Biomedical subjects

M Arita

Publications and source records attributed to M Arita.

At least 91 records · Page 5Linked to original sources

PubMed1998

NO and cGMP facilitate adenosine production in rat hearts via activation of ecto-5'-nucleotidase.

We examined whether nitric oxide (NO), a possible cardioprotective substance, can increase the production of interstitial adenosine in the ventricular myocardium. A flexibly mounted microdialysis technique was used to measure the concentration of interstitial adenosine and to assess the activity of ecto-5'-nucleotidase in in vivo rat hearts. The microdialysis probe was implanted in the left ventricular myocardium of anesthetized rats and perfused with Tyrode solution containing adenosine 5'-monophosphate (AMP) at a rate of 1.0 microl min-1. The concentration of adenosine in the effluent (dialysate) was measured by high-performance liquid chromatography. Dialysate adenosine obtained during perfusion with the AMP-containing solution through the probe originated from the hydrolysis of AMP by endogenous ecto-5'-nucleotidase, and the level of adenosine reflected the activity of ecto-5'-nucleotidase in the tissue. S-Nitroso-N-acetylpenicillamine (SNAP, 0.3-3 mM), an NO donor, increased the dialysate adenosine measured in the presence of AMP (100 microM) in a concentration-dependent manner. However, in the presence of an NO-oxidizing agent, 2-(4-carboxyphenyl-4,4,5, 5-tetramethylimidazoline)-1-oxyl 3-oxide (carboxy-PTIO, 1 mM), the effect of SNAP was abolished. Another NO donor, (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409, 1 mM) also increased adenosine production. 8-Bromo-cGMP (0.1-3 mM), a membrane-permeable cGMP analogue and a potent activator of cGMP-dependent protein kinase, increased the level of AMP-primed dialysate adenosine in a concentration-dependent manner. These results suggest that NO facilitates the production of interstitial adenosine in rat hearts in situ, via cGMP-mediated activation of ecto-5'-nucleotidase.

5'-Nucleotidase↗

PubMed1998

Effects of hydroxyl radicals on KATP channels in guinea-pig ventricular myocytes.

We studied the effects of oxygen free radicals on the ATP-sensitive potassium channel (KATP channel) of guinea-pig ventricular myocytes. Single KATP channel currents were recorded from inside-out patches in the presence of symmetrical K+ concentrations (140 mM in both bath and pipette solutions). Reaction of xanthine oxidase (0.1 U/ml) on hypoxanthine (0.5 mM) produced superoxide anions (.O2-) and hydrogen peroxide (H2O2). Exposure of the patch membrane to.O2- and H2O2 increased the opening of KATP channels, but this activation was prevented by adding 1 microM glibenclamide to the bath solution. In the presence of ferric iron (Fe3+: 0.1 mM), the same procedure produced hydroxyl radicals (.OH) via the iron-catalysed Haber-Weiss reaction.OH also activated KATP channels; however, this activation could not be prevented by, even very high concentrations of glibenclamide (10 microM). These different effects of glibenclamide suggest that the mode of action of these oxygen free radicals on KATP channels is different and that.OH is more potent than.O2-/H2O2 in activating KATP channels in the heart.

Adenosine Triphosphate↗

PubMed1998

Effects of the ATP-sensitive K channel opener nicorandil on the QT interval and the effective refractory period in patients with congenital long QT syndrome. Investigator Group for K-Channel Openers and Arrhythmias.

