Biomedical subjects

K Abe

Publications and source records attributed to K Abe.

At least 505 records · Page 28Linked to original sources

PubMed2000

[A case of neuro-Behçet's disease with HLA B54 and predominant cerebral white matter lesions].

We report a 55-year-old woman with neuro-Behçet's disease with HLA B54 and predominant cerebral white matter lesions. She showed a cryptogenic high fever and cerebral cortical symptoms such as perseveration, limbkinetic apraxia and dementia. CSF study showed an increase of cell count and protein and a decrease of sugar. MRI showed diffuse T2-high signal intensity mainly in the subcortical white matter of left parieto-occipital lobes and basal ganglia. Her clinical signs greatly improved after administration of prednisolone. Her HLA type was not B51 but B54. Though our patient did not completely satisfy clinical criteria for neither neuro-Behçet's disease nor Sweet's syndrome, she showed partial features of both Behçet's disease and Sweet's syndrome.

Behcet Syndrome↗

PubMed2000

[A case of Gerstmann-Sträussler-Scheinker syndrome (P102L) accompanied by optic atrophy].

We report a patient with Gerstmann-Sträussler-Scheinker syndrome (GSS102) who developed optic atrophy. He had been complaining of slowly progressive postural unsteadiness and pain in both legs for 3 years. Visual acuity subacutely worsened in the last half year. His father and two aunts, who already died, had been diagnosed to have dementia. It is uncertain whether they had optic atrophy or not. He was alert but apathetic. Neurological examination revealed cerebellar ataxia, painful dysesthesia and loss of deep tendon reflexes in the lower limbs. Fundoscopic examination revealed bilateral optic atrophy without retinal degeneration, which has never been reported in GSS. A brain MRI showed mild atrophy of cerebellar hemispheres without signal abnormalities of optic nerves. DNA analysis of prion gene revealed point mutation at codon 102 (P102L), which was relatively common mutation in GSS. Other mutations were not found. Only two patients of Creutzfeldt-Jakob disease with optic atrophy have been reported. This case seems to be important to investigate why optic tracts are generally spared in prion disease.

Gerstmann-Straussler-Scheinker Disease↗

PubMed2000

[Familial pure akinesia].

We report a 67-year-old man and his family presenting pure akinesia (PA). He developed bradykinesia. A neurological examination showed a lack of facial expression but no tremor or rigidity. His eye movement was full, and he had frozen gait and pulsion symptoms. There was no evidence of dementia. Levodopa therapy was not effective. Magnetic resonance imaging revealed no brainstem and cerebellar atrophy. 99mTc-ECD-SPECT had no further abnormality. His father and brother had similar symptoms as him. We conclude that this family is the first reported example of pure akinesia with autosomal dominant inheritance.

Aged↗

PubMed2000

Effects of microiontophoretically-applied opioid peptides on Purkinje cells in the cat cerebellum.

AIM: The purpose of the present study was to examine the effects of microiontophoretically-applied opioid peptides on Purkinje cell of the cerebellum. METHODS: The effects of microiontophoretically-applied morphine, leucine-enkephalin (Leu-Enk), methionine-enkephalin (Met-Enk), and dynorphin 1-13 (Dyn) on the spontaneous discharge of Purkinje cells in the cerebellum of the anesthetized cat were examined. RESULTS: Microiontophoretic applications of Leu-Enk and morphine produced inhibitory and excitatory responses, respectively in Purkinje cells. Application of both morphine and Leu-Enk induced dose-dependent responses. The excitatory responses were antagonized by naloxone, whereas the inhibitory responses were not. Bicuculline, a GABA-A antagonist, completely abolished both the Leu-Enk- and morphine-induced-inhibitory responses. Iontophoretic application of Met-Enk and dyn produced inhibitory responses only. Met-enk- and dyn-induced inhibition was antagonized by naloxone. CONCLUSION: In Purkinje cell activity, microiontophoretically applied Leu-Enk- and morphine-induced excitation is connected with opiate receptors, whereas inhibition is related to the GABA receptor. However, Met-Enk and dyn produced only inhibitory effects via an opiate receptor in the cerebellum of cats.

Action Potentials↗

PubMed1999

Saffron extract prevents acetaldehyde-induced inhibition of long-term potentiation in the rat dentate gyrus in vivo.

