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Biomedical subjects

D Inoue

Publications and source records attributed to D Inoue.

At least 37 records · Page 2Linked to original sources
PubMed1991

[Effects of ouabain, caffeine, and diltiazem, on spontaneous cyclic Ca2+ release from sarcoplasmic reticulum in the skinned papillary muscles of guinea pigs].

The aim of this study was to assess whether ouabain has a direct action on the sarcoplasmic reticulum (SR) sufficient to be responsible for the mechanism of the inotropic action, and whether caffeine and diltiazem, which inhibit ouabain-induced afterpotential and after-contraction, can inhibit the effects of ouabain on the SR. As one of the functions of SR, spontaneous cyclic contractions (cyclic Ca2+ release from the SR) in saponin-treated skinned fibers of guinea pig papillary muscles were used. Ouabain 10(-9)-10(-7) M increased the frequency of cyclic contractions and induced an incomplete muscle relaxation. Caffeine 1-5 mM and diltiazem 1-5 mM induced a sustained tension. In the fibers treated with ouabain, caffeine and diltiazem induced a sustained tension. In Brij-58 treated skinned fibers, 10(-9) M ouabain did not change the Ca2+ sensitivity of the contractile system. It is now known that ouabain increases intracellular calcium transients. An incomplete muscle relaxation of cyclic contractions seems to be due to both increased SR Ca2+ release and decreased Ca2+ reuptake by SR. Thus, we suppose that ouabain-induced increase in intracellular calcium transients is due to increased intracellular Ca2+, which may be one of the mechanisms in the inotropic action. The masking effects of caffeine and diltiazem on the ouabain-induced increase in cyclic contractions seem to be responsible for the inhibitory effects of drugs on digitalis-induced afterpotential and after contraction.

Animals↗
PubMed1990

Possible binding site of thyrotropin binding inhibitor immunoglobulin (TBII) on the thyrotropin (TSH) receptor, which is different from TSH binding site.

A synthetic decapeptide, P-194, which has the sequence No. 103 to 111 of hTSH receptor structure with an additional N-terminal tyrosine, did not bind TSH nor affected its receptor binding and thyroid stimulating activity. Preincubation of P-194 with sera from thyroid patients caused a significant decrease in TBII activity in almost all 12 TBII positive sera and an increase of thyroid stimulating activity in 3 of 7 Graves' IgG studied. In addition, [125I] P-194 bound to serum IgG fraction from thyroid patients with a positive correlation with TBII (N = 35, r = 0.509, p less than 0.01). The P-194 portion may be, at least a part of, TBII binding site distinct from the TSH binding site on the TSH receptor.

Animals↗
PubMed1990

Establishment of a human undifferentiated thyroid cancer cell line producing several growth factors and cytokines.

A cell line was established from undifferentiated giant cell carcinoma of the thyroid. The authors obtained cells from a 44-year-old patient admitted because of a rapidly growing anterior neck mass. The patient had significant leukocytosis and hypercalcemia shortly before her death. An autopsy revealed epidermoid metaplasia of the tumor cells. The cells (HTC/C3) had lost most of their differentiated functions. However, their thyroid nature was shown by peroxidase staining and by enzyme-linked immunostaining with Hashimoto patients' sera. The tumor extract was found to contain parathyroid (PTH)-like activity. Significant amounts of colony stimulating factor (CSF), which was further defined to be GM-CSF, and interleukin-1 alpha (IL-1 alpha) were detected in the conditioned media. Epidermal growth factor (EGF) binding to the HTC/C3 showed rich EGF receptors. Furthermore, the conditioned medium inhibited the binding of 125I-mEGF to HeLa cells, and transforming growth factor (TGF) was found repeatedly in the media.

Adult↗
PubMed1990

Effect of diltiazem on spontaneous cyclic Ca2+ release from sarcoplasmic reticulum.

We used saponin-treated skinned fibers isolated from papillary muscles of the right ventricle of guinea pigs to compare the effects of diltiazem on the spontaneous cyclic Ca2+ release from the sarcoplasmic reticulum (SR) of cardiac muscle with the effects of caffeine. Both diltiazem and caffeine increased the frequency of cyclic contractions in EGTA (ethyleneglycol-bis-(beta-aminoethylether) N,N,N',N'-tetra-acetate)-free solution and induced an incomplete, concentration-dependent relaxation of the muscle. The results suggest that the spectrum of the pharmacological effects of diltiazem on the SR is similar to that for caffeine, that is diltiazem accelerates the spontaneous Ca2+ release from the SR and suppresses Ca2+ reuptake by the SR, and that diltiazem as well as caffeine may act on the SR in vivo in a specific condition.

Animals↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

[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↗
PubMed1990

[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↗
PubMed1990

[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↗
PubMed1990

[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↗
PubMed1990

[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↗
PubMed1990

[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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