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Biomedical subjects

D Inoue

Publications and source records attributed to D Inoue.

At least 109 records · Page 6Linked to original sources

Prolonged effects of recombinant human interleukin-1 alpha on mouse thyroid function.

Rapid and prolonged effects of recombinant human interleukin-1 alpha (IL-1 alpha) on mouse thyroid were studied. After daily administration of 15 micrograms or 1 microgram IL-1 for 7 consecutive days, serum T4 concentrations rapidly fell to undetectable levels but returned to near control level after the cessation of IL-1. On the 31st day, 3 weeks after the drug cessation, a significant depression of serum T4 was observed again. In addition, the IL-1-treated mouse thyroid showed an in vitro unresponsiveness to TSH, with an increase of pituitary TSH (2.24-fold by 15 micrograms IL-1). To understand underlying mechanisms further, serial observations were performed. Thyroidal T4 contents increased initially, decreased to a low level at day 14, and returned to approximately the control level. IL-1 administration induced an increase in the basal thyroidal cAMP level for a prolonged period. Its response to TSH showed a gradual decline to a level approximately 30% of the control by the 31st day. Pituitary TSH contents on the 22nd and 31st days showed significant elevations. Slight decreases in thyroidal TSH binding and T4 contents also were seen concomitantly. These studies indicate that an administration of a large dose of IL-1 results in a dramatic decrease in serum T4 primarily through the inhibition of T4 release from the thyroid. The results also indicate the induction of a prolonged hypothyroid state due to the unresponsiveness to TSH via a postreceptor mechanism.

Animals↗

Suppressing effects of caffeine on postextrasystolic potentiation in papillary muscles of guinea pigs.

It is well known that the strength of postextrasystolic potentiation (PESP) is dependent on the prematurity of the ectopic beat, though the fundamental mechanism of the potentiation is still obscure. In this study, the effect of a resting interval on the strength of PESP was investigated in isolated papillary muscles of guinea pigs in the presence or absence of caffeine, which inhibits the functions of sarcoplasmic reticulum (SR). PESP of a fixed coupling interval increased and then decreased as the resting interval was prolonged. The maximum of PESP was obtained at a resting interval of 3 to 4 sec. The dependency of PESP on a coupling interval was decreased considerably by 5 x 10(-4) M caffeine and removed completely by 10(-2) M caffeine. Although 5 x 10(-4) M caffeine decreased the degree of contraction of postextrasystole, the maximum contraction of postextrasystole was still obtained at a resting interval of 3 to 4 sec. After the application of 10(-2) M caffeine, the postextrasystolic contraction gradually declined as the resting interval was prolonged. We conclude that SR Ca release contributes largely to a mechanism of PESP and increases in contribution as the coupling interval of an extrastimulation shortens, and that the optimal resting interval is determined by a balance between the activity of SR function and the activity of the sarcolemmal Ca extrusion mechanism.

Animals↗

Similarity and dissimilarity between clinical and laboratory findings, especially anti-thyrotropin receptor antibody in ophthalmic Graves' disease without persistent hyperthyroidism and hyperthyroid Graves' disease.

The aim of this study was to investigate thyroid states, significance of anti-TSH receptor antibodies and the clinical courses of patients with euthyroid Graves' ophthalmopathy. The clinical and laboratory finding of 30 patients with euthyroid Graves' ophthalmopathy were briefly as follows: 1) normal sized thyroid or small goiter; 2) negative or weakly positive thyrotropin binding inhibitor immunoglobulin (TBII); 3) normal thyroid [99 m-Tc] pertechnetate uptake; and 4) frequent observations of low serum TSH values. Besides TBII, thyroid stimulating antibody (TSAb) was measured under low salt and isotonic conditions using FRTL-5 rat thyroid cells. Both TBII and TSAb titers were lower in euthyroid Graves' ophthalmopathy than in hyperthyroid Graves' disease. Serum TSH levels frequently became low in patients considered as euthyroid upon the first examination as well as in Graves' patients in remission, reflecting preceding or mild hyperthyroidism. In follow-up studies, these patients with mildly elevated thyroid hormone levels and low TSH levels seldom reached a state of persistent hyperthyroidism, when TBII was negative or only weakly positive.

Adult↗

The effects of an extra-stimulation on post-extra-systolic potentiation in papillary muscle of rats.

