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Biomedical subjects

M Yano

Publications and source records attributed to M Yano.

At least 523 records · Page 29Linked to original sources
PubMed1993

Age-related modification of regional left ventricular filling in normal subjects.

Left ventricular diastolic filling has been reported to be impaired with advancing age in normal subjects. To investigate the influence of regional ventricular diastolic asynchrony on global ventricular filling as a function of age and to assess the location of asynchronous regions within the left ventricle, radionuclide ventriculography was conducted in 48 normal subjects aged 15 to 73 years. Left ventricular regional filling was assessed by dividing the left ventricular region of interest into 4 quadrants, from which global, septal, apical and lateral time-activity curves and first-derivative curves were derived. Indexes of global left ventricular systolic function at rest did not correlate with age. However, indexes of global early diastolic filling declined significantly with age; peak filling rate normalized to end-diastolic volume (r = -0.42; p < 0.01), to stroke volume (r = -0.48; p < 0.001) and to peak ejection rate (r = -0.47; p < 0.001) decreased with advancing age. Global time to peak filling rate also increased with aging (r = 0.41; p < 0.01). Early diastolic asynchrony was measured as the sum of the absolute values of the time differences from global peak filling rate to that in each of three quadrants (delta TPFR). delta TPFR increased with age (r = 0.37; p < 0.01). Global peak filling rate normalized to end-diastolic volume (r = -0.40; p < 0.01), to stroke volume (r = -0.45; p < 0.01) and to peak ejection rate (r = -0.51; p < 0.001) decreased significantly with increasing delta TPFR. Time to peak filling rate of the lateral region occurred first (163 +/- 33 ms), followed by the apical (184 +/- 38 ms) and finally the septal region (195 +/- 35 ms). With regard to the sequence of regional filling, this suggests that a physiologic asynchrony exists in resting condition in normal subjects. Times to peak filling rate in the septal and apical regions were modestly correlated with age (r = 0.29; p < 0.05, r = 0.30; p < 0.05 respectively), but that in the lateral region did not show significant correlation with age. This may indicated that the effects of advancing age on the regional filling differ in regions within the left ventricle. These results suggest that aging alters left ventricular early diastolic filling in association with the increase in physiologic asynchrony.

Adolescent↗
PubMed1993

[Evaluation of CEA, SLX and CA125 in active pulmonary tuberculosis].

Serum tumor markers (CEA, SLX, CA125) were evaluated in 123 patients with active pulmonary tuberculosis. The results were as follows: Elevated serum CEA, SLX and CA125 levels were found in 16.9%, 39.5% and 44.4%, respectively, of patients with active pulmonary tuberculosis. Markedly elevated serum CA125 levels were found in some cases. On chest X-ray films, the factors associated with elevation of serum tumor marker levels were examined. Serum CEA and SLX levels were correlated with the extent of disease. Pleural effusion had no influence on serum tumor marker levels. Serum SLX levels were higher in patients without a tuberculous cavity than in those with a tuberculous cavity. After therapy with antituberculous drugs, the mean values of serum SLX and CA125 levels significantly decreased. The decrease in mean value of serum CEA levels was not significant, but in 4 of 8 cases, elevated serum CEA levels were normalized after therapy. On the other hand, two cases with increased serum CEA or SLX level died of respiratory failure. These results suggest that to follow up patients with elevated serum tumor markers is useful for the evaluation of disease activity of pulmonary tuberculosis. Further elevation of serum tumor marker levels after antituberculous therapy may indicate the presence of cancer or deterioration of the disease.

Adolescent↗
PubMed1993

Hepatic copper accumulation in patients with primary biliary cirrhosis.

Liver biopsy specimens from 18 patients with primary biliary cirrhosis were examined histochemically and by energy-dispersive x-ray microanalysis. Using two indices, we classified hepatic copper accumulation into three stages based on the Cu x-ray intensity of cuproproteins that had accumulated in hepatocyte lysosomes and on the binding ratio of postulated copper transfer proteins between the cytosol and lysosomes. Eight patients were in stage 1 with an initial accumulation of lysosomal cuproproteins, mediated by transfer proteins not saturated with copper. Two patients were in stage 2, in which transfer proteins were saturated with copper. The first two stages gave negative results for histochemical copper. The remaining eight patients were in stage 3, in which copper accumulation detected by histochemical included transfer proteins saturated with copper and large amounts of lysosomal cuproproteins. Five patients (one each in stages 1 and 2, and three in stage 3) underwent a second liver biopsy after treatment with 600 mg of ursodeoxycholic acid daily for 14 to 39 months. Results of blood chemistry tests improved, but liver histologic findings and copper accumulation were unchanged in all five patients. It seems likely that ursodeoxycholic acid does not affect the copper accumulation in hepatocyte lysosomes that reflects the state of cholestasis in patients with primary biliary cirrhosis.

