Biomedical subjects
Publications and source records attributed to T Takeda.
Dopaminergic neuroblastoma comprised 12% of the patients under 1 year of age, and 83% of the older ones. Seven cases were missed by the mass-screening system performed at age 6 months and were detected after 16 months. Three of these advanced cases were positive only for dopamine. These findings supports our second mass-screening system using dopamine evaluation at age 14 months.
This study was designed to determine and compare airway responses to synthetic human adrenomedullin(AM) and proadrenomedullin N-terminal 20 peptide (PAMP) in anesthetized guinea pigs in vivo. 10(-7) M AM and PAMP significantly inhibited acetylcholine-and histamine-induced bronchoconstriction. However, this significant bronchodilator effect of PAMP lasted about five minutes, which was much shorter than that of AM. In addition, the bronchodilator effect of AM is approximately 100-fold more potent than PAMP. We demonstrated that PAMP had a potent bronchodilator activity, and induced a rapid and short-lasting bronchodilation. These findings suggest that AM and PAMP may play important roles in airway functions.
Cyclosporine A (CSA) stimulates vascular endothelial cell production of endothelin-1 (ET-1). The present study was designed to test two hypotheses: (1) CSA stimulates ET-1 secretion in cultured rat mesangial cells, and (2) cardiac natriuretic peptides, atrial and brain natriuretic peptides (ANP and BNP), inhibit the above-mentioned secretion in these cells. CSA stimulated ET-1 secretion in a concentration-dependent manner between 10 and 100 ng/mL. In contrast, high concentrations of CSA (10 and 100 micrograms/mL) were cytotoxic and failed to stimulate ET-1 secretion. Rat ANP (1-28) and rat BNP-45 exhibited clearly concentration-related inhibition of CSA-induced ET-1 secretion. This inhibition by ANP and BNP was paralleed by an increase in the cellular level of cyclic guanosine-3',5'-monophosphate (cGMP). Rat ANP (5-25) was less effective than rat ANP (1-28) with respect to inhibiting ET-1 secretion and increasing cellular cGMP. Addition of a cGMP analog, 8-bromo-cGMP, reduced CSA-induced ET-1 secretion. On the other hand, addition of a cyclic adenosine-3',5'-monophosphate (cAMP) analog, 8-bromo-cAMP, did not affect CSA-induced ET-1 secretion. These findings suggest that CSA in low concentrations stimulates ET-1 production in cultured rat mesangial cells, and that cardiac natriuretic peptides inhibit this stimulated production, probably through a cGMP-dependent process.
The present study was designed to examine the effect of synthetic adrenomedullin (AM), a novel vasorelaxant peptide originally isolated from human pheochromocytoma, on intracellular cyclic adenosine monophosphate (cAMP) formation in cultured rat mesangial cells. The effect of AM on cAMP formation in rat mesangial cells was compared with its effect in cultured rat vascular smooth muscle cells. cAMP levels were determined by radioimmunoassay after stimulation for 30 minutes with different concentrations (10(-10) to 10(-7) mol/L) of rat and human AM. Rat and human AM concentration-dependently (10(-9) to 10(-7) mol/L) stimulated cAMP formation in cultured mesangial cells. This stimulatory effect of rat AM was significantly greater than human AM. The stimulatory effect of rat AM in mesangial cells was significantly weaker than its potency in vascular smooth muscle cells. These preliminary data suggest that mesangial cells, as well as vascular smooth muscle cells, possess AM receptors functionally coupled to adenylate cyclase.
From 1985 to 1989, 69 patients with non-Hodgkin's lymphoma (NHL) were treated by members of the Children's Cancer and Leukemia Study Group of Japan with a protocol consisting of vincristine, prednisolone, cyclophosphamide, doxorubicin, high-dose methotrexate (HD-MTX), mercaptopurine and cytarabine; central nervous system (CNS) prophylaxis with intrathecal MTX and hydrocortisone (NHL855). The 4-year event-free survival (EFS) was 78% (S.E., 10%) for patients with localized disease (n = 18) and 38% (S.E., 7%) for those with advanced disease (n = 51). Among the patients with advanced disease, those with non-lymphoblastic lymphoma tended to have a better 4-year EFS than those with lymphoblastic lymphoma (52% vs. 25%). Based on these findings, we initiated a new protocol NHL890 in which patients were assigned to two different chemotherapies according to the histology. Non-lymphoblastic subtype was treated almost identically to NHL855 while asparaginase and VP-16 were newly added in the consolidation-maintenance phase in advanced-stage lymphoblastic lymphoma. Sixty-seven patients with advanced disease were assessable. The overall 4-year EFS for advanced disease improved to 69% (S.E., 6%). A significant improvement was gained in the lymphoblastic lymphoma with a 4-year EFS of 56% (S.E., 11%) as compared with 25% (S.E., 9%) in the preceding study (P < 0.05). These findings suggest the importance of histology in the treatment of advanced-stage non-Hodgkin's lymphoma in childhood.
