Pharmacokinetic study of FK 506 in the rat.
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Administration, Oral↗
Biomedical subjects
K Noda
Publications and source records attributed to K Noda.
Effects of hippocampal neurotoxicant, trimethyltin, on corticosterone response to a swim stress and glucocorticoid binding capacity in the hippocampus in rats.
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Animals↗
Thiamine pyrophosphatase activity in the Golgi apparatus of calcitonin-treated osteoclasts.
The thiamine pyrophosphatase (TPPase) activity described by Novikoff and Goldfisher was examined in osteoclasts affected by calcitonin in order to elucidate whether the morphological and functional changes of the osteoclasts have an influence over the secretion function of their Golgi apparatus. The Golgi apparatus of osteoclasts of which the ruffled border had disappeared and bone resorption discontinued as the result of treatment with calcitonin showed a slight TPPase activity. The reaction products of the enzyme in these inactive osteoclasts were distinctly fewer than that of control osteoclasts, which were not affected by calcitonin. From these results, it is suggested that there may be a connection between the morphological and functional changes of osteoclasts and the secretion function of the Golgi apparatus.
Animals↗
Alkaline phosphatase activity in the osteoclasts induced by experimental tooth movement.
The localization of alkaline phosphatase (Alpase) activity in the osteoclasts was examined cytochemically. Alpase activity was located in the basolateral membrane in mature osteoclasts having ruffled borders and clear zones, and also in the basolateral membrane in the osteoclasts lacking a ruffled border or a clear zone on the bone surface. But in the preosteoclasts situated away from the bone surface the enzyme activity was noted in the whole plasma membrane. These results suggest that the localization of Alpase activity may be altered in relation to the changes in morphology associated with the functional activity of the osteoclasts.
Alkaline Phosphatase↗
[Alcohol-induced variant angina and considerations of its mechanism: a case report].
A 64-year-old man had episodes of angina pectoris several hours after ingestion of alcohol. Otherwise, anginal attacks never occurred. He was diagnosed as having variant angina based on the typical ST elevation in leads II, III and aVF during the anginal attacks. We performed an alcohol challenge test on his 4th admission day. He was given 540 ml of "sake" at 6:00 p.m. and anginal attacks with ST elevations occurred 9.5 hours after its ingestion. The peak value of plasma ethanol was 136 mg/dl at 9:00 p.m. and it returned to 0 when angina occurred. By alcohol ingestion, urinary excretion of Mg increased in association with a slight decrease in serum Mg. The ratio of serum Ca to Mg was increased from 4.0 at the control state before taking alcohol to 4.5 at the occurrence of anginal attack. Mg content in red blood cells and in plasma catecholamines did not differ between before and after ingesting alcohol. We concluded that the change in the extracellular Ca-Mg equilibrium may contribute to the mechanism of alcohol-induced variant angina.
Aged↗
[Investigation of 5-fluorouracil (5-FU) levels and pyrimidine nucleoside phosphorylase activities in the tissues from patients with uterine cervical and ovarian cancers after oral administration of 5'-DFUR].
The usefulness of 5'-DFUR in both patients with uterine cervical and ovarian cancers was investigated by determining pyrimidine nucleoside phosphorylase (PyNPase) activities and 5-FU levels in cancerous and normal tissues resected from them after oral administration of 5'-DFUR. In uterine cervical cancer, each group of 9 cases administered single dose of 400 mg of 5'-DFUR and 7 cases administered 400 mg of 5'-DFUR 3 times a day continuously for 7 days was investigated. In ovarian cancer, all of 9 cases were administered 400 mg of 5'-DFUR 3 times a day continuously for 7 days. In conclusion, PyNPase activities in the tissues of uterine cervical and ovarian cancers were higher than those in the normal tissues. 5-FU tissue levels in the cancerous tissues were significantly higher than in the normal tissues and blood as well. This tendency was observed in each of the single and continuous administration groups. These results suggest that the tumor selectivity which is one of characteristics of 5'-DFUR could be expected also for cancer in the field of gynecology.
