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Biomedical subjects

K Kawamoto

Publications and source records attributed to K Kawamoto.

At least 217 records · Page 12Linked to original sources

[Clinical studies of long-term administration of OK-432 in patients with gynecologic cancer].

The clinical value of OK-432 treatments, was evaluated in 215 patients with various types of gynecologic cancer. Five KE OK-432 was administrated by intramuscular injection every other day for up to 5 years, unless severe side-effects were observed. The 5-year survival rate was determined in 51 patients in the OK-432 group and 93 patients in the control group. The survival rate in the OK-432 group was significantly higher in the cervical cancer patients in stages III and IV than in the control group, at from 20 to 29 months and from 37 to 42 months. These results indicated that long period administration of OK-432 might improve the survival rate in patients with gynecologic cancer, especially in those with advanced cervical cancer.

Adult↗

[Experimental and clinical evaluations of flow cytometric DNA-aneuploidy for the determining malignancy of head and neck tumors].

Using flow cytometry, basic experiments and clinical trials to investigate DNA aneuploidy were performed. The site of the peak in the DNA histogram was found to be unstable in the flow cytometric assay. However, relatively stable DNA indices can be obtained if only internal standards, such as human lymphocytes, etc., are added to the samples, thus results in a more precise detection of aneuploidy. In 11 cases of head and neck tumors, DNA aneuploidy was observed in six out of seven cases that were histopathologically diagnosed as being malignant tumors, showing a correlation with the pathological studies as a whole. Further clinical studies may prove that the present method can be useful for the pathological, supplementary diagnostic and prognostic evaluations.

Aneuploidy↗

Chlorinated organic compounds in urban air in Japan.

Air pollution by the principal chlorinated organic compounds chloroform, carbon tetrachloride, 1,1,1-trichloroethane, trichloroethylene and tetrachloroethylene was investigated over a period of approximately 1 year at 15 sites in an urban area. Each compound was detected in the range from approximately 0.1 to several ppb; the concentrations of these compounds, with the exception of carbon tetrachloride, were higher than their global pollution levels. The concentrations of 1,1,1-trichloroethane and trichloroethylene especially were very high in the industrial regions, and the concentration of tetrachloroethylene was very high in the industrial and commercial regions. Concentrations were low in spring and summer and high in fall, winter and the rainy season. The correlation between the reciprocal of wind speed and concentrations was found to be subject to seasonal variations. Intake of chlorinated organic compounds by man from the air was estimated from the data to be larger than the allowable intakes determined by WHO and EPA for drinking water.

Air Pollutants↗

Efficacy of defibrinogenation and steroid therapies on sudden deafness.

Effects of defibrinogenation therapy and steroid therapy for sudden deafness were compared by paired double-blind testing. The average hearing recovery for five frequencies (250 to 4000 Hz) was more than 30 dB; overall improvement rate was 57.3% (47/82) for the patients assigned to defibrinogenation therapy and 38.7% (31/80) for the patients assigned to steroid therapy. Thus, the former treatment resulted in significantly better hearing recovery.

Administration, Oral↗

New sensitivity test using flow cytometry.

Flow cytometry (FCM) has been used to evaluate not only the malignancy of tumor cells but also the effects of chemotherapy. Here a new application of FCM for selecting the best antineoplastic agent in the chemotherapy for brain tumors is reported. Through our preliminary study using established brain tumor cell lines, the system for this sensitivity test was developed. Antineoplastic agents were placed in contact with monolayer-cultured cells; then cell viability and changes in the DNA histogram were analyzed by FCM. Cell viabilities were measured with the fluorescein diacetate (FDA) staining method, and the DNA histogram was analyzed by the propidium iodide (PI) staining method. The best antineoplastic agent was determined based on changes in cell viability and cell cycle. In other words, when markedly decreased viability as compared with that of the control, is measured by FCM, then the agents can be considered to have had a cytocydal effect on the tumor cells, and thus the sensitivity of the agents is able to be evaluated. If the viability of the tumor cell is observed to be similar to that of the control, the cytostatic effects of the agents are able to be evaluated only if a marked change is observed in the DNA histogram. After the preliminary study, this system was applied clinically to malignant brain tumor cases, resulting in success in selecting the best antineoplastic agent for each individual case. Our sensitivity test using this FCM established in vitro system has much potential value for clinical use.

Brain Neoplasms↗

In vitro effect of beta-lactam antibiotics and N-methyltetrazolethiol on microsomal vitamin K epoxide reductase in rats.

Liver microsomal vitamin K epoxide reductase activity was determined by measuring the formation of menaquinone-4 from the substrate menaquinone-4 2,3-epoxide. The enzyme was active when dithiothreitol (DTT) was used as a reducing agent, and the activity increased gradually with increasing concentrations of DTT. Glutathione and cysteine also functioned as reductants, but these physiological reductants showed less than 15% of the activity detected with 0.5 mM DTT. Addition of various beta-lactam antibiotics to the assay mixture for vitamin K epoxide reductase caused a slight inhibition of the activity. N-Methyltetrazolethiol (NMTT) and other heterocyclic thiol compounds also inhibited the enzyme activity in vitro depending on their concentrations. Most of these antibiotics and heterocyclic thiol compounds inhibited the enzyme activity only 10-25% in the in vitro assay system even when higher concentrations were added (5-10 mM). Among the compounds tested, methyl-thiadiazolethiol was the only compound that caused 50% inhibition of the enzyme activity. NMTT-induced inhibition was diminished gradually by increasing DTT concentrations. Kinetic analysis of the inhibitory action of heterocyclic thiol compounds showed competitive inhibition against the reductant DTT and non-competitive inhibition against the substrate. On the other hand, warfarin, a typical anticoagulant, showed different patterns in the inhibitory action: non-competitive inhibition against DTT and mixed-type inhibition against the substrate.

