bluuebunny/crossref_metadata_2025 huggingface dataset:
Megakaryocyte ploidy in thrombocytosis: Improved microdensitometric measurements with a new image analysis system
Authors: Woods M. J. , Greaves M. , Trowbridge E. A.
Published: July 2010

Abstract: Megakaryocyte (MK) nuclear deoxyribonucleic acid (DNA) content was measured on a new image analysis system. Feulgen‐stained bone marrow aspirate smears were analysed from 9 patients with thrombocytosis. Average optical density (OD) of stained nuclei was evaluated by pixel discrimination over 128 grey levels. Projected nuclear area was delineated manually. The product of these two parameters gave an index of nuclear DNA content. Neutrophils were used as 2N reference cells. Reproducibility of OD, nuclear area and their product was excellent for individual cells (CV <2.0% for MKs, <4.0% for neutrophils). The average CV for DNA content of 18 groups of 10 neutrophils was 5.5% (range 3.0–9.7%). A significant linear regression existed between MK nuclear area and DNA content (p < 0.001) for 627 MKs in essential thrombocythaemia (ET) and 346 MKs in reactive thrombocytosis (RT). Compared with RT, more 8N and 64N MKs were seen in ET (p < 0.05). 128N MKs were unique to ET. Image analysis of MK ploidy may assist the clinical discrimination between primary and secondary thrombocytosis.
Bone marrow karyotypes in 94 children with acute leukemia
Authors: Heim S. , Békàssy A. N. , Garwicz S. , Heldrup J. , Kristoffersson U. , Mandahl N. , Wiebe T. , Mitelman F.
Published: July 2010

Abstract: During the last 10 years, we have cytogenetically analyzed at diagnosis bone marrow cells from a total of 94 children with acute leukemia. Of the 78 children with acute lymphatic leukemia (ALL), 53 (68%) had clonal acquired chromosome abnormalities; in the group with acute nonlymphatic leukemia (ANLL), the corresponding proportion was 13 out of 16 (81%). Among the cytogenetically abnormal ALL patients, the most numerous subset was the hyperdiploid cases with stemlines containing 51 or more chromosomes (26 of 53 abnormal cases; 49%). This is a clearly higher proportion than has been reported in large series from other centers. Deletions of 6q were present in 8 cases and rearrangements of 12p in 5. Of the 7 T‐cell ALLs, 3 had translocations of the distal part of 7q, i.e., of the region where the beta T‐cell receptor is encoded. Only 2 of 26 (8%) patients with leukemic stemlines with more than 50 chromosomes have relapsed; the remainder are still in first remission (mean observation time 42 months). This may be contrasted with 6 of 25 (24%) relapses among the cytogenetically normal (observation time 41 months), and 8 of 27 (30%) relapses among ALL patients with aberrations but with less than 51 chromosomes (observation time 26 months). Our results support the conclusion that the finding of a markedly hyperdiploid leukemia karyotype is indicative of good prognosis in ALL.
High‐dose cytosine arabinoside and mitoxantrone in previously‐treated acute leukemia patients
Authors: Lejeune C. , Tubiana N. , Gastaut J. A. , Maraninchi D. , Richard B. , Launay M. C. , Sainty D. , Sebahoun G. , Carcassonne Y.
Published: July 2010

Abstract: 35 patients with refractory or relapsed acute leukemia received salvage chemotherapy using high‐dose cytosine arabinoside 2 g/m2 intravenously for 3 hours every 12 h, in 8 doses, followed by continuous infusion of mitoxantrone 12 mg/m2/day for 2 d. 9 patients had acute myeloblastic leukemia (AML), (4 relapsed, 5 refractory), 20 had acute lymphoblastic leukemia (ALL) (11 relapsed, 9 refractory) and 6 had chronic myelogenous leukemia (CML) in the blastic phase (BP). 4 out of 9 AML and 16 out of 20 ALL achieved complete remission. Median survival was 6 months for all patients and 10 months for responders. A short (1.5 months) chronic phase was achieved in 3 patients with CML. The main toxic effect was hematologic. A pharmacokinetic study was performed on mitoxantrone. No correlation was found with clinical response. The combination of mitoxantrone and ara‐C is an effective antileukemic regimen, especially in ALL.
Antilymphocyte immunoglobulins stimulate peripheral blood lymphocytes to proliferate and release lymphokines
Authors: Taniguchi Yoshio , Frickhofen Norbert , Raghavachar Aruna , Digel Werner , Heimpel Herman
Published: July 2010

Abstract: Five different preparations of antilymphocyte immunoglobulins (ATG) and antithymocyte immunoglobulins (ALG) with good or little clinical response were compared for their hematopoietic and immunological activities. All ATG/ALG lots demonstrated complement‐mediated cytotoxicity on peripheral blood mononuclear cells. They had different titers of antibody specificities against lymphocyte cell membrane antigens. Neither clinically effective nor ineffective lots demonstrated any apparent colony stimulating activity on bone marrow mononuclear cells. Purified Natural Killer cells failed to be stimulated by ATG/ALG in liquid culture. ATG/ALG demonstrated potent T‐cell stimulating activity comparable to phytohemagglutinin. This stimulation was blocked by anti‐IL‐2 receptor monoclonal antibodies, and was inhibited dose‐dependently by cyclosporin‐A. Some clinically ineffective ATG/ALG lots also stimulated T cells to release lymphokines. The differences in these characteristics among ATG/ALG lots provide some clues to guide further efforts to elucidate a key mechanism of therapeutic effectiveness.
Haemophilia, AIDS and lung epithelial permeability
Authors: O'Doherty M. J. , Page C. J. , Harrington C. , Nunan T. , Savidge G.
Published: July 2010

