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1.
  • Abt, I, et al. (författare)
  • Inclusive V-0 production cross sections from 920 GeV fixed target proton-nucleus collisions
  • 2003
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer. - 1434-6044. ; 29:2, s. 181-190
  • Tidskriftsartikel (refereegranskat)abstract
    • Inclusive differential cross sections dsigma(pA)/dx(F) and dsigma(pA)/dp(t)(2) for the production of K-S(0), Lambda, and (&ULambda;) over bar particles are measured at HERA in proton-induced reactions on C, Al, Ti, and W targets. The incident beam energy is 920 GeV, corresponding to roots = 41.6 GeV in the proton-nucleon system. The ratios of differential cross sections dsigma(pA)(K-S(0))/dsigma(pA)(Lambda) and dsigma(pA)((&ULambda;) over bar)/dsigma(pA) (Lambda) are measured to be 6.2 +/- 0.5 and 0.66 +/- 0.07, respectively, for x(F) approximate to -0.06. No significant dependence upon the target material is observed. Within errors, the slopes of the transverse momentum distributions da,Ald t also show no significant dependence upon the target material. The dependence of the extrapolated total cross sections sigma(pA) on the atomic mass A of the target material is discussed, and the deduced cross sections per nucleon sigma(pN) are compared with results obtained at other energies.
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2.
  • Abt, I, et al. (författare)
  • Measurement of the b(b)over-bar production cross section in 920 GeV fixed-target proton-nucleus collisions
  • 2003
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer. - 1434-6044. ; 26:3, s. 345-355
  • Tidskriftsartikel (refereegranskat)abstract
    • Using the HERA-B detector, the b (b) over bar production cross section has been measured in 920 GeV proton collisions on carbon and titanium targets. The b (b) over bar production was tagged via inclusive bottom quark decays into J/psi by exploiting the longitudinal separation of J/psi --> l(+)l(-) decay vertices from the primary proton-nucleus interaction. Both e(+)e(-) and mu(+)mu(-) channels have been reconstructed and the combined analysis yields the cross section sigma(b (b) over bar) = 32(-12)(+14)(stat) (+6)(-7)(sys) nb/nucleon.
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3.
  • Olsson-Strömberg, Ulla, et al. (författare)
  • Successful mobilization of Ph-negative blood stem cells with intensive chemotherapy + G-CSF in patients with chronic myelogenous leukemia in first chronic phase
  • 2006
  • Ingår i: Leukemia and Lymphoma. - 1042-8194 .- 1029-2403. ; 47:9, s. 1768-73
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the study was to investigate the feasibility of mobilizing Philadelphia chromosome negative (Ph-) blood stem cells (BSC) with intensive chemotherapy and lenograstim (G-CSF) in patients with CML in first chronic phase (CP1). During 1994-1999 12 centers included 37 patients <56 years. All patients received 6 months' IFN, stopping at median 36 (1-290) days prior to the mobilization chemotherapy. All received one cycle of daunorubicin 50 mg/m2 and 1 hour infusion on days 1-3, and cytarabine (ara-C) 200 mg/m2 24 hours' i.v. infusion on days 1-7 (DA) followed by G-CSF 526 microg s.c. once daily from day 8 after the start of chemotherapy. Leukaphereses were initiated when the number of CD 34+ cells was >5/microl blood. Patients mobilizing poorly could receive a 4-day cycle of chemotherapy with mitoxantrone 12 mg/m2/day and 1 hour i.v infusion, etoposide 100 mg/m2/day and 1 hour i.v. infusion and ara-C 1 g/m2/twice a day with 2 hours' i.v infusion (MEA) or a second DA, followed by G-CSF 526 microg s.c once daily from day 8 after the start of chemotherapy. Twenty-seven patients received one cycle of chemotherapy and G-CSF, whereas 10 were mobilized twice. Twenty-three patients (62%) were successfully (MNC >3.5 x 10(8)/kg, CFU-GM >1.0 x 10(4)/kg, CD34+ cells >2.0 x 10(6)/kg and no Ph+ cells in the apheresis product) [n = 16] or partially successfully (as defined above but 1-34% Ph+ cells in the apheresis product) [n = 7] mobilized. There was no mortality during the mobilization procedure. Twenty-one/23 patients subsequently underwent auto-SCT. The time with PMN <0.5 x 10(9)/l was 10 (range 7-49) and with platelets <20 x 10(9)/l was also 10 (2-173) days. There was no transplant related mortality. The estimated 5-year overall survival after auto-SCT was 68% (95% CI 47 - 90%), with a median follow-up time of 5.2 years.We conclude that in a significant proportion of patients with CML in CP 1, intensive chemotherapy combined with G-CSF mobilizes Ph- BSC sufficient for use in auto-SCT.
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4.
