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Biomedical subjects

N Ueda

Publications and source records attributed to N Ueda.

At least 109 records · Page 6Linked to original sources

Biochemical and immunohistochemical evidence for selective expression of novel epithelial lipoxygenases.

Human tracheal epithelial cells contain an arachidonate 15-lipoxygenase, while the same cells from animals (including bovine, ovine, canine, porcine) cells express a 12-lipoxygenase. The epithelial 12-lipoxygenase is antigenically related to the leukocyte 12-lipoxygenase but is biochemically distinct from platelet and leukocyte forms of the enzyme, in that it is more efficient at metabolizing a wider array of fatty acid substrates. We have suggested that this lipoxygenase heterogeneity may provide a basis for different functional roles for the enzyme in different cell types. In addition, animal epithelial 12-lipoxygenase and human epithelial 15-lipoxygenase are antigenically related and have similar but distinct distributions in the lung. Our findings might suggest that the species diversity for epithelial lipoxygenases represents molecular divergence within a family of closely related genes with perhaps closely related functions.

Animals

Inflammatory pseudotumor of the facial nerve as a cause of recurrent facial palsy: case report.

This is a report of a case presenting recurrent facial palsy due to inflammatory pseudotumor of the facial nerve. The patient was a 41-year-old man suffering from facial palsy on the right side once in 1983, which recurred in 1988. The initial facial palsy was cured after conservative treatments including steroid administration. Three months after the recurrence, the same treatments were attempted without noticeable effect. He was referred to our clinic two and half months later. Electromyographic examination indicated pronounced denervation of the facial nerve. Imaging study including high resolution CT and MRI revealed a mass lesion around the geniculate ganglion. Facial neuroma was initially suspected. Surgical exploration revealed a tumor involving the geniculate ganglion and the horizontal portion of the facial nerve. The tumor was resected through a combined transmastoid and middle cranial fossa approach, followed by nerve grafting. Histologically, the tumor proved to be an inflammatory pseudotumor originating from the nerve sheath, although the etiologic factor causing the inflammation was not verified.

Adult

[A case of graft-versus-host disease following irradiated fresh blood transfusion].

We reported a case of a fatal graft-versus-host disease (GVHD) which developed in a 65-year-old, male patient which was considered to have been induced by irradiated fresh blood donated by his son after a coronary bypass surgery. Fresh blood was obtained from his relatives, and a 15 Gy irradiation was performed before transfusion. The diagnosis of acute GVHD was made by clinical symptoms and histological examinations of the skin and the bone marrow. He died of sepsis on the 19th post-operative day. The HLA typing of the lymphocytes, revealed that the patient had A 2, A 24, Bw 52, Bw 62, Cw 4, DR 2, and his son had A 24, Bw 52, DR 2. A 24 and Bw 52 were homogeneous making his son histocompatible with one of the patient's haplotype. This might well be attributable to the occurrence of GVHD in this case, meaning that 15 Gy irradiation was not sufficient for the prevention of this disease.

Aged

Localization of arachidonate 12-lipoxygenase in parenchymal cells of porcine anterior pituitary.

12-Lipoxygenases oxygenate arachidonic acid producing its 12S-hydroperoxy derivative and are well known as platelet and leukocyte enzymes. When a peroxidase-linked immunoassay of the enzyme according to the avidin-biotin method was applied to the cytosol fractions from various parts of porcine brain, a considerable amount of the enzyme was found in the anterior pituitary. The enzyme level (about 200 ng/mg cytosol protein) corresponded to about 6% of the enzyme content in porcine peripheral leukocytes. Posterior and intermediate lobes showed about one-tenth of the enzyme level of anterior pituitary. Other parts of porcine brain contained the 12-lipoxygenase in amounts below 7 ng/mg cytosol protein. The cytosol fraction (0.7 mg of protein) of anterior pituitary produced 12S-hydroxy-5,8,10,14-eicosatetraenoic acid from 25 microM arachidonic acid in about 34% conversion at 24 degrees C for 5 min, giving a specific enzyme activity about 3 nmol/min/mg protein. Furthermore, various octadecapolyenoic acids were oxygenated almost as fast as the arachidonate 12-oxygenation. When anterior pituitary was investigated immunohistochemically with anti-12-lipoxygenase antibody, most of the immunostained cells were certain parenchymal cells with granules, which were not blood cells. These biochemical and immunohistochemical results provide a good reason for considering that 12-lipoxygenase does play an important role in pituitary function.