Angiotensin II (Ang II) regulates a variety of physiological functions, including contraction of smooth muscle. Peptide leukotrienes (LTs) have recently been reported to be potent bronchoconstrictors and may play a role in the pathogenesis of airway inflammation. However, the possibility that Ang II and peptide LTs interact in the control of airway function has not been studied. In this study, we showed that Ang II receptors are present on guinea pig airway, and that they are of the AT1 subtype. We showed the possibility that Ang II induced the release of peptide LTs from guinea pig airway by activation of the AT1 receptor pathway. Our findings thus suggest that interaction between Ang II and peptide LTs might increase airway inflammation in the guinea pig.
PURPOSE: Secretion of brain natriuretic peptide (BNP), a cardiac hormone, is accelerated via hypertrophied ventricles in experimental hypertension. The present study examined whether regression of left ventricular (LV) hypertrophy by long-term treatment with an angiotensin-converting enzyme inhibitor (ACEI) affects plasma BNP concentration in patients with essential hypertension. PATIENTS AND METHODS: Thirty-one hypertensive patients with LV hypertrophy were treated with ACEI (16 with enalapril; 15 with lisinopril) for 1 year. Serial changes were recorded in LV mass index, LV systolic function, and plasma concentrations of BNP and atrial natriuretic peptide (ANP). RESULTS: ACEI therapy significantly reduced LV mass index at 6 months, and more so at 1 year. Septal and posterior wall thicknesses were also reduced. Plasma BNP and ANP were markedly elevated at study entry, but only BNP levels correlated with LV mass index. Both peptide levels declined after 6 months, and this decline was enhanced at 1 year. There was a close relation between BNP decline and LV mass index reduction overall and with enalapril and lisinopril separately. Changes in ANP and in LV mass index were not related. CONCLUSION: Long-term ACEI therapy can reduce elevated plasma BNP. In this study, changes in BNP reflected the magnitude of regression of LVH. Plasma BNP may be a useful marker for LVH during antihypertensive therapy in patients with essential hypertension and LVH.
The present paper reports three cases of sensorineural hearing loss of suspected autoimmune origin. Cases 1 and 2 were bilateral sensorineural hearing loss which responded to steroid therapy. Case 3 was bilateral fluctuant sensorineural hearing loss in conjunction with systemic lupus erythematosus. The pathogenesis of autoimmune sensorineural hearing loss is not yet fully understood. In two patients, hearing levels improved or stabilized following the use of osmotic expanders. The clinical results suggest that endolymphatic hydrops may participate in autoimmune sensorineural hearing loss.
RATIONALE AND OBJECTIVES: As a preliminary study for application of phase-contrast X-ray imaging to medicine, we measured the X-ray refractive index of human blood and its influence on image contrast. METHODS: Using an X-ray interferometer, the X-ray phase shifts caused by human blood and its ingredients were measured from the interval of interference fringes. RESULTS: The X-ray phase shift caused by blood was 3% larger than that caused by serum. CONCLUSION: The large phase shift caused by blood is due to red blood cells, which contain hemoglobin molecules with iron atoms. It is possible that blood produces a structure in a phase-contrast X-ray image.
RATIONALE AND OBJECTIVES: For intravenous (i.v.) coronary arteriography, a real-time two-dimensional (2D) imaging system is being developed using above-K-edge monochromatic X-rays alone. The potential diagnostic value of this system was examined in the current study. METHODS: The angiographic system consisted of an asymmetric silicon (311) monocrystal, an image intensifier, and a charged-coupled device camera. It was constructed at the beam line of the Tristan Accumulation Ring. Monochromatic X-rays of 33.32 keV were used, and each image was recorded over 2 msec. RESULTS: Ventricular wall motion and the anatomy of the coronary arteries could be seen in dogs by sequential images obtained without subtraction. The left anterior descending coronary artery, left circumflex coronary artery, and right coronary artery and the branches of these vessels were observed. The parts of the coronary arteries overlapping the aorta and left ventricle were revealed somewhat during washout of the contrast material. CONCLUSION: For a 2D imaging system, monochromatic i.v. coronary angiography using an energy above the iodine K-edge might be able to image the coronary arteries without subtraction. However, the image quality needs to be improved by increasing the X-ray flux, decreasing background radiation scatter from the object, and decreasing contamination with 99-keV X-rays.
