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Biomedical subjects

K Takeuchi

Publications and source records attributed to K Takeuchi.

At least 721 records · Page 40Linked to original sources

Simultaneous determination of nerve-induced adenine nucleotides and nucleosides released from rabbit pulmonary artery.

Electrical field stimulation elicits the release of catecholamines, adenine nucleotides, and adenosine from the rabbit pulmonary artery in a frequency dependent manner. To enhance our ability to investigate the release of endogenous adenine nucleotides and adenosine from this and other biological preparations, a new analytical procedure has been developed. This procedure involves the use of an internal standard, 9-beta-D-arabinofuranosyladenine (IS), the derivatization of ATP, ADP, AMP, adenosine (Ado), and IS with chloroacetaldehyde, the isocratic high-performance liquid chromatographic separation of these ethenopurine derivatives on an Ultron N-phenyl HPLC column, and their detection and quantitation by fluorescence spectroscopy. This procedure has enhanced sensitivity and reliability over existing procedures due to the stability of the chromatographic baseline and the use of an internal standard. When this analytical procedure was utilized to measure the adenine nucleotides and Ado that are released from the rabbit pulmonary artery in response to electrical field stimulation, it was observed that the release of endogenous ATP, ADP, AMP, and Ado exceeded that of endogenous norepinephrine. A molar ratio (6-amino purines:catecholamines) of approximately 2000:1 was obtained at a stimulation frequency of 16 Hz. This observation suggests an important extracellular role for adenine nucleotides and nucleosides in the physiology of vascular tissues.

Acetaldehyde↗

[Radiotherapy for vulvar cancer].

Fifteen patients who had primary vulvar cancer treated with radiotherapy as an initial treatment at Hyogo Medical Center for Adults and Hyogo Cancer Center from January 1971 to December 1990 are presented. Two patients were stage 0, one stage I, three stage II and nine stage III. Nine patients received electron irradiation with or without interstitial irradiation and intracavitary vaginal irradiation. Five patients received megavoltage X-ray irradiation using AP/PA parallel opposed fields including the pelvic nodes and perineum followed by boost irradiation of electrons, interstitial irradiation and intracavitary vaginal irradiation. The total dose delivered to the primary tumor ranged from 50 to 100 Gy (73 Gy on average). The actuarial 5-year survival rate of the patients was 43.6%. Complete regression (CR) was achieved in 60% of the patients. However, CR was not achieved in any of five patients with palpable inguinal nodes. In contrast, all the patients who had tumors of less than 2 cm in diameter achieved CR. Five of nine CR cases relapsed. First sites of failure were vagina, groin and vulvar region. Recurrence occurred more than four years after treatment in three cases. Necrosis occurred in five of nine CR cases.

Adult↗

Effects of nitric oxide synthase inhibitors on duodenal alkaline secretion in anesthetized rats.

We examined the effects of NG-nitro-L-arginine methyl ester (L-NAME), the nitric oxide (NO) synthase inhibitor, on duodenal HCO3- secretion in anesthetized rats. L-NAME (1-5 mg/kg i.v.), given as a single injection, increased HCO3- secretion in a dose-dependent manner. This effect of L-NAME was mimicked by NG-monomethyl-L-arginine (50 mg/kg i.v.) and was significantly antagonized by the simultaneous administration of L-arginine (200 mg/kg i.v.) but not D-arginine. The increased HCO3- response to L-NAME was also significantly reduced in vagotomized animals. These findings suggest that the inhibition of NO biosynthesis leads to an increase of duodenal HCO3- secretion, partly mediated by the vagus nerves.

Amino Acid Oxidoreductases↗

Contribution of cardiac renin-angiotensin system to ventricular remodelling in myocardial-infarcted rats.

