bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrastructural Analysis of Haemopoiesis in W/Wv Anaemic Mice
Authors: Shaklai Matityahu , Tavassoli Mehdi
Published: March 2008

Summary. This study is an ultrastructural analysis of haemopoiesis in W/Wv anaemic mice in whom the anaemia is caused by a defect in the haemopoietic stem cell. Cellularity of marrow is normal but there is an increase in the proportion of less mature cells suggesting a delay in maturation. In addition, heterochromatin constitutes a higher proportion than normal of the nucleus in most stages of maturation suggesting a defect in DNA activation. The findings suggest that in this strain not only the differentiation of the haemopoietic stem cell but also the maturation of the committed cell is defective.
Erythrocyte Delta‐aminolaevulinic Acid Dehydratase Activity and changes in Delta‐aminolaevulinic Acid Concentration in Various Forms of Anaemia
Authors: Campbell B. C. , Meredith P. A. , Moore M R. , Goldberg A.
Published: March 2008

Summary. Whole blood delta‐aminolaevulinic acid (ALA) concentrations and crythrocyte ALA dehydratase activity have been measured in patients with iron deficiency anaemia, megaloblastic anaemia and secondary anaemia, and in normal subjects. ALA concentration was found to tbe significantly increased in all types of anaemai compared with normal. Erythrocyte ALA dehydratase activity was significantly increased in iron deficiency and megaloblastic anaemia but not in secondary anaemia.
The Determinants of Irreversibly Sickled Cells in Homozygous Sickle Cell Disease
Authors: Serjeant G. R. , Serjeant E. , Desai P. , Masona K. P. , Sewelall A. , England J. M.
Published: March 2008

Summary. The relationship between the irreversibly sickled cell (ISC) count and other haematological parameters has been investigated. Positive correlations occurred with the MCH, MCHC, and with two expressions of intracellular Hb S content. Since the ISC has a high MCHC, the positive correlations with MCHC and with factors derived from the MCHC may be difficult to evaluate. Negative correlations occurred with total haemoglobin and Hb F. The MCHC was found to affect the relationship between HbF and ISC count, a low MCHC being associated with, and probably determining, lower ISC counts at any level of Hb F. It is proposed that a low MCHC may inhibit ISC formation and the practical implicaions of this are discussed.
Some Immunological Investigations on Antithrombin III ‘Budapest’
Authors: Lane Janet L.
Published: March 2008

Summary. Immunoelectrophoretic studies were carried out on plasma from a patient with an abnormal antithrombin III molecule (antithrombin III ‘Budapest’). One‐dimensional immunoelectrophoresis using a commercial antibody to antithrombin III (antibody to α2,‐AtIII) showed two precipitin peaks of α2‐AtIII antigen. Two‐dimensional immunoelectrophoresis showed two precipitin peaks, one with normal electrophoretic mobility, the other with increased electrophoretic mobility. It was shown that α2‐AtIII antigen with normal mobility was identical to normal α2‐AtIII, and that the α2‐AtIII antigen with increased electrophoretic mobility was antigenically deficient, and appeared to be present in higher concentration than the normal α2‐AtIII antigen. Although one‐dimensional immunoelectrophoresis on plasma from the patient's son showed only one peak, two‐dimensional immunoelectrophoresis revealed that the son also had two populations of α2‐AtIII, one with normal mobility, the other with increased mobility. However, the α2‐AtIII antigen with normal mobility appeared to be present in higher concentration than the α2‐AtIII antigen with increased mobility. One‐ and two‐dimensional immunoelectrophoresis using a different commercial antibody to α2‐AtIII showed only one precipitin peak using the patient's plasma. The precipitin peak observed following two‐dimensional immunoelectrophoresis was asymmetric and showed increased mobility.
Localization and Role of Calcium in the Erythrocyte Coat: Effects of Enzymes and Storage
Authors: Frisch B. , Lewis S. M.
Published: March 2008

Summary. The effects of various treatments on erythrocyte shape, surface, cell coat and calcium binding sites have been investigated by means of high voltage electron microscopy (HVM), scanning electron microscopy (SEM) and conventional electron microscopy (TEM). Papain caused the formation of small blisters within the cellular surface as well as crenation and‘budding’of the erythrocytes. Afer neuraminidase treatment, long filaments were observed to radiate from the surface of the erythrocyte. The other enzymes investigated, RNAse, DNAse, phospholipase, protease and trypsin, produced no demonstrable effect on the cellular structure, nor (with the possible exceptionof trypsin) on the cell coat as seen by subsequent staining with ruthenium red. Putative calcium binding sites on and in the erythrocyte membrane were demonstrated. Following incubation with radioactive calcium, activity was found in the erythrocyte membranes. Calcium binding could be reduced by prior treatment of the erythrocyte with EDTA, neuraminidase, and to a lesser extent, by papain and trypsin. Other enzymes had no demonstrable effect. Stored erythrocytes showed a progressive diminution in calcium binding over a period of up to 4 weeks.
Cell Studies in Prolymphocytic Leukaemia
Authors: Singh A. K. , Vaughan‐Smith S. , Sawyer Barbara , O'Connor T. W. E. , Thomson A. E. R. , Wetherley‐Mein G.
Published: March 2008

Summary. A case of prolymphocytic leukaemia, showing several features not yet reported in this disease, is reported.

The majority of lymphocytes in the peripheral blood and bone marrow had markers of both B‐ and T‐lymphocytes. The simultaneous presence of receptors for sheep RBC and surface immunoglobulins on individual cells was demonstrated and the endogenous origin of these markers was established.

