Biomedical subjects

K Kogure

Publications and source records attributed to K Kogure.

At least 199 records · Page 11Linked to original sources

PubMed1993

Effect of a novel thromboxane A2 receptor antagonist, S-1452, on postischemic brain injury in rats.

BACKGROUND AND PURPOSE: Arachidonate metabolites have been implicated in the development of cerebral injury after ischemia. Particular importance has been placed on the balance of thromboxane A2 and prostaglandin I2 because of its regulative activity on platelet functions and arterial tone. The purpose of the present study was to shed light on the role of thromboxane A2 in postischemic brain injury. METHODS: We evaluated the effects of S-1452, a novel thromboxane A2 receptor antagonist, on brain edema, infarct areas, and survival rate in rats with middle cerebral artery occlusion. A transient middle cerebral artery occlusion model was produced by inserting a piece of silicon-coated nylon thread into the internal carotid artery. RESULTS: The ratio of plasma thromboxane B2 to 6-keto-prostaglandin F1 alpha significantly rose at 0 hour (P < .05), 1 hour (P < .01), 3 hours (P < .05), and 12 hours (P < .05) and then nearly returned to the normal level at 24 hours after reperfusion following 1-hour occlusion. Pretreatment with S-1452 (5, 10, or 50 mg/kg PO) significantly attenuated the increase in postischemic water content in the cerebral cortex perfused by the anterior cerebral artery and the cerebral cortex perfused by the middle cerebral artery in a dose-dependent manner but slightly attenuated it in the caudate putamen 24 hours after reperfusion following 1-hour occlusion. Pretreatment with S-1452 (10 mg/kg PO) also significantly decreased the areas of infarction in the front parts of the cerebrum. The survival rate of animals after 2 hours of occlusion tended to be improved by treatment with S-1452 (10 mg.kg-1.d-1 PO), although there was no statistical significance. CONCLUSIONS: Our results suggest that thromboxane A2 is closely related to postischemic brain injury in the early phase of recirculation and that S-1452 may have a protective effect on postischemic brain injury.

6-Ketoprostaglandin F1 alpha↗

PubMed1993

Altered gene expression in cerebral ischemia.

BACKGROUND: Using the techniques of molecular biology, recent experimental studies have shown that cerebral ischemia induces a variety of changes in gene expression in the brain. SUMMARY OF REVIEW: During the early postischemic stages, protein synthesis in the brain is generally suppressed, but specific genes are expressed and their corresponding proteins may be synthesized, such as immediate-early gene products (c-fos, c-jun, and zinc finger gene), heat-shock proteins, and amyloid precursor protein. The ability of neurons to induce such stress responses, which depends on both the severity of ischemia and the intrinsic nature of the neuronal populations, may be directly associated with neuronal death and survival after ischemia. Nerve growth factor and fibroblast growth factor are also induced after ischemia and may be related to repair processes, in which a role of glial cells is suggested. Postischemic events that may be associated with the altered gene expression include (1) induction of tolerance to ischemia after pretreatment with sublethal ischemia, (2) slow, progressive neuronal changes and the development of neuronal plasticity after ischemia, and (3) delayed neuronal changes in remote areas outside the cerebral ischemic focus. CONCLUSIONS: Because a variety of harmful stresses, including ischemia, elicit the same stress response and because this response is induced when total protein synthesis in the brain is nearly completely suppressed, this response may be vital to cell survival and repair. A successful induction of this response may induce resistance and survival of neurons after ischemia. However, failure or abortion of the response and persistent stresses may lead to neuronal death and possibly long-term changes and degeneration.

Amyloid beta-Protein Precursor↗

PubMed1993

Effects of repeated cerebral ischemia on extracellular amino acid concentrations measured with intracerebral microdialysis in the gerbil hippocampus.

