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Biomedical subjects

K Takakura

Publications and source records attributed to K Takakura.

At least 253 records · Page 14Linked to original sources
PubMed1991

Amelioration of delayed neuronal death in the hippocampus by nerve growth factor.

Selective neuronal death in the CA1 sector of the hippocampus [delayed neuronal death (DND)] develops several days after transient global cerebral ischemia in rodents. Because NGF plays a potential role in neuronal survival, it was decided to study its effect in DND. We report here that intraventricular injection of NGF either before or after 5 min forebrain ischemia in the Mongolian gerbil significantly reduced the occurrence of DND. The tissue content of NGF in the hippocampus was decreased 2 d after ischemia and recovered to the preischemic level by 1 week. By the Golgi staining technique, changes first began in the dendrites of affected neurons as early as 3 hr. Such changes could be ameliorated by NGF treatment. Although previous knowledge of NGF is limited to the survival of cholinergic neurons in the CNS, it is assumed that other mechanisms must be operating in the hippocampus, for example, postsynaptic modification at dendrites or aberrant expression of NGF receptors possibly at the initial excitation period by glutamate. Furthermore, because previous work has shown that inhibition of protein synthesis reduces the occurrence of DND, a program leading to cell death might also be operating via de novo synthesis of certain protein(s), collectively termed "killer protein," because of a lack of NGF.

Animals↗
PubMed1991

[Choroid plexus tumors in infancy].

Twelve infants with choroid plexus tumors were reviewed retrospectively. Enlarging head circumference, bulging fontanelle, and vomiting were the major symptoms and signs appearing 2 to 5 weeks (mean = 3.7 weeks) before diagnosis. The average age at diagnosis was 7.7 months. Total removal was performed in 11 patients with choroid plexus papilloma, and partial removal was achieved in 1 patient with a choroid plexus carcinoma. A cerebrospinal fluid (CSF) diversionary shunt was placed temporarily in 6 infants and permanently in 4. Of the two patients not requiring CSF diversionary shunt, 1 needed a subdural-peritoneal shunt postoperatively. Histologically, 11 of 12 tumors were choroid plexus papillomas, and one was a choroid plexus carcinoma. All 12 patients were followed up for 4 months to 11 years (mean = 5.6 years). Eleven of 12 patients were alive at the time of their last check-up. All 11 survivors had normal psychomotor and neurological development. The treatment and outcome of choroid plexus tumors and management of associated hydrocephalus are discussed.

Carcinoma↗
PubMed1991

[Comparison of the M1-blocker with the H2-blocker regarding their effects on gastric pH and viscosity under general anesthesia].

In a prospective, controlled, randomized trial measuring the gastric juice pH and viscosity, 30 patients under general anesthesia received M1-blocker; pirenzepine or H2-blocker; ranitidine. The gastric juice pH value was significantly higher (P less than 0.05) both in the pirenzepine and the ranitidine group than in the control group. While in the pirenzepine group the viscosity of gastric juice was unchanged, in the ranitidine group it was reduced. The results suggest that pirenzepine offers more effective prophylaxis against stress ulcer than ranitidine.

Adult↗
PubMed1990

Reduction of delayed neuronal death by inhibition of protein synthesis.

Brief forebrain ischemia in rodents causes delayed neuronal death selectively in the CA1 pyramidal cells of hippocampus. Treatment with a reversible protein synthesis inhibitor, anisomycin, significantly reduced the occurrence of delayed neuronal death in the Mongolian gerbil. This result indicates that de novo synthesis of certain protein(s), collectively termed 'killer protein' is required, possibly due to deprivation of nerve growth factor or other trophic factors.

Animals↗
PubMed1990

Astrocytic localization of the immunoreactivity for protein kinase C isozyme (type III) in human brain.