The lymphocytes had some of the functional characteristics seen in chronic lymphocytic leukaemia (CLL). In vitro cell death in the presence of colchicine (colchicine ultrasensitivity) and polystyrene bead column retention were of the same order as seen in CLL. In contrast with the findings in CLL, these cells were markedly radioresistant in vitro.

The dominant clinical features‐anaemia and constitutional symptoms‐appeared to be related to hypersplenism associated with massive splenomegaly. The relevance of these findings is discussed.
The Regulation of Erythropoiesis in Protein‐Energy‐Malnutrition
Authors: Fondu Pierre , And Per Hågå , Halvorsen Sverre
Published: March 2008

Summary

The erythropoietin (ESF) content of plasma and urine has been studied in children with protein‐energy‐malnutrition (PEM) living in the Kivu province at an altitude of 1467–2000 m.

On admission, packed cell volume (PCV) was moderately reduced; after 2 months of refeeding PCV had increased but was still lower than in the controls. Plasma ESF was increased on admission and in patients refed for 2 months. The expected positive correlation between serum and urine ESF levels was found after refeeding but not on admission; the last finding could not be explained by the presence of erythropoiesis inhibiting factor(s) in the urine.

In spite of the normal 2,3‐DPG and P50 previously described in PEM in Kivu, the anaemia associated with this disease is not merely an adaptation to lowered oxygen consumption and there must be some disturbances in the responsiveness of bone marrow to ESF. The high ESF values observed after 2 months of refeeding confirm that the restoration of the red cell volume proceeds slowly.
Erythrocyte Populations in Pyruvate Kinase Deficiency Anaemia Following Splenectomy
Authors: Leblond Pierre F. , Coulombe Louise , Lyonnais Jean
Published: March 2008

Summary. The deformability of three previously described morphological populations of erythrocytes from splenectomized pyruvate kinase (PK) deficient patients was assessed using both Nucleopore filtration and micropipette techniques. Mean deformability was decreased in fresh cells from all patients studied. Selective measurements indicated that immature lobulated reticulocytes in each patient were the least deformable cells, followed by bizarre echinocytes characterized by a hyperviscous behaviour, and by thin macrocytic discocytes whose values were closest to those of control erythrocytes. We conclude that poorly deformable reticulocytes in these patients, after initial trapping in the spleen, are unable to return to the circulation because of their inordinate dependence on mitochondrial oxydative phosphorylation for maintenance of a sufficient intracellular concentration of adenosine triphosphate (ATP); hence their rapid and selective destruction. Splenectomy therefore may be beneficial by allowing such cells to mature more slowly in the circulation of these patients until they develop crenation and hyperviscosity, two manifestations of profound ATP depletion possibly leading to destruction by the liver.
Clinical Staging in Multiple Myeloma
Authors: Woodruf R. K. , Wadsworth J. , Malpas J. S. , Tobias J. S.
Published: March 2008

Summary. Analysis of 237 patients with myeloma, retrospectively classified according to the staging system proposed by Durie and Salmon, showed highly significant differences (P < 0.0001) in the survival of patients with low, intermediate and high tumour cell masses (Stages I, II and III respectively). The median survival for Stage I patients was 64 months, Stage II 32 months, and Stage III 6 months. The median survival of patients presenting with renal impairment was only 2 months, compared to 21 months for those presenting with normal renal function (P < 0.0001). The use of this clinical staging system, which is based on myeloma protein synthesis rates and the calculation of total body tumour cell mass, should be considered in planning future trials of therapy in this disease.
Ferritin as a Cytosol Iron Transport Intermediate in Human Reticulocytes
Authors: Speyer Barbara E. , Fielding J.
Published: March 2008

Summary. The major iron‐bearing cytosol components of human reticulocytes identified after incubation with 59Fe–125I‐transferrin have been studied further. Component C previously found to behave consistently as an intermediate in the iron transport pathway to haem is shown to consist entirely of ferritin. After a short pulse of labelled transferrin incubation, chase experiments showed a fall of ferritin label with time and a corresponding increase in haemoglobin‐iron incorporation. There was no loss of ferritin to the culture medium. Restriction of iron uptake by reticulocytes using both p‐hydroxymercuribenzoate inhibition of uptake and incubation with progressively lower saturations of iron‐transferrin gave linearly related incorporation of 59Fe into ferritin and haemoglobin at all levels of iron uptake, thus negating the concept of ferritin as an ‘overspill’ form of reticulocyte iron. The results suggest that cytosol ferritin is an obligatory intermediate in reticulocyte iron transport.
Suppressive Effect of Ferritin on in Vitro Lymphocyte Function
Authors: Matzner Yaacov , Hershko Chaim , Polliack Aaron , Konijn Abraham M. , Izak Gabriel
Published: March 2008

Summary. This study describes the effect of ferritin on lymphocyte function in vitro. Peripheral blood lymphocytes isolated from normal donors were incubated with purified human splenic ferritin, and the mitogenic effect of phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) and mixed lymphocyte reaction (MLR) were assessed by the uptake of 3H‐thymidine (3H‐TdR). Ferritin (0·25–5·0 μg/ml culture) caused a marked suppression of PHA and Con A blastogenesis but had no suppressive effect on PWM‐induced transformation. Maximal suppression was obtained at a ferritin concentration of 1 μg/ml and this was not enhanced by increasing ferritin concentrations. Ferritin also reduced the Con A capping phenomenon in normal lymphocytes from 22% to 6%, suppressed the MLR reaction but had no effect on the ability of normal lymphocytes to form E, EA and EAC rosettes or on in vitro lymphocyte cytoxicity against the K‐562 cell line. Visual proof of the suppressive effect of ferritin on mitogen induced blastogenesis was provided by scanning electron microscopy, and direct evidence for the ability of lymphocytes to bind ferritin was obtained from studies with radioiodine labelled ferritin. The above findings indicate that ferritin suppresses certain parameters of T‐lymphocyte function in vitro. The relation of the present findings to recognized abnormalities of T‐cell function encountered in certain neoplastic disorders associated with high serum ferritin levels is at present unknown.
Morphological Abnormalities in Cultured Erythroid Colonies (BFU‐E) from the Blood of Two Patients with HEMPAS
Authors: Vainchenker W. , Guichard J. , Breton‐Gorius J.
Published: March 2008

