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S Inoue

Publications and source records attributed to S Inoue.

At least 1,045 records · Page 58Linked to original sources

Studies on age-dependent plasma platinum pharmacokinetics and ototoxicity of cisplatin.

The age-related difference of cisplatin (CDDP) pharmacokinetics and ototoxicity were studied in 6 children with solid tumors who received CDDP infusion. CDDP was administered intravenously for 6 hours at a dosage of 30-120 mg/m2 and plasma-free platinum concentrations were determined by atomic absorption spectrophotometry. Plasma-free platinum concentrations ranged from 1.0 to 2.1 micrograms/ml at the end of infusions and declined rapidly with T1/2 of 0.6-1.5 hours. Pharmacokinetic parameters of plasma-free platinum were analyzed in 13 CDDP infusions by the one-compartment open model method. Parameters (Ke, Cl, T1/2 and Vd) of free platinum pharmacokinetics were 0.66 hr-1, 7.71l/hr, 1.35 hr and 15.71l in the younger group (age: 1.7-6.5 years old) and 1.44 hr-1, 11.41l/hr, 0.61 hr and 8.99l in the older group (age: 12.2-15.7 years old), respectively. Up to 600 mg/m2 of the cumulative dosage of CDDP caused minimal ototoxicity in the older group; however, in the younger group, hearing loss at a high frequency zone (6000 and 8000 Hz) began to appear at a cumulative dosage of 200 mg/m2 and progressed to middle zone (3000 Hz) when dosages surpassed 400 mg/m2. These data indicate that the pharmacokinetic difference in age possesses a large distribution volume (Vd) and that slower elimination of the drug in a younger age group is an important factor for age-dependent ototoxicity.

Adolescent↗

Effect of extradural compliance and resistance on spread of extradural analgesia.

We have studied the effect of extradural compliance and extradural resistance on the spread of extradural analgesia. In 111 patients aged 21-75 yr, compliance and resistance of the extradural space were calculated by a mathematical analysis (using the Windkessel theory) of the extradural pressure-response curve to injection of a given volume of local anaesthetic. The calculated mean extradural compliance was 0.39 (SD 0.13) ml mm Hg-1 and this increased with advancing age (P less than 0.01). The total number of analgesic segments blocked was related to extradural compliance (P less than 0.01). Segmental dose requirement was related inversely to extradural compliance (P less than 0.01). Calculated extradural resistance was 26.8 (14.5) mm Hg s ml-1 and this decreased with advancing age (P less than 0.05). The total number of analgesic segments blocked was related inversely to extradural resistance (P less than 0.05). Segmental dose requirement was related to extradural resistance (P less than 0.05).

Adult↗

Intracoronary endothelin-1 increases coronary retrograde pressure by constricting arterioles.

STUDY OBJECTIVE: The aim was to determine the site of coronary vasoconstriction induced by endothelin, by investigating the response in terms of retrograde pressure and reactive hyperaemia. EXPERIMENTAL MATERIAL: Twelve anaesthetised mongrel dogs, 12-14 kg, were used for the studies. DESIGN: The left anterior descending coronary artery was cannulated and perfused with blood through an extracorporeal bypass. The effects of intracoronary endothelin-1 (1-500 pmol) on coronary blood flow, coronary flow reserve (the peak reactive flow and the repayment after 15 s coronary occlusion), and retrograde coronary pressure during coronary occlusion were studied (n = 7). The retrograde coronary flow was collected from the bypass at each dose (n = 5). MEASUREMENTS AND MAIN RESULTS: At doses of greater than 20 pmol the coronary flow decreased dose dependently and reached almost zero flow at 500 pmol. The coronary flow reserve also decreased; however, the retrograde pressure was raised dose dependently at doses of greater than 10 pmol. At a dose of 500 pmol, the retrograde pressure was increased to 61 mm Hg [82(SEM 12)% of the coronary perfusion pressure]. Retrograde flow remained unchanged throughout the experiment. CONCLUSIONS: The endothelin-1 induced rise in retrograde pressure is in accordance with a dose dependent reduction in coronary flow reserve, and collateral flow was not augmented by endothelin. It is concluded that the effect of endothelin-1 on coronary circulation in situ was mainly due to the constriction of small resistant vessels.

Animals↗

Postoperative recurrence of hepatocellular carcinoma.

