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T Otsuki

Publications and source records attributed to T Otsuki.

158 records · Page 9Linked to original sources
PubMed1982

Studies on channeling of carbamoyl-phosphate in the multienzyme complex that initiates pyrimidine biosynthesis in rat ascites hepatoma cells.

Carbamoyl-phosphate synthetase II of higher animals, the first enzyme of de novo pyrimidine biosynthesis, forms a multienzyme complex with aspartate carbamoyltransferase and dihydroorotase, the second and third enzymes of the pathway. The hypothesis that the complex serves to channel carbamoyl-phosphate, synthesized by the first enzyme of the complex, to the second enzyme was tested using a highly purified complex preparation from Yoshida ascites hepatoma cells (AH 13). Experimentally, aspartate carbamoyltransferase in the complex was allowed to compete with exogenously added ornithine carbamoyltransferase, another carbamoyl-phosphate-utilizing enzyme, for carbamoyl-phosphate which was either synthesized endogenously or added exogenously. The ratios of amounts of the two enzymic products, carbamoyl-aspartate and citrulline, were compared. In the absence of enzyme stabilizers dimethyl sulfoxide or glycerol, a slight channeling of the intermediate in the complex was observed. The further addition of 5-phosphoribosyl 1-pyrophosphate, MgUTP (positive and negative allosteric effectors of carbamoyl-phosphate synthetase II), 30% (v/v) dimethyl sulfoxide or 30% (w/v) glycerol did not affect the extent of channeling. It was slightly increased in the presence of 7.5% (v/v) dimethyl sulfoxide plus 2.5% (w/v) glycerol. Any shift of the assay temperature, pH or concentration of MgATP or of the enzyme complex resulted in little further increase in the extent of channeling. Even when a larger amount of the enzyme complex was used to approximate physiological conditions, there was no increase in the extent of channeling either without or with allosteric effectors. MgUTP even abolished channeling under these conditions. These results indicate that carbamoyl-phosphate can be channeled in the multienzyme complex of AH 13 cells, but the extent of channeling is very small, contrary to expectation.

Animals↗
PubMed1981

Phosphorylation and dephosphorylation of carbamoyl-phosphate synthetase II complex of rat ascites hepatoma cells.

Carbamoyl-phosphate synthetase II [EC 6.3.5.5] of rat ascites hepatoma cells (AH 13), the first and regulatory enzyme of de novo pyrimidine nucleotide biosynthesis, exists as a multienzyme complex (molecular weight, 870,000) with aspartate carbamoyltransferase [EC 2.1.3.2] and dihydroorotase [EC 3.5.2.3] (Mori, M. & Tatibana, M. (1975) J. Biochem. 78, 239-242). The purified complex was phosphorylated by the catalytic subunit of cAMP-dependent protein kinase [EC 2.7.1.37] of rabbit skeletal muscle. The incorporation of 32Pi was 2.2 mol/mol of the complex. The phosphorylation was completely inhibited by the inhibitor protein of the cAMP-dependent protein kinase. Among the substrates and effectors of the enzyme complex tested, only MgUTP, an allosteric inhibitor of carbamoyl-phosphate synthetase II, strongly inhibited the phosphorylation; this inhibition was due probably to the competition of MgUTP with y inhibited by the inhibitor protein of the cAMP-dependent protein kinase. Among the substrates and effectors of the enzyme complex tested, only MgUTP, an allosteric inhibitor of carbamoyl-phosphate synthetase II, strongly inhibited the phosphorylation; this inhibition was due probably to the competition of MgUTP with y inhibited by the inhibitor protein of the cAMP-dependent protein kinase. Among the substrates and effectors of the enzyme complex tested, only MgUTP, an allosteric inhibitor of carbamoyl-phosphate synthetase II, strongly inhibited the phosphorylation; this inhibition was due probably to the competition of MgUTP with the substrate MgATP for the protein kinase. The complex that was phosphorylated by cAMP-dependent protein kinase was dephosphorylated by phosphoprotein phosphatase [EC 3.1.3.16] of rat skeletal muscle. The complex was also phosphorylated by cAMP-independent protein kinase activity present in the extract of AH 13 cells and dephosphorylated by phosphoprotein phosphatase activity of the same origin. These results suggest that the complex is subject to phosphorylation and dephosphorylation in the living cells. Phosphorylation of the complex by cAMP-dependent protein kinase was associated only with a slight change, albeit definite, in the activity of carbamoyl-phosphate synthetase II under the assay conditions. Thus, the physiological significance of phosphorylation-dephosphorylation remains to be further studied.