The localization of 3 major types of protein kinase C (PKC) was immunohistochemically studied in human brain using monoclonal antibodies raised against each of the types. Immunoreactivity for type I was observed in neuronal cells in cerebrum and Purkinje cells in cerebellum. Immunoreactivity for type II was mainly observed in neuropil of cerebral cortex and in the molecular and granular layers of cerebellum. Occasional neurons in cerebrum were also stained. Immunoreactivity for type III was almost exclusively localized in astrocytes in gray and white matter, subpial astrocytes, and cerebellar Bergmann's glia. The present study suggests that the type III of PKC is preferentially expressed in astrocytes in human brain.

Antibodies, Monoclonal↗
PubMed1990

Cerebral microvessel endothelium is producing endothelin.

Endothelin, a potent vasoconstrictor peptide, was recently isolated from the supernatant of the cultured endothelia of the porcine aorta and is now supposed to be the most likely candidate for the endothelium-derived contractile factor (EDCF), which is responsible for the endothelium-dependent vasoconstriction by various stimuli. In this study, the production of endothelin by the endothelia of porcine cerebral microvessels was revealed by the Northern blot analysis with porcine endothelin cDNA probe and the enzyme-linked immunosorbent assay (ELISA) with anti-porcine endothelin antibody. Our results raise the possibility that the endothelia of cerebral microvessels regulate the local blood flow within the brain through the production of endothelin.

Animals↗
PubMed1990

Effects of ebselen (PZ51) on ischaemic brain oedema after focal ischaemia in cats.

Using a transorbital middle cerebral artery (MCA) occlusion model in cats, we evaluated the anti-oedema effects of a new anti-inflammatory agent, ebselen (PZ51), on ischaemic cortical oedema caused by prolonged ischaemia and recirculation. Local cerebral blood flow was measured by the hydrogen clearance method in the MCA territory and the corresponding cortical specific gravity was assessed by a microgravimetric technique. Ebselen had no significant effect on normal and ischaemic lCBF, while it significantly ameliorated post-ischaemic hypoperfusion following recirculation. In the severely ischaemic regions, microgravimetry showed the beneficial effects on the ischaemic oedema caused by prolonged ischaemia and recirculation as well. Although the exact site of action is undetermined in this study, the observed effects of ebselen may be ascribed to this agent's broad-spectrum of anti-inflammatory activities.

Animals↗
PubMed1990

Dose escalation trial of a novel calcium antagonist, AT877, in patients with aneurysmal subarachnoid haemorrhage.

The initial dose-escalating clinical trial of a novel calcium antagonist, AT877, in patients with aneurysmal subarachnoid haemorrhage is reported. AT877 is characterized by its strong spasmolytic activity, its inhibition of intracellular calcium ion activity, and the inhibition of several protein kinases. A total of 113 patients (Hunt and Hess grades I to IV) who had undergone surgery within 3 days of aneurysmal rupture entered the study. Patients were divided into 5 groups according to the total daily dose of AT877: I: 20 mg; II: 40 mg; III: 60 mg; IV: 90 mg; and V: 120-180 mg. AT877 was given by intravenous infusion over 30 min two or three times a day for 14 days after surgery. Although AT877 did not completely abolish angiographic vasospasm, severe vasospasm was seen less frequently in patients given higher doses. Vasospasm was the cause of a poor clinical outcome (Glasgow outcome scale rating 3 or greater) in 19%, 7%, 9%, 8%, and 6% of the patients in groups I to V, respectively. The results indicated a favourable clinical effect of AT877 at doses above 40 mg per day. Only mild hypotension was seen, even when 60 mg of AT877 was infused over 30 min. AT877 appears to be effective in patients with subarachnoid haemorrhage. Part of its effect may be attributable to protection of the brain from ischaemic insults due to chronic cerebral vasospasm. However, the drug still needs to be evaluated in a placebo-controlled double-blind trial (which is currently being carried out).

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

70-75 kd molecules expressed on LGL and T cells recognized by a mitogenic monoclonal antibody YTA-1; co-modulation and functional association with the interleukin 2 receptor p75.

