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Biomedical subjects

H Itoh

Publications and source records attributed to H Itoh.

At least 829 records · Page 46Linked to original sources
PubMed1994

Molecular cloning of human prostacyclin receptor cDNA and its gene expression in the cardiovascular system.

BACKGROUND: Prostacyclin elicits a potent vasodilation and inhibition of platelet aggregation through binding to its membrane receptor. The impairment of prostacyclin receptor activity is implicated in various human cardiovascular diseases. In the present study, we succeeded in the isolation and characterization of human prostacyclin receptor cDNA and elucidated its gene expression in human tissues. METHODS AND RESULTS: We isolated a cDNA clone encoding the human prostacyclin receptor from a human lung cDNA library. The isolated cDNA clone encodes a 386-amino acid protein with seven putative transmembrane domains, which belongs to the G protein-coupled receptor superfamily. [3H]iloprost, a prostacyclin receptor agonist, specifically bound to the receptor transiently expressed in COS-7 cells. The binding was inhibited in the rank order of iloprost = cicaprost, another prostacyclin receptor agonist, > prostaglandin E1 (PGE1) >> PGE2, PGF2 alpha, PGD2, STA2. In addition, iloprost dose-dependently stimulated cAMP generation in these COS-7 cells. These results are consistent with the characteristics of the human prostacyclin receptor. Northern blotting analysis on human tissues revealed that prostacyclin receptor mRNA is abundantly expressed in the aorta, lung, atrium, ventricle, and kidney. CONCLUSIONS: We cloned human prostacyclin receptor cDNA and elucidated its abundant gene expression in the human cardiovascular system. The present study will lead to better understanding of the significance of prostacyclin in humans and further facilitate the clinical application of prostacyclin.

Amino Acid Sequence↗
PubMed1994

Alteration of response to neuropeptide Y in the nucleus tractus solitarius of spontaneously hypertensive rats.

In normotensive rats, microinjections of neuropeptide Y (2.5 to 25 pmol) into the unilateral nucleus tractus solitarius elicited dose-dependent vasodepressor and bradycardiac responses accompanied by an inhibition of sympathetic nerve firing. After microinjections of the alpha 2-adrenergic receptor antagonist yohimbine (100 ng) into the nucleus tractus solitarius, the depressor and bradycardic responses to the injection of neuropeptide Y (25 pmol) into the nucleus tractus solitarius were significantly attenuated. In contrast, pretreatment with the alpha 1-adrenergic receptor antagonist doxazosin (200 ng) injected into the nucleus tractus solitarius did not alter these responses. In spontaneously hypertensive rats, microinjections of neuropeptide Y (25 pmol) into the nucleus tractus solitarius also elicited depressor and bradycardic responses that were significantly less than those of normotensive Wistar-Kyoto rats. However, pretreatment with yohimbine (100 ng) in the nucleus tractus solitarius did not diminish these depressor responses in spontaneously hypertensive rats. Depressor responses to neuropeptide Y, which was administered after yohimbine pretreatment, were also less in Wistar-Kyoto rats than in spontaneously hypertensive rats. The results suggest that the depressor and bradycardic responses elicited by neuropeptide Y were accompanied by the inhibition of sympathetic nerve activity. These responses may be mediated in part by alpha 2-adrenergic receptor in the nucleus tractus solitarius. The impairment of alpha 2-adrenergic receptor-mediated responses to neuropeptide Y in spontaneously hypertensive rats may contribute to the development of hypertension.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1994

Molecular cloning of the complementary DNA and gene that encode mouse brain natriuretic peptide and generation of transgenic mice that overexpress the brain natriuretic peptide gene.

