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Biomedical subjects

T Matsubara

Publications and source records attributed to T Matsubara.

At least 361 records · Page 20Linked to original sources

Beneficial effect of nipradilol (K-351) on acute myocardial ischemia. Study of the relationship between regional myocardial blood flow and energy metabolism.

To examine the effects of nipradilol on ischemic myocardium, experiments were performed on regional myocardial blood flow (MBF) and energy metabolism in anesthetized, open-chest dogs. Nipradilol at a dose of 0.3 mg/kg was i.v.-administered 10 min after coronary ligation. MBFs at various sites, including ischemic and non-ischemic areas, were determined by the hydrogen gas clearance method. The levels of ATP and creatine phosphate (CP) at the site of MBF determination were measured 60 min after ligation, and mitochondrial function (RCI, QO2) in the ischemic and non-ischemic areas was determined. Following nipradilol administration, aortic pressure and heart rate were significantly lowered. In ischemic areas with MBF below 40 ml/min/100 g, nipradilol had no influence on MBF. However, the tissue level of ATP in nipradilol treated hearts was significantly higher as compared with untreated hearts. In the area of mild ischemia with MBF of 40-60 ml/min/100 g, nipradilol preserved the tissue ATP and CP levels in spite of a decrease in MBF. Moreover, an inhibition of the decrease in mitochondrial respiratory function was observed in ischemic areas with MBF below 20 ml/min/100 g. Thus, nipradilol administered following ischemia preserved ATP content and mitochondrial function in the ischemic myocardium with reduction of heart rate and aortic pressure. This suggests that nipradilol exerts a cardioprotective effect in acute ischemia. It seems that the cardioprotective effect is due to a decrease in myocardial oxygen demand and preservation of mitochondrial function.

Adenosine Triphosphate↗

Sex difference in adrenergic receptor-mediated glycogenolysis in rat livers.

Catecholamine-induced stimulation of hepatic glycogenolysis in male and female rats was studied by detecting the cytosolic free Ca2+ concentration ([Ca2+]i), cAMP generation and adrenergic receptor function. Increase in alpha 1-adrenergic receptor-mediated [Ca2+]i and beta-adrenergic receptor-mediated cAMP generation were examined using isolated hepatocytes. No difference was found in the alpha 1-adrenergic receptor-mediated response of [Ca2+]i in fura-2-loaded hepatocytes between males and females, while epinephrine-induced cAMP accumulation in hepatocytes was about 3-fold higher in females. The alpha 1- and beta-adrenergic receptor properties of the plasma membrane were evaluated by ligand binding studies using [3H]prazosin (alpha 1-adrenergic antagonist) and [125I]iodocyanopindolol (beta-adrenergic antagonist); and little sex difference was found in either affinity or the number of binding sites of [3H]prazosin and [125I]iodocyanopindolol. Activation of adenylate cyclase by forskolin and GTP-gamma-S was also similar for both sexes. These results suggest that the sex difference of beta-adrenergic response is due to a difference in the guanine nucleotide regulatory binding proteins (G proteins) and/or beta-adrenergic receptor-Gs protein (the stimulatory G protein of adenylate cyclase) coupling ability.

Adenylyl Cyclases↗

The osteogenetic potential of fracture haematoma. Subperiosteal and intramuscular transplantation of the haematoma.

We studied the precise role of the fracture haematoma in healing by the experimental transplantation of the haematoma at two days and four days after fracture of the rat femur to subperiosteal and intramuscular sites. We used bone marrow and peripheral blood haematomas for control experiments. The transplanted two-day fracture haematoma produced new bone by endochondral ossification at the subperiosteal site, but not at the intramuscular site. Four-day fracture haematoma produced new bone formation at both subperiosteal and intramuscular sites. These results suggest that fracture haematoma has an inherent osteogenetic potential.

Animals↗

Angiotensin II generation in mesenteric arteries in rats: effects of nephrectomy, deoxycorticosterone and dexamethasone.

Angiotensin II (ANG II) generation in the mesenteric arteries was studied in four groups of rats: deoxycorticosterone (DOCA)/salt treated, glucocorticoid treated, nephrectomized and control rats. Basal plasma renin activity (PRA) was undetectable in the nephrectomized group and suppressed in the DOCA/salt treated rats, but was increased in the rats treated with glucocorticoid. The Basal plasma ANG II concentration changed comparably with PRA in all four groups of rats. In the control rats, ANG II was released from the mesenteric arteries at a rate of 43.0 +/- 12.0 pg/h, and it was not decreased by nephrectomy. In DOCA/salt rats and glucocorticoid rats, ANG II release significantly decreased to 12.8 +/- 7.1 and 6.9 +/- 1.5 pg/h, respectively. Captopril treatment significantly reduced ANG II release from the mesenteric arteries in both controls and nephrectomized rats, but did not influence ANG II output in DOCA/salt rats or in glucocorticoid treated rats. In nephrectomized rats, captopril lowered blood pressure in association with a significant reduction in the mesenteric ANG II formation. These results indicate that the renal and vascular renin-angiotensin system (RAS) may be independently regulated, and in nephrectomized animals the vascular RAS contributes in part to the maintenance of blood pressure. The present results also suggest that volume expansion per se and/or pharmacological intervention by DOCA and glucocorticoid could modulate vascular ANG II generation.

