bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional hyposplenia after allogeneic bone marrow transplantation is detected by epinephrine stimulation test and splenic ultrasonography
Authors: Knecht Hans , Jost Res , Gmür Jürg , Burger Johanna , Fehr Jörg
Published: July 2010

Splenic function was evaluated after subcutaneous epinephrine injection (0.5 mg/m2) in 15 bone marrow transplant (BMT) recipients, 10 healthy volunteers and 5 healthy asplenic men. Healthy volunteers and BMT recipients with minor primary induction chemotherapy (mRx) showed similar rise in platelet (plt) and neutrophil granulocyte (PMN) counts and similar contraction of spleen. Patients with intensive primary induction chemotherapy (MRx), however, had significantly smaller spleens and spleen contraction (p < 0.02) and no plt increase (p < 0.05) when compared with healthy volunteers. 2 patients with MRx even exhibited a decrement of plt count after epinephrine, similar to that observed in all 5 healthy asplenic subjects tested. Our results suggest that mRx and conditioning for BMT including total body irradiation (TBI) does not alter the splenic function, but that the combination of MRx and conditioning regimen including TBI may cause functional hyposplenism, sensitively revealed by reduction in plt count after epinephrine stimulation.
IgE‐producing low‐grade non‐Hodgkin lymphoma
Authors: Sundström Christer , Nilsson K. , Brenning G.
Published: July 2010

An unusual case of IgE‐producing non‐Hodgkin lymphoma (NHL) is presented. The patient's history included a 6‐year period of increasing IgE level before a low grade NHL was diagnosed. The patient developed lymph node, skin, bone marrow and lung infiltrations. With a cytostatic combination therapy a temporary improvement was achieved, but the patient died from progressive disease after 2 yr. The morphological appearance of the tumour varied between that of LP immunocytoma and a centrocytic lymphoma. Immunophenotype studies showed intracytoplasmic IgE lambda in tumour cells and B‐cell surface phenotype (BB‐1 pos; OKT 10 pos; PCA weakly pos and SIgE lambda).
Analysis of peroxidase‐negative acute unclassifiable leukemias by monoclonal antibodies. 1. Acute myelogenous leukemia and acute myelomonocytic leukemia
Authors: Imamura Nobutaka , Tanaka Ryuji , Kajihara Hiroki , Kuramoto Atsushi
Published: July 2010

In this study, pretreatment peripheral and/or bone marrow blasts from 12 patients with acute unclassifiable leukemia (AUL) expressing the myeloid‐related cell‐surface antigen (CD 11) were isolated for further analysis. Despite a lack of myeloperoxidase (MPO) activity, 1 patient's blasts contained cytoplasmic Auer rods. The circulating blasts from another patient expressed MPO while maintaining the same surface phenotype during 20 months of clinical follow‐up. In addition, the blasts from 3 cases demonstrated both myelomonocytic and monocyte‐specific surface antigens, whereas the remaining 9 cases completely lacked any monocyte‐specific antigen detectable by monoclonal antibodies, Mo2, My4 and Leu M3 (CD 14). The first case eventually was diagnosed as acute myelomonocytic leukemia and the second as acute myelogenous leukemia by means of immunophenotypic analysis using flow cytometry (FACS IV). In addition, the presence of MPO protein was identified in the cytoplasm of blast cells from 5 patients with AUL by means of a cytoplasmic immunofluorescence test using a monoclonal antibody (MA1). Our study indicates that non‐T, non‐B AUL expressing OKM1 (CD 11) antigens include acute leukemias which are unequivocally identifiable as being of either myeloid or myelomonocytic origin. However, further investigations, including immunophenotypic and cytoplasmic analysis, ultrastructural cytochemistry and gene analysis with molecular probes (tests applicable to normal myeloid cells), are necessary in order to determine the actual origin of blasts and to recognize the differentiation stages of the various types of leukemic cells from patients with undifferentiated forms of leukemia.
Aplastic anemia associated with in vitro inhibition of erythropoiesis by bone marrow‐adherent cells*
Authors: Merchav Shoshana , Tatarsky Ilana , Sharon Rivka
Published: July 2010

A patient with aplastic anemia that evolved following pure red cell aplasia is described. Cultures of the patient's marrow cells revealed greatly reduced numbers of primitive (BFU‐E) and relatively mature (CFU‐E) erythroid progenitors, but normal numbers of multipotential (CFU‐GEMM) precursors. The BFU‐E/CFU‐GEMM and CFU‐E/BFU‐E ratios in the patient's marrow cell cultures were also reduced. T cell‐ or antibody‐mediated inhibition of in vitro erythropoiesis could not be demonstrated in this patient. However, the patient's marrow‐adherent cells suppressed the growth of autologous and allogeneic BFU‐E and CFU‐E, without influencing the growth of CFU‐GEMM. Medium conditioned by the patient's adherent cells failed to inhibit the growth of normal erythroid precursors. Our findings suggest a role for marrow‐adherent cells in the pathogenesis of aplastic anemia in this patient.
Recombinant interferon‐alpha‐2b treatment of hairy‐cell leukaemia: Experience with a low‐dose schedule
Authors: Hasselbalch Hans , Braide Inger , Lisse Ida , Röckert Lise‐Lotte , Swolin Birgitta , Carneskog Jan , Hagberg Hans , Hippe Erik , Jensen Mogens K. , Lundin Per , Malm Claes , Nielsen Bendt , Rödjer Stig , Westin Jan , Zador Göran
Published: July 2010

