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Biomedical subjects

J Watanabe

Publications and source records attributed to J Watanabe.

At least 433 records · Page 24Linked to original sources
PubMed1988

Retroperitoneal seminoma with simultaneous occurrence in the prostate.

We report a case of retroperitoneal seminoma with simultaneous occurrence in the prostate. The testes were normal on physical and ultrasound examination. In this case a multicentric occurrence of seminoma was considered rather than metastasis from the retroperitoneum to the prostate. Systemic chemotherapy with vincristine, peplomycin and cisplatin was effective for the prostatic as well as the retroperitoneal lesion.

Dysgerminoma↗
PubMed1988

Radioimmunotherapy of transplanted small cell lung cancer with 131I-labelled monoclonal antibody.

Monoclonal antibody TFS-4 has previously been shown to react selectively with human small cell lung cancer (SCLC). We evaluated the use of 131I-labelled TFS-4 for the treatment of established human SCLC transplanted in nude mice. The specific accumulation of the antibody in the transplanted tumour was recorded by both scintigraphic and biodistribution studies. Administration of 200 microCi 131I-labelled TFS-4 inhibited tumour growth when compared with the same radiation dose of the control monoclonal antibody. The therapeutic effect was dose-dependent and complete disappearance of the tumour was observed transiently in one out of the three animals following the administration of 500 microCi 131I-labelled TFS-4.

Adenocarcinoma↗
PubMed1988

Age-dependent pulmonary first-pass elimination of propranolol in rats.

Plasma levels of propranolol after 2.5 mg kg-1 given i.v. and i.a. have been compared in 3- to 4-week-old rats to evaluate the effect of age on pulmonary first-pass elimination of the drug. In 5- to 52-week-old rats, the area under the plasma concentration-time curve (AUC) after an intra-arterial dose was always larger than that after the i.v. dose. The plasma elimination half-lives after both routes of administration were almost identical, but tended to increase with age between weeks 7 and 104. First-pass pulmonary clearance and extraction ratio tended to decrease with age between weeks 7 and 52.

Aging↗
PubMed1988

Propranolol uptake with high capacity by rat perfused lung.

Lung isolated from 7-week-old rats was perfused with pH 7.4 Krebs-Ringer bicarbonate buffer solution (35 mL) containing 1 to 100 micrograms mL-1 of propranolol and 3% BSA at the recirculation rate of 8 mL min-1. Almost parallel bi-exponential drug concentration-time curves were obtained at the initial load lower than 10 micrograms mL-1, whereas relatively slow, mono-exponential decline was found after perfusion at 100 micrograms mL-1. Pharmacokinetic analysis for the perfusate propranolol concentration-time curves when loaded at 1 to 10 micrograms mL-1 yielded almost comparable values for the pulmonary perfusion clearance (0.387 +/- 0.092 to 0.486 +/- 0.095 mL min-1 g-1). In contrast, this parameter was significantly reduced at 100 micrograms mL-1 (0.113 +/- 0.042 mL min-1 g-1). The present findings suggest a trend towards saturation kinetics in the in-vitro pulmonary clearance of propranolol.

Animals↗
PubMed1988

Influences of pressure surrounding the heart and intracardiac pressure on the diastolic coronary pressure-flow relation in excised canine heart.

We investigated the change in the instantaneous diastolic left coronary pressure-flow relation (DPFR) when the pressure surrounding the heart (SHP), right heart pressure (RHP), and left heart pressure (LHP) were systematically varied. Eight excised and maximally vasodilated canine hearts placed in an air-tight chamber were used. To obtain a capacitance-free DPFR, coronary perfusion pressure was slowly decreased (about 2 mm Hg/sec) during a prolonged diastole. The zero-flow pressure (Pf = 0) and the slope of the DPFR were analyzed. The mean values of the slope did not change significantly throughout the interventions. The mean value of Pf = 0 in the control state (SHP = RHP = LHP = 0 mm Hg) was 6.0 +/- 2.0 mm Hg (mean +/- SD, n = 8), significantly higher than the venous outflow pressure, RHP (p less than 0.001), and the other two pressures (p less than 0.001). When SHP was raised to 15 and 30 mm Hg, while the other pressures remained at 0 mm Hg, the mean values of Pf = 0 increased to 20.9 +/- 2.4 and 35.6 +/- 3.1 mm Hg (p less than 0.001 and p less than 0.0005, respectively, vs. control). The mean values of Pf = 0 when only RHP was elevated to 15 and 30 mm Hg were 16.0 +/- 1.5 and 29.3 +/- 1.5 mm Hg (p less than 0.001 and p less than 0.0005 vs. control). On elevation of LHP to 15 and 30 mm Hg, the mean values of Pf = 0 were 12.0 +/- 2.8 and 17.3 +/- 3.6 mm Hg (p less than 0.01 and p less than 0.01 vs. control). When both SHP and LHP were almost evenly elevated to about 15 and 30 mm Hg, the mean values of Pf = 0 were raised to 22.0 +/- 2.9 and 35.3 +/- 3.2 mm Hg, respectively. These mean values were not significantly different from those when only SHP was elevated to the comparable levels. The observation that Pf = 0 exceeded RHP in the control state and that RHP, which was elevated above the preceding Pf = 0, was identical with the present Pf = 0 supports the vascular waterfall mechanism when RHP is low. Furthermore, the evidence that the degree of DPFR shift was almost linearly dependent on the SHP level rather than on the LHP level indicates that the pressure on the epicardial side is one of the factors that determines the pressure at the top of the vascular waterfall.