The mechanism of post-extrasystolic potentiation (PESP) is unclear. It has previously been suggested that changes in both the calcium release from the sarcoplasmic reticulum (SR) and the transsarcolemmal calcium influx are factors in the development of PESP in guinea-pigs. This experiment investigated the effects of a resting interval and a coupling interval on PESP in rat papillary muscles, which have a well-developed SR. An extra-stimulation was induced at various coupling intervals and a variety of post-extrasystolic intervals were set. The PESP was not dependent on the coupling interval. The post-extrasystolic interval at which the maximal % PESP was obtained was about 90 sec, and post-extrasystolic interval-% potentiation of the PESP relationship curve consisted of an ascending limb and a descending limb. Caffeine eliminated the PESP in a concentration-dependent manner. These findings suggest that SR calcium release plays an important role in the mechanism of PESP in rats. This is consistent with results from guinea-pigs, and implies that the calcium capacity and/or retention of the SR may characterize the post-extrasystolic interval-% PESP relationship in muscle from different species.

Action Potentials↗

[Electrophysiological effects of flecainide acetate on guinea-pig left atrial cells].

Using conventional glass microelectrode technique, electrophysiological effects of flecainide acetate on guinea-pig left atrial muscle fibers were examined. Resting membrane potential was not affected by flecainide at any concentrations tested (10(-7) M-3 X 10(-5) M), although overshoot potential was significantly decreased at the concentration over 3 X 10(-6) M. Effective refractory period significantly increased at 10(-5) M. The reduction of Vmax was about 25% and 50% by 3 X 10(-6) M and 10(-5) M, respectively at 1 Hz. At 3 X 10(-6) M, Vmax decreased by about 10%, 15%, 22%, 33%, and 34% at 0.2, 0.5, 1, 2, and 3 Hz respectively. Flecainide, decreased Vmax of atrial muscle fibers in a dose and frequency dependent manner. It is suggested that flecainide might be effective in the treatment of atrial tachyarrhythmias.

Action Potentials↗

[Diclonal gammopathy (IgG kappa, IgA lambda) with nephrotic syndrome terminating into IgA lambda myeloma after three years--report of a case].

A 43-year-old man was admitted to our hospital because of legs edema and periorbital edema in Dec. 1983. Laboratory findings showed massive proteinuria (3.7 g/day), Bence Jones protein (BJP) in urine, and hypoproteinemia. Peripheral blood examinations were normal and a bone marrow aspiration showed hypocellularity with slight increase of monocytes and plasma cells. Serum immunoelectrophoresis showed two M-components (IgG kappa, IgA lambda). Serum IgG was 1,690 mg/dl, IgA 379 mg/dl and IgM 160 mg/dl. No remarkable findings were obtained in bone survey, Ga-scintigraphy and rectal biopsy, and a diagnosis of diclonal gammopathy with nephrotic syndrome was made. In Aug. 1986, serum IgA started to increase rapidly with concomitant decrease IgG. He died of pneumonia due to pancytopenia in Dec. 1986, when serum IgG was 450 mg/dl, IgA 1,014 mg/dl, and IgM less than 39 mg/dl. Immunoelectrophoresis showed two M-components (IgG kappa, IgA lambda) in serum and BEP (kappa, lambda), IgG (kappa) and IgA (lambda) in urine. An autopsy showed massive infiltration of myeloma cells which were positive for lambda light chain in bone marrow, suggesting a development of myeloma from a diclonal gammopathy in about 3 years.

Adult↗

[Long-term follow-up of electrocardiographic changes in patients with asymmetric apical hypertrophy].

The serial electrocardiographic (ECG) changes of 20 patients with asymmetric apical hypertrophy (AAH) were retrospectively reviewed relative to their clinical symptoms, echocardiography and Doppler echocardiography, and thallium-201 perfusion scintigraphy. These patients were followed 4-18 years (mean 8 years). Patterns of the serial ECG changes were as follows: Seven patients (group Ia) had an increase of 10 mm or greater in the highest R wave amplitude in the precordial leads, with newly-developed giant T wave inversion. Five patients (group Ib) had relatively stable ECGs and the changes in the R wave amplitudes of less than 10 mm. Six patients (group IIa) had a decrease of 10 mm or greater in the highest R wave amplitude with mild decreases of negative T wave amplitudes. In the remaining two patients (group IIb) right bundle branch block developed. At the last follow-up study, group IIa had lower R wave amplitudes and longer QTc than did those in group I. The follow-up periods and their mean age did not differ among the groups. At the initial evaluation, exercise limitation was rare in group I; whereas, most of the patients in group II presented symptoms such as palpitation, chest pain or exertional dyspnea. These cardiac symptoms developed slowly but progressively during the follow-up period, and their incidence increased both in groups I and II at the final observation. Left ventricular (LV) wall thickness at the chordal level showed normal values and did not differ between the two groups, but apical wall thickness was greater in group II than in group I. Two-dimensional echocardiography showed a spade-like deformity of the LV in group II. In group I, the LV deformity was less marked and was not noted at the initial examination. Color Doppler echocardiography frequently revealed "paradoxical flow" expelled from the obliterated apex to the base in the early diastolic filling period in group II. Left ventriculography confirmed asynchronous contraction, hyperkinesis in the basal segment and dyskinesis at the apical segment, resulting in this abnormal intraventricular blood flow profiles. Serial studies by thallium-201 (TL) perfusion scintigraphy disclosed that four of the eight patients in group II developed localized hypoperfusion at the apex where a high and homogeneous uptake of TL was previously noted.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[Elucidation of reversibility in myocardial injury during hypoxia and reoxygenation in papillary muscles of rats].

