bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneous Blast Cell Crises in Philadelphia Negative Chronic Granulocytic Leukaemia
Authors: Hughes Andrew , McVerry B. A. , Walker H. , Bradstock K. F. , Hoffbrand A. V. , Janossy G.
Published: March 2008

Summary. A case of Philadelphia negative chronic granulocytic leukaemia (Ph1‐ CGL) is described showing features only previously demonstrated in Ph1+ disease. These features include: (1) lymphoid blast crisis, determined by morphology and immunological marker analysis; (2) dual blast cell populations that can be distinguished both morphologically and by immunological markers; (3) clonal evolution, as shown by the emergence of chromosome markers and in one of the cell lines a change in membrane phenotype. These changes were apparently associated with the emergence of a relatively drug resistant subclone of leukaemic cells. This study demonstrates that the lymphoid blast crisis of CGL, and its sequelae, can occur in Ph1‐ cases. It is similar in respect to morphology, enzyme, and membrane markers and responsiveness to vincristine and prednisolone therapy to the lymphoid blast crisis seen in Ph1+ CGL. This suggests that the Philadelphia chromosome is a clonal marker only, and its presence is not directly related to the subsequent clinical course of the disease.
A Complex Ph1 Translocation in a Patient with Primary Thrombocythaemia
Authors: Fitzgerald P. H. , McEwan Christine , Fraser Jan , Beard M. E.J.
Published: March 2008

Summary. Routine blood examination of a 27‐year‐old female revealed a platelet count of 2000 109/1. Bone marrow cells showed the Philadelphia chromosome which was one product of a complex rearrangement of chromosomes 9, 22 and X. Her platelet count was lowered by plateletphoresis and chemotherapy. She remains in good health 19 months later, but her thrombocythaemia is considered to be an early manifestation of chronic myeloid leukaemia.
Heat‐induced Radial Segmentation of Leucocyte Nuclei: a Non‐specific Phenomenon Accompanying Inflammatory and Necrotizing Diseases
Authors: Neftel K. A. , Müller O. M.
Published: March 2008

Summary. Heat‐induced radial segmentation (RS) of leucocyte nuclei in vitro (2 h at 41°C) is a heretofore unknown phenomenon, accompanying inflammatory and necrotizing diseases. This phenomenon appears to be identical with the known oxalate‐induced radial segmentation and is caused by contractile microfilaments and microtubuli radiating from the centriole. Preincubation of washed leucocytes from healthy donors with plasma of patients showing the phenomenon of RS did not induce RS and preincubation of washed RS‐leucocytes with normal plasma did not suppress RS. RS, however, could be induced by intravenous endotoxin injection in a healthy volunteer and could be prevented in part by addition of Vincristine to the blood samples. The phenomenon corresponds to an incomplete, heat‐inducible amitosis. The cause of the thermolability of the mitotic apparatus in various diseases remains unclear.
Peripheral Neuropathy and Plasma Cell Neoplasias: a Report of 10 Cases
Authors: Delauche Marie Christine , Clauvel Jean Pierre , Seligmann Maxime
Published: March 2008

Summary. Ten patients with peripheral polyneuropathy associated with plasma cell neoplasias are reported. Progressive sensorimotor polyneuropathy was the presenting complaint in all patients. CSF protein concentration was elevated in most patients. The electrophysiological and pathological changes were consistent with a primary segmentary demyelinating disease. All patients were male and younger than the average patient with myeloma. None presented with high tumour mass or overt multiple myeloma. Six were affected with single or multiple plasmacytomas with osteolytic lesions. Unusual haematological features such as polycythaemia, thrombocytosis and lymphadenopathy were often combined with the polyneuropathy. Skin hyperpigmentation, gynaecomastia and diabetes mellitus were noted in some patients. Complete recovery of the polyneuropathy was observed in some patients after either cyclophosphamide and corticosteroid therapy or radiotherapy of localized plasmacytoma, suggesting a direct relationship between the plasmacytic proliferation and the neuropathy. The nature of the postulated factor produced by the plasma cells and responsible for nerve injury is discussed and the importance of a careful search for plasma cell proliferation in men with obscure polyneuropathies is outlined.
Effect of Oxymetholone on Human Cyclic Haematopoiesis
Authors: Roozendaal K. J. , Dicke K. A. , Boonzajer Flaes M. L.
Published: March 2008

Summary. A 62‐year‐old woman had recurrent fluctuations of neutrophil, monocyte, reticulocyte and platelet counts with a cycling time of 38.5 d. Periodic fluctuations of granulo‐, erythro‐ and megakaryopoiesis were also demonstrated in her bone‐marrow. Oxymetholone reduced the magnitude of the profound cyclic fluctuations in all these cell lines. During treatment a reduced number of in vitro CFU‐C of the progenitor myeloid series from the bone marrow was observed. Using the patient leucocytes as feeders for normal control marrow cells, indication was found for a fluctuation in colony stimulating activity in vitro, rising above normal at the nadir of the WBC.
Effects of Shortened Erythropoietin Exposure on Sheep Marrow Cultures
Authors: Roodman G. D. , Kaplan J. M. , Kaplan M. E. , Zanjani E. D.
Published: March 2008

Summary. To determine whether erythropoietin (Ep) is required only to trigger, or also to sustain the growth of erythroid progenitor (CFU‐E) in vitro, the effect of limiting the time of exposure of sheep bone marrow CFU‐E to Ep on erythroid colony (EC) formation was examined. Restricting the in vitro exposure of CFU‐E to 2–24 h, either by brief preincubation with Ep or by neutralization of Ep present in culture with anti‐Ep, resulted in a 70–90% reduction of EC formation, and the colonies that were produced were of a small size. In contrast, no inhibition of EC size or number occurred when CFU‐E were exposed to Ep for more than 24 h. These results suggest that Ep also modulates the proliferative events subsequent to the initial triggering of CFU‐E which lead to the formation of erythrocytes.
Inhibitor of in Vitro Neutrophil Migration in Sera of Children with Homozygous Sickle Cell Gene during Pain Crisis
Authors: Akenzua Gregory I. , Amiengheme Okpiaifo R.
Published: March 2008

