bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth response to cytokines of circulating myeloid progenitors from myelodysplastic patients at diagnosis and more than 600 days after diagnosis
Authors: Tennant Graham B. , Bowen David T. , Jacobs Allan
Published: July 2010

Abstract: Myeloid colony growth from the peripheral blood of myelodysplastic (MDS) patients was assessed for abnormal in vitro response to haemopoietic growth factors (granulocyte colony‐stimulating factor (G‐CSF), macrophage colony‐stimulating factor (M‐CSF), granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), interleukin‐1 (IL‐l), interleukin‐3 (IL‐3)). Abnormal colony growth, increased or reduced, was observed with each of the factors. No specific growth pattern was related to any of the French‐American‐British classification (FAB) types of disease. MDS patients who had survived >600 days after diagnosis (n = 34) showed significantly fewer abnormalities than patients assayed at the time of diagnosis (n = 37), the major difference being less frequent stimulation of colony growth. These findings indicate that the time of sampling relative to diagnosis needs to be considered when interpreting the in vitro response to growth factors of myeloid colonies from MDS patients.
Human neutrophil migration into skin chambers is associated with ProductionI of NAP‐1/IL8 and C5a
Authors: Follin P. , Wymann M. P. , Dewald B. , Ceska M. , Dahlgren C.
Published: July 2010

Abstract: Respiratory burst activity initiated by the chemoattractants NLP, rC5a and rNAP‐l/IL8 was investigated in human exudated and peripheral blood neutrophils. Exudated cells were isolated after migration into a skin chamber and the respiratory burst activity was measured as chemiluminescence amplified by luminol and horseradish peroxidase. The response to NLP (5 times 10−8mol/l) was significantly enhanced (p < 0.01) in the exudated cells but was significantly decreased after stimulation (5 times 10−8mol/l) with rC5a and rNAP‐l/IL8 (p<0.05 and p<0.01, respectively). Analysis revealed that, in the chamber fluid, the activated complement C5a was generated during exudation (p<0.01). Determinations of NAP‐l/IL8 showed that this substance was also produced and released into the chamber fluid (p<0.01). No correlation was found between the number of exudated cells and the amount of C5a or NAP‐l/IL8 in the exudation fluid, thus indicating that, in vivo, the exudation process is controlled by multiple factors and not by the quantity of a single chemoattractant. The present study shows that NAP‐l/IL8 and C5a are produced in humans during an aseptic inflammation, and that this occurs in parallel to the migration of neutrophils into the skin chambers. The significant desensitization of the exudated cells to NAP‐l/IL8 and C5a reflects a previous exposure to these attractants. These results suggest that the novel tissue‐derived cytokine NAP‐l/ILS plays a role in human neutrophil exudation in vivo.
Autologous bone marrow transplantation for non‐Hodgkin's lymphoma
Authors: McMillan A. K. , Goldstone A. H.
Published: July 2010

Abstract:  Autologous bone marrow transplantation (ABMT) is now so widely applied in the treatment of relapsed high‐ and intermediate‐grade non‐Hodgkin's lymphoma (NHL) that it is very important to analyse the evidence on which this practice is based and ask in precise terms what the place of this technique should be. This article will review the data that have been published and discuss the randomised studies now in progress. The possible use of ABMT in other areas such as consolidation of remission and its use in low‐grade lymphoma will also be examined. The EBMT data quoted are taken from the 1990 review of the register for ABMT in malignant lymphoma which was presented to the XVIth meeting of the EBMT in the Hague in 1990.
Physiological response to phlebotomies for autologous transfusion at elective hip‐joint surgery
Authors: Birgegård Gunnar , Danersund Antero , Högman Claes , Milbrink Jan , Wide Leif
Published: July 2010

Abstract:  In order to study the physiological response to phlebotomies for autotransfusion, an autotransfusion program was designed for 10 patients undergoing hip‐joint replacement surgery for arthrosis. 4 phlebotomies of 450 ml each were performed within 12 days. Blood samples were taken immediately before phlebotomy for blood hemoglobin (Hb), serum erythropoietin (Epo), reticulocyte count (ret) and erythrocyte 2,3‐diphospho‐glycerate (DPG). All 4 phlebotomies could be performed in 9/10 patients, and only 1 patient had significant symptoms (fatigue). The operation was performed 2 weeks after the last phlebotomy. None of the patients had recovered the initial Hb level at operation (24.8 ± 9 per liter lower than initially), and they were all even more anemic after the operation (36.8 ± 16.9 g/1 lower than initially). Serum Epo increased from 13.6 ± 7.2 IU to 30.6 ± 12.2 (SD) IU per liter, and reticulocyte counts increased to a maximum of 3.68 ± 1.69%. DPG increased in all patients except the one who had significant fatigue. It is concluded that the patients tolerated the phlebotomy program well but that a significant anemia developed. The compensatory increase in erythropoietin and reticulocyte count, adequate for this degree of anemia, was small compared to the increase seen at more severe anemia, indicating that there may be a role for pharmacological stimulation of erythropoiesis in blood predeposit programs.
Transforming growth factor β expression in human marrow stromal cells
Authors: Nemunaitis J. , Tompkins C. K. , Andrews D. F. , Singer J. W.
Published: July 2010

