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Biomedical subjects

M Tsukamoto

Publications and source records attributed to M Tsukamoto.

At least 55 records · Page 3Linked to original sources

A new antitumor antibiotic, BE-19412A, produced by a streptomycete.

A new antitumor substance, designated BE-19412A, was isolated from the culture broth of Streptomyces sp. A19412. The active principle was extracted from the mycelium by methanol and purified by Silica gel and Sephadex LH-20 column chromatographies. BE-19412B was prepared by methylation of BE-19412A. BE-19412A and B exhibited cytotoxic activity against murine and human tumor cell lines. BE-19412A prolonged the survival of CDF1 mice bearing i.p. implanted Ehrlich carcinoma cells.

Animals↗

Cardiovascular effects of (2RS,3SR)- 2-aminomethyl-2,3,7,8-tetrahydro-2,3,5,8,8-pentamethyl-6H-furo- [2,3-e]indol-7-one hydrochloride (UK-1745), a novel cardiotonic agent with vasodilatory and antiarrhythmic properties.

The cardiovascular effects of (2RS,3SR)-2-aminomethyl-2,3,7,8- tetrahydro-2,3,5,8,8-pentamethyl-6H-furo[2,3-e]indol-7-one hydrochloride (CAS 170684-14-7, UK-1745), a novel cardiotonic agent, were investigated using in vitro and in vivo preparations. In paced left atria isolated from guinea pigs, both UK-1745 and vesnarinone (CAS 81840-15-5) showed a concentration-dependent positive inotropic effect. In spontaneously beating guinea pig right atria, both agents caused only a minimal chronotropic effect. In isolated, blood-perfused canine papillary muscle preparations, UK-1745 and vesnarinone injected intra-arterially into the anterior septal artery (ASA) increased the developed tension in a dose-dependent manner. In isolated, blood-perfused canine sinoatrial node preparations, both agents injected into the right coronary artery (RCA) did not cause any appreciable changes in the sinus rate. UK-1745 increased the blood flow through the ASA and the RCA in a dose-dependent manner, whereas vesnarinone did not. In anesthetized open-chest dogs, UK-1745 injected intravenously increased cardiac contractility and cardiac output, and decreased left ventricular end-diastolic pressure, systemic vascular resistance and heart rate. In experimentally induced acute heart failure in anesthetized open-chest dogs, intravenously injected UK-1745 effectively improved hemodynamic functions. In conscious instrumented dogs, orally administered UK-1745 increased LV dP/dtmax with insignificant changes in systemic blood pressure and heart rate. In mice, orally administered UK-1745 protected the development of ventricular fibrillation induced by chloroform inhalation, whereas vesnarinone did not. Thus, in respect of inotropic and chronotropic effects, UK-1745 closely resembled vesnarinone, but differed from vesnarinone in respect of coronary vasodilating and antiarrhythmic effects. The results suggest that UK-1745 is a novel positive inotropic agent with vasodilatory and antiarrhythmic properties, without significant chronotropic action, and may be beneficial for the treatment of congestive heart failure.

Anesthesia↗

[Biocompatibility of polyvinylalcohol gel as a vitreous substitute].

Polyvinylacohol (PVA) gel cross linked by gamma irradiation was assessed as a possible vitreous substitute. In our previous, reports, elevation of intraocular pressure and inflammatory changes in the vitreous cavity after operation were observed in some of the experimental animals. Four types of PVA gel (sol) were produced by a newly refined method. We improved the gel systhesis process to remove the monomer and contamination. Colored rabbits were used for this experiment. Vitreous replacement was performed after vitrectomy. This was followed clinically by ophthalmoscopy, tonometry, fundus photography, electroretinogram, chemotaxis, and laser-flare-cell-metering. Histopathological examination by light microscopy was performed after 3 months. PVA gel has good biocompatibility in the vitreous cavity, and gel with a network similar to that of the vitreous body showed the best biocompatibility. Although it is necessary to investigate the biocompatibility over the long term and to evaluate the tamponade effect, PVA gel will be a bood candidate for a vitreous substitute.

Animals↗

[Multiple overlapping Wiktor stenting for the treatment of diffuse lesions of small coronary arteries].

