bluuebunny/crossref_metadata_2025 huggingface dataset:
Successful haploidentical mismatched bone marrow transplantation in severe combined immunodeficiency: T cell removal using CAMPATH‐I monoclonal antibody and E‐rosetting
Authors: Morgan G. , Linch D. C. , Knott L. T. , Davies E. G. , Sieff C. , Chessells J. M. , Hale G. , Waldmann H. , Levinsky R. J.
Published: March 2008

Summary. Six patients with severe combined immunodeficiency were transplanted with bone marrow from their HLA haploidentical parents. T‐lymphocytes were removed by complement mediated lysis with a monoclonal antibody (CAMPATH‐I) followed by resetting with sheep erythrocytes. The patients were pre‐conditioned with marrow ablative chemotherapy, using busulphan and cyclophosphamide. There was graft take in five patients, with evidence of transient acute graft‐versus‐host disease only. Three patients are alive and well > 5 months after transplant, and one who is 12 months post graft has full reconstitution of cell mediated and humoral immunity, including specific antibody response to immunization. Transplantation across major histocompatibility barriers can be successfully achieved using this method of treatment of donor marrow.
Observations on the distribution of the Zwa (P1a1) antigen on fixed and unfixed platelets
Authors: Saunders P. W. G. , Durack B. E. , Narang H. K.
Published: March 2008

Summary We have investigated the distribution of the Zwa antigen on unfixed platelets and platelets fixed in paraformaldehyde by examining thin sections of platelets by electron microscopy. Fixation of the platelets produces an even distribution of antigen around the surface membrane of the platelets. Unfixed platelets show clustering in some areas with other areas apparently free of antigen. In addition to this clustered antigen distribution, the unfixed platelets also show invaginations and vesicles containing antigen. The significance of these findings is discussed.
Six cases of hereditary spherocytosis revealed by human parvovirus infection
Authors: Lefrere Jean Jacques , Courouce Anne‐Marie , Girot Robert , Bertrand Yves , Soulier Jean‐Pierre
Published: March 2008

Summary Recent research has shown that the human parvovirus is a causative agent of aplastic crisis in hereditary haemolytic anaemias. We report six cases—four children and two adults—of hereditary spherocytosis revealed by aplastic crisis due to human parvovirus infection.
Chromosome and cell culture studies in eosinophilic leukaemia
Authors: Parreira L. , Tavares de Castro J. , Hibbin. J. A. , Marsh J. C. W. , Marcus R. E. , Babapulle V. Brito , Spry C. J. F. , Goldman J. M. , Catovsky D.
Published: March 2008

Summary A cytogenetic analysis was carried out on bone marrow cells from 11 patients who presented with hypereosinophilia and the clinical features of the idiopathic hypereosinophilic syndrome. One of these patients was found to have trisomy 8 affecting the myeloid series, including eosinophils. In this patient, marrow eosinophils also showed asynchrony of nuclear‐cytoplasmic maturation, and there were increased numbers of myeloid progenitor cells in the blood. Six months later, blast cell transformation occurred, and he died soon afterwards. These findings show that abnormalities in the karyotype of bone marrow cells and culture of blood progenitor cells may help to identity eosinophilic leukaemia among patients who present with features of the idiopathic hypereosinophilic syndrome.
The incidence and possible relevance of Bence‐Jones protein in the sera of patients with multiple myeloma
Authors: Sinclair D. , Dagg J. H. , Smith J. G. , Stott D. I.
Published: March 2008

Summary We present results showing that the detectable incidence of Bence‐Jones protein in the sera of patients with multiple myeloma is equivalent to the highest detectable incidence of Bence‐Jones protein in highly concentrated urine when tested by immuno‐isoelectric focusing. In a series of 25 multiple myeloma patients, immuno‐isoelectric focusing showed the incidence of Bence‐Jones proteinaemia to be 68% compared with a detectable incidence of Bence‐Jones proteinuria of 32–64% by immunoelectrophoresis and immuno‐isoelectric focusing depending upon the urine concentration factor. In view of the variability of factors governing urinary Bence‐Jones protein levels, such as renal catabolism, reabsorption and losses during concentration, we suggest that monitoring of serum Bence‐Jones protein by immuno‐isoelectric focusing should be carried out in conjunction with measurements of urinary Bence‐Jones protein in multiple myeloma.
In vitro culture of proerythroblasts: characterization of proliferative response to erythropoietin and steroids
Authors: Udupa K. B. , Crabtree H. M. , Lipschitz D. A.
Published: March 2008

