bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetics of circulating haematopoietic progenitors during chemotherapy‐induced mobilization with or without granulocyte colony‐stimulating factor
Authors: Liu Kai‐Yan , Akashi Koichi , Harada Mine , Takamatsu Yasushi , Niho Yoshiyuki 
Published: March 2008

Summary. Kinetics of circulating haematopoietic progenitors was analysed during chemotherapy‐ or chemotherapy plus granulocyte colony‐stimulating factor (G‐CSF)‐induced mobilization of peripheral blood stem cells. Circulating progenitors including colony‐forming unit granulocyte/macrophage (CFU‐GM), burst forming‐unit erythroid (BFU‐E) and multilineage colony forming unit (CFU‐Mix) were studied serially on alternate days during a recovery phase from chemotherapy for consolidation of complete remission. In 18 patients with acute leukaemia, 27 courses of consolidation chemotherapy were performed with a combination of an intermediate‐dose cytosine arabinoside with etoposide (Ara‐C/Etop) or mitoxantron (Ara‐C/Mit). G‐CSF (5 μg/kg) was administered during the recovery phase in 6/14 courses with Ara‐C/Etop and in 4/13 courses with Ara‐C/Mit. G‐CSF induced a significant and synchronized increase of circulating CFU‐GM, BFU‐E and CFU‐Mix by more than 4‐fold at their peaks. The peak of CFU‐GM was significantly correlated with that of both BFU‐E and CFU‐Mix, irrespective of additional G‐CSF mobilization. G‐CSF also produced a significant increase of monocytes in a synchronized fashion with an increase of circulating CFU‐GM. Interestingly, peripheral blood monocytes spontaneously produced high concentrations of IL‐6; a significant correlation was observed between absolute monocyte counts and plasma levels of IL‐6 or peak levels of CFU‐GM.These observations indicate that the addition of G‐CSF to chemotherapy‐induced mobilization can facilitate further expansion of a blood progenitor pool during the haematopoietic recovery, probably through the stimulation of monocytes to proliferate and to induce their monokine production such as IL‐6. The data also suggest that absolute monocyte counts may be a useful indicator to predict the peak of circulating progenitors for collecting autologous blood stem cells.
The molecular basis of HPFH in a British family identified by heteroduplex formation
Authors: Craig J. E. , Sheerin S. M. , Barnetson R. , Thein S. L. 
Published: March 2008

Summary. Single‐base substitutions in the immediate 5′‐flanking region of the fetal Gγ and Aγ globin genes have been associated with non‐deletional forms of hereditary persistence of fetal haemoglobin (HPFH). Previously, the sole promoter mutation associated with HPFH in British individuals has been the T to C substitution at position – 198 relative to the Aγ globin gene CAP site.We have investigated a British family with Gγ HPFH and found a T to C substitution at position – 175 of the Gγ globin gene. The mutation was first detected by examining the amplified 5’regions of both the Gγ and Aγ globin genes for heteroduplex formation after electrophoresis in a Hydrolink gel. The potential of such a system for the study of sequence variations in the γ gene promoter regions associated with elevated HbF expression has been evaluated.Previously reported cases of an identical mutation in an American‐Black and a Sardinian family display haematological phenotypes remarkably similar to that of the British family described here.
Confirmation of viral safety of dry heated factor VIII concentrate (8Y) prepared by Bio Products Laboratory (BPL): a report on behalf of U.K. Haemophilia Centre Directors*
Authors: Rizza C. R. , Fletcher M. L. , Kernoff P. B. A. 
Published: March 2008

Summary. Twenty‐seven factor VIII deficient patients who had previously not been treated with blood or blood products were studied after infusion of a total of 24 batches of NHS factor VIII (8Y) concentrate produced by Bio‐Products Laboratory, Elstree. Follow‐up was carried out according to guidelines laid down by the International Society for Thrombosis and Haemostasis.Serial estimations of amino transferase level carried out over a 26‐week period revealed no elevation of these enzymes attributable to hepatitis. Studies of various virological markers found no evidence of infection with hepatitis C, hepatitis B or HIV following transfusion. This confirms a previous finding that severe dry heating of factor VIII at 80°C for 72 h seems to reduce the risk of transmitting hepatitis C from approximately 90% to a rate of 0–11%.
Gastro‐intestinal bleeding in acquired von Willebrand's disease: efficacy of high‐dose immuno‐globulin where substitution treatments failed
Authors: White Lucy A. , Chisholm Morag 
Published: March 2008

