Heterosis in survival of transferred mouse embryos.
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Biomedical subjects
Publications and source records attributed to K Iida.
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The comparative sensitivities of exercise (supine ergometer), isoproterenol (ISP) infusion and cold pressor test (CPT) for detecting myocardial ischemia in patients with effort angina (45 cases) and vasospastic angina (16 cases) were investigated. Twenty-three patients with atypical chest pain served as normal controls. Left ventricular function was evaluated by computerized quantitative analysis using the following three graphic methods: 1) radionuclide angiography during exercise (EX-RI) and ISP infusion (ISP-RI), 2) two-dimensional echocardiography during ISP infusion (ISP-2DE) and CPT (CP-2DE) and 3) digital subtraction angiography during CPT (CP-DSA). The incidence of regional wall motion abnormalities (WMA) induced by these three stress tests in patients with effort angina were as follows: 83% in EX-RI, 80% in ISP-2DE, 80% in ISP-RI, 75% in CP-2DE and 86% in CP-DSA. In patients with vasospatic angina, the WMA were as follows: 40% in EX-RI, 0% in ISP-RI and 71% in CP-DSA. In patients with atypical chest pain, the WMA were 0% in EX-RI, 0% in ISP-RI, 8% in ISP-2DE, 13% in CP-2DE and 13% in CP-DSA. The left ventricular ejection fraction (EF) was unchanged during ISP (from 65 +/- 11% to 68 +/- 12%) and it decreased both during exercise (from 64 +/- 10% to 58 +/- 9%, p less than 0.05) and during CPT (from 69 +/- 10% to 65 +/- 9%, p less than 0.05) in patients with effort angina. In patients with vasospastic angina, the EF was unchanged both during exercise (from 70 +/- 7% to 68 +/- 13%) and during the CPT (from 76 +/- 5% to 75 +/- 4%), while it increased during ISP infusion (from 63 +/- 8% to 79 +/- 7%, p less than 0.01). In patients with atypical chest pain, the EF was increased both during exercise (from 72 +/- 7% to 79 +/- 5%, p less than 0.01) and during ISP infusion (from 67 +/- 5% to 78 +/- 7%, p less than 0.01), while it was unchanged during CPT (from 77 +/- 7% to 76 +/- 8%). In exercise and in ISP infusion tests, WMA were provoked concomitantly with ST segment deviations in nearly all patients. However, during CPT, WMA were produced without the occurrence of ST segment deviations. Myocardial ischemia due to organic coronary artery stenosis was difficult to distinguish from coronary artery spasm by exercise test. However, the susceptibility to ISP infusion and CPT differed in producing WMA in patients with vasospastic angina.(ABSTRACT TRUNCATED AT 400 WORDS)
To investigate the variability and the mechanism of negative T waves in hypertrophic cardiomyopathy (HCM), especially giant negative T waves in apical hypertrophy, from view point of adrenergic function, ECG was studied by treadmill exercise test and under administrations of beta-adrenergic agonist (isoproterenol) and antagonist (propranolol) in 33 patients with HCM and negative T waves. Apical hypertrophy was seen in 16 cases, and giant negative T waves were seen in 24 cases. By treadmill exercise test, negative T waves became less deep in all cases of HCM (-1.2 +/- 0.5 mV-----0.6 +/- 0.5 mV, p less than 0.001). The higher exercise level the patients attained, the less deep the negative T waves became. Isoproterenol caused the same reversal of negative T waves as the exercise test, but heart rate and rate pressure product attained by isoproterenol were significantly smaller than those by exercise. R wave amplitude did not change with isoproterenol. Propranolol made negative T waves deeper at rest and inhibited the reversal of negative T waves caused by exercise. In conclusion, negative T wave in HCM, especially giant negative T wave in apical hypertrophy, is variable. Beta-adrenergic function may be at least one of its mechanisms.
To evaluate the prognostic value of the left ventricular response to isoproterenol infusion in patients with dilated cardiomyopathy (DCM), 25 patients, 17 men and eight women, were studied. According to responses of left ventricular function to isoproterenol (0.02 microgram/kg/min), the patients were classified in two groups: the normal response group, in which fractional shortening increased by more than 10% (n = 10); and the low response group, in which fractional shortening increased by 10% or less (n = 15). A follow-up spanning four to 40 months with an average of 21 months disclosed that six patients died, two deteriorated, and six had no change in the low response group, while seven patients were improved, three stabilized, and no one deteriorated or died in the normal response group. There was a difference in the clinical courses of the two groups. Thus, the left ventricular response to isoproterenol proved useful in predicting the course of DCM.