Summary This study characterized variables affecting the in vitro liquid culture of proerythroblasts. When bone marrow from mice depleted of haemoglobin containing cells, was cultured in vitro in the presence of human urinary erythropoietin (Ep) a significant degree of erythroid cell proliferation and maturation occurred as measured directly by 3H‐thymidine (3H‐TdR) incorporation into DNA (autoradiographical measurement). Proliferation increased indirect proportion to the dose of Ep added to the culture. We also demonstrated a highly significant positive correlation between proliferation measured directly by 3H‐TdR incorporation into DNA or indirectly by 59Fe incorporation into haem. Ep was a potent stimulator of proerythroblast proliferation. We also examined the role of the androgenic and non‐androgenic steroids on in vitro proliferation. All the hormones tested were stimulatory but only in the presence of Ep. The androgenic steroids primarily affected the more mature erythroid precursors whereas the glucocorticoids were more general growth promoters. Their addition in physiologic concentration to liquid culture reduced Ep requirements. Thus when both testosterone and hydrocortisone were added to culture the Ep concentration that produced the same degree of proliferation as a culture containing Ep alone was decreased by 90%. This finding is important as it indicates that in vitro culture conditions can be created that more closely mimic in vivo erythropoiesis where Ep requirements are far less.
Post‐transfusion purpura (PTP) due to anti‐Zwb(‐PIA2): the significance of IgG3 antibodies in PTP
Authors: Taaning E. , Killmann S.‐A. , Morling N. , Ovesen H. , Svejgaard A.
Published: March 2008

Summary. The first two patients with post‐transfusion purpura (PTP) due to platelet antibodies against the Zwb antigen are reported. The anti‐Zwb specificity could be demonstrated only with an enzyme‐linked immunosorbent assay (ELISA) but not with the immunofluorescence or the complement fixation test due to coexistent potent multispecific HLA antibodies. One of the patients had never received blood transfusion until 24 d before the development of thrombocytopenic purpura.

In both patients, anti‐Zwb of IgG1 and IgG3 subclasses defined by monoclonal antibodies were present during the thrombocytopenic period but the antibodies of IgG3 subclass disappeared concomitantly with clinical improvement. The association between the IgG3 subclass of anti‐Zw antibodies and the destruction of autologous platelets in Zw‐immunized individuals was investigated further. All of four PTP patients had anti‐Zw antibodies of the IgG1 and IgG3 subclasses during the thrombocytopenic period while all of 20 mothers of children affected with alloimmune neonatal thrombocytopenia (AINT) had anti‐Zwa of only the IgG1 and not IgG3 subclass at the time of delivery of thrombocytopenic children (P<10‐4). Thus, the destruction of autologous platelets in PTP is associated with the presence of anti‐Zw of the IgG3 subclass which may be of importance in the pathogenesis of PTP.
Megakaryocytopoiesis in vitro of patients with essential thrombocythaemia: effect of plasma and serum on megakaryocyte colony formation
Authors: Komatsu Norio , Suda Toshio , Sakata Yoichi , Eguchi Mitsuoki , Kaji Kazuhiko , Saito Masaki , Miura Yasusada
Published: March 2008

Summary. TO clarify the mechanism of increased numbers of megakaryocytes in patients with essential thrombocythaemia (ET), we studied in vitro megakaryocytopoiesis in ET and other myeloproliferative disorders, using a megakaryocyte colony assay in methylcellulose containing plasma or serum and medium conditioned by phytohaemagglutinin (PHA) stimulated leucocytes (PHA‐LCM). Megakaryocytic colony formation was supported well by heparinized or citrated plasma and citrated serum which was harvested after clot formation of citrated plasma. Whole serum was inhibitory for megakaryocytic colony growth. The addition of platelet releasates and partially purified platelet derived growth factor (PDGF) resulted in a decrease in the number of megakaryocytic colonies. These findings suggested that platelet‐derived factor(s) in serum was inhibitory to megakaryocytic colony formation.