Sixty-nine patients with hepatocellular carcinoma underwent curative hepatic resections as primary cases from 1981 to 1986. Seven patients died in the hospital after operation. The other 62 patients left the hospital and were closely followed for 25 to 78 months. Recurrence of carcinoma became obvious in 41 (66%) of 62 patients. The clinical and pathologic features of these 41 patients were not significantly different from those of the other patients. Recurrent tumors were found in the residual liver in 38 patients (93%), in the bone in 2 (5%), and in the lung in 1 (2%). Recurrence was diagnosed within 1 year, between 1 and 2 years, and more than 2 years after the operation in 22 (56%), 10 (26%), and 7 (18%) patients, respectively. It was difficult to determine the exact time of recurrence in two patients. There was a significant negative correlation between the size of primary tumor and time until recurrence; the larger the primary tumor, the shorter the time until recurrence. Among the 29 patients who underwent local excisions for their primary tumors, 19 recurrences were observed. Eighteen were found in the residual liver, in the same segment as the primary tumor, or in one near it. Larger hepatic resection for primary tumors is thus advocated to prevent recurrence.

Adult↗

Equilibrium radionuclide ventriculography in Duchenne's cardiomyopathy.

Myocardial dysfunction in 14 patients with Duchenne's muscular dystrophy (DMD) was evaluated by Tc-99m HSA multigated radionuclide ventriculography (MGRV). Follow-up studies were performed on eight patients for 5 years. Left ventricular ejection fraction and standard deviation of the phase angle were abnormal in all patients older than 15 years. Hypokinetic changes and phase delay were recognizable in most patients older than 17 years. Peak filling rate decreased in patients older than 17 years. MGRV was considered an effective method for evaluating serial changes in cardiomyopathy of patients with DMD.

Adolescent↗

Isolation of Listeria monocytogenes from raw milk and its environment at dairy farms in Japan.

The incidence of Listeria monocytogenes contamination in raw milk from farm bulk tanks and silage was investigated monthly at 20 dairy farms in Aomori prefecture, Japan, from January to July in 1989. Listeria sp. was isolated from one sample (5%) of raw milk collected in May, but L. monocytogenes was not isolated from raw milk. L. monocytogenes was isolated from two samples of silage (10%) collected in June. Silage, cow feces, sawdust bedding, dust and soil in these farms were tested for listerias, and we confirmed listerias contamination of the environment in the dairy farms.

Animals↗

Leukotoxic activity of Clostridium perfringens of equine origin.

Leukotoxic activity of equine isolates of Clostridium perfringens type A was examined. Thirty-seven isolates (94.9%) of 39 isolates demonstrated leukotoxic effects on mouse peritoneal macrophages. Phase contrast microscopy revealed that the toxic preparations induced rounded protoplasmic extrusion and sometimes destruction of the cells, leaving some membrane fragments. These findings suggest that the leukotoxic activity could be considered to be a virulence factor of C. perfringens.

Animals↗

Effects of dietary iodine on chemical induction of thyroid carcinoma.

Effects of dietary iodine on the induction of thyroid carcinoma using N-nitrosobis(2-hydroxypropyl)amine (BHP) were studied. Male Wistar rats were fed with an iodine-adequate diet (IAD group), an iodine-rich diet (IRD group) and an iodine-deficient diet (IDD group), respectively, until the time of sacrifice. From the 2nd experimental month, animals were injected with BHP once a week for 10 weeks. In the IAD and IRD groups, benign nodules and papillary carcinoma were found. The incidence of rats with benign nodules was 100% in both groups and animals with papillary carcinoma in the IAD and IRD groups comprised 33% and 29%, respectively. The area of the thyroid gland occupied by nodular lesions was much narrower in the IRD group than in the IAD group. In the IDD group, the thyroid showed marked enlargement due to multiple nodular proliferation of follicle cells. The incidence of rats with carcinoma was 100%, and not only papillary but also follicular carcinoma and one pulmonary metastasis were found. As the iodine content of the diet decreased, the nodular lesions increased in width and number, and the incidence of carcinoma in rats became higher. These effects of dietary iodine are probably related to the goitrogenic and/or promoting effects of TSH.

Administration, Oral↗

Effects of monensin on subcellular structure, thyroglobulin secretion and peroxidase activity of cultured thyroid cells obtained from patients with hyperthyroidism.

