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Biomedical subjects

N Ueda

Publications and source records attributed to N Ueda.

At least 37 records · Page 2Linked to original sources
PubMed1992

Mesangial cell growth in genetically hypertensive rats and effect of calcium antagonists upon this growth.

Mesangial cells play an important role in physiological and pathophysiological regulation of glomerular functions. To explore the involvement of deranged mesangial cell functions in the pathogenesis of hypertension, the growth activity of mesangial cells was compared in stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY). Upon exposure to fetal calf serum, the growth rate was significantly higher in mesangial cells cultured from glomeruli of 4-week old SHRSP than in those of age-matched WKY. This abnormally high growth of SHRSP mesangial cells was significantly inhibited by dihydropyridine calcium antagonists. Of the three antagonists tested, manidipine was the most potent inhibitor. Significant growth inhibition occurred at a concentration as low as 10(-12) M; inhibition as high as 65% was found at 10(-6) M. Calcium antagonists, particularly manidipine, may prevent or delay the development of hypertension not only through vasodilation but also through inhibition of mesangial cell growth. By slowing mesangial cell proliferation, calcium antagonists also may slow the progression of hypertension-induced glomerular sclerosis.

Animals↗
PubMed1992

[Clinical significance of posttetanic count (PTC) during onset and spontaneous offset of neuromuscular blockade induced by vecuronium].

To compare the clinical difference of posttetanic count (PTC) during onset and spontaneous offset, the changes of PTC during an intense neuromuscular blockade induced by vecuronium (0.08 mg.kg-1, i.v.) were measured using a neuromuscular transmission analyzer in 64 adult patients anesthetized with nitrous oxide and halothane. Furthermore, intubation score was evaluated when zero PTC was obtained. The obvious movement of diaphragm associated with endotracheal intubation was observed in 9 out of 20 patients (45%) even when it was performed after obtaining zero PTC. The difference of PTC responses between the onset and the offset was found. The difference was that, during the onset, a tetanic response was observed obviously and the height of the posttetanic single twitch was low, and during offset, even when no response was observed, the height of a posttetanic single twitch response was high with the same PTC. These facts indicate that the same PTC has different clinical significance during onset and offset.

Adult↗
PubMed1992

[Co-operative clinical evaluation of 5'-DFUR tablets for breast cancer at 31 institutions].

A phase II study of 5'-deoxy-5-fluorouridine (5'-DFUR) tablets for breast cancer was done at 31 institutions in Japan. Forty-five patients were registered and 44 of them were eligible for the study. Of the 40 patients whose results could be evaluated, 11 (28%) responded (four complete responses and seven partial responses). Side effects, such as diarrhea, anorexia, leukocytopenia, and liver dysfunction were observed in 24 of the 44 patients. The side effects were mild and transient. 5'-DFUR is a promising drug for breast cancer treatment, and its tablet form makes chemotherapy easier for the patient.

Administration, Oral↗
PubMed1992

Ectopic ACTH-producing adenocarcinoma of the stomach.

A 73-year-old female was admitted to our hospital because of weight loss and pretibial edema. Plasma levels of adenocorticotropic hormone (ACTH) and cortisol were elevated, and neither hormone showed circadian rhythm. Dexamethasone (2 mg for 2 days) failed to reduce the urinary excretion of 17-hydroxycorticosteroids and the plasma cortisol level. The stomach biopsy specimens showed a moderately-differentiated papillo-tubular adenocarcinoma. Computed tomography of the abdomen showed multiple metastases to the liver. Immunohistochemical staining of the autopsy specimens showed immunoreactive ACTH in the primary tumor cells of the stomach as well as the metastatic tumor cells of the liver. On the basis of the clinical, histological and immunohistochemical findings, we diagnosed this patient as having ectopic ACTH syndrome caused by adenocarcinoma of the stomach.

ACTH Syndrome, Ectopic↗
PubMed1992

[A method for the simultaneous determination of iothalamic acid and creatinine clearance by coupled-column liquid chromatography].

