Biomedical subjects

K Abe

Publications and source records attributed to K Abe.

At least 523 records · Page 29Linked to original sources

PubMed1999

Changes in prostacyclin, thromboxane A2 and F2-isoprostanes, and influence of eicosapentaenoic acid and antiplatelet agents in patients with hypertension and hyperlipidemia.

Prostacyclin (PGI2), thromboxane A2 (TXA2) and F2-isoprostanes, prostaglandin F2-like compounds, have wide and contrasting spectrum of biological activities and may influence blood pressure and atherogenesis. To investigate the dynamics of PGI2, TXA2 and F2-isoprostanes in patients with hypertension and hyperlipidemia (HH group), we measured the major urinary metabolites of PGI2: 6-keto PGF1alpha (Keto) and 2,3-dinor-6-keto PGF1alpha, (Dinor), those of TXA2:TXB2 and 11-dehydro TXB2 (Dehydro), and urinary 8-isoprostane (Iso) in 34 patients. Urinary excretion of Dinor was significantly lower in patients than in controls and that of Dehydro was significantly higher in patients than in controls. Keto, TXB2 and Iso were not significantly different between them. Antiplatelet agents decreased not only TXA2 metabolites but also PGI2 metabolites. Urinary C-peptide immunoreactivity was correlated with Dinor and Dehydro. After administration of eicosapentaenoic acid (EPA), total cholesterol (T-cho) and triglycerides (TG) significantly decreased. Although prostanoids did not show significant change, changes in T-cho were correlated with changes in Dinor and changes in Iso. These results suggest that PGI2 and TXA2 of systemic origin might be related to the pathophysiology of hypertension and hyperlipidemia and that the dynamics of PGI2, TXA2 and F2-isoprostanes might be related to not only blood pressure regulation but also lipid and glucose metabolism.

Aspirin↗

PubMed1999

Therapeutic advantage of angiotensin converting enzyme inhibitors in chronic glomerulonephritis.

Hypertension in chronic progressive renal disease is a major clinical problem leading to renal function loss. We studied the influence of ambulatory blood pressure (ABP) and the effect of hypertension therapy on renal function in 116 patients with chronic glomerulonephritis. Patients were subdivided as hypertensive, normotensive and hypotensive according to the level of ABP and age. Hypotensive subjects showed improvement of renal function and normotensive subjects showed slower rate of progression of renal function loss than hypertensives, suggesting the adequate level of ABP was 100-125/55-75 mm Hg in patients less than 40 years old, 100-135/60-80 mm Hg in patients 40-60 years old, and 105-140/60-85 mm Hg in patients over 60 years, respectively. The renal protection of calcium antagonists was associated with achieving lower blood pressure levels, whereas the blood pressure level did not affect progression of renal function in patient treated with angiotensin converting enzyme (ACE) inhibitor. ACE inhibitor, but not calcium antagonists, showed a reduction of urinary protein excretion. Thus, the mechanisms of renal protection were different between ACE inhibitors and calcium antagonists.

Adolescent↗

PubMed1999

Immunoreactive Akt, PI3-K and ERK protein kinase expression in ischemic rat brain.

In order to clarify the role of protein kinases in ischemic brain injury, the spatiotemporal expression of immunoreactive serine-threonine kinase Akt, phosphatidylinositol 3-kinase (PI3-K) and extracellular signal-regulated kinase (ERK) were examined at 3, 8, or 24 h after permanent middle cerebral artery occlusion (MCAO) in rats. Weak staining for these protein kinases was found in both cortical and caudate neurons in sham controls. The staining for Akt-1 and PI3-K was increased at 3-8 h in the ischemic penumbral region and declined at 24 h. A slight induction of these kinases was observed in the ischemic core region. Robust expression of ERK was noted at 3-8 h in most neurons in the area of ischemia. At 24 h, ERK continued to be expressed in the ischemic penumbra, but decreased in the ischemic core. These findings suggest that the signaling for Akt and PI3-K are different from the ERK dependent signal transduction during ischemic brain injury.

