bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating megakaryocyte progenitors in myeloproliferative disorders are hypersensitive to interleukin‐3
Authors: Kobayashi Shoko , Teramura Masanao , Hoshino Shigeru , Motoji Toshiko , Oshimi Kazuo , Mizoguchi Hideaki 
Published: March 2008

Summary. Previous studies have reported that megakaryocyte progenitors in myeloproliferative disorders (MPD) formed spontaneous megakaryocyte colonies without the addition of megakaryocyte colony‐stimulating factor (Meg‐CSF). To determine whether this spontaneous colony formation is due to autocrine proliferation of MPD megakaryocyte progenitors or to hypersensitivity to Meg‐CSF that might exist in the culture system, we investigated colony‐forming unit‐megakaryocytes (CFU‐Meg) in the peripheral blood of 11 MPD patients, using serum‐free cultures. Spontaneous megakaryocyte colonies were observed in serum‐free cultures of nonadherent mononuclear cells (NAdMNC) obtained from MPD patients with thrombocytosis, whereas the NAdMNC of MPD patients without thrombocytosis, that of patients with reactive thrombocytosis and normal subjects never formed spontaneous colonies. However, the spontaneous colonies from MPD patients with thrombocytosis disappeared in cultures using highly purified CD34‐positive cells as target cells.To study the hypersensitivity of megakaryocyte progenitors to Meg‐CSF, dose‐response experiments were performed with interleukin‐3 (IL‐3). CFU‐Meg from MPD patients with thrombocytosis showed maximal growth at the concentrations of IL‐3 lower than those for normal subjects. CFU‐Meg of MPD patients without thrombocytosis and that of patients with reactive thrombocytosis showed the same colony growth response to IL‐3 as that of normal subjects. This result indicates that the CFU‐Meg of MPD patients with thrombocytosis are hypersensitive to IL‐3. It also suggests that spontaneous colony formation by NAdMNC is not due to the autocrine growth of megakaryocyte progenitors but is due to the hypersensitivity of megakaryocyte progenitors to Meg‐CSF, such as IL‐3, released by accessory cells. Furthermore, it is possible that such hypersensitivity of CFU‐Meg to IL‐3 might be a pathogenic factor in MPD with accompanying thrombocytosis.
Plasma fibrinogen in women: relationships with oral contraception, the menopause and hormone replacement therapy
Authors: Lee Amanda J. , Lowe Gordon D. O. , Smith William C. S. , Tunstall‐Pedoe Hugh 
Published: March 2008

Summary.Plasma fibrinogen was measured in 4837 women aged 25‐64 years as part of the Scottish Heart Health Study and Scottish MONICA population surveys. The relationships of oral contraceptive use, the menopause and hormone replacement therapy were examined.Univariate analyses found that women with a history of oral contraceptive use, premenopausal women and those on hormone replacement therapy all had significantly lower fibrinogen levels than women who had never used oral contraceptives, postmenopausal women and non‐hormone replacement users respectively. These differences persisted after age standardization.On multivariate analysis, menopausal status and hormone replacement therapy had independent effects on fibrinogen levels. Together with the common risk factors, 9.9% of the total variation in plasma fibrinogen levels was explained. However, less than 1% of this was from the combined menopausal and hormonal factors.These results confirm a postmenopausal rise in fibrinogen level which may be relevant to an increased risk of coronary heart disease. In addition, a protective effect with hormone replacement therapy is noted, although this was probably due to selection bias.
Immunological effects of intermediate purity clotting factor concentrates: failure to affect lymphocyte activation in vivo
Authors: Higgins Julie A. , Giangrande Paul L. F. , Kernoff Peter B. A. , Goodall Alison H. 
Published: March 2008

