Conversion to full donor chimerism following donor lymphocyte infusion is associated with disease response in patients with multiple myeloma.

Donor lymphocyte infusions (DLIs) have been demonstrated to induce clinical responses in patients with relapsed multiple myeloma after allogeneic bone marrow transplantation, but the immunologic mechanisms involved have not been well characterized. In patients with chronic myelocytic leukemia (CML), remissions following DLI are invariably associated with conversion to complete donor hematopoiesis, suggesting that the target antigens of this response are expressed on both normal and CML-derived hematopoietic stem cells. In the present study, we examined hematopoietic chimerism and the complexity of the T-cell receptor (TCR) repertoire in 4 patients with relapsed multiple myeloma who received infusions of donor CD4+ lymphocytes. Three of 4 patients had a clinical response that began 1 to 2 months after DLI. All 3 responding patients developed lymphocytosis at the initiation of response that was due to a 2- to 4.5-fold increase in the number of CD3+ T cells. In 1 patient, this was due primarily to increases in CD3+ and CD8+ cells; in 2 patients, to increased numbers of CD3+ and CD8+ and CD3+ and CD4+ T cells. In all responding patients, conversion to complete donor hematopoiesis occurred in the first 2 months after DLI. The single nonresponding patient remained it 100% recipient hematopoiesis. The TCR repertoire complexity was examined by polymerase chain reaction amplification of complementary-determining region 3 (CDR3) derived from 24 Vbeta gene subfamilies. In 2 patients, the initiation of myeloma response and conversion to complete donor hematopoiesis was associated with normalization of TCR complexity. Complete donor chimerism and normal TCR complexity remained stable in all patients and did not change with subsequent relapse or development of graft-versus-host disease (GVHD). Thus, conversion to full donor chimerism was temporally associated with the antimyeloma effect of DLI but not with the development of GVHD. Nevertheless, the maintenance of stable donor hematopoiesis did not prevent disease relapse and was not associated with prolonged remission. The selective relapse of myeloma cells without concomitant return of mixed hematopoietic chimerism suggests that myeloma tumor cells in some patients develop resistance to immune destruction.     

分枝桿菌(Mycobacterium sp.M12)降解甾醇侧链的研究

分枝杆菌(Mycobacterium sp.M12)能将胆固醇,3β-乙酰氧基胆固醇,谷甾醇以及3β-乙酰氧基谷甾醇降解成△³-雄甾烯-3,17-二酮(4AD)及少量的△^1.4-雄甾烯-3,17-二酮(ADD)。4AD的收率分别为69%,70%,26%,22%。对该菌株降解胆固醇侧链的最适条件进行了研究。     

Selective damage to erythroblasts by 55-Fe

The low energy and short range of 55-Fe Auger electrons were utilized in mice to deliver lethal intracellular radiation to iron-incorporating erythropoietic precursors with minimal radiation damage to other bone marrow cells. The ensuing intramedullary, selective erythropoietic death was demonstrated by absolute and differential bone marrow cell counts and by decreased blood uptake of 59-Fe. The decreased number of colony-forming units in spleen colony assay and the decreased ability of tranplanted bone marrow to protect fatally irradiated mice shows that the bone marrow was partially depleted of pluripotent stem cells. These data are interpreted to indicate an increased pluripotent stem cell utilization in response to increased demand for differentiation of stem cells along the erythropoietic pathway.     

Determinants of acquisition of MR imaging units in an era of prospective payment

A survey was undertaken to examine the impact of Medicare's Prospective Payment System (PPS) and other recent changes in the health care environment on providers' decisions regarding acquisition of high-cost technologic equipment. The survey group included 199 hospitals and freestanding imaging centers known to have acquired magnetic resonance (MR) imaging units, as well as a random sample of 400 hospitals whose acquisition decisions were unknown to the authors. Fifty-eight percent of the known adopters and 61% of the randomly selected hospitals responded to the survey. Nonadopters' decisions were dominated by economic considerations, including the high cost of MR imagers and concerns about Medicare's reimbursement policies. Competition and a desire to provide the highest quality of care are counterbalancing the retardant effects of PPS, however, and are stimulating widespread diffusion of MR imagers.