To investigate the contribution of the cardiac renin-angiotensin system to ventricular dilatation after myocardial infarction, we examined the effects of 3-week treatments with an angiotensin converting enzyme inhibitor, delapril, and a selective angiotensin II type 1 (AT1) receptor antagonist, TCV-116, on haemodynamics and ventricular angiotensin II contents in myocardial-infarcted rats. TCV-116 reduced mean aortic pressure, and prevented the increase of right and left ventricular weight, left ventricular end-diastolic pressure and volume of myocardial-infarcted rats, to a similar extent to delapril. Thus, AT1 receptor-mediated action of angiotensin II plays a central role in the development of ventricular dilatation. Angiotensin II contents in the right and non-infarcted left ventricles (6.0 +/- 1.0 and 5.9 +/- 0.7 pg/g tissue, respectively, mean +/- S.E.M.) of myocardial-infarcted rats were not different from those of sham-operated rats. However, angiotensin II contents in the infarcted scar (21.7 +/- 3.5 pg/g) of myocardial-infarcted rats were 4.2-fold higher than those in the left ventricle of sham-operated rats. Delapril reduced angiotensin II contents in the right and non-infarcted left ventricles, and the scar by 48, 81 and 60%, respectively, but did not reduce plasma angiotensin II in myocardial-infarcted rats. TCV-116 also decreased angiotensin II in the right and non-infarcted left ventricles by 57 and 56%, respectively, while increased plasma angiotensin II by 4.3-fold. Thus, the prevention of ventricular dilatation by these two agents was associated with the decrease in ventricular angiotensin II contents. These observations suggest that the cardiac renin-angiotensin system rather than the circulating system may play an important role in ventricular dilatation after myocardial infarction.

Analysis of Variance↗

Methoxamine enhances the release of endogenous noradrenaline from rabbit ear artery: possible involvement of ATP.

The effect of methoxamine, an alpha 1-adrenoceptor agonist, on the electrically-evoked release of endogenous noradrenaline was examined in the isolated rabbit ear artery. Noradrenaline was quantified by high performance liquid chromatography-electrochemical detection. The release of adenine nucleotides and nucleosides by methoxamine was examined using high performance liquid chromatography-fluorescence detection. The release of noradrenaline evoked by electrical field stimulation (EFS) at 4 Hz was reduced by tetrodotoxin 0.3 mumol/l and clonidine 1 mumol/l by approximately 80% and 50%, respectively. On the other hand, methoxamine at 10 but not 1 mumol/l enhanced the release of noradrenaline to approximately twice the control, and the enhancement was prevented by prazosin 1 mumol/l. The facilitatory action of methoxamine was also abolished after desensitization of P2-purinoceptors by alpha,beta-methylene ATP 30 mumol/l as well as by the presumed P2-purinoceptor antagonist suramin given at 10 mumol/l. Exogenous ATP 10 mumol/l significantly enhanced the EFS-evoked release of noradrenaline, and the enhancement was abolished by alpha,beta-methylene ATP and suramin. None of the drugs changed the spontaneous outflow of noradrenaline. These results indicate that endogenous ATP, acting at prejunctional purinoceptors, may participate in the facilitatory effect of methoxamine. Indeed, methoxamine 10 mumol/l significantly enhanced the spontaneous outflow of ATP and, less so, ADP. The methoxamine evoked release of ATP and ADP was antagonized by prazosin 1 mumol/l. It is concluded that methoxamine releases endogenous ATP from postjunctional sites which then, via prejunctional purinoceptors, facilitates action potential-evoked release of noradrenaline in rabbit ear artery.

Adenine Nucleotides↗

Mechanism by which histamine increases gastric mucosal blood flow in the rat. Role of luminal H+.

The mechanism by which histamine increases gastric mucosal blood flow (GMBF) was investigated in the anesthetized rat. The experiment was performed in the presence of tripelennamine, an H1 antagonist, to focus on the relationship between acid secretion (H2-receptor-mediated response) and GMBF. The stomach was mounted on a Lucite chamber, perfused with saline, and GMBF was measured by laser Doppler flowmetry simultaneously with acid secretion. Under these conditions, histamine at the submaximal dose significantly increased GMBF as well as acid secretion, and this increase of GMBF was completely blocked when acid secretion was inhibited by cimetidine or omeprazole. The elevation of GMBF caused by histamine was also significantly attenuated when luminal H+ was removed by intraluminal perfusion with NaHCO3 or glycine. Glycine by itself did not affect the increase of acid secretion induced by histamine and the increase of GMBF caused by isoproterenol, yet significantly inhibited the GMBF response induced by pentagastrin. Intraluminal perfusion with HCl also produced an increase of GMBF in a concentration-related manner, even in the presence of omeprazole during histamine infusion. Pretreatment of the animals with indomethacin significantly blocked the GMBF responses induced by either histamine or luminal HCl. These results suggest that the increase of GMBF during acid secretion induced by histamine may be caused by luminal H+ and involve endogenous prostaglandins in its mechanism.

