[In vitro studies on the kinetic property of cardiac contractile proteins].
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Biomedical subjects
Publications and source records attributed to T Sugimoto.
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Parathyroid hormone-related peptide (PTHrP) has substantial homology with both human and rat parathyroid hormone (66% and 73%, respectively) in the first 15 amino acids. PTHrP (1-34) stimulates cyclic adenosine monophosphate (cAMP) release in bone and kidney, and these effects are felt to occur through interaction with the parathyroid hormone (PTH) receptor. Differences in the biologic potency between rat PTH(1-34) and human PTH(1-34)--and between PTHrP and PTH--have been described in a variety of experimental systems. In this study, we compared the bioactivity of these three amino-terminal synthetic fragments on the stimulation of cAMP formation in an isolated perfused rat femur preparation. Dose-response experiments demonstrated that PTHrP(1-34) was more potent in stimulating cAMP release than human PTH(1-34), whereas PTHrP(1-34) and rat PTH(1-34) were equipotent. Despite the fact that the extraction of immunoreactive rat PTH(1-34) and human PTH(1-34) was the same, rat PTH(1-34) was more potent in stimulating adenylate cyclase activity than human PTH(1-34). These data show that the isolated perfused rat femur preparation is an effective method for evaluation of the effects of PTH and PTHrP. Despite significant structural differences in the binding domain between rat PTH(1-34) and PTHrP(1-34), the effects of rat PTH(1-34) and PTHrP(1-34) are similar. Because the structure of rat PTHrP(1-34) and human PTHrP(1-34) are identical, and because it is desirable to utilize homologous systems to study the potency and effects of test peptides, it would appear that rat PTH(1-34) is the most appropriate peptide for comparison with PTHrP in rat-based experimental systems.
The effects of papaverine, a smooth muscle relaxant agent, on the voltage-dependent Ca++ current were examined in isolated smooth muscle cells from the guinea pig trachea. The tight-seal whole cell voltage clamp technique was used. Papaverine (1-100 microM) inhibited the Ba++ inward current (IBa) through the voltage-dependent L-type Ca++ channel in a concentration-dependent fashion. The inhibitory effect of papaverine on IBa appeared to have both tonic and use-dependent components. In addition to the reduction of the maximal conductance of IBa, papaverine (20 microM) shifted the quasi-steady-state inactivation curve of IBa to more negative membrane potentials by approximately 10 mV. These effects of papaverine on IBa were completely reversible. Although it has been suggested that papaverine inhibited phosphodiesterase to increase intracellular cyclic AMP, phosphodiesterase inhibitors (theophylline, 500 microM, and 3-isobutyl-1-methylxanthine, 500 microM), isoproterenol (2 microM) and dibutyryl cyclic AMP (1 mM) did not affect IBa. Thus, papaverine inhibits IBa in a way independent of intracellular cyclic AMP. Papaverine also had inhibitory effects on other membrane currents (i.e., the voltage-dependent transient outward K+ current and the Ca(++)-activated oscillatory K+ current), which may result in an enhancement of the excitability of the cells. These results suggest that inhibition of the voltage-dependent L-type Ca++ channel is involved in the papaverine-induced relaxation of the tracheal smooth muscle.
Neuroblastoma (NB), primitive neuroectodermal tumor (PNET), Ewing's sarcoma and rhabdomyosarcoma (RMS) are solid malignant tumors in childhood. Microscopically these tumors are grouped as small-round-cell tumors, and a different diagnosis is sometimes difficult. Cell surface membrane antigen, cytoskeletal protein and N-myc amplification and over-expression were analyzed in these cell lines and tumor tissues for the accurate diagnosis. NB and PNET could be distinguished from Ewing's sarcoma and RMS by the panel of monoclonal antibodies against cell surface membrane antigens. The cytoskeletal protein analysis is useful for the diagnosis of RMS and leiomyosarcoma. Alpha-smooth muscle actin and/or desmin were demonstrated in the S-type (epithelial-like) cells in 3 NB cell lines, suggesting the differentiation pathway of NB into smooth muscle cells. N-myc amplification and over-expression were observed in NB cell lines as well as one RMS cell line. The occurrence of N-myc amplification and over-expression in the RMS cell line cautions us against using N-myc as a distinguishable marker for NB.
