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Biomedical subjects

K Sakamoto

Publications and source records attributed to K Sakamoto.

At least 901 records · Page 50Linked to original sources

[Effect of carbon tetrachloride on blood coagulation and fibrinolytic activities in rats].

Blood coagulation and fibrinolytic activities were studied in rats with hepatic injury induced by carbon tetrachloride (CCl4). Acute hepatic injury was induced by single oral administration of 0.5, 1.0, 2.0 and 3.0 ml/kg of CCl4. Experiments were performed on the parameters of blood coagulation activities (TEG, HPT, TT, PRCT, PT, PTT, fibrinogen, factor XIII and AT III) and those of fibrinolytic activities (PLG, alpha 2PI) and plasma total protein, GOT, GPT, Ht, L/B ratio. All determinations were measured at 24 hr after administration of CCl4. Blood coagulation and fibrinolytic activities in rats were weakened in accordance with the dosage of CCl4 administration. Below CCl4 administration of 1.0 ml/kg, the GOT and GPT values increased in accordance with the dosage. However, with CCl4 administration of above 1.0 ml/kg, these values stayed at almost the same level. On the other hand, the relationship between the dosage of CCl4 and logarithmic values of HPT, PT, PTT, factor XIII and PLG all showed a good straight line.

Animals↗

Comparative studies on rat primary cultured and isolated hepatocytes in the evaluation of a therapeutic agents for liver disease.

We have investigated the effect of a therapeutic agent for liver disease, Laennec, on the GOT leakage from freshly isolated and primary cultured rat hepatocytes which were treated with CCl4. By treatment with Laennec together with CCl4, the GOT leakage from isolated hepatocytes increased and that from cultured hepatocytes decreased, compared to those incubated only with CCl4. The results suggest that it is better to use primary cultured hepatocytes than to use freshly isolated hepatocytes to evaluate therapeutic agents for liver disease.

Animals↗

Studies on alterations in blood coagulative and fibrinolytic activities after single and multiple administrations of carbon tetrachloride in mice.

The time course of alterations in coagulative and fiblinolytic activities was studied in CCl4-induced liver disease in mice. Liver disease was induced by administration of 20% CCl4 in olive oil (p.o.). After single administration of CCl4, significant prolongation of r and k values and decrease in the ma value of thromboelastogram and apparent prolongation of PT and PTT were seen at 24 hr. Fibrinogen content decreased from 12 to 72 hr after single administration, while a mild but significant decrease in fibrinogen was observed after multiple administrations. The activity of factor XIII increased from 5 to 12 hr and then decreased from 24 to 168 hr after single administration. The activity of the hepaplastintest and Antithrombin III decreased apparently after single and multiple administrations. The plasminogen content and the activity of alpha 2-plasmin inhibitor decreased severely after single and multiple administrations. These results indicate that the coagulative and fibrinolytic activities were decreased to the most lowest value at 24 or 48 hr after single administration of CCl4, and the severe suppression of fibrinolysis and the mild decrease in coagulative activity were observed after multiple administrations of CCl4. The reason for the different effects between single and multiple administrations on coagulative and fibrinolytic systems was discussed.

Acute Disease↗

[A study of the antineoplastic activity of K18].

K18 is a new drug produced by a combination of Melphalan and human immunoglobulin. K18 produced an inhibitory effect on the proliferation of human gastric and colon cancer transplanted in to nude mice. Also, combination effects of K18 with MMC and 5-FU were recognized in the same system. In a study of distribution after K18 administration, the accumulation and retention of this drug in the tumor region were observed. In the case of Melphalan administration, these phenomena were not observed. The antitumor activity of tumor homogenate was evaluated using a colony-forming assay with KB cells. As to the Melphalan-treated group, a four-hour homogenate reduced the number of colonies but a 48-h one did not. In the K18-treated group, the four-hour homogenate decreased the number slightly and the decrease became obvious with 48-h homogenate. In cell cycle analysis using K18 or Melphalan administration, gathering of S-phase cells was observed, but these changes appeared later with K18 than with Melphalan. This result showed that the effect of K18 was produced by the alkylating activity of Melphalan which was combined with immunoglobulin. For clinical application, K18 was administered to cancer patients at a dose of 60-90 mg every day. Two cases of good response were achieved. No side effect was observed. This remarkable efficacy and low degree of side effects in clinical application is probably due to the higher affinity and accumulation of K18 in the tumor region. K18 is a useful new drug for clinical application alone, or in combination with other chemotherapeutic drugs.