Summary. We report a case of acquired von Willebrand's disease with severe and persistent gastro‐intestinal bleeding from multiple bleeding points. He received maximum substitution treatment including factor VIII concentrates, cryoprecipitate and platelets. He also received DDAVP. There was no change in the rate of blood loss.He was then treated with high‐dose intravenous gammaglobulin and the blood loss stopped abruptly. He remained well for several months when bleeding recommenced and he again responded promptly to gamma‐globulin. This is a useful maintenance treatment for patients with acquired von Willebrand's disease.
Sweet's syndrome associated with myelodysplasia: possible role of cytokines in the pathogenesis of the disease
Authors: Reuss‐Borst M. A. , Pawelec G. , Saal J. G. , Horny H. P. , Müller C. A. , Waller H. D. 
Published: March 2008

Summary. The clinical course of a 56‐year‐old female patient with Sweet's syndrome (SS) preceded by a myelodysplastic syndrome (MDS) is described. During the acute phase of the disease with high remittent fever, painful skin lesions and maximal leucocytosis IL‐6 and G‐CSF serum levels were extremely high, while TNF‐alpha was only slightly elevated and gamma‐interferon and IL1‐β were not increased. On clinical improvement IL‐6 serum levels rapidly fell, whereas G‐CSF values already slightly elevated before the manifestation of the disease slowly declined.High G‐CSF levels triggered by a yet unknown factor could explain the leucocytosis, neutrophilic dermatosis and skin lesions in SS, while IL‐6 probably induced the associated clinical symptoms of fever and pain.
Analysis of rearranged immunoglobulin genes indicating a process of clonal evolution in chronic lymphocytic leukaemia
Authors: Hakim Itzchak , Rechavi Gideon , Brok‐Simoni Frida , Grossman Zehava , Amariglio Ninetta , Mandel Mathilda , Ramot Bracha , Ben‐Bassat Isaac , Katzir Nurit 
Published: March 2008

Summary. Chronic lymphocytic leukaemia (CLL) is known to be a stable monoclonal neoplasm. In contrast to early studies demonstrating no more than two hybridizing immunoglobulin heavy chain bands corresponding to the two expected alleles, we have demonstrated an unexpected multiband pattern when the HindIII‐digested DNA samples from 38 CLL patients were analysed by Southern blot hybridization using JH and Cμ gene probes. In order to characterize the genetic basis for the multiband pattern, we molecularly cloned the immunoglobulin heavy chain genes of one of the patients whose leukaemic DNA sample demonstrated three hybridizing JH bands and a loss of the germline band. The cloned rearranged immunoglobulin genes could be divided, based on the restriction mapping and the hybridization with the various probes, into two basic patterns representing two alleles. In one of the cloned rearranged immunoglobulin genes a secondary rearrangement occurred that resulted in the addition of 300 base‐pair long sequence into the switch region, and the creation of a HindIII restriction site.The results of the study suggest that clonal evolution occurs in some CLL, and that many of these neoplasms are indeed oligoclonal due to the accumulation of secondary genetic changes.
Blood neutrophil increment after a single injection of rhG‐CSF or rhGM‐CSF correlates with marrow cellularity and may predict the grade of neutropenia after chemotherapy
Authors: Hansen Per Boye , Johnsen Hans E. , Ralfkiaer Elisabeth , Hansen Niels Ebbe 
Published: March 2008

Summary. The grade of neutropenia after chemotherapy seems to be correlated to the bone marrow cellularity as judged by biopsies. Prolonged blood neutropenia after sequential chemotherapy reduces dose intensity and increases the risk of severe infections. A predictive non‐invasive test for marrow cellularity is needed in the attempt to predict chemotherapy‐induced blood neutropenia.Thirty‐one patients with haematological disorders were studied with measurements of blood absolute neutrophil counts (ANC) 24 h after a single subcutaneous injection of recombinant human granulocyte colony stimulating factor (rhG‐CSF) or granulocyte‐macrophage CSF (rhGM‐CSF). Before cytokine administration all patients had bone marrow biopsies performed.The median increase in blood ANC 24 h after cytokine administration was 15·9 × 109/l (range 3·7–34·2) in 18 patients with normo‐ or hypercellular marrows and only 0·4 × 109/l (range 0·0–11·2) in 13 patients with hypocellular marrows (P<0·00001). An increase in ANC or more than 5 × 109/l was predictive for normo‐ or hypercellular bone marrows with a sensitivity and specificity of 94% and 84%, respectively.A subsequent pilot study in selected patients with prolonged neutropenia was performed. The ANC increment in 12 cases before chemotherapy correlated to the grade of neutropenia and may predict the risk of febrile neutropenia.It is suggested that blood responsiveness to myeloid growth factors correlates with marrow cellularity and may identify outpatients with risk for severe neutropenia after cyclic chemotherapy.
Concurrent label method with 111In and 51Cr allows accurate evaluation of platelet viability of stored platelet concentrates
Authors: Holme S. , Heaton A. , Roodt J. 
Published: March 2008

