Biomedical subjects

K Kogure

Publications and source records attributed to K Kogure.

At least 109 records · Page 6Linked to original sources

PubMed1995

[Prostaglandin E1 bladder instillations for late-onset hemorrhagic cystitis following allogeneic bone marrow transplantation].

Between July, 1990 and March, 1994, 31 patients with hematological malignancies or severe aplastic anemia underwent allogeneic bone marrow transplantation (BMT) at the Second Department of Internal medicine, Chiba University Hospital. Among the 29 evaluable patients who survived over 100 days after transplant, 11 patients (37.9%) developed late-onset hemorrhagic cystitis with a median time of onset of 57 days (range 11-205) from BMT. Adenovirus type 11 was isolated from the urine of 4 patients. Five patients recovered with fluid hydration and forced diuresis, while 6 patients had persistent gross hematuria with clot formation, 5 of whom also developed hydronephrosis. Seven-day courses of 500 micrograms prostaglandin E1 (PGE1) bladder instillations was initiated to control hematuria in these 6 patients. Complete resolution of gross hematuria was achieved in 4, and partial response with decreased clot formation and partial clearing of the urine was observed after 4 of 9 courses of the treatment. Although all patients experienced bladder spasm or lower abdominal pain during the PGE1 instillations, these symptoms were manageable with sedative drugs and morphine. No systemic side effect was apparent. PGE1 bladder instillations is a safe and useful treatment for severe, life-threatening late-onset hemorrhagic cystitis after allogeneic BMT.

Administration, Intravesical↗

PubMed1994

Histamine depletion in brain caused by treatment with (S)alpha-fluoromethylhistidine enhances ischemic damage of gerbil hippocampal CA2 neurons.

The effect of (S)alpha-fluoromethylhistidine (FMH), a specific inhibitor of histamine synthesis from histidine, on ischemic damage was examined in gerbil brain after forebrain ischemia. Two h after subcutaneous FMH injection, the histamine content of the brain was significantly reduced. Neuronal loss in the CA2 region of the hippocampus 7 days after 3 min ischemia was enhanced by treatment with FMH. These results indicate that depletion of brain histamine aggravates neuronal death of hippocampal CA2 neurons after 3 min ischemia.

Animals↗

PubMed1994

Increased expression of heme oxygenase mRNA in rat brain following transient forebrain ischemia.

Heme oxygenase is a rate-limiting enzyme in heme catabolism, the end of which include iron, carbon monoxide and bilirubin. Expression of the inducible form of heme oxygenase (HO-1) was investigated in rat brain following 20 min of forebrain ischemia by Northern blot and in situ hybridization analyses. The level of HO-1 mRNA was undetectable in the cerebral cortex of sham control, but increased following ischemic insult, reached the maximum after 12 h of reperfusion, and then decreased. In sham control brain, HO-1 mRNA was detectable only in the scattered neuron-like cells within the dentate gyrus hilus. At 12 h of reperfusion, the remarkable increase in HO-1 mRNA levels was observed in both neuronal and glia-like cells distributed in the neocortex, hippocampus and thalamus.

Animals↗

PubMed1994

Astroglial and microglial reactions in the gerbil hippocampus with induced ischemic tolerance.

Preconditioning of the brain with sublethal ischemia protects against neuronal damage following subsequent longer periods of ischemia (ischemic tolerance). In this study, we investigated astroglial and microglial reactions in the hippocampus following ischemia in a gerbil model of ischemic tolerance. Two minutes of forebrain ischemia (preconditioning ischemia) or sham operation was followed by 3 min of ischemia (second ischemia) 3 days later. The brains were perfusion-fixed after 4 h, 1 day, 2 days, and 7 days. Paraffin sections were used for the visualization of astrocytes by immunostaining against glial fibrillary acidic protein (GFAP) and for the visualization of microglia by histochemical staining with isolectin-B4 from Griffonia simplicifolia. The preconditioning ischemia induced a moderate increase in astroglial and microglial staining. Two days after the second ischemia, GFAP staining further increased in astrocytes in the hippocampus with ischemic tolerance. In the CA1 region of the hippocampus without ischemic tolerance, in contrast, microglial activation with increased staining and morphological changes was pronounced. After 7 days, neuronal destruction resulted in the CA1 region without tolerance, where hypertrophic reactive astroglia and reactive microglia with phagocytic transformation accumulated intensely. However, the ischemic preconditioning prevented the CA1 neuronal damage and the activation of microglia was subsiding after 7 days. Thus, activation of glial cells occurred in a graded fashion in response to different degrees of neuronal injury. Astroglial but not microglial activation may have implications in neuronal survival in ischemic tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Autoradiographic distribution of neurotransmitter and second messenger system receptors in animal brains.

