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Biomedical subjects

K Takeda

Publications and source records attributed to K Takeda.

At least 1,063 records · Page 59Linked to original sources

Development of hyperthyroidism following primary hypothyroidism: a case report with changes in thyroid-related antibodies.

We report a 48-year-old woman who developed hyperthyroidism following primary hypothyroidism. The serum T4 level was initially low and serum TSH level was high with clinical signs of hypothyroidism. The thyroid gland was not enlarged. Therapy with L-T4 was started. Three years later she developed hyperthyroidism; serum free T4 increased to 29.1 pmol/l after cessation of L-T4 therapy. The 123I thyroid uptake was increased with no suppression by exogenous T3. When she was hypothyroid, the activity of thyroid stimulating antibodies (TSAb) in serum measured by cyclic AMP production in cultured porcine thyroid cells were negative at 93.4% (normal less than 140%), while thyroid stimulation-blocking antibodies (TSBAb) determined by inhibition of TSH-induced cyclic AMP increase were positive at 96.1% (normal less than 40%). When hyperthyroidism subsequently occurred, TSBAb became negative (30.9%), while TSBAb became positive (163.3%). The findings indicate that hypothyroidism due to the potent TSBAb activity is not always persistent, but can be changed when various types of thyroid-relating antibodies change in the course of the disease.

Antibodies↗

Histamine-induced inward currents in cultured endothelial cells from human umbilical vein.

1. The membrane response to applied histamine of cultured endothelial cells from human umbilical vein was studied by use of whole cell and single channel patch clamp techniques. A value of -27 +/- 1.4 mV was found for the resting potential under whole cell current clamp. No voltage-gated currents were seen at either the macroscopic or single channel levels. 2. At holding potentials of -20 to -40 mV, histamine evoked slow rising, long lasting whole cell inward currents. The inward current was associated with depolarization and decreased input resistance. The calcium ionophore A23187 provoked similar whole cell inward currents. 3. Single channel currents were observed in cell-attached and inside-out patches for both histamine and A23187. The single channel conductance was about 20 pS with a mean open time of 5 ms and a reversal potential of 0 mV in symmetrical potassium solutions. Internal sodium blocked outward going currents. 4. For cell-attached patches, histamine-dependent channel activity required external calcium and was also seen when histamine was present in the bath but not the pipette. Recording from inside-out patches revealed that decreases in 'internal' calcium resulted in the disappearance of channel activity. 5. The histamine-dependent inward current appears to involve calcium-dependent activation of cationic channels.

Calcimycin↗

Isolation of cDNA clones for mouse cytoskeletal gamma-actin and differential expression of cytoskeletal actin mRNAs in mouse cells.

We described the structures of mouse cytoskeletal gamma-actin cDNA clones and showed that there is strong conservation of the untranslated regions with human gamma-actin cDNA. In addition, we found that the expression levels of beta- and gamma-actin mRNAs are differentially controlled in various mouse tissues and cell types but are coordinately increased in the cellular growing state. These results suggest that there are multiple regulatory mechanisms of cytoskeletal actin genes and are consistent with the argument that beta- and gamma-actins might have functional diversity in mammalian cells.

Actins↗

Effect of angiotensin II on Ca2+ kinetics and contraction in cultured rat glomerular mesangial cells.

