Symposium on clinical aspects of sleep-disordered breathing and circulation. Diagnosis; guideline for diagnosis, and multimodal staging system.
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Clinical Protocols↗
Biomedical subjects
M Mishima
Publications and source records attributed to M Mishima.
[Characterization of tolerogen-producing cells and lymphoid tissues where self-tolerance is induced--a study on allogeneic bone marrow chimeras established with spontaneous leukemia prone mice].
SL/Kh strain of mice provides a spontaneous pre-B cell leukemia model and AKR/J mice provides a spontaneous thymoma model. Using these leukemia-prone mice, protective influence of bone marrow (BM) transplantation and tolerance induction to a host antigen, Mls-1a, after BM reconstitution were studied. When SL/Kh mice were reconstituted with BM cells from allogeneic C57BL/6 mice, these [B6-->SL] chimeric mice survived longer than non-treated SL or [SL-->SL] syngeneic chimeras. These findings are compatible to those obtained with [B6-->AKR] chimeras. In [D2-->SL] and [D2-->AKR] chimeras, V beta 6+ T cells reactive to Mls-1a had been clonally eliminated 5 weeks after BM reconstitution. On the other hand, minor graft versus host reaction (GVHR) abrogated the clonal elimination of V beta 6+ T cells in both [D2-->SL] and [D2-->AKR] chimeras. This abrogation appeared to be attributable to early disappearance of Mls-1a producing host T cells in the GVHR chimeras. The cells responsible for the Mls-1a production were revealed to be mainly CD8+CD44+ T cells by in vitro mixed lymphocyte reaction (MLR), although other T cell subsets also induced MLR under certain conditions. Administration of the CD8+CD44+ T cells from (AKR x BR)F1 mice induced clonal elimination of V beta 6+ T cells in the thymus and lymph nodes of [BR-->BR] syngeneic chimeras. By contrast, CD8+CD44- T cells induced partial reduction of V beta 6+ T cells only in lymph nodes. CD4+ T cells of Mls-1a type showed no tolerogenicity in this in vivo study, although these CD4+ T cells as well as CD8+ T cells evoked potentially MLR against Mls-1a. The present findings indicate that host CD8+CD44+ T cells are a major source of Mls-1a production in [Mls-1b-->Mls-1a] BM chimera system and suggest that CD44 expression on T cells is associated not only with high Mls-1a production but also with lymphoid tissues where the tolerogenic cells migrate.
Animals↗
[Delegation of authority based on review of decision making process. Reform of report system of the nursing department].
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Decision Making, Organizational↗
Purification of a low molecular weight microtubule binding protein from sea urchin eggs.
A low molecular weight microtubule binding protein(SU-MAP34) was purified from sea urchin eggs. This protein bound strongly to the microtubule formed from purified echinoderm tubulin but showed no cross-linking of microtubules. Monospecific antibody against SU-MAP34 was produced and an immunoblotting analysis showed that this protein was not a breakdown product of a protein of a higher molecular mass. Whole cell staining and confocal laser scanning microscope observation showed that SU-MAP34 localized on the filamentous structure of mitotic apparatus and this structure was identified as the microtubule with double staining using anti-SU-MAP34 and anti-tubulin. An immunoblotting experiment showed an enrichment of SU-MAP34 in a microtubule protein fraction prepared using taxol from a crude extract of the cell.
Animals↗
Pharmacokinetics and pharmacodynamics of intravenous OPC-18790 in humans: a novel nonglycosidic inotropic agent.