50 patients with hairy cell leukaemia (HCL) were treated with recombinant interferon (IFN) alpha‐2b 2.0 × 106 IU/m2 subcutaneously three times weekly to evaluate the efficacy of low‐dose IFN therapy in inducing and maintaining remission of the disease. At the time of this report 48 patients, of whom 22 were splenectomized, had been treated for at least 3 months and were considered evaluable for response. The median observation time on IFN‐alpha‐2b was 11 months (range 3 to 20). 4 cases with atypical disease (spongy lymphoid myelofibrosis) were also included. All patients responded to IFN. After 3 months 11/48 patients (23%) had achieved a partial remission (PR) with normalization of peripheral blood values. After 6 months 27/43 patients (63%) had achieved a favourable response; complete remission (CR) was recorded in 4 and PR in 23 patients. The proportion of patients with favourable responses (CR + PR) increased with the duration of therapy and after 12 months of therapy 23/28 (82 %) patients showed CR or PR, 9 patients (32 %) being in CR. Splenectomized patients disclosed a trend towards a more rapid response. It is concluded that IFN‐alpha‐2b is a highly effective first‐line therapy for HCL
Experimental basis of standardized specimen collection: The effect of the site of venipuncture on the blood picture, the white blood cell differential count, and the serum albumin concentration
Authors: Leppänen E.
Published: July 2010

The effect of the specimen collection site on blood picture and WBC differential count was investigated in 13 and 25 volunteers, respectively. Lower values were found for the mature neutrophils and higher monocyte values in ear and finger blood compared to venous blood. There were no statistically significant differences in the WBC differential count values found in the ear and finger specimens. A higher S‐Alb concentration was found in ear and finger specimens compared to venous blood. The average WBC concentration was higher in the ear and finger specimens than in the venous blood (7.66 × 109/1, 7.11 × 109/1 and 6.88 × 109/1, respectively). Also the platelet concentration exhibited a statistically significant difference, the mean concentrations being 273 × 109/1, 260 × 109/1 and 231 × 109/1 in the vein, finger and ear specimens, respectively. The differences found are partly explained by peripheral ultrafiltration of intravascular fluid, leading to haemoconcentration, and partly by the different properties of different white blood cells. In conclusion, the specimens for blood picture and WBC differential count should always be obtained from the same site, especially in follow‐up cases.
Pattern of platelet‐associated immunoglobulin (classes and IgG subclasses) in childhood immune thrombocytopenic purpura
Authors: Taaning Ellen , Petersen Sten
Published: July 2010

Platelet‐associated Ig classes and IgG subclasses were studied by a semiquantitative platelet ELISA test in 17 children with immune thrombocytopenic purpura (ITP). An elevation of PAIg was found in 94% of the children. In nearly all cases increased amounts of PAIgG of subclass G1 was seen, and in half of the cases increased amounts of PAIgM were also seen. No statistical difference in the composition of PAIg classes and PAIgG subclasses in acute and in chronic ITP was found. However, a correlation of increased amount of PAIgG3 and very low platelet count (20 × 109/1) was observed.
Stimulus‐specific defect in oxidative metabolism of polymorphonuclear granulocytes in polycythemia vera
Authors: Samuelsson Jan , Lindström Peter , Palmblad Jan
Published: July 2010

We investigated polymorphonuclear granulocyte (PMN) function in polycythemia vera (PV) in relation to healthy controls. PMN oxidative metabolism, assessed by chemiluminescence (CL), was significantly lower in PV patients after stimulation with leukotriene B4 (LTB4) and f‐Met‐Leu Phe (fMLP) (60% of control), whereas no difference in CL was seen after stimulation with phorbol myristate acetate (PMA) (120% of controls). Spontaneous and fMLP‐induced PMN adherence to an albumin‐coated plastic surface, as well as spontaneous migration and LTB4 — and fMLP‐induced chemotaxis, were similar to controls. This suggests the presence of a stimulus‐specific defect in PMN oxidative metabolism in PV.
HIV‐serology and lymphocyte subsets in relation to therapy and clinical development in haemophiliacs
Authors: Böttiger Blenda , Blombäck Margareta , Berntorp Erik , Egberg Nils , Nilsson Inga Marie , Schulman Sam , Stigendal Lennart , Biberfeld Gunnel
Published: July 2010

389 Swedish patients with haemophilia A, B or von Willebrand's disease were examined for HIV‐1 antibodies. T‐cell subsets were measured in 260 of them. HIV‐1 antibodies were found in 98 of these patients. Of the 199 patients with severe or moderate haemophilia A, 44% were seropositive. They had seroconverted between 1979 and 1983. HIV‐1‐seropositive patients had significantly decreased numbers of CD4 cells and increased numbers of CD8 cells. The seronegative haemophilia A patients had significantly increased numbers of CD8 cells. The T‐cell subsets were followed for a median of 40 months in 73 seropositive patients. All groups of patients, at different clinical stages, showed decreasing numbers of CD4 cells. The most pronounced decrease was seen in the patients who developed AIDS, followed by the group which developed HIV‐related signs or symptoms. HIV antigen in serum and antibody pattern in Western blot and ELISA were followed in 89 patients. HIV‐1 antigen was present and p24 antibodies were lacking in 11% and 13% of asymptomatic subjects, in 13% and 20% of patients with persistent generalized lymphadenopathy, in 33% and 38% of patients with other HIV‐related signs or symptoms and in 5/6 of the AIDS patients, respectively. In conclusion, the decrease of CD4 cells and the presence of HIV antigen and/or absence of p24 antibodies were found to be prognostic markers for HIV disease.
Induction of human basophil histamine release by a novel protein kinase C activator, sn‐1,2‐isopropylidene‐3‐decanoyl‐glycerol (IpOCOC9): Partial characterization of secretagogue characteristics
Authors: Bergstrand Håkan , Lundquist Britta , Michelsen Peter
Published: July 2010

