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H Tada

Publications and source records attributed to H Tada.

At least 181 records · Page 10Linked to original sources
PubMed1998

The fibronectin production is increased by thrombospondin via activation of TGF-beta in cultured human mesangial cells.

Thrombospondin (TSP) is a multifunctional glycoprotein that is synthesized by a variety of cells including mesangial cells (MCs). To clarify the effect of TSP on the pathogenesis of diabetic nephropathy, we studied the effect of glucose concentrations on TSP synthesis in cultured human MCs. Thereafter, the effects of TSP on the activation of transforming growth factor beta (TGF-beta) and fibronectin production were investigated in MCs. Incubating MCs with elevated glucose levels for 6 days resulted in an increase in TSP synthesis, measured by an enzyme-linked immunosorbent assay, both in culture media and cell layers. Treatment of MCs with TSP (final concentrations 1 and 5 microg/ml) for 24 h resulted in an increase (1.3- and 2.1-fold, respectively) in active TGF-beta, which was determined with an enzyme-linked immunosorbent assay using TGF-beta-soluble receptor type II, in the culture media without having any effect on the production of total TGF-beta. Exposure of MCs to TSP caused enhancement of fibronectin production in both media and cell layers in a TSP dose-dependent manner with the maximum at a TSP concentration of 1 microg/ml. The TSP-induced increase in fibronectin production from MCs was completely prevented by concomitant treatment with 10 microg/ml anti-TGF-beta neutralizing antibody. These results indicate that the TSP production is promoted by a high ambient glucose concentration in human MCs and that TSP, in turn, causes an increase in fibronectin production via activation of TGF-beta.

Antibodies↗
PubMed1998

Purification and characterization of a recombinant human cripto-1 protein.

Cripto-1 (CR-1) is a novel protein that contains a modified EGF-like motif and that does not directly bind to any of the known erb B type-1 receptor tyrosine kinase receptors. To more clearly define the biological effects of CR-1 and to more adequately compare the structure-function relationships of CR-1 with other members of the EGF family of growth factors, we have expressed a modified, full-length recombinant human CR-1 protein (rhCR-1) in E. coli and have devised a procedure for the solubilization, refolding and purification of a biologically active form of this protein. We have generated the mature form of hCR-1 from computer assisted predictions of potential signal peptide cleavage sites. Expression of the modified rhCR-1 protein in E. coli was limited to the inclusion bodies. The rhCR-1 protein was found to be expressed at high levels in bacterial cells when fused to a histidine-tag sequence. Refolding of rhCR-1 was found to be difficult because of the large number of cysteine residues in the protein which results in protein aggregation. By chemically modifying the cysteine residues in the rhCR-1 protein with 3-trimethylammoniopropyl methanethiosulfonate, additional positive charges have been introduced into the protein by this disulfiding reagent. This modification facilitates solubilization of the protein when rhCR-1 is denatured. The solubilized, denatured protein was then purified by CM cation exchange and C4 reverse phase HPLC chromatography and refolded in a redox buffer. The refolded, modified rhCR-1 protein was found to be biologically active by its ability to inhibit beta-casein expression, to stimulate the tyrosine phosphorylation of Shc and the activation of MAPK and by its capacity to facilitate branching growth of mouse mammary epithelial cells in type I collagen gels.

Animals↗
PubMed1998

[Multimodality treatment for non-small cell lung cancer from the surgical standpoint].

Mediastinal lymph node metastasis is the most important issue in surgical treatment for non-small cell lung cancer. Systematic lymphadenectomy made its stage accurate. Its significance for prognosis is not clear. Adjuvant radiotherapy reduced local recurrence, but could not improve the prognosis. Adjuvant chemotherapy only sometimes improves it the survival. A meta-analysis reported that adjuvant chemotherapy for completely resected patients could lead to a 5% improvement in 5-year survival. Induction chemotherapy for N2 disease should assure good results compared to historical control. A randomized control study of induction chemotherapy vs. surgery alone revealed that this modality is worthwhile, but no lonsensus was obtained. Concurrent chemoradiotherapy could bring about a down stage that leads to a better prognosis, and is a promising strategy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Considerations for surgical treatment of patients with upper lumbar disc herniations.