Concern has been expressed that intermediate purity clotting factor concentrates may cause immunological abnormalities in haemophilic patients, distinct from those related to HIV infection. Early reports of lymphocyte dysfunction in anti‐HIV seronegative haemophiliacs pointed to activation of their lymphocytes; a potential cause of CD4 + ve lymphocyte decline in anti‐HIV seropositive patients. Recent reports have suggested that the use of high purity FVIII concentrates might retard the rate of decline in CD4 + ve lymphocytes in haemophiliacs infected with the HIV virus.Expression of markers of acute and chronic activation of T and B lymphocytes was measured in heavily treated anti‐HIV seronegative haemophiliacs using two‐colour flow cytometry. No T or B lymphocyte stimulation was observed. Cellular markers of activation were absent and CD4 + ve lymphocyte counts and serum IgG levels were normal. Anti‐HIV seropositive haemophiliacs showed T and B cell activation consistent with HIV infection. The extent of lymphocyte activation in individual patients was unrelated to the type, amount or frequency of FVIII received.These findings do not support the hypothesis that lymphocytes of haemophiliacs are affected directly by the regular administration of intermediate purity concentrates so as to accelerate the progression of HIV disease.
The diagnostic significance of serum ferritin indices in patients with malignant and reactive histiocytosis
Authors: Lukina E. A. , Levina A. A. , Mokeeva R. A. , Tokarev Yu. N. 
Published: March 2008

Iron metabolism was studied in 10 patients with malignant histiocytosis (MH), in 16 patients with histiocytosis‐X (Langerhans cell histiocytosis) and in 34 patients with reactive proliferation of the mononuclear phagocytes (MPS). Eight MH patients had a considerably increased level of serum ferritin (SF). The average level of SF was 6070 ± 957 mg/1 for MH patients, which is significantly greater than the SF level for HX and RH patients.The study of the serum ferritin profiles suggests that the main pathogenetic mechanism of hyperferritinaemia in MH is the synthesis and secretion of ferritin by neoplastic mononuclear phagocytes.From this, hyperferritinaemia in MH may be considered as pathognomic of this disease and used as an additional diagnostic criterion. In addition, SF is the most informative parameter for the clinical practice among the indices of the functional state of MPS.
Recombinant human erythropoietin in autologous blood donors: a dose‐finding study
Authors: Biesma D. H. , Kraaijenhagen R. J. , Dalmulder J. , Marx J. J. M. , Van De Wiel A. 
Published: March 2008

A dose‐finding study of recombinant human erythropoietin (rhEPO) was performed in 60 autologous donors who donated 2 units of blood prior to orthopaedic or vascular surgery. The correction of phlebotomy‐induced anaemia was studied in four groups of 15 patients who received 500 U/kg, 250 U/kg, 125 U/kg or no (controls) rhEPO subcutaneously twice per week during a 3‐week period. Haemoglobin concentration in the 500 U/kg, 250 U/kg and 125 U/kg group and in the controls reached respectively 99·2, 98·8, 91·9 and 87·1% of pre‐phlebotomy value. Flow cytometric analysis of reticulocytes showed a steady increase of reticulocyte count as the dose increased. Maximal levels of high fluorescence reticulocytes which represent early changes of erythropoiesis were reached after 7 d and decreased thereafter in each group. Serum ferritin decreased significantly to approximately 50% of baseline values in all groups; no differences in the decrease of serum ferritin were observed between the patients who received rhEPO and the controls. No severe adverse events were observed.This study demonstrates a dose‐related effect of rhEPO on erythropoiesis in autologous donors during the first 2 weeks. No further increase of reticulocytes was observed despite continued rhEPO therapy, which may be due to the inability of the mononuclear phagocytic system to release additional iron. To restore pre‐phlebotomy haemoglobin concentration, a dose of 250 U/kg rhEPO was sufficient.
Rapid and sensitive diagnosis of cytomegalovirus and Pneumocystis carinii pneumonia in patients with haematological neoplasia by using capillary polymerase chain reaction
Authors: Honda Junichi , Hoshino Tomoaki , Natori Hideyo , Tokisawa Shiro , Akiyoshi Hiroya , Nakahara Shin , Oizumi Kotaro 
Published: March 2008