We have previously found that alcohol extract of Crocus sativus L. (CSE), commonly known as saffron, prevents ethanol-induced inhibition of hippocampal long-term potentiation (LTP). In the present study, CSE (250 mg/kg, p.o.) was also effective in preventing acetaldehyde-induced inhibition of LTP in the dentate gyrus of anesthetized rats. These results suggest that CSE can prevent aversive effects induced by ethanol and its metabolite acetaldehyde.

Acetaldehyde↗

PubMed1999

Insulin-like growth factor-1 affects expressions of cyclin-dependent kinase 5 and its activator p35 in reperfused rat brain.

Insulin-like growth factor-1 (IGF-1) was applied topically on the brain surface of reperfused rat brain after 60 min of transient middle cerebral artery (MCA) occlusion. In contrast to the cases treated with vehicle, the infarct volume was greatly reduced at 24 h of reperfusion by the treatment with IGF-1. Immunohistochemical analysis in the MCA territory showed that the increase of cyclin-dependent kinase 5 (cdk5) was greatly reduced, and that the decrease of the critical regulatory subunit of cdk5, p35, was preserved with treatment of IGF-1. The present results suggest that IGF-1 has a significant effect on ameliorating brain injury after transient focal brain ischemia with affecting the expressions of cdk5 and its activator p35.

Animals↗

PubMed1999

Selective inhibition of formyl-methionyl-leucyl-phenylalanine (fMLF)-dependent superoxide generation in neutrophils by pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase.

It has been shown previously that inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, such as compactin, lovastatin, and pravastatin, block cholesterol synthesis, suppress lymphocyte functions, and beneficially affect atherogenesis. Recently, it was reported that compactin and lovastatin inhibit the respiratory burst of DMSO-differentiated HL-60 cells, an effect reversed by mevalonic acid. The mode of action of these inhibitors in this role is not understood fully. Thus, we studied the mechanism of inhibition of neutrophil superoxide (O2*-) generation by pravastatin and found that pravastatin at 0.5 mM inhibited the receptor-mediated tyrosine kinase (TK)-dependent pathway of O2*- generation and also luminol chemiluminescence but not the protein kinase C (PKC)-dependent or the TK- and PKC-independent pathways of O2*- generation in neutrophils. Pravastatin also inhibited the tumor necrosis factor-alpha- and formyl-methionyl-leucyl-phenylalanine-induced phosphorylation of a tyrosine of a 115-kDa protein. These effects were not reversed by mevalonate. From these results it is concluded that pravastatin inhibited receptor-mediated O2*-generation by decreasing tyrosine phosphorylation but not by inhibiting the formation of an intermediate in the biosynthesis of cholesterol.

Drug Interactions↗

PubMed1999

Effect of ATP on astrocyte stellation is switched from suppressive to stimulatory during development.

Adenosine 5'-triphosphate (ATP) functions as a neurotransmitter or neuromodulator in the brain. To understand the role of ATP during brain development, we investigated the effects of ATP on morphology of cultured astrocytes obtained from the cerebral cortices of embryonic day 18 (E18) and postnatal day 2 (PN2) rats. In E18 astrocytes, ATP (10-1000 microM) alone did not affect astrocyte morphology, but significantly suppressed astrocyte stellation induced by the beta-adrenoceptor agonist isoproterenol or the membrane-permeable cyclic AMP analog dibutyryl cyclic AMP. The suppressive effect of ATP in embryonic astrocytes was selectively mimicked by P2U purinoceptor agonists. ATP had no effect on stellation induced by the protein kinase C (PKC) activator phorbol ester. It is probable that ATP, via P2U purinoceptors, suppresses cyclic AMP-dependent regulatory mechanism for stellation in embryonic astrocytes. On the other hand, PN2 astrocytes differentiated into stellate cells in response to ATP. The ATP-stimulated stellation in PN2 astrocytes was mimicked by adenosine, and blocked by P1 purinoceptor antagonists. It is probable that ATP is broken down into adenosine, which stimulates P1 purinoceptors, inducing stellation in postnatal astrocytes. These findings suggest that the effect of ATP on astrocyte stellation is switched from suppressive (P2U purinoceptor-mediated) to stimulatory (P1 purinoceptor-mediated) during late embryonic to neonatal stages. ATP may be a critical factor that determines timing of astrocyte differentiation during development.

