Human natural killer (NK) cells originate from CD34(+) hematopoietic progenitor cells, but the discrete stages of NK cell differentiation in vivo have not been elucidated. We identify and functionally characterize, from human lymph nodes and tonsils, four NK cell developmental intermediates spanning the continuum of differentiation from a CD34(+) NK cell progenitor to a functionally mature NK cell. Analyses of each intermediate stage for CD34, CD117, and CD94 cell surface expression, lineage differentiation potentials, capacity for cytokine production and natural cytotoxicity, and ETS-1, GATA-3, and T-BET expression provide evidence for a new model of human NK cell differentiation in secondary lymphoid tissues.

Activated monocytes produce proinflammatory cytokines (monokines) such as interleukin (IL)-12, IL-15, and IL-18 for induction of interferon-gamma (IFN-gamma) by natural killer (NK) cells. NK cells provide the antiinflammatory cytokine transforming growth factor (TGF)-beta, an autocrine/negative regulator of IFN-gamma. The ability of one signaling pathway to prevail over the other is likely important in controlling IFN-gamma for the purposes of infection and autoimmunity, but the molecular mechanism(s) of how this counterregulation occurs is unknown. Here we show that in isolated human NK cells, proinflammatory monokines antagonize antiinflammatory TGF-beta signaling by downregulating the expression of the TGF-beta type II receptor, and its signaling intermediates SMAD2 and SMAD3. In contrast, TGF-beta utilizes SMAD2, SMAD3, and SMAD4 to suppress IFN-gamma and T-BET, a positive regulator of IFN-gamma. Indeed, activated NK cells from Smad3(-/-) mice produce more IFN-gamma in vivo than NK cells from wild-type mice. Collectively, our data suggest that pro- and antiinflammatory cytokine signaling reciprocally antagonize each other in an effort to prevail in the regulation of NK cell IFN-gamma production.

The ABO blood group is of great importance in blood transfusion and organ transplantation. However, the mechanisms regulating human ABO gene expression remain obscure. On the basis of DNase I-hypersensitive sites in and upstream of ABO in K562 cells, in the present study, we prepared reporter plasmid constructs including these sites. Subsequent luciferase assays indicated a novel positive regulatory element in intron 1. This element was shown to enhance ABO promoter activity in an erythroid cellspecific manner. Electrophoretic mobilityshift assays demonstrated that it bound to the tissue-restricted transcription factor GATA-1. Mutation of the GATA motifs to abrogate binding of this factor reduced the regulatory activity of the element. Therefore, GATA-1 appears to be involved in the cell-specific activity of the element.

BACKGROUND.Although studies comparing conventional imaging modalities with 18F‐fluorodeoxyglucose positron emission tomography (18F‐FDG‐PET) for the detection of lymphoma and although the relations between 18F‐FDG‐PET and histologic types were reported previously, most studies were not systematic and involved relatively small numbers of patients.METHODS.Two hundred fifty‐five patients with lymphoma had their disease staged using 18F‐FDG‐PET, and 191 of those patients also were assessed using gallium‐67 scintigraphy (67Ga). Disease sites were identified on a site‐by‐site basis using computed tomography scans and/or magnetic resonance imaging. The results of these conventional imaging modalities were compared with the results from 8F‐FDG‐PET and 67Ga, and correlations between the imaging results and pathologic diagnoses were evaluated by using the World Health Organization classification system.RESULTS.Of 913 disease sites in 255 patients, 18F‐FDG‐PET identified >97% of disease sites of Hodgkin lymphoma (HL) and aggressive and highly aggressive non‐Hodgkin lymphoma. For indolent lymphoma, the detection rate of 18F‐FDG‐PET was 91% for follicular lymphoma (FL); 82% for extranodal marginal zone B‐cell lymphoma of mucosa‐associated lymphoid tissue, irrespective of plasmacytic differentiation; and approximately 50% for small lymphocytic lymphoma (SLL) and splenic marginal zone lymphoma (SMZL). The results from 67Ga were similar to those from 18F‐FDG‐PET for most histologic subtypes. However, the sensitivity of 67Ga was unexpectedly poor for FL, for mantle cell lymphoma (MCL), and for the nasal type of natural killer/T‐cell lymphoma (NK/T‐nasal), ranging from 30% to 38%.CONCLUSIONS.18F‐FDG‐PET was useful for all histologic subtypes of lymphoma other than SLL and SMZL. Compared with 67Ga, the authors strongly recommend the use of 18F‐FDG‐PET in patients with FL, MCL, and NK‐nasal. Cancer 2007. © 2007 American Cancer Society.

Background: Although cases of anaphylaxis caused by sugammadex have been reported, its incidence remains uncertain. Conversely, no studies have evaluated the incidence of anaphylaxis to neostigmine. Methods: This was a retrospective multicentre observational study of patients who underwent surgery under general anaesthesia between 2012 and 2016 to compare the incidence of anaphylaxis with sugammadex with that of neostigmine at four tertiary hospitals in Japan. To ensure the quality of diagnosis, only cases with a clinical history suggestive of anaphylaxis, along with positive results from in vitro or in vivo testing, were assessed. Results: From a total of 49 532 patients who received general anaesthesia included in this study, 18 cases of anaphylaxis were reported, of which six were attributable to sugammadex and none to neostigmine. There were no fatalities attributable to anaphylaxis. The incidence of anaphylaxis caused by all drugs or by sugammadex was calculated as 0.036% (95% confidence interval [CI]: 0.022e0.057%) and 0.02% (of the number of sugammadex cases) (95% CI: 0.007e0.044%), respectively. Conclusions: The results suggest that neostigmine might be safer than sugammadex when assessing only the incidence of anaphylaxis. We believe that there is room for reconsideration of the choice of reversal agent for neuromuscular blocking agents by all anaesthetists. Clinical trial registration: UMIN000022365; UMIN000033561.