Nine patients treated by surgery for upper lumbar disc herniations were reviewed. Of nine patients with upper lumbar disc herniations at the L1-L2 or L2-L3 level, five were treated by anterior procedures, whereas four underwent posterior procedures. Four of the five patients on whom anterior procedures were performed underwent additional spinal instrumentation using the Kaneda device and Z-plate system. Clinical symptoms improved in all nine patients. Confirmation of the type and level of disc herniation and increased thoracolumbar kyphosis must be taken into consideration when the optimal surgical procedure and spinal instrumentation method are selected.

Adult↗
PubMed1998

[Anti-receptor antibody and autoimmune disease].

Many receptors are located on the cell surface, and accessible by anti-receptor autoantibodies. After binding to the receptor, anti-receptor autoantibodies may activate the receptor, mimicking the effect of its genuine ligand, or inhibiting activation by ligands. Therefore, anti-receptor autoantibodies have pathogenic importance in several autoimmune diseases, such as Graves' disease, myasthenia gravis, Type B insulin resistance syndrome, and so on. The measurement of anti-receptor autoantibodies is often essential in the diagnosis of these diseases. There are two kinds of measurement procedures. One measures only binding or inhibition of ligand binding to the receptors. That test is simple and available in many laboratories, but cannot distinguish the function--stimulation or inhibition--of autoantibodies. However, procedures that can measure function are rather complicated and may not be available in some laboratories. Not only important for diagnosis, anti-receptor autoantibodies can also be utilized to study receptor-ligand interactions and receptor activation. Recently, there are many studies wherein genetically modified receptors are used for analysis. Here, we will present some our results, as examples.

Autoantibodies↗
PubMed1998

[Cystic fibrosis].

Explore the source record for details and available documents.

1-Methyl-3-isobutylxanthine↗
PubMed1998

[Marked airway constriction due to relapsing polychondritis].

A 40-year-old woman was admitted to our hospital presenting with dry cough, sore throat, and fever. Her right auricle was markedly swollen and her ocular conjunctiva were reddened, suggesting scleritis. A chest computed tomogram showed narrowing of the trachea due to enlarged mediastinal soft tissues. These clinical findings suggested the patient had relapsing polychondritis. A cartilage biopsy from her right auricle was taken to confirm the diagnosis. Pathological findings revealed loosening and dissolution of cartilage and infiltration of lymphocytes, which were consistent with relapsing polychondritis. Although prednisolone was given to the patient, her symptoms were not alleviated. Methylprednisolone pulse therapy and oral diaminodiphenylsulfone were added to the patient's treatment regimen. With this combination, her symptoms gradually subsided. Constriction of the airway has been cited as one of the prognostic factors in relapsing polychondritis. In view of the danger of sudden death caused by airway obstruction, close observation of the patient in this case was considered necessary.

Adult↗
PubMed1998

[Allergic granulomatous angiitis associated with cerebral infarction, myo-pericarditis and acute respiratory failure due to eosinophilic pneumonia].

We encountered a 23-year-old woman with allergic granulomatous angiitis (AGA) associated with cerebral infarction, myo-pericarditis, and acute respiratory failure due to extended eosinophilic pneumonia. She underwent emergency treatment at our hospital because of right hemiparesis and impaired consciousness. AGA was suspected because the patient had a history of bronchial asthma accompanied by pulmonary infiltrations with eosinophilia, and presented with diffuse pulmonary infiltrates, pericardial effusion, diffuse hypokinesis of myocardium, cerebral infarction and marked peripheral eosinophlia. Pulmonary eosinophilia was confirmed by examination of broncho-alveolar lavage fluid. Myocardial tissue biopsy specimens revealed fibrous granulation indicative of myocarditis. The patient responded well to corticosteroid therapy.

Acute Disease↗
PubMed1997

Immunosuppressive activity of cloned natural killer (NK1.1+) T cells established from murine tumor-infiltrating lymphocytes.