Summary. There is conflicting evidence for a causal relationship between infection and haematological crisis of sickle cell disease. To find out whether changes in leucotaxis occur during pain crisis, in‐vitro neutrophil migration was determined in 38 children with Hb SS during steady state and during pain crisis. Migration of neutrophils of sickle cell patients was 29 12 μm in steady state and 27.5 10.5 μm during pain crisis. These rates were comparable to migration of neutrophils of control children with normal haemoglobin of 34 9.6 μm. However, with addition of autologous serum to the cell suspension, neutrophil migration of patients in pain crisis was significantly retarded (16 13 μm) as compared to those in steady state (26 10.2 μm) and control children (28.7 10 μm). Sera of children in pain crisis also inhibited migration of neutrophils of healthy adults with normal Hb. Pooled normal plasma reversed inhibitory action of pain crisis serum on autologous and homologous neutrophil migration; but pain crisis plasma did not.

Chemotactic effect of sera of Hb SS children in steady state or pain crisis and control children on neutrophils of eight adults with normal Hb were similar and comparable to that of pooled normal serum. Thus, children with sickle cell disease develop chemotactic inhibitor(s) in their circulation during pain crisis. This may lead to defective leucotaxis and enhanced susceptibility to infection.
Congenital Methaemoglobinaemia due to NADH Methaemoglobin Reductase Deficiency: Successful Treatment with Oral Riboflavin
Authors: Hirano M. , Matsuki T. , Tanishima K. , Takeshita M. , Shimizu S. , Nagamura Y. , Yoneyama Y.
Published: March 2008

Summary. A Japanese family with congenital methaemoglobinaemia is described. The family pedigree was compatible with autosomal recessive type of inheritance. The increased methaemoglobin concentration was ascribed to the red cell NADH diaphorase deficiency associated with the almost complete lack of one of the two peaks of the diaphorase activity as separated by DEAE Sephadex column chromato‐graphy. The NADH diaphorase and NADH methaemoglobin reductase deficiency was limited to the red cells. The methaemoglobin content in the blood of the propositus was 17.8% and isoelectric focusing analysis on a polyacrylamide gel plate showed that the haemoglobin consisted of 65.2% oxyhaemoglobin (α2+β2+)2, 29.6% half‐oxidized forms, 20.9% (α+β2+)2 and 8.7% (α2+β+)2, and 3% full‐oxidized methaemoglobin (α+β+)2. Oral administration of riboflavin 120 mg/d resulted in a gradual but significant decrease in the level of the met‐form haemoglobins in parallel with a gradual increase in the red cell flavin content. Riboflavin is considered to be effective by activating the NADPH diaphorase (NADPH flavin reductase) system and appears to be useful for the treatment of congenital methaemoglobinaemia.
Antibody‐dependent Cell‐mediated Cytotoxicity (ADCC) of Penicillin‐treated Human Red Blood Cells
Authors: Yust Israel , Frisch B. , Goldsher Naomi
Published: March 2008

Summary. Penicillin‐treated human red blood cells (RBC) were lysed by the cooperation of autologous nonsensitized peripheral blood mononuclear cells and human anti‐penicillin serum. Using a rapid (3 h) assay of antibody‐dependent cell‐mediated cytotoxicity (ADGC), lysis was proportional to serum (anti‐penicillin antibody) concentration, to incubation time and to the concentration of attacking cells, which were obtained from normal human peripheral blood by Ficoll‐Hypaque separation. Incubation of these lymphoid effector cells on a nylon column prior to the tests depleted the number of phagocytic (latex positive) cells in the effluent; there was a concomitant drop in cytotoxic activity. Enrichment of mononuclear phagocytes in the attacking cell population by albumin gradient separation led to an increase in cytotoxicity. Granulocytes separated by Ficoll‐Hypaque were not active in this system. Using specific antisera the antibody was found to be of the IgG1 sub‐class. Anti‐penicillin antibody activated the complement system in vitro, but failed to induce lysis of penicillin‐treated RBC in the presence of complement without attacking cells.

These results suggest that ADCC may participate in the destruction of RBC in penicillin‐induced haemolysis in vivo.
Morphology and Kinetics of Erythropoiesis in Haemoglobin H Disease
Authors: Wickramasinghe S. N. , Hughes Madeleine , Wasi Prawase , Fucharoen Suthat
Published: March 2008

Summary. Some aspects of erythroblast function have been investigated in two Thai patients with haemoglobin H disease. Electron microscope and high resolution autoradiographic studies revealed that (1) some erythroblasts and marrow reticulocytes contained branching intracytoplasmic inclusions and (2) the presence of such inclusions did not necessarily prevent the entry of cells either from the G1 phase into the S phase or from the G2 phase into mitosis. The distribution of early polychromatic erythroblasts in the different stages of the cell cycle was determined by the technique of combined Feulgen microspectrophotometry and 3H‐thymidine autoradiography and found to be essentially normal. It is concluded that although the presence of an excess of α‐chains in the β‐thalassaemia syndromes has been previously shown to be associated with a gross impairment of erythroblast proliferation, the presence of an excess of β‐chains in HbH disease is not.
Ferritin Concentration in Normal and Abnormal Erythrocytes Measured by Immunoradiometric Assay with Antibodies to Heart and Spleen Ferritin and Mössbauer Spectroscopy
Authors: Jacobs A. , Peters S. W. , Bauminger E. R. , Eikelboom J. , Ofer S. , Rachmilewitz E. A.
Published: March 2008

