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Blood Cancer Journal (1)
The British Journal of Radiology (1)
Murase, K (3)
Fujinawa, H (1)
Hayashi, T (1)
Horiguchi, H (1)
Iyama, S (1)
Kakumu, S (1)
Kamihara, Y (1)
Kato, J (1)
Kawano, Y (1)
Kikuchi, S (1)
Kitamura, A (1)
Kobayashi, S (1)
Kobune, M (1)
Matsushita, T (1)
Miyanishi, K (1)
Ono, K (1)
Sakamoto, N (1)
Sato, T (1)
Sato, Y (1)
Takada, K (1)
Takimoto, R (1)
Tsubouchi, A (1)
Yoshioka, K (1)
Year of Publication
Stromal cells expressing hedgehog-interacting protein regulate the proliferation of myeloid neoplasms
Blood Cancer Journal
Aberrant reactivation of hedgehog (Hh) signaling has been described in a wide variety of human cancers including cancer stem cells. However, involvement of the Hh-signaling system in the bone marrow (BM) microenvironment during the development of myeloid neoplasms is unknown. In this study, we assessed the expression of Hh-related genes in primary human CD34+ cells, CD34+ blastic cells and BM stromal cells. Both Indian Hh (Ihh) and its signal transducer, smoothened (SMO), were expressed in CD34+ acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)-derived cells. However, Ihh expression was relatively low in BM stromal cells. Remarkably, expression of the intrinsic Hh-signaling inhibitor, human Hh-interacting protein (HHIP) in AML/MDS-derived stromal cells was markedly lower than in healthy donor-derived stromal cells. Moreover, HHIP expression levels in BM stromal cells highly correlated with their supporting activity for SMO+ leukemic cells. Knockdown of HHIP gene in stromal cells increased their supporting activity although control cells marginally supported SMO+ leukemic cell proliferation. The demethylating agent, 5-aza-2′-deoxycytidine rescued HHIP expression via demethylation of HHIP gene and reduced the leukemic cell-supporting activity of AML/MDS-derived stromal cells. This indicates that suppression of stromal HHIP could be associated with the proliferation of AML/MDS cells.
acute myeloid leukemia (AML); myelodysplastic syndrome (MDS); human hedgehog-interacting protein (HHIP); stromal cells
Experimental verification of protective effect of hydrogen-rich water against cisplatin-induced nephrotoxicity in rats using dynamic contrast-enhanced CT
The British Journal of Radiology
Our aim was to assess the protective effect of hydrogen-rich water against cisplatin-induced nephrotoxicity in rats using dynamic contrast-enhanced CT (DCE-CT). DCE-CT studies were performed in 30 rats (8 weeks old) on days 0, 2, 4 and 7 using multidetector row CT. The rats were divided into three groups: a control group (n = 6) with free access to standard water and without cisplatin injection, a non-treatment group (n = 12) with free access to standard water and injected with cisplatin (3.6 mg kg–1 body weight) intraperitoneally on day 0 and a treatment group (n = 12) with free access to hydrogen-rich water starting from 7 days before cisplatin injection. The contrast clearance per unit renal volume (K1) was estimated from the DCE-CT data using the Patlak model. The contrast clearance of the entire kidney (K) was obtained by multiplying K1 by the renal volume. The serum creatinine level was also measured on day 7. The K1 and K values normalised by those on day 0 in the treatment group were significantly greater than those in the non-treatment group on days 2, 4 and 7. There were no significant differences in the normalised K value between the treatment and control groups on days 2 and 7. The serum creatinine level in the treatment group was significantly lower than that in the non-treatment group and was not significantly different from that in the control group. This study demonstrated that hydrogen-rich water ameliorates renal dysfunction due to cisplatin-induced nephrotoxicity in rats.
Enhancement of antibody production to hepatitis B surface antigen by anti-idiotypic antibody.
Studies were undertaken to determine whether anti-idiotypic antibody (anti-Id) against antibody to hepatitis B surface antigen (anti-HBs) could modulate in vitro anti-HBs production by human peripheral blood mononuclear cells stimulated with pokeweed mitogen. Peripheral blood mononuclear cells from patients positive for serum anti-HBs produced significantly increased amounts of anti-HBs by the addition of IgG fraction of anti-anti-HBs as well as purified HBsAg in a soluble form when compared to those in cultures with pokeweed mitogen alone. F(ab')2 but not Fc fragments of anti-anti-HBs significantly enhanced anti-HBs levels in cultures. Anti-anti-HBs or HBsAg alone, however, did not induce anti-HBs production. Anti-HBs production was not observed by the additions of these additives when peripheral blood mononuclear cells from chronic HBsAg carriers and control individuals were used. These findings indicate that anti-Id modulates the immune response to HBsAg.
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