Administration, Oral↗
[Roentgenographic and computed topographic observations on benign bone tumor and tumor-like lesions treated by simple curettage without bone grafting].
Curettage without bone graft was performed in fifteen patients with benign bone tumors and tumor-like lesions. We studied the bone formation after curettage by plain radiography and computed tomography for six or more months. Average period before full-weight-bearing in thirteen patients of the lower extremities was three and a half months. We found no pathological fractures after curettage in any of the patients. Increases in radiodensity and reconstruction of the bone were observed in serial plain radiographs within three months. Computed tomography revealed that the center of the lesions persisted without bone formation, although thickening of cortex bone was predominant. From the data obtained here, it appears that bone grafts may not be necessary in patients, especially in younger ones, with benign bone tumors and tumor-like lesions.
Adolescent↗
[An early phase II study of CPT-11 in gynecologic cancers. Research Group of CPT-11 in Gynecologic Cancers].
An early Phase II study of CTP-11, a new derivative of Camptothecin, in gynecologic cancers was carried out by a cooperative study group of 9 institutions. Forty-six patients were enrolled, and there were 14 cases of ovarian cancers, 7 of cervical cancer, 6 of uterine body cancers and 1 of endometrial stromal sarcoma which satisfied study criteria. The response rate in ovarian cancers was 21.4%, and in cervical cancers 42.9%, among an overall rate of 21.4%. Three out of 6 patients with objective response had undergone previous chemotherapies including cisplatin, suggesting that CPT-11 was effective for patients with no response or refractory to these therapies. Leukopenia was a major adverse reaction with an incidence of 60.0% (grade 2 or more). Gastrointestinal symptoms such as nausea vomiting, anorexia and diarrhea were frequently observed (grade 2 or more; 13.3-43.3%). These were generally tolerable except in a few cases. Besides these reactions, alopecia was also observed (33.3%), but severe adverse reactions such as nephropathy were not. These results suggested that CPT-11 was effective against ovarian cancer and cervical cancer. The recommended dose regimen for a late phase II study is considered to be 100 mg/m2 once weekly and 150 mg/m2 once every 2 weeks.
Adult↗
Decreased vasoactive intestinal polypeptide (VIP) level in cerebrospinal fluid from diabetic patients with neuropathy.
The concentration of vasoactive intestinal polypeptide (VIP) was measured in cerebrospinal fluid (CSF) obtained from diabetic patients with neuropathy and their age-matched control subjects. VIP level in CSF from diabetic patients was significantly decreased as compared with that from the controls (12.9 +/- 3.1 pg/ml vs. 35.4 +/- 3.3 pg/ml, p less than 0.01). Decreased VIP level in CSF may relate with diabetic neuropathy in particular sexual dysfunction.
Adult↗
[Clinical significance of serum sialyl Tn antigen in patients with gynecological cancer. STN Study Group].
Serum sialyl Tn antigen was assayed in gynecological cancer and benign patients by means of "STN OTSUKA" kits. Fifty-eight of 140 (41.1%) ovarian cancer patients showed a significant elevation of sialyl Tn antigen in serum above the cut-off level of 45 unit/ml (mean +2SD) determined from normal controls. There was no feature of positive frequency in tissue type, including serious carcinoma (47.6%), mucinous carcinoma (45.5%), clear cell carcinoma (30.4%) and endometrioid carcinoma (55.6%), but the positive frequency of mucinous carcinoma (36.8%) was higher than that of serous carcinoma (11.1%) in stage I. Compared with other markers, sialyl Tn antigen showed a very much lower false-positive rate (3.6%) in benign gynecological diseases. In the diagnosis of ovarian cancers, the combination assay of sialyl Tn antigen and CA 125 increased diagnostic efficiency compared with any other combination assays. Therefore, sialyl Tn antigen will be a useful tumor marker for ovarian cancers.
