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Biomedical subjects

T Matsubara

Publications and source records attributed to T Matsubara.

At least 271 records · Page 15Linked to original sources

Effects of prolonged application of isoprenaline on intracellular free magnesium concentration in isolated heart of rat.

1. The effect of prolonged application of isoprenaline on intracellular free-Mg2+ concentration ([Mg2+]i) was examined by use of 31P-nuclear magnetic resonance (31P-n.m.r.) in rat isolated hearts. Left ventricular pressure (LVP) was simultaneously measured. 2. [Mg2+]i was estimated from the separation of the alpha- and beta-ATP peaks, using the dissociation constant of MgATP 38 microM (established previously). In normal (phosphate-free, Krebs-Henseleit) solution, [Mg2+]i was approximately 0.4 mM. 3. When isoprenaline was applied for 100 min, a transient increase in [Mg2+]i was observed during the initial 25 min, whilst concentrations of ATP ([ATP]) and phosphocreatine ([PCr]) decreased and [Pi] correspondingly increased. During the subsequent 75 min of isoprenaline application, [Mg2+]i decreased below its resting levels. Washout of isoprenaline restored [Mg2+]i and [PCr], but [ATP] remained low. These changes elicited by isoprenaline were not observed in the presence of propranolol, a typical alpha-adrenoceptor blocker. 4. Isoprenaline increased both LVP and heart rate. The increased LVP and heart rate slowly returned to lower values during prolonged application of isoprenaline, but remained higher than those before application. 5. The transient rise in [Mg2+]i elicited by isoprenaline could be attributed to the decrease in [ATP] resulting in a release of Mg2+. The subsequent decrease in [Mg2+]i during the prolonged applications suggests that beta-adrenoceptor stimulation itself facilitates Mg(2+)-extruding mechanism(s).

Adenosine Triphosphate↗

Decreased expression of CD23 on peripheral blood macrophages/monocytes during acute Kawasaki disease with coronary artery lesions.

CD23 has been reported to be a macrophage/monocyte activation antigen. We focused on the expression of CD23 by peripheral blood macrophages/monocytes in 5 Kawasaki disease (KD) patients with coronary artery lesions (CAL) and compared these values with those of 35 patients without CAL. The expression of CD23 on peripheral blood macrophages/monocytes was assayed by a fluorescence-activated cell sorter using monoclonal antibodies CD23 and CD14. Absolute counts of CD23+CD14+ macrophages/monocytes in KD patients with CAL did not increase during the acute stage, while these values in KD patients without CAL increased. In addition, this decreased expression of CD23 on peripheral blood macrophages/monocytes in patients with CAL did not change during the acute stage, regardless of IVGG therapy. Our results suggest that the decreased expression of CD23 on peripheral blood macrophages/monocytes in patients with CAL is part of the regulatory system of CD23 antigen during acute KD.

Acute Disease↗

Aneurysm of the posterior cerebral artery: report of eleven cases--surgical approaches and procedures.

Eleven cases of an aneurysm of the posterior cerebral artery are reported. All 11 aneurysms were saccular, and 3 were either giant or large. The aneurysms arose from the P1 segment in three patients, the P1-P2 junction in three patients, the P2 segment in three patients, and from the P3 segment in two patients. In all, 10 patients underwent surgery. All P1 and P1-P2 junction aneurysms were treated with the pterional approach. Three P2 and two P3 aneurysms were managed by the subtemporal approach. Two small aneurysms in the series were treated by coating the aneurysmal dome, two by clipping the afferent artery, and all other saccular type aneurysms were treated by clipping the aneurysmal neck. Seven patients had either an excellent or good outcome; two had poor results; and one patient died. The operative approaches and procedures are also discussed in relation to the anatomy of posterior cerebral artery aneurysms.

Adolescent↗

Are diabetic hearts more resistant to ischemia/reperfusion injury?