Summary. Immunoradiometric assays using antibodies to spleen and heart ferritin were combined with Muössbauer studies on normal and pathological erythrocytes. All erythrocytes examined were found to contain greater amounts of heart type than spleen type ferritin. The ferritin concentration in erythrocytes from patients with β thalassaemia, sickle cell disease and sideroblastic anaemia is much higher than in normal cells. When the concentration of ferritin‐like iron in the pathological erythrocytes measured by Mössbauer spectroscopy is compared to the total amount of ferritin assayed by the two antibodies in the same haemolysates the iron/protein ratio ranges between 0.3 and 3.4. The iron/protein ratio in iron‐filled ferritin molecules is about 0.56 and values in excess of this suggest that the iron detected in these cells is a mixture of ferritin molecules, partly denatured ferritin polymers and ‘haemosiderin’. There is a possibility that erythrocytes contain an immunologically distinct type of ferritin that is not detected by existing assays, but we have no direct evidence for this.
Histone Variant Composition of Normal and Leukaemic Human Lymphocytes: Analysis by Gel Electrophoresis of Whole Cells and Nuclei
Authors: Froussard Patrick , Tempelis Laurence D. , Levy Stuart B.
Published: March 2008

Summary. The histone variant composition of normal and leukaemic lymphocytes was analysed using a method which circumvented endogenous cellular proteolysis. Whole cells were solubilized in buffer containing protamine which released the histones from the DNA and allowed their immediate analysis by Triton X‐100‐acetic acid‐urea gel electrophoresis. The results were comparable to those obtained with histones which had been acid‐extracted from cells, nuclei or chromatin; however, the new method was more reproducible since proteolysis was controlled. By histone variant analysis, chronic lymphocytic leukaemia patients could be separated into two groups. One group had lymphocytes with a histone H2a variant ratio of about 1.0; this finding resembled lymphocytes (75‐85% T cells) from normal individuals. The larger group had lymphocytes with a reproducibly lower histone H2a variant ratio; these cells had a relative increase in the second variant, H2a.2. The two groups of patients could not be distinguished by clinical disease state. No other differences were noted in the histone variant composition of lymphocytes from normal and leukaemic individuals.
Haemoglobin Synthesis by Fetal Erythroid Cells in an Adult Environment
Authors: Bunch Christopher , Wood W. G. , Weatherall D. J. , Robinson J. S. , Corp M. J.
Published: March 2008

Summary. Although the developmental switch from fetal to adult haemoglobin production has been well characterized in terms of protein synthesis, very little is known about its control at the cellular level. In order to determine whether the switch is controlled by environmental factors or programmed into the haemopoietic cell population, we have studied the effects of transplantation of fetal and adult haemopoietic cells into lethally irradiated lambs on haemoglobin synthesis by the transplanted cells. In two lambs which were irradiated but not transplanted, two lambs which were grafted with autologous marrow, and one lamb which was grafted from an allogeneic twin, haemoglobin synthesis showed an adult pattern following transplantation, with γ‐chain synthesis never exceeding 7% of non‐α chain production. Of 11 lambs transplanted with fetal haemopoietic cells, only two showed evidence of engraftment. During the 24‐26 d that these animals survived, haemoglobin synthesis showed a predominantly fetal pattern, though there was a gradual increase in β‐chain production of donor origin. This increase occurred earlier than would be expected from the gestational age of the transplanted cells, but more slowly than might be expected if environmental factors were entirely responsible for expression of adult or fetal haemoglobin synthesis.
Racial Differences in Ristocetin‐induced Platelet Aggregation
Authors: Buchanan George R. , Holtkamp Christine A. , Levy Eric N.
Published: March 2008

Summary. Several investigators have reported defective ristocetin‐induced platelet aggregation (RIPA) in individuals whose red blood cells contain sickle haemoglobin, but the race of control subjects in these studies was not stated. Therefore, maximal amplitude of RIPA was examined in 75 normal whites and blacks, 16 of whom had sickle trait defined by haemoglobin electrophoresis and sickle prep. Final ristocetin concentrations in platelet rich plasma were 1·1,1·2 and 1·5 mg/ml. Mean aggregation at 1·1 mg/ml was significantly less in blacks (mean 31%) than in whites (mean 72%) (P < 0·001). 60% of blacks but only 11% of whites had less than 50% RIPA at 1·1 mg/ml. RIPA was entirely absent in 19% of blacks. Differences in RIPA between black and white subjects were also present at ristocetin concentrations of 1·2 and 1·5 mg/ml but were less striking. RIPA in 25 children with homozygous sickle cell anaemia was similar to that in the normal AA and AS blacks. Differences in RIPA could not be explained by age, sex, presence of sickle haemoglobin, or medications. Addition of normal plasma or platelets did not correct reduced RIPA in seven blacks, and their plasma inhibited normal RIPA responses.