Human leukocytes were found to release histamine at exposure for the synthetic glyceride derivative sn‐1,2‐isopropylidene‐3‐decanoyl‐glycerol (IpOCOC9). The following characteristics for the IpOCOC9‐induced basophil histamine release were recorded. A. In the order of 25% of the cellular histamine content was extruded at 206 μmol/l and 45% at 690 μmol/l of the compound, respectively. B. Removal of extracellular Ca2+variably affected IpOCOC9‐triggered release. C. The presence of N‐ethylmaleimide (10 μmol/l) or p‐bromophenacylbromide (10 μmol/l) markedly reduced IpOCOC9‐induced histamine release. D. The time course of the release triggered by IpOCOC9was intermediate to those characterizing the release triggered by 4β‐phorbol 12‐myristate 13‐acetate (PMA) and by formyl‐methionyl‐leucyl‐phenylalanine (FMLP). E. Cells desensitized to IgE‐receptor‐mediated stimulation were hyperresponsive to stimulation with IpOCOC9. F. Cells treated with a low concentration of 2‐deoxyglucose were not hyperresponsive to IpOCOC9. These data show that IpOCOC9, a PMN/leukocyte protein kinase C stimulator, acts as a non‐cytotoxic secretagogue for human basophils with a mode of action which in some, but not all respects, mimics that of PMA. In particular, IpOCOC9‐triggered release resembles that reported by other authors for hyperosmolar triggering of release by mannitol.
Aggressive treatment improves survival in adult acute lymphoblastic leukemia
Authors: Smedmyr B. , Killander A. , Simonsson B. , Sundström C.
Published: July 2010

20 consecutive adult patients with acute lymphoblastic leukemia were treated with an intense induction regimen including vincristine, doxorubicin, prednisolone, L‐asparaginase and cyclophosphamide. 16 patients (80%) achieved complete remission and were then given CNS prophylaxis and 3 years of maintenance therapy. With minimum follow‐up of 24 months, the median duration of first remission is 37 + months. Out of 10 patients who have completed maintenance therapy, 2 have relapsed after 14 and 22 months, respectively, and 7 are in continuous complete remission 1 + — 55+ months off therapy.
Vacuoles in red cells from splenectomized subjects originate during cell life: Association with glycosylated haemoglobin?
Authors: de Haan L. D. , Werre J. M. , Ruben A. M. Th. , Huls A. H. , de Gier J. , Staal G. E. J.
Published: July 2010

Whole blood from splenectomized subjects (n = 8) contained a substantial percentage of vacuolated (‘pitted’) red cells (34.7±8.3%), while blood from controls revealed none. The percentage of haemoglobin A1 (HbA1) had increased significantly compared with controls (p < 0.01). Fractionation on cell density revealed that the number of ‘pitted’ cells and the HbA1 percentage were associated with increased cell density. Fractionation on cell volume showed that ‘pitted’ cells are equally distributed in fractions with varying mean cell volume (MCV) and that decreasing MCV was associated with a linear rise of HbA1. It appeared that, shortly after splenectomy (n = 4), ‘pits’ develop early in cell life and that also older cells, after previous splenic contact, are capable of pit formation. A positive correlation found between the number of ‘pitted’ cells and the percentage of HbA1 might point to an impaired release of HbA1, manifest in the presence of ‘pits’. The increased percentage of HbA1 in whole blood from splenectomized subjects may thus be explained.
Short‐term intensive treatment (V.A.A.P.) of adult acute lymphoblastic leukemia and lymphoblastic lymphoma
Authors: Willemze R. , Peters W. G. , Colly L. P.
Published: July 2010

Increased dosages of cytosine arabinoside (Ara‐C) have been shown to be active in remission induction and consolidation treatment of patients with primary refractory acute lymphoblastic leukemia (ALL) and lymphoblastic non‐Hodgkin's lymphoma (lyNHL). From August 1983 to December 1986 we treated 25 patients with ALL (9) and lyNHL, stage III and IV (16), median age 22 (range 15–48 yr) with a protocol consisting of remission induction with vincristine, prednisone, adriamycine and Ara‐C (1 g/m2 twice daily as 2‐h infusion d1–6) and intrathecal methotrexate, followed by consolidation courses with vincristine, prednisone, adriamycine and Ara‐C (3 g/m2, twice daily as 2‐h infusion d1–4) and intrathecal methotrexate. Some patients received CNS and/or mediastinal irradiation. No maintenance was given. 18 patients (72%) achieved complete remission (5 of the 11 previously treated and 13 of the 14 previously untreated patients). Consolidation courses were given to 17 patients. 5 of them relapsed in the bone marrow (3), skin (1) and CNS plus bone marrow (1) at 5, 5, 6, 6 and 24 months. The duration of complete remission ranged from 5 to 51+ months; the median could not yet be calculated. Short‐term intensive treatment might be a worthwhile approach for ALL and lyNHL.
The effects of splenic irradiation on lymphocyte subpopulations in chronic B‐lymphocytic leukemia
Authors: Terstappen L. W. M. M. , de Grooth B. G. , van Berkel W. , Ten Napel C. H. H. , van Reijn M. , Greve J.
Published: July 2010

We describe the effect of splenic irradiation (SI) (0,5–1 Gy weekly) on lymphocyte subpopulations for 7 patients with progressive B chronic B‐lymphocytic leukemia (B‐CLL). Using specific cellular characteristics we could distinguish normal from abnormal cells. The irradiation resulted in a decrease of lymph node size, reduction in spleen volume and decrease in peripheral blood lymphocytes. The one exception was a patient with a prolymphocytoid transformation of B‐CLL. For 3 patients SI had to be interrupted or stopped because of severe cytopenia. Quantitation of malignant B cells and normal T lymphocytes revealed that the total irradiation dose which resulted in a specific decrease of malignant lymphocytes varied from patient to patient. Normal T‐cell subpopulations, which were increased before SI, decreased to normal or abnormally low values during SI. In previously untreated patients, natural killer (NK) cell numbers decreased more rapidly than T‐cell subpopulations. For 2 patients refractory to chemotherapy an increase of NK cells was observed upon SI.
Correlation between plasma levels of selenium and antithrombin‐III
Authors: Aursnes Ivar , Smith Pål , Arnesen Harald , Åkesson Bjørn
Published: July 2010