Analysis of Variance↗

Beneficial effects of low-flow perfusion resumed early after zero-flow ischemia on myocardial energy metabolism and mechanical function: 31P-NMR study in the isolated perfused rat heart.

Effects of low-flow perfusion after zero-flow ischemia on myocardial mechanical function and energy metabolism were studied with 31P nuclear magnetic resonance spectroscopy, using isolated perfused rat hearts. After control perfusion, hearts were randomly divided into five experimental groups: Groups I and II were subjected to zero-flow ischemia of 40 and 60 min, respectively. In groups III-V the perfusion was resumed at a rate of 0.1 ml/min after 40 (group III), 30 (group IV) and 20 (group V)-min of zero-flow ischemia in order to compare the effects of low-flow perfusion with those of persistent zero-flow. After these interventions all the hearts were perfused for 40 min at a normal flow rate. Compared with the hearts exposed to total ischemia of 60 min, the preservation of high energy phosphate compounds (HEP) was better in groups with early low-flow perfusion; Creatine phosphate (CrP) levels, which had decreased rapidly after induction of zero-flow ischemia, increased gradually after initiation of the low-flow perfusion and reached significantly higher levels at the end of ischemic period in groups IV and V than in group II (p less than 0.05). The decrease in adenosine triphosphate (ATP) was likewise significantly suppressed by low-flow perfusion (groups IV and V greater than group II). Restoration of CrP levels after complete reperfusion was also significantly greater in group V than in group II. The recovery of ATP after complete reperfusion was also much better in group V being comparable to those in group I, although the total duration of ischemia was longer in group V than in group I. These results indicate the beneficial effects of low-flow perfusion on the preservation during ischemia and recovery after reperfusion of myocardial HEP.

Adenosine Triphosphate↗

Increased superoxide anion release from chondrocytes in response to interleukin 1 and interferons.

In order to investigate a possible mechanism of degradation of cartilage matrix in chronic inflammation, superoxide anion (O2-) release from chondrocytes after stimulation with interleukin 1 (IL 1) and interferons (IFNs) has been studied. Both of these cytokines enhanced O2- release in a dose- and time-dependent fashion. Increased of the O2- release by these cytokines inactivated by heat or acid pretreatment was not observed. These results suggest that the cytokines released in the process of local immune reactions can stimulate the chondrocytes to promote generation and release of O2-. Released O2- may be associated with degradation of cartilage matrix by chondrocytes themselves activated in the process of chronic arthritis.

Animals↗

[Serum gamma interferon levels in relation to tumor necrosis factor and interleukin 2 receptor in patients with Kawasaki disease involving coronary-artery lesions].

Serum levels of gamma interferon (IFN-gamma) were determined by a sandwich radioimmunoassay in 45 patients with Kawasaki disease (KD), 14 with measles, 3 with streptococcal infection, 17 with anaphylactoid purpura, 6 with various vasculitis and also in 10 healthy children. Serum levels of IFN-gamma were seen to increase during the acute phase of KD and measles. In addition, serum levels of tumor necrosis factor (TNF) and interleukin 2 receptor (IL-2R) were measured simultaneously in 45 patients with KD. In KD patients with coronary-artery lesions (CAL), the percentage of positive cases for TNF (greater than or equal to 10 units/ml), IL-2R (greater than or equal to 1056 units/ml) and IFN-gamma (greater than or equal to 0.3 units/ml) was higher than that in patients without CAL. Several cytokines in association with activated monocytes/macrophages and T lymphocytes were detected in the serum during acute KD. These results suggest that aggressive activation of immuno-competent cells develops in KD involved CAL.

Adolescent↗

[Clinical analysis of malignant meningiomas].

