bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating cytokines in sickle cell patients during steady state
Authors: Croizat Helena 
Published: March 2008

SummaryPlasma levels of GM‐CSF, IL‐3, IL‐6 and IL‐1(α,β) were investigated in steady‐state sickle cell patients. We find that SS patients with low levels of HbF (< 9% [LFSS]) are characterized by elevated plasma GM‐CSF, whereas in patients with high levels of HbF (HFSS), GM‐CSF is not detectable. In contrast, HFSS patients exhibited increased plasma IL‐3 (m = 84.8 ± 57pg/ml), whereas LFSS patients had lower or no detectable plasma IL‐3. IL‐1(α,β) and IL‐6 were also detected in plasma from some SS patients, but there was no correlation with HbF levels. Normal controls tested negative for all cytokines, except for one individual positive for IL‐3. These results are compatible with a model in which the level of haemopoietic stress determines the level of participation of GM‐CSF or IL‐3 in the regulation of SS circulating BFU‐E.
Prevention of MHC‐alloimmunization by UV‐B irradiation in a murine model: effects of UV dose and number of transfused cells
Authors: Grijzenhout M. A. , Aarts‐Riemens M. I. , Claas F. H. J. , Prooijen H. C. van 
Published: March 2008

SummaryThe optimal dose of UV‐B radiation for prevention of in vivo alloimmunization (AI) against major histocompatibility complex (MHC) antigens was investigated in a murine transfusion model. Two groups with five C57BL/6 mice (H2b) each were transfused at weekly intervals with 1 x 105 or 1 x 106 DBA/2 (H‐2d) leucocytes. Both suspensions induced anti‐H‐2d antibodies in all mice after the second transfusion. The minimal UV‐B dose required for abolition of alloreactivity in the mixed leucocyte reaction (MLR) was 0.6 J/cm2. This dose completely prevented the onset of MHC‐AI in all five mice transfused with six suspensions containing 1 x 105 leucocytes. In contrast, suspensions with 1 x 106 leucocytes and exposed to 0.6 J/cm2 induced immunization in 4/5 mice. Further increase of the dose to 1.8 or 5.4 J/cm2 did not prevent the onset of MHC‐AI. The use of UV radiation for prevention of secondary MHC‐AI was investigated in five mice with a primed immune system. Transfusion of suspensions with 1 x 105 leucocytes and irradiated at a dose of 1.8J/cm2 did not prevent booster reactions. We conclude that the number of leucocytes per transfusion determines the efficacy of UV irradiation for the prevention of MHC‐AI. For UV irradiation of human platelet concentrates (PCs) we propose to reduce the number of leucocytes by centrifugation prior to UV exposure. UV‐B irradiation of PCs with high numbers of leucocytes may not be effective for prevention of alloimmunization.
Lymphoid blast crisis at the onset of chronic myelogenous leukaemia: molecular evidence
Authors: Roman Jose , Andres Pilar , Jimenez Maria A. , Torres Antonio 
Published: March 2008

SummaryA patient with a typical haematological pattern of acute lymphoblastic leukaemia with BCR and IgH rearrangements was brought into complete remission by treatment. A few weeks later she developed the typical peripheral and bone marrow pattern of chronic myelogenous leukaemia (CML) with persistence of the BCR rearrangement and disappearance of the IgH rearrangement, suggesting that this case is an example of CML presenting in blast crisis without a detectable chronic phase.
Sequential relapses of blastic crisis may involve different clones of cells with different molecular abnormalities
Authors: And A. Foti , Cline M. J. 
Published: March 2008

SummaryA patient with typical Ph1‐positive CML was studied during sequential phases: (1) initial chronic phase, (2) first myeloid blast crisis, (3) second chronic phase, and (4) accelerated disease leading to a second blast crisis. A point mutation in codon 239 of the p53 gene and a novel chromosome 17 alteration appeared concomitantly with the first blast crisis and then disappeared with re‐establishment of a second chronic phase. They did not reappear with the second acute phase, indicating that the clone responsible for the original blast crisis had been suppressed and supplanted by another clone of malignant cells. This observation suggests that in at least some CML patients drug therapy can suppress or eliminate an aggressive malignant cell clone, but that the underlying molecular defect in haemopoietic cells (in this case the c‐ABL translocation) persists and other aggressive clones with different molecular lesions eventually arise. Our observations and inferences are consistent with the hypothesis advanced by Fialkow et al (1991) to explain clonal remissions in acute non‐lymphocytic leukaemia.
The effects of gestation on circulating progenitor cells
Authors: Jones H. M. , Nathrath M. , Thomas R. M. , Edelman P. , Rodeck C. H. , Linch D. C. 
Published: March 2008

