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Biomedical subjects

H Hayakawa

Publications and source records attributed to H Hayakawa.

At least 19 recordsLinked to original sources
PubMed1992

Characterization of atrial natriuretic peptide in urine from rats treated with a neutral endopeptidase inhibitor.

To explore the mechanisms for the natriuretic effects of a neutral endopeptidase inhibitor, candoxatril, the concentration of atrial natriuretic peptide (ANP) and its molecular forms in the urine of Dahl salt-sensitive (S) rats were examined. Candoxatril-induced natriuresis (+120%, p less than 0.05) was associated with a marked increase in the urinary ANP excretion (+1200%, p less than 0.05). Analysis by Sephadex G-50 gel filtration revealed that molecular weight of the major fraction of immunoreactive (ir-) ANP in the plasma of candoxatril-treated Dahl S rats was 3K, whereas that in the urine was 2.5 K. Further analysis by reverse phase high performance liquid chromatography showed that ir-ANP in the plasma of Dahl S rats was alpha-rANP (1-28), while that in the urine from rats treated with candoxatril was alpha-rANP (1-25). These results indicate that candoxatril inhibits the complete degradation of ANP in the kidney, thereby increasing the amount of biologically active ANP reaching the distal nephron and contributing to natriuresis.

Analysis of Variance↗
PubMed1992

Pulmonary surfactant phospholipids modulate priming of rabbit alveolar macrophages for oxidative responses.

We investigated the effect of individual phospholipids contained in pulmonary surfactant (PS) on the macrophage-activating factor (MAF)-induced priming of rabbit alveolar macrophages (AMs) for oxidative responses elicited by phorbol myristate acetate (PMA) or opsonized zymosan (Op-Zym). AMs were incubated with MAF with or without phospholipids for 18 h. After incubation, oxidative responses were elicited with PMA (0.5 micrograms/ml) or Op-Zym (250 micrograms/ml) and monitored by chemiluminescence (CL) assays. The data indicate that natural surfactant inhibited MAF-induced priming of rabbit AMs for PMA- or Op-Zym-elicited oxidative responses. Artificial surfactant inhibited PMA-elicited CL responses but enhanced Op-Zym-elicited CL responses. Individual phospholipids differed in modulative activities. Dioleoyl phosphatidylcholine (DOPC), dipalmitoyl phosphatidylglycerol (DPPG), and phosphatidylinositol (PI) inhibited MAF-induced priming when the oxidative responses were elicited with PMA. Whereas DPPG inhibited Op-Zym-elicited oxidative responses, dipalmitoyl phosphatidylcholine (DPPC) and DOPC primed AMs for increased Op-Zym-elicited oxidative responses. DOPC did not affect the binding of phorbol dibutyrate to AMs, which suggests that reduced cell binding of phorbol ester was not responsible for the inhibition of PMA-elicited oxidative responses in AMs treated with DOPC. Similarly, DPPC, DOPC, and DPPG did not affect the number of zymosan particles phagocytosed by AMs compared to the control, which suggested that enhanced or reduced Op-Zym-elicited oxidative responses by phospholipids were not due to altered phagocytic activity of AMs. In conclusion, our data indicate that individual surfactant phospholipid differently modulates priming of AMs for oxidative responses, and the effect of individual phospholipids does not account for the effect of complete PS on priming of AMs.

Animals↗
PubMed1992

Acute tubulointerstitial nephritis with uveitis syndrome presenting as multiple tubular dysfunction including Fanconi's syndrome.

We describe an 11-year-old male patient with acute tubulointerstitial nephritis with uveitis (TINU) syndrome. He presented with easy fatigability, pallor, nocturia and weight loss. Laboratory examination disclosed anaemia, polyclonal hypergammaglobulinaemia, low molecular weight proteinuria, glycosuria, aminoaciduria, proximal and distal renal tubular acidosis, a urine concentration defect and decreased creatinine clearance. The multiple renal tubular dysfunction and slight glomerular dysfunction subsided spontaneously. Bilateral anterior uveitis was manifested 7 months after the onset of the disease. This is the first reported case of TINU syndrome with multiple proximal and distal tubular dysfunction including a complete type of Fanconi's syndrome.

Acidosis, Renal Tubular↗
PubMed1992

DNA analysis of two patients with a non-fluorescent Y chromosome.

Results of DNA study on two patients of gonadal dysgenesis with a 45,X/46,X,Ynf (non-fluorescent Y chromosome) karyotype are described. In one patient who developed gonadoblastoma, all 12 loci on the non-fluorescent part of Yq were detected. Another patient did not have gonadoblastoma at 20 years, and only the proximal 6 loci out of 12 were detected.

