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Biomedical subjects

N Nishimura

Publications and source records attributed to N Nishimura.

At least 73 records · Page 4Linked to original sources

[Pharmacokinetics and the lung uptake of lidocaine during epidural anesthesia].

In order to investigate the pharmacokinetics of lidocaine especially the lung uptake during epidural anesthesia, we measured the lidocaine concentrations of arterial and central venous blood simultaneously using a homogeneous enzyme immunoassay. Then the lung extraction ratio was calculated as (1-arterial lidocaine concentration/central venous lidocaine concentration) X 100%. With only epidural anesthesia, the lung uptake of lidocaine was above 30% during the first 40 minutes, but was less after additional administration. After general anesthesia with thiamylal, enflurane, nitrous oxide and oxygen, the lung uptake was 30 approximately 40% following initial and additional administrations. There was a positive correlation between the lung extraction ratio and the central venous lidocaine concentration 5 minutes after the initial administration. Having used laryngotracheal lidocaine spray during endotracheal intubation, the lung extraction ratio could not be calculated since this resulted in direct lidocaine administration to the lungs. In conclusion, the lung plays an important role in keeping the arterial lidocaine concentration low.

Adult

[Electrophysiological effects of magnesium sulfate on human conduction system].

Electrophysiological studies were performed to evaluate the effects of MgSO4 on human conduction system. Nine patients who received 20 mg/kg of MgSO4 did not show any significant changes in the electrophysiological parameters except for prolongations in the PR and AH intervals. After the infusion of 40 mg/kg of MgSO4 in eleven patients, sinus cycle length and corrected sinus node recovery time were increased but statistically insignificantly. Sinoatrial conduction time, the PR interval and AH interval were increased. The effective refractory period (ERP) of right atrium, ERP of atrioventricular node (AV node), ERP of right ventricule and ERP/QTc were increased significantly. These findings suggests that the antiarrhythmic effects of magnesium were due to (1) suppression of the functions of the sinus and AV nodes, and (2) shortening of the duration of the ventricular vulnerable period during the cardiac cycle and prevention of ventricular arrhythmias related reentry mechanism.

Adolescent

[A case of anomalous origin of right coronary artery from the left sinus of Valsalva with ventricular aneurysm ventricular tachycardia and paroxysmal A-V block].

A 51-year old man was admitted to our hospital, because of syncope. During admission, he had three episodes of syncopal attack. During the episodes, monitor ECG showed two times of ventricular tachycardia and one of paroxysmal A-V block. The left ventriculogram showed dilatation of left ventricle with posterobasal aneurysm, anterobasal and apical hypokinesis. The left coronary artery was normal. The right coronary artery originated from the left sinus of Valsalva and passed through between aortic root and pulmonary trunks. There was no atherosclerotic lesions in both coronary arteries. Non-sustained ventricular tachycardia was induced by triple premature stimulations. The inverse relation between the coupling interval of premature stimulation and the echo interval was recognized. Lidocaine (50 mg IV), Flecainide (300 mg/day), Mexiletine (450 mg/day), and Aprindine (60 mg/day) prevented ventricular tachycardia. Rapid atrial pacing induced paroxysmal A-V block. Permanent pacemaker was implanted because of syncope due to paroxysmal A-V block and ventricular tachycardia was prevented by Aprindine. Recently, the case with anomalous origin of the coronary artery increased by the popularity of coronary angiography. But, this case considered to be rare because of complication with ventricular aneurysm and lethal arrhythmia (ventricular tachycardia and paroxysmal A-V block).

Coronary Vessel Anomalies

[Kinetics of catecholamines in amniotic fluid implicated with onset of labor pain].

