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N Tamura

Publications and source records attributed to N Tamura.

At least 127 records · Page 7Linked to original sources

Suppression of mitogen-induced IL-2R alpha expression in PBL by serum from microfilaraemic rats chronically infected with Brugia pahangi.

To study immunological responses in filarial infections, interleukin-2 receptor alpha (IL-2R alpha) expression in the peripheral blood lymphocytes (PBL) of Lewis rats infected with Brugia pahangi was observed by flow cytometry. During infection, no increase in IL-2R alpha was observed in either microfilaraemic or amicrofilaraemic rats. The PBL of rats were stimulated with phytohaemagglutinin (PHA) and the frequency of IL-2R alpha-positivity was examined. After microfilariae appeared, the increase in the rate of IL-2R alpha-positivity in microfilaraemic rats was less than in amicrofilaraemic rats. The anergy of IL-2R alpha expression in microfilaraemic rats was restored when their lymphocytes were cultured with normal rat serum. IL-2R alpha expression in normal uninfected rats decreased when cultured with serum from microfilaraemic rats. These results suggest that microfilariae-related factors in rat serum suppress PHA-induced IL-2R alpha expression in PBL and thus inhibit cell proliferation and host immunity.

Animals↗

Syncytial cell formation in vivo by type C retroviral particles in the systemic lupus erythematosus (SLE) lung.

Significant numbers of syncytial cells were observed in the bronchoalveolar lavage fluid (BALF) of a 42-year-old patient who had SLE with interstitial pneumonia. Electron microscopic study of the BALF cells and positive reverse transcriptase activity in the supernatant of the cultured cells revealed unknown retroviral particles in the BALF cells. No antibodies to known human retroviruses or proviral sequences were detected. Type C retroviral particles and positive reverse transcriptase activity were also observed in co-cultured U937 cells. To evaluate the pathogenic role of unknown type C retroviral particles, screening for antibodies to this retroviral particle was performed by immunofluorescence in 26 patients with idiopathic pulmonary fibrosis, 17 patients with SLE, 22 patients with lung cancer, and 58 healthy volunteers. Serum antibody to this putative type C retrovirus was detected in 24% of SLE patients, 27% of idiopathic pulmonary fibrosis patients, none of the lung cancer patients and 2% of healthy volunteers. Although no direct evidence of this virus as the pathogen for SLE could be demonstrated, a possible role in the development of SLE and interstitial pneumonia might be suggested.

Adult↗

Thrombin stimulates production of transforming growth factor-beta by cultured human mesangial cells.

Fibrin formation within the glomeruli occurs in various forms of human and experimental glomerulonephritis and it may play an important role in progressive glomerular injury. Transforming growth factor-beta (TGF-beta) has been shown to participate in the glomerular accumulation of extracellular matrix in glomerulonephritis. We investigated whether thrombin, an important coagulation factor, could modulate the production of TGF-beta by cultured human mesangial cells (HMC). TGF-beta levels in the culture supernatants were measured by ELISA using a specific antibody. The TGF-beta concentration was significantly increased by incubation of HMC with thrombin in a time-dependent manner. The stimulating effect of thrombin on TGF-beta was inhibited by addition of hirudin (a natural thrombin inhibitor) and argatroban (a synthetic thrombin inhibitor). In addition DFP-inactivated thrombin, which has no enzymatic activity, did not stimulate TGF-beta production. A protein kinase C inhibitor (H7) and a tyrosine kinase inhibitor (herbimycin A) also inhibited thrombin induced TGF-beta production. These findings suggested that thrombin may modulate the synthesis of TGF-beta via protein kinase C- and tyrosine kinase-dependent mechanisms in cultured HMC. Thus thrombin may participate in the accumulation of extracellular matrix in glomeruli through the augmentation of TGF-beta production.

Cells, Cultured↗

Opposite regulation of Gax homeobox expression by angiotensin II and C-type natriuretic peptide.