Reduced platelet aggregation to low concentrations of ristocetin is a normal finding in many blacks, is not related to the presence of sickle haemoglobin, and appears to be due to a plasma inhibitor against RIPA.
Growth of Human Erythroid and Erythroid‐Granulocytic Colonies in Culture without Addition of Exogeneous Erythropoietin
Authors: Nishihira Hirokazu , Kigasawa Hisato
Published: March 2008

Summary. Growth of human erythroid and erythroid‐granulocytic colonies was investigated in a fibrinogen clot culture system. CFU‐E, BFU‐E, CFU‐C and the mixed colonies were grown in cultures in medium conditioned by phytohaemagglutinin‐stimulated human mononuclear cells, with small amounts of aplastic anaemia serum, but no exogeneous erythropoietin (Epo). The level of Epo in the culture was 0·015 U. The mixed colonies constituted 8‐22% of the total of colonies grown. The results indicate that high dose Epo is not required to grow BFU‐E and the mixed colonies in cultures containing erythroid potentiating factor(s), and the frequency of bipotent haemopoietic stem cells in human bone marrow or peripheral blood may be higher than that reported previously.
Ferritin Polymers and the Formation of Haemosiderin
Authors: Hoy T. G. , Jacobs A.
Published: March 2008

Summary. When ferritin is isolated from Chang liver cells in culture iron loading is found to be associated with changes in the surface of the protein shell characterized by a change in immunoreactivity to anti ‘heart’and anti ‘spleen’antibodies at each specific pI and an overall shift in isoferritins to a lower pI range (Hoy & Jacobs, 1981). Ferritin polymers have been isolated from human tissues and their biochemical properties assessed in terms of these surface changes and the iron/protein ratio of the molecules.

The results suggest that changes in the surface of ferritin molecules are associated with the formation of stable polymers. These are precursors of clumps of ferritin and eventually haemosiderin. Changes in the surface of the molecule may provide a signal for polymerization and incorporation of the protein within the lysosomes.
T‐Cell Subpopulations in Multiple Myeloma: Correlation with Clinical Disease Status
Authors: Oken Martin M. , Kay Neil E.
Published: March 2008

Summary. T‐lymphocyte subpopulations bearing Fc receptors for IgM (Tμ) or for IgG (Tγ) were studied in blood specimens obtained from 40 normal volunteers and from 16 patients with multiple myeloma. The myeloma patients showed a significant imbalance in T‐cell subpopulations characterized by an increase in the percentages of Tγ cells to 30·0 ± 3·9% (mean ± SEM) compared with 12·0 ± 3·0% for the controls (P < 0·001). The patients exhibited a decreased proportion of Tμ cells (13·4 ± 4·1%) compared with the control value of 55 ± 7% (P < 0·001). When the results were analysed according to clinical status it was the patients with indolent or well‐controled disease and not those with progressive disease who exhibited an elevated proportion of Tγ cells. The elevation of Tγ cells or of a subpopulation of suppressor cells should be further studied as a possible mechanism of disease control in multiple myeloma.
Molecular ferrokinetics in the rabbit
Authors: Groen Roger , Hendricksen Peter , Young Stephen P. , Leibman Adela , Aisen Philip
Published: March 2008

Summary. Using urea‐polyacrylamide gel electrophoresis it has been possible to distinguish the molecular forms of transferrin in rabbit serum. When 59Fe‐labelled diferric transferrin is injected into normal, anaemic or hypertransfused, polycythaemic rabbits, iron is removed from diferric transferrin in essentially pairwise fashion. Exchange of iron between transferrin and tissues was also studied using predominantly monoferric transferrin labelled with 59Fe or 125I, and with 125I‐labelled apotransferrin. The return of iron from tissue stores to circulating transferrin occurs one atom at a time to either site of the protein and, possibly, in pairwise fashion as well. The rate of clearance of iron from diferric transferrin differs from that of monoferric transferrins, and the rates at which iron is returned to empty sites of transferrin also differ, so that serum iron is not a kinetically homogeneous pool in the rabbit.
Quantitative evaluation of erythropoietic activity in dysmyelopoietic syndromes
Authors: Cazzola M. , Barosi G. , Berzuini C. , Dacco M. , Orlandi Ester , Stefanelli M. , Ascari E.
Published: March 2008

Summary. Based on the morphological appearances of the bone marrow and peripheral blood, 43 patients with dysmyelopoietic syndromes were categorized into four types: refractory anaemia with excess of blasts, chronic myelomonocytic leukaemia, primary acquired sideroblastic anaemia and refractory anaemia with cellular marrow, without excess of blasts and/or ring sideroblasts. Ferrokinetics allowed three distinct groups of patients to be defined. All cases of refractory anaemia with excess of blasts and chronic myelomonocytic leukaemia were classified in the same group. They were characterized by relative marrow failure and had a high likelihood of developing acute leukaemia. At the other end of the spectrum, individuals with primary acquired sideroblastic anaemia had high erythropoietic activity which was largely ineffective. They had a benign clinical course without evidence of leukaemic transformation. In the middle group, in terms of erythropoietic activity, lay patients with refractory anaemia with cellular marrow and a few individuals with primary acquired sideroblastic anaemia. Their clinical course and risk of developing acute leukaemia were intermediate between the other two groups. These findings indicate that separate entities may exist within the spectrum of dysmyelopoietic syndromes. In clinical practice, they may be recognized by morphological studies and other simple laboratory means.
Acute megakaryoblastic leukaemia associated with intrinsic platelet dysfunction and constitutional ring 21 chromosome in a young boy
Authors: Pui Ching‐Hon , Williams Dorothy L. , Scarborough Victoria , Jackson Carl W. , Price Robert , Murphy Sharon
Published: March 2008

A 3‐year‐old boy with pancytopenia and a paucity of circulating blast cells was found to have acute megakaryoblastic leukaemia. Histopathologic investigation of the bone marrow biopsy disclosed replacement by megakaryoblasts and mild‐to‐moderate reticulin fibrosis. the megakaryocytic origin of these cells was confirmed by their staining properties and by cross‐reactivity with rabbit anti‐rat platelet serum. Treatment with adriamycin and cytosine arabinoside induced a complete remission of this otherwise rapidly fatal disease. Before chemotherapy, the patient's platelets showed decreased aggregation in response to thrombin and adenosine diphosphate, as well as a defective thrombin‐induced serotonin release reaction. Neither functional defect resolved after remission induction, indicating that the platelets were intrinsically abnormal. Most striking was the finding of a constitutional chromosomal defect, a ring No. 21 chromosome, in addition to an abnormal malignant stem line. This appears to be the first reported instance of a constitutional r(21) chromosome associated with acute leukaemia.
Plasma betathromboglobulin and serum fragment E in acute partial stroke
Authors: De Boer A. C. , Turpie A. G. G. , Butt R. W. , Duke R. J. , Bloch R. F. , Genton E.
Published: March 2008