We attempted the simultaneous detection of cytomegalovirus DNA (CMV‐DNA) and Pneumocystis carinii (carinii‐DNA) in sputum samples obtained from 20 patients with haematological neoplasm with pneumonia, using rapid cycle DNA amplification (capillary PCR). We used a thermal cycler for capillary PCR which featured recirculation of hot air for rapid temperature control of 10 μl reaction samples in thin glass capillary tubes.We extracted DNA from patients' sputa using a simple method. A comparison of the results obtained using the phenol extraction–ethanol precipitation method and those obtained using our simple method was made, and demonstrated complete agreement between the two. For detection of CMV‐DNA and P. carinii‐DNA with capillary PCR it was not necessary to vary temperature setting based on the primers used. Therefore, capillary PCR was used for the simultaneous detection of CMV and P. carinii.After amplification, the total time required for which was 20 min, amplified products were electrophoresed on agarose gels and visualized with ethidium bromide. Product sensitivity was higher with capillary PCR than with conventional PCR.We conclude that capillary PCR amplification is a valuable tool for rapid and simple diagnosis of CMV and P. carinii pneumonias.
Endogenous haemopoietic growth factors in neutropenia and infection
Authors: Cebon Jonathan , Layton Judith E. , Maher Darryl , Morstyn George 
Published: March 2008

Summary Haemopoietic growth factors (HGFs) are being administered to patients with neutropenic fever; however, little is known about the endogenous HGF response in these patients. Specific assays were used to study four HGFs, granulocyte (G‐) CSF, granulocyte‐macrophage (GM‐) CSF, macrophage (M‐) CSF and interleukin (IL‐) 6 levels in the blood of patients with neutropenic fever (46 episodes). For comparison, levels were also measured in three control populations: normals (20), afebrile neutropenic (14), and bacteraemic but not neutropenic patients (20).In febrile patients, levels of G‐CSF (median, range) (0·46, <0·10–142 ng/ml), IL‐6 (0·054, 0·05·24–3 ng/ml), and M‐CSF (18·5, 9·9–79·1 ng/ml) were elevated compared with afebrile subjects (<0·10, <0·0–1–6·2 ng/ml), (0·008, 0·002–0·024 ng/ml) and (6·45, < 5·0–31·3 ng/ml) respectively. GM‐CSF was not elevated (<0·02, <0·02–8·0 ng/ml) compared with afebrile subjects (0·021, < 0·02–0·20 ng/ ml).Variables significantly associated (P < 0·05) with elevated cytokine levels were determined by multiple regression analyses. Factors associated with G‐CSF elevation were fever, neutropenia, pathogen type and raised bilirubin and creatinine. In contrast, neutropenia was not associated with IL‐6 elevation although there was an association between IL‐6 elevation and fever, Gram‐negative and fungal infections and raised creatinine and bilirubin. M‐CSF elevation was associated with fever, renal impairment and known pathogen. Elevated G‐CSF and IL‐6 levels normalized rapidly (hoursdays) with the resolution of infection, whereas M‐CSF concentrations remained elevated for up to 10 d. Cytokine levels remained elevated in septic neutropenic patients who did not recover.In summary, G‐CSF, IL‐6 and M‐CSF levels were significantly elevated in sepsis. In contrast, GM‐CSF levels were not elevated. These studies should assist the development of therapeutic strategies using HGFs in the treatment of sepsis.
Improved survival for acute lymphoblastic leukaemia in infancy: the experience of EORTC‐Childhood Leukaemia Cooperative Group
Authors: Ferster Alina , Bertrand Yves , Benoit Yves , Boilletot Annie , Behar Catherine , Margueritte Geneviève , Thyss Antoine , Robert Alain , Mazingue Françoise , Souillet Gérard , Philippe Noël , Solbu Gabriel , Suciu Stefan , Otten Jacques 
Published: March 2008