Patients with previous myocardial infarction were tested for antithrombin‐III (AT‐III) activity and selenium levels in their plasma and compared with sex‐ and age‐matched healthy control individuals. Patients and controls showed a positive correlation between AT‐III and selenium levels (r = 0.27, p = 0.015). After calculatory adjustment for this correlation, selenium was found to be significantly negatively correlated with disease. Multivariate analysis of differences between patients and controls indicated that triglyceride levels in serum had the greatest discriminatory ability (r2 = 0.169), followed by AT‐III (r2 = 0.072) and selenium (r2 = 0.056). The increased AT‐III levels were correlated with the use of warfarin and beta blockers in the patients, but these drugs could not explain the comparatively low selenium levels in the patients. Serum total cholesterol and plasma fatty acid composition had no discriminatory power in multivariate testing. The various fatty acids did not show co‐variation with the selenium levels. The clinical significance of these observations is not clear, but they are consistent with the hypothesis that selenium is an important determinant in cardiovascular disease. The relation between AT‐III and selenium should be further evaluated.
Myelokathexis associated with multiple congenital malformations: Immunological study on phagocytic cells and lymphocytes
Authors: Plebani A. , Cantù‐Rajnoldi A. , Collo G. , Allavena P. , Biolchini A. , Pirelli A. , Schoeller M. Clerici , Masarone M.
Published: July 2010

A 5‐yr‐old boy was first seen at the age of 11 months when he presented with growth retardation, skeletal dysmorphisms and neutropenia. Since then he has remained leukopenic except when he has pulmonary infections with a marked leukocytosis. Despite his neutropenia, marked myeloid hyperplasia was evident on marrow smear examination; many cells showed abnormally hypersegmented nuclei, with unusual shape or pyknotic nuclei. Phagocytic cells showed impaired phagocytosis, candidacidal activity, metabolic burst and chemotaxis. Moreover, the patient's serum generated less chemotactic activity than normal serum. These data indicate a selectively complex defect of the neutrophil during differentiation associated with the presence of an inhibitor of chemotactic factors in the patient's serum.
Impaired low‐density lipoprotein receptor activity in chronic B‐lymphocytic leukaemia cells
Authors: Juliusson Gunnar , Vitols Sigurd
Published: July 2010

Cellular degradation of 125I‐labelled low‐density lipoprotein (LDL) was analysed in freshly isolated blood mononuclear cells from 26 patients with chronic B‐lymphocytic leukaemia (CLL) and 8 healthy subjects, and in cells following 1, 2 and 3 d of culture in medium containing 10% human lipoprotein‐deficient serum (LPDS). Fresh CLL cells had lower LDL degradation rates than mononuclear cells from healthy subjects (p < 0.01). The LDL degradation rates increased during culture (p < 0.001), but to a lesser degree in CLL cells than in normal blood mononuclear cells (p < 0.001). The cellular degradation rate of 125I‐LDL was markedly inhibited by an excess of unlabelled LDL, indicating that most of the 125I‐LDL that was degraded had been internalized following binding to the high‐affinity cell surface receptor. There was a positive correlation between the LPDS‐induced LDL degradation of CLL cells and the thymidine uptake in CLL cell cultures with (r = 0.70, p < 0.001) and without (r = 0.59, p < 0.01) the B cell mitogen, Epstein‐Barr virus. The results indicate that LDL receptors might be involved in the regulation of CLL cell proliferation.
Immunoelectronmicroscopic investigation of Hodgkin's Disease with monoclonal antibodies against histiocytes
Authors: Hansmann M. L. , Radzun H. J. , Nebendahl C. , Parwaresch M. R.
Published: July 2010

8 cases of Hodgkin's disease (HD nodular sclerosis (n = 3), HD mixed type (n = 2), and nodular paragranuloma (n = 3)) were investigated with monoclonal antibodies against histiocytes (Ki‐M1, Ki‐M3, Ki‐M4, Ki‐M6, and Ki‐M7). Reactivity of H‐ and SR‐cells with the monoclonal antibodies Ki‐M3 and Ki‐M7 could be shown at the ultrastructural level in cases of HD of nodular sclerosis and mixed type. In nodular paragranuloma no positive H‐, SR‐ nor L & H‐cells could be demonstrated. The reaction site of the monoclonal antibodies in H‐ and SR‐cells was comparable to those in histiocytes.
Low dosage alpha‐interferon treatment in patients with advanced cutaneous T‐cell lymphoma
Authors: Hagberg H. , Juhlin L. , Scheynius A. , Tjernlund U.
Published: July 2010

Treatment with high dose (10–50 × 106 IU/m2 three times a week) of alpha‐interferon (α‐IFN) has been shown to induce remissions in about 50% of patients with cutaneous T‐cell lymphoma. The optimal α‐IFN dose, however, is not known. 4 patients with advanced cutaneous T‐cell lymphoma were therefore treated with α‐IFN in low doses of 2–4 × 106 IU/m2 three times a wk. 1 complete, 1 partial and 1 minor remission were observed. Skin biopsies before and during treatment were taken from 2 of the patients and showed improvement. Low doses of α‐IFN can thus induce remission in patients with cutaneous T‐cell lymphoma.
Relationship of clinical and immunological abnormalities in haemophilia A to F VIII therapy and HIV exposure: A longitudinal study
Authors: Eagleton M. C. , Whelan C. A. , Sarsfield P. , Carr B. , Temperley I. J. , Feighery C.
Published: July 2010