SummaryThe frequency of BFU‐E in second‐trimester fetal blood (484 ± 104/105) falls progressively during gestation to a value of 69 ± 41/105 in cord bloods of 36 weeks gestation and beyond, but this is still significantly greater than adult blood values of 14 ± 8 (P < 0.01). BFU‐E obtained from unfractionated peripheral blood mononuclear cells from fetuses/neonates less than 36 weeks gestation were more sensitive to erythropoietin than adult BFU‐E, but the sensitibvity of highly purified BFU‐E obtained from secondtrimester fetal liver was similar to that in adult cells. Almost maximal growth of BFU‐E from purified fetal progenitor cells could be achieved with erythropoietin alone, whereas adult cells required the presence of other factors with ‘burstpromoting activity’.
Detection of fetal RhD sequence from peripheral blood of sensitized RhD‐negative pregnant women
Authors: Lo Y‐M. D. , Noakes L. , Bowell P. J. , Fleming K. A. , Wainscoat J. S. 
Published: March 2008

SummaryA sensitive PCR‐based assay was developed to amplify fetal‐derived rhesus D (RhD) sequence from peripheral blood of RhD‐negative pregnant women with circulating anti‐D. RhD‐PCR positivity was detected in 7/22 samples from women bearing RhD‐positive fetuses. despite the presence of varying levels of anti‐D. Evidence is presented with suggests that rising matermal anti‐D levels might reduced circulating fetal cell numbers. Further development of this assay may have implications in the clinical management of RhD‐sensitized pregnancies and aid the understanding of the physiology of feto‐maternal cell trafficking.
Clonal and non‐clonal karyotypically abnormal cells in haemophagocytic lymphohistiocytosis
Authors: KANEKO YASUHIKO , MASEKI NOBUO , SAKURAI MASAHARU , IDO MASARU , TSDNEMATSU YUKIKO , MIZUTANI SHUKI , HATTORI TATSUYA , SHIMIZU HIROYUKI , EGUCHI HARUHIKO , OKA TOSHIAKI , MIYAKE MUNENORI , HORIKOSHI YASUO , SUCHI TAIZAN 
Published: March 2008

We studied chromosomes in bone marrow (BM) or peripheral blood cells of nine patients with haemophagocytic lymphohistiocytosis (HLH); three of them had a family history of HLH and four others underwent concurrent Epstein‐Barr virus (EBV) infection. In addition to a large population of normal mitotic cells, karyotypically abnormal clonal cells were found in two patients, abnormal clonal cells and a nonclonal (single) abnormal cell in one, and nonclonal abnormal cells in three. All the six patients with chromosome abnormalities died of progressive disease; one of them also had EBV infection and EBV‐associated clonal proliferation. Two of three patients with EBV infection and only normal mitotic cells in BM completely recovered from the disease.Although HLH did not show histological and/or haema‐tological evidence of a neoplastic disease, clonal chromosome abnormalities and the fatal clinical outcome found in some of the patients suggest that the disease may be heterogenous and include malignancy. HLH patients with karyotypically abnormal clonal cells in BM should warrant more intensive chemotherapy than that presently being applied to them and should be considered as candidates for BM transplantation.
All‐trans retinoic acid shows multiple effects on the survival, proliferation and differentiation of human fetal CD34+ haemopoietic progenitor cells
Authors: ZAULI GroRGio , VISANI GIUSEPPE , VITALE MARCO , GIBELLINI DAVIDE , BERTOLASO LUCIA , CAPITANI SILVANO 
Published: March 2008

