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Biomedical subjects

S Uchida

Publications and source records attributed to S Uchida.

At least 325 records · Page 18Linked to original sources

Cloning and expression of apical membrane water channel of rat kidney collecting tubule.

Concentrating urine is mandatory for most mammals to prevent water loss from the body. Concentrated urine is produced in response to vasopressin by the transepithelial recovery of water from the lumen of the kidney collecting tubule through highly water-permeable membranes. In this nephron segment, vasopressin regulates water permeability by endo- and exocytosis of water channels from or to the apical membrane. CHIP28 is a water channel in red blood cells and the kidney proximal tubule, but it is not expressed in the collecting tubule. Here we report the cloning of the complementary DNA for WCH-CD, a water channel of the apical membrane of the kidney collecting tubule. WCH-CD is 42% identical in amino-acid sequence to CHIP28. WCH-CD transcripts are detected only in the collecting tubule of the kidney. Immunohistochemically, WCH-CD is localized to the apical region of the kidney collecting tubule cells. Expression of WCH-CD in Xenopus oocytes markedly increases osmotic water permeability. The functional expression and the limited localization of WCH-CD to the apical region of the kidney collecting tubule suggest that WCH-CD is the vasopressin-regulated water channel.

Amino Acid Sequence↗

Morning increase in hemodynamic response to exercise in patients with angina pectoris.

The present study was conducted to determine whether or not there is diurnal variation in the hemodynamic responses to stimuli that increase myocardial oxygen demand, and the effects of such variation on electrocardiograms (ECG). Fifteen patients with angina pectoris, 17 patients with old myocardial infarction, and 8 healthy controls were examined in this study. Graded exercise stress testing was conducted in the supine position, once in the morning and once in the afternoon, using a bicycle ergometer. A standard 12-lead ECG was recorded before, immediately after, and 3, 5, and 10 min after the end of the exercise. The exercise ECG and blood pressure changes were compared among the groups and, within each group, the results after morning and afternoon exercise were compared. Hemodynamic responses, including heart rate, blood pressure, and the pressure-rate product, showed greater increases in the morning than in the afternoon in angina patients and controls, in association with greater depression of the electrocardiographic ST-segment. In contrast, patients with old myocardial infarction exhibited no difference in hemodynamic responses or the ST-pattern from morning to afternoon. The results suggest that diurnal variation of hemodynamic responses to increased oxygen demand may explain, at least partly, why myocardial ischemia of effort angina is more severe in the morning than in the afternoon.

Adult↗

Regulation of cortical collecting duct function: effect of endothelin.

We recently showed that endothelin-1 (ET-1) increases cell Ca2+ in the mouse cortical collecting duct. To clarify the cellular action and target cell of ET-1, electrophysiologic techniques and cell Ca2+ measurement were applied to rabbit cortical collecting ducts perfused in vitro. When 10(-8) mol/L ET-1 was added to the bath, a transient increase followed by a sustained increase in cell Ca2+ was observed. A sustained increase in cell Ca2+ lasted 10 to 20 minutes and was associated with a decrease in lumen-negative transepithelial voltage. To confirm the target cell type of ET-1, confocal laser microscopy was used. An increase in cell Ca2+ was observed in the same cell, which also showed an increase in cell Ca2+ in response to arginine vasopressin (AVP), which indicated that the principal cell has ET-1 receptors in the basolateral membrane. When ET-1 was applied to the bath, total cellular membrane resistance (Ri) decreased initially and then gradually increased because of inhibition of the luminal Na+ channel. An initial decrease in Ri was considered an influx of Ca2+ from the basolateral membrane. To further determine the source of an increase in cell Ca2+, the effect of ET-1 was tested in the absence of external Ca2+ and in the presence of a Ca2+ channel blocker in the bath. Cell Ca2+ did not respond to ET-1 in the absence of external Ca2+, a condition in which an AVP-stimulated increase in cell Ca2+ was preserved.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antibody recognition of the recombinant human nuclear antigens RNP 70 kD, SS-A, SS-B, Sm-B, and Sm-D by autoimmune sera.

