of NK1.1 + CD3int using invariant V alpha 14 chain. In 6.5-Gy mice, allogeneic cells were rejected by extrathymic T cells of recipient origin. The stored CD3int cells from the liver of 9-Gy mice evoked similar GVHD when transferred into 6.5-Gy irradiated C3H/He mice. These results suggest that CD3int cells of extrathymic origin are a major population for the induction of GVHD under immunosuppressive conditions.

Adoptive Transfer↗
PubMed1998

Different moieties of tautomycin involved in protein phosphatase inhibition and induction of apoptosis.

The effects of tautomycin and its derivatives on protein phosphatases PP1 and PP2A and their apoptosis-inducing activity toward human leukemia Jurkat cells were examined, and the relationship between chemical structure and function was discussed. Among the compounds we examined, tautomycin was the most potent inhibitor and the most effective inducer of apoptosis. It inhibited PP1 and PP2A enzymatic activity concentration-dependently with IC50 values of 20 and 75 pM, respectively, in the presence of 0.01% Brij-35, and an LC50 value of 1 microM. Esterification of the anhydride moiety of tautomycin markedly increased the IC50 for the protein phosphatases. The C1'-C7' fragment of tautomycin had no inhibitory effect, but the fragment containing the C22-C26 moiety was inhibitory. These results suggest that the C22-C26 moiety is essential for inhibition of protein phosphatase activity and that the anhydride moiety enhances the inhibition. However, the esterification of the anhydride did not decrease, nor did the inclusion of the C22-C26 moiety increase the apoptosis-inducing activity. On the other hand, the C1-C18 moiety of tautomycin was essential for induction of apoptosis, and the conformation and the arrangement of functionalities of the C18-C26 carbon chain affected the apoptosis activity. However, modification of C1-C18, C1-C21, or C1-C26 compounds had little effect on phosphatase inhibitory activity. Our results strongly suggest that different moieties of tautomycin are involved in protein phosphatase inhibition and induction of apoptosis.

Antifungal Agents↗
PubMed1998

Inhibition of human T-cell leukemia virus type 1 replication by antisense env oligodeoxynucleotide.

Human T-cell leukemia virus type 1 (HTLV-1) infection is associated with adult T-cell leukemia and HTLV-associated myelopathy/tropical spastic paraparesis. Inhibition of HTLV-1 transmission is important to prevent the above HTLV-1-associated diseases. We used the antisense oligodeoxynucleotides (oligos) complementary to the first splice junction, rex responsive site, gag, env, tax, rex, and p21 and evaluated the effects on the syncytium formation between HTLV-1 producing human T-cell line, C9/PL cells, and HTLV-1-uninfected human glioma cell line, U251-MG cells. The syncytium formation was significantly inhibited the virion production assayed by antisense oligos to env, tax, gag, p21, and rex, with antisense oligo to env being the most inhibitory. Antisense oligos to env and tax also inhibited reverse transcriptase activity. Antisense oligo to env may have a potential as a preventive measure of HTLV-1 replication and transmission in vivo.

Base Sequence↗
PubMed1998

Critical role of NK1+ T cells in IL-12-induced immune responses in vivo.

CD1-dependent NK1+ T cells rapidly produce IL-4 upon stimulation through the TCR. These cells may therefore play an important role in the initiation of Th2 responses. Here, we show that NK1+ T cells constitutively express receptors for IL-12 and IFN-gamma, and that IL-12 induces production of perforin in these cells. Moreover, while IL-12 induces high levels of IFN-gamma and cytotoxic activity of hepatic or splenic mononuclear cells against tumor cells, this effect of IL-12 is significantly reduced in CD1-deficient mice with impaired NK1+ T cells development. These results indicate that NK1+ T cells play a critical role in IL-12-induced production of IFN-gamma to initiate Th1 immune responses and as IL-12-induced cytotoxic effector cells to initiate antitumor immunity.

Animals↗
PubMed1998

The incidence and characteristics of silent cerebral infarction in elderly diabetic patients: association with serum-soluble adhesion molecules.