To elucidate the role of NK1.1+ T cells in the antitumor immune response, we established cloned NK1.1+ T cell lines from tumor-infiltrating lymphocytes (TIL) of B16 melanoma, and examined their mode of action in generating antitumor effector T cells both in vitro and in vivo. An NK1.1+ T cell clone (TM4.2) was phenotypically CD3+ TCR-alphabeta+ CD4- CD8- NK1.1+, and CD28+. The TM4.2 cells suppressed the in vitro generation of anti-B16 melanoma CTLs, but not the effector function of CTLs. The results using a transwell membrane suggested that their suppressive activity was mediated by both soluble factors and a direct cell to cell interaction. As for the soluble factors, the suppressive activity of the culture supernatant of TM4.2 cells was neutralized by anti-TGF-beta mAb, and the TM4.2 cells actually produced a considerable amount of TGF-beta. On the other hand, the TM4.2 cells showed a high level of cytolytic activity against B cell blasts and CD80-transfected P815, and such cytolytic activity was reduced by the addition of anti-CD80 mAb. In addition, NK1.1+ T cells in the freshly isolated TIL were revealed to express CD28. Furthermore, the TM4.2 cells suppressed the in vitro generation of anti-allo CTLs irrespective of the MHC haplotype. Finally, the TM4.2 cells suppressed the in vivo antitumor immune response. Collectively, these findings demonstrate that NK1.1+ T cells in TIL show immunosuppressive activity in the antitumor immune response through the production of TGF-beta and the preferential cytolysis of B7-expressing cells.

Animals↗
PubMed1997

Role of myocyte nitric oxide in beta-adrenergic hyporesponsiveness in heart failure.

BACKGROUND: The positive inotropic response to beta-adrenergic stimulation is attenuated at the isolated myocyte level in heart failure. Nitric oxide (NO) has a negative inotropic effect and attenuates the response to isoproterenol. It has been suggested that NO synthesis is increased in failing myocytes. However, the pathophysiological consequences after induction of NO in myocyte contractility are less clear in the setting of heart failure. METHODS AND RESULTS: We examined the effects of an NO synthase (NOS) inhibitor on contractile function in myocytes isolated from 11 dogs with rapid pacing-induced heart failure (ejection fraction, 29 +/- 2%) and 8 control dogs (ejection fraction, 74 +/- 3%). Sarcomere shortening velocity was measured as an index of contractility under four experimental conditions: at baseline, after adding isoproterenol (ISO; 1 nmol/L), after an NOS inhibitor (N pi-nitro-L-arginine methyl ester [L-NAME], 0.1 nmol/L), and after L-NAME plus ISO. L-NAME alone had no effects on basal sarcomere shortening velocity in either control or heart failure myocytes. However, L-NAME significantly augmented the inotropic response to isoproterenol in heart failure myocytes (107.1 +/- 7.3% [ISO alone] versus 140.6 +/- 10.7% [ISO plus L-NAME] increase from baseline; P < .05) but not in control myocytes (135.5 +/- 9.9% [ISO alone] versus 137.1 +/- 11.4% [ISO plus L-NAME]; P = NS). Myocardial NOS activity measured by the conversion of arginine to citrulline was significantly increased in dogs with heart failure compared with that in control dogs. CONCLUSIONS: The increased NO induction in failing myocytes does not alter baseline sarcomere mechanics but attenuates the positive inotropic response to isoproterenol. Thus, myocyte NO plays an important role in the autocrine regulation of the contractile function of myocytes in congestive heart failure.

Adrenergic beta-Agonists↗
PubMed1997

Mild mitral regurgitation reduces exercise capacity in patients with idiopathic dilated cardiomyopathy.

We evaluated 30 patients with dilated cardiomyopathy (New York Heart Association functional Class II or III with medical treatment) to assess the effect of mild mitral regurgitation (MR) on exercise capacity in patients with congestive heart failure. They were classified into two groups based on results of left ventriculography: MR present (n = 10) and MR absent (n = 20). The severity of the MR by left ventriculography was grade I (mild) in all patients with MR. Steady-state hemodynamic data and angiographic data did not differ significantly between the two groups. Heart rate and systolic blood pressure at rest and in response to symptom-limited exercise testing did not differ between the groups. However, the peak work load was significantly lower in the group with MR than that in the group without MR (101 +/- 32 vs. 142 +/- 29 W, respectively; p < 0.005). Peak oxygen uptake and peak oxygen pulse were also significantly lower in the group with MR than in that without MR (peak oxygen uptake: 18 +/- 23 +/- 5 ml/min/kg; p < 0.05, peak oxygen pulse: 6.6 +/- 2.6 vs. 9.5 +/- 2.7 ml/min/beat: p < 0.01, respectively). Thus, mild MR had a detrimental effect on the exercise capacity in patients with dilated cardiomyopathy.

