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Biomedical subjects

T Minato

Publications and source records attributed to T Minato.

12 recordsLinked to original sources

Plasma levels of type II phospholipase A2 and nitrite/nitrate in patients with burns.

Type II phospholipase A2 (type II PLA2), nitrite/nitrate (NOx), tumor necrosis factor-alpha (TNF-alpha) and endotoxin were studied in burn patients. Type II PLA2 values and NOx values were both significantly higher in the group that died, the group with shock as a complication and the group with multiple organ dysfunction syndrome (MODS) as a complication, than in the group that survived, the group without shock as a complication and the group without MODS as a complication, respectively. The results suggested that type II PLA2 and nitric oxide (NO) may play a major role in the pathology of burn patients. Significant correlations were found between TNF-alpha and type II PLA2 values and between type II PLA2 and NOx values, suggesting the possibility of involvement in each other's production.

Adult

Quantitative analysis of mutually competitive binding of human Raf-1 and yeast adenylyl cyclase to Ras proteins.

Ras proteins appear to have two distinct downstream effectors, adenylyl cyclase in Saccharomyces cerevisiae and a product of raf-1 protooncogene in higher organisms. We found that in vitro activation of adenylyl cyclase by yeast Ras2 and human H-Ras proteins is subject to competitive inhibition by its leucine-rich repeats domain and by the N-terminal regulatory domain of human Raf-1 protein. Kinetic analyses of the inhibition patterns enabled us to determine exact dissociation constants (Kd) of the two polypeptides for Ras2 and H-Ras. The leucine-rich repeats domain bound to the posttranslationally modified Ras2 with the Kd of approximately 13 nM, which was close to the value (7 nM) of the whole adenylyl cyclase. The Kd of Raf-1 for the modified H-Ras, 3.5 nM, was significantly lower than that for Ras2, 24 nM, whereas adenylyl cyclase bound preferentially to Ras2. Similar inhibition was also observed in vivo by suppression of RAS2Val-19-dependent heat shock sensitivity and of Ras-dependent cAMP response to glucose upon overexpression of Raf-1 in yeast. These results indicate that the leucine-rich repeats domain contains the Ras protein-binding site and that Raf-1 and adenylyl cyclase, sharing no structural homology with each other, bind to a similar, if not identical, region of Ras with comparable affinities.

Adenylyl Cyclase Inhibitors

Submandibular hemangioma as the initial manifestation of Kasabach-Merritt syndrome.

Kasabach-Merritt syndrome (thrombocytopenia, consumption coagulopathy and occasional hemolysis) is an infrequent but often fatal complication of rapidly growing hemangiomas in infants. We describe a 1-month-old infant with a huge hemangioma involving the left submandibular region associated with a severe consumptive coagulopathy, who was successfully treated with transfusion of blood products, prednisone and radiation therapy. It is stressed that pediatric otorhinolaryngologists should always be aware of the lethal status of this condition in infants.

Combined Modality Therapy

Antibody mimicking the action of RAS proteins on yeast adenylyl cyclase: implication for RAS-effector interaction.

Polyclonal antisera were raised against various subregions of Saccharomyces cerevisiae adenylyl cyclase in order to examine the molecular mechanism of interaction between adenylyl cyclase and RAS proteins. One of the antisera was found to activate adenylyl cyclase to an extent comparable to that activated by saturating amounts of yeast RAS2 protein produced in Escherichia coli. The stimulatory effect of this antiserum was shown to be additive with RAS2 protein when both antisera and RAS2 protein were present at low concentrations. At saturating amounts of RAS2 protein, the antisera did not exhibit additional stimulatory effects, suggesting that the actions of RAS2 protein and the antisera are complementary with each other. The antigenic determinant for the antibody involved in the activation was mapped to a 14-amino-acid segment, 1452-NSVDNGADVANLSY-1465, located between the leucine-rich repeats and the catalytic domain of adenylyl cyclase. Certain missense mutations affecting this 14-amino acid segment significantly reduced the response of adenylyl cyclase to both activating antibody and RAS proteins. These results suggest that this segment of adenylyl cyclase is intimately involved in the mechanism by which RAS proteins activate this downstream effector.

Adenylyl Cyclases

[Two cases of hemorrhagic shock and encephalopathy syndrome].

A 10-month-old male infant (case 1) and another male infant aged 1 year and 11 months (case 2) were admitted to our department because of fever, watery diarrhea and convulsion. On admission, they were unconscious and showed rigidity of the limbs. Laboratory examination revealed a marked increase in GOT and GPT, a decrease in platelet and antithrombin III and an increase in FDP. Metabolic acidosis was found by blood gas analysis. Brain CT showed an extensive area of low density in case 1, and low density centering on the cerebral basal ganglia and brainstem in case 2. Rotavirus was detected in case 2 by fecal examination. The clinical pictures in these cases closely resembled those of hemorrhagic shock and encephalopathy (HSE) reported by Levin et al. in 1983. The etiology of this disease is currently unknown, and its prognosis is poor. The relationship between this disease and rotavirus should be examined in future studies.

Brain Diseases