Animals↗

[Operative approach to a dumbbell-shaped tumor in the anterior cranial fossa. A case of olfactory neuroblastoma].

We present a case of giant olfactory neuroblastoma with special reference to a new operative approach in cases of dumbbell-shaped tumor in the anterior cranial fossa. Our new approach is characterized as follows: resection of the bilateral orbital roof and frontal sinus en bloc, following bifrontal conventional craniotomy. Accordingly, retraction of the frontal lobe is minimized and it is possible to obtain, with ease, a good operative field extending to the region adjacent to the tuberculum sellae. Using this technique combined with the transsphenoidal approach, even in the case of marked extracranial downward extension of a dumbbell-shaped tumor, it should be possible to remove the tumor totally. This approach should open a way to a wide range of application.

Adult↗

Regeneration of neurohypophyseal hormone-producing neurons in hypophysectomized immature rats.

Age-related changes in the regeneration of vasopressin (AVP) and oxytocin (OXT) axons after hypophysectomy in rats was immunohistochemically examined. Rats were hypophysectomized at 9, 16, 23, 30 and 90 days of age, and sacrificed 10 days after the operation. AVP or OXT immunoreactivity in the external layer of the median eminence (ME) was generally stronger in hypophysectomized immature rats than in hypophysectomized adult rats, and the age-related difference in immunoreactivity was more conspicuous for AVP axons than OXT ones. The cell body size of AVP or OXT neurons in hypophysectomized adult rats was not significantly different from the value of unoperated or initial control rats. However, the neurons in immature rats became significantly larger after hypophysectomy, compared with those of initial controls. These results indicate that AVP- and OXT-producing neurons in immature rats, as early as at 9 days of age, are endowed with the capacity of axonal rearrangement to the external layer of the ME after hypophysectomy, and that the stronger immunoreactivity in the external layer of the ME in immature rats than in the adult may be due to the differences in the rate of synthesis of neurohypophyseal hormones and the regenerative potency of neurons.

Aging↗

A rare case of Maffucci's syndrome combined with tuberculum sellae enchondroma, pituitary adenoma and thyroid adenoma.

Maffucci's syndrome is a rare, congenital mesodermal dysplasia combined with dyschondroplasia and haemangiomatosis, and there are only about 150 reported cases. This syndrome is often combined with other neoplasms. Our case was associated with goitre, enchondroma of the tuberculum sellae and pituitary adenoma; the latter brought about disturbance of vision. Including ours, four cases of Maffucci's syndrome associated with pituitary adenoma are found in the literature. In the case of Maffucci's syndrome, it is necessary to examine associated disease as well as associated pituitary adenoma and skull base enchondroma, similar to the correlation of von Recklinghausen's disease with acoustic neurinoma.

Adenoma↗

Intestinal absorption and metabolism of homoursodeoxycholic acid in rats.

Intestinal absorption, hepatic biotransformation and intestinal bacterial modification of the C25 homolog of ursodeoxycholic acid, homoursodeoxycholic acid, and its glycine conjugate, glycohomoursodeoxycholic acid, were studied in rats. Homoursodeoxycholic acid, like ursodeoxycholic acid, was efficiently absorbed from the intestine and rapidly excreted into the bile. Most (greater than 95%) of the absorbed homoursodeoxycholic acid was found to undergo beta-oxidation to form two C23 bile acids, norursodeoxycholic acid and nor-beta-muricholic acid during passage through the liver. Bacterial modification of homoursodeoxycholic acid was very similar to that of ursodeoxycholic acid. In the rat intestinal tract, glycohomoursodexycholic acid was deconjugated to form unconjugated homoursodeoxycholic acid which was then 7 beta-dehydroxylated to form homolithocholic acid.

Animals↗

Effects of beta-lactam antibiotics and N-methyltetrazolethiol on the alcohol-metabolizing system in rats.

The disulfiram-like effect of various beta-lactam antibiotics containing N-methyltetrazolethiol (NMTT) on the alcohol-metabolizing system was studied using rats. Their administration caused decreased activities in low Km aldehyde dehydrogenase (ALDH) and acetaldehyde oxidation in the liver, with marked depression from several hours to 2 days after the treatment. Blood acetaldehyde level increased markedly when ethanol was administered 18-24 hr after pretreatment with antibiotics. A similar time course change in the effect was obtained when disulfiram was administered. The following results obtained in the present study indicate that the disulfiram-like effect associated with these antibiotics was not mediated by the whole molecular structures of these drugs: Firstly, the antibiotics were eliminated rapidly from the plasma and liver, and the disulfiram-like effect was followed by a disappearance of the drugs. Secondly, the concentration of antibiotics required to inhibit mitochondrial low Km ALDH activity in vitro was very high compared with their liver concentration. Thirdly, rapid onset of disulfiram-like effects occurred after administration of NMTT itself, and a pronounced elevation of blood acetaldehyde level was observed when ethanol was administered 3-5 hr after the NMTT injection. Fourthly, almost the same amounts of NMTT were released in the body after the intravenous administration of various NMTT-containing antibiotics, as judged by the urinary excretion. These results suggest that the disulfiram-like effect of beta-lactam antibiotics is mediated by NMTT released from them.

Acetaldehyde↗