The effect of 4-(3,7,11,15-tetramethyl-6,10,14-hexadecatrienoyl)morpholine (E-0712), a new synthetic compound, on liver injury induced by two hepatotoxins in rats was studied. Oral doses of E-0712 four times at 0, 6, 12 and 18 hr significantly attenuated elevated SGPT values and prolonged prothrombin time (PT) at 24, 36, 48, 60 and 72 hr in rats with a single s.c. dose of D-galactosamine in which SGPT values and PT reached the peak within 48 hr. In cases in which a dose of carbon tetrachloride (i.p.) produced peak SGPT values and PT within 36 hr attenuation occurred likewise at 24, 36 and 60 hr. In the control and E-0712-treated rats dosed with D-galactosamine or carbon tetrachloride, SGPT values were positively correlated with PT at 24 hr. In addition, morphological degrees of acidophilic body formation or centrizonal necrosis were significantly reduced by E-0712. These results suggest that E-0712 protects against liver injury, particularly hepatocellular necrosis, induced by D-galactosamine and carbon tetrachloride in rats.

Alanine Transaminase↗

PubMedDate not supplied

Decreased collagen accumulation by a prolyl hydroxylase inhibitor in pig serum-induced fibrotic rat liver.

Hepatic fibrosis was induced in rats by repeated i.p. injections of pig serum. The hepatic hydroxyproline content increased to 2.1 times the normal control level at 6 weeks and to 3.2 times at 10 weeks. When P-1894B, an inhibitor of prolyl hydroxylase, was administered, there was a dose-dependent inhibition of the increase to nearly normal control levels at 6 and 10 weeks. There was also by histology a dose-dependent reduction in the degree of hepatic fibrosis. Hepatocellular damage was minimal and its extent did not vary with the degree of fibrosis or the treatment. P-1894B dose dependently reduced the hydroxylation of peptidyl proline in the fibrotic liver. These data suggest that P-1894B inhibited hepatic fibrogenesis by direct action on collagen but not by protection against hepatocellular damage leading to collagen formation. A prolyl hydroxylase inhibitor may be a candidate for use in treatment of hepatic fibrosis.

Animals↗

PubMedDate not supplied

Correlation of aberrant proliferation with T-cell growth factor in adult T-cell leukemia cells.

Peripheral blood lymphocytes from seven patients with adult T-cell leukemia (ATL) were found to lack PHA-responsiveness. However, in most of the cases, minute but distinct proliferation could be induced and maintained by human spleen cell conditioned medium containing PHA or by a combination of PHA and conditioned medium of gibbon cell line, MLA-144 (MLA-144 CM). These results indicate that the lack of response to mitogens of ATL cells might be attributed not only to the failure of these cells to produce T-cell growth factor (TCGF) upon activation, but also to their poor responsiveness to TCGF. Furthermore, a direct proliferative response to mitogen-free MLA-144 CM was shown in two out of seven patients; these two patients experienced rapidly progressive clinical courses. This observation raises the possibility that TCGF promotes the growth of ATL cells in vivo, and is related to the clinical course of the disease.

Adult↗

PubMedDate not supplied

Adult T-cell leukemia cells expressing OKT 17 antigen in the activated state.

The surface phenotype and the functional activities of leukemic cells from seven patients with adult T-cell leukemia (ATL) were studied using monoclonal antibodies OKT 3, 4 and 8, anti-Tac, and OKT 17. The latter defines the heterogeneity of the activated T4+ T cell subset. In all cases, ATL cells with the typical OKT3-T4+ T8- phenotype expressed OKT 17 antigen. In addition, in five out of the seven cases the fresh ATL cells possessed Tac antigen which is expressed on activated T cells in varying degree. After cultivation with PWM, most populations of ATL cells acquired Tac even in the cases expressing little antigen in uncultured preparations. However the PWM activated ATL cells did not lose OKT 17 antigen. Functional assays showed the suppressor activity of ATL cells on normal B cell differentiation in three out of six cases examined. These results suggest that ATL cells most probably arise from a particular subset characterized by OKT 17 antigen within the activated OKT4+ T cell subset.

Adolescent↗

PubMedDate not supplied

Heterogeneity of the in vitro growth patterns in adult T-cell leukemia cells.

Adult T-cell leukemia (ATL) presents heterogeneous clinical features, especially in its clinical course. To clarify the differences in the cell characteristics of these heterogeneous forms, we studied in vitro growth of ATL cells. Nine ATL patients were divided into two groups; 5 acute (group A) and 4 chronic (group B). Although in vitro spontaneous growth was observed only in 3 out of 5 cases in group A, the growth patterns were heterogeneous. When crude interleukin 2 (IL-2) was added to the culture, cells from all the cases in Group A showed marked proliferative responses; these patterns were also heterogeneous. On the other hand, cells in group B displayed no or poor response. The degree of Tac (IL-2 receptor) expression was high in group A but low in group B. These observations suggest that clinical heterogeneity might reflect, at least in part, the cellular heterogeneity in IL-2 responsiveness as seen in vitro.

Adult↗