OPC-18790, a nonglycosidic intropic agent, is now under clinical development for treatment of congestive heart failure. Two separate studies (one placebo-controlled) were conducted to evaluate its pharmacokinetics and pharmacodynamics after intravenous administration to a total of 36 healthy male subjects. The drug was administered both rapidly as a .05-, .1-, .2-, or .4-mg/kg intravenous dose, and as a 1-hour infusion of .5, 1.0, 2.5, 5.0, 10.0, or 15.0 micrograms/kg/minute. Echocardiograms (ECHO) were evaluated before and immediately and 4 hours after the rapid administrations. Blood pressure (BP), heart rate (HR), and QTc in the electrocardiogram also were monitored in the rapid administration study. OPC-18790 was generally well tolerated by all subjects. Maximum peak plasma concentration and area under the curve increased linearly with dose in both studies. The t1/2, total body clearance of drug from plasma (CL), and the dose fraction excreted unchanged in the urine (fe) were comparable and dose-independent at the doses tested in both studies. The overall mean values of t1/2 alpha, t1/2 beta, CL, and fe were .08 +/- .01 hours, 3.64 +/- .22 hours, .46 +/- .01 L/kg, and 43.5 +/- 1.0%, respectively. Echocardiograms showed that, immediately after rapid administration of up to .4 mg/kg, OPC-18790 increased left cardiac function dose-proportionally (P < .05 to .01): the ejection fraction by 21.1% and fractional shortening by 26.5% compared with the predose values, blood pressure, heart rate, and QTc did not differ between subjects given OPC-18790 and these receiving placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Effect of successful angioplasty following thrombolysis on infarct size and left ventricular function.
The role of the angioplasty following thrombolysis in acute myocardial infarction has been discussed in several studies, however the effect of successful angioplasty on infarct size and left ventricular function has not been properly evaluated. Successful reperfusion was achieved in 79 out of 104 patients with primary anterior acute myocardial infarction. These patients were classified as follows, according to the type of intervention during the acute phase: 50 patients in which thrombolysis was successful (the thrombolysis group); 12 patients who underwent successful immediate angioplasty following successful thrombolysis (the immediate angioplasty group); and 17 patients in which rescue angioplasty was successful (the rescue angioplasty group). The 25 patients whose infarct-related vessels were not reperfused after intervention were classified as the non-reperfused group. Infarct size, evaluated as defect volume by T1-201 SPECT, 1 month after the onset, was 840 +/- 154 units (mean +/- S.D.) in the immediate angioplasty group and was similar to that in the thrombolysis group (948 +/- 88 units), but significantly smaller than in the non-reperfused group (1759 +/- 108 units). There were no significant differences in left ventricular function in the immediate angioplasty group and the thrombolysis group. Successful rescue angioplasty did not have any beneficial effect on left ventricular functions or infarct size, when compared with the failed thrombolytic group (1105 +/- 169 units vs. 1617 +/- 169 units). End-diastolic volume (52 +/- 3 ml/m2) in the successful rescue angioplasty group, however, was significantly smaller than in the failed thrombolysis group (67 +/- 3 ml/m2).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Functional studies on MEL-14+ and MEL-14- T cells in peripheral lymphoid tissues.
Functions of MEL-14+ T cells and MEL-14- T cells in peripheral lymphoid tissues were analyzed and compared. The MEL-14- T cells, representing a minor subpopulation of spleen and lymph node T cells, generated considerably higher mixed lymphocyte reaction and mitogen responses than the MEL-14+ T cells in any lymphoid tissues studied. Furthermore, upon stimulation with ConA the MEL-14- CD8+ T cells produced significantly larger amounts of IL-2 and IFN-gamma than MEL-14+ CD8+ T cells did. A similar but less marked observation was obtained with the CD4+ T cell population. Furthermore, when B10.BR mice were immunized with AKR (Mls-1a) spleen cells, the proportion of the Mls-1a reactive V beta 6+ T cells from draining lymph nodes increased and a substantial proportion of the increasing V beta 6+ T cells was shown to be MEL-14-. The present findings on the whole indicate that MEL-14- T cells in the peripheral lymphoid tissues are at functionally high levels and may represent memory cells which have been previously stimulated in vivo.
Animals↗
Assessment of acute pleural effusion in dogs by computed tomography.