ET plasma supported the megakaryocytic colony formation by normal or ET bone marrow cells better than normal plasma. Moreover, in ET bone marrow cells, spontaneous megakaryocytic colonies were formed in the absence of PHA‐LCM. Increased megakaryocytopoiesis in ET may be ascribed to (i) increased megakaryocyte‐colony stimulating activity (Meg‐CSA) in plasma and (ii) increased sensitivity to Meg‐CSA or autonomous proliferation of megakaryocytic progenitor cells.
Heparin‐induced thrombocytopenia: further studies of the effects of heparin‐dependent antibodies on platelets
Authors: Chong B. H. , Castaldi P. A.
Published: March 2008

Summary.Studies were performed with the sera of five patients with heparin‐induced thrombocytopenia. Each patient serum was found to cause heparin‐dependent aggregation of normal and Bernard‐Soulier syndrome platelets but not Glanzmann's thrombasthenia or fixed normal platelets. This antibody effect was blocked by inhibition of both aerobic and anaerobic metabolism and an increase in intraplatelet c‐AMP with prostaglandin Ei. These findings suggest that the antibody‐induced platelet aggregation was not a passive agglutination of cells but an active process requiring metabolic energy and membrane glycoproteins IIb/IIIa but not glycoprotein lb. In addition, platelet aggregation by four patient sera was inhibited by aspirin or apyrase indicating a prostaglandin synthesis and ADP‐dependent mechanism and the reaction could be suppressed by dipyridamole alone. However, platelet aggregation induced by the serum of one patient was only inhibited partially by the combination of aspirin and apyrase suggesting mediation of the antibody effect in part by a pathway independent of extracellular ADP and prostaglandin synthesis and this antibody reaction could only be completely suppressed by a combination of aspirin and dipyridamole. Heterogeneity exhibited by these antibodies may influence the choice and effectiveness of antiplatelet therapy in heparin‐induced thrombocytopenia.
Mast cell leukaemia: evidence for bone marrow origin of the pathological clone
Authors: Dalton R. , Chan L. , Batten E. , Eridani S.
Published: March 2008

Summary. A 57‐year‐old female patient, admitted for an acute abdominal syndrome, was found to have an extensive proliferation of mast cells both in the peripheral blood and the bone marrow. Cytochemical studies confirmed the mast cell characteristics of the pathological cell population, while the immuno‐phenotype strongly suggested a bone marrow origin of this malignancy.

The course of the disease was not affected by antiproliferative treatment and the patient, after progressive general deterioration, died of intractable haemorrhage. On both clinical and haematological criteria it seems possible to distinguish this rare case of primary mast leukaemia from the more common form of tissue mastocytosis with secondary leukaemia.
Acute lymphoblastic leukaemia after bone marrow transplantation for aplastic anaemia
Authors: Klingemann H.‐G. , Storb R. , Sanders J. , Deeg H. J. , Appelbaum F. R. , Thomas E. D.
Published: March 2008

Summary

An 11 · 5‐year‐old girl developed acute lymphoblastic leukaemia 7 months after bone marrow transplantation for severe aplastic anaemia. Before transplantation there were neither morphologic nor cytogenetic abnormalities to suggest preleukaemia. The conditioning regimen consisted only of cyclophosphamide. At the time of development of acute lymphoblastic leukaemia, chromosome analysis showed the blasts to be of host origin with clonal abnormalities including monosomy 7. Such a preleukaemic syndrome presenting as severe aplastic anaemia is a very rare event (the case reported here is the only one of 436 patients in Seattle) and cannot be reliably excluded before transplantation.
T cell‐mediated inhibition of haematopoiesis in aplastic anaemia: serial assay of inhibitory activities of T cells to autologous CFU‐E during immunosuppressive therapy
Authors: Hanada Takashi , Aoki Yasuko , Ninomiya Haruhiko , Abe Tsukasa
Published: March 2008