Brain natriuretic peptide (BNP) is a cardiac hormone that occurs predominantly in the ventricle. To study the roles of BNP in chronic cardiovascular regulation, we isolated mouse BNP cDNA and genomic clones, and generated transgenic mice with elevated plasma BNP concentration. The mouse BNP gene was organized into three exons and two introns. Two BNP mRNA species were identified, which were generated by the alternative mRNA splicing. The ventricle was a major site of BNP production in mice. Mouse preproBNP was a 121- (or 120-) residue peptide, and its COOH-terminal 45-residue peptide was the major storage form in the heart. Transgenic mice carrying the human serum amyloid P component/mouse BNP fusion gene were generated so that the hormone expression is targeted to the liver. In the liver of these mice, considerable levels of BNP mRNA and peptide were detected, reaching up to 10-fold greater than in the ventricle. These animals showed 10- to 100-fold increase in plasma BNP concentration accompanied by elevated plasma cyclic GMP concentration, and had significantly lower blood pressure than their nontransgenic littermates. The present study demonstrates that these mice provide a useful model system with which to assess the roles of BNP in cardiovascular regulation and suggests the potential usefulness of BNP as a long-term therapeutic agent.

Alternative Splicing↗
PubMed1994

Molecular cloning of hamster brain and atrial natriuretic peptide cDNAs. Cardiomyopathic hamsters are useful models for brain and atrial natriuretic peptides.

Brain and atrial natriuretic peptides (BNP and ANP) are cardiac hormones with diuretic, natriuretic, and vasodilatory activities. Cardiomyopathic hamsters are widely used animal models of heart failure. Due to the structural divergence of BNP among species, examination on pathophysiological roles of BNP using cardiomyopathic hamsters is so far impossible. We therefore isolated hamster BNP and ANP cDNAs, and investigated synthesis and secretion of these peptides in normal and cardiomyopathic hamsters. The COOH-terminal 32-residue peptide of cloned hamster preproBNP with 122 amino acids, preceded by a single arginine residue, supposedly represents hamster BNP showing < 50% homology to rat BNP. Alpha-hamster ANP, 28-residue peptide, is identical to alpha-rat ANP. In hamsters, BNP and ANP occur mainly in the ventricle and the atrium, respectively. The 32-wk-old hypertrophic cardiomyopathic BIO14.6 strain exhibited ventricular hypertrophy. The 32-wk-old dilated cardiomyopathic BIO53.58 strain remained at the stage without apparent heart failure. In BIO14.6 and BIO53.58 strains at this age, ventricular BNP and ANP gene expressions are augmented, and the plasma BNP concentration is elevated to 136 and 108 fmol/ml, respectively, three times greater than the elevated plasma ANP concentration, which well mimics changes of the plasma BNP and ANP concentrations in human heart failure. Cardiomyopathic hamsters, therefore, are useful models to investigate the implication of BNP in human cardiovascular diseases.

Amino Acid Sequence↗
PubMed1994

Transforming growth factor-beta stimulates, and glucocorticoids and epidermal growth factor inhibit brain natriuretic peptide secretion from cultured human amnion cells.

We previously reported the massive secretion of brain natriuretic peptide (BNP) from human amnion cells and suggested the possible role of BNP in the maintenance of human pregnancy. In this study, to elucidate the regulatory mechanism of BNP secretion from amnion cells, we measured the BNP level in the culture medium of amnion cells by RIA after incubation in the presence of various substances. Among the agents examined, cortisol (1 x 10(-7) to 1 x 10(-6) mol/L), dexamethasone (1 x 10(-8) to 1 x 10(-6) mol/L), and epidermal growth factor (EGF; 2 x 10(-11) to 2 x 10(-8) mol/L) inhibited BNP secretion from the cultured amnion cells in a dose-dependent manner. By contrast, transforming growth factor-beta (TGF beta; 4 x 10(-11) to 4 x 10(-9) mol/L) caused a 3- to 5-fold increase in BNP secretion. TGF beta-augmented BNP secretion was abolished by the addition of cortisol or EGF to the culture medium. Moreover, in this study, we revealed the presence of bioactive TGF beta in human amniotic fluid (approximately 4 x 10(-10) mol/L). The present finding of tight regulation of BNP secretion from amnion cells by cortisol, EGF and TGF beta, all at the concentrations physiologically present in human amniotic fluid, implies a physiological role of BNP secretion from amnion cells in the pregnant uterus.