Growth arrest-specific homeobox (Gax) gene was isolated from rat aorta cDNA library and its expression was largely confined to the cardiovascular tissues. Gax gene was rapidly downregulated by platelet-derived growth factor in vascular smooth muscle cells (VSMCs) and overexpressed Gax was reported to reduce the neointimal thickening after balloon injury in vivo. We have demonstrated that angiotensin II (Ang II) stimulates vascular growth. In contrast, we also reported that C-type natriuretic peptide (CNP) is secreted from vascular endothelial cells to act as a novel endothelium-derived relaxing peptide and inhibits vascular growth via cGMP cascade. In the present study, we examined the effects of Ang II and CNP on Gax gene expression in VSMCs. In quiescent rat aortic VSMCs. Gax mRNA (2 3 kb) level became negligible 6 hours after the addition of Ang II (10(-6) mol/L). The inhibitory action of Ang II on Gax mRNA expression (ED50: 10(-11) mol/L) was almost completely blocked by an AT1R antagonist, CV11974. In contrast, CNP 10(-6) mol/L augmented Gax mRNA expression to exhibit 1.8-fold increase of the control 12 hours after the stimulation. This effect of CNP was mimicked by the addition of 8-bromoadenosine 3'-5'-cyclic monophosphate. The addition of C-ANF[4-23], an atrial natriuretic peptide-C receptor-specific agonist and devoid of stimulating cGMP production, exhibited no effect on Gax mRNA expression. Simultaneous administration of Ang II and CNP revealed that CNP (10(-6) mol/L) significantly attenuated the inhibitory action of Ang II (10(-10) mol/L) on Gax mRNA expression. These results suggest that Gax is a common transcription factor involved in the signaling pathway of vascular growth for Ang II and CNP and regulates the cell cycle and/or phenotype of VSMCs for vascular remodeling in hypertension and atherosclerosis.

Angiotensin II↗

Shear stress augments expression of C-type natriuretic peptide and adrenomedullin.

Shear stress is known to dilate blood vessels and exert antiproliferative effects on vascular walls: these effects have been ascribed to shear stress-induced upregulation of endothelium-derived vasoactive substances, mainly nitric oxide and prostacyclin. We have demonstrated the significance of C-type natriuretic peptide (CNP) as a novel endothelium-derived relaxing peptide (EDRP) that shares a cGMP pathway with nitric oxide. Adrenomedullin is a recently isolated EDRP that elevates intracellular cAMP as prostacyclin does. To elucidate the possible role of these EDRPs under shear stress, we examined the effect of physiological shear stress on CNP mRNA expression in endothelial cells derived from the human umbilical vein (HUVECs), bovine aorta (BAECs), and murine lymph nodes (MLECs) as well as adrenomedullin mRNA expression in HUVECs. CNP mRNA was stimulated prominently in HUVECs under shear stress of 15 dyne/cm2 in a time-dependent manner (4 hours, sixfold increase compared with that in the static condition; 24 hours, 30-fold increase). Similar results were obtained in BAECs (4 hours, twofold increase; 24 hours, threefold increase) and MLECs (4 hours, threefold increase; 24 hours, 10-fold increase). Augmentation of CNP mRNA expression that was dependent on shear stress intensity was also observed (5 dyne/cm2, 2.5-fold increase of static; 15 dyne/cm2, 4.5-fold increase). Increased CNP secretion was also confirmed by the specific radioimmunoassay for CNP. Adrenomedullin mRNA expression in HUVECs increased under shear stress of 15 dyne/cm2 in a time-dependent manner (4 hours, 1.2-fold increase of static: 24 hours, threefold increase) and shear stress intensity-dependent manner (15 dyne/cm2, threefold increase compared with that at 5 dyne/cm2). These results suggest that the coordinated augmentation of mRNA expression of these novel EDRPs may constitute shear stress-dependent vasodilator and antiproliferative effects.

Adrenomedullin↗

Alveolar macrophages produce the Env protein of a human endogenous retrovirus, HERV-E 4-1, in a subgroup of interstitial lung diseases.