Summary. The results of cytological and ultrastructural analyses of erythroid burst colonies derived from the peripheral blood of two patients with HEMPAS have been compared to those obtained in normal controls. Using the plasma clot technique, in studies on 10 subjects we confirmed that most of the colonies consisted of erythroblasts with a synchronous and normal maturation involving a wave of nuclear extrusion at day 13. In contrast, the majority of well‐haemoglobinized colonies from HEMPAS consisted of numerous bi‐ or multinucleated erythroblasts displaying the supplementary double membrane beneath their plasma membrane. This excessive membrane may be present as a continuous or fragmented structure in different erythroblasts from the same colony. These findings suggest that the progeny derived from one BFU‐E may vary considerably in their morphological defects. Furthermore, one third of the packed colonies appeared to be formed by non‐haemoglobinized cells which were clearly identified by electron microscopy as very early erythroblasts. These cells were unable to mature and subsequently lysed. Thus dyserythropoiesis occurred in culture both at early and late stages of maturation. These studies clearly demonstrate that HEMPAS is a disorder resulting from defective erythroid committed cells.
Effect of Antilymphocyte Globulin on Granulocyte Precursors in Aplastic Anaemia
Authors: Faille A. , Barrett A. J. , Balitrand N. , Ketels F. , Gluckman E. , Najean Y.
Published: March 2008

Summary. Granylocyte colony forming units (CFU‐C) were studied in 22 patients with severe aplastic anaemia before and after treatment with antilymphocyte globulin (ALG). Nine patients showed a clinical response to ALG characterized by a rise in the granulocyte count to over 1 × 109/1 within 30 d. These patients were distinguished in vitro from non‐responders by an increase in CFU‐C numbers after incubation of bone marrow cells with ALG, and by the presence of inhibitors of normal CFU‐C in the serum in six out of seven patients tested. In responding patients bone marrow CFU‐C rose while most non‐responding patients showed no change or a fall in CFU‐C after treatment. In addition in three out of four responding patients examined serum inhibitors disappeared after treatment. The horse ALG used in this study also stimulated normal CFU‐C in vitro. This evidence is contrary to the hypothesis that ALG stimulates CFU‐C in aplasia by inactivating an abnormal suppressor lymphocyte population.

The nature of the stimulation by ALG remains unclear. But in practice the effect of ALG on bone marrow cells and study of CFU‐C inhibitors in serum could be used to select patients likely to respond to ALG treatment.
Myelofibrosis in Chronic Granulocytic Leukaemia
Authors: Clough Virginia , Geary C. G. , Hashmi K. , Davson J. , Knowlson T.
Published: March 2008

Summary. Serial trephine biopsies were performed in 45 cases of chronic granulocytic leukaemia (CGL) in order to determine the frequency and significance of secondary myelofibrosis in the evolution of the disease. Histological changes were graded 1–5b, ranging from no increase in reticulin to dense osteomyelosclerosis. Many cases showed a progressive increase from Grade 1 to Grade 3, and accelerated disease, or blast crisis, often supervened when Grade 3 changes were present. However, a significant number of cases showed Grade 4 and 5 changes, which were indistinguishable histologically from those found in agnogenic myeloid metaplasia (AMM) (idiopathic myelofibrosis), at the time of diagnosis. These patients did not always show a rapidly fatal course and may be considered as an example of ‘transitional myeloproliferative disorder’, with features intermediate between CGL and AMM.
Studies in Desferrioxamine and Ferrioxamine Metabolism in Normal and Iron‐Loaded Subjects
Authors: Summers M. R. , Jacobs A. , Tudway D. , Perera P. , Ricketts C.
Published: March 2008

Summary. Plasma concentrations of desferrioxamine and ferrioxamine were measured following bolus injections of desferrioxamine and during 24 h infusions of the drug. [59Fe]ferrioxamine clearance and urinary iron excretion were also measured.

Higher plasma ferrioxamine concentrations are found in iron loaded subjects and higher desferrioxamine concentrations in subjects with normal iron loads. There is a correlation between the circulating concentration of ferrioxamine during an infusion and the 48 h urinary iron excretion. The data suggests that the amount of iron chelated in vivo is related to an increase in the size of an intermediate chelatable pool rather than the total amount of the iron load. The well‐recognized delay in urinary iron excretion appears to be related to active tubular reabsorption of ferrioxamine.
Hereditary Acanthocytosis Associated with the McLeod Phenotype of the Kell Blood Group System
Authors: Symmans W. A. , Shepherd C. S. , Marsh W. L. , ØYen R. , Shohet S. B. , Linehan B. J.
Published: March 2008

Summary. Some boys with X‐linked chronic granulomatous disease (CGD) have red cells of the rare McLeod phenotype in the Kell blood group system. Only one example of this phenotype has previously been described in a non‐CGD subject. We have studied a 10‐year‐old boy and a maternal brother who do not have CGD and whose red cells are of the McLeod type. The boy presented as a haematological problem with red‐cell abnormalities. These were acanthocytosis, anisocytosis and ‘tailing’ in the osmotic fragility curve, changes now known to occur with the McLeod phenotype. Subsequent studies revealed his rare blood group.