The present study was designed to investigate the cardiac impairment during ischemia/reperfusion injury in rats with streptozotocin-induced diabetes vs controls. Male rats were divided into three groups: controls, one-week diabetic rats (1wDM) and four-week diabetic rats (4wDM). In the isolated working heart, left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and maximum positive and negative dP/dt were measured before ischemia and after 20 min of global ischemia followed by 30 min reperfusion. In the pre-ischemic state, hearts of 4wDM showed a significant (p < 0.05) depression of the maximum positive and negative dP/dt compared with those of controls and 1wDM. There were no significant differences in LVDP and LVEDP among the three groups. The incidence of reperfusion-induced ventricular fibrillation (VF) was 75% for controls, 15% for 1wDM rats, and 27% for 4wDM rats. In hearts without reperfusion-induced VF, there were no differences in the three groups, between the pre- and post-ischemic values in LVDP, LVEDP, and maximum positive and negative dP/dt. These findings suggest that diabetic hearts exhibit no susceptibility to ischemia/reperfusion injury.

Animals↗

Cypridina luciferin analog reduces the incidence of ischemia/reperfusion-induced ventricular fibrillation.

A Cypridina luciferin analog (CLA), considered to be a sensitive and specific agent for the assay of superoxide, was assessed in isolated hearts for its effects on ischemia/reperfusion injury. Hearts of anesthetized male Wistar rats were isolated and perfused with a modified Krebs-Henseleit bicarbonate buffer to serve as non-recirculating working heart preparations. After 15 min of perfusion to achieve stability, they underwent 20 min of global ischemia and were then reperfused for 30 min with or without 250 microM of CLA, dissolved in the perfusate. The incidence of ventricular fibrillation was only 13% in the CLA group, whereas it was 88% in the controls. The CLA treatment was further associated with significantly increased left ventricular developed pressure and cardiac output; and in contrast, the left ventricular end-diastolic pressure was significantly reduced, as compared with the control group. Thiobarbiturate reacting substance content in the hearts of the CLA group was significantly decreased (27.5 +/- 2.4 versus 36.9 +/- 9.7 mumol/g dry weight). This study thus indicates that CLA may be useful for alleviating ischemia/reperfusion injury (reperfusion-induced arrhythmia and damage to heart function) involving free radicals.

Adenosine Triphosphate↗

Effects of diabetes on lipid peroxidation and scavenger activity in ischemia/reperfusion injury.

This study examined the effects of ischemia/reperfusion on cardiac function and diabetes-associated lipid peroxidation and scavenger induction in isolated working hearts. Cardiac function in diabetic rats was depressed in proportion to the duration of diabetes. Plasma levels of malondialdehyde (MDA) were increased significantly after diabetes of 1-week duration (1wD). MDA levels in the myocardium were increased significantly after 4-weeks (4wD) and tissue superoxide dismutase (SOD) activity was also elevated significantly in 8-week diabetic rats (8wD) as compared to control values. In both controls and diabetics, tissue MDA concentrations increased significantly during the first 3 min of reperfusion following 20 min of ischemia, compared with preischemia levels. At the end of reperfusion, tissue MDA levels decreased in controls and 1wD hearts, but remained elevated in the 4wD and 8wD cases. The SOD activity in 8wD hearts decreased significantly after 20 min of global ischemia followed by 30 min reperfusion, compared with preischemia levels. By contrast, there were no significant differences between preischemic and after-reperfusion data for parameters of cardiac function in 8wD rats. Thus, lipid peroxidation appears to have little influence on cardiac function during ischemia/reperfusion in rats with chronic diabetes.

Animals↗

Soluble ICAM-1 levels in serum during acute infectious mononucleosis.

Intercellular adhesion molecule-1 (ICAM-1) has been reported as a T-cell, B-cell or macrophage/monocyte activation antigen. We investigated whether soluble ICAM-1 levels in serum increased during the acute stage in 11 patients with infectious mononucleosis (IM). Serum ICAM-1 levels were measured by a double determinant immunoassay using 2 monoclonal antibodies in the FAST system. Serum ICAM-1 levels in patients with IM increased during the acute stage. There was a positive correlation between serum ICAM-1 levels and absolute counts of peripheral blood mononuclear cells. Our results suggest that the elevated serum ICAM-1 levels are based on the increased counts of activated peripheral blood mononuclear cells and that ICAM-1 is a part of the regulatory system of immune reactions during acute IM.