Animals↗
PubMed1988

Glucagon receptors in endothelial and Kupffer cells of mouse liver.

To determine whether hepatic sinusoidal cells contain glucagon receptors and, if so, to study the significance of the receptors in the cells, binding of [125I]-glucagon to nonparenchymal cells (mainly endothelial cells and Kupffer cells) isolated from mouse liver was examined by quantitative autoradiography and biochemical methods. Furthermore, the pathway of intracellular transport of colloidal gold-labeled glucagon (AuG) was examined in vivo. Autoradiographic and biochemical results demonstrated many glucagon receptors in both endothelial cells and Kupffer cells, and more receptors being present in endothelial cells than in Kupffer cells. In vivo, endothelial cells internalized AuG particles into coated vesicles via coated pits and transported the particles to endosomes, lysosomes, and abluminal plasma membrane. Therefore, receptor-mediated transcytosis of AuG occurs in endothelial cells. The number of particles present on the abluminal plasma membrane was constant if the amount of injected AuG increased. Therefore, the magnitude of receptor-mediated transcytosis of AuG appears to be regulated by endothelial cells. Kupffer cells internalized the ligand into cytoplasmic tubular structures via plasma membrane invaginations and transported the ligand exclusively to endosomes and lysosomes, suggesting that the ligand is degraded by Kupffer cells.

Animals↗
PubMed1988

Binding of 1-(2-ethoxyethyl)-2-(hexahydro-4-methyl-1, 4-diazepin-1-yl) benzimidazole difumarate (KG-2413) to serum or plasma proteins in man, guinea pig and rat.

Human, guinea pig and rat sera or plasma protein binding of 1-(2-ethoxyethyl)-2-(hexahydro-4-methyl-1, 4-diazepin-1-yl)benzimidazole difumarate (KG-2413) were investigated by equilibrium dialysis. There were pronounced interspecies differences in binding affinity and binding capacity which were the highest in guinea pig and human species, respectively. In humans, the binding index (n1P1/Kd1) of isolated alpha 1-acid glycoprotein (alpha 1-AG) was seven times higher than that of isolated albumin, and the dissociation constant for human serum at the high affinity binding site was comparable to that for alpha 1-AG. These facts suggested that the free base of KG-2413 was mainly bound to alpha 1-AG in human serum. The contribution of albumin to the binding of KG-2413 in guinea pig and rat plasma may be relatively small. The interspecies differences in KG-2413 binding observed in this study may be due to species differences in the binding affinity and/or capacity of alpha 1-AG.

Adolescent↗
PubMed1988

Salivary excretion of 5-fluorouracil. II. Fluctuation of saliva/plasma concentration ratio and salivary clearance during a constant rate intravenous infusion in beagle dogs.

Salivary excretion of 5-fluorouracil (5-FU) was investigated during constant rate intravenous infusion (0.306 mg/kg/min) in three male beagle dogs. Parotid (Pr) and mandibular-sublingual (MS) saliva were collected separately by stimulating salivation with 10% citric acid. After the start of 5-FU infusion, plasma and salivary 5-FU concentration increased rapidly to approach their steady state levels. There was a significant correlation between each saliva and plasma 5-FU concentration (p less than 0.01). The saliva/plasma drug concentration ratio (S/P ratio) and salivary pH were significantly higher in Pr than in MS saliva (p less than 0.001), similar to the results following bolus intravenous administration of 5-FU in beagle dogs. Both S/P ratio and salivary clearance increased with time before steady state. Thereafter, these values approached almost constant levels and their fluctuations became smaller than those following the bolus intravenous administration. These results showing S/P ratio and salivary clearance of 5-FU were affected by the plasma drug concentration, suggested the possibility that non-linear pharmacokinetics may be involved in the salivary excretion of 5-FU.

Animals↗
PubMed1988

A non-opioid mechanism in the inhibitory effect of ginseng saponins on electrically evoked contractions of guinea-pig ileum and mouse vas deferens.