We investigated species difference in binding of major neurotransmitters and intracellular second messengers in the gerbil brain and the rat brain using receptor autoradiography. [3H]Phorbol 12,13-dibutyrate (PDBu), [3H]inositol 1,4,5-trisphosphate (IP3), [3H]PN200-110, [3H]muscimol, [3H]MK-801, [3H]cyclohexyladenosine (CHA),and [3H]quinuclidinyl benzilate (QNB) were used to label protein kinase C, IP3 receptor, L-type calcium channel, gamma-aminobutyric acidA (GABAA) receptor, N-methyl-D-aspartate (NMDA) receptor, adenosine A1 receptor, and muscarinic cholinergic receptor, respectively. Autoradiographic distributions of the bindings of most neurotransmitters and second messengers were particularly found in the limbic system and basal ganglia in both gerbil and rat brains. However, marked differences in these bindings between the gerbil brain and the rat brain were also recognized in the above regions. In particular, among 7 ligands used, the gerbil had high [3H]PDBu and [3H]CHA binding sites throughout the brain compared to those in the rat brain except for a few areas. By contrast, the rat exhibited high [3H]MK-801 binding sites in various brain regions, as compared with the gerbil brain. Thus, the gerbil differ from the rat with respect to the binding sites of major second messengers and neurotransmitters in the brain. The results may help better elucidate the relationship or species difference between gerbils and rats for neuronal function and behavioral pharmacology.

Animals↗

PubMed1994

Effect of pentobarbital on postischemic MK-801, muscimol, and naloxone bindings in the gerbil brain.

We investigated the postischemic alterations in [3H]MK-801, [3H]muscimol, and [3H]naloxone binding in the gerbil brain, and examined the effect of pentobarbital against these alterations. [3H]MK-801, [3H]muscimol, and [3H]naloxone were used to label N-methyl-D-aspartate (NMDA), gamma-aminobutyric acidA (GABAA), and opiate receptors, respectively. Transient cerebral ischemia was induced for 10 min, and pentobarbital (40 mg/kg) was administered intraperitoneally 30 min before ischemia. Five hours after ischemia, no conspicuous alteration in [3H]MK-801, [3H]muscimol, and [3H]naloxone binding was found in the striatum and hippocampus. Seven days after ischemia, [3H]MK-801 and [3H]naloxone binding was significantly decreased in the striatum and hippocampal area where histological neuronal damage was noted. By contrast, no significant change in [3H]muscimol binding was seen in the above regions except for the hippocampal CA3 sector. The treatment of pentobarbital caused a significant alteration in the binding of [3H]naloxone and [3H]muscimol in various brain areas 5 h after ischemia. However, this drug showed no significant change in [3H]MK-801 binding in the brain. Seven days after ischemia, pentobarbital partly ameliorated a significant reduction in [3H]MK-801 and [3H]naloxone binding in the striatum and hippocampus. A histological study also showed that pentobarbital afforded neuronal protection against the damage to the brain except for the hippocampal CA1 sector 7 days after ischemia. These results suggest that NMDA and opiate receptors are damaged after ischemia, whereas GABAA receptors are unaffected. They also demonstrate that opiate receptors are severe affected by the treatment of pentobarbital, compared with NMDA and GABAA receptors. These findings are of interest in relation to the mechanism of ischemic neuronal damage.

Animals↗

PubMed1994

Role of cell adhesion molecules in brain injury after transient middle cerebral artery occlusion in the rat.