The effects of monensin on subcellular structure, release of thyroglobulin (TG) and peroxidase (PO) activity were investigated using primary cultures of thyroid cells obtained from patients with Basedow's disease (Basedow's cells). TG concentration in the culture medium was measured by a sandwich enzyme immunoassay and the amount of TG in cultured cells was measured with an identical sandwich enzyme immunoassay after lysis of the cells with Triton X-100. PO activity of cultured cells was measured by a biochemical method. Addition of TSH (10 mU/ml/day) to the culture medium increased the synthesis and release of TG. When monensin (1 micron/l) was added to the medium on the last day of a 3-day incubation with TSH, the Golgi complex showed vacuolative change ultrastructurally, and the amount of intracellular TG was increased, whereas the amount of TG in the culture medium and PO activity became lower than those in the control group. These results suggest that in cultured Basedow's cells, TG is secreted through the Golgi complex, and that the activity of PO is elevated after processing in the Golgi complex.

Cells, Cultured↗

An immunohistochemical study of calcitonin-containing cells in benign and malignant thyroid lesions.

Parafollicular cells (C-cells) in benign and malignant thyroid lesions were studied immunohistochemically with a polyclonal anti-calcitonin (CT) antibody. The C-cells were seen most frequently in the middle third of the lateral lobes in the thyroid gland of normal individuals and patients with Graves' disease and chronic thyroiditis, although in the latter the number of such cells was significantly decreased (p less than 0.05). In adenomatous goiter, C-cells were present in nodular lesions from an early stage of nodule development (frequency about 19%), whereas in the later stage these cells were rarely observed inside type 1 nodules, which were generally characterized by an admixture of follicles with considerably different sizes. However, C-cells were not observed inside type 2 nodules, which were composed of similar-sized follicles, or in the parenchyma of 56 cases of benign and malignant thyroid tumors. These findings suggest that since C-cells are present in nodular lesions, the histogenesis of adenomatous goiter is quite different from that of follicular adenoma; thyroid neoplasms generally contain no C-cells in the parenchyma.

Adenoma↗

Hypothalamic obesity due to hydrocephalus caused by aqueductal stenosis.

A case is presented of 14 year old female with hypothalamic obesity due to hydrocephalus caused by aqueductal stenosis. Evidence of hypothalamic obesity included 1) acute hyperphagia and weight gain, 2) neuroradiology showed hydrocephalus with focal enlargement of the third ventricle, 3) endocrinological studies revealed hyperinsulinaemia and impaired growth hormone (GH) response to arginine, but normal GH response to growth hormone-releasing factor (GRF) and 4) Torkildsen's ventriculo-cisternal shunting resulted in improvement in hyperphagia and obesity.

Adolescent↗

Isolation of multiple cytomegalovirus strains from a patient with adult T cell leukemia.

A 66-year-old male with adult T cell leukemia had an ulcer on the left medial thigh. The biopsy of the skin lesion revealed enlarged endothelial cells with acidophilic intranuclear inclusion bodies, suggesting cytomegalovirus (CMV) infection. At autopsy, CMV was isolated from a nodular skin lesion of the scrotum. The urine constantly tested positive for CMV. Restriction endonuclease cleavage analysis of DNA of the isolates from the skin and urine indicated that this patient was infected with two different strains of CMV.

Aged↗

Modulation of arginine-induced insulin and glucagon secretion by the hepatic vagus nerve in the rat: effects of celiac vagotomy and administration of atropine.

We hypothesized the existence of vagal arginine sensors in the liver which modulate arginine-induced pancreatic hormone secretion. The present study was carried out to examine the efferent pathways and receptor mechanisms from arginine sensors using selective vagotomies and autonomic drugs on the secretion of insulin and glucagon after ip injection of L-arginine (1 g/kg BW) in rats in an unanesthetized and unrestrained state. Hepatic vagotomy (sectioning of the hepatic branch of the vagus nerve) enhanced both plasma insulin and glucagon concentrations after ip arginine more than those in sham-vagotomized (control) rats. The effect of hepatic vagotomy was blocked by adding celiac vagotomy (sectioning of the celiac branches of the vagus nerve) or by previous administration of atropine methyl nitrate (10 mg/kg BW), but not by phentolamine (1 mg/kg BW) or propranolol (2 mg/kg BW). Celiac vagotomy alone did not affect the plasma insulin concentration; however, it reduced the plasma glucagon concentration after ip arginine compared to that in sham-vagotomized rats. Administration of atropine alone did not affect plasma insulin or glucagon concentrations after ip arginine. These results suggest that celiac branches of the vagus nerve act as efferent pathways to the pancreas through a muscarinic receptor mechanism in the hepatic arginine sensor-mediated pancreatic neuroendocrine system. The physiological role of these hepatic sensors may be to prevent arginine-induced exaggerated pancreatic hormone secretion and maintain blood glucose homeostasis.

