bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucose‐6‐Phosphate Dehydrogenase Johannesburg: A New Variant with Reduced Activity in a Patient with Congenital Non‐spherocytic Haemolytic Anaemia
Authors: Balinsky Doris , Gomperts E. , Cayanis Eftihia , Jenkins T. , Bryer Davey , Bersohn I. , Metz J.
Published: March 2008

Summary. A new variant of the red‐cell enzyme glucose‐6‐phosphate dehydrogenase has been found in a Caucasoid woman and her 5‐yr‐old son. Both presented with congenital non‐spherocytic haemolytic anaemia. The variant was found to have reduced activity and greatly increased thermolability. The enzyme was unstable even in the cold; glycerol was found to stabilize it during purification. The Michaelis constant for glucose‐6‐phosphate was found to be higher than normal, whilst that for NADP was slightly lower than normal. Electrophoretic mobility was slightly decreased. Utilization of 2‐deoxy‐glucose‐6‐phosphate and deamino‐NADP, and the shape of the pH‐activity curve, were normal.
Red Cell Membrane Protein in Antibody Induced Haemolytic Anaemia
Authors: Gomperts E. D. , Metz J. , Zail S. S.
Published: March 2008

Summary. Red cell stroma from nine cases of autoimmune haemolytic anaemia (AIHA) was extracted using dilute acetic acid. The isolated protein was then electrophoresed on 8 m urea starch gel. In six cases an absence of one band and absence or decreased intensity of a second band in the slowest moving group was observed. The pattern was the same as that of hereditary spherocytosis. Whereas these six cases demonstrated specific antibody activity, the other cases of AIHA in whom antibody specificity could not be demonstrated failed to show membrane electrophoretic alterations. The electrophoretic patterns of acetic acid extracted membrane protein obtained from red cells from Rh‐incompatible haemolytic disease of the newborn were similar to those cases of AIHA showing membrane protein alterations; that of ABO incompatible haemolytic disease of the newborn did not. Attempts to induce membrane protein alterations by exposing red cells to antibodies in vitro were unsuccessful.
The Prevalence of the Rarer Inherited Haemoglobin Defects in Adult Jamaicans
Authors: Ahern E. J. , Swan A. V. , Ahern V. N.
Published: March 2008

Summary. The prevalence of several haemoglobin defects, including the traits for β‐thalassaemia (0.8%), hereditary persistence of foetal haemoglobin (0.2%) and the abnormal delta chain haemoglobin, Hb B2 (2.4%), were determined from the combined results of surveys conducted on adults in a suburban and a rural community. Mean Hb A2 levels of 2.6 ± 0.4%, 5.3 ± 0.5% and 2.0 ± 0.2% were found in 639 Hb A homozygotes, seven β‐thalassaemia traits and three traits for hereditary persistence of foetal haemoglobin (HPFH), respectively. Levels of alkali resistant haemoglobin (A.R. Hb) ranged from 0.6 to 7.3% in the β‐thalassaemia traits and were 21.0, 19.0 and 16.0% in the three HPFH traits; the remaining 770 subjects in whom A.R. Hb was measured had a mean value of 0.6 ± 0.6%.
Monitoring Successive Batches of British Comparative Thromboplastin
Authors: Hills M. , Ingram G. I. C.
Published: March 2008

Summary. Procedures used in the independent monitoring of British Comparative Thromboplastin are described. Recent results from batches of similar thromboplastin have been analysed for differences in their sensitivity to the anticoagulant defect. On the basis of observed variability, the minimum number of tests required to achieve a given level of discrimination between standardized and modified thromboplastins has been calculated to determine the number of readings which should be obtained to give a reasonable certainty of detecting unsatisfactory batches.
Reappraisal of the Role of Anti‐i in Haemolytic Anaemia in Infectious Mononucleosis
Authors: Wilkinson Lee S. , Petz Lawrence D. , Garratty George
Published: March 2008

Summary. Current literature implies that haemolytic anaemia in infectious mononucleosis is regularly caused by the temporary production of high thermal amplitude cold agglutinins of anti‐i specificity. More recently, Capra et al (1969) suggested interaction between IgG anti‐i and anti‐IgG antibodies as the cause of haemolytic anaemia in infectious mononucleosis. A detailed serologic evaluation of three patients during moderate to severe haemolytic anaemia in infectious mononucleosis revealed high thermal amplitude anti‐i in only one. This patient's direct antiglobulin test (DAT) was negative using anti‐IgG but was 3 + using anti‐C3 and ‐C4. The serum antibody titre against cord or adult Oi cells was 512 at 4°C and 4 at 31°C. The anti‐i was inhibited by mercaptoethanol, and anti‐IgG was not found in the patient's serum. Patient 2 had a negative DAT and patient 3 had a 2 + DAT using anti‐C3 and anti‐C4. Anti‐i was present only in low titre at 4°C and was unreactive at 20°C. It was inhibited by mercaptoethanol. These patients' sera contained anti‐IgG antibodies. In none of our patients were warm autoantibodies detected. This data demonstrates that haemolytic anaemia in infectious mononucleosis is not necessarily associated with high thermal amplitude anti‐i. Further, since the anti‐i antibodies in patients 2 and 3 were of low titre, were inhibited by mercaptoethanol, and did not react at physiologic temperatures, the mechanism of haemolysis in these patients does not seem related to the interaction of anti‐IgG and IgG anti‐i antibodies. Further work is necessary to clarify the mechanism of haemolytic anaemia in infectious mononucleosis.
Haemoglobin D Iran: β222 Glutamic Acid→Glutamine (B4)
Authors: Rahbar Samuel
Published: March 2008

Summary.