RATIONALE AND OBJECTIVES: We obtained image contrast in pathologic specimens without the use of contrast material by using phase-contrast imaging with synchrotron X-rays. METHODS: An experiment was performed at the three-pole superconducting vertical wiggler beam line BL-14B at the Photon Factory in Tsukuba, Japan. The X-ray phase-contrast imaging system consisted of a double crystal monochromator, an asymmetrically cut crystal monochromator, a triple Laue-case X-ray interferometer, and film. The pathologic specimen was a sample from human liver that had metastatic carcinoma. RESULTS: The X-ray phase-contrast images of the pathologic specimen clearly depicted the cancerous lesion without the use of contrast enhancement, and the image showed good correlation with the photograph of the specimen. The X-ray absorption image did not differentiate between the normal liver tissue and the tumor. CONCLUSION: The results of this preliminary experiment reveal that for materials such as biologic specimens with a low atomic number, X-ray phase-contrast imaging better differentiates tissues than does the absorption contrast imaging commonly used in radiology.
The distribution and virulence of Vibrio cholerae serogroups other than O1 and O139 in India before, during and after the advent of O139 serogroup was investigated. A total of 68 strains belonging to 31 different 'O' serogroups were identified during the study period. With the exception of O53, there was no spatial or temporal clustering of any particular non-O1 non-O139 serogroup at any given place. Two of the 68 strains examined produced cholera toxin (CT) which could only be partially absorbed with anti-CT immunoglobulin G. Tissue culture assay revealed that some of the non-O1 non-O139 strains produced factors which evoked either a cell rounding or cell elongation response depending upon the medium used. This study indicates that serogroups other than O1 and O139 should also be continuously monitored.
Sixty-nine strains of Vibrio cholerae O1 isolated at different times were analysed to investigate if there were any differences among the O1 strains isolated before, during and after the advent of the O139 serogroup. Of the 69 O1 strains examined, 68 belonged to the Ogawa serotype while one belonged to the Inaba serotype. With the exception of one strain all other strains of V. cholerae O1 belonged to the eltor biotype. A single O1 strain isolated before the emergence of the O139 serogroup could not be classified as either eltor or classical biotype because it was resistant to both classical and eltor specific bacteriophages. Marked variations in the susceptibility to antibiotics of V. cholerae O1 isolated during the different periods were observed. In addition, strains of V. cholerae isolated after the epidemic of serogroup O139 in Calcutta showed an expanding R-type with resistance to a variety of drugs as compared to the O1 strains isolated before the advent of the O139 serogroup. From this study, it is clear that there is a substantial mobility in genetic elements of V. cholerae O1 which necessitates a continuous monitoring to keep abreast of the changing traits of the etiologic agent of cholera.
Tetrahymena 14-nm filament protein (49K protein) is a bifunctional protein with roles in the cytoskeleton and as citrate synthase. Previous studies in our laboratory showed that elongation factor 1 alpha (EF-1 alpha) copurifies with the 49K protein upon polymerization and depolymerization of the 49K protein. In this study, the 49K protein was isolated from partially purified 49K protein fraction containing EF-1 alpha. Using the purified 49K protein and/or purified EF-1 alpha, the interaction between 49K protein and EF-1 alpha in filament formation was investigated electronmicroscopically and it was demonstrated that purified 49K protein was capable of forming 14-nm filaments without EF-1 alpha. The 49K protein/citrate synthase has been suggested to form filaments in mitochondria. Here we show that the citrate synthase activity of 49K protein is decreased by polymerization and increased by depolymerization, suggesting a possible modulating mechanism of citrate synthase activity by monomer-polymer conversion in mitochondria in situ.