The purpose of this study was to investigate the relationship between complications arising from silent cerebral infarction (SCI) and changes in the levels of serum-soluble adhesion molecules in 82 elderly diabetic patients aged 60 years and older. SCI was found in 43 % of the 82 patients, with incidence increasing in relation to age. The prevalence of SCI was higher in subjects with hypertension, poor metabolic control and increased fibrinolysis. The levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin (sE-selectin) were higher in diabetic patients than in non-diabetic subjects (p < 0.05, p < 0.001, and p < 0.05, respectively). Also, sICAM-1 and sVCAM-1 were found at increased levels in diabetic patients with SCI compared to those without SCI (p < 0.01 and p < 0.05, respectively). In particular, the level of sICAM-1 was increased in patients with SCI due to perforating arterial occlusion, while the level of sVCAM-1 was increased in patients with SCI due to cortical arterial occlusion. However, no significant difference was found in sE-selectin levels. Overall average of the intima and media thickness (IMT) of the common carotid arteries increased with age. IMT proved to be greater in patients with SCI than in patients without SCI (p < 0.05), and showed a weak but significant positive correlation with sVCAM-1, while no correlation was found with either sICAM-1 or sE-selectin levels. In conclusion, measurement of serum adhesion molecules may be useful for diagnosing the early stages of brain damage and for prophylactic treatment which may prevent the onset or progression of SCI.

Aged↗
PubMed1998

Therapeutic effects of AE0047, a novel calcium antagonist, on progression of brain damage after stroke in stroke-prone spontaneously hypertensive rats.

1. The potential of AE0047, a novel calcium antagonist, to remedy brain damage of stroke-prone spontaneously hypertensive rats (SHRSPs) with signs of stroke was compared with those of nicardipine and hydralazine. 2. AE0047 (1 and 3 mg/kg/day) given daily to diseased SHRSPs prevented mortality and improved neurological symptoms. Histological examination also supported the effectiveness of AE0047 against the progression of the disease. 3. Nicardipine (10 mg/kg/day) and hydralazine (10 mg/kg/day) were less effective than AE0047 in a dose equal to or more than the hypotensive dose, respectively. 4. AE0047 may be beneficial for treating the acute stage of stroke in humans by virtue of its long-lasting hypotensive action and undefined direct actions on the cerebral vasculature.

Animals↗
PubMed1998

Characterization of NK cells and extrathymic T cells generated in the liver of irradiated mice with a liver shield.

We previously reported that c-kit+ stem cells which give rise to extrathymic T cells are present in the liver of adult mice. Further characterization of extrathymic T cells in the liver of adult mice is conducted here. When mice with a liver shield were lethally (9.5 Gy) irradiated, all mice survived. All tested organs showed a distribution pattern of hepatic lymphocytes on day 7. The distribution pattern in the liver was characterized by an abundance of NK (CD3- IL-2Rbeta+) and extrathymic T cells (CD3int IL-2Rbeta+) before and after irradiation. To determine their function, post-irradiation allogeneic bone marrow transplantation (BMT) was performed in mice with or without a liver shield. Allogeneic BM cells were rejected in mice with a liver shield and specific activation of CD8+ CD3int IL-2Rbeta+ cells was induced. At that time, potent cytotoxicity of liver mononuclear cells (MNC) against allogeneic thymocytes was induced. Both NK1.1+ and NK1.1- subsets of CD3int cells expanded in these mice. An in vivo elimination experiment of the subsets indicated that the NK1.1+ subset of CD3int cells (i.e. NK T cells) was much more associated with the rejection of allogeneic BM cells. However, even after the elimination of NK T cells, allogeneic BM cells were rejected. In this case, granulocytes expanded in parallel with NK1.1- subsets. Granulocytes may also be associated with the rejection of allogeneic BM cells. These results suggest that the liver is an important haematopoietic organ even in adult life.

Animals↗
PubMed1998

Oligoclonality of TCRint cells with a low diversity of TCR complementarity-determining region 3 in mice with graft-versus-host disease.