We have raised a mAb YTA-1 which recognizes 75 kd antigen (Ag) on large granular lymphocytes (LGL) and T cells using a human natural killer (NK)/LGL cell line YT as the immunogen. YTA-1 mAb not only enhanced the growth of peripheral blood mononuclear cells (PBMC) but also down-regulated both high- and intermediate-affinity interleukin 2 receptors (IL-2R) on resting PBMC. When incubated with 5-50 micrograms/ml of YTA-1 mAb at 37 degrees C, up to 50% of high- and intermediate-affinity IL-2R of the Tac+ YT subclone (YTCl.1) were down-regulated within 120 min. YTA-1 mAb also down-regulated the intermediate-affinity IL-2R on YT2C2 cells, which express only IL-2Rp75. On the other hand, 5 nM recombinant IL-2 down-regulated the expression of YTA-1 Ag on YT cells after 120 min culture, indicating a close association between YTA-1 Ag and IL-2R. However, YTA-1 mAb did not affect the low-affinity IL-2R on an HTLV-1+ T cell line MT-1. Furthermore, interleukin 1 receptor (IL-1R) on YT cells was not affected by YTA-1 mAb. It appears that the down-regulation by YTA-1 mAb is selective for IL-2Rp75 of the IL-2R complex. Pre-incubation of YT cells with 20 micrograms/ml YTA-1 mAb accelerated the internalization of IL-2Rp75 but did not accelerate that of IL-2Rp55, indicating that YTA-1-induced down-regulation of IL-2R is associated with the internalization of IL-2Rp75.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1990

Inhibitory effects of interleukin-1 on follicle-stimulating hormone induction of aromatase activity, progesterone secretion, and functional luteinizing hormone receptors in cultures of porcine granulosa cells.

Effects of interleukin-1 (IL-1) on FSH-induced differentiation of immature porcine granulosa cells in vitro were examined in short-term (48-h) cultures. IL-1 inhibited FSH induction of aromatase activity and of LH-stimulated cAMP accumulation by granulosa cells. Both these inhibitory actions of IL-1 were concentration-dependent. Significant inhibitory effects were observed with as low as 0.05-0.25 ng/ml of IL-1, with maximal effects at 25 ng/ml. IL-1 also significantly inhibited increases in [125I]iodo-LH binding and progesterone secretion induced by FSH, as well as reducing basal levels of aromatase activity and LH-stimulated cAMP accumulation. Studies on the mechanisms of IL-1 actions on FSH-induced differentiation of immature porcine granulosa cells revealed that IL-1 reduced cAMP accumulation by the cells in response to FSH in a time- and concentration-dependent manner. IL-1 also inhibited induction of aromatase activity and LH-stimulated cAMP accumulation induced by dibutyryl cAMP, suggesting that IL-1 also affects the steps distal to cAMP generation. In contrast, IL-1 had no effect on progesterone secretion induced by dibutyryl cAMP, suggesting that post-cAMP steps of progesterone secretion were unaffected by IL-1.

Animals↗
PubMed1990

Development of a new microsurgical robot for stereotactic neurosurgery.

The robot technology was introduced into a new stereotactic neurosurgery system for applications to biopsy, blind surgery, and functional neurosurgery. The authors have developed a newly designed prototype microsurgical robot, designed to allow a biopsy needle to reach the target such as a cerebral tumor within a brain automatically on the basis of the X, Y, and Z coordinates obtained by CT scanner. This robot is so small that it can be driven in a CT scanner gantry. It consists mainly of the link mechanism and the insertion mechanism. We constructed the link mechanism and investigated its working space.

Biopsy, Needle↗
PubMed1990

Immunohistochemical localization of prostaglandin F2 alpha in reperfused gerbil brain.