Summary. To evaluate the effect of all‐trans retinoic acid (RA) on fetal haemopoiesis, we performed serum‐free liquid and semisolid cultures using CD34+ cells purified from mid‐trimester human fetal blood samples. RA, at both physiological (10‐n and 10‐12M) and pharmacological (10‐6 and l(r7M) concentrations, significantly (P<0.01) promoted the survival of fetal CD34+ cells in liquid cultures from day 3 onwards, by suppressing apoptosis induced by serum and growth factor deprivation. On the other hand, RA alone had no significant effect on the proliferation and differentiation of fetal haemopoietic progenitors.In the presence of optimal concentrations of recombinant interleukin‐3 (IL‐3), stem cell factor (SCF), granulocyte/ macrophage‐colony stimulating factor (GM‐CSF), and erythropoietin (Epo), low and high doses of RA induced striking differential effects on CD34+ cell proliferation in liquid cultures and colony formation in semisolid assays. In fact, 1CTU M and 1CT12M RA were able to: (i) significantly (P<0.05) increase 3H‐thymidine uptake by fetal CD34+ cells in liquid cultures, and (ii) variably promote the growth of pluripotent (CFU‐GEMM, P<0.05), early (BFU‐meg) and late (CFU‐meg, P<0.01) megakaryocyte, granulocyte/macrophage (CFU‐GM. P<001) and erythroid (BFU‐E) progenitors in semisolid cultures. On the contrary, 10‐6 and 10‐7 M RA induced: (i) an overall inhibition (P<0.01) of CD34+ cell growth in liquid cultures; (ii) a marked suppression of BFU‐E colony formation (P<0.01) at all Epo concentrations examined (0‐002‐4IU/ml); and (iii) a significant (P<0.()1) stimulation of CFU‐GM with a shift from mixed granulocyte/ macrophage to pure granulocyte colonies, whereas it had little effect on the growth of CFU‐GEMM, BFU‐meg and CFU‐meg.Our data, as a whole, demonstrate that RA has direct complex effects on the survival, growth and clonal expansion of fetal haemopoietic progenitor cells, mainly depending on the presence of recombinant cytokines, the type of progenitor and the concentrations of RA.
A phase I/II trial of recombinant human interleukin‐6 in patients with aplastic anaemia
Authors: SCHREZENMEIER HUBERT , MARSH JUDITH C. W. , STROMEYER PATRICIA , MULLER HILKB , HEIMPEL HERMANN , GORDON‐SMITH EDWARD C. , RAGHAVACHAR ARUNA 
Published: March 2008

Summary. In a phase I/II study, 11 patients with marrow failure (10 with acquired aplastic anaemia and one with pancytopenic Fanconi anaemia) were treated with recombinant human interleukin‐6 (rhIL‐6) to assess the safety and tolerability of rhIL‐6 and its effects on peripheral blood counts, bleeding complications and transfusion requirements. All patients with acquired aplastic anaemia were refractory to immunosuppressive treatment or had relapsed after immunosuppressive therapy and were not bone marrow transplantation candidates. Recombinant hIL‐6 was to be given as a once‐daily subcutaneous injection for 28 d at doses ranging from 0‐5 to 5‐0βg/kg. After an observation period of 2 weeks, five patients received a second treatment course of 28 d.Only one patient had a sustained increase in platelet count from 18 000 to 72 000/fA. Bleeding occurred in four patients and caused premature discontinuation of rhIL‐6 therapy in three patients. A deterioration of pre‐existing anaemia was observed in nine patients. No significant changes of leucocyte counts were observed during the first cycle. During the second cycle the peripheral blood monocyte counts decreased significantly. No significant changes in bone marrow cellularity were observed. Recombinant hIL‐6 induced a dose‐dependent increase in acute‐phase reactants in all patients. Other adverse events included fever, headache, arthralgia, tachycardia and hypertension. In conclusion, rhIL‐6 given alone at low doses does not increase platelet counts in the majority of patients with aplastic anaemia and can precipitate a sudden worsening of pre‐existing anaemia and thrombocytopenia. This study was discontinued prematurely on account of the toxicity of rhIL‐6 seen in patients with aplastic anaemia.
Molecular defect of a phosphoglycerate kinase variant associated with haemolytic anaemia and neurological disorders in a large kindred
Authors: Turner G. , Fletcher J. , Elber J. , Yanagawa Y. , Dave V. , Yoshida A. 
Published: March 2008