Adenosine Triphosphate↗
PubMed1981

[Computed tomography of ruptured arteriovenous malformations in the acute stage (author's transl)].

Eighteen patients with angiographically proved intracranial arteriovenous malformation (AVM) were studied by computed tomography (CT) and their clinical features were reviewed at the same time. The pathophysiology of ruptured AVM in the acute stage was discussed. Seven of the 18 patients were performed CT scan within 7 days after the onset. Although all but one of the patients showed symptoms and signs suggestive of subarachnoid hemorrhage (SAH), intracerebral hematoma was demonstrated in all cases and two of them were accompanied by ventricular rupture. On the more, no high density lesion was demonstrated in cerebral cisterns by plain CT scan as seen in the acute stage of ruptured cerebral aneurysms. Six patients were performed contrast study within 7 days after the onset and showed no enhancement effect. On the contrary, nine of 10 patients performed contrast study more than 8 days after the onset showed enhancement effect. It has been commonly postulated that subarachnoid hemorrhage is the main pathophysiology of ruptured AVM. However, out study on CT scan of ruptured AVM demonstrated that intracerebral hematoma or ventricular hemorrhage is the chief underlying pathophysiology of ruptured AVM in the acute stage.

Adolescent↗
PubMed1981

[A case of trapped fourth ventricle which developed after a surgery of AVM (author's transl)].

We represent a case of cystic dilatation of the fourth ventricle resulted from obstruction of the foramina of Luschka and Magendie and of the aqueduct of Sylvius which developed after a surgery of AVM. A 42-year-old woman was admitted to our clinic for the operation of AVM located at the trigone of lateral ventricle and the lateral wall of midbrain. VPS had been performed previously because of acute hydrocephalus resulted from several attacks of ventricular hemorrhage. Total removal of the AVM was performed. The patient was stuporous after the surgery, and CT scan showed marked distension of the fourth ventricle with shifted third ventricle and slightly dilated supra-tentorial ventricular system. Although a revision of the abdominal side of VPs performed and the lateral and the third ventricles were shunted effectively, the fourth ventricle continued to show remarkable distension. Since it was considered that the occlusion of the foramina of Luschka and magendie due to previous episodes of ventricular hemorrhage and the blockage of the aqueduct of Sylvius 'trapped' the fourth ventricle, suboccipital craniotomy and re-opening of the foramen of Magendie was performed. The arachnoid membrane around the cisterna magna was strongly adhered to the dura mater. When incision was made on the arachnoid membrane between the cerebellar tonsils, slightly turbid and xanthochromic CSF spurted out and some old clots were also aspirated from the opened fourth ventricle. The size of the fourth ventricle returned normal on CT scan ten days after the operation, and the patient recovered progressively afterwards.

Adult↗
PubMed1981

[Preventive effect on intracranial arterial vasospasm using combined ventriculo-cisternal and cisternal drainage (author's transl)].

Cerebral vasospasm following subarachnoid hemorrhage (SAH) is one of the most important problems in the treatment of ruptured intracranial aneurysms. Several reports have recently emphasized that oxyHb from erythrocytes might be responsible for vasospasm. In this study, the hem-oxygenase which converts oxyHb to bilirubin was analyzed and the increase of hem-oxygenase in the CSF after SAH was reconfirmed. In 23 cases of ruptured intracranial aneurysms, combined ventriculo-cisternal drainage and cisternal drainage designed by us was performed after clipping of aneurysms in early stage after rupture. Through a Y-shaped tube the CSF accumulated in the cistern and was drained extracranially through cisternal drainage. As a result, 2 (9%) of the 23 patients treated with the drainage showed symptomatic vasospasm. On the other hand, 13 (33%) of 39 patients without the drainage showed symptomatic vasospasm. It may be concluded that the drainage may contribute to prevention of cerebral vasospasm after SAH.

Adult↗
PubMed1981

[Primary cerebral neuroblastoma--case report (author's transl)].