Abstract: Lung 99mTc DTPA transfer was measured in HIV antibody‐positive haemophiliacs (11 smokers, 26 nonsmokers, 5 patients with Pneumocystis carinii pneumonia (PCP)). Lung 99mTc DTPA transfer as a marker of lung epithelial permeability was measured as the half time of transfer (from airspace into blood). This half time was faster in smokers compared to nonsmokers and the transfer curve was monoexponential. In nonsmokers no difference was observed between asymptomatic HIV‐positive haemophiliacs and normal subjects, with the exception of the lung bases. At the lung bases in HIV‐positive haemophiliac nonsmokers the transfer was faster than in normal individuals, implying increased alveolar permeability. Pneumocystis carinii pneumonia resulted in a rapid transfer of 99mTc DTPA (mean T50 of 2 minutes) and the transfer curve was biphasic, confirming previous observations in homosexual HIV antibody‐positive patients with PCP. These changes returned to a monoexponential profile by 6 weeks following successful treatment. The DTPA lung transfer study may enable clinicians to instigate therapy for PCP without the need for initial bronchoscopy and provide a noninvasive method for the reassessment of patients should further respiratory signs or symptoms develop. This method is considered to be highly cost‐effective in that it obviates the use of factor VIII concentrates required to cover bronchoscopic procedures and, with its early application and ease of use as a follow‐up investigation, permits the evaluation of patients on an outpatient basis, thus reducing hospital costs.
Idarubicin (4‐demethoxydaunorubicin) as single agent for remission induction of previously untreated acute promyelocytic leukemia: A pilot study of the Italian cooperative group GIMEMA
Authors: Avvisati G. , Mandelli F. , Petti M. C. , Vegna M. L. , Spadea A. , Liso V. , Specchia G. , Bernasconi C. , Alessandrino E. P. , Piatti C. , Carella A. M.
Published: July 2010

Abstract: Because of the reported high sensitivity of acute promyelocytic leukemia to daunorubicin, we treated 27 consecutive, newly diagnosed, acute promyelocytic leukemia (APL) patients with the new anthracycline idarubicin (IDA) as induction therapy. IDA dosage ranged from 0.25 to 0.30 mg/kg/day and the drug was administered as single agent during a single induction course of 6 days. A total of 22/27 patients (81%) achieved complete remission, 4 (15%) died during induction and 1 patient was resistant to IDA. Extrahematological toxicity was acceptable. A total of 13/22 patients having achieved CR are still alive and in first CR after a median follow‐up of 12 months. As for the treatment ot the coagulopathy present in APL: 17/27 (63%) received tranexamic acid (6 g/daily) in continuous infusion for total of 7 d. None of the patients treated with tranexamic acid experienced thromboembolic complications. In conclusion, this multicentric pilot study confirms the antileukemic potency of IDA and the high sensitivity of APL to anthracycline derivatives.
Deletion of 14q in non‐Hodgkin's lymphoma
Authors: Kristoffersson Ulf , Heim Sverre , Johnsson Anna , Mandahl Nils , Olsson Hakan , Åkerman Måns , Mitelman Felix
Published: July 2010

Abstract: 6 patients with non‐Hodgkin's lymphoma [3 with small cell lymphocytic lymphoma of B‐cell type (SL), and 1 each with follicular centroblastic/centrocytic, centroblastic, and immunoblastic lymphoma] and with the acquired cytogenetic abnormalities del(14) (q22) or del(14) (q24) are described. An evaluation of these 6 cases and 41 other lymphatic neoplasms with 14q deletion known from the literature revealed that 37 had a breakpoint in bands q22 to q24. The deletions occur significantly more often in lymphomas of SL morphology and in the leukemic counterpart, chronic lymphocytic leukemia, than in other types of lymphatic malignancies (p< 0.001).
Relationship of thrombin generation to peripheral blast cell count in patients with acute myeloblastic leukemia (AML)*
Authors: Scharf Rüdiger E. , Schneider Wolfgang
Published: July 2010

Abstract: Disseminated intravascular coagulation (DIC) commonly occurs in patients with acute promyelocytic leukemia (APL, FAB‐M3) but may also be seen in other subtypes of AML. DIC in patients with AML has been attributed to procoagulants released from granular fractions of leukemic blast cells. The present study was designed (i) to evaluate thrombin activity in patients with AML by measuring plasma levels of fibrinopeptide A (FPA) prior to chemotherapy, and (ii) to examine whether a relationship between FPA levels and the number of peripheral blast cells exists. Plasma levels of FPA were determined using a commercially available RIA kit. To remove fibrinogen and the majority of elastase‐induced fibrinopeptides (Aα 1–21) known to crossreact with the FPA (Aα 1–16) antiserum used in this assay, plasma samples were treated with bentonite prior to further processing. The study was conducted on 5 patients with APL and on 22 patients with other subtypes of AML. Peripheral blast cell counts at initial diagnosis ranged from 2100 to 56000/μl in patients with APL and from 1900 to 151000/μl in patients with other AML subtypes. The mean (± 1 SEM) pretreatment plasma level of FPA was significantly higher (p = 0.021) in the 5 patients with APL (38.2 ± 8.3 ng/ml) than in patients with other AML subtypes (8.1 ± 0.7 ng/ml). No relationship was found between peripheral blast cell counts and the corresponding FPA levels in the total group of 27 patients. However, when considering the 5 patients with APL separately, a significant correlation was observed between peripheral blast cell number and FPA plasma levels (r = 0.88, p = 0.050). This study confirms that thrombin generation is considerably greater in patients with acute promyelocytic leukemia than in other subtypes of AML. We conclude that type and number of circulating blast cells and their related capacity to express procoagulent activities appear to be major determinants of excessive fibrinogen degradation in AML.
Timing of diagnosis and lymphocyte accumulation patterns in chronic lymphocytic leukemia: Analysis of their clinical significance
Authors: Molica Stefano , Reverter Juan Carlos , Alberti Antonio , Montserrat Emilio
Published: July 2010