Animals↗

The state of the art on the chemical characterization of diesel particulates in Japan.

In this paper, the state of the art of the chemical characterization of diesel particulates in Japan is presented. However, some of these results are only preliminary. The principal contents may be summarized as follows: Characterization of Diesel Particulates; Examples of the application of the chemical characterization to various studies are described. Measurements for elemental composition and distributions of molecular weight and boiling point of diesel particulates and related samples were carried out to gain a better understanding of the main components of diesel particulates. Determinations of carbonaceous components, elemental carbon and organic carbon, in diesel particulates were made by a thermal carbon analyzer, and these results were applied to the study of the relations between such components and the driving conditions of diesel vehicles and to the estimate of emission rates of carbonaceous components from on-road diesel vehicles in a highway tunnel. It seems that the thermal carbon analyzer can be used to advantage in the determination of such carbonaceous components. Artifacts of PAH and 1-NP during Collection of Diesel Particulates; In order to minimize the artifacts of PAH during collection of diesel particulates, three methods were investigated for the artifacts of BkF, BaP and BghiP; two methods incorporated the removal of reactive gaseous components such as NO2, with an ACF method and an impinger method, and the third was a high dilution sampling method. These results suggest that the high dilution sampling method is very promising. From the results of various studies including model experiments, it is clear that the artifact formation of 1-NP is of first order dependence on total amounts of nitrate on carbon black and diesel particulates, not on gaseous nitric acid, although second order dependence of the artifact formation on NO2 concentration is ambiguous. Aside from the above studies, the relation between 1-NP concentrations in diesel exhaust and NO2 concentrations in the dilution tunnel with changing the dilution ratio at a fixed driving condition was utilized for an estimate of the artifact formation of 1-NP, and the estimated results are discussed in connection with the reaction order of the artifact formation on NO2 concentration. Concentrations of Various Components in Diesel Exhaust and Ambient Air; Analytical results are presented for the PAH, mononitro-PAH and dinitro-PAH in particulate samples collected from the exhaust of both IDI and DI diesel vehicles and the ambient air in several areas in Japan and China.(ABSTRACT TRUNCATED AT 400 WORDS)

Air↗

Establishment of a cell line of gallbladder carcinoma (GBK-1) producing human colony stimulating factor.

A cell line designated GBK-1 was established from a patient with anaplastic carcinoma of the gallbladder, marked neutrophilia and fever, and has been propagated for the past 18 months. The cells grew as a monolayer sheet with a doubling time of 43 hr. The GBK-1 cells were of a pleomorphic polygonal epitheloid shape and they were transplantable into nude mice. Mice bearing the tumor developed marked granulocytosis. In the culture supernatant of GBK-1 cells, high colony stimulating factor (CSF) activity was evident with both human bone marrow cells and C57BL mouse bone marrow cells, and granulocytic colonies, macrophage colonies or granulocyte-macrophage mixed colonies were produced. The CSF activity was distributed in the molecular weight range of 25,000 to 60,000 with two distinct peaks at molecular weights of approximately 50,000 and 30,000. CSF activity was inactivated by heat treatment at 70 degrees for 30 min. GBK-1 is a new human cell line that produces heat-labile human GM-CSF.

Animals↗

Requirements of adherent cells for activating Lyt-1+2- T cells as well as for functioning as antitumor effectors activated by factor(s) from Lyt-1+2- T cells.