Abstract:  The effects of hematopoietic cytokines on the expression of transforming growth factors (TGFβ) mRNA and the effect of TGFβ on cytokine and on a major extracellular matrix protein, collagen I, mRNA expression was studied in human marrow stromal cells. As with other cultured mesenchymal cells, stromal cells constitutively express TGFβ1 but not TGFα mRNA. In simian virus 40 (SV40)‐transformed stromal cells downregulation of TGFβ1 expression was observed 2 hours after incubation with recombinant human (rh) tumor‐necrosis factor α (TNFα) and 144 h after addition of rh granulocyte macrophage colony‐stimulating factor (GM‐CSF). Neither interleukin‐(IL‐1)β nor IL‐6 had an observable effect on TGFβ1 mRNA expression. TGFβ upregulated collagen I mRNA expression. These data suggest that cytokines may influence TGFβ mRNA expression.
Regeneration of CALLA (CD10+), TdT+ and double‐positive cells in the bone marrow and blood after autologous bone marrow transplantation
Authors: Smedmyr Bengt , Bengtsson Mats , Jakobsson Åke , Simonsson Bengt , Öberg Gunnar , Tötterman Thomas H.
Published: July 2010

Abstract:  In this prospective study we investigated the frequency of CD10+, TdT+ and CD10+ TdT+ mononuclear cells in the bone marrow (BM) and peripheral blood (PB) before and after autologous bone marrow transplantation (ABMT). 49 patients treated for acute lymphoblastic or myeloblastic leukaemia, malignant lymphoma or multiple myeloma were included. A significant increase in CD10+ cells occurred in BM in both children and adults after ABMT. In children, we also found a significant increase in CD10+ cells in PB. In individual patients remaining in remission, up to 34% CD10+ cells having a normal Ig kappa/lambda light chain ratio were recorded after ABMT. In children, the percentage of TdT+ and CD10+ TdT+ cells increased significantly in BM. In most cases the CD10/TdT‐ratio was greater than 1.0, but during early regeneration after ABMT this ratio was less than 1.0 in several patients remaining in complete remission. In patients remaining in remission, CD10+ TdT+ cells were detected in the blood in only 2 out of 140 samples tested, and the proportion of these cells never exceeded 0.03%. We conclude that quantitation of CD10+ TdT+ cells in peripheral blood is helpful in the evaluation of complete remission in patients treated for pre‐B‐ALL.
Small‐dose iron tolerance test and body iron content in normal subjects
Authors: Costa Attilia , Liberato Lucio N. , Palestra Pietro , Barosi Giovanni
Published: July 2010

Abstract: The small‐dose iron tolerance test (SD‐ITT) was performed in 37 healthy subjects (20 females and 17 males). The area under the curve (AUC) of serum iron variations after the test dose (10 mg of iron as iron sulphate) was corrected by the expected plasma iron disappearance rate, the expected subject's plasma volume and the measured spontaneous time‐dependent serum iron variations, and was used as a summary measure of the outcome, Q‐ITT. Q‐ITT correlated strictly with the maximum serum iron increase (SImax). Q‐ITT gave positive (greater than zero) values in only 14 out of the 37 subjects (11 females and 3 males). Serum ferritin proved to be the best discriminating parameter between positive and non‐positive subjects, and was inversely correlated with Q‐ITT in the positive ones. In 2 male subjects, aged 43 and 34 years, SD‐ITT proved to be highly sensitive to the progressive decrease of mobilzable body iron content during repeated venesections. In these patients the threshold for a positive test result was obtained at values lower than 1050 and 950 mg of body iron content, respectively. The threshold‐dependent sensitivity, simplicity, and repeatability of this method favor its becoming a useful technique for studying the up‐regulation of iron absorption in normal subjects and in pathological conditions.
Platelet function and interferon alpha‐2a treatment in essential thrombocythaemia
Authors: Catani L. , Gugliotta L. , Cascione M. L. , Belmonte M. Mattioli , Vianelli N. , Belardinelli A. R. , Tura S.
Published: July 2010

Abstract:  The effects of interferon (IFN) alpha‐2a treatment on platelet function were evaluated in 20 patients affected by essential thrombo‐cythaemia (ET). Baseline data documented the well‐known abnormalities of in vitro platelet aggregation and the constant presence of a Δ‐storage pool deficiency. The therapy in all patients reduced the platelet count, and in the majority of them caused a partial improvement of in vitro platelet aggregation. Although the mean intraplatelet ADP level improved during treatment, it always remained below the normal range documenting persistence of the Δ‐storage pool deficiency. The plasma β‐TG levels, which initially were high, significantly decreased during treatment, but the β‐TG ratio and the platelet β‐TG values always remained within the normal range ‐ this suggests an absence of platelet activation either before or during therapy. Our results demonstrate that, despite significantly reducing the platelet count, IFN alpha‐2a treatment only partially corrects the qualitative platelet abnormalities in ET.
Prenatal diagnosis of thalassemia and hemoglobinopathies in Switzerland
Authors: Beris Photis , Darbellay Regis , Dornier Catherine , Hochmann Agnes , Miescher Peter
Published: July 2010

Abstract:  During a 10‐month period, 10 couples originating from Africa (3), the tropics (1) and the thalassemia‐belt region (6), living in Switzerland, requested prenatal diagnosis of hemoglobinopathies. Hb SS (twice), Hb Bart's (Hydrops fetalis) and β‐thalassemia major were diagnosed either by gene mapping or by direct detection of the mutations in DNA amplified by the PCR procedure. Whenever it was possible to obtain fetal blood or tissue, diagnosis was confirmed. In one Vietnamese man, concomitant existence of α‐thal 1 with β‐thalassemia resulted in an unusually high Hb level because of balanced α and β globin synthesis. The 10 couples examined originated from 7 different countries and presented at least 7 different Hb pathologies. This variety of pathologies represents the main difficulty for prenatal diagnosis of hemoglobinopathies in a non‐endemic country. A diagnostic approach to overcome this problem is developed.
Chronic myeloid leukaemia lymphoid blast crisis. Relevance of molecular analysis at the bcr and immunoglobulin heavy chain gene level in monitoring response to therapy and residual disease
Authors: Coco F. Lo , Diverio D. , Frontani M. , Wang Y.‐Z. , Montefusco E. , De Fabritiis P. , Arcese1 W. , De Rossi G. , Mandelli F.
Published: July 2010