  • Tehranchi, Ramin, et al. (författare)
  • Aberrant mitochondrial iron distribution and maturation arrest characterize early erythroid precursors in low-risk myelodysplastic syndromes
  • 2005
  • Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 106:1, s. 247-253
  • Tidskriftsartikel (refereegranskat)abstract
    • Early erythroblasts from patients with refractory anemia (RA) and RA with ringed sideroblasts (RARS) show constitutive mitochondrial release of cytochrome c. Moreover, mature erythroblasts in RARS, but not in RA, display aberrant accumulation of mitochondrial ferritin (MtF). We analyzed cytochrome c release, MtF expression, and gene expression during erythrold differentiation in bone marrow cells from myelodysplastic syndrome (MDS) patients and healthy controls. Whereas none or few cultured erythrold cells from healthy individuals and RA patients expressed MtF, those from RARS patients showed MtF expression at an early stage, when cells were CD34(+) and without morphologic signs of erythroid differentiation. The proportion of RARS erythroblasts that were MtF(+) increased further upon in vitro maturation. Moreover, a significant overexpression of mRNA encoding cytochrome c, and proapoptotic Bid and Bax, was seen in freshly isolated cells from MDS patients. Genes involved in erythroid differentiation were also dysregulated in MDS cells. Importantly, GATA-1 expression increased during normal erythroid maturation, but remained low in MDS cultures, indicating a block of erythroid maturation at the transcriptional level. In conclusion, aberrant MtF expression in RARS erythroblasts occurs at a very early stage of erythrold differentiation and is paralleled by an up-regulation of genes involved in this process.
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7.
  • Machaczka, Maciej, et al. (författare)
  • Substrate reduction therapy with miglustat for type 1 Gaucher disease : a retrospective analysis from a single institution
  • 2012
  • Ingår i: Upsala Journal of Medical Sciences. - 0300-9734 .- 2000-1967. ; 117:1, s. 28-34
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION:Gaucher disease (GD) is an infrequent progressive multisystem lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme, glucocerebrosidase. A retrospective, single-center analysis of the clinical experience concerning the use of miglustat (N-butyldeoxynojirimycin), an oral inhibitor of glucosylceramide synthase, in type 1 Gaucher disease (GD1) was conducted to evaluate the efficacy, adverse events (AE), and outcome of miglustat therapy.PATIENTS AND METHODS:Six adult Caucasian patients with GD1 (two women and four men), aged 21-81 years (median age 59 years), were treated with miglustat between October 2005 and April 2011. All but one patient (83%) carried at least one allele with c.1226A>G (N370S) mutation in the GBA1 gene.RESULTS:Weight loss, diarrhea, poor appetite, and tremor were frequently reported AE by the patients. All of them experienced at least 2 AE, and three patients (50%) experienced at least 4 AE. Only two out of six patients (33%) have used miglustat longer than 12 months, of which only one used it longer than 15 months.CONCLUSIONS:The major obstacle to successful miglustat therapy in GD1 was the high proportion of patients discontinuing their treatment due to the AE and the worsened quality of life. Further efforts are needed to improve tolerability of miglustat and, in consequence, compliance of patients treated with this orphan drug.
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9.
  • Nilsson, Lars, et al. (författare)
  • The molecular signature of MDS stem cells supports a stem-cell origin of 5q - myelodysplastic syndromes
  • 2007
  • Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 110:8, s. 3005-3014
  • Tidskriftsartikel (refereegranskat)abstract
    • Global gene expression profiling of highly purified 5q-deleted CD34(+)CD38(-)Thy1(+) cells in 5q(-) myelodysplastic syndromes (MDSs) supported that they might originate from and outcompete normal CD34(+)CD38(-)Thy1(+) hematopoietic stem cells. Few but distinct differences in gene expression distinguished MDS and normal stem cells. Expression of BMI1, encoding a critical regulator of self-renewal, was up-regulated in 5q- stem cells. Whereas multiple previous MDS genetic screens failed to identify altered expression of the gene encoding the myeloid transcription factor CEBPA, stage-specific and extensive down-regulation of CEBPA was specifically observed in MDS progenitors. These studies establish the importance of molecular characterization of distinct stages of cancer stem and progenitor cells to enhance the resolution of stage-specific dysregulated gene expression.
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10.
  • Tehranchi, Ramin, et al. (författare)
  • Persistent malignant stem cells in del(5q) myelodysplasia in remission.
  • 2010
  • Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 363:11, s. 1025-1037
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The in vivo clinical significance of malignant stem cells remains unclear. METHODS: Patients who have the 5q deletion (del[5q]) myelodysplastic syndrome (interstitial deletions involving the long arm of chromosome 5) have complete clinical and cytogenetic remissions in response to lenalidomide treatment, but they often have relapse. To determine whether the persistence of rare but distinct malignant stem cells accounts for such relapses, we examined bone marrow specimens obtained from seven patients with the del(5q) myelodysplastic syndrome who became transfusion-independent while receiving lenalidomide treatment and entered cytogenetic remission. RESULTS: Virtually all CD34+, CD38+ progenitor cells and stem cells that were positive for CD34 and CD90, with undetectable or low CD38 (CD38−/low), had the 5q deletion before treatment. Although lenalidomide efficiently reduced these progenitors in patients in complete remission, a larger fraction of the minor, quiescent, CD34+,CD38-/low, CD90+ del(5q) stem cells as well as functionally defined del(5q) stem cells remained distinctly resistant to lenalidomide. Over time, lenalidomide resistance developed in most of the patients in partial and complete remission, with recurrence or expansion of the del(5q) clone and clinical and cytogenetic progression. CONCLUSIONS: In these patients with the del(5q) myelodysplastic syndrome, we identified rare and phenotypically distinct del(5q) myelodysplastic syndrome stem cells that were also selectively resistant to therapeutic targeting at the time of complete clinical and cytogenetic remission. (Funded by the EuroCancerStemCell Consortium and others.)
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