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41.
Steenbergen EJ; Verhagen OJ; van Leeuwen EF; van den Berg H; von dem Borne AE; van der Schoot CE 《Blood》1995,86(2):692-702
Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL. 相似文献
42.
Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease. 总被引:1,自引:0,他引:1
Collins CE Benson MJ Burnham WR Rampton DS 《Alimentary pharmacology & therapeutics》1996,10(3):315-320
BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147- 325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61- 140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64- 206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease. 相似文献
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Marshall Alison L. Bauman Adrian E. Owen Neville Booth Michael L. Crawford David Marcus Bess H. 《Annals of behavioral medicine》2003,25(3):194-202
Background: Intervention trials with self-selected participants have shown that mailed stage-targeted print materials can increase participation
in physical activity in the short term. We examined the effects of a mailed stage-targeted print intervention designed to
promote physical activity, in a random sample of adults living in a regional city.Method: Participants (n = 462, 40–60 years of age) were randomly allocated to an intervention in - 227) or control group (n - 235).
Measures included validated 2-week physical activity recall and stage of motivational readiness for physical activity. The
intervention consisted of a single mailing of a letter and full-color stage-targeted booklets (specific to precontemplation,
contemplation, preparation, and action/maintenance) 1 week postbaseline. Follow-up interviews were conducted at 2 and 6 months
postbaseline.Results: After 2 months, participants in the intervention group were significantly More likely to meet the current American College
of Sports Medicine/Centers for Disease Control and Prevention recommendation for sufficient physical activity than those in
the control group (adjusted odds ratio [OR] - 2.40; 95% confidence interval [CI] = 1.44–3.99). After 6 months, intervention
participants who reported receiving and reading the intervention materials were significantly more likely to be meeting the
sufficient physical activity criterion compared with the control group (adjusted OR = 2.03; 95% Cl = 1.16–3.56).Conclusions: The stage-targeted print intervention was effective in promoting short-term increases in physical activity and was most
effective for participants who recognized and used the materials. This low-cost, generalizable intervention has demonstrated
potential as a practical population-based physical activity promotion strategy. Further research is required before widespread
dissemination would be justified, as additional strategies may be required to ensure sustained change.
This project was supported by a National Heart Foundation of Australia Research Project Grant. David Crawford was supported
by a Nutrition Research fellowship from the National Heart Foundation. 相似文献
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Gilbert A Lawrence John Crawford 《Journal of clinical oncology》2003,21(24):4660-1; author reply 4661-2