[125I]iothalamic acid clearance is used for the estimation of glomerular filtration rate. Therefore, we developed a coupled-column liquid chromatography for the simultaneous determination of iothalamic acid and creatinine in human serum and urine samples to calculate their clearance. The liquid chromatograph consisted of an automatic injector, four columns and four switching valves. Timing of sample injection and switching of valves were controlled by a combination of timer units. Diluted samples were injected into a column of weakly acidic ion exchanger (Asahipak ES-502C, 30 degrees C, C1), and iothalamic acid excluded from the column was purified by gel chromatography on a hydrophilic gel (Asahipak GS-320H, 50 degrees C, C2) and then by ion exchange chromatography on a weakly basic anion exchanger (Asahipak ES-502N, 50 degrees C, C3). Creatinine that was eluted from C1 after iothalamic acid was transferred to Asahipak GS-320H (37 degrees C, C4) and C1 was backflushed until 10 min before the next sample was injected. Samples were injected every 55 min. The mobile phase was a sodium propionate buffer prepared by dissolving 0.035 mol of NaOH and 0.35 mol of propionic acid in 1 kg of ultra pure water, and its flow rate was 1.1 ml per min. Creatinine clearance calculated from the data obtained by this method was higher than that obtained by Jaffé's method, because serum creatinine concentrations obtained by this method were lower than those obtained by Jaffé's method. Iothalamic acid clearance (y) calculated from the data on serum and urine samples of clearance time 105-135 min showed a close correlation with inulin clearance (x) calculated from the data obtained by the anthrone method, for which aliquots of the same samples were used (y = 1.066 x -1.429 ml/min, r = 0.997, n = 15).

Chromatography, Liquid↗
PubMed1992

[A new analytical method for simultaneous measurement of iothalamate and iohexol].

Glomerular filtration rate (GFR) is believed to be the overall index of renal function, and the renal clearance of inulin (Cin) obtained during constant intravenous infusion has long been accepted as the gold standard of GFR measurement. Because of a number of technical difficulties inherent in the assay of inulin concentration in urine and plasma, its utility in clinical practice is limited. Iothalamate, urographic contrast medium, which behaves and is excreted in a fashion similar to inulin, has been accepted as a good filtration marker. We examined whether GFR could be estimated by ionic contrast media, "iothalamate" and non-ionic contrast media, "iohexol", when the high-performance liquid chromatography (HPLC) system was used as the analytic method. In our HPLC system, iothalamate and iohexol could be simultaneously determined. The assay results gave linearity within the wide range of concentrations tested. In seventeen subjects, the renal clearances of creatinine, iothalamate, and iohexol (Ccr, Ciot, and Cioh) were compared with that of inulin. The slopes with zero intercept of Ccr vs Cin, Ciot vs Cin, and Cioh vs Cin were 1.24 +/- 0.02, 1.06 +/- 0.02, and 0.83 +/- 0.02, respectively. In conclusion, an excellent correlation of renal clearance of iothalamate with that of inulin was obtained in patients with a wide range of renal function and normal volunteers. This justifies the use of the single injection of iothalamate and HPLC system as the analytic method in the measurement of GFR.

Chromatography, High Pressure Liquid↗
PubMed1992

[Clinical application of data measured by automated blood cell counter].

Rapid progress has been made in automated blood cell counting techniques using several kinds of apparatuses based on different mechanisms of measurement. We report a method of clinical application of the measurements made by an automated blood cell counter in the diagnosis and treatment of diseases, and discuss its usefulness, and its weaknesses that require improvement.

Blood Cell Count↗
PubMed1991

Mucosal dysplasia of the liver and the intraductal variant of peripheral cholangiocarcinoma in hepatolithiasis.

Four cases are reported of the intraductal variant of peripheral cholangiocarcinoma among surgical specimens from 32 cases of hepatolithiasis. The cancers arose from the periphery of the stone-containing bile duct and spread chiefly along the luminal surface. Microscopically, these tumors showed papillary proliferation and therefore were diagnosed as the intraductal spreading type of peripheral cholangiocarcinoma. Mucosal dysplasia also was noticed in the vicinity of the tumors. In six other cases, mucosal dysplasia was observed in the periphery of the stone. Immunohistochemically, anti-CA 19-9 staining was observed diffusely in the cytoplasm of dysplastic lesions and carcinomas. Anti-carcinoembryonic antigen staining was restricted to the luminal surface and/or the supranuclear region of the cytoplasm in carcinomas. It was not identified in dysplastic cells. These results suggest that the mucosal dysplasia occasionally observed near stones is a precursor of the intraductal spreading type of peripheral cholangiocarcinoma in the presence of hepatolithiasis. The authors hypothesize that the lining epithelium of the large bile duct, when persistently exposed to biochemically altered bile, may undergo a carcinomatous transformation through a stage of mucosal dysplasia.