Amnion↗
PubMed1994

Micrographia due to focal cerebral lesions as seen in the dysarthria-clumsy hand syndrome.

Five patients with dysarthria-clumsy hand syndrome developed micrographia. Four had lacunar infarctions involving the putamen or the genu of the internal capsule; the fifth patient had a small hemorrhage in the putamen. Micrographia may be a sign of focal cerebral disease, and basal ganglia dysfunction may be involved in the supratentorial dysarthria-clumsy hand syndrome.

Aged↗
PubMed1994

Therapeutic effect of reticuloendothelial system (RES)-avoiding liposomes containing a phospholipid analogue of 5-fluorouracil, dipalmitoylphosphatidylfluorouridine, in Meth A sarcoma-bearing mice.

Reticuloendothelial system (RES)-avoiding liposomes are known to accumulate in tumor tissues due to passive targeting. Dipalmitoylphosphatidylfluorouridine (DPPF), a potent antitumor agent readily incorporated into the lipid bilayer, was embedded in RES-avoiding liposomes modified with a uronic acid derivative, palmityl-D-glucuronide (PGlcUA). The therapeutic effect of DPPF in PGlcUA-liposomes was examined in tumor-bearing mice. Free or liposomal DPPF was injected intravenously into BALB/c mice bearing subcutaneously implanted Meth A sarcomas. The RES-avoiding liposomal formulation using PGlcUA was effective in reducing tumors, and prolonging survival time compared with free DPPF and also DPPF in conventional liposomes. Therefore, PGlcUA-liposomes might be of practical use as drug carriers for anticancer agents, especially their derivatives for embedding in liposomal membranes.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1994

Studies on photochemical reactions of air pollutants. XII. Photochemical epoxidation of aldrin with suspended particulates in air.

Suspended particulates collected in Yokohama, Japan over various 24-h periods were found to cause the photochemical epoxidation of aldrin to dieldrin in good yield. trans-Stilbene did not undergo the epoxidation. Upon irradiation of aldrin together with the suspended particulates in quasi-air consisting of 18O2. 100% incorporation of 18O into dieldrin was obtained. Thus, the oxygen atom in dieldrin originated not from the particulates, but from oxygen in air.

Air Pollutants↗
PubMed1994

Studies on a novel, potent and orally effective cholecystokinin A antagonist, FK-480. Synthesis and structure-activity relationships of FK-480 and related compounds.

We prepared various novel tricyclic 1,4-benzodiazepine derivatives as cholecystokinin (CCK) A antagonists, which were evaluated preliminarily for inhibition of 125I-CCK-8 binding to rat pancreatic membranes in vitro and inhibiting effect on CCK-8-induced inhibition of charcoal meal gastric emptying in mice. On the basis of structure-activity relationship (SAR) studies, as well as the stability and availability of the starting materials of those compounds, (S)-N-[1-(2-fluorophenyl)-3,4,6,7-tetrahydro-4-oxo- pyrrolo[3,2,1-jk][1,4]benzodiazepin-3-yl]- 1H-indole-2-carboxamide (9f, FK-480) was selected as a candidate compound for further evaluation. The absolute configuration of the precursor of FK-480, (3S)-amino-1,4-benzodiazepine derivative ((S)-8a, R1 = F) was determined by an X-ray crystallographic study of its ureido derivative with (S)-alpha-methylbenzyl isocyanate. FK-480 is now undergoing clinical studies for the treatment of chronic pancreatitis.

Animals↗
PubMed1994

Inhibitory action of a (1-->6)-beta-D-glucan-protein complex (F III-2-b) isolated from Agaricus blazei Murill ("himematsutake") on Meth A fibrosarcoma-bearing mice and its antitumor mechanism.