Fas antigen (CD95) is a membrane-associated molecule that mediates apoptotic cell death and may play a role in the induction and maintenance of T cell tolerance. To elucidate the involvement of Fas antigen in human autoimmune diseases, we analysed Fas antigen expression by peripheral T cells from patients with SLE and rheumatoid arthritis (RA), using three-colour flow cytometry. Both CD4+ and CD8+ T cells from SLE patients expressed Fas antigen in a higher density than did these cells from healthy donors and from RA patients. Enhancement of Fas antigen density was noted in Fas+CD45RO+ memory T cells from SLE patients. More remarkably, a significant expression of Fas antigen was observed in CD45RO- naive T cells from SLE patients. CD4+CD45RO- T cells from SLE patients co-expressed Fas antigen and early to intermediate activation antigens such as CD25 and CD71, and late activation antigen HLA-DR in only FashiCD4+ naive T cells. Such up-regulation of Fas antigen expression in SLE patients seems to be clinically meaningful, because mean fluorescence intensity (MFI) of Fas antigen on CD4+ T cell subsets inversely correlates with the absolute size of CD4+ T cell subsets in peripheral blood of SLE patients. These results suggest that T cells with increased Fas antigen expression may be highly susceptible to apoptotic cell death, in vivo. A putative mechanism for lymphopenia in SLE patients is discussed.
Yersinia enterocolitica produces heat-stable enterotoxin (Y-ST) as one of its virulence factors. The yst gene, however, frequently and spontaneously becomes inactive (silent) during storage, which is accompanied by concurrent changes in some biological properties such as colony morphology, growth rate, carbon fermentation and ornithine decarboxylase activity. Northern blot analysis revealed that the level of mRNA for yst was repressed. To investigate the regulatory region, we transformed a yst-silent strain with a chromosomal gene library of Y-ST producing an isogenic counterpart. Out of 3604 clones, one clone resumed the Y-ST production and concurrently other biological properties. An open reading frame in this clone was designated as yrp, yersinia regulator for pleiotropic phenotype. Deduced from the nucleotide sequence, Yrp was a small protein of I01 amino acids with no similarity with any regulatory factor described, but showed high homology with an Escherichia coli host factor 1 required for Q beta-replicase, and with an Azorhizobium caulinodans NrfA required for the expression of nifA. The yrp gene mutation caused decreased negative supercoiling of plasmids, as did hfq. The yrp gene could similarly complement Y-ST production in two other silent strains of Y. enterocolitica. In all three silent strains examined, we found various mutations in the yrp region.
1. To determine biochemically the incipient timing of cerebral stroke in stroke-prone spontaneously hypertensive rats (SHRSP) the relation between the glutathione peroxidase (GSH-Px) activity in erythrocytes and the extent of stroke lesion was investigated. 2. When the blood pressure of SHRSP was maintained over 250 mmHg, the GSH-Px activity was lowered and the body weight also decreased. In the SHRSP where the GSH-Px activity in erythrocytes dropped below 23 units/mL blood, the incidence of cerebral stroke was 98% (n = 88/90). 3. The haemoglobin and haematocrit level were unchanged even after the GSH-Px activity dropped to 23 units/mL blood. 4. Lowering of GSH-Px activity in erythrocytes observed during continued hypertension was found to be due to decreased GSH-Px protein, but not to an inactivation of enzymes, as evidenced from immunochemical titration. 5. Lowering of GSH-Px activity in erythrocytes was found to be closely related with the incidence of cerebral stroke in SHRSP. These findings suggest that tracing of the GSH-Px activity in erythrocytes in SHRSP may serve as an indicator for prediction and prognosis of stroke lesion.
1. Hyperglycaemia is believed to be a major cause of diabetic vascular complications such as accelerated atherosclerosis. In order to elucidate the effect of hyperglycaemia on vascular response in spontaneously hypertensive rats (SHR), the natriuretic peptides receptor responses to vascular smooth muscle cells (VSMC) which are thought to suppress atherosclerosis were studied under high glucose (HG:22.2 mmol/L) conditions. 2. The total number of cells in SHR is higher and natriuretic peptides receptor response is smaller than that of cells in the Wistar-Kyoto (WKY) rat. Membrane bound protein kinase C (PKC) activity in HG or SHR is higher compared to that of cells in normal glucose (NG:5.6 mmol/L) or WKY. Cells cultured in HG for at least 2 passages had higher total cell number and receptor mediated cGMP formation were suppressed compared to cells cultured in NG both in SHR and WKY. Specific PKC inhibitor PKC (19-36) 1 mu mol/L prevented HG induced suppression of natriuretic peptides response. 3. These results show that hyperglycaemia may be linked to suppressed natriuretic peptides receptor response which is caused by increased PKC activity both in WKY and SHR. This suppressed response may cause the accelerated atherosclerosis by hyperglycaemia.