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Biomedical subjects

N Ueda

Publications and source records attributed to N Ueda.

At least 217 records · Page 12Linked to original sources

[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

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

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

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

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

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

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

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

A prenylflavone, artonin E, as arachidonate 5-lipoxygenase inhibitor.

Several naturally occurring prenylflavones were tested for their inhibitory actions on arachidonate 5-lipoxygenase purified from porcine leukocytes. Of the compounds tested, artonin E (5'-hydroxymorusin) exhibited the most potent inhibition on arachidonate 5-lipoxygenase (IC50 = 0.36 microM). Arachidonate 12-lipoxygenase purified from porcine leukocytes and human platelets, 15-lipoxygenase from rabbit reticulocytes and fatty acid cyclooxygenase from bovine vesicular glands were inhibited by the compound only at higher concentrations (IC50 = 2.3, 11, 5.2 and 2.5 microM, respectively).

Animals

Clinicopathological studies on solid and cystic tumors of the pancreas.

Three cases of pancreatic tumor in two females (case 1, case 3) and one male (case 2) were reported. Macroscopically cases 1 and 3, which were surrounded by a thick fibrous capsule, developed toward the outside of the pancreas and the cut surface showed mainly cystic degenerative areas filled with necrotic and hemorrhagic materials. In contrast with these two cases, case 2 was buried in the pancreatic tissue and the cut surface showed cystic degenerative areas in its center with a thick fibrous capsule and tumor cell nests invading beyond the capsule to the parenchyma of the pancreas. Microscopically each tumor was identical. The solid areas on the periphery were composed of sheets of polygonal uniform cells subdivided by delicate fibrovascular stalks. Near the degenerative areas, tumor cells lay on a delicate fibrovascular core in one or two layers, with pseudopapillary patterns. Mitotic figures were very rare. All three cases demonstrated immunoreactivity for alpha-1-antitrypsin, but not for islet hormones, tumor markers nor neuron-specific enolase. Although electronmicroscopically, zymogen granules were detected in cases 2 and 3, and annulate lamellae in cases 1 and 3, ductal cell character features were not so developed. From the above, these tumors were diagnosed as solid and cystic tumors of the pancreas. Furthermore, it was suggested that they differentiated in the direction of acinar cells.

Adolescent

Anaesthetic management of phaeochromocytoma associated with tricuspid atresia.

The anaesthetic management of a patient with phaeochromocytoma, tricuspid atresia and pulmonary vascular stenosis is reported. The patient received no preoperative preparation with adrenergic blockers. Anaesthesia was induced and maintained with fentanyl, diazepam and sevoflurane. Intraoperative blood pressure was controlled with sodium nitroprusside, sevoflurane, phentolamine, and propranolol. For hypotension after resection of the tumour norepinephrine was required. This patient did not have a systemic to pulmonary shunt procedure performed, so the maintenance of pulmonary blood flow in the presence of haemodynamic instability during operation for phaeochromocytoma was a major concern. Monitoring of oxyhaemoglobin saturation (SpO2) with a pulse oximeter was considered to be useful because SpO2 may reflect pulmonary flow. During serious haemodynamic disturbances due to the manipulation of the tumour, the heart rate was inversely correlated with SpO2, but the relationship between mean arterial pressure and SpO2 was weak. Therefore, control of heart rate appeared to be more important than control of blood pressure in this case.

Adolescent

High-performance liquid chromatographic determination of pyrophosphate in the presence of a 20,000-fold excess of orthophosphate.

An HPLC method was based on anion-exchange separation of pyrophosphate (diphosphate) and orthophosphate and postcolumn spectrophotometric detection at 140 degrees C with a molybdenum(V)-molybdenum(VI) reagent. The reagent was easy to prepare, stable for at least 6 months at room temperature, and ready for the determination of pyrophosphate and orthophosphate by the so-called heteropoly blue method without use of any reducing agent. A photodiode-array detector for HPLC indicated the spectral characteristics of the heteropoply blue complex that was detectable at 330-800 nm. The HPLC method had a wide dynamic range from 3 x 10(-7) to 5 x 10(-4) M for both pyrophosphate and orthophosphate with a relative standard deviation of measurement of 10 approximately 2%. Pyrophosphate of 5 x 10(-7) and 5 x 10(-6) M, respectively, could be determined in the presence of a 20,000-fold excess of orthophosphate; 0.01 and 0.1 M.

Chromatography, High Pressure Liquid

Mixed tumor of salivary gland type arising in the bronchus.

During bronchoscopy for atelectasis of the middle lobe, a 61-year-old man was found to have a polypoid mass obstructing the bronchus. Right middle and lower lobectomy disclosed a tumor growing into the lumen of the middle lobe bronchus. The histological features of the tumor were indistinguishable from those of the mixed tumor of the salivary gland. A review of the literature reveals only 7 cases of this extremely rare tumor.

Adenoma, Pleomorphic

Syntheses of 5,7,8- and 5,6,7-trioxygenated 3-alkyl-3',4'-dihydroxyflavones and their inhibitory activities against arachidonate 5-lipoxygenase.

5,6,7- and 5,7,8-Trioxygenated 3',4'-dihydroxyflavones were derivatized by introducing alkyl groups of various chain lengths at the 3-position of the flavone skeleton. These compounds were tested as inhibitors for arachidonate 5-lipoxygenase purified from porcine leukocytes. Modification of the 3-position with an alkyl group of 6-10 carbons markedly decreased the IC50 values. 3-Hexyl-3',4'-dihydroxy-5,7, 8-trimethoxyflavone inhibited 5-lipoxygenase with an IC50 value of 58 nM. The platelet and leukocyte 12-lipoxygenases, 15-lipoxygenase of reticulocytes, and cyclooxygenase of vesicular gland were inhibited less potently (IC50 = 0.4, 0.4, 2.7, and 30 microM). Thus, the compound was a relatively selective inhibitor for 5-lipoxygenase.

Animals