Plasma betathromboglobulin (BTG) and serum fragment E (FgE) were measured serially by radioimmunoassay for 7 d in 67 patients admitted with acute partial stroke. Twelve patients progressed within 7 d of admission. Plasma BTG was not different from normal in patients with acute partial stroke and did not increase significantly with stroke progression. Serum FgE was elevated in patients with acute partial stroke compared with normal values, and was significantly higher in patients who progressed compared with those who remained stable. The results indicate that fibrin formation may be more important in the process of stroke progression than activation of platelets.
ELIMINATION OF T‐LYMPHOCYTES FROM HUMAN BONE MARROW WITH MONOCLONAL T‐ANTIBODIES AND CYTOLYTIC COMPLEMENT
Authors: Granger Sylvia , Janossy G. , Francis Gillian , Blacklock Hilary , Poulter L. W. , Hoffbrand A. V.
Published: March 2008

Complement‐mediated cytolysis has been used to remove T‐lymphocytes from suspensions of human peripheral blood and bone marrow. Selective T‐cell removal was investigated by three monoclonal antibodies, OKT3, MBG6 and OKT11A. All three removed > 90% of T‐cells but combinations were necessary to kill > 99% of T‐cells in vitro. The macrophage‐granulocyte and erythroid colony forming cells of the bone marrow were spared. The method can be applied on bulk BM samples during clinical BM transplantation and will be useful to establish whether the virtually complete removal of T‐lymphocytes totally prevents transplant associated graft‐versus‐host disease in man.
The British type of non‐deletion HPFH: characterization of developmental changes in vivo and erythroid growth in vitro
Authors: Wood W. G. , MacRae I. A. , Darbre P. D. , CLegg J. B. , Weatherall D. J.
Published: March 2008

Further studies of a unique British family with a rare type of hereditary persistence of fetal haemoglobin (HPFH) have confirmed that this condition appears to result from a regulatory defect affecting globin gene expression. Adult heterozygotes for this disorder have 3.5–10.0% Hb F while homozygotes have 18–21% Hb F and in both cases the Hb F contained predominantly Aγ chains (89–94%). In all other respects these individuals were haematologically normal. Two obligate heterozy‐gotes were studied from birth, at which time both the proportion of Hb F and the Gγ/Aγ ratio were completely normal. There was a delayed decline in Hb F which continued well into childhood and a parallel decline in the proportion of Gγ chains. The growth of erythroid bursts showed no difference in number, size or erythropoietin responsiveness between homozygous HPFH, heterozygous HPFH or normal family members. Haemoglobin synthesis in these bursts showed the normal pattern of asynchrony between γ and β chain synthesis but there was an overall increase in γ chain production in the HPFH cases, particularly the homozygotes, compared to normal. In addition, the abnormal Gγ/Aγ ratio was faithfully reproduced in vitro. This condition appears to result, therefore, from a regulatory abnormality affecting the postnatal repression of γ chain synthesis.
Collagen synthesis by bone marrow stromal cells: a quantitative study
Authors: Bentley S. A.
Published: March 2008

Collagen‐producing, marrow‐derived adherent cells (MDAC) provide a microenvironment which supports haemopoietic stem cell (HSC) proliferation in vitro. To investigate the relationship between collagen‐producing cells in intact marrow and in MDAC cultures, quantitative studies of collagen synthesis were performed.

Collagen synthesis by fresh murine bone marrow cells was 0.22% of total protein synthesis and collagen types I and III were synthesized in a ratio of approximately 5:1. During MDAC cultivation, the collagen synthesis fraction increased to 2.3%. The relative amounts of type I and type III remained more or less constant. The MDAC monolayers showed characteristic pleomorphism, and were shown to support HSC proliferation in continuous bone marrow culture for periods of at least 5 weeks.

These results suggest that MDAC culture, under the conditions reported, selects a specific type of bone marrow connective tissue cell, probably a reticulum cell, which synthesizes collagen types I and III in a ratio of approximately 5:1.
Quantitation of RNA‐dependent platelet DNA polymerase in patients with myeloproliferative disorders
Authors: Strayer David R. , Brodsky Isadore , Caranfa Mary Jo , Gillespie David H.
Published: March 2008

Platelets from 28 patients with the myeloproliferative diseases (MPD) polycythaemia vera (9), essential thrombocythaemia (6), myelofibrosis with myeloid metaplasia (5) and chronic myelogenous leukaemia (8) were examined for an RNA‐dependent DNA polymerase activity using standardized conditions permitting highly reproducible quantitation. Low levels of activity were detected in platelets of normal individuals, but platelets of nearly all MPD patients (25/28) possessed higher levels. The polymerase activity correlated with diagnosis (P= 0.001) and did not correlate with platelet counts (P>0.2). Quantitation of this RNA‐dependent DNA polymerase activity may be a useful parameter in the diagnosis of myeloproliferative disorders.
Canine cyclic haematopoiesis: bone marrow adherent cell influence of CFU‐C formation
Authors: Jones J. B. , Jolly J. D.
Published: March 2008

Canine cyclic haematopoiesis (CH) appears to be a multipotential stem cell defect, possibly due to an intrinsic marrow defect. The in vitro adherent marrow cells of the cyclic haematopoietic (CH) dog were cultured as underlayers beneath normal dog nonadherent marrow cells. The marrow granulocyte‐committed colony forming units (CFU‐C) of the normal dog nonadherent cells were cyclically influenced by the CH adherent cell underlayers. The CH adherent cells collected on the ninth or tenth day following the onset of neutropenia did not stimulate CFU‐C formation while those collected on the sixth day stimulated as many as 108 colonies. The CH adherent cells collected on other cycle days supported increased CFU‐C formation with the exception of cycle day 3 which inconsistently stimulated growth. These data show that the CH marrow in vitro adherent cells alternately stimulate and inhibit in vitro granulopoiesis of normal dog marrows.
Effects of human serum on the release of haemopoietic growth factors
Authors: Nissen Catherine , Moser Yolanda , Speck Bruno
Published: March 2008

Summary.

