Biomedical subjects

H Kato

Publications and source records attributed to H Kato.

At least 19 recordsLinked to original sources

PubMed1992

Adenosine A2 receptor antagonist facilitates the reversal of long-term potentiation (depotentiation) of evoked postsynaptic potentials but inhibits that of population spikes in hippocampal CA1 neurons.

The effects of the adenosine A2 receptor antagonist CP-66713 on the reversal of long-term potentiation (LTP) were studied in CA1 neurons of guinea pig hippocampal slices. Reduction of LTP (depotentiation, DP) was effected by delivering a train of low-frequency afferent stimuli (depotentiation stimulation, DPS) which was given 20 min after tetanus (100 Hz, 100 pulses). DPS (1 Hz, 1000 pulses) was applied during perfusion of CP-66713 (10 microM). In the presence of CP-66713, DPS reduced the potentiated component of the slope of the field EPSP (S-EPSP) and the amplitude of the population spike (A-PS) by 101.7% and 19.1% of the potentiated amount, respectively (mean, n = 8). The reduction of LTP of the S-EPSP was significantly larger than the control (68.5% (mean, n = 6)) while that of the A-PS was significantly smaller than the control (80.1% (mean, n = 6)). Based on these results, we conclude that the inhibition of DP in the EPSP, the facilitation of DP in the PS, and the consequent attenuation in the EPSP-PS relationship follow from activation of adenosine A2 receptors.

Animals↗

PubMed1992

The helix-loop-helix/leucine repeat transcription factor USF can be functionally regulated in a redox-dependent manner.

We showed previously that the DNA-binding capacity of the helix-loop-helix/leucine repeat transcription factor USF43 is lowered dramatically under nonreducing conditions. This report defines the molecular basis of this effect by showing (i) that the only two USF43 cysteine residues, both present within the helix-loop-helix protein-protein interface domain, are required for this regulation, (ii) that the sulfhydryl groups of these cysteine residues are the actual targets of this regulation, (iii) that oxidation of these groups results in both intra- and intermolecular nonrandom covalent links, (iv) that this redox modulation of USF43 DNA-binding potential can translate in vitro into a specific modulation of its ability to activate transcription from a USF-responsive promoter. The implications of these modulations of USF43 function in response to redox changes are discussed with regard to the apparent paradox of USF strong activation potential and its ubiquitous distribution in all cell types tested.

Amino Acid Sequence↗

PubMed1992

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

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

Animals↗

PubMed1992

Adult coronary artery disease probably due to childhood Kawasaki disease.

We have surveyed adult survivors of childhood Kawasaki disease (KD) who had coronary artery disease that could be ascribed to KD. In response to questionnaires sent to cardiologists throughout Japan, 21 patients (17 men, 4 women, aged 20-63 years) with coronary lesions and a definite (2) or suspected (19) history of KD were reported. 5 patients had presented with acute myocardial infarction, 6 previous myocardial infarction, 9 angina pectoris, and 1 dilated cardiomyopathy. 16 patients had obstructions in two or more coronary arteries. 3 had died and 18 were alive with serious sequelae (mitral regurgitation, arrhythmias, congestive heart failure). Childhood KD should be included in the differential diagnosis of coronary artery disease in young adults.

Adult↗

PubMed1992

Glucocorticoids increase Ca2+ influx through dihydropyridine-sensitive channels linked to activation of protein kinase C in vascular smooth muscle cells.

To clarify whether protein kinase is associated with glucocorticoid-induced Ca2+ influx into vascular smooth muscle cells, we investigated the effects of protein kinase inhibitors on dexamethasone-induced 45Ca2+ uptake and dihydropyridine binding in A7r5 cells. Protein kinase C inhibitors (staurosporine and UCN-01) abolished the dexamethasone-induced 45Ca2+ uptake and [methyl-3H]PN 200-110 binding. In contrast, KT5720 and KT5823, which are more specific inhibitors of cAMP-dependent protein kinase and cGMP-dependent protein kinase, respectively, did not affect the effects of dexamethasone. Treatment with 100 nM dexamethasone for 48 hours increased protein kinase C activity in A7r5 cells. These results suggest that glucocorticoids increase Ca2+ influx through dihydropyridine-sensitive channels, linked to activation of protein kinase C in vascular smooth muscle cells.

Alkaloids↗

PubMed1992

Effects of alkyl substitutions of xanthine skeleton on bronchodilation.