Abstract:  Southern blot analyses were performed in sequential DNA samples from 4 patients with Ph' + chronic myeloid leukaemia (CML) who underwent lymphoid or mixed blast crisis (BC). Genomic rearrangements at the breakpoint cluster region (bcr) and immunoglobulin heavy chain (IgH) gene level provided, in these cases, a sensitive and specific evaluation of response to therapy both in terms of blasts and Ph' + cell suppression. Recurrent BC was molecularly characterized in the 4 patients, showing each time identical individual specific DNA rearrangement patterns. Residual blasts were detected in 2 cases during intervening chronic phases by IgH rearrangements. Such findings highlight the specificity of these molecular markers, clearly indicating the failure of ablative therapy in eradicating the neoplastic clone. Finally, molecular and phenotypic identity in individual recurrent BC also suggested, in our cases, a lack of clonal evolution during disease progression.
A plea to overcome the concept of “staging” and related inadequacy in multiple myeloma
Authors: Gobbi Paolo G. , Bertoloni Daniele , Grignani Giovanni , Pieresca Carla , Rossi Andrea , Rutigliano Leonardo , Merlini Giampaolo , Riccardi Alberto , Ascari Edoardo
Published: July 2010

Abstract: From a retrospective multivariate study on 107 multiple myeloma (MM) patients, serum β2‐microglobulin (β2M) proved to be the best prognostic discriminator, better than each of the currently used staging systems (Durie and Salmon's [DS], Merlini, Waldenström and Jayakar's [MWJ] and the British Medical Research Council's [BMRC]). The predictive ability of each staging system is better improved by combining consideration of β2M as a continuous rather than a binary variable (even at its best prognostic cut‐off). The combination of BMRC with β2M demonstrated the highest prognostic value, followed by those involving DS or MWJ. Ease and measurability of clinical parameters at diagnosis, parametric type of statistical model assumed for description of survival, and supply of direct estimate of expected survival are the characteristics of the MWJ system that suggest it is best able to integrate β2M correctly in a prognostic index. The basic concepts and the clinical use of the available staging systems for MM are criticized along the following lines: a) the need to include new and homogeneously weighted parameters in future prognostic systems ‐ b) the lack of direct correspondence between treatment requirements (according to stage) and available therapeutic resources ‐ c) evidence of the rough stratification of the actual survival expectancy, as permitted by the current staging systems. A direct, and as accurate as possible estimate of prognosis ‐ based on easy and measurable parameters evaluable at diagnosis ‐ should replace the current classification of patients according to stages. This estimate should mark the clinical evaluation at diagnosis, should flexibly indicate treatment even according to different protocols or centers, and should allow very accurate statistical corrections for different survival expectancy at diagnosis when evaluating different treatments in clinical trials.
Transglutaminase differentiation during maturation of human blood monocytes to macrophages
Authors: Seiving Birgitta , Ohlsson Kjell , Linder Carina , Stenberg Pal
Published: July 2010

Abstract:  There are divergent reports in the literature on the character of transglutaminases in monocytes and macrophages. The aim of the present study was to further elucidate the characteristics and functions of various transglutaminases in monocytes and macrophages. Peripheral human blood monocytes were plated and cultured for up to a month and examined for transglutaminase. Freshly prepared monocytes contained cellular Factor XIII only. Successively during culturing, the monocytes matured into macrophages. Cellular Factor XIII correspondingly disappeared and tissue transglutaminase increased during the same time. After approximately 2 weeks in culture only tissue transglutaminase was detected and this remained for the rest of the culturing period. The tissue transglutaminase content was induced by addition of 2 μmol/1 retinoic acid. Addition of retinoic acid was not critical for transglutaminase differentiation. Transglutaminase could be associated with phagocytosis of 125I‐trypsin‐α2‐macroglobulin complexes. The phagocytotic capacity of monocytes was approximately 1/4 compared to macrophages cultured for 14 days. Phagocytosis was measured as cellular complex degradation to monoiodo‐tyrosine, released to the culture medium. The monocytes and macrophages were incubated at 4 ° C and 37 ° C, with and without addition of the transglutaminase inhibitor monodansylthiacadaverine. Addition of 100 μmol/1 monodansylthia‐cadaverine caused approximately 2/3 inhibition of phagocytosis. These results suggest that transglutaminase differentiates from cellular Factor XIII into tissue type transglutaminase during maturation of monocytes into macrophages and that the differentiation is associated with trans‐glutaminase‐dependent phagocytosis.
Bioavailability of carbonyl iron: A randomized, double‐blind study
Authors: Devasthali Shirish D. , Gor‐deuk Victor R. , Brittenham Gary M. , Bravo Joanne R. , Hughes Margaret A. , Keating Louise J.
Published: July 2010

