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Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 1,081 records · Page 60Linked to original sources

Attenuated renal production of dopamine in patients with low renin essential hypertension.

Our previous studies have shown that a suppressed pressure natriuresis may contribute to the hypertensive mechanism in patients with essential hypertension (EHT), particularly in low renin patients (LRH). In this study, in order to clarify the role of renal dopaminergic activity in the blunted natriuresis of LRH, the conversion of 1-dopa (DOPA) to dopamine (DA) in the kidneys was investigated in 9 normotensive subjects (NT) and 20 EHT, including 15 normal renin EHT (NRH) and 5 LRH. All subjects were hospitalized and received a constant diet (Na:120mEq, K:75mEq daily). Plasma DOPA concentration (p-DOPA:HPLC-ECD), creatinine clearance (Ccr), urinary excretion of sodium (UNaV) and DA (UDA), as well as fractional excretion of sodium (FENa) were measured before and after the single oral administration of 1-DOPA (400mg). DOPA administration caused a significant increase of p-DOPA, UDA and FENa with undetectable DOPA levels in the urine in EHT. In addition, under the basal condition, UDA correlated positively with p-DOPA or the product of p-DOPA x Ccr, which might reflect the DOPA delivery at the renal proximal tubule. No significant difference was found in p-DOPA and the product of p-DOPA x Ccr among NT, NRH and LRH. However, the ratio of UDA/(p-DOPA x Ccr), which may indicate the conversion from DOPA to DA in the kidneys, was lower in EHT, especially in LRH, than that in NT. These results suggest that a reduced renal conversion from DOPA to DA may contribute to the attenuated natriuresis as well as renal dopaminergic activity in LRH.

Adolescent↗

Interrelationship between plasma ionized calcium, plasma noradrenaline (NA) and pressor response to infused NA in patients with essential hypertension.

We evaluated the role of calcium metabolism on plasma noradrenaline concentration (pNA) and pressor response to infused noradrenaline (NA-R) in patients with mild-to-moderate essential hypertension (EHT). Mean arterial pressure (MAP), plasma ionized calcium (pCa2+), and NA-R were measured at the basal condition in 17 EHT and after the administration of calcium antagonist, nifedipine (60mg, t.i.d., for 4 weeks) in 9 EHT. Under basal condition, pCa2+ correlated positively with pNA and negatively with NA-R in EHT. Following nifedipine therapy, persistent reductions of MAP and NA-R, a transient increase in pNA and a sustained increase of urinary excretion of calcium were observed. On the other hand, no significant change in pCa2+ was found during the therapy. Percent change in MAP following 4 weeks of nifedipine administration correlated positively with pCa2+ and pNA before the therapy. In addition, change in NA-R by nifedipine therapy correlated positively with the basal values of pCa2+ and PNA and negatively with NA-R before the treatment. A significant negative correlation between NA-R and pNA was observed following nifedipine therapy as well as the basal state. However, the slope of the regression line between NA-R and pNA decreased significantly after the treatment as compared to the basal state. These results suggest that calcium metabolism relating sympathetic nerve activity and NA-R may contribute to the hypertensive mechanism in EHT. The hypotensive effects of nifedipine may be caused partly by the attenuation of sympathetic nerve activity and NA-R.

Blood Pressure↗

A new antitumor antibiotic, FR900840. III. Antitumor activity against experimental tumors.

FR900840 [2S)-2-amino-2-carboxyethyl (3R)-2-diazo-3-hydroxybutyrate), a new antibiotic with antitumor activity was isolated from the fermentation broth of Streptomyces sp. No. 8727. Its antitumor activity was examined in three mouse tumor systems and ten human tumor systems. FR900840 had no clear effect on mouse ascitic tumors, P388 and L1210, and the B16 melanoma line, but had prominent antitumor effects on several human solid tumors. Its antitumor activity against A549 human lung adenocarcinoma was stronger than those of vinblastine, doxorubicin and cisplatin. These results suggest that FR900840 may become a useful prototype antitumor drug.