Structure-activity relationships in a series of 1,3,7-trialkyl-xanthine were studied with guinea pigs. Relaxant actions in the tracheal muscle were increased with alkyl chain length at the 1- and 3-positions of the xanthine skeleton, but decreased by alkylation at the 7-position. Positive chronotropic actions in the right atrium were potentiated with 3-alkyl chain length but tended to decrease with 1-alkylation and diminish by 7-substitution. Consequently, while the 1- and 3-substitutions were equally important for the tracheal smooth muscle relaxation, the substitution at the 1-position was more important than the 3-substitution for bronchoselectivity. The 7-alkylation may be significant to cancel heart stimulation. There were good correlations between the smooth muscle relaxant action and the cyclic AMP-PDE inhibitory activity in 3-substituents and the affinity for adenosine (A1) receptors in 1-, 3-, and 7-substituents. This suggests that not only the cyclic AMP-PDE inhibitory activity but also the adenosine antagonistic activity is important in the bronchodilatory effects of alkylxanthines. Among these xanthine derivatives, 1-butyl-3-propylxanthine and its 7-methylated derivative showed high bronchoselectivity in the in vitro and in vivo experiments compared to theophylline and enprofylline and may be new candidates for bronchodilator.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1992

Surgical treatment of thoracic esophageal carcinoma directly invading the lung.

BACKGROUND: The authors examined 63 patients with thoracic esophageal carcinoma directly invading the adjacent lung. Four of them had esophago-pulmonary fistulas. One patient received exploratory thoracotomy and exposure to radiation, and 62 underwent esophagectomy with mediastinal and abdominal lymph node dissection. A resection of the seized lung and the esophagus was performed in 39 patients (Group A), and 23 received esophagectomy with part of the tumor remaining intact (Group B). METHODS: The results of treatment were compared between the two groups. RESULTS: Operative blood loss, mortality, and complications in both groups showed no difference. The average number of dissected lymph nodes in Group A was significantly larger than that in Group B (P less than 0.01). Histologic examination revealed that 22 (56.4%) lesions in Group A invaded the pulmonary parenchyma, a finding that indicates the difficulty of gross diagnosis of tumor infiltration. Five-year survival rates for patients in Groups A and B were 21.1% and 8.7%, respectively. The survival curve for patients in Group A was significantly better than for those in Group B (P less than 0.05). CONCLUSIONS: Pulmonary resection and aggressive lymph node dissection are recommended for patients with esophageal carcinoma that invades the adjacent lung.

Aged↗

PubMed1992

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

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

Amino Acids↗

PubMed1992

Purification and properties of aminopeptidase H from chicken skeletal muscle.

Aminopeptidase H was purified from fresh chicken breast muscle by ammonium sulfate fractionation and successive chromatographies on DEAE-cellulose, Ultrogel AcA 34, activated thiol-Sepharose 4B, phenyl-Sepharose CL-4B and DEAE-cellulose again. The purified enzyme migrated as a single band on SDS/PAGE. Aminopeptidase H exhibits activity against both L-leucine beta-naphthylamide and alpha-N-benzoyl-DL-arginine beta-naphthylamide. The molecular mass of this enzyme was found to be 52 kDa on SDS/PAGE and 400 kDa on Sepharose 6B column chromatography. The optimum pH for the hydrolysis of both substrates was 8.0 and this activity was remarkably enhanced by reducing agents. The enzyme was strongly inhibited by monoiodoacetate and leupeptin, but not affected by EDTA, phenylmethylsulfonyl fluoride, pepstatin, bestatin or puromycin. Aminopeptidase H has been shown to hydrolyze di-, tri- and tetrapeptides in the manner of an aminopeptidase, as well as the beta-naphthylamide derivatives of amino acids. However, the enzyme has not been shown to hydrolyze proteins such as hemoglobin, bovine serum albumin, myofibrillar proteins or sarcoplasmic proteins.

Amino Acid Sequence↗

PubMed1992

Protection of rat hippocampus against ischemic neuronal damage by pretreatment with sublethal ischemia.

We examined whether preconditioning with sublethal ischemia protects against neuronal damage following subsequent lethal ischemic insults. Forebrain ischemia for 3 min in Wistar rats increased heat shock protein-70 immunoreactivity in the hippocampal CA1 subfield but produced no neuronal damage. Preconditioning with 3 min of ischemia followed by 3 days of reperfusion protected against hippocampal CA1 neuronal damage following 6 and 8 min of ischemia but not damage after 10 min of ischemia. The result strongly suggests that stress response induced by sublethal ischemia protects against ischemic brain damage.