Acute Disease↗

The osteogenic potential of fracture hematoma and its mechanism on bone formation--through fracture hematoma culture and transplantation of freeze-dried hematoma.

This study was conducted to provide further evidence of the inherent osteogenic potential of the fracture hematoma. The fracture hematoma was separated into its cellular and extracellular elements. The hematoma cells were cultured to study bone formation by the cellular elements alone. Bone formation acceleration factor was added to the cultured fracture hematoma cells. The cell responded to this stimulation by differentiation into chondrocytes. Fracture hematoma was freeze-dried to study the presence of osteoinduction by the extracellular factors in the fracture hematoma. The freeze-dried fracture hematoma was packaged in methylmethacrylate pellets and within capsules of hydroxyapatite. These pellets and capsules in response to extracellular humoral factors from the freeze-dried fracture hematoma. The results of experimental implantation of the cultured fracture hematoma cells revealed that these cells had the potential to differentiate into chondroblasts or osteoblasts when bone induction factors and bone acceleration factor was added to their media. These extracellular humoral factors are known to be present in the fracture hematoma.

Animals↗

[Perfusion imaging with 99mTc PPN-1011 for the assessment of myocardial area at risk and the efficacy of PTCA/PTCR in myocardial infarction and unstable angina].

The determination of the myocardium at risk before intervention and the change in that region after intervention constitute a promising measurement tool for the assessment of acute therapy. We used 99mTc PPN-1011 in 4 patients with acute myocardial ischemia (2 patients with acute myocardial infarction, 2 unstable angina) and subsequent successful reperfusion. All 4 patients had perfusion defect on the pre-reperfusion image. Perfusion abnormality on post-reperfusion image was all improved significantly compared with pre-reperfusion image, suggesting the efficacy of acute treatment in acute myocardial ischemia. We conclude that 99mTc PPN-1011 scintigraphy is useful method for the assessment of myocardial area at risk and the efficacy of PTCA/PTCR in myocardial infarction and unstable angina.

Aged↗

Role of liver-type glucose transporter (GLUT2) in transport across the basolateral membrane in rat jejunum.

To obtain information on the regulation of glucose transport across the basolateral membrane (BLM) of intestinal epithelial cells, we measured the number of [3H]cytochalasin B binding sites and the level of liver-type glucose transporter (GLUT2) protein in the BLM in the jejunum of rats (i) with diabetes (ii) given a high-carbohydrate diet or (iii) with experimental hyperglycemia (12 h infusion of a high-glucose solution). A glucose uptake and the number of D-glucose inhibitable [3H]cytochalasin B binding sites in BLM vesicles were significantly increased in all three conditions. Western blot analysis showed that the amount of GLUT2 protein in BLM vesicles was increased in rats with diabetes and those given a high-carbohydrate diet, but not in those with experimental hyperglycemia. These results suggest that there is a mechanism for rapid regulation of glucose transport in the BLM that does not depend on change in the amount of GLUT2.

Animals↗

UK-14,304, R(-)-alpha-methyl-histamine and SMS 201-995 block plasma protein leakage within dura mater by prejunctional mechanisms.

Intravenous administration of an alpha-adrenoceptor agonist, UK-14,304, a histamine H3 receptor agonist, R(-)-alpha-methyl-histamine (alpha-MeHA) or SMS 201-995 (a synthetic octapeptide analogue of somatostatin), blocked plasma protein (125I-albumin) extravasation within rat and/or guinea pig dura mater following unilateral electrical trigeminal ganglion stimulation or capsaicin administration. The extravasation caused by the administration of the neuropeptide mediator, substance P, was not inhibited by any of the three compounds. Blockade by UK-14,304 was completely antagonized by pretreatment with the highly selective alpha 2-antagonist, idazoxan, as was alpha-MeHA by pretreatment with the highly selective histamine H3 antagonist, thioperamide. Taken together, the results are consistent with blockade by prejunctional alpha 2, histamine H3 and probably somatostatin receptors which may be coupled to inhibition of neuropeptide release. Because 5-HT1-like agonists, which are useful for treating migraine and related headaches, share similar inhibitory properties in this in vivo model, the significance of prejunctional alpha 2, histamine H3 and somatostatin receptors to treatment of vascular headaches is suggested.

