Japanese traditional medicine, Senn-kinn-naidaku-sann up-regulates Toll-like receptor 4 and reduces murine allergic rhinitis.

OBJECTIVE: To determine the mechanisms by which a traditional herbal medicine, Senkinnaidakusan (SKNS), controls Th2 responses, we examined the production of IL-12 by murine macrophages treated with SKNS. RESULTS: Treatment with SKNS significantly increased TLR4 mRNA in macrophages. Furthermore, pre-treatment with SKNS enhanced the production of IL-12 by macrophages stimulated with LPS. When SKNS was orally administered to C3H/HeN mice at the induction phase after OVA sensitization, the serum levels of OVA-specific immunoglobulin (Ig)E and IgG1 decreased, Interleukin (IL)-4 production by spleen T cells in response to OVA was significantly suppressed, while interferon (IFN)-gamma production was increased. After nasal challenge of OVA, eosinophilic infiltration in the nasal mucosa and the number of sneezes were significantly inhibited in SKNS-treated mice compared with control mice. Besides, expression of IL-5 in the nasal mucosa was also inhibited. Using another strain of mice, C3H/HeJ (TLR4 negative), there was no difference in OVA-specific Igs or splenic cytokine production between the SKNS treatment and non-treatment groups. The eosinophilic infiltration in the nasal mucosa, the number of sneezes and IL-5 expression in the nasal mucosa were also not effected even after SKNS treatment. CONCLUSION: These results suggest that oral administration of SKNS inhibits Th2 responses by enhancement of IL-12 release from macrophages via up-regulation of TLR4 expression.

[Clinical results of repeated intraperitoneal administration of CDDP in patients with ovarian cancer].

CDDP was intraperitoneally administered to 45 ovarian cancer patients (9 cases in Stage Ic, 9 cases in Stage II, 19 cases in Stage III and 8 cases in Stage IV) as the first line chemotherapy to examine response rates and cumulative survival rates by Kaplan-Meier method. Among 18 cases with measurable tumor, there were 5 CR cases, 6 PR cases, 4 NC cases and 3 PD cases. Eleven out of 18 responded, for a response rate of 61.1%. The 3- and 5-year survival rates were 88.9% and 88.9% in Stage I, 46.7% and 0% in Stage II, 48.6% and 41.7% in Stage III, and 0% and 0% in Stage IV, respectively. The 3- and 5-year survival rates in patients with residual tumor smaller than 2 cm in diameter after the first surgery in Stage III or IV were 76.9% and 61.4% respectively, in contrast to 11.5% and 11.5% in patients with residual tumor of 2 cm or larger in diameter. Thus, a significantly better prognosis was demonstrated in patients with residual tumor smaller than 2 cm. These results indicate that intraperitoneal administration of CDDP demonstrated high response rates and proved to be useful as the first line chemotherapy, yet did not manage to improve the long-term prognosis of patients with progressive cancer.

[Role of C-kinase in development and function of human placental chorionic tissue].

C-kinase is an intracellular protein kinase which is activated by Ca2+ and phospholipid, and plays a crucial role in signal transduction and cell proliferation. To clarify the possibility that C-kinase regulates the growth or maturation of placental tissues, I have purified C-kinase from human placental chorion by sequential column chromatography, determined the substrate specificity of the purified C-kinase, and then investigated the effects of various hormones on the phosphorylation of placental chorionic membrane proteins. The results were as follows: 1) pH optimum of C-kinase was 8.0, apparent Ka for Ca2+ was 1 X 10(-5) M and Ka for phosphatidylserine was 80 micrograms/ml. 2) One of the cytoskeletal proteins, filamin, was phosphorylated specifically by the purified C-kinase. 3) The C-kinase activity increased with placental growth. The enzyme activity in the 3rd. trimester of pregnancy was 5 times higher than that in the 1st. trimester. 4) C-kinase activity was inhibited by hCG and markedly stimulated by DHA or DHAS. These results suggest that C-kinase is involved in the specific functions of the placenta.

[Ca2+, phospholipid-dependent protein kinase (C-kinase) in the rat placental chorion].

C-kinase is one of the enzymes which phosphorylate cellular proteins, and is reported to be involved in transmission of the extracellular signals regarding hormones, etc. to inside the cell. This enzyme is widely distributed in many tissues and organs and several C-kinase-mediated cellular responses were reported. However, in the placenta, the presence of C-kinase has not been reported. In this paper we reported for the first time the purification of C-kinase from rat placental chorion and investigated the physiological functions of C-kinase. The results were as follows: A considerable amount of C-kinase was detected in the membrane fraction of rat placenta. C-kinase specifically phosphorylated several membrane proteins, and the phosphorylation pattern was different from those of mid pregnancy and late pregnancy. The C-kinase activity in late pregnancy was 6 times higher than that of mid pregnancy. Hemin and Polylysine inhibited partially-purified membrane-bound C-kinase. Substrate specificity C-kinase from rat placenta was similar to those from other organs.

Effects of linoleic acid and cations on the activity of a novel high-molecular weight protease, ingensin, from human placenta.

A linoleic acid-sensitive protease, ingensin, was purified to homogeneity from human placenta. The physical properties of the placental ingensin were found to be very similar to those of skeletal muscle ingensin [Ishiura et al. (1985) FEBS Lett. 189, 119-123]. The purified ingensin was activated by linoleic acid and SDS. The linoleic acid-activated form was inhibited preferentially by divalent cations, whereas the SDS-activated form was inhibited by monovalent cations instead.