Summary Out of 744 newly diagnosed ALL children under the age of 18 years treated according to the EORTC‐CLCG protocols 58831 and 58832, 28 (4%) were infants less than 1 year of age. An elevated risk factor, which takes into account the sizes of the liver and spleen and the number of circulating blasts, was present in 25 cases.Most patients had non‐common ALL. Among 15 patients studied by cytogenetics, nine present chromosonal abnormalities, six of them having a t(4:11) translocation.Complete remission was achieved in 86% of cases. One patient died in complete remission of therapy‐related infection. The overall EFS is 43%. It is not statistically different in very young infants as compared to infants older than 6 months. Except for patients with AUL or with t(4:11) translocation, a continuous complete remission rate above 50% can be achieved with a median follow‐up of 4 years.The results obtained in infant ALL with EORTC‐CLCG protocols are currently better than those obtained with some other protocols, but remains inferior when compared to the ones obtained in older children. Thus, further improvements are needed and should be evaluated in large cooperative trials.
Fibrin degradation product D‐dimer induces the synthesis and release of biologically active IL‐1β, IL‐6 and plasminogen activator inhibitors from monocytes in vitro
Authors: Robson S. C. , Shephard E. G. , Kirsch R. E. 
Published: March 2008

Summary Disseminated intravascular coagulation, characterized by circulating fibrin(ogen) degradation products (FDP), is associated with both acute and chronic inflammatory conditions. Since the association of FDP with monocytes could influence the release of cytokines and other regulatory proteins with significant clinical ramifications, we have studied cytokine synthesis and release following the interaction of D‐dimer (DD), a terminal degradation product of fibrin, with human monocytes in vitro.Adherent peripheral blood monocytes were incubated with purified DD for 24 and 48 h and secreted or cell‐associated IL‐1β and IL‐6 antigen levels and activity determined. DD (50 μg/ml) boosted the secretion of IL‐1β antigen from median control levels of 659 pg/ml to 2704 pg/ml and that of IL‐6 antigen from 806 pg/ml to > 3000 pg/ml at 48 h (P<0.05). Similar increases in extracellular biologically active IL‐1 and IL‐6 were observed. Although DD increased cell associated IL‐1 β antigen levels from median values of 188 to 1600 pg/106 cells and IL‐6 antigen from 660 to 2215 pg/106 cells (P < 0.05). cell‐associated IL‐1 functional activity decreased from control levels of 98 inhibitor units ml to 65 units/ml for cells exposed to DD. Secreted plasminogen activator inhibitor (PAI) bioactivity and PAI type 2 antigen levels were significantly increased following exposure of monocytes to DD. This may explain the decreased cell associated IL‐1 activity observed in our study as PAI are known to inhibit biologically active membrane bound IL‐1.Our finding that DD enhances monocyte release of biologically active cytokines suggests the presence of positive feedback pathways for fibrinogen synthesis by hepatocytes. Furthermore, the association of monocytes with DD may potentiate localized coagulation processes by subsequent alterations in pericellular proteolysis.
The molecular basis of β thalassaemia in Punjabi and Maharashtran Indians includes a multilocus aetiology involving triplicated α‐globin loci
Authors: Garewal Gurjevan , Fearon Clair W. , Warren Tina C. , Marwaha Neelam , Marwaha Ram K. , Mahadik Chitra , Kazazian Haig H. 
Published: March 2008