This study was established to examine the longitudinal consequences of F VIII therapy on immune function in 24 patients with haemophilia A. Antibodies to the human immunodefiency virus (HIV) were found in 15 of 16 patients with severe haemophilia and in 2 of 8 patients with mild disease. The principal clinical and immunological abnormalities were restricted to the HIV antibody‐positive patients: T helper cell lymphopenia (< 0.55 × 109/l) in 10 patients, persistent glandular lymphadenopathy in 4 patients and depressed response to skin recall antigens in 7 of 9 HIV‐positive patients tested. Although no extension of these immunological and clinical abnormalities developed in the 18‐month period of monitoring, T helper cell counts and platelet counts were significantly lower in a group of patients with established long duration HIV seropositivity (since 1982/1983) in comparison with the remaining seropositive patients. This suggests that a progressive pathological process is associated with infection by this virus, but the factors which determine the long‐term sequelae are still unknown.
Age‐related differences and circadian and seasonal variations of myelopoietic progenitor cell (CFU‐GM) numbers in mice
Authors: Sletvold Olav , Laerum Ole Didrik , Riise Trond
Published: July 2010

The effect of aging on the myelopoietic progenitor cell (CFU‐GM) numbers in mice was studied with special emphasis on biological rhythms in hemopoiesis. Female C3H mice, 16‐, 21‐ and 26‐month‐old, were investigated versus 3‐month‐old controls every 3 hours during the 24‐h period at three different times of the year. Strong circadian rhythms were observed in both CFU‐GM concentration and content in the femur of all age‐groups. The amplitudes and the 24‐h mean values were declining in mice aged 21 and 26 months. From 16 months of age, a significant advance of circadian peak phases was observed. The overlapping was variable during the 24‐h period. The present results may explain previous inconsistencies regarding myelopoietic progenitor cell numbers in aging mice. Some seasonal differences in rhythmicity patterns were also observed. Fitting of original data to single sinus functions was highly significant, although important details sometimes were obscured.
Cytogenetic follow‐up of 100 patients submitted to bone marrow transplantation for Philadelphia chromosome‐positive chronic myeloid leukemia: Cooperative Study Group on Chromosomes in Transplanted Patients
Authors: Zaccaria Alfonso
Published: July 2010

100 Ph+ CML patients submitted to BMT were studied cytogenetically before grafting and serially after transplantation. The 12 European institutions participating in the study, including transplant units and laboratories of cytogenetics, collected a total of 520 studies. The Ph chromosome was observed after BMT in 22 patients who did not enter relapse during the observation time (10–1400 days — median 420 d) following initial detection of the chromosome. This abnormality was observed in 1 to 30% of the cells analyzed. In 10 patients, abnormal cells were detected only within the first 90 d after BMT, in 5 patients both before and after 90 d and in 7 patients only after 90 d. 44% of these 22 patients had a moderate‐to‐severe cGVHD. Future studies are needed in order to better evaluate the real incidence of persistent disease and the correlations with the GVHD.
The spleen in Felty's syndrome: A histological, morphometrical, and immunohistochemical study
Authors: van Krieken J. H. J. M. , Breedveld F. C. , te Velde J.
Published: July 2010

A histological study employing morphometrical and immunohistochemical methods was performed in 3 spleens removed because of Felty's syndrome (FS). A comparison was made with control spleens and with spleens removed from patients with idiopathic thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia (AIHA). In FS, the spleen is enlarged, mainly due to expansion of the red pulp. The sinuses are enlarged, too, and contain many macrophages. 2 of our specimens showed many hyperplastic germinal centers; the 3rd contained no germinal centers. Only in the former cases did splenectomy lead to an increase in the number of circulating granulocytes. Immunohistologically, FS spleens differed from the control, the ITP, and the AIHA spleens. The results have provided further evidence indicating that the pathogenesis of granulocytopenia in FS differs from that of autoimmune hematocytopenias, and have given rise to the hypothesis that, in FS, the spleen is the site of interaction between immune complexes and granulocytes.
Inhibition of leucocyte migration by cancer chemotherapeutic agents and its prevention by free radical scavengers and thiols
Authors: Szczepańska Izabella , Kopeć‐Szlezak Joanna , Malec Janina
Published: July 2010

The exposure of human blood in vitro to a range of concentrations of adriblastine, hydroxyurea, methotrexate, 5‐fluorouracil, 6‐mercaptopurine, cytosine arabinoside and nitrogen mustard induced reduction in leucocyte migration rate in all drug dilutions under study. The reduction was dose‐dependent. This effect was used to examine the protection of alfa tocopherol, acetylosalicylic acid and thiourea against drug‐induced cytotoxicity. It has been found that at the suitable concentration of the protecting agent, a preventive effect of tocopherol against toxicity of all drugs, except nitrogen mustard, can be achieved. Acetylosalicylic acid protected the cells against adriblastine, cytosine arabinoside, hydroxyurea and methotrexate toxicity. Thiourea prevented the toxic effect of adriblastine, fluorouracil, hydroxyurea, methotrexate and nitrogen mustard.
EF Bart's disease: Interaction of the abnormal α‐ and β‐globin genes
Authors: Fucharoen S. , Winichagoon P. , Thonglairuam V. , Wasi P.
Published: July 2010

