bluuebunny/crossref_metadata_2025 huggingface dataset:
The Chromosomes of Bone‐Marrow Cells of Haematologically Normal Men and Women
Authors: Walker Lorna M. Secker
Published: March 2008

Summary. An analysis was made of the chromosomes of 1301 marrow cells from 59 haematologically normal men and women. No case of total aneuploidy was found. The overall incidence of aneuploidy in the population of 1301 marrow cells was 10.3%; hypodiploid 10%, hyperdiploid 0.3%. In the group of 15 individuals where 50 cells could be analysed the proportion of aneuploid cells differed very significantly from person to person. In contrast to the situation in myeloproliferative disorders, hyperdiploidy in normal bone marrow cells was rare. The significance of differences between normal bone marrow cells and normal blood lymphocytes and between normal bone marrow cells and those in chronic myelo‐proliferative disorders is discussed. A significant loss of G‐group chromosomes in the aneuploid cells of the two oldest males (73 yr) was demonstrated. There was a low incidence of chromosomal and chromatid aberrations.
Secondary Polycythaemia due to a Uterine Fibromyoma Producing Erythropoietin
Authors: Wrigley P. F. M. , Malpas J. S. , Turnbull A. L. , Jenkins G. C. , McArt A.
Published: March 2008

Summary. A case is described of a woman with polycythaemia secondary to a uterine fibromyoma. The polycythaemia disappeared after the removal of the tumour. The tumour tissue and also fluid from cysts within the tumour showed erythropoietic activity when estimated by the polycythaemic mouse assay employing two dose levels and a standard related to the WHO erythropoietin standard. It is suggested that polycythaemia in this case was caused by the production of erythropoietin and not by an indirect pressure effect from the tumour.
The HL‐A System in Lymphoblastic Leukaemia
Authors: LAWLER SYLVIA D. , KLOUDA P. T. , HARDISTY R. M. , TILL MORWENNA M.
Published: March 2008

Summary The HL‐A system was studied in 58 Caucasian patients with acute lymphoblastic leukaemia and their available close relatives. No gross disturbance in the distribution of the internationally defined antigens was found in the patients or their families. The high frequency of the FJH antigen is discussed. Segregation ratios within the families were, as expected, on a random basis. The haplotypes occurring most frequently in the patients were those found also to be commonest in the normal population. Suceptibility to aute lymphoblastic leukaemia could thus not be related to any particular HL‐A phenotype or genotype.
The Measurement of Reticuloendothelial Iron Release using Iron–Dextran
Authors: Beamish M. R. , Davies A. G. , Eakins J. D. , Jacobs A. , Trevett D.
Published: March 2008

An index of reticuloendothelial cell release of iron for erythropoiesis can be derived from simultaneous measurements of iron—dextran and transferrin‐bound iron utilization. Reticuloendothelial iron release was found to be reduced in patients with Hodgkins disease, chronic renal failure and some cases of rheumatoid arthritis. It was increased in patients with iron deficiency.
Serum Lysozyme and Vitamin B12 Binding Capacity in Myeloproliferative Disorders
Authors: Catovsky D. , Galton A. G. , Griffin Chantal , Hoffbrand A. V. , Szur L.
Published: March 2008

Summary Estimations of serum lysozyme (muramidase), total B12 binding capacity (TB12BC) and folate were performed in 122 patients: 69 with myeloproliferative disorders (39, polycythaemia rubra vera (PRV); 10, chronic granulocytic leukaemia, Ph1‐chromosome positive (CGL); 20, myelosclerosis) and 53 with other disease which affect leucocyte production or turnover (17, monocytic leukaemias; 20, megaloblastic anaemia; 15, neutropenia; and a single case of red cell aplasia progressing to a myeloproliferative disorder).

The highest serum lysozyme levels were found in monocytic leukaemia. Serum lysozyme concentrations were also elevated in myelosclerosis and to a lesser extent in CGL and in PRV. High levels in PRV occurred in patients developing myelosclerosis or with active disease, resistant to treatment. Significantly higher concentrations of lysozyme were present in patients with myelosclerosis following PRV than in patients with the primary form of the disease. Patients with myeloproliferative diseases and high lysozyme concentrations tended to have low serum folate levels.

Slightly raised levels were found in about 50% of patients with megaloblastic anaemia. Moderately high serum lysozyme concentrations also occurred in patients with neutropenia and hypercellular bone marrows but not in those with hypocellular marrows.

TB12BC concentrationswere increased in the myeloproliferative disorders, especially in CGL and to a lesser extent in myelosclerosis and least of all in PRV. The results suggest that serum lysozyme reflects granulocyte turnover (except in monocytic leukaemia) while TB12BC (providing liver function is normal) correlates closely with the total blood (and possibly marrow and splenic) granulocyte pool. The ratio between serum lysozyme and TB12BC proved to be a useful index of the balance between granulocyte turnover and total granulocyte pool in individual patients.
The Hereditary Transmission of Congenital ‘True’Hypoprothrombinaemia
Authors: Girolami A.
Published: March 2008

SUMMARY. The family pedigrees of three patients with congenital ‘true’hypoprothrombinaemia are reported. By means of a specific prothrombin assay three groups of patients could be separated, namely: homozygote, heterozygote and normal.

The one‐stage factor II level in the homozygotes varied between 9% and 16%. Similar levels were obtained by means of other prothrombin assays.

The prothrombin level in the heterozygotes varied between 43% and 75% (average 58.1·9.7).

The prothrombin level in the normal relatives of the homozygote patients varied between 84% and 130% (average 96.7·10.2).