There are several controversies related to labor initiation in term. I therefore tried to analyse the relationship between the onset of labor and the dynamics of catecholamine-concentrations in amniotic fluid using the LC-EC method. Results are as follows. 1. Dopamine levels in amniotic fluid increased with gestational age. 2. Norepinephrine and Dopamine levels were higher in women with uterine contraction than in those without uterine contraction. 3. PGF2 alpha production in amnion increased significantly when it was incubated thirty minutes with CAs compared to that incubated only with Hanks' BSS. The PGE production rate in amnion was five or six times as great as that in PGF2 alpha. In conclusion, it is supposed that CAs in amniotic fluid may play a role in the initiation of uterine contraction.

Amnion

Establishment and characterization of a cultured cell line derived from nitrosamine-induced pancreatic ductal adenocarcinoma in Syrian golden hamsters.

Seven kinds of pancreatic ductal adenocarcinomas induced by N-nitrosobis(2-hydroxypropil)amine in Syrian golden hamsters were established as transplantable tumor lines on syngeneic animals. These tumor lines were all well or moderately differentiated adenocarcinomas, showing various velocities of growth, unrelated to the grade of histological differentiation. A cell line, designated HaP-T1, was established in continuous tissue culture from one of these homografts. The cells grew in a monolayered sheet with an approximately 17-hour population doubling time. Chromosomal analysis revealed that the modal chromosomal number of the cell line was 44. HaP-T1 cells showed apparent tumorigenicity both on syngeneic hamsters and athymic nude mice, but they grew much faster when injected into the former animals. Morphological characteristics of HaP-T1 cells and tumors induced by HaP-T1 inoculation in both animals revealed apparent epithelial characteristics resembling ductal adenocarcinoma of the pancreas. These transplantable tumor models will contribute to the further investigation in the field of pancreatic cancer.

Animals

Inhibition of DNA synthesis by protein kinase C-activating phorbol esters in NIH/3T3 cells.

Fibroblast growth factor (FGF) plus insulin induced DNA synthesis in and proliferation of NIH/3T3 cells. The protein kinase C-activating phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), inhibited both the DNA synthesis and cell proliferation induced by FGF plus insulin. The concentration of TPA required for 50% inhibition of the DNA synthesis was about 5 nM. Phorbol-12,13-dibutyrate, another protein kinase C-activating phorbol ester, also inhibited the DNA synthesis but 4 alpha-phorbol-12,13-didecanoate, known to be inactive for this enzyme, was ineffective. DNA synthesis started at about 12 h after the addition of FGF plus insulin. The inhibitory action of TPA on the DNA synthesis was observed when it was added within 12 h after the addition of FGF plus insulin. These results suggest that phorbol esters exhibit an antiproliferative action through protein kinase C activation in NIH/3T3 cells, and that this action of phorbol esters is due to inhibition of the progression from the late G1 to the S phase of the cell cycle.

Animals

General pharmacology of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazole difumarate. 2nd communication: Effects on the circulation and the other systems.

Effects of 1-(2-ethoxyethyl)-2(4-methyl-1-homopiperazinyl)benzimidazole difumarate (KB-2413) on the circulation and the other systems were compared with those of ketotifen and chlorpheniramine. 1. Among the effects on the circulation and the respiratory system, KB-2413 as well as ketotifen and chlorpheniramine transiently inhibited respiration at 3 mg/kg i.v. and slightly decreased blood pressure in dogs. KB-2413 slightly decreased heart rate in dogs, but ketotifen slightly increased it. 2. KB-2413 at 100 mg/kg p.o. slightly decreased the volume of gastric juice in rats and dose-dependently increased biliary secretion in rats in the dose range of 10-100 mg/kg i.d. On the other hand, ketotifen and chlorpheniramine decreased biliary secretion. 3. KB-2413 inhibited the spontaneous movements of various isolated smooth muscles at a high concentration of 10(-4) g/ml. 4. The autonomic system in cats and the motor nervous system in rats were not influenced by KB-2413 at 3 mg/kg i.v. 5. The blood clotting system, blood sugar level, urine volume and urinary electrolytes in rats were not affected by KB-2413 in the dose range of 10-100 mg/kg p.o. 6. KB-2413 inhibited carrageenin-induced rat paw edema at 100 mg/kg p.o. In conclusion, KB-2413 showed a less potent effect on the circulation and the other systems than ketotifen and chlorpheniramine, and no results suggested serious side effects of KB-2413.

