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Biomedical subjects

K Nagata

Publications and source records attributed to K Nagata.

At least 901 records · Page 50Linked to original sources

Plasma membranes purified from myeloid leukemia cells before and after differentiation. I. Characterization of spectrin-like proteins and increased association of actin.

Two-step sucrose density gradient centrifugation was used to isolate the plasma membrane of a myeloid leukemia cell line (Ml). Calspectin (or fodrin) was identified in the Triton-insoluble fraction from the plasma membrane, and the molecular size and actin- and calmodulin-binding activity were studied. During differentiation of this cell line, which accompanied the induction of cell motility and phagocytic activity, the membrane-bound actin increased dramatically, whereas calspectin increased only slightly. Therefore, calspectin does not appear to have a major function in the increased binding of actin filaments to the plasma membrane, a requirement for the induction of cell motility.

Acid Phosphatase↗

Blood volume expansion with hetastarch in acute ischaemic stroke: the effects on local cerebral blood flow and computer mapped EEG.

Focal cerebral ischaemia was induced in seven anaesthetized monkeys by unilateral middle cerebral artery (MCA) occlusion. Local cerebral blood flow (CBF) and computer mapped EEG (CME) changes were then studied as blood volume and cardiac output (CO) were varied. CO was increased by colloidal volume expansion and decreased by exsanguination. Local CBF fell to 24 +/- 9% of control values in ischaemic areas following MCA occlusion and increased to 43 +/- 19% of control values (p less than 0.01) when CO was increased by 130 +/- 70% with colloid infusion. Local CBF to nonischaemic regions was not altered significantly by blood volume expansion. Exsanguination led to return of CO to control levels and was associated with reduction of local CBF in ischaemic regions to 24 +/- 12% of control values (p less than 0.05). CME showed bifrontal or ipsilateral slow wave foci (delta) following MCA occlusion. Blood volume expansion brought about a marked reduction of this slow wave activity and exsanguination led to recurrence of the slow wave foci. This data demonstrated that colloidal blood volume expansion induced an increase in local CBF and improved neuroelectric status of ischaemic brain following MCA occlusion. It was also shown that a reduction of blood volume and cardiac output resulted in a reduction in local CBF and a worsening of neuroelectric status in ischaemic areas. This study supports the contention that blood volume and cardiac output maintenance is extremely important in the management of acute ischaemic stroke.

Animals↗

A major collagen-binding protein of chick embryo fibroblasts is a novel heat shock protein.

Heat shock proteins of chick embryo fibroblasts were analyzed on SDS polyacrylamide gradient gels and were found to include not only three previously well-characterized proteins of 25,000, 73,000, and 89,000 D, but also a 47,000-D protein. Two-dimensional gel electrophoresis revealed that this protein was unusually basic (pI = 9.0) and corresponded to a recently characterized, major gelatin- and collagen-binding protein. The induction of synthesis of this 47,000-D membrane glycoprotein after heat stress of fibroblasts was particularly apparent in preparations isolated by gelatin-affinity chromatography. Regulation of this 47,000-D phosphoprotein was more sensitive than that of three major heat shock proteins in that a substantial stimulation of synthesis occurred at even 42 degrees C, as well as at higher temperature. Phosphorylation of the 47,000-D protein was not altered after heat shock. These studies establish this phosphorylated membrane glycoprotein as a member of the heat shock/stress protein family, and they add collagen binding to the unexpectedly diverse spectrum of biochemical activities induced by exposure of cells to stress.

Animals↗

Suppressive effect of interferon inducer, polyriboinosinic acid-polyribocytidylic acid on induction of uridine diphosphate-glucuronyltransferases and monooxygenases in liver microsomes of rats.

The effect of polyriboinosinic acid-polyribocytidylic acid [poly(I).poly(C)] on glucuronyltransferase activities toward 4-nitrophenol and 4-hydroxybiphenyl in liver microsomes of Wistar rats was examined by its single or co-administration with 3-methylcholanthrene and phenobarbital. The increased 4-nitrophenol glucuronyltransferase activity by treatment with 3-methylcholanthrene was significantly suppressed following the co-administration with poly(I).poly(C), although the activity was not affected by the treatment with poly(I).poly(C) alone. In addition, 4-hydroxybiphenyl glucuronyltransferase activity decreased or tended to decrease by the treatment with poly(I).poly(C) alone, and the activity induced by phenobarbital was strikingly decreased following the co-administration with poly(I).poly(C). This result suggested that poly(I).poly(C) comprehensively decrease the induction of glucuronyltransferases regardless of their multiple forms. Furthermore, contents of cytochromes P-450 and b5 were also decreased by the treatment with poly(I).poly(C) alone or the co-administration with the inducers. Concomitantly, arylhydrocarbon hydroxylase and benzphetamine N-demethylase activities were significantly decreased by the treatment alone or the co-administration with the inducers. These findings supported a view that the suppressive effect of poly(I).poly(C) may be derived from the prevention of de novo synthesis of the apoprotein of the enzymes and/or the increased degradation.

Animals↗

Effect of co-administration of interferon inducer, polyriboinosinic acid-polyribocytidylic acid, with SKF 525-A on hepatic drug metabolizing enzymes of rats.