Five human nuclear antigens, RNP 70 kD, SS-A, SS-B, Sm-B and Sm-D, were produced in E. coli using the expression vector pSEM. cDNAs encoding these antigens were ligated to a truncated lacZ' gene of the vector and the beta-galactosidase fusion proteins were efficiently expressed as intracellular inclusion bodies after isopropyl-beta-thiogalactopyranoside induction. The antibody reactivities of these fusion proteins were evaluated by Western blot and by ELISA employing panel sera from patients with autoimmune diseases such as systemic lupus erythematosus, Sjögren's syndrome or mixed connective tissue disease. The three fusion proteins, RNP 70 kD, SS-B, and Sm-B, showed good reactivities in both systems, whereas the other two fusion proteins, SS-A and Sm-D, showed poor and no reactivity in both systems, respectively. It can be concluded that RNP 70 kD, SS-B and Sm-B recombinant antigens are useful reagents for the differential diagnosis of the autoimmune diseases.

Autoantigens↗

Neural mechanisms of the reflex inhibition and excitation of gastric motility elicited by acupuncture-like stimulation in anesthetized rats.

The effects of acupuncture-like stimulation of the various segmental areas on gastric motility were examined in anesthetized rats. An acupuncture needle (diameter 340 microns) was inserted into the skin and underlying muscles at a depth of 4-5 mm and was twisted right and left once every second for 60 s. Gastric motility in the pyloric region was measured with the balloon method. Gastric motility was inhibited by acupuncture-like stimulation applied to the abdomen and lower chest region, and was often excited when the limbs were stimulated, in all cases in which stimuli were delivered to the skin and muscles, the skin alone, and the underlying muscles alone. The inhibitory gastric response to abdominal stimulation was accompanied by an increase in the activity of the gastric sympathetic efferent nerve and was abolished by severance of either the sympathetic nerve branches to the stomach or the lower thoracic spinal nerves. The abdominal stimulation enhanced the activity of the lower thoracic spinal afferent nerves. The excitatory gastric response to hindpaw stimulation was accompanied by an increase in the activity of the gastric vagal efferent nerve and was abolished by severance of either the bilateral vagi or the femoral and sciatic nerves. The hindpaw stimulation enhanced the activity of the femoral and sciatic afferent nerves. In the spinalized animals, the inhibitory gastric response elicited by abdominal stimulation was present, and the hindpaw stimulation did not produce any gastric response. We conclude that the inhibitory gastric response elicited by acupuncture-like stimulation of the abdomen is a reflex response. Its afferent nerve pathway is composed of abdominal cutaneous and muscle afferent nerves, the efferent nerve pathway is the gastric sympathetic nerve, and its reflex center is within the spinal cord. The excitatory gastric response elicited by acupuncture-like stimulation of a hindpaw is also a reflex response. Its afferent nerve pathway is composed of hindpaw cutaneous and muscle afferent nerves, the efferent nerve pathway is the gastric vagal efferent nerve, and its reflex center requires the presence of the brain. Furthermore, the excitatory and the inhibitory gastric reflex responses were not influenced by i.v. administration of naloxone (0.4-4 mg/kg), suggesting that endogenous opioids are not involved in the present reflexes.

Abdomen↗

Effects of oral theophylline on sick sinus syndrome.

OBJECTIVES: We sought to determine the effect of theophylline on cardiac pauses in sick sinus syndrome. BACKGROUND: Sick sinus syndrome, a relatively benign condition, is usually treated with pacemaker implantation without any proved effectiveness. Thus, an appropriate pharmacologic therapy would be useful. METHODS: Theophylline (200 to 400 mg/day for 1 month) was initially administered orally to 17 patients with sick sinus syndrome, which is manifested by sinus pauses of > 2.5 s. Eleven of the 17 patients subsequently received theophylline for an additional 8 to 37 months. Twenty-four-hour Holter recordings were obtained before treatment, at the end of 1 month of treatment and then at 6-month intervals. RESULTS: Theophylline decreased the frequency of sinus pauses from 256 +/- 230 to 23 +/- 62 pauses per 24 h and decreased the duration of the longest pauses from 4.7 +/- 1.8 to 2.2 +/- 0.97 s after 1 month of treatment. Subjective symptoms associated with cardiac pauses disappeared in 16 of 17 patients. Ventricular premature beats increased in frequency but did not last longer than two beats. Three patients experienced adverse effects. Nine of the 11 patients receiving long-term treatment had a good outcome, but 2 patients required a pacemaker because of the reappearance of long sinus pauses. CONCLUSIONS: The results suggest that oral theophylline may be beneficial for the treatment of patients with sick sinus syndrome.