We investigated whether intraalveolar inflammatory cells such as alveolar macrophages or lymphocytes produced the gene product of a type-C human endogenous retrovirus (HERV), HERV-E 4-1, which might initiate an immune response resulting in interstitial lung disease. We evaluated HERV-E 4-1 Env protein production by bronchoalveolar lavage fluid (BALF) cells and PBL in 109 patients with sarcoidosis, idiopathic pulmonary fibrosis (IPF), lung cancer, and rheumatoid lung disease as well as 26 normal control individuals. Production of HERV-E 4-1 Env protein by alveolar macrophages was observed using indirect immunofluorescence in 3 IPF patients and 3 sarcoidosis patients (6/135). No peripheral blood lymphocytes showed HERV-E 4-1 Env protein production. Antibodies to HERV-E 4-1 Env protein were detected in the BALF of all six patients by immunoblot analysis, while none of the normal control individuals showed HERV-E 4-1 Env protein antibody in the BALF. All examined BALF cells showed HERV-E 4-1 env mRNA transcript expression by reverse transcription-polymerase chain reaction. No significant influence of point mutation or DNA polymorphism on HERV-E 4-1 Env protein production was recognized. In conclusion, local production of HERV-E 4-1 Env protein and defective tolerance of HERV gene products with resultant antibody production may contribute to the pathogenesis of IPF or sarcoidosis in some patients.

Amino Acid Sequence↗

Systemic lupus erythematosus associated with transverse myelitis and parkinsonian symptoms.

A 31-year old woman developed transverse myelitis after 10 years remission since she was first diagnosed as systemic lupus erythematosus. Although pulse methyl prednisolone resolved her myelitis, Parkinson-like symptoms developed subsequently after reduction of steroid. Treatments including apheresis did not improve her Parkinson-like symptoms such as rigidity, akinesia, impairment of speech and mask-like facial expression. Levodopa was effective as a symptomatic therapy. Orally administered cyclophosphamide eventually led her to remission and withdrawal from levodopa. Her clinical course and the absence of other possible causes prompted us to conclude that Parkinsonian symptoms as well as transverse myelitis may have developed as manifestations of central nervous system lupus.

Adult↗

[Relapsing polychondritis: a case with respiratory failure].

A 48-year-old woman was admitted to our hospital with respiratory failure (Hugh-Jones IV-V). She was diagnosed as relapsing polychondritis 6 years ago. Her respiratory failure was due to pharyngial stenosis, deformity and inflammation of a trachea and lobar bronchus, and bronchial collapse. Her tracheobronchochondritis was managed by 500-700 mg/day of hydrocortisone and 50 mg/day of cyclophosphamide. Laboratory examination revealed only slight elevation of CRP and no elevation of anti-type II collagen antibody, although these parameters were very high on her first admission when she had severe polyarthritis, polychondritis of nose and auricles. Bronchoscopic findings were compatible with tracheobronchomalacia since pharyngial stenosis due to inflammatory pharyngitis and bronchial collapse due to tracheobronchochondritis were shown without lung parenchymal damage. We referred to the literature on tracheobronchomalacia which was associated by the varieties of respiratory and rheumatic diseases.

Female↗

[Renal lesions of rats induced by antibodies to cultured rat glomerular epithelial cells and mesangial cells].

Renal lesions of rats induced by antibodies to cultured rat glomerular epithelial cells (GEC) and mesangial cells (GMC) were studied. Antibodies to cultured rat GEC and GMC were produced by immunization of rabbits with GEC and GMC respectively. The rats injected with anti-GEC antibody showed a small amount of urinary protein, glomerular deposition of rabbit IgG and subepithelial dense deposits observed by electron microscopy. Proteinuria was suppressed in the rats in which complement was depleted with cobra venom factor. Western blot analysis demonstrated a band of 200 KD in GEC lysates reacted with anti-GEC antibody. The rats injected with anti-GMC antibody showed little urinary protein, glomerular deposition of rabbit IgG and mesangial dense deposits. Western blot analysis demonstrated two bands of 43 and 14 KD in GMC lysates reacted with anti-GMC antibody. These data showed that the injection of anti-GEC antibody or anti-GMC antibody induced similar lesions to passive Heymann nephritis and anti Thy 1.1 nephritis. This study suggested that antigenicity of structural glomerular cells is important as the antigens of glomerulonephritis.

Animals↗

[Tricorn protease].

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Amino Acid Sequence↗

[A successful surgical repair of congenital mitral stenosis due to commissural papillary muscle fusion].