Congenital or idiopathic long QT syndrome is characterized by a frequently lethal ventricular arrhythmia called torsades de pointes (TdP) as well as a prolonged QT interval. The long QT interval related to an abnormal gene of the Na+ channel has been shown to be shortened by mexiletine. However, the action of K+ channel openers on the QT interval associated with abnormal genes of the K channel has yet to be studied. Seven patients of five families with long QT syndrome were included in this study, of whom six had syncope and six had documented TdP. Either long QT interval or sudden cardiac death had been observed in family members of all seven patients. At 1 to 3 weeks after admission, when TdP or frequent ventricular arrhythmia had subsided, nicorandil, an ATP-sensitive K channel opener, was administered orally at a dose of 15 mg/day in five patients and at 30 mg/day in the remaining two patients, and the effects were assessed on the third day after drug administration. In four patients, the effective refractory period was measured in the right ventricle before and after administration of K channel opener administration. The QT interval (QTc) prior to administration of the K channel opener was 0.60 +/- 0.09 ms (mean +/- SD) (0.61 +/- 0.10 second(1/2)), which was shortened to 0.54 +/- 0.05 ms (0.55 +/- 0.06 second(1/2)) on the third day of drug administration (P < .05 for both): 10.4 +/- 8.0% (8.6 +/- 5.5%). The QT interval at varying preceding R-R intervals on Holter electrocardiograms showed a shift toward the right as a result of the drug administration. The effective refractory period showed a significant prolongation, 256 +/- 26 ms versus 280 +/- 22 ms before and after drug administration, respectively (P <.05). Intravenous administration of nicorandil resulted in no significant change in heart rate or blood pressure, while QTc showed a tendency to shorten, but nonsignificantly (P = .08). However, a hump on the monophasic action potential was abolished, especially at the long preceding R-R interval induced by premature stimulation of the ventricle. It is concluded that nicorandil shortens the QT interval slightly when administered orally, whereas the effective refractory period shows a slight prolongation. The physiologic and clinical significance of these effects needs to be studied further.

Administration, Oral↗

PubMed1998

Mechanism of preservation of myocardial calcium channel function by pyruvate cardioplegic solution.

We evaluated the effects of adding pyruvate to a cardioplegic solution on the preservation of the dihydropyridine-sensitive calcium (Ca2+) current responses to beta-adrenergic stimulation in rabbit cardiac myocytes by measurement of single-channel open probability. Single ventricular myocytes were isolated and stored in St. Thomas' solution with or without pyruvate at 4 degrees C for 2, 6, 12, or 24 hours, and cell-attached single Ca2+ channel currents recordings were made at 20 degrees to 22 degrees C after each storage period. When 0.1 micromol/L isoproterenol (ISO) was applied to the cells, the percent mean open probability of the Ca2+ channels tested in freshly isolated cells was 181% +/- 27% (n = 12) of control values. These responses decreased with an increasing duration of the hypothermic storage and were only 112% +/- 22% (n = 5) of control values after 24 hours of storage in the absence of pyruvate. Conversely, the responses were significantly preserved, to as much as 143% +/- 17% (n = 7), in the presence of 10 mmol/L pyruvate in the storage solution. The application of forskolin to stimulate adenylate cyclase or a membrane-permeable cyclic adenosine monophosphate mimicked the effects of ISO when the myocytes were stored with pyruvate. Pyruvate did not alter the open-channel kinetics or single-channel conductance and lacked any apparent direct effect on the Ca2+ channel activity. We suggest that pyruvate added to the hypothermic storage solution preserves the high-energy phosphates in myocytes that are responsible for Ca2+ channel phosphorylation via beta-adrenergic stimulation. (J Lab

Animals↗

PubMed1998

A 1,064 bp fragment from the promoter region of the Col11a2 gene drives lacZ expression not only in cartilage but also in osteoblasts adjacent to regions undergoing both endochondral and intramembranous ossification in mouse embryos.

We isolated a 1,064 bp promoter fragment that extended from the 3'-end of the adjacent gene for retinoic X receptor-beta to beyond the most clearly defined start site of the mouse Col11a2 gene. The fragment was then joined to a beta-galactosidase gene and used to prepare transgenic mice. Three independent lines of transgenic mice were generated. The reporter beta-galactosidase gene was expressed in essentially all cartilaginous tissues in 15.5-day-old mouse embryos. In addition, the construct was expressed in osteoprogenitors within developing periosteum and in osteoblasts within mineralized bone. This pattern of expression was evident during both endochondral and intramembranous bone formation. Therefore, the results suggest that 1,064 bp promoter fragment can drive tissue-specific expression of the Col11a2 gene.