Abstract:  49 female blood donors with iron‐deficiency anemia were treated with equal doses of iron either as carbonyl iron or ferrous sulfate in a randomized, double‐blind fashion. The prevalence of side‐effects was similar in the two groups. Mean values for hemoglobin concentration, mean corpuscular volume, corrected reticulocyte count, platelet count, serum iron, total iron‐binding capacity, transferrin saturation or erythrocyte proto‐porphyrin did not differ significantly between the two groups throughout the study. After 16 weeks of therapy, the mean increase in hemoglobin iron was similar in both groups (p = 0.2). Estimates of net changes in total body iron suggested that the overall bioavailability of carbonyl iron was high, about 70% that of ferrous sulfate.
Feasibility of autologous bone marrow transplantation for early consolidation of follicular non‐Hodgkin's lymphoma
Authors: Fouillard L. , Gorin N. C. , Laporte J. Ph. , Douay L. , Lopez M. , Isnard F. , Jouet J. P. , Walter M. P. , Morel P. , Fenaux P. , Aoudjhane M. , Stachowiak J. , Devidas A. , Bauters F. , Najman A.
Published: July 2010

Abstract:  In contrast to intermediate‐ and high‐grade non‐Hodgkin's lymph‐omas (NHL), patients with follicular lymphomas retain a poor prognosis in the long run. Several reports suggested that they are incurable by conventional chemotherapy. 10 patients with follicular NHL were autografted for consolidation of early remission. One of these patients treated in 1979 received the TACC regimen with unpurged marrow. The other 9 (8 in first, 1 in second remission) treated since July 1987 received the BEAM regimen followed by autologous bone marrow transplantation (ABMT) with marrow purged in vitro by mafosfamide at levels individually adjusted. There were no toxic deaths. 8 patients remain in unmaintained CR 15 to 43 months post‐ABMT ‐ 2 are beyond 2 years. The patient autografted in 1979 has relapsed 9 yr later. ABMT is feasible with no indue toxicity for consolidation of follicular NHL early in first remission, as an alternative aggressive strategy. Further studies and a longer follow‐up will be needed to evaluate its antitumor efficacy.
A sequential histological study of bone marrow fibrosis in idiopathic myelofibrosis
Authors: Hasselbalch Hans , Lisse Ida
Published: July 2010

Abstract:  A sequential histological study of bone marrow biopsies from 36 patients with idiopathic myelofibrosis was performed to investigate the accumulation of connective tissue in the bone marrow during the course of the disease and the influence of therapy on this process. The degree of bone marrow fibrosis was graded semiquantitatively from 0 (normal) to + 5 (extensive collagen fibrosis and ostemyelosclerosis). The median interval between the first and final biopsy was 25 months (range 3 to 103) in patients with chronic idiopathic myelofibrosis and 2 months (range 1 to 14) in patients with a syndrome of acute myelofibrosis. In most patients with chronic IMF the bone marrow fibrosis remained unchanged. Regression of bone marrow fibrosis in 9 patients with chronic IMF was associated with immunosuppressive/‐cytotoxic treatment or splenectomy. Severe bone marrow fibrosis completely resolved during intensive chemotherapy of a patient with acute myelofibrosis. No relationship existed between spleen size and the degree of bone marrow fibrosis.
Utilization of red‐cell FAD by methaemoglobin reductases at the expense of glutathione reductase in heterozygous β ‐thalassaemia
Authors: Perry G. M. , Anderson B. B.
Published: July 2010

Abstract:  FAD‐dependent methaemoglobin reductases (MHR) were studied in red cells in heterozygous β‐thalassaemia to investigate how they related to low FAD‐dependent glutathione reductase (GR). In contrast to GR, MHR activities were usually normal or increased. In particular, whether expressed in relation to haemoglobin or number of red cells, NADPH‐MHR activity was markedly increased in most subjects, probably being a response to increased oxidative stress. Oral riboflavin had no effect on MHR activities, indicating saturation with FAD even though GR was deficient. A strong correlation between percent stimulation of GR by FAD and NAPDH‐MHR activity indicates that FAD is utilized by MHR at the expense of GR. This could be an important influence on GR in heterozygous β‐thalassaemia. Thus, the low activity resulting from an inherited deficiency of FAD is decreased further.
Stromal colonies can be grown from the non‐adherent cells in human long‐term bone marrow cultures
Authors: Clarke E. , McCann S. R.
Published: July 2010

Abstract:  The absence of a pluripotent stem cell assay for human cells means that we must rely on assays of committed progenitors as a means for examining the ability of long‐term bone marrow culture (LTBMC) to support haemopoiesis. The CFU‐GM assay has been employed by many authors to demonstrate that the proliferative capacity and differentiation potential has been retained in LTBMC. In this study the non‐adherent cells from human LTBMC were set up using a liquid culture technique for the clonal proliferation of stromal colonies (CFU‐F). Weekly plating of the non‐adherent cells produced CFU‐F for up to 7 wk. Morphological, cytochemical and antigenic characterisation of these colonies revealed that they were identical to those grown from bone marrow de novo. LTBMC can now be used to identify the interactions between the haemopoietic inductive microenvironment and stromal progenitors and allow us to investigate the precise role of cell‐cell interactions or cytokine influences on the proliferative capacity of stromal cell progenitors.
Cardiotoxicity of epirubicin and doxorubicin: A double‐blind randomized study
Authors: Lahtinen R. , Kuikka J. , Nousiainen T. , Uusitupa M. , Lansimies E.
Published: July 2010