A family study has established that an uncle also has acanthocytic red cells and the McLeod phenotype. In addition the boy's sister, mother and maternal grandmother all show red‐cell mosaicism with double populations of McLeod acanthocytes and normal red cells of common Kell type. The gene that determines inheritance of the McLeod phenotype is X‐linked and the mosaicism present in female carriers is believed to result from X chromosome inactivation by the Lyon effect. The study provides further evidence that the McLeod phenotype arises by inheritance of a variant X‐linked modifying gene and not through inheritance of a variant gene at the Kell autosomal locus. It also represents the first occasion that a person of rare blood group has been recognized because of an associated anomaly in red cell morphology.
Coagulation Abnormalities Produced by Plasma Exchange on the Cell Separator with Special Reference to Fibrinogen and Platelet Levels
Authors: Keller A. J. , Chirnside Ann , Urbaniak S. J.
Published: March 2008

Summary. Five patients with immunopathologic renal disease, 12 with malignant paraproteinaemia and one with myasthenia gravis underwent a total of 179 plasma exchanges on a continuous flow cell separator. Replacement fluids devoid of coagulation factors were used in 160 exchanges while 19 exchanges were replaced with Fresh Frozen Plasma. Coagulation screening was done immediately before and 30 min after each plasma exchange. Plasma fibrinogen concentrations fell to a mean of 25% of initial levels during individual exchanges. Sequential reduction to 10.7% was observed after five consecutive daily exchanges and in one patient fell to 1.2% after 10 daily exchanges. Low levels of fibrinogen could be maintained with daily or alternate daily exchanges. Platelet counts fell to a mean of 50% of pre‐exchange levels during individual exchanges. Consecutive daily exchanges resulted in mean reductions to 20.7% after 5 d, but further reductions were not observed with longer periods of exchange. Platelet counts recovered to pre‐exchange values during exchange intervals of 2 or more days. Mild clinical bleeding episodes, probably related to low platelet counts, occurred in one exchange in each of three patients. Haemostasis was rapidly achieved in these patients by infusions of platelet concentrates. Coagulation screening, including prothrombin ratio, thrombin time, reptilase time and partial thromboplastin time with kaolin showed progressively greater abnormalities as the intervals between exchanges shortened. The low incidence of clinical haemorrhagic episodes, three of 179 exchanges (2.2%), despite markedly abnormal coagulation parameters, emphasizes the safety of the procedure even in moribund patients. We conclude that the use of FFP in intensive exchange programmes solely for the prevention of spontaneous haemorrhagic phenoma is unjustified.
Detection and Quantification of Platelet‐bound Antibodies with Immunoperoxidase
Authors: Leporrier Michel , Dighiero Guillaume , Auzemery Martine , Binet J. L.
Published: March 2008

Summary. The use of immunocytochemical techniques enables one to quantify antibodies bound to cell membranes. We have tested the platelets of subjects with immune thrombocytopenic purpura by this method. The washed platelets were incubated in the presence of antiglobulin conjugated with an equimolar amount of peroxidase. The fixed peroxidase was revealed and quantified by an enzymatic reaction using orthodianizidine‐H2O2. From the results the number of immunoglobulin molecules per platelet was calculated. The test was calibrated so as to eliminate non‐specific fixation of the reagent. Under these conditions the platelets of subjects with idiopathic thrombocytopenic purpura bound a much larger amount of detectable immunoglobulin (800–21 000 molecules per platelet) than those of normal subjects (235 × 74 sites per platelet) or subjects with non‐immune thrombocytopenia (395 ± 203 molecules per platelet).
Factor VIII Procoagulant Activity, Factor VIII Related Antigen and von Willebrand Factor in Newborn Cord Blood
Authors: Fukui H. , Takase T. , Ikari H. , Murakami Y. , ŌKubo Y. , Nakamura K.
Published: March 2008

Summary. The mean level of factor VIII procoagulant activity (VIII:C) and factor VIII related antigen (VIIIR:AG) was normal in 100 newborn cord plasmas, whereas that of von Willebrand factor (VIIIR:WF) activity was slightly lower than normal. On crossed immunoelectrophoresis, 20 of 50 newborn infants had an increased anodal mobility of VIIIR:AG. When the cord plasma showing an abnormal electrophoretic pattern was mixed with normal plasma, two precipitation peaks with a broad base were found. Similar mixing experiments with the abnormal cord plasma and plasma from a patient with atypical von Willebrand's disease did not normalize the electrophoretic mobility of VIIIR:AG. Gel filtration of the cord plasma with an abnormal electrophoretic pattern of VIIIR:AG, showed that the three activities were all detected at the position corresponding to a molecular weight of about 800 000. The results suggest the presence of qualitative abnormalities of the factor VIII molecule in half of full‐term newborn cord plasma.
The Ph1 Chromosome in Childhood Leukaemia
Authors: Chessells J. M. , Janossy G. , Lawler S. D. , Walker L. M. Secker
Published: March 2008

Summary. Ph1 positive leukaemia was diagnosed in eight of 123 (6.5%) consecutive new cases of childhood leukaemia. Four patients presented as typical chronic granulocytic leukaemia (CGL) and four as acute leukaemia, two of the four children with CGL have since developed blast crisis. Morphological and immunological characterization of the blasts in these six acute cases was suggestive of a lymphoid crisis in three, a mixed crisis in two, and a myeloid crisis in one. Remission was achieved in five of the six patients but lasted more than a year in only two; in one of these two patients the blasts at the time of crisis lacked the Ph1 chromosome and in the other, who presented in myeloid crisis, remission ended in a lymphoid crisis. Cytogenetic studies showed unusual translocations in two of the eight children. Serial examination showed that in three children the proportion of Ph1 positive cells in the marrow was reduced to less than 6% at the time of remission from acute leukaemia.