Animals↗

SPS-B, a physiological sleep regulator, from the brainstems of sleep-deprived rats, identified as oxidized glutathione.

We previously reported regarding the "sleep-promoting substance (SPS)," which was isolated from the brainstem extract of sleep-deprived rats, the existence of multiple active components including uridine and SPS-B. Intracerebroventricular infusion of crude SPS-B exhibited significant enhancing effects on both slow wave sleep and paradoxical sleep in unrestrained rats. Further investigation of SPS-B has resulted in its final identification as oxidized glutathione (GSSG, gamma-glutamylcysteinylglycine disulfide). Authentic GSSG similarly administered in rats also significantly enhanced sleep which was indistinguishable from normal physiological sleep. We propose GSSG as a candidate endogenous sleep substance.

Animals↗

[Studies on anti-allergic agent. I. 1,2,3-trisubstituted-2-propen-1-one derivatives, 3,4-disubstituted-4-oxo-2-butenoic acids and the related compounds].

A new series of 1,2,3-trisubstituted-2-propen-1-one derivatives (9a-v, 10a-j, 13a-c, 14a-j) and 3,4-disubstituted-4-oxo-2-butenoic acids (6a-i, 7a-n) with azole compounds were synthesized. Inhibitory activities against rat passive cutaneous anaphylaxis (PCA) reaction and histamine release from rat mast cells were tested. The ester derivatives (7a-n, 14a-j) exhibited a more potent inhibitory activity against histamine release compared with alkylamine (9a-v), beta-hydroxyethoxy (10a-j) and carboxylic acid (6a-i, 13a-c) derivatives, but somewhat weaker in their anti-PCA activity. Structure-activity relationships were discussed.

Animals↗

Hyper-response of insulin release to arginine in streptozotocin-induced diabetic rats with hepatic vagotomy.

Vagal glucose receptor and arginine sensor have been found to exist in the liver of normal rats. The present study was designed to examine whether these sensory receptor systems function in streptozotocin-induced mildly diabetic rats. One week after streptozotocin injection (35 mg/kg body wt. iv), hepatic vagotomy and installation of a jugular vein catheter were performed. Three days after the surgery, intraperitoneal glucose (1 g/kg body wt.) or arginine (1 g/kg body wt.) stimulation was done with the rat in an unanesthetized and unrestrained state. Hepatic vagotomy significantly reduced glucose-induced insulin release with an increase in plasma glucose in control and diabetic rats. The rate of reduction of plasma insulin release was similar in the two groups. Hepatic vagotomy also significantly enhanced arginine-induced insulin release in both groups, but in control rats there was no change in the response to plasma glucose, while in diabetic rats there was a significant reduction. The rate of enhancement of plasma insulin release by hepatic vagotomy was significantly greater in diabetic than in control rats. The results indicate that streptozotocin-induced mildly diabetic rats have hyperfunction of the arginine sensor and normofunction of the glucose receptor and modulate insulin release through these receptor systems in the liver.

Animals↗

Evaluation of the timing to reduce the initial dose of antithyroid drugs in patients with Graves' disease.

The present study was undertaken to evaluate whether the normalization of the serum TSH level in a supersensitive assay during the initial treatment with antithyroid drugs (ATD) is a useful indicator for the reduction of the initial dose of ATD in 50 patients with hyperthyroidism due to Graves' disease. The initial dose of ATD was continued until the achievement of the euthyroid state, and was then reduced either before the serum TSH level was in the normal range in 9 of 29 patients treated with methimazole (MMI) (group MMI-1) and 8 of 21 treated with propylthiouracil (PTU) (PTU-1), or after the serum TSH level was in/above the normal range in 20 of 29 treated with MMI (MMI-2) and 13 of 21 treated with PTU (PTU-2). Although there were no significant differences in age, sex, thyroid function, prevalence of autoantibodies, goiter size, duration of the disease or the initial and modified doses of ATD, the mean durations of the administration of the initial dose of ATD in MMI-2 and PTU-2 were significantly longer than those in MMI-1 and PTU-1, respectively. As a result, 4 (44%) in group MMI-1, 20 (100%) in MMI-2, 2 (25%) in PTU-1 and 7 (54%) in PTU-2 developed low free T4 levels, and 1 (11%) in MMI-1, 15 (75%) in MMI-2 and 3 (23%) in PTU-2 developed low free T3 levels. Serum TSH levels increased over the normal range in 3 (33%) in MMI-1, 18 (90%) in MMI-2 and 5 (39%) in PTU-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