Abstract:  24 patients with non‐Hodgkin lymphoma were randomized into two multidrug regimens including either epirubicin (N = 12) or doxorubicin (N = 12) to establish the cardiotoxicity of each treatment modality. At cumulative doses of 400–500 mg/m2 left ventricular ejection fraction (LVEF) at rest determined by radionuclide angiocardiography decreased significantly more in the doxorubicin (‐ 15 ± 11 %) than in the epirubicin group (0 ± 13%, p < 0.005). During epirubicin therapy no clinically significant cardiotoxicity developed, but a decrease larger than 10% in LVEF was seen in 4 of 12 patients at a mean cumulative level of 450 mg/m2. During doxorubicin therapy 1 patient developed a heart failure at a cumulative level of 200 mg/m2 and, altogether, in 7 patients LVEF decreased more than 10%. The monitoring of cardiac toxicity is imperative in patients treated with doxorubicin and is advisable if the patient is expected to receive epirubicin at more than 450 mg/m2.
Surgical restaging of advanced Hodgkin's disease after first line chemotherapy
Authors: Feriné C. , Brice P. , Bourstyn E. , D'Agay M. F. , Lepage E. , Miclea J. M. , Fermand J. P. , Extra J. M. , Frija J. , Colin P. , Gisselbrecht G.
Published: July 2010

Abstract:  47 patients with stages IIIB and IV Hodgkin's disease underwent laparotomy with splenectomy as restaging procedure after first‐line chemotherapy (CT) which included 4 cycles of CT ABV/IMEP/PCAV/ABV. After surgical restaging (SR), all patients were scheduled to receive 2 additional cycles IMEP/PCAV followed by TNI 20 Gy and patients with residual clinical abnormality or positive restaging surgery received a 20 Gy boost to these areas. 11 patients (23.4%) were found to have active disease in the spleen (10 patients) and/or the lymph nodes (3 patients) after SR. In the spleen, foci of active disease had a size in millimeters and confirm the limits of clinical restaging. According to the response to CT, 5 of the 35 patients (14%) clinically restaged as good responders had active disease; 6 of the 12 patients (50%) clinically restaged as poor responders had active disease. SR is of interest in selected patients with slowly responding disease to determine the indication of an extended field RT for responding patients and salvage therapy for patients resistant to CT.
Cell cycle arrest and DNA damage after melphalan treatment of the human myeloma cell line RPMI 8226
Authors: Fernberg Jan‐Olof , Lewensohn Rolf , Skog Sven
Published: July 2010

Abstract:  Exposure of a myeloma cell line (RPMI 8226) to a 30‐minute pulse of melphalan (1‐phenylalanine‐mustard) resulted in a cell cycle progression delay characteristic for DNA cross‐linking agents. Reduction of outflow of cells from late S‐ and G2‐phases was more pronounced as compared to that from G1‐phase. The consequence is a progressive accumulation of cells in late S‐ and G2‐phases. At restoration of outflow of cells from late S‐ and G2‐phases, complete removal of DNA interstrand cross‐links, as measured by DNA alkaline elution, was noted. At this time less than 50% of maximum DNA‐protein cross‐links were removed. Further we found no correlation between restored outflow of cells from the G2‐phase and removal of DNA‐protein cross‐links during the follow‐up time of 72 h. No DNA double strand breaks as measured by DNA neutral elution were formed during the observation period. The data suggest that removal of DNA interstrand cross‐links seems prerequisite for the outflow of cells from G2 after melphalan treatment.
A novel monoclonal antibody specific for human pre‐B cell leukemia/lymphoma
Authors: Nakamura Naoya , Morimura Yutaka , Abe Masafumi , Wakasa Haruki
Published: July 2010

Abstract:  A novel monoclonal antibody, designated WH 14‐antibody (WH14‐Ab), was produced by using a non‐T ALL cell line (HBL‐3) as an immunogen. 35S‐labelled immunoprecipitate revealed that the antigen reacting with WH14‐Ab was estimated to be 30 Kd. Immunoglobulin isotype of WH14‐Ab was IgGl. In the normal hematopoietic tissue, WH14‐Ab reacted with a small number of monocytes (<30%) in the peripheral blood, but neither with the lymphocytes nor granulocytes. WH14‐Ab reacted with HBL‐3 and REH, but not with other B‐cell leukemia/lymphoma and EBV‐transformed cell lines. In addition, WH14‐Ab reacted with most non‐T ALL and pre‐B lymphoblastic lymphoma. WH14‐Ab did not react with all T‐cell lymphomas. These findings indicate that the WH14‐Ab may recognize the cell surface determinant shared by immature B cells, especially pre‐B cells, in the B‐cell lineage. WH14‐Ab may be useful not only for the detection of pre‐B cell leukemia/Iymphomas but also for the investigation of maturation and differentiation of B‐cell lineage.
Magnetic resonance imaging in idiopathic hemochromatosis
Authors: Andersen P. B. , Birgegard G. , Nyman R. , Hemmingsson A.
Published: July 2010

Abstract:  The therapeutic management of patients with idiopathic hemochromatosis (IH) requires an accurate estimate of hepatic iron overload in order to prevent tissue fibrosis and organ failure. Magnetic resonance imaging (MRI) was used to estimate liver iron overload in 5 patients with IH and in 8 normal controls. Signal intensity ratio between liver and subcutaneus fat in T1‐, proton‐ and T2‐weighted images was significantly lower in IH when compared with normal controls, and increased gradually during treatment by phlebotomy. Mean serum ferritin at diagnosis was 755 μg/1 (range: 648–900) in IH and 85 μg/1 (range: 19–232) in normal controls. A high correlation (r = ‐ 0.93) was present between liver signal intensity ratio and serum ferritin; both changed in parallel during removal of iron by phlebotomy. MRI may provide a safe and accurate method of detecting iron overload in the precirrhotic phase of IH, obviating the need for liver biopsy. It may also be used to monitor treatment.
Fc III receptors (FcRIII) on granulocytes: A specific and sensitive diagnostic test for paroxysmal nocturnal hemoglobinuria (PNH)
Authors: Bessler Monica , Fehr Jorg
Published: July 2010