A case of congenital mitral stenosis, patent ductus arteriosus, pulmonary hypertension was reported. At one year of age, the patient underwent surgical division of PDA because of persistent left heart failure. She went well after the operation. At seven year of age, she was readmitted to our hospital for easy fatigability. The cardiac catheterization revealed remarkably elevated pulmonary arterial pressure and pulmonary capillary wedged pressure. She underwent a surgical intervention for the mitral stenosis at eight year of age. At operation, the mitral valve exhibited the characteristics of type IIc according to Carpentier's classification: thickened and dysplastic leaflet, extremely short chordae tendanae fused with papillary muscles, obliteration of interchordal space and hypertrophic two papillary muscles. We replaced the valve with 23 mm Carbomedicus prosthetic valve because it seemed to be difficult to repair the native valve satisfactorily without residual stenosis or insufficiency. Her postoperative course was uneventful and the pulmonary arterial pressure and pulmonary capillary wedged pressure decreased remarkably one year after the operation.

Child↗

[BUN, Bence Jones protein, and chromosomal aberrations predict survival in multiple myeloma].

The prognostic significance of of some clinical features in 41 patients with multiple myeloma (including 2 patients with plasma cell leukemia) from our institution was analyzed. Out of 14 variables isolated from the univariate analysis (P < 0.05), only three (BUN, Bence Jones protein, and chromosomal aberrations) were significant in the multivariate model (P < 0.05). Derived from these three variables, three subpopulations of patients were identified. The first group included 20 patients with a low risk of death and their median survival has not been reached. In particular, no one died during the first 60 months in this group. The second group also included 14 patients with an intermediate risk of death and a median survival of 49.2 months. The third group comprised seven patients with a high risk of death during 24 months after diagnosis and a median survival of 31.6 months (P < 0.0001). Finally, Durie & Salmon's myeloma staging system was demonstrated in the present series, and it showed prognostic validity for each stage (P < 0.0222). Compared with Durie & Salmon's staging system, our prognostic model for multiple myeloma was more useful to predict prognosis when applied to the present series.

Adult↗

Tricorn protease (TRI) interacting factor 1 from Thermoplasma acidophilum is a proline iminopeptidase.

Tricorn protease (TRI), a high molecular mass complex from the archaeon T. acidophilum, forms the core of a modular proteolytic system; upon interacting with low molecular mass factors intrinsic activities are enhanced and novel activities are generated. Here we characterize the first factor, F1, which turns out to be homologous with several bacterial proline iminopeptidases (PIPs). Surprisingly, it cleaves not only typical PIP substrates such as H-Pro-AMC, but a wide spectrum of amino acid substrates and several peptide substrates without a proline at the N-terminus. The pip gene encodes a 293 amino acid residue protein with a molecular mass of 33,487 Da. By means of site-directed mutagenesis we identified Ser105 and His271 as the active site nucleophile and proton donor, respectively. Experiments with inactive mutant PIPs indicate that the activities elicited by interacting with TRI are contributed by PIP.

Amino Acid Sequence↗

Tricorn protease--the core of a modular proteolytic system.

Large macromolecular assemblies have evolved as a means of compartmentalizing reactions in organisms lacking membrane-bounded compartments. A tricorn-shaped protease was isolated from the archaeon Thermoplasma and was shown to form a multisubunit proteolytic complex. The 120-kilodalton monomer assembled to form a hexameric toroid that could assemble further into a capsid structure. Tricorn protease appeared to act as the core of a proteolytic system; when it interacted with several smaller proteins, it displayed multicatalytic activities.

Amino Acid Sequence↗

Genomic organization, expression, and chromosomal mapping of the mouse adrenomedullin gene.

We have isolated and characterized the mouse adrenomedullin (AM) gene (Adm) and determined its chromosomal location. The gene spans approximately 2.1 kb and is organized into four exons separated by three introns. The transcription start site was determined to be the adenine nucleotide at -618. The mouse AM 5'-flanking region contains a TATA box-like sequence and several cis-acting regulatory elements. Analysis of the nucleotide and deduced amino acid sequences revealed that mouse preproAM is a 184-amino-acid polypeptide, from which AM and proAM N-terminal 20 peptide are cleaved. Using restriction fragment length variants on a DNA panel of interspecific backcross mice, we mapped Adm to a distal region of mouse chromosome 7.

Adrenomedullin↗