Animals↗

PubMed1992

Synthesis and structure-activity relationships of elafin, an elastase-specific inhibitor.

Elafin, an elastase-specific inhibitor isolated from human skin, and its related peptides were synthesized by the solution procedure, and their inhibitory activities were measured against various enzymes. During the oxidative folding reactions of the reduced peptides, the ratio of the active product to the inactive product was varied by changing the concentration of guanidine HCl and the amount of redox reagents. The disulfide structures of fully active synthetic elafin and the inactive product were determined by amino acid analysis, gas-phase sequencing and mass spectrometry of their proteolytic fragments. The relationship between structure and inhibitory activities and/or the folding reaction was examined and the amino terminal part of the elafin molecule was found to have a great influence on the folding reactions, but not on the inhibitory activities.

Amino Acid Sequence↗

PubMed1992

Cauliflower mosaic virus reverse transcriptase. Activation by proteolytic processing and functional alteration by terminal deletion.

We have previously expressed the cauliflower mosaic virus (CaMV) reverse transcriptase (RTase) gene, the ORFV gene, in yeast in an active form (RTase-Y). An activity gel analysis revealed that the molecular size of RTase-Y as well as an RTase associated with the CaMV particles (RTase-V) is 60 kDa. This size is about 18 kDa smaller than that of the inactive form previously expressed in Escherichia coli (RTase-E) (78 kDa), which corresponds to the coding capacity estimated for the ORFV gene. To investigate the possible involvement of proteolytic processing in the de novo synthesis of CaMV RTase, we constructed a series of deletions from either terminus or both termini of the ORFV coding sequence and expressed them in E. coli. Among the various truncated RTases, those (denoted delta N) that lack N-terminal peptide fragments 143-185 amino acids long were active on the synthetic RNA template-primer, poly(rC)-oligo(dG). Those RTases (denoted delta C) lacking C-terminal peptide fragments 50-102 amino acids long and those lacking both termini (denoted delta NC) were also active on this template. However, only the delta N RTases showed enzyme properties indistinguishable from the RTase-Y in that they transcribed natural RNA into DNA and required either Mg2+ or Mn2+ for their activity. The length of the deletion corresponded approximately to the difference of the molecular weights between RTase-Y and RTase-E. These results suggest that CaMV RTase is translated in an inactive precursor form and then converted to an active form by proteolytic processing during de novo synthesis. We have also demonstrated that C-terminal deletions cause a loss of activity on a natural RNA template accompanied by an alteration in metal ion requirement. The inability to incorporate dTTP accounts for the loss of activity on the natural RNA template. However, the affinities for dTTP and the corresponding template, poly(rA)-oligo(dT), were found to be unaltered.

Binding Sites↗

PubMed1992

Molecular cloning of cDNAs for human fibroblast nucleotide pyrophosphatase.

Nucleotide pyrophosphatase (NPPase) activity is markedly elevated in cultured skin fibroblasts from patients of Lowe's syndrome. cDNA clones encoding the NPPase were isolated using synthetic oligonucleotide probes designed on the basis of partial amino acid sequence of the enzyme purified from human placenta. The complete sequences of these clones yielded a merged sequence of 3508 bases. The polypeptide chain of the enzyme was deduced to comprise 873 amino acids with a calculated molecular weight of 99,703 and had the characteristics of a class II transmembrane protein. Ten potential N-glycosylation sites were detected in the protein. RNA blot analysis showed that human fibroblasts contain two minor mRNAs of 7.0 and 8.2 kb, respectively, in addition to a major 3.6-kb species that coincides with the merged cDNA in size. A computer search of a nucleotide sequence data-base revealed that plasma cell membrane glycoprotein PC-1, whose function was unknown at the time, is identical with the NPPase. Comparison of the amino acid sequence of the NPPase with the active site sequence of bovine 5'-nucleotide phosphodiesterase allowed the assignment of a putative active site domain to the central region of the COOH-terminal extracellular domain of the NPPase. The gene for human NPPase was localized to chromosome 6 at q22-q23 by in situ hybridization with a fragment of the NPPase cDNA.

Amino Acid Sequence↗

PubMed1992

MK-801, but not anisomycin, inhibits the induction of tolerance to ischemia in the gerbil hippocampus.