Summary The X‐chromosome‐linked phosphoglycerate kinase (PGK) deficiency associated with severe chronic and acute haemolytic anaemia and mental disorders was first described in a large Chinese kindred in 1969. The molecular abnormality of this original variant remained to be identified. The red cell PGK activity was only about 5%, but the activity of the patients’lymphoblastoid cells was about 15% of normal. The PGK mRNA content of the patients’lymphoblastoid cells were normal. Analysis of the patients’mRNA showed the existence of a nucleotide transversion A ± T at position 491 (counting from adenine of the initiation codon). The mutation should cause an amino acid substitution Aspval at position 163 of the enzyme. The replacement of the acidic aspartic acid by a hydrophobic valine is expected to induce drastic structural instability resulting in severe enzyme deficiency in the patients’tissues.The genotypes of two affected males, their mothers and 22 females of the family were identified by the PCR‐mediated method using their genomic DNA samples. 13/24 females examined were found to be variant heterozygous. In this large family, affected males over three generations have died at a pre‐adult age. Post‐ and pre‐natal genotyping of the family members may prevent future problems.
Prevention of donor‐specific T‐cell unresponsiveness after buffy‐coat‐depleted blood transfusion
Authors: van Prooijen H. C. , Aarts‐Riemens M. I. , van Oostendorp W. R. , Hene R. J. , Gmelig‐Meyling F. H. J. , de Weger R. A. 
Published: March 2008

SummaryThe immunosuppressive effect of blood transfusions has been demonstrated in several clinical studies. The effect is probably mediated by HLA‐class‐H‐bearing donor leucocytes, because results from laboratory tests show specific down‐regulation of the recipient's T‐cell response after administration of blood from donors sharing one HLA haplotype with the recipient.In the present study we evaluated the immunosuppressive potential of buffy‐coat‐depleted red cell transfusions in patients waiting for renal transplantation, by measuring the frequency of cytotoxic precursor T cells before and after transfusion. The buffy coat was removed from whole blood by the Optipress system and resulted in ±97% depletion of lymphocytes and monocytes. A single transfusion of HLA‐haplotype‐matched buffy‐coat‐depleted red cells induced donor‐specific down‐regulation of T‐cell responses in only two of 14 patients. Since HLA‐class‐H‐bearing cells are also involved in the induction of anti‐HLA antibodies, we evaluated retrospectively the incident of HLA alloimmunization after a single transfusion of buffy‐coat‐depleted red cells. No anti‐HLA antibodies were found in 140 patients at risk for primary immunization.We conclude that the poor immunological responses found after a single transfusion of HLA‐haplotype‐matched buffy‐coat‐depleted red cells is due to the small number of residual HLA‐class‐II‐bearing donor cells. This blood component should not be used for induction of immunosuppression.
Comparative quantitative expression of bcl‐2 by normal and leukaemic myeloid cells
Authors: Bradbury D. A. , Russell N. H. 
Published: March 2008

Summary. Expression of the bcl‐2 oncoprotein by AML blasts has previously been demonstrated to be heterogenous with high levels of bcl‐2 expression being associated with a low complete remission rate and poor survival. We have quantified bcl‐2 expression in AML blasts in relation to expression of the CD34 antigen and in comparison to CD34‐positive cells from normal bone marrow. When expressed as molecules of equivalent soluble fluorochrome (MESF) per cell, AML blast cell bcl‐2 expression varied from 11.1 to 99.9 × lO3 (median 39.4 × 103, n=56) with 28.5% of patients expressing high MESF values (>50 × 103) and 16% of patients expressing low MESF values (<20 × 103), the remainder expressing intermediate values. There was no significant difference between intensity of bcl‐2 expression and FAB classification in the de novo AML cases, and there was no significant differences between de novo and secondary AML cases. Blasts from CD34+ AML patients expressed significantly higher levels of bcl‐2 (mean MESF 43.6 × 103, n =36) than CD34− AML patients (mean MESF 31.7 × 103, n=19).In five cases of CD34+ AML, bcl‐2 expression was determined on purified CD34+ and CD34− blast cell populations. In all cases CD34+ blasts were found to express significantly higher bcl‐2 MESF values compared to the CD34− fraction.Purified CD34+ cells from normal bone marrow consistently expressed high levels of bcl‐2 (MESF >75 × 103 n = 4), which was comparable to that found on CD34+ AML cells. Our results suggest that the poor prognosis previously associated with AML blasts expressing the CD34 antigen may in part be related to high expression of bcl‐2. Also the ability to measure bcl‐2 in AML blasts quantitatively by flow cytometry and to categorize patients into discrete groups may be of value as a prognostic indicator in AML.
Resistance to activated protein C in healthy women taking oral contraceptives
Authors: Olivieri Oliviero , Friso Simonetta , Manzato Franco , Guella Anna , Bernardi Francesco , Lunghi Barbara , Girelli Domenico , Azzini Margherita , Brocco Giorgio , Russo Carla , Corrocher Roberto 
Published: March 2008