Adenoma, Bile Duct↗
PubMed1991

Alterations in cardiac function and subcellular membrane activities after hypervitaminosis D3.

The present study was designed to induce massive accumulation of calcium in the myocardium and to evaluate the effect of calcium overload on myocardial contractile function and biochemical activity of cardiac subcellular membranes. Rats were treated with an oral administration of 500,000 units/kg of vitamin D3 for 3 consecutive days, and their hearts were sampled on the 5th day for biochemical analysis. On the 4th and 5th days, heart rate, mean aortic pressure, left ventricular systolic pressure and left ventricular dP/dt were significantly lowered in vitamin D3-treated rats, demonstrating the existence of appreciable myocardial contractile dysfunction. Marked increases in the myocardial calcium (67-fold increase) and mitochondrial calcium contents (24-fold increase) were observed by hypervitaminosis D3. Mitochondrial oxidative phosphorylation and ATPase activity were significantly reduced by this treatment. A decline in sarcolemmal Na+, K(+)-ATPase activity was also observed, while relatively minor or insignificant changes in calcium uptake and ATPase activities of sarcoplasmic reticulum were detectable. Electron microscopic examination revealed calcium deposits in the mitochondria after vitamin D3 treatment. The results suggest that hypervitaminosis D3 produces massive accumulation of calcium in the myocardium, particularly in the cardiac mitochondrial membrane, which may induce an impairment in the mitochondrial function and eventually may lead to a failure in the cardiac contractile function.

Adenosine Triphosphatases↗
PubMed1991

Arachidonate 5-lipoxygenase of porcine pancreas: its localization in acinar cells.

Arachidonate 5-lipoxygenase has been found so far in various types of leukocyte. When a homogenate of porcine pancreas was incubated with arachidonic acid, 5-hydroxy-6,8,11,14-eicosatetraenoic acid was predominantly produced concomitant with small amounts of compounds derived from leukotriene A4. After differential centrifugation of the homogenate, the 5-lipoxygenase activity was found predominantly in the 1000 x g pellet and 105,000 x g supernatant. When porcine pancreas was investigated immunohistochemically with anti-5-lipoxygenase antibody, Langerhans islets were unstained, and infiltration of 5-lipoxygenase-positive leukocytes was hardly observed. In contrast, acinar cells were positively stained. Immunoelectron microscopy demonstrated the localization of the enzyme along the nuclear membranes of the acinar cells.

Animals↗
PubMed1991

Porcine leukocyte 5- and 12-lipoxygenases are iron enzymes.

5- and 12-lipoxygenases isolated from porcine leukocytes were investigated by electron paramagnetic resonance at X-band and atomic absorption spectroscopy. For comparison potato 5-lipoxygenase was studied under identical experimental conditions. All three lipoxygenases contained between 0.7 and 0.9 Fe atoms/enzyme molecule. As isolated, both mammalian enzymes exhibited a characteristic EPR signal at low magnetic field with a maximum at g = 5.20 indicative of a high-spin ferric iron center. The signal was not affected by the oxidants 12-hydroperoxyeicosatetraenoic acid or arachidonic acid, nor was it affected by the reductant nordihydroguaiaretic acid. In the case of the potato enzyme an intense EPR signal with resonances at g = 7.50, 6.39 and 5.84 was only observed after addition of an oxidant, such as 9-hydroperoxyoctadecadienoic acid.

Animals↗
PubMed1991

Signal transduction mechanism of interleukin 6 in cultured rat mesangial cells.

