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Biomedical subjects

K Takagi

Publications and source records attributed to K Takagi.

At least 721 records · Page 40Linked to original sources

Effect of 4-(4'-chlorobenzyloxy)benzyl nicotinate (KCD-232) on triglyceride and fatty acid metabolism in rats.

The effects of KCD-232, a new hypolipidemic agent with a structure of 4-(4'-chlorobenzyloxy) benzyl nicotinate, on triglyceride (TG) and fatty acid (FA) metabolism were studied in rats. KCD-232 dose-dependently reduced both liver and serum TG levels. From in vivo and in vitro studies, the hypotriglyceridemic action of KCD-232 was shown to be based on the inhibition of hepatic TG synthesis due to both decreased FA synthesis and increased FA oxidation in the liver. Of two metabolites of KCD-232, i.e. 4-(4'-chlorobenzyloxy)benzoic acid (MII) and nicotinic acid, MII was found to be responsible for the decreased synthesis and increased oxidation of FA in the liver, the latter apparently being due to increased mitochondrial oxidation activated by MII. MII was demonstrated to form a xenobiotic TG in which one fatty acid moiety was substituted by MII and to form a thioester with CoA by rat liver microsomes. This thioester, MII-CoA, inhibited fatty acid syntheses from [14C]acetate, [14C] acetyl-CoA and [14C]malonyl-CoA in cell-free enzyme systems from rat liver both with and without an NADPH-generating system, whereas MII as such showed no effect. MII-CoA were therefore considered to be a chemical entity for the inhibition of hepatic fatty acid synthesis by KCD-232 and was suggested to inhibit fatty acid synthetase directly.

Acetates↗

Ataxia-telangiectasia with dysgerminoma of right ovary, papillary carcinoma of thyroid, and adenocarcinoma of pancreas.

The first case of ataxia-telangiectasia (AT) with dysgerminoma of the right ovary, papillary carcinoma of the thyroid, and adenocarcinoma of the pancreas is reported. There is the characteristic trend of the occurrence of the malignant neoplasms in AT. Lymphoreticular neoplasms and leukemia are most frequently seen in the younger patients with AT. On the other hand, epithelial malignant neoplasms are frequently seen in the longer survivors with AT. Literature also shows that nucleomegaly is due to precocious or abnormal aging.

Adenocarcinoma↗

Community outbreak of Yersinia pseudotuberculosis.

An outbreak of Yersinia pseudotuberculosis in Kurashiki, Japan is described. This is the first conclusive report of a community outbreak of this microorganism. A total of 535 pupils, five teachers, and one food attendant contracted the organism. Causative organisms were detected in 19 out of 30 patients. All isolated strains belonged to serotype VA. Out of 653 sera of the pupils, 488 showed elevated agglutinin titers ranging from 1:80 to 1:1,280 or more within a period of 3 months.

Adult↗

Clinical evaluation of theophylline binding to plasma protein in bronchial asthmatic patients.

Theophylline binding to plasma protein was studied with seven bronchial asthmatic inpatients. The extent of protein binding was monitored using an ultrafiltration device, EMIT FreeLevelTM System 1, whose performance is pH independent between 7.5 and 8.5 and concentration independent between 2 and 10 mcg/ml. When protein-free theophylline solutions are used a linear pH dependency was observed between 7.0 and 8.3. With theophylline-spiked human plasma using the same samples, the binding was found to be concentration-independent in the range 5 to 40 mcg/ml. The intra- and inter-individual variations in theophylline binding to plasma proteins were relatively large. A calculation procedure for predicting free fractions at normal physiological plasma pH, 7.4, using the observed free fraction at a given plasma pH is proposed. A good correlation was obtained between plasma and salivary theophylline concentrations. Salivary levels alone, however, are unreliable for monitoring theophylline therapy.

Asthma↗

Tension maintenance, calcium content and energy production of the taenia of the guinea-pig caecum under hypoxia.

When potassium (45.4 mM) was applied to isolated taenia of guinea-pig caecum, the muscle developed a rapid phasic and sustained tonic tension during aerobic conditions bubbled with 95% O2:5% CO2. Under hypoxic conditions bubbled with 95% N2:5% CO2, the taenia lost its ability to respond to high potassium with sustained tonic contraction, although it still showed rapid phasic contraction. Raising the glucose concentration from 5.5 to 55.5 mM in the presence of high potassium during hypoxia caused development of a sustained contraction which was 50% that of the muscle in aerobic conditions. In the presence of high potassium, the ATP content of the taenia decreased in hypoxia, but increased with increasing glucose concentration. When the taenia was exposed to hypoxic conditions, the amount of lactate released from the muscle increased. Raising the glucose concentration caused a further increase in lactate release in the presence of high potassium under hypoxia. Good correlations (gamma greater than 0.9) were observed between tension development, the ATP content and lactate release of the taenia in the presence of high potassium under hypoxia when the glucose concentration was varied between 5.5 and 55.5 mM. The total calcium content was increased by the presence of high potassium under aerobic conditions and the increase was abolished when the muscle was exposed to hypoxic conditions. Under hypoxia the total calcium content was not increased by raising the glucose concentration in the presence of high potassium. The cellular calcium content of the taenia, determined by the lanthanum method, was increased in the presence of high potassium under aerobic and hypoxic conditions, but the content was smaller in hypoxic conditions than in aerobic conditions. Under hypoxic conditions, raising the glucose concentration in the presence of high potassium did not affect the cellular calcium content. These results suggest that under hypoxic conditions the potassium-induced sustained contraction of the taenia is increased by raising the glucose concentration owing to increased ATP production through the glycolytic pathway, but not through mechanisms increasing the intracellular Ca concentration.