The mechanism by which tumor-specific Lyt-1+2- T cells exhibit their antitumor effect in collaboration with an adherent cell population was investigated with the use of a double diffusion chamber. The double diffusion chamber was prepared by separating the two chambers from each other by a Millipore membrane and implanted in the peritoneal cavity of C3H/He mice. When one chamber contained normal C3H/He spleen cells plus syngeneic viable MH134 hepatoma cells and the other contained normal C3H/He spleen cells plus syngeneic viable X5563 plasmacytoma cells, tumor cells in both chambers continued to proliferate. In contrast, the injection of spleen cells immunized to the MH134 tumor into one (the first) chamber containing MH134 tumor cells not only resulted in the growth inhibition of MH134 tumor cells, but also exhibited an appreciable inhibitory effect on the growth of X5563 tumor cells admixed with normal spleen cells in the other (second) chamber. The growth inhibition of X5563 tumor cells in the second chamber was mediated by Lyt-1+2- T cells specific for MH134 tumor cells admixed in the first chamber. Such tumor-specific Lyt-1+2- T cell function was dependent on the existence of adherent cells in the first chamber, and adherent cells in the second chamber were also required for the X5563 growth inhibition. In addition, when the second chamber containing adherent cells, instead of the connection to the first chamber, was provided with macrophage-activating factor (MAF), X5563 growth inhibition was also observed. These results indicate that adherent cells are required for activating tumor-specific Lyt-1+2- T cells and for functioning as nonspecific antitumor effector cells activated by factor(s) such as MAF from Lyt-1+2- T cells.

Animals↗

Clinical evaluation of an immunoradiometric assay for CA15-3 antigen associated with human mammary carcinomas: comparison with carcinoembryonic antigen.

Serum levels of CA15-3, a mammary tumor associated antigen recognized by two different murine monoclonal antibodies (115D8 and DF3), were investigated in patients with mammary carcinoma and other benign or malignant diseases. The reference value of the serum CA15-3 level was obtained as 24 units/ml at the 99% confidence limit among healthy individuals (n = 462). Elevation of serum CA15-3 levels was observed in 24.3% of overall patients with mammary carcinoma. Serum CA15-3 levels in breast cancer patients correlated with the clinical stage; higher percentages of positivity were observed in those with advanced breast cancer (stage IV, 64.7%, recurrent, 52.4% and metastatic, 70.3%). Furthermore, elevated serum CA15-3 levels in breast cancer patients responded well to the effect of therapy. Although the serum CA15-3 test gave percentages of positivity of breast cancer similar to those found by the serum CEA test, the serum CA15-3 test revealed lower percentages of positivity than the serum CEA test among patients with benign breast lesions, liver cirrhosis or other carcinomas. These results suggest that the serum CA15-3 antigen level provides a very useful marker for diagnosis and clinical monitoring of patients with breast cancer.

Adolescent↗

Colony-stimulating factor producing carcinoma of the gallbladder.

A patient with an anaplastic carcinoma of the gallbladder accompanied by marked neutrophilia was found to have high colony-stimulating factor (CSF) activity in the urine and serum. The supernatant of the cultured tumor cells (6th passage) showed high and specific CSF activity. These specimens induced the formation of granulocyte colonies, macrophage colonies or granulocyte-macrophage mixed colonies by both human and C57BL mouse bone marrow cells in soft agar. These results suggest that this tumor is a human granulocyte-macrophage (GM)-CSF producing tumor.

Animals↗

[Kinetics and possible mechanism of thermotolerance: a review].

Thermotolerance examined in vitro studies was reviewed in related to their kinetics, modifying factors and also the possible mechanisms. Heat treatments which reduce the survivals at same level at different temperature 42, 43, 44, 45 degrees C induces a same degree of thermotolerance and the thermotolerance decayed in same manner. These findings showed that thermotolerance induced by acute hyperthermia and that by chronic hyperthermia are not different in the nature. Examinations of heat sensitivities and kinetics of thermotolerance among different cell lines indicated that there is a possible relationship between the cellular sensitivity to heat and the magnitude of thermotolerance. The HSP has been found to be the most likely related factor in thermotolerance. But, their functions have not yet been clearly observed. Further research on HSP and thermotolerance is necessary to elucidate the possible mechanism of thermotolerance development.

Cell Cycle↗