We conclude that Ph1 positive leukaemia in childhood presents frequently as acute leukaemia and may even mimic ‘good risk’ acute lymphoblastic leukaemia. The response to treatment cannot be predicted by morphological or immunological characterization of blast cells. Storage of bone marrow for possible autologous transplantation should be considered in children who achieve remission.

Ormond Street, London WC1N3JH.
Serial Changes in Coagulation and Viscosity during Sickle‐Cell Crisis
Authors: Richardson S. G. N. , Matthews K. B. , Stuart J. , Geddes A. M. , Wilcox R. M.
Published: March 2008

Summary. Coagulation activity and whole‐blood viscosity were measured in the steady state, and serially during painful crisis, in eight patients with sickle‐cell anaemia. Platelet and coagulation activation occurred in the steady state and became more pronounced early in crisis. Whole‐blood viscosity increased during crisis in parallel with plasma fibrinogen.

Similar changes were found in a parallel study of 20 patients with localized bacterial or viral infection who did not have sickle‐cell anaemia. Reports of platelet activation, hypercoagulability, and hyperviscosity during painful crisis therefore reflect secondary changes arising from vascular stasis, precipitating infection, and an acute‐phase protein reaction. Although secondary, these changes may contribute to vascular occlusion by an additive effect in vessels already partially occluded by sickled cells.
Abnormal Peripheral Blood Lymphocytes and Bone Marrow Infiltration in Non‐Hodgkin's Lymphoma
Authors: Garrett J. V. , Scarffe J. H. , Newton R. K.
Published: March 2008

The blood lymphocytes of 21 normal blood specimens, 20 patients with various malignant disorders and 63 patients with non‐Hodgkin's disease lymphoma, all with lymphocyte counts below 6 x 109/l, were examined by sheep red cell rosetting, fluorescent antisera to surface immunoglobulin and for sensitivity to colchicine. The results were correlated with bone marrow infiltration and lymph node histological findings. The ratio of kappa to lambda light chains in the surface immunglobulin was used to determine if an abnormal clone of lymphocytes was present. In the normals and the non lymphoma controls the expected normal ratio of approximately 2k to 1λ was found with a narrow spread. In non‐Hodgkin's lymphoma cases there was a wide spread of ratios with half the cases outside the range of the controls. These cases were considered to have a clone of abnormal lymphocytes in the blood although their routine blood and differential counts were usually normal. There was a very significant correlation of the presence of a clone with ultrasensitivity to colchicine and with involvement of the bone marrow. 81% of the cases with a histological diagnosis of well‐differentiated diffuse lymphocytic lymphoma, 64% of those with poorly differentiated diffuse but only 22% of those with diffuse histiocytic had an abnormal lymphocyte clone demonstrated by an abnormal k:λ ratio.
Bone Marrow Fibre Production in Myelofibrosis: a Quantitative Study
Authors: Bentley S. A. , Herman C. J.
Published: March 2008

A digital image processing technique has been used to quantitate bone marrow fibre in histological material (both biopsy and necropsy) from 17 cases of myelofibrosis. An attempt was made to correlate the results of these measurements with other diagnostically relevant parameters. Bone marrow fibre was found to correlate significantly with absolute neutrophil count, the absolute count of immature granulocytic cells and with the number of immature granulocytic cells expressed as a percentage of the total leucocyte count. There was no significant correlation between marrow fibre content and platelet count for the series as a whole, but for those cases in which measurements were made following splenectomy these parameters were highly correlated. Bone marrow fibre content did not appear to correlate with liver or spleen weight at necropsy, nor with the duration of clinical manifestations of the disease. The significance of these findings is discussed.
Inherited Lack of Transcobalamin II in Serum and Megaloblastic Anaemia: a Further Patient
Authors: Burman J. F. , Mollin D. L. , Sourial N. A. , Sladden R. A.
Published: March 2008

Summary. We have studied a patient, unrelated to the patients previously described, with inherited lack of the vitamin B12 binding protein Transcobalamin II. Severe haematological abnormalities were found within a few weeks of birth and responded to treatment with both vitamin B12 and folic acid. He was maintained in partial remission with such treatment until adolescence, except for a time in early childhood when folic acid alone was given and he suffered severe neurological deterioration. At the age of 18 years he was admitted to hospital because of convulsions; the deoxyuridine suppression test showed intracellular deficiency of B12 despite a normal serum B12 and normal haemoglobin concentration.