Summary

T cell‐mediated inhibition of autologous erythroid colony formation was found in two patients with aplastic anaemia. Each patient was treated separately with ALG and methylprednisolone. Peripheral blood T cells were cryopreserved serially during the course of the disease. The inhibitory activity of T cells was assayed after remission using autologous bone marrow. The inhibitory activity of T cells was lost following the treatment and preceded haematopoietic recovery.
Abnormalities of von Willebrand factor in myeloproliferative disease: a relationship with bleeding diathesis
Authors: Fabris Fabrizio , Casonato Alessandra , Del Ben Maria Grazia , Marco Luigi De , Girolami Antonio
Published: March 2008

Summary

We studied factor VIII related properties in 24 patients with increased platelet number. Twenty‐one were affected by myeloproliferative disorders (eight had polycythaemia vera, 13 had essential thrombocythaemia) and three had secondary thrombocytosis. Normal levels of VIII: C and VIIIR: Ag were found while a significant (P<0.05) decrease of VIIIR:RCOF (43 ± 13%) related to a lack of larger multimers of VWF (39 ± 12%) was observed in 57% of patients with myeloproliferative disorders. A normal VWF pattern was found in the three patients with secondary thrombocytosis. The highest incidence of VWF abnormalities occurred in patients with essential thrombocythaemia (70%) in comparison with polycythaemic patients (38%). A significant (P<0.03) correlation between platelet count and the values of both VIIIR: RCOF and VWF multimeric pattern was observed only in patients with polycythaemia vera. The lowest levels of VIIIR: RCOF and the greatest loss of larger VWF multimers (less than 30%) were observed in two patients who presented bleeding symptoms at the time of study and a prolonged bleeding time. In addition, the relationship between VWF pattern and bleeding diathesis was supported by the fact that 75% of the patients with VWF abnormalities had bleeding history.
Immunological abnormalities in myelodysplastic syndromes I. SERUM IMMUNOGLOBULINS AND AUTOANTIBODIES
Authors: Mufti G. J. , Figes Ann , Hamblin T. J. , Oscier D. G. , Copplestoni J. A.
Published: March 2008

Summary

The immunoglobulin levels and autoantibody profiles of 104 patients with primary myelodysplastic syndromes (MDS), classified according to the FAB criteria, were analysed. Eight patients, four with coexistent non‐Hodgkin's lymphomas, three with chronic lymphocytic leukaemia and one with a lymphoplasmacytoma, were excluded from the final analysis of immunoglobulin levels. Serum protein electrophoresis and immunoelectro‐phoresis revealed the presence of monoclonal gammopathy in 12 patients (12·5%). Of the remaining 84 patients, a polyclonal rise in serum immunoglobulins was present in 27 (32%) while a further 16 (19%) had low immunoglobulin levels. The direct antiglobulin test was positive in eight out of 98 patients tested (8·1%), and organ and non‐organ specific autoantibodies were present in 15 out of 67 patients tested (22·3%). Two patients had associated pernicious anaemia (PA), two hypothyroidism, and one PA with hypothyroidism. Three patients had sero‐negative rheumatoid arthritis. These results demonstrate that there is a high incidence of immunological abnormalities in MDS.
The treatment of hairy‐cell leukaemia with 2′‐deoxycoformycin
Authors: Johnston J. B. , Glazer R. I. , Pugh L. , Israels L. G.
Published: March 2008

