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Biomedical subjects

K Kawamoto

Publications and source records attributed to K Kawamoto.

At least 271 records · Page 15Linked to original sources

Antineoplastic effects in rats of 5-fluorocytosine in combination with cytosine deaminase capsules.

5-Fluorocytosine (5-FC) lacks antineoplastic activity in human subjects because of the absence of cytosine deaminase (CDase) in mammalian cells. Intratumoral conversion of 5-FC into 5-fluorouracil (5-FUra) by locally implanted capsules containing CDase followed by systemic administration of 5-FC can be expected to induce antineoplastic activity at a local site with minimal systemic toxicity. In vitro and in vivo experiments were performed to evaluate this hypothesis. Spectrophotometric analysis confirmed the deamination of 5-FC to 5-FUra by CDase extracted from cultivated Escherichia coli. In vitro studies showed that 5-FC combined with CDase induced significant growth-inhibitory effects on the cultured glioma cells. An active CDase capsule, made of cellulose tubing, was newly designed for local implantation. 5-FC concentrations in the s.c. tumors of the rats given these CDase capsules, followed by 5-FC administration, showed a sufficient amount of delivery of 5-FC to the tumor tissue. 5-FUra appearing in the tumor reached the level of 8.0 micrograms/g at 2 h and stayed at more than 1.0 microgram/g at between 1 and 6 h. Significant reduction of the tumor growth and cytotoxic changes were observed. The passive cutaneous anaphylaxis reaction demonstrated no allergic reaction to the host due to the capsule. These results suggest that this chemotherapeutic method is effective for human brain tumors.

Animals↗

Synthesis of homoursodeoxycholic acid and [11,12-3H]homoursodeoxycholic acid.

Homoursodeoxycholic acid and [11,12-3H]homoursodeoxycholic acid were synthesized from ursodeoxycholic acid and homocholic acid, respectively. Ursodeoxycholic acid (Ia) was converted to 3 alpha, 7 beta-diformoxy-5 beta-cholan-24-oic acid (Ib) using formic acid. Reaction of the diformoxy derivative (Ib) with thionyl chloride yielded the acid chloride (II) which was treated with diazomethane to produce 3 alpha, 7 beta-diformoxy-25-diazo-25-homo-5 beta-cholan-24-one (III). Homoursodeoxycholic acid (IV) was formed from the diazoketone (III) by means of the Wolff rearrangement of the Arndt-Eistert synthesis. N-Bromosuccinimide oxidation of homocholic acid (V), which was prepared from cholic acid by the same procedure described above, afforded 3 alpha, 12 alpha-dihydroxy-7-oxo-25-homo-5 beta-cholan-25-oic acid (VI). Reduction of the 7-ketohomodeoxycholic acid (VI) with sodium in 1-propanol gave 3 alpha, 7 beta, 12 alpha-trihydroxy-25-homo-5 beta-cholan-25-oic acid (VII). The methyl ester of 7-epihomocholic acid (VII) was partially acetylated to give methyl 3 alpha, 7 beta-diacetoxy-12 alpha-hydroxy-25-homo-5 beta-cholan-25-oate (VIII) using a mixture of acetic anhydride, pyridine and benzene. Dehydration of the diacetoxy derivative (VIII) with phosphorus oxychloride yielded methyl 3 alpha, 7 beta-diacetoxy-25-homo-5 beta-chol-11-en-25-oate (IX). Reduction of the unsaturated ester (IX) with tritium gas in the presence of platinum oxide catalyst followed by alkaline hydrolysis gave [11,12-3H]homoursodeoxycholic acid.

Chemical Phenomena↗

Ultrastructural changes and proliferation of pituicytes in mouse posterior lobe during water deprivation and rehydration.

Ultrastructural changes and proliferation of pituicytes during water deprivation and rehydration were studied in the posterior lobe of C57BL/Tw mice. Deprivation for 3 days brought about a significant increase in the number of electron-dense bodies (lysosomes) in pituicyte perikarya and their processes. The frequency of pituicytes enclosing neurosecretory axons in their cytoplasm significantly decreased as compared with that of the controls. 12-hour rehydration following deprivation for 3 days induced extensive development of rough endoplasmic reticulum and Golgi apparatus and an increase in frequency of neurosecretory axons enwrapped by pituicyte cytoplasm. However, at 2 days of rehydration the morphology of pituicytes was no more different from that of the controls. Mitotic figures of pituicytes were not encountered throughout the deprivation period of 6 days, but rehydration for 12 h and 1, 2, or 3 days following deprivation for 3 or 6 days was effective in eliciting an increase in mitotic activity. The present results indicate that pituicytes in the mouse posterior lobe are intimately related with the secretory mechanism of neurosecretory material from the neurosecretory axons and that the proliferation of pituicytes is stimulated in conditions of reaccumulation of neurosecretory material.

Animals↗

Effect of hypothermia upon the electrocochleogram and auditory evoked brainstem response.

The effects of hypothermia upon electrocochleogram (ECochG) and auditory evoked brainstem response (ABR) were studied in 10 children who underwent the open heart surgery under hypothermic anesthesia. The latencies of N1, waves III and V in response to click of 115 dB p.e. SPL were prolonged at the rate of 0.12 +/- 0.02, 0.25 +/- 0.04 and 0.43 +/- 0.05 msec/degree C, respectively. The N1 amplitude was initially increased, returned to the precooling value at about 26 degrees C and decreased thereafter. SP was increased in amplitude by hypothermia and never disappeared throughout the observation. At the time of rewarming, SP appeared first, followed by N1 and finally by waves III and V. The results obtained in the present study were discussed in the light of the sensitivity of the sensory hair cells, peripheral nerves and CNS to the hypothermic condition.