Animals↗

PubMed1999

Genetic association analysis between CYP2D6*2 allele and tardive dyskinesia in schizophrenic patients

Previous studies have shown a possible association between tardive dyskinesia (TD) and debrisoquine 4-hydroxylase (CYP2D6) polymorphisms, which result in absent enzyme activity. We have recently found a positive association between TD and the CYP2D6*10 allele, which codes for the intermediate metabolizer (IM) phenotype and is characterized by decreased but not absent CYP2D6 activity in Japanese schizophrenic patients. In addition, the CYP2D6* 2 allele with the HhaI site mutation in exon 6 has also been reported to be an IM allele and a risk factor for Parkinson's disease (PD) in the Japanese population. In the present study, we investigated potential contributions of the CYP2D6*2 allele to TD using case-control and regression analysis in 99 schizophrenic patients. No significant differences in genotypic and allelic frequencies were found between patients with and without TD. Even after using regression analysis to adjust for the confounding variables, there was no significant association of the CYP2D6*2 genotype with either outcome variable, the occurrence of TD or the total AIMS score. These results suggest that the CYP2D6*2 allele may not contribute to the pathogenesis of TD.

Journal Article↗

PubMed1999

Rat liver in vivo replicative DNA synthesis test for short-term prediction of nongenotoxic (Ames-negative) hepatocarcinogenicity: a collaborative study of the Nongenotoxic Carcinogen Study Group of Japan.

A collaborative study was conducted to evaluate whether a replicative DNA synthesis (RDS) test using the rat liver can detect nongenotoxic (Ames-negative) hepatocarcinogens with three or seven daily administrations at dose-levels effective in long-term bioassays. The assay methods were well-validated by the 14 participants. Of six compounds tested, carbon tetrachloride (50 and 100 mg/kg), clofibrate (125 and 250 mg/kg), diethylstilbestrol (0.125 and 0.25 mg/kg) and urethane (100 mg/kg) gave positive results, methyl carbamate (200 and 400 mg/kg) exerted equivocal effects, and D,L-ethionine (125 mg/kg) failed to elevate RDS. These findings suggest that the RDS test can detect many nongenotoxic rat hepatocarcinogens with short-term administration at dose-levels used in long-term bioassays.

Animals↗

PubMed1999

Topical application of neurotrophin-3 attenuates ischemic brain injury after transient middle cerebral artery occlusion in rats.

In order to examine the effect of neurotrophin-3 (NT-3) on ischemic brain injury, NT-3 was topically applied to brain surface just after 90 min of middle cerebral artery occlusion (MCAO) in rats. NT-3 significantly reduced the infarct size at 24 h of reperfusion. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick labeling (TUNEL) staining and immunohistochemical study for caspase-3 and heat shock protein 72 (HSP72) showed that NT-3 treatment decreased the number of cells with DNA fragmentation and caspase-3 and HSP72 expressions. These data suggest that NT-3 protects neuronal cells from ischemic injury, and it is possibly associated with inhibition of DNA fragmentation.

Administration, Topical↗

PubMed1999

Preferential impairment of nitric oxide-mediated endothelium-dependent relaxation in human cervical arteries after irradiation.

BACKGROUND: Vascular abnormalities are a major cause of postoperative complications in irradiated tissues. Endothelial cell dysfunction characterized by diminished endothelium-dependent relaxation may be involved. We examined the endothelium-dependent relaxation and morphology of the endothelium in irradiated human cervical arteries. METHODS AND RESULTS: Irradiated arteries were taken from the neck region of patients who had radiation therapy. Arteries from patients who did not receive radiation therapy were used as controls. Endothelium-dependent relaxation to acetylcholine and A23187 was impaired in irradiated arteries. Norepinephrine-induced contraction and sodium nitroprusside-induced relaxation were unchanged. In control arteries, N(omega)-nitro-L-arginine and indomethacin each caused a partial inhibition of endothelium-dependent relaxation. In irradiated arteries, the impaired endothelium-dependent relaxation was unaffected by these agents, but it was abolished by high K(+). Acetylcholine produced similar degrees of hyperpolarization in control and irradiated arteries. Immunohistochemical examination for endothelial nitric oxide synthase indicated no expression in the endothelium of irradiated arteries. Electron scanning microscopy showed morphologically intact endothelial cells in irradiated arteries. CONCLUSIONS: In irradiated human cervical arteries, the nitric oxide- and prostacyclin-mediated endothelium-dependent relaxation, but not endothelium-derived hyperpolarizing factor-mediated relaxation, are specifically impaired, without significant morphological damage of the endothelium. The impaired nitric oxide-mediated relaxation was associated with a lack of endothelial nitric oxide synthase expression. Our results suggest the importance of impaired endothelial function in irradiated human blood vessels, which may partly explain the development of vascular stenosis and poor surgical wound healing in irradiated tissues.

Acetylcholine↗

PubMed1999

Astrocyte stellation induced by tyrosine kinase inhibitors in culture.

