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Biomedical subjects

S Takaya

Publications and source records attributed to S Takaya.

At least 73 records · Page 4Linked to original sources
PubMed1990

Liver, kidney, and thoracic organ transplantation under FK 506.

The new immunosuppressive drug FK 506 was used from the outset with low doses of prednisone to treat 120 recipients of primary liver grafts and 20 more patients undergoing liver retransplantation. The patient survival rate after 2 to 8 months in the primary liver transplantation series is 93.3%, with original graft survival of 87.5%. Of the 20 patients in the hepatic retransplant series, 17 (85%) are living. Almost all of the surviving patients have good liver function. In addition 11 hearts, 2 double lungs, and a heart-lung have been transplanted under FK 506, with survival of all 14 patients. With all of the organ systems so far tested, including the kidney (which has been reported elsewhere), rejection usually has been controlled without additional drugs and with lower average steroid doses than in the past. Nephrotoxicity has been observed, but not to an alarming degree, and there has been a notable absence of hypertension. There is a suggestion that serum cholesterol may be lowered by FK 506, but this is unproved. Although the adverse reactions of FK 506 and the immunosuppressive mechanisms resemble those of cyclosporine, our preliminary observations suggest that FK 506 may have a more advantageous therapeutic index.

Adolescent↗
PubMed1989

The influence of liver dysfunction on cyclosporine pharmacokinetics--a comparison between 70 per cent hepatectomy and complete bile duct ligation in dogs.

The influence of experimentally induced hepatic dysfunction on the pharmacokinetics of Cyclosporine A (CsA) was determined in dogs. The pharmacokinetics of oral (PO) and intravenous (IV) CsA were studied before and after 70 per cent hepatectomy or complete bile duct ligation (CBDL). Changes in liver function were monitored by serial measurements of serum bilirubin, and by the maximum removal rate (Rmax) and plasma disappearance rate (ICG-K) of indocyanine green (ICG). Concentrations of CsA in whole blood were measured by HPLC. Seventy per cent hepatectomy caused significant liver dysfunction: the ICG-Rmax decreased by 47.7 +/- 7.1 per cent (mean +/- SD) and the ICG-K decreased by 61.3 +/- 9.7 per cent during the first week after hepatectomy. At the same time, the systemic clearance (CLs) of IV-CsA decreased by 43.9 +/- 8.2 per cent, the area under the concentration curve (AUC) of IV-CsA increased by 35.4 +/- 20.8 per cent and the bioavailability of CsA decreased by 26.4 +/- 14.8 per cent. CBDL also induced significant liver dysfunction: the ICG-Rmax decreased by 39.1 +/- 12.8 per cent and the ICG-K decreased by 65.6 +/- 3.6 per cent in the second week after the operation. During the same period, the AUC of PO-CsA decreased by 69.9 +/- 10.7 per cent and the bioavailability of CsA also decreased markedly by 73.9 +/- 15.6 per cent. These data indicate that hepatic impairment significantly influences the pharmacokinetics of CsA, not only by the changes in intestinal absorption, but also by those in hepatic metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Pharmacokinetics of the cyclosporine-ketoconazole interaction in dogs.

Numerous clinical reports have documented an increase in trough blood concentrations of cyclosporine in transplant recipients treated concomitantly with ketoconazole. The objective of this study was to elucidate the mechanism(s) underlying the cyclosporine-ketoconazole interaction using a choledochoureterostomy dog model. Five male beagle dogs received a 4 mg/kg, i.v. bolus dose of cyclosporine either alone or on day seven of a 10-day, 13 mg/kg/day, oral dosing regimen of ketoconazole. Blood samples were collected prior to and at predetermined times for 60 hrs after the cyclosporine dose, while the bile/urine mixture was collected quantitatively for 96 hours after the cyclosporine dose. Ketoconazole decreased the systemic clearance of cyclosporine from 7.0 ml/min/kg to 2.5 ml/min/kg. The terminal disposition rate constant was also decreased significantly from 0.0794 to 0.0354 hrs-1. Ketoconazole caused no significant changes in cyclosporine steady state volume of distribution, or plasma unbound fraction. Ketoconazole did not significantly alter the excretion of cyclosporine and various cyclosporine metabolites in the bile/urine mixture. Inhibition of hepatic drug metabolizing enzymes appears to be the primary reason for the ketoconazole induced elevation in cyclosporine concentration.

