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K Kitamura

Publications and source records attributed to K Kitamura.

At least 523 records · Page 29Linked to original sources
PubMed1995

Mechanisms of adrenomedullin-induced vasodilation in the rat kidney.

To explore the mechanisms of adrenomedullin-induced vasorelaxation, we tested the effects of adrenomedullin on renal function in rats in vivo and measured the release of endothelium-derived nitric oxide from isolated perfused rat kidney (using a chemiluminescence assay) and the diameters of the glomerular arterioles in the hydronephrotic kidney. Adrenomedullin decreased blood pressure in a dose-dependent manner (3 nmol/kg: -29 +/- 2% [SEM]; P < .01) and slightly increased the glomerular filtration rate and urinary sodium excretion (+108%; P < .05). These changes were associated with significant increases in urinary excretion of cyclic AMP (+54%; P < .05). Adrenomedullin decreased renal vascular resistance (10(-7) mol/L adrenomedullin: -41 +/- 2%; P < .001) and increased release of nitric oxide (+5.1 +/- 0.7 fmol/min per gram kidney weight; P < .001) in the isolated kidney. This increase in nitric oxide release was abolished by the inhibitor NG-monomethyl-L-arginine, and it also reversed the decrease in renal vascular resistance seen with adrenomedullin. Renal responses of deoxycorticosterone acetate-salt hypertensive rats to adrenomedullin were significantly smaller than those of control rats for both release of nitric oxide (10(-7) mol/L adrenomedullin: +0.8 +/- 0.2 fmol/min per gram kidney weight; P < .01 versus control) and renal vasodilation (-28 +/- 6%; P < .05). Videomicroscopic analysis revealed that adrenomedullin increased the diameters of both afferent and efferent arterioles (3 nmol/kg: +11%; P < .05). Thus, adrenomedullin-induced renal vasodilation is partially endothelium dependent and is attenuated in deoxycorticosterone acetate-salt hypertension, probably due to endothelial damage.

Adrenomedullin↗
PubMed1995

Proadrenomedullin NH(2)-terminal 20 peptide, a new product of the adrenomedullin gene, inhibits norepinephrine overflow from nerve endings.

Proadrenomedullin NH(2)-terminal 20 peptide (PAMP) and adrenomedullin, which are derived from proadrenomedullin, exhibit remarkable hypotensive action. We investigated the effect of PAMP and adrenomedullin on peripheral sympathetic neutral transmission. Using perfused rat mesenteric arteries, PAMP (0, 1, 5, and 10 pmol/ml) decreased norepinephrine overflow by periarterial electrical nerve stimulation in a dose-dependent fashion (0.244 +/- 0.043, 0.231 +/- 0.048, 0.195 +/- 0.061 and 0.168 +/- 0.051 ng/gram tissue weigh: NS, P < 0.05, and P < 0.02, respectively). In contrast to PAMP, adrenomedullin (1, 5, and 10 pmol/ml) did not change it. In contrast, vasoconstrictive response of mesenteric arteries to exogenous norepinephrine was significantly attenuated by 10 pmol/ml of adrenomedullin but not by the same dose of PAMP. Calcitonin gene-related peptide (8-37) [CGRP(8-37)], a CGRP receptor antagonist, inhibited the vasodilatory effect of adrenomedullin but could not suppress the sympathoinhibitory effect of PAMP. Neither a nicotinic antagonist, hexamethonium, nor a presynaptic alfa2 antagonist, yohimbine, blocked the sympathoinhibitory effect of PAMP. Thus, it suggests that PAMP and adrenomedullin, which are derived from the same gene, exhibit different hypotensive mechanisms: PAMP inhibits neural transmission at peripheral sympathetic nerve ending, although adrenomedullin directly dilates vascular smooth muscle, possibly through CGRP-like receptor.

Adrenomedullin↗
PubMed1995

A new cognition-enhancing agent, (R)-(-)-1-(benzo[b]thiophen-5-yl)- 2-[2-(N,N-diethylamino)ethoxy]ethanol hydrochloride. Effects on memory impairment in rats generated by cerebral embolization and basal forebrain lesions.