Adult↗
PubMed1997

Efficient production of a functional mouse/human chimeric Fab' against human urokinase-type plasminogen activator by Bacillus brevis.

Expression/secretion vectors for the production of Fab' and single-chain (sc) Fab' by Bacillus brevis have been constructed. For the production of Fab', the cDNAs encoding the L chain and Fd' fragment (Fd with the hinge region) of a mouse-human chimeric Fab' against human urokinase-type plasminogen activator were fused directly with the translation-start and signal-peptide-encoding regions of the mwp gene, the gene for one of the major cell-wall proteins of Bacillus brevis. The two fused genes were placed tandemly downstream from the promoter of the cell-wall protein gene operon (cwp) of B. brevis. For the production of scFab', the two cDNAs were linked with a synthetic oligonucleotide encoding a flexible peptide linker of 17 or 24 amino acids, and fused with the translation start and signal-peptide-encoding regions of the mwp gene. Fab' was efficiently produced by B. brevis, being accumulated at a level of 100 mg/l in the culture medium in a simple shake-flask culture, which is the highest level obtained so far for a gram-positive bacterium. On the other hand, the scFab' remained at a level of a few milligrams per liter in the culture medium. The Fab' produced by B. brevis showed comparable antigen-binding activity to that of the parental antibody. The L chain and Fd' fragment, constituting the Fab', had the correct N-terminal amino acid sequences. These results indicate that B. brevis is a very promising host for the production of native Ig fragments.

Amino Acid Sequence↗
PubMed1997

Protective effect of D-alpha-tocopherol on the function of human mesangial cells exposed to high glucose concentrations.

Altered functions of mesangial cells (MCs) induced by high glucose levels are thought to play an important role in the pathogenesis of diabetic nephropathy. We investigate whether D-alpha-tocopherol (Toc), an antioxidant, can prevent malfunction of cultured human MCs induced by high-glucose media. Incubating MCs with 33 mmol/L glucose caused increased lipid peroxide (LPO) levels, disturbed cell replication, enhanced cytotoxicity, enhanced activity of the diacylglycerol (DAG)-protein kinase C (PKC) pathway, and overproduction of fibronectin and eicosanoids (6-keto prostaglandin F1 alpha [PGF1 alpha] and thromboxane B2 [TXB2]). The amount of LPO in MCs grown in 5 mmol/L glucose was reduced by the addition of Toc in a dose-dependent manner. Since the maximum effect of Toc on decreasing LPO was achieved at a concentration of 100 mumol/L, this dose was selected for the following experiments. Addition of Toc prevented increased LPO levels and [51Cr]-release from MCs induced by high-glucose media without affecting cell number. Toc decreased the total DAG level and PKC activity in membrane fractions in MCs cultured at both 5 and 33 mmol/L glucose. Furthermore, glucose-induced overproduction of fibronectin and eicosanoids from MCs was completely abolished by Toc. These results strongly suggest that Toc ameliorates glucose-induced malfunctions of MCs in vitro.

Cell Count↗
PubMed1997

Effects of autoantibodies on the course of pregnancy and fetal growth.

OBJECTIVE: To assess the effects of autoantibodies on the course of pregnancy and fetal growth. METHODS: One thousand one hundred seventy-nine healthy women with singleton gestations were screened in early pregnancy for seven kinds of autoantibodies: antithyroid microsomal antibody, antithyroglobulin antibody, two kinds of rheumatoid factor, antinuclear antibody, anti-DNA antibody, and antimitochondrial antibody. RESULTS: In 228 cases (19.3%), at least one autoantibody was found; however, overlap of autoantibodies in the same individual was unexpectedly rare, and only two cases were positive for as many as four autoantibodies. A significantly higher rate of spontaneous abortion was observed in antibody-positive subjects, especially those with antithyroid microsomal (10.4%) or antinuclear antibodies (16.0%), compared with all antibody-negative subjects (5.5%). There were no significant differences in any outcome assessed among subjects positive for antithyroglobulin antibody, anti-DNA antibody, or antimitochondrial antibody compared with all antibody-negative subjects. None of the seven autoantibodies affected the rates of preterm delivery, stillbirth, pregnancy-induced hypertension, malformation, or gender ratio. CONCLUSION: Antithyroid microsomal antibody and antinuclear antibody are the only autoantibodies that increase the abortion rate.

Adult↗