Search PubMed⌕ Search

Biomedical subjects

N Kume

Publications and source records attributed to N Kume.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Oxidized LDL].

Explore the source record for details and available documents.

Electrophoresis, Polyacrylamide Gel↗
PubMed2000

Molecular cloning of a novel scavenger receptor for oxidized low density lipoprotein, SR-PSOX, on macrophages.

Receptor-mediated endocytosis of oxidized low density lipoprotein (OxLDL) by macrophages has been implicated in foam cell transformation in the process of atherogenesis. Although several scavenger receptor molecules, including class A scavenger receptors and CD36, have been identified as OxLDL receptors on macrophages, additional molecules on macrophages may also be involved in the recognition of OxLDL. From a cDNA library of phorbol 12-myristate 13-acetate-stimulated THP-1 cells, we isolated a cDNA encoding a novel protein designated SR-PSOX (scavenger receptor that binds phosphatidylserine and oxidized lipoprotein), which acts as a receptor for OxLDL. SR-PSOX was a type I membrane protein consisting of 254 amino acids, expression of which was shown on human and murine macrophages with a molecular mass of 30 kDa. SR-PSOX could specifically bind with high affinity, internalize, and degrade OxLDL. The recognition of OxLDL was blocked by polyinosinic acid and dextran sulfate but not by acetylated low density lipoprotein. Taken together, SR-PSOX is a novel class of molecule belonging to the scavenger receptor family, which may play important roles in pathophysiology including atherogenesis.

Amino Acid Sequence↗
PubMed2000

Transforming growth factor-beta(1) increases the expression of lectin-like oxidized low-density lipoprotein receptor-1.

Lectin-like oxidized low-density lipoprotein (Ox-LDL) receptor-1 (LOX-1) is a novel cell-surface receptor for Ox-LDL, which can be expressed by vascular endothelial cells, smooth muscle cells, and macrophages. On the other hand, transforming growth factor (TGF)-beta(1), which plays crucial roles in vascular remodeling and the pathogenesis of atherosclerosis, has been shown to inhibit expression of class A scavenger receptors and CD36 in macrophages. Here we provide the evidence that TGF-beta(1) (0.1-10 ng/mL) induces LOX-1 protein and mRNA expression in both bovine aortic endothelial cells and smooth muscle cells in a dose- and time-dependent fashion, probably at the transcriptional level. TGF-beta(1) also upregulates LOX-1 mRNA expression in murine peritoneal macrophages. Thus TGF-beta(1) can highly induce LOX-1 expression in vascular endothelial cells, smooth muscle cells, and macrophages, suggesting that TGF-beta(1) appears one of the key regulators that modulates expression of scavenger receptors.

Animals↗
PubMed2000

Biosynthesis and post-translational processing of lectin-like oxidized low density lipoprotein receptor-1 (LOX-1). N-linked glycosylation affects cell-surface expression and ligand binding.

LOX-1 (lectin-like oxidized low density lipoprotein receptor-1) is a type II membrane protein belonging to the C-type lectin family that can act as a cell-surface receptor for atherogenic oxidized low density lipoprotein (Ox-LDL) and may play crucial roles in atherogenesis. In this study, we show, by pulse-chase labeling and glycosidase digestion, that LOX-1 is synthesized as a 40-kDa precursor protein with N-linked high mannose carbohydrate chains (pre-LOX-1), which is subsequently further glycosylated and processed into the 48-kDa mature form within 40 min. Furthermore, when treated with an N-glycosylation inhibitor, tunicamycin, both tumor necrosis factor-alpha-activated bovine aortic endothelial cells and CHO-K1 cells stably expressing bovine LOX-1 (BLOX-1-CHO) exclusively produced a 32-kDa deglycosylated form of LOX-1. Cell enzyme-linked immunosorbent assay, flow cytometry, and immunofluorescence confocal microscopy demonstrated that the deglycosylated form of LOX-1 is not efficiently transported to the cell surface, but is retained in the endoplasmic reticulum or Golgi apparatus in tumor necrosis factor-alpha-activated bovine aortic endothelial cells, but not in BLOX-1-CHO cells. Radiolabeled Ox-LDL binding studies revealed that the deglycosylated form of LOX-1 expressed on the cell surface of BLOX-1-CHO cells has a reduced affinity for Ox-LDL binding. Taken together, N-linked glycosylation appears to play key roles in the cell-surface expression and ligand binding of LOX-1.

Amidohydrolases↗
PubMed2000

Hemodynamic and metabolic state of hyperfixation with 99mTc-HMPAO brain SPECT in subacute stroke.