Antigens, Neoplasm↗
Proteolytic conversion of xanthine dehydrogenase from the NAD-dependent type to the O2-dependent type. Amino acid sequence of rat liver xanthine dehydrogenase and identification of the cleavage sites of the enzyme protein during irreversible conversion by trypsin.
The primary structure of rat liver xanthine dehydrogenase (EC 1.1.1.204) was determined by sequence analysis of cDNA and purified enzyme. The enzyme consists of 1,319 amino acid residues with a calculated molecular mass of 145,034 Da, including initiation methionine, and is homologous to the previously reported Drosophila melanogaster enzyme (Lee, C. S., Curtis, D., McCarron, M., Love, C., Gray, M., Bender, W., and Chovnick, A. (1987) Genetics 116, 55-66; Keith, T. P., Riley, M. A., Kreitman, M., Lewontin, R. C., Curtis, D., and Chambers, G. (1987) Genetics 116, 67-73) with an identity of 52%. The enzyme exists originally as the NAD-dependent type in a freshly prepared sample. When the purified NAD-dependent type enzyme was digested with trypsin, it cleaved into three fragments with molecular masses of 20, 40, and 85 kDa and was irreversibly converted to the O2-dependent type. Comparison of the amino-terminal sequences of the three peptide fragments with the cDNA-deduced sequence reveals that the 20-, 40-, and 85-kDa peptide fragments correspond residues to 1-184, 185-539, and 540-1319 of the enzyme, respectively. Comparison of the 5'-p-fluorosulfonylbenzoyladenosine-labeled peptide sequence of the chicken enzyme (Nishino, T., and Nishino, T. (1989) J. Biol. Chem. 264, 5468-5473) reveals that the NAD binding site is associated with the 40-kDa fragment portion of the enzyme. Hydropathy analysis around the cysteine residues suggests that the 2Fe/2S sites are associated with the 20-kDa fragment portion of the enzyme.
Amino Acid Sequence↗
[Ovarian metastasis in patients with cervical cancer].
The study included a total of 634 patients with cervical cancer; 311 were in stage I b and 323 were in stage II. All patients received radical hysterectomy at the Department of Obstetrics and Gynecology, Kinki University, between May 1975 and December 1986. One out of 311 patients in stage I b (0.3%) and eight out of 323 patients in stage II (2.5%) had ovarian metastases confirmed histologically. Nine patients who had ovarian metastases were investigated about stages, histological types of the cervical cancer (WHO and CPL classification), incidence of metastases in pelvic lymph nodes, corpus infiltration, parametrial infiltration, and peritoneal cytology. Results obtained were as follows: 1. As to histological types, patients with adenocarcinoma and/or PL type in CPL classification had high incidence of ovarian metastases. 2. Patients with corpus infiltration had high incidence of ovarian metastases. 3. Metastases to both ovary and pelvic lymph nodes tended to occur on the same side, but ovarian metastases and parametrial infiltration did not necessarily occur on the same side. We suggest removal of ovaries, even before menopause, in patients with cervical cancer who have cervical adenocarcinoma, or corpus infiltration, or are suspicious for metastases in more than two pelvic lymph nodes.
Adenocarcinoma↗
Determination of denopamine in human and dog plasma by high-performance liquid chromatography with electrochemical detection.
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Animals↗
Physical properties of Bi2Sr2Can-1CunOy (n=1,2,3).
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Journal Article↗
Pharmacokinetic analysis of absorption and metabolism of dopamine and a dopamine prodrug in dogs.