Immunohistochemical localization of prostaglandin (PG) F2 alpha synthesized during recirculation following experimental forebrain ischemia was studied in Mongolian gerbils. The bilateral carotid arteries were clamped for 5 minutes, and the brains were frozen in situ after 5 minutes of recirculation. Sham-operated gerbils not subjected to arterial occlusion served as controls. Cryostat sections containing dorsal hippocampus 10 microns in thickness were incubated in rabbit anti-PGF2 alpha serum and stained with avidin-biotin-peroxidase complex after fixation in carbodi-imide and Zamboni's solution. In specimens from control animals, blood vessels were faintly stained with anti-PGF2 alpha serum, while neurons and glial cells were less intensely stained or unstained. Specimens from reperfused gerbils demonstrated strongly positive staining for PGF2 alpha in blood vessels, neurons (especially hippocampal pyramidal neurons), and glial cells. Staining for PGF2 alpha in the reperfused animals was substantially diminished by pretreatment with indomethacin (10 mg/kg, i.p.). The results indicate that recirculation after forebrain ischemia results in an increase in PGF2 alpha in neurons, glial cells, and blood vessels.

Animals↗
PubMed1990

[Immunohistochemical study on Rosenthal fibers in gliomas using anti-GFAP and anti-ubiquitin antibodies].

Immunohistochemically we investigated Rosenthal fibers (RFs) on specimen surgically removed from patients with glioma (three cerebellar astrocytomas, three optic gliomas, two spinal cord astrocytomas, one spinal ganglioglioma). Pathological diagnoses were pilocytic astrocytoma, fibrillary astrocytoma, and ganglioglioma. We utilized sections from the formalin-fixed paraffin-embedded tissues and stained them with H & E, PTAH, PAS as well as with anti-GFAP (glial fibrillary acidic protein) antibody (Ab) and two anti-ubiquitin Abs...anti-PHF (paired helical filament) monoclonal Ab (DF2) which recognizes ubiquitin (H. Mori in Science) and anti-ubiquitin polyclonal Ab provided by Dr. Haas. The primary antibodies were diluted with Tris-saline as follows: anti-GFAP (1:500), DF2 (culture medium without dilution), anti-ubiquitin (2 micrograms/ml). Sections were deparaffinized and incubated with primary antibodies overnight at room temperature. They were visualized by the avidin-biotin-peroxidase complex (ABC) procedure (Vectastain, Vector, USA) and counterstained with hematoxylin. Negative control sections were treated by omitting the primary antibodies. In the representative specimen we compared H & E, anti-GFAP and anti-ubiquitin staining on 3 microcrons serial sections. RFs were eosinophilic (bright red on H & E), purply-stained with PTAH (metachromasia), black with Heidemhein's iron-hematoxylin, and negative with PAS. Anti-GFAP Ab stained glial filaments diffusely in the cytoplasm and cell process of astrocytomas in every case. The peripheral parts of most RFs were intensely stained with anti-GFAP. The whole part of some RFs showed dark staining, and no part of a few RFs showed positive reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

[Drug sensitivity test against malignant gliomas].

In treating brain tumors with chemotherapy, the choice of drug is most important since human tumors have different drug sensitivities and growth rates. We have been studying the therapeutic effect of anticancer drugs against malignant brain tumors in the following in vivo models. 1) Human glioma-bearing nude mice. 2) Methylcholantrene-induced 203Gl mouse glioma-bearing immunocompetent C57BL/6 mice. 3) Human gliomas transplanted into the chorioallantoic membrane of chick embryos. We evaluated the advantages of each model for anti-cancer drug sensitivity tests. 1) Human glioma-bearing nude mice were found to be most useful in predicting the direct effects of anticancer drugs. We evaluated the effects of several drugs such as ACNU or interferons in six glioma strains transplanted into nude mice. 2) Immunocompetent C57BL/6 mice models were found useful in predicting the therapeutic effects of biological response modifiers. In this model, we can also evaluate changes in immunological parameters such as NK activities or T cell subsets. 3) In the drug sensitivity test using the CAM of chick embryos, various kinds of gliomas could be grafted with a high rate of success. The tumor reduction rate of the sensitivity test using this system tended to agree with that using nude mice. This test was found to be useful in predicting the effect of drugs against gliomas directly resected from individual patients.

Animals↗