Adult↗
PubMed1993

Intrahepatocellular localization of copper in Wilson's disease.

It is well known that excess copper plays a role in the pathogenesis of Wilson's disease; however, the hepatic copper contents, determined either histochemically or biochemically, are not always correlated with the activity of Wilson's disease. To better understand copper-induced cytotoxicity, intrahepatocellular localization of copper was studied in five patients with Wilson's disease. The liver specimens were obtained by biopsy to confirm the clinical diagnosis of Wilson's disease before treatment. Neither hepatic copper content nor histochemical copper deposits were correlated with any of the biochemical indices studied. Energy-dispersion X-ray microanalysis was done on the nuclei, lysosomes and lysosome-free cytoplasm of hepatocytes. Lysosomes had the highest Cu X-ray intensity but no correlation was shown between the lysosomal copper content and biochemical indices. The nucleus/lysosome-free cytoplasm ratio of the copper content was correlated with the serum levels of aminotransferases. These results suggest that the copper increasing gradient from the lysosome-free cytoplasm to the nucleus is associated with hepatocyte necrosis, and probably causes irreversible nuclear damage.

Adolescent↗
PubMed1993

[A case of endobronchial chondroma in a patient with atypical mycobacterial infection].

A case of endobronchial chondroma in a 74-year-old man with atypical mycobacterial infection is reported. Bronchoscopy was performed in order to exclude the possibility of malignancy. At bronchoscopic examination, a hemispherical polypoid tumor with smooth surface was found at the orifice of left B3 and was removed by transbronchial biopsy forceps. Histologically the tumor was composed of cartilage tissue. About 1 year after forceps resection, no growth of the tumor was seen in the left upper lobe bronchus on bronchoscopic examination. Endobronchial chondroma is relatively rare. We discuss the clinical features of 19 cases of endobronchial chondroma so far reported in Japan, including our case.

Aged↗
PubMed1993

[Three cases of lung cancer with calcification--demonstration by chest CT].

We report three cases of lung cancer with calcification shown on chest CT scans. Case 1 was a 63-year-old man with well differentiated squamous cell carcinoma of the lung. Chest CT scan showed pronounced central calcification within the tumor. Case 2 was a 57-year-old woman with small cell carcinoma of the lung. Chest CT scan showed diffuse amorphous calcification within the tumor. Case 3 was a 70-year-old man with lung cancer for which pathologic data was not available. Chest CT scan showed punctate and linear calcification of the cavity wall within the tumor. Microscopic examinations revealed dystrophic calcification in cases 1 and 2. Calcification has long been recognized as a distinguishing radiologic feature of a benign pulmonary mass, however, the presence of calcification within a tumor on chest CT scan does not exclude the diagnosis of lung cancer.

Aged↗
PubMed1993

Defective calcium-dependent signal transduction in B lymphocytes of a certain common variable immunodeficiency.

Two different common variable immunodeficiency patients were studied. Patient 1 showed hypogammaglobulinemia in all major classes of gammaglobulins and slightly reduced percentages of circulating CD19+ cells, CD20+ cells and surface IgG-or IgA-bearing cells with a normal percentage of surface IgM-bearing cells. Patient 2 showed normal levels in IgM with IgG and IgA deficiencies and almost normal percentages of circulating CD19+ cells, CD20+ cells and surface IgM-, IgG- or IgA-bearing cells. The proliferative responses of peripheral blood mononuclear cells to B cell mitogen, Staphylococcus aureus Cowan I, were reduced in patient 1 but not in patient 2. The intracellular calcium concentrations in lymphoblastoid cell lines (LCLs) transformed by Epstein-Barr virus from patient 2 were increased after anti-mu stimulation. The concentrations were scarcely increased in LCLs from patient 1. These results suggest that B cells of patient 1 have a defective Ca(2+)-dependent signal transduction pathway, resulting in a failure of cell activation and cell proliferation. The defect in B cells of patient 2 may exist on immunoglobulin gene switching or expression rather than the Ca(2+)-dependent signal transduction pathway.

