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Biomedical subjects

M Kurimoto

Publications and source records attributed to M Kurimoto.

283 records · Page 16Linked to original sources

Simultaneous exposure to interleukin-18 and interleukin-10 in vitro synergistically augments murine spleen natural killer cell activity.

Interleukin-18 (IL-18) enhances interferon gamma (IFNgamma) production and natural killer (NK) cell activity, and elicits protective antitumor effects in vivo. IL-18 and IL-12 synergistically augment IFNgamma production reportedly because IL-12 enhances IL-18 receptor (IL-18R) expression. We now show that IL-18 also synergizes with IL-10 to augment murine splenic NK activity against Yac-1 cells in a standard 4-h chromium-release assay, but IFNgamma production is only slightly enhanced. This pattern of NK activity was also observed with severe combined immunodeficient (SCID) mouse spleen cells indicating that the cytokines were not acting on T or B cells. The cytokines had no priming activity on the spleen cells and, when cells were left unstimulated for 24 h in culture, little NK activity was induced when IL-18 was added for the next 24 h. The reverse transcriptase/polymerase chain reaction revealed that IL-18 receptor (IL-18R) mRNA was expressed early during in vitro spleen cell culture but none was expressed after culture for 24 h regardless of the stimulus. Binding of 125I-labeled IL-18 revealed that exposure to IL-10 only slightly increased IL-18R expression. Expression of perforin mRNA was constitutive and was unaffected by the cytokines; however, Fas ligand (FasL) mRNA expression was strong in cultures with IL-18 alone or combined with IL-10. When Fas-expressing cells and their parental cells were used as targets, weak Fas-mediated cytolytic activity was observed after exposure to IL-18, and this was further enhanced by combination with IL-10. Finally, the augmentation of NK activity was abrogated by the inhibitor concanamycin A, indicating that the enhanced NK activity is perforin-dependent.

Animals↗

Surgically resected brain stem cavernous angioma in an infant.

An infantile case of surgically resected brain stem cavernous angioma is presented. This 21-month-old boy was admitted to our department after repeated severe pontine hemorrhage. A deeplying lesion with hematoma was successfully removed via the IV ventricle approach. Few infantile cases of this lesion have been presented previously, and the approaches to brain stem cavernous angiomas in infants are discussed.

Brain Neoplasms↗

Clinical utility of three-dimensional time-of-flight magnetic resonance angiography for the evaluation of intracranial aneurysms.

Magnetic resonance (MR) angiographic studies of 14 patients with intracranial aneurysms (AN) were analyzed retrospectively as compared with contrast angiographic studies. Eighteen of 19 (95%) lesions were detected, and the relation between AN and their parent vessels was precisely assessed. The diameter of the smallest aneurysm detected in our case was 3 mm. However, small vessels around AN were not visualized. Therefore, MR angiography (MRA) is definitely not a substitute for preoperative contrast angiography. MRA is a useful screening tool for nonruptured AN, but further refinement is required to evaluate emergency ruptured AN.

Adolescent↗

Antitumor activity of interleukin-18 on mouse glioma cells.

Interleukin-18 (IL-18) exhibits antitumor activity in various laboratory models. In the current study, brain tumors in naive mice regressed after an intratumoral injection of a single dose of recombinant IL-18 (rIL-18). Intraperitoneal rIL-18 substantially delayed the growth of subcutaneously inoculated gliomas but not gliomas located in the brain. Efficacy was reduced when studies were performed in mice depleted of natural killer cells. Although intracerebral administration of rIL-18 increased the serum interferon-gamma concentration, the antitumor effect of IL-18 was not mediated by interferon-gamma. These data suggest the therapeutic potential for control of tumor growth by intratumoral administration of rIL-18 in patients with glioma.

Animals↗

Establishment of an in vivo human myeloid leukemia model in the SCID mouse.