Abstract:In order to evaluate the clinical significance of the timing of diagnosis in chronic lymphocytic leukemia (CLL), we studied the diagnostic latency (DL), a variable related both to lymphocyte count and to lymphocyte doubling time (LDT), which points out the interval between the date of CLL diagnosis and the time at which it could have been made (lymphocyte count in peripheral blood of at least 5.0 × 109/l). In two different series accounting for 221 previously untreated CLL patients the trends of the DL tended to decrease as the risk increased. In other words, the more advanced the clinical stage the shorter the DL. On the other hand, the values of lymphocyte accumulation rate (LAR), which defines the speed at which the number of lymphocytes increases over the time, were significantly lower in earlier stages of disease. Both DL and LAR had a significant impact on survival when investigated by means of univariate analysis. In a Cox's regression analysis applied to a training set of 122 patients, the combination of international clinical stages, LAR and age had the strongest value in predicting survival. The resulting model was validated in an independent subset of 99 patients (test‐set cases) leading to a classification of patients into low‐, intermediate‐, and high‐risk groups with 5‐year survival rates of 89%, 31% and 8%, respectively, and with distinctively different annual mortality rates (p < 0.001). Finally, when multivariate analysis was applied to study disease progression, LAR was the first variable to enter the regression model (p = 0.0001).
Different haematopoietic growth factors have different capacity in overcoming the in vitro interferon gamma‐induced suppression of bone marrow progenitor cells
Authors: Zoumbos Nicholas C. , Baranski Bruce , Young Neal S.
Published: July 2010

Abstract: Interferon gamma (IFNγ) inhibits haematopoiesis in vitro and an in vivo role in bone marrow suppression has been implied from clinical studies. We investigated the capacity of three recombinant (r), human (h), haematopoietic growth factors to overcome the in vitro IFNγ inhibition of bone marrow progenitor cells in a methylcellulose culture system. Granulocyte macrophage‐colony stimulating factor (GM‐CSF) partially reversed IFNγ‐induced suppression of granulocyte‐macrophage colony formation, by increasing colony forming units‐granulocyte macrophage (CFU‐GM) in a proportion ranging from 54–101%. Interleukin‐3 (IL‐3) and granulocytecolony stimulating factor (G‐CSF) were much less effective. For erythropoiesis, IL‐3 was much more effective and partially reversed IFNγ‐mediated inhibition by increasing burst forming units‐erythroid (BFU‐E) in a proportion ranging from 52–138%. GM‐CSF and G‐CSF had no significant effect on IFNγ‐induced suppression of BFU‐E. In conclusion, haematopoietic growth factors have different capacity to overcome IFNγ‐induced suppression of marrow progenitor cells in vitro. The findings may have therapeutic implications, as combinations of growth factors may be more effective in treating bone marrow failure syndromes.
Fibroblast colony‐forming cells with high sensitivity to serum mitogen(s) exist in bone marrow of patients with chronic myelocytic leukemia
Authors: Kimura Akiro , Katoh Osamu , Hyodo Hideo , Kusumi Shizuyo , Kuramoto Atsushi
Published: July 2010

Abstract: Marrow fibroblast colony formation was studied in patients with myeloproliferative disorders, using human serum or platelet‐derived growth factor plus plasma‐derived serum as growth‐stimulating factors. Colony numbers negatively correlated with the patient's age, but were not different from those of controls. However, both maximum and average cell numbers per colony were significantly increased in patients with chronic myelocytic leukemia (CML) as compared to controls. These results suggest that fibroblast colony‐forming cells with high sensitivity to human serum mitogen(s) exist in a CML bone marrow. These may possibly be involved in one of the mechanism concerned with promoting fibrosis in this disease.
Humoral immunity of the oral cavity during remission‐induction therapy in patients with acute myeloid leukaemia
Authors: Bergmann Olav J.
Published: July 2010

Abstract:To evaluate whether local oral humoral immunity changes during remission‐induction therapy of newly diagnosed acute myeloid leukaemia, 10 consecutive adult patients were investigated during 4 weeks. The concentrations of the oral secretory immunoglobulins A and M were increased during the first 7 days but, when corrected for changes in the salivary flow rate, the secretion rates of S‐IgA and S‐IgM remained unchanged, relative to the values before chemotherapy. In comparison, the concentrations of the serum immunoglobulins A, G and M were decreased, like the leukocyte and thrombocyte counts, during the first 14 d. It is concluded that the chemotherapeutic agents appear to act differently upon the local plasma cells associated with oral secretory glands and plasma cells in the bone marrow, and that the secretion rate of oral immunoglobulins remains constant during remission‐induction therapy.
Changes of the blood lymphocyte population following 32P treatment for polycythemia vera
Authors: Blomgren Henric , Petrini Björn , Wasserman Jerzy , von Stedingk Lars‐Viktor , Svedmyr Erik
Published: July 2010

Abstract: Orally administrated Na232PO4 mainly accumulates in bone marrow where it emits β‐particles which may damage cells. Previously, we showed that 32P treatment for polycythemia vera (PVC) increased the phytohemagglutinin reactivity and proportions of T cells in the blood. Now we have examined the effects of 32P treatment for PCV on natural killer (NK) and B‐lymphocyte subsets which are considered to undergo their maturation in bone marrow. A mean isotope dose of 240 MBq given to 14 patients reduced the peripheral lymphocyte counts to 60% at 6 weeks. B cells and NK cells were reduced to the highest relative extent followed by HNK‐1 cells and T cells. Although the proportion of NK cells was reduced to 50% there was no concomitant reduction of NK activity against K562 cells. Pokeweed mitogen‐triggered secretion of IgM was significantly reduced, but not that of IgG or IgA. It is suggested that lymphocytes which mature in bone marrow may be affected to the highest extent by 32P treatment in PCV.
Influence of recombinant alpha and gamma interferons on the in vitro proliferation of myeloid and leukemic progenitors
Authors: Delforge A. , Vandenplas B. , Lagneaux L. , Loos M. , Bron D. , Debusscher L. , Stryckmans P.
Published: July 2010