The prothrombin level in a group of normal subjects unrelated to the homozygotes varied between 86% and 115% (average 98.0·7.9).

These data are compatible with the assumption that the disorder is transmitted as an autosomal incompletely recessive trait. The heterozygotes are usually asymptomatic but may have epistaxis, excessive bleeding after tooth extraction and menorrhagia.
Methods for the Production of Clinically Effective Intermediate and High‐Purity Factor‐VIII Concentrates
Authors: Newman Jack , Johnson Alan J. , Karpatkin Margaret H. , Puszkin Saul
Published: March 2008

Summary. An intermediate‐ and a high‐purity factor‐VIII concentrate for clinical use have been prepared on a large scale by cryoethanol precipitation, extraction of the precipitate with tris buffer, and fractionation with polyethylene glycol. With bench‐scale fractionation, the intermediate material is 22‐fold purified on the average and the mean yield is 63%, while the high‐purity factor VIII is 274‐fold purified with a mean yield of 62%. With fractionation of 100 1. or more of fresh frozen plasma, the intermediate material shows a 30% yield and 14‐30‐fold purification; the high‐purity factor VIII shows an 18% yield and 125–350‐fold purification using 5.8 g/100 ml polyethylene glycol (PEG). A yield of nearly 30% should be possible with PEG, 4–5 g/100 ml. Both factor‐VIII preparations are stable for over a year in the lyophilized state at 4°C. Other plasma proteins can be fractionated from the residual plasma by routine Cohn procedures.
The Presence of Contractile Proteins in Platelet Microparticles Isolated from Human and Animal Platelet‐free Plasma
Authors: Crawford N.
Published: March 2008

Summary. Microparticles have been prepared from human and animal plateletfree plasma by dilution of the plasma to lower the specific gravity followed by high‐speed ultracentrifugation. The protein, cholesterol, and phospholipid content (and cholesterol‐phospholipid ratios) of these microparticles have been determined and compared with values obtained with whole platelet homogenates and various isolated platelet subcellular fractions. Immunological investigations on the microparticles and on the density gradient fractions of platelet homogenates suggest that the particles may have their origin either in the surface membrane or within the intracellular membrane structures of the blood platelets. The microparticles have an associated ATP‐ase activity which, though lower in specific activity than isolated platelet ‘contractile protein’ (thrombosthenin), has similar characteristics in response to divalent cations, mersalyl and ouabain. Thrombosthenin antisera and antisera to the microparticles both inhibit clot retraction in vitro at high dilution and also inhibit the Mg2+ ATP‐ase activity of platelet homogenates and platelet thrombosthenin. When tested against platelet subcellular fractions from sucrose density gradients both these antisera showed precipitating antibodies to the low density membrane fraction. This fraction consists almost entirely of small vesiculated and larger sheet membrane fragments. In ultrastructure, the microparticles resemble the fine granular material present in the interior of thin‐walled sacs which may often be seen in electron‐micrographs prepared from fresh platelets. These sacs are believed to be the result of either budding of the pseudopodia or herniation of the cytoplasmic contents through the platelet wall.
Acrylamide Gel Electrophoresis of Fibrinogen and Fibrin Degradation Products
Authors: Niewiarowski Stefan , Nandi Manis
Published: March 2008

Summary. Thin layer two phase acrylamide gel electrophoresis was used for separation of fibrinogen and fibrin degradation products which were subsequently quantitated by scanning. The use of 6 m urea in the spacer gel greatly improved separation. Three main fibrinogen fragments X, Y and D and minor fragments E1, E2 and E3 were identified. During plasmin digestion of fibrinogen, Fragment X gradually decreased and Fragment D increased. The concentration of Fragment Y was rather low as would be expected of an intermediate product in the conversion of X to D. At various times of proteolysis, there was good agreement between the level of Fragment X determined by electrophoresis and the amount of protein precipitated at low concentration of protamine sulphate (PS) from the digest pretreated with thrombin. The study supports the concept of two varieties of Fragment X, one with fibrinopeptides (Xfp)—in fibrinogen degradation products (FDP)—and one devoid of fibrinopeptides (X°)—in fibrin degradation products (fdp). During electrophoresis without urea, Fragment X° undergoes extensive polymerization in the slots and gel because of its dissociation from complexes with Fragments Y and D. In the presence of urea, Fragment X° of the early fibrin digest had slower electrophoretic mobility than Fragment Xfp. The mobility of other fibrinogen fragments was not affected by thrombin.
Reticulocyte Sequestration in Spleens of Normal, Anaemic and Leukaemic Rats
Authors: Dornfest Burton S. , Handler Eugene S. , Handler Evelyn E.
Published: March 2008

Summary. Isolated spleens of normal, anaemic, and leukaemic rats were perfused with blood containing 2.7% reticulocytes collected from non‐bled rats and 12.1 and 22.4% reticulocytes collected from bled rats. From 2 to 11% of the reticulocytes in the blood were sequestered in the spleens, depending on (1) the level of reticulocytes in the blood, (2) whether the cells were macrocytic or normal‐sized reticulocytes, (3) the length of time of perfusion, and (4) the physiological condition of the spleen. The higher the reticulocyte percentage in the blood the greater the number of reticulocytes sequestered. A higher percentage of macrocytic reticulocytes was sequestered than normal‐sized reticulocytes. The longer the perfusion the greater the number of cells sequestered, the percentage of cells sequestered decreasing with time. No differences were observed between the sequestering capacity of spleens of normal and anaemic rats but the capacity of spleens of leukaemic rats was usually decreased. The results indicate that the rat spleen can sequester reticulocytes but that this capacity would not perceptibly influence blood reticulocyte levels in the intact animal.
Annotation: THE ANAEMIA OF CHRONIC DISORDERS
Authors: Cartwright G. E. , Lee G. R.
Published: March 2008