Agammaglobulinemia↗
PubMed1993

[A case of giant advanced breast cancer responding remarkably to CEFT therapy].

A fifty-two-year-old female was admitted with unresectable advanced giant breast cancer, which was attached to the chest wall and had a bone metastasis to the thoracic vertebrae. At first, depression and fixation were performed for the bone metastasis, and 2 courses of CEFT therapy were administered. One course was intra-arterial chemotherapy. After 2 courses of treatment, the tumor size was not changed, but tumor marker, CT and physical findings showed a remarkable improvement, and mastectomy could be performed. It was suggested that this regimen is very effective for advanced giant breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Suppressive effects of the endothelin receptor (ETA) antagonist BQ-123 on ET-1-induced reduction of lipoprotein lipase activity in 3T3-L1 adipocytes.

Endothelin (ET)-1 reduced heparin-releasable lipoprotein lipase (LPL) activity in 3T3-L1 adipocytes in a concentration-dependent manner. However, a selective ETB receptor agonist, [Ala1,3,11,15]ET-1, did not act like ET-1. The ET-1-induced decrease in LPL activity was suppressed by a selective ETA receptor antagonist, BQ-123: the concentration-response curve for the ET-1 reduction of LPL activity was shifted to the right in the presence of BQ-123 in a concentration-dependent manner. This antagonistic effect of BQ-123 clarifies that the ETA receptor is responsible for the ET-1-induced reduction of LPL activity in 3T3-L1 adipocytes, which suggests that there is therapeutic potential for ETA antagonists in LPL-related lipoprotein disorders.

3T3 Cells↗
PubMed1992

Protective effect of a selective endothelin receptor antagonist, BQ-123, in ischemic acute renal failure in rats.

To elucidate the pathophysiological role of endogenous endothelin (ET), we examined the effects of the newly synthesized ETA receptor-selective antagonist, BQ-123, on ischemic acute renal failure induced by bilateral clamping of renal artery and vein followed by reperfusion in rats. BQ-123, when given by i.v. infusion of 0.5 mg/kg per min for 2.5 h during the pre- and post-ischemic period, was found to prevent the decrease in creatinine clearance and increases in blood urea nitrogen, plasma creatinine and the fractional excretion of sodium. Morphological observation also showed an effect of BQ-123, i.e. prevention of proximal tubular (S3 segment) necrosis. At 2 h after the start of reperfusion, the ET-1 content in the kidney increased to its maximal level. At this time, the Ca2+ content in the mitochondrial fraction of the renal cortex increased, with a concomitant increase in blood urea nitrogen. However, these increases were limited by treatment with BQ-123. Thus, BQ-123 was effective to both prevent mitochondrial Ca2+ accumulation in the early phase of ischemic acute renal failure and protect proximal tubular cells from post-ischemic degeneration. We conclude that ET may be at least partially involved in the pathogenesis of tubular cell injury in this acute renal failure model.

Acute Kidney Injury↗
PubMed1992

Endothelin-1 enhances vascular permeability in the rat heart through the ETA receptor.

Intravenous injection of endothelin-1 (ET-1, 0.1 and 1 nmol/kg) resulted in a dose-dependent increase in vascular permeability in the coronary circulation of conscious rats. The increase was almost completely abolished by the selective ETA receptor antagonist, BQ-123 (1 mg/kg). The ET-1 analogue, [Trp(For)21]ET-1, which is devoid of the depressor but not the pressor activity, evoked changes in protein extravasation similar to those with ET-1. These data indicate that the permeability effect of ET-1 is mediated through the ETA receptor.

Animals↗
PubMed1992

A novel ETA antagonist (BQ-123) inhibits endothelin-1-induced phosphoinositide breakdown and DNA synthesis in rat vascular smooth muscle cells.

