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Biomedical subjects

S Ohtsuka

Publications and source records attributed to S Ohtsuka.

At least 91 records · Page 5Linked to original sources

Ventricular wall stress revisited. A keystone of cardiology.

Wall stress has been used as one of the parameters of myocardial mechanics. The present review focuses on recently developed data on ventricular wall stress, especially in relation to other newly developed areas in cardiology. In hypertensive hearts, there is a broad continuous spectrum in the structural and functional changes: those with low wall stress (inappropriate hypertrophy), those with normal wall stress (appropriate hypertrophy) and those with high wall stress (inadequate hypertrophy). Among them, the responses to neurohumoral stimuli are various, and their clinical features and courses also varied. These differences in wall stress among the different categories of hypertensive hearts may be caused by the variable influences of non-mechanical factors, such as molecular, metabolic and neurohumoral ones. Wall stress is an essential determinant of myocardial oxygen consumption, and is also an important determinant of the myocardial contractile state and diastolic function. In contrast to excitation-contraction coupling, contraction-excitation feedback has been studied, suggesting the importance of wall stress regulating electrical phenomena. The interrelationship between mechanical factors (including wall stress) and non-mechanical factors (including molecular, metabolic, neurohumoral and genetic ones) has been investigated intensively. In conclusion, wall stress (or force on the myocardial cell) may be a keystone in cardiology, relating to each of the cardiac phenomena. If wall stress deviates from the normal range, even with compensatory mechanisms, severe cardiac events occur. The compensatory mechanisms for wall stress may act as a risk factor on the heart, especially when the wall stress remains outside the normal range.

Electrocardiography↗

Coronary circulation in dogs with an experimental decrease in aortic compliance.

OBJECTIVES: This study was designed to investigate the effects of decreased aortic compliance on the coronary circulation. BACKGROUND: A decrease in aortic compliance due to arteriosclerosis is observed in patients with coronary artery disease. However, the effects of decreased aortic compliance on the coronary circulation have not yet been investigated sufficiently. METHODS: Hemodynamics, subendocardial electrocardiogram (ECG), myocardial segmental length and myocardial blood flow were investigated in six dogs with aortic bandaging (bandaged group) and five dogs with a sham operation (control group) at rest and during pacing 4 weeks after surgery. RESULTS: Aortic compliance in the bandaged group was less than that in the control group (0.24 +/- 0.20 vs. 0.50 +/- 0.22 ml/mm Hg, p < 0.05). Pulse pressure and the tension-time index were significantly greater in the bandaged group than in the control group, but systemic vascular resistance was not altered significantly. The subendocardial/subepicardial flow ratio was lower in the bandaged group than in the control group (0.95 +/- 0.31 vs. 1.57 +/- 0.26, p < 0.05). In the region supplied by the left circumflex artery with a stenosis that was adjusted to eliminate reactive hyperemia, rapid atrial pacing (heart rate 200 beats/min) further decreased endocardial flow and the endocardial/epicardial flow ratio in the bandaged group. Moreover, both the reduction of segmental shortening and the ST elevation on the subendocardial ECG in the left circumflex-supplied region during pacing were greater in the bandaged group. CONCLUSIONS: These results indicate that decreased aortic compliance greatly increases the risk of subendocardial ischemia in the presence of coronary stenosis.

Animals↗

Involvement of epidermal growth factor in inducing obesity in ovariectomized mice.

Ovariectomy (Ovx) of mice significantly increases the epidermal growth factor (EGF) concentration in the submandibular gland. To elucidate the role of this elevated EGF in obesity of Ovx mice, we examined the effects of sialoadenectomy (Sx) and anti-EGF rabbit antiserum administration on the body weight (BW) gain and carcass fat deposition in Ovx animals. Studies were performed in four groups of mice consisting of control, Ovx, Ovx+Sx, and Ovx+anti-EGF groups. Ovx increased the BW gain compared with the control animals, whereas Sx and anti-EGF significantly reduced it. Although the relative weights (weight ratio to BW) of the liver and kidney were not significantly changed by Ovx, Sx, or anti-EGF treatment of Ovx mice, the relative weights of mesenteric, parametrial, and subcutaneous fat tissues were increased in Ovx mice, and this increase was significantly reduced by Sx or anti-EGF administration. Ovx induced adipocyte hypertrophy, and this effect was eliminated by Sx and anti-EGF. Moreover, acyl-CoA synthetase mRNA level was increased by Ovx, and this increase was reduced by Sx and anti-EGF in mesenteric fat tissue. These findings suggest that elevation of EGF may play a role in the induction of obesity in Ovx mice.