Adenocarcinoma↗

Gravity-dependent atelectasis. Radiologic, physiologic and pathologic correlation in rabbits on high-frequency oscillation ventilation.

The authors identify the radiologic features of progressive atelectasis induced under conditions of reduced lung volume. Control (n = 5) and experimental (n = 7) animals were placed on high-frequency oscillation (HFO) ventilation (mean airway pressure: 3 cm H2O) for 6 hours. In the experimental animals, lung volume was artificially reduced by pneumoperitoneum during HFO ventilation. Computed tomography scans and chest radiographs were obtained every hour, and arterial blood gases analyzed. No changes were detected in the control animals. In the experimental animals, in which hypoxemia developed, homogeneous opacity in the dependent lung was found on CT images, and chest radiographs showed a diffuse homogenous shadow with loss of lung volume. Study of pathologic sections from the lung showed that the roentgenographic findings represented atelectasis. The lung was divided into three zones, from dependent to nondependent regions: severe atelectasis, mild atelectasis, and normal lung. Hyperinflations eliminated atelectasis seen on the CT images and alleviated hypoxemia; however an undesirable effect that causes barotrauma also was observed.

Animals↗

Kinetics of chlorpromazine block of sodium channels in single guinea pig cardiac myocytes.

Block of sodium current by chlorpromazine in single ventricular myocytes isolated from guinea pigs was studied using the whole cell patch clamp technique. Chlorpromazine in micromolar concentrations reduced the amplitude of peak sodium current associated with step depolarizations from a holding potential of -140 mV. Concentration-response curves obtained with a holding potential of -140 mV were best fit by a 2:1 stoichiometry, and were shifted in the direction of lower concentrations when a holding potential of -100 mV was used. In agreement with this observation, the steady-state inactivation curve was shifted to more negative potentials by chlorpromazine. The block was not associated with any change in the time course of sodium current activation or inactivation during a depolarizing step. Chlorpromazine also produced marked use-dependent block as demonstrated by a cumulative increase in the block during a train of depolarizing pulses. This use dependence was due to a higher affinity of chlorpromazine for the inactivated state of sodium channels than for the resting state and to a very slow repriming of the drug-bound sodium channels from inactivation. These blocking actions could contribute to the antiarrhythmic effects of chlorpromazine at low concentrations and to the cardiotoxic effects at high concentrations.

Animals↗

Amiodarone blocks calcium current in single guinea pig ventricular myocytes.

Ca++ current (lca) block by amiodarone and the underlying mechanisms thereof were investigated in guinea pig single ventricular myocytes using the single suction pipette whole cell voltage clamp method. The dose-response curve revealed a 1:1 stoichiometry for binding of amiodarone to its receptor with an apparent dissociation constant of 5.8 microM in the resting state. Amiodarone, 5 microM did not significantly alter the time course of ICa decay, but did shift the steady-state inactivation curve for lca in the hyperpolarizing direction by 9.2 +/- 3.1 mV. Development of block at depolarized potentials was voltage-dependent between -20 and 10 mV with time constants of 112 +/- 33 and 755 +/- 212 msec at 10 mV. In the presence of 0.2 microM amiodarone, recovery from inactivation was fitted by a double exponential most likely indicating rapid recovery of the drug-free Ca++ channels and slow recovery of the drug-associated Ca++ channels with time constants of 44 +/- 12 and 108 +/- 403 msec, respectively, at -80 mV. The proportion of the current recovering via the slow phase was 36 +/- 7%. By using this value, we estimated the dissociation constant in the inactivated state to be 0.36 microM. Amiodarone's marked use-dependent block of lca is explicable in terms of its high affinity for, and slow dissociation from, Ca++ channels in the inactivated state. These results suggest that amiodarone blocks lca in both the resting and inactivated states.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗

[Erythropoiesis and hemolysis in hemodialysis patients].