Abstract: We have compared the effect of alpha 2‐C and gamma recombinant interferons (rIFNs) on normal myeloid progenitors (N‐CFU‐GM), chronic myeloid leukemia (CML) progenitors (CML‐CFU‐GM) and leukemic progenitors (L‐CFU) of acute non‐lymphoblastic leukemia (ANLL) patients. Within 14 days of continuous exposure in culture, a dose‐dependent inhibition of CFU‐GM was seen for most normal subjects. Resistance to rIFNs was frequent in leukemic patients and even more in acute leukemia than in CML. Stimulation of clonogenic cell growth was seen for a minority of leukemic patients. When only the sensitive cases were considered, no difference in sensitivity was noticed between normal, CML and ANLL patients. A good correlation was observed between the activity or the lack of activity of alpha and gamma rIFNs.
Acute nonlymphocytic leukemia (ANLL) with isochromosome i(17q) as the sole chromosomal anomaly: a distinct entity?
Authors: Wen H. J. , Kuse R. , Hossfeld D. K.
Published: July 2010

Abstract: 3 patients with acute nonlymphocytic leukemia (ANLL) and an isochromosome (17q) as the sole chromosomal defect are reported. Besides this cytogenetic pattern, they shared several clinical and hematological features such as male sex, advanced age, spleno‐ and/or hepatomegaly and a suspected preceding myeloproliferative syndrome. Bone marrow cytology was characterized by hypercellularity, prominent baso‐ and eosinophilia, decreased erythropoiesis and marked increase of dysmorphic megakarocytes. We suggest that some or most patients with ANLL and i(17q) as the sole cytogenetic defect represent blastic transformation of an underlying chronic myeloproliferative disorder rather than de novo ANLL.
Relationship of foetal haemoglobin levels and βs haplotypes in homozygous sickle cell disease
Authors: Falusi A. G. , Kulozik A. E.
Published: July 2010

Abstract: The foetal haemoglobin (HbF) levels and the haplotypes of βs chromosomes in sickle cell anaemia patients in Nigeria were evaluated. The mean HbF level was 5.9 ± 3.8% with a range of 0.9–16.7%. 80% of the patients had HbF values below 8% and 94% had HbF levels below 10%. No significant difference in haematological parameters was seen between those with less than 2% HbF and those with greater than 8% HbF. The presence (+) or absence (−) of eight restriction endonuclease enzyme sites within the βs globin gene cluster (haplotype) on chromosome 11 were mapped. The common haplotype (− − − − + + − +) in 97% of the chromosomes examined closely correlates with the low levels of foetal haemoglobin generally observed in sickle cell patients in the same population.
Time‐variations of pretreatment peripheral blood S + G2/M‐phase size determined by flow cytometry in adult acute myeloid leukaemia
Authors: Guerci A. , Scheid P. , Feugier P. , Pierrez J. , Frenkiel N. , Guerci O.
Published: July 2010

Abstract: The circadian and seasonal variations of pretreatment proliferative activity of peripheral blood (PB) as PB S + G2/M‐phase size was determined by flow cytometry in 61 adult patients with acute myeloid leukaemia (AML). Pretreatment PB S‐phase (p < 0.002), G2 + M‐phase (p < 0.008) and S + G2/M‐phase size are statistically correlated to the time of sampling, with the highest phase size at the end of the day. Time‐variations of the blast cell count are slightly significant (p = 0.049). Cytological diagnosis‐related differences in S + G2/M‐phase (p < 0.003) and white blood cell count (p < 0.04) time‐variations are observed. For all patients, no seasonal variations can be drawn, but in AML 1 (p < 0.029) and AML 4–5 patients (p < 0.003), the circadian variations of S + G2/M are affected by the seasons. The present results suggest that time may be taken into account in the monitoring of chemotherapy in acute leukaemia.
Diagnoses in patients with severe pancytopenia suspected of having aplastic anemia
Authors: Keisu M. , Öst Å.
Published: July 2010

Abstract: There were 100 patients with pancytopenia notified to the Swedish part of an international study of aplastic anemia (Aa) (1983–1986). Aa was the cause in 16 patients and 50 patients had different conditions explaining their pancytopenia, whereas in 34 patients no obvious explanation was found at the time of discovery of their pancytopenia. A follow‐up study in 1987 comprised the patients with Aa (n = 16) and the patients with uncharacterized pancytopenia (n = 34.3 additional patients had then been diagnosed as having Aa whereas 3 patients had a diagnosis of a low‐grade NHL and 8 patients a diagnosis of MDS. No (or an inadequate) bone marrow sample had been taken in 9 of the 34 patients. This study shows that pancytopenia may be found in many serious conditions. Patients with pancytopenia should be carefully followed as Aa can develop slowly and as the MDS diagnosis can be difficult to establish at an early stage.
Two pathways for iron uptake by guinea pig reticulocytes
Authors: Zhan Hui , Pollack Simeon , Weaver Janet
Published: July 2010