Adrenergic alpha-Agonists↗

Capillary gas chromatographic method for the determination of the thromboxane A2 receptor antagonist S-1452 and its metabolites in human plasma.

A capillary gas chromatographic method for the determination of a newly developed thromboxane A2 antagonist, S-1452, and its metabolites in human plasma has been developed. This nitrogenous compound was detected as the free acid (+)-S-145 using a nitrogen-phosphorus detector. The two metabolites bisnor-(+)-S-145 and tetranor-(+)-145 were also assayed. The three compounds, which all possess carboxylic acid group, were converted into their hexafluoro-2-propyl esters with hexafluoropropan-2-ol-pentafluoropropionic anhydride as reagent. The esterification resulted in a decreased background response from the detector, and hence higher sensitivity and better precision. The glucuronides of the three compounds were also assayed after alkaline hydrolysis. The plasma concentration of the glucuronide of I was more than twice that of the free acid. This method allows determination of the three compounds at more than 2 ng/ml with a precision of 2-6% and an accuracy variation of less than +/- 5%. The analysis was performed within 2 min after injection to assay the sample rapidly from the Phase I test. The method is suitable for pharmacokinetic studies.

Bridged Bicyclo Compounds↗

Capillary gas chromatographic method for the determination of the thromboxane A2 receptor antagonist S-1452 and its metabolites in human urine.

A capillary gas chromatographic method using a sulphur-specific detector (Hall's electrolytic conductivity detector) was established to determine the thromboxane A2 antagonist S-1452 and its metabolites in human urine. The target species were the free acid (+)-S-145 of the drug and its nine metabolites: the three hydroxyl forms of (+)-S-145 (I, II and III), bis-nor-(+)-S-145 (IV) the hydroxylated forms of IV (V and VI), tetranor-(+)-S-145 (VII) and the hydroxylated forms of VII (VIII and IX). These ten compounds, which have the same sulphur-containing functional group in common, were determined simultaneously. Their conjugated forms, which were assumed to be glucuronides, were also assayed after hydrolysis. The first derivatization was esterification with diazomethane. The second, for the hydroxylated compounds, was trimethylsilylation with bis(trimethylsilyl)trifluoroacetamide. The ten analytes appeared as separate peaks without mutual interference during 5 min. Hall's detector distinguished the ten analytes selectively from the other urinary components, which removed the need for complex clean-up procedures and led to higher sensitivity with a lower noise level. The method is sensitive enough for the assay of substances present at more than 0.1 micrograms/ml of urine. All the compounds could be determined with a high level of precision and accuracy, with 2-5% relative standard deviation and within +/- 5% deviation from the actual value. Day-to-day measurements verified the reproducibility of the method. Recovered substances were quantified by following the time course, and the analytical data together with previously obtained plasma data clarified the metabolism pharmacokinetically.

Bridged Bicyclo Compounds↗

Immediate effects of percutaneous transvenous mitral commissurotomy on pulmonary hemodynamics at rest and during exercise in mitral stenosis.

Hemodynamics were evaluated during exercise in 33 patients with mitral stenosis who underwent percutaneous transvenous mitral commissurotomy (PTMC). PTMC was performed using an Inoue balloon. Each patient underwent a supine ergometer exercise test before and on the day after PTMC. Ergometer work load was started at 20 W and increased in increments of 20 W at 3-minute intervals until terminated by the patient's fatigue or shortness of breath. Mitral valve area increased by 0.8 +/- 0.4 cm2 (1.1 +/- 0.3 to 1.9 +/- 0.4 cm2, p less than 0.001). Mean mitral pressure gradient decreased (12 +/- 5 to 6 +/- 2 mm Hg, p less than 0.001). Pulmonary arterial pressure significantly decreased and the cardiac index significantly increased both at rest and during exercise after PTMC. Before PTMC, the increases in pulmonary arterial pressure, total pulmonary resistance and pulmonary arteriolar resistance during exercise were greater in patients with a mitral valve area less than 1.0 cm2 than in patients with an area greater than or equal to 1.0 cm2. After PTMC, total pulmonary resistance still increased during exercise. However, pulmonary arteriolar resistance did not change during exercise in patients with a mitral valve area greater than or equal to 1.5 cm2, whereas it increased in patients with an area less than 1.5 cm2. An enlarged mitral valve area greater than or equal to 1.5 cm2, which may prevent pulmonary vasoconstriction and permits a greater increase in pulmonary blood flow during exercise, is considered a good result immediately after PTMC.