We used computed tomography (CT) to examine the effects of infusing 60 ml/kg of saline into the pleural space of four anesthetized paralyzed dogs ventilated with a constant tidal volume at a positive end-expiratory pressure of 0.5 kPa. The dogs were positioned supine, and the thoracic cavity was scanned from apex to base before and immediately after effusate loading. Each CT image was analyzed semi-automatically on a 486 personal computer with custom-designed software. We found that, despite right-side infusion, the effusate was distributed bilaterally no doubt because of the incomplete canine mediastinum. In general, the volume change of the lung was one-third and that of the chest wall was two-thirds that of the total volume infused. Most of the lung volume was contained in the caudal one-third of the lung pre-effusion, and most of the lung volume loss due to effusion was from this same region. Chest wall volume increased and in a more uniform manner post-effusion. The decrease in lung volume resulted in an increase in the mean density of the lung and an increase in its vertical density gradient as the lung was lifted upward toward the sternum by the effusate. The lung lost vertical height while the chest wall increased both its vertical and lateral dimensions after effusate loading. These results suggest that expansion of the chest wall helps preserve lung volume in the presence of acute pleural effusion. We have also demonstrated that CT is a useful tool for assessing changes in volume, shape, and density of the respiratory system.
Animals↗
Acute pulmonary response to intravenous histamine using forced oscillations through alveolar capsules in dogs.
We measured the time course of alveolar input impedance using two alveolar capsule oscillators after intravenous bolus administration of 20 mg of histamine in open-chest dogs. Impedances (24-200 Hz) were obtained every 2 s after an injection for 100 s. Each impedance was fit with a model consisting of a pathway (with resistance and inertance) leading from the alveolar capsule into a subpleural region (with elastance EA) that, in turn, was connected to the lung compartment (consisting of the remainder of the lung and positive end expiratory pressure system) via another pathway (with resistance RA). In all cases (6 dogs, 2 capsules each), the resistance and inertance leading from the alveolar capsules were negligible. The correlation of the relative increases in RA obtained from the two capsule oscillators in each dog was not significant. The correlation for EA also was not significant. The times at which RA achieved values of 20% greater than baseline were not significantly correlated between the two capsules, as was the case for EA. However, the baseline values of EA and RA from a given capsule were significantly correlated, as were their fractional increases with histamine. These results show that both the magnitude and timing of changes in local lung resistance and elastance are spatially extremely heterogeneous.
Airway Resistance↗
[Effects of infarct-related artery patency on left ventricular function during exercise and remodeling].
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Adult↗
An automated method to assess the distribution of low attenuation areas on chest CT scans in chronic pulmonary emphysema patients.
We developed an automated method to recognize the lung in a computed tomographic (CT) image. With computer-assisted analysis, we were able to describe the continuous low attenuation (less than -960 Hounsfield units) areas (CLA) on chest CT scans. The size (CLAs) and number (CLAn) of the CLA and the percentage of total lung area occupied by low attenuation area (LAA%) were measured using CT scans obtained from 24 patients with chronic pulmonary emphysema (CPE) and 13 control patients. The automated algorithm recognized the lung areas successfully in all patients. The CLAs and LAA% were significantly higher, and CLAn was significantly lower in patients with CPE than in controls. There was a significant correlation between CT parameters and pulmonary function test results. The histograms of the size of CLA could be represented as a power function in each patient. This automated method should be useful in objectively defining the affected areas in the lungs of patients with CPE.
Aged↗
[Cell morphology and surface markers in three patients with granular lymphocyte proliferative disorders of the T-cell type].
We studied the relationship between cell morphology and surface markers in three patients with granular lymphocyte proliferative disorders. In the two patients with CD3+ CD4-CD8+ cells, there were no atypical cells, and the granules were uniformly fine: In the third patient, who had CD3+ CD4+ CD8- cells, atypical nuclei and the irregular granules in in size were observed. The granules were stained with beta-glucuronidase showing localized coarse features and made clumps, in the staining pattern characteristic of granular lymphocytes. The patient with CD4- CD8+ cells showed cytotoxic T cell phenotype, and the other DN cells type (usually associated with a CD3+ CD4- CD8- phenotype). We obtained conflicting data about OK-NK and Leu 11 antibodies, which recognized CD16 antigen.