The title compound (T-588) has been evaluated for its ameliorating effect on memory impairment generated by cerebral embolization and by a basal forebrain (BF) lesion in male Wistar rats. The memory and learning deficits induced by injection of carbon-microspheres into the internal carotid artery were significantly improved by T-588 at oral dose of 3-10 mg/kg, as determined by an active avoidance response assay, whereas the reference drugs (tacrine, idebenone and indeloxazine) proved almost inactive in the same assay procedure. As far as the embolization was concerned, a significant decrease in cerebral acetylcholine and monoamines was observed. The effect on the memory impairment caused by an electrolytic lesion of the BF was assessed by a passive avoidance task. T-588 exhibited a bell-shaped dose-response curve and was most active at 1 mg/kg (oral dose), while tacrine showed equal activity at 10 mg/kg.

Animals↗
PubMed1995

Studies on cognitive enhancing agents. I. Antiamnestic and antihypoxic activities of 2-dimethylaminoethyl ethers and related compounds.

N-(2-Dimethylaminoethyl)carboxamide (1a-d), 2-dimethylaminoethyl alkyl ether (2a, b), and 2-dimethylaminoethyl 2-hydroxy-2-phenethyl ether (3a-c) and its amino and methylene analogues (3d, 4) have been screened for antiamnestic and antihypoxic activities in mice. A clear reversing effect on electroconvulsive shock-induced amnesia was found with 1a-d, 2a,b, and 2-dimethylaminoethyl 2-hydroxy-2-phenylethyl ether (3a). However, a protective effect against hypoxia was only observed with 3a. Compound 3a, which displayed the dual activity, was further investigated for ameliorating effect on CO2-induced memory impairment, and it was found to be more potent than indeloxazine and bifemelane. In addition, the acute toxicity of 3a in mice was significantly lower than that of tacrine, but its serum-to-brain penetration ability in rats was less than that of the reference drugs.

Amnesia↗
PubMed1995

Studies on cognitive enhancing agents. II. Antiamnestic and antihypoxic activities of 1-aryl-2-(2-aminoethoxy)ethanols.

A series of 2-(2-aminoethoxy)-1-phenylethanols having a variety of N- and phenyl-substitution patterns as well as 5- and 6-membered heteroaryl counterparts of our prototype compound 1 (2-(2-dimethylaminoethoxy)-1-phenylethanol) have been prepared and evaluated for antiamnestic and antihypoxic activities. Compound 3b, the 3-methylphenyl analogue of 1, proved to be significantly more potent than 1 in reversing electroconvulsive shock-induced amnesia as well as CO2-induced learning-impairment in mice. It exhibited low acute toxicity in mice and afforded a greater brain/serum concentration ratio than 1 after oral administration to rats.

Amnesia↗
PubMed1995

Studies on cognitive enhancing agents. III. Antiamnestic and antihypoxic activities of a series of 1-bicycloaryl-2-(omega-aminoalkoxy)ethanols.

2-(2-Aminoethoxy)-1-hydroxyethyl derivatives of bicyclic arenes (naphthalene, thianaphthene, benzofuran, and indole) were prepared and screened for antiamnestic (AA) and antihypoxic (AH) activities which were evaluated by measuring the reversing potency in electroconvulsion-induced amnesia and the protective effect against hypoxia, respectively, in mice. Compound 3o, 1-(benzo[b]thiophen-5-yl)-2- (2-diethylaminoethoxy)ethanol, showed the best AA and AH activity profile, being superior to our prototype compound, 2-(2-dimethylaminoethoxy)-1-phenylethanol (1). Elongation of the ethylene linkage in the side chain of 3o to 3- and 4-carbon moieties brought about a significant decrease in AH activity. Compound 3o was further investigated for its protective effect against CO2-induced memory impairment and for acute toxicity in mice. It is ten-fold more potent than tacrine in the amnesia-reversal assay and is considerably less toxic than tacrine.