Activated neutrophils appear to be directly involved in tissue injury after focal cerebral ischemia and reperfusion. Intercellular adhesion molecules-1 (ICAM-1) and CD11/CD18 integrins have been implicated in ischemia-reperfusion induced neutrophil endothelial adhesion and transmigration. We therefore investigated the roles of CD11a/CD18 (LFA-1) and ICAM-1 in cerebral ischemia-reperfusion injury by using monoclonal antibodies, WT1 (anti-CD11a), WT3 (anti-CD18), and 1A29 (anti-ICAM-1). Rats were subjected to 1 h of middle cerebral artery occlusion (MCAO). Individual antibodies were administered at a dose of 5 mg/kg intraperitoneally at 15 min before ischemia and immediately after reperfusion. Rats were killed at 24 h after reperfusion, and brain edema, neutrophil infiltration and infarct size were measured. Sustained enhancement of ICAM-1 expression on capillaries was observed up to 24 h (beginning between 1 and 3 h after reperfusion). While, leukocytes began to infiltrate into the ischemic hemisphere between 6 and 12 h after reperfusion. Treatment with individual antibodies against cell adhesion molecules reduced edema formation and infarct size in addition to neutrophil accumulation 24 h after reperfusion. These results strongly implicate the invasion of neutrophils in the development of post-ischemic brain injury, and suggest that interactions between CD11a/CD18 and ICAM-1 contribute to neutrophil infiltration into the ischemic brain.

Animals↗

PubMed1994

Ischemic tolerance can be induced repeatedly in the gerbil hippocampal neurons.

We investigated whether ischemic tolerance can be induced repeatedly in the gerbil hippocampal neurons. The gerbils were firstly treated with two episodes of 2-min forebrain ischemia 1 day apart, which procedure is known to induce ischemic tolerance. After 4 weeks of recirculation, the animals were subjected to a 2-min period of preconditioning ischemia again and then to a 3-min period of ischemia after 3 days. The hippocampal CA1 neurons were destroyed 7 days after 3-min ischemia without the second preconditioning but not in animals with the second preconditioning. Thus, ischemic tolerance can be induced repeatedly when the first ischemic tolerance has disappeared.

Animals↗

PubMed1994

Induction of NADPH-diaphorase activity in the hippocampus in a rat model of cerebral ischemia and ischemic tolerance.

Preconditioning of the brain with sublethal ischemia induces tolerance to subsequent lethal periods of ischemia (ischemic tolerance). In this study, we used NADPH-diaphorase histochemistry to investigate the postischemic changes of nitric oxide synthase (NOS) in the hippocampus in a rat model of cerebral ischemia and ischemic tolerance. Forebrain ischemia was induced by 4-vessel occlusion for 3 min as an ischemic preconditioning. Three days after the preconditioning or sham operation, second ischemia was induced for 6 min. A transient increase in NADPH-diaphorase activity, beginning after 2 h and maximal after 1 day, was observed in CA1 pyramidal neurons of rats subjected to 3 min of preconditioning ischemia as well as 6 min of subsequent ischemia both with and without preconditioning. In addition, expression of NADPH-diaphorase activity was seen in reactive glial cells in the damaged CA1 region of animals subjected to 6 min of ischemia without preconditioning. Thus, direct involvement of increased NADPH-diaphorase activity in ischemic tolerance was not suggested because the increased NADPH-diaphorase activity preceded the induction of ischemic tolerance which takes place 1-7 days after preconditioning. However, the present findings suggest that the induction of neuronal NADPH-diaphorase activity occurs in response to cerebral ischemia.

Amino Acid Oxidoreductases↗

PubMed1994

Alteration of adenosine A1 receptor binding in the post-ischaemic rat brain.

Chronological changes of adenosine A1 receptor binding of the rat brain were determined by in vitro [3H]cyclohexyladenosine (CHA) autoradiography after 90 min of middle cerebral artery (MCA) occlusion and after such occlusion followed by different periods of recirculation. One day after the ischaemia, [3H]CHA binding sites decreased significantly in the cerebral cortex (p < 0.05) and lateral segment of the caudate putamen (p < 0.01), both supplied by the occluded MCA; thereafter, the binding sites decreased progressively in those ischaemic foci. On the contrary, there was no alteration on day 1, but 3 days after ischaemic insult, a significant decrease of [3H]CHA binding sites was first detected in the ipsilateral thalamus and the substantia nigra, both areas which had not been directly affected by the original ischaemic insult. This post-ischaemic delayed phenomenon observed in the thalamus and the substantia nigra developed concurrently with 45Ca accumulation, which was studied in our previous study. Based on the present study, alteration of adenosine A1 receptor binding activities is involved not only in the ischaemic foci, but also in the remote areas associated neuroanatomically with the ischaemic foci. We suggest that multi-focal post-ischaemic alterations of adenosine A1 binding activities may exacerbate clinical symptoms of patients at a chronic stage of stroke.

Adenosine↗

PubMed1994

Delayed damage of striatal interneurons after cerebral ischemia in the gerbil.