Acetate-CoA Ligase↗

Platelet cyclic GMP. A potentially useful indicator to evaluate the effects of nitroglycerin and nitrate tolerance.

BACKGROUND: The present study was designed to investigate the intracellular production of cyclic GMP (cGMP) in platelets in response to nitroglycerin and to determine the potential clinical value of platelet cGMP as an indicator of the effects of nitroglycerin and nitrate tolerance. METHODS AND RESULTS: Platelet cGMP levels and the diameters of the coronary arteries before and 2 minutes after intracoronary injection of 200 micrograms nitroglycerin were measured in 15 patients who had previously received nitrates (nitrates group) and in 16 who had not received any nitrates (no-nitrates group). Platelet cGMP levels increased significantly after nitroglycerin injection in the two groups, but plasma cGMP levels and plasma atrial natriuretic peptide levels did not change. The percent increase in platelet cGMP levels and the percent dilatation of the left anterior descending (LAD) and left circumflex (LCx) coronary arteries after nitroglycerin injection were higher in the no-nitrates group than in the nitrates group (platelet cGMP levels: artery, 74.2 +/- 18.3% versus 11.5 +/- 4.2%, P < .01; vein, 73.6 +/- 22.9% versus 9.0 +/- 3.1%, P < .01; coronary dilatation: LAD, 46.7 +/- 6.0% versus 9.9 +/- 2.5%, P < .01, LCx, 51.2 +/- 8.7% versus 6.1 +/- 3.0%, P < .01). The percent increase in platelet cGMP levels was significantly correlated with the percent dilatation of the coronary arteries (LAD: r = .90, P < .01; LCx: r = .92, P < .01) in the no-nitrates group and not in the nitrates group. CONCLUSIONS: These results indicate that platelet cGMP can be used as an indicator for in situ evaluation of nitroglycerin effects and that patients who have received nitrates develop nitrate tolerance, which affects intracellular production of cGMP and vasodilation in the response to nitroglycerin.

Atrial Natriuretic Factor↗

[UV-microspectrophotometric and flow cytometric analysis of the same samples using DAPI/HP staining].

A simple one-step double staining with DAPI and hematoporphyrin (HP) was used for UV-microspectrophotometric (UV-MSPM) and flow cytometry (FCM) analysis of the same samples. The specimens analyzed included fresh biopsy and/or surgical materials, trimmed 50 microns-thick paraffin sections and smears (with the latter not available for FCM). We provided the special technology for preserving the cytoplasm as far as possible to permit measurement of cell size and N/C ratio. DAPI indicates DNA content under 365 nm and HP of total protein content under 670 nm UV-MSPM. The DAPI can measure the nuclear size and the latter the cell size. DAPI/HP staining yielded much more accurate measurements than staining with FITC and PI. The use of both MSPM and FCM with cell sorting on the same samples is very helpful in cytology and histopathology for evaluating and differentiating borderline lesions and grade of malignancy, as well as oncostatic effectivity. Our goal is to combine this technology with the automated cytologic screening system CYBEST, which was developed by Tanaka et al, based on a morphometric device.

Adenocarcinoma↗

Characterization and localization of alpha-connectin (titin 1): an elastic protein isolated from rabbit skeletal muscle.

A simplified procedure to isolate alpha-connectin (titin 1, TI), a gigantic elastic protein, from rabbit skeletal muscle is described. A rapid column chromatography step to concentrate alpha-connectin is introduced. Separation of alpha-connectin from beta-connectin is introduced. Separation of alpha-connectin from beta-connectin (titin 2, TII) in the presence of 4 M urea at pH 7.0 did not cause any change in the secondary structure of alpha-connectin as judged by circular dichroic spectra. Ultraviolet absorption spectra and the amino acid composition of alpha-connectin (MW, approximately 3 x 10(6)) were similar to those of its proteolytic product, beta-connectin (MW, approximately 2 x 10(6)). Circular dichroic spectra suggested that both alpha- and beta-connectin consist of 60% beta-sheet and 30% beta-turn. It thus appears that the whole elastic filament of connectin has a folded beta-strand structure. Proteolysis of alpha-connectin by calpain resulted in formation of beta-connectin and smaller peptides. The alpha-connectin interacted with both myosin and actin filaments similarly to beta-connectin. Polyclonal antibodies raised against 1200 kDa peptides obtained from aged rabbit skeletal myofibrils reacted with alpha-connectin (titin 1, TI) but only weakly with beta-connectin (titin 2, TII) in rabbit skeletal muscle. Immunoelectron microscopy and indirect immunofluorescence microscopy revealed that the antibodies bound at the Z-line and at the epitope regions in the I-band near the binding site of a monoclonal antibody SM1 whose position depends on sarcomere length. It thus appears that beta-connectin extends from the edge of M-line to the above epitope region in the I-band.