His serum failed to promote the uptake of radioactive B12 by bone marrow cells, and analysis of serum B12 binding proteins demonstrated the lack of Transcobalamin II. Treatment with injections of 1000 μg of B12 three times weekly corrected the abnormality shown in the deoxyuridine suppression test; following this treatment, together with changes in anticonvulsive therapy, he remains healthy without occurrence of further convulsions, and is haematologically normal.
Clinical and Laboratory Findings in the Initial Diagnosis of Homozygous Beta Thalassaemia in Fars Province, Iran
Authors: Nasab A. Hashemi
Published: March 2008

Summary. The initial clinical and laboratory presentations in 141 cases of homozygous β thalassaemia in Fars Province, Iran, are presented. About one third of the patients were first diagnosed when they were over 4 years of age. The possible reasons for the high prevalence of the disease in Iran is described.
Viability of Red Cells Stored in Diminished Concentration of Citrate
Authors: Mishler John Milton , Darley John H. , Haworth Catherine , Mollison P. L.
Published: March 2008

Summary. A comparison was made between the post‐transfusion survival of red cells stored in standard ACD‐A and in modified ACD‐A, containing two‐thirds the amount of citrate. Measurements of survival after 28 d storage in both solutions were made in each of six subjects. Mean post‐transfusion survival with the two solutions was almost identical. When the results in one subject in whom survival was particularly bad with both solutions were omitted mean values at 24 h were 74.0% for standard ACD‐A and 74.9% for modified ACD‐A. It is concluded that viability is just as well maintained in modified ACD‐A as in standard ACD‐A. The results also provide further evidence of large differences between donors with respect to the maintenance of red cell viability during storage.
Myeloproliferative Disorders Terminating in Acute Micromegakaryoblastic Leukaemia
Authors: Efrati P. , Nir E. , Yaari A. , Berrebi A. , Kaplan H. , Dvilanski A.
Published: March 2008

Summary. Two cases of myeloproliferative disorder—one of myelofibrosis with agnogenic myeloid metaplasia and one of chronic granulocytic leukaemia terminating in acute micromegakaryoblastic leukaemia—are presented. The clinical course is described, and results are reported of morphological, cytometric, cytochemical and cytogenetic studies, as well as cell culture of blood cells in soft agar and in fluid medium.
The Effect of Iron Deficiency on Whole Blood Viscosity in Polycythaemic Patients
Authors: Hutton R. D.
Published: March 2008

Summary. Iron deficiency leads to a significant increase in whole blood viscosity in polycythaemic patients. This can be corrected by simultaneous treatment with iron and venesection. In patients with polycythaemia secondary to hypoxia the haemoglobin concentration may be increased by treating coexisting iron deficiency, without altering the whole blood viscosity, thus increasing oxygen availability to the tissues. Values for whole blood viscosity can be derived from the peripheral blood Hb and MCH, allowing therapeutic decisions to be made on the basis of a simple haematological examination.
Typical Hairy‐Cell Leukaemia with IgGk Paraproteinaemia
Authors: Cawley J. C. , Burns G. F. , Bevan A. , Worman C. P. , Smith J. L. , Gray L. , Barker C. R. , Hayhoe F. G. J.
Published: March 2008

Summary. A case of hairy‐cell leukaemia (HCL) with IgG(k) paraprotein is described. The typical clinico‐pathological features of the patient are stressed, and it is shown that the hairy cells (HCs) were producing and secreting IgGk. The case is placed in a more general context by the demonstration that HCs from other typical cases of HCL produce and secrete IgG. These findings conclusively demonstrate that HCL is a B‐cell disease.
Glucose‐6‐Phosphate Dehydrogenase Deficiency and Neonatal Jaundice in Jamaica
Authors: Gibbs W. N. , Gray R. , Lowry M.
Published: March 2008

Summary. Glucose‐6‐phosphate dehydrogenase (G6PD) deficiency was detected in 16 (69.6%) of a group of 23 neonates who had unexplained moderate or severe jaundice. This proportion is significantly more than the 9.4% observed or the 22.2% expected in Jamaican neonates who are not moderately or severely jaundiced (P<0.003), and significantly more than the 12.6% observed or the 21.0% expected in older Jamaican children and adults (P<0.003). Phenobarbitone therapy and phototherapy reduced the need for exchange transfusion but this was necessary in eight patients. Two babies developed kernicterus and one died. On the other hand, only two of 21 neonates who were identified as G6PD deficient at birth subsequently became moderately or severely jaundiced, and this could be attributed to other causes in both cases. These findings indicate that apparently spontaneous neonatal juandice is important in infants who have the G6PD A— enzyme. However, the jaundice is probably precipitated by unknown factors to which the G6PD deficient neonate is more susceptible than the infant who is not G6PD deficient. There is also a slightly increased incidence of G6PD deficiency in neonates who develop jaundice because of ABO or Rh(D) iso‐immune disease, infection or prematurity.
Effects of 5‐Fluorouracil on Mouse Bone Marrow
Authors: Radley J. M. , Scurfield G.
Published: March 2008

Summary.5‐Fluorouracil (150 mg/kg) was injected intravenously into 11‐week‐old male mice. Its effects on marrow structure over the following 9 d were assessed using light microscopic examination of semi‐thin transverse sections of decalcified humeri.

The extravascular compartment became markedly depleted of cells and decreased in size, reaching a minimum on day 5 post‐treatment. Proliferating haematopoietic cells disappeared within 2 d. Post‐replicative erythrocytic cells underwent extra‐vascular phagocytosis by resident macrophages, whilst mature granulocytes continued to pass into the circulation. Repopulation was underway by day 6, and re‐expansion of the extravascular compartment by day 7 when megakaryocytes, of larger than normal average size, occupied most of the extravascular compartment. Megakaryocyte dominance gave way over days 8 and 9 as other haematopoietic cells proliferated and the extravascular compartment continued to enlarge. The significance of the results is discussed in relation to marrow micro‐circulation, egress of haematopoietic cells into the circulation, and cell proliferation in the marrow. Endotoxin, administered 4 h after 5‐fluorouracil, accelerated depletion of the marrow and recovery of haematopoiesis by about 1 d.
Distribution of Erythrocyte Nucleotides in Pyrimidine 5′‐Nucleotidase Deficiency
Authors: Torrance J. D. , Whittaker D.
Published: March 2008