Abstract: We have demonstrated that the intracellular processing of transferrin to effect iron removal involves two pathways, one sensitive to rotenone and the other not. We have also found that the effect of the rotenone is dependent on the transferrin concentration: iron uptake was suppressed with concentrations of transferrin in the micromolar range, and was not suppressed at physiologic concentrations of transferrin. Rotenone does not disturb transferrin's interaction with its extracellular receptor, indicating that its action must be intracellular. The following model is suggested: that separate pathways are entered by transferrin in the cell. The first pathway is preferentially utilized when transferrin is in short supply. It begins with an intracellular site which has a high affinity (and low capacity) for either iron or transferrin. The second pathway begins with an intracellular site which has a high capacity (but low affinity) for either iron or transferrin and is utilized when transferrin is in physiologic concentration (and the low‐capacity, high‐affinity site is saturated); the pathway it initiates is dominant when transferrin is abundant. We speculate that the high‐affinity low‐capacity pathway may serve to direct intracellular iron to sites which would be critically injured by iron excess.
Clinical, biochemical and cytokinetic parameters for distinguishing smouldering and rapidly proliferating variants of acute leukaemia
Authors: Nüssler V. , Sauer H. , Pelka‐Fleischer R. , Hölzel D. , Wilmanns W.
Published: July 2010

Abstract: In a retrospective study, 10 patients with smouldering leukaemia (SML) were examined between 1982 and 1987. These patients typically showed the morphological criteria of acute myelogenous leukaemia (>30% blasts in the bone marrow) in most cases together with a long survival time (median 16 months; 5 patients more than 22 months; 5 patients between 2.3 and 6.3 months) without the use of aggressive chemotherapy. At initial diagnosis the blast cell populations of patients with SML were characterized by significantly reduced cytosolic thymidine kinase activity (TK), thymidine‐incorporation (dTR) and deoxyuridine incorporation (dUR) into DNA as well as reduced amounts of DNA‐synthesizing S‐phase‐cells (%S) in the bone marrow (BM), compared to those patients with a rapidly proliferating acute myelogenous leukaemia (AML) and to healthy individuals. None of the SML‐patients showed clinical symptoms such as night‐sweat, weight‐loss, hepato‐ and splenomegaly or lymphadenopathy at initial diagnosis. For characterization of SML vs AML we recommend the use of the biochemical parameter TK activity and the observed absence of the above‐mentioned clinical symptoms. The transition to the rapidly proliferating type of AML can be recognized by an increase in the values of the biochemical and cytokinetic parameters. The blast count in the bone marrow is not suitable as a diagnostic criterion for the definition of SML vs AML or its transition to the rapidly proliferating type of AML.
Impaired receptor binding and decrease in isoelectric point of lactoferrin after interaction with human monocytes
Authors: Birgens Henrik S. , Kristensen Lars Ø.
Published: July 2010

Abstract:The iron‐binding glycoprotein lactoferrin binds to specific receptors on human monocytes as an initial step implicated in monocytic iron deposition. In this study, the properties of lactoferrin were studied after its interaction with human monocytes. Rebinding of lactoferrin to its monocytic receptor was grossly impaired and a small decrease in isoelectric point from 8.9 to 8.8 was observed. In contrast, antigenic and iron‐binding properties of lactoferrin were preserved, the molecular weight by SDS‐polyacrylamide gel electrophoresis was unchanged and no low‐molecular fragments were detected by gel‐filtration. These findings indicate that lactoferrin molecules cannot operate in a cyclic manner to deposit iron. Furthermore, these results might contribute towards explaining the complex disappearence kinetics observed for lactoferrin in plasma.
Platelet aggregation and pseudothrombocytopenia induced by 1‐desamino‐8‐D‐arginine vasopressin (DDAVP) in type IIB von Willebrand's disease patient
Authors: Casonato Alessandra , Fabris Fabrizio , Girolami Antonio
Published: July 2010

Abstract: Our study shows that the thrombocytopenia described in type IIB von Willebrand's disease (vWd) after 1‐desamino‐8‐D‐arginine vasopressin (DDAVP) infusion is, at least partially, a pseudothrombocytopenia. There was a discrepancy in platelet counts in blood anticoagulated with EDTA (< 10 times 103/μl) or citrate (55 times 103/μl) in one patient with type IIB vWd and chronic thrombocytopenia (80 times 103/μl) after DDAVP infusion. Furthermore, DDAVP induced a normalization of patient's prolonged bleeding time. Spontaneous platelet aggregation (SPA) observed in platelet‐rich plasma before DDAVP infusion was inhibited completely by monoclonal antibodies which block binding of fibrinogen, vWf and fibronectin to GPIIb‐IIIa. SPA was partially inhibited by a monoclonal antibody which blocks the binding of vWf to GPIb. After DDAVP, in contrast, SPA partially persisted in the presence of anti‐GPIIb‐IIIa monoclonal antibodies but was completely inhibited by anti‐GPIb monoclonal antibody. Therefore GPIb and GPIIb‐IIIa complex seem to play a different role in SPA before and after DDAVP infusion into type IIB vWd.
The effects of folate deficiency on thymidylate synthetase activity, deoxyuridine suppression, cell size and doubling time in a cultured human myeloid cell line
Authors: Matthews J. H. , Shiels S. , Wickramasinghe S. N.
Published: July 2010