EF Bart's disease is an uncommon form of thalassaemia intermedia resulting from the co‐inheritance of α‐thalassaemia and haemoglobin E in the same subject. Starch‐gel electrophoresis revealed two phenotypes in 19 patients with EF Bart's. 16 patients had Hbs CS + E + F + Bart's and the remainder had Hbs E + F + Bart's. DNA mapping and haemoglobin electrophoresis indicated that there are four genotypes, involving 5 abnormal globin genes, responsible for this thalassaemia syndrome.
Day‐to‐day variations in serum iron, serum iron binding capacity, serum ferritin and erythrocyte protoporphyrin concentrations in anaemic subjects
Authors: Romslo Inge , Talstad Ingebrigt
Published: July 2010

Day‐to‐day variations in serum iron, serum iron binding capacity, serum ferritin and erythrocyte protoporphyrin were determined on 2 successive days in 48 patients with anaemia. The correlation coefficients between the paired determinations were 0.86, 0.89, 0.95 and 0.95, and the day‐to‐day coefficients of variation (in per cent) were 33, 11, 12 and 13 for serum iron, serum iron binding capacity, erythrocyte protoporphyrin and serum ferritin, respectively. Thus, in patients with anaemia, day‐to‐day variations in serum iron, serum iron binding capacity, erythrocyte protoporphyrin and serum ferritin are at least as high as in healthy controls. The results indicate important limitations in the use, particularly, of serum iron in the clinical investigation of anaemia.
Haematopoiesis in the aged as studied by in vitro colony assay
Authors: Hirota Yuichi , Okamura Seiichi , Kimura Nobuhiro , Shibuya Tsunefumi , Nino Yoshiyuki
Published: July 2010

Changes occurring in human haematopoiesis with advancing age were studied using an in vitro haematopoietic colony assay in 22 elderly subjects with unexplained anaemia, and in 15 elderly and 15 young subjects without anaemia. Both elderly groups were found to have significantly lower numbers of bone marrow early erythroid‐committed progenitors (BFU‐E) than the young controls. The elderly anaemic group also showed significantly lower numbers of granulocyte/macrophage progenitors (CFU‐GM) than the young controls. However, the responses of the erythroid‐committed progenitors in the elderly groups to erythropoietin and burst‐promoting activity were similar to those observed in the young controls. Therefore, it is probable that anaemia tends to occur easily in elderly individuals as a result of reduction of reserves of haematopoietic progenitors with advancing age.
Methimazole‐induced agranulocytosis: Growth inhibition of myeloid progenitor cells by the patient's serum
Authors: Douer Dan , Eisenstein Zemach
Published: July 2010

The mechanism for agranulcytosis induced by antithyroid drugs is not established. The few available studies have proposed an immune‐mediated process against mature granulocytes. We investigated the effect of methimazole and propylthiouracil and serum from a patient with methimazole‐induced agranulocytosis on marrow myeloid colony growth. In the presence of normal serum or patient's recovery serum, antithyroid drugs had no effect on the growth of CFU‐GM colonies from normal or patient's marrow. However, the patient's serum obtained during agranulocytosis inhibited the in vitro myeloid colony growth from both autologous and allogeneic bone marrow. These results are compatible with an immune‐mediated mechanism for methimazole‐induced agranulocytosis rather than a direct toxic effect of the drug on abnormally sensitive cells.
Biosynthesis and processing of myeloperoxidase — A marker for myeloid cell differentiation
Authors: Nauseef William M. , Olsson Inge , Arnljots Kristina
Published: July 2010

Myeloperoxidase (MPO), a heme protein, is a major component of azurophilic granules of neutrophils. Optimal oxygen‐dependent microbicidal activity depends on MPO as the critical enzyme for the generation of hypochlorous acid and other toxic oxygen products. MPO is synthesized during the promyelocytic stage of myeloid differentiation, the stage at which azurophilic granules are formed. Like other lysosomal enzymes, MPO is synthesized as a larger precursor which is subsequently processed and transported intracellularly to the lysosomes. The primary translation product is a single 80‐kDa protein which undergoes cotranslational N‐linked glycosylation to produce a 92‐kDa glycoprotein. Glucosidases in the endoplasmic reticulum or early cis Golgi convert the proMPO to a 90‐kDa form which is sorted into a prelysosomal compartment that undergoes final proteolytic maturation to native MPO, a pair of heavy‐light protomers with subunits of 60 kDa and a 12 kDa. These events contrast with similar processes seen with other lysosomal enzymes in two ways. First, alkalinization of lysosomes with NH4+ does not alter processing or transport, in contrast to the pH dependence of these processes for other lysosomal enzymes. However, some studies indicate retardation of processing in the presence of the proton ionophore monensin. Second, intracellular transport of MPO is not apparently mediated by the mannose‐6‐phosphate receptor system. The gene for MPO is on the long arm of chromosome 17 (17q22, 23) near the breakpoint of the 15, 17 translocation of acute promyelocytic leukemia. The gene spans approximately 14 kb and contains 11 introns and 12 exons. The cloned full‐length cDNA is approximately 2.2 kb and both normal bone marrow and cultured promyelocytic leukemia cells express two species of mRNA. Inherited MPO deficiency, a relatively common disorder, is associated with the absence of mature MPO but the presence of proMPO, consistent with a post‐translational defect. Studies at the molecular level aimed at identifying the underlying genetic defect are thus far consistent with that hypothesis. In addition, the basis for the observed association between acquired MPO deficiency and some myeloid leukemias can now be studied at the molecular level using these probes.
Effect of androgens on the response to antithymocyte globulin in patients with aplastic anaemia
Authors: Kaltwasser J. P. , Dix U. , Schalk K. P. , Vogt H.
Published: July 2010