By means of positron emission tomography (PET), we investigated the hemodynamic and metabolic state of the hyperfixation identified as the increased accumulation with 99mTc-d,l-hexamethylpropyleneamine oxime (HMPAO) by single photon emission computed tomography (SPECT) in patients with subacute stroke. We studied four patients with subacute stroke having hyperfixed areas evaluated with CBF, CMRO2, OEF and CBV by PET. The hyperfixation rate with 99mTc-HMPAO was obtained by comparing the surplus rate with standardized CBF. The OEF and CMRO2 values in the hyperfixed areas of 4 patients were significantly lower than those in normal 5 controls (p < 0.01), but CBF and CBV were almost the same in patients and normal controls, but the hyperfixation rate of 0.30 +/- 0.15 in 4 patients correlated well with CBV (r = 0.97, y = 11.75x + 0.42; p < 0.05). Hyperfixation with 99mTc-HMPAO in the infarct area revealing a mismatch between CMRO2 and CBF meant relative luxury perfusion. The hyperfixation rate determined by 99mTc-HMPAO brain SPECT correlated with CBV in the PET study. We can conclude that one of the main factors which caused hyperfixation was vasodilatation as well as the blood brain barrier disruption and the neovascularization.

Adult↗
PubMed2000

Relative preservation of peripheral lung function in smoking-related pulmonary emphysema: assessment with 99mTc-MAA perfusion and dynamic 133Xe SPET.

In this study the cross-sectional functional differences between the central and peripheral lung in smokers with pulmonary emphysema were evaluated by lung perfusion and dynamic xenon-133 single-photon emission tomography (SPET). The subjects were 81 patients with a long-term smoking history and relatively advanced emphysema, 17 non-smoker patients with non-obstructive lung diseases and six healthy non-smokers. Regional lung functional difference between the peripheral and central lung was assessed in the upper, middle and lower lung zones by technetium-99m macroaggregated albumin SPET and dynamic 133Xe SPET. The distribution of emphysematous changes was assessed by density-mask computed tomography (CT) images which depicted abnormally low attenuation areas (LAAs) of less than -960 Hounsfield units. Two hundred and eighty-eight (59.2%) lung zones of 63 (77.7%) patients with pulmonary emphysema showed relative preservation of lung function in the peripheral lung, with a curvilinear band of normal perfusion (a stripe sign) and a significantly faster 133Xe half-clearance time (T(1/2)) than in central lung (P<0.0001). Of these lung zones, 256 (88.8%) showed central-dominant LAA distributions on density-mask CT images, but the remaining 32 zones did not show any regional preference in LAA distribution. Conversely, 117 (24.0%) lung zones of 19 (23.4%) patients showed periphery-dominant perfusion defects and LAA distributions, with significantly prolonged T(1/2) in the peripheral lung area (P<0.0001). The remaining 81 lung zones of the patients with pulmonary emphysema and all the lung zones of the healthy subjects and patients with non-obstructive lung diseases did not show a stripe sign, and no differences were observed in T(1/2) values and LAA distributions between the central and peripheral lung. Relative preservation of peripheral lung function seems to be a characteristic feature in smoking-related pulmonary emphysema, and may indicate a lower susceptibility of peripheral parenchyma to the development of this disease.

Case-Control Studies↗
PubMed2000

Alteration of myocardial metaiodobenzylguanidine uptake after treatment of phaeochromocytoma and neuroblastoma.

The relationships between changes in myocardial uptake of metaiodobenzylguanidine (MIBG) and those in circulating catecholamines and cardiac function after treatment of phaeochromocytoma and neuroblastoma were evaluated. Iodine-123 or iodine-131 MIBG scintigraphy was performed before and after surgical resection and/or chemotherapy for primary tumours in nine patients with phaeochromocytoma and 13 patients with neuroblastoma. Changes in myocardial MIBG uptake after treatment were estimated by the heart-to-upper mediastinum (H/M) uptake ratios on the images obtained 24 h after MIBG injection, which were compared with serum levels of noradrenaline (NA) and adrenaline (A). Cardiac function was assessed by echocardiography, with measurements of the left ventricular ejection fraction (LVEF). Before treatment, eight patients with phaeochromocytoma and three with neuroblastoma showed poor myocardial MIBG uptake, with highly elevated circulating NA and A. Echocardiography, however, did not show cardiac dysfunction in these patients with the exception of two patients with phaeochromocytoma. With normalization of NA and A levels after treatment, all of these patients except for the two with persistent cardiac dysfunction showed restoration of myocardial MIBG uptake. The H/M ratios increased significantly after treatment in both patient groups, i.e. with phaeochromocytoma and with neuroblastoma (P<0.0001 and P<0.05, respectively), and these ratios correlated inversely with circulating NA and A before and after treatment. By contrast, there was no significant correlation between H/M ratios and LVEF in these two groups. These results indicate that suppression of myocardial MIBG uptake usually may not be related to cardiac dysfunction and may be reversible following normalization of excess catecholamine levels after treatment in patients with neuroadrenergic tumours. However, the suppression may persist in the presence of catecholamine-induced cardiac dysfunction. The assessment of myocardial MIBG uptake can be a helpful adjunct in monitoring the normalization of circulating catecholamine levels and also in identifying the presence of cardiac dysfunction in treated patients with neuroadrenergic tumours.