A new haemoglobin D (Iran) has been described. The substitution was in the beta chain at residue 22 (B4), which is the most frequently mutated area in human haemoglobin. No clinical symptoms were associated with this haemoglobin.
Antifibrinolytic Treatment in Haemophilia: A Controlled Trial of Prophylaxis with Tranexamic Acid
Authors: Bennett A. E. , Ingram G. I. C. , Inglish P. J.
Published: March 2008

Summary.

A randomized controlled trial of the antifibrinolytic agent amino‐methylcyclohexane carboxylic acid (AMCA, Tranexamic acid) in the prophylactic treatment of haemophilia is reported. The active treatment (2 g daily) or indistinguishable inert tablets were given for 12 consecutive periods of 28 days. The effect of the active treatment was minimal and incapacity from the disease and the need for the administration of factor VIII were not reduced. It is considered that sound evidence does not exist for recommending the prophylactic use of antifibrinolytic drugs in haemophilia.
Relationship between Blast‐Cell Morphology and Occurrence of a Syndrome of Disseminated Intravascular Coagulation
Authors: Sultan C. , Heilmann‐Gouault M. , Tulliez M.
Published: March 2008

Summary.

Eighteen out of 140 cases of acute myeloid leukaemia (AML) have presented a syndrome of disseminated intravascular coagulation; 17 of them had obviously similar morphological features which clearly defined them as so‐called acute promyelocytic leukaemia (APL). There is a close relationship between the morphology of the blast cells and the occurrence of a syndrome of disseminated intravascular coagulation.
Erythrocyte Membrane Vacuole Formation in Hereditary Spherocytosis
Authors: Schrier Stanley L. , Ben‐Bassat Isaac , Bensch Klaus , Seeger Muriel , Junga Irene
Published: March 2008

Summary. There is impaired drug‐induced vacuole formation in red cells from patients with hereditary spherocytosis (HS). The spherocytic shape per se accounts in part for the decreased vacuole formation seen, but there are constraints in HS red cell vacuole formation above that explicable by spheroidicity. Electron‐microscopy indicates that the vacuoles produced in HS have one‐third normal diameter. We propose that the decreased vacuole formation in HS is a result of a genetically determined abnormality of the membrane which limits its ability to invaginate and deform. The variability in vacuole formation from one HS family to another, but relative consistency within families, suggests that hereditary spherocytosis comprises a syndrome of related erythrocyte membrane disorders.

Vacuole fromation in ghosts in normal in HS. This unanticipated finding suggests that the phenomenon of ghost endocytic vacuole formation may have requiements that by‐pass the defect in the HS membrane.
May‐Hegglin Anomaly: A Defect in Megakaryocyte Fragmentation?
Authors: Godwin Herman A. , Ginsburg A. David
Published: March 2008

Summary. Studies have been performed on six members of one family with May‐Hegglin anomaly (MH) five of whom manifested a mild bleeding tendency. All were thrombocytopenic (25000–1420007/μl). Platelet kinetic studies (51Cr) showed normal survival (two autologous, one MH to normal, one normal to MH). Mean platelet volume was increased; content (per platelet) of cholesterol, phospholipid, and tyrosine was elevated 3‐ to 6‐fold. Total body platelet mass calculated from these parameters was normal. Tests of platelet function demonstrated normal adhesiveness to collagen, normal prothrombin consumption, and enhanced platelet factor 3 activity. Bleeding time was prolonged (5/5), platelet retention by glass beads was diminished (3/3), clot retraction was poor (5/5), and aggregation by ADP, adrenaline and collagen was similar to that of normal platelets at the same low concentration.

It is considered that the bleeding tendency probably reflects thrombocytopenia per se as do those tests of platelet function that are impaired. Review of the published cases supports this contention. Normal platelet survival, normal total circulating platelet mass, and intrinsically normal platelet function suggest that the giant platelets and the thrombocytopenia result from impaired and disorderly megakaryocyte fragmentation.
Elution Correction in 51Cr Red Cell Survival Studies
Authors: Bentley S. A. , Glass H. I. , Lewis S. M. , Szur L.
Published: March 2008

Summary. Red cell survival has been studied in 13 normal adults using simultaneous labelling with DF32P and 51Cr; elution correction factors have been determined for the51 Cr labelling in which ACD NIH formula A has been used as an anticoagulant with ICSH recommended method. The mean rate of 51Cr elution was 1.0% per day and there was no demonstrable early loss of either51 Cr or DF32P. The mean value for mean cell lifespan was found to be