Search PubMed⌕ Search

Biomedical subjects

N Nishimura

Publications and source records attributed to N Nishimura.

At least 199 records · Page 11Linked to original sources

Changes in serum bile acid composition in relation to histological findings after liver transplantation in piglets.

Changes in the composition of serum bile acids were investigated after orthotopic liver transplantation in piglets. Serum levels of all bile acid components rapidly increased during the anhepatic phase and then quickly decreased, returning to the preoperative state within 6 h of revascularization of the allograft. In the animals in which extrahepatic biliary stenosis was a complication, serum total bile acids (TBA) increased remarkably. A marked increase of hyocholic acid and marked decrease of hyodeoxycholic acid were noted; as percentages of TBA, the average levels per day were 91.3 +/- 1.3 and 5.0 +/- 1.3%, respectively. No change in chenodeoxycholic acid (CDCA) was observed. In the animals suffering acute rejection without extrahepatic biliary stenosis, serum TBA increased slightly and the percentage of CDCA rose, the average level being 29.6 +/- 1.5%. These results suggest that the measurement of the composition of serum bile acids may serve as a useful means of assessing allograft function after liver transplantation.

Animals↗

Localization of metallothionein in female reproductive organs of rat and guinea pig.

We demonstrated the localization of metallothionein (MT) in rat uterus and ovaries and in guinea pig mammary glands. During the cyclic changes from one estrous period to the next, strong MT immunostaining was found in the glandular epithelium of the endometrium and weak immunostaining was observed in the simple columnar epithelium. Interestingly, during estrus, the intensity of MT immunostaining decreased in the cytoplasm, whereas during metestrus, diestrus, and proestrus the intensity of strong and similar immunostaining was observed in both the cytoplasm and nucleus. During proestrus and estrus, the number of vaginal epithelial cells containing MT increased on the luminal side of the epithelium and inside the lumen. In rat ovary, strong immunostaining was observed in the cytoplasm and nucleus of granulosa-lutein cells of the corpus luteum and in the cytoplasm of the ovum. In mammary gland of non-pregnant guinea pig, very strong but scattered MT immunostaining was demonstrated in both cytoplasm and nucleus of some epithelial cells of the lactiferous ducts. The mammary tissue of the pregnant guinea pig showed an increase in MT staining in alveolar cells that had proliferated due to pregnancy. The presence of MT in the female reproductive organs, the tissues of which actively grow under the control of female sex hormones, indicates some as yet unknown association of MT with cell proliferation and differentiation.

Animals↗

Immunohistochemical localization of metallothionein in developing rat tissues.

Metallothionein (MT) is a cysteine-rich, low molecular weight protein inducible by heavy metal ions and various endogenous factors. Using an indirect immunofluorescent technique, we studied the localization of MT in developing rat tissues (kidney, small intestine, and liver). In kidney of the neonate and fetus, MT was found in both the cytoplasm and the nucleus of renal tubular epithelia. Localization of MT changed with shift of zonation in the renal cortex during development. Metallothionein was found mainly in the inner zone of the cortex but not in tubules of the neogenic zone on Day 4. Until Day 18, tubular cells containing MT were observed in a part of the cortex adjacent to the medulla, followed by a significant decrease in immunostaining by Day 27. In small intestine of the neonate, MT was localized predominantly in Paneth and goblet cells which play secretory roles. The number of goblet cells with strong immunostaining for MT was maximal on Day 27. In liver of 20-day fetuses and of 4-day-old neonates, both the cytoplasm and the nucleus of hepatocytes exhibited strong immunofluorescence. The intensity of MT staining diminished with development, and by 18-27 days after birth no immunofluorescence was observed in the nucleus. We further studied a possible association of MT with development by localizing MT in livers obtained from partially hepatectomized and laparotomized rats. Hepatectomy led to the appearance of MT not only in the nucleus and cytoplasm of hepatocytes but also in sinusoids and bile canaliculi. After laparotomy, MT immunofluorescence was observed only in the cytoplasm. The present results suggest a possible involvement of MT in cell proliferation and differentiation, as well as in transport and secretion of this metal-binding protein.

Animals↗

Effect of protein binding on high performance liquid chromatography analysis of drugs with an internal-surface reversed-phase silica column.

The effect of protein binding on the high performance liquid chromatography (HPLC) elution profile of drugs injected directly onto an internal-surface reversed-phase (ISRP) silica column was investigated. When a relatively large volume (greater than or equal to 100 microliters) of the sample solution containing warfarin and bovine serum albumin (BSA) was applied directly onto the ISRP column and elution was carried out with the mobile phase containing an organic modifier, two distinct peaks, both due to warfarin, appeared separated from the protein peak. The peak splitting was not observed in the case of antipyrine-BSA mixed solution, where the protein binding is weak. It was found that the drug bound at the strong-binding site on the BSA molecule was released slowly during the process of chromatography and was eluted as the first peak with a shorter retention time, while the drug bound at the weak-binding site was released quickly, and was eluted as the second peak together with the free drug. The warfarin-BSA interaction at the strong-binding site was evaluated, under minimum influence from the other binding site, from the warfarin concentration obtained from the first peak and the free warfarin concentration determined by the ultrafiltration method.

Animals↗

Determination of free drug in protein binding equilibrium by high-performance frontal analysis using internal-surface reversed-phase silica support.

An internal-surface reversed-phase silica column was employed in the frontal analysis method to determine free drug concentration in warfarin (Wf)-bovine serum albumin (BSA) mixed solution and in indomethacin(Im)-BSA mixed solution. When a 4-ml portion of aqueous solution containing 2-30 microM Im and 28 microM BSA and a 10-ml portion of aqueous solution containing 0.5-175 microM Wf and 28 microM BSA were applied, the elution curves reached a plateau level corresponding to both free drug and drug-BSA complex (beta-plateau), followed by another plateau due to free drug alone (gamma-plateau). The drug concentration at the gamma-plateau agreed well with the free drug concentration determined after ultrafiltration of the same solution. The gamma-plateau was observed even when the applied volume was reduced to a level which was insufficient to produce the beta-plateau. The injection of a 400-microliters portion of the 0.5-100 microM Im and 28 microM BSA mixed solution and a 90-microliters portion of 50 microM Im and 550 microM BSA mixed solution onto the ISRP silica column gave a clear gamma-plateau. Compared to the conventional frontal analysis, the present method can determine a wide range of drug levels with much smaller injection volume. This method is applicable to plasma. By a single frontal analysis, both free and total concentrations of carbamazepine in plasma were determined simultaneously.

Animals↗

[A case report of emergency Bentall re-operation].

A 51-year-old male of Marfan syndrome with annuloarotic ectasia underwent the Bentall operation. One and a half months later, he suddenly fell into the left ventricular failure associated with lung edema. Echocardiogram revealed total occlusion of the graft and aortic valve detachment was suspected. An emergency operation was performed. The aortic valve was completely detached due to infectious endocarditis. As anastomosed portions of the proximal coronary arteries and distal aorta were intact, these rims of the old graft were reserved. A new composite graft was anastomosed distally to the above reserved graft rims and sutured proximally to the trimmed aortic valvular ring. The patient survived the re-operation despite many post-operative complications such as mediastinitis, colon bleeding, renal failure and severe hepatic dysfunction.

Aorta↗

[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↗