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T Noda

Publications and source records attributed to T Noda.

At least 19 recordsLinked to original sources
PubMed1992

Serum calcium-decreasing factor (caldecrin) from porcine pancreas has proteolytic activity which has no clear connection with the calcium decrease.

We purified a serum calcium-decreasing factor, which showed chymotrypsin-like protease activity, from porcine pancreas to homogeneity. The factor administered to mice intravenously at a dose of 20 micrograms/kg b.w. decreased serum calcium by 15%. Treatment of the factor with the serine protease inhibitor, PMSF, caused a leftward shift in the dose-response curve, showing strengthened activity. It also caused a decrease in serum calcium and hydroxyproline levels in rats. At a dose of 10 ng/ml, the factor inhibited 45Ca release from cultured fetal long bone stimulated by parathyroid hormone (PTH) and PTH-related protein, but not by interleukin-1 alpha, prostaglandin E1 and 1,25-dihydroxy vitamin D3. No other well-known pancreatic proteases had these effects. In view of the results of experiments using protease inhibitor and pancreatic proteases, and in view of the specificity of this factor in vitro, we propose that the factor exerts its serum calcium-decreasing activity most probably not through proteolytic degradation of PTH, but through an inhibition of PTH action on bones by a yet undefined mechanism.

Animals↗
PubMed1992

Comparative teratogenicity of di-n-butyltin diacetate with n-butyltin trichloride in rats.

Teratological tests were conducted on di-n-butyltin diacetate (DBTA), and n-butyltin trichloride (MBTC). Pregnant Wistar rats were treated orally with DBTA at doses of 0, 1.7, 5.0, 10.0, and 15.0 mg/kg/day or with MBTC at doses of 0, 50, 100, 200, and 400 mg/kg/day during days 7-17 of gestation. Cesarean sections were performed on day 20 of gestation. Thymic atrophy of the pregnant rats was observed in a dose-dependent manner by DBTA treatment. The incidence of dead or resorbed fetuses and total resorption fetuses increased at the highest dose of DBTA. The incidence of fetuses with external malformations, such as cleft mandible, cleft lower lip, ankyloglossia (tongue-tie) and schistoglossia (cleft tongue), increased in a dose-dependent manner by DBTA treatment. The incidence of fetuses with skeletal malformations such as anomaly of mandibular fixation, fused ribs, fused cervical vertebral arches and fused thoracic vertebral arches also increased at 10.0 and 15.0 mg/kg. However, MBTC, one of the main metabolites of di-n-butyltin, failed to show any evidence of tetatogenic activity at any doses tested. The results indicate that DBTA has potent teratogenic effects on rat fetuses, and DBTA is different from MBTC with respect to teratogenic effects.

Animals↗
PubMed1992

Establishing a diagnosis of adrenal metastasis from hepatocellular carcinoma by 99mTc-PMT hepatobiliary scintigraphy.

A 69-year-old woman was diagnosed as having hepatocellular carcinoma (HCC) with liver cirrhosis in October, 1984 and treated by transcatheter arterial embolization (TAE). In June, 1990 she was found to have a huge mass in the left hypochondrium which ultrasonography and computed tomography (CT) scan revealed to be a lett adrenal mass. A 99mTc pyridoxyl-5-methyl tryptophan (99mTC-PMT) hepatobiliary scintigraphy was positive and confirmed metastatic HCC. Although the adrenal mass was large, the HCC itself was controlled well with TAE. The adrenal mass was removed surgically in July, 1990 and the histological findings were compatible with HCC metastasized to the adrenal gland.

Adrenal Gland Neoplasms↗
PubMed1992

Cardiovascular actions of OPC-18790: a novel positive inotropic agent with little chronotropic action.