To understand the role of tyrosine kinases in regulation of astrocyte morphology, we investigated the effects of tyrosine kinase inhibitors on morphology of cultured rat cortical astrocytes. Cultured astrocytes exhibited flattened, polygonal morphology in the absence of stimulation, but changed into process-bearing stellate cells in the presence of the tyrosine kinase inhibitor genistein (3-100 microM). Genistein-induced astrocyte stellation was abolished by treatment with colchicine or paclitaxel, indicating the involvement of cytoskeletal elements. The effect of genistein was mimicked by another tyrosine kinase inhibitor herbimycin A, but not by daidzein, an inactive analog of genistein. These results suggest that tyrosine kinases are in an activated state in the absence of stimuli and contribute to the maintenance of polygonal morphology of cultured astrocytes.

Animals↗

PubMed1999

A novel transgenic technique that allows specific marking of the neural crest cell lineage in mice.

Neural crest cells are embryonic, multipotent stem cells that give rise to various cell/tissue types and thus serve as a good model system for the study of cell specification and mechanisms of cell differentiation. For analysis of neural crest cell lineage, an efficient method has been devised for manipulating the mouse genome through the Cre-loxP system. We generated transgenic mice harboring a Cre gene driven by a promoter of protein 0 (P0). To detect the Cre-mediated DNA recombination, we crossed P0-Cre transgenic mice with CAG-CAT-Z indicator transgenic mice. The CAG-CAT-Z Tg line carries a lacZ gene downstream of a chicken beta-actin promoter and a "stuffer" fragment flanked by two loxP sequences, so that lacZ is expressed only when the stuffer is removed by the action of Cre recombinase. In three different P0-Cre lines crossed with CAG-CAT-Z Tg, embryos carrying both transgenes showed lacZ expression in tissues derived from neural crest cells, such as spinal dorsal root ganglia, sympathetic nervous system, enteric nervous system, and ventral craniofacial mesenchyme at stages later than 9.0 dpc. These findings give some insights into neural crest cell differentiation in mammals. We believe that P0-Cre transgenic mice will facilitate many interesting experiments, including lineage analysis, purification, and genetic manipulation of the mammalian neural crest cells.

Animals↗

PubMed1999

Diffusion-weighted and magnetization transfer imaging of the corpus callosum in Alzheimer's disease.

We investigated structural changes of the corpus callosum in patients with Alzheimer's disease (AD) using sagittal diffusion-weighted (DW) and magnetization transfer (MT) imaging. Patients with AD (n=23) had a significantly decreased area only in the posterior portion of the corpus callosum. Apparent diffusion coefficient (ADC) values perpendicular to the commisural fiber orientation were significantly higher in the anterior portion of the corpus callosum without definite atrophy, as well as in the posterior portion with significant atrophy, in patients with AD than in controls (n=16) and thus diffusion in these regions showed a significantly lower degree of anisotropy in patients than in controls. MT ratios were also significantly lower in patients with AD in the anterior and posterior portions of the corpus callosum than in controls. These findings probably reflect structural changes in the corpus callosum including axonal loss and/or demyelination. DW and MT imagings may be useful in detecting degeneration of the corpus callosum in AD.

Aged↗

PubMed1999

Regulation of vascular endothelial growth factor production and angiogenesis by the cytoplasmic tail of tissue factor.

Tissue factor (TF), a transmembrane receptor for coagulation factor VII/VIIa, is aberrantly expressed in human cancers. We demonstrated a significant correlation between TF and vascular endothelial growth factor (VEGF) production in 13 human malignant melanoma cell lines (r(2) = 0.869, P < 0.0001). Two of these cell lines, RPMI-7951, a high TF and VEGF producer, and WM-115, a low TF and VEGF producer, were grown s.c. in severe combined immunodeficient mice. The high-producer cell line generated solid tumors characterized by intense vascularity, whereas the low producer generated relatively avascular tumors, as determined by immunohistologic staining of tumor vascular endothelial cells with anti-von Willebrand factor antibody. To investigate the structure-function relationship of TF and VEGF, a low-producer melanoma cell line (HT144) was transfected with a TF cDNA containing the full-length sequence, a cytoplasmic deletion mutant lacking the coding sequence for the distal three serine residues (potential substrates for protein kinase C), or an extracellular domain mutant, which has markedly diminished function for activation of factor X. Cells transfected with the full-length sequence produced increased levels of both TF and VEGF. Transfectants with the full-length sequence and the extracellular domain mutant produced approximately equal levels of VEGF mRNA. However, cells transfected with the cytoplasmic deletion mutant construct produced increased levels of TF, but little or no VEGF. Thus, the cytoplasmic tail of TF plays a role in the regulation of VEGF expression in some tumor cells.