3-Iodobenzylguanidine↗
PubMed2000

Irreversible long-term pulmonary functional impairments after adenovirus type-7 pneumonia: assessment with xenon-133 ventilation and Tc-99m MAA perfusion studies.

A 3-year-old child presented with severe type-7 adenoviral pneumonia, after the resolution of diffuse pulmonary infiltrates of the pneumonia. Xenon-133 ventilation and Tc-99-m macroaggregated albumin (MAA) perfusion studies revealed a localized airflow obstruction and matched perfusion defect, and marked air trapping in the remaining lungs, and these abnormalities were not detected and not suspected even with CT. Thereafter, in a relatively short period, the child developed persistent bronchiectatic changes and pulmonary hyperinflation throughout the lungs. However, the scintigraphic findings were not significantly changed. This is the first description of radionuclide scintigraphic findings which clearly showed an irreversible long-term functional effect of adenoviral pneumonia.

Adenovirus Infections, Human↗
PubMed2000

Coexisting renal vein thrombosis and bilateral adrenal hemorrhage: renoscintigraphic demonstration.

A rare case of simultaneous renal vein thrombosis and bilateral adrenal hemorrhage is presented, showing the utility of Tc-99m DTPA and DMSA renal scans to identify the condition and to assess renal function. The characteristic appearances of suprarenal tracer-free areas encircled by peripheral radioactive rims over the inferiorly displaced kidneys on a Tc-99m DTPA renal scan, and that of the flattened upper poles of the kidneys on a Tc-99m DMSA scan, were pathognomonic and strongly indicative of bilateral adrenal hemorrhage. These two scans also showed markedly diminished tracer uptake in the poorly functioning right thrombosed kidney. Follow-up imaging using these two renal scans well demonstrated the functional and morphologic alterations and recovery of the kidneys.

Adrenal Gland Diseases↗
PubMed2000

Tc-99m MIBG imaging in a huge clinically silent pheochromocytoma with cystic degeneration and massive hemorrhage.

I-131 metaiodobenzylguanidine scintigraphy showed marked accumulation in the walls of a clinically silent, huge cystic adrenal mass with a prominent hemorrhage in a 48-year-old man. Although a careful reexamination of the histologic specimen finally lead to a diagnosis of pheochromocytoma, the appearances of this mass on computed tomography and magnetic resonance imaging were not specific for this neoplasm, and even pathologic analysis initially indicated, incorrectly, that this lesion was a hemorrhagic hemangioma. This case shows that I-131 metaiodobenzylguanidine scintigraphy is useful for correctly diagnosing an adrenal mass with prominent cystic or hemorrhagic degeneration.

3-Iodobenzylguanidine↗
PubMed2000

Oxidized-LDL and atherosclerosis. Role of LOX-1.

The accumulation of substantial numbers of monocyte/macrophages and activated T lymphocytes in focal areas of the arterial intima appears to be a hallmark of atherosclerosis. Our report demonstrated that lysophosphatidylcholine (lyso-PC), a polar phospholipid component that is increased in atherosclerotic lipoproteins, such as oxidized LDL and remnant lipoproteins in diabetic and Type 3 hyperlipidemia, can upregulate adhesion molecules for monocytes and T lymphocytes, and growth factors, such as heparin-binding epidermal growth factor-like growth factor and PDGF A and B chains. Recently, we identified the novel receptor for oxidized LDL, named LOX-1. We summarize the importance of the interaction between oxidized LDL and its receptor, LOX-1, in terms of early stage atherogenesis.

Animals↗
PubMed2000

Inducible expression of LOX-1, a novel receptor for oxidized LDL, in macrophages and vascular smooth muscle cells.

Macrophages appear to take up oxidized low density lipoprotein (Ox-LDL) by multiple receptor-mediated pathways. This study, therefore, has been performed to determine if LOX-1, a novel receptor for Ox-LDL, which was identified in vascular endothelial cells, is also expressed in macrophages. Expression of LOX-1 can be induced after macrophage-like differentiation in human peripheral blood monocytes as well as THP-1 cells. Furthermore, expression of LOX-1 in macrophages is also upregulated by an inflammatory cytokine TNF-alpha, which was shown to be present in atherosclerotic arterial wall. Expression of this novel receptor LOX-1 may play an important role in Ox-LDL uptake and subsequent foam cell formation in macrophages.

Animals↗