BACKGROUND AND PURPOSE: To clarify the role of elevated extracellular amino acid concentrations during ischemia on the cumulative neuronal damage after repeated cerebral ischemic insults, using a microdialysis technique we measured concentrations of the amino acids glutamate, glutamine, glycine, taurine, and gamma-aminobutyric acid in the gerbil hippocampus over three 2-minute forebrain ischemic insults induced at 1-hour intervals. METHODS: Under light anesthesia, the bilateral common carotid arteries were occluded with aneurysm clips at 1-hour intervals. Samples were collected by microdialysis at 10-minute intervals, and the amino acid concentrations were determined using a high-performance liquid chromatography system. RESULTS: During and immediately after the first ischemic insult, concentrations of glutamate, glycine, and taurine, but not glutamine, increased significantly. Glutamate and taurine concentrations rose again during the second and third ischemic insults, but the increases were smaller than those during the first insult. By contrast, glutamine concentrations increased slightly but significantly during the second and third ischemic insults. The extracellular concentration of gamma-aminobutyric acid before the ischemic insults was below the level of detectability but increased markedly during each ischemic insult, with similar declines in the amounts released during later insults. Concentrations of all amino acids returned to baseline after 10 minutes of reperfusion and remained at baseline until the subsequent ischemic insult was induced. CONCLUSIONS: It is well established that glutamate released during ischemia plays a crucial role in ischemia-induced neuronal death. However, the present results indicate that cumulative neuronal damage following sublethal ischemic insults is not caused by an exaggerated release of excitatory amino acids during subsequent ischemic insults but strongly suggest that increased intracellular reactions leading to cell death play a major role.

Amino Acids↗

PubMed1993

Effect of inorganic phosphate on iron-induced lipid peroxidation in rat liver mitochondria.

The effect of inorganic orthophosphate (Pi) on iron-induced lipid peroxidation in non-respiring rat liver mitochondria was studied and compared with that of adenosine 5'-diphosphate (ADP) at pH 7.4. Under the experimental conditions used, lipid peroxidation was induced by Fe2+ in conjunction with Pi and/or ADP, but not by Fe2+ alone. The characteristics of Fe(2+)-induced lipid peroxidation supported by Pi and by ADP were different: ADP-supported peroxidation took place after a lag-time and proceeded until all the O2 in the incubation medium was consumed, whereas the Pi-supported peroxidation exhibited a longer lag-time and a higher rate, but stopped when half the O2 was consumed. These features were ascribed to the fact that Pi forms active iron-oxygen complexes more rapidly than ADP, but the lifetimes of these complexes are less than those of the complexes with ADP. Furthermore, the ability of Pi to form active iron-oxygen complexes was found to be less than that of ADP. Fe2+, in conjunction with Pi and/or ADP, was found to induce lipid peroxidation in respiring mitochondria, although to a lesser extent than in non-respiring mitochondria.

Adenosine Diphosphate↗

PubMed1993

Simultaneous demonstration of neurotransmitter and receptor systems of the rat brain using in vivo double autoradiography.

Neurotransmitter and receptor systems of the rat brain were simultaneously observed by in vivo double autoradiography using a novel imaging plate analyzer system which was developed by Fuji Photo Film Co., Ltd. The animals were subjected to intravenous administration of [18F]-6-fluoro-L-dopa ([18F]-DOPA) and [3H]YM-09151-2, a highly selective dopamine D2 antagonist. The radioactivities of [18F]-DOPA and [3H]YM-09151-2 were found to be highly concentrated in the striatum, demonstrating presynaptic and postsynaptic sites of the dopaminergic nigrostriatal tract, respectively. The [3H]YM-09151-2 was also found to be accumulated in the substantia nigra which is known to correspond with the distribution of dopamine D2 receptors. This method was shown to be useful for investigation of animal models with brain diseases.

Animals↗

PubMed1993

The auditory evoked middle-latency responses (MLRs): their normative variation and generators.

Auditory evoked middle-latency responses (MLRs) to clicks were recorded in 68 normal adults (ages from 21 to 59 year-old) at 16 scalp locations, all referred to a balanced non-cephalic reference. Both Na and Pa components were clearly demonstrated in all the subjects studied through the digital high-pass filtering. Both Na and Pa components were distributed dominantly over the frontal area in all subjects. The amplitudes of Na and Pa were significantly higher with binaural stimulation than with a monaural stimulation, and the existence of binaural interaction was also suggested. Binaural effect was more prominent in Pa than in Na component. When the data recorded from F3 and F4 electrodes were compared, most of F3/F4 amplitude ratios of Na and Pa were included between 0.7 and 1.5. The F3/F4 ratio should be useful indices for the diagnosis of excessive laterality. We also demonstrated gradual phase shifts of Na and Pa between the frontal and temporo-occipital area in about one-third of the records. This phenomenon strongly suggests that both Na and Pa components are derived from complex generators.

Acoustic Stimulation↗

PubMed1993

Dominantly inherited cytoplasmic body myopathy in a Japanese kindred.

