bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone marrow sinus and cell egress in human leukaemia: a morphometric study of core biopsies using wide‐field electron microscopy
Authors: Nagaoka Takashi , Kuto Fumio , Watanabe Yoshihiko , Fujino Yumi , Hirasawa Yasushi , Tokuhiro Hideo 
Published: March 2008

SummaryBone marrow biopsy specimens obtained from 24 untreated patients with several types of acute leukaemia (AL) and eight patients with chronic myelocytic leukaemia (CML) were prepared without decalcification for electron microscopy. A new type of transmission electron microscope (LEM 2000) was used for wide‐field observation, and the venous sinuses were morphometrically evaluated on micrographs using an automatic image analyser. No differences were found between either AL or CML bone marrows and the controls in the diameter, circumference, or luminal and endothelial area of sinuses. No degenerative changes were observed in the sinus endothelium of either the AL or CML patients, but the adventitial cell cover in sinuses was significantly less in both AL (P < 0.001) and CML (P < 0.001) patients than in the controls, indicating a close relationship between the decrease in adventitial cell cover and increase in migrating leukaemia cells. In addition, the sinus endothelium in CML had significantly (P <0.03) more pores than in AL patients and three or more leukaemic cells in migration through the same large pore were occasionally found in the CML patients. These findings suggest that leukaemic cell migration in AL differs from that in CML.
Colony formation by megakaryocytic progenitors in essential thrombocythaemia
Authors: Juvonen E. , Partanen S. , Ruutu T. 
Published: March 2008

SummaryColony formation by megakaryocytic progenitors (CFU‐M) from the blood or bone marrow of 12 patients with essential thrombocythaemia was studied in vitro with the methyl cellulose assay. When the cultures were stimulated with plasma from a patient with aplastic anaemia and with phytohaemagglutinin stimulated conditioned medium (PHA‐LCM), the patients showed a significant trend towards higher circulating CFU‐M numbers when compared with the controls; three of the patients exceeded our normal range. In the bone marrow cultures there were no differences in the number or morphology of megakaryocytic colonies between the patients and the controls. When normal human plasma was the only source of colony stimulating activity. 11 out of 12 patients, but none of the controls, showed megakaryocytic colony formation. The same patients also had ‘spontaneous’ erythroid colony growth without the addition of exogeneous erythropoietin into the cultures. Only one of the patients with essential thrombocythaemia (ET) had normal megakaryocytic and erythroid colony formation. The present study shows that, in most patients with ET ‘spontaneous’ CFU‐M colony formation occurs in suboptimal culture conditions, a phenomenon obviously analogous to the spontaneous erythroid colony formation seen in the myeloproliferaative disorders.
Characteristics of red cell pyruvate kinase (PK) and pyrimidine 5'nucleotidase (P5N) abnormalities in acute leukaemia and chronic lymphoid diseases with leukaemic expression
Authors: Corrons J. L. Vives , Pujades M. A. , Sierra J. , Ribera J. M. 
Published: March 2008

SummaryRed cell pyruvate kinase (PK), pyrimidine 5'nucleotidase (P5N) and reduced glutathione content (GSH) were studied in 126 untreated patients with acute leukaemia (AL, 80 cases), chronic lymphocytic leukaemia (B‐CLL, 38 cases) and B‐cell lymphoma with leukaemic expression (LSCL, eight cases). Acute leukaemias were classified into lymphoblastic (ALL) and non‐lymphoblastic (ANLL), the latter have been further sub‐divided into four different variants according to FAB morphological criteria (1976). A significant decrease of PK activity was observed only in the ANLL group, leading to a clear‐cut difference with the ALL group where a normal value was obtained. The decrease of P5N activity was similar in all the morphological variants of ANLL and no abnormalities in the low PEP assay system or after fructose 1.6‐bisphosphate (Fru 1.6‐P2) activation were observed. P5N activity was found to be significantly decreased in all groups of patients except in B‐CLL, where it was normal. In regards to the different morphological groups of ANLL, a striking decrease of P5N activity was observed in the M3 variant. Although red cell GSH content was significantly increased in all groups of patients, no correlation was demonstrated between the raised GSH levels and the decreased P5N activities.
Cytogenetic characteristics of therapy‐related acute nonlymphocytic leukaemia, preleukaemia and acute myeloproliferative syndrome: correlation with clinical data for 61 consecutive cases
Authors: Pedersen‐Bjergaard Jens , Philip Preben 
Published: March 2008