We examined whether MK-801, an N-methyl-D-aspartate (NMDA)-receptor antagonist, or anisomycin, a reversible protein synthesis inhibitor, inhibits the induction of ischemic tolerance following preconditioning with sublethal ischemia in gerbil hippocampus. Preconditioning with 2 min of ischemia, which induced heat shock protein-72 immunoreactivity, prevented hippocampal CA1 neuronal damage following 3 min of ischemia produced 3 days later. MK-801, but not anisomycin, inhibited the induction of tolerance although the heat shock protein synthesis was reduced in both groups. The present result suggests that NMDA receptor activation, causing stress response, induces the ischemic tolerance.

Animals↗

PubMed1992

Chromosomal deletions and K-ras gene mutations in human endometrial carcinomas.

Forty-two endometrial carcinomas of various stages of progression were analyzed to search for loss of chromosomal regions and for point mutations of ras genes and amplification of Int-2 gene. This approach is particularly favorable for observation of genetic events and their significance in the process of neoplastic conversion by considering the clinico-pathological characteristics of each tumor. At least 3 genetic events, including 18q, 17p deletions, and point mutations at codon 12 of the K-ras gene, are implicated in the development of endometrial carcinomas. Likely targets for allelic losses on chromosomes 18q and 17p are the DCC gene and the p53 gene sequences, respectively. Overall numbers of allelic losses in individual tumors appeared to increase in case of advanced stage tumors, thereby indicating the association of allelic loss accumulation with tumor progression. The genetic features seen in 2 juvenile-type adenocarcinomas and 2 clear-cell carcinomas suggested the possibility that etiological factors providing selective pressure for particular mutation sub-sets during carcinogenesis are probably heterogeneous.

Adult↗

PubMed1992

Simultaneous determination of a new gastrointestinal prokinetic agent (HSR-803) and its metabolites in human serum and urine by high-performance liquid chromatography using automated column-switching.

A method based on high-performance liquid chromatography using column-switching is described for the simultaneous determination of HSR-803 and its metabolites in human serum and urine. The system uses a six-port valve with a Nucleosil CN pre-column for on-line sample clean-up, and direct injection of samples. The limits of quantitation in serum and urine were 5 and 20 ng/ml for HSR-803 and 50 and 200 ng/ml for the metabolites, respectively. The coefficients of variation for the intra- and inter-day accuracies were between 0.8 and 7.1% for each compound. This method was applied to the pharmacokinetic studies in humans after oral administration of HSR-803.

Benzamides↗

PubMed1992

Effects of pretreatment with sublethal ischemia on the extracellular glutamate concentrations during secondary ischemia in the gerbil hippocampus evaluated with intracerebral microdialysis.

To elucidate the role of glutamate in the pathogenesis of altered neuronal vulnerability following sublethal ischemia, we measured the extracellular concentrations of glutamate in the gerbil hippocampus using a microdialysis technique. During and immediately after 3-min forebrain ischemia, the extracellular glutamate level showed a striking increase. However, pretreatment with 2-min ischemia 1 h or 4 days before secondary 3-min ischemia did not alter the amount of glutamate released. The result indicates that cumulative damage and tolerance, which take place after pretreatment with sublethal ischemia, are not induced through modification of the amount of glutamate released during secondary ischemia.

Animals↗

PubMed1992

Enhancement of phospholipase C delta 1 activity in the aortas of spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR), which develop hypertension approximately 10 weeks after birth, are considered to provide a good animal model for human essential hypertension. We report here that the abnormal activation of phospholipase C delta 1 (PLC-delta 1) may be one of the main causes of hypertension. Levels of the second messengers inositol 1,4,5-trisphosphate and diacylglycerol are found to be higher in the aortas of 12-week-old SHR than in age-matched normotensive Wistar-Kyoto rats (WKY), although the levels in the aortas of 7-week-old SHR, which have normal blood pressure, are the same as in WKY. Moreover, PLC activity is also higher in the aortas of 12-week-old SHR. Judging from Western blot analysis and immunoabsorption of PLCs, this activation is found to be due to that of PLC-delta 1. PLC-delta 1 from rat aorta is expressed significantly from 7 to 12 weeks, which correlates with the development of hypertension in SHR. The activity of PLC-delta 1 in the aortas of 12-week-old SHR is more markedly activated at low Ca2+ concentration than that of age-matched WKY. These results suggest that the abnormal enhancement of PLC-delta 1 activity is responsible for accumulation of inositol 1,4,5-trisphosphate and diacylglycerol, leading to continuous hypertonicity of vascular smooth muscle in SHR. The activity of PLC-delta 1 in the aortas of 12-week-old SHR is significantly higher at low Ca2+ concentration than that of normotensive WKY.

1-Phosphatidylinositol 4-Kinase↗