Although the anaemia associated with chronic disorders is one of the most frequently encountered forms of anaemia, particularly in hospital patients, it has not received the distinction which it deserves, in part, perhaps, because of the lack of an appropriate name. The term ‘simple chronic anaemia’ is most inappropriate because the pathogenesis of the anaemia involves the delicate control mechanisms of erythropoiesis and these are not simple. The title ‘anaemia of chronic infections’ is much too restrictive, for the anaemia occurs in patients with cancer, lymphoma, rheumatoid arthritis, collagen vascular diseases, fractures, severe tissue injury and many other disorders. ‘Anaemia of chronic disorders’, though a less restrictive title, is unsatisfactory because many other types of anaemia occur in these disorders, such as blood loss, overt haemolytic anaemia of various types, reactions to drugs, myelophthisic anaemia, and the anaemia of renal failure. Furthermore, the name gives no hint as to the diagnostic features or pathogenesis of the anaemia. A more descriptive, but somewhat more cumbersome, title might be ‘sideropenic anaemia with reticuloendothelial siderosis.’
Ultrastructural Localization of Iron in the Human Jejunum in Iron Overload (Bantu Siderosis)
Authors: Theron J. J. , Mekel R. C. P. M.
Published: March 2008

Summary. Light and electron microscopical studies of intestinal biopsies from 22 patients with advanced Bantu siderosis revealed that ferritin‐iron was deposited in dense membrane‐bound ferritin bodies, in apical vesicles and in Golgi vesicles of the jejunal absorptive cells. Acid phosphatase was demonstrated within the ferritin bodies and it was concluded that these bodies were lysosomes. Ferritin molecules were also observed in the intercellular space between epithelial cells and cells of the lamina propria, and within the lumen of capillaries.

Electron‐dense material, presumably ‘haemosiderin’ occurred in the Golgi cisternae of the concave face of the Golgi complex of jejunal epithelial cells. In the lamina propria, iron in the form of ferritin and haemosiderin was observed mainly in macrophages, but ferritin was also deposited within fibroblasts.
Prognosis in Hodgkin's Disease Related to the Lymphocyte Count
Authors: Swan H. T. , Knowelden J.
Published: March 2008

Summary. Case notes of 328 histologically‐diagnosed patients with Hodgkin's disease have been studied in respect to sex, age of presentation, lymphocyte count in the peripheral blood and survival. Lymphocyte counts were accepted only if they had been made before the first course of radiotherapy or cytotoxic chemotherapy.

A clear difference in prognosis has been demonstrated in three lymphocyte groups. The worst prognosis was associated with lymphocyte counts of less than 1000/μl in which group the proportion of patients surviving 5 yr was only 12%. The prognosis was better where the initial counts were between 1000 and 1500/μl, the 5‐yr survival being 26%, and was best where the lymphocyte counts were above 1500/μl, the 5‐yr survival being 35%.
Iron Kinetics in the Skin
Authors: Cavill I. , Jacobs A.
Published: March 2008

Summary. The clearance of transferrin‐bound iron from the interstitial fluid of skin has been measured in normal and iron‐deficient subjects. It is possible to interpret the results by means of a two‐compartment model and to calculate the rate of entry and exit of iron in skin cells. There is a decrease in the amount of iron entering skin cells in patients with iron‐deficiency anaemia.

The demonstration of an intracellular exchangeable iron pool in the skin suggests that there may also be large parenchymal pools in other organs, which are indirectly in equilibrium with the plasma pool.
Erythrocyte Delta‐Aminolaevulic Acid Dehydrase Activity in Anaemia
Authors: Battistini V. , Morrow J. J. , Ginsburg D. , Thompson G. , Moore M. R. , Goldberg A.
Published: March 2008

Summary. A method is described for measuring the activity of the enzyme δ‐aminolaevulic acid dehydrase (ALA‐dehydrase) in the erythrocytes of normal subjects and of patients with macrocytic anaemia due to vitamin‐B12 and folic‐acid deficiency, iron‐deficiency anaemia, lead poisoning and the secondary anaemias of rheumatoid arthritis and carcinomatosis.

A significant increase in pre‐treatment enzyme activity was found in the macrocytic anaemias, whether due to a deficiency of vitamin B12 or folie acid. A further rise of ALA‐dehydrase activity occurred in close relationship with the reticulocyte response, returning to pre‐treatment levels as their numbers fell. Enzyme activity returned to normal in 2 mth.

Enzyme activity was significantly diminished in lead poisoning. No significant difference from normal was found in iron‐deficiency anaemia, or in the secondary anaemias of rheumatoid arthritis and carcinomatosis.