Summary We have analysed 201 β‐thalassaemia (β‐thal) genes from natives of the Punjab (156) and Maharashtra states of India and found the causative mutation in 200 of them. The most common β‐globin gene mutations differed significantly between these two groups and between these groups and Indian immigrants in the U.S.A. and the U.K. In the Punjabi Indians the IVS‐1, nt 1 (G–T) mutation accounted for nearly one‐quarter of β‐thal genes, whereas it was 5% or less in the other groups. Likewise, the cap+ 1 mutation was much more prevalent in the Punjabis, whereas the nonsense codon 15 allele had a higher frequency in the Maharashtrans of the Bombay region. The common IVS‐1, nt5 allele had a frequency of 60% of β‐thal genes in the Maharastrans, 35% in North American immigrants, and only 23% in the Punjabis. Two‐thirds of all β‐thal genes in Punjab were found in the merchant caste (Khatri‐Arora), whereas the menial caste (Shudra) was highly represented among those with β‐thal genes in Maharashtra. Two novel β‐globin alleles were each found once; a frameshift codon 55 (+ A) in Maharashtrans and a frameshift codons 47–48 (+ ATCT) in Punjabis.Of three Punjabi patients with β‐thal intermedia in whom only a single severe β‐globin gene mutation was found, two had six α‐globin genes (homozygosity for a triplicated α‐globin locus) instead of the normal α‐globin gene number of four. Thus, these two individuals had a multilocus aetiology of β‐thal and their parents have the unusual recurrence risk of 1 in 8 for conceiving a third with β‐thal intermedia. Since 15% of 126 α‐globin clusters studied in Punjabis contained either single (10%) or triplicated (5%) α‐globin genes, the α‐globin gene number is a frequent modifier of the phenotype of β‐thal in this ethnic group.
In vitro growth of human fetal CD34+ cells in the presence of various combinations of recombinant cytokines under serum‐free culture conditions
Authors: Zauli Giorgio , Vitale Marco , Visani Giuseppe , Marchisio Marco , Milani Daniela , Capitani Silvano 
Published: March 2008

Summary. CD34+ cells were purified from midtrimester human fetal blood and adult bone marrow samples and seeded in serum‐free fibrin‐clot cultures in order to evaluate the number and the responsiveness to recombinant cytokines of pluripotent (CFU‐GEMM), erythroid (BFU‐E), megakaryocyte (BFU‐meg and CFU‐meg) and granulocyte/macrophage (CFU‐GM) haemopoietic progenitor cells.The number of the different haemopoietic progenitors/1 × 103 CD34+ cells, except CFU‐meg, was significantly higher in fetal blood than in adult bone marrow in cultures stimulated by any combination of cytokines including interleukin‐3 (IL‐3), granulocyte/macrophage colony stimulating factor (GM‐CSF) or stem cell factor (SCF) plus erythropoietin (Epo). Nevertheless, whereas adult BFU‐E showed a maximal growth in the presence of Epo plus IL‐3 or Epo plus SCF, fetal BFU‐E showed an optimal growth in the presence of Epo alone, the sensitivity of fetal BFU‐E to suboptimal concentrations of Epo being approximately 10–15‐fold higher than that of adult BFU‐E. Addition of optimal concentrations of IL‐3, GM‐CSF or SCF, alone or in various combinations, to Epocontaining cultures induced a significant increase in both the number and size of fetal CFU‐GEMM, and CFU‐GM, and a parallel decrease of fetal BFU‐E. Finally, SCF potently syner‐gized with IL‐3 in increasing the growth of both classes of fetal megakaryocyte progenitors, BFU‐meg and CFU‐meg.
Clonal history of a human follicular lymphoma as revealed in the immunoglobulin variable region genes
Authors: Zhu D. , Hawkins R. E. , Hamblin T. J. , Stevenson F. K. 
Published: March 2008

