[Effect of epinephrine on the microvascular blood flow in the tongue of rabbits using Laser Doppler Flowmeter].
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Biomedical subjects
Publications and source records attributed to K Sano.
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The phorbol ester TPA may be intercalated into the membrane phospholipid bilayer and selectively binds to every molecule of C-kinase in exhibiting its full enzymatic activity. Available evidence suggests that C-kinase is the receptive protein of this tumor promoter, and the results presented seem to provide clues for clarifying the mechanism of controlling cell growth and differentiation.
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Cellular synchronization chemoradiotherapy was performed in 122 patients with glioblastoma and malignant astrocytoma (GrIII) registered between April 1977 and August 1982. The study was a non-randomized clinical phase II trial. The chemotherapeutic agents employed as synchronizers during the irradiation were VM26 (epipodophyllotoxin) and vincristine (VCR) as plant alkaloids and ACNU as a nitrosourea. Either VM26 or VCR was administered on D1, D2 and D3 at the dosage of 1 mg/kg (0.025 mg/kg-VCR) body weight. ACNU was administered on D2 and D3 at the dosage of 1 mg/kg body weight. The duration of the chemotherapy was eight to fourteen days at the initial induction stage and almost eight weeks at the maintenance stage. Thus, two synchronization arms of VM26 + ACNU and VCR + ACNU were employed. The regimen-VM 26 + ACNU + Radiation (Rad) could yield the initial induction of CR + PR-30%, NC-50%, and PG-15% in 58 cases. Long-term survival, calculated by the cumulative survival rate, was as follows: one year, 58%; two years, 42%; three years, 32%; four years, 30%, and five years, 25%. The regimen VCR + ACNU + Rad could yield the initial induction of CR + PR-28%, NC-49%, and PG-23% in 64 cases. The cumulative survival rate was calculated as follows: one year, 55%; two years, 42%; three years, 27%; four years, 22%, and five years, 22%. As a control, particularly for the survival rate, the data of the All-Japan Registry were revised to correspond to our study population. The survival rate of simple radiation cases thus revised was as follows: one year, 43%; two years, 23%; three years, 11%; four years, 7%, and five years, 5%. The comparison between VM 26 plus ACNU and VCR plus ACNU yielded a higher initial induction response of 35% for the former (vs. 28% for the latter), although it is difficult to make a judgement on the excellence of the regimen involving VM 26 plus ACNU, because this trial was clinical phase II. On the other hand, compared with the data from the All-Japan Registry, each regimen of cellular synchronization radiation therapy could achieve statistically more excellent responses both in the initial induction and the long-term survival (p less than 0.01). Thus, cellular synchronization radiation therapy is a hopeful therapeutic method for malignant glioma, with less side effects and statistically confirmed higher responses.(ABSTRACT TRUNCATED AT 400 WORDS)
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In human platelets, thrombin activates Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C) and mobilizes Ca2+ concomitantly, whereas 12-O-tetradecanoylphorbol-13-acetate (TPA) may be intercalated into membranes and directly activates protein kinase C without mobilization of Ca2+ in sufficient quantities. A series of experiments with TPA and Ca2+-ionophore (A23187) indicates that activation of protein kinase C is a prerequisite requirement for release of serotonin, and that this enzyme activation and Ca2+ mobilization act synergistically to elicit a full cellular response. Both cyclic AMP and cyclic GMP inhibit activation of protein kinase C by prohibiting the signal-dependent breakdown of inositol phospholipid to produce diacyl-glycerol, but none of these cyclic nucleotides prevents the TPA-induced activation of this enzyme.