Abstract: To help understand the pathogenesis of megaloblastic anaemia, we have studied folate‐deprived HL60 cells. Cells grown with no added folic acid developed macrocytosis, a prolonged doubling time, a grossly increased deoxyuridine‐suppressed value, and markedly reduced thymidylate synthetase activity. Cells in medium containing 50 nmol/l added folic acid became macrocytic with similar biochemical changes, but their doubling time was only marginally prolonged. In 100 nmol/l added folic acid, there was slight macrocytosis and a normal doubling time, but marked biochemical alterations were still present. The findings demonstrate that folate deficiency causes diminished thymidylate synthetase activity and macrocytosis in human myeloid cells, but that such cells may nevertheless demonstrate no prolongation of their doubling time, indicating either that their supply of thymidine triphosphate (TTP) is sufficient, or that mis‐incorporation of deoxyuridine triphosphate (dUTP) is occurring. This suggests that the ineffectiveness of haemopoiesis in folate deficiency may result from damage to bone marrow cells in some way other than arrest in S‐phase by a reduced delivery of TTP to the DNA replication fork.
Tissue plasminogen activator levels in different types of polycythemia
Authors: Cohen A. M. , Gelvan A. , Kadouri A. , Creter D. , Djaldetti M.
Published: July 2010

Abstract: The plasma level of tissue plasminogen activator antigen (t‐PA‐Ag) was examined in 86 patients with polycythemia (29 polycythemia vera, 11 secondary polycythemia and 46 with spurious polycythemia) and 24 healthy volunteers. Tissue plasminogen activator antigen was significantly decreased in patients with polycythemia vera in comparison with healthy controls. On the other hand, in patients with spurious polycythemia and secondary polycythemia t‐PA‐Ag concentration was significantly increased. There was no significant difference in t‐PA‐Ag levels in polycythemic patients with or without thromboembolic disease. A significant correlation was detected between t‐PA‐Ag level and hemoglobin or hematocrit concentration in patients with polycythemia vera (p = 0.02, r = 0.43). However, in patients with secondary polycythemia and spurious polycythemia, no significant correlation between t‐PA‐Ag and hemoglobin level was found. Plasminogen activator inhibitor (PAI) levels in patients with polycythemia vera and healthy volunteers did not differ significantly.
Chromosomal abnormality limited to T4 lymphocytes in a patient with T‐cell chronic lymphocytic leukaemia
Authors: Larramendy Marcelo L. , Peltomäki Päivi , Salonen Erkki , Knuutila Sakari
Published: July 2010

Abstract: Cytogenetic, immunologic and DNA studies were performed on a patient with the T‐cell type of chronic lymphocytic leukaemia. Standard G‐banding karyotype analysis revealed clonal chromosome abnormalities with the karyotype 42–44,XY,‐11,‐12,‐13,‐16,‐21,‐22,i(8q),inv(14) (q11q32), t(15;?)(p11;?), + 4–6mar/43–44,X,t(Y;14)(p11;q11),‐11,‐12,‐13,‐21,‐22,i(6p),i(8q),inv(14)(q11q32),t(15;?)(q11;?),+ 1–3mar. MAC (morphology, antibody, chromosomes) methodology, which allows the immunophenotyping of mitotic cells, showed that the chromosome abnormalities were restricted to CD4‐positive helper/inducer T lymphocytes and that CD8 suppressor/cytotoxic T cells and B lymphocytes possessed a normal karyotype. The results also indicate that the proportion of abnormal metaphases and the overall mitotic activity after 3.5 days of stimulation in vitro were highest when PHA and TPA were used as mitogens. When the culture period in the presence of PHA + IL‐2 was extended, the proportion of the abnormal cell population decreased in direct relation to the length of the culture period, ranging from 100% at3.5 dto0% at 31 d after stimulation. Southern blotting analysis revealed rearrangements of both the immunoglobulin heavy chain gene and the β T‐cell receptor gene.
Patchy haemopoiesis in long‐term remission of idiopathic aplastic anaemia
Authors: Hotta Tomomitsu , Murate Takashi , Inoue Chikako , Kagami Toyonari , Tsushita Keitaro , Jin‐Yuan Wang , Saito Hidehiko
Published: July 2010

ABSTRACT: 13 patients with idiopathic aplastic anaemia in remission for more than 2 years were examined to define the haemopoietic status by means of bone marrow scintigraphy, ferrokinetics and bone marrow culture for haemopoietic progenitor cells. Haemoglobin levels reached the normal range in all these patients although mild neutropenia and thrombocytopenia were still observed in 5 patients. Bone marrow scintigrams using indium‐111 showed normal distribution in 2, diffuse low accumulation in 3, patchy distribution in 7, and expanded distribution with patchy uptake in 1 patient. The defective haemopoiesis was also confirmed by ferrokinetic and bone marrow culture studies. The patchy haemopoiesis appears to characterize the residual marrow damage in remission of idiopathic aplastic anaemia.
Cancer procoagulant in acute lymphoblastic leukemia
Authors: Alessio M. G. , Falanga A. , Consonni R. , Bassan R. , Minetti B. , Donati M. B. , Barbui T.
Published: July 2010

In a previous study we characterized cancer procoagulant (CP), a 68 kd cysteine proteinase which directly activates coagulation factor X in various subtypes (from M1 to M5) of acute non‐lymphoblastic leukemia (ANLL). The aim of this study was to determine whether CP is also expressed by acute lymphoblastic leukemia (ALL) cells. Blasts from 25 ALL patients were extracted and tested for their procoagulant properties. 16 samples (64%) shortened the recalcification time of normal human plasma, and 9 (36%) did not. 8 of the 16 active samples showed properties compatible with CP, i.e. independence from factor VII in triggering blood coagulation and sensitivity to cysteine proteinase inhibitors. Selected samples also cross‐reacted with a polyclonal antibody raised against purified CP. The specific activity of CP in ALL extracts was significantly lower than in most ANLL types previously studied (all but M4). These finding indicate that CP can be a property of the lymphoid phenotype although its expression may be lower than in the myeloid phenotype.
Low incidence of bleeding from HIV‐related thrombocytopenia in drug addicts and hemophiliacs: Implications for therapeutic strategies
Authors: Finazzi G. , Mannucci P. M. , Lazzarin A. , Gringeri A. , Arici C. , Ciaci D. , Terzi R. , Barbui T.
Published: July 2010