Enzyme assay in the erythrocytes of bled rabbits showed that the enzyme activity was directly related to the number of reticulocytes present.
Placental Transfer of Iron in the Rabbit
Authors: Douglas T. A. , Renton J. P. , Watts C.
Published: March 2008

Summary. The uptake of 59Fe by rabbit placenta at different stages of gestation was determined, and subsequently the uptake of 59Fe by the subcellular fractions of the rabbit placenta during the last third of gestation was measured. The iron‐containing compounds in the non‐particulate fraction of the rabbit placenta during the last third of gestation were isolated and characterized.
Combined Glucosephosphate Isomerase and Glucose‐6‐Phosphate Dehydrogenase Deficiency of the Erythrocytes: A New Haemolytic Syndrome
Authors: Schröter Werner , Brittinger Günter , Zimmerschmitt Erich , König Erika , Schrader Detlev
Published: March 2008

Summary. A new haemolytic syndrome associated with the combination of genetically determined glucosephosphate isomerase and glucose‐6‐phosphate dehydrogenase deficiency of the erythrocytes was demonstrated in a German family. The propositus (a male), homozygous for the glucosephosphate isomerase deficiency and hemizygous for the glucose‐6‐phosphate dehydrogenase deficiency, has suffered from a moderate chronic nonspherocytic haemolytic anaemia since early childhood with haemolytic crises during infections and after the ingestion of haemolytic drugs. The family members, heterozygous or hemizygous for both of the enzyme defects, are phenotypic normal individuals. From the biochemical data it is concluded that the glucose‐6‐phosphate dehydrogenase deficiency might partly protect the glucosephosphate isomerase‐deficient cells of the propositus by supporting the accumulation of glucose‐6‐phosphate, thus potentiating the markedly decreased glucosephosphate isomerase activity. In this case the enzyme may operate nearer to substrate saturation than do cells with glucosephosphate isomerase deficiency only.
Globin Synthesis in Sideroblastic Anaemia I α AND β PEPTIDE CHAIN SYNTHESIS
Authors: White J. M. , Brain M. C. , Ali M. A. M.
Published: March 2008

Summary. The in vitro synthesis of the α and β peptide chains of globin have been measured in 11 patients suffering from sideroblastic anaemia (four congenital and seven idiopathic acquired). In the I0 patients who were anaemic the findings were similar. The synthesis of the globin chains was found to be defective in two respects; firstly, synthesis was asynchronous with an apparent deficiency of the synthesis of α chains, and, secondly, a large proportion of both α and β chains synthesized were not associated with haem but were free in the cell in the form of αβ dimers. Addition of haem to the incubation mixture greatly stimulated the synthesis of both chains, removed the free dimer pool and appeared to stimulate a chain synthesis. The finding that a large proportion of the α and β chains synthesized are not associated with haem but are free within the cell as a dimer pool, is very strong evidence that the underlying defect in sideroblastic anaemia is haem deficiency. The defective synthesis of a chains relative to β chains is as yet unexplained but may account for the low haemoglobin A2 associated with this condition.
Absorption of Vitamin B12 in the Guinea‐Pig III. THE FORMS OF VITAMIN B12 IN ILEAL MUCOSA AND PORTAL PLASMA IN THE FASTING STATE AND DURING ABSORPTION OF CYANOCOBALAMIN
Authors: Peters T. J. , Linnell J. C. , Matthews D. M. , Hoffbrand A. V.
Published: March 2008

Summary. The forms of vitamin B12 in guinea‐pig ileum, liver and portal plasma were studied using a chromatographic‐bioautographic technique. 5’Deoxyadeno‐sylcobalamin was the principal cobalamin in each tissue although significant amounts of methylcobalamin were detected in plasma. An unidentified cobalamin was also found in all three tissues.

During the absorption of labelled cyanocobalamin a proportion of this analogue was converted to 5’deoxyadenosylcobalamin in the ileum; preliminary experiments suggest that the site of inter‐conversion was the mitochondria of the ileal epithelial cells. A significant proportion of the cyanocobalamin was transferred to the portal plasma unchanged however, indicating that the mitochondrial localization of vitamin B12 during its absorption, shown in previous studies, is not solely related to the conversion of vitamin B12 analogues from one form to another.
Cytomegalovirus Infection in Blood Donors—A Prospective Study
Authors: Perham T. G. M. , Caul E. O. , Conway P. J. , Mott M. G.
Published: March 2008

Summary. One hundred and ninety‐five blood donors for 10 patients who had open‐heart surgery and fresh blood transfusion were screened for cytomegalovirus (CMV). Complement‐fixing antibody to CMV was present in 55%, but no CMV was isolated. The 21 blood donors, for two of the 10 patients who became infected with CMV post‐operatively, were recalled, but there was no evidence of recent infection with CMV.

Of the 10 patients, three died and could therefore not be studied in the post‐operative period. Of the remaining seven patients, one excreted the virus pre‐ and post‐operatively, and three acquired CMV post‐operatively, after receiving fresh blood with complement‐fixing titres to CMV ranging from 1/8 to 1/128. None of the three non‐CMV infected patients had antibody to CMV; one received CMV antibody‐free fresh blood and the other two received fresh blood with titres ranging from 1/16 to 1/64.

These results are discussed and, though numbers are small, the question of using blood within 36 hr of donation should be carefully reconsidered because of the risk of cytomegalovirus transmission.
A Study of Storage Iron in the Pregnant Rat
Authors: Wyllie John C. , Kaufman Nathan
Published: March 2008

Summary. It has been established that maternal storage iron is depleted during pregnancy in order to supply part of the iron required by the developing foetus and by the increasing red cell mass of the mother. It is also accepted that ferritin and haemosiderin are equally available as sources of storage iron.

We measured the quantity of ferritin and haemosiderin in the liver and spleen of the rat at intervals during the latter half of pregnancy and have shown that ferritin iron is reduced whereas haemosiderin iron remains unchanged. The 2 and 24 hr uptake of 59Fe by these compounds was also measured. 59Fe is incorporated into both compounds; the uptake of 59Fe by ferritin falls in late pregnancy. Newlydeposited 59Fe is withdrawn from ferritin but not from haemosiderin.