Adenosine Triphosphate↗

Comparison of 5-fluorouracil with ftorafur in adjuvant chemotherapies with combined inductive and maintenance therapies for gastric cancer.

A group of 243 patients with gastric cancer was subjected to a prospective randomized trial of adjuvant chemotherapy after curative gastrectomy. One of the three arms (regimen A) is induction therapy with a three-drug combination of mitomycin C (MMC), 5-fluorouracil (5-FU), and cytosine arabinoside (ara-C) followed by intermittent oral administration of 5-FU for two years (MFC + F). In regimen B, 5-FU in regimen A is replaced by ftorafur, administered on the same schedule as regimen A (MF'C + F'). Regimen C is the control, in which patients are treated by surgery alone. Regimen A was proven effective for the suppression of relapse in the limited groups of moderately locally advanced cancer; five-year survival rates of the subset of stages I, II, and III were 72.1% with regimen A and 53.1% with regimen C (P less than .05). Regimen B yielded a better survival than the control, although the difference did not reach statistical significance. The results seem to favor 5-FU as adjuvant chemotherapy for gastric cancer.

Adult↗

[Bleomycin, vinca alkaloid and cis-diamminedichloroplatinum combination chemotherapy for advanced testicular tumors].

Thirteen patients with advanced testicular tumors (seminoma 2, non-seminoma 11) were treated with combination chemotherapy involving BLM, vinca alkaloid and CDDP (BVP) as induction therapy and followed with CPM, VCR and CDDP as maintenance therapy. BVP and COP administration was repeated every 3 and 4 to 8 weeks for 1 year, if there were no serious side effects. The overall response rate (CR + PR) was 92% with a 69% CR rate. At a mean follow-up of 30 months (7-52 month range), 54% of the patients were alive with no evidence of disease. Bulky metastases, failure to respond to prior chemotherapy and teratomatous metastases were considered to be poor prognostic factors. The toxicity of BVP was similar to that reported for CDDP, except that allergic reaction occurred in 3 patients after several courses of treatment. Two of the 3 went into anaphylactic shock.

Adult↗

Endoscopic intramural injection of anti-neoplastic emulsion.

With the aim of establishing a topical chemotherapy against stomach carcinoma, 5-fluorouracil (5-FU) emulsion (oil/water type) for injection has been developed. The drug distribution was analyzed by 5-FU bioassay and radiographic examination of soft parts, for which radiopaque Lipiodol was employed in an oil phase. In order to examine local toxicity, tissue retention, and transfer to lymph nodes of 5-FU emulsion, the drug was administered perorally to rats and injected intramurally through the gastric serosa into laparotomized dogs. Following this series of experiments, which gave satisfactory results, the time courses of drug concentration in the gastric wall and regional lymph nodes were studied as a pre-clinical trial, by applying endoscopic intramural injection of 5-FU emulsion or solution in dogs. The anti-metastatic and anti-neoplastic effects of 5-FU emulsion were investigated in an experimental model of lymph node metastasis in mice. The emulsion was more effective in subduing metastasis and tumor growth than the solution, and the effectiveness of the former was further augmented by the use of repeated injections rather than a single injection. This method of endoscopic injection of 5-FU emulsion should be of great value as a local therapeutic measure against stomach carcinoma itself as well as against metastatic lesions in the lymph nodes.

Administration, Oral↗

[Studies on carcinoma of the remnant stomach after distal gastrectomy].

Sixty-one patients with carcinoma of the remnant stomach after distal gastrectomy were admitted by the end of 1982. Twenty-six of them were gastrectomized for benign disease such as peptic ulcer and 35 for malignant disease such as gastric carcinoma. The age of the benign group was 58, and the average interval from the first operation was 19 years. The corresponding figures for the malignant group were 63 and 8 years, respectively. In the malignant group, the methods of anastomosis at the first operation were 18 cases of Billroth-I (B-I) and 17 of B-II. The lesion was located at the surgical stump in 7 patients and distant from the stump in 14 patients in this group. In the benign group, there were 10 cases of B-I and 16 of B-II, and no differences were seen in the location. Early carcinoma was noted in 11 patients, and 34 were advanced. Differentiated adenocarcinoma was observed in 25 cases and undifferentiated in 20 in the resected specimen. Although no metastases were seen in early cases, the rate of lymph node metastasis was 70%, and the five-year survival rate was 21% in advanced cases, and 80% in early cases.

Adult↗

[The effects of DDP on the seminiferous epithelium of rats].

Adult male rats were injected intraperitoneally with 2 mg, 4 mg and 6 mg Cis-diamminedichloroplatinum (DDP) per kg body weight. The animals were then sacrificed on the 7th, 24th or 35th day. Two specimens of testis from each rat were stained by H.E. technique, then the Pachytene primary spermatocytes and Sertoli cells in the cross sectioned tubules at stage IV-V, IX-X and XIII-XIV were counted. Significant decrease of Pachytene/Sertoli(P/S) valueinstage IX-X tubules on the 24th day (p less than 0.01) suggests that DDP has a cytotoxic effect on early differentiated type A spermatogonia (A1).

Animals↗