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Biomedical subjects

K Shimamoto

Publications and source records attributed to K Shimamoto.

At least 271 records · Page 15Linked to original sources

Role of adenosine receptor activation in myocardial infarct size limitation by ischaemic preconditioning.

OBJECTIVE: The aims were to examine the role of adenosine receptors in the mechanism of preconditioning in a chronic rabbit model of myocardial infarction; to assess whether the preconditioning effect is blocked by an adenosine receptor antagonist, 8-phenyltheophylline; and to determine whether an adenosine A1 receptor agonist, R(-)N6-2-phenylisopropyl adenosine (R-PIA), mimics infarct size limitation by preconditioning. METHODS: Myocardial infarction was induced in male rabbits by occlusion of the left coronary artery for 30 min, which was followed by 72 h reperfusion. Before the 30 min ischaemia, rabbits were subjected to one of the following six protocols: (1) untreated control; (2) intravenous injection of 8-phenyltheophylline; (3) preconditioning with 5 min ischaemia; (4) pretreatment with 8-phenyltheophylline plus preconditioning; (5) intravenous injection of R-PIA; or (6) R-PIA plus atrial pacing (240.min-1). Infarct size and area at risk were determined by histology and fluorescent particles, respectively. RESULTS: Preconditioning significantly limited infarct size, normalised as a percent of area at risk (%IS/AR), to 19.2 (SEM 2.3)% v control value of 46.5(2.8)%. 8-Phenyltheophylline alone did not modify the %IS/AR, but its injection before preconditioning attenuated the preconditioning effect such that IS/AR = 34.4(2.5)%. While R-PIA did not achieve statistically significant myocardial salvage, R-PIA plus atrial pacing limited infarct size to 33.7(3.0)% (p<0.05 v control). The R-PIA group had severe hypotension and their infarct sizes were inversely correlated with diastolic blood pressure at reperfusion. There was no such correlation in the R-PIA plus pacing group in which bradycardia and hypotension induced by R-PIA were attenuated by atrial pacing. CONCLUSIONS: The infarct size limiting effect of preconditioning was attenuated by 8-phenyltheophylline, and pretreatment with R-PIA was able to limit myocardial infarct size when severe hypotension was avoided by atrial pacing. These findings suggest that adenosine receptor activation plays a crucial role in the mechanism of preconditioning.

Animals↗

Plasma calcitonin gene-related peptide levels in patients with various hypertensive diseases.

OBJECTIVE: To clarify the pathophysiological role of calcitonin gene-related peptide (CGRP) in hypertensive diseases. METHOD: Using a sensitive radioimmunoassay established in our laboratory, plasma CGRP levels were evaluated in control subjects and in patients with essential hypertension, phaeochromocytoma or primary aldosteronism. RESULTS: The CGRP levels in the three hypertensive groups were significantly higher than in normal controls, but no statistically significant difference was observed among CGRP levels in the three hypertensive groups. In the three cases of secondary hypertensives (one patient with phaeochromocytoma and two with primary aldosteronism), a significant decrease in plasma CGRP levels and a marked reduction in blood pressure were observed after adrenalectomy. CONCLUSION: These results suggest that increased plasma CGRP levels in hypertensive patients could be a compensatory reaction to elevated blood pressure.

Adrenal Gland Neoplasms↗

Agonist analysis of 2-(carboxycyclopropyl)glycine isomers for cloned metabotropic glutamate receptor subtypes expressed in Chinese hamster ovary cells.

1. 2-(Carboxycyclopropyl)glycines (CCGs) are conformationally restricted glutamate analogues and consist of eight isomers including L- and D-forms. The agonist potencies and selectivities of these compounds for metabotropic glutamate receptors (mGluRs) were studied by examining their effects on the signal transduction of representative mGluR1, mGluR2 and mGluR4 subtypes in Chinese hamster ovary cells expressing the individual cloned receptors. 2. Two extended isomers of L-CCG, L-CCG-I and L-CCG-II, effectively stimulated phosphatidylinositol hydrolysis in mGluR1-expressing cells. The rank order of potencies of these compounds was L-glutamate > L-CCG-I > L-CCG-II. 3. L-CCG-I and L-CCG-II were effective in inhibiting the forskolin-stimulated adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation in mGluR2-expressing cells. Particularly, L-CCG-I was a potent agonist for mGluR2 with an EC50 value of 3 x 10(-7) M, which was more than an order of potency greater than that of L-glutamate. 4. L-CCG-I evoked an inhibition of the forskolin-stimulated cyclic AMP production characteristic of mGluR4 with a potency comparable to L-glutamate. 5. In contrast to the above compounds, the other CCG isomers showed no appreciable effects on the signal transduction involved in the three mGluR subtypes. 6. This investigation demonstrates not only the importance of a particular isomeric structure of CCGs in the interaction with the mGluRs but also a clear receptor subtype specificity for the CCG-receptor interaction, and indicates that the CCG isomers would serve as useful agonists for investigation of functions of the mGluR family.