Summary. In pyrimidine 5′‐nucleotidase deficiency, erythrocytes contain elevated levels of pyrimidine nucleotides. The composition of this nucleotide pool was examined by ion exchange chromatography on Dowex formate columns using a linear ammonium formate elution gradient. In contradistinction to normal erythrocytes, adenine nucleotides accounted for only 32% of the nucleotide pool. The remainder consisted of 50% cytidine and 16% uridine nucleotides. The remaining 2% was not identified. The most abundant compound appeared to be UDP glucose whilst high levels of CTP, CMP and an unidentified cytidine compound less polar than CMP accounted for most of the cytidine nucleotide pool. The possibility that the abnormal nucleotides were due to an elevated reticulocyte count was excluded and it was also shown that erythrocytes from subjects heterozygous for pyrimidine 5′‐nucleotidase deficiency did not have detectable levels of the abnormal nucleotides.
Effective Iron Chelation following Oral Administration of an Isoniazid‐Pyridoxal Hydrazone
Authors: Hoy T. , Humphrys J. , Jacobs A. , Williams A. , Ponka P.
Published: March 2008

Summary. When isoniazid and pyridoxal are mixed in equimolar quantities a hydrazone is formed which is able to complex with iron. The oral administration of this compound to rats in single doses of 25–100 mg/kg leads to an increase in faecal iron excretion up to 8 times the normal level. In tissue culture the compound is able to remove iron from Chang cells. The results suggest that this compound may be of potential value for the oral therapy of iron overload.
The Post‐Aspirin Bleeding Time: a Screening Test for Evaluating Haemostatic Disorders
Authors: Stuart Marie J. , Miller Merrill L. , Davey Fredrick R. , Wolk Joel A.
Published: March 2008

Summary. To evaluate the usefulness of the template bleeding time post‐aspirin ingestion, this test was performed with other tests of haemostasis in 28 controls and 71 patients. The mean bleeding time (B. T.) in 24/28 true controls was 3.5+1 min (1 SD). Following the ingestion of 600 mg aspirin the B. T. was 6.3 + 1.4 min. Four out of 28 false ‘controls’with negative bleeding histories were documented to have asymptomatic von Willebrand's disease and abnormal post‐aspirin B. T. Of the 71 patients studied, 22 had initial B. T. that were abnormal (16 with classical von Willebrand's disease and six with platelet dysfunction). Of the remaining 49 patients with initially normal B. T., 30 had abnormal post‐aspirin B. T. Of these 30 patients 13 had von Willebrand's disease. In eight, initially the abnormal B. T. post‐aspirin was the only abnormality demonstrable but later they were shown to have von Willebrand's disease. In four the abnormal post‐aspirin B. T. was combined with abnormal Ristocetin aggregations and a positive family history. These patients were presumed to have a variant of von Willebrand's disease. The remaining five had platelet dysfunctional states. Of the 19 patients with normal initial post‐aspirin B. T., 16 demonstrated no haemostatic abnormality, and three were proven to have von Willebrand's disease. The aspirin tolerance test raised the sensitivity of the B. T. as a screening test for haemostasis from 40% to 94% in the abnormal patient population.
Biochemical and Histological Analysis of Bone Marrow Collagen in Myelofibrosis
Authors: Charron Dominique , Robert Ladislas , Couty Marie‐Claude , Binet Jacques‐Louis
Published: March 2008

Summary. Total protein, collagen (hydroxyproline) and glycoproteins (hexosamine) content of control and myelofibrosis (MF) bone marrow samples was determined using a sequential extraction procedure. MF marrow extracts contained higher amounts of collagen than control extracts. The collagen content appeared to increase with the duration of the disease. In more recent MF cases (<2 years) at least 60% of the total collagen was extracted in 0.5 m NaCl. this proportion decreases to 33% in older cases (> 4 years), indicating a progressive insolubilization (crosslinking) of collagen.

The hexosamine content of the extracts decreased in MF as compared to controls reflecting a decrease in glycosaminoglycans (and possibly of structural glycoproteins). The reticulin content of the same bone marrows was estimated by a quantiative morphometric procedure. There was a positive correlation between the morphometrically estimated reticulin surface and the total hydroxyproline content of the marrow samples. The slopes of the least square lines correlating increase of reticulin surface to hydroxyproline content were, however, significantly different in control and MF marrows, indicating a 44% higher increase in histochemically detectable reticulin per unit increase in hydroxyproline content than in the control marrows. This result may indicate a more efficient fibrogenetic process in MF marrow than in normal bone marrow.