Primary cerebral neuroblastoma is rare. The case reported here was a 2-year-old girl who was comatose on admission to the Mito National Hospital. She had experienced headache and vomiting during the last two months. Neurological examination showed bilateral papilledema, left oculomotor palsy and bilateral Babinski's sign. A-P view of the left carotid angiogram showed square shift of the anterior cerebral artery to the right, and the lateral view showed upward and anterior displacement of the middle cerebral artery. CT revealed large mass lesion in the left parieto-temporal lobe, which was slightly enhanced on the contrast study. Subtotal removal of the tumor was performed on the day of admission. On the 15th postoperative day, she was started on radiation therapy to the brain and received 1900 rads. Vincristin and ACNU were administrated with radiation therapy. She improved progressively five weeks after the operation and CT demonstrated marked shrinkage of the tumor. However, signs of increased intracranial pressure were reappeared and she died six months after the operation. Autopsy showed well defined soft and grayish white tumor in the occipito-temporal lobe, which extended to the left thalamus and basal ganglia. No other tumor was present extracranially. Microscopic examination demonstrated Homer-Wright rosette and zonal filament. Pathological diagnosis was neuroblastoma.

Brain Neoplasms↗
PubMedDate not supplied

Secretory IgA in saliva and academic stress.

Several reports have proposed that the concentration of secretory immunoglobulin A (S-IgA) in saliva is an indicator of psychological stress. With this in mind, we decided to examine it in 10 second year medical student volunteers at Kawasaki Medical School course between May 4 and July 13, 2000 and discussed the relationship between S-IbA and the stress from academic examinations. Saliva was collected three times (on rising, at forenoon, and at bedtime) every Thursday. During this period, sporadic academic examinations were held twice and term end examination occurred during the last two weeks. Results showed the concentration of S-IgA significantly higher at the on rising time-point than at the other two time-points. There was also a tendency for the S-IgA level in saliva to be higher on the day before academic examinations and during them and lower on the days between these examinations. In addition, daily variations in the S-IgA concentration sometimes seemed to be disturbed by other academic stress. Therefore it may be possible to use this measurement to monitor psychological stress in students and workers.

Adult↗
PubMedDate not supplied

Reduced function of CD4+25+ regulatory T cell fraction in silicosis patients.

The quality and quantity of CD4+25+ regulatory T cells (Treg) in silicosis patients (SIL) were examined and compared with results from healthy donors (HD) because SIL often develop autoimmune diseases along with pulmonary disorders. Peripheral blood mononuclear cells from 57 SIL and 50 HD were analyzed for Treg. Treg frequency and clinical parameters were subjected to a factor analysis. Treg and CD4+25- T cells (Tneg) from five HD and five SIL, sorted by flow-cytometer, were used for functional assays of Treg, the expression pattern of Treg specific genes (FoxP3, GITR and CTLA-4) and activation-related genes (CD122 and CD123). Although the actual frequency of Treg did not differ between SIL and HD, the age-corrected level was reduced in SIL. The factor analysis showed that Treg frequency was positively associated with the serum level of IL-2. The inhibitory effect of Treg on Tneg activation was decreased when the Treg:Tneg ratio was 1:1/4 to 1/2. In addition, Treg dominancy of FoxP3 and CTLA-4 expression and Tneg dominancy of CD132 expression found in HD were lost in SIL. These results indicated that the Treg fraction in SIL may be substituted with chronically activated T cells due to recurrent exposure to silica, resulting in a reduction in the frequency and function of Treg. Since the reduction of Treg may precede the clinical manifestation, as silicosis may be a pre-clinical status for autoimmune diseases, control of Treg function using cell and/or gene therapy may be a good way to manage autoimmune disease.

Aged↗
PubMedDate not supplied

Effect of the nitrosourea anti-tumor chemotherapeutical agent MCNU on five human myeloma cell lines.

We investigated the effects of MCNU (methyl-6)3-(2-chloroethyl)-3-nitrosoureido)-6-deoxy- alpha-D-glucopyranoside), a nitrosourea anti-tumor agent developed in Japan, on cell growth and differentiation in five human myeloma cell lines and compared it with relative expression levels of MDR-1 gene. Although 10 microg/ml of MCNU inhibited cell growth in KMM-1 and KMS-5 lines, other three cell lines required 20-40 microg/ml of MCNU to obtain similar growth inhibition. Accumulation up to the G2 phase of the cell cycle was observed in KMM-1 and KMS-5 lines and the cloning efficiency of KMS-5 cells was reduced by MCNU. On the other hand, expression of surface markers on these lines was not altered remarkably except for increased expression of CD38 on KMS-5 cells. However, the effect of MCNU on these cell lines did not correlate to relative expression levels of MDR-1 gene analyzed by RT-PCR. MCNU may inhibit the growth of myeloma cells by the accumulation of these cells up to the G2 phase, but may not affect their differentiation.

Antineoplastic Agents↗