Unstimulated peripheral blood cells incubated without serum release unexpectedly high amounts of colony‐stimulating activity (CSA) and burst‐promoting activity (BPA). This ‘basal’release of haemopoietic growth factor activity is strongly reduced by the presence of normal human serum. Serum from patients with aplastic anaemia partly lacks this inhibitory activity on the release of CSA and BPA.
The role of the cellular sodium pump in human granulopoiesis in vitro
Authors: Steed A. J. , Boardman K. M. , Delamore I. W.
Published: March 2008

Summary.

The specific sodium pump antagonist ouabain was used to study the effect of sodium pump inhibition on granulopoietic colony formation by normal human bone marrow cells cultured in soft agar for 7 d. Suppression of colony formation was dose‐dependent and occurred at a low and reproducible concentration. The use of an extended range of concentrations (1 × 10−19m to 1 × 10−4m) revealed no additional effect. Inhibition occurred when colony formation was stimulated by either normal human white blood cells in a soft agar underlayer, or the inclusion of pre‐formed colony‐stimulating activity. Sensitivity to inhibition was similar under either set of conditions, the 50% inhibitory concentrations being 2.70 ± 0.43 (SE) × 10−8m and 2.83 ± 0.21 (SE) × 10−8m respectively. This is interpreted as showing an effect primarily on the colony‐forming cells rather than on the cellular production of colony‐stimulating activity. Inhibition of colony formation by ouabain was opposed by the addition of extra potassium to the culture medium, confirming that the inhibition was mediated via a perturbation of monovalent cation exchange. Inhibition by 2 × 10−7m ouabain appeared to be reversible by simple washing after exposure for up to 24 h, suggesting that the inhibitory effect of ouabain is not primarily cytotoxic.
Lithium enhances growth of human leukaemia cells in vitro
Authors: Gauwerky C. E. , Golde D. W.
Published: March 2008

Summary.

Lithium is known to cause leucocytosis in normal humans, and lithium salts have been used therapeutically in attenuating leucopenia in patients undergoing chemotherapy. Recent reports also described leukaemia development during lithium treatment. We have investigated the effect of lithium chloride on the proliferation of human myeloid, erythroblastic, and T‐ and B‐lymphoblast leukaemia cells in vitro. Colony formation by cells of the myeloid leukaemia lines HL‐60 and KG‐1 was enhanced by lithium chloride, and maximal stimulation was seen at 5 x 10−4 M. Lithium also increased the proliferation of KG‐1a cells, a subline of KG‐1 cells that does not respond to colony‐stimulating factor, indicating a direct growth‐promoting effect on myeloid leukaemia cells. Lithium was found to enhance colony formation by the T‐lymphoblast cell line MOLT 4 and the B‐lymphoblast line IM‐9 at concentrations between 10−6 and 10−3 M. The addition of lithium chloride to murine Friend or human K‐562 erythroleukaemia cells also caused an augmentation in colony formation. These observations may have relevance to the therapeutic use of lithium in patients with haematological malignancies.
Subnormal platelet response to thromboxane A2 in a patient with chronic myeloid leukaemia
Authors: Okuma Minoru , Takayama Hiroshi , Uchino Haruto
Published: March 2008

Summary.

A new type of acquired platelet dysfunction was found in a chronic myeloid leukaemia patient with petechiae and thrombocytosis. Platelet aggregation induced by arachidonic acid (AA), collagen and A23187 was decreased, secondary aggregation by ADP and epinephrine was defective and ristocetin‐induced aggregation was completely reversible. No platelet ATP was released by AA and collagen. Only high concentrations of AA (≤ 2 mM) induced minimal reversible aggregation. 14C‐serotonin uptake by the platelet and platelet adenine nucleotide contents were normal. Normal AA metabolism was demonstrated by thin‐layer radiochromatographic analysis of the metabolites of 14C‐AA and the determination of thiobarbituric acid reactive substances produced by the incubation of AA or thrombin with the platelets. Minimal reversible aggregation was observed when patient's platelet‐rich plasma was added to a reaction mixture in which thromboxane A2 (TXA2) had been generated. TXA2 produced by patient's platelets showed normal platelet‐aggregating activity. These results suggest that a subnormal platelet response to TXA2 is included as a mechanism for this acquired hypofunction of the platelet.
IS TRANSFERRIN NORMAL IN IDIOPATHIC HAEMOCHROMATOSIS?
Authors: Jenkins T. , Bothwell T. H. , Maier G. , Laidler Avril
Published: March 2008

Summary.