These results indicate that ferritin is the major source of storage iron in the pregnant rat. Ferritin iron is reduced in the liver and spleen because of a decreased uptake of iron as well as an increased mobilization.
Primary Rhesus Immunization of Male Volunteers
Authors: Cook I. A.
Published: March 2008

Summary. To provide high titre plasma for the preparation of anti‐D immunoglobulin, three groups of group A Rh negative (cde/cde) male volunteers, totalling 34 men, were immunized with Group A Rh positive (cDE/cde) blood. Twenty‐three men (68%) developed Rhesus antibodies. The importance of adequate safeguards in the planning of such immunization schemes, as well as continued medical supervision, is stressed.
Mechanisms of Acquired Defects of the Stabilization of Fibrin
Authors: Losowsky M. S. , Walls W. D.
Published: March 2008

Summary. The causes of undemonstrable plasma fibrin‐stabilizing‐factor (FSF, factor XIII) activity in various diseases have been investigated. Results suggest impaired synthesis of the enzyme in three patients with portal cirrhosis, and one with acute hepatic necrosis. Impaired activation of factor XIII seems a possible explanation in one patient with portal cirrhosis. Evidence of a plasma inhibitor of factor XIII was obtained in six patients with chronic renal failure and two with acute hepatic necrosis. The inhibitor present in renal failure was non‐dialysable, relatively heat labile and not adsorbed by either aluminium hydroxide or bentonite.
Metabolic Observations on Platelets from Patients with Familial Thrombopathic Thrombocytopenia
Authors: Baadenhuijsen H. , Hirschhäuser C. , Kurstjens R. , Ewals M. , Haanen C.
Published: March 2008

Summary. Glycolytic enzyme activities and adenine nucleotide content were studied in normal platelets and in platelets from patients with hereditary thrombopathic thrombocytopenia. This study revealed that most of the enzyme activities, the nucleotide content, and the platelet volumes of the patients were increased to two to three times the normal values. Taking into account the increased platelet volumes, the enzyme activities and nucleotide content were almost normal except for the activities of enolase, pyruvate kinase, and lactate dehydrogenase, which remained increased. Related to the platelet volume there was a normal lactate production and an impaired oxygen consumption. The existing platelet factor‐3 deficiency, changes in lipid composition, and absence of collagen‐induced platelet aggregation, together with the findings here described, are interpreted as manifestations of an underlying, genetically determined, disturbance in membrane structure.
Studies of the Peripheral Blood of the Port Jackson Shark (Heterodontus portusjacksoni) with Particular Reference to the Thrombocyte
Authors: Stokes E. E. , Firkin B. G.
Published: March 2008

Summary. Morphological features of the peripheral blood of the ancestral elasmo‐branch Heterodontus portusjacksoni, a shark species, are described. The red cell is nucleated and contains many membrane‐lined vacuoles which are derived from mitochondria. The granulocytic series resembles that of the mammals in appearance and in some phagocytic properties. The thrombocytes possess a number of similarities to mammalian platelets, but exhibit many differences. They aggregate readily, but this is temperature reversible and is independent of thrombin and ADP. They show a remarkable affinity for latex particles. Unlike many other species, fibrin formation and thrombocyte aggregation are apparently independent phenomena occurring in parallel rather than in series. Tritiated thymidine studies and the observation of mitotic figures in the peripheral blood suggest that at least part of the red cell and thrombocyte proliferation occurs in the circulating blood.
Cytomegalovirus Infection in Childhood Leukaemia
Authors: Sutton R. N. P. , Darby C. W. , Gumpel S. M.
Published: March 2008

Summary. Serological evidence of infection with cytomegalovirus was established in six out of 27 children with leukaemia observed over a period of 37 mth; overt illness was observed in three of these six. Infection with cytomegalovirus apparently did not influence the prognosis of the underlying disease and there was no evidence that immunoglobulin deficiency predisposed to infection.
Fibrinogen Survival with [75Se]Selenomethionine during l‐Asparaginase Therapy
Authors: Brodsky Isadore , Kahn S. Benham , Vash George , Ross Evelyn M. , Petkov Goldie
Published: March 2008

Summary. Fibrinogen anabolism and catabolism in four patients (acute lymphoblastic leukaemia; lymphosarcoma cell leukaemia; generalized lymphosarcoma; hypernephroma) were determined with [75Se]selenomethionine during a period of hypofibrinogenaemia induced by l‐asparaginase. The anabolic phase was normal but the fibrinogen survival decreased to 1.5–4.0 days (normal range, 7.8 ± 2.8 days). Heparin therapy did not affect either the fibrinogen levels or abnormal thrombin times. In two patients with widespread Hodgkin's disease in whom l‐asparaginase therapy was started after the labelling of fibrinogen with [75Se]selenomethionine, the fibrinogen survival was normal. The results suggest the production of an intrinsically abnormal fibrinogen with a decreased survival during l‐asparaginase administration.
Döhle Bodies and Acute Myeloblastic Leukaemia in One Family: A New Familial Disorder?
Authors: Goudsmit R. , v. Leeuwen A. M. , James J.
Published: March 2008