Abstract:  The FcRIII on human granulocytes is a glycosyl‐phosphatidylinositol‐anchored membrane protein. In PNH, proteins with this type of membrane linkage are known to be deficient on blood cells. The purpose of this study was to assess the diagnostic value of flow cytometric FcRIII quantification on granulocytes in PNH. Immunofluorescence measurements were performed in 105 patients, including 7 patients with PNH, 16 patients with aplastic anemia, and 12 with myelodysplastic syndrome, by a whole blood immunofluorescent staining procedure using monoclonal antibodies to FcRIII. In all 7 PNH patients and in 3 patients with aplastic anaemia, a distinct FcRIII‐deficient granulocyte population of variable size was found. None of the remaining patients showed a similar population of FcRIII‐deficient granulocytes. Quantification of FcRIII‐deficient neutrophils is shown to be a highly specific and sensitive diagnostic test for PNH. It is easy, fast and highly reproducible and, therefore, suitable for routine diagnostic and follow‐up studies in PNH patients and patients with aplastic anemia.
Peripheral blood T lymphocytes in patients with monoclonal gammopathies: Expanded subsets as depicted by capacity to bind to autologous monoclonal immunoglobulins or reactivity with anti‐V gene‐restricted antibodies
Authors: Österborg A. , Janson C. H. , Bergenbrant S. , Holm G. , Lefvert A‐K , Wigzell H. , Mellstedt H.
Published: July 2010

Abstract:  The presence of T cells binding F(ab‘)2 fragments of the idiotypic immunoglobulin was examined by immunofluorescence in peripheral blood of patients with monoclonal gammopathy. In 3 out of 11 tested patients, 1–15% idiotype‐binding T cells of either CD4 or CD8 phenotype were found. In 1 patient both a CD4+ and a CD8+ idiotype‐binding T‐cell fraction were present. In 1 patient the idiotype‐binding T cells also reacted with a mAb directed against the variable parts of the TCR α or β chains, further indicating a clonal origin at the α/β level. 3 patients had an expanded predominant T‐cell receptor V gene usage based on the reactivity with the limited panel of TCR mAb, but these “clonal” T cells did not bind the idiotype. The study supports the existence of idiotype‐specific T cells in peripheral blood of patients with monoclonal gammopathy. Such cells might have a regulatory role on the monoclonal B‐cell clone and may be an important target for immunotherapy.
Leukocyte removal filtration of platelet concentrates. A study of platelet loss using 111In‐labelled platelets and dynamic gamma camera scintigraphy
Authors: Wadenvik Hans , Kutti Jack , Lindholm Annika
Published: July 2010

Abstract:  111In labelled platelets and gamma camera scintigraphy were used for the study of the platelet loss during leukocyte removal filtration of stored platelets. Two different filters were examined, Imugard IG500 and Pall PL 100, and platelet pools containing varying number of platelet concentrates were filtered. It was found that a sizeable amount of the platelets was trapped within the filter. Some of the trapped platelets could be recovered by rinsing the filters with normal saline. The most appropriate rinsing volume to recover lost platelets seemed to match with the “dead space” volume within the filter. It is concluded that radiolabeled platelets and gamma camera scintigraphy appears to be an excellent method to investigate the dynamic events of platelet loss during leukocyte removal filtration. This technique should be well applicable for the study of technological advances in filter construction.
Danazol: in vitro effects on human hemopoiesis and in vivo activity in hypoplastic and myelodysplastic disorders
Authors: Selleri C. , Catalano L. , De Rosa G. , Fontana R. , Notaro R. , Rotoli B.
Published: July 2010

Abstract:  We examined the effects of danazol on in vitro growth of human bone marrow and peripheral blood progenitor cells from 15 normal donors and 5 myelodysplastic patients, and on in vivo hemopoiesis in 30 patients with hypoplastic or myelodysplastic disorders. At concentrations similar to that reported as the plasma level after oral administration, danazol significantly increased CFU‐GM colony growth in all normal donors, while the influence on CFU‐E, BFU‐E, CFU‐MK and CFU‐GEMM colony growth was less evident. The stimulatory effect on CFU‐GM was observed even after accessory cell depletion. No stimulatory effect either in vitro on the growth of all hemopoietic progenitors or in vivo was observed in 15 myelodysplastic patients, while 7 complete and 3 partial hematological responses occurred in 15 patients with hypoplastic disorders. In conclusion, our results suggest that danazol exerts a direct stimulatory activity in vitro at least on CFU‐GM, and a hemopoietic stimulatory effect in vivo in hypoplastic but not in myelodysplastic disorders.
Biochemical identification of the antigen recognized by the monoclonal pan‐B cell antibody Y29/55
Authors: Rentsch Beatrix , Bucher Urs , del Re Guido P. Brun
Published: July 2010

Abstract:  To examine the biochemical structure of the antigen recognized by the monoclonal pan‐B cell antibody, Y29/55, the Daudi‐ and Jurkat‐cell lines were labeled by two different methods and immunoprecipitation experiments were carried out. After surface labeling with iodine, two bands with molecular weights of about 38 and 42 kD were observed. The same two proteins were precipitated after biosynthetic labeling with (35S)‐methionine from B cells and, to a lesser extent, from T cells. Therefore, it seems that the same proteins, or proteins with similar molecular weight, exist intracellularly in T cells as exist on the surface of, and possibly intracellularly, in B cells. It was confirmed that 80–90% of normal blood‐derived B cells were stained with Y29/55 by indirect immunofluorescence. Double‐labeling experiments with the pan‐B cell antibodies Leu 16 (CD 20) and Leu 12 (CD 19) showed a B‐cell population which could be stained with both antibodies (Y29/55 and Leu 16 or Y29/55 and Leu 12). A minor cell population was stained with the antibody Y29/55 alone. Our findings indicate that the antibody Y29/55 recognizes a B‐cell antigen, which has not been described previously.
Folate‐deficient human lymphoblasts: changes in de novo purine and pyrimidine synthesis and phosphoribosylpyrophosphate
Authors: Van Der Weyden Martin B. , Rose Ian S. , Newitt Paula
Published: July 2010