The effects of a novel cyclic pentapeptide (BQ-123), an endothelin (ET) antagonist selective for the ETA receptor subtype, on phosphoinositide breakdown and DNA synthesis stimulated by ET-1 were studied in cultured rat vascular smooth muscle cells (VSMC). BQ-123 competitively inhibited the binding of [125I]ET-1 to VSMC with the apparent Ki of 4 x 10(-9) M. BQ-123 dose-dependently inhibited formation of inositol-1,4,5-trisphosphate and [3H]thymidine uptake stimulated by ET-1. These data suggest that the ET-1-induced DNA synthesis in VSMC is mainly mediated by ETA receptor subtype.

Animals↗
PubMed1992

Biochemical properties of endothelin converting enzyme in renal epithelial cell lines.

This is the first report clearly demonstrating the presence of endothelin (ET) converting enzyme (ECE) in non-vascular cells (renal epithelial cell lines, MDCK and LLC-PK1). ECEs derived from these epithelial cells were very similar to the endothelial ECE in the following biochemical properties: 1) The optimum pH was 7.0; 2) the Km value for big ET-1 was approximately 30 microM; 3) the enzyme was potently inhibited by EDTA, o-phenanthroline and phosphoramidon; and 4) the enzyme did not convert big ET-2 or big ET-3. These data suggest that phosphoramidon-sensitive ECE is involved in the processing of big ET-1 to ET-1 in the renal tubule.

Animals↗
PubMed1992

Different distribution of endothelin receptor subtypes in pulmonary tissues revealed by the novel selective ligands BQ-123 and [Ala1,3,11,15]ET-1.

We have demonstrated the different distribution of two distinct endothelin (ET) receptor subtypes in porcine pulmonary tissues using a radioligand binding assay. The clear differentiation of the subtypes was made possible by the discovery of two compounds, BQ-123 and [Ala1,3,11,15]ET-1 (4AlaET-1), that are highly selective for ETA and ETB receptors, respectively. In the bronchus and lung parenchyma, BQ-123 inhibited 65% and 30% of [125I]ET-1 binding on the sensitive sites, while 4AlaET-1 displaced 25% and 60%, respectively. The combination of the two compounds completely inhibited ET-1 binding in both tissues. An autoradiographic study of [125I]ET-1 binding using BQ-123 and 4AlaET-1 also supported the different localization of two ET receptor subtypes in pulmonary tissues. In particular, the blood vessels and bronchi are rich in ETA, but the lung parenchyma is rich in ETB.

Amino Acid Sequence↗
PubMed1992

Biological profiles of highly potent novel endothelin antagonists selective for the ETA receptor.

We describe novel potent endothelin (ET) antagonists that are highly potent and selective for the ETA receptor (selective to ET-1). Of the synthetic analogs based on ETA antagonist BE-18257A isolated from Streptomyces misakiensis (IC50 value for ETA receptor on porcine aortic smooth muscle cells (VSMCs); 1.4 microM), the compounds BQ-123 and BQ-153 greatly improved the binding affinity of [125I]ET-1 for ETA receptors on VSMCs (IC50; 7.3 and 8.6 nM, respectively), whereas they barely inhibited [125I]ET-1 binding to ETB receptors (nonselective with respect to isopeptides of ET family) in the cerebellar membranes (IC50; 18 and 54 microM, respectively). Associated with the increased affinity for ETA receptors, these peptides antagonized ET-1-induced constriction of isolated porcine coronary artery. However, there was a small amount of ET-1-induced vasoconstriction resistant to these antagonists, which paralleled the incomplete inhibition of [125I]ET-1 binding in the membrane of the aortic smooth muscle layer. These data suggest that the artery has both ETA and ETB receptors responsible for ET-1-induced vasoconstriction. The antagonists shifted the concentration-response curve to the right for ET-1 in the coronary artery, and increased the apparent dissociation constant in the Scatchard analysis of [125I]ET-1 binding on the VSMCs without affecting the binding capacity, indicative of the competitive antagonism for ETA receptor. In conscious rats, pretreatment with the antagonists markedly antagonized ET-1-induced sustained pressor responses in dose-dependent fashion without affecting ET-1-induced transient depressor action, suggesting that the pressor action is mediated by ETA receptors, while the depressor action is mediated by ETB receptors. In addition, pretreatment with the potent antagonists prevented ET-1-induced sudden death in mice. Thus, these potent ETA antagonists should provide a powerful tool for exploring the therapeutic uses of ETA antagonists in putative ET-1-related disorders.

Amino Acid Sequence↗