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Effects of manidipine, a new calcium antagonist, and delapril, an angiotensin converting enzyme inhibitor, on glucose and lipid metabolism were investigated in mild to moderate hypertensive patients with non-insulin-dependent diabetes mellitus (NIDDM). The patients were treated with either manidipine 10 mg/day (n = 12, mean age 63 +/- 2 years) or delapril 30 mg/day (n = 8, 62 +/- 3 years) for 12 weeks. Glucose and insulin (IRI) responses to 75 g oral glucose load, glycosylated hemoglobin A1c (Hb A1c), serum levels of total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, triglyceride and apolipoproteins, and 24 h urinary excretion of C-peptide were measured before and at the end of treatment. Both manidipine and delapril showed adequate hypotensive effects. Neither manidipine nor delapril affected blood glucose and IRI responses to glucose load. Manidipine showed no effect on lipids whereas delapril increased HDL cholesterol (47 +/- 5 mg/dL to 61 +/- 7, p < 0.05), although total cholesterol and triglyceride were not altered. The ratio of TC-HDL cholesterol/HDL cholesterol was decreased by delapril (3.44 +/- 0.30 to 2.61 +/- 0.45, p < 0.05). There were no significant changes in apolipoproteins. Both manidipine and delapril have adequate antihypertensive actions without unfavorable effects on glucose and lipid metabolism in hypertensive patients with NIDDM. Delapril seems to have a beneficial effect on lipid metabolism.
To determine the relative superiority of a prosthesis in the mitral position, in vivo hemodynamics were examined by Doppler echocardiography, and the results were compared with other types of mechanical mitral valves including 63 Björk-Shiley convexo-concave (BS) values, 30 Duromedics (DM) valves, and 58 Medtronic Hall (MH) valves. For this comparison, the following indices were evaluated: peak velocity of mitral flow (PV), mitral valve orifice area (MVA), mitral valvular regurgitation, New York Heart Association (NYHA) classification, pulmonary capillary wedge pressure (PC), cardiac index (CI) and valve-related complications. On Doppler echocardiograms, PV ranged from 1.2 to 2.0 m/sec with a mean of 1.6 m/sec. There was no evident relationship between the PV and the valve size in each type of prosthesis, and no significant difference in the PVs among the valves. The mean MVA was 2.6 cm2 (25 mm DM, 25 mm MH), which was regarded satisfactory from a clinical standpoint. MVA increased with the increase in the valve size in all types of valves, and of all sizes, MVA was larger in the DM and MH groups than in the BS group. Similarly, the incidence of valvular regurgitation was relatively low in all groups, and the degree of regurgitation proved to be grade II or less in all cases. As for the clinical results, clinical symptoms (NYHA) and hemodynamic states (PC, CI) improved postoperatively, with the differences among the types of prosthetic valves being insignificant. The incidences of thromboembolism, valvular thrombosis, valve failure and prosthetic endocarditis were relatively low in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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An enzyme immunosorbent assay of neopterin and biopterin on a polystyrene microtiter plate has been developed. A conjugate of neopterin or biopterin to bovine serum albumin was used to raise a specific antiserum against neopterin or biopterin in rabbits. An incubation mixture of the antiserum and samples prepared from human serum underwent another antigen-antibody reaction with the hapten fixed on the microtiter plate. The amount of antibody bound to the fixed hapten, which is inverse to the amount of hapten in the sample, was determined by using anti-rabbit IgG-horseradish peroxidase conjugate in a usual manner by measuring absorbance at 490 nm after reaction with o-phenylenediamine and hydrogen peroxide. The minimal detectable amounts of neopterin and biopterin were approximately 0.1 pmol. The specificity of the assay was so high that the assay system for neopterin completely distinguished it from biopterin, as judged from the cross-reaction of 0.002%, and vice versa. The amounts of neopterin and biopterin in human serum determined by the present method agreed well with those determined by high-performance liquid chromatography. We used the present method to determine the concentrations of neopterin in serum from healthy control subjects and patients with cancers and systemic lupus erythematosus; the results were consistent with literature data.