Animals

Identification of a novel arachidonate 12-lipoxygenase in bovine tracheal epithelial cells distinct from leukocyte and platelet forms of the enzyme.

We examined the characteristics of an arachidonate 12-lipoxygenase in bovine tracheal epithelial cells in relation to the enzyme expressed in leukocytes and platelets. Homogenous preparations of intact or disrupted tracheal epithelial cells metabolized arachidonic acid predominantly to (12S)-hydroxyeicosatetraenoic acid, and subcellular fractionation by differential centrifugation demonstrated that the 12-lipoxygenase activity was localized predominantly to the 100,000 x g supernatant (cytosol fraction). Analysis of cytosolic enzymatic activity for pH dependence (maximum activity at pH 7.4-8.0), divalent cation effects (no dependence on cations), and kinetic characteristics (lag phase elimination by addition of hydroperoxide) exhibited similarity to leukocyte and platelet 12-lipoxygenases. Immunoprecipitation experiments demonstrated that the epithelial 12-lipoxygenase reacted with a monoclonal antibody (lox-2) directed against leukocyte 12-lipoxygenase but not with an antibody (HPLO-3) against the platelet enzyme. Immunoaffinity chromatography of the epithelial 100,000 x g supernatant fraction using lox-2 linked to Affi-Prep 10 yielded a single predominant protein band (Mr = 72,000) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis identical in apparent mass to the bovine leukocyte lipoxygenase. Western blotting using a polyclonal antibody to leukocyte 12-lipoxygenase showed peroxidase staining of the same 72-kDa protein band. Activity assays of the purified enzymes demonstrated that substrate specificity for the epithelial 12-lipoxygenase was similar to that of the leukocyte enzyme, but the epithelial enzyme more efficiently converted 18-carbon fatty acids to the corresponding monohydroxylated conjugated dienes. We conclude that bovine tracheal epithelial cells express a 12-lipoxygenase that has immunological reactivity similar to leukocyte and distinct from platelet 12-lipoxygenase and possesses substrate specificity distinct from both enzymes. We further suggest that lipoxygenase heterogeneity may provide a basis for different functional roles for the enzyme in different cell types.

Animals

Clinical experience of biliary tract carcinoma associated with anomalous union of the pancreaticobiliary ductal system.

Between 1978 and 1988, 15 patients with gallbladder cancer and 2 patients with bile duct cancer were seen among 49 patients with anomalous union of the pancreaticobiliary ductal system. Radiographic findings revealed two types of this anomalous condition: one in which the pancreatic duct entered the common bile duct (type 1) and one in which the common bile duct entered the pancreatic duct (type 2). In gallbladder cancer, the common bile duct presented no dilatation, or in some patients, mild dilatation, and type-1 anomalous union was frequently found among these patients. In contrast, the two patients with bile duct cancer had cystic dilatation of the common bile duct and type-2 anomalous union. The bile amylase level, which was determined in seven patients, was extremely high in all the patients. Histopathologically, the tumors in most patients showed papillary to papillo-tubular proliferation in the mucosal layer while atypical epithelial hyperplasia was noted in the vicinity of the tumor area. These findings suggest that this congenital anomaly in both ducts results in a loss of the normal sphincteric mechanism of the duodenal papilla, and that chronic relapsing cholecystitis or cholangitis, caused by the reflux of pancreatic juice into the biliary tract, can induced progressive changes to atypical epithelial hyperplasia which may develop into carcinoma.

Adult

Morphological study of cholesterol hepatolithiasis. Report of three cases.

Three cases of pure cholesterol intrahepatic stones are compared morphologically to those of calcium bilirubinate stones. Cholesterol stones were found in the intrahepatic bile duct of the left lateral lobe in two cases and in both the left lateral and the right posterior lobe in one. Although the chronic inflammatory reaction and fibrous thickening of bile duct wall were similar in both types of hepatolithiasis, the proliferation of intrahepatic periductal glands and the production of mucin were rather mild, compared to that is the liner containing calcium bilirubinate stones. Multiple intramural cholesterol calculi and cholesterin granulomas (cholesterin crystals surrounded by foreign-body giant cells) were found within the cystically dilated small bile duct branches and/or conduits of periductal glands. The calculi and granulomas were characteristic for cholesterol hepatolithiasis. These findings suggest that the formation of the cholesterol stones differs from that of calcium bilirubinate stones; the perturbation of factors influencing cholesterol nucleation in the hepatic bile may be related to the changed microenvironment of the intrahepatic bile ducts, which is followed by the formation of cholesterol stones.

