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Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 217 records · Page 12Linked to original sources
PubMed1989

Effects of hypothermia on rat brain pHi and phosphate metabolite regulation by 31P-NMR.

The effects of arterial alphastat regulation on brain intracellular pH (pHi) and several phosphate metabolites were assessed in anesthetized rats during hypothermia (28.6 +/- 0.2 degrees C) and normothermia (36.2 +/- 0.2 degrees C) by using 31P high-field (8.5 T) nuclear magnetic resonance (NMR). There were significant differences in pHi and metabolite ratios at the two temperatures under conditions of equal minute ventilation. During hypothermia, the brain pHi was 0.09 U higher, the phosphocreatine-to-inorganic phosphate (PCR/Pi) ratio 49% larger, and Pi-to-ATP 20% lower than at normothermia. These changes were fully reversible on warming the animal. The change in brain pHi/temperature was -0.011U/degrees C (95% confidence interval -0.007 to -0.016). The brain's ability to regulate its pHi and phosphate metabolism during hypercapnic acid-base stress was studied by using 10% CO2 ventilation. Hypothermic rats showed a larger fall in brain pHi (0.145 +/- 0.01 U, 7.15-7.01) with 10% CO2 than normothermic rats (0.10 +/- 0.02 U, 7.06-6.96). Similarly ventilated rats had a larger fall in arterial pH with 10% CO2 at hypothermia (0.36 +/- 0.04 U) than normothermia (0.24 +/- 0.01 U), so the delta brain pH/delta arterial pH was the same at both temperatures. The brain PCr-to-Pi ratio decreased approximately 20% during 10% CO2 breathing in both hypothermic and normothermic animals. Brain pHi and metabolite ratios returned to base line 30-50 min after CO2 washout in both groups. In summary, lowering body temperature while maintaining constant ventilation leads to changes in brain pHi and metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Jet flow-regulated expiratory resistance to maintain constant CPAP during the entire respiratory phase.

We have developed a new continuous positive airway pressure (CPAP) device that consists of a microcomputer, a pressure transducer, and a pair of electronic interface valves. One of these valves creates the inspiratory demand flow, and the other creates the opposing jet flow by acting as an expiratory valve to maintain a constant CPAP. By controlling the two electronic interface valves, the airway pressure can be kept constant during the entire respiratory cycle. We compared our device with CPAP systems supplied with commercially available ventilators: the Puritan-Bennett 7200a, the Bear 5, the Servo 900C, and the CV 2000. A two-chambered spring loaded model lung was used to simulate inspiration and a piston pump model lung to simulate active exhalation. We compared both the inspiratory triggering work (WWIt) and expiratory flow-resistive work (WE) of each ventilator while in CPAP mode by calculating the corresponding areas of the pressure-volume loops using electrical integration. The WWIt of our apparatus and demand-flow ventilators was much smaller than that of the CV 2000. In our device, WE was also much smaller than those of the others. These results indicate that our device can be used for CPAP without causing airway pressure fluctuation, and therefore, without imposing an extra workload on the patient.

Humans↗
PubMed1989

Analysis of historical control litter parameters of reproduction toxicity studies in Sprague-Dawley derived rats.

Control litter data from reproduction toxicity studies in SD derived rats bred in our closed colony were investigated for historical changes, differences due to study design or generations, seasonal variations and effects of vehicle-treatment. The litter size did not change visibly during the entire 16-year period, but the number of live fetuses differed significantly between study designs or generations. The fetal weight gradually increased during these years. The malformation rate decreased, while the rate of 14 th ribs remained stable. There were no seasonal variations and no effects of vehicle-treatment.

Animals↗
PubMed1989

Interaction of noradrenaline and dopamine in patients with essential hypertension or with pheochromocytoma.

To analyse the interaction of noradrenaline (NA) and dopamine (DA) release, the present study compared urinary outputs of total NA and DA as well as plasma levels of total NA and DA in normotensive (NT) subjects, in patients with essential hypertension (EHT) and in a patient with pheochromocytoma. Significant correlations between total NA and DA in urine were observed in NT subjects, in patients with EHT and in a patient with pheochromocytoma. A significant correlation was observed in plasma total NA and DA of blood collected from several veins except for the tumor vein, by indwelling catheter, in a patient with pheochromocytoma. These results suggest that DA is released from sympathetic nerve terminals in response to an augmented release of NA.

Adrenal Gland Neoplasms↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

[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↗
PubMed1989

[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↗
PubMed1989

[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↗
PubMed1989

[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↗