OPC-18790 [(+/-)-6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]- 2(1H)-quinolinone], a novel positive inotropic agent, was investigated in several in vitro and in vivo experiments to elucidate its cardiovascular effects and its mechanism of action. In isolated blood-perfused dog heart preparations, OPC-18790 increased contractile force at 10 to 1,000 nmol i.a.; increased coronary arterial blood flow at 30 to 1,000 nmol; and decreased sinus rate slightly at 1,000 nmol. Atrio-ventricular nodal conduction was slightly facilitated with OPC-18790 (10 to 1,000 nmol), whereas ventricular automaticity tended to decrease. OPC-18790 (10(-6) to 10(-4) M) increased contractile force in isolated ventricular muscles of dogs, cats, rabbits and guinea pigs but not rats. OPC-18790 increased left ventricular contractile force dose-dependently in anesthetized open-chest dogs and in conscious dogs with slight or no changes in heart rate and blood pressure. The positive inotropic effect of OPC-18790 was not affected by beta-blockade. OPC-18790 (10(-5) to 10(-4) M) prolonged the duration of action potential in guinea pig papillary muscles. Na+, K(+)-ATPase was not inhibited, but peak-III phosphodiesterase (low Km cyclic AMP specific fraction, inhibited by cyclic GMP) was inhibited by OPC-18790 (IC50 = 0.41 x 10(-6) M) in dog myocardium. However, such an inhibitory action of phosphodiesterase can hardly be reconciled with the lack of a positive chronotropic effect shown by OPC-18790. Thus, these results suggest that OPC-18790 may have an additional mechanism. The cardiovascular effects revealed by this study suggest that OPC-18790 may exert a beneficial effect in the treatment of congestive heart failure.

Animals↗
PubMed1992

Nodular regenerative hyperplasia of the liver with portal vein thrombosis and hyperplasia of the adrenal gland.

Nodular regenerative hyperplasia (NRH) of the liver is an uncommon entity of unknown origin and pathogenesis. We report here a case of NRH of the liver which was associated with portal vein thrombosis and adrenal hyperplasia. A 48-year-old man who was admitted for further examination of portal hypertension and splenomegaly, died of acute myocardial infarction. Autopsy revealed an enlarged heart with occluded coronary arteries and fresh multiple necrosis in the myocardium. The spleen and the liver were enlarged. In the liver diffusely distributed nodules of regenerative hyperplasia were noted. Organized thrombi of the portal vein and adenomatous hyperplasia of the left adrenal gland were also noted. Antinuclear antibody was positive in the serum.

Adrenal Glands↗
PubMed1992

Role of gastric glutathione in smoke flavouring-induced gastric injury in rats.

Some commercial liquid smoke flavourings have been shown to induce acute gastric mucosal injury in rats when given orally as a large single dose. The present study was carried out to examine the mechanism of action in rats of two selected smoke flavourings containing about 10% total acids as acetic acid. These flavourings and 10% acetic acid decreased the concentration of glutathione (GSH) in the glandular stomach. The decrease in gastric GSH was coupled with smoke flavouring-induced gastric injury. Pretreatment with N-ethylmaleimide, a GSH depletor, enhanced acetic acid-induced gastric injury. Pretreatment with cysteine, a sulphhydryl compound, protected rats against smoke flavouring-induced gastric injury. Aqueous fractions of the smoke flavourings, after removal of non-polar compounds and acidic organic compounds (including acetic acid) by diethyl ether extraction, decreased the gastric GSH concentration considerably and had a marked reactivity in vitro with GSH, but these fractions by themselves showed no ability to induce gastric injury. Addition of 10% acetic acid to these aqueous fractions caused greater gastric injury than 10% acetic acid alone, which suggests that these aqueous fractions contain the (unidentified) compound(s) that facilitate acetic acid-induced gastric injury. These findings indicate that gastric endogenous and exogenous sulphhydryls play an important part in gastric cytoprotection.

Acetates↗
PubMed1992

A non-autophagic pathway for diversion of ER secretory proteins to lysosomes.

