ABSTRACT
The Ets transcription factor PU.1, encoded by the gene Sfpi1, functions in a concentration-dependent manner to promote myeloid and B-cell development and has been implicated in myeloid and lymphoid leukemias. To determine the consequences of reducing PU.1 concentration during hematopoiesis, we analyzed mice with two distinct hypomorphic alleles of Sfpi1 that produce PU.1 at approximately 20% (BN) or approximately 2% (Blac) of wild-type levels. Myeloid development was impaired in these mice, but less severely than in Sfpi1 null mice. To identify the downstream target genes that respond to changes in PU.1 concentration, we analyzed ex vivo interleukin-3 dependent myeloid cell lines established from Sfpi1(BN/BN), Sfpi1(Blac/Blac) and Sfpi1(-/-) fetal liver cells. Unexpectedly, many T-cell and natural killer cell genes were expressed in Sfpi1(-/-) cells and repressed in a dose-dependent manner in Sfpi1(Blac/Blac) and Sfpi1(BN/BN) cells. This pattern of dose-dependent T/NK-cell gene repression also occurred in ex vivo interleukin-7 dependent progenitor B cell lines. These results suggest that PU.1 functions in a concentration-dependent manner to repress T-cell and natural killer cell fates while promoting myeloid and B-cell fates.
Subject(s)
Killer Cells, Natural/physiology , Myeloid Cells/physiology , Precursor Cells, B-Lymphoid/physiology , Proto-Oncogene Proteins/physiology , Repressor Proteins/physiology , T-Lymphocytes/physiology , Trans-Activators/physiology , Animals , Binding Sites , Cell Differentiation , Computational Biology , Female , Flow Cytometry , Gene Expression Profiling , Humans , Immunoblotting , Integrases/metabolism , Interleukin-3/pharmacology , Interleukin-7/pharmacology , Male , Mice , Mice, Knockout , Oligonucleotide Array Sequence Analysis , Precursor Cells, B-Lymphoid/cytology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Transgenes/physiologyABSTRACT
Radioiodine and thionamide treatment are the most frequently used treatment modalities for thyrotoxicosis in Europe and North America with surgery being reserved for selected cases. * In our clinic patients were offered all three modalities via simultaneous interview with an endocrinologist and a surgeon, with international risk benefit data for radioiodine and thionamide therapy, and local risk benefit data for total thyroidectomy provided. * When given the choice, at least 15% of patients opted for total thyroidectomy over the other modalities. * In our series of 100 consecutive surgical patients there was a 4% malignancy rate. * Total thyroidectomy should be offered equally, with radioiodine and thionamide treatment, as a first line treatment modality in the management of thyrotoxicosis.
Subject(s)
Antithyroid Agents/therapeutic use , Iodine Radioisotopes/therapeutic use , Thyroidectomy , Thyrotoxicosis/therapy , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Thyrotoxicosis/surgery , Treatment OutcomeABSTRACT
The effect of halothane and nitrous oxide on the capacity of natural killer (NK) lymphocytes from female patients with benign and malignant breast disease to kill the tumour cell line K562, was studied in vitro. There was no depression of activity of NK lymphocytes when exposed to 2% halothane and 66% nitrous oxide either alone or in combination. However, NK lymphocyte activity was depressed at higher concentrations of halothane and the decrease in activity was significant (P less than 0.01) when 4% halothane was used. These findings suggest that exposure to clinically-used concentrations of halothane and nitrous oxide does not interfere with the NK lymphocyte response of the host.