Summary. A 17‐yr‐old male patient with congenital lymphoedema and an atrial septal defect (secundum type) suffered from repeated periods of unexplained fever and had an iron resistant anaemia. A high proportion of his neutrophil granulocytes consistently showed Dohle bodies. Two sisters and two brothers showed the same phenomenon. Two of these died at an early age from acute myeloblastic leukaemia. The implications of this phenomenon are discussed and the possibility that these patients may represent a new familial disorder is considered.
Glycolytic and Respiratory Enzyme Activity in Relation to Leucocyte Maturation
Authors: Stuart J. , Simpson Jennifer S. , Wallin Josephine M.
Published: March 2008

Summary. Low activity of intramitochondrial dehydrogenases and of a mitochondrial membrane hydrogen shuttle system has been demonstrated cytochemically in the lymphoblast and in three Burkitt lymphoma cell lines; this contrasts with a relatively high activity of extramitochondrial glycolytic enzymes and may render these cells abnormally sensitive to glycolytic enzyme inhibition. This pattern of enzyme activity was not seen in normal and leukaemic myeloid cells at any stage of maturation, nor in lymphoid cells undergoing benign hyperplasia, and appears to be related to mitochondrial number. This explanation is in contrast to previous claims of specific enzyme deletions in solid tumours and in mouse lymphoma.
Factor VIII (Antihaemophilic Factor) in Tissues Detected by Antibody Neutralization
Authors: Bloom A. L. , Giddings J. C.
Published: March 2008

Summary. Antibody to factor VIII was obtained from the plasma of patients with potent inhibitors and by immunizing rabbits with concentrated factor VIII. This was prepared by cryoprecipitation of normal plasma, treatment with Arvin, chromatography on sepharose 6B and ultrafiltration. Various tissues were washed, homogenized and examined for factor‐VIII antigen by determining their ability to neutralize the activity of inhibitor or antisera. Factor‐VIII antigen was consistently derected in relatively large amounts in human spleen and kidney homogenates and less consistently in the liver. None was found in homogenates of brain and lung and only small and variable quantities were found in other human tissues tested.
Fibrin Monomer and Platelet Aggregation in Vitro and in Vivo
Authors: Müller‐Berghaus G. , Heinrich D.
Published: March 2008

Summary. The effect of fibrin monomer or fibrinogen‐fibrin monomer complexes (FFMC) on platelet aggregation was studied in vitro and in vivo. FFMC produced by limited action of thrombin in vitro did not cause spontaneous platelet aggregation and neither accelerated nor inhibited platelet aggregation induced by ADP or collagen. If FFMC were converted to gels by treatment with ethanol, platelets aggregated spontaneously. When purified rabbit fibrin monomer was infused into rabbits pretreated with heparin to block the intravascular generation of thrombin, platelet counts did not decrease significantly, indicating the lack of a plateletaggregating effect of FFMC. It is concluded that FFMC, derived from thrombin action on fibrinogen, do not initiate or accelerate platelet aggregation.
Hereditary Microcytic Anaemia in the Mouse; Studies in Iron Distribution and Metabolism
Authors: Bannerman R. M. , Edwards J. A. , Kreimer‐Birnbaum M. , McFarland E. , Russell E. S.
Published: March 2008

Summary. Iron distribution and metabolism have been studied in hereditary iiiicrocytic anaemia of tlie mouse (gene symbol mk), an autosonial recessive trait cliaractcrizcd by hypoclironiia and microcytosis. Evidence of iron deficiency was hutid in the forin of depleted body stores, hyposidcraemia, an increased total iron biiiding capacity of tlic plasma and a high free erythrocyte‐protoporyhyrin level. I lowcvcr, the failure to find citlicr rapid clearance and high utilization of tracer doses of 59Fe or a complete response to pareliteral iron treatment indicated that simple iron deficiency was not the cause of tlie anaemia. It is suggested that generalized impairmcn t in tlie cellular uptake of iron involvingthe transfer of iron from the intestinal lumen to tlic mucosa and from tlie plasma to the erythroblast may provide a unitary explaiiation of licreditary microcytic anaemia.
A Controlled Trial of Joint Aspiration in Acute Haemophilic Haemarthrosis
Authors: Ingram G. I. C. , Mathews J. A. , Bennett A. E.
Published: March 2008

Summary. Twelve severely affected haemophiliacs presenting with 22 acute haemarthroses of the knee were admitted to a trial in which, with their consent, they were treated either by intravenous infusion of human antihaemophilic factor alone or by aspiration of the knee joint in addition. The trial was restricted to patients with haemarthroses of intermediate size, as only in this situation were the indications for aspiration considered doubtful. Thus, patients were excluded if there was insufficient knee swelling to make it likely that blood could be withdrawn, or if aspiration was positively indicated by distension causing continuous pain at rest.

By the next day, a significantly greater average range of movement had been regained in the 11 aspirated knees than in the 11 knees not aspirated, although at 5 days the average improvements were nearly equal. In planning treatment of individual cases, this benefit must be set against the painfulness of the procedure.
Determinants of Prothrombinase Activity and Modification of Prothrombin Conversion by Thrombin‐Treated Factor V
Authors: Kandall Carol , Akinbami T. K. , Colman R. W.
Published: March 2008

Summary. The development of an intrinsic two‐stage assay for factor V using highly purified protein components is described. Phospholipid, activated factor X, calcium ion and factor V are incubated together to form a prothrombinase. After addition of prothrombin, sequential aliquots are removed and tested for thrombin activity using fibrinogen as a substrate. The rate of thrombin generation is linear for at least 10 min and increases with increasing concentrations of factor V or activated factor X. At a fixed concentration of activated factor X, a linear relationship is observed between the logarithm of the initial rate of thrombin generation and the logarithm of the factor V concentration. Oligomeric forms of factor V generate parallel but non‐identical concentration curves indicating differing abilities to form prothrombinase.