This in vitro study was undertaken to determine the changes in Ca2+ kinetics and cell shape of cultured putative glomerular mesangial cells in the rat in response to angiotensin II (ANG II). Intracellular Ca2+ ([Ca2+]i) was measured using quin 2. ANG II-stimulated Ca2+ efflux was also determined. ANG II induced rapid concentration-dependent increases in [Ca2+]i and Ca2+ efflux. ANG II also induced contraction of mesangial cells as assessed by alterations in cell shape. Even in Ca2+-free medium, ANG II increased [Ca2+]i and Ca2+ efflux, but to a lesser extent. Under this condition, contraction of mesangial cells induced by ANG II was also observed. Readdition of extracellular Ca2+ after the ANG II-induced increase in [Ca2+]i caused a second and slower [Ca2+]i increase. High potassium (50 mM) induced a change of [Ca2+]i, but to a lesser extent compared with the ANG II-induced change. The Ca2+ channel blocker verapamil (5 x 10(-5) M) partially inhibited ANG II-induced Ca2+ influx but totally blocked the increase in [Ca2+]i induced by high potassium. Verapamil did not inhibit ANG II-stimulated Ca2+ efflux or the change in cell shape. Dantrolene (10(-4) M), a blocker of Ca2+ release from endoplasmic reticulum, inhibited ANG II-stimulated Ca2+ efflux and change in cell shape. These results indicate that ANG II rapidly increases [Ca2+]i in cultured rat mesangial cells, in part by mobilizing Ca2+ from dantrolene-sensitive intracellular pools and in part through activation of receptor-operated and voltage-dependent Ca2+ channels. The [Ca2+]i mobilization, however, seems to be the primary modulator of initial glomerular mesangial cell contraction.

Aminoquinolines↗

AVP-induced Ca fluxes and contraction of rat glomerular mesangial cells.

Arginine vasopressin (AVP) is known to exert Ca mobilization and contraction in glomerular mesangial cells and vascular smooth muscle cells. However, the relationship between changes in intracellular Ca and transmembrane Ca fluxes is not clear at the present time. Therefore, this study was undertaken to determine the effect of AVP on cytosolic calcium ([Ca2+]i) and Ca fluxes as estimated by measurements of 45Ca2+ efflux. Changes of [Ca2+]i in response to AVP were directly measured in monolayers of adherent cultured mesangial cells. AVP induced rapid concentration-dependent increases in [Ca2+]i and Ca2+ efflux. AVP also induced contraction of mesangial cells. This effect was blocked only by the V1 (pressor)-antagonist, d(CH2)5Tyr(Me)AVP. Stimulation of Ca2+ efflux and changes in [Ca2+]i by AVP completely desensitized the mesangial cells to a subsequent identical challenge of AVP with no cross-tachyphylaxis to other hormones. Even in Ca2+-free medium, AVP increased [Ca2+]i and Ca2+ efflux, but to a lesser extent. Under this condition, contraction of mesangial cells induced by AVP was also observed. Readdition of extracellular Ca2+ following the AVP-induced increase in [Ca2+]i caused a second and slower [Ca2+]i increase. In Ca2+-containing conditions, lanthanum ion-reduced AVP evoked [Ca2+]i stimulation to the value observed in Ca2+-free medium. The Ca2+ channel blocker, verapamil, partially inhibited AVP-induced Ca2+ influx but totally blocked the increase in [Ca2+]i induced by high K. Verapamil did not inhibit AVP-stimulated Ca2+ efflux and cell contraction. Dantrolene, a blocker of Ca2+ release from endoplasmic reticulum, inhibited AVP-stimulated Ca2+ efflux and cell contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoquinolines↗

Central attenuation of aortic baroreceptor reflex in prehypertensive DOCA-salt-loaded rats.

To determine whether the arterial baroreceptor reflex can act to oppose the development of hypertension, deoxycorticosterone acetate (DOCA)-salt hypertension was produced in sinoaortic-denervated and sham-operated rats. Systolic blood pressure measured by tail cuff started to increase in both sinoaortic-denervated and sham-operated rats 7 days after DOCA treatment, and the hypertension developed identically in both denervated and sham-operated rats. These findings suggest that the baroreceptor reflex cannot act against the development of hypertension. To determine whether the baroreceptor reflex is attenuated before the development of hypertension, bradycardiac and sympathoinhibitory responses to i.v. injections of norepinephrine were examined. Bradycardic and sympathoinhibitory responses were significantly smaller in DOCA-salt-treated rats in both prehypertensive (5th day after DOCA-salt treatment) and hypertensive stages (21st day after treatment). In urethane-anesthetized DOCA-loaded and control rats on the 5th day after treatment, aortic depressor nerve stimulation elicited frequency-dependent depressor and bradycardic responses accompanied by inhibition of sympathetic nerve activity in both DOCA-loaded and control rats. However, those responses were significantly smaller in DOCA-loaded rats than in control rats. These results suggest that the central component of the baroreceptor reflex mediated by the aortic depressor nerve is impaired before hypertension develops and that this impairment may contribute to the development of hypertension in DOCA-salt-treated rats.