Actins↗

Chicken leg muscle alpha-connectin as studied by a monoclonal antibody to the 1200 kDa fragment.

Chicken leg gracilis muscle contained only alpha-connectin (ca 3000 kDa) without beta-connectin. When myofibrils were kept standing for 20 hr at 4 degrees C, alpha-connectin was degraded to beta-connectin (ca 2000 kDa) and 1200 kDa peptide. The latter was prepared from myofibrils and purified by gel filtration in the presence of SDS. A monoclonal antibody, alpha 7, to this 1200 kDa fragment was prepared. The antibody reacted with the 1200 kDa fragment and its mother molecule alpha-connectin, but not with beta-connectin. Immunoelectron microscopy using alpha 7, as well as other antibodies to chicken breast muscle beta-connectin, revealed that the 1200 kDa peptide covered the portion of alpha-connectin from the Z line to the N2 line region in the I band of chicken leg gracilis muscle sarcomeres. The results were in good agreement with those observed in rabbit skeletal muscle.

Animals↗

Decreased aortic compliance aggravates subendocardial ischaemia in dogs with stenosed coronary artery.

OBJECTIVES: The existence of decreased aortic compliance due to arteriosclerosis has been documented in patients with coronary artery disease. The aim of this study was to investigate the effects of decreased aortic compliance on coronary artery disease. METHODS: To simulate coronary artery disease, a fixed stenosis was made in the left circumflex coronary artery in dogs. Ten anaesthetised open chest dogs were used. Aortic compliance was decreased by banding the thoracic aorta with adjustable plastic rings. The level of coronary stenosis was adjusted to reduce the baseline flow by no more than 10% but enough to eliminate reactive hyperaemia induced by a 10 s occlusion. Measurements of haemodynamics, regional myocardial segment length, subendocardial ECG, and myocardial tissue PO2 were performed at five stages (initial control stage, rest and pacing stages without aortic banding, and rest and pacing stages with the aortic banding). RESULTS: Haemodynamic variables were not changed at any stage, except for increased pulse pressure secondary to the aortic banding. During pacing with aortic banding, subendocardial PO2 (Endo) levels were decreased, and subepicardial PO2 (Epi) levels were increased, compared to those without the aortic banding [Endo: 43.2(SD 9.8) v 36.8(10.0) mm Hg, p < 0.05; Epi: 34.0(11.5) v 44.4(7.9) mm Hg, p < 0.05]. ST elevation on the subendocardial ECG was greater, and myocardial segment shortening was less with the aortic bandage during pacing. CONCLUSIONS: When the work of the heart is increased, a decrease in aortic compliance tends to compromise ischaemic myocardium further in the presence of an induced stenosis of a major coronary artery.

Animals↗

Binding sites for interleukin-6 in the anterior pituitary gland.

Interleukin-6 (IL-6) binding site in the rat anterior pituitary gland was characterized using radioiodinated human recombinant (hr) IL-6. Results showed that the anterior pituitary gland contained 170 binding sites per cell of a single class with a dissociation constant of 2.7 x 10(-9) M. The binding of 125I-hrIL-6 to the rat anterior pituitary gland was competitively inhibited by unlabeled hrIL-6, but not by hrIL-1 alpha, hrIL-1 beta, hrIL-2 or hr-interferon-gamma, indicating these binding sites are specific for IL-6. We also demonstrated mouse IL-6 receptor gene expression in the rat anterior pituitary gland by Northern blot analysis. Furthermore, the IL-6 receptor was detected on human gonadotrophs by the double immunofluorescence method. Our findings demonstrate the presence and expression of IL-6 binding site in the rat anterior pituitary gland and the presence of IL-6 binding site on human gonadotrophs, suggesting the important role of IL-6 binding site in pituitary hormone release in both species.

Animals↗