Family studies were done to ascertain whether there is linkage between the transferrin locus and the HLA loci on chromosome 6. The findings in four families in which there was variation at the transferrin locus did not demonstrate any linkage, with 17 of the 30 offspring of heterozygous parents being recombinants and 13 non‐recombinants. These results indicate that the HLA linked defect responsible for increased iron absorption in idiopathic haemochromatosis is not a consequence of any abnormality in the primary structure of transferrin.
Evaluation of the supertansfusion regimen in homozygous beta‐thalassaemia children
Authors: Masera G. , Terzoli S. , Avanzini A. , Fontanelli G. , Mauri R. A. , Piacentini G. , Ferrai M.
Published: March 2008

Summary. The maintenance of physiological levels of haemoglobin is beneficial in the management of patients with thalassaemia major since it leads to better tissue oxygenation, reduction of blood volume, and reduced intestinal absorption of iron. We have studied 11 patients with thalassaemia major while treating them for 4‐12 months with a standard transfusion regimen (mean pre‐transfusion Hb 10.2 g/dl) and then for a second period of 7‐18 months with a supertransfusion regimen (mean pre‐transfusion Hb 12.3 g/dl). Blood consumption was 16.71 ± 2.0 ml/kg/month in the first period; it rose to 20.30±3.5 ml/kg/month in the first 5 months of the second period, and then returned to the values of the first period (16.53±2.0 ml/kg/month). There were no significant differences in blood consumption between the two transfusion regimens, after the 5‐month equilibration period.
Monoester lipase activity in the red cells of patients with various blood disordrs
Authors: Gastaut J. A. , Vérine A. , Crcassonne Y. , Boyer J.
Published: March 2008

Summary. Membrane‐bound monoester lipase (MEL) activity was measured by a radiochemical assay in intact red blood cells (RBC) from 77 patients with various blood disorders. MEL activity levels in their RBC were compared with levels in normal subjects. The increase in MEL activity was greatest in RBC of regenerative anaemias (N=8) and blastic crisis of chronic granulocytic leukaemias (7) whereas a lesser, although significant, increase was found in acute non‐lymphoblastic leukaemias (14). MEL activity was markedly decreased in RBC of erythroleukaemias (N=5) and decreased to a lesser extent in acute lymphoblastic leukaemias (10) and in chronic myeloproliferative disorders other than chronic granulocytic leukaemias (8). MEL activity levels were roughly correlated with reticulocyte counts, but the relationship was not of predictive value in individual cases. Further exploration of the possible diagnostic or prognostic implications of these variations in enzyme levels seems warranted.

A monoester lipase (MEL) activity has been recently identified and characterized as a membrane‐bound enzyme in red blood cell (RBC) from rats (Arnaud et al, 1979) and human subjects (Boyer et al, 1981). No attempt has been made so far to search for abnormalities of this enzyme. We have therefore measured MEL activity in RBC of 77 patients with various blood disorders.
Bone marrow transplantation for acute lymphoblastic leukaemia
Authors: Barrett A. J. , Kendra J. R. , Lucas C. F. , Joss D. V. , Joshi R. , Desai M. , Jones K. Hugh , Phillips R. H. , Rogers T. R. , Tabara Z. , Williamson S. , Hobbs J. R.
Published: March 2008

Summary. Twenty patients have undergone bone marrow transplantation for acute lymphoblastic leukaemia (ALL). Eighteen patients were in complete remission and two had <10% leukaemic blasts in the marrow aspirate in the week prior to transplantation. Eighteen patients were grafted from HLA/MLC compatible siblings. One identical twin and one fully compatible parent were also used as donors. Two patients died of graft‐versus‐host disease and one of radiation‐induced pneumonitis. Four have subsequently relapsed. Thirteen patients remain well and in remission from 202 to 1126 d post transplantation. These results show that morbidity and mortality from the bone marrow transplantation procedure is low. However, the major obstacle to permanent success in marrow tranplantation of patients with ALL is recurrence of the disease (35% actuarial disease free survival at 1126 d).
Nucleoside incorporation into DNA and RNA in acute leukaemia: differences between the various leukaemia sub‐types
Authors: Piga A. , Sylwestrowicz T. , Ganeshaguru K. , Breatnach F. , Amos R. , Prentice H. G. , Hoffbrand A. V.
Published: March 2008

Summary. The incorporation of the labelled deoxyribonucleosides 3H‐deoxythymidine (3H‐TdR), H3‐deoxycytidine (3H‐CdR), 3H‐deosyadenosine (3H‐AdR), 3‐deoxyguanosine (3G‐GdR), 3H‐deoxyuridine (3H‐UdR) and of labelled uridine (3H‐UR) into DNA and RNA was studied in bone marrow (BM) and peripheral blood (PB) cells from 10 normal donors and 11 patients with acute myeloblastic leukaemia, 13 with acute non‐T non‐B common ALL (c‐ALL) and seven with thymic acute lymphoblastic leukaemia. 3H‐TdR incorporation was highest into the DNA of normal BM cells, 3H‐CdR into DNA in Thy‐ALL and 3‐UdR into of c‐All cells. Purine deoxynucleoside (3H‐AdR and 3‐GdR) incorporation was highest in AML cells and they were incorporated mainly into RNA indicating that before utilization they are partially degraded from the deoxyribose to the corresponding ribose form. In all but three leukaemia samples, the 3H‐UdR/3H‐TdR incorporation ratio was above the range found in normal bone marrow, suggesting the leukaemic cells are more dependent than a normal mixed marrow cell population on the de novo pathway of thymidylate synthesis. The incorporation of nucleosides by peripheral blood cells was usually much lower than by the corresponding bone marrow cells, irrespective of blast percentage.
B‐CLL cells express true endogenous E receptor after culture with T‐cells and mitogens
Authors: Worman C. P. , Cawley J. C.
Published: March 2008

Summary. Culture studies of peripheral blood mononuclear cells from seven typical cases of B‐cell chronic lymphatic leukaemia (CLL) showed that, in the presence of PHA or Con A and ≧20% autologous or allogeneic T‐cells, CLL cells express true sheep erythrocyte (E) receptor after 2‐5 d, but fail to stain with a panel of anti‐T‐cell sera. In contrast to similarly cultured hairy cells (HCs), the cultured CLL cells continue to express light‐chain‐restricted surface immunoglobulin (SIg) and show no change in their morphology.