Diltiazem (DTZ), a calcium slow channel blocker, is estimated to be highly effective for myocardial protection and the prevention of perioperative coronary spasms (PCS). However, the use of high doses of DTZ sometimes results in difficulty in coming off cardiopulmonary bypass due to negative chronotropic activity. Nicorandil (NCD) has remarkable coronary vasodilating effect but possesses little negative chronotropic activity. The purpose of this study was to compare NCD with DTZ with respect to effect on myocardial protection during coronary artery bypass grafting (CABG). As parameters, excess lactate (delta XL), redox potential (delta Eh), left and right ventricular stroke work indices (LVSWI, RVSWI), cardiac index (C.I.), systemic vascular resistance index (SVRI.), myocardial isoenzymes (CK-MB, LDH1), number of PCS and recovery time of chronotropic action were used. delta XL, delta Eh, LVSWI, RVSWI, C.I., SVRI, CK-MB, LDH1 were measured at 0, 1, 3, 6, 9, 18 and 24 hours after the removal of aortic cross clamping. The degree of chronotropic action was evaluated by the length of the recovery time to self beat or normal sinus rhythm after the removal of aortic cross clamping. Forty patients who underwent CABG with retrograde cold blood cardioplegia between Dec. 1989 and May 1991 were divided into the NCD group (n = 20), in which 1.1 micrograms/kg/min NCD was continuously administered from the beginning of the operation and the DTZ group (n = 20), in which the initial St. Thomas cardioplegia containing 5 mg/L and subsequent cold blood cardioplegia solution contained DTZ 3.5 mg/L, for a total DTZ dose of less than 10 mg.(ABSTRACT TRUNCATED AT 250 WORDS)
We experienced a case of 62-year-old man with ischemic cardiomyopathy and mitral regurgitation. He had a heart failure of New York Heart Association class IV together with unstable angina. His further examination showed an enlarged left ventricle with markedly reduced ejection fraction (12.9%) and ischemic mitral regurgitation of grade III associated with 3-vessel disease. He underwent three coronary artery bypass graftings and mitral annuloplasty by a modification of Kay's method. He showed a remarkable improvement of heart failure and cardiac function together with a disappearance of mitral regurgitation. He discharged from hospital in NYHA class II on the 50th postoperative day and lives an almost normal life now. Operative indication and management of ischemic cardiomyopathy and mitral regurgitation were discussed.
By reviewing the outcome, we studied the propriety of our principles for the treatment of type A acute aortic dissection in 45 patients, encountered during the 10-year period between 1981 and 1990. We conducted a comparative study of patients with a thrombosed false lumen (type T) and a patent false lumen (type P) to examine the effect of an acutely thrombosed false lumen on the prognosis of this disease. For the 25 patients treated in the first 6 years (1981-1986), operation was performed as soon as exact diagnosis was made, regardless of the presence of complications and the type or severity of the disease. Early death occurred in 9/20 operated cases and in 4/5 unoperated cases, so 13/25 patients died for a 52.0% mortality rate. For the 20 patients who received treatment in the latter period (1987-1990), we gave priority to conservative treatment for type T cases that were free from complications, and adopted a treatment method attaching greater importance to the resection of intimal tears. As a results, early deaths were observed in only 4 type P patients (20.0%) who underwent operation, a significant better result (p < 0.05). For patients in whom we were able to excise the intimal tear (30.0%, early mortality rate), the results were better than in those in whom the intimal tear were left alone (53.8%). The results were particularly good in type T patients (25.0% of them underwent intimal tear resection and 71.4% underwent no operation for the intimal tear).(ABSTRACT TRUNCATED AT 250 WORDS)
We evaluated the effectiveness and side effects of terodiline hydrochloride in 109 patients with urinary frequency and urinary incontinence. The drug was administered at a dose of 24 mg once a day or 12 mg twice a day for 4 weeks. Symptoms such as urinary frequency and urinary incontinence were alleviated in 101 out of 109 patients (92.7%). Mild side effects such as thirst, dysuria, sense of residual urine, orthostatic hypotension and arrhythmia were observed in 9 out of 109 patients (8.2%). Side effects such as orthostatic hypotension and arrhythmia were observed on the 28th day or the 20th day of the administration, but these symptoms disappeared with discontinued use of this medicine. The results obtained from this study suggest that terodiline hydrochloride may be greatly useful for the patients with urinary frequency and urinary incontinence. But we must take account of the side effects such as orthostatic hypotension and arrhythmia.