Animals↗

In vitro transcription and replication of the mumps virus genome.

By the use of lysolecithin-permealized extracts from mumps virus-infected HeLa cells, we have developed an in vitro system, which not only directed the synthesis of mumps virus mRNAs but also supported replication of the genomic RNA. Furthermore, upon transcription of the P gene, both faithful and edited copies of the P gene were detected by RNase mapping with a riboprobe. Thus this system seems to promote biochemical analyses of underlying mechanisms operative in mumps virus gene expression and replication, including RNA editing.

Cell-Free System↗

Quantification of human splenic blood flow (quantitative measurement of splenic blood flow with H2(15)O and a dynamic state method: 1).

Positron emission tomography (PET) by means of a dynamic state method and H2(15)O was performed to quantify splenic blood flow in 20 patients who had no hepatic functional disorders. Non-linear regression analysis was applied to determine splenic blood flow. In calculating arterial input function for the spleen, our original exponential method was used to facilitate computerization. Mean splenic blood flow per 100 g of spleen (SBF) was 168.0 ml/min/100 g with a standard error (SE) of 12.4 ml/min. The mean spleen-blood partition coefficient for water (rho) was 0.767 with a SE of 0.020. Significant correlations were noted between the values for SBF obtained by the exponential method and linear method in which individual increasing values for arterial 15O concentration were used rectilinearly (r = 0.96, p < 0.005) and also between the values for rho obtained by the two methods (r = 0.95, p < 0.005). In order to validate the application of a one compartment model to an organ with a large blood volume such as the spleen, a further experiment was performed with a water flow model simulating splenic circulation. We succeeded in quantifying regional splenic blood flow by PET. It was thought that the quantification of splenic blood flow by our method would be beneficial in the study of splenic circulation, which is expected to be altered under conditions of portal hypertension, liver dysfunction and shock, etc.

Adult↗

Relationship between liver function and splenic blood flow (quantitative measurement of splenic blood flow with H2(15)O and a dynamic state method: 2).

We measured splenic blood flow in 55 patients by means of quantitative splenic positron emission tomography (PET), a novel, dynamic state method with H2(15)O as a tracer. Twenty-four of the 55 patients suffered from liver cirrhosis (LC), 25 showed no evidence of cirrhosis (NR) and 6 patients were diagnosed as having chronic hepatitis (CH). Splenic blood flow per 100 g weight of the spleen (SBF) was significantly correlated with splenic volume (r = -0.39, p < 0.005). The indocyanine green retention test at 15 min (r = -0.39, p < 0.005) and the hepaplastin test (r = 0.37, p < 0.025) also correlated significantly with SBF. The means and 95% confidence intervals for the LC, CH, and NR groups were 117.5 ml/min/100 g (96.6-138.4), 102.5 ml/min/100 g (60.6-144.4), and 160.3 ml/min/100 g (139.8-180.8), respectively. The differences in SBF between these 3 groups were significant (p < 0.01). We conclude that regional splenic blood flow is not proportionate to splenic volume, although the splenic volume does increase with the progressive chronic changes observed in hepatic diseases.

Adult↗

Difference in regional hepatic blood flow in liver segments--non-invasive measurement of regional hepatic arterial and portal blood flow in human by positron emission tomography with H2(15)O.