Intracisternal granules (ICG) develop in the rough ER of hyperstimulated thyrotrophs or thyroid hormone-secreting cells of the anterior pituitary gland. To determine the fate of these granules, we carried out morphological and immunocytochemical studies on pituitaries of thyroxine-treated, thyroidectomized rats. Under these conditions the ER of thyrotrophs is dramatically dilated and contains abundant ICG; the latter contain beta subunits of thyrotrophic hormone (TSH-beta). Based on purely morphologic criteria, intermediates were identified that appeared to represent stages in the transformation of a part rough/part smooth ER cisterna into a lysosome. Using immunocytochemical and cytochemical markers, two major types of intermediates were distinguished: type 1 lacked ribosomes but were labeled with antibodies against both ER markers (PDI, KDEL, ER membrane proteins) and a lysosomal membrane marker, lgp120. They also were reactive for the lysosomal enzyme, acid phosphatase, by enzyme cytochemistry. Type 2 intermediates were weakly reactive for ER markers and contained both lgp120 and lysosomal enzymes (cathepsin D, acid phosphatase). Taken together these results suggest that in hyperstimulated thyrotrophs part rough/part smooth ER elements containing ICG lose their ribosomes, their membrane is modified, and they sequentially acquire a lysosome-type membrane and lysosomal enzymes. The findings are compatible with the conclusion that a pathway exists by which under certain conditions, secretory proteins present in the ER as well as ER membrane and content proteins can be degraded by direct conversion of ER cisternae into lysosomes.

Acid Phosphatase↗
PubMed1992

Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction.

For determination of the physiological role and mechanism of vacuolar proteolysis in the yeast Saccharomyces cerevisiae, mutant cells lacking proteinase A, B, and carboxypeptidase Y were transferred from a nutrient medium to a synthetic medium devoid of various nutrients and morphological changes of their vacuoles were investigated. After incubation for 1 h in nutrient-deficient media, a few spherical bodies appeared in the vacuoles and moved actively by Brownian movement. These bodies gradually increased in number and after 3 h they filled the vacuoles almost completely. During their accumulation, the volume of the vacuolar compartment also increased. Electron microscopic examination showed that these bodies were surrounded by a unit membrane which appeared thinner than any other intracellular membrane. The contents of the bodies were morphologically indistinguishable from the cytosol; these bodies contained cytoplasmic ribosomes, RER, mitochondria, lipid granules and glycogen granules, and the density of the cytoplasmic ribosomes in the bodies was almost the same as that of ribosomes in the cytosol. The diameter of the bodies ranged from 400 to 900 nm. Vacuoles that had accumulated these bodies were prepared by a modification of the method of Ohsumi and Anraku (Ohsumi, Y., and Y. Anraku. 1981. J. Biol. Chem. 256:2079-2082). The isolated vacuoles contained ribosomes and showed latent activity of the cytosolic enzyme glucose-6-phosphate dehydrogenase. These results suggest that these bodies sequestered the cytosol in the vacuoles. We named these spherical bodies "autophagic bodies." Accumulation of autophagic bodies in the vacuoles was induced not only by nitrogen starvation, but also by depletion of nutrients such as carbon and single amino acids that caused cessation of the cell cycle. Genetic analysis revealed that the accumulation of autophagic bodies in the vacuoles was the result of lack of the PRB1 product proteinase B, and disruption of the PRB1 gene confirmed this result. In the presence of PMSF, wild-type cells accumulated autophagic bodies in the vacuoles under nutrient-deficient conditions in the same manner as did multiple protease-deficient mutants or cells with a disrupted PRB1 gene. As the autophagic bodies disappeared rapidly after removal of PMSF from cultures of normal cells, they must be an intermediate in the normal autophagic process. This is the first report that nutrient-deficient conditions induce extensive autophagic degradation of cytosolic components in the vacuoles of yeast cells.

Acetates↗
PubMed1992

The comparison of sun protection factor values with different light sources.

Sun protection factors (SPFs) were evaluated with three light sources (sunlight, a xenon arc solar simulator, and fluorescent lamps) in indoor and outdoor studies. Two types of light, UV-A+B and UV+Visible, were obtained from the solar simulator. The untanned backs of twenty-four healthy male volunteers were used as test sites. A broad spectrum sunscreen containing SPF 6, according to the manufacturer, was used. The sunscreen tested was applied at 2 mg/cm2. The actual SPF values were 4.8 with sunlight, 6.0 with UV-A+B, 4.9 with UV+Visible, and 11.8 with fluorescent lamps. There were no significant differences between the SPF values with sunlight and those with the solar simulator; the SPF value for fluorescent lamps was significantly higher. The SPF with UV-A+B of the solar simulator was similar to that with sunlight; the use of this light served to reduce pain on tested subjects. Therefore, UV-A+B from the solar simulator seems to be the most appropriate artificial light source for evaluating sunscreens.