Summary. The precision and reproducibility of 111In and 51Cr platelet radiolabel agents for in vivo kinetic studies of stored platelet concentrates (PC) were investigated. The objective was to develop a precise method with concurrent labelling of two platelet populations using different isotopes, which would allow identification of small differences in in vivo platelet quality. Identical labelling procedures were used to investigate the effects of PC storage age, different methods of red cell (RBC) and white cell (WBC) contamination correction, and label elution correction on the results of 111In and 51Cr kinetic studies. 111In and 51Cr platelet survival curves from the same PC, even when uncorrected for elution and RBC contamination, exhibited excellent correlation, irrespective of the age of the concentrate and its viability. However, slightly higher, but statistically significant, post‐infusion per cent recoveries with 51Cr labelled platelets were found. Two factors were identified as the cause for this difference. There was a higher affinity of contaminating RBC/WBC in PC for 51Cr than for 111In. With determination of RBC/WBC activity by centrifugation/density separation, RBC/WBC fractions from the injectate were found to contain 12.6 ± 3·8%v 7·1 ± 3·6% of total 51Cr and 111In activity, respectively, in 20 studies. In addition, there was a significantly higher 111In activity in plasma immediately post‐infusion than with 51Cr, 5·2 ± 1·3%v 2·8 ± 1·6%, respectively, suggesting more label elution or carryover. After correction for the activity of RBC/WBC and for elution or carryover, essentially identical 51Cr/111In platelet survival curves were found. In 31 stored PC studies, the absolute average difference between 51Cr and 111In per cent recoveries was only 4 ± 3% in a group of donors whose platelet recoveries ranged from 10% to 80%. Similarly, the average difference between 51Cr and 111In survival was only 8±4 h within a range of survivals from 40 to 220 h.In conclusion, after correction for elution and contaminating RBC/WBC binding, these studies show that 51Cr and 111In may be used interchangeably for labelling of stored PC, and that small differences between test and control platelets could be reliably detected using concurrent labelling with simultaneous infusion.
Somatostatin analogue scintigraphy of malignant lymphomas
Authors: Vanhagen P. M. , Krenning E. P. , Reubi J. C. , Mulder A. H. , Bakker W. H. , Oei H. Y. , Löwenberg B. , Lamberts S. W. J. 
Published: March 2008

Summary Normal as well as activated lymphocytes, macrophages and leukaemic cells have previously been shown by radio receptor analysis to express receptors for somatostatin. An 111In labelled somatostatin analogue was already used successfully in the visualization of a variety of neuro‐endocrine tumours.We investigated 10 consecutive patients with malignant lymphomas (Hodgkin's disease and non‐Hodgkin's lymphomas). In all patients the lymphoma deposits could be visualized with somatostatin receptor imaging.In four patients additional tumour localizations were observed as compared to the results of combined physical and radiological (CT and ultrasound) examinations. In four cases tissue biopsies were taken and confirmed by autoradiography to be somatostatin receptor positive.These data indicate that malignant lymphomas may express somatostatin receptors in sufficient numbers and density to allow in vivo tumour visualization with a radiolabelled somatostatin analogue.
The management of recurrent acute myelogenous leukaemia at a single centre over a fifteen‐year period
Authors: Davis C. L. , Rohatiner A. Z. S. , Lim J. , Whelan J. S. , Oza A. M. , Amess J. , Love S. , Stead E. , Lister T. A. 
Published: March 2008

Summary. One hundred and sixty‐two patients initially treated at St Bartholomew's Hospital between 1974 and 1988 developed recurrent acute myelogenous leukaemia (AML). In the majority, the intention was to administer intensive chemotherapy again; 22/162 were re‐treated palliatively. A second complete remission (CR) was achieved in 50/126 (40%) evaluable patients. Several different regimens were employed over this time period; the treatment used was the only factor that correlated with achievement of second CR (P=0.04). Ten of the 50 patients received myeloablative therapy with either allogeneic or autologous bone marrow transplantation in second CR. The median duration of second CR for those patients who did not proceed to intensive consolidation with bone marrow transplantation was 7 months. There was no correlation between second remission duration and age, or with the administration of either intensive or conventional consolidation therapy.The median survival from first recurrence for all patients was 4 months, increasing to only 5 1/2 months for those re‐treated with chemotherapy and to 12 months for those patients in whom a second CR was achieved, confirming the very poor prognosis of these patients.
T cell function in children with acute lymphoblastic leukaemia
Authors: Nash K. A. , Mohammed G. , Nandapalan N. , Kernahan J. , Scott R. , Craft A. W. , Toms G. L. 
Published: March 2008