Organ blood flow can be quantitatively measured by positron emission tomography (PET). As the liver has dual blood supplies, arterial and portal, regional hepatic blood flow had not been measured quantitatively. However, we succeeded in simultaneously measuring both regional hepatic arterial and portal blood flow by PET in non-stressed patients. Mean regional portal hepatic blood flow in patients with normal liver and cirrhotic liver was 57.5 and 36.7 ml/minutes/100 g, respectively. Mean regional arterial blood flow was 42.5 and 30.7 ml/minutes/100 g, respectively. A significant difference between regional portal hepatic blood flows in normal and cirrhotic patients was noted. Mean regional portal hepatic blood flow in the lateral, medial, anterior, and posterior segments of the liver was 29.8, 43.4, 50.0, and 40.9 ml/minutes/100 g, respectively. Mean regional arterial blood flow in each liver segment was 37.6, 30.0, 28.2, and 31.6 ml/minutes/100 g, respectively. A significant difference between regional portal hepatic blood flows in lateral and anterior segment was noted. The p value was less than 0.025 and the 95% confidence interval of the difference between means was from -20.2 to -2.7 ml/minutes/100 g by ANOVA. These results showed that regional hepatic blood flow is not the same in all the liver segments.

Adult↗

Clinical and histologic features of alcohol drinkers with congestive heart failure.

To clarify the difference between alcoholic cardiomyopathy and dilated cardiomyopathy and to investigate the characteristics of alcoholic cardiomyopathy, right ventricular endomyocardial biopsy was performed, and the two diseases were compared clinically and histologically. Changes in the cardiothoracic ratio, cardiac index, and systolic blood pressure/end-systolic volume index were greater after treatment in patients with alcoholic cardiomyopathy than in patients with dilated cardiomyopathy. Histologically, myocytic hypertrophy, fibrosis, and nuclear change were less significant in the former than in the latter. Among patients with alcoholic cardiomyopathy, the cardiac index in those with less fibrosis was greater than in those with more fibrosis. Thus patients with alcoholic cardiomyopathy had more preserved and reversible cardiac function and fewer histologic changes than the patients with dilated cardiomyopathy. Reversibility of cardiac function in patients with alcoholic cardiomyopathy correlated inversely with the severity of histologic changes.

Adult↗

Delayed hemolytic transfusion reaction with anti-Jkb erythrocyte antibody after open heart surgery.

A patient suffering from delayed hemolytic transfusion reaction with anti-Jkb erythrocyte antibody after open heart surgery is reported on. On preoperation evaluation, a 42-year-old woman who had never been transfused exhibited a negative erythrocyte autoantibody. After the operation of aortic valve replacement and open mitral commisurotomy, she developed a severe hemolytic anemia with a positive rare anti-Jkb erythrocyte antibody on the 14th postoperative day. Precautions are discussed which need to be taken to distinguish delayed hemolytic transfusion reaction from mechanical hemolysis caused by extracorporeal circulation and prostheses.

Adult↗

Effects of inotropic stimulation on phosphate compounds in ischaemic canine hearts.

OBJECTIVE: The aim was to evaluate regional coronary blood flow, contractile function, and concentration of phosphate compounds with inotropic stimulation in moderately ischaemic canine hearts. METHODS: Dogs were prepared with instrumentation for the determination of regional coronary blood flow (non-radioactive microsphere method), contractile function (sonomicrometry), and haemodynamics. Myocardial phosphate compounds were measured simultaneously by the phosphorus-31 magnetic resonance spectroscopic technique. RESULTS: In the non-ischaemic condition, dobutamine increased regional coronary blood flow and enhanced contractile function with no significant changes in myocardial phosphate compounds. After constricting the left anterior descending coronary artery, dogs were divided into two groups according to their heart beat response to dobutamine, classified as no pronounced tachycardia with dobutamine (group NT), and pronounced tachycardia (group T). In group NT, dobutamine increased regional coronary blood flow and improved regional contractile function with no significant effect on myocardial phosphate compounds. In group T, dobutamine failed to increase regional coronary blood flow or to improve contractile function, but there was a significant increase in the inorganic phosphate to creatinine phosphate ratio. CONCLUSIONS: Dobutamine increased coronary blood flow and augmented contractile function without significant changes in phosphate compounds in the moderately ischaemic heart, when pronounced tachycardia was not induced. The augmentation of contractile function occurred without prominent improvement in energy metabolism.

Animals↗

Regulation of gastroduodenal bicarbonate secretion by capsaicin-sensitive sensory neurons in rats.