Pharmacokinetic compartment models were constructed to describe the absorption and metabolism of dopamine (DA) and DA prodrug, N-(N-acetyl-L-methionyl)0,0-bis-eth-oxycarbonyl) dopamine(1). Plasma concentrations of DA, DA-SO4, and DOPAC after oral administration of DA to dogs, were analysed using the pharmacokinetic model assuming the contribution of first-pass metabolism for the formation of DA-SO4 and DOPAC. Though plasma concentration of DA was quite different from that of DA-SO4 or DOPAC, these data were simultaneously analysed with a good fitting curve. The apparent absorption rate constant of DA(K1) was proved to be much smaller than the apparent formation rate constants of DA-SO4(K2) or DOPAC(K3). It was found that the compartment model is useful for the evaluation of absorption and metabolic inactivation of DA. Plasma concentration of DA, N-(N-acetyl-L-methionyl)dopamine(2), DA-SO4, and DOPAC after oral administration of 1 were simultaneously analysed using the compartment model including the first-pass metabolism and two-fraction dissolution process. Good fitting curves were obtained. The apparent formation rate constant of 2(K4) is larger than that of DA-SO4(K5) or DOPAC(K6); thus it was shown that two protective groups of 1 reduced the metabolism of DA and 2 specially played an important role to the reduction of first-pass metabolism. From these results, it was found to be possible to give a pharmacokinetic interpretation for the mechanism of reduction of first-pass metabolism of DA.
3,4-Dihydroxyphenylacetic Acid↗
Variant angina due to deficiency of intracellular magnesium.
A 51-year-old man was diagnosed as having variant angina by documentation of typical ST elevation during anginal attack and also by showing coronary arterial spasm (#2 and #12) during hyperventilation on coronary arteriography. Large quantities of calcium blocking agents and nitrates could not improve his symptoms. Lack of intracellular magnesium was suspected from a daily excretion of urine magnesium (5.3 mEq) and magnesium tolerance test (56.7%). After hourly infusion of magnesium sulfate (80 mEq), coronary spasm could not be induced by ergonovine.
Angina Pectoris, Variant↗
Growth-inhibiting effect of tumor necrosis factor on human umbilical vein endothelial cells is enhanced with advancing age in vitro.
We have examined the effects of in vitro aging on the growth capacity of human umbilical vein endothelial cells (HUVECs) under the influence of tumor necrosis factor (TNF) with or without interferon-gamma (IFN-gamma). The growth and colony-forming abilities of control cells were impaired with advancing age in vitro, especially at later stages (more than 70-80% of life span completed). It was found that treatment with TNF inhibited growth and colony-forming efficiency at any in vitro age. The effects of TNF were shown to increase with increasing in vitro age, as reflected by a more pronounced increase in doubling times, a decrease in saturation density, and a reduction in colony-forming efficiency. However, the characteristics of TNF receptors, including the dissociation constant, and the number of TNF-binding sites per cell-surface area remained rather constant. The effect of TNF was augmented by IFN-gamma at a dose that alone affected growth and colony formation only slightly. The augmentation by IFN-gamma was also found to depend on in vitro age; the synergy with TNF in the deterioration of colony-forming ability was observed only in "aged" cells. These results suggest that the intrinsic responsiveness of HUVECs to growth-inhibiting factors, as well as to growth-stimulating factors, changes during aging in vitro.
Aging↗
In situ perfusion system for oral mucosal absorption in dogs.
To evaluate oral mucosal absorption of drugs in dogs, a newly designed in situ perfusion system with a circulating perfusion chamber was developed. The utility of the perfusion system was investigated by using three drugs: salicylic acid (SA), sulfadimethoxine (SM), and diltiazem (DIL). The oral mucosal absorption of the drugs could be adequately described by first-order rate processes. The absorption rate was independent of the amount of un-ionized drug, which varied with the pH of the solution. The absorption of SA was similar for various oral mucosal sites and for repeated experiments using the same site. Pharmacokinetic analysis for the plasma or medium concentration of SA after perfusion showed that SA was absorbed at the rate constant of 0.071 h-1, and that approximately 70% of SA absorbed from oral mucosa was transferred to the circulating blood.
Absorption↗