Amino Acids, Dicarboxylic↗

Hepatocellular carcinoma: evaluation with color Doppler US and MR imaging.

Fifteen patients with hepatocellular carcinoma underwent examination with color Doppler ultrasound (US), magnetic resonance (MR) imaging, dynamic computed tomography (CT), and angiography. Doppler signals ranging from 0.22 to 3.48 kHz could be obtained from within the tumor in 14 of 15 patients. The resistive index was 0.38-0.77. Color Doppler signals were visualized in nine of 15 lesions with a Doppler shift greater than 0.7 kHz. The Doppler signals and the resistive index of the tumor vessels became lower as the vessels progressed into the center of the lesion. The appearance of tumor vessels recognized on MR images obtained with gradient-recalled acquisition in the steady state (GRASS) in 11 of 15 lesions was compared with that on CT scans and angiograms. Tumors that were hyperintense on GRASS images obtained with a flip angle of 15 degrees transmitted Doppler signals of considerably higher amplitude compared with the isointense lesions. Both color Doppler US and MR imaging provided useful information for characterizing intratumoral blood flow.

Angiography↗

Dipyridamole potentiates the myocardial infarct size-limiting effect of ischemic preconditioning.

BACKGROUND: Recent studies implicated a key role for adenosine (ADO) receptor activation in the enhancement of ischemic tolerance by ischemic preconditioning. In this study, we aimed to test the hypothesis that dipyridamole, an ADO transport inhibitor, enhances the preconditioning effect. METHODS AND RESULTS: Six groups of rabbits underwent 30-minute coronary occlusion and 72-hour reperfusion. Infarct size (IS) and the area-at-risk (AR) were determined by histology and by use of fluorescent particles, respectively. IS expressed as the percentage of AR (%IS/AR) was 46.5 +/- 3.4% (n = 13) in control rabbits. Preconditioning with 2-minute ischemia tended to limit %IS/AR (%IS/AR, 35.5 +/- 3.5%, n = 9), and that possible protection was abolished by pretreatment with 10 mg/kg 8-phenyltheophylline (8-PT), an ADO receptor antagonist (%IS/AR, 43.9 +/- 5.8%, n = 9). Administration of dipyridamole (0.25 mg/kg) before the 2-minute preconditioning markedly limited %IS/AR to 13.8 +/- 2.6% (n = 12), indicating the potentiation of the preconditioning effect by this agent. Furthermore, this enhancement of preconditioning effect by dipyridamole treatment was significantly attenuated by 8-PT (%IS/AR, 27.6 +/- 2.1%, n = 11). Dipyridamole given before the 30-minute ischemia, without preconditioning, did not reduce %IS/AR (55.3 +/- 5.2%, n = 7), and a previous study from this laboratory had demonstrated that the present dose of 8-PT alone did not modify IS in the rabbit. CONCLUSIONS: Dipyridamole significantly potentiated the IS-limiting effect of preconditioning. This finding strongly supports the hypothesis that stimulation of ADO receptors by endogenous ADO, which builds up during preconditioning ischemia, mediates the increased ischemic tolerance afforded by preconditioning.

Adaptation, Physiological↗

Fragmentation hemolysis in a patient with hypertrophic obstructive cardiomyopathy and mitral valve prolapse.

We encountered a 65-year-old female with hypertrophic obstructive cardiomyopathy and mitral valve prolapse who had infective endocarditis and hemolytic anemia. The infecting organism of endocarditis was group A streptococci. With regard to the etiology of the hemolytic anemia, fragmentation hemolysis was considered because fragmented red cells and elevated lactic dehydrogenase were observed. Haptoglobin was markedly decreased. Coombs' test, Ham's test and abnormal hemoglobin were negative. She had not had a hemolytic attack in the past. Ultrasonic cardiography showed asymmetrical septal hypertrophy, mitral valve prolapse and 285 mmHg of calculated pressure gradient in the left ventricle. Cardiac catheterization showed 115 mmHg of left intraventricular pressure gradient and mitral regurgitation (grade 2). Hemolysis was slightly improved after treatment with propranolol. Thus, fragmentation of the normal red cells seemed to be due to shear stress.