We reported the calcium release of sarcoplasmic reticulum (SR) is the major source of activator calcium to postrest contraction (PRC), and that the transsarcolemmal calcium influx is (the major source of activator calcium) to regular contraction in rats. In this study we investigated the combined effects of hypoxia and glucose elimination on PRC and regular contraction. In other words, using papillary muscles of rats, to elucidate the characteristics of reversible or irreversible myocardial injury after ischemia, we investigated the effects of hypoxia on both SR and sarcolemmal functions. After 90 min hypoxia (the first hypoxia-90 min), regular contraction was significantly more reduced than PRC (p less than 0.001; n = 16). With 90 min of reoxygenation, the recovery from hypoxic injury of PRC was better than recovery from injury of regular contraction (p less than 0.01; n = 16). After either 30 min hypoxia (the second hypoxia-30 min) or 60 min hypoxia (the second hypoxia-60 min), regular contraction was also more reduced than PRC, respectively (p less than 0.001; n = 8). However, the recovery from both the second hypoxic injury-30 min and the second hypoxic injury-60 min of PRC was not significantly different from that of regular contraction, respectively (NS; n = 8). Percentages of diastolic tension, which were normalized by baseline regular contraction, increased during hypoxia and decreased incompletely after reoxygenation. After the first reoxygenation of 90 min, 1 microM noradrenaline significantly augmented the magnitude of regular contraction (p less than 0.05; n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Different sensitivity of sinus node and atrioventricular node to adenosine triphosphate].

We showed that higher concentration of adenosine 5'-triphosphate (ATP) was required to prolong the spontaneous cycle length of the sinus node (SN) than that required to prolong the spontaneous cycle length of the atrioventricular node (AVN). Spontaneously beating preparations of SN and AVN of rabbit (n = 8) were superfused with Tyrode solution containing 10(-8)-10(-3)M ATP, and action potential was recorded. The negative chronotropic action of ATP was dependent on the concentration. The required concentration of ATP to prolong spontaneous cycle length significantly (p less than 0.01) was 10(-5)M in SN and 10(-6)M in AVN, respectively. At concentrations higher than 10(-6)M, the degree of prolongation was greater in AVN than in SN (p less than 0.01). 10(-7)M dipyridamole enhanced this effect of ATP, while 10(-4)M theophylline reduced it. Action potential duration of 50% repolarization was not changed significantly in either SN or AVN at concentrations up to 10(-3)M. Maximum diastolic potential (MDP) was hyperpolarized from 10(-8)M to 10(-4) M. Hyperpolarization of MDP induced by ATP was greater in AVN than in SN but it was not statistically significant. MDP was depolarized by 10(-3) M ATP in both SN and AVN. The maximum velocity of depolarization was slightly larger in both SN and AVN as the concentration of ATP was increased in the perfusate. However, it was not statistically significant. 10(-3) M ATP decreased the maximum velocity of depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

[Utility of reinjection method in stress Tl-201 myocardial scintigraphy to assess viability of the infarcted myocardium].

To assess viability of the infarcted myocardium, we performed stress Tl-201 myocardial scintigraphy using reinjection method in 37 patients with old myocardial infarction, and in 13 patients of them, Tl myocardial imagings were performed in resting state on the other day within 4 weeks after this examination. In this method, 111 MBq (3 mCi) of thallium was injected at the peak of exercise and initial and delayed images were acquired, then additionally 37 MBq (1 mCi) of thallium was injected after delayed scanning (reinjection) and we obtained post-reinjection images. Delayed images showed redistribution in 15 patients (41%), and no redistribution in 22 patients (59%). In post-reinjection images, 7 (19%) of 15 patients with redistribution and 3 (8%) of 22 patients without redistribution showed improvement of thallium uptake, in total 10 patients (27%) had additional thallium uptake in infarcted regions. And the degree of thallium uptake in post-reinjection images were almost equal to that in resting images. In conclusion, myocardial imaging using thallium reinjection method may be useful for the assessment of viability of the infarcted myocardium.