To evaluate the grade of tricuspid regurgitation (TR) associated with mitral valve disease and to ascertain the operative procedure for the involved tricuspid valve, epicardial pulsed Doppler echocardiography (PDE) was performed during cardiac surgery. Thirty-two patients with mitral valve disease were studied, 17 of whom had only mitral valve lesion; the remaining 15 had combined mitral and aortic valve disease. The patients' ages ranged from 24 to 63 years and averaged 48.3 years. There were nine men and 23 women. Echocardiographic examinations were performed using a Toshiba SSH-60A for parasternal study and a SSH-11A combined with a SDS-10A with a specially-devised flat transducer for intraoperative use. Intraoperatively, the PDE performed was from the right side of the right atrium (RA), referenced by a four-chamber view and a long-axis view of the right ventricular inflow. The sampling volumes were positioned in the inflow of the right ventricle, immediately above the tricuspid valve, the middle and upper areas of the RA, and adjacent to the interatrial septum. PDE was performed before and immediately after the operative procedure and before chest closure. By severity, TR was classified as non -, mild +/-, moderate +, and severe ++, according to the distances attained by the TR signals from the tricuspid valve orifice, and the velocities and durations of the TR signals during systole. The TR signal was recorded in 23 of 32 patients before surgery, whereas it was determined more adequately in 28 patients by intraoperative epicardial PDE. The gradings of TR via the parasternal approach before surgery were as follows: no TR, in nine cases; mild TR, in three; moderate, in 13; and severe, in seven. Intraoperatively, four patients had none; eight had mild TR; 14, moderate TR; six, severe TR before surgical intervention, respectively. In cases with mild or no TR before surgery, TR was rarely detected by contrast echocardiography using saline solution injected into the right ventricle during surgery. The moderate or severe cases before surgery had moderate or severe TR according to the contrast method during surgery, except for one case not operated on for tricuspid valve disease. Tricuspid valve replacement was performed for two patients, and tricuspid annuloplasty or valvuloplasty for eight.(ABSTRACT TRUNCATED AT 400 WORDS)
Tumor volume measurement using tumor-margin clipping radiography was performed for estimating tumor regression of eight pancreatic adenocarcinomas treated with intraoperative electron irradiation. Half of the tumors regressed exponentially from the first day of treatment, but the other half increased slightly within the first week, after which volume reduction occurred. The volume-halving time was calculated from the regression curve. A wide distribution of volume-halving times as well as initial tumor volumes was seen in all patients. No correlation was found between these variables, but the former correlated well with survival time (r2 = 0.80). This well-known technique may offer a chance to foresee the prognosis of the disease by determining the volume-halving time.
To study the transfer of cefuzonam (CZON, L-105) into female genital organs, concentrations of the compound in pelvic dead space exudate were measured in cases of radical hysterectomy due to cervical cancer and analyzed by the two-compartment model. When CZON 1 g was drip-infused intravenously, the concentration in the cubital vein blood was 46.95 micrograms/ml at 1 hour after the start of infusion. Concentrations in the pelvic dead space exudate reached the peak of 11.29 micrograms/ml at 2.44 hours after the start, were higher than 4 micrograms/ml after 8 hours and were higher than 1.7 micrograms/ml after 12 hours. The area under the concentration-time curve in the pelvic dead space exudate was 77.85 micrograms X hr/ml. From these results CZON was considered to be effective when administered at 1 g against infections of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, and haemophilus influenzae, but increased dose levels seemed necessary against infections of Staphylococcus epidermidis and Bacteroides fragilis. In 3 cases of obstetric and gynecological infections the efficacy of CZON was good in 2 cases and unknown in the other case.