Amnesia↗
PubMed1995

DNA sequence changes in mutations in the tonB gene on the chromosome of Escherichia coli K12: insertion elements dominate the spontaneous spectra.

To obtain insight into the nature and mechanisms of spontaneous mutations, Escherichia coli K12 strain TM31 was constructed to determine, by DNA sequencing, the mutational spectrum of the tonB gene on the chromosome. We inserted the chloramphenicol resistant gene 1.6 kb upstream of the tonB gene, thus making it possible to retrieve the mutated tonB gene from the chromosome by shotgun cloning using a drug-resistant marker. The spontaneous mutation frequency in the tonB gene, which was judged by its colicin B-resistant phenotype, is 3-10 x 10(-7). Spontaneous mutations were dominated by large insertions that are identified by DNA sequencing to be IS elements; IS1 dominated, but IS2, IS5, and IS10 were also obtained. In uvrA- strain, transposition of both IS10-R and IS10-L are equally increased, suggesting the interaction of the UvrA protein and IS10 transposition. The base substitutions are the second largest group of mutations, among which G:C-->A:T transition is predominant. Deletions also contribute significantly in wild type with regard to DNA repair and uvrA- strains, but not recA- strain, suggesting that the RecA protein is involved to some extent in deletion formation. Endpoints of these deletions do not always correlate with the presence of repeated sequences, indicating the absence of homologous recombination for deletion formation.

Base Sequence↗
PubMed1995

Alpha-subunit of beta-conglycinin, an allergenic protein recognized by IgE antibodies of soybean-sensitive patients with atopic dermatitis.

One of the major allergenic proteins in the soybean 7S-globulin fraction, which was recognized by sera of about 25% soybean-sensitive patients with atopic dermatitis, was identified as alpha-subunit of beta-conglycinin. The IgE antibodies recognizing the alpha-subunit did not show a cross-reactivity against both alpha'- and beta-subunits known to be highly homologous to alpha-subunit, and also against other allergenic components identified in soybeans [Ogawa et al., J. Nutr. Sci. Vitaminol., 35, 555-565 (1993)]. The IgE-binding site(s) was estimated to be located on the peptide 232-283 of alpha-subunit.

Adolescent↗
PubMed1995

Exercise-induced secretion of brain natriuretic peptide in essential hypertension and normal subjects.

To determine the major stimuli for the release of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP), we measured their plasma concentrations in 14 normal subjects and 19 patients with essential hypertension during exercise with a bicycle ergometer. The plasma levels of both hormones at baseline were significantly higher in the hypertensive group than in the controls (p < 0.05). The exercise raised both the plasma BNP and ANP, with concomitant increases in systolic blood pressure (SBP), heart rate (HR) and plasma norepinephrine (NE) or epinephrine (Epi) in each group. In the controls the change in ANP correlated with those in SBP, HR and NE (p < 0.05), and similarly the change in BNP with those in SBP, HR, NE and Epi (p < 0.05). In multivariate regression analysis only NE was found to be a significant stimulus for ANP secretion, whereas SBP or Epi was related to BNP release. In the hypertensives the change in ANP correlated with those in HR and NE, but on multivariate regression analysis the change in ANP correlated only with that in HR. The change in BNP in the hypertensives correlated only with that in HR. These findings indicate that in normal subjects the exercise-induced release of BNP and ANP is more sensitive to a similar but slightly different sympathetic stimulus, whereas in hypertensives the major stimulus for the release of both hormones is heart rate, indicating that the mediators for BNP or ANP release are altered by some factors involved in hypertension.

Adult↗
PubMed1995

Pituitary adenylate cyclase-activating polypeptide stimulates the synthesis of dopamine in cultured bovine adrenal chromaffin cells.