Adenine Nucleotides↗

PubMed1999

Reduction of tyrosine kinase B and tyrosine kinase C inductions by treatment with neurotrophin-3 after transient middle cerebral artery occlusion in rat.

Infarct volume and immunoreactivities for trkB and trkC in rat brain were compared at 24 h after 90 min of transient middle cerebral artery occlusion (MCAO) between animal groups with or without neurotrophin-3 (NT-3, 10 microg/250 g animal). Treatment of rat brain with topical application of NT-3 significantly reduced infarct volume (P = 0.02) and trkB and trkC inductions. These data suggest that NT-3 reduced the ischemic injury along with the reduction of trkB and trkC inductions.

Administration, Topical↗

PubMed1999

Induction of glial cell line-derived neurotrophic factor and c-ret porto-oncogene-like immunoreactivity in rabbit spinal cord after transient ischemia.

The mechanism of spinal cord injury has been thought to be related with tissue ischemia, and spinal motor neuron cells are suggested to be vulnerable to ischemia. To evaluate the mechanism of such vulnerability of motor neurons, we attempted to make a reproducible model of spinal cord ischemia. Using this model, the inductions of glial cell line-derived neurotrophic factor (GDNF) and the c-ret porto-oncogene (RET) receptor tyrosine kinase were investigated with immunohistochemical analyses for up to 7 days of the reperfusion following 15 min of ischemia in rabbit spinal cord. Spinal cord sections from animals sacrificed at 8 h, 1, 2, and 7 days following the 15 min of ischemia were immunohistochemically evaluated using monoclonal antibodies for GDNF and RET. Following the 15 min of ischemia, the majority of the motor neurons showed selective cell death at 7 days of reperfusion. Immunoreactivity of GDNF and RET were induced at 8 h of reperfusion selectively in motor neuron cells. No glial cells were stained in the spinal cord sections. The induction of GDNF and RET proteins at the early stage of reperfusion may be related to the transient functional recovery of neurons after ischemia.

Animals↗

PubMed1999

Motor neglect following left thalamic hemorrhage: a case report.

We present a report on a patient who developed unilateral motor neglect of the right hemibody after a left thalamic hemorrhage. He presented with pure motor neglect without aphasia, ideomotor apraxia, or unilateral spatial neglect due to a lesion in the centromedian parafascicular (CMPF) and ventrolateral (VL) nuclei of the left thalamus. Although unilateral motor neglect is usually associated with right hemispheric lesions, a left thalamic lesion may also result in isolated motor neglect.

Adult↗

PubMed1999

Cholesterol does not affect the toxicity of amyloid beta fragment but mimics its effect on MTT formazan exocytosis in cultured rat hippocampal neurons.

It has recently been reported that methyl-beta-cyclodextrin-solubilized cholesterol protects PC12 cells from amyloid beta protein (Abeta) toxicity. To ask if this is the case in brain neurons, we investigated its effect in primary cultured rat hippocampal neurons. In basal culture conditions with no addition of Abeta, methyl-beta-cyclodextrin-solubilized cholesterol at concentrations of 30-100 microM was toxic to neurons, but at concentrations of 1-10 microM promoted neuronal survival. Methyl-beta-cyclodextrin-solubilized cholesterol at 1-10 microM was also effective in protecting neurons from toxicity of 20 microM Abeta. However, these effects were all mimicked by methyl-beta-cyclodextrin alone, but not by cholesterol solubilized by dimethylsulfoxide or ethanol. The effects of methyl-beta-cyclodextrin-solubilized cholesterol on neuronal survival and Abeta toxicity are probably attributed to the action of methyl-beta-cyclodextrin, but not cholesterol. Alternatively, we found that methyl-beta-cyclodextrin-solubilized cholesterol at lower concentrations ( > 10 nM) inhibited cellular reduction of 3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide (MTT) by promoting the exocytosis of MTT formazan. This effect was shared by dimethylsulfoxide- or ethanol-solubilized cholesterol, but not by methyl-beta-cyclodextrin, supporting that it is attributed to the action of cholesterol. These results suggest that cholesterol does not protect neurons from Abeta toxicity, or rather inhibits cellular MTT reduction in a similar manner to Abeta.

Amyloid beta-Peptides↗

PubMed1999

In vivo gene transfer of an extracellular domain of platelet-derived growth factor beta receptor by the HVJ-liposome method ameliorates bleomycin-induced pulmonary fibrosis.