Conventional T cells (i.e. TCRhigh) are generated by the main stream of T-cell differentiation in the thymus. However, primordial T cells (i.e. TCRint) are generated by extrathymic pathways and an alternative intrathymic pathway. Since TCRint cells contain self-reactive clones, the diversity of the T-cell antigen receptor (TCR) complementarity-determining region (CDR) 3 was examined. The predominant Vbeta8.2+ clones among TCRint cells were selected for DNA sequencing. Thymectomized, irradiated mice subjected to bone-marrow transplantation (BMT) were used; graft-versus-host disease (GVHD), B6-->(B6xC3H/He)F1 and syngeneic BMT, B6-->B6. In these combinations, only TCRint cells were generated. Vbeta8.2+ cells with a low diversity of CDR3 of V-gene expanded in GVHD mice. Vbeta8.2+ cells of TCRint and TCRhigh cells in normal mice were polyclonal, showing that the former has a lower diversity of CDR3 than the latter. The clonality of activated TCRhigh cells was examined, in which CD3high cells (bml2 mice) were injected into 1 Gy-irradiated B6 nude mice. Some Vbeta8.2+ clones among TCRhigh cells were expanding but the diversity of CDR3 was greater than that of CD3int cells, despite the fact that the recognition site of the H-2 difference was smaller. Taken together with invariant usage of V alpha14, these results suggest that TCRint cells have a low diversity of CDR3 of Vbeta genes.

Amino Acid Sequence↗
PubMed1998

Endogenously occurring beta-carboline induces parkinsonism in nonprimate animals: a possible causative protoxin in idiopathic Parkinson's disease.

To examine whether simple beta-carbolines induce parkinsonian-like symptoms in vivo via N-methylation, the simple beta-carbolines norharman (NH), 2-mono-N-methylated norharmanium cation (2-MeNH+), and 9-mono-N'-methylnorharman (9-MeNH) were systematically administered to C57BL/6 mice for 7 days. These substances induced bradykinesia with reduction of locomotion activity. NH or 2-MeNH+ decreased dopamine (DA) contents to 50-70% of values in controls in the striatum and midbrain. 9-MeNH potently decreased not only DA but also serotonin content in various regions. Immunohistochemical examination revealed that the numbers of tyrosine hydroxylase (TH)-positive cells in the substantia nigra pars compacta of NH- and 9-MeNH-treated mice were diminished to 76 and 66% of values in control mice, respectively. The formation of a toxic metabolite, 2,9-di-N,N'-methylated norharmanium cation (2,9-Me2NH+), was 14 and eight times higher in the brain of mice receiving 9-MeNH than that in NH- and 2-MeNH+-treated mice, respectively. In cultured mesencephalic cells from rat embryo, 2,9-Me2NH+ selectively killed TH-positive neurons only at a lower dose but was toxic to all neurons at higher doses. Thus, the excess formation of 2,9-Me2NH+ would induce nonspecific neurotoxicity. These results indicated that 9-indole nitrogen methylation should be the limiting step in the development of the toxicity. NH, a selective dopaminergic toxin precursor, is sequentially methylated to form 2,9-Me2NH+, which could be an underlying factor in idiopathic Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Expression of alpha-fetoprotein and prostate-specific antigen genes in several tissues and detection of mRNAs in normal circulating blood by reverse transcriptase-polymerase chain reaction.

BACKGROUND: alpha-Fetoprotein (AFP) and prostate-specific antigen (PSA) in serum are widely used as tumor markers in the evaluation of prognosis and management of patients with hepatocellular carcinoma and prostate cancer, respectively. To establish the molecular diagnosis of cancer, reverse transcriptase polymerase chain reaction (RT-PCR) for AFP and PSA was used to identify circulating cancer cells in the blood of cancer patients. Here, we examined the tissue-specificity of AFP and PSA and tested whether AFP and PSA are suitable targets in the detection of certain cancer cells by RT-PCR using peripheral blood samples. METHODS: Tissue specificity of AFP and PSA was analyzed by Northern blotting and RT-PCR. Probes for AFP and PSA were hybridized with poly A+ RNAs from 50 human tissues. RT-PCR for AFP and PSA mRNA was performed using several cancerous tissues and normal tissues and peripheral blood cells from seven healthy volunteers. RESULTS: Broad expression of AFP was observed in several tissues and a large amount of AFP mRNA was found in fetal liver. PSA was expressed in prostate, salivary gland, pancreas and uterus. By RT-PCR, AFP and PSA mRNA were detected in several tumors, including salivary pleomorphic adenoma, hilar bile duct carcinoma, pancreatic carcinoma, transitional cell carcinoma of urinary bladder and thyroid papillary carcinoma. Furthermore, AFP and PSA mRNAs were frequently detected by RT-PCR, even in peripheral blood cells from healthy volunteers. CONCLUSIONS: Neither AFP nor PSA showed tissue-specific expression. AFP and PSA mRNA were detected in several diseased and non-diseased tissues and normal circulating blood by RT-PCR.

