bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is interferon alpha in cutaneous T‐cell lymphoma a treatment of choice?
Authors: Papa G. , Tura S. , Mandelli F. , Vegna M. L. , Defazio D. , Mazza P. , Zinzani P. L. , Simoni R. , DePita O. , Ferranti G. , Ghetti P. L. , Criscuolo D. 
Published: March 2008

This study was designed to evaluate the therapeutic efficacy and toxicity of recombinant interferon alpha‐2a (rIFN alfa‐2a) given as initial systemic therapy in untreated mycosis fungoides and/or Sezary's syndrome patients, at a slowly escalating schedule up to the maximal tolerated dose. At the same time this schedule was administered in patients who had relapsed or were refractory to previous treatment; 28 newly diagnosed and 15 previously treated patients entered the study. IFN was given daily with dose escalation from 3 to 18 MU. The last follow‐up in June 1990 indicates that 90% of previously untreated patients who obtained a complete remission remain in continuous complete remission after 18 to 40 months and that 75% of previously untreated patients who obtained partial remission remain in partial remission after 20–44 months. The event‐free survival projected, calculated using the Kaplan and Meier product limit technique, was 21% of all patients at 54·7 months (40% in the previously untreated groups and 14% in the previously treated group:P=0·12).In conclusion, interferon is very effective as a single agent in cutaneous T‐cell lymphomas.
Immunoglobulin gene ‘fingerprinting’: an approach to analysis of B lymphoid clonality in lymphoproliferative disorders
Authors: Deane Miriam , Norton John D. 
Published: March 2008

SummaryRearrangement of the immunoglobulin heavy chain (IgH) gene is widely exploited as a marker of B cell lineage and clonality in the pathology of lymphoproliferative disorders. We have developed a simple, polymerase chain reaction (PCR) based method for detecting IgH gene rearrangement which relies on the observation that by using a panel of PCR amplimers specific for each of the six heavy chain variable region families in conjunction with a common joining region amplimer, clonal rearrangement can be detected in over 90% of cases of B lymphoid malignancy. By using radiolabelled amplimers and exploiting the size heterogeneity resulting from independent IgH rearrangement events. we show that high resolution gel electrophoresis can be used to generate a‘fingerprint’representing the spectrum of B cell clonality in complex populations of B lymphocytes. The method effectively scans the entire IgH gene rearrangement repertoire and is capable of detecting rare clonal or oligoclonal B lymphoid cell populations. In normal bone marrow mononuclear cells. clonal IgH rearrangement could be readily detected at a sensitivity of 10−3. We illustrate the application of the method in assessing the spectrum of B cell clonality occurring in an autoimmune condition, Hashimoto's thyroiditis, and in a malignant B cell disorder, chronic lymphocytic leukaemia. In addition, we explore the potential application of the technique in tracking minimal residual disease and for monitoring clonal evolution in acute lymphoblastic leukaemia.
Analysis of ras gene mutations in childhood myeloid leukaemia
Authors: Farr Christine , Gill Robert , Katz Fay , Gibbons Barbara , Marshall Christopher J. 
Published: March 2008

SummaryPrevious studies have shown that approximately 30% of adult acute myeloid leukaemias and 20% of adult acute lymphoid leukaemias contain point mutated ras oncogenes. In order to assess whether ras oncogenes are also involved in childhood leukaemias, we have used polymerase chain reaction (PCR) amplification and synthetic oligonucleotide probes to study the nature and frequency of ras gene mutations in childhood leukaemias, concentrating largely on the acute myeloid leukaemias (AML). Thirty‐four childhood presentation AML DNAs were screened for mutations in and around codons 12, 61 and 117 of N‐. K‐ and H‐ras. Eight of these samples (24%) contained ras mutations. As in the adult disease, the gene predominantly involved was N‐ras (6/8), with occasional activation of K‐ras (2/6). The most common base change was a G→A transition at codon 12 or 13 (4/8). Of the patients with mutant ras. 4/8 were diagnosed as AML FAB subtype M5. Five of the 34 childhood AMLs analysed displayed abnormalities of chromosome 7. However, none of these cases contained a mutant ras gene.One AML patient was studied at relapse, 14 months after initial presentation. The presentation mutation (N61p3) was not detectable, although a new mutation (N13Cys) was readily identified. This observation extends our original finding with presentation and relapse samples of adult AML, in which it was uncommon for the relapse sample to contain the same ras mutation as the presentation DNA.In addition, two out of five patients diagnosed as juvenile CML were found to harbour mutant ras.
Neutrophil‐bound immunoglobulin in HIV infection is of autoantibody nature
Authors: Klaassen R. J. L. , Vlekke A. B. J. , Kr. vondem Borne A. E. G. 
Published: March 2008