Adult↗
PubMed1992

Development of an atraumatic small centrifugal pump for second-generation cardiopulmonary bypass.

A small and light direct-drive centrifugal pump has been developed for cardiopulmonary bypass. In the development process, blood compatibility studies including a hemolysis study, an in vitro fluid dynamic performance study, and in vivo durability and feasibility studies were performed. The centrifugal pump with a 50 mm diameter impeller resulted in almost the same index of hemolysis value as did a Bio-Medicus centrifugal pump. Heat dissipation from the motor was prevented by using a flexible drive cable. Forty-eight-hour sealing durability around the driving axis was accomplished by using a fluoro-rubber V-ring that connected to the hard chrome-plated stainless steel. In vitro and in vivo performances of the pump were satisfactory. Thrombus formation behind the impeller was prevented by using a holed impeller that generated blood flow from the back to the surface of the impeller. Elimination of air during priming procedures was also easier with this modification. This centrifugal pump has one-quarter of the priming volume, size, and weight of magnetically coupled centrifugal pump systems.

Animals↗
PubMed1992

Reduction of corticosterone-induced muscle proteolysis and growth retardation by a combined treatment with insulin, testosterone and high-protein-high-fat diet in rats.

An experiment was conducted to clarify the combined effect of simultaneous administrations of insulin (Ins, 4 units/100 g body weight/day) and testosterone propionate (TP, 2 mg/100 g body weight/day) and feeding a high-protein-high-fat (HPHF) diet (50% protein, 36% fat) on corticosterone (CTC, 10 mg/100 g body weight/day)-induced muscle proteolysis or growth retardation in young growing male rats. After 6 days prefeeding of the standard (STD) diet (25% protein, 9% fat) and the HPHF diet, hormones were injected subcutaneously for 4 days. Urine was collected every day for the 4-day experimental period to measure N tau-methylhistidine excretions. The results were as follows. The growth was markedly inhibited and muscle proteolysis was accelerated by the CTC treatment. Feeding HPHF diet reduced CTC-induced muscle proteolysis and the growth retardation, and administrations of Ins and TP further reduced the proteolysis and the growth retardation. From these results, it is thought that administrations of Ins and TP and feeding HPHF diet minimize the muscle protein wasting by counteracting insulin resistance caused by CTC, and masking the CTC receptor.

Animals↗
PubMed1992

[Antiproliferative actions of medroxyprogesterone acetate (MPA) to human ovarian cancer cell lines in vitro].

The cytostatic effect of medroxyprogesterone acetate (MPA; an oral luteohormone preparation) on two cell lines of ovarian carcinoma cultured in vitro (SHIN-3 and MN-1) was studied. At the same time, changes in the morphology and colony formation of these cancer cells after exposure to the drug were examined. 1) The doubling time of SHIN-3 cells in the logarithmic growth phase was prolonged 2.5 times at a MPA dose of 10(-8)M and 3.2 times at a MPA dose of 10(-5)M. The drug, however, exerted no significant cytostatic effect on MN-1 cells. 2) When the IC50 of MPA was assessed by counting live SHIN-3 cells in an FCS-added medium, it was 2.7 x 10(-5)M. When the same assessment was done with a medium without serum, IC50 was 6.4 x 10(-6)M. 3) After 120 hours of incubation in a medium containing 10(-8)M of MPA, CA125 (a tumor marker) production by SHIN-3 cells was suppressed by 35%. The suppression rate was 79% for SHIN-3 cells incubated in a medium containing 10(-5) of MPA. 4) The cytoplasm of SHIN-3 cells, incubated in a MPA-added medium, showed the formation of small mucous vacuoles and expansive degeneration, accompanied by a marked increase in size and thinning of the nucleus. 5) In an experiment on colony formation with collagen gel, the colony size decreased MPA concentration dependently, and was accompanied by the appearance of lobulated colonies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma, Mucinous↗
PubMed1992

[Establishment and characterization of human ovarian fibrosarcoma cell line and its sensitivity to anticancer agents].