Summary. The variable region genes used to encode the immunoglobulin expressed by tumour cells of a patient with follicular lymphoma have been identified and sequenced. Initially, a lymph node biopsy was analysed and revealed usage of VH and Vκ genes which had numerous substitutions as compared with the closest germ line genes. The pattern of mutations in VH was consistent with a role for positive selection by antigen. In addition, there was evidence in both VH and Vκ sequences for clonal heterogeneity.After 5 years, which included treatment with chemotherapy, the patient relapsed with tumour cells present in the blood. Analysis of the V‐genes used by the emerging tumour revealed a single homogeneous sequence for both VH and VL, which, in each case, matched closely one of the sequences in the original lymph node biopsy.These results indicate that selection. possibly mediated by antigen, can operate on a cell destined to give rise to lymphoma, and that intraclonal variation can occur after the neoplastic event. However, in this case, late relapse in the blood is dominated by a single clone.
Poor response to intensive chemotherapy in de novo acute myeloid leukaemia with trilineage myelodysplasia
Authors: Kuriyama Kazutaka , Tomonaga Masao , Matsuo Tatsuki , Kobayashi Tohru , Miwa Hiroshi , Shirakawa Shigeru , Tanimoto Mitsune , Adachi Koichi , Emi Nobuhiko , Hiraoka Akira , Tominaga Nobuhiko , Imai Kuniyuki , Asou Norio , Tsubaki Kazuo , Takahashi Isao , Minami Saburoh , Yoshida Minoru , Murakami Hirokazu , Minato Keisuke , Oshima Toshiteru , Furusawa Shinpei , Ohno Ryuzo 
Published: March 2008

Summary. The findings of morphologically dysplastic features in haemopoietic cells in de novo acute myeloid leukaemia (AML) has been named AML with trilineage myelodysplasia (AML/TMDS). We analysed the clinical data, karyotypes, and treatment outcomes of 230 de novo AML patients treated with the Japan Adult Leukaemia Study Group AML‐87 protocol. 40 (17%) patients had AML/TMDS. Platelet count was significantly higher (F=0·006) and bone marrow blasts were fewer (P=0·01) in the AML/TMDS group than in the AML without TMDS. Abnormal karyotype was shown in 12/30 patients (40%) analysed.The complete remission (CR) rate for AML/TMDS was significantly lower than AML without TMDS (63%v 81%) (P=0·01). The overall survival curves showed that the 40 patients with TMDS had a significantly worse survival than the 190 without TMDS (P=0·0005). AML/TMDS also showed significantly worse disease‐free survival (DFS) (P=0·0001).Multivariate analysis revealed that the absence of TMDS in AML was the most significant factor in obtaining CR (P=0·01) and a significant factor in predicting longer DFS (P=0·04). Our data suggest that AML/TMDS responds poorly to intensive chemotherapy. Further study is required to determine the best treatment strategy for AML/TMDS and the biological differences between AML/TMDS and other types of AML.
Protein C, antithrombin III and plasminogen: effect of age, sex and blood group
Authors: Dolan G. , Neal K. , Cooper P. , Brown P. , Preston F. E. 
Published: March 2008

Summary. We conducted a cross‐sectional study of antithrombin III (ATIII), protein C (PC) and plasminogen (Plg) concentrations in a population of healthy plasma donors in the Trent Region. The distribution of values for protein C was log normal whereas for ATIII and Plg the distributions were positively skewed and differed significantly from normal and log normal. Males had higher antithrombin III concentrations (mean 1·10 iu/ml, range 0·72–1·65) than females (mean 1·07 iu/ml, range 0·75–1·69) (P=0·001) and levels increased with age in women. Younger women aged 25–34 had significantly lower plasma concentrations of ATIII compared to males of similar age. For protein C, concentrations were higher in males (mean 1·07 u/ml, range 0·37–2·11) than in females (mean 1·01 u/ml, range 0·59–1·61) (P<0·001) and levels increased with age in both sexes (P<0·001). In women, a novel difference in protein C concentration between ABO blood groups was noted. There was no significant difference in plasminogen concentration between males and females, and in women plasminogen decreased with age (r=–0·205, P<0·001).We conclude that these variations in ATIII and protein C with age and sex are important considerations in the determination of reference ranges for these proteins.