Administration, Oral↗

Total knee arthroplasty in Charcot's joint.

The authors report three cases with neuropathic (Charcot) knee joint due to tabes dorsalis in which total knee arthroplasty (TKA) was performed. Three cases (5 joints) were observed for more than 8 years after TKA. No ataxia was seen before or after surgery. The postoperative clinical course had been satisfactory in two cases (3 joints) for 9-10 years after TKA with no evidence of loosening. Although the other case had medial condylar fracture of the right upper tibia during postoperative treatment, the clinical course of the right knee had been satisfactory over the 7 years since revision arthroplasty using a tibial component with a long stem. This case also had loosening of the left tibial component 8 years after TKA. Total knee arthroplasty appears to be useful for the treatment of Charcot's joint with no ataxia at Eichenholtz' stage of coalescence and reconstruction if (1) proper surgical techniques to establish good ligamentous balancing and bony alignment by releasing ligaments are employed; (2) an adequate amount of bone is resected and remaining bony defects are reinforced with bone graft; (3) long-stem components are used on both the femoral and tibial sides.

Aged↗

Cardiovascular effects of NSP-804 and NSP-805, novel cardiotonic agents with vasodilator properties.

The cardiovascular properties of NSP-804 (4,5-dihydro-6-[4-[(2-methyl-3-oxo-1-cyclopentenyl)-amino] phenyl]-3(2H)-pyridazinone) and NSP-805 (4,5-dihydro-5-methyl-6-[4-[(2-methyl-3-oxo-1-cyclopentenyl) amino]phenyl]-3(2H)-pyridazinone), novel cardiotonic agents, were investigated in vitro and in vivo in comparison with those of other cardiotonic agents. In isolated guinea pig left atria, the positive inotropic EC50 values (microM) in order of potency were about 0.18 (NSP-805), 0.39 (indolidan), 1.1 (MCI-154), 1.7 (NSP-804, milrinone), 2.0 (denopamine), 4.0 (papaverine), 4.4 3-isobutyl-1-methylxanthine, IBMX, 6.5 (imazodan), and 27 (amrinone). In anesthetized dogs, intravenous (i.v.) injection of NSP-804 and NSP-805 produced dose-dependent increases in left ventricular VVdp/dtmax and decreases in aortic blood pressure (ABP) with relatively small increases in heart rate (HR). The ED50 values (micrograms/kg) for LVdP/dtmax of NSP-804, NSP-805, denopamine, milrinone, MCI-154, and indolidan were 15, 12, 22, 23, 15, and 7.3, respectively. When the drugs were administered intraduodenally to anesthetized dogs, the ED50 values (micrograms/kg) for LVdP/dtmax of NSP-804, NSP-805, milrinone and indolidan were approximately 30, 10, 200, and 25 respectively. In the propranolol-induced heart failure model, NSP-804 and NSP-805 completely improved the hemodynamic state of heart failure to normal levels. The in vitro positive inotropic effects of NSP-804 and NSP-805 were accompanied by increases in tissue cyclic AMP and abolished by carbachol. NSP-805 was the most potent and selective inhibitor of guinea pig cardiac phosphodiesterase (PDE) III among the agents examined, and NSP-804 was a potent and selective inhibitor of PDE III similar to indolidan. The cardiovascular properties determined in this study suggest that both NSP-804 and NSP-805 may have beneficial effects for treatment of congestive heart failure (CHF).

Animals↗

Endothelin-1 and -3 binding to ETB receptors in rat renal tubules.

To increase understanding of endothelin (ET) function in the kidney, we investigated binding of the radioligand of endothelin isopeptides to microdissected rat nephron segments. Specific ET-1 binding was highest in the inner medullary collecting duct, whereas the cortical and outer medullary collecting ducts showed moderate binding, as did the glomeruli. There was slight ET-1 binding to the early portion of the proximal tubule. Other nephron segments displayed little ET-1 binding. The binding profile of ET-3 along the nephron markedly resembled that of ET-1. Scatchard analyses of ET-1 and ET-3 binding to cortical collecting ducts revealed a single class of receptor for both ET-1 and ET-3. Displacement of [125I]-ET-1 binding by unlabeled ET-3 was similar to that produced by unlabeled ET-1. Moreover, a specific ETB agonist, BQ-3020, almost completely inhibited [125I]-ET-1 binding in cortical collecting ducts, whereas a specific ETA antagonist, BQ-123, had little effect. These data indicate that cortical collecting ducts express ETB receptors, to which both ET-1 and ET-3 bind equally.