Animals

The mechanism of cadmium-induced lysozyme enhancement in rabbit kidney.

The effect of cadmium on the renal lysozyme level was examined by injecting male albino rabbits subcutaneously with 1 mg cadmium/kg body weight three times a week for 1 or 3 months. The lysozyme level in the renal brush border membrane of the cadmium-treated animals was elevated ten-fold. The lysozyme activity in the liver and small intestine tissue homogenates of rabbits was elevated by a 1-month treatment with cadmium, markedly elevated in the kidney, but markedly reduced in the spleen and lungs. Exposure to cadmium for 3 months produced an essentially similar effect on the enzyme level in the tissue, except for the lungs in which the lysozyme level returned to the preinjection level. This marked increase in the lysozyme level in the kidney of cadmium-treated rabbits was confirmed by an indirect immunofluorescent antibody technique. In control animals, intracellular distribution of the enzyme was selectively distributed to only a small number of proximal tubules, with none distributed in the medulla or glomerulus. However, after expose to cadmium, the renal tubules showed strongly positive lysozyme staining. In addition to an increase in intensity of the specific fluorescence, this enzyme was widely distributed not only in the proximal convoluted portion, but also in the straight portion of the proximal tubules, which essentially showed no enzyme activity under normal conditions. The enzyme in these cells was evenly distributed throughout the cytoplasm. The plasma lysozyme level increased immediately after the administration of cadmium, and detectable amounts of the enzyme began to appear in urine from the 3rd week after the first injection, with a 1-week lag after the maximum level of lysozyme in the plasma. This high level of plasma lysozyme, varied two-to four-fold over the control, and lysozymuria continued throughout the experiment. The concentration of cadmium in the renal cortex was 141 micrograms/g wet tissue at 1 month, and 208 micrograms at 3 months. In conclusion, the cadmium-induced enhancement of the lysozyme level in the renal cortex may be due primarily to the elevation of the lysozyme level in plasma by cadmium. The enzymatic high net positive charge, characteristic of lysozyme, may contribute greatly to this mechanism. In addition, the excretion of a large amount of lysozyme into the urine observed in a later stage may be due to the concomitant occurrence of leakage from the destroyed tubular cells and reduced tubular reabsorption of filtered enzyme, whereas lysozymuria at an early stage may be solely due to excess amounts of plasma lysozyme.

Animals

Increased production of aspartase in Escherichia coli K-12 by use of stabilized aspA recombinant plasmid.

Recombinant plasmid pYT471, which consists of the aspartase gene (aspA) and the multicopy vector pBR322, was lost from cells of Escherichia coli K-12 at high frequencies in medium in which aspartase was abundantly formed due to release from catabolite repression. This plasmid loss was not completely prevented by the selective pressure of antibiotic addition. To increase the stability of the aspA plasmid, pNK101 (pBR322::aspA-par) was constructed by using the partition locus (par) derived from the low-copy vector pSC101. In E. coli K-12 cells, pNK101 was lost at a frequency as low as 0.4% per cell generation in nonselective medium, whereas pYT471 was lost at a frequency as high as 8.5%. Cells harboring this stable plasmid produced ca. 30-fold more aspartase than did cells harboring the unstable plasmid after 30 cell generations. Thus, we could increase aspartase production by stabilizing the aspA recombinant plasmid.

Ammonia-Lyases

[Anti-allergic effects of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazole fumarate (KB-2413)].