The continued SIg positivity and staining with a panel of monoclonal antibodies indicated that the high proportion of E+ cells could not be attributed to the outgrowth of normal T‐cells or to mitogen‐induced non‐specific stickiness. Repeated addition of supernatants from cultured T‐cells caused no phenotypic changes and therefore excluded the possibility of shedding and passive acquisition of E receptor.

The points of similarity and difference between the responses of CLL cells and HCs cultured in a like manner are briefly considered in relation to the possible lineages of these two cell types.
Serotonin uptake and storage in human platelet density subpopulations
Authors: Caranobe C. , Sie P. , Boneu B.
Published: March 2008

Summary. Serotonin uptake and storage were studied in human platelet density subpopulations which were isolated after isopycnic centrifugation on a discontinuous iso‐osmolar stractan gradient. Kinetic parameters of the serotonin uptake were calculated (Km, Vi max) and the granular storage capacity was determined by comparing the total amount taken up in the presence or absence of reserpine, a specific inhibitor of the uptake at the granular level. Mean platelet volume and the number of mepacrine‐labelled dense bodies were also determined. The results show that the active metabolic process of serotonin uptake is identical whatever the platelet subpopulation but the storage capacity is greater in the densest fraction which contains more dense bodies than the lightest one. Thus active serotonin uptake appears as another well‐defined platelet metabolic process which is independent of platelet density; this argues against the conception that light platelets could be old platelets with reduced functional capacities.
Cytogenetics of acute lymphoblastic leukaemia in children as a factor in the prediction of long‐term survival
Authors: Secker‐Walker L. M. , Swansbury G. J. , Hardisty R. M. , Sallan S. E. , Garson O. M. , Sakurai M. S. , Lawler S. D.
Published: March 2008

Summary. A chromosomal classification of 93 children with acute lymphoblastic leukaemia (ALL) is presented. The chromosomal categories were normal, hyperdiploid, pseudodiploid and hypodiploid; the chromosomally abnormal cases were classified according to the presence of an abnormal clone. The longest follow‐up was 9 years. Infants and older children were over‐represented in the pseudodiploid category: this association was statistically significant. Patients in the hyperdiploid and hypodiploid categoreis had the longest first remissions and overall first remissions and overall survival and those in the pseudodiploid category the shortest. These effects were statistically siginigicant even when the effect of age and leucocyte count were taken into account. Thus chromosomal findings at diagnosis in ALL can be used as an independent prognostic factor.
Asynchronous expression of granulocyte membrane receptors in megaloblastic anaemia
Authors: Scott C. S. , Bynoe A. G. , Roberts B. E. , Hough D.
Published: March 2008

Summary. The expression of Fc(1gG) and C3b membrane receptors by granulocytes and their precursors was examined in 23 cases of megaloblastic anaemia which were graded I‐III according to morphological severity. Fractionated bone marrow and peripheral blood granulocyte receptors were assessed by rosette formation with optimally sensitized ox erythrocytes and the results compared with those found in 14 normal marrows. Promyelocyte Fc and C3b receptor activities in megaloblastic anaemia did not differ from normal whilst the number of Fc receptor positive myelocytes and later cells showed a significant increase (P<0.05 in Grade I, P<0.01 in Grades II and III) proportional to the severity of megaloblastosis. An increase in the number of C3b receptor positive granulocytes was seen in early megaloblastic anaemias and, in contrast to Fc receptor expression, showed the highest receptor activities in the Grade I1 cases. The most significant changes in receptor expression were seen at the metamyelocyte stage and appear to be related to the numbers of these cells found in the megaloblastic marrows. It is suggested that these alterations are primarily related to asynchronous granulocyte maturation and the application of these findings to the study of granulocytic disorders is discussed.
THE MOLECULAR BASIS FOR β° THALASSAEMIA INTERMEDIA IN AN IRANIAN INDIVIDUAL
Authors: Trent R. J. , Wainscoat J. S. , Huehns E. R. , Clegg J. B. , Weatherall D. J.
Published: March 2008

Summary. A symptomless Iranian patient homozygous for β thalassaemia has haematological changes similar to the β thalassaemia trait. This remarkably mild phenotype is probably the result of coexistent α thalassaemia and increased γ chain synthesis. Restriction endonuclease mapping analysis of the β globin genes indicates that the patient is homozygous for a single nucleotide substitution at the 5’donor splice junction in the second intervening sequence of the β globin gene. No other changes were observed in the non‐α globin gene cluster. It seems unlikely that the augmented γ chain synthesis in this patient is related to the molecular defect responsible for his β° thalassaemia.
Circulating erythroid progenitors in patients with ‘spent’polycythaemia vera and myelofibrosis with myeloid metaplasia
Authors: Kornberg Abraham , Fibach Eitan , Treves Aliza , Goldfarb Ada , Rachmilewitz Eliezer A.
Published: March 2008

Summary. The ability of circulating progenitor cells from patients with polycythaemia vera (PV) and myelofibrosis with myeloid metaplasia (MMM) to develop erythroid colonies was studied in cultures with and without erythropoietin. In all normal controls, patients with secondary polycythaemia and MMM, erythroid colonies developed only after the addition of erythropoietin. Only in patients with PV, both in the active and spent phases of the disease, erythroid colonies developed in the absence of erythropoietin. The results indicate the perpetuation of erythropoietindependent, as well as erythropoietin‐independent progenitors in both phases of this disease. Although spent PV often clinically resembles MMM, there is a basic difference in the behaviour of the circulating erythroid progenitors in these diseases which may serve as a useful tool in discriminating MMM from spent PV, when there is no history of active PV.