The records of 608 intravenous drug addicts and 124 hemophiliacs diagnosed in 1985 to be seropositive for HIV were reviewed to identify patients with thrombocytopenia. The records of 54 drug addicts (8.9%) and 14 hemophiliacs (11.2%) who had chronic thrombocytopenia were then followed through June 1989 to estimate the incidence of bleeding episodes. The records of 55 HIV‐seronegative patients with idiopathic thrombocytopenic purpura (ITP), comparable for age, platelet count at diagnosis and duration of follow‐up, were used for comparison. Patients with ITP were significantly different from those with HIV‐associated thrombocytopenia in having a higher proportion of females (M/F ratio 13/42 v 53/15, p<0.001) and more intensive treatment (treated: 62% v 21%, p<0.001; splenectomized 37% v 1.5%, p<0.001). The incidence of major bleeding was not significantly different in drug addicts, hemophiliacs and ITP patients (0.98, 1.82 and 1.17/100 patients/year). Among drug addicts, bleeding was significantly more frequent in women than in men (3.4 v 0/100 patients/year, p<0.05). Our results indicate that the incidence of major bleeding in patients with HIV‐associated thrombocytopenia is low and similar to that observed in more intensively treated ITP patients.
Tranexamic acid therapy in acute myeloid leukemia: Possible reduction of platelet transfusions
Authors: Ben‐Bassat Isaac , Douer Dan , Ramot Bracha
Published: July 2010

We studied the clinical efficacy and safety of the antifibrinolytic drug tranexamic acid (TA) in patients undergoing chemotherapy for acute leukemia. 54 newley diagnosed AML patients were treated with 1g of TA every 6 hours until the platelet count rose to above 20 × 109/l. Platelet transfusions were given, irrespective of the count, only when oral, mucosal or significant skin bleeding manifestations were observed. During induction, the average number of days with thrombocytopenia below 20 × 109/l was 14.4 ±7.4 and 4.6 ±4.1 transfusions were given in each course. During consolidation, the average number of thrombocytopenic days was 8.4 ± 8.5 and only 1.7 ± 1.8 transfusions were administered. In 11.5% of the induction and 32.1% of the consolidation courses, no platelet support was required. TA was tolerated very well and no side effects or thromboembolic complications were observed. Only in 6 of the 78 induction courses did a major bleeding event occur and there were none in any of the 53 consolidation courses. Thus it seems that TA therapy allowed a significant reduction in the use of platelet transfusions without submitting the patients to greater bleeding risks.
Risk assessment in myelodysplastic syndromes: Value of clinical, hematologic and bone marrow histologic findings at presentation
Authors: Morra E. , Lazzarino M. , Castello A. , Inverardi D. , Coci A. , Alessandrino E. P. , Brusamolino E. , Bernasconi P. , Orlandi E. , Bonfichi M. , Merante S. , Zei G. , Bernasconi C.
Published: July 2010

We analyzed the prognostic value of clinical, hematologic and bone marrow (BM) histologic findings at presentation in 94 patients with myelodysplastic syndromes (MDS) (28 RA; 2 RARS; 34 RAEB; 6 CMML; 24 RAEB‐t). With survival as the dependent variable, stepwise multivariate analysis indicated as the prognostically most important factors among the MDS taken as a whole: latency from the first symptoms to diagnosis, age, and percentage of BM blasts. In each main MDS group the most unfavorable initial characteristics were: l)low Hb, no macro‐megaloblastosis, male sex for RA/RARS; 2) low Hb and low platelet levels for RAEB/CMML; 3) granuloblastic hyperplasia and high BM blastosis for RAEB‐t. Of the BM histologic parameters, only the percentage of blasts had significant prognostic value. Histologic assessment of BM blastosis, however, did not differ statistically from that based on cytologic examination of BM smears, so that marrow histology seemed not essential for initial prognostic assessment in MDS patients. The finding of abnormal localization of immature precursors (ALIP) in BM biopsies was associated with a negative trend without reaching statistical significance. Using four objective parameters of proven significance (age, Hb, platelets, and BM blasts) we devised a staging system of immediate clinical utility for prognostic stratification and risk‐adapted therapeutic choices.
A longitudinal study of class and subclass antibody response to pneumococcal vaccination in splenectomized individuals with special reference to patients with Hodgkin's disease
Authors: Grimfors G. , Söderqvist M. , Holm G. , Lefvert A. K. , Björkholm M.
Published: July 2010

Antibody class and subclass response to pneumococcal vaccination was monitored in 173 splenectomized individuals. The distribution according to indication for splenectomy was Hodgkin's disease (HD; n = 41), non‐Hodgkin lymphoma (NHL; n = 25), autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (n = 17), accidental splenectomy during abdominal surgery for malignant (AMA; n = 15) and benign (ABE; n = 42) disease and splenectomy due to splenic rupture caused by trauma (TRAUMA; n = 33). Pre‐vaccination total IgG pneumococcal antibody values (i.e. against the whole antigen = the vaccine) in the NHL patients were lower than in the ABE and TRAUMA groups (p<0.05). The response to vaccination in HD and NHL patients did not differ from that in the other patient groups. Furthermore, pre‐vaccination values did not differ between HD patients vaccinated before splenectomy and treatment and those vaccinated after, although the f
Platelet‐derived growth factor and its receptor in blood cell differentiation and neoplasia
Authors: Pantazis Panayotis , Goustin Anton Scott , Nixon Jon
Published: July 2010