The response to isoproterenol was studied in 9 patients with hypertrophic cardiomyopathy (HCM) and asymmetric septal hypertrophy (ASH), 9 patients with HCM and symmetric hypertrophy (SH), and 9 normal controls (NC), using digitized M-mode echocardiography. There was no significant difference in fractional shortening (FS) between ASH and SH, nor between SH and NC before isoproterenol infusion. During isoproterenol infusion, however, FS was significantly greater in ASH (60 +/- 6%) than in SH (53 +/- 7%) and NC (49 +/- 5%) (p less than 0.05, p less than 0.01, respectively), and normalized peak rate of change of left ventricular dimension during systole (pVs) was greater in ASH (7.7 +/- 1.5/s) than in SH (5.2 +/- 0.8/s) and in NC (4.9 +/- 0.8/s) (p less than 0.001, p less than 0.001, respectively). This study shows that the response to isoproterenol of ASH differs from those of SH and of NC and suggests hypersensitivity of the beta-adrenergic receptor system in ASH and the possibility that ASH is a different clinical entity than SH.
In 21 patients with typical exercise-induced anginal pain but normal coronary arteriograms (group N) and in 14 patients with angiographically proved coronary stenosis (group C), symptom-limited ergometer exercise ECG and radionuclide angiocardiography were performed twice on two different days. Exercise-induced ST changes showed larger variations between the two exercise tests in group N than in group C ([delta ST1-delta ST2]: 0.07 +/- 0.06 mV in group N, 0.03 +/- 0.03 mV in group C, p less than 0.05). Rate pressure product and left ventricular ejection fraction at exercise also showed larger variations between the two tests in group N than in group C (p less than 0.001, p less than 0.05, respectively). However, substantial overlaps existed in some cases in the two groups. In conclusion, some of the patients with exercise-induced anginal pain but normal coronary arteriograms may have a variable threshold of exertional chest pain probably caused by variation in coronary vascular tone, and the other patients may have a fixed threshold of chest pain caused by other mechanisms.
Incubating conditions which induced actin paracrystal-like intracellular structures (actin rods) were investigated by using several cell lines. We have found that an incubation of cells of a mouse fibroblastic cell line, C3H-2K, in an isotonic solution of NaCl containing 1 mM MgCl2, 1 mM CaCl2 and 10 mM MES, pH 6.5, induced disintegration of stress fibers and formation of actin rods in the cytoplasm. Actin rods were induced also by incubating in salt buffers in which Na+ of the above solution was substituted by most cations except K+ or Rb+. When the actin rod-forming cells were transferred back to DMEM containing 10% FBS, actin rods disappeared and stress fibers subsequently re-formed within 1 h at 37 degrees C. Although the induction was observed in NaCl buffer at a wide range of pH values (5.5-10), the optimal pH was 6.5. Formation of actin rods is dependent upon cellular metabolism, as it was inhibited at 4 degrees C, or by metabolic inhibitors. Incubation in NaCl buffer induced actin rods in HeLa, L, NRK, BALB/c 3T3 and Swiss 3T3 cells, but not in CEF or MEF cells. A decrease in cell volume was observed parallel with the induction of actin rods, except for CEF and MEF cells. Alterations in intracellular concentrations of Na, K or Ca were not correlated with the induction, however. Actin rods were also induced in C3H-2K cells by a brief treatment with non-ionic detergents. Tween 80 at concentrations as low as 0.003% was effective for the induction, but did not increase the passive membrane transport of p-nitrophenylphosphate. In contrast to the induction by NaCl buffer, treatment with Tween 80 induced numerous tiny actin rods at 4 degrees C, which became larger when further incubated at 37 degrees C. Double immunofluorescence staining with anti-actin antibody and anti-vinculin antibody showed that vinculin plaques remained at least in an early stage of the actin rod formation. We discuss the mechanism for the induction of actin rods based upon the present findings.
Incubation of cultured cells of mouse C3H-2K fibroblastic cell line and other mammalian cell lines at 42.0-43.0 degrees C for 30 min or longer caused disintegration of normal actin structures including stress fibers, and induced formation of intranuclear actin paracrystal-like structures, called actin rods. When cells exposed to the elevated temperatures were shifted back to 37 degrees C, normal actin structures were regained. Pretreatment of cells at moderately high temperatures such as 38.5 degrees C inhibited formation of the actin rods upon subsequent exposure to 42.0 degrees C. Neither microtubules nor intermediate filaments were disrupted by the heat treatment. Several heat shock proteins were found to be synthesized under the conditions where actin rods were induced. However, there is no causal relationship between two cellular events, the induction of intranuclear actin rods and the synthesis of heat shock proteins.