This study evaluated the usefulness of multiple overlapping stenting for the treatment of a diffuse lesion in a single and small coronary artery. We studied 48 consecutive patients with a lesion of a vessel with reference diameter < 3.0 mm who received Wiktor stent implants due to suboptimal result or threatened closure after plain old balloon angioplasty (POBA). The patients were divided into 2 groups: Group D, 18 patients with a diffuse lesion with length > or = 15.0 mm who were treated with 2 overlapping Wiktor stents; and Group S, 30 patients with a discrete lesion who were treated with a single Wiktor stent. Two patients with a discrete lesion were not included in Group S because of failure of stenting. Stenting was successful in all patients in Group D. One patient in Group S developed subacute thrombosis after stenting. Follow-up angiography was performed after 6 months. Before treatment, the lesion lengths in Groups D and S were 24.2 +/- 10.0 and 9.2 +/- 4.4 mm, the reference diameters were 2.56 +/- 0.32 and 2.69 +/- 0.33 mm, and the minimal lumen diameters were 0.42 +/- 0.34 and 0.53 +/- 0.40 mm, respectively, with no significant difference in the latter 2 parameters. Restenosis occurred in 72% and 30% (p = 0.01) and revascularization of the target lesion was successful in 67% and in 30% (p = 0.03), in Groups D and S, respectively, both significantly higher in Group D. Follow-up study revealed that the minimal lumen diameter and the net gain were significantly greater in the overlapping portion of the 2 stents than in the proximal and distal portions in Group D, with no significant difference in restenosis rate between these 3 portions. Multiple overlapping stenting using Wiktor stents is useful for diffuse lesions with unfavorable results after POBA even if the affected vessel is smaller than 3.0 mm. However, patients should be carefully observed because restenosis occurs frequently.

Aged↗

Expression of cytokine receptors on follicular dendritic cells.

Follicular dendritic cells (FDCs) in the lymphoid follicle (LF) are essential to the sequential processes of B-cell proliferation, selection, and differentiation. Although the importance of some cytokines in these processes has been pointed out, there is little information about the follicular localization of their receptors. We investigated, with special reference to FDCs, the localization of cytokine receptors as well as cytokines themselves in human tonsils by several means, including immunochemistry, immunoelectron microscopy, reverse transcriptase polymerase chain reaction, and in situ hybridization. FDCs in the follicular apical light zone expressed transforming growth factor-beta receptor II (TGF-betaR II), granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSFRalpha; CDw116), tumor necrosis factor receptor I (TNFR I; CD120a), interleukin-1 receptor II (IL-1R II; CDw121b), IL-2 receptor beta (IL-2Rbeta; CD122), IL-4 receptor (IL-4R; CDw124), and IL-6 receptor (IL-6R; CD126), among the 10 receptors examined. Those in the basal light zone expressed strongly TNFR I and weakly GM-CSFR alpha, IL-1R II, IL-2Rbeta, IL-4R, and IL-6R, and often those in the outer and mantle zones expressed GM-CSFR alpha, IL-4R, and IL-6R. FDCs in the apical light zone expressed only TGF-beta among the 7 cytokines examined. On the other hand, follicular lymphocytes mainly in the light zone expressed 9 kinds of receptors, with the exception being TGF-betaR II; expression was rather frequent for TNF-alpha, IL-1alpha, and IL-2 and less frequent for TGF-beta, GM-CSF, IL-4, and IL-6. These data indicate that only FDCs mainly in the light zone express many cytokine receptors, although FDCs may produce the cytokine, TGF-beta. Cytokines may act not only on some follicular lymphocytes but also on most FDCs in the light zone expressing cytokine receptors.

Animals↗

A Free Cyclotrigermenium Cation with a 2pi-Electron System

The reaction of tetrakis(tri-tert-butylsilyl)cyclotrigermene with trityl tetraphenylborate in benzene produces tris(tri-tert-butylsilyl)cyclotrigermenium tetraphenylborate [(tert-Bu3SiGe)3+BPh4-], which can be isolated as a yellow solid that is stable in the absence of air. The crystal structure of the cyclotrigermenium ion reveals a free germyl cation with a 2pi-electron system. The three germanium atoms form an equilateral triangle similar to the carbon analog, the cyclopropenium ion.

Journal Article↗

Anti-endothelial cell antibodies to the endothelial hybridoma cell line (EAhy926) in systemic lupus erythematosus patients with antiphospholipid antibodies.

The endothelial hybridoma (EAhy926) cell line was employed to clarify whether antiphospholipid antibodies (aPA) [lupus anticoagulant (LA), antiprothrombin antibody (aPT) and/or anticardiolipin antibody (aCL)] and anti-endothelial cell antibodies (AECA) are identical, and establish whether beta2-glycoprotein I (beta2-GPI) is needed for reactivity of aPA to endothelial cells. Ig-G AECA was positive in 9/30 SLE patients with aPA (30.0%) and 10/22 SLE patients negative for aPA (45.5%). Ig-M AECA was positive in one SLE patient with aPA and one SLE patient without aPA. AECA-positivity was not significantly different among unfixed, TNF-stimulated and fixed EAhy926. The influence of beta2-GPI on the reactivity of serum to EAhy926 was minimal, and absorption experiments of serum with cardiolipin-liposome/beta2-GPI or phosphatidylserine-liposome/prothrombin gave little evidence of cross-reactivity of aPA and AECA. The results of our study suggest that aPA and AECA may have partially cross-reacted, but were different antibodies. However, further study is needed to clarify the clinico-pathological significance of AECA.