The rate of thrombin generation eventually decreases and a maximum thrombin concentration is attained. This phenomenon is not attributable to substrate exhaustion or to decay of prothrombinase activity. Evidence for the formation of an inhibitor during prothrombin conversion, which is directed against both prothrombinase and the reaction of thrombin with fibrinogen, is offered.

Activation of factor V by thrombin is demonstrable in the two‐stage intrinsic system and in a modified extrinsic sequential technique. In both systems the time course and extent of activation are similar to those observed using a one‐stage extrinsic assay.

Thrombin formation began immediately with or without prior exposure of factor V to thrombin. The ‘lag time’ observed by some previous workers is shown to be an artifact due to inappropriate extrapolation of the standard thrombin curve.
The Lysis of Paroxysmal Nocturnal Haemoglobinuria Red Cells by Serum and Cobra Factor
Authors: Kabakĉi Tomris , Rosse W. F. , Logue G. L.
Published: March 2008

Summary. The complement‐sensitive red cells of patients with paroxysmal nocturnal haemoglobinuria (PNH) are haemolysed in the presence of serum and a protein factor present in cobra venom (CoF). The reaction of CoF and a serum factor, C3 proactivator, requires Mg2+. Once this interaction has taken place, the activation of C3 and the terminal components of complement can occur in the presence of EDTA and result in the lysis of PNH red cells.

The concentration of reactants may be adjusted so that all of the complementsensitive red cells of PNH patients and the red cells of no other patients are lysed. A simple but specific and precise test for the presence of the complement‐sensitive red cells of PNH was devised. Normal human red cells treated with trypsin and neuraminidase are not lysed, whereas these cells treated with glutathione or 2‐aminoethylisothiouronium bromide (AET) are lysed.
The Effects of Phenylhydrazine‐Induced Haemolysis on the Behaviour of Regenerating Marrow Stroma
Authors: Tavassoli M. , Maniatis Alice , Crosby W. H.
Published: March 2008

Summary. Fragments of marrow tissue autotransplanted in a subcutaneous site, regenerate and give rise to a haemopoietic nodule surrounded by a shell of bone. The process originates from supporting stroma of implanted marrow. Phenylhydrazine‐induced acute haemolysis stimulates the growth of these implants and results in almost 100% increase in the weight of implants. This effect is probably the result of an increased demand for erythropoiesis and implies an interaction between blood‐forming cells and the marrow stroma. Phenylhydrazine‐induced chronic haemolysis, on the other hand, suppresses the growth of implants and results in a markedly lower rate of take and decreased weight of implants. This appears to be a direct effect of phenylhydrazine on cell proliferation in the regenerating implant.
The Susceptibility to Autoxidation of Human Red Cell Lipids in Health and Disease
Authors: Stocks J. , Offerman E. L. , Modell C. B. , Dormandy T. L.
Published: March 2008

Summary. The susceptibility of human red cells to autoxidation was measured (i) in various groups of normal subjects, (ii) in haemolytic states, and (iii) in non‐haemolytic disease. Many types of haemolytic disease—notably thalassaemia major and autoimmune haemlytic anaemia—were associated with a greatly and persistently increased susceptibility of the red cell lipids to autoxidation. In two patients with haemolytic disease this was the only biochemical abnormality found. Susceptibility to autoxidation is about three times higher in the newborn period than it is in adult life; and there is a comparatively wide scatter in old age.
Microangiopathic Haemolytic Anaemia (MHA)
Authors: Brain M. C.
Published: March 2008

Summary. The study of microangiopathic haemolytic anaemia in Professor Dacie's Department in the decade 1959–69 represents an unusual achievement in medical research in which one group of workers have put forward a hypothesis regarding a disease process, have subsequently confirmed it both in experimental animals and in man, and have shown the benefit of treatment based on their observations, and, furthermore, the work has received independent confirmation. Although MHA is but one of the many notable contributions made by Professor Dacie and his colleagues it is, perhaps, unique in the extent to which it was elucidated by his Department. Although it is self‐evident, it must be stated that the study of MHA would not have come about without Professor Dacie's curiosity and interest in abnormal red‐cell morphology, and that his stimulus and encouragement, especially to myself, made the elucidation of MHA possible.
Observations on the Mechanism of the Haematological Changes in the Haemolytic Uraemic Syndrome of Infancy
Authors: Metz J.
Published: March 2008

Summary. The haemolytic uraemic syndrome of infancy (HUSI) is one of a group of diseases described by Brain, Dacie and Hourihane under the generic name ‘microangiopathic haemolytic anaemia’ (MHA). Survival studies using labelled red cells support the concept that increased haemolysis results from damage to the red cells sustained in small blood vessels. Studies with labelled platelets and fibrinogen fail to provide evidence for continuing intrarenal coagulation once the classic triad of haemolytic anaemia, thrombocytopenia and renal failure has been established.
Folate in Tropical Sprue
Authors: Klipstein F. A.
Published: March 2008