Adenoma, Pleomorphic↗
PubMed1998

Cloning, expression, and characterization of a root-form phosphoenolpyruvate carboxylase from Zea mays: comparison with the C4-form enzyme.

A full-length cDNA for maize root-form phosphoenolpyruvate carboxylase (PEPC) was isolated. In the coding region, the root-form PEPC showed 76 and 77% identity with the C4- and C3-form PEPCs of maize, respectively, at the nucleotide level. At the amino acid level, the root-form was 81 and 85% identical to the C4- and C3-form PEPCs, respectively. The entire coding region was inserted into a pET32a expression vector so that it was expressed under the control of T7 promoter. The purified recombinant root-form PEPC had a Vmax value of about 28 mumol min-1 (mg protein)-1 at pH 8.0. The K(m) values of root-form PEPC for PEP and Mg2+ were one-tenth or less of those of C4-form PEPC when assayed at either pH 7.3 or 8.0, while the value for HCO3- was about one-half of that of C4-form PEPC at pH 8.0. Glucose 6-phosphate and glycine had little effect on the root-form PEPC at pH 7.3; they caused two-fold activation of the C4-form PEPC. The Ki (L-malate) values at pH 7.3 were 0.12 and 0.43 mM for the root- and C4-form PEPCs, respectively. Comparison of hydropathy profiles among the maize PEPC isoforms suggested that several stretches of amino acid sequences may contribute in some way to their characteristic kinetic properties. The root-form PEPC was phosphorylated by both mammalian cAMP-dependent protein kinase and maize leaf protein kinase, and the phosphorylated enzyme was less sensitive to L-malate.

Amino Acid Sequence↗
PubMed1998

[Retrospective analysis of the relationship between HUS incidence and antibiotics among patients with Escherichia coli O157 enterocolitis in the Sakai outbreak].

An outbreak of Escherichia coli O157:H7 infection occurred in July 1996 in Sakai City. About 5000 children were infected, 122 of whom developed hemolytic uremic syndrome (HUS). In this outbreak, almost all patients were administrated some type of antibiotics. The effects of antibiotics on E. coli O157 associated hemorrhagic colitis (HC) have been controversial. In this study, we focused on the effects of antibiotics on development of HUS in the HUS in the Sakai outbreak. We retrospectively determined the antibiotics administrated within three days after the onset of HC, clinical courses, and laboratory data of 301 patients who were hospitalized and identified as Escherichia coli O157 infection by stool culture, from results of questionnaires sent by the Osaka Prefecture Medical Association to hospitals in Osaka Prefecture. The antibiotics used could be identified for 216 patients. The incidence of HUS among these patients was 11.6%. They were divided into 19 groups based on the type of antibiotics administrated. The incidence of HUS in the new quinolone (3.7%) group was low, but was high in the intravenous cephalosporin (18.2%) group. The differences in the incidence of HUS among the 19 antibiotic groups was significant (p < 0.05) on analysis of covariance which eliminated the contributions of variables including age, sex and laboratory data. These findings indicate that the suitable antibiotics can prevent the development of E. coli O157-associated HUS.

Adolescent↗
PubMed1998

Alteration in the GyrA subunit of DNA gyrase and the ParC subunit of DNA topoisomerase IV in quinolone-resistant clinical isolates of Staphylococcus epidermidis.

We examined 22 clinical isolates of Staphylococcus epidermidis to analyze the association of alterations in GyrA and ParC with fluoroquinolone resistance. The simultaneous presence of GyrA and ParC alterations was associated with a high level of fluoroquinolone resistance in the clinical isolates of S. epidermidis.

4-Quinolones↗