Antibodies↗

The method for keeping low perfusion flow weaning from centrifugal pumps: an evaluation of hemolysis in the circulator units.

Currently, the clinical application of extracorporeal and assisted circulation using centrifugal pumps is becoming popular. However, a problem in the use of centrifugal pumps is the difficulty in controlling the flow rate when it is a low range. Although we have been controlling the flow rate with a control unit that simply squeezes the blood outlet tube from the outside, hemolysis resulting from turbulent flow in the tube was discovered. Therefore, this control procedure was evaluated experimentally. Two groups were tested as follows: in Group A (n = 10), the tube was squeezed from the outside using the control unit, and in Group B (n = 10), no control unit was used. Blood in each circuit was circulated at 1,500 rpm, and the flow rate was controlled to 250 ml/min using the control unit for Group A. Time-course changes of lactate dehydrogenase (LDH) and free hemoglobin in the blood were measured during 8 h of circulation. There were no significant differences between the 2 groups in the mean values of LDH and free hemoglobin. Therefore, the present low flow rate control provided by the control unit makes it appear to be a simple and useful apparatus for controlling blood circulation using centrifugal pumps.

Analysis of Variance↗

A novel motility effect of tachykinins in normal and inflamed colon.

The role of tachykinins in stimulating phasic and giant migrating contractions (GMCs) in the normal and inflamed colon in conscious dogs was investigated by close-intra-arterial infusions of test substances. At low doses (0.1 nmol), substance P and neurokinin (NK1) receptor agonist ([Sar9,Met(O2)11]substance P] stimulated phasic contractions only. At higher doses (2.0 nmol), they stimulated phasic contractions and GMCs. The phasic contractions were blocked partially but significantly by prior close-intra-arterial infusions of tetrodotoxin and atropine but not by hexamethonium. NK1 receptor antagonist partially but significantly inhibited the phasic contractile response to substance P, whereas NK2 and NK3 receptor antagonists had no significant effect. The contractile response to NK2 receptor agonist was less than one-half of the response to substance P; NK3 receptor agonist did not stimulate any contractile activity. The stimulation of GMCs by higher doses of substance P was not blocked by prior infusions of atropine, tetrodotoxin, or NK1, NK2, and NK3 receptor antagonists, nor was the contractile response to substance P blocked by H1 and H2 receptor antagonists. Inflammation depressed the phasic contractile response but enhanced the stimulation of GMCs by substance P. The ability of substance P to stimulate GMCs is novel and suggests its potential role in increasing the frequency of these contractions during colonic inflammation.

Animals↗

Effects of excitative and sedative music on subjective and physiological relaxation.

Previous investigations using heart rate as a measure have not clarified the excitative-sedative effects of music. One of the sources of this failure was considered to be use of the index of heart rate. The present purpose was to examine the excitative-sedative effect of music on indices of the sympathetic and the parasympathetic nervous activities through spectral analysis of heart rate. The presented stimuli were three excitative musical pieces and three sedative ones. Subjective feelings about music were measured by an adjective checklist concerning musical activity. Heart-rate variabilities divided into two components of Low Frequency, mainly affected by the sympathetic nervous system and of High Frequency, mainly affected by the parasympathetic nervous system. Six types of heart-rate indices were employed: (1) mean increments from posttrial base, (2) coefficient of variances of heart rate, (3) mean powers of Low Frequency, (4) coefficient of component variances of Low Frequency, (5) mean powers of High Frequency, and (6) coefficient of component variances of High Frequency. From the factor analysis based on responses to an adjective checklist, there was a single major activity factor. Activity scores showed some were high during excitative pieces and others low during sedative ones. For heart rate, excitative-sedative effects of music were observed only in indices related to High Frequency. This result suggests that musical effect was observed in measures of the parasympathetic nervous system but not in the sympathetic nervous system.

Acoustic Stimulation↗

A facilitator in self-reported perception of physical symptoms: the role of contingency between physical symptom and aversive event.