Abstract:  Peripheral blood lymphocytes from healthy volunteers cultured with phytohaemagglutinin in a folate‐deficient medium exhibit megaloblastic maturation and reduced cellular folate content. For these cells, changes in de novo purine and pyrimidine synthesis and cellular phosphoribosylpyrophosphate (PRPP) have been determined. Mitogen‐stimulated cells cultured with undialyzed pooled human serum (PHS) exhibit undetectable de novo purine synthesis, a three‐fold increase in PRPP content and augmented de novo pyrimidine synthesis; these changes are independent of cellular folate status. Folate‐replete cells cultured with PHS which was dialyzed to reduce purine compounds concentrations show markedly increased de novo purine synthesis. The PRPP content and pyrimidine synthesis rates of these cells are similar to those of folate‐replete cells cultured with undialyzed PHS. Folate‐deficient cells cultured in dialyzed PHS show a 10‐fold reduction in purine synthesis and a corresponding increase in PRPP levels. Pyrimidine synthesis was moderately reduced. The purine bases hypoxanthine and adenine markedly reduced the augmgmented purine synthesis of folate‐replete cells or the increased PRPP content of folate‐deficient cells cultured with dialyzed PHS. These findings suggest that cellular folate status is critical for de novo purine synthesis only when coupled with purine bases restriction and that the latter are efficient regulators of de novo purine synthesis.
Variations in serum erythropoietin and transferrin receptor during phlebotomy therapy of hereditary hemochromatosis: A case report
Authors: Thorstensen Ketil , Egeberg Kjartan , Romslo Inge , Dalhøj Jørn , Wiggers Preben
Published: July 2010

Abstract:  Serum levels of transferrin receptor and erythropoietin were determined in 2 patients with hereditary hemochromatosis undergoing phlebotomy therapy. The objective of the study was to determine changes in serum transferrin receptor and serum erythropoietin occurring during therapy, and to investigate if such changes could be useful to monitor the therapy. The study showed that serum transferrin receptor, and to a lesser extent serum erythropoietin, may be better parameters than serum ferritin as indicators of when phlebotomy should be discontinued. The most sensitive parameter, however, appeared to be the serum transferrin ratio.
Immunological properties of ferritin during in vitro maturation of human monocytes
Authors: Worrall M. , Worwood M.
Published: July 2010

Abstract:  Ferritin in macrophages from human liver and spleen is rich in L subunits but, in the peripheral blood monocytes from which tissue macrophages are derived, the ferritin contains a high proportion of H subunits. We have studied the maturation of monocytes in vitro and the immunological properties of cellular ferritin during this process. Mononuclear cells were isolated from peripheral blood of normal subjects and patients with idiopathic haemochromatosis. Monocytes were obtained by incubation on plastic. The adherent cells were incubated in medium with or without added iron (ferric ammonium citrate) for 20 hours and harvested. Monocytes were also incubated for 7 days before incubation with iron. Ferritin concentrations were determined using immunoassays specific for H and L rich isoferritins. Freshly isolated monocytes were found to have similar concentrations of H‐ and L‐rich isoferritins. Incubation with iron caused an increase in both H‐ and L‐type ferritins. After incubation for 7 d the ferritin present in the normal cell lysates was L‐rich and incubation with iron caused accumulation of L‐, but not H‐type ferritin. Maturation of monocytes is thus associated with the loss of H‐rich isoferritins. There were no differences between normal subjects and patients with idiopathic haemochromatosis in ferritin concentrations. In vitro maturation provides an excellent model for studying the developmental control of ferritin synthesis and breakdown.
Value of maintenance therapy with chemotherapy or interferon during remission of acute myeloid leukaemia
Authors: Palva I. P. , Almqvist A. , Elonen E. , Hänninen A. , Jouppila J. , Järventie G. , Koivunen E. , Kätkä K. , Lahtinen R. , Oivanen T. , Pelliniemi T. T. , Rajamäki A. , Remes K. , Ruutu T. , Timonen T. , Wasastjerna C. , Vilpo J. , Volin L. , Vuopio P.
Published: July 2010

Abstract:  108 consecutive patients with de novo acute myeloid leukaemia at ages 15 to 59 years were treated in a prospective controlled multicentre trial. Induction with combination TAD resulted in a complete remission in 85 cases (79%). After a cyclic consolidation programme for 6 months, 73% of the remissions continued. The maintenance therapy was at random either nothing, or alpha interferon, or monthly 5 day courses with thioguanine and cytarabine. The median duration of all remissions was 13 months; that of those in the control and interferon arms 15 months each, and in the chemotherapy arm 18 months. The median survival of all the 108 patients was 16 months; that of those in the control arm 20 months, in the interferon arm 33 months and in the chemotherapy arm 26 months. At 5 yr, 31%, 22% and 31%, respectively, were alive. The survival curves did not differ from each other significantly. Maintenance treatment after an intensive induction and a moderately intensive consolidation was of no benefit in this study. Interferon did not improve the prognosis.
Further studies of the defective stimulus‐response coupling for the oxidative burst in neutrophils in polycythemia vera
Authors: Samuelsson Jan , Berg Anders
Published: July 2010

Samuelsson J, Berg A. Further studies of the defective stimulus‐response coupling for the oxidative burst in neutrophils in polycythemia vera. Eur J Haematol 1991: 47: 239–245.