30 patients with aplastic anaemia (18/30 with severe aplastic anaemia) were prospectively randomized to be treated with 100 mg/kg ATG with or without the oral androgen Methenolone (3 mg/kg). 15 of 30 patients responded. Among the 15 patients receiving ATG plus androgen, 11 patients (73%) responded, including 8 complete and 3 partial responses. 4 of the 15 patients (31%) receiving ATG only responded, including 2 complete and 2 partial responses. The difference in response rate was statistically significant (p = 0.01). The survival rate in the total population of 30 patients was 64%. The survival rate in the group receiving ATG plus androgen was 87%; in the group receiving ATG only it was 43%. The difference in survival rates between both groups did not reach statistical significance (p = 0.15). Toxicity of ATG and androgens was considerable but manageable. These data support the result of the recent European reevaluation of a large pool of patients by the EBMT (39), that androgens in addition to ATG increase survival in patients with aplastic anaemia. They are, however, in contradiction to a controlled American study showing no benefit of a combined treatment with androgens as compared to ATG only. Further controlled studies on a larger number of patients are indicated to determine the therapeutic efficacy of androgens in addition to immunosuppression in aplastic anaemia.
Thymidine‐dependent effect of granulocyte‐derived inhibitor on granulocyte‐macrophage progenitor cells (GM‐CFC)
Authors: Bøyum Arne , Helgestad Jon , Løvhaug Dagfinn
Published: July 2010

We have compared the effect of granulocyte extract (GRE) on proliferation of hemopoietic cells from various sources, using two different cultures media, CMRL 1066 and McCoy 5A. GRE caused a strong (80–90%) inhibition of granulocyte‐macrophage colony forming cells (GM‐CFC) in cultures with medium CMRL 1066. GM‐CFC in human blood and human and mouse bone marrow were equally sensitive to the inhibitor. The inhibitor had a maximal effect in the concentration range corresponding to GRE from 2 × 105 to 2 × 106 cells per 1 ml culture dish. At higher GRE concentration the inhibition was reduced. GM‐CFC from human blood and mouse marrow were suppressed in cultures with McCoy's medium as well, but to a lesser extent than in CMRL 1066 cultures. On the other hand, in cultures with human bone marrow cells (BMC) and McCoy's medium, GRE had no inhibitory effect. CMRL 1066 medium contains a number of components not present in McCoy's medium. In a systematic study where these substances were added one by one to McCoy's medium we found that inhibition by GRE depended upon the presence of thymidine. At a thymidine concentration of 3 × 10−5 mol/l GRE strongly suppressed GM‐CFC in human blood and bone marrow. This thymidine concentration itself had no effect. Other nucleosides or components of the CMRL 1066 did not potentiate the suppressive effect of GRE.
Kinetics of hemopoietic stem cells in a hypoxic culture
Authors: Ishikawa Y. , Ito T.
Published: July 2010

The influence of low oxygen tension on the clonal growth of hemopoietic stem cells in vitro was examined. The numbers of colonies of neutrophil, macrophage, and eosinophil progenitors (CFU‐C), derived from human bone marrow, increased at a rate 1.7 times higher in low oxygen tension (7% O2) than in a gas phase that contained air (19% O2). The erythroid (BFU‐E) and multipotential (CFU‐mix) progenitors increased about 2.4 times in 7% O2, and the increase in the composed cell type of mixed colonies showed no rate difference in either gas phase. Under atmospheric conditions, a mouse mast cell progenitor (CFU‐mast) formed colonies, with the addition of 2‐mercaptoethanol (2‐ME). Under low oxygen tension, the CFU‐mast formed colonies without 2‐ME, but a further enhancement was observed with the addition of 2‐ME. Blood gas analysis of human bone marrow showed a pO2 of 51.8 ± 14.5 mmHg, which was closed to O2 tension in a gas phase culture media containing 7% O2. This data shows that the physiological O2 tension enhances hemopoietic stem cell proliferation in vitro, and that a part of the enhancing effect by 2‐ME is due to a prevention of O2 toxicity at 19% O2.
Characteristics of circulating megakaryocyte progenitors (CFU‐MK) in patients with primary myelofibrosis
Authors: Han Z. C. , Briere J. , Nedellec G. , Abgrall J. F. , Sensebe L. , Parent D. , Guern G.
Published: July 2010

Characteristics of circulating CFU‐MK and the effect of serum and plasma on CFU‐MK growth were studied in 14 patients with primary myelofibrosis (MF) using short‐ and long‐term culture methods. The number of CFU‐MK in short‐term cultures was significantly increased in the non‐splenectomized patient group (p < 0.01). Without added PHA‐LCM and normal serum, spontaneous colony formation was found in 9 out of 10 patients. In long‐term blood cultures from 6 MF patients, 3 untreated patients formed confluent adherent layers and produced in suspension an equal number or an even greater number of nucleated cells, megakaryocytes and CFU‐MK than those obtained in long‐term bone marrow culture from normal individuals. 2 splenectomized patients showed neither an increased numbers of CFU‐MK nor the capacity to develop an adherent layer. The serum and plasma of MF patients failed to stimulate megakaryocyte colony formation by normal bone marrow in a normal fashion. These findings indicate a megakaryocytopoietic abnormality, and a central role of the spleen in extramedullary haematopoiesis in MF.
Red cell ferritin and iron stores in patients with chronic disease
Authors: Brown Ross D. , Benfatto John , Gibson John , Kronenberg Harry
Published: July 2010