Interleukin 6 (IL-6) is one of the potent autocrine growth factors for mesangial cells. We investigated the signal transduction mechanism of IL-6 in cultured rat mesangial cells. IL-6 induced a transient increase of inositol 1,4,5-trisphosphate (Ins 1,4,5-P3) followed by a transient and sustained increase of intracellular calcium concentration, suggesting that IL-6 stimulates phosphoinositide turnover. IL-6 also stimulated prostaglandin E2 (PGE2) production. The IL-6-concentration dependency in PGE2 production was similar to that in Ins 1,4,5-P3 production. We concluded that the action of IL-6 on mesangial cells is exerted at least partially through the enhancement of phosphoinositide turnover and PGE2 production.

Animals↗
PubMed1991

Catalytic properties of human platelet 12-lipoxygenase as compared with the enzymes of other origins.

Arachidonate 12-lipoxygenases of porcine and bovine leukocytes were different in substrate specificity and immunogenicity from the enzyme of bovine platelets (Arch. Biochem. Biophys. (1988) 266, 613). In order to extend the comparative studies on the two types of 12-lipoxygenase, we purified the enzyme from the cytosol of human platelets by immunoaffinity chromatography to a specific activity of about 0.3 mumol/min per mg protein at 37 degrees C. The purified enzyme was active with eicosapolyenoic acids and docosahexaenoic acid. Linoleic and linolenic acids were poor substrates in contrast to the high reactivity of the leukocyte enzymes with these octadecapolyenoic acids. The finding that the human platelet enzyme catalyzed 15-oxygenation of 5S-hydroxy-6,8,11,14-eicosatetraenoic acid, raised a question if lipoxins were produced by incubation of the enzyme with leukotriene A4. However, the leukotriene A4 was scarcely transformed to lipoxin isomers by 12-lipoxygenases of human and bovine platelets. In sharp contrast, the porcine and bovine leukocyte enzymes converted leukotriene A4 to various lipoxin isomers by the reaction rates of 3% and 2% of the arachidonate 12-oxygenation. Thus, 12-lipoxygenases of human and bovine platelets were catalytically distinct from the porcine and bovine leukocyte enzymes in terms of their reactivities not only with linoleic and linolenic acids, but also with leukotriene A4 as lipoxin precursor.

Animals↗
PubMed1991

Pseudoperoxidase activity of 5-lipoxygenase stimulated by potent benzofuranol and N-hydroxyurea inhibitors of the lipoxygenase reaction.

The purified 5-lipoxygenase from porcine leukocytes was found to catalyse the degradation of lipid hydroperoxides in the presence of potent inhibitors of the lipoxygenase reaction. Derivatives of diphenyl-N-hydroxyureas, 4-hydroxybenzofurans and 5-hydroxydihydrobenzofurans all stimulated the 5-lipoxygenase-mediated destruction of 13-hydroperoxyoctadecadienoic acid (13-HPOD). The reaction was dependent on inhibitor and hydroperoxide concentrations (1-10 microM) and could not be detected using heat-inactivated enzyme, when ATP and Ca2+ were omitted or when the hydroperoxide was replaced by the corresponding alcohol. The stability of the inhibitors during this pseudoperoxidase reaction was investigated by measuring the recoveries of 5-hydroxy-2-phenethyl-6-(3-phenoxypropyl)-2,3-dihydrobenzofuran and N-(4-chlorophenyl)-N-hydroxy-N'-(3-chlorophenyl)urea from the reaction mixtures using reverse-phase h.p.l.c. By using an equimolar concentration of 13-HPOD and inhibitor (10 microM) and under conditions where 50% of the 13-HPOD was consumed, the concentration of the benzofuranol decreased by 30%, whereas the N-hydroxyurea derivative could be completely recovered from the reaction mixture. A stimulation of the pseudoperoxidase reaction could be detected only with very effective inhibitors of leukotriene B4 biosynthesis by human leucocytes [IC50 (concn. causing 50% inhibition) less than 100 nM], but not with closely related structural analogues of lower potency or other inhibitors such as nordihydroguaiaretic acid, quercetin or the hydroxamate A-64077. These results demonstrate that 5-lipoxygenase possesses a pseudoperoxidase activity and indicate that potent inhibitors in both N-hydroxyurea and benzofuranol series can function as reducing agents for the enzyme.

Animals↗