Summary. Modern intensive chemotherapy has dramatically improved the prognosis of acute lymphoblastic leukaemia (ALL) in children. However, once remission has been established, quality of life and even survival may be threatened by exacerbation of viral infections in the prolonged period of continuation therapy necessary to prevent relapse. Often the viruses involved in the most severe infections are from the herpesvirus and paramyxovirus groups, suggesting that patients suffer from a defect in the cellular immunity thought essential to control such cell‐associated infections. This may result from a T cell defect and, in this study, T cell responsiveness of patients under therapy for leukaemia has been investigated. In vitro proliferative responses of peripheral blood leucocytes (PBL) to the T cell mitogen phytohaemagglutinin (PHA) were impaired in children with ALL before treatment and in the induction of remission. Impairment was attributable to reduced T cell numbers, the presence of inhibitors in the patient's serum and direct damage to lymphocytes. On achieving remission, proliferative responses to PHA of both CD4+ and CD8+ T cell subsets quickly returned to normal levels with the switch to continuation chemotherapy. Proliferative responses to Herpes simplex virus antigens were also apparently normal in the majority of patients tested in remission.Further investigations, however, have suggested a persisting defect in CD8+ lymphocyte function. Gamma interferon secretion by PHA‐stimulated PBLs was severely reduced for children with ALL in remission when compared with control children of similar age. Further, cytotoxic T lymphocyte responses to allogeneic cells could only be induced in PBL isolated from two of 13 children in remission from ALL whilst all control children of similar age and adults produced anti‐allogenetic responses.
CD2+ CD19+ acute lymphoblastic leukaemia in 16 children and adults: clinical and biological features. The Groupe d'Etude Immunologique des Leucémies (G.E.I.L.)
Authors: Lenormand B. , Vannier J. P. , Bene M. C. , Falkenrodt A. , Bayle C. , Favre M. , Garand R. , Griveau A. M. , Briquet M. T. , Reman O. , Boutard P. , Tilly H. , Faure G. , Monconduit M. 
Published: March 2008

A small population of CD2+CD19+ lymphoid cells have been suggested to be common lymphoid progenitors. CD2+CD19+ biphenotypic ALL account for less than 2% of ALL. We analysed the clinical and laboratory features of a series of 16 patients with CD2+CD19+ ALL.The incidence of tumoural syndrome was comparable to a previously published series of pre B‐ALL but significantly different from that of T‐ALL. The mean age of the 11 children of this series was 101 ±46 months, and differed significantly from that of children with pre B‐ALL (P<0.01). Complete remission was obtained for all patients except two adults. Only three relapses have been observed.Regardless of the presence of CD2+, the 16 ALL could be classified as pre B‐ALL, according to the nomenclature used by the GEIL. Nine samples could be analysed by Southern blotting. Seven had rearranged IGH genes, usually on both chromosomes. IGK rearrangement was observed in three cases. Only one case had rearranged both TCRG and TCRβ. The patterns observed here and those reported previously follow that of the pre B‐ALL which confirms the engagement of most CD2+CD19+ biphenotypic ALL in the B‐lineage.
Microenvironmentally dependent effects on murine haemopoiesis by a prolonged interleukin‐1 treatment
Authors: Haan G. de , Dontje B. , Loeffler M. , Nijhof W. 
Published: March 2008