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In human platelets stimulated by thrombin and collagen, diacylglycerol is rapidly produced from phosphatidylinositol. Concurrently, an endogenous protein having a molecular weight of about 40,000 (40K protein) is phosphorylated, and serotonin is released. These reactions are all inhibited by a prior treatment of platelets with prostaglandin E1, dibutyryl cyclic AMP, sodium nitroprusside, or with 8-bromo-cyclic GMP, which are known as potent inhibitors for platelet activation. Ca2+-activated phospholipid-dependent protein kinase (protein kinase C) preferentially phosphorylates 40K protein. As judged by fingerprint analysis, the sites in 40K protein that are phosphorylated during the platelet activation appear to be identical with those phosphorylated by protein kinase C in a purified cell-free system. 12-O-Tetradecanoylphorbol-13-acetate, which directly activates protein kinase C by substituting for diacylglycerol, stimulates 40K protein phosphorylation and release reaction without inducing diacylglycerol formation. Tetracaine, which inhibits protein kinase C by competing with phospholipid, blocks 40K protein phosphorylation and serotonin release without inhibiting the receptor-linked diacylglycerol formation. The results indicate that thrombin and collagen activate platelets in almost similar mechanisms and that protein kinase C may lie on a common pathway which leads to the release of serotonin. However, analysis with indomethacin indicates that the role of thromboxane A2 appears to be more predominant for the action of collagen, and it is suggestive that this arachidonate metabolite activates platelets in an analogous mechanism to thrombin.
A calmodulin antagonist, W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide), inhibited induction of the acrosome reaction of sea urchin spermatozoa by egg jelly at 20-50 microM, but W-5 did not. The latter, a chlorine-deficient derivative of W-7, has a lower affinity for calmodulin than does W-7. These results suggest that a Ca2+-calmodulin-dependent process plays an important role in the triggering process of the acrosome reaction of sea urchin spermatozoa.
The renal distribution of 125I-labelled metallothionein (125I-MT), administered as a tracer dose to female Wistar rats, has been investigated by light and electron microscopical autoradiography. 125I-MT was absorbed rapidly and 80% of the administered dose was observed in the kidney within 60 min after dosing. At 30 min, a high density of silver grains due to 125I, was observed by light microscopy in the convoluted proximal tubules. Electron microscopical autoradiography showed that silver grains were located in large apical vacuoles and cytoplasmic bodies (heterolysosomes) of the endocytotic system in the apical or middle regions of the cells lining convoluted proximal tubules. The results suggest that endocytotic systems are associated with 125I-MT absorption by epithelial cells lining the renal convoluted proximal tubules. The apparent inconsistency on the distribution pattern of silver grains due to 109Cd-labelled MT and 125I-labelled MT in these is also discussed.
The authors encountered 95 cases of germinoma (two-cell pattern pinealoma) and teratoma involving the third ventricle and the pineal region from 1962 to 1980. Germinoma is radiosensitive. However, removal (extensive or total) of the tumour followed by postoperative irradiation showed better results than simple radiotherapy. In the recent 62 cases, 5-year and 10-year survival rates were 80.2% and 69.3% respectively (in children under 15 years, both were 86.9%). Teratoma is not radiosensitive and requires operation. For operating on a pineal germinoma, either an infratentorial supracerebellar approach or an occipital transtentorial approach is indicated. A teratoma, however, is sometimes too large for these approaches, when exposed, and therefore, the author prefers the transcallosal approach (for huge tumours the frontal transcallosal approach). Technical details will be reported and discussed.
Thirty-four cases of brain stem haematoma encountered in the past eight years were surveyed. Among these, three cases had haematomas caused by cryptic vascular malformations. These cases underwent direct operation (removal of haematoma) and are well and working. The haematomas of the other 31 cases were probably of hypertensive origin. Among them, eight cases with haematomas less than one cm in the largest diameter as shown in the CT (Group A), survived more than one month and six of them are still living, four of them working. In cases with a haematoma more than one cm in the largest diameter on the CT (Groups B and C), 13 cases died and four cases are living. Indications for operation are doubtful even for cases of Group A, except for cases with acute hydrocephalus or cases with suspected cryptic angiomas.