Adult↗
N-isopropyl-p-iodoamphetamine receptors in normal and cancerous tissue of the human lung.
N-Isopropyl-p-iodoamphetamine (IMP) receptors in normal human lung tissue were characterized using a radioligand binding assay with iodine-125 IMP as the ligand. Saturation binding studies revealed the presence of two binding sites with dissociation constant (Kd) values of 53 +/- 2 and 4687 +/- 124 nM and maximum binding capacity (Bmax) values of 7 +/- 1 and 133 +/- 27 pmol/mg protein (n = 5) respectively. The IC50 values of various amines were as follows: IMP, 9 x 10(-5) M; propranolol, 5 x 10(-4) M; haloperidol, 6 x 10(-4) M; ketamine, 9 x 10(-3) M; dopamine, 1 x 10(-2) M. The IMP receptors of cancerous tissue obtained from human lung also had two binding sites with Kd values of 54 +/- 2 and 5277 +/- 652 nM and Bmax values of 7 +/- 1 and 103 +/- 21 pmol/mg protein (n = 3) respectively. There was no significant difference in binding parameters between normal and cancerous lung tissue. These results demonstrate the existence of IMP receptors and suggest that cancer does not affect the nature of IMP receptors in human lung tissue.
Adult↗
Evaluation of the penetration depth of transdermally applied 3% GA MHPh 2Na-10% lidocaine gel in man.
In order to estimate the penetration depth of transdermal 3% GA MHPh 2Na-10% lidocaine gel mixture, the following physiological functions of the skin were examined before and after a 60 min occulusive application of the gel in 16 adult volunteers. Thermal sweat expulsins ceased completely on the gel-treated ventral surface of one forearm in all the firs 5 subjects, though it continued on the untreated contrast area of the other forearm. Sympathetic skin response (SSR) was also no longer induced on the gel-treated middle finger in 1 of another 3 subjects and was severely depressed in the other 2 subjects, while the SSR on the untreated index finger appeared constantly. Vasomotion of the skin circulation on another 3 subjects, remained unaffected on both the gel-treated and the untreated fingers. Extraction of a leg-hair in the treated area did not induce pain sensation in all the last 5 subjects. In addition to the transcellular main roots, some of the transcutaneously applied gel seems to penetrate deeply into the skin through the appendageal roots such as the eccrine sweat glands and the pilosebaceous glands.
Journal Article↗
Supported angioplasty with synchronized retroperfusion in high-risk patients with left main trunk or near left main trunk obstruction.
To test the feasibility of synchronized retroperfusion (SRP) as a support device of percutaneous transluminal coronary angioplasty (PTCA) for high-risk patients, 10 patients with left main trunk or near left main trunk obstruction underwent PTCA with SRP. An 8.5F retroperfusion catheter was inserted from the antecubital vein into the coronary sinus. Arterial blood was supplied through the catheter into the myocardium with a retroperfusion pump during the diastolic phase by means of ECG triggering. In all patients, the narrowings were successfully dilated and an improvement of more than 20% in the luminal diameter stenosis was achieved; however, narrowing of more than 50% (58%) remained in one patient. In all patients, systemic hemodynamics was maintained for more than 30 seconds during balloon inflation. In seven patients, a 60-second balloon inflation was possible without any collapse of systemic hemodynamics. To test the protective effect of SRP on myocardial ischemia and impairment of systemic hemodynamics, balloon inflation without SRP was performed in eight patients after successful dilatation. The duration for balloon inflation with SRP (71 +/- 30 seconds; n = 8) was significantly longer than that without SRP (56 +/- 30 seconds; n = 8). The decrease in systolic aortic pressure, the increase in pulmonary diastolic pressure, and ST-T segment elevation in the precordial lead of ECG during balloon inflation with SRP were less than those during balloon inflation without SRP. After PTCA, angina was not provoked by exercise stress testing in any of the 10 patients. We concluded that SRP is a beneficial support device of PTCA for high-risk patients.