Adult↗
PubMed1992

The effects of electroconvulsive shock or imipramine on subtypes of alpha 1-adrenoceptors in the frontal cortex of the rat.

The effects of repeated treatment (14 days) with electroconvulsive shock (ECS) or imipramine on binding sites on alpha 1-adrenoceptors in the rat were studied. The binding of [3H]prazosin studied with WB4101 and phentolamine, as binding inhibitors, showed the existence of two subtypes of alpha 1-adrenoceptor (alpha 1A and alpha 1B). Proportions of the alpha 1A and alpha 1B binding sites were about 3:7 in the frontal cortex and 9:1 in the hippocampus. Pretreatment of the membranes with chlorethylclonidine (CEC) almost abolished the alpha 1B binding sites. Inhibition of the binding of [3H]prazosin studied with antidepressants (imipramine, desipramine, maprotiline and mianserin) showed that these drugs bound to alpha 1-adrenoceptors with low affinity, in an apparent monophasic manner. The characteristics of the alpha 1A and alpha 1B binding sites were studied by the binding assay with [3H]prazosin, in the presence of a small concentration (2 nM) of WB4101 to mask the alpha 1A binding sites, as well as the assay without WB4101, for the total alpha 1-adrenoceptor (alpha 1A and alpha 1B) binding. Repeated treatment with electroconvulsive shock increased but that with imipramine decreased, the density of the alpha 1B binding sites in the frontal cortex, without change of the affinity. Neither treatment affected the alpha 1A binding sites in the frontal cortex. The alpha 1-adrenoceptors (alpha 1A and alpha 1B) in the hippocampus were not affected at all by these repeated treatments. The electroconvulsive shock-induced increase in the alpha 1B binding sites in the frontal cortex of the rat could contribute to differences in clinical effects between electroconvulsive shock and antidepressant drugs.

Adrenergic alpha-Antagonists↗
PubMed1992

Dissociation of collagenase-tissue inhibitor of metalloproteinases-1 (TIMP-1) complex--its application for the independent measurements of TIMP-1 and collagenase activity in crude culture media and body fluids.

Collagenase-tissue inhibitor of metalloproteinases-1 (TIMP-1) complex was prepared from activated collagenase and TIMP-1 purified from culture media of human skin fibroblasts. After having been confirmed to be a complex by zinc chelate chromatography, the complex was demonstrated to dissociate by passage through an anti-TIMP-1 monoclonal antibody-affinity column. On the basis of above evidence, a simple strategy was set up for the independent measurements of TIMP-1 concentration, and both active and total collagenase activities in crude culture media and body fluids.

Body Fluids↗
PubMed1992

Isolation and characterization of cDNA and genomic sequences for mouse O6-methylguanine-DNA methyltransferase.

An enzyme, O6-methylguanine-DNA methyltransferase, is present in various organisms and plays an important role in repair of DNA damaged by alkylating agents. The enzyme transfers methyl groups from O6-methylguanine and other methylated moieties of the DNA to its own molecule. As a first step to construct animal models with altered levels of the enzyme activity, we cloned cDNA and genomic DNA sequences for mouse methyltransferase and elucidated their structures. The nucleotide sequence of the cDNA revealed an open reading frame comprising 211 amino acid residues. The mol. wt of mouse O6-methylguanine-DNA methyltransferase, calculated from the predicted amino acid sequence, was 22,400, and the methyltransferase protein of this size was present when the cDNA was expressed in methyltransferase-deficient human cells. The predicted amino acid sequence of the mouse methyltransferase exhibits an intense homology with those of human and bacterial counterparts. Using the cDNA as a probe, part of the mouse gene for methyltransferase was isolated. The gene consisted of at least four exons and spanned greater than 145 kb. Sequences around the exon/intron junctions for the mouse gene are almost the same as those for the human species.

Amino Acid Sequence↗
PubMed1992

Specific amino acid sequences required for O6-methylguanine-DNA methyltransferase activity: analyses of three residues at or near the methyl acceptor site.

O6-Methylguanine-DNA methyltransferase plays an important role in preventing tumor induction. To elucidate the significance of a highly conserved amino acid sequence of methyltransferase protein, amino acid substitutions were introduced by site-directed mutagenesis of cloned cDNA for human methyltransferase and the activity and stability of mutant forms of enzyme were examined. When cysteine-145, to which the methyl transfer occurs, was replaced by other amino acids, all of the mutants isolated showed the methyltransferase-negative phenotype. From one of the negative mutants, methyltransferase-positive revertants were isolated, all of which carried codons for cysteine. Thus the cysteine residue is essential for acceptance of the methyl group and cannot be replaced by other amino acids. Using this negative and positive selection procedure, analyses were extended to other residues near the acceptor site. At the histidine-146 site, four substitutions (phenylalanine, methionine, asparagine and glutamine) exhibited the positive phenotype but the levels of methyltransferase activity in these mutants were low. With valine-148 substitutions there were six types of positive revertants, among which mutants carrying isoleucine, cysteine and alanine showed significantly high levels of methyltransferase activity. Some mutant forms of cDNA were expressed in methyltransferase-deficient human cells, and the results obtained with Escherichia coli cells were confirmed.

