Biomedical subjects

K Kogure

Publications and source records attributed to K Kogure.

At least 55 records · Page 3Linked to original sources

PubMed1998

Inhibitory effects of pentamethine trinuclear cyanine dyes on ADP/Fe2+-induced lipid peroxidation in rat liver mitochondria: changes in the mode of action with the hydrophobic nature of the dyes.

The effects of various pentamethine trinuclear cyanine dyes, each of which has three alkyl chains, on ADP/Fe2+-induced lipid peroxidation in rat liver mitochondria were examined. Although the dye having the shortest -C2H5 chains (tri-S-C2(5)) did not show any appreciable effect, the dyes having -C4H9 (tri-S-C4(5)), -C7H15 (tri-S-C7(5)), and -C12H25 (tri-S-C12(5)) chains significantly inhibited lipid peroxidation, the most potent inhibitory effect being observed with tri-S-C7(5). The mode of antiperoxidation effect of the dyes was dependent on the length of the alkyl chains. The relatively hydrophilic dye tri-S-C4(5) was suggested to scavenge radicals more efficiently at or near the membrane surface rather than in the interior of the lipid membrane, whereas the more hydrophobic dye tri-S-C7(5) was suggested to scavenge radicals efficiently in the membrane rather than at or near the membrane surface. The hydrophilic/hydrophobic balance of the dye was found to regulate the site of action of the dyes.

Adenosine Diphosphate↗

PubMed1998

Effect of rolipram on age-related changes in cyclic AMP-selective phosphodiesterase in the rat brain: an autoradiographic study.

Rolipram is a clinically effective antidepressant with cyclic AMP-selective phosphodiesterase (cyclic-AMP PDE) inhibiting action. In this study, we investigated the effect of chronic treatment with rolipram on age-related changes in cyclic-AMP PDE in the rat brain visualized and quantitated by in vitro [3H]rolipram autoradiography. Rolipram (0.01 mg/kg and 0.1 mg/kg) or its vehicle was administered orally to 15-week-old (young) and 80-week-old (aged) Wistar rats once a day for 4 weeks. In control young rats, high [3H]rolipram binding was seen in the hippocampus, the cerebellum and the neocortex. In control aged rats, the [3H]rolipram binding decreased strikingly in almost all brain regions. Chronic treatment of the young rats with rolipram reduced the [3H]rolipram binding in a dose-dependent manner. By contrast, the same treatment of the aged rats induced no or minimal changes. These results suggest that 1) cyclic-AMP PDE in the rat brain is subject to age-associated decline, and 2) the response to rolipram treatment is different between young and aged rats.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1998

Age-related effects of rolipram on [3H]quinuclidinyl benzilate and [3H]phorbol 12,13-dibutyrate binding in the rat brain.

Cholinergic neurotransmission and protein kinase C (PKC) in the brain play important roles in the processes of cognitive function. In this study, we examined the effect of chronic treatment with rolipram, a 3',5'-cyclic adenosine monophosphate (cyclic AMP)-selective phosphodiesterase inhibitor, on age-related changes in [3H]quinuclidinyl benzilate (QNB) and [3H]phorbol 12,13-dibutyrate (PDBu) binding, which labeled brain muscarinic cholinergic receptors and PKC, respectively. Rolipram was administered per os to young (15 weeks old) and old (80 weeks old) Wistar rats at dosage of 0.01 mg/kg and 0.1 mg/kg once a day over 4 weeks. Then, quantitative in vitro autoradiography was performed. Control old rats showed elevations in [3H]PDBu binding in the hippocampus and the cerebellum compared to young rats, but [3H]QNB binding was largely unchanged. Chronic treatment of the old rats with the higher dose of rolipram led to reductions in [3H]QNB and [3H]PDBu binding in many brain regions. However, the same treatment of the young rats induced no or minimal effect. Thus, the response of the brain to rolipram was different between young and old rats. These results suggest that the cyclic AMP-selective phosphodiesterase system in the brain is modified during aging, modulating subsequently cholinergic neurotransmission and PKC activity exclusively in old rat brains.