An autosomal dominant progressive myopathy with diffuse cytoplasmic bodies (CBs) is described. In four successive generations, 12 patients suffered from weakness and atrophy of muscles in the distal extremities, neck, thorax and shoulder girdles. The mean age at onset was 42 years old, and the patients became disabled after 5 to 10 years due to chronic respiratory failure. The level of serum creatine kinase was normal or slightly elevated. An electromyogram showed a predominant myopathic change with a slight neurogenic change. Autopsy of 2 cases revealed numerous CBs in the skeletal muscles. Smooth and cardiac muscles were also affected. CBs were present predominantly in type I fibers in skeletal muscles. Males were more frequently affected than females (2:1). An electron microscopic examination showed dense central cores of myofilaments surrounded by radiating filaments. Characteristics of clinical course and histopathological findings in a new kindred are discussed in this rare disease.

Adult↗

PubMed1993

[A case of meningeal carcinomatosis showing myelopathy--detection of TNF-alpha in infiltrating CSF cells and brain tissue sections of cerebellum].

A 41-year-old woman had radical mastectomy for breast cancer with metastasis of axial lymph nodes three years previously. In February 1990, she noticed swelling of lymph nodes in right suparclavicular region. A lymph node biopsy revealed cancer cells. Immediately, radiation therapy was performed. However, in August serum levels of CA 15-3 and LDH were markedly elevated. Two months later the patient complained of severe headache, dysarthria, shoulder pain and anorexia. Neurological examination revealed stiff neck, weakness of bilateral facial muscles, deviation of tongue to the left and no sensory disturbance. A CSF sample by lumbar puncture showed 26/mm3 in cell counts, 204 mg/dl of protein and 11 mg/dl of glucose. In addition, CSF cytology revealed malignant cells four to five times as large as lymphocytes. Immediately, and intrathecal administration of methotrexate (MTX) was started. However, one week later she developed complete paraplegia with sensory disturbance below the L1 levels and an incontinentia urine. CSF examination performed again, and showed 97/mm3 in cell counts, 792 mg/dl of protein and 91 mg/dl of glucose. On October 10, a CT scan of the head showed contrast enhancement along cerebellar folia and narrowing of quadrigeminal cistern. On November 31, sagittal T1W1 with Gadolinium revealed an enhancing stripes along the spinal cord at the Th10 to L4 levels. This finding was suggested to be meningeal carcinomatosis. On December 8, she died. At autopsy, brownish hemorrhagic mass was noticed in the bilateral cerebellar tonsils, and severe downward displacement of the tonsils.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

[Prostaglandin E1 bladder instillations for a patient with severe hemorrhagic cystitis after allogeneic bone marrow transplantation].

A 39-year-old female with AML (M2) underwent allogeneic bone marrow transplantation (BMT) on July 8th, 1991. The post transplantation course had been going well until day 85 post BMT, when severe hemorrhagic cystitis with right hydronephrosis and ureter stenosis developed. Adenovirus type 11 was isolated from the urine. She received instillations of prostaglandin E1 (PGE1) directly into the bladder after the appearance of clots in the urine. Complete resolution of hematuria was obtained by two courses of this treatment. PGE1 bladder instillations seem to be effective for the control of hematuria caused by severe hemorrhagic cystitis after BMT.

Adenovirus Infections, Human↗

PubMed1993

[Correlation between induction of ischemic tolerance and expression of heat shock protein-70 in the rat hippocampus].

We investigated the correlation between protection against ischemic neuronal damage by preconditioning with sublethal ischemia and the expression of heat shock protein-70 (HSP70). Three minutes of forebrain ischemia in the rat induced by four-vessel occlusion and 3 days of reperfusion was followed by 6, 8, and 10 minutes of ischemia. Seven days after the second ischemia, the brains were used for histology. Two hours, 1, 3, and 7 days after 3 or 6 minutes of ischemia, the brains were used for immunohistochemistry with an antibody raised against HSP70. Three minutes of ischemia produced no neuronal damage in the hippocampus. Six, 8, and 10 minutes of ischemia produced severe neuronal damage to CA1. However, CA1 neurons were preserved in animals subjected to 6 and 8 minutes of ischemia following preconditioning with 3 minutes of ischemia. Immunostaining showed that HSP70 was induced in the CA1 subfield 3 days after 3 minutes of ischemia. HSP70 was stained in the CA1, CA3, and CA4 subfields 1 and 3 days after 6 minutes of ischemia with or without preconditioning. However, HSP70 was also stained in CA1 2 hours and 7 days after 6 minutes of ischemia following preconditioning. These results strongly suggest that stress response induced by sublethal ischemia protects against ischemic neuronal damage. However, the protection was not seen when HSP70 synthesis was delayed. Presence of HSP70 during and immediately after ischemia may be critical for the protection against ischemic neuronal damage following preconditioning.