Abstract:  We have previously reported that the chemiluminescence (CL) response of neutrophils (PMN) from patients with polycythemia vera (PV) was abnormally low when induced by surface receptor‐dependent stimuli, fMLP and leukotriene B4, but normal when elicited by phorbol myristate acetate (PMA). This study documents that this discrepancy of the CL response to fMLP and PMA remained over a wide range of stimuli concentrations, was not due to iron‐deficient PV cells and was also observed with the nitroblue tetrazolium assay. Moreover, another surface receptor‐dependent agonist, platelet‐activating factor, conferred a significantly lower CL response in PV PMN relative to controls. Treatment with alpha interferon or GM‐CSF, to increase fMLP receptors, resulted in a similar enhancement of fMLP‐induced CL in PV and controls. CL was normal when induced by a number of non‐surface receptor‐dependent stimuli. Release of lactoferrin in response to fMLP (and PMA) was normal (as was previously reported fMLP‐induced chemotaxis and adherence). Thus, this defect is highly specific for oxidative metabolism, and localized to discrete step(s) of the stimulus‐response coupling for fMLP, leukotriene B4 and PAF, but conceivably not due to impairment of the dynamic interaction of fMLP with its receptor.
Kinetics of transfused neutrophils in peripheral blood and BAL fluid of a patient with variant X‐linked chronic granulomatous disease
Authors: Emmendorffer Andreas , Lohmann‐Matthes Marie‐Luise , Roesler Joachim
Published: July 2010

Abstract:  Patients with chronic granulomatous disease (CGD), an uncommon inherited disorder of phagocytes resulting in the defective production of reactive oxygen intermediates, are prone to bacterial and fungal infections. In the case presented, therapeutic efforts including white cell transfusions, and amphotericin B and IFNγ administration were undertaken to treat pneumonia caused by Aspergillus fumigatus. During a phase of artificial respiration, transfused white cells in peripheral blood and bronchoalveolar lavage fluid were monitored in order to examine their kinetics and functional activity. Using flowcytometrical methods, host‐derived and transfused neutrophils could be distinguished by cytochrome b558 expression using the monoclonal antibody 7D5 for immunofluorescent staining as well as by production of reactive oxygen intermediates. Transfused PMN could be detected in both compartments and their kinetics could be followed up to 24 hours after transfusion. Using flowcytometry, even small numbers of transfused PMN could be measured during episodes of extreme leukocytosis. Since functionally intact transfused PMN were found in the bronchioalveolar lavage fluid, white cell transfusions in combination with antibiotic and immunomodulating therapy should be considered a part of the therapeutic regimens for life‐threatening infections in CGD patients.
Pregnancy‐associated aplastic anemia ‐Report of 3 cases
Authors: van Besien Koen , Tricot Guido , Golichowski Alan , Padilla Lillie , Hoffman Ronald
Published: July 2010

Abstract: 3 patients with pregnancy‐associated aplastic anemia are reported. Management throughout most of the pregnancy consisted of supportive care. In 2 patients an improvement in blood counts occurred after delivery and, in 1 of these, the pancytopenia recurred during a subsequent pregnancy. In 1 case no improvement occurred after delivery and the patient ultimately required an allogeneic bone marrow transplantation. The outcome of these 3 cases demonstrates that pregnancy‐associated aplastic anemia can be managed successfully. The improvement that often occurs after delivery suggests a pathogenetic role for pregnancy in the development of this disease.
Moderate haemophilia B in a female carrier caused by preferential inactivation of the paternal X chromosome
Authors: Kling Stefan , Coffey Alison J. , Ljung Rolf , Sjorin Elsy , Nilsson Inga Marie , Holmberg Lars , Giannelli Francesco
Published: July 2010

Abstract:  The case of a female with moderate haemophilia B is reported. She is the only affected member of her family, and factor IX RFLP analysis shows her to have inherited no maternal markers for polymorphisms located in the first intron and 8 Kb 3′ of the polyadenylation signal (Ddel and Hhal, respectively). This clearly indicates a deletion involving at least the last 7 exons of the factor IX gene. Her other factor IX gene inherited from her healthy father is normal as her son is also healthy. This suggests the patient's haemophilia to be due to gross bias in the proportion of factor IX‐producing cells with an inactive paternal X chromosome. Methylation studies on the 5′ region of the PGK gene show that virtually all the patient's lymphocytes carry a hypermethylated and presumably an inactive paternal X chromosome. The reason for this bias in the activity of her two X chromosomes is not clear, as no chromosomal alterations were found.
A new risk grouping for IgD myeloma based on analysis of 165 Japanese patients
Authors: Shimamoto Yoshinori , Anami Yoichi , Yamaguchi Masaya
Published: July 2010

Abstract: The common staging systems for myeloma do not include IgD myeloma because its rarity makes analysis difficult. We studied a series of 165 Japanese patients with IgD myeloma retrospectively to assess which of the easily assessable parameters present at the time of diagnosis were of prognostic significance. The important individual variables detected in a previous univariate analysis were placed in a multiple regression model to identify the major prognostic factors for survival. This analysis showed that light‐chain subtype and white blood cell (WBC) count had a strong predictive relationship for the length of survival. These two factors were used to construct a model containing four categories of patients at increased risk for shortened survival. These categories divided the patients into three groups with respective 5‐year survival rates of 66% (low risk), 23% (moderate risk), and 0% (high risk). This new risk grouping showed prognostic validity for IgD myeloma.