We investigated the role of capsaicin-sensitive sensory neurons in regulation of gastroduodenal HCO3- secretion in anesthetized rats. The stomach (under acid inhibition by omeprazole 60 mg/kg i.p.) or the duodenum was perfused with saline (pH 4.5) and HCO3- output was determined by pH change in the perfusate. Both the duodenum and stomach responded to prostaglandin E2 (PGE2; 300 micrograms/kg i.v.) or luminal acid by a significant increase in pH and HCO3- output. These tissues also responded to luminal application of capsaicin (0.3-6 mg/ml for 30 min), resulting in a significant increase of pH and HCO3- output in a concentration-related manner. The HCO3- stimulatory action of capsaicin was markedly attenuated by functional ablation of capsaicin-sensitive sensory neurons, significantly mitigated by indomethacin, and exhibited tachyphylaxis after repeated application at a high concentration. The acid-induced pH and HCO3- responses were also significantly mitigated by sensory deafferentation and by indomethacin, whereas those induced by PGE2 remained unaffected. In addition, defunctionalization of these sensory nerves resulted in macroscopically visible damage in the duodenum when acid secretion was concomitantly stimulated by histamine. We conclude that capsaicin-sensitive sensory neurons may be involved in the regulatory mechanism of gastroduodenal HCO3- secretion and contribute to protection of the mucosa against acid. Endogenous PGs may be involved in the HCO3- stimulatory action mediated by capsaicin-sensitive sensory neurons.

Afferent Pathways↗

Brain atrophy and intellectual impairment in tardive dyskinesia.

Fourteen chronic schizophrenic patients with tardive dyskinesia (TD) and 13 without TD were given psychological tests and CT scans. The low density rate (LDR), i.e., the ratio of the X-ray absorption (corresponding nearly to that of cerebrospinal fluid) of a brain lesion to the X-ray absorption of the whole brain, was used as an index of brain atrophy (HN-method). The LDR of the left hemisphere of the TD patients was significantly higher than that of non-TD patients in the basal nucleus and lateral ventricle, and the LDR of the right hemisphere for the TD patients was significantly higher than that of non-TD patients in the basal nucleus. The Hasegawa Dementia Rating Scale (HDRS) and Bender-Gestalt Test (BGT) for the TD patients were significantly lower than those for the non-TD patients. Our study revealed that brain atrophy was greater in TD than in non-TD patients and tended to be more pronounced in the left hemisphere, and that the degree of intellectual impairment was greater in the TD patients than in the non-TD group. The results suggest that schizophrenic brains with TD tend to be more easily damaged than those without TD, that this tendency predominates on the left side, and that intellectual impairment in TD is related to brain atrophy.

Adult↗

Identification of an amino acid that defines the fusogenicity of mumps virus.

Recombinant cDNA clones representing the fusion (F) and hemagglutinin-neuraminidase (HN) proteins of two mumps virus strains different in fusogenicity were constructed. Upon transfection of COS7 cells, extensive cell fusion was observed only when cells expressed the F protein of the fusing strain together with the HN protein derived from either strain. Mutational analyses further showed that the amino acid at position 195 of the F protein plays a critical role in determining the extent of cell fusion induced by mumps virus, since replacement of Ser-195 by Tyr significantly reduced the fusion inducibility of otherwise fusion-competent F protein.

Animals↗

Ion channel activity of influenza A virus M2 protein: characterization of the amantadine block.

The influenza A virus M2 integral membrane protein has ion channel activity which can be blocked by the antiviral drug amantadine. The M2 protein transmembrane domain is highly conserved in amino acid sequence for all the human, swine, equine, and avian strains of influenza A virus, and thus, known amino acid differences could lead to altered properties of the M2 ion channel. We have expressed in oocytes of Xenopus laevis the M2 protein of human influenza virus A/Udorn/72 and the avian virus A/chicken/Germany/34 (fowl plague virus, Rostock) and derivatives of the Rostock ion channel altered in the presumed pore region. The pH of activation of the M2 ion channels and amantadine block of the M2 ion channels were investigated. The channels were found to be activated by pH in a similar manner but differed in their apparent Kis for amantadine block.

Amantadine↗