Summary. We administered recombinant human IL‐lβ (400 ng/d, s.c.) for 10 d to normal C57B1 mice and determined daily granuloid and erythroid parameters in marrow, spleen and blood.In the marrow CFU‐GM numbers were not affected but later granuloid cell stages were moderately enhanced (170%). In the spleen, however, CFU‐GM numbers were sharply increased (1600%). whereas the granuloid precursors only doubled. Blood granulocytes increased transiently to 275% on day 5. In the marrow all erythroid parameters were severely reduced. This reduction was partially compensated by the spleen where initially only BFU‐E and with some delay also more mature erythroid cells accumulated. At the end of the treatment mice were slightly anaemic. When mice were treated with IL‐1 and erythropoietin (10 U/d) simultaneously, the inhibitory effects on erythropoiesis were less severe. In agreement with in vivo results, IL‐1 inhibited in vitro colony growth of CFU‐E from normal bone marrow and spleen but spleen CFU‐E from 5 d IL‐1 treated mice were insensitive.We conclude that IL‐1 can induce stimulation or inhibition of haemopoietic progenitor cells depending on their micro‐environment.
Partial engraftment of donor bone marrow cells associated with long‐term remission of haemophagocytic lymphohistiocytosis
Authors: Landman‐Parker J. , Deist F. Le , Blaise A. , Brison O. , Fischer A. 
Published: March 2008

Summary. We used polymerase chain reaction amplification of minisatellite sequences or of a Y chromosome‐specific sequence and Southern blotting to analyse long‐term engraftment (12–82 months) after bone marrow transplantation (BMT) for familial haemophagocytic lymphohistiocytosis (FHL). Six children aged from 1 to 18 months were transplanted with bone marrow from an HLA‐identical sibling in five cases and from an HLA‐nonidentical related donor (one mismatched HLA antigen) in one. The conditioning regiment included VP 16–213 (900 mg/m2), busulfan(16 mg/kg), cyclophosphamide (200 mg/kg) and, in one case. aracytine (2 g/m2).Four patients are alive without therapy more than 3 years after BMT; the other two relapsed 1 year after BMT. DNA was extracted from separated polymorphonuclear cells and mononuclear cells, as well as from separated E + and E — cells in one case and CD16 + (natural killer) and CD16 — cells in two cases. Engraftment was partial in the four long‐term survivors. Recipient cells were largely predominant in three of them as well as in one of the patients who relapsed (the donor also developed FHL 18 months after BMT). E +, E‐, CD16 + and CD16— cells presented the same pattern of chimaerism. Engraftment failed to occur in the patient who received an HLA‐nonidentical bone marrow. These results indicate that partial engraftment is compatible with longterm remission of FHL and that the presence of a small proportion of cells of donor origin can prevent FHL‐related lymphocyte and macrophage activation.
Respective effects of soluble interleukin‐1 receptor and tumour necrosis factor receptor on IL‐1 and TNF‐α‐induced DNA synthesis of common acute lymphoblastic leukaemia blasts in vitro
Authors: Carter Anna , Haddad Nuhad , Draxler Ilana , Israeli Ella , Raz Batya , Tatarsky Ilana 
Published: March 2008

This study investigates the capacity of human recombinant interleukin‐1α (IL‐1α), IL‐1β and tumour necrosis factor‐α (TNF‐α) to induce DNA synthesis of highly purified blasts from nine adult common acute lymphoblastic leukaemias (cALL) in 7 d liquid culture.IL‐1α, IL‐1β and TNF‐α stimulated 3H‐TdR uptake in leukaemic blasts in a dose‐dependent fashion. The IL‐1‐induced DNA synthesis of cALL cells could not be prevented by the addition of neutralizing antibodies against IL‐3, GM‐CSF, IL‐6 or TNF‐α. Similarly, the TNF‐α‐stimulated 3H‐TdR incorporation of leukaemic blasts was not affected by the addition of antibodies towards IL‐1α, IL‐1β, IL‐3, GM‐CSF or IL‐6. These observations suggest that IL‐1 as well as TNF‐α stimulated growth could not be attributed to the endogenous production of factors, corresponding to the antibodies used in these experiments. Both IL‐1 as well as TNF‐α mediate their action through interaction with specific cell surface receptors.Recently two distinct types of IL‐1 receptors (IL‐1‐Rs), IL‐1R (p80) and IL‐1‐R (p65), as well as two distinct types of TNF‐receptors (TNF‐Rs), TNF‐R (p55) and TNF‐R (p75) have been identified. Both types of TNF‐Rs exist also in soluble forms (sTNF‐Rs), while soluble IL‐1‐Rs (sIL‐1‐Rs) have not yet been found naturally. In this study we show that sIL‐1‐R as well as sTNF‐R modulate the effects of their corresponding cytokine in a dose‐dependent bimodal fashion: at lower concentrations they augmented while at higher concentrations they inhibited the cytokine‐stimulated DNA synthesis of cALL blasts in vitro. It may therefore be concluded from this study that soluble receptors for both IL‐1 and TNF. at least in vitro, are functional and interfere with their corresponding cytokine bioactivity.