Animals↗

PubMed1993

[Chromosomal abnormalities in Castleman's disease with high levels of serum interleukin-6].

Chromosomal abnormalities in Castleman's disease with high levels of serum IL-6 were reported. A 69-year-old male was found to have superficial lymph node swelling and polyclonal hypergammaglobulinemia, when he was admitted to the department of otolaryngology for carcinoma of the tongue in July 1991. In December, he was referred to our department after completing radiation therapy. Laboratory examination revealed 7.7 g/dl hemoglobin, 10.8 g/dl total protein, and 56.0% gamma-globulin. Serum electrophoresis revealed polyclonal hypergammaglobulinemia and no Bence-Jones protein. Bone marrow aspirates showed an increase of plasma cells to 21.8%. Serum IL-6 was 252 pg/ml. Chromosomal analysis of cells in the lymph node showed a karyotype of 46,XY,t(7;14)(p22;q22). The lymph node histology showed marked hyperplasia of plasma cells at interfollicular areas. These plasma cells were stained with both anti-kappa and anti-lambda antibody. He was diagnosed as multicentric form Castleman's disease. Treatment with prednisolone and melphalan resulted in improvement of clinical findings such as anemia, lymph node swelling and hypergammaglobulinemia in concurrence with decrease in serum levels of IL-6. Since the IL-6 gene is located on 7p21-22, the translocation 7; 14 may be related to the high level of serum IL-6.

Aged↗

PubMed1992

Different thresholds of HSP70 and HSC70 heat shock mRNA induction in post-ischemic gerbil brain.

Thresholds of induction of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after transient global ischemia in gerbil brain were investigated by in situ hybridization using cloned cDNA probes selective for each mRNA species. In sham control brain, HSP70 mRNA was little present, while HSC70 mRNA was present in most cell populations. A 0.5-min occlusion of bilateral common carotid arteries did not affect the amount of HSP70 and HSC70 mRNAs. The selective induction of HSC70 mRNA was observed in dentate granule cells at 1 h, and in most cells of hippocampus especially dentate gyrus at 3 h after 1 min of ischemia when induction of HSP70 mRNA was not evident in the identical brain. The selective induction diminished by 2 days. However, after 2 min of ischemia, HSP70 and HSC70 mRNAs were induced together in hippocampal cells from 1 h of the reperfusion, and the co-induction prolonged in CA1 cells until 2 days. Body temperatures monitored at rectum increased after the reperfusion with a peak at 30 min. The degree of increase of the body temperature was significantly higher in the case after 2-min ischemia than in the cases after 0.5- and 1-min ischemia. Although HSP70 and HSC70 mRNAs are generally co-induced in stressful conditions, our results suggest the different thresholds of the induction between HSP70 and HSC70 mRNAs after transient brain ischemia. The selective induction of HSC70 mRNA which is not accompanied by the induction of HSP70 mRNA may relate to the differences of the duration of ischemia and the degree of the increase of body temperature after ischemia.

Animals↗

PubMed1992

Repeated focal cerebral ischemia in gerbils is associated with development of infarction.

We induced repeated focal cerebral ischemia in gerbils. Single 5-min ischemia produced neuronal damage limited to the ipsilateral CA1 and CA4 hippocampus. Two 5-min ischemic insults spaced at a 1-h interval caused selective neuronal damage to the CA1, CA3 and CA4 hippocampus, striatum, neocortex, and thalamus. Three 5-min ischemic insults at 1-h intervals produced infarction. Thus, repeated focal ischemia produced cumulative brain damage by conversion of sublethal damage into selective neuronal damage and of the neuronal damage into infarction.

Animals↗

PubMed1992

Cyclosporin A protects against ischemia-reperfusion injury in the brain.

We investigated the protective effect of Cyclosporin A (CsA) against ischemia-reperfusion injury in the brain using a transient focal ischemia model in rats. In CsA-treated rats, ischemic brain edema formation 1 day after reperfusion in the cerebral cortex perfused by the middle cerebral artery (MCA) and infarct size were decreased compared with those in olive oil treated control rats. These results suggest that CsA is beneficial in reducing ischemia-reperfusion injury, possibly by the suppression of immunological reactions.