A number of investigators have reported augmented expression of PDGF in lungs with idiopathic pulmonary fibrosis (IPF) or with other types of pulmonary fibrosis. To accomplish such a regulation of PDGF activity, we constructed an expression plasmid of the extracellular domain of PDGF receptor beta chain (XR), which lacks intracellular tyrosine kinase domain and transmembrane portions, and estimated the therapeutic effects of XR gene transfer through the trachea on bleomycin-induced lung fibrosis of C57BL/6 mice using the hemagglutinating virus of Japan(HVJ)-liposome method. The XR gene transfer ameliorated the increases in the wet weight and hydroxyproline content and the histopathologic changes of the lung induced by bleomycin. These findings suggest that PDGF plays a crucial role in the pathogenesis of pulmonary fibrosis, and that XR gene transfer using the HVJ-liposome method may limit the progression of pulmonary fibrosis.

Animals↗

PubMed1999

Electrophysiological actions of a novel K(+) channel opener MCC-134 on rabbit portal vein smooth muscle.

The effects of a newly synthesized K(+) channel opener, 1-[4-(1H-imidazol-1-yl)benzoyl]-N-methylcyclobutane-carbothioamide (MCC-134) on membrane currents and intracellular Ca(2+) mobilization were investigated in rabbit portal vein smooth muscle cells. Under voltage-clamped conditions, MCC-134 dose-dependently induced K(+)-selective currents (I(MCC); EC(50) 5.3 microM) showing little desensitization but fast deactivating properties on washout of drugs. I(MCC) was completely blocked by 10 microM glibenclamide, not affected by iberiotoxin (500 nM), charybdotoxin (200 nM) or apamin (500 nM), and inhibited by nonspecific K(+) channel blockers, tetraethylammonium (1-10 mM), 4-aminopyridine (0.1-1 mM) and Ba(2+) (0.01-0.1 mM). Intracellularly applied nucleotide diphosphates (1 mM) were effective at maintaining I(MCC) (apparent potency; ADP<==GDP falling dotsIDP<UDP), whereas intracellular ATP exhibited a biphasic, i.e., augmentative and inhibitory effect(s) on I(MCC). Single channel activities of about 15 pS (40/140 mM extra-/intracellular K(+)) fully accountable for macroscopic I(MCC) were activated by MCC-134. MCC-134, at a concentration as high as 100 microM, suppressed voltage-dependent Ca(2+) and noradrenaline-induced cation currents, and concomitant elevations in the intracellular Ca(2+) concentration ([Ca(2+)](i)).

Adenosine Diphosphate↗

PubMed1999

Second transmembrane segment of FtsH plays a role in its proteolytic activity and homo-oligomerization.

The FtsH (HflB) protein of Escherichia coli is a membrane-bound ATP-dependent zinc protease. The role(s) of the N-terminal membrane-anchoring region of FtsH were studied by fusion with a maltose-binding protein (MBP) at five different N-termini of FtsH. The MBP-FtsH fusions were expressed in the cytoplasm of E. coli, and were purified as soluble proteins. The four longer constructs, which have a second transmembrane segment and the C-terminal cytoplasmic region in common, retained ATP-dependent protease activity toward heat-shock transcription factor sigma(32), and were found to be homo-oligomers. In contrast, the shortest construct which has the C-terminal cytoplasmic region but not the second transmembrane segment showed neither protease activity nor oligomerization. Therefore, the second transmembrane segment, which neighbors the C-terminal cytoplasmic region of the FtsH, participates in not only its membrane-anchoring, but also its protease activity and homo-oligomerization.

ATP-Binding Cassette Transporters↗

PubMed1999

Acid-labile ATP and/or ADP/P(i) binding to the tetraprotomeric form of Na/K-ATPase accompanying catalytic phosphorylation-dephosphorylation cycle.