We succeeded in establishing a human myelogenous leukemia model in severe combined immunodeficient (SCID) mice by transplanting 2 x 10(7) ML-2 cells intraperitoneally (i.p.) with cyclophosphamide (CTX) pretreatment. Two months after transplantation, 9 of 10 mice developed leukemia and leukemia cells were detected in the peripheral blood (PB) and bone marrow (BM). The main findings at autopsy were peritoneal and pleural effusions and large tumor masses involving the peritoneal organs. However, successful transplantation required injection of a large number of cells. We therefore established a new cell line, ML-2S, from the PB of a mouse with ML-2 leukemia. Although only 2 x 10(6) ML-2S cells were inoculated, ML-2S induced the same pattern of leukemic dissemination reminiscent of the parent ML-2 cells. Compared to ML-2, progression of ML-2S was slow, suggesting that ML-2S is suitable as a leukemia model to study treatment. Furthermore, we confirmed that ML-2S cells are of human origin using isoenzyme analysis and also that ML-2S and ML-2 cells have the same phenotypic character by cell surface marker analysis.

Animals↗

Apoptosis of human leukemia cells induced by Artepillin C, an active ingredient of Brazilian propolis.

Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) is an active ingredient of Brazilian propolis that possesses anti-tumor activity. When Artepillin C was applied to human leukemia cell lines of different phenotypes, namely, lymphocytic leukemia (7 cell lines of T-cell, 5 cell lines of B-cell), myeloid and monocytic leukemia and non-lymphoid non-myeloid leukemia cell lines in vitro, Artepillin C exhibited potent cytocidal effects and induced marked levels of apoptosis in all the cell lines. The most potent effects were observed in the T-cell lines. Apoptotic bodies and DNA fragmentation were induced in the cell lines after exposure to Artepillin C. DNA synthesis in the leukemia cells was clearly inhibited and disintegration of the cells was confirmed microscopically. Apoptosis of the leukemia cells may be partially associated with enhanced Fas antigen expression and loss of mitochondrial membrane potential. In contrast, although Artepillin C inhibited the growth of pokeweed mitogen (PWM)-stimulated normal blood lymphocytes, it was not cytocidal to normal unstimulated lymphocytes. These results suggested that Artepillin C, an active ingredient of Brazilian propolis, has anti-leukemic effects with limited inhibitory effects on normal lymphocytes.

Antineoplastic Agents↗

Interleukin-18 in patients with congestive heart failure: induction of atrial natriuretic peptide gene expression.

Activated inflammatory responses appear to play a role in the development of congestive heart failure (CHF). We investigated interleukin-18 (IL-18), which is a cytokine synthesized by activated macrophage, changes in patients with CHF. We evaluated 11 Japanese patients with angina pectoris (n=4) or CHF (n=7). Blood was sampled immediately after admission and at 1, 2, 3, 6, and 9 hours after admission and then every 12 hours until 5 days after admission. Plasma IL-18 concentrations were measured by an enzyme-linked immunosorbent assay. Expression of atrial natriuretic peptide (ANP) mRNA and protein synthesis was examined in cardiac myocyte by stimulation of IL-18. Plasma IL-18 concentration was significantly higher in patients with CHF than in 15 healthy volunteers (51+/-21 pg/mL, and 28+11 pg/mL, respectively, P<0.05). Increased expression of ANP mRNA was demonstrated in IL-18 treated myocytes. Protein synthesis in myocytes was increased by IL-18 in a dose-dependent manner. Increased secretion of IL-18 is induced in patients with CHF and correlates with the severity of myocardial damage and dysfunction.

Adult↗

Prevention of azoxymethane-induced intestinal tumors by a crude ethyl acetate-extract and tryptanthrin extracted from Polygonum tinctorium Lour.