Female↗

Effect of paced cycle length on sinus node effective refractory period before and after autonomic blockade in patients with sick sinus syndrome.

Effect of basic paced cycle length on sinus node effective refractory period was studied in 22 patients with sick sinus syndrome. Sinus node effective refractory period was measured using three different paced cycle lengths before and after pharmacologic autonomic blockade. Sinus node effective refractory period could be measured at one cycle length, at least, in 59% of the patients before blockade, however, it could be measured at two or more cycle lengths in only 18% of patients because of the chaotic response of sinus node against premature stimuli. It could be measured after pharmacologic autonomic blockade in 68% of the patients at two or more paced cycle lengths. On the other hand, the rest of the patients showed no measurable sinus node effective refractory period at any cycle length, for their sinus node effective refractory periods were shorter than their right atrial effective refractory periods. The comparison of sinus node effective refractory period at different paced cycle lengths was unsuccessful before pharmacologic autonomic blockade, while the refractory period was significantly prolonged as cycle length was shortened after blockade. We concluded that (1) sinus node effective refractory period in humans is prolonged as paced cycle length decreases, (2) the autonomic reflex is the major disturbing factor in measuring sinus node effective refractory period, and pharmacologic autonomic blockade can be usefully employed to eliminate a chaotic sinus nodal response, (3) when sinus node effective refractory period is shorter than right atrial effective refractory period, a shorter paced cycle length should be used for definite measurement of the former.

Adolescent↗

Combined effects of hypoxia and elimination of glucose on resting and postextrasystolic potentiated contractions of papillary muscle of guinea pigs.

We studied the combined effects of hypoxia and the absence of glucose on postextrasystolic potentiated and resting contractions in papillary muscle of guinea pigs. Postextrasystolic potentiations (PESPs) were evoked following trains of 40 externally applied continuous stimulations. During hypoxia resting (regular) contractions decreased to about 25% of baseline tension at 30 degrees C, whereas postextrasystolic potentiated contractions decreased to about 35% of baseline measurement of postextrasystolic potentiated contraction. In contrast, with reoxygenation, PESPs recovered quickly while resting contractions recovered gradually. Caffeine abolished the potentiation of post-extrasystolic contraction not only in normoxia but also in hypoxia. We speculate that calcium release from the sarcoplasmic reticulum (SR) is attributable to PESP for the most part, and that the trans-sarcolemmal calcium influx generally contributes to the steady-state tensions developed by continuous stimulations. In addition, it seems that PESP works in a ischemic heart to compensate for the decreased tension during hypoxia as a potentiation by a premature ventricular contraction. Trans-sarcolemmal calcium influx might be affected more easily than the SR calcium release, by a combination of hypoxia and the absence of glucose, that is, the sarcolemma may be more susceptible to hypoxic injury than the SR.

Animals↗

The contribution of an extrasystole to postextrasystolic potentiation in papillary muscles of guinea pigs.

It is well known that a short rest period during the regular stimulation of isolated cardiac muscle induces a transient increase of subsequent twitch tension, although the mechanism of postextrasystolic potentiation (PESP) is still unclear. This paper is concerned with the contribution of an extrasystole to the PESP using isolated papillary muscle of guinea pigs. We have found that the length of the coupling interval of the extra-stimulation prior to the rest interval affected the degree of PESP in a coupling interval-dependent way at the same rest period, and the PESP of the same coupling ratio increased and decreased at the rest period was prolonged. Theophylline increased the strength of steady-state twitch tensions, whereas the dependency of PESP on a coupling ratio of extra-stimulation was removed and the PESP decreased with prolonged rest periods. The evidence suggests that the coupling ratio of extra-stimulation might vary the relative contributions of trans-sarcolemmal Ca influx and Ca release from the sarcoplasmic reticulum.

Animals↗

[Thallium-201 myocardial perfusion imaging during transient coronary occlusion at the time of PTCA: comparison with stress imaging].

To evaluate myocardial perfusion during transient coronary arterial occlusion, thallium-201 was administered intravenously during percutaneous transluminal coronary angioplasty (PTCA) in 12 patients with effort angina, and the resulting perfusion images were compared with those of exercise stress obtained before PTCA. Thallium-201 was injected at the last inflation of an angioplastic balloon and occlusion was maintained for 60 to 90 sec. Three projections of planar images were obtained immediately after PTCA, using a portable gamma camera in an angiography room. These perfusion images obtained during PTCA and exercise were visually interpreted and compared. Myocardial perfusion defects due to the responsible vessel occlusion were observed at early imaging after PTCA, and were fully redistributed three hrs post injection. In 10 patients without angiographically imaged collateral vessels, there were no significant differences in perfusion between images during PTCA and during exercise. Two patients whose collaterals were observed during coronary angiography before PTCA had higher perfusion scores during PTCA than during exercise. We concluded that intravenous injection of thallium-201 during PTCA is a useful means for assessing alteration of myocardial perfusion due to transient coronary occlusion without increasing the risk of angioplastic procedures, and that it provides more precise information about the jeopardized myocardium, perfused by antegrade blood flow.