Twenty patients with primary cardiac tumors were operated on during the past ten years. The age of 15 female and 5 male patients ranged from 17 to 73 years. Eighteen patients had myxomas, 16 of which located in the left atrium and 2 in the right atrium. Systemic embolism occurred in 8 patients, subsequently caused cerebral infarction in 4, ischemia of extremities in 2, myocardial infarction in 1 and pulmonary infarction in 1. Emergency operation was performed in 5 patients because of severe congestive heart failure. In all cases, removal of myxoma was performed together with the excision of the wall to which the pedicle attached with the use of cardiopulmonary bypass. One patient with pulmonary infarction underwent resection of the infarcted lung simultaneously. Only one patient with severe heart failure died of pulmonary insufficiency one month after the operation. Another patient with cerebral infarction underwent clipping of cerebral aneurysm which appeared later in the infarcted area. The 17 patients including the latter patient showed a good recovery and no local recurrence during the follow-up period of 1 to 120 months. Two patients had malignant tumors, which were malignant fibrous histiocytoma of the left atrium and leiomyosarcoma of the pulmonary artery, respectively. Both of these rare tumors were resected noncuratively and led to the death because of their local recurrence with distant metastasis, though they received adjuvant chemotherapy. The symptoms, complications, diagnoses, surgical treatment and outcome of the primary cardiac tumors are reviewed in this study.
The efficacy and problem of coronary artery bypass grafting (CABG) in patients with severely impaired left ventricular function (left ventricular ejection fraction < or = 30%) were assessed in 27 patients of whom 17 (group 1) underwent emergent CABG and 10 (group 2) elective between Jan 1984 to Aug 1990. As a whole, history of myocardial infarction (24/27, 88.9%), large left ventricular volume with reduced ejection fraction (LVEDVI 126.08 +/- 25.91 ml/m2, LVESVI 93.04 +/- 21.02 ml/m2, LVEF 25.04 +/- 4.75%) and multiple vessel disease with at least one vessel total occlusion (20/27, 74.1%) were characteristically seen in these patients. The patients of group 1 were significantly older (mean 66.12 +/- 5.68 vs 57.10 +/- 8.08, p < 0.01) and needed more frequent preoperative support with IABP (17/17 vs 4/10, p < 0.01). Using Thallium-201 scintigraphy, in 10 patients of group 1 and 9 of group 2, myocardial viability in the proposed bypass area was evaluated before operations. Average 2.37 +/- 0.79 grafts were placed and continuous retrograde cold blood cardioplegia via the coronary sinus was employed for myocardial protection. Two mitral annuloplasty (MAP) for ischemic mitral regurgitation and 2 cryoablation for the treatment of ventricular tachycardia were performed concomitantly. Operative mortality was 47.1% in group 1 and none in group 2 (p < 0.05). Two cases of MAP died, but two cases of cryoablation survived. Postoperative LVEF was improved significantly only in group 2 (p < 0.05), but during the follow-up period of 7 months to 6 years, all 19 survivors expect one remains with NYHA class I or II.(ABSTRACT TRUNCATED AT 250 WORDS)