Abstract. There are many clinical and experimental reports demonstrating that estrogens and insulin interact when affecting their target organs. Estrogen receptors consist of two isoforms, estrogen receptors-alpha (ER-α) and -beta (ER-β), but their roles in insulin-induced glucose uptake in mature adipose tissue have yet to be clarified. To evaluate the roles of ER-α, expressed predominantly in adipocytes, we have investigated the effects of estradiol (E2), an ER-α selective agonist (PPT), and its selective antagonist (MPP) on glucose uptake and insulin action in 3T3-L1 adipocytes. 3T3-L1 adipocytes were exposed to E2 or PPT and/or MPP at different concentrations. The cells were then subjected to 2-deoxy-D-glucose transport assay, western blot analysis, or RT-PCR analysis. Treatment of these cells with E2 or PPT resulted in biphasic effects on glucose transport, that is high (10 -5 M or 3 × 10 -6 M each) and low (10 -8 M) doses produced inhibition and stimulation, respectively. The favorable effect observed at 10 -8 M of E2 was diminished by treatment with MPP. Western bolt analysis revealed that these effects of E2, PPT and MPP paralleled the level of IRS-1 tyrosine phosphorylation. However, IRS-1 serine phosphorylation, suppressor of cytokine signaling (SOCS)-1,-2,-3 and protein tyrosine phosphatase 1B (PTP1B) expression did not change compaired to control subjects. Our data clearly show that ER-α contributes to insulin stimulated glucose uptake through regulation of the tyrosine phosphorylation of IRS-1 protein.

We report a case of therapy-related myelodysplastic syndrome (t-MDS) in adult T-cell lymphoma. A 69-year-old man suffered from cutaneous adult T-cell lymphoma, which was treated with radiation to the skin and combination chemotherapy of CHOP-V-MMV and VEPA-B. After 14 months of these therapies, anemia and thrombocytopenia appeared, and bone marrow aspiration smears showed immature myeloblasts, dysplastic erythroblasts, and micromegakaryocytes. Therapy-related MDS of refractory anemia with an excess of blasts was diagnosed. Cytogenetic study of the bone marrow cells showed 5q- and additional abnormalities. Rearrangement of the MLL gene was observed in the bone marrow cells. Mutations of N-ras codons at 12,13, and 61, p53 tumor suppressor gene, and monoclonal integration of human T-lymphotrophic virus -1 provirus DNA were not observed in the bone marrow cells. The patient died of pneumonia 21 months after diagnosis of cutaneous adult T-cell lymphoma.

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: A 54 year old Japanese man was introduced to Saiseikai General hospital for an evaluation of an abnormal chest X-ray film. Abnormal soft tissue area was observed in the mediastinum surrounding anterior area of the trachea on chest CT. Because the mediastinal tumor showed slow enlargement after temporal decrease and surgical resection of the tumor was performed 3 years after the first visit. Pathologically, diffuse proliferation of oval-shaped plasmacytic or small lymphocytic cells with eccentrically-located nuclei with rough chromatin were observed in the tumor. Immunohistochemically, these cells were positive for CD20, weakly positive for IgM, negative for CD3, CD5, CD10, suggesting lymphoplasmacytic lymphoma (LPL). The patient was treated with rituximab after the surgical treatment, and showed no exacerbation for 3.5 years after surgery. LPL localized to the paratracheal mediastinum is rare, and a surgical approach is important for prompt and proper diagnosis.

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