Cardiac Catheterization↗

Differential mechanisms of induction of ornithine decarboxylase in rat intestine by L- and D-amino acids.

A single intragastric administration of glycine, L- and D-alanine, and L-and D-serine into rats resulted in a more than 20-fold stimulation of intestinal mucosal ornithine decarboxylase (ODC) within 4 h. The stimulation of ODC activity was accompanied by an increase in the amount of immunoreactive ODC protein. The induction of ODC by D-amino acids was in all likelihood attributable to an enhanced accumulation of ODC-specific mRNA species as revealed by Northern blot and dot-blot hybridization analyses. However, the induction by glycine and L-amino acids was not explainable by changes of mRNA since the changes in mRNA contents were only marginal. Since the turnover rates of L-serine-induced and D-serine-induced intestinal ODC protein were the same as the non-induced control, we concluded that the induction by glycine and L-amino acids was brought about by an increased efficiency of translation of the ODC message.

Amino Acids↗

Increased levels of circulating intercellular adhesion molecule 1 in Kawasaki disease.

OBJECTIVE: We investigated whether levels of intercellular adhesion molecule 1 (ICAM-1) antigen shed into the circulation increase during acute Kawasaki disease (KD). We also compared ICAM-1 levels in acute KD with those in anaphylactoid purpura (AP) and in measles. METHODS: Serum ICAM-1 levels were measured by a double-determinant immunoassay using 2 monoclonal antibodies in the FAST (Falcon assay screening test) system. Serum levels of tumor necrosis factor alpha (TNF alpha) were measured by a specific and sensitive sandwich enzyme immunoassay. RESULTS: Patients with KD, but not those with AP or measles, had increased levels of shed ICAM-1 antigen in serum samples obtained during acute stages. Moreover, during the acute stage, KD patients with coronary artery lesions (CAL) had still higher levels of shed ICAM-1 than did those without CAL. We found a positive correlation between serum levels of shed ICAM-1 and levels of TNF alpha during acute KD. CONCLUSION: Our findings suggest that the serum ICAM-1 level is an important immunologic parameter for determining the severity of vascular damage during acute KD.

Cell Adhesion Molecules↗

Coronary angioplasty using an over-the-wire balloon catheter through a new 6 French guiding catheter.

A new 6 French (F) guiding catheter with a large, teflon-coated internal lumen (4.2F) was developed, permitting use of the standard ultralow profile (less than 3F) over-the-wire system. This small coronary angioplasty system (6F-PTCA) was evaluated in 48 lesions in 45 of 137 patients (33%) who underwent coronary angioplasty between September 1990 and January 1991. The mean age was 64 years (range 49 to 82); 37 (82%) were male. The procedure was via the brachial artery in 28 patients (62%). The overall primary success rate was 96%. It was 100% via the brachial artery and 90% via the femoral artery. There were no major complications. The puncture compression time with the 6F-PTCA via the brachial artery and via the femoral and with 8F-PTCA via the femoral was 3.8, 9.6, and 16.9 hr, respectively (P less than 0.001), although the procedure time of the 6F-PTCA via brachial and via femoral and of the 8F-PTCA was not significantly different. The mean hospital stay was 3.1, 4.5, and 5.5 days, respectively (P less than 0.01). A small hematoma occurred in 2 patients (4.4%) after the 6F-PTCA and in 3 (3.3%) after 8F-PTCA, and a large hematoma (greater than 5 cm) was noted in 7 patients (7.6%) after 8F-PTCA. These results indicate that coronary angioplasty using the over-the-wire system through the new 6F guiding catheter is technically feasible. Moreover, this approach, especially when advanced via the brachial artery, could shorten the hemostasis time and facilitate early ambulation.

Aged↗