Serum and red cell ferritin were determined in a heterogeneous group of 59 patients with chronic disease undergoing a bone marrow biopsy. There was very little correlation between serum and red cell ferritin (r = 0.53). Although serum ferritin increased in relation to increased bone marrow iron stores, only 1 out of 8 patients with absent marrow iron stores and none of 8 patients with reduced marrow iron stores had a decreased serum ferritin. In contrast, 6 of 8 patients with absent iron stores had a reduced red cell ferritin concentration. There was no significant difference between the mean red cell ferritin of the patients with reduced, normal and mildmoderately increased marrow iron stores (30, 26 and 34 ag/cell). Red cell ferritin was decreased in 78% of a group of 32 patients with a low mean cell volume. In the patients studied, red cell ferritin was a better indicator of absent iron stores than serum ferritin. However, red cell ferritin did not detect a reduction in the iron status until the marrow iron stores were completely depleted. Apparently, during normal erythropoiesis the primitive erythroblasts continue to take up iron irrespective of the amount of iron available in the stores.
Buoyant density characterization of neoplastic cell populations in patients with chronic B‐lymphocytic leukemia
Authors: Åman Pierre , Gordon John , Mellstedt Håkan , Biberfeld Peter , Klein George
Published: July 2010

Leukemic cells from a series of patients with chronic B‐lymphocytic leukemia (CLL) were analyzed for their buoyant density on discontinuous Percoll gradients. The density profile varied markedly between different patients and also between samples from different body compartments within the same patient. A good correlation was observed between buoyant density and maturation stage of the leukemic clones as judged by Ig‐expression and their reactivity with a panel of monoclonal antibodies. Phorbol‐ester‐induced changes in the leukemic cells were found to be accompanied by a general decrease in their buoyant density. No correlation between density and clinical parameters such as cell counts, clinical stage and survival could be noted. Buoyant density characterization of leukemic B‐cell populations is seen as a useful, rapid and simple marker of compartmentalization within the B‐lymphocyte maturation spectrum but its clinical relevance remains to be established.
Ultrasonic characterization of splenic tissue in myelofibrosis: Further evidence for reversal of fibrosis with chemotherapy
Authors: Manoharan Arumugam , Chen Chang F. , Wilson Laurence S. , Griffiths Kaye A. , Robinson David E.
Published: July 2010

Fibrosis in patients with myelofibrosis (MF) is seen not only in the bone marrow but also around the metaplastic foci in the spleen and liver. Following our observation of reversal of bone marrow fibrosis in MF patients treated with chemotherapy, we undertook ultrasonic splenic tissue characterization studies using sound speed measurements to assess the effect of such therapy on the splenic fibrosis. Single studies in 19 patients showed overlapping ranges among the three sub‐groups classified according to the grade of bone marrow fibrosis, but the mean values in these sub‐groups showed a trend towards decreasing sound speed with increasing marrow fibrosis. Sequential studies in 9 of these patients showed increased splenic sound speed with decreasing marrow fibrosis in 8 patients following treatment, with a reversal of this pattern seen in 1 patient 1–2 years post‐treatment. These results suggest simultaneous reversal of fibrosis in the bone marrow and the spleen in MF patients receiving effective chemotherapy.
Unexplained lymphadenopathy in sickle cell disease
Authors: Keidan A. J. , Hamon M. D. , Franklin I. M. , Mawson S.
Published: July 2010

Progressive lymphadenopathy in a previously healthy female adult with homozygous sickle cell disease (SCD) was found to be due to infection with the human immunodeficiency virus (HIV). Detailed questioning identified several risk factors for HIV in this apparently low‐risk patient. Parenteral therapy and heterosexual relationships while abroad may place such SCD patients at risk of HIV infection and its sequelae. The additional risk due to the underlying immunological abnormalities which have been identified in SCD patients is unclear in the absence of prospective studies or reported cases.
Prognostic parameters in myelodysplastic syndromes: A multiple regression analysis
Authors: Riccardi Alberto , Giordano Monica , Giordano Paolo , Cassano Enrico , Girino Margherita , Cazzola Mario , Scivetti Paolo , Danova Marco , Ucci Giovanni
Published: July 2010

The influence on survival of 21 basic clinical and hematologic parameters was evaluated in 72 patients with previously untreated myelodysplastic syndromes (MDS). Only five parameters were significant by both survival curves and multiple regression analyses: hemoglobin level, bone marrow (BM) cellularity (estimated from trephine BM biopsies), BM blast percentage, age and BM erythro/myeloid (E/M) ratio. Using these parameters, multiple regression analysis enabled us to predict 34% of the survival of all MDS patients (p < 0.002), 38% of that of patients who had stable disease (p < 0.04) and over 80% of that of patients who developed acute leukemia (p < 0.02). High BM cellularity was the most predictive factor for the development of leukemia. No factor was predictive for patients who died of cytopenic or other complications.
Hyper‐responsiveness to DDAVP for patients with type I von Willebrand's disease and normal intra‐platelet von Willebrand factor
Authors: Rodeghiero F. , Castaman G. , Di Bona E. , Ruggeri M. , Lombardi R. , Mannucci P. M.
Published: July 2010

Desmopressin (DDAVP) has gained wide acceptance as the drug of first choice in the treatment or prevention of haemorrhages in the majority of patients with von Willebrand's disease (vWd). However, data concerning the clinical effectiveness of DDAVP refer generally to mild vWd, with factor VIII and vW factor levels usually above 20% of normal. In 14 patients with type I vWd characterized by very low plasma levels of factor VIII coagulant activity (VIII:C) and vWf, measured as ristocetin cofactor activity (lower than 20% and 3% of normal respectively), but with a normal intraplatelet content of vWf, a test infusion of DDAVP (0.4 μg/kg) elicited a very marked increase of VIII:C and vWf and normalized the bleeding time. All these patients subsequently underwent tooth extraction after DDAVP infusion. The incidence of bleeding was remarkably low, with only two minor late bleeding episodes easily stopped by repeating DDAVP infusion. Compared to the cases of type 1 vWd with unknown intrapletelet vWf content reported in the literature, this subgroup of patients had a more marked, albeit short‐lived, increment of VIII:C and vWf.