The effects of F III-2-b (Agaricus blazei Murill polysaccharide) with or without 5-fluorouracil (5-FU) on immune responses were investigated in Meth A tumor-bearing and normal mice. The i.p. administration of F III-2-b (10 mg/kg/day x 30) moderately inhibited the growth of Meth A tumor cells implanted s.c. in mice. Development of implanted tumors was strongly inhibited by the combination of F III-2-b and 5-FU. The picryl chloride-induced delayed type hypersensitivity (PC-DTH) response in mice was depressed after the implantation of tumor and treatment with 5-FU. F III-2-b restored the suppression of PC-DTH by 5-FU, but did not increase the PC-DTH of normal mice. F III-2-b not only enhanced the degree of spleen cell-mediated sheep red blood cells (SRBC) hemolysis (quantitative hemolysis of SRBC), the indexes of the spleen and thymus, and the number of spleen cells but also restored the suppressive effect of 5-FU. In the group receiving F III-2-b, the percentages of splenic Thy1.2-, L3T4- and asialo GM1-positive cells were significantly increased as compared with the tumor-bearing mice treated with saline. Furthermore, the L3T4+/Lyt2+ ratio showed a tendency to increase, and the Lyt2+ ratio was markedly decreased. These results suggest that the antitumor effect of F III-2-b may be correlated with the changing pattern of the Thy1.2-, L3T4- and asialo GM1-positive cells.

Agaricus↗
PubMed1994

An automated method to assess the distribution of low attenuation areas on chest CT scans in chronic pulmonary emphysema patients.

We developed an automated method to recognize the lung in a computed tomographic (CT) image. With computer-assisted analysis, we were able to describe the continuous low attenuation (less than -960 Hounsfield units) areas (CLA) on chest CT scans. The size (CLAs) and number (CLAn) of the CLA and the percentage of total lung area occupied by low attenuation area (LAA%) were measured using CT scans obtained from 24 patients with chronic pulmonary emphysema (CPE) and 13 control patients. The automated algorithm recognized the lung areas successfully in all patients. The CLAs and LAA% were significantly higher, and CLAn was significantly lower in patients with CPE than in controls. There was a significant correlation between CT parameters and pulmonary function test results. The histograms of the size of CLA could be represented as a power function in each patient. This automated method should be useful in objectively defining the affected areas in the lungs of patients with CPE.

Aged↗
PubMed1994

Clinical application of pulsatility index of flow volume to detect the hemodynamic changes in IUGR fetus.

We attempted to assess feto-placental circulation in fetuses with intrauterine growth retardation (IUGR) by calculating the pulsatility index of flow volume (PIQ) based on the quantitative measurement of blood flow. Doppler sound was processed by an analog to digital converter and a frequency analyzer. Multiplication of frequency and signal strength of the Doppler sound at a certain time theoretically represents a value proportional to flow volume. Using this value, we calculated PIQ of the descending aorta, umbilical artery, and middle cerebral artery in normal fetuses, IUGR fetuses, and distressed fetuses during 24-41 weeks gestation. The PIQ of the fetal descending aorta in the IUGR fetus was significantly higher than that of the normal fetus. When cutoff value was set to mean +1 SD, abnormal PIQ was observed in 88% of IUGR fetuses. In contrast, the abnormal pulsatility index of maximal flow velocity (PIV) of the descending aorta was observed in only 62% of IUGR fetuses. In the distressed fetuses, both PIQ and PIV of the umbilical artery increased, and these indices of the middle cerebral artery markedly decreased. It is suggested that the increased PIQ of the descending aorta is an early indicator of changes in the fetal circulation in IUGR fetuses.

Aorta↗
PubMed1994

Percutaneous biopsy for adrenal tumors using ultrasonically guided puncture.

Percutaneous biopsy for adrenal tumors was performed on 12 patients using ultrasonically guided puncture. Of the 12 tumors, 11 were detected incidentally by ultrasonography or computed tomography. In 11 cases, cytological or pathological diagnosis was obtained without any complication. Among these, surgical operation was carried out in 4 cases, in which biopsy findings were confirmed by the examination of the surgical specimens. The other 7 cases were being followed up without surgery. The rate of correct discrimination between benign and malignant adrenal tumors by biopsy was 91% (10/11 cases) in this series. It is accordingly considered that adrenal biopsy is the choice to confirm the diagnosis of nonfunctioning adrenal tumors because of its efficacy and ease of use.