SummaryHere we report the serological and immunochemical characterization of neutrophil‐bound Ig (NBIg) and neutrophil‐binding Ig in the serum of 15 individuals infected by the human immunodeficiency virus (HIV). We found no correlation between the presence or amount of NBIg or neutrophil‐binding Ig in serum and either the serum concentration of IgG or the level of immune complexes (IC), as determined by the C1q‐binding test. Twelve of the 15 eluates prepared from the neutrophils of the HIV‐infected individuals reacted with donor neutrophils. These results indicate that NBIg in these men was not adhered IC nor passively absorbed Ig. This was supported by analysis of the sera of 13 of the 15 men by sucrose density‐gradient centrifugation: neutroPhil‐binding Ig consisted predominantly of monomeric IgG. However, also low levels of IC capable of binding to neutrophils were detected in nine sera. Immunofluorescence studies revealed that neutrophil‐binding Ig in the sera reacted with neutrophil‐specific, non‐polymorphic antigens that are not attached to the cell membrane via phosphatidylinositol linkage and, more specifically, not located on neutrophil FcRIII. None of the sera and eluates showed reactivity in the immunoprecipitation technique. Moreover, none of the eluates reacted with blotted neutrophil glycoproteins, whereas three sera reacted reproducibly and five sera reacted occasionally with a number of glycoproteins of different molecular weights in this technique. The latter results probably represent reactivity against cryptic and/or cytoplasmic antigens. Thus, NBIg in HIV infection has an autoantibody nature, but the full identity of the target antigens could not be clarified. These characteristics are not essentially different from those of the autoantibodies in classical autoimmune granulocytopenia.
The treatment of anaemia in the myelodysplastic syndromes with recombinant human erythropoietin
Authors: Bowen David , Culligan Dominc , Jacobs Allan 
Published: March 2008

SummaryRecombinant human erythropoietin was administered subcutaneously to 10 patients with myelodysplasia (MDS) who had haemoglobin concentrations less than 10 g/dl. in an attempt to relieve their anaemia. Doses of 60 units/kg/d rising to 90 units/kg/d were given over a maximum period of 16 weeks.Two out of 10 patients showed a steady rise in haemoglobin concentration during treatment. One patient with refractory anaemia had a sustained rise from 9.9 g/dl 11.3 g/dl. and one patient with refractory anaemia with excess blasts (RAEB) had a rise from 9.5 g/dl to 11.4 g/dl but then relapsed with the development of an iron deficient state. Serum concentrations of immunoreactive EPO varied considerably between patients, but both responders had relatively low baseline levels.Both responders were also new diagnoses and had received no red cell transfusions. The criteria for response to recombinant human erythropoietin therapy, as well as the indications for therapy remain to be clarified.
Interferon‐γin vivo reverses the increased platelet levels of platelet‐derived growth factor and transforming growth factor‐β in patients with myelofibrosis with myeloid metaplasia
Authors: Martyré Marie‐Claire , Magdelenat Henri , Calvo Fabien 
Published: March 2008

SummaryWe previously reported high platelet‐derived growth factor (PDGF) and transforming growth factorβ (TGF‐β) levels in platelets from patients with myelofibrosis with myeloid metaplasia. We report here the effects of in vivo administration of recombinant human interferon‐γ on these growth factor levels. Of six patients who entered this study in our institution, four completed the 6‐month therapy trial with interferon‐γ PDGF and TGF‐β levels in platelets were evaluated before and after treatment. PDGF levels were determined using a radioimmunoassay and TGF‐β activity was measured using an inhibition growth assay on CC164 cells. In these four patients, IFN‐γ therapy led to a reduction of the increased PDGF and TGF‐β levels in platelets towards the normal range. PDGF and TGF‐β values decreased by 25–45% and 32–46%, respectively. An acute deterioration was observed in one patient 5 months after the end of IFN‐γ therapy. In this patient, the deterioration of his clinical state correlated with an increase in intraplatelet PDGF and TGF‐β levels.
Post‐transfusion recovery of function of 5‐day stored platelet concentrates
Authors: Owens M. , Holme S. , Heaton A. , Sawyer S. , Cardinali S. 
Published: March 2008