The effect of a crude ethyl acetate (AcOEt)-extract and tryptanthrin extracted from the Indigo plant (Polygonum tinctorium Lour.) on azoxymethane (AOM)-induced intestinal tumors was examined in F344 rats. The rats were given subcutaneous (s.c.) injections of either AOM (15 mg/kg body weight (b.w.)) once a week for 3 weeks to induce atypical crypt foci (ACF) as a known cancer precursor, or AOM (7.5 mg/kg b.w.) once a week for 10 weeks to induce intestinal tumors. The rats were also administered the AcOEt-extract (500 mg/kg b.w.) or tryptanthrin (50 mg/kg b.w.) orally, 5 days a week, for 7 or 30 weeks, starting two days before the first administration of AOM. All rats were killed 4 or 20 weeks after the last treatment. In the short-term experiment, the incidence of ACE and atypical crypts (AC) in the groups receiving the AcOEt-extract and tryptanthrin was significantly lower than in the control group. In the tumor-inducing experiment, intestinal tumor incidence in the tryptanthrin group was lower than in the AOM-control group (5% versus 26%), and small intestine tumor incidence in the AcOEt-extract and tryptanthrin groups were lower than in the AOM-control group (0% and 0% versus 23%). These results show that the AcOEt-extract of Indigo and tryptanthrin have cancer chemopreventive activity.

Acetates↗

Interleukin 18 enhances Fas ligand expression and induces apoptosis in Fas-expressing human myelomonocytic KG-1 cells.

Interleukin-18 (IL-18) induces apoptosis in human myelomonocytic KG-1 cells as determined by agarose gel electrophoresis, and flow cytometry after propidium iodide (PI) staining. Apoptosis was detected 20 hours from the start of culture at concentrations of 100 ng/ml of the cytokine. Although IL-18 induces the production of large amounts of interferon gamma (IFN-gamma) by KG-1 cells, conditioned media could not induce apoptosis of fresh cells. The protein expressions of p53 and Fas ligand by KG-1 cells, which constitutively express the Fas antigen (CD95), were found to increase after exposure to IL-18 for 20 hours. Both Fas ligand and its receptor were found to be functional by in vitro assays on Fas-expressing target cells and an agonist anti-Fas antibody, respectively. In conclusion, IL-18 enhances the expression of Fas ligand by Fas-expressing KG-1 cells and induces apoptosis in the cells through a mechanism probably involving the Fas pathway.

Apoptosis↗

High expression of glycosphingolipids involved in procoagulant activity of cancer cells.

To investigate the involvement of tumor-associated antigens such as sLe(a) and sLe(x), as well as Le(y) glycosphingolipid in the procoagulant activity of cancer cells, we examined the relationship between the inhibitory effect of anti-sLe(a) or anti-sLe(x) antibodies on the procoagulant activity of cancer cells, and cell surface expression of sLe(a) and sLe(x) antigens. We observed that the procoagulant activity of cancer cells which highly expressed sLe(a) or sLe(x) antigens (expression rate >70%) was significantly inhibited by the relevant antibodies. These data suggested that not only Le(y) but also sLe(a) and sLe(x) antigens play an important role in coagulation induced by various cancer cells.

Adenocarcinoma↗

Augmentation of in vitro interleukin 10 production after in vivo administration of interleukin 18 is activated macrophage-dependent and is probably not involved in the antitumor effects of interleukin 18.

We have previously shown that interleukin (IL)-18 protects mice from intraperitoneal transplantation with syngeneic Meth A sarcoma, and in the process induces the production of large amounts of IL-10 from mitogen-stimulated treated mouse spleen cells, with a simultaneous augmentation of natural killer (NK) cell activity. Using in vivo and in vitro cell depletion methods, we now show that the cells producing IL-10 are neither NK cells nor macrophages (M phi), but that the IL-10 production is dependent on the presence of treated mouse M phi. Anti-IL-12 and anti-CD40L neutralizing antibodies could not inhibit the production of IL-10. Although IL-18-treated normal mouse enriched T cells stimulated with anti-CD3 and anti-CD28 antibodies failed to produce IL-10, the cytokine was also undetectable in culture supernatants of IL-18-treated nude mouse spleen cells, indicating that T cells were directly involved in the induced production of IL-10. Flow cytometry for intracellular IL-10 confirmed that CD8+ T cells and other, as yet unidentified spleen cell sub-sets were secreting IL-10, but only a small percentage of CD4+ cells produced IL-10. In vivo experiments using anti-IL-10 antibody indicated that IL-10 may not be directly involved in the antitumor effects of IL-18.

Animals↗