Animals↗

PubMed1998

Effects of lysophosphatidylcholine on the production of interstitial adenosine via protein kinase C-mediated activation of ecto-5'-nucleotidase.

1. Adenosine plays a crucial role in the evolution of ischemic preconditioning. With the use of microdialysis techniques in in situ rat hearts, we assessed the activity of ecto-5'-nucleotidase (a key enzyme responsible for adenosine production), and examined the effects of lysophosphatidylcholine (LPC) on the production of interstitial adenosine. 2. The microdialysis probe was implanted in the left ventricular myocardium of anesthetized rat hearts and perfused with Tyrode solution containing adenosine 5'-monophosphate (AMP, 100 microM). With this system, the dialysate adenosine originates from the dephosphorylation of AMP, catalyzed by endogenous ecto-5'-nucleotidase. The level of dialysate adenosine is a measure of the ecto-5'-nucleotidase activity in vivo. 3. LPC at concentrations of 25 and 50 microM significantly increased the level of dialysate adenosine to 122.7+/-4.3% (n=4, P<0.05) and 158.6+/-7.2% (n=5, P<0.05) of the control, respectively. Chelerythrine (200 microM), a protein kinase C (PKC) inhibitor, completely abolished the increase of dialysate adenosine afforded by LPC (50 microM) (n=5). 4. These data provide the first evidence that LPC does increase the concentration of interstitial adenosine in rat hearts in situ, through the PKC-mediated activation of endogenous ecto-5'-nucleotidase.

Adenosine↗

PubMed1998

Interaction of poliovirus with its purified receptor and conformational alteration in the virion.

Polypeptides of amino acids 1 to 241 (PVR241) and 1 to 330 (PVR330) of the human poliovirus receptor (hPVR) were produced in a baculovirus expression system. PVR241 contained extracellular domains 1 and 2 of hPVR, and PVR330 contained extracellular domains 1, 2, and 3. These peptides were purified by immunoaffinity column chromatography with an anti-hPVR monoclonal antibody (MAb). After the purification, PVR241 and PVR330 appeared to retain their native conformation as judged by reactivity with an anti-PVR MAb that recognized domain 1 of hPVR in a conformation-dependent manner. The virulent Mahoney strain of poliovirus type 1 was mixed with the purified PVRs in various concentrations. An average of at least 43 PVR330 molecules were able to bind to one virion particle under the conditions used. The equilibrium dissociation constant between the PVR330 molecule and the PVR binding site (canyon) on the virion was determined to be 4.50 +/- (0.86) x 10(-8) M at 4 degrees C. Higher rates of conformational change of the virus (160S) to 135S and 80S particles were observed as the concentration of PVR330 was increased. In this in vitro system, the ratio of the amount of the 135S particle to that of the 80S particle seemed to be always constant. After the disappearance of the 160S particle, the amount of the 80S particle was not increased by further incubation at 37 degrees C. These results suggested that the 80S particle was not derived from the 135S particle under the conditions used in this study.

Animals↗

PubMed1998

Clinical suppression of bradycardia dependent premature ventricular contractions by the potassium channel opener nicorandil.

OBJECTIVE: To assess the clinical antiarrhythmic effect of nicorandil, a potassium channel opener; on premature ventricular contractions. DESIGN AND PATIENTS: The effect of oral nicorandil (15 to 60 mg daily for four weeks) on premature ventricular contractions was investigated in 20 patients (11 female, nine male, mean (SD) age 63 (17) years) who underwent 24 hour ambulatory ECG. Patients were classified into two groups based on the relation between the frequency of premature ventricular contractions and heart rate: (1) those with a positive correlation (n = 9); and (2) those with a bidirectional correlation (n = 11), characterised by an increased frequency of premature contractions at low heart rates and a decreased frequency at high heart rates. RESULTS: Nicorandil reduced the frequency of premature ventricular contractions by 75% in five patients in group 2, but was not effective in any patient in group 1. The heart rate at which the frequency of premature ventricular contractions peaked was significantly lower in the five responders in group 2 than in the six non-responders (63.2 (3.7) v 76.3 (12.4) beats/min, p < 0.05). CONCLUSIONS: Nicorandil may suppress premature ventricular contractions when they occur mainly at a low heart rate.