Amino Acid Sequence↗
PubMed1992

Sodium channel states control binding and unbinding behaviour of antiarrhythmic drugs in cardiac myocytes from the guinea pig.

OBJECTIVE: The aim was to investigate whether cardiac sodium channel states (rested, activated, inactivated) regulate the binding and unbinding behaviour of antiarrhythmic drugs on the receptor sites. METHODS: Single ventricular myocytes of adult guinea pig heart were obtained by an enzymatic dissociation method in the Langendorff manner. The channel state dependent blocking effects on cardiac sodium current (INa) of quinidine and disopyramide were studied under the whole cell variation of the patch clamp technique. RESULTS: 10 microM quinidine and 20 microM disopyramide produced similar levels of tonic block and use dependent block. The steady state inactivation curve (h infinity curve) was shifted parallel in the negative potential direction by quinidine (10 microM) and disopyramide (20 microM) to the same extent (-10 mV). Removal of the fast inactivation process of INa by chloramine-T did not reduce tonic and use dependent block by these drugs. Onset block study using a double pulse protocol revealed that block developments by both drugs were fitted to the sum of double exponential functions. However, time constant of fast phase of block by disopyramide was faster than that by quinidine, while slow phase was not significantly different. Definition of time courses of unbinding (recovery) at -140 mV indicated that quinidine dissociated relatively slowly as compared to disopyramide. CONCLUSIONS: Quinidine produces more potent tonic and use dependent block of INa by binding to sodium channels at both rested and inactivated states, while disopyramide has a higher affinity for activated state. Therefore, sodium channel states regulate the binding and unbinding behaviour of antiarrhythmic drugs. Furthermore, the fast inactivation process is not essential in producing tonic and use dependent block by antiarrhythmic drugs.

Action Potentials↗
PubMed1992

Induced synthesis of O6-methylguanine-DNA methyltransferase in rat hepatoma cells exposed to DNA-damaging agents.

When the rat hepatoma cell line H4IIE was treated with DNA-damaging agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), ultraviolet light and gamma-rays, the O6-methylguanine-DNA methyltransferase activity increased 2 to 3 times over the level seen in non-treated cells. SDS/polyacrylamide gel electrophoresis followed by fluorography revealed that a single species of methyltransferase protein with a molecular weight of 25,500 was present in both non-treated and treated cells. Northern blot analysis using a cloned rat cDNA as a probe revealed that the enzyme activity increased because transcription of the gene was enhanced. The level of enzyme activity increased within 48 h after UV irradiation and remained at a higher level for 150 h. Following UV irradiation, the cells become more resistant than the normal cells to MNNG.

Animals↗
PubMed1992

Alpha- and beta-adrenergic receptors in children with essential hypertension.

Platelet alpha 2- and lymphocyte beta-adrenergic receptors were examined in eight children aged 10-16 years with essential hypertension, and in 11 age-matched normotensive children. Both alpha 2- and beta-adrenergic receptor concentrations showed no significant differences between children with essential hypertension and normotensive children. According to other studies, physiological fluctuations in catecholamines determine lymphocyte beta-adrenergic receptor concentrations, although down-regulation in platelet alpha 2-adrenergic receptors has not been observed. The present findings suggest that there may be no abnormalities in alpha 2- and beta-adrenergic receptors in essential hypertension in childhood, although a hyperadrenergic state has been reported to be of some relevance to the pathogenesis of essential hypertension in young adolescents.

Adolescent↗
PubMed1992

A case of cardiac foreign bodies associated with four types of tachycardias.

A case of cardiac foreign bodies leading to development of four varieties of automatic tachycardia is reported. A 51-year-old male with aortic regurgitation was admitted to our hospital because of palpitations. An electrocardiogram revealed junctional tachycardia with or without left bundle branch block, and two types of fascicular tachycardias. Computed tomography showed metallic foreign bodies from a fractured guidewire in the membranous portion of the interventricular septum, which was inadvertently retained when he underwent diagnostic cardiac catheterization at the age of 27.

Bundle-Branch Block↗
PubMed1992

[Nested polymerase chain reaction for the diagnosis and follow-up of tuberculous meningitis: a case report].