Alanine Transaminase↗

PubMed1992

Autoradiographic analysis of cyclic adenosine monophosphate phosphodiesterase using [3H]rolipram in the postischemic rat brain.

Postischemic alteration of cyclic adenosine monophosphate phosphodiesterase was investigated in the rat brain, using [3H]rolipram in vitro autoradiography. After 90 min of middle cerebral artery (MCA) occlusion, [3H]rolipram binding sites decreased rapidly in the brain areas supplied by the occluded MCA. Moreover, 3 days after the ischemia, significant decreases of [3H]rolipram binding sites were observed in the thalamus and the substantia nigra, both areas had not been directly affected by the original ischemic insult. These results suggest that alteration of second messenger pathways may be involved in neuronal degeneration caused by transsynaptic process and that alteration of intracellular signal transduction may precede the neuronal damage in the exo-focal postischemic brain areas.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1992

Protective effects of serotonin reuptake inhibitors, citalopram and clomipramine, against hippocampal CA1 neuronal damage following transient ischemia in the gerbil.

To clarify the role of serotonin in cerebral ischemia, we examined the effects of selective serotonin reuptake inhibitors, citalopram and clomipramine, on ischemic neuronal damage in the gerbil. Pretreatment with citalopram (40 mg/kg i.p.) and clomipramine (20 mg/kg i.p.) protected against neuronal destruction of hippocampal CA1 pyramidal cells following 5 min of forebrain ischemia. Furthermore, microdialysis assays showed that a striking increase in extracellular excitatory amino acid levels during ischemia was significantly inhibited by pretreatment with citalopram and clomipramine. However, citalopram (40 mg/kg i.p.) did not alter the extracellular amino acid concentrations in normal gerbils. Thus, serotonin reuptake inhibitors have a protective effect against ischemic neuronal damage. Furthermore, the present result suggests that the protective effect is mediated through prevention of the accumulation of extracellular excitatory amino acids during and after ischemia.

Amino Acids↗

PubMed1992

Distributions of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after transient focal ischemia in rat brain.

The distribution of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNA after 30 min of middle cerebral artery (MCA) occlusion was investigated in rat brain by in situ hybridization using cloned cDNA probes selective for the mRNAs. While HSP70 mRNA was hardly present at caudate and dorsal hippocampal levels of the sham brain this mRNA was greatly induced in cells of the MCA territory 1 h after reperfusion. Although the maximum amount of induced HSP70 mRNA in the caudate was much smaller than that in the cortex the maximum induction in the caudate (3 h) preceded that in the cortex (8 h). In contrast to the case of HSP70 mRNA, HSC70 mRNA was present in most cells of the sham brain, and was especially dense in hippocampal CA3 cells. Further induction of HSC70 mRNA was observed after reperfusion in the same cell populations, as in the case of HSP70 mRNA. HSC70 mRNA levels were significantly reduced in the caudate at 8 h when small amounts of HSP70 mRNA were still elevated. In the ipsilateral granule cells of the dentate gyrus and hippocampal CA3 cells a slight but significant induction of HSC70 mRNA was observed from 1 h to 1 day, while obvious induction of HSP70 mRNA never occurred. All the induced signals of HSP70 and HSC70 mRNA were diminished or returned to the sham level by 7 days, except for HSC70 mRNA in the caudate. These results are the first observations of the distribution of HSP70 and HSC70 mRNA after transient focal ischemia of rat brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Possible involvement of interleukin-1 in ischemic brain edema formation.

To determine the contribution of interleukin 1 (IL-1) on ischemic brain edema formation, the effect of recombinant human interleukin 1 beta (rhIL-1 beta), or zinc protoporphyrin (ZnPP) as an IL-1 blocker, on brain edema was studied in rats. The animals were subjected to 60 min of ischemia in a middle cerebral artery occlusion model. Immediately after reperfusion, rhIL-1 beta at a dose of 10 ng/2 microliters, or ZnPP at doses of 1 and 10 micrograms/2 microliters were topically applied into lateral cerebroventricle. In rhIL-1 beta-treated rats, ischemic brain edema formation was significantly increased in the dorsal and ventral areas of the caudate putamen 24 h after reperfusion, compared to that of vehicle-treated control rats. Furthermore, in ZnPP-treated rats, brain edema was decreased in both caudate-putamen areas. This suggests that IL-1 plays an important role in pathogenesis for post-ischemic brain edema.

Animals↗