Animals↗

Coronary angiography of Kawasaki disease with the coronary vasodilator dipyridamole: assessment of distensibility of affected coronary arterial wall.

The authors evaluated the distensibility of the coronary arterial wall by pharmacoangiography with intravenous administration of dipyridamole in 38 patients with Kawasaki disease. In the acute stage of the illness, the coronary arteries were evaluated for aneurysms by two-dimensional echocardiography. After the acute stage of the illness, selective coronary cineangiographies were performed by Seldinger's method under general anesthesia before and after intravenous administration of 0.6 mg/kg of dipyridamole for four minutes. The calibers of aneurysms and normal appearing segments of coronary arteries, at most 7 segments in 1 patient, were measured before and after dipyridamole administration on the high-quality cineangioanalyzer and percentages of coronary arterial dilatation were calculated. In 14 cases without evidence of coronary arterial lesions, the distensibility was 10.2 +/- 4.7% (mean +/- SD). The distensibility of 32 aneurysms in 16 cases was 0.6 +/- 1.1% and was significantly decreased (p less than 0.001). In 24 cases with coronary arterial lesions, aneurysms, stenosis, or obstruction, the distensibility of normal appearing segments of coronary arteries was 4.5 +/- 4.9% and was significantly decreased (p less than 0.001). This method is useful in evaluating distensibility and appears to be effective in detecting pathologic changes of the coronary arterial wall, even if it appears normal in shape. The patient with previously diseased coronary arteries should be kept under careful longterm surveillance.

Acute Disease↗

Effect of urea, glycerol, and mannitol on basilar and labyrinthine arteries.

We studied the effect of urea, glycerol, and mannitol on basilar and labyrinthine arteries of dogs in vitro by use of tension recording methods. When the tissue was exposed to urea or glycerol, temporary relaxation of smooth muscles was initially observed, but was followed by gradually increasing contraction. With mannitol, relaxation of the smooth muscles remained stable as long as mannitol existed in the bathing solution. When the specimens were washed with normal Krebs solution after exposure to any of these three substances, large phasic contractions of the smooth muscles were observed. While only theoretical, we propose a possible explanation for the different effects of these three drugs in the improvement of hearing loss that results from Meniere's disease.

Animals↗

Enhanced thyroid iodine metabolism in patients with triiodothyronine-predominant Graves' disease.