Animals↗

Hypertonicity stimulates transcription of gene for Na(+)-myo-inositol cotransporter in MDCK cells.

Myo-inositol is a major compatible osmolyte accumulated in the hypertonic renal medulla and in Madin-Darby canine kidney (MDCK) cells cultured in hypertonic media. Myo-inositol is taken up by MDCK cells on a Na(+)-coupled transporter whose activity increases sixfold 24 h after cells are switched to hypertonic medium. To investigate the mechanism of regulation of the cotransporter by hypertonicity, we used the cDNA encoding the canine Na(+)-myo-inositol cotransporter that we recently cloned to measure the abundance of the mRNA for the cotransporter and its rate of transcription after changes in osmolality. When MDCK cells were switched from isotonic to hypertonic medium, cotransporter mRNA abundance rose 10-fold in 16 h. Transcription of the cotransporter gene also rose and 16 h after the switch reached a peak approximately 15-fold that in isotonic cells. When cells were switched back to isotonic medium, mRNA abundance and transcription of the gene returned to isotonic levels in 8 h and transport rate reached isotonic levels in 48 h. Thus transcription appears to be the primary step in regulation of myo-inositol transport by hypertonicity.

Animals↗

Endothelin-1 and endothelin-3 binding to rat nephrons.

The existence of endothelin (ET) receptor subtypes has recently been implicated in the different biological effects of ET in various tissues. Indeed, the cDNAs for two types of ET receptors, ETA and ETB, have been cloned. To further gain insights into ET function in the kidney we examined 125I-labeled ET-1 and ET-3 binding to microdissected rat nephron segments. Specific ET-1 binding was highest in the inner medullary collecting duct, whereas the cortical and outer medullary collecting ducts as well as glomeruli showed moderate binding. There was low, although not significant, ET-1 binding to the early portion of the proximal tubule. Other nephron segments displayed little ET-1 binding. The binding profile of ET-3 along the nephron markedly resembled that of ET-1. Scatchard analyses of binding of ET-1 and ET-3 using cortical collecting ducts revealed a single class of receptor for both ET-1 and ET-3; apparent dissociation constants were 2.05 +/- 0.72 and 2.58 +/- 0.32 nM, and maximal binding capacity values were 0.408 +/- 0.058 and 0.511 +/- 0.047 fmol/mm, respectively. Displacement of 125I-ET-1 binding by unlabeled ET-3 was similar to that produced by unlabeled ET-1. Furthermore, a specific ETB agonist, BQ 3020, almost completely inhibited 125I-ET-1 binding in cortical collecting ducts, whereas a specific ETA antagonist, BQ 123, had little effect. These data indicate that cortical collecting ducts express ETB receptors, to which both ET-1 and ET-3 bind equally.

Animals↗

Medium tonicity regulates expression of the Na(+)- and Cl(-)-dependent betaine transporter in Madin-Darby canine kidney cells by increasing transcription of the transporter gene.

Betaine is one of the major compatible osmolytes accumulated by kidney derived Madin-Darby canine kidney cells cultured in hypertonic medium. Betaine is accumulated by Na(+)- and Cl(-)-dependent uptake from the medium. To gain insight into the mechanism by which hypertonicity evokes an increase in the Vmax of the betaine transporter in Madin-Darby canine kidney cells, we measured the relative abundance of mRNA for the transporter in cells shifted to a hypertonic medium and found parallel increases in mRNA abundance and cotransporter activity. The increase in mRNA levels preceded the increase in transporter activity slightly. Transcription of the gene for the transporter rose rapidly and to the same relative extent as mRNA abundance in cells shifted to hypertonic medium, indicating that transcription of the gene for the cotransporter plays a major role in regulating the accumulation of betaine in response to hypertonicity.

Animals↗

Relationship between pressure-rate product and myocardial oxygen consumption of normal and hypertrophic right ventricles in open-chest dogs.