Summary Platelets show a rapid reduction in their responsiveness to aggregating agents during storage for transfusion, but little is known about reversal of this defect in vivo after transfusion. In this study, fresh and stored platelets from the same donor (n=12) were labelled with 111In or 51Cr, respectively, mixed, and simultaneously infused. Blood samples were taken for up to 5 d post‐infusion, and the functional behaviour of the labelled platelets ex vivo was measured by retention on glass bead columns, and by whole blood aggregability to ADP, epinephrine and ristocetin. Aggregation was determined by filtering aggregated samples through a column of cotton wool to remove the aggregates, and quantitated as per cent decrease in radioactive counts. The study showed that, although infused radiolabelled 5 d stored platelets had a significantly lower aggregability towards ADP and epinephrine immediately (1 h) after infusion (32% and 29%, respectively, of fresh platelet values), a complete restoration to fresh platelet levels was found 24–72 h post‐infusion, with no further change observed over the ensuing 5 d with either fresh or stored labelled platelets. A slightly (6–9%) lower adhesion to both uncoated and collagen‐coated beads was found for the stored platelets throughout the 5 d period of study post‐infusion.In conclusion, these studies show that, with ex vivo testing, platelets stored for 5 d quickly recovered adhesion and aggregability capabilities similar to that of fresh platelets, suggesting that the functional lesion developed during storage is quickly and completely reversed after infusion.
Effect of orally active hydroxypyridinone iron chelators on human lymphocyte function
Authors: Pattanapanyasat K. , Webster H. K. , Tongtawe P. , Kongcharoen P. , Hider R. C. 
Published: March 2008

Summary Several iron chelators, 3‐hydroxypyridin‐4‐ones (CP) and desferrioxamine (DF) were compared for their effect on DNA synthesis, cell viability and expression of cell proliferation markers. Short‐term (4 h) exposure of human peripheral blood mononuclear cells to CP or DF inhibited the proliferative response of cells to concanavalin A (Con A). Inhibition by CP and DF showed a dose‐dependent effect with CP compounds more active than DF. Increased inhibitory activity of CP over DF was partly due to the lipophilic properties of CP. Pre‐saturation of CP and DF with exogenous ferric ion either diminished or prevented the inhibitory effect. At high chelator concentrations or prolonged (72 h) exposure of the cells to chelators, inhibition occurred but poor cell viability was observed.In contrast to their inhibition of DNA synthesis, these iron chelators showed little effect on protein synthesis and the expression of transferrin receptors and interleukin‐2 (IL‐2) receptors. These findings suggest that both DF and CP compounds exert their effect by chelation of ferric ion with subsequent inhibition of DNA synthesis.
Establishment of a novel granulocytic sarcoma cell line which can adhere to dermal fibroblasts from a patient with granulocytic sarcoma in dermal tissues and myelofibrosis
Authors: Kobayashi Masanobu , Imamura Masahiro , Soga Ryosuke , Tsuda Yuuji , Maeda Shiro , Iwasaki Hiroshi , Sugiura Makoto , Ohizumi Hiroko , Musashi Manabu , Morioka Masanobu , Okabe Mihiro , Sakurada Keisuke , Kasai Masaharu , Miyazaki Tamotsu 
Published: March 2008

Summary A novel human myeloid cell line, designated HSM‐1, has been established from the pleural effusion of a patient with granulocytic sarcoma (GS) who had been followed as having primary myeiofibrosis for 10 years. When he was diagnosed as having granulocytic sarcoma in dermal tissues, no evidence of malignant transformation into leukaemia was found in both the peripheral blood and bone marrow. The established cell line was positive for myeloperoxidase, Sudan black B. Naphthol AS‐D chloroacetate esterase. Surface marker analysis revealed that HSM‐1 expressed CD4. CD13, CD11a, CDllb, Leu8. CD49b. CD49d, CD49e, CD29 and HLA‐DR.To clarify why the unusual myeloid tumours developed in non‐haematopoietic tissues, we examined the capability of HSM‐1 to bind to skin fibroblast layers. The HSM‐1 cells were found to bind to both bone marrow stromal layers and skin fibrobiast layers. Among the other myeloid ceil lines tested, none was found to bind to skin flbroblast layers. These findings suggest that the GS cell line may be derived from a haematopoietic precursor cell which can bind to skin fibroblasts and is localized in non‐haematopoietic tissues resulting in the formation of extramedullary myeloid metaplasia. HSM‐1 is a useful tool for analysing the characteristics of granuiocytic sarcoma and homing receptors for haematopoietic stem cells.
Comparison of plasma cell infiltration in bone marrow biopsies and aspirates in patients with multiple myeloma
Authors: Terpstra W. E. , Lokhorst H. M. , Blomjous F. , Th. Meuwissen O. J. A. , Dekker A. W. 
Published: March 2008