Angioplasty, Balloon↗

[Ultrasonic tissue characterization by spectral analysis of myocardial textural pattern].

Based on the fact that ultrasonic myocardial textural patterns are more irregular in the pathological myocardium than in the normal, evaluation of the myocardial tissue character was attempted in vivo using spectral analysis. Parasternal left ventricular long-axis echocardiograms were obtained from five patients with old myocardial infarction diagnosed by history, electrocardiography and coronary angiography. These echocardiograms were transferred to an image analyzer and digitized (256 x 256 x 8). The waveforms of the gray-scale-changes from the normal myocardium showed periodicity in each 8-pixel cycle, but those from the infarcted myocardium did not. To quantify pattern changes in gray-scale values in the ultrasound beam direction, spectral analysis was performed by the maximum entropy method (MEM). There were four peaks in the MEM spectra both in the normal and infarcted myocardia, but there was a great significance in these patterns: with high, steep peaks in normal MEM spectra, and low, blunt peaks in infarcted ones. By discriminatory analysis of these four peak values, normalized by the whole spatial frequencies as multivariate, the misclassification rate was 4.8-22.7% in anteroseptal infarctions and 5.0-20.0% in posterior infarctions. Thus, spectral analysis of the myocardial textural pattern has advantages for analyzing routine echocardiograms without corrections by any absolute ultrasonic references. Furthermore, the misclassification rate is so low that we are able to characterize myocardial tissue.

Echocardiography↗

[Effect of mexiletine on human atrial vulnerability].

The effect of mexiletine on human atrial vulnerability was investigated in 14 subjects (8 with paroxysmal atrial fibrillation, 2 with paroxysmal atrial tachycardia, 2 with ventricular tachycardia, 1 with sick sinus syndrome and 1 with Wolff-Parkinson-White syndrome). During the electrophysiologic study, after 8 consecutive stimuli (A1) were delivered through the electrode catheter positioned at high right atrium, premature stimulus (A2) was introduced, and following measurements were made; 1) Aw: atrial activity width of A1, 2) maximum atrial fragmentation (MAF): the longest atrial activity width of A2, which was expressed by the relative value against Aw, 3) fragmented atrial activity zone (FAZ): the zone of the coupling interval (A1A2) with the prolongation of the atrial activity width at A2 more than 150% against Aw, 4) conduction delay zone (CDZ): the zone of A1A2 with the prolongation more than 20 msec of the intraatrial conduction time at A2 from high right atrium to coronary sinus or low right atrium against the intraatrial conduction time at A1, and 5) right atrial effective refractory period (RAERP). These measurements were repeated after the intravenous administration of mexiletine (2 mg/kg/10 min). 3 cases (case 12, 13 and 14), whose FAZ and CDZ were 0 msec, were excluded from the following evaluation. Mexiletine showed little effect on Aw and RAERP, but significantly shortened MAF and FAZ (p less than 0.001 and p less than 0.05, respectively). CDZ were also reduced in 3 cases and remained unchanged in 6 cases, though no statistical difference of CDZ was recognized between before and after the administration of mexiletine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effects of ulinastatin on the reticuloendothelial system (RES) of rabbits in endotoxin shock.

Carbon clearance, concentration of fibronectin (Fn) in the blood and arterial ketone body ratio (AKBR) have been measured in the rabbit in order to evaluate the RES phagocytic activity and the effect of ulinastatin on it in endotoxin (ET) shock. The following results were obtained: 1) carbon deposition by ET injection was found in organs (lung and kidney) which did not show it in the control group. The reasons for this might be considered that the RES was blocked because of phagocytizing ET and tissue debris, so that the carbon which could not be processed by the RES spilled over and became clogged; 2) the RES phagocytic activity were found to decline from an early stage after injection of a lethal dose of ET due to a decline in Fn productivity and an increase in Fn consumption; and, 3) ulinastatin suppressed the decrease of Fn and the carbon deposition in the kidney in ET shock. These results are suggestive of the usefulness of ulinastatin as an anti-shock agent, preserving the RES phagocytic activity through the inhibition of Fn consumption.

Journal Article↗