Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic derivatives of linoleic acid found in beef and dairy products. CLA has been reported to reduce body fat. To examine the mechanism(s) of CLA reduction of fat mass, female C57BL/6J mice were fed standard semipurified diets (10% fat of total energy) with or without CLA (1% wt/wt). Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick endlabeling (TUNEL) and DNA fragmentation analysis revealed that fat-mass decrease by CLA was mainly due to apoptosis. Tumor necrosis factor (TNF)-␣ and uncoupling protein (UCP)-2 mRNA levels increased 12-and 6-fold, respectively, in isolated adipocytes from CLA-fed mice compared with control mice. Because it is known that TNF-␣ induces apoptosis of adipocytes and upregulates UCP2 mRNA, a marked increase of TNF-␣ mRNA with an increase of UCP2 in adipocytes caused CLA-induced apoptosis. However, with a decrease of fat mass, CLA supplementation resulted in a state resembling lipoatrophic diabetes: ablation of brown adipose tissue, a marked reduction of white adipose tissue, marked hepatomegaly, and marked insulin resistance. CLA supplementation decreased blood leptin levels, but continuous leptin infusion reversed hyperinsulinemia, indicating that leptin depletion contributes to the development of insulin resistance. These results demonstrate that intake of CLA reduces adipose tissue by apoptosis and results in lipodystrophy, but hyperinsulinemia by CLA can be normalized by leptin administration. Diabetes 49:1534-1542, 2000 C onjugated linoleic acid (CLA) is a group of positional and geometric isomers of conjugated dienoic derivatives of linoleic acid. The major dietary sources of CLA for humans are beef and dairy products (1). There is a great interest in CLA because of its anticarcinogenic and antiatherogenic properties and its ability to reduce body fat while enhancing lean body mass (2). Reduction of body fats by CLA was observed in pigs (3), mice (4,5), and hamsters (6).In this study, we investigated the mechanism(s) of CLAmediated reduction of fat mass in mice. Reduction of fat mass by CLA was due to apoptosis. Initially, we expected the beneficial effect of CLA-induced fat mass decrease, such as improvement of insulin resistance and reduction of blood triglyceride concentration. Unexpectedly, however, rapid reduction of fat mass by CLA resulted in marked insulin resistance and hepatomegaly. These metabolic abnormalities are characteristics of lipodystrophy (7,8). During this study, Delany et al. (9) also reported that CLA reduced body fat but resulted in hyperinsulinemia and liver enlargement in AKR/J male mice. To understand the mechanism(s) of CLAinduced lipodystrophy, we examined expression levels of several genes important in energy expenditure and lipid and carbohydrate metabolism in adipose tissues and isolated adipocytes. Furthermore, effects of leptin infusion on CLAinduced insulin resistance were also examined. RESEARCH DESIGN AND METHODSExperimental protocols. Female C57BL/6J mice were obt...

We have established a novel cell line, designated as TF-1, from a patient with erythroleukemia, which showed complete growth dependency on granulocyte-macrophage colony-stimulating factor (GM-CSF) or on interleukin-3 (IL-3) and carried a homogeneous chromosomal abnormality (54X). Erythropoietin (EPO) also sustained the short-term growth of TF-1, but did not induce erythroid differentiation. These three hematopoietic growth factors acted on TF-1 synergistically. Transforming growth factor-beta and interferons inhibited the factor-dependent growth of TF-1 cells in a dose-dependent fashion, and monocyte-colony stimulating factor and interkeukin-1 enhanced the GM-CSF-dependent growth of TF-1. Ultrastructural studies revealed some very immature features in this cell line. Although TF-1 cells do not express glycophorin A or carbonyl anhydrase I, the morphological and cytochemical features, and the constitutive expression of globin genes, indicate the commitment of TF-1 to erythroid lineage. When induced to differentiate, TF-1 entered two different pathways. Specifically, hemin and delta-aminolevulinic acid induced hemoglobin synthesis, whereas TPA induced dramatic differentiation of TF-1 into macrophage-like cells. In summary, TF-1 is a cell line of immature erythroid origin that requires GM-CSF, IL-3, or EPO for its growth and that has the ability to undergo differentiation into either more mature erythroid cells or into macrophage-like cells. TF-1 is a useful tool for analyzing the human receptors for IL-3, GM-CSF, and EPO or the signal transduction of these hemopoietic growth factors.

Cytomegalovirus infection was detected rather frequently (21 percent) in the surgical specimens of ulcerative colitis, and all cases were steroid resistant. The possibility of cytomegalovirus infection should always be taken into account in patients with ulcerative colitis who are resistant to steroid therapy.

Histologic examination lacks the sensitivity to detect micrometastases in gastric cancer lymph nodes. In the present study, we applied a real-time RT-PCR approach to the quantitative detection of micrometastases in gastric cancer lymph nodes and compared diagnostic power with routine histology and immunohistochemistry. We studied 392 lymph nodes from 21 gastric cancer patients who underwent curative surgery. Real-time quantitative RT-PCR was performed on a LightCycler instrument using a hybridization probe for carcinoembryonic antigen (CEA) and cytokeratin-20 (CK20) as marker genes. Immunohistochemistry with antibodies to wide-keratin was also performed in the lymph nodes to compare the sensitivity and specificity. Median

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