Platelet‐derived growth factor (PDGF) is a family of dimeric protein molecules synthesized by differentiated, non‐dividing and proliferating blood cells. Experimental findings indicate that PDGF is involved in development and/or maintenance of physiological functions of certain normal blood cells. Also, PDGF synthesis correlates with certain blood cell proliferative diseases caused either spontaneously or associated with viral infection. There is increasing evidence that the diverse effects of PDGF in both normal and abnormal physiological functions of blood cells may be regulated at the level of its receptor. New experimental findings are discussed relating to PDGF receptors in normal leukemic, and virally‐infected human cells of myeloid and lymphocytic lineages. At specific developmental stages this regulation may take the form of PDGF and its receptor being expressed or co‐expressed; the unmodified or modified form of receptor that specifically interacts with PDGF; the cellular site at which the PDGF‐receptor interacts with its ligand; and co‐expression of the PDGF‐receptor with other receptors associated with specific cell lineage or functions. Elucidation of events involved in synthesis, processing, and interactions of PDGF isoforms and their respective receptors will enable us to develop pharmacological means that may either interfere with, or enhance these desired blood cell functions. This review focuses on PDGF and its receptor in human blood cell differentiation and neoplasia.
Diagnostic value of glycosylated hemoglobin in intravascular hemolysis after cardiac surgery
Authors: Chao‐Hung Ho , Wing‐Keung Chau , Tarng‐Jenn Yu , Kwok‐Kei Cheng
Published: July 2010

Glycosylated hemoglobin (GH), hemoglobin (Hb), hematocrit, LDH and serum bilirubin were measured pre‐operatively, and 1–10 days and 11–42 d post‐operatively in 42 patients undergoing cardiac surgery. Their mean age was 39.90 years, ranging from 4 to 68 yr. In the early post‐operation days, Hb and hematocrit, but not GH percentage, were significantly decreased. This demonstrates that, at this stage, acute blood loss rather than hemolysis is more prominent. In the later post‐operative days, GH, but not Hb or hematocrit, decreased significantly. This indicates the presence of chronic hemolysis with bone marrow compensation. In our study, the incidence of chronic mild hemolysis after cardiac surgery was very high (68.8%). We conclude that GH determination is a simple, easy and sensitive method to detect chronic hemolysis and we suggest measuring it in every case with suspicion of hemolysis.
Serum homocysteine in routine evaluation of potential vitamin B12 and folate deficiency
Authors: Hall C. A. , Chu R. C.
Published: July 2010

Total serum homocysteine (Hcy) was measured in patients with either low serum folate, low serum vitamin B12 (B12), or potential metabolic defects, in order to evaluate Hcy as an indicator of the tissue status of the two vitamins. An increased Hcy supported the diagnosis of frank tissue deficiency in those patients in whom tissue deficiency was evident by other means. A Hcy within the reference interval enabled the clinician to identify those patients whose low serum vitamin level and symptoms did not reflect a tissue deficiency of B12 or folate of clinical consequence. Children with inherited disturbances of B12 metabolism, and whose serum B12 was within the reference interval, were correctly identified by an increased Hcy. A declining Hcy was evidence of correction of a deficiency even when other laboratory or clinical measurements of a response were obscured.
Structural chromosomal abnormalities of 3q in myelodysplastic syndrome/acute myeloid leukaemia with Sweet's syndrome
Authors: Billström R. , Heim S. , Kristoffersson U. , Mandahl N. , Mitelman F.
Published: July 2010

Structural rearrangements in the long arm of chromosome 3, del(3)(q12q25) and t(3;5)(q21–25;q31–33), were observed in bone marrow cells from 2 patients with myeloid neoplastic disorders (myelodysplastic syndrome and acute myeloid leukaemia) and acute febrile neutrophil dermatosis (Sweet's syndrome). 3 of the 4 patients with leukaemia‐associated Sweet's syndrome and acquired chromosome abnormalities known from the literature also had 3q changes, in 2 involving band 3q21.
Natural killer cell activity in monoclonal gammopathies: Relation to disease activity
Authors: Österborg A. , Nilsson B. , Björkholm M. , Holm G. , Mellstedt H.
Published: July 2010

Natural killer (NK) activity and NK‐related cell surface markers (CD16, CD56, CD57) of peripheral blood lymphocytes were studied in patients with multiple myeloma and MGUS (monoclonal gammopathy of undetermined significance). A strong correlation (p < 0.0001) was found between the numbers of cells positive for the different NK cell surface markers. The proportion of CD16+cells correlated highly to the lytic capability (lytic units/106cells) of K562 cells (p < 0.0001). High NK activity and high numbers of cells with NK‐related cell surface markers were found in patients with a low tumor burden compared to controls, whereas low values were seen in patients with an advanced disease. The results indicate that NK cells might be involved in the disease process in monoclonal gammopathies, perhaps by exerting a regulatory function on the proliferating B‐cell clone.
Tumor‐necrosis factor induces cell cycle arrest in multipotential hematopoietic stem cells: a possible radioprotective mechanism
Authors: Warren D. J. , Slørdal L. , Moore M. A. S.
Published: July 2010

Tumor‐necrosis factor (TNF) and interleukin‐1 (IL‐1) have been shown to confer protection of hematopoiesis in mice challenged with radiation. Herein, a series of experiments designed to elucidate the underlying mechanism is presented. After TNF administration, colony‐stimulating activity, but no IL‐1 activity, was detectable in mouse plasma. In endogenous CFU‐S assays, TNF enhanced the survival of multipotential progenitors when administered before, but not after, irradiation. In experiments with fractionated irradiation, the radioprotective effect of TNF was distinctly different from that of IL‐1. In vivo and in vitro thymidine suicide assays demonstrated that TNF wholly or partially abolished cell cycling of the CFU‐S hematopoietic compartment. These data imply that TNF may inhibit the cell cycle in hematopoietic progenitor cell populations.