Aged↗

Hypocalcemic cardiomyopathy in a patient with idiopathic hypoparathyroidism.

An idiopathic hypoparathyroidism-induced cardiomyopathy patient had severe long-lasting hypocalcemia. The dramatic improvement of cardiac function with correction of only the serum calcium concentration could be quantitatively demonstrated on both echocardiogram and ventriculogram. The concentration of the extracellular calcium ion was considered to have a direct effect on the strength of the myocardial contraction through excitation-contraction coupling. Furthermore, elevated serum creatine phosphokinase and lactate dehydrogenase levels which were thought to be delivered from skeletal muscle returned to the normal range concomitant with the correction of hypocalcemia. The serum calcium concentration and these enzyme level showed significant inverse correlations.

Cardiomyopathies↗

The renal kallikrein-kinin system at the prehypertensive stage of hypertension.

In essential hypertension, renal dopaminergic activity and PGE2 was suppressed as was the renal kallikrein-kinin system. The suppression of the renal depressor systems may play an important role in the etiology of hypertension through sodium and body fluid retention. At the prehypertensive stage of essential hypertension, renal dopaminergic activity was suppressed, which induced the retention of body fluids and sodium. On the other hand, the renal prostaglandin E2 was augmented, and it seemed to be a compensatory mechanism for sodium retention. We could not confirm the suppression of the renal kallikrein-kinin system at the prehypertensive stage of hypertension. Although all renal depressor systems are suppressed in essential hypertension, the suppression of the renal kallikrein-kinin system and PGE2 seem to be very important in the etiology of hypertension. Further study is necessary to clarify when both systems are suppressed.

Animals↗

Activation of kinins on myocardial ischemia.

In experimental ischemic dog heart with coronary-constriction, no increase of coronary blood flow, Max dP/dt or MVO2 with no change of kinin in arterial blood were exhibited. Following sympathetic nerve stimulation, remarkable increases of kinin in coronary sinus blood were observed with a significant elevation of left ventricular end-diastolic pressure and an augmented production of lactate from the heart as well as an ischemic change of ECG-ST. Infusion of kinin into the left main coronary artery resulted in no change in the mean systemic blood pressure, coronary blood flow, coronary vascular resistance, cardiac function, myocardial metabolism or ECG-ST in the control and coronary-constricted groups. These data suggest that kinin was released significantly from the ischemic heart, however, such a level of kinin has no significant effect on coronary circulation or myocardial metabolism. In ischemia-reperfusion rabbit hearts, no significant influence of the ACE inhibitors, captopril and ramiprilat, were observed. Species differences may be responsible for the beneficial role of ACE inhibitors in the limitation of infarct size in the dog hearts, possessing collateral flow, that are not seen in the rabbit heart with poor collateral flow.

Angiotensin-Converting Enzyme Inhibitors↗

[A case of idiopathic chronic interstitial nephritis progressed to renal failure without proteinuria nor hematuria].

A case of idiopathic interstitial nephritis who underwent to chronic renal failure without history of hematuria nor proteinuria is discussed. A 46 years old woman who showed gradually elevation of serum creatinine (1.3-2.5 mg/dl) admitted on our hospital. On occasions of pregnancy, health examination or hospital visit, she has never been pointed out hematuria nor proteinuria. Immunological disorders such as SLE, metabolic diseases, urinary tract obstruction and chronic urinary tract infection were excluded by the examinations after admission. Because of the severe enzymuria (beta 2-microglobulin, N-acetyl glucosaminidase), chronic interstitial nephritis was considered, and renal biopsy was performed. Severe tubulointerstitial changes were observed histologically, however, glomerular damage was comparatively mild. From these results, she was diagnosed idiopathic chronic tubulointerstitial nephritis. In this case, hematuria and proteinuria were absent until severe renal dysfunction. This may be caused by that inflammation was located to the tubulointerstitial area. The observation of enzymuria seemed to be important to diagnosis and follow-up of the interstitial nephritis.

Chronic Disease↗

[Diagnostic accuracy of breast sonography. Comparison among three different techniques].