Animals↗

PubMed1999

Induction of glial cell line-derived neurotrophic factor receptor proteins in cerebral cortex and striatum after permanent middle cerebral artery occlusion in rats.

In an attempt to elucidate whether glial cell line-derived neurotrophic factor (GDNF) receptors are induced after ischemic brain injury, possible expression of immunoreactive GDNF receptor-alpha1 (GFRalpha-1) and c-ret (RET) was examined at 3, 8, or 24 h after permanent middle cerebral artery occlusion (MCAO) in rats. Immunohistochemical study showed that both GFRalpha-1 and RET staining cells which were not detected in sham control brain, were present in the ipsilateral cortex and caudate at 3 to 8 h after permanent MCAO, and then decreased but remained to some extent at 24 h. Positive cells for both GDNF receptors were predominantly in cortical neurons of ischemic penumbral area. Western blot analysis confirmed the induction of those receptors after permanent MCAO. This rapid induction of GFRalpha-1 and RET, which correlates with the similar induction of GDNF under these conditions, may play a role in the early response to ischemic brain injury.

Animals↗

PubMed1999

Magnetization transfer ratio in cerebral white matter lesions of Binswanger's disease.

We measured the magnetization transfer (MT) ratios in white matter lesions of Binswanger's disease (BD) and compared them with BD and with similar-appearing changes in non-demented elderly subjects and cerebral infarction. Four subject groups were studied: 30 patients with BD and periventricular hyperintensity (PVH) on MRI, 29 patients with ischemic cerebrovascular event with PVH but no dementia, 17 patients with old cerebral infarction, and 26 elderly control subjects. MT ratios were calculated for areas of PVH in BD and non-demented subjects, of infarction, and of normal-appearing white matter in controls. The decrease in MT ratios for areas in PVH of non-demented subjects and BD and in infarction compared with normal white matter in controls was 12, 20, and 35%, respectively. The MT ratio in PVH of BD was significantly lower than that in PVH of non-demented subjects, but not to the levels seen in areas of infarction. There was a significant high correlation between the Mini-Mental State Examination score and MT ratio for area of PVH (r = 0.790). MT ratio distinguishes PVH in BD patients from those in non-demented subjects, suggesting underlying histopathological differences. Tissue damage in white matter lesions of BD may be more severe than that in non-demented subjects, but not as much as with complete infarction.

Aged↗

PubMed1999

Oxidative damage and breakage of DNA in rat brain after transient MCA occlusion.

As thrombolytic therapy for treatment of ischemic stroke was propagated, much attention has been paid to reperfusion brain injury. Oxidative stress is one of the most important factors that exacerbate tissue damage by reperfusion. Thus, we investigated the extent of oxidative damage in rat brain after transient middle cerebral artery (MCA) occlusion by immunohistochemical analysis for 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is one of the best markers of oxidative damage. Furthermore, in order to investigate its role in neuronal cell death, we performed terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) study, and compared the results with that of 8-OHdG immunohistochemistry. There was no immunoreactive 8-OHdG in sham-operated brain, but it became present in neurons of MCA territory at 3 h of reperfusion after 90-min ischemia. At 48 h after reperfusion, cerebral tissue of MCA territory was severely destroyed, and many cells in that area revealed TUNEL positivity. Some neurons in MCA territory showed mild immunoreactivity for 8-OHdG at that time, but it was strongest in neurons in the outer area of MCA territory. Those cells did not show TUNEL positivity, suggesting that 8-OHdG production is not necessarily followed by early cell death. Here, it was demonstrated that oxidative DNA damage occurs in more extended area than that where cell death is recognized. Although this damage does not cause early cell death, this might result in more prolonged cell dysfunction and eventual neuronal loss. Anti-oxidant therapy might be required for treatment of stroke in the future.

Animals↗

PubMed1999

Both oxidative stress-dependent and independent effects of amyloid beta protein are detected by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) reduction assay.