Immunohistochemical changes of striatal interneurons in the gerbil were investigated 1 h-7 days after 10 min cerebral ischemia. Marked reduction of parvalbumin-immunoreactive interneurons was seen in the striatum from 24 h after ischemia. MAP2 (microtubule-associated protein 2) immunoreactivity markedly decreased in striatal neurons 5 h after ischemia but was unaffected in interneurons. Thereafter, a severe loss of MAP2 immunoreactivity in the interneurons was found 48 h and 7 days after ischemia. The results demonstrate that transient cerebral ischemia can cause a loss of parvalbumin and MAP2 immunoreactivity in interneurons in the dorsolateral striatum in a delayed fashion as compared with a rapid loss of striatal neurons.

Animals↗

PubMed1994

Steady state transcript levels of the type II hexokinase and type 1 glucose transporter in human tumor cell lines.

The steady state transcript levels of two hexokinase isozymes and type 1 glucose transporter in human tumor cell lines were analyzed. In HepG2 cells, both type II hexokinase and type 1 glucose transporter were highly expressed. However, in cell lines A431 and HeLa, in which the expression level of type 1 glucose transporter was lower than that in HepG2 cells, the amount of type II hexokinase transcript was almost negligible.

Amino Acid Sequence↗

PubMed1994

Effects of naftidrofuryl oxalate, a 5-HT2 antagonist, on neurotransmission and transduction systems in the gerbil hippocampus.

We investigated the effects of age and nafidrofuryl oxalate (Naftidrofuryl), a 5-HT2 antagonist, on neurotransmission and transduction systems in the gerbil hippocampus using quantitative autoradiography. [3H]Quinuclidinyl benzilate (QNB), [3H]cyclohexyl-adenosine (CHA), [3H]MK-801, and [3H]muscimol were used to label muscarinic acetylcholine, adenosine A1, N-methyl-D-aspartate (NMDA), and gamma-aminobutyric acid-A (GABAA) receptors, respectively. [3H]PN200-110 labeled L-type Ca2+ channels. [3H]Forskolin, [3H]cyclic adenosine monophosphate (cAMP), [3H]phorbol 12,13-dibutyrate (PDBu), and [3H]inositol 1,4,5-triphosphate (IP3) were used to label adenylate cyclase, cAMP-dependent protein kinase, protein kinase C (PKC), and IP3 receptors, respectively. Approximately 20% reductions in [3H]QNB, [3H]forskolin, and [3H]PDBu binding were observed in the hippocampus of 9-month-old gerbils in comparison with 5-week-old gerbils. Treatment with Naftidrofuryl (10 mg/kg, i.p., once a day for 7 days) ameliorated these reductions. No changes were found in [3H]CHA, [3H]MK-801, [3H]muscimol, [3H]PN200-110, [3H]cAMP, and [3H]IP3 binding. The results suggest that Naftidrofuryl may have beneficial effects on the age-related alterations in signal transmission and transduction systems in the brain. Because the acetylcholine system, adenylate cyclase, and PKC are considered to be involved in learning and memory processes, the result may have clinical implications.

Adenosine↗

PubMed1994

An immunohistochemical observation of manganese superoxide dismutase in rat substantia nigra after occlusion of middle cerebral artery.

We investigated immunohistochemically the localization and changes of manganese superoxide dismutase (Mn-SOD) in substantia nigra after 1 h of middle cerebral artery (MCA) occlusion in the rat with reperfusion periods of 1, 3, 7, and 14 days. In normal rats, Mn-SOD immunoreactivity was observed intensely in many large neurons in substantia nigra pars reticulata (SNr) and weakly in neurons in the pars compacta (SNc). The immunoreactivity of the neurons in both SNr and SNc was reduced after 1 day and almost lost 3 days after MCA occlusion, although these neurons showed completely normal morphology. The immunoreactivity recovered only in the large neurons in SNr from the 7th day and well preserved after 2 weeks, when SNr showed obvious atrophy. The results indicate that oxidative stress may be involved in the pathogenesis of the secondary postischemic neurodegeneration in SN.

Animals↗

PubMed1994

An immunohistochemical study of copper/zinc superoxide dismutase and manganese superoxide dismutase following focal cerebral ischemia in the rat.