The protective effect of SKF 525-A on the suppression of cytochrome P-450 content and monooxygenase activities by treatment with CoCl2 and polyriboinosinic acid-polyribocytidylic acid [poly(I.C] was compared as a part of studies of suppression of drug metabolizing enzymes by interferon inducers. Induction of heme oxygenase activity by CoCl2 and poly (I.C) was not altered by simultaneous treatment with SKF 525-A. Depression of cytochrome P-450 content and benzphetamine N-demethylase activity by treatment with CoCl2 was prevented by co-treatment with SKF 525-A. This effect was explained by the prevention of release of heme from cytochrome P-450 by forming metabolic intermediate complexes with metabolites of SKF 525-A. On the other hand, poly(I.C) significantly suppressed P-450 content and benzphetamine N-demethylase and benzo [a] pyrene hydroxylase activities, even under simultaneous treatment with SKF 525-A. This inhibition by poly (I.C) was accompanied by weak staining of proteins corresponding to cytochrome P-450 in SDS gel electrophoresis. In addition, the activity of non-heme enzyme, 4-hydroxybiphenyl glucuronyltransferase, was suppressed by treatment with poly (I.C) but not by CoCl2-treatment. These findings strongly suggested that, unlike CoCl2, poly (I.C) suppressed cytochrome P-450 content and monooxygenase activities due to decreased synthesis or increased degradation of the apoprotein of cytochrome P-450 with slight contribution of the induced heme oxygenase.

Animals↗

Transcatheter arterial embolization for spontaneous rupture of hepatocellular carcinoma.

For the last 6 yr, we had 47 cases of spontaneous rupture of hepatocellular carcinoma causing hemorrhage into the peritoneal cavity. Thirty-three cases were treated by supportive care and 14 cases by emergency transcatheter arterial embolization. Fourteen cases underwent emergency transcatheter arterial embolization and abdominal pain developed in 71.4%, shock in 50.0% and bloody ascites in all cases and the hematocrit of bloody ascites ranged between 1.0% and 40%. On hepatic angiogram, the mean tumor extent rate was 47.9% and the extravasation of the contrast material was noted in 35.7%. The mean survival time of 14 cases that underwent emergency transcatheter arterial embolization was 98.5 days and 13.0 days in 33 cases with supportive care. The former was significantly longer than the latter.

Adult↗

[Clinical studies on imipenem/cilastatin sodium in pediatric field].

Clinical studies on imipenem/cilastatin sodium (MK-0787/MK-0791) was carried out in 12 patients in pediatric field. The overall efficacy rate was 83.3%. As for adverse reaction, soft stool was observed in 1 patient. In clinical laboratory findings, there was 1 patient with granulocytopenia.

Adolescent↗

[The normal range of cerebral atrophy during aging: statistical analysis of 500 normal subjects].

We previously reported the newly developed quantitative measurement of the cerebral atrophy (pixel count method), and advocated the value CCR (CSF-cranial ratio) as the index of the volumetric measurement of the cerebral atrophy. As the pixel count method is somewhat troublesome, we tried to compare the various linear measurement methods with pixel count method by means of multivariant analysis, and reported a single formula to calculate CCR from the linear measurement methods. Now we studied 500 normal subjects using the pixel count method and examined the normal range of the cerebral atrophy during aging by means of the maximum likelihood method. The normal range was estimated as follows; 0.32 less than y less than 5.78 (t less than 48), 0.068 t--2.944 less than y less than 0.368 t--11.884 (t greater than 48). Using these formula and this newly reported normal range, we can easily predict whether the cerebral atrophy is pathological or not.

Aging↗

Purification and complete amino acid sequence of canine pancreatic secretory trypsin inhibitor.

Pancreatic secretory trypsin inhibitor (PSTI) was purified from canine pancreatic juice by HPLC. Canine PSTI inhibited bovine trypsin activity stoichiometrically and strongly with a dissociation constant of below 10(-9) M. The amino acid sequence of canine PSTI was determined by conventional methods. It had one more amino acid residue at the amino-terminus than other mammalian PSTIs, i.e. human, porcine, bovine and ovine.

Amino Acid Sequence↗

The effects of multiple combination chemotherapy with vincristine, cyclophosphamide (Endoxan), methotrexate, 5-fluorouracil, adriamycin and prednisolone (VEMFAH) for advanced breast cancer.

Thirty-eight patients with advanced breast cancer were treated with the 'VEMFAH' multiple-drug combination chemotherapy, consisting of vincristine (V), cyclophosphamide (Endoxan; E), methotrexate (M), 5-fluorouracil (F), adriamycin (A), and prednisolone (H). Disease response was evaluated by the UICC criteria. Among the 35 evaluable cases, 4 complete responses (CR), 23 partial responses (PR), 2 cases of no change (NC), and 6 of progressive disease (PD) were observed. The response rate (CR + PR) was 77.1%. The median duration of response was 52 weeks (8-192 weeks) or 12 months. In 32 patients who received more than two courses of therapy the 50% survival time of responders was 27.0 months, which was significantly longer than the 10.3 months of nonresponders (P less than 0.05). Except for 2 patients who developed myocardial damage, the therapy was never terminated because of side effects. Cumulative cardiotoxicity was not apparent in this study. This multiple-drug combination chemotherapy with 'VEMFAH' is concluded to be an effective treatment for advanced and disseminated breast cancer.

Adult↗