Adult

Eight and 12 week courses of cyclophosphamide in nephrotic syndrome.

Seventy-three children with steroid dependent minimal change nephrotic syndrome were randomly allocated to receive treatment with cyclophosphamide (2 mg/kg/day) for either eight or 12 weeks, in combination with prednisolone. All patients had previously relapsed while the dosage was being reduced or within 14 days of discontinuing prednisolone in the six months before receiving cyclophosphamide treatment (steroid dependent), and had severe steroid toxicity. Thirty two patients were treated with cyclophosphamide for eight weeks, and 41 for 12 weeks. There were no differences between the two groups in age at onset of nephrosis or entry into the study, sex ratio, duration of nephrosis, number of relapses before entry, and follow up period after entry. The relapse free rate of patients treated for eight weeks (25%) was similar to that of those treated for 12 weeks (24%) five years after stopping the treatment, and the mean relapse free interval and the sparing effect of cyclophosphamide (if any) on subsequent treatment with steroids did not differ between the groups. We conclude that cyclophosphamide should be used for no longer than eight weeks at a dose of 2 mg/kg/day in children with steroid dependent minimal change nephrotic syndrome.

Child

Effect of corticosteroids on some hemostatic parameters in children with minimal change nephrotic syndrome.

Effect of corticosteroids (steroids) on some hemostatic parameters was serially studied in 23 children with minimal change nephrotic syndrome (MCNS). Increased platelet count, erythrocyte sedimentation rate (ESR), cholesterol, fibrinogen, fibrin(ogen) degradation products (FDP), alpha 2-macroglobulin (alpha 2M), alpha 2-antiplasmin (alpha 2AP) and protein C, and reduced antithrombin III (ATIII) and plasminogen (Plg) were noted in relapse before steroid therapy began. With institution of oral prednisolone, FDP started to fall, and platelet count, cholesterol, alpha 2M, ATIII, Plg, alpha 2AP and protein C started to increase despite unchanged nephrotic state from that before the therapy. In remission induced by prednisolone, platelet count, cholesterol, alpha 2M, ATIII, Plg, alpha 2AP and protein C were still increased, but normalized off therapy. ESR, fibrinogen, FDP, alpha 2M and protein C correlated inversely with serum albumin and directly with cholesterol and urine protein excretion. In contrast, ATIII and Plg correlated directly with serum albumin and inversely with cholesterol and urine protein excretion. A direct correlation was only noted between alpha 2AP and the dose of prednisolone. The data indicate that steroids appear to be a thrombogenic factor by accerelating thrombocytosis and hyperlipidemia, and by reducing plasma fibrinolysis in children with MCNS.

Adolescent

[Quantification of tenderness of masticatory muscle].

As more dentists diagnose and treat the patient with temporomandibular disorders, muscle palpation has been recognized as a valuable diagnostic method. But this method was depended on sensibility and experience of the operator. The purpose of this study was to establish the quantification of muscle palpation by new pressure pain threshold apparatus. Pressure pain threshold (PPT) was determined by the subject when a ramp force applied to the skin changed from "pressure" to "pain". The subjects for the experiments were 90 normal males, 100 normal females and one patient with temporomandibular disorders. Total of 12 sites, anterior temporal M., posterior temporal M., superficial portion of masseter M. and deep portion of masseter M., were measured. The results obtained were as follows: 1. The females showed lower PPT than the males. 2. No difference of PPT between right and left sides was recognized in normal subject, but the significant difference in the patient. 3. PPT of the normal subjects were significantly higher in the posterior temporal M. than the other sites and lower in the superficial portion of masseter M. than the other sites.

Facial Pain

Diffuse gallium-67 uptake in radiation pneumonitis.

To evaluate the clinical usefulness of Ga-67 imaging for the assessment of radiation pneumonitis, 12 patients who had developed radiation pneumonitis after receiving radiotherapy alone for non-small-cell lung cancer from 1979 through 1988 were reviewed. Diffuse bilateral Ga-67 uptake occurred in 5 out of the 12 cases; in the other 7 cases, Ga-67 uptake was confined to the irradiation lung. Conversely, chest radiography showed infiltrates only in the irradiated lung. Histopathology of the lung in four out of the five cases that showed diffuse Ga-67 uptake in the lung, however, revealed that the lung outside the radiation field with Ga-67 uptake was consistent with interstitial pneumonitis induced by radiation. These results suggest that radiation pneumonitis could extend beyond the irradiated lung and that Ga-67 imaging is more useful than chest radiography for the assessment of the spatial extent of radiography pneumonitis.