We investigated immunohistochemically the localization and changes of copper/zinc superoxide dismutase (CuZn-SOD) and manganese superoxide dismutase (Mn-SOD) in the rat brain following 1 h of middle cerebral artery (MCA) occlusion. In normal brain, immunoreactivity to both SODs was observed in medium-sized neurons in the striatum and in many neurons in the neocortex. Mn-SOD was predominantly stained in cortical interneurons. The immunostaining of both SODs rapidly decreased or disappeared in neurons in the lateral segment of the striatum (ischemic center) 4 h after MCA occlusion, when the neurons were degenerating. Most neurons in the neocortex (ischemic penumbra) decreased their CuZn-SOD immunoreactivity but not Mn-SOD immunoreactivity 4 h after ischemia, when only a few neurons showed histopathological changes. CuZn-SOD immunoreactivity in almost all cortical neurons disappeared 1 day after ischemia, but Mn-SOD immunoreactivity was still preserved in interneurons, when cortical neurons showed typical pathological changes. Some cortical neurons in the boundary zone between normal and infarcted areas showed intense immunostaining to both SODs and glial SOD immunoreactivity appeared after 3 and 7 days. These results suggest that early loss of the scavenging system of free radicals may lead to neuronal damage after ischemic insult, and that induced SODs in the boundary zone between the normal and infarcted areas may act as a defense mechanism against damage.

Animals↗

PubMed1994

Multi-focal metabolic disturbances in human brain after cerebral infarction studied with 18FDG and positron emission tomography.

We measured cerebral metabolic rates for glucose (CMRGlc) in the remote brain areas of 7 patients, who were affected by unilateral cortical infarction, at a chronic stage using 2[18F]-fluoro-2-deoxy-D-glucose and positron emission tomography. There were significant decreases of CMRGlc compared with each control value (p < 0.01), not only in the cerebral cortex directly damaged by the ischaemic insult, but also in the ipsilateral thalamus and in the contralateral cerebellum, areas in which no lesions had been detected by MRI or CT scan. The present study indicates that different mechanisms may be responsible for multi-focal metabolic disturbances in the remote areas after stroke. We suggest that these multi-focal brain dysfunctions may exacerbate clinical symptoms at a chronic stage of stroke.

Adult↗

PubMed1994

NMDA receptor (NMDAR1) expression in the rat hippocampus after forebrain ischemia.

The influence of transient forebrain ischemia on the temporal alteration of NMDA receptor (NMDAR1) mRNAs in the hippocampal formation was analysed by in situ hybridization, RNA blot and in vitro receptor autoradiography ([3H]3-((+)2-carboxypiperazin-4-yl)-propyl-1- phosphonic acid). In the CA1 subfield of the hippocampus, decrease of NMDAR1 mRNA levels was not observed until death of the CA1 pyramidal cells. Reactive astrocytes, which appear after CA1 pyramidal cell death, expressed few NMDAR1. The CA3 and dentate gyrus also showed a reduction of NMDAR1 mRNA levels 7 days after ischemia. Temporal profiles of NMDAR1 mRNA levels correlated well with those of NMDA receptor-binding in the CA1 and CA3/dentate gyrus. These results indicate that NMDA receptors in the CA1 are predominantly located on the CA1 pyramidal cells and that these receptors are preserved during early recirculation period. Histologically intact neurons in the CA3 and dentate gyrus also had marked modulation in glutamatergic neurotransmission after ischemia.

Animals↗

PubMed1994

Effects of naftidrofuryl oxalate, a 5-HT2 antagonist, on neuronal damage and local cerebral blood flow following transient cerebral ischemia in gerbils.

Effects of naftidrofuryl oxalate (naftidrofuryl), a 5-HT2 antagonist, on neuronal damage and local cerebral blood flow was examined in a gerbil model of transient forebrain ischemia. Effect of ketanserin tartrate (ketanserin), another 5-HT2 antagonist, on neuronal damage was also examined. Pretreatment with naftidrofuryl or ketanserin prevented hippocampal CA1 neuronal loss after 5 min of transient ischemia. Naftidrofuryl did not improve hippocampal blood flow during and 1 h after transient ischemia determined by [14C]iodoantipyrine autoradiography but increased blood flow in the caudate-putamen 1 h after transient ischemia. The results show that: (1) the 5-HT2 antagonists protect against hippocampal CA1 neuronal damage; and (2) the protective effect of naftidrofuryl may not be caused by a hemodynamic mechanism but by a direct inhibitory neuromodulation via 5-HT2 antagonistic action.

Animals↗