Summary In 54 patients with multiple myeloma plasma cell infiltration was compared in bone marrow biopsies and aspirates. In 48% of cases plasma cell infiltration was comparable, in 48% infiltration in the aspirate was lower than in the biopsy. In only two cases more plasma cells were found in the aspirate. Eleven patients (20%) had less than 20% plasma cells in the aspirate and more than 50% in the biopsy. Underestimation of plasma cell load especially seems to occur in patients with a focal growth pattern of multiple myeloma or when strong fibrosis is present. 69% of patients with stage III. according to Durie & Salmon (1975), and 76% of patients with a high β2‐microglobulin had more than 50% plasma cells in the biopsy, indicating that these parameters, which are based on tumour load, are influenced by other factors as well.The bone marrow biopsy is of superior value for direct estimation of the tumour load in multiple myeloma compared to bone marrow aspirates. A prospective study is needed to determine its prognostic significance.
Enhancement of human T cell responses to allogeneic stimuli by factor VIII concentrates
Authors: Batchelor Alison , Michael Steel C. , Ludlam Christopher A. 
Published: March 2008

Summary The effect of factor VIII concentrate, from commercial and National Health Services manufacturers, on in vitro lymphocyte proliferative response to allogeneic stimulator cells was investigated.Factor VIII preparations‘purified’by ion exchange or by monoclonal antibody affinity had no effect in this assay but lymphocyte proliferation in response to allogeneic cells was markedly and consistently enhanced by some intermediate purity factor VIII concentrates and. to a lesser extent, by a factor IX preparation. These preparations did not stimulate lymphocyte proliferation in the absence of other mitogens. The co‐mitogenic factor(s) present in intermediate purity factor VIII was not identified. However, enhanced proliferation was not due to factor VIII itself, nor to albumin or fibronectin. The clinical relevance of the immunomodulatory activity of intermediate purity factor VIII concentrates in vitro is discussed.
The production of human monoclonal antiplatelet auto‐antibodies derived from human lymphocytes of normal origin: reactivity to DNA, anionic phospholipids and platelet proteins
Authors: Denomme Gregory A. , Kelton John G. , Bell David A. 
Published: March 2008

Summary Human hybridoma monoclonal antiplatelet antibodies were produced using tonsillar lymphocytes from a nonthrombocytopenic male fused to the lymphoblastoid cell line GM 4672. Twenty of 472 (4%) IgM producing hybridomas had antiplatelet reactivity as detected by ELISA. Thirteen of these antiplatelet antibody producing hybridomas with clonality ensured by limiting dilution were tested for anti‐genie specificity. Two different and mutually exclusive groups of antiplatelet antibodies were identified. The first group of antiplatelet antibodies (four clones) showed reactivity that was limited to DNA and anionic phospholipids. Antibodies from the second group (seven clones) showed reactivity by immunoblotting to a variety of platelet proteins including platelet glycoprotein IIb. These antibodies did not bind DNA nor anionic phospholipids.These studies indicate that lymphocytes of normal human origin have the genetic potential to produce antiplatelet autoantibodies. These antiplatelet antibodies segregate on the basis of their target antigens into two major groups, which mimic the target antigens held responsible for antiplatelet autoantibodies in disease. These include glycoproteins (typical of chronic idiopathic thrombocytopenic purpura) and DNA and/or anionic phospholipids (typical of the lupus anticoagulant syndrome).
Interleukin‐2 induces activation of coagulation and fibrinolysis: resemblance to the changes seen during experimental endotoxaemia
Authors: Baars Johanna W. , de Boer Jan Paul , Wagstaff John , Roem Dorina , Eerenberg‐Belmer Anke J. M. , Nauta Jos , Pinedo Herbert M. , Hack C. Erik 
Published: March 2008