In order to investigate the pathogenesis of renal anemia, erythroid marrow cellularity, factors affecting erythropoiesis and hemolysis, hemolysis starting point by Parpart method and red cell life-span were studied in 21 patients undergoing hemodialysis (HD). Mean value of serum erythropoietin level (EPO) in HD patients was 28.4 mU/ml, which value was nearly equal to that in healthy subjects. Total erythroblast count was higher than normal up to 25.2% in HD patients with Ht below 25% (A group), on the other hand, in HD patients with Ht above 25% (B group) it was 21 6%, nearly equal to normal. Total erythroblast counts positively correlated to EPO level, but did not correlate to ribonuclease, aluminium and parathyroid hormone. Red cell life-span was 23.4 days in A group, and it was 19.8 days in B group Hemolysis starting point was observed at 0.61% NaCl in B group, and at 0.56% in A group. Hemolysis starting point negatively correlated to red cell life-span, but did not correlate to BUN, serum creatinine and serum guanidino compound. Hb level negatively correlated to nuclear cell counts of bone marrow in HD patients, and positively correlated to hemolysis starting point. These results suggested that erythroblast count was controlled by both erythropoietin and hemoglobin levels in HD patients. Hemoglobin level in HD patients was maintained by balance of counteracting factors between erythropoiesis and hemolysis.

Erythrocyte Aging↗

[Variability of respiratory function variables in healthy aged men].

We studied six healthy young males (young group; mean age 30.0 +/- SD 1.8 years, FVC 4.5 +/- 80.45 l and FEV1.0/FVC 87.6 +/- 4.3%), and five aged healthy males (aged group; age 63.8 +/- 3.0 years, FVC 3.40 +/- 0.22 l and FEV1.0/FVC 75.9 +/- 3.2%) to evaluate the variability of pulmonary function. We measured flow-volume curves, closing volumes, functional residual capacities (FRC) and airway resistances (Raw) five times in different days in each person. The coefficients of variation in FVC and FEV1.0 in both groups were less than 5%, and there were no significant differences in these coefficients between the two groups. Although the coefficients in FEV1.0/FVC in both group were less than 5%, there was a significant difference between the two groups. The coefficients in flow at 50% FVC (V50), maximal midexpiratory flow (MMF) and peak expiratory flow rate (PEFR) in the aged group were significantly larger than those in the young group. The coefficients in closing volume, FRC, Raw and specific airway conductance (SGaw) using body plethysmography exceeded 10% in both groups, and the coefficients in Raw and SGaw in the aged group were significantly larger than those in the young group. These results suggest that aging worsens the variabilities of respiratory function in FEV1.0/FVC, MMF, V50, Raw and SGaw.

Adult↗

[Treatment of acute lymphocytic leukemia in adult].

Since April, 1978 to October, 1988, 66 acute lymphocytic leukemia (ALL) patients aged 15 to 79 (21 L1, 43 L2, 2 L3/6 Ph1+) were treated with 3 different therapeutic protocols. The drugs used for induction were VCR (VDS) + Pred, followed by DNR + VCR (VDS) + 6MP + Pred and VCR (VDS) + L-asp + Pred in protocol I, Ad + VCR + Pred in protocol II and DNR + VCR + Pred in protocol III. Complete remission (CR) was attained in 72.7% of 66 patients. The CR rate of each group as followings; 71.4% in protocol I and 75.0% in protocol II and III, respectively. The median duration of remission was 10.2 months + and the probability of being in continuous CR at 3 years was 21.9%. For the 48 patients in remission the median survival was 17.8 months and the probability of being alive at 3 years was 24.3%. The intensified induction and consolidation therapy is expected in the cure oriented treatment of adult ALL.

Adolescent↗

[Acute massive mediastinal hemorrhage three weeks after mitral valve replacement in a patient with systemic lupus erythematosus].

Systemic lupus erythematosus (SLE) is one of the most common autoimmune diseases and patients suffering from this disease often died of massive hemorrhage. We report the case of a patient who died of acute massive hemorrhage three weeks after mitral valve replacement. The patient, a 42 year-old woman, had been diagnosed as having valvular heart disease at the age of 10. She underwent mitral commissurotomy at the ages of 18 and 32. SLE was diagnosed 8 years previously and corticosteroid therapy was initiated. The patient was experiencing exertional dyspnea again 1 year ago and mitral valve replacement was performed for recurrent stenosis. The postoperative course seemed to be uneventful, but on the 21st postoperative day, acute massive mediastinal hemorrhage occurred, and the patient eventually died of septicemia. Massive hemorrhage in SLE patients usually occur in the central nervous system or alimentary tract. However, bleeding can occur anywhere, so great care must be taken in regulating anticoagulant therapy.