There are few reports on the relationship between right ventricular performance and its myocardial oxygen consumption (RVMVO2). The present study was conducted to investigate the relationship between RVMVO2 and the mechanical performance of normal and hypertrophic right ventricles in open-chest dogs. Right ventricular hypertrophy (RVH) was induced by producing chronic right ventricular pressure overload by banding the pulmonary arteries of 8 puppies for 6 months. The experiment was performed under basal conditions and after increasing the RVMVO2 in the eight dogs with RVH as well as in 20 normal dogs. The RVMVO2 showed significant positive relationships with right coronary (RCA) flow, right ventricular systolic pressure, and right ventricular pressure-rate product (PRP) in both the normal right ventricle and RVH hearts. However, the slope between the PRP and RVMVO2 was significantly steeper in the normal right ventricle (RV) than in the hypertrophic RV. When the PRP was normalized for the thickness of the right ventricular free wall, the slope of the two regression lines merged into a single line of fit. These results suggest that the pressure-rate product can be used to predict myocardial oxygen demand not only in the normal RV but also in well-compensated, hypertrophic RV. Isoproterenol induced smaller increases in cardiac output in the dogs with RVH than in those with normal RV. It also appears that the cardiac output of the hypertrophic RV is less sensitive to beta-adrenoceptor stimulation than that of the normal RV.

Animals↗

Root-uptake of radioiodine by rice plants.

Root-uptake of iodine by rice plants from two different soil types was studied using an 125I tracer. At harvest, the 125I concentration was lowest in brown rice (hulled rice) followed by the rachis, stem and leaves. The transfer factors of iodine for brown rice grown on Andosol and Gray lowland soil (fine texture) respectively were 0.007 and 0.002. The ratio of the radioiodine concentrations between flag leaf (first leaf blade) and brown rice was about 400. Transfer factors in plants grown on Andosol were higher than those grown on Gray lowland soil. This may be related to the high 125I concentration in the Andosol soil solutions, particularly after the flowering period. The adsorption and desorption of iodine in the soil was effected by flooding with water and also by the cultivation of rice plants. The radioiodine concentration in the soil solutions first increased in the upper soil layer than in the lower layer. The desorption pattern of iodine was influenced by the soil types.

Iodine Radioisotopes↗

Effects of inosine on adenosine-induced coronary vasodilation in the open chest dog.

The effects of inosine (CAS 58-63-9) on adenosine-induced coronary vasodilation were studied in open-chest dogs. Inosine and hypoxanthine were infused into the coronary artery at a rate to obtain respective calculated coronary plasma concentrations of 10(-5) mol/l, and the dose-coronary flow response of adenosine was recorded with and without inosine or hypoxanthine infusion. When the maximum coronary dilation was obtained, 10 ml of 2 x 10(-3) mol/l 8-phenyltheophylline (8-PT) solution was injected into the femoral vein. Additionally, adenosine deaminase activity was measured in vitro in the presence of various concentrations of either inosine or hypoxanthine. It was found that inosine, but not hypoxanthine, intensified the coronary vasodilatory effect of adenosine, which was abolished by 8-PT injection: EC50 of adenosine was reduced from 10(-5.43) mol/l to 10(-5.90) mol/l by inosine. Inosine and hypoxanthine did not affect adenosine deaminase activity at concentrations of 10(-4) mol/l or less. These findings indicate that inosine intensifies the coronary vasoactivity of adenosine, independent of inhibition of adenosine deaminase activity.

Adenosine↗

[A case of an idiopathic enlargement of the right atrium, lacking in prominent right atrium contour and mimicking left pericardial defect on the chest X ray].

A 47-year-old man was admitted for evaluation of heart murmur in 1982. On admission, two-dimensional echocardiogram showed a giant right atrium with mild tricuspid regurgitation, but a chest X ray showed no prominent right atrium contour. Echocardiographic finding at various postures and chest X ray with artificial pneumothorax indicated little likelihood of left pericardial defect. An angiocardiogram and computed tomography showed the dilated right atrium with clockwise rotation. There was no indication of right atrial overload. Therefore, we made the diagnosis of an idiopathic enlargement of the right atrium. For about 10 years after discharge, we have followed up this patient. He has received no treatment and has been asymptomatic. On the other hand, echocardiography shows that the right atrium has gradually enlarged. Electrocardiogram has clearly revealed only a tall and slender peaked P wave in chest leads for the last 5 years. This may indicate not only an increasing load on the right atrium but also that the enlarged atrium is getting closer to the walls of the chest. We report this case of an idiopathic enlargement of the right atrium lacking in prominent right atrium contour, and mimicking left pericardial defect on chest X ray.

Cardiomegaly↗