Summary

Eight patients with hairy‐cell leukaemia (HCL) complicated by pancytopenia were treated with low dose regimens of the adenosine deaminase (ADA) inhibitor 2′‐deoxycoformycin (DCF). All patients had significant haema‐tological and clinical improvement. One patient who had been splenectomized and five patients with mild to moderate splenomegaly achieved normal blood counts within 2 months, which have been maintained for up to 18 months. Complete remissions occurred in two patients and four patients had 50–95% marrow clearance of hairy cells. The initial DCF treatments produced a 1–3 g/dl fall in the haemoglobin levels and one patient had a temporary reduction in granulocyte and platelet counts. Five patients had nausea/vomiting, and/or lethargy following DCF, but there was no correlation between the plasma levels of deoxyadenosine and adenosine and the incidence or severity of these side effects. An increased incidence of infection and drug hypersensitivity may reflect the effects of DCF on the immune system. Low dose DCF is a highly effective agent in HCL.
Acute megakaryoblastic leukaemia in children
Authors: Elizabeth A. , Cairney L. , Mckenna Robert , Arthur Diane C. , Nesbit Mark E. , Woods William G.
Published: March 2008

Summary

We report four children with acute megakaryoblastic leukaemia (AMKL) and compare their clinical course with 16 previously reported cases of AMKL in children. In adults, AMKL has been reported as a rapidly progressive disease characterized by pancytopenia associated with bone marrow fibrosis, absence of organomegaly, and unresponsiveness to therapy. Although some of the childhood cases present with these features, the clinical course can be quite variable, particularly in young children, with both organomegaly and leuco‐cytosis occurring. Down syndrome, or other constitutional abnormalities of chromosome 21 were present in four of 20 reported cases. Two of the four cases reported herein were initially diagnosed cytologically as childhood acute lymphoblastic leukaemia (ALL). All four patients achieved a complete remission, and three remain in remission from 34 to 56 months from diagnosis. Greater recognition of AMKL in the future will help to clarify the disease characteristics, prognosis and optimal treatment of this unusual form of leukaemia.
Anti‐granulocyte opsonic activity and autoimmune neutropenia
Authors: Hadley A. G. , Holburn A. M. , BUNCH C. , CHAPEL H.
Published: March 2008

Summary

Sera from patients with unexplained neutropenia have been assayed for anti‐granulocyte opsonic activity using a chemiluminescence technique which measures the metabolic response of human monocytes to antibody‐coated granulocytes. This rapid and simple technique was more sensitive than indirect immunofluorescence in the detection of anti‐granulocyte antibodies.
Lymphocyte function after autologous bone marrow transplantation (BMT): a comparison with patients treated with allogeneic BMT and with chemotherapy only
Authors: Armitage R. J. , Goldstone A. H. , Richards J. D. M. , Cawly J. C.
Published: March 2008

Summary

T‐ and B‐cell function after autologous bone marrow transplantation (ABMT) was assessed and compared with that found after allogeneic BMT and after chemotherapy only. In all 16 patients with acute leukaemia in remission treated with high‐dose chemotherapy and single or double ABMT, T‐helper numbers and function in an assay measuring PWM‐iriduced lg synthesis were grossly defective and closely resembled the defects observed after allo‐BMT involving chemoradiotherapy (six patients). T‐helper activity was more variable after chemotherapy only (eight patients), but in individual patients the defect was as great as that observed after BMT. In contrast, suppressor activity was comparably increased in all patient groups and increased numbers of Leu 15+ Dr+ Tac‐ suppressor T cells were consistently observed, suggesting chronic activation of suppressor T cells, the cause of which remains unknown. B‐cell function was also uniformly impaired in all patients tested. It is therefore concluded that defective immune function after BMT is not due to alloimmunc or radiotherapy‐mediated effects. Furthermore, since many patients were studied a prolonged period after BMT and had no T cells with a thymic phenotype and no evidence of infection, it is unlikely that the delects are secondary to cellular immaturity following marrow regeneration or to superadded infection. The gross immune defects observed after various forms of BMT are likely, therefore, to be directly attributable to the chemotherapy involved.
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

Summary

Bone 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.
Evidence against immune haemolysis in falciparum malaria in Thailand
Authors: Merry A. H. , Looareesuwan Sornchai , Phillips R. E. , Chanthavanich Pornthep , Supanaranond Wichai , Warrell D. A. , Weatherall D. J.
Published: March 2008