The above results confirm the collagenous nature of the fibrous reticulin like material deposited in MF marrows and suggests a correlation between the progression of the disease and the rate of synthesis and deposition of collagen fibres.
Alpha Thalassaemia in American Blacks: a Study of a Family with Five Cases of Haemoglobin H Disease
Authors: Bellevue R. , Dosik H. , Rieder R. F.
Published: March 2008

Summary. Five cases of HbH disease were discovered in a large family of American Blacks. Anaemia was mild with PCV ranging from 0.275 to 0.405. The amount of HbH was 2–6%. Studies of haemoglobin synthesis in peripheral blood reticulocytes demonstrated marked deficits in α globin production with an average α/β ratio of 0.31 (range 0.22–0.36). Eighteen additional family members had evidence of thalassaemia trait and were provisionally classified as either α‐that‐1 (average MCV of 65.2 fl; range 59–70) or α‐thal‐2 (average MCV 79.6 fl; range 74–88). A subject with α‐thal‐1 trait had an α/β ratio of 0.56; the average for five cases of α‐thal‐2 was 0.73. One other family member was thought to be homozygous for α‐thal‐2 trait and exhibited an MCV of 65 fl with an α/β ratio of 0.5. These data reconfirm that in Blacks with α thalassaemia the proportion of HbH is lower and the severity of anaemia is less than in certain other racial groups, e.g. Southeast Asians. However, the degree of hypochromia and microcytosis and the imbalance in α and β globin synthesis appear to be similar in Blacks and other races. These results suggest that the milder clinical course of HbH disease in Blacks is not a result of greater α globin production in that population of thalassaemics.
The Importance of the Genetic Picture and Globin Synthesis in Determining the Clinical and Haematological Features of Thalassaemia Intermedia
Authors: Gallo E. , Massaro P. , Miniero R. , David D. , Tarella C.
Published: March 2008

Summary. Twelve carriers of thalassaemia intermedia were studied. Their clinical and haematological picture was distinctly different from that in both heterozygotes and haematological picture was distinctly different from that in both heterozygotes and homozygotes for β thalassaemia. Several genetic patterns were found responsible for thalassaemia intermedia: β/δβ thalassaemia, α2β/β thalassaemia, β/β thalasaemia‐heterocellular HPFH. In a few subjects the genetic picture indicated that the patients were homozygous for β thalassaemia, in spite of the mildness of the clinical sitution. The lack of genetic uniformity was reflected in very wide Hb A2 (2.5–8.7%) and Hb F (7.5–96.9%) ranges, as opposed to the noticeable degree of biochemical uniformity indicated by the very similar imbalance of globin chain synthesis: 0.33–0.54 for the non‐α/α chain ratio in the peripheral blood. The mean for this parameter (0.43 ± 0.05) was significantly different (P<0.001) from that observed in heterozygous carriers (0.60 ± 0.10) and homozygous carriers (0.11 ± 0.05) for β thalassaemia. The marrow blood displayed a comparable pattern. It is therefore suggested that the severity of thalassaemia is attributable to the degree of chain synthesis imbalance.
The Lymphocyte Production Pathway in Bone Marrow: Possible Significance of the Size Spectrum of Lymphocytes and their Precursors
Authors: Patinkin D. , Grover N. B. , Yoffey J. M.
Published: March 2008

Summary. It is now generally accepted that transitional (‘lymphoid’) cells are the precursors of small lymphocytes. Such cells have a heterogeneous size spectrum and show high proliferative capacity. To facilitate the study of the kinetics of lymphocyte production, a detailed investigation of cell sizes of the transitional cell‐lymphocyte compartment was carried out using a Coulter counter modified to permit a very rapid and accurate examination of cells in suspension. Enriched populations of ‘lymphoid’ cells, obtained after io d rebound from hypoxia at half an atomosphere, were enriched further by bovine albumin and Ficoll gradients to give density fractions containing two types of cells. Differential counts of stained smears of these fractions enabled a comparison to be made between the size distribution and the specific cell types. Four distinct cell types were characterized in terms of volume and density: small and intermediate‐sized lymphocytes (volume 53–59 f1, albumin fractions 19–23%), small transitional cells (154–150 f1, 21–23%), medium transitional cells (206–218 f1, 17–19%) and large transitional cells (350–400 f1, 21–27%). These findings are consistent with the view that there are at least three mitoses in the course of the lymphocyte production pathway in the bone marrow.
Role of Serum Folate Binders in the Delivery of Folate to Tissues and to the Fetus
Authors: Fernandes‐Costa Francisco , Metz Jack
Published: March 2008

Summary. Specific folate binding protein (FBP) and non‐specific folate binding protein have been prepared from pooled serum from patients in late pregnancy. The two classes of folate binder were labelled with 75Se‐selenofolate and injected into non‐pregnant and pregnant rabbits. Selenofolate bound to specfic FBP was delivered predominantly to the liver, in both pregnant and non‐pregnant animals. Fetal tissue took up selenofolate from the non‐specific FBP only. Specific FBP thus functions to deliver folate to stores and respresentas a storage pool of folate. The non‐specific FBP are responsible for the delivery of folate to the fetus, and probably also to sites of utilization.
Diagnosis of Haematological Disease using Anti‐i
Authors: Shumak Kenneth H. , Beldotti Lorraine E. , Rachkewich Rose A.
Published: March 2008

Summary. Using cytotoxicity and antibody‐binding tests, the i antigen was measured on the blood lymphocytes of normal subjects and of patients in whom a diagnosis of chronic lymphocytic leukaemia (CLL) was considered because of a slight lymphocytosis in the blood and bone marrow. Among 25 patients, 15 had a normal amount of i antigen; in 10 there was a marked reduction in i antigen, such as is found in typical CLL. Similar studies were done on lymphocytes from 15 patients with clinical and morphological findings usually associated with lymphosarcoma cell leukaemia (LSL). Nine had a normal amount of i antigen; in six there was a marked reduction of i antigen, suggesting a diagnosis of CLL. A study of the subsequent clinical course and final diagnosis in these patients suggests that the reduction in lymphocyte i antigen characteristic of typical CLL occurs in patients with early CLL who have only slight lymphocytosis, but not in patients with slight lymphocytosis from other causes. Similarly, a reduction in lymphocyte i antigen is found in patients with morphologically atypical CLL but not in patients with LSL.