Adult↗

PubMed1998

Anticoagulants in Takayasu's arteritis associated with crescentic glomerulonephritis and nephrotic syndrome: a case report.

The authors describe a 46-year-old Japanese woman who had Takayasu's arteritis associated with nephrotic syndrome due to mesangial proliferative glomerulonephritis with crescent. Although a few cases of focal and segmental mesangial proliferative glomerulonephritis associated with Takayasu's arteritis have been reported, nephrotic syndrome has not been reported previously in this situation.

Anti-Inflammatory Agents↗

PubMed1998

Etiology of community-acquired pneumonia in hospitalized patients: a 3-year prospective study in Japan.

STUDY OBJECTIVE: To compare the etiology of community-acquired pneumonia in Japan and Western countries, the causative pathogens were prospectively investigated in patients requiring hospitalization. DESIGN: Prospective study over a 3-year period. SETTING: A community general hospital in Japan. PATIENTS: Three hundred twenty-six episodes of community-acquired pneumonia in 318 patients admitted to the hospital between July 1994 and June 1997. METHODS: The microbiological diagnosis was based on the results of quantitative sputum culture, blood culture, and other invasive procedures, including transthoracic needle aspiration or bronchoscopic examination. Serologic tests for Mycoplasma pneumoniae, Chlamydia spp, Legionella spp, and viruses were also routinely performed. RESULTS: Causative pathogens were identified in 199 episodes (61%). Streptococcus pneumoniae was the most common pathogen (23%), followed by Haemophilus influenzae (7.4%), M pneumoniae (4.9%), and Klebsiella pneumoniae (4.3%). The Streptococcus milleri group and Chlamydia pneumoniae were detected in 3.7 and 3.4% of the episodes, respectively. Pneumonia due to Legionella spp was recognized in only two patients. CONCLUSIONS: The etiology of community-acquired pneumonia in Japan did not differ markedly when compared with that of Western countries except for the low incidence of Legionella pneumonia. C pneumoniae and the S milleri group, which are emerging or newly recognized pathogens, were also significant causative microorganisms.

Adolescent↗

PubMed1998

Adrenocorticotropic hormone-secreting pheochromocytoma.

A 41-year-old female had pheochromocytoma which secreted adrenocorticotropic hormone (ACTH). She was admitted to our hospital because of weight loss and excessive sweating. Not only urinary metanephrine but also plasma ACTH was extremely high. An abdominal echogram showed a cystic tumor in the left adrenal gland. An abdominal magnetic resonance imaging scan showed a hyperintense T2-weighted abnormality inside the tumor. Left adrenalectomy was done. The tumor consisted of benign pheochromocytoma cells diffusely stained with anti-ACTH antibody. The present case did not show any typical Cushingoid symptoms which are common in ACTH-secreting pheochromocytomas.

Adrenal Gland Neoplasms↗

PubMed1998

Pulmonary Mycobacterium avium disease in a young patient with idiopathic CD4+ T lymphocytopenia.

A case of pulmonary Mycobacterium avium (M. avium) disease associated with idiopathic CD4+ T lymphocytopenia is reported. A rapidly growing pulmonary nodule was detected on a chest roentgenogram in a young man. Bronchoscopic examination revealed M. avium infection. Hematological studies showed a low CD4+ cell count in the absence of any identifiable immunodeficiency, including human immunodeficiency virus (HIV) infection. With the combination of chemotherapy and surgery, he had a good clinical outcome. Idiopathic CD4+ T lymphocytopenia should be considered in patients with unexplained opportunistic infection.

Adult↗

PubMed1998

Effect of alpha-tocopherol status on alpha-tocopherol transfer protein expression and its messenger RNA level in rat liver.