Summary. The administration of Interleukin‐2 (IL‐2) causes the release or generation of other cytokines such as tumour necrosis factor (TNF) which, by disturbing the anticoagulant properties of the endothelium, may induce a procoagulant state in patients receiving this drug.We therefore evaluated the effects of IL‐2 on coagulation and fibrinolysis in 14 patients receiving 12 or 18 × 106 IU/m2/d of IL‐2 given as a 15 min infusion for 5 d. Blood samples were drawn at short intervals after the first IL‐2 infusion. The parameters were analysed by way of analysis for repeated measures (F tests rather than t tests).During the first day, thrombin‐antithrombin (TAT) complexes started to increase 2 h after the IL‐2 infusion, reaching peak levels at 4 h (n= 14; 11.2±6.4 μg/l v 49.8±49.2 μg/l, P < 0.01). Plasmin α2 antiplasmin (PAP) complexes showed a similar pattern rising from a mean baseline value of 17.5±7.6 nmol/l to 66.48±47.7 nmol at 4 h (P < 0.01). In four patients the peak of PAP preceeded that of TAT. Tissue plasminogen activator (tPA) rose from a mean baseline value of 4.9±3.7 μg/l to 26.3±13.5 μg/l at 4 h (P < 0.01). Plasminogen‐activator‐inhibitor‐1 (PAI‐1) levels increased from 59.35 μg/l to 113.39 μg/l at 6 h (P < 0.01). tPA PAI‐1 complexes increased from 0.15 ±0.07 to 0.69±0.21 nmol/l at 6 h (P < 0.01).Our study indicates that IL‐2 activates the coagulation and fibrinolytic systems in vivo. The changes resemble the perturbations observed after endotoxin/TNF administration. These abnormalities may play a role in the side‐effects induced by IL‐2 therapy.
Age‐related incidence and other epidemiological aspects of myelodysplastic syndromes
Authors: Aul C. , Gattermann N. , Schneider W. 
Published: March 2008

Summary. Although most haematologists perceive a rising prevalence and incidence of myelodysplastic syndromes (MDS), reliable epidemiological data on these disorders are largely lacking. The bone marrow register of the University of Düsseldorf allowed us to assess among other epidemiological features the incidence of MDS. which was compared to that of acute myeloid leukaemia (AML). Among a total of 18416 different patients registered between 1975 and 1990, 584 cases of MDS (3.2%) and 506 cases of AML (2.8%) were identified. Over the study period, the percentage of newly diagnosed MDS rose from 1.3% to 4.5%, while there was no upward trend for AML. Among all patients undergoing bone marrow biopsy, the proportion of those over 60 years of age increased from 41.9% in 1975 to 54.1%in 1990. Wefounda strong correlation between the proportion of elderly patients and the relative frequency of MDS diagnoses. Thirty‐one patients (5.3%) were classified as a secondary MDS because of previous treatment with cytotoxic chemotherapy and/or irradiation for a variety of malignancies. Twelve patients were identified in whom occupational exposure to organic solvents could not be ruled out.For calculating age‐specific incidence rates, the analysis was confined to the town district of Düsseldorf (575000 inhabitants), because exact demographical data were available for this population. In the last quinquennium of the study period (1986–90), myelodysplastic syndromes were more frequent than AML in the age group 50–70 years (4.9 v 1.8/100000/year). In patients over 70, the incidence of MDS was more than 3 times that of AML (22.8 v 6.7/100000). In this group, men had a higher incidence of MDS (33.9/100000) than women (18/100000). Crude annual incidence (all age groups) was also higher for MDS (4.1/100000) than for AML (2.1/100000) in recent years.We conclude that MDS are relatively common haematological neoplasias. The rising incidence in recent years is probably not due to changes in aetiological factors, but may reflect increased awareness on the part of physicians and extended use of diagnostic procedures in elderly patients.
Haemoglobin F levels in sudden infant deaths
Authors: Pagan D. G. , Walker A. 
Published: March 2008

Summary. Fetal haemoglobin levels have been measured prospectively in 1 35 autopsy cases of sudden, unexpected infant deaths (51 pre‐term. 104 full term) using standard laboratory methods. These results have been compared with Hb F values from a normal control group of 570 living infants (145 pre‐term, 425 full‐term) with a post‐conceptional age < 90 weeks. The gestational age was established for all live controls and sudden infant deaths.The results show that full‐term (> 38 weeks gestational age) sudden infant death victims as a group have significantly elevated Hb F levels (χ= 25.20. P<0.001) when compared to the gestational age matched control group. Pre‐term (< 38 weeks gestational age) SIDs show no significant differences from the pre‐term control group (χ2= 1.20, n.s.) The division of the controls into pre‐ and full‐term groups demonstrates major differences between the post‐natal Hb F fall in pre‐ and full‐term infants. Use of post‐conceptional age as a growth marker does not produce comparability with full‐term infants.Extensive controls were carried out to confirm the reliability of post‐mortem Hb F assays, and comparability with in vivo estimation. No significant or systematic differences between pre‐ and post‐mortem samples were identified, nor were any significant differences found on post‐mortem storage up to 72 h.