The effects of KB-2413 on four types of allergic reactions classified by Coombs and Gell were investigated. KB-2413 inhibited homologous passive cutaneous anaphylaxis and passive anaphylactic bronchoconstriction in guinea pigs mediated by IgE-like antibody, and ED50 values were 0.0017 mg/kg, p.o., and 0.022 mg/kg, p.o., respectively. KB-2413 also inhibited IgG-mediated anaphylactic bronchoconstriction in guinea pigs actively sensitized with egg albumin. Both complement-dependent immune hemolysis and complement-independent hypotonic hemolysis were inhibited by KB-2413 in a concentration-dependent manner. KB-2413 had no effect on the Forssman systemic reaction. The passive Arthus reaction in guinea pigs sensitized with anti-egg albumin rabbit serum was unaffected by KB-2413. However, the early stage of the active Arthus reaction in rabbits sensitized with egg albumin was inhibited. KB-2413 had an inhibitory effect on the efferent phase of delayed-type hypersensitivity induced by picryl chloride (PC-DTH) in mice. On the other hand, the afferent phase of PC-DTH in mice was unaffected. These results suggest that KB-2413 strongly suppresses type I allergic reactions, and it slightly suppresses type II, III and IV allergic reactions.

Animals

Inhibition of chemical mediator release from human leukocytes and lung in vitro by a novel antiallergic agent, KB-2413.

The effect of KB-2413 on IgE-mediated histamine and LTC4 release from leukocytes obtained from asthmatic patients who were sensitive to mites, and from human lung tissues passively sensitized with IgE myeloma serum was studied. KB-2413 inhibited the IgE-mediated chemical mediator release concentration dependently at a range of 10(-4) to 3 x 10(-3) M. KB-2413 did not enhance histamine release at a higher concentration unlike ketotifen. These findings suggest that the inhibitory effect of KB-2413 on the release of chemical mediators contributes to the anti-allergic activity of this compound.

Benzimidazoles

[Histological study of muscle in the experimental hypophosphatemic rat].

Using hypophosphatemic rat maintained on a low phosphate diet as a model for human rickets and osteomalacia, the skeletal muscle was histochemically and electron microscopically examined, in comparison with specimens obtained from normal control animals. In muscles obtained from hypophosphatemic animals, the type 2 muscle fibers were increased in number, and the type 1 fibers were atrophic. Electron microscopic studies revealed some atypical structures of mitochondria with fusion of cristae in the muscle spindles of intrafusal muscle fibers. The presynapse, the secondary cleft, and the endplate plasm were significantly atrophic in the extrafusal neuromuscular junction. Mitochondrial vacuolization was observed in the presynapse. These results indicated the presence of immature muscle fibers, dysfunction of the energy metabolism of the mitochondria and neurogenic disorders in hypophosphatemic muscles.

Animals

[Usefulness of caerulein in suppressing post-TAE complications of the gallbladder].

While transcatheter hepatic arterial embolization (TAE) has been extensively performed as a form of treatment for nonresectable malignant hepatic tumors, complications, such as abdominal pain, fever or leukocytosis due to gallbladder infarction by embolic materials frequently occur and have not yet been overcome. We devised a new procedure for reducing the incidence of gallbladder infarction by administering caerulein prior to TAE. Between 1984 and 1986, 63 patients with hepatocellular carcinoma were treated by TAE with the use of Gelfoam. These patients were divided into 3 groups. Fourteen patients underwent TAE in which the tip of the catheter was placed in the right hepatic artery distal to the origin of the cystic artery (group A). In the other patients the tip of the catheter was placed proximal to the origin of the cystic artery; 40 patients were not treated by caerulein (group B); 9 patients were administered caerulein 20 micrograms intramuscularly 15 to 30 minutes prior to TAE. The incidence of complications after TAE, such as abdominal pain, fever over 38 degrees C, leukocytosis and ultrasonographical abnormalities of the gallbladder was compared in these 3 groups. The results showed that in group C (TAE after administration of caerulein), the incidence of complications was significantly decreased compared with group B(TAE without caerulein). The authors suggest that post-TAE infarction of the gallbladder is effectively diminished by contracting it with caerulein.

Carcinoma, Hepatocellular