Some patients with hyperthyroid Graves' disease have increased serum T3 and normal or even low serum T4 levels during treatment with antithyroid drugs. These patients with elevated serum T3 to T4 ratios rarely have a remission of their hyperthyroidism. The aim of this study was to investigate thyroid iodine metabolism in such patients, whom we termed T3-predominant Graves' disease. Mean thyroid radioactive iodine uptake was 51.0 +/- 18.1% ( +/- SD) at 3 h, and it decreased to 38.9 +/- 20.1% at 24 h in 31 patients with T3-predominant Graves' disease during treatment. It was 20.0 +/- 11.4% at 3 h and increased to 31.9 +/- 16.0% at 24 h in 17 other patients with hyperthyroid Graves' disease who had normal serum T3 and T4 levels and a normal serum T3 to T4 ratio during treatment (control Graves' disease). The activity of serum TSH receptor antibodies was significantly higher in the patients with T3-predominant Graves' disease than in control Graves' disease patients (60.5 +/- 19.2% vs. 20.4 +/- 18.2%; P less than 0.001). From in vitro studies of thyroid tissue obtained at surgery, both thyroglobulin content and iodine content in thyroglobulin were significantly lower in patients with T3-predominant Graves' disease than in the control Graves' disease patients. Thyroid peroxidase (TPO) activity determined by a guaiacol assay was 0.411 +/- 0.212 g.u./mg protein in the T3-predominant Graves' disease patients, significantly higher than that in the control Graves' disease patients (0.129 +/- 0.112 g.u./mg protein; P less than 0.01). Serum TPO autoantibody levels determined by immunoprecipitation also were greater in T3-predominant Graves' disease patients than in control Graves' disease patients (52.6 +/- 27.7% vs. 32.4 +/- 11.4%; P less than 0.05). Binding of this antibody to TPO slightly inhibited the enzyme activity of TPO, but this effect of the antibody was similar in the two groups of patients. The data suggest enhanced iodine metabolism in the thyroid gland of patients with T3-predominant Graves' disease, which may relate to the discordant T3 overproduction in patients with this type of Graves' disease.

Adolescent↗

Human left ventricular end-systolic pressure-volume relationship in a cylinder model.

The relationship between myocardial total force and length at the end of systole appears to be linear, and the slope of this relationship is considered to be an appropriate index of myocardial contractile state, independent of preload and afterload. However, direct measurements of this relation may be impossible in the intact human heart, and thus, alternative indices such as the left ventricular end-systolic stress-length, stress-strain, pressure-volume, and pressure-dimension slopes have been proposed to evaluate myocardial contractility in the intact heart. However, the mathematical relationship between the myocardial end-systolic total force-length relation and any of these left ventricular end-systolic relations remains unclear. In this study, assuming a linear myocardial end-systolic total force-length relation in an intact ventricle, we obtained mathematical formulae for the left ventricular end-systolic stress-strain, pressure-radius, and pressure-volume relations, using a cylinder model of the left ventricle. The results obtained using these formulae and the cylinder model were found to match accurately findings obtained from earlier experimental and clinical studies of these left ventricular end-systolic relations. Thus, this model could mathematically account for the relationships between the slopes of the myocardial end-systolic total force-length relation and these left ventricular end-systolic relations.

Blood Pressure↗

Evaluation of monoclonal antibody against human pulmonary surfactant apoprotein.

Lung sections of 104 newborn infants stored for 20 to 25 years and of seven cases of paraquat (PQ) intoxication were examined to detect the pulmonary surfactant apoprotein with the monoclonal antibody PE10 by immunoperoxidase staining technique. Specific peroxidase staining was observed in alveolar Type II cells and on alveolar walls of normal adult lungs. In the lungs of liveborn infant up to 28 weeks' gestation, peroxidase staining was negative. However, faint positive staining was observed in a specimen of 29 weeks' gestation, and the rate of positive staining increased with gestational age. Fifteen cases of newborn lungs with hyaline membranes revealed no positive staining except one. In the lungs of stillborn infants, peroxidase staining was weak and the rate of negative staining was more than that of liveborn infants. The specimens of PQ intoxication up to 5 days survival showed positive staining on alveolar walls, while those of 10 days or more survival, in which fibrotic changes and hyaline membranes were developed, showed no positive staining.

Adult↗

Side effects of topical corticosteroids and their prevention.