It seems generally accepted that meningiomas are benign tumors, and that malignant meningiomas are not common. The pathological criteria for judging whether meningiomas are malignant or not are controversial. Hemangiopericytic type, high cellularity, brain invasion, high mitotic rate, necrotic foci, and papillary type are regarded as histological characteristics of malignant meningiomas. Of a series of 105 patients with surgically treated meningioma, 25 patients demonstrated malignant characteristics (24%). The overall recurrence rate in our patients was 14%. The incidence of recurrence in 25 patients with pathologically malignant characteristics, and recurrence in 80 patients with pathologically benign characteristics were 32% and 9%, respectively. In comparison with benign meningiomas, recurrent factors in malignant ones included Simpson grade II operation, attachment of skull base, and no radiation-therapy. In conclusion, our criteria for malignant meningiomas have proved to be acceptable, and these cases should be treated with radiation therapy after surgery.

Adult↗

Clinical and histologic observations of monoarthritis. Anticipation of its progression to rheumatoid arthritis.

Synovial biopsies were performed on 84 patients with monoarticular synovitis from 1960 to 1984. Twenty-seven (32%) of 84 patients were pathologically differentiated; however, the other patients remained classified as nonspecific monoarthritic. Follow-up studies of nonspecific monoarthritis ranging from five to 25 years (average, 15 years) were carried out in 34 patients. Five patients (15%) disclosed polyarticular involvement and were diagnosed as having classic rheumatoid arthritis (RA) within five years after initial biopsy (RA group). In the remainder (non-RA group), 19 patients recovered completely and nine of ten patients complained of a slight degree of joint involvement. A good prognosis was observed in younger patients and in those who showed minimal histologic changes in the synovium. Initial laboratory examinations, including a white cell count, erythrocyte sedimentation rate, C-reactive protein, and agglutination test, did not show any differences between the RA and the non-RA groups. To determine predicting factors for RA, a comparative histologic study of the initial specimens was performed. Specimens from the RA group showed a predominant appearance of lymphoid aggregates, high endothelial postcapillary venules, and proliferative plasma cell infiltration. These histologic features suggest the future appearance of RA; therefore, careful observation and early treatment should be considered for these patients.

Activities of Daily Living↗

Pulmonary sclerosing hemangioma of the lung. A type II pneumocytoma by immunohistochemical and immunoelectron microscopic studies.

Three cases of pulmonary sclerosing hemangioma were studied by immunohistochemical and immunoelectron microscopic methods using a panel of antibodies. Six cases of adenocarcinoma of the lung, three cases of normal mesothelium, and three cases of mesothelioma were used as controls. The cytoplasm of some of the sclerosing hemangioma tumor cells was positive for the anti-lung surfactant apoprotein monoclonal antibody (PE-10). These cells were the pale cells of the solid areas, the cells covering the papillary projections, and the cells lining the cleft-like spaces. These cells also were positive for conventional epithelial cell markers. Some cells also were positive for vimentin. Electron microscopic study showed that the predominant cell was a poorly differentiated pneumocyte. Immunoelectron microscopic study also demonstrated that PE-10 existed in the rough endoplasmic reticulum of some of the cells in the solid areas, in the same way as normal type II pneumocytes. We concluded that the sclerosing hemangioma is an epithelial tumor with differentiation towards type II pneumocytes.

Aged↗

Depression of liver microsomal vitamin K epoxide reductase activity associated with antibiotic-induced coagulopathy.

Hypoprothrombinemic changes in blood coagulation parameters, such as prolongation of prothrombin time, increase in the level of plasma protein induced by vitamin K absence, and decrease in plasma prothrombin level, were detected in rats fed a vitamin K-deficient diet. These changes were enhanced by the administration of beta-lactam antibiotics containing N-methyltetrazolethiol, thiadiazolethiol or methyl-thiadiazolethiol. Microsomal vitamin K epoxide reductase activity was suppressed with the maximum effect at 1-2 days after the treatment and with recovery, thereafter, gradually to the normal level after 5-7 days. Hypoprothrombinemic alterations in blood coagulation parameters following a single administration of antibiotic to vitamin K-deficient rats were somewhat delayed compared with the change in the epoxide reductase activity, but the effects of the antibiotic on both blood coagulation parameters and the enzyme activity disappeared completely 7 days after the antibiotic treatment. Antibiotic-induced depression of the epoxide reductase activity was observed even in the vitamin K sufficient rats, although the hypoprothrombinemic changes in the blood coagulation parameters did not develop. Vitamin K administration could normalize the blood coagulation parameters in the hypoprothrombinemic rats caused by treatment with the antibiotics but without recovery of the decreased epoxide reductase activity. These results suggest that some antibiotics inhibit liver microsomal vitamin K epoxide reductase, which causes hypoprothrombinemia to develop under vitamin K-deficient conditions.

Animals↗

Rate enhancement of the electron transfer the adrenodoxin-adrenodoxin reductase system by dicarboxylic acids.