The number of complement receptor for C3b (CR1) molecules in erythrocytes from patients with renal diseases was measured by an immunoradiometric assay using monoclonal antibodies against CR1. IgA nephritis patients with high serum creatinine value (Scr) showed markedly elevated levels of CR1, whereas patients with normal Scr had normal CR1 levels. A similar increase in CR1 number was observed in membranoproliferative glomerular nephritis with high Scr. CR1 of these patients functioned normally as a cofactor of C3b inactivator in cleaving immune complex-bound C3b. In contrast, a high frequency (5/6) of negative staining of glomerular CR1 was observed in IgA nephritis patients with high Scr by immunofluorescence study. We postulate that the disease-associated, acquired factors at least in part contribute to the abnormal expression of CR1: elevated levels in erythrocytes and defective expression on glomeruli.
Two high molecular weight heat shock proteins, HSP90 (Mr, 90,000) and HSP100 (Mr, 100,000), were separately purified from extracts of cultured cells of a mouse lymphoma cell line, L5178Y. Both of the HSPs exist in homodimeric form under physiological conditions. Their physicochemical properties are quite similar to each other. Each of the purified HSPs was shown to coprecipitate with rabbit skeletal muscle actin under actin-polymerizing conditions. Both HSP90 and HSP100 increased the low-shear viscosity of filamentous actin solutions in a dose-dependent manner, which suggests that these HSPs cross-link actin filaments. Although some molecular properties and the effects described above on actin solution of HSP90 and HSP100 resemble those of alpha-actinin, the HSPs were distinguished from alpha-actinin by various means, including visualization of molecular shapes by electron microscopy with the aid of the low-angle rotary shadowing technique. Immunofluorescence staining by specific antisera against HSP90 revealed that HSP90 was localized in ruffling membranes in addition to the cytoplasmic space.
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The duration of the acceleration phase of pulmonary systolic flow was measured by pulsed Doppler echocardiography in 39 normal subjects and 67 patients with heart disease to evaluate the reliability of this Doppler index as an estimate of pulmonary arterial pressure. The mean (SD) Doppler index in patients with abnormal mean pulmonary arterial pressure (greater than 15 mm Hg) was significantly shorter than that in normal subjects (110 (30) ms vs 150 (10) ms). The Doppler index was significantly related to the mean pulmonary arterial pressure (r = -0.75) the pulmonary blood flow (r = 0.46), and the total pulmonary vascular resistance (r = -0.68). Forty four of 45 patients with an abnormal index (less than or equal to 120 ms) showed abnormal mean pressure (greater than 15 mm Hg). Without exception patients with a low index (less than or equal to 90 ms) had distinct pulmonary hypertension (greater than or equal to 25 mm Hg). Twelve of 22 patients with a normal index (greater than or equal to 130 ms), however, also showed abnormal pressures. Nine of the 12 had an atrial septal defect and they had high pulmonary arterial pressure associated with high blood flow. Eighteen patients with valvar heart disease, whose mean pulmonary arterial pressure ranged from 16 mm Hg to 24 mm Hg, had a significantly shorter acceleration phase and a higher total vascular resistance than 11 patients with atrial septal defect in whom the pressure range was similar (120(20) ms vs 140 (20) ms, 3.8 (1.1) hybrid resistance unit vs 1.6 (0.5)). Thus although the acceleration time of the pulmonary systolic flow is useful for the evaluation of pulmonary hypertension, it is a complex index that is affected not only by pulmonary arterial pressure but also by pulmonary blood flow and pathological changes in the pulmonary vascular bed.
Since a dynamic exercise stress test cannot always be performed adequately in elderly patients, an alternative method is needed for evaluation of coronary reserve. We studied two-dimensional echocardiographic (2-DE) and electrocardiographic (ECG) responses to infusion of isoproterenol (ISP) at a rate of 0.02 micrograms/Kg/min in 40 elderly patients with chest pain. The results were compared with exercise ECG (EX-ECG) tests and exercise radionuclide angiocardiography (EX-RNA) in 13 of these patients. No serious complications were encountered in the ISP test. The diagnostic sensitivity for coronary artery disease (CAD) was 71% for ISP-2-DE, 71% for ISP-ECG, 86% for EX-ECG and 71% for EX-RNA. The specificity for CAD was 83% for ISP-2-DE, 33% for ISP-ECG, 50% for EX-ECG and 100% for EX-RNA. In conclusion, the ISP-2-DE test is a safe, easily available and useful method for the assessment of coronary artery disease in elderly patients.
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