SummaryCytogenetic studies were performed on a new series of 23 patients with therapy‐related acute non‐lymphocytic leukaemia, preleukaemia or an acute myeloproliferative syndrome. In our total series of now 61 cases studied by chromosome banding techniques, at least one of the abnormalities – 7, 5q –, 7q– or – 5 or some related unbalanced translocations, primarily – 7, +t(1q7p), was observed in 40 patients. The critical region for the deletions of chromosome no. 5 comprises bands 5q22 to 5q33 and of chromosome no. 7 bands distal to 7q22. The third most frequently involved chromosome was no. 21, rearranged at band 21q22 in the three patients with 21q + and in one patient with 21q –. An i(21q) was observed in two patients, a –21 in four patients and a –22, + t(21q22q) and a –5.–21, + t(5p21q) in one patient each. Other characteristic abnormalities included total loss or rearrangements of the short arm of chromosome no. 17, observed in nine patients. One patient had a –12, three others had rearrangements resulting in a partial or total loss of the short arm of chromosome no. 12. A 19q + with translocation to band 19q13 was observed in three cases, a – 18 in three cases and a 3p– in four cases. Thirty‐one patients with multiple chromosome aberrations experienced a significantly shorter survival as compared to 13 patients with a normal karyotype (P= 0·02) and 17 patients with one single chromosome aberration (P<0·01).
Two different quadruplicated α globin gene arrangements
Authors: Gu Y. C. , Landman H. , Huisman T. H. J. 
Published: March 2008

SummaryThe discovery of two different types of α globin gene quadruplication is reported. One with the αααα(anti 3·7)/haplotype was present in four members of a Black family from Georgia, while a second with the αααα(anti 4·2)/haplotype was observed in two members of an Indonesian family. Consistent clinical and haematological manifestations could be observed in these heterozygotes.
Haematologic manifestations of the human immune deficiency virus (HIV)
Authors: Zon Leonard I. , Arkin Charles , Groopman Jerome E. 
Published: March 2008

SummaryA variety of haematologic abnormalities are associated with infection by HIV, the human retrovirus that is the primary aetiologic agent of the acquired immunodeficiency syndrome (AIDS). We have reviewed the haematologic findings in well‐characterized cohorts of patients with AIDS, AIDS‐related complex (ARC) and asymptomatic homosexual men at risk for this retrovirus. Anaemia, granulocytopenia and thrombocytopenia were found in increasing prevalence according to the severity of clinical disease associated with retroviral infection. Bone marrow aspirations and biopsies revealed frequent hypercellularity, dysplasia, plasmacytosis and lymphoid infiltrates. These marrow morphologic findings were strongly associated with anaemia and granulocytopenia. Review of transfusion records of patients with HIV antibodies revealed a 21% prevalence of a positive direct antiglobulin test. The pathophysiology of the observed haematologic abnormalities may involve direct retroviral infection of bone marrow progenitors, abnormal regulation of haematopoiesis and/or autoimmune phenomena.
Measurement of phagocytosis utilizing [14C]cyanate‐labelled human red cells and monocytes
Authors: Bussolino Federico , Turrini Franco , Arese Paolo 
Published: March 2008

SummaryHuman red cells were labelled with [14C]cyanate, non‐oxidant, permeant reagent that binds irreversibly to amino groups in proteins. Cyanate did not modify GSH levels, nor glucose‐6‐phosphate dehydrogenase (G6PD) activity when added at the labelling concentration i.e. c. 0·5 DIM. Phagocytes were human monocytes, isolated and plated on 16 mm diameter plastic wells. Each well was plated with 40–70 × 103 cells. Monocytes were quantified by DNA assay with the DNA intercalating fluorescent compound Hoechst 33258. The basal phagocytic rate of normal red cells by monocytes was 0·34/pm0·21 red cell per monocyte. Treatment of normal red cells with 20 μM diamide. or 50–100 μM chromate enhanced this rate 10–15‐fold. 10 μM diamide or chromate were sufficient to stimulate phagocytosis of G6PD‐deficient (Mediterranean variant) red cells.
Lymphocyte phenotype and lymphokines following anti‐thymocyte globulin therapy in patients with aplastic anaemia
Authors: Platanias Leonidas , Gascon Pedro , Bielory Leonard , Griffith Patricia , Nienhuis Arthur , Young Neal 
Published: March 2008