The effect of pituitary adenylate cyclase-activating polypeptide1-38 (PACAP1-38) on the synthesis of dopamine in cultured bovine adrenal chromaffin cells was examined. PACAP1-38 stimulated [14C]dopamine synthesis from [14C]tyrosine, in a concentration-dependent manner, causing maximal stimulation at 10(-7)M. This stimulatory action of PACAP1-38 was not significantly inhibited by staurosporine (an inhibitor of protein kinase C) or in the cells in which protein kinase C was down-regulated by prolonged exposure to TPA (an activator of protein kinase C), whereas it was partially attenuated in Ca(2+)-free medium. PACAP1-38 increased the formation of [3H] inositol phosphates, [Ca2+]i, 45Ca2+ uptake and cAMP level. The peptide also stimulated the phosphorylation of tyrosine hydroxylase, the enzyme catalyzing the rate-limiting step in dopamine synthesis. Dopamine synthesis and tyrosine hydroxylase phosphorylation stimulated by the maximal effective concentration of dibutyryl cAMP or high K+, which activates Ca2+ uptake, were further enhanced by PACAP1-38. These results indicated that PACAP1-38 may stimulate the activities of cAMP- and calcium-dependent protein kinases in cultured bovine adrenal chromaffin cells, resulting in increase in the synthesis of dopamine probably by stimulation of phosphorylation of tyrosine hydroxylase.

Animals↗
PubMed1995

Plasma adrenomedullin in various diseases and exercise-induced change in adrenomedullin in healthy subjects.

Adrenomedullin is a novel hypotensive peptide recently discovered in human pheochromocytoma. In the present study, we measured the plasma immunoreactive adrenomedullin of healthy subjects and patients with various diseases. Immunoreactive adrenomedullin was found to circulate in blood of the healthy subjects at a considerable concentration (3.3 +/- 0.3 fmol/ml). Plasma adrenomedullin was significantly increased in the patients with congestive heart failure (5.4 +/- 0.3 fmol/ml), essential hypertension (5.3 +/- 0.4 fmol/ml) and renal disease (4.9 +/- 0.4 fmol/ml). In healthy volunteers physical exercise significantly increased the plasma adrenomedullin concentration. The increase of adrenomedullin was inversely related to systolic blood pressure. These findings indicate that adrenomedullin participates in the circulation control in both physiological and diseased conditions. Although the exact origin of circulating adrenomedullin is still unknown, it is thought to be released rapidly by acute exercise, thereby regulating the cardiovascular system by its vasodilating activity.

Adrenomedullin↗
PubMed1995

Relaxation effect of an audiovisual system on dental patients. Part 2. Palus-amplitude.

Dental care services include relaxation of patients to reduce their displeasure at and tension during treatment. For this purpose, it is common to use audio or audiovisual programs, that is, to let them listen to music or watch TV. However, the former utilizes only the auditory sense, and the latter is disadvantageous in that a TV set is a rather large-scale unit. In the present study, we determined the relaxation effect of an audiovisual instrument on dental patients. The instrument, which gives virtual vision, was composed of a lightweight eyeset of the snow goggle type that has a built-in TV screen, with earphone and accessories. The relaxation effect was determined using a polygraph.

Adult↗
PubMed1995

Infrared/video ENG recording of positional nystagmus in subjects with peripheral vestibular disease.

We performed simultaneous infrared/video and electronystagmorgraphy (ENG) recordings of eye movements in 417 patients with disequilibrium. Of that number, 54 patients with the following two criteria participated in this study: verified diagnosis of peripheral vestibular disease and the presence of positional nystagmus recorded by ENG and an infrared/ video recording system. Although horizontal nystagmus was the most common, torsional, vertical and oblique nystagmus were also demonstrated in these patients. The most striking finding was the high incidence of oblique nystagmus closely related to a significant right-left difference of the caloric response in benign positional vertigo.

Adolescent↗
PubMed1995

Influence of changed blood pH on anionic sites in the labyrinth.