Mechanical arc scanning is widely used for breast sonography in Japan. The authors have used three different kinds of devices over the past seven years. The diagnostic accuracy was compared among three groups of patients with pathologically confirmed breast masses. In group A, 309 cases (77 carcinomas) were evaluated with a 10 MHz contact compound scanner, and the sensitivity, specificity and accuracy rates were 77.9%, 97.8% and 92.9%, respectively. In group B, 306 cases (56 carcinomas) were evaluated with a 5 or 7.5 MHz mechanical arc scanner, and the sensitivity, specificity and accuracy rates were 89.3%, 84.8% and 85.6%, respectively. In group C, 296 cases (71 carcinomas) were evaluated with a 7.5 MHz real time scanner, and the sensitivity, specificity and accuracy rates were 95.8%, 92.4% and 93.2%, respectively. In cases with T1 breast cancer, the methods had sensitivities of 60.0%, 85.7% and 94.5%, respectively. The sensitivity of the real-time scanner was not significantly different from that of the mechanical arc scanner. In conclusion, the hand-held real-time scanner with high-frequency transducer is a simple, useful device with high diagnostic accuracy for breast examination and can be used as a substitute for the mechanical arc scanner.

Breast↗

Increased production of angiotensin II in the adrenal gland of stroke-prone spontaneously hypertensive rats with malignant hypertension.

Angiotensin(Ang) contents in the adrenal gland of stroke-prone spontaneously hypertensive rats(SHRSP) and age-matched Wistar Kyoto rats(WKY) were determined using reverse phase high performance liquid chromatography combined with a specific radioimmunoassay. In normotensive 5 wk-old SHRSP, the adrenal renin activity was about 3 times higher than that of age-matched WKY while the adrenal Ang I and Ang II concentrations did not differ from those of WKY. In the severely hypertensive 25 wk-old SHRSP, the adrenal Ang II and Ang I, and plasma aldosterone concentrations were about 5-fold, 2-fold and 4-fold, respectively, increased compared with levels in the WKY. In the 25 wk-old SHRSP 24 h after bilateral nephrectomy, the adrenal Ang II and plasma aldosterone levels were not decreased and were 10 and 3 times, respectively, higher than those of nephrectomized control WKY. Thus, the enhanced local generation of Ang II in the adrenal gland may contribute to the increased release of aldosterone in SHRSP with malignant hypertension.

Adrenal Glands↗

Changes in preference for receptor subtypes of configurational variants of a glutamate analog: conversion from the NMDA-type to the non-NMDA type.

The (2S,3R,4S) isomer of 2-(carboxycyclopropyl)glycines (CCG) (L-CCG-IV) is a potent NMDA-type agonist in the mammalian central nervous system. L-CCG-IV is a conformationally restricted glutamate analogue in which the cyclopropyl group fixes the glutamate chain, and closely mimics the folded conformation of L-glutamate. (6R)-Substituted L-CCG-IV, however, demonstrated pharmacological properties of non-NMDA type agonists in the newborn rat spinal motoneuron while (6S)-CCG derivatives showed similar properties to the parent compound, L-CCG-IV. In the dorsal root fiber of newborn rats, (6R)-methoxymethyl and benzyloxymethyl substituted L-CCG-IV caused kainate-like depolarization. The depolarizing potency of (6R)-benzyloxymethyl substituted L-CCG-IV was slightly lower than that of kainate, demonstrating a relatively high potency.

Amino Acids, Dicarboxylic↗

Introduction and transposition of the maize transposable element Ac in rice (Oryza sativa L.).

To develop a transposon tagging system in an important cereal plant, rice (Oryza sativa L.), the maize transposable element Ac (Activator) was introduced into rice protoplasts by electroporation. We employed a phenotypic assay for excision of Ac from the selectable hph gene encoding resistance to hygromycin B. Southern blot analysis of hygromycin B-resistant calli showed that the Ac element can transpose from the introduced hph gene into the rice chromosomes. Sequence analysis of several Ac excision sites in the hph genes revealed sequence alterations characteristic of the excision sites of this plant transposable element. The Ac element appears to be active during development of transgenic rice plants from calli. Moreover, hybridization patterns of different leaves from the same plant indicated that some Ac elements are stable whereas others are able to transpose further during development of leaves. The results indicate that the introduced Ac element can transpose efficiently in transgenic rice plants.

Base Sequence↗