The Na/K-ATPase has been shown to bind 1 and 0.5 mol of (32)P/mol of alpha-chain in the presence [gamma-(32)P]ATP and [alpha-(32)P]ATP, respectively, accompanied by a maximum accumulation of 0.5 mol of ADP-sensitive phosphoenzyme (NaE1P) and potassium-sensitive phosphoenzyme (E2P). The former accumulation was followed by the slow constant liberation of P(i), but the latter was accompanied with a rapid approximately 0.25 mol of acid-labile P(i) burst. The rubidium (potassium congener)-occluded enzyme (approximately 1.7 mol of rubidium/mol of alpha-chain) completely lost rubidium on the addition of sodium + magnesium. Further addition of approximately 100 microM [gamma-(32)P]ATP and [alpha-(32)P]ATP, both induced 0.5 mol of (32)P-ATP binding to the enzyme and caused accumulation of approximately 1 mol of rubidium/mol of alpha-chain, accompanied by a rapid approximately 0.5 mol of P(i) burst with no detectable phosphoenzyme under steady state conditions. Electron microscopy of rotary-shadowed soluble and membrane-bound Na/K-ATPases and an antibody-Na/K-ATPase complex, indicated the presence of tetraprotomeric structures (alphabeta)(4). These and other data suggest that Na/K-ATP hydrolysis occurs via four parallel paths, the sequential appearance of (NaE1P:E.ATP)(2), (E2P:E.ATP:E2P:E. ADP/P(i)), and (KE2:E.ADP/P(i))(2), each of which has been previously referred to as NaE1P, E2P, and KE2, respectively.

Adenosine Diphosphate↗

PubMed1999

Involvement of NH(2)-terminal sequences in the negative regulation of Vav signaling and transforming activity.

Deletion of the NH(2)-terminal 65 amino acids of proto-Vav (to form onco-Vav) activates its transforming activity, suggesting that these sequences serve a negative regulatory role in Vav function. However, the precise role of these NH(2)-terminal sequences and whether additional NH(2)-terminal sequences are also involved in negative regulation have not been determined. Therefore, we generated additional NH(2)-terminal deletion mutants of proto-Vav that lack the NH(2)-terminal 127, 168, or 186 amino acids, and assessed their abilities to cause focus formation in NIH 3T3 cells and to activate different signaling pathways. Since Vav mutants lacking 168 or 186 NH(2)-terminal residues showed a several 100-fold greater focus forming activity than that seen with deletion of 65 residues, residues spanning 66 to 187 also contribute significantly to negative regulation of Vav transforming activity. The increase in Vav transforming activity correlated with the activation of the c-Jun, Elk-1, and NF-kappaB transcription factors, as well as increased transcription from the cyclin D1 promoter. Tyrosine 174 is a key site of phosphorylation by Lck in vitro and Lck-mediated phosphorylation has been shown to be essential for proto-Vav GEF function in vitro. However, we found that an NH(2)-terminal Vav deletion mutant lacking this tyrosine residue (DeltaN-186 Vav) retained the ability to be phosphorylated by Lck in vivo and Lck still caused enhancement of DeltaN-186 Vav signaling and transforming activity. Thus, Lck can stimulate Vav via a mechanism that does not involve Tyr(174) or removal of NH(2)-terminal regulatory activity. Finally, we found that NH(2)-terminal deletion enhanced the degree of Vav association with the membrane-containing particulate fraction and that an isolated NH(2)-terminal fragment (residues 1-186) could impair DeltaN-186 Vav signaling. Taken together, these observations suggest that the NH(2) terminus may serve as a negative regulator of Vav by intramolecular interaction with COOH-terminal sequences to modulate efficient membrane association.

3T3 Cells↗

PubMed1999

Specific direct radioimmunoassay of angiotensin II (AT II) in human plasma and the effect of angiotensin converting enzyme (ACE) inhibitor.

Specific direct radioimmunoassay of angiotensin II (AT II) in human plasma was developed to evaluate the dynamics of endogenous AT II in various types of hypertension. Detection limit of this method was less than 2.3 pg/ml, and normal value is less than 25 pg/ml. Cross reactivity of antibody with AT I and III was 0.037% and 21%, respectively. There were good correlation between the value measured by direct method, and that of extraction method (r = 0.96, P < 0.01) and plasma renin activity (r = 0.80, P < 0.01). By oral administration of ACE inhibitor (captopril 50 mg), AT II levels were suppressed to 10 pg/ml or less in most patients with essential hypertension, renal parenchymal hypertension and renovascular hypertension up to 2 h. However, AT II levels in patients treated with ACE inhibitors chronically were not different from the AT II levels in patients without ACE inhibitor. In primary aldosteronism AT II was extremely low levels. AT II markedly increased by the stimulation test using furosemide (1 mg/kg i.v.). These results suggest that this method may be useful to clarify the pathophysiology of hypertension and the escape of the inhibition by ACE inhibitor.

Angiotensin II↗