Using polyethyleneimine as a cationic probe, changes in the anionic sites of the labyrinthine basal laminae occurred during acidosis and alkalosis. Hartley-strain guinea pigs (200-300 g) with normal Preyer's reflex were injected i.v. with 0.5% polyethyleneimine (PEI, mol. wt 1800) solution adjusted to pH 7.3 with HCI via an axillary vein. The animals were divided into three groups: control, acidosis, and alkalosis. Acidosis was produced by inducing hypoxia, and alkalosis by injecting 7% NaHCO3. In controls, anionic sites were demonstrated on the basal laminae in the labyrinth. During both acidosis and alkalosis, a decreased number of anionic sites were observed on the basal laminae of the capillary walls in both stria vascularis and subepithelial layer of the vestibular sensory epithelium. However, an increase in anionic sites was observed on the basal lamina in Reissner's membrane during both acidosis and alkalosis.

Acidosis↗
PubMed1995

Cytokeratin expression patterns by one- and two-dimensional electrophoresis in pars flaccida cholesteatoma and pars tensa cholesteatoma.

Expression patterns of cytokeratins (CKs) in normal skin, in pars flaccida type cholesteatoma (PFTC), and in pars tensa type cholesteatoma (PTTC) were examined by means of one- and two-dimensional electrophoretic techniques. Both CKs 14 and 5 pair (CKs 14/5) and CKs 10/1 were found in all materials. Neither CKs 16/6 nor 19 was found in the skin. CKs 16/6 and 19 were both found in 3 out of 5 PFTCs, only CKs 16/6 in 1 out of 5 and neither CKs 16/6 nor 19 in 1 out of 5. CKs 16/6 and 19 were both found in 1 out of 3 PTTCs, only CKs 16/6 in 1 out of 3 and neither CKs 16/6 nor 19 in 1 out of 3. There was no significant difference in the CKs expression patterns between PFTC and PTTC. The expression of CKs 16/6 and 19 suggested that their matrix epithelia were hyperproliferative. However, not all of the cholesteatomas were always hyperproliferative. Patterns of the terminal differentiation of CKs 1, 5, 10 and 14 in the PFTC or the PTTC were basically the same as those in the skin. In the cholesteatoma, eack CK gradually diminished in molecular weight in the cornified layer and debris. Desmosomal proteins were abundant in skin but not in cholesteatomas.

Adult↗
PubMed1995

[Detection of a mutation in mitochondrial DNA in a family with sensorineural deafness and diabetes mellitus as the predominant clinical features].

An A to G transition at nucleotide 3,243 in the tRNA(Leu(UUR)) gene of mitochondrial DNA (mtDNA) has been suggested to be the disease-related mutation for MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes). Recently, the same mutation has also been found in several pedigrees with maternally inherited diabetes mellitus and sensorineural deafness. We report here a family showing the association of deafness and diabetes mellitus, as the predominant clinical features, with this mutation. The mutation was detected by restriction-enzyme analysis of the relevant PCR-amplified segment of the mtDNA, in two generations. In this family, it is noteworthy that two members with the mutation had some symptoms of MELAS such as short stature, seizures and mental retardation and that one had no clinical symptoms though the mtDNA mutation was identified in his blood. The findings in this family demonstrate the diversity of clinical expression of the mtDNA mutation and suggest that a combination of sensorineural deafness and diabetes mellitus is only one typical presentation of the various phenotypic features caused by the 3,243 mutation.

Adolescent↗
PubMed1995

[Audiologic evaluation in a family showing diabetes mellitus and deafness associated with a mutation in mitochondrial DNA].

An A to G transition at nucleotide 3,243 in the tRNA(Leu)(UUR) gene of mitochondrial DNA has recently been identified as a pathogenic point mutation which is associated with diabetes mellitus and sensorineural deafness in several pedigrees. We have also reported a family showing the association of deafness and diabetes mellitus as the predominant clinical features with this mutation. Audiologic data from two patients in this family are presented. Both had a bilaterally symmetrical sensorineural hearing loss at all frequencies. As is often the case with deafness associated with a mitochondrial disorder, the pure-tone threshold values were maximal at high frequencies in both patients. The audiologic work-up presented not only cochlear characteristics but also signs suggestive of retrocochlear disturbance with poor speech discrimination scores as compared to pure-tone thresholds, although auditory brain-stem responses showed neither wave delay nor prolonged interpeak latencies.

Adolescent↗