SummaryTwenty‐two patients with adult onset aplastic anaemia were analysed before and after therapy with antithymocyte globulin (ATG). Lymphocyte phenotype, lymphokine levels or production, and haematopoietic progenitor cell number were measured 3 months after therapy: clinical response was determined 1 year post‐therapy. By flow cytometry there was a significant reduction in both the proportion and absolute number of peripheral blood lymphocytes expressing activation antigen Tac (IL‐2 receptor) and in the proportion of HLA‐DR+ lymphocytes. For T cells bearing HLA‐DR, there were proportional decreases in both activated helper and suppressor cells. There was no statistically significant difference pre‐ATG to post‐ATG in the absolute numbers of total, helper and suppressor lymphocytes. In all 10 haematologic responders the number of Tac bearing lymphocytes after ATG therapy was in the normal range, but half of 12 non‐responding patients continued to have abnormally elevated numbers of Tac+ T cells. The proportion of Tac+ cells were not related to transfusion history. γ‐interferon levels in serum by radioimmunoassay were elevated in almost half the aplastic patients; post‐ATG. γ‐interferon was detectable in only three patients. Haematologic response to ATG therapy was associated with increased numbers of haematopoietic progenitors post‐treatment, but pre‐treatment values were not predictive of a response. These results are consistent with a pathogenic role for activated T‐cells and their lymphokine products and suggest that the target of ATG therapy may be a Tac+ lymphocyte.
Granulocyte antibodies in leukaemic chronic lymphoproliferative disorders
Authors: Rustagi Pradip K. , Han Tin , Ziolkowski Lynn , Farolino Deborah L. , Currie Mark S. , Gerald  , Logue L. 
Published: March 2008

SummaryThe anti‐granulocyte activity of serum from patients with B‐cell chronic lymphocytic leukaemia (CLL) and other lymphoproliferative disorders was investigated. Granulocyte‐binding IgG was measured in 34 patients with CLL, 13 patients with hairy cell leukaemia, one patient with prolymphocytic leukaemia, two patients with Sézary cell leukaemia, and seven patients with chronic T‐cell lymphocytosis who had a predominance of circulating large granular lymphocytes. Anti‐granulocyte activity was absent in CLL and its variants, but present in the majority of granulocytopenic patients with chronic T‐cell lymphocytosis. In one of these patients, granulocytopenia was associated with complement activating IgG granulocyte antibody. Thus, antibody mediated granulocyte injury appears to be an unusual occurrence in chronic lymphocytic leukaemia, but is a frequent complication of chronic T‐cell lymphocytosis.
Pre‐transfusion non‐invasive quality assessment of stored platelet concentrates
Authors: Bellhouse Elisabeth L. , Inskip Mary J. , Davis J. G. , Entwistle C. C. 
Published: March 2008

SummaryThe Platelet Monitor System has been designed to assess routinely prepared platelet concentrates (P.C.) during storage. The system is based upon observations of changes in light transmission induced by platelets in intact packs. It is practical, provides constant gentle agitation for P.C., and non‐invasively give continuous semi‐quantitative evidence of the probable numbers of discoid platelets within each pack. The information yielded correlates both with established in vitro parameters of platelet behaviour, and with in vivo survival of platelets in normal healthy volunteers.The device safely provides the Blood Banker with the means to achieve on‐going assessment of methods and improvements‐or failings‐in P.C. production. To the clinician it offers information throughout and even beyond present arbitrary storage limits, about which P.C. are likely to be of least or greatest value to a thrombocytopenic patient.
Platelet glycoprotein IIb as a target antigen in two patients with chronic idiopathic thrombocytopenic purpura
Authors: Tomiyama Y. , Kurata Y. , Mizutani H. , Kanakura Y. , Tsubakio T. , Yonezawa T. , Tarui S. 
Published: March 2008

