The characteristics and outcomes of PCP differ significantly depending on HIV status. The existence of underlying pulmonary diseases may be associated with the prognosis of HIV-negative patients with PCP.

To identify the functional domains of the human thrombopoietin (TPO) receptor essential for proliferation and megakaryocytic differentiation, we introduced human wild type c-mpl cDNA and deletion mutants of c-mpl cDNA into the human erythropoietin (EPO)-dependent cell line UT-7/EPO that does not express endogenous c-Mpl. TPO induced the proliferation and megakaryocytic differentiation of UT-7/EPO expressing wild type c-Mpl, as evidenced by increased levels of the CD41 antigen specific for cells of the megakaryocytic lineage and by changes in morphology. Mutational analysis of the cytoplasmic domain of c-Mpl identified four functional regions: (a) two C-terminal regions (amino acids 575-586 and 615-630) containing a domain essential for cell proliferation and megakaryocytic differentiation but not for DNA synthesis; (b) a region (amino acids 587-614) containing a negative domain for TPOinduced cell proliferation and megakaryocytic differentiation; and (c) a region (amino acids 565-574) including a box2 motif that is required for DNA synthesis. These deletion mutants will provide useful materials for analyzing the signals specific for TPO-induced proliferation and megakaryocytic differentiation.Thrombopoietin (TPO) 1 supports the proliferation and differentiation of megakaryocyte progenitor cells as well as the differentiation of megakaryocytes. TPO exerts its action by binding to a specific cell surface receptor encoded by the protooncogene c-mpl (1-5). The c-mpl protooncogene was first identified as the cellular homolog of the viral oncogene v-mpl in the myeloproliferative leukemia virus (6). Based on homology with a member of the cytokine receptor superfamily, however, the c-mpl gene was predicted to encode a cytokine receptor (7-9). Experiments with an antisense oligomer against c-mpl and c-mpl-deficient mice revealed that the c-mpl gene encodes the receptor for TPO.Like other members of the cytokine receptor superfamily, two regions of conserved sequences termed box1 and box2 have been identified in the intracellular domain of c-Mpl (8, 10), and it was found that these motifs are essential for TPO-induced mitogenesis (11,12). In addition, transfection experiments with murine mutated c-mpl cDNA into UT-7 showed that the region distal to box2 is necessary for TPO-induced megakaryocytic differentiation (12). However, since c-mpl transcripts and c-Mpl proteins are detectable in UT-7 by reverse transcriptase polymerase chain reactions (RT-PCR) and Western blotting (8, 13), the transfectants may respond to TPO through endogenous c-Mpl but not exogenous c-Mpl. Indeed, TPO supported the proliferation and megakaryocytic differentiation of UT-7/GM, a subline of . 2 In this study we introduced human c-mpl cDNA into UT-7/EPO that does not express endogenous c-Mpl and generated in vitro models for cellular proliferation and megakaryocytic differentiation. MATERIALS AND METHODSHematopoietic Growth Factors and Reagents-Recombinant human TPO and rabbit anti-human c-Mpl polyclonal antibody were provided by the Kirin Brewery C...

We report a rare case of extramedullary plasmacytoma, which arose either in the ileum or the ileal mesentery. A 70-year-old woman presented with a high fever and symptoms of bowel obstruction. Computed tomography and magnetic resonance imaging showed a large heterogeneous tumor in the peritoneal cavity. Serum immunoelectrophoresis revealed a biclonal increase of IgA-Kappa and IgG-Kappa. At surgery, we found that the parenchyma of the fragile tumor had firm communication with the ileal mesentery, and the cavity of the tumor communicated with the ileal lumen. After a temporary regression following surgery and chemotherapy, the tumor grew rapidly. Although there was no evidence of progression to multiple myeloma, the patient died of cachexia less than 4 months after surgery.

Allogeneic bone marrow transplantation and donor lymphocyte infusion are powerful treatments for chemotherapy-resistant leukemia. Tumor eradication is attributed to a graft-versus-leukemia reaction by the donor-derived cytotoxic T lymphocytes (CTLs), but the same cell population may cause severe graft-versus-host disease. One strategy to suppress harmful CTL activity is to incorporate a suicide gene into the donor lymphocytes prior to infusion, and to destroy these cells when they aggressively attack nonmalignant host tissues. In this study, we investigated the feasibility of using a Fas-estrogen receptor fusion protein (MfasER) to control T cell-mediated cytotoxicity, based on our previous finding that the chimera transmits a oday, allogeneic cell therapies such as bone marrow transplantation (BMT) and donor lymphocyte infusion (DLI) are indispensable means of treating hematological malignancies and achieve a life-long cure in many patients. The advantage of such therapies over conventional chemotherapy is at least twofold. First, an intensified, myeloablative dose of chemoradiotherapy can be given during the pre-transplant period. Second, immunocompetent allogeneic donor T lymphocytes eradicate residual malignant cells. This combat reaction by the donor T cells is called a graft-versus-leukemia (GVL) effect.

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