Aged

[Effect of PMUE therapy (CDDP, MMC, UFT, etoposide) in terminal gastric cancer].

CDDP, MMC, UFT and Etoposide (PMUE)-combined therapy was applied to 60 cases of terminal gastric cancer to examine its effectiveness. PMUE therapy consists of i.v. injection of CDDP 75 mg/body and MMC 10 mg/body on day 1, i.v. injection of Etoposide 50 mg/body on days 3, 4 and 5 and consecutive daily administration of UFT 400 mg/body, with 3 weeks as one course. Of 42 cases having estimable lesions, 23 (53.8%) showed high rate of effectiveness (PR). Especially, of 23 cases receiving no previous treatment, 15 (65.2%) benefitted by the therapy (PR) and 9 (69.2%) of 13 non-resected cases, to a wonderful extent. Five non-resected cases showed such a reduction in tumor size as made gastrectomy possible. As for the prognosis, one year-survival rate was 34.3, 49.0 and 16.0% for all 42 cases, 23 effective cases and 19 ineffective cases, respectively, with significant (p less than 0.001) prognostic prolongation for effective cases compared with ineffective ones. Side effects were digestive symptoms (85.7%), epilation (81.0%) and myelopathy (73.8%), which were all transitory and recovered. The present PMUE therapy was regarded as one of the best combined chemotherapies for terminal gastric cancer.

Administration, Oral

[Idiopathic autoimmune hemolytic anemia successfully treated with danazol].

A 50 year old female suffered from idiopathic autoimmune hemolytic anemia. She was initially treated with prednisolone, and anemia was improved moderately. However, maintenance of Hb value was difficult with the decreased dosage of prednisolone. She was subsequently administered danazol, and anemia was completely improved. It is worth to use danazol for the treatment of the patient of autoimmune hemolytic anemia who is refractory to prednisolone therapy.

Anemia, Hemolytic, Autoimmune

Sensitivity of immunoaffinity-purified porcine 5-lipoxygenase to inhibitors and activating lipid hydroperoxides.

The requirement for hydroperoxide activation and the effect of inhibitors from different structural classes on 5-lipoxygenase activity were determined on the immunoaffinity-purified enzyme from porcine leukocytes. The 5-lipoxygenase activity was measured using a continuous spectrophotometric assay monitoring the increase in conjugated diene formation (A235) upon incubation of the enzyme with arachidonic acid. Under standard assay conditions, the reaction progress curves showed little or no lag phase, with a rapid first-order decay in enzyme activity (T1/2 = 0.7 to 1.1 min). Both the initial rate of the reaction and total product formation were stimulated by the addition of ATP, Ca2+ and phosphatidylcholine (PC). PC (24 micrograms/ml) was also found to increase the recovery of radiolabeled arachidonic acid from the assay mixture and thus part of the stimulation may be due to an increase in substrate availability and reduction of surface adsorption effects. The requirement of hydroperoxides for the initiation of the reaction was shown by the induction of 0.1 to 1-min lag phases using NaBH4 or glutathione peroxidase and by the reduction in lag times by 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and 13-hydroperoxyoctadecadienoic acid (13-HPOD). The following compounds were evaluated as inhibitors of the 5-lipoxygenase reaction and caused a 50% decrease in product accumulation (IC50) at the indicated concentrations: quercetin, L-651,896, L-656,224, MTPPH and L-651,392 (0.3-0.5 microM); diphenyldisulfide (2-5 microM); phenidone (5-10 microM); AA861 (4-10 microM) and BW755C (4-15 microM). In addition, the presence of inhibitors extended the initial lag phase of the reaction and increased the dependence of the initiation of the reaction on exogenous lipid hydroperoxides. The inhibition by phenidone was accompanied by a 2-fold increase in the rate of enzyme inactivation, whereas other compounds such as AA861 and L-656,224 did not show this effect. The results indicate that the presence of inhibitors can modify the kinetics of 5-lipoxygenase at the levels of the initiation of the reaction and the rate of enzyme inactivation, with variations depending on the structural class of the inhibitor and the concentration of lipid hydroperoxides.

Adenosine Triphosphate