Summary.We have investigated the target antigens recognized by anti‐platelet antibodies in patients with chronic idiopathic thrombocytopenic purpura (ITP) using an immunoblot procedure which could electrically separate the glycoprotein (GP) IIb/IIIa complex into GPIIb and GPIIIa. Various platelet proteins, having molecular weights of 167, 160, 145, 135, 124, 102, 92 and 80 kD, were recognized by circulating antibodies in 11 of 40 ITP patients. We identified the 145 kD antigen band, seen in two ITP patients, as GPIIb using thrombasthenic platelets as a source of target antigens. In one patient the anti‐GPIIb antibody reacted with autologous GPIIb. These studies provide direct evidence for the presence of autoantibodies against GPIIb in some ITP patients.
Sickle cell disease in North London
Authors: Kehinde M. O. , Marsh Judith C. W. , Marsh G. W. 
Published: March 2008

Summary.We have examined our experience of sickle cell disease in the London Borough of Haringey over the past 20 years. There are currently (1986) 145 patients on the Haringey Sickle Cell Register and when comparison is made with other centres, admission for painful crises in Hb SS disease is more frequent than in Jamaica, but the acute chest syndrome appears to be less common in the United Kingdom than in Jamaica. Splenomegaly is less frequent in Hb SC patients in this country and there is also a lower incidence of leg ulceration in both Hb SS and Hb SC disease in the United Kingdom than in Jamaica.The incidence of alloimmunization among transfused sickle cell disease individuals in Haringey is 21%, the most frequently encountered antibodies being anti‐E and anti‐Kell.All pregnant patients with sickle cell disease were managed with regular blood transfusion throughout pregnancy starting at 12 weeks of gestation. There were no fetal or maternal mortalities, although three babies born were ‘small for dates’ despite uneventful antenatal courses and adequate Hb A levels being achieved in the mother.Examination of the effect of seasonal variation on the incidence of hospital admissions for painful crises reveals no significant clustering of cases in a particular month or season of the year.
Effective multiagent chemotherapy in children with advanced B‐cell lymphoma: who remains the high risk patient?
Authors: Philip T. , Pinkerton R. , Biron P. , Ladjadj Y. , Bouffet E. , Souillet G. , Phillippe N. , Frappaz D. , Freycon F. , Chauvin F. , Brunat‐Mentigny M. 
Published: March 2008

Summary. Between 1981 and 1985. 50 patients, mainly children and adolescents, with advanced B‐cell lymphoma were entered on a protocol comprising eight drugs: cyclo‐phosphamide. vincristine, prednisolone. high dose methotrexate. adriamycin. BCNU. cytosine arabinoside and thioguanine. Treatment to the central nervous system consisted of intrathecal methotrexate and cytosine‐arabinoside in association with high dose methotrexate without irradiation. Data was collected prospectively with regard to response rate, treatment related complications and survival. Histology was reviewed in all referred cases and in 21 there was supportive evidence from immunological and cytogenetic studies. The overall complete response rate was 86%: 31/36 stage III and 12/14 stage IV. There were four treatment related deaths. The overall disease‐free survival is 75% with a median follow up of 32 months. In the group of stage IV patients 5/7 with only marrow involvement, 2/4 with isolated CNS involvement and 1/3 with combined CNS and marrow infiltration survive. All the patients with CNS involvement at presentation underwent consolidation treatment with high dose chemotherapy and bone marrow transplant.These results demonstrate the very high curability of B‐cell lymphoma using intensive multiagent therapy even with advanced abdominal disease. Bone marrow infiltration does not appear to be an adverse prognostic factor in isolation from bulk disease or CNS involvement. There remain, however, two groups of patients in whom further intensification of therapy is indicated, namely, those with initial CNS involvement, especially in combination with marrow infiltration, and those with extensive multiorgan involvement at presentation who fail to achieve remission with initial therapy. For the other patients, the large majority, a reduction in the intensity and duration of therapy is currently under study.
Platelets in idiopathic thrombocytopenic purpura are increased in size but are of normal density
Authors: Illes Ilona , Pfueller Sharron L. , Hussein Sonay , Chesterman Colin N. , Martin John F. 
Published: March 2008

SummaryTo determine whether platelet size and volume are related to one another or to platelet age, subpopulations of platelets from patients with idiopathic thrombocytopenic purpura (ITP) have been produced on the basis of density using Percoll gradients. The density distribution of platelets from patients with ITP and from patients with other forms of thrombocytopenia (thought to be nonimmune in nature) was the same as in normal controls. However, the platelets in each density subpopulation from ITP patients were increased in size. β‐thromboglobulin (βTG) content of platelets from each patient group and the normals increased with density and tended to be higher in ITP than in normal controls. βTG concentration per unit platelet volume and its level in plasma were similar in ITP patients and in normal controls. This suggests that the apparently normal density of ITP platelets was not a result of degranulation of large, dense platelets. Thus platelet size and density are independently determined and the increased size of platelets in immune thrombocytopenia may be the result of abnormalities in their production.
Molecular characterization of a normal Hb A2β‐thalassaemia determinant in a Sardinian family
Authors: Oggiano L. , Pirastu M. , Moi P. , Longinotti M. , Perseu L. , Cao† A. 
Published: March 2008