Studies were designed to explore the role of vitamin E nutritional status in regulating the synthesis of alpha-tocopherol transfer protein (alphaTTP) in rat liver. In vitamin E-replete rats, expression of this protein and its specific messenger RNA (mRNA) was decreased by about 300% compared with rats with normal vitamin E levels. In vitamin E-depleted rats, the alphaTTP-specific mRNA level increased to about 150% of that in the normal vitamin E group. However, protein expression remained constant. These findings indicate that the synthesis of alphaTTP can be regulated by the vitamin E nutritional status.

Animals↗

PubMed1998

Electrical and mechanical abnormalities in the heart of a schizophrenic patient with hyponatremia derived from water intoxication.

Electrical and mechanical abnormalities were studied in the heart of a schizophrenic male patient with severe hyponatremia and concomitant low plasma osmolarity induced by excessive water intake (so-called "water intoxication syndrome") by recording electrocardiography and echocardiography. There was a significant positive correlation between the plasma osmolarity and serum sodium concentration. The QRS duration of electrocardiography, an index of the ventricular electrical conduction velocity, tended to be prolonged and the left ventricular ejection fraction calculated by echocardiography decreased in proportion to the reduction of the serum sodium concentration. Lowering extracellular sodium concentration theoretically slows electrical conduction velocity, and was observed in this patient. On the other hand, low external sodium concentration should increase cardiac contractility via suppression of the forward mode operation of the sodium-calcium exchange mechanism, thereby increasing the intracellular free calcium concentration. However, this was not the case in our patient, because ejection fraction was not increased but rather significantly decreased with the lowering of serum sodium concentration. We speculate that in patients with water intoxication, the negative inotropism of the heart caused by low plasma osmolarity prevails over the positive inotropism caused by low serum sodium concentration.

Calcium↗

PubMed1997

alpha-tocopherol transfer protein stimulates the secretion of alpha-tocopherol from a cultured liver cell line through a brefeldin A-insensitive pathway.

Vitamin E (alpha-tocopherol) is a fat-soluble antioxidant that is transported by plasma lipoproteins in the body. alpha-Tocopherol taken up by the liver with lipoprotein is thought to be resecreted into the plasma in very low density lipoprotein (VLDL). alpha-Tocopherol transfer protein (alphaTTP), which was recently identified as a product of the causative gene for familial isolated vitamin E deficiency, is a cytosolic liver protein and plays an important role in the efficient recycling of plasma vitamin E. To throw light on the mechanism of alphaTTP-mediated alpha-tocopherol transfer in the liver cell, we devised an assay system using the hepatoma cell line McARH7777. Using this system, we found that the secretion of alpha-tocopherol was more efficient in cells expressing alphaTTP than in matched cells lacking alphaTTP. Brefeldin A, which effectively inhibits VLDL secretion by disrupting the Golgi apparatus, had no effect on alpha-tocopherol secretion, indicating that alphaTTP-mediated alpha-tocopherol secretion is not coupled to VLDL secretion. Among other agents tested, only 25-hydroxycholesterol, a modulator of cholesterol metabolism, inhibited alpha-tocopherol secretion. This inhibition is most likely mediated by oxysterol-binding protein. These results suggest that alphaTTP present in the liver cytosol functions to stimulate secretion of cellular alpha-tocopherol into the extracellular medium and that the reaction utilizes a novel non-Golgi-mediated pathway that may be linked to cellular cholesterol metabolism and/or transport.

Animals↗

PubMed1997

Stimulation of alpha 1-adrenoceptors and protein kinase C-mediated activation of ecto-5'-nucleotidase in rat hearts in vivo.