Adult↗

[Ultrasound imaging of the muscle in muscular dystrophy].

Ultrasound imaging of muscle was performed on 40 patients of Duchenne muscular dystrophy on lower and upper extremities. In the control subjects, there was good visualization of bone and fascia with echo-free muscle tissue. With progression of the disease, the muscle echo was increased with corresponding loss of fascia echo in muscular dystrophy. A few advanced cases showed relatively echo-free muscle because of diffuse adipose tissue infiltration. Ultrasound imaging can reveal the muscular lesion and its distribution, and is valuable for monitoring the progression of the disease.

Adolescent↗

[Quantitative comparison of ventilator-induced work during simulated CPAP in eight demand-flow valve ventilators].

The ventilator-induced work during continuous positive airway pressure (CPAP) mode in demand-valve ventilators was evaluated by using a piston pump as a simulator for active breathing. A piston pump delivered and withdrew a stroke volume of 500 ml at rates of 10, 20 and 40 cycle.min-1 with a sinusoidal waveform. A hot-wire flowmeter and a differential pressure transducer were interposed between the pump and ventilators and their signals were fed to a microcomputer to display a pressure-volume loop. The area of the loop was divided into the four parts. Inspiratory work associated with the opening of the demand valve was represented by the area of baseline airway pressure (BPa) during inspiration. The remaining area during inspiration reflected the work done by the ventilators. Expiratory work for overcoming the flow resistance of the expiratory apparatus was represented by the area above BPa during exhalation. The fourth was the area below the baseline during exhalation. The Puritan-Bennett 7200a, the Bear 5, the Siemens Servo 900C, the Hamilton Veolar, the Bird 6400ST, the Engström Erica, the Dräger EV-A, and the CPU-1 were examined at varying CPAP and pressure support levels. Because of demand valve oscillation throughout inspiration, the inspiratory workload of the Bear 5, the Siemens Servo 900C, the Hamilton Veolar, the Bird 6400ST, and the Dräger EV-A could not be calculated. Expiratory flow-resistive work was higher in the Siemens Servo 900C and the Bird 6400ST than the others. The present system can assess the entire performance of ventilators, and may serve to compare ventilators' performance.

Evaluation Studies as Topic↗

[Endothelin and endogenous digitalis-like substance in cardiovascular regulation: a review].

Recent findings on endothelin, an endothelium-derived vasoconstrictor substance and endogenous digitalislike Na+, K+-ATPase inhibitor (s) obtained from animal and clinical experiments are reviewed. Endothelin is one of the most potent vasoconstrictive substances ever found; the pressor responses last for more than one hour after the bolus injection in rats. Because the pressor responses have not been attenuated by any known receptor-antagonists, the vasoconstriction is mediated by the endothelin receptors. Since messenger RNA for endothelin increases with thrombin, it may be involved in the damages of blood vessels. Radioimmunoassay for endothelin revealed that immunoreactive endothelin is increased in plasma of patients with chronic renal failure. Therefore, the plasma level of endothelin can be an index for some circulatory disorders. Since the Na+, K+-ATPase inhibitor cross-reacts with antidigoxin and antiouabain antibody, it is called a digitalis-like substance. We have demonstrated that cells containing the immunoreactive-substance to antidigoxin and antiouabain antibodies are restricted in the paraventricular and supraoptic nucleus of the hypothalamus, and that the plasma digoxinlike immunoreactivity increases with intracerebroventricular and intravenous infusions of hypertonic saline in rats. Because plasma concentrations of the immunoreactive substance significantly correlate with blood pressure, the substance seems to be involved in hypertension associated with excess intake of sodium salt.

Animals↗