The rate of electron transport in the cytochrome P-450 system in adrenocortical mitochondria was studied with purified adrenodoxin reductase, adrenodoxin and cytochrome c. Oxaloacetate enhanced the rate at concentrations of less than 1 mM; malate, succinate and fumarate enhanced the rate to a lesser extent; and pyruvate and alpha-ketoglutarate had no appreciable effect. The rate enhancement was observed when the reagents were preincubated with adrenodoxin, but not with adrenodoxin reductase. Rate enhancement was also evident when the rate limiting step was at adrenodoxin in the electron transport system.

Adrenodoxin↗

Inhibition of in vitro vascular endothelial cell proliferation and in vivo neovascularization by low-dose methotrexate.

Neovascularization in the rheumatoid synovium plays an important role in the propagation of rheumatoid synovitis because the emigration of mononuclear cells and the growth of pannus are critically dependent on the development of small blood vessels. Inhibition of local vascular endothelial cell (EC) proliferation, which is essential for growth of these vessels, therefore, would have the potential to suppress rheumatoid inflammation. We investigated the effects of methotrexate (MTX), low doses of which are commonly administered to rheumatoid arthritis patients, on DNA synthesis by human umbilical vein EC in vitro and on rabbit corneal neovascularization in vivo. MTX inhibited both basal and EC growth factor-stimulated tritiated deoxyuridine (3H-UdR) incorporation into EC in a dose-dependent manner. Significant inhibition was observed at a concentration of 5 x 10(-9) M, which is that attained in the serum of treated patients. Neovascularization in vivo was also suppressed by low-dose intramuscular injections. These results suggest that MTX has an antiangiogenic effect, and may suppress rheumatoid inflammation through the reduction of synovial small blood vessels responsible for mononuclear cell infiltration and proliferation of synovial tissue.

Animals↗

Possible association of aldosterone producing adenoma and non-functioning adrenal tumor.

A 37-year-old woman presented with hyperaldosteronism, suppressed renin levels, and a left adrenal mass on CT scanning. Selective adrenal venous sampling indicated a marked rise of the aldosterone level in the right adrenal vein, while the level in the left vein was low. On laparotomy, an aldosterone producing adenoma (APA) of 12x10x5 mm in size was found in the right adrenal gland and was resected, while the left mass was left in situ. The post-operative course showed normalization of both the clinical and biochemical features of primary aldosteronism, with no sign of recurrence or of enlargement of the remaining adrenal mass in 2.5 years of follow up, suggesting the possible coexistence of a "non-functioning" tumor. This case demonstrates the importance of adrenal venous sampling for the localization of APA particularly since the presence of the APA may be masked by a visualized but unrelated adrenal mass.

18-Hydroxycorticosterone↗

Microsurgical procedures for management of giant middle cerebral aneurysm causing increased intracranial pressure.

There have not been many cases reported of giant aneurysms of the middle cerebral artery with a remarkable mass and causing increased intracranial pressure, and the successful operation for resecting an aneurysm is still low. Considering it essential that the mass of an aneurysm should be reduced and the blood flow of parent and distal arteries should be preserved, we are reporting two successful results.

Adult↗

Structural analysis of choline phospholipids by fast atom bombardment mass spectrometry and tandem mass spectrometry.

The structures of intact choline phospholipids were determined by positive and negative ion mode fast atom bombardment mass spectrometry, tandem mass spectrometry, and B2/E and B/E constant linked scan mass spectrometry. The molecular weight of the choline lipid could be clearly determined by the appearance of [M + H]+ or [M + Na]+ in the positive ion mode and triplet ions, e.g., [M - 15]-, [M - 60]-, and [M - 86]-, in the negative ion mode. The structures of the triplet ions were assigned to [M - CH3]-, [M - HN(CH3)3]-, and [M - CH2 = CHN(CH3)3]-, respectively, by the MS/MS of each triplet ion, and the origin of the triplet ions was found as the matrix-ion adduct to the target molecule by using the B2/E linked scan technique. The polar group could be identified by the existence of ions indicating glycerophosphocholine and its cleavage products and by the presence of the triplet ions in the negative ion mode. Positional determination of the distribution of constituent fatty acyl groups was carried out by comparing the intensity of deacylated ions from positions 1 and 2 in the positive ion mode and of the ions produced by MS/MS of the triplet ions. From the mass number of the [RCOO]- ion which appeared in the negative ion mode, the molecular weight and degree of unsaturation of the fatty acyl group were determined. The position of double bond(s) in the acyl group was determined from the MS/MS of the [RCOO]- ion.

Lysophosphatidylcholines↗