The goal of topical corticosteroid therapy is to maximise the clinical benefits of this highly effective group of drugs, while minimising their adverse effects. Many types of steroid-induced skin lesions and skin atrophy can occur by such mechanisms as the suppression of cell proliferation, immunosuppression, or hormonal activity, and a trend towards an increased incidence of steroid-induced dermatological disturbances has been observed in recent years. Systemic effects have also been documented. To reduce the risk of local and systemic effects, it is necessary to consider factors such as the intrinsic potency of a drug, type of vehicle used and frequency of application. A potent drug may be changed to a less potent one, or the dosage reduced. Once-daily application is often as effective as three-times-daily application, and intermittent application can also be recommended. The concept of an 'ante-drug' promises new developments in topical corticosteroid therapy. An 'ante-drug', e.g. difluprednate, has potent efficacy but fewer side effects than conventional therapy, since it acts at the application site and then is metabolised to less active or inactive compounds before reaching the systemic circulation. It is likely that future corticosteroids will have the attributes of an ante-drug, thus greatly reducing the risk of systemic effects. At present, however, it is still necessary to recognise the influence of various drug and patient factors that contribute to side effects, in order to balance clinical efficacy with an acceptable side effect profile.

Administration, Topical↗

Adrenergic receptor effects and antihypertensive actions of beta-adrenoceptor-blocking agents with ancillary properties.

The acute antihypertensive effects and possible underlying mechanisms of 3 beta-adrenergic-blocking drugs with alpha-blocking activity, i.e. labetalol, drugs with alpha-blocking activity, i.e. labetalol, nipradilol and arotinolol, were studied in conscious spontaneously hypertensive rats (SHR) and compared with the effects of prazosin, propranolol and hydralazine. Prazosin produced a dose-dependent antihypertensive effect which paralleled inhibition of the pressor response to phenylephrine. Labetalol (30 mg/kg), nipradilol (30 and 100 mg/kg) and arotinolol (30 and 100 mg/kg) also produced a fall in blood pressure. However, inhibition of the pressor response to phenylephrine was not seen in association with the antihypertensive effect after the lower dose of nipradilol and arotinolol. Propranolol (100 mg/kg) did not lower blood pressure. These results suggest that a mechanism(s) other than an alpha-adrenergic-blocking effect plays a role in the acute antihypertensive effects produced by the lower dose of nipradilol and arotinolol.

Adrenergic alpha-Antagonists↗

Plain chest radiograph with computed radiography: improved sensitivity for the detection of coronary artery calcification.

The ability of computed radiography (CR) with photostimulable phosphor to detect coronary artery calcification (CAC) was compared with conventional radiography with the film-screen method. Posteroanterior and lateral chest radiographs were reviewed that had been obtained with both methods in 77 patients with a variety of heart diseases. Cineangiography confirmed that 31 patients had CAC (left CAC in 31 patients, right CAC in 11) and that 46 patients had no CAC. For left CAC, the sensitivity of CR was 71%, significantly higher than that of conventional radiography (32%, p less than .01). For right CAC, the sensitivity of CR was only 27%, but that of conventional radiography was 0%. The specificities in detecting CAC were similar for both methods (CR, 96%; conventional method, 100%). Fine anatomic details of calcified foci were seen more clearly on CR. Chest imaging with the CR system is a promising method for detecting CAC.

Adolescent↗

Distribution and morphology of macrophages in palatine tonsils.

The distribution and morphology of macrophages were studied by immunohistochemical and electronmicroscopic methods in three diseases of the palatine tonsils: tonsillar hypertrophy, recurrent tonsillitis and tonsils with focal infection. We confirmed the presence of two types of macrophages in the tonsils, a monocyte-macrophage cell line and dendritic cells with subtypes, Langerhans' and interdigitating reticulum cells. In the lymphoepithelial symbiosis area and in the subepithelial area, the monocyte-macrophage cells and the dendritic cells had similar distributions and densities. Since these two types of cells were sometimes in contact with each other, they may function in close cooperation. In tonsils with focal infection, there were fewer dendritic cells in the lymphoepithelial symbiosis area, and the germinal centers were less well developed than in the other tonsillar diseases. These findings suggest that in tonsils with focal infection, insufficient amounts of antigen may be presented by the dendritic cells to helper T-lymphocytes.

Adolescent↗