1. To determine whether protein kinase C (PKC)-mediated activation of ecto-5'-nucleotidase would increase interstitial adenosine concentrations in the rat heart in vivo, we made use of the microdialysis technique and a flexibly mounted probe, which was implanted in the left ventricular myocardium and perfused with Tyrode solution. 2. The baseline level of dialysate adenosine was 0.51 +/- 0.09 microM (n = 16). Perfusion of adenosine 5'-monophosphate (AMP, 100 microM) through the probe increased the dialysate adenosine concentration markedly to 9.25 +/- 0.46 microM (n = 15). alpha, beta-Methyleneadenosine 5'-diphosphate (AOPCP, 100 microM), an inhibitor of ecto-5'-nucleotidase, abolished the AMP-induced increase in dialysate adenosine, but did not affect the baseline level of adenosine. These observations suggest that the dialysate adenosine obtained during the perfusion with AMP, but not the baseline levels of adenosine, originated from the dephosphorylation of AMP by ecto-5'-nucleotidase. Thus, the level of adenosine measured during AMP perfusion gives an index of the activity of ecto-5'-nucleotidase in the tissue. 3. Noradrenaline (10 microM) increased the adenosine concentration measured in the presence of 100 microM AMP (i.e. the activity of ecto-5'-nucleotidase) by 38.7 +/- 9.6% (n = 5, P < 0.05), an increase which was inhibited by an antagonist of the alpha 1-adrenoceptor (prazosin, 50 microM) or of PKC (chelerythrine, 10 microM). Further application of either the alpha 1-adrenoceptor agonist methoxamine (100 microM) or the diacylglycerol analogue 1,2-dioctanoyl-sn-glycerol (DOG, 100 microM) also increased the adenosine concentration by 35.1 +/- 10.0% (n = 6, P < 0.05) or 40.6 +/- 8.3% (n = 5, P < 0.05), respectively. 4. The presence of okadaic acid (50 microM), an inhibitor of protein phosphatase, enhanced the noradrenaline-induced increase in adenosine concentration by 112.4 +/- 35.9% (n = 4, P < 0.05), to a level significantly (P < 0.05) greater than the increase caused by noradrenaline alone (38.7 +/- 9.6%). 5. These data provide the first evidence that alpha 1-adrenoceptor stimulation and the subsequent activation of PKC can increase adenosine concentrations in interstitial spaces of ventricular muscle in vivo, through activation of endogenous ecto-5'-nucleotidase.

5'-Nucleotidase↗

PubMed1997

Affinity for alpha-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs.

alpha-Tocopherol transfer protein (alphaTTP), a product of the gene which causes familial isolated vitamin E deficiency, plays an important role in determining the plasma vitamin E level. We examined the structural characteristics of vitamin E analogs required for recognition by alphaTTP. Ligand specificity was assessed by evaluating the competition of non-labeled vitamin E analogs and alpha-[3H]tocopherol for transfer between membranes in vitro. Relative affinities (RRR-alpha-tocopherol = 100%) calculated from the degree of competition were as follows: beta-tocopherol, 38%; gamma-tocopherol, 9%; delta-tocopherol, 2%; alpha-tocopherol acetate, 2%; alpha-tocopherol quinone, 2%; SRR-alpha-tocopherol, 11%; alpha-tocotrienol, 12%; trolox, 9%. Interestingly, there was a linear relationship between the relative affinity and the known biological activity obtained from the rat resorption-gestation assay. From these observations, we conclude that the affinity of vitamin E analogs for alphaTTP is one of the critical determinants of their biological activity.

Animals↗

PubMed1997

Binding of antibodies against GM1 and GD1b in human peripheral nerve.

Human dorsal root ganglia (DRG), and ventral and dorsal roots were immunostained with rabbit antibodies recognizing GM1, GD1b, or both. Sera from rabbits immunized with GM1 or GD1b were separated in affinity columns into three fractions: Rab1, Rab2, and Rab3. Rab1 recognized only GM1, and Rab2 only GD1b; whereas Rab3 recognized both GM1 and GD1b, presumably by binding to the terminal galactosyl beta 1-3N-acetylgalactosaminyl residue. Rab2 and Rab3 immunostained most of the nerve cell bodies in the DRG and paranodal myelin of the ventral and dorsal roots, whereas Rab1 produced no significant immunostaining. These results show that GD1b is localized on the DRG neurons and the paranodal myelin of human peripheral nerve. These places may be the binding sites for anti-GD1b antibodies, including those cross-reactive with GM1, in the sera from patients with autoimmune neuropathies. GM1 may be dispersed in human DRG and dorsal and ventral roots.

Animals↗