We presented a case of tuberculous meningitis in which a nested polymerase chain reaction was useful for its rapid diagnosis and follow-up. A 5-month-old girl was hospitalized for gastrointestinal complaints of 4 days' duration. She initially had no meningeal signs, but showed a bulging of the anterior fontanel on the 10th day of her illness. Cerebrospinal fluid examination revealed a cell count of 886/3 microliters (80% lymphocytes), protein of 20 mg/dl, and glucose of 27 mg/dl. Tuberculous meningitis was suspected clinically and an antituberculous therapy was commenced on the 13th day. Although repeated attempts to culture Mycobacterium tuberculosis were negative, the DNA of the organism was detected sequentially from the cerebrospinal fluid of the 13th and 16th day by the method of a nested polymerase chain reaction. The final diagnosis of tuberculous meningitis was established on the basis of the positive results of the nested polymerase chain reaction, a positive tuberculin test, and typical cerebrospinal fluid findings. She recovered rapidly in response to the therapy and was discharged from the hospital without any neurological sequelae on the 89th day. The follow-up samples of the nested polymerase chain reaction resulted as negative after the 26th day of the illness.

Female↗
PubMed1992

Role of endogenous ANP in sodium excretion in rats with experimental pulmonary hypertension.

To explore the roles of endogenous atrial natriuretic peptide (ANP) in the volume regulation, we examined effects of antiserum for ANP or a neutral endopeptidase inhibitor, thiorphan, in rats with monocrotaline (MCT)-induced pulmonary hypertension. ANP concentrations in the plasma and right ventricle and ANP mRNA in the right ventricle of MCT-treated rats were higher than in vehicle-treated rats. The administration of the ANP antiserum into the MCT-treated rats did not affect the right atrial pressure or blood pressure but significantly decreased urinary excretion of Na by 60%. No decrease occurred in the control rats. Thiorphan dose dependently increased the urinary excretion of Na by 140% without influencing the right atrial pressure or blood pressure. This natriuresis was associated with 50 and 450% increases in ANP concentrations in the plasma and urine, respectively. The degrees of increases in urinary Na excretion, ANP, and guanosine 3',5'-cyclic monophosphate were significantly greater in the MCT-treated rats than in the control rats. Thus an increased secretion of ANP in pulmonary hypertension actually contributes to Na excretion. The augmentation of endogenous ANP activity may further potentiate the compensatory role of this peptide in the regulation of body fluid volume.

Animals↗
PubMed1992

Right atrial myxoma presenting with recurrent episodes of pulmonary embolism.

We observed a right atrial myxoma presenting with recurrent episodes of pulmonary embolism, the diagnosis of which was made approximately 2 years after the initial symptoms appeared. We emphasize the importance of prompt recognition and subsequent surgical treatment of cardiac myxoma because embolism by tumor fragments is a potentially fatal complication of this condition.

Adult↗
PubMed1992

Cellular mechanisms for synthesis and secretion of atrial natriuretic peptide and brain natriuretic peptide in cultured rat atrial cells.

To investigate the cellular mechanism for the synthesis and secretion of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), we examined the effects of vasoactive agents on the secretion rates and gene expression of ANP and BNP in cultured rat atrial cells. Endothelin (10(-7) M, +61%), 12-O-tetradecanoylphorbol 13-acetate (TPA, 10(-6) M, +62%), the calcium ionophore A23187 (10(-6) M, +95%), and Bay K 8644 (10(-6) M, +34%) (p < 0.05 each) all increased the secretion of ANP into the culture media in a dose-dependent fashion. On the other hand, endothelin (10(-7) M, +57%) and TPA (10(-6) M, +55%) (p < 0.01 each) increased the secretion of BNP in a dose-dependent manner, whereas A23187 (10(-6) M, -45%, p < 0.001) suppressed the secretion of BNP in a dose-dependent manner, and Bay K 8644 caused no significant effects on BNP secretion. The molecular forms of intracellular ANP were exclusively gamma-ANP, whereas those of BNP were gamma-BNP and its carboxy terminal 45-amino-acid peptide, BNP-45. The ratio of media to cell contents was much higher in BNP than in ANP. Northern blot analysis revealed that both ANP mRNA and BNP mRNA levels were significantly increased by 10(-7) M endothelin (ANP mRNA, +52%; BNP mRNA, +36%; p < 0.05 each) and 5 x 10(-5) M 1-oleoyl-2-acetylglycerol (ANP mRNA, +296%; BNP mRNA, +133%; p < 0.01 each) but not by 10(-6) M A23187. Thus, the secretion of ANP is stimulated by both the elevation of [Ca2+]i and the activation of protein kinase C, whereas its synthesis is increased mainly by the activation of protein kinase C. The synthesis and secretion of BNP are augmented by the activation of protein kinase C rather than the elevation of [Ca2+]i. Furthermore, the processing and secretion of ANP and BNP may be regulated in different manners.

Animals↗