Anesthesia, General↗

[Anticancer effect of peplomycin on advanced recurrent breast cancer].

The anticancer effect of peplomycin (PEP) on advanced or recurrent breast cancer was investigated clinically and histopathologically. Stage III (n = 12), Stage IV (n = 2) and recurrent (n = 6) breast cancer patients were treated with PEP of which 10 mg were administered 3 times a week for 3 weeks either intravenously (n = 13) or intra-arterially (n = 7, via a catheter inserted into the subclavian artery). A decrease in tumor volume of more than 50% was obtained in 38.5% of the intravenously treated cases and in 28.6% the intra-arterially treated cases. Histologically, grades II b and III were observed in 66% of patients according to Oboshi's classification. These investigations suggest the effectiveness of PEP on breast cancer.

Adult↗

A multi-centre, double-blind study of serrapeptase versus placebo in post-antrotomy buccal swelling.

A multi-centre, double-blind, placebo-controlled trial was carried out to investigate the clinical efficacy of the anti-inflammatory enzyme serrapeptase in a total of 174 patients who underwent Caldwell-Luc antrotomy for chronic empyema. Eighty-eight patients received 10 mg serrapeptase 3 times on the day before operation, once on the night of the operation and 3 times daily for 5 days after operation; the other 86 received placebo. Changes in buccal swelling after operation were observed as a parameter of the response to treatment. The degree of swelling in the serrapeptase-treated patients was significantly less than that in the placebo-treated patients at every point of observation after operation up to the 5th day (p less than 0.01 to p less than 0.05). Maximal swelling throughout all the post-operative points of observation was also significantly smaller in size in the serrapeptase-treated group than in the placebo-treated group. No side-effects were reported.

Adolescent↗

[Epidemiological studies on gastric cancer in Nagasaki].

One thousand-four hundred and twenty-four cases of gastric cancer registered at the Nagasaki Tumor Registry between 1973 and 1977 were studied. The incidence of gastric cancer tended to be higher in persons exposed to the atomic bomb within 2.0 km from the hypocenter, especially in young persons, than in non-exposed individuals, but the difference was not statistically significant. Compared with the nonexposed, the corrected relative risk of gastric cancer in persons exposed within 2.0 km from the hypocenter was 1.28 in males and 1.11 in females. In terms of histologic type or location, the incidence of gastric cancer showed no statistically significant difference between the exposed and nonexposed persons.

Adult↗

[Flow cytometric studies of human brain tumors. Part 4: Metastatic tumors].

The distribution of DNA content in 12 cases of metastatic brain tumor, 6 cases of primary lung cancer and 6 cases of primary breast cancer were studied by flow cytometry. According to the pattern of DNA histogram, 12 specimens of metastatic brain tumors were classified into 3 types. Six cases of type I showed a sharp peak in 2C with large numbers of cells in 4C, 4 cases of type II showed the highest peak near 3C with a small peak in 2C, and 2 cases of type III showed a shift of the peak to the right near 4-5C. Type II and III seemed to have two different kinds of the cells which were mixed with normal brain cells or blood cells showing small peak in 2C and tumor cells showing the highest peak in 3C to 5C. Primary lung cancer and breast cancer were also divided into 2 types of DNA histogram, which were similar to those of metastatic brain tumors as type I and type II. Although there was no case of metastatic brain tumor having a DNA histogram of primary tumor in the same case, DNA patterns of metastatic brain tumors might be related to those of primary tumors because of the similarity of the histograms. It was difficult to disclose the primary sites or histological types of metastatic brain tumors from the type of DNA histograms but flow cytometric analysis revealed the characteristic patterns such as type II and III in metastatic brain tumors. We consider that these patterns might be of clinical diagnostic value in flow cytometric study.

Adenocarcinoma↗

Structural studies on an antitumor polysaccharide from Microellobosporia grisea.

The structure of the antitumor polysaccharide from the actinomycete Microellobosporia grisea has been investigated. By methylation and periodate-oxidation studies, the polysaccharide was shown to consist of (nonreducing) D-mannosyl groups, (1 leads to 4)-linked D-glucosyl residues, and 3,6-branched, (1 leads to 4)-linked D-glucosyl residues in the approximate molar ratios of 2:1:1. Periodate oxidation of the polysaccharide, followed by borohydride reduction and mild hydrolysis with acid yielded glycerol, erythritol, 2-O-beta-D-glucopyranosyl-D-erythritol, and 5-O-beta-D-glucopyranosyl-2,4-bis(hydroxymethyl)-1,3-dioxane, which were isolated in the molar ratios of 2.0:0.14:0.74:0.35. Partial hydrolysis of the polysaccharide gave alpha-D-Manp-(1 leads to 6)-D-Glcp, beta-D-Glcp-(1 leads to 4)-D-Glcp, alpha-D-Manp-(1 leads to 3)-D-Glcp, and beta-D-Glcp-(1 leads to 4)-[alpha-D-Manp-(1 leads to 3)-]-D-Glcp. From these results, it is proposed that the polysaccharide is mainly composed of tetrasaccharide repeating-units having the following structure. (formula: see text)

Actinomycetales Infections↗