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Biomedical subjects

K Kusama

Publications and source records attributed to K Kusama.

At least 73 records · Page 4Linked to original sources

Induction of sarcomas in rats by subcutaneous injection of dinitropyrenes.

The carcinogenicities of potent mutagenic dinitropyrenes were examined by their subcutaneous injections into male F344/ DuCrj rats. Animals were injected with 0.2 mg each of 1,3- and 1,8-dinitropyrenes (1,3- and 1,8- DNPs ) dissolved in 0.2 ml of dimethyl sulfoxide (DMSO) twice a week for 10 weeks. In rats treated with 1,8-DNP, sarcomas were induced at the sites of injection in all 10 animals tested between the 113th and 127th experimental days. In rats treated with 1,3-DNP, 10 of 10 rats developed sarcomas between days 119 and 320. Some tumors induced by these chemicals were transplantable into the same strain of rats. No tumors developed in control rats, which received only DMSO.

Animals↗

Carcinogenicity in mice of a mutagenic compound, 2-amino-3-methylimidazo[4,5-f]quinoline, from broiled sardine, cooked beef and beef extract.

A potent mutagenic compound, 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ), isolated from broiled sardines, cooked beef and beef extract was tested for carcinogenicity in CDF1 mice of both sexes. Mice were given diet containing 0.03% IQ or control diet for up to 675 days. Tumors were observed mainly in the liver, forestomach and lung. In the mice given IQ, the incidences of these tumors were as follows: liver tumors - 41% in males and 75% in females; tumors of the forestomach - 41% in males and 31% in females; lung tumors - 69% in males and 42% in females. In the control mice, incidences of these tumors were as follows: liver tumors - 9% in males and 8% in females; tumors of the forestomach - 3% in males and 0% in females; lung tumors - 21% in males and 18% in females. The incidences of tumors in the liver, forestomach and lung were significantly higher in mice given IQ than in control mice.

Animals↗

Discovery, isolation and structure of novel cephamycins of Streptomyces chartreusis.

By the use of HPLC technique after treatment with beta-lactamases, two novel cephamycins, SF-1623 and SF-1623B, were discovered and isolated from the fermentation broth of Streptomyces chartreusis SF-1623. The structures of SF-1623 and SF-1623B were determined to contain 3-sulfothiomethyl and 3-hydroxymethyl groups respectively, by chemical and enzymatic transformation reactions. Studies on the fermentation condition and process for the large scale preparation of antibiotic SF-1623 are also described.

Bacteria↗

An ultrastructural and immunohistochemical study on mandibular lesion of Letterer-Siwe disease.

A mandibular lesion from an infant with Letterer-Siwe disease was studied by electron microscopy and immunohistochemistry. Ultrastructurally, two types of cells were identified; clear and dark cells. Clear cells had indented nuclei and langerhans cell granules, while dark cells were characterized by the occasional presence of a large number of lysosomes. Lysozyme was usually not detectable in proliferating cells with indented nuclei, but it was strongly positive in cells without indented nuclei. The latter also usually contained IgG, although the occurrence of cytoplasmic IgM, A, D and E seemed to be negative in both types of cells. Thus clear cells showed a close resemblance to Langerhans cells and dark cells had features of ordinary histiocytes. Although the intimate relationship between these two types of cells remains obscure, our findings suggest that Letterer-Siwe disease may be a reactive or tumorous condition of a cellular subpopulation of Langerhans cells with a proliferation of differentiated histiocytes.

Antigen-Antibody Reactions↗

Induction of non-apoptotic cell death by sodium 5,6-benzylidene-L-ascorbate in a human salivary gland tumor cell line.

We investigated whether sodium 5,6-benzylidene-L-ascorbate (SBA) induces apoptotic cell death in a human salivary gland tumor cell line HSG, using two different cytochemical methods. Millimolar concentrations of SBA dose-dependently reduced the viable cell number of HSG cells, accompanied by the detachment of dying cells from the culture plates. The nuclei of the dying cells were not stained with TUNEL reagent, indicating the lack of DNA nicks or fragments. On the other hand, the nuclei of epigallocatechin gallate (EGCG)-treated cells (positive control) were TUNEL-positive, demonstrating the production of DNA nicks or fragments. Furthermore, the cytoplasms of SBA-treated cells were not stained with M30 monoclonal antibody, which reacts with the degradation products of cytokeratin 18 by the activated caspases, in contrast to those of EGCG-treated cells. These results suggest that SBA induces non-apoptotic cell death, possibly necrosis, in HSG cells.

Antibodies, Monoclonal↗

Inhibition of epigallocatechin gallate-induced apoptosis by CoCl2 in human oral tumor cell lines.

Epigallocatechin gallate (EGCG) induced apoptotic cell death in two human oral tumor cell lines (HSC-2, HSG), as judged by TUNEL method which detects DNA nick. Furthermore, the cytoplasm of EGCG-treated HSG cells was stained by M30 monoclonal antibody, which detects the degradation product of cytokeratin by activated caspase. The apoptosis-inducing activity of EGCG was significantly reduced by millimolar concentrations of CoCl2. CoCl2 also inhibited the cytotoxic activity of sodium ascorbate, gallic acid and curcumin, but not that of sodium-5, 6-benzylidene-L-ascorbate (SBA). This suggests that SBA, an antitumor agent, induces cell death by a different mechanism from that of other antioxidants used in this study. The possible role of CoCl2 for cell survival was discussed.

Antioxidants↗

Use of the monoclonal antibody M30 for detecting HSG cell apoptosis.

An immunocytochemical method using a monoclonal antibody (MoAb), M30, which reacts with the product resulting from the cleavage of cytokeratin 18 by activated caspase, was applied to detect the apoptosis of human salivary gland tumor (HSG) cells induced by epigallocatechin gallate (EGCG), gallic acid (GA) and sodium ascorbate (SA). EGCG, GA and SA dose-dependently induced HSG cell death. Immunoreactive products were significantly observed in the cytoplasm of HSG cells after treatment with all these compounds. The reactions occurred with lower concentrations of these agents and after shorter treatment times, in comparison with DNA fragmentation detected by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method. These results suggest that immunocytochemical staining with the MoAb M30 may be useful for detecting the apoptosis-inducing activities of various chemical compounds.

Antibodies, Monoclonal↗

Induction of apoptosis by dopamine in human oral tumor cell lines.

Dopamine dose-dependently reduced the viable cell number of both human salivary gland tumor HSG and oral squamous cell carcinoma HSC-2, HSC-4, and NA cells. CoCl2 significantly reduced both the cytotoxic activity and radical intensity of dopamine (determined by ESR spectroscopy). Dopamine produced DNA fragments (demonstrated by TUNEL method) and induced degradation of cytokeratin by activated caspase in HSG cells (detected by an immunocytochemical method, using a specific M30 monoclonal antibody). FACS analysis demonstrated that dopamine induced DNA fragmentation, a biochemical hallmark of apoptosis, in human promyelocytic leukemia HL-60 cells. The addition of catalase did not prevent the apoptosis-inducing activity of dopamine, reducing the possibility of the involvement of H2O2 for dopamine-induced apoptosis. Dopamine transiently induced p38 mitogen-activated protein kinase (MAP kinase) phosphorylation. However, an inhibitor of p38 MAP kinase phosphorylation, SB203680, failed to inhibit the dopamine-induced apoptosis. These data suggest that p38 phosphorylation at an early stage may not be a causative event for apoptosis.

Apoptosis↗