SummaryIn this study we have carried out haplotype analysis at the β‐globin gene cluster and defined the β‐thalassaemia mutations in a large Sardinian family, ascertained through a proband with thalassaemia major, in which several members were carriers of a β‐thalassaemia allele characterized by microcytosis, hypochromia and normal Hb A2 levels (type 2 normal Hb A2 heterozygous β‐thalassemia). The proband was a compound heterozygote for the β°‐39 and the β+ IVS‐2, nt 745 mutations and all the β‐thalassaemia heterozygotes with normal Hb A2 showed the β+ IVS‐2, nt 745 mutation, always associated with haplotype VII. Because of the consistent association of a specific β‐thalassaemia mutation and normal Hb A2 levels, we postulate that this β‐thalassaemia chromosome carries a δ gene (δ‐thalassaemia) which is unable to increase the δ‐globin output in response to β‐thalassaemia.
Disappearance of HLA and platelet‐specific antibodies in acute leukaemia patients alloimmunized by multiple transfusions
Authors: Murphy M. F. , Metcalfe P. , Ord J. , Lister T. A. , Waters A. H. 
Published: March 2008

SummaryAlloimmunization by platelet transfusions was studied in 154 patients with acute leukaemia. 17 patients had HLA antibodies at initial presentation induced by previous transfusions or pregnancies; one of these also had platelet‐specific antibodies and one other patient had platelet‐specific antibodies alone. A further 38 patients developed HLA antibodies during therapy; three also had platelet‐specific antibodies and two patients developed platelet‐specific antibodies alone. Of these, 37 patients with HLA antibodies including three with platelet‐specific antibodies and one patient with platelet‐specific antibodies alone survived their initial therapy and formed the basis of this study.Antibodies once detected persisted throughout the study in seven of the 37 patients with HLA antibodies including one patient with platelet‐specific antibodies and in the patient with platelet‐specific antibodies alone. HLA antibodies disappeared after discontinuation of transfusions in six patients, and after switching to HLA matched platelet transfusions and leucocyte‐poor blood in eight patients: two of the latter patients also had platelet‐specific antibodies which disappeared. The other 16 patients with HLA antibodies lost their antibodies despite continued transfusions.
Nuclear c‐myc protein, maturation, and cell‐cycle status of human haemopoietic cells
Authors: Bains M. A. , Hoy T. G. , Baines P. , Jacobs A. 
Published: March 2008

SummaryHuman c‐myc protein, p62c‐myc, has been quantitated by flow cytometry in the nuclei of normal marrow and peripheral blood cells, and the HL60 cell line. Marrow and peripheral blood cells exhibit nuclear c‐myc protein throughout the cell‐cycle, at an average level 2–3–fold lower than HL60 cells. In no cells did p62c‐myc vary more than 2‐fold throughout the cell cycle. A small subset of marrow Go/G1 cells, enriched in early myeloid and blast cell fractions, contained p62c‐myc at levels equal to or even exceeding those of HL60.Overall c‐myc protein content was higher in myeloid, compared to erythroid and lymphoid marrow fractions. Within the myeloid lineage, the highest average p62c‐myc level was present in cells of intermediate maturation, i.e. myelocytes and metamyelocytes. In the erythroid lineage, c‐myc protein level was highest in the most immature cells and declined with maturation. Significant amounts of p62c‐myc were present in post‐mitotic, end‐stage neutrophils, but were barely detectable in cycling late erythroblasts or in quiescent lymphocytes and monocytes. HL60 cells, despite c‐myc gene amplification and increased gene expression, contain c‐myc protein at a level corresponding to promyelocytes in normal human marrow. The virtual absence of p62c‐myc in cycling late erythroblasts, and its presence in post‐mitotic end‐stage granulocytes, suggests that c‐myc protein may have functions unrelated to cell proliferation.