Aging↗

PubMed1997

Effect of dicetylphosphate or stearic acid on spontaneous transfer of protein from influenza virus-infected cells to dimyristoylphosphatidylcholine liposomes.

Membrane proteins, such as viral spike, were transferred spontaneously from influenza virus-infected cells to various liposomes. The protein transfer was enhanced by the presence of negative charged component dicetylphosphate (DCP) or stearic acid (SA) in dimyristoylphosphatidylcholine (DMPC) liposomes. The lowering of membrane fluidity did not relate to the effect of DCP or SA on protein transfer in this study. We considered that the alteration of membrane properties, such as construction of the surface or stability of transferred protein in liposomes, due to the specific structure of DCP or SA is responsible for the enhancement of spontaneous protein transfer by the presence of the amphiphilic components.

Animals↗

PubMed1997

Delayed neuronal death prevented by inhibition of increased hydroxyl radical formation in a transient cerebral ischemia.

The salicylate-trapping method was used to detect hydroxyl radicals by measurement of stable adduct dihydroxybenzoic acid (DHBA). Ten minutes of forebrain ischemia followed by reperfusion induced the increase in DHBA in rat hippocampal perfusates. Postischemic treatment with a free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), significantly reduced the increase in DHBA and suppressed delayed neuronal death in the hippocampal CA1 region.

Animals↗

PubMed1997

New therapeutic possibility of blocking cytokine-induced neutrophil chemoattractant on transient ischemic brain damage in rats.

Earlier we indicated that neutrophilic invasion into cerebral parenchyma is an important step in rat cerebral ischemia-reperfusion injury and the production of chemotactic factors, cytokine-induced neutrophil chemoattractant (CINC) precede the neutrophilic invasion. The aim of the present study was to evaluate the role of CINC production and the therapeutic possibility of blocking CINC activity in the transient ischemic brain damage in rats. Focal transient ischemia was produced by intraluminal occlusion of the right middle cerebral artery for 60 min. An enzyme immunoassay was used to measure the brain concentration of CINC and myeloperoxidase activity in ischemic areas was measured as a marker of neutrophilic accumulation. An immunohistochemical staining technique was used to detect the immunopositive cells for anti-CINC antibody. Further, application of anti-CINC antibody or anti-neutrophil antibody to rats was used to evaluate the role of CINC production. In ischemic areas, CINC production was detected and peaked 12 h after reperfusion, which followed 60 min of ischemia. Intraperitoneal injection of anti-neutrophil antibody 24 h before and immediately after reperfusion significantly reduced the brain water content and partially reduced the CINC production in ischemic areas. Further, immunohistochemical staining showed that anti-CINC antibody was found on the endothelial surface of venules and on parts of neutrophils that had invaded the ischemic area 6 to 24 h after reperfusion. Also, treatment with anti-CINC antibody reduced ischemic edema formation 24 h after reperfusion and the size of infarction areas 7 days after reperfusion. It thus appears that CINC, mainly produced by endothelium activated by factors released from neutrophils, plays an important role in ischemic brain damage. Furthermore, the blocking of CINC activity with antibody suggests an immuno-therapeutic approach to the treatment of stroke patients.

Animals↗

PubMed1997

Effects of chronic treatment with a cyclic AMP-selective phosphodiesterase inhibitor, rolipram, on excitatory amino acid neurotransmission systems in young and aged rat brains.