Perceptions of physical symptoms are influenced not only by the passive process of physiological stimuli but also by psychological factors such as the contingency between a physical symptom and an aversive event which we examined here in two experiments. 18 subjects in Exp. 1 and 14 subjects in Exp. 2 performed motor tasks. In the Physical condition, an aversive event was contingent on the physical symptom of 'racing heart' in Exp. 1, and on the symptom of 'overstraining shoulder muscles' in Exp. 2. In the Motor condition, an aversive event was contingent on the response of the 'disordered pace of motor tasks' in both experiments. Self-reported scores on attention to and perception of the physical symptoms under the Physical condition were higher than those under the Motor condition. However, there were no differences in the actual physical responses between the two conditions. These results suggest that a contingency between a physical symptom and an aversive event facilitates attention to and perception of the physical symptom.

Adolescent↗

BE-32030 A, B, C, D and E, new antitumor substances produced by Nocardia sp. A32030.

New antitumor substances, designated BE-32030A, B, C, D and E, were isolated from the culture broth of Nocardia sp. A32030. The active principles were extracted from the mycelium by methanol and purified by Sephadex LH-20 and reversed-phase column chromatographies and finally by reversed-phase HPLC. BE-32030A, B, C, D and E inhibited the growth of P388 murine leukemia, DLD-1 human colon cancer, PC-13 human lung cancer and MKN-45 human stomach cancer cell lines.

Animals↗

Effective prevention of thrombocytopenia using adenovirus-mediated transfer of HST-11FGF-4 gene: in vivo and in vitro studies.

A novel biological function of HST-1 protein (FGF-4) was investigated by constructing an adenovirus vector containing the HST-1 cDNA and applied for thrombocytopenia as a gene therapy. A single intraperitoneal injection of the replication-deficient adenovirus containing the HST-1 gene (Adex1HST-1) into mice caused a two-fold increase in peripheral platelet count for 30 days, and effectively prevented experimentally induced thrombocytopenia. Studies of Adex1HST-1-infected or HST-1 protein-treated megakaryocytic Dami cells suggested that HST-1 protein promotes megakaryocyte maturation, and increases cytokine secretion from megakaryocyte and adhesive interactions between megakaryocyte and endothelial cells. Colony assay revealed that HST-1 protein stimulated CFU-MK (colony-forming unit of megakaryocyte) not alone but synergistically with early-acting cytokines such as IL-3 or Tpo (c-mpl ligand) as a megakaryocyte potentiating factor. These results have important implications for clinical application of the Adex1HST-1 for thrombocytopenia.

Adenoviridae↗

[Evaluation of 123I-MIBG clearance from the myocardium; comparison of two methods--SPECT & planar methods].

In 123I-metaiodobenzylguanidine (MIBG) scintigram, MIBG clearance from the heart is used to evaluate the severity of various heart diseases. There are two methods for calculating MIBG clearance. One involves planar images (planar method) and the other uses a bull's eye map (SPECT method). In 158 patients and 10 normal subjects, we compared these two methods. Fifteen minutes and 4 hours after intravenous injection of 111 MBq MIBG, planar images and SPECT images were obtained. Then clearance from the heart was calculated by each method. Abnormal increase was defined as present if clearance was more than the mean + standard deviation of 10 normal subjects. Then, we examined the sensitivity with which each method could detect clearance abnormality in 158 patients. Thirty-two patients showed abnormality only on SPECT images, while planar images alone showed abnormalities in only 5 patients. The reason the SPECT method was more sensitive than the planar method may be as follows; in the case of decreased MIBG clearance from the lung, for example, in congestive heart failure, clearance by planar method is apparently decreased. Thus, the SPECT method can detect clearance abnormality more sensitively than the planar method, and if we evaluate MIBG clearance from the heart by the planar method, we must take into account MIBG clearance from the lung.

3-Iodobenzylguanidine↗

[Redo operation for recurrent pulmonary artery aneurysm associated with pulmonary stenosis and regurgitation].

A 63-year-old woman who underwent surgical correction of a recurrent pulmonary artery aneurysm associated with pulmonary stenosis and regurgitation is reported. On April 1986, she underwent commissurotomy of pulmonary valve, reconstruction of right ventricle out flow tract using a Polystan monocusp patch and pulmonary aneurysmorrhaphy for pulmonary artery aneurysm. Pathological examination of the resected pulmonary arterial wall revealed mucoid degeneration of media and fragmentation of elastic fiber. Nine years after the operation, recurrence of pulmonary artery aneurysm, pulmonary stenosis and regurgitation were recognized. On September 1995, she underwent redo operation with graft replacement of pulmonary artery and pulmonary valve replacement using woven Dacron prosthesis containing a Carpentier-Edwards bioprosthetic valve. We should choose as an initial procedure with graft replacement for pulmonary artery aneurysm with fragility of the pulmonary arterial wall. She is now doing very well at one year and 5 months after the redo operation.

Aneurysm↗