Immunological studies in tropical splenomegaly syndrome in Uganda

An immunological evaluation carried out in eight patients with the tropical splenomegaly syndrome showed no evidence of impairment in cellular or humoral immunity, though raised levels of macroglobulins were noted in four patients. Hence gross immunological deficiency cannot be associated with the intense lymphoreticular proliferation observed in this disorder.     

Tropical Splenomegaly Syndrome in Zambia: Further Observations and Effects of Cycloguanil and Proguanil

Nineteen Zambian patients with the tropical splenomegaly syndrome and sinusoidal lymphocytosis on liver biopsy were studied. The association of macrobulinaemia with the tropical splenomegaly syndrome has again been confirmed. Sixteen patients were treated with antimalarials—12 with cycloguanil pamoate alone, 3 with cycloguanil and proguanil, and 1 with proguanil alone. Twelve patients were observed for periods of sufficient length for the drug effect to be assessed, and in 11 there was a good response in terms of decrease in spleen size.Cycloguanil pamoate may be of value both for prophylaxis and treatment in areas where tropical splenomegaly syndrome is endemic.     

Expression and function of CCAAT/enhancer binding proteinbeta (C/EBPbeta) LAP and LIP isoforms in mouse mammary gland, tumors and cultured mammary epithelial cells

CCAAT/Enhancer binding proteins (C/EBPs) play important roles in the regulation of cell growth and differentiation. This study investigated the expression and function of C/EBPbeta isoforms in the mouse mammary gland, mammary tumors, and a nontransformed mouse mammary epithelial cell line (HC11). C/EBPbeta mRNA levels are 2-5-fold higher in mouse mammary tumors derived from MMTV/c-neu transgenic mice compared with lactating and involuting mouse mammary gland. The "full-length" 38 kd C/EBPbeta LAP ("Liver-enriched Activator Protein") isoform is the predominant C/EBPbeta protein isoform in mammary tumor whole cell lysates, however, the truncated 20 kd C/EBPbeta LIP ("Liver-enriched Inhibitory Protein") isoform is also present at detectable levels (mean LAP:LIP ratio 5.3:1). The mammary tumor C/EBPbeta LAP:LIP ratio decreases 70% (from 5.3:1 to 1.6:1) when lysate preparation is switched from a rapid whole cell lysis protocol to a multistep nuclear/cytoplasmic fractionation protocol. In contrast to mammary tumors, only the C/EBPbeta LAP isoform is detectable in the mammary gland whole cell and nuclear lysates; the truncated "LIP" isoform is undetectable regardless of isolation protocol. Ectopic over expression of C/EBPbeta LIP or C/EBPbeta LAP did not alter HC11 growth rates. However, C/EBPbeta LIP over expressing HC11 cells (LAP:LIP ratio of approximately 1:1) exhibited a consistent 2-4 h delay in G(0)/S phase transition. C/EBPbeta LIP overexpressing HC11 cells did not express beta-casein mRNA (mammary epithelial cell differentiation marker) in response to lactogenic hormones. This defect in beta-casein expression was not corrected by carrying out the differentiation protocol in the presence of an artificial extracellular matrix. These results demonstrate that the "full-length" C/EBPbeta LAP isoform is the predominant C/EBPbeta protein isoform expressed in mouse mammary gland in vivo and mouse mammary epithelial cell cultures in vitro. C/EBPbeta LIP detected in mammary tumor lysates may result from in vivo production or ex vivo isolation-induced proteolysis of C/EBPbeta LAP. Ectopic overexpression of C/EBPbeta LIP (LAP:LIP ratio of approximately 1:1) inhibits mammary epithelial cell differentiation (beta-casein expression).