Rolipram selectively inhibits cyclic AMP-specific phosphodiesterase, and leads to an increase in cyclic AMP levels in the brain. In this study, we investigated the effects of chronic rolipram treatment on excitatory and inhibitory amino acid neurotransmission systems in young and aged Wistar rat brains. We used in vitro autoradiography with [3H]MK-801, [3H]glycine, D[3H]aspartate, and [3H]muscimol to label N-methyl-D-aspartate (NMDA) receptors, glycine modulatory sites, glutamate transport sites, and gamma-aminobutyric acid-A (GABA) receptors, respectively. Rolipram (0.01 or 0.1 mg/kg, per os) or its vehicle (distilled water) was administered once a day for 4 weeks. The highest binding of [3H]MK-801, [3H]glycine, and D-[3H]aspartate was seen in the hippocampus in vehicle-treated rats. No significant differences in these binding activities were seen between young and aged rat brains. [3H]Muscimol binding was the highest in the cerebellum, and decreased in many brain regions in aged rats. The chronic rolipram treatment resulted in (1) an increase in [3H]MK-801 binding in the dentate gyrus in both young and aged rats, (2) remarkable reductions in D-[3H]aspartate binding in many regions of both young and aged rats, and (3) no or minimal changes in [3H]glycine and [3H]muscimol binding. These results suggest that the chronic rolipram treatment modifies the excitatory amino acid neurotransmission system.

Aging↗

PubMed1997

Uric acid changes in serum during different forms of hepatic vascular inflow occlusion.

The present study was conducted to develop an efficient marker which can evaluate the influence of the occlusion of hepatic vascular inflow, which technique is commonly used in major liver surgery or in liver transplantation. Serum samples from the rats induced by hepatic vascular inflow occlusion were analyzed with high performance liquid chromatography with the electrochemical detection, and a substance which changed in accordance with the duration of the occlusion was obtained. Both the retention time and the ultraviolet absorption spectra of the substance completely agreed with those of an authentic uric acid and the substance was ultimately determined to be uric acid. To evaluate the changes in serum uric acid during different forms of hepatic vascular inflow occlusion we devised the four types of experimental model, viz. the occlusion of hepatic artery, portal vein, both hepatic artery and portal vein and both hepatic artery and portal vein of left hepatic lobes. From the device of experiments our results indicated that in the early stage of hepatic vascular inflow occlusion the high values of serum uric acid did not reflect the damage of hepatic circulation but rather responded to the intestinal congestion. Our results also indicated that even after the declamping of hepatic vascular inflow if high values of serum uric acid are prolonged it means the deterioration of the portocaval circulation including both intestinal and hepatic circulation. So that the evaluation of the severity of injured liver due to hepatic vascular inflow occlusion should be done with the caution especially in vivo study when uric acid values are used as a marker.

Animals↗

PubMed1997

Role of hippocampal serotonergic neurons in ischemic neuronal death.

To clarify the serotonergic mechanisms involved in the protection against ischemic neuronal damage, ZD-211 (citalopram HBr), a serotonin (5-hydroxytryptamine; 5-HT) re-uptake inhibitor, or buspirone, a 5-HT1A agonist, was locally administered into the hippocampus of gerbils. Additionally, to clarify the role of the 5-HT nervous system in the hippocampus during ischemic neuronal damage, animals were subjected to the local administration of 5,7-dihydroxytryptamine (5,7-DHT), a 5-HT neurotoxin, before ischemia challenge. Gerbils received intrahippocampal administration of ZD-211 (200 nmol/animal) or buspirone (20 nmol/animal) before 5-min ischemia. 5,7-DHT was intrahippocampally administered 7 days before a 2-min non-lethal ischemia challenge. In vehicle-treated animals subjected to 5 min of ischemia, almost all hippocampal CA1 pyramidal neurons were lost. The treatment with ZD-211 or buspirone showed a significant protective effect, and the number of neurons was significantly increased compared to vehicle-treated animals. Pretreatment with NAN-190, a 5-HT1A antagonist, completely abolished the protective effect of ZD-211 or buspirone. In the 5,7-DHT-treated animals, the number of neurons was significantly reduced following 2 min of ischemia compared to vehicle-treated animals in which this period of ischemia is non-lethal. Thus, intrahippocampal treatment with ZD-211 or buspirone can protect neuronal damage following transient ischemia in gerbils. These effects of ZD-211 and buspirone were mediated through the 5-HT1A receptor in the hippocampus. Furthermore, the destruction of the 5-HT nervous system in the hippocampus aggravated ischemic neuronal damage. Therefore, this study showed that the enhanced activity of the 5-HT nervous system in the hippocampus may protect against neuronal damage following cerebral ischemia.