Both ginseng total saponins (GTS) and one of its constituents, protopanaxatriol saponins (PT), inhibited the electrically evoked contractions of guinea-pig ileum (GPI) in a concentration dependent manner in a range of 1-100 micrograms/ml, and this effect was irreversible at high concentrations of the saponins. Protopanaxadiol saponins (PD) had a transient and weak effect. On the other hand, in mouse vas deferens (MVD), the contractions were increased by PT and PD, however, GTS was almost without effect. The inhibitory effect of morphine was arithmetically increased by pretreatment with 100 micrograms/ml of these saponins in GPI preparations, while the inhibitory effect of the contractions was potentiated in MVD preparations. Neither the inhibition of contractions in the GPI preparation nor the facilitation of contractions in the MVD preparation by these ginseng saponins was reversed by 1 microM naloxone, in contrast to naloxone antagonism of morphine-induced contractions in both preparations. GTS and PT caused a dose-dependent inhibition of BaCl2-induced contraction of GPI. It is concluded that the mechanism on the inhibitory or facilitated effect of ginseng saponins on electrically evoked contractions in GPI and MVD preparations may be separated from the effect of opioids, and the mechanism may be based on the direct action of the saponins on smooth muscles preparations.

Animals↗
PubMed1988

Distinctive effect of ginseng saponins on development of morphine tolerance in guinea-pig ileum and mouse vas deferens.

Studies on the effect of ginseng saponins on the development of tolerance to morphine have been carried out using isolated preparations of guinea-pig ileum (GPI) and mouse vas deferens (MVD). Incubation of GPI preparation with morphine resulted in the development of tolerance to the inhibitory effect of morphine on the electrically evoked contractions. Ginseng total saponins and one of the constituents, protopanaxatriol saponin, suppressed the development of morphine tolerance in a concentration dependent manner in GPI preparation, though another constituent, protopanaxadiol saponin, did not affect the tolerance development substantially. In the MVD preparation, the development of tolerance to the morphine effect was observed as well, but none of the ginseng saponins affected it. It has been well established that electrically evoked contractions of GPI and MVD are mediated by acetylcholine and norepinephrine, respectively, and presumably their release is regulated presynaptically by opioid receptors. The fact that ginseng saponins suppressed the development of morphine tolerance only in the GPI preparation suggest that the inhibitory effect is mediated through and effect on the cholinergic system, without the involvement of direct action on opioid receptors.

Animals↗
PubMed1988

Inter-organ relation between salivary gland and kidney in lithium excretion. I. Effects of continuous stimulation of salivation on salivary, renal and systemic clearances of lithium in dog.

The effects of continuous stimulation of salivation on salivary, renal and systemic clearances of lithium were investigated following bolus intravenous administration of lithium chloride (0.145 meq/kg) in three beagle dogs. The salivation was frequently stimulated with citric acid solution, then parotid saliva and mandibular-sublingual saliva were collected separately by means of permanent fistulae. Although the continuous stimulation of salivation markedly increased the salivary clearance of lithium, no significant change was observed in plasma concentrations or systemic clearance of lithium. This was because the decrement in the renal clearance of lithium canceled out the effect of increased salivary clearance. It is suggested that the reabsorption of lithium in the renal tubule was enhanced under the continuous stimulation of salivation, and this seemed to be caused by loss of water or sodium through the salivary glands.

Animals↗
PubMed1988

Load dependency of end-systolic pressure-volume relations in isolated, ejecting canine hearts.

If characteristic muscle properties such as myocardial viscosity and/or shortening deactivation influence left ventricular ejection in the whole heart, the slope of the left ventricular end-systolic pressure-volume relation should be a function of both the contractile state and the loading mode. Thus, the load dependence of the end-systolic pressure-volume relation was examined using isolated, perfused canine hearts ejecting saline into a hydraulic loading system. The instantaneous left ventricular volume was measured with a plethysmograph. Under constant coronary flow and heart rate, two regression lines for end-systolic pressure-volume relations in two sets of loading modes were obtained: (1) Preload (left ventricular end-diastolic pressure; 4-15 mmHg) changes under fixed afterload impedance (preload changes); (2) Afterload impedance (peripheral resistance; 1.9-9.6 x 10(3) dyn sec cm-5) changes under fixed left ventricular end-diastolic volume (afterload changes). The slope of the end-systolic pressure-volume relation with afterload changes was steeper than that with preload changes (6.3 +/- 0.7 vs 4.8 +/- 0.6 mmHg/ml, p less than 0.05). Accordingly, under constant coronary flow, the slope of the end-systolic pressure-volume relation depended on loading conditions within the physiological range of afterload impedance and preload. This finding supports our hypothesis and implies that the slope change is of limited value as a contractile index in the ejecting heart.

Animals↗