Aged↗
Myocardial hibernation in the infarcted region cannot be assessed from the presence of stress-induced ischemia: usefulness of delayed image of exercise thallium-201 scintigraphy.
To examine the relationship between the improvement of wall motion in infarcted regions after percutaneous transluminal coronary angioplasty (PTCA) and thallium-201 uptake in the delayed image of exercise thallium-201 scintigraphy before PTCA, 14 patients with anterior old myocardial infarction were studied. Exercise thallium-201 scintigraphy was performed before PTCA of left anterior descending artery, and mean percent thallium-201 uptake of abnormal segments was calculated in the initial and 4-hour delayed images. Left ventricular angiography was performed during catheterization, before, and 4 to 13 months after PTCA; and regional ejection fraction of anterior wall was calculated. Atrial pacing stress test with the measurement of lactate concentration of aorta and great cardiac vein was performed during catheterization before PTCA. In five patients with mean percent thallium-201 uptake in the delayed image < or = 50% (group I), regional ejection fraction did not increase after PTCA (23% +/- 9% to 24% +/- 12%). In the other nine patients with mean percent thallium-201 uptake > 50% (group II), regional ejection fraction increased significantly after PTCA (39% +/- 18% to 47% +/- 14%; p < 0.05). There was no significant difference in regional ejection fraction, lactate extraction ratio during maximal pacing, and the redistribution of exercise thallium-201 scintigraphy between the two groups before PTCA. Thus the delayed image before PTCA is useful to detect reversible nonfunctioning viable myocardium (hibernating myocardium) in the infarcted region. However, the wall-motion abnormality and the degree of stress-induced ischemia in the infarcted region before PTCA may not be necessarily useful for the detection of hibernating myocardium.
Aged↗
Attenuation of increased regional myocardial oxygen consumption during exercise as a major cause of warm-up phenomenon.
OBJECTIVES: The aim of this study was to test the hypothesis that the warm-up phenomenon is attributable to a reduction of increased myocardial oxygen consumption rather than to increased coronary blood flow during exercise. BACKGROUND: The underlying mechanism of the warm-up phenomenon is not elucidated. METHODS: Thirteen patients with effort angina were subjected to two consecutive supine ergometer exercise tests performed 15 min apart. All patients had severe proximal stenosis (> 90%) in the left anterior descending coronary artery. Great cardiac vein flow was measured before and during exercise. Both regional myocardial oxygen consumption and adenosine release were determined. RESULTS: Exercise was continued for significantly longer before angina onset in the second than in the first exercise test (507 +/- 44 vs. 410 +/- 42 s, p < 0.01). The extent of ST segment depression in lead V5 of the electrocardiogram (ECG) was larger at the time of angina onset in the first (1.7 +/- 0.2 mm) than in the second (1.1 +/- 0.2 mm, p < 0.01) exercise test. Neither systemic hemodynamic variables nor great cardiac vein flow differed between the first and second exercise tests. In contrast, regional myocardial oxygen consumption assessed at 3 min of exercise was significantly (p < 0.01) less in the second than in the first test (8.0 +/- 0.8 vs. 8.7 +/- 0.9 ml/min). Adenosine release during the second test was higher (p < 0.05) than in the first test (2.5 +/- 0.5 vs. 3.9 +/- 0.5 nmol/min at 3 min of the first and second tests, p < 0.01). CONCLUSIONS: These results indicate that the warm-up phenomenon is not attributable to increased coronary flow but to attenuation of increased regional myocardial oxygen consumption, which may be mediated by adenosine A1 receptor activation.
Adaptation, Physiological↗