5,7-Dihydroxytryptamine↗

PubMed1997

Post-ischaemic alteration of excitatory amino acid transport sites in the gerbil hippocampus.

Sodium-dependent [3H]D-aspartate binding as a marker of excitatory amino acid transport sites in the gerbil hippocampus was evaluated by quantitative receptor autoradiography 1 h to 7 days after transient cerebral ischaemia for 10 min. Sodium-dependent [3H]D-aspartate binding in the hippocampal CA1 and CA3 sectors significantly increased in the early post-ischaemic stage. After 7 days, a conspicuous elevation of sodium-dependent [3H]D-aspartate-binding was observed in the hippocampal CA1 sector and dentate gyrus. However, no significant change in the binding was found in the hippocampal CA3 sector. A histological study revealed that transient ischaemia caused severe neuronal damage in the hippocampal CA1 sector and mild damage in the hippocampal CA3 sector. However, no ischaemic neuronal damage was observed in the dentate gyrus. An immunohistochemical study also showed that numerous reactive astrocytes were evident in the hippocampus, particularly in the hippocampal CA1 sector, 7 days after ischaemia. These results demonstrate that transient cerebral ischaemia can cause marked elevation in excitatory amino-acid transport sites in the hippocampus. Furthermore, our results suggest that the post-ischaemic increase in excitatory amino acid transport sites might reflect expression of reactive astrocytes. These findings are of interest in relation to the mechanisms of ischaemic hippocampal damage.

Animals↗

PubMed1997

Humoral factor(s) produced by pressure overload enhance cardiac hypertrophy and natriuretic peptide expression.

Chronic pressure overload is known to increase cardiac mass and expression levels of both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNAs. Although mechanical stretching of cardiac myocytes could cause these changes, humoral factor(s) secondary to pressure overload may also be involved. To dissociate humoral effects from the effects of mechanical loading on cardiac hypertrophic responses, we examined expression of ANP and BNP at both mRNA and protein levels and proportions of myosin isoforms in transplanted cervical hearts that were mechanically unloaded under conditions with or without hypertension by aortic coarctation. Seven days after transplantation, cardiac atrophy that usually occurs in transplanted hearts without hypertension by coarctation was prevented in the transplanted hearts with hypertension by coarctation. The levels of expression of ANP and BNP mRNAs were increased in the transplanted hearts with relative to those without hypertension by coarctation. The plasma level of angiotensin II was higher in rats with than without hypertension by coarctation. Plasma endothelin-1 levels were not significantly different between the two groups. In addition, levels of expression of ANP and BNP mRNAs were increased in the transplanted hearts without hypertension relative to those in the in situ hearts. The proportion of the V3 myosin isoform was also increased in the transplanted hearts without hypertension relative to the in situ hearts. These results indicate that humoral factor(s) secondary to the pressure overload produced by aortic coarctation enhanced the cardiac hypertrophic response and elevated the levels of mRNAs encoding these embryonic markers. Moreover, our findings regarding ANP and BNP expression in the transplanted hearts provide additional evidence that the fetal genes are reexpressed during the process of cardiac atrophy as well as in cardiac hypertrophy.

Angiotensin II↗

PubMed1997

Development of a membrane fusible drug carrier from erythrocytes by the spontaneous transfer of viral fusion protein from influenza virus-infected cells.

In order to develop a membrane fusible drug carrier from human erythrocytes, we attempted the reconstitution of influenza virus fusion protein hemagglutinin (HA) to an erythrocyte membrane. In this study, we succeeded in the preparation of HA-reconstituted erythrocytes (HA-erythrocytes) by the incubation of erythrocytes with influenza virus-infected CV-1 cells, and confirmed the ability of HA-erythrocytes to fuse with the cell membrane. Furthermore, by using an HA-reconstituted ghost (HA-ghost), which entrapped fluorescent-labeled ovalbumin, 25% of the protein was incorporated into cells through the fusion of the HA-ghost with the cell membrane.