Summary.Evidence of immune mediated haemolysis was sought in 83 patients withP. falciparummalaria in eastern Thailand. Amongst 73 patients with uncomplicated infection 12 (16.4%) had a weakly positive direct antiglobulin test (DAT). The incidence in 32 children aged 8–16 years was similar to that in adults. Of 10 patients with cerebral malaria, six adults, all of whom were in unrousable coma, had a positive DAT. Erythrocyte‐bound IgG1accounted for the positive DAT in all cases; sensitization with complement or other IgG subclasses was not found. Patients with uncomplicated malaria had a median value of 70 IgG molecules per erythrocyte compared with 65 molecules per cell in 67 healthy controls. This difference was not statistically significant but could account for the lower incidence of a positive DAT in control subjects (4.5%). There was no correlation between the number of IgG molecules per cell and the degree of anaemia during the acute or convalescent phases of the infection. There is no evidence from this study that an immunohaemolytic process contributes to the anaemia of falciparum malaria in eastern Thailand.
Colony formation by megakaryocytic progenitors in essential thrombocythaemia
Authors: Juvonen E. , Partanen S. , Ruutu T.
Published: March 2008

Colony 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

Red 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

Cytogenetic 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

The 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

A 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

Human 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

Twenty‐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

The 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

The 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

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

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.
Changes of the phenotype of erythroid progenitor cells (BFU‐E, CFU‐E) and their progenies during early steps of differentiation
Authors: Peschel C. , Konwalinka G. , Geissler D. , Braunsteiner H. , Knapp W.
Published: March 2008

Summary. Early differentiation processes of human erythroid progenitor cells (BFU‐e. CFU‐e) have been studied during in vitro proliferation using a panel of monoclonal antibodies with known reactivity on different levels of the erythroid cell line. Two antibodies recognizing structures on BFU‐e (VIP‐2b, BMA 021). two antibodies reactive with CFU‐e and nucleated red cells (5F1, CLB‐Ery‐3) and one antibody directed against glycophorin A (VIE‐G4) were used for this study. Normal human bone marrow cells were induced to proliferation in an erythroid progenitor cell assay and, after different periods of incubation, agar cultures were treated with these antibodies and complement. Thereafter, the remaining erythroid cells were incubated again to continue their proliferation with the same stimulators as before. The changes of the phenotype of BFU‐e and CFU‐e progenies during in vitro proliferation were determined by the reduction of colony formation in comparison with untreated control cultures. Our results indicate that the loss of HLA‐DR antigens and the p45 structure is accompanied by the acquisition of structures recognized by the antibodies 5F1 and CLB‐Ery‐3. After 5–7 d of incubation BFU‐e derived progenies exhibit the same antigenic structure as has been found for CFU‐e. Glycophorin A expression could only be demonstrated at a late differentiation stage of the erythroid cell lineage.
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.
Simultaneously increased expression of the c‐myc and, mU chain genes in the acute blastic transformation of a chronic lymphocytic leukaemia
Authors: Torelli Umberto L. , Torelli Giuseppe M. , Emilia Giovanni , Selleri Licia , Venturelli Donatella , Artusi Tullio , Donelli Amedea , Colò Alessandro , Fornieri Claudio
Published: March 2008

Summary. A B‐cell chronic lymphocytic leukaemia terminated, 5 years from the onset, with a blast crisis. Karyotype analysis showed that the terminal lymphoblastic population evolved from the original B lymphocytic clone. The levels of expression of several oncogenes, as well as the μ chain gene, were assayed by Northern blot hybridization analysis of RNA extracted from the lymphoid populations before and after the acute transformation'. A seven‐ to eight‐fold increase in the expression of c‐myc and p chain genes was observed in the blast population. c‐myb. c‐fes. c‐tiaras were not expressed either before or after the blastic transformation.
Red cell Th activation: biochemical studies
Authors: Herman Jay H. , Whiteheart Wally , Shirey R. Sue , Johnson Robert J. , Kickler Thomas S. , Ness Paul M.
Published: March 2008