We succeeded in establishing a cell line (KEN-3) for subculture from a fibrosarcoma which originated in the ovary in a girl aged 17 years. Its characteristics and sensitivity to anticancer agents are reported in this paper. 1. Characteristics of established cell line. Lined cells consist of multinucleated giant cells mixed among many spindle-shaped cells. They grow in small colonies and have none of the pavement-like arrangement characteristic of epithelial tumor cells. The number of chromosomes ranged from 45 to 128 (mode: pseudo-triploidy region, 65). The doubling time, cellular density and plating efficiency were 76.9 hours, 5.4 x 10(5)/cm2 and 30.2%, respectively. Concerning tumor markers, CEA and sialyl SSEA-1 were only produced in small quantities. Subculture was possible subcutaneously in the nude mouse with no capacity for the production of ascites. 2. Susceptibility to anticancer agents and GP170 expression. The in vitro susceptibility to about 12 types of anticancer agents was investigated with the MTT assay. IC50/PPC was shown to be less than 1 for Adriamycin only. The sensitivity to CDDP (IC50/PPC: 4.8) was low, and no sensitivity was observed at all to DTIC, which is used frequently for mesenchymal tumors. GP170 (mdr-1 products) was positive in established cells in immunohistochemical stain.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

[Usefulness of intraperitoneal carboplatin administration-- pharmacokinetic analysis].

A bolus of carboplatin (CBDCA) 200-450mg/body (148-292mg/m2) with 500ml saline was administrated into the abdominal cavity (ip) of 4 patients with ovarian cancer and 2 patients with uterine endometrial cancer, and concentrations of free and total platinum (Pt) in the blood and ascites were measured with the passage of time. Moreover, the results were analyzed with a 2-compartment model and moment analyses in order to study in vivo kinetics of CBDCA at the time of the ip administration. 1) The shift of Pt to blood through ip administration depended on the peritoneal clearance. Cmax in blood was seen one hour after ip in patients with a normal peritoneum, and was seen between 4 and 6 hours after ip in patients with peritonitis carcinomatosa. The level was lower in the latter group. 2) The non-binding rate of Pt with protein in the ascites at the time of the ip administration was correlated with the CBDCA concentration in the ascites. 3) The non-binding rate was 80% or more both in the ascites and in the blood within 4 hours after ip. The high level of the nonbinding rate appeared to cause prolongation of the presence of the free-Pt in the ascites and blood, especially in patients with peritonitis carcinomatosa. 4) AUC level in blood was equal to or higher than that observed when the same dose was administered iv. The levels of free-Pt and AUC in the abdominal cavity were 2 to 5 times higher than those in blood in patients with a normal peritoneum, and 7 to 14 times higher in patients with peritonitis carcinomatosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Carboplatin↗
PubMed1992

[Urinary trypsin inhibitor as an acute phase reactant].

Early in this century, trypsin inhibiting activity has already been recognized in patients with acute infection or renal disease. In addition to these, conditions such as coronary thrombosis, surgical operation, artificial fever by heat-killed bacilli, malignancy, leukemia, later stage of normal pregnancy, etc. have been known to cause the elevated excretion of UTI in urine. Typically, maximal excretion of UTI has been observed within one or two days after the onset. It appears that recent studies have overcome the complexity of UTI molecule. Automated measurement of urinary trypsin inhibitor (UTI) in urine sample was carried out by either enzymic or immunologic method. UTI as well as erythrocyte sedimentation rate and C-reactive protein enables us to monitor acute phase response, being confirmed in cases of abdominal surgery.

Abdomen↗
PubMed1991

Correction of ornithine transcarbamylase (OTC) deficiency in spf-ash mice by introduction of rat OTC gene.

We introduced rat ornithine transcarbamylase (OTC) gene into OTC-deficient spf-ash mice by mating spf-ash heterozygotes with transgenic mice which carried recombinant DNA composed of 1.3 kb of the 5' flanking region of the gene fused onto rat OTC cDNA. The liver OTC activity of hemizygous spf-ash mice which carried the transgene was about twice that of nontransgenic spf-ash mice, and the small intestinal OTC activity was 6 times higher; the values being 12% and 27% of the control levels, respectively. The transgenic spf-ash mice showed normal hair growth without sparse fur, nearly normalized urinary orotic acid excretion and normalized serum citrulline concentration.

Animals↗