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay has been widely used for evaluating amyloid beta protein (Abeta) toxicity. However, the potency of Abeta in inhibiting cellular MTT reduction and the underlying mechanism have been reported with some discrepancies among researchers. To understand what makes such discrepancies, the effect of Abeta detected by MTT reduction assay was re-examined in detail by using cultured rat hippocampal neurons. Micromolar concentrations (>10 microM) of Abeta caused a decrease in cell viability, which resulted in a decrease in MTT reduction per well regardless of assay time. The micromolar Abeta-induced decrease of cellular MTT reduction was significantly attenuated by antioxidants (catalase, propyl gallate or Trolox). On the other hand, nanomolar Abeta did not affect cellular MTT reduction activity at an initial stage of assay (<1 h), and decreased the total production of MTT formazan by accelerating the exocytosis of MTT formazan when MTT assay was performed for a longer time (>2 h). The assay time-dependent, nanomolar Abeta-induced decrease of cellular MTT reduction was not at all affected by antioxidants. Furthermore, subtoxic concentration of H2O2 failed to mimic the effect of nanomolar Abeta on MTT reduction. These results indicate that micromolar Abeta-induced, oxidative cell death is detected by MTT assay regardless of assay time, whereas nanomolar Abeta-induced acceleration of MTT formazan exocytosis is not mediated by oxidative stress and detected only when MTT assay is performed for a longer time. The time of MTT assay should be properly chosen depending on the purpose of the study.

Amyloid beta-Peptides↗

PubMed1999

Stimulation of the 5-HT1A receptor selectively suppresses NMDA receptor-mediated synaptic excitation in the rat visual cortex.

We have previously found that stimulation of serotonin 5-HT1A receptors inhibits the induction of long-term potentiation (LTP) in the rat visual cortex. In the present study, the selective 5-HT1A receptor agonist 8-hydroxy-2-(N,N-dipropylamino)tetralin (8-OH-DPAT) significantly reduced N-methyl-d-aspartate (NMDA) receptor-mediated synaptic responses recorded in Mg2+-free medium in rat visual cortical slices. In addition, there was good correlation between the inhibitory effects of 8-OH-DPAT on NMDA responses and LTP. These results suggest that 5-HT1A receptor stimulation inhibits the induction of LTP by suppressing NMDA receptor-mediated synaptic excitation in the rat visual cortex.

2-Amino-5-phosphonovalerate↗

PubMed1999

Absence of hepatitis G virus within liver tissue of patients undergoing liver transplantation for cryptogenic cirrhosis.

BACKGROUND: Epidemiological studies have detected up to a 9% incidence of hepatitis G (HGV)-RNA in patients with acute and chronic liver disease of unknown etiology. We sought to clarify the role of HGV as a causative agent in cryptogenic cirrhosis by analyzing archival liver tissue for HGV-RNA in patients undergoing orthotopic liver transplantation. METHODS: Using a computer database, we identified 54 patients who underwent orthotopic liver transplantation for cryptogenic cirrhosis. After using rigorous serologic and histopathologic screening guidelines, 20 patients were studied, 7 of whom had concurrent hepatocellular carcinoma (HCC). RNA was extracted from archival paraffin-embedded liver tissue; HGV sequences were amplified by nested reverse transcription-polymerase chain reaction using primers designed from the 5' noncoding region. RESULTS: HGV-RNA was absent from all 20 liver specimens, including those 7 with HCC. Beta-actin RNA, used as a positive control for cellular RNA, was isolated from all 20 liver specimens, including the 7 with HCC. CONCLUSIONS: Utilizing a highly sensitive reverse transcription-polymerase chain reaction assay for HGV-RNA, we were unable to detect HGV-RNA within the livers of patients with cryptogenic cirrhosis or in the HCC arising within them. This lends further evidence to HGV infection not being a cause of cryptogenic cirrhosis and not being associated with the development of HCC in cryptogenic cirrhosis.

Actins↗

PubMed1999

Anti-P-selectin antibody attenuates rat brain ischemic injury.

We examined a protective effect of anti-P-selectin monoclonal antibody against rat ischemic brain injury with 24 h of middle cerebral artery occlusion (MCAO). Anti-rat P-selectin monoclonal antibody, was intravenously injected at a dose of 1 mg/kg at 5 min before MCAO. Control animals received the same volume of vehicle. MCAO was accomplished by an insertion of nylon thread with silicone coating for 24 h. Application of anti-P-selectin antibody significantly reduced infarct size and brain water content at 24 h of MCAO. Although leukocyte infiltration was not normally detected, it became remarkably evident at 1 day of MCAO. However, treatment with ARP 2-4 significantly reduced the number of leukocytes. These results demonstrated that administration of monoclonal antibody against P-selectin attenuated infarct size and brain edema, which was associated with reduction of leukocyte infiltration.

Animals↗