Sphingomyelinosis (spm), an autosomal recessive mutation in mice originally occurred in the C57BL/KsJ inbred strain. Spm/spm mice of this genetic background show striking hepatosplenomegaly with a marked accumulation of sphingomyelin and cholesterol due to a deficiency of sphingomyelinase. However, in spm/spm mice of C57BL/6J and DBA/2J backgrounds, hepatosplenomegaly was not pronounced in spite of marked elevation of hepatic lipid concentrations. The lifespan of C57BL/6J-spm/spm and DBA/2J-spm/spm mice was shorter than that of C57BL/KsJ-spm/spm mice. This appeared to be associated with the comparatively rapid rise in hepatic lipid concentrations, which in turn might be related to the absence of hepatomegaly. Histological study revealed the formation of massive foam cell clusters in the livers and spleens of C57BL/KsJ-spm/spm mice, whereas in the case of C57BL/6J-spm/spm and DBA/2J-spm/spm mice, diffusely scattered foam cells were found. These findings suggest that the functions of reticuloendothelial system (RES) play a crucial role in the development of hepatosplenomegaly in response to lipid accumulation.

Animals↗

PubMedDate not supplied

Initial daily interferon administration can gain more eradication of HCV-RNA in patients with chronic hepatitis C, especially with serum intermediate viral load.

BACKGROUND/AIMS: We studied the effect of initial daily administration of interferon for the treatment of chronic hepatitis C, especially in patients with intermediate viral load. METHODOLOGY: Consecutive patients who met the inclusion criteria were randomly enrolled into two groups in this study. All patients analyzed could be treated with interferon-alpha for 6 months. Patients in group A were administered 6 million units of interferon-alpha subcutaneously daily initially for 2 weeks and then thrice weekly. Patients in group B were treated with the same dose of interferon-alpha thrice weekly from the first administration. We decided the criteria of complete remission as the absence of serum HCV-RNA at both points of the end of interferon treatment and 6 months later. RESULTS: Due to the relationship between the efficacy and serum viral load, we decided the criteria of the intermediate load as the quantitative value of serum HCV-RNA to be not lower than 10(5.0) and not higher than 10(6.5) copies/ml. Seventy-six and 78 patients, whose genotype and quantitative value of serum HCV-RNA could be measured before treatment, were analyzed in group A and B, respectively. The rate of complete remission in group A (40.8%) was higher than that in group B (25.6%), significantly (p = 0.046). In the intermediate viral load group, the rate of complete remission in group A (52.3%) was significantly higher than that in group B (29.3%) (p = 0.045). In the patients with genotype 1 b virus, the rate of complete remission had a tendency to be higher in group A (33.3%) than in group B (17.4%) (not significant). In the patients with genotype 2, the rate of complete remission was higher in group A (77.8%) than in group B (41.2%) (significant, p = 0.041). CONCLUSIONS: These results suggest that the initial daily interferon administration is necessary to gain a higher rate of serum HCV-RNA eradication in patients with intermediate viral load in chronic hepatitis C.

Adult↗

PubMedDate not supplied

Protein kinase C inhibitor, H-7 suppresses the growth activity of hepatoma-derived growth factor.

BACKGROUND/AIMS: A well-differentiated hepatocellular carcinoma-derived cell line, HuH-7 proliferates autonomously in serum-free medium. Human hepatoma-derived growth factor, which was purified from the conditioned medium of HuH-7 cells, stimulates the growth of HuH-7 cells by an autocrine fashion, and fibroblasts and endothelial cells by a paracrine fashion. We investigated the role of protein kinase C in the proliferation of HuH-7 cells and the growth activity of hepatoma-derived growth factor. METHODOLOGY: The effects of a selective protein kinase C inhibitor, H-7 on the proliferation of HuH-7 and 3T3 fibroblasts stimulated by hepatoma-derived growth factor were examined by DNA synthesis and cell growth assay. RESULTS: H-7 suppressed the growth of HuH-7 cells. The ID50 of H-7 on the growth of HuH-7 cells was about 25 microM, and the growth of HuH-7 cells was almost completely inhibited by not less than 50 microM of H-7. H-7 inhibited the growth activity of hepatoma-derived growth factor for Swiss 3T3 fibroblasts. The ID50 of H-7 on the activity of hepatoma-derived growth factor for 3T3 fibroblasts was about 25 microM, too. HA1004, used as a negative control of H-7, failed to inhibit the growth of HuH-7 cells and the activity of hepatoma-derived growth factor. The growth of HuH-7 cells was stimulated significantly by about 40% by a protein kinase C activator, SC-9. H-7 did not suppress hepatoma-derived growth factor production in HuH-7 cells. CONCLUSIONS: These findings suggest that protein kinase C plays an important role in the growth of HuH-7 hepatoma cells and may be participated as a pathway in signal transduction of hepatoma-derived growth factor.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMedDate not supplied

Intestinal Behçet's disease associated with myelodysplastic syndrome with chromosomal trisomy 8--a report of two cases and a review of the literature.

Two cases of intestinal Behçet's disease, which developed in the state of myelodysplastic syndrome with trisomy 8, are presented. Both cases are included in the incomplete type of Behçet's disease, with recurrent aphthous stomatitis, skin lesions, genital ulcers or vascular involvement and punched-out ulcers in the cecum, without ocular involvement. The chromosomal analyses revealed chromosomal abnormalities, including trisomy 8, in both cases. Chromosomal trisomy 8 was shown in all 6 cases with the intestinal Behçet's disease associated with myelodysplastic syndrome reported previously, including our patients. Their histories indicated that myelodysplastic syndrome might have started before the development of intestinal Beçet's disease. Theses findings suggested that chromosomal trisomy 8 might play an important role in the pathogenesis, at least in some groups, of intestinal Behçet's disease.

Adult↗