Animals↗

PubMed1997

[Wide occurrence of enterohemorragic Eschrichia coli O157 in natural freshwater environment].

Recent outbreaks of hemorrhagic colitis by Escherichia coli O157 urge us to clarify the source, distribution, and fate of those pathogens. We hypothesized that E. coli O157 enter into viable but nonculturable state (VBNC) so that the conventional culture method fails to detect those strains from natural environment. In the microcosm using sterilized river water, E. coli O157 gradually lost their viability. Total count using epifluorescent microscopy and the direct viable count (DVC), however, stayed almost constant for more than a month, indicating that the cells fell into the VBNC state. In order to see the distribution of E. coli O157 in natural environment, the DVC method and fluorescent antibody technique were applied. All river water samples from five different places in and near Tokyo metropolitan area showed occurrence of cells reacted with the antibody applied. This indicates that E. coli O157 may be widely distributed in freshwater environment as normal inhabitants. The understanding of VBNC state of E. coli O157 should be essential to investigate on the behavior of this pathogen in nature and find out a suitable method to prevent from further outbreaks.

Cell Survival↗

PubMed1997

Molecular and biochemical events within the brain subjected to cerebral ischemia (targets for therapeutical intervention).

We review the molecular and biochemical events that occur within the brain during cerebral ischemia, based on recent investigations of focal cerebral ischemia models. Occlusion of the middle cerebral artery in rats produces focal ischemia. In contrast to the core where ischemia is severe and infarction develops rapidly, areas surrounding the core (called the penumbra) show a more moderate decrease of blood flow and can tolerate longer durations of ischemic stress. Reperfusion and pharmacological interventions can help to salvage the penumbra. Ischemic insult alters the genomic properties of the brain cells and selective production of heat shock proteins can be seen. Heat shock proteins are necessary in the repair of cell integrity, and is thought to be induced as a rescue program. Pre-ischemic induction of these proteins is known to cause ischemic tolerance, and methods to manipulate genes into inducing HSPs may be effective in protecting neurons from ischemia. Genes that promote apoptosis are also expressed after ischemia, and may cause secondary expansion of the infarction. Strategies to denote expression of these genes may be effective in reducing ischemic neuronal death. Activation of the inflammatory cells such as neutrophils and macrophages, in the ischemic region, may cause further post-ischemic damage. Investigations on the role and mechanics of inflammatory systems in ischemic neuronal injury may present a new target for therapeutic intervention against stroke.

Animals↗

PubMed1996

Progressive expression of immunomolecules on activated microglia and invading leukocytes following focal cerebral ischemia in the rat.

In order to evaluate the involvement of inflammatory reactions following focal cerebral ischemia in the rat, we immunohistochemically visualized microglial cells and blood-borne leukocytes (neutrophils and monocytes) using various antibodies directed against immunomolecules expressed on these cells. Focal cerebral ischemia was produced by intraluminal occlusion of the right middle cerebral artery for 1 h. The brains were perfusion-fixed at 4 h, 1 day, 3 days, 7 days and 14 days after ischemia. Frozen brain sections were prepared and stained with monoclonal antibodies to complement receptor type 3 (OX42), major histocompatibility complex (MHC) class I and class II antigens (OX18 and OX6, respectively), a pan-macrophage/monocyte marker (ED1), intercellular adhesion molecule-1 (ICAM-1), LFA-1 alpha chain (CD11a) and beta chain (CD18), and T cells (CD5). In ischemic areas where infarction developed later, microglial cells were destroyed (beginning at 4 h), neutrophils migrated (1-3 days), and then monocytes/macrophages infiltrated and covered the entire lesions (3-14 days). The invading leukocytes expressed CD11 and CD18 adhesion molecules on their cell surface while ICAM-1 was expressed on endothelial cells. In surrounding areas, in contrast, there was a rapid activation of microglia showing morphological changes and upregulation of OX42 immunoreactivity (4 h-7 days), especially in the transitional rim of the infarct (7 days). ED1 and MHC antigens were expressed on both activated microglia and invading leukocytes. Thus, developing infarction was accompanied by accumulation of inflammatory cells of both intrinsic (microglia) and extrinsic (leukocytes) origins. Thus, results suggest that the relative importance of each source is determined by the time after ischemia and the site within the lesion, and that the expression of immunological molecules plays an important role in eliciting such inflammatory reactions.