Animals↗
PubMed1986

[A case of pineal teratoma with intraventricular free fat seen in CT scan].

Detection of an intraventricular or intratumoral fat-fluid level on the plain craniograms has been known as a characteristic sign indicating the presence of intracranial teratomatous tumors. On CT scans, however, only thirteen cases have been previously reported to be found an intraventricular and/or subarachnoid free fat associated with spontaneous ruptures of these tumors. We reported a case of pineal teratoma with intraventricular free-fat seen on CT scans. A nine-year-old male with precocious puberty was admitted to our hospital complaining a moderate nonpulsatile headache. Neurological examinations were normal without signs of meningeal irritation. The serum and CSF titer of HCG were raised markedly. The laboratory data of the CSF were normal and there were no pathological cells in the CSF. The CT scans revealed a large heterogeneous mass containing multiple areas of negative density in the pineal region. There were negative density droplets in the bilateral frontal horn on the same CT scans indicating a presence of free fats. At surgery, an yellowish oily material was drained from the tumor, but there was no sign of meningitis over the cortical surface of the occipital lobe. An intraventricular free fat on CT scan have been reported in fourteen cases including ours following the first case described by Fawcitt in 1976. Although most of the cases presented headache, only two cases was diagnosed clinically as chemical meningitis. Pathological changes indicating granulomatous meningitis, however, were noted in five cases, all of them presenting seizure attacks.

Brain Neoplasms↗
PubMed1979

Rat hyperplastic hepatic nodules and primary hepatomas retaining abnormally high pyruvate kinase L type activity.

As reported in our previous paper (Sato et al., Cancer Res., 38: 3086-3093, 1978), most of the hyperplastic hepatic nodules and primary hepatomas induced by N-2-fluorenylacetamide (2-FAA), diethylnitrosamine (DENA), and 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) showed that pyruvate kinase liver (L) type decreases and the prototypic M2 type increases concomitantly with dedifferentiation of tissues. However, at least 14 samples among 120, mostly hyperplastic nodules and highly differentiated hepatomas induced by 2-FAA or DENA, retained exceptionally high activities of the L type, while other enzymes of carbohydrate metabolism in these tissues deviated toward a common pattern similar to that in the fetal liver. Individual patterns of 9 enzymes including pyruvate kinase of carbohydrate metabolism in these samples are arranged and discussed as examples of unbalanced enzyme deviation in hepatocarcinogenesis.

Animals↗
PubMed1977

Enzyme alteration in skeletal muscle of mice with muscular dystrophy.

1. Developmental enzyme alterations were investigated in skeletal muscle of the hereditary progressive muscular dystrophy (PMD) mice of C57BL/6J strain. 2. Enzymes examined were classified into three groups according to changes of activities in dystrophy muscle during ageing. Activities of creatine kinase (EC 2.7.3.2), pyruvate kinase (EC 2.7.1.40), glycogen phosphorylase (EC 2.4.1.1), and fructose-biphosphate aldolase (EC 4.1.2.13), each of which had the respective muscle specific isoenzyme of extremely high activity in normal adult skeletal muscle, decreased rapidly in dystrophy muscle from the early stage of the disease with ageing. Activities of glycogen synthase (EC 2.4.1.11) and hexokinase (EC 2.7.1.1) were higher in dystrophy muscle in the early stage but decreased gradually to lower levels than those in the control with ageing. Activities of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) were always much higher in dystrophy muscle than in the control, with no relation to ageing. 3. Isoenzymes of creatine kinase, pyruvate kinase and phosphorylase in dystrophy muscle were mainly the muscle types, indicating that muscle differentiation was not blocked profoundly even in dystrophy muscle. In limited cases, especially in the early stage of the disease, very weak activities of the non-muscle fetal type isoenzymes of creatine kinase and phosphorylase were detected, apparently associated with partial muscle regeneration in dystrophy muscle.

Aging↗