Unmasking of LPA1 receptor-mediated migration response to lysophosphatidic acid by interleukin-1ß-induced attenuation of Rho signaling pathways in rat astrocytes.

Action mechanism of lipopolysaccharide (LPS), interleukin-1ß (IL-1ß), and lysophosphatidic acid (LPA) to regulate motility, an important process of astrogliosis, was investigated in rat astrocytes. While LPA exerted no significant effect on the cell migration, the prior treatment of the cells with LPS or IL-1ß resulted in the appearance of migration activity in response to LPA. The LPS induction of the migration response to LPA was associated with the production of IL-1ß precursor protein and inhibited by the IL-1 receptor antagonist. The IL-1ß treatment also allowed LPA to activate Rac1. The LPA-induced Rac1 activation and migration were inhibited by pertussis toxin, a small interfering RNA specific to LPA(1) receptors, and LPA(1) receptor antagonists, including Ki16425. However, the IL-1ß treatment had no appreciable effect on LPA(1) receptor mRNA expression and LPA-induced activation of ERK, Akt, and proliferation. The induction of the migration response to LPA by IL-1ß was inhibited by a constitutively active RhoA. Moreover, LPA significantly activated RhoA through the LPA(1) receptor in the control cells but not in the IL-1ß-treated cells. These results suggest that IL-1ß inhibits the LPA(1) receptor-mediated Rho signaling through the IL-1 receptor, thereby disclosing the LPA(1) receptor-mediated G(i) protein/Rac/migration pathway.

Interferon-alpha-induced changes in metallothionein expression in liver biopsies from patients with chronic hepatitis C.

An association between reactive oxygen species and liver damage has been postulated in the course of hepatitis C virus (HCV) infection. Metallothionein (MT), induced by HCV core protein and interferon (IFN), plays a role in scavenging free radicals. MT expression in liver biopsies obtained from 21 patients with chronic HCV infection before and after IFN-alpha therapy was investigated. Changes in Knodell histological activity index (HAI) scores, MT protein levels (immunohistochemistry), MT-I and MT-II messenger (m)RNA expression levels (in situ hybridization) and proliferating cell nuclear antigen (PCNA) labelling index were determined and compared in serial liver specimens. MT staining was clustered around the portal tracts with inflammatory cells and fibrosis. The pattern of MT protein before IFN-alpha therapy was similar in all patients, but was higher in IFN-sustained responders than in nonresponders after IFN-alpha therapy. HAI scores and PCNA labelling indexes were significantly reduced after IFN-alpha therapy. MT-II mRNA expression correlated positively with PCNA index before therapy and with HAI scores after therapy (P<0.05). No correlation was found between MT-I mRNA and HAI scores or PCNA index. The findings indicate that IFN-alpha-induced hepatic MT may participate in the therapeutic effects of IFN-alpha for HCV. In addition, MT-II mRNA expression may be involved in cell proliferation in the livers of patients with chronic HCV infection.

Two subtypes in colorectal mucinous carcinoma in relation to microsatellite instability.

BACKGROUND/AIMS: Although some investigators have attempted to divide colorectal mucinous adenocarcinoma into two entities, there have been few reports describing microsatellite instability of each subtype. In this study, we elucidated the clinicopathological features of subtypes in mucinous carcinoma, especially the relationship between microsatellite instability and each subtype. METHODOLOGY: The present study included 33 patients with mucinous colorectal cancer. The 33 patients were classified into two groups; the papillotubular type group (n = 22) and the mucocellular type group (n = 11). The clinicopathological aspects and microsatellite instability were examined. RESULTS: Significant differences were found between the papillotubular type group and the mucocellular type group regarding the following findings such as lymphatic invasion, lymph node metastasis, peritoneal metastasis, and Dukes stage. The mucocellular type group had 2 cases with high-frequency microsatellite instability, 7 cases with low-frequency microsatellite instability and 2 cases with microsatellite stability. Conversely, the papillotubular type group included 12 cases with high-frequency microsatellite instability, 3 cases with low-frequency microsatellite instability and 7 cases with microsatellite stability. The ratio of cases with high-frequency microsatellite instability in the mucocellular type group (18.1%) was significantly lower than that of the papillotubular type group (54.5%) (P = 0.0463). The 5-year survival rate of the mucocellular type group (29.1%) was significantly lower than that of the papillotubular type group (70.3%) (P = 0.0282). CONCLUSIONS: Colorectal mucinous carcinoma needs to be classified into two groups, papillotubular type and mucocellular type, because of significant differences in microsatellite instability and patients' survival.

Ulcerative colitis associated with Takayasu's disease in two patients who received proctocolectomy.

Ulcerative colitis (UC) associated with Takayasu's disease (TD) is not common in Japan. Here, we report two patients with both diseases who received a total proctocolectomy. Patient 1, a 41-year-old woman with chronic continuous type UC, was first diagnosed with TD at the age of 10 years. Subsequently, she was diagnosed with UC and rectal cancer. HLA typing showed A2, A31(19), B52(5), and DR2(DRB1*1502). Coronary angiography showed 90% narrowing of the right coronary artery (RCA). After alleviating the RCA narrowing by percutaneous transluminal coronary angioplasty (PTCA), we performed a total proctocolectomy and ileostomy. Patient 2, a 20-year-old woman, was first diagnosed with TD at the age of 13 years. Severe symptoms, indicating fulminant UC, started 1 month prior to hospitalization. She was judged as needing surgery because the symptoms were not alleviated even with high doses of prednisolone. HLA typing showed A2, A31(19), B52, B61(40), DR2(DRB1*1502), and DR4 (DRB1*0405). Aortography showed a narrowing of the right renal artery; however, her renal function was normal. Based on these findings, we performed a three-stage operation for total proctocolectomy. Previously, we have reported that the DRB1*1502 and DRw11 genes were closely related to the intractability of UC. To date, we have not determined whether or how the DRB1*1502 gene might be related to TD. As the number of cases of UC associated with TD increases, it will be necessary to examine their DR2 subtypes.

Enhancement of hydrogen production by a photosynthetic bacterium mutant with reduced pigment.

A novel mutant MTP4 was created from the wild-type strain Rhodobacter sphaeroides RV by UV irradiation for the enhancement of hydrogen production. The amount of light absorbed by MTP4 was lower than that by the wild-type strain at any wavelengths ranging from 350 to 1000 nm. This nature enables the illumination of cells in the deeper parts of a reactor. The contents of bacteriochlorophylls and carotenoids of the chromatophores prepared from MTP4 under the conditions for hydrogen production were reduced to 41 and 49% of those from the wild-type strain RV, respectively. Analysis of the light-harvesting (LH) complexes by SDS-PAGE showed that the amounts of LH1s and reaction centers (RCs) in MTP4 were retained, whereas that of LH2s was much less than that in RV. Although MTP4 had less pigments, its growth rate was equivalent to that of RV over a wide range of light intensities. MTP4 produces hydrogen with a stable manner. Using a plate-type reactor, it produced 50% more hydrogen than RV. A novel method of pigment reduction was found to be effective for the enhancement of hydrogen production per unit reactor.