Animals↗

PubMed1996

Alteration of enzyme function of the type II hexokinase C-terminal half on replacements of restricted regions by corresponding regions of glucokinase.

To know the structural properties responsible for the enzymic activity of the 50-kDa C-terminal half of type II hexokinase (HKII-C) derived from rat hepatoma cell line AH130, we constructed cDNAs of HKII-C and its recombinants in which restricted regions containing highly conserved sequences, referred to as regions 2 and 3, were replaced by the corresponding regions of glucokinase. The binding domains of ATP and glucose were proposed to exist in these regions, respectively. Then, the HKII-C and chimera HKII-Cs were overexpressed in Escherichia coli BL21(DE3)pLysS. They all exhibited hexokinase activity, and their activities were inhibited by glucose-6-phosphate (Glc-6-P) competitively for ATP and uncompetitively for glucose. The replacement of region 2 of HKII-C by the corresponding region of glucokinase increased the affinity for glucose and decreased the affinity for Glc-6-P, but it did not significantly affect the affinity for ATP. In contrast, the replacement of region 3 did not cause an appreciable change in hexokinase activity. These findings suggest that region 2 is associated with the binding of ATP and Glc-6-P, and that the latter binding site is located close to the ATP binding site. In addition, region 2 was suggested to be directly related with the binding of glucose and other hexoses.

Amino Acid Sequence↗

PubMed1996

Effects of cerebral ischemia on dopamine receptors in the gerbil striatum.

Dopamine D1 and D2 receptors and uptake sites were studied in the gerbil striatum and frontal cortex 1 h to 7 days after 10 min of cerebral ischemia caused by occlusion of the bilateral common carotid arteries. [3H]SCH23390 ([N-methyl-3H]R[+]-8-chloro-2, 3,4,5-tetrahydro-3-methyl-5-phenyl-7-ol-benzazepine), [3H]nemonapride and [3H]mazindol were used as markers of dopamine D1 receptors, D2 receptors and uptake sites, respectively. A significant reduction in [3H] SCH23390 binding was found in the striatum from 48 h after ischemia. In contrast, during the recirculation periods, [3H]nemonapride and [3H]mazindol binding was mostly unaffected in this region which was the most vulnerable to ischemia. The frontal cortex, where ischemic neuronal damage was mild, also showed no significant changes in [3H]SCH23390, [3H]nemonapride and [3H]mazindol binding after ischemia. Thus, cerebral ischemia that was associated with cell loss in the striatum resulted in a selective reduction of dopamine D1 receptors and not D2 receptors. No changes in dopamine D1 or D2 receptors were observed in frontal cortex. If massive dopamine release occurs with cerebral ischemia, it is not reflected by modification in the number of uptake sites located on dopamine terminals.

Animals↗

PubMed1996

The effect of long-term post-ischemic bifemelane hydrochloride treatment on cholinergic systems in the gerbil hippocampus.

Bifemelane hydrochloride (BF) is a modulator of various neurotransmitter systems. The effect of BF on the cholinergic system was studied in the gerbil hippocampus at 100 days after ischemic damage. Marked enhancement of AChE staining was noticed in the CA1 of saline-treated animals at 100 days after ischemia, while the post-ischemic enhancement of AChE staining intensity was milder in BF-treated animals. Muscarinic receptor density was markedly decreased in the CA1 subfield after ischemia. Interestingly, BF-treated animals showed higher muscarinic receptor binding in many brain areas, particularly in the dentate gyrus. These results indicate that BF modulates cholinergic neuronal plasticity in the ischemic hippocampus after long-term survival.

Acetylcholinesterase↗