Adrenal Gland Neoplasms↗
PubMed1994

A monoclonal antibody to C-type natriuretic peptide--preparation and application to radioimmunoassay and neutralization experiment.

C-type natriuretic peptide (CNP), the third member of natriuretic peptides, has recently been discovered from the porcine brain. Using a polyclonal antiserum to CNP, we demonstrated that CNP-like immunoreactivity (CNP-LI) is present mainly in the central nervous system. Recently, however, we have discovered the production and secretion of CNP in vascular endothelial cells. These observations suggested that CNP may act not only as a neuropeptide but also as a local regulator of vascular tone or growth. In order to further clarify the pathophysiological significance of CNP, we aimed at the preparation of a monoclonal antibody to CNP. A monoclonal antibody to CNP, KY-CNP-I, has been produced. This monoclonal antibody belongs to the immunoglobulin G1 subclass and has high affinity for CNP. Using this monoclonal antibody, we established a specific radioimmunoassay (RIA) for CNP. The RIA detected CNP-LI in rat brain extracts and culture media conditioned with bovine endothelial cells. In addition, the pretreatment of cultured aortic smooth muscle cells with KY-CNP-I attenuated cyclic GMP production induced by CNP in vitro. The preadministration of KY-CNP-I to rats also attenuated plasma cyclic GMP increase after intravenous injection of CNP in vivo. These results indicate that this monoclonal antibody is a useful tool to clarify the pathophysiological role of CNP as a neuropeptide and as a local vascular regulator.

Animals↗
PubMed1994

Relationship between maximal pulmonary ventilation during exhaustive exercise and postexercise plasma potassium concentration in man.

The present study was undertaken to examine the relationship between maximal pulmonary ventilation (VEmax) and potassium concentration ([K+]) or lactate concentration ([La]) of venous blood in man. Nine healthy men performed exercise on a bicycle ergometer at a constant rate of 60 rpm until volitional fatigue. VEmax ranged from 100.4 to 153.2 l/min. In all subjects, potassium concentration measured at 1 min ([K+]1.0) after maximal exhaustive exercise was the highest, and it returned quickly to the resting level within a few minutes during recovery. VEmax was significantly correlated (r = 0.750, p < 0.05) to [K+]1.0, but not to lactate concentration determined at 1 min ([La]1.0) during recovery. These results suggest that a higher increase in blood [K+] may, at least partly, contribute to a greater augmentation of VE during exhaustive exercise.

Adult↗
PubMed1994

Partial splenic embolization for the treatment of chronic idiopathic thrombocytopenic purpura.

OBJECTIVE: The purpose of this study was to assess the effectiveness of partial splenic embolization in the treatment of chronic idiopathic thrombocytopenic purpura. SUBJECTS AND METHODS: Twenty-six patients with chronic idiopathic thrombocytopenic purpura underwent partial splenic embolization and were followed up for 6-61 months. The condition was refractory to steroids in 20 of 26 patients. The other six patients, in whom a response to steroids was shown, could not be withdrawn from steroid therapy because their platelet counts decreased with any decrease in steroid dose. Five of 26 patients underwent splenectomy after partial splenic embolization, and the other patients were followed up without medical treatment until platelet counts decreased below 3 x 10(10)/l. The therapeutic effect of partial splenic embolization was defined on the basis of the platelet count at the last follow-up after partial splenic embolization: complete response, greater than 10 x 10(10)/l; partial response, 5 x 10(10)/l to 10 x 10(10)/l; and no response, less than 5 x 10(10)/l without medication. RESULTS: Partial splenic embolization brought a complete response in seven (33%) of 21 patients, a partial response in eight (38%), and no response in six (29%). In four of five patients, who later underwent splenectomy, response to partial splenic embolization was coincident with the response to splenectomy. No serious complications occurred, but minor complications such as abdominal pain, fever, and nausea were observed in most patients. CONCLUSION: This study suggests that partial splenic embolization might be useful as an alternative to splenectomy in the treatment of chronic idiopathic thrombocytopenic purpura.

Adult↗