Summary. Resistance to activated protein C (APC) is at present considered the most frequent laboratory abnormality in patients with deep‐vein thrombosis. An increased risk for venous thrombosis is associated to the use of oral contraceptives (OC).We studied APC sensitivity in 50 healthy women taking OC and in 50 healthy controls, matched for age, smoking habit, educational and social levels, and the main biochemical routinary parameters. Subjects with a personal or familial history of thrombosis and also with chronic or acute diseases were excluded. Protein C, protein S, antithrombin III and lupus anticoagulant activity (LAC) were also evaluated. Increased fibrinogen and protein C levels, decreased protein S, and shortened PT and APTT were also observed in women taking OC. APC sensitivity ratio (APC‐SR) was significantly lower in the OC group than in a control group (2.6 ± 0.38 v 2.81 ±0.35, P<0.01). Seven of eight women with APC ratio ≤ 2 (APC resistant) were OC users: the difference of prevalence was statistically significant (chi‐squared test, P&lt:0′05). Only two out of eight women were found heterozygous for the Leiden factor V mutation. Two APC‐resistant women without the Leiden mutation subsequently discontinued OC and both then normalized their APC‐SR. We conclude that acquired factors, i.e. oral contraceptives, may play an important role in determining plasma APC resistance.
Pulsed high‐dose dexamethasone in refractory chronic idiopathic thrombocytopenic purpura: a report on 10 cases
Authors: Caulier Marie Thérèse , Rose Christian , Roussel Marie Thérèse , Huart Claude , Bauters Francis , Fenaux Pierre 
Published: March 2008

Summary. We treated 10 patients who had chronic refractory idiopathic thrombocytopenic purpura (ITP) with high‐dose dexamethasone (DXM, 40mg/d for 4 sequential days every month). The interval from diagnosis ranged from 49 to 300 months, and patients had previously received a median of 5.5 treatments (including splenectomy in nine cases). Median platelet count was 14 × 109/1 (range 6‐26 × 109/1) at the onset of DXM and eight patients had bleeding symptoms. Eight patients received at least three cycles of DXM.Five patients had a response (i.e. platelet count at least doubled and increased by >20 × 109/1), including one almost complete remission and four minor responses (MR).Of the MR, one was probably due to concurrent IVIg administration, and all four MR were transient, in spite of further cycles of DXM. In three patients DXM was a failure after three or four cycles. In two patients DXM had to be stopped after one course because of major side‐effects (systemic hypertension with stroke and insulin‐dependent diabetes, respectively).In our experience, high‐dose DXM had a relatively limited effect in chronic refractory ITP and was associated with severe side‐effects in some cases.
Clinical significance of serum cytokine patterns during start of fever in patients with neutropenia
Authors: Engervall Per , Andersson Birger , Björkholm Magnus 
Published: March 2008

Summary. Serum concentrations of tumour necrosis factor alpha (TNF‐α), interleukin‐1 receptor antagonist (IL‐1ra), interferon gamma (IFN‐γ), interleukin‐6 (IL‐6) and interleukin‐10 (IL‐10) were studied in 31 patients with haematological malignancies during febrile neutropenia. Samples were obtained when blood cultures were performed (time 0) and, when possible, after 2, 4, 6, 12 and 24 h. Increased levels of all cytokines were detected after start of fever with peak values in gram‐negative (Gr−) bacteraemias after 2 h (TNF‐α, IL‐lra and IFN‐γ), 4h (IL‐6) and 6 h (IL‐10), respectively. At time 0 the median TNF‐α value was higher in the Gr− group (80 pg/ml; range 54‐516 pg/ml) as compared to both gram‐positive bacteraemias (Gr+, 14pg/ ml; range 7‐60 pg/ml; P < 0 05) and blood culture negative episodes (BCN, 8pg/ml; range 0‐87pg/ml; P<0 05).Furthermore, the peak values of TNF‐α, IL‐lra, IL‐6 and IL‐10 during the 24 h study period were significantly and/or numerically higher in the Gr‐ group in comparison to the Gr+ and BCN groups, respectively. It may be concluded that neutropenic patients have increased levels of both pro‐ and anti‐inflammatory cytokines at start of fever, with the highest values recorded during the first hours in Gr‐ bacteraemias. Prospective studies will show whether monitoring of serum cytokines may be used as an early diagnostic tool before results of blood cultures are available, which may have important therapeutic implications.