Summary. The peanut agglutinin from Arachis hypogea is a lectin that reacts with red blood cells expressing the Th antigen. The Th antigen has been said to be qualitatively similar to the T antigen, a well‐defined antigen due to desialylation of glycophorin A and B that also reacts with the peanut agglutinin. We examined Th activated red blood cells from two patients with Fanconi's anaemia using 125I radio‐labelled peanut agglutinin as a probe in Western blotting of red blood cell membrane proteins. We also probed the surface of intact Th activated red blood cells for structures related to the T antigen using [3H]sialic acid and a purified sialyltransferase. Neither of these techniques found antigens on the Th activated red blood cells that were similar to the antigen found on T activated red blood cells. These results show that the Th antigen in Fanconi's anaemia is qualitatively different to the antigen found in T activation.
Haplotypes and α globin gene analyses in sickle cell anaemia patients from Kenya
Authors: Ojwang P. J. , Ogada T. , Beris P. , Hattori Y. , Lanclos K. D. , Kutlar A. , Kutlar F. , Huisman T. H. J.
Published: March 2008

Summary. Over 60 patients from the Luo and Luhya tribes of Western Kenya, aged 1–23 years. with severe sickle cell anaemia were evaluated through haematological and gene mapping analyses. Nearly all (56 of 58 tested) were homozygous for haplotype 20 (Antonarakis et al, 1984) which is also frequently present in SS patients of the Central African Republic. All patients had a severe haemolytic anaemia with low Hb F levels and low levels of Gγ chains. An α‐thalassae‐mia‐2 heterozygosity (‐α/αα; ‐ 3·7 kb deletion) was present in 26 of 53 patients tested: one patient was a homozygote [f(—α) = 0·255]. The α‐thal‐2 was type I in all but one subject with this deficiency; the one exception had an α‐thal‐2 heterozygosity, type II. Heterozygosity for the α‐thal‐2 did not affect the clinical condition nor the haematology; Hb F levels were somewhat lower in SS patients with —α/αα than in those with αα/αα. A high frequency was observed for the absence of an Xba I restriction site 5′ to the ξ globin gene; the frequency of this anomaly [f(Xba I‐)] was estimated at 0·39 for the chromosome with two α globin genes and at 0·74 for that with the α‐thal‐2 deletion. An Apa I restriction site polymorphism was observed in the IVS‐II of the α2 globin gene; 13 α2 genes of 53 normal (αα/) chromosomes had this restriction site which was absent in the hybrid α globin gene of the —α/ chromosome.
Cytogenetic study of myeloid and erythroid colonies in chronic myeloid leukaemia with stable Ph1 mosaicism
Authors: Cramer Ph. , Vainchenker W. , Brouet J. C. , Berger R.
Published: March 2008

Summary. We have investigated two chronic myeloid leukaemic (CML) patients with a stable Ph1 mosaicism to see whether the Ph1 positive cells belonged to more than one lineage. Individual erythroid and granulocytic colonies were cytogenetically examined. Ph1‐positive and Ph1‐negative colonies were found both in the erythroid and granulocytic lineage supporting the contention that CML with a stable Ph1 mosaicism as well as classical CML involves a pluripotent stem cell.
Congenital dyserythropoietic anaemia type II (HEMPAS): characterization of aberrant intracellular organelles by immunogold electron microscopy
Authors: Fukuda Michiko N. , Klier George , Scartezzini Paolo
Published: March 2008

Summary. Erythrocytes and reticulocytes obtained from peripheral blood of a congenital dyserythropoietic anaemia type II patient were examined by immunoelectron microscopy using anti‐band 3 and anti‐glycophorin A antibodies. Vacuoles which have membranous structures inside were stained heavily by these antibodies, indicating the presence of band 3 and glycophorin A in these vacuoles. Empty vacuoles which open to the cell surface and those present in cytoplasm were also stained by these antibodies at the inside of the wall. These observations suggest that the vacuoles are functioning for trapping and discarding the defective plasma membranes. On the other hand, small vesicles and ferritin‐loaded vacuoles were not stained by these antibodies. In these experiments, peripheral cisternae and most of the intracellular membranous structures at blebs and clefts were not stained by the antibodies. Therefore, they are probably part of the endoplasmic reticulum or are derived from intracellular organelles but not from the plasma membranes.
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

To 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.