Summary. Persons who acquire tropical sprue lose their ability to absorb folate from the diet. This is due to inability to hydrolyse polyglutamate forms in most cases and additionally to absorb monoglutamate folate in instances of severe mucosal damage. Neither the specific site of impaired deconjugation nor the acutal defect in the transport process are known. Malabsorption of folate results in a sequence of events similar to that which occurs when folate is deleted from the diet: prompt fall in serum concentration followed by development of megaloblastic changes in the bone marrow and eventually anaemia. Reduced tissue stores, if present due to inadequate intake or increased requirement, increases the rapidity of folate depletion. Prompt but partial response of the mucosal abnormality to treatment with folic acid indicates that once acquired, folate deficiency acts in some unexplained manner to perpetuate the intestinal lesion.
Slow Rate of Haemichrome Formation from Oxidized Haemoglobin Bart's (γ4): A Possible Explanation for the Unequal Quantities of Haemoglobins H (β4) and Bart's in Alpha‐Thalassaemia
Authors: Rachmilewitz E. A. , Harari E.
Published: March 2008

Summary

Haemoglobins A, H (β4) and Bart's (γ4) obtained from two adult patients with haemoglobin H and persistent haemoglobin Bart's were separated and eluted from starch block electrophoresis. The spectrum of oxidized haemoglobin Bart's separated from the two patients indicated the presence of a haemichrome. In this respect, the properties of oxidized y‐chains are similar to those of oxidized haem‐bear‐ing α‐chains and haemoglobin H.

The rate of haemichrome formation was found to be different for each sub‐unit in the following order α > β > γ > α2β2. These in vitro observations correlate well with the properties of excess haemoglobin subunits present in vivo in red cells of patients with the thalassaemia syndrome: α‐chains precipitate as inclusion bodies in the bone marrow and β‐chains mainly in peripheral mature red cells while precipitates of γ‐chains have not been identified. On the other hand, γ‐chains are the most stable in a soluble form while α‐chains, even when present in excess, can hardly be detected in a soluble form.

In the heterozygote for α‐thalassaemia an average of 6.0% haemoglobin Bart's usually diminishes during the first year without being replaced by a similar amount of haemoglobin H. In haemoglobin H disease large quantities of haemoglobin Bart's are replaced by much smaller amounts of haemoglobin H. Assuming that the genetic defect in α‐chain production is the same in foetal and adult life, the differences in solubility and stability between γ and β‐oxidized chains may explain this phenomenon. Since γ‐chains are stable in their oxidized form, they do not precipitate readily in contrast with β‐chains which form inclusion bodies.
Bone Marrow Involvement in Burkitt's Lymphoma: Results of a Prospective Study
Authors: Bluming Avrum Z. , Ziegler John L. , Carbone Paul P.
Published: March 2008

Summary

Eighty‐five previously untreated patients with Burkitt's lymphoma were studied prospectively for the development of generalized bone marrow involvement by tumour. Fourteen (16%) of the patients in this series manifested marrow tumour involvement at some time during the course of their disease and seven of these presented with this complication. Only 20% of the affected patients had a peripheral leukaemic picture with a high percentage of circulating tumour cells. The prognosis associated with this complication appeared to be slightly worse in patients developing this picture following initial therapy than in those presenting with it. Pretreatment bone marrow lymphocyte counts were found to be 50% higher in patients who later developed bone marrow tumour involvement than in those who remained free of this complication. The implications of these observations are discussed.
Uptake of Latex and Thorotrast by Human Platelets In Vitro: Effect of Various Chemicals Demonstrating Differing Mechanisms and Metabolic Requirements
Authors: Mant M. J. , Firkin B. G.
Published: March 2008

Summary

In vitro platelet uptake of latex and thorotrast has been studied in the presence of a number of chemicals which inhibit metabolism and alter platelet ukrastructure. Latex uptake appears to require energy from anaerobic glycolysis and divalent cations, and is relatively easily influenced by substances which alter platelet ukrastructure. Platelet ATPases play either no role or only a minor one, and intact microtubules are unnecessary. Energy requirements for thorotrast uptake appear to be minimal or absent, divalent cations are not needed, and gross alteration of platelet ukrastructure still allows small amounts of thorotrast to gain entry into a few platelets. Platelet ATPases and intact microtubules are unnecessary for thorotrast uptake. It is concluded that latex uptake is probably by an active phagocytic process and thorotrast uptake is by a different mechanism. The relationship of increased citric acid cycle activity to degranulation and particle uptake is discussed, and it is suggested that this respiratory burst is unnecessary for either of these events, and that it is not a necessary accompaniment of platelet phagocytosis, nor specific for this process.
The Effects of Collagen and Kaolin on the Intrinsic Coagulant Activity of Platelets. EVIDENCE FOR AN ALTERNATIVE PATHWAY IN INTRINSIC COAGULATION NOT REQUIRING FACTOR XII
Authors: Walsh P. N.
Published: March 2008

Summary

Collagen and kaolin have been shown by other workers to initiate intrinsic coagulation by activating factor XII in plasma and to have complex effects on platelets. Because of the presence of collagen at sites of vascular injury there is good reason to believe that collagen has physiological importance in haemostasis. The present experiments were done to determine the effects of collagen and kaolin on platelets and to distinguish the platelet effects from the activity which these surface‐active agents produce in plasma.

Using an albumin‐density‐gradient separation (ADGS) method for washing platelets free of loosely adsorbed coagulation factors, it is shown here that collagen can induce a coagulant activity in platelets which initiates intrinsic coagulation. This activity is independent of factor XII, provided factor XI is present. It is postulated that this collagen‐induced coagulant activity of platelets provides an alternative pathway, by‐passing factor‐XII activation, for initiating intrinsic coagulation. The existence of this alternative pathway may provide an explanation for the absence of a haemostatic defect in Hageman trait. The effects of kaolin were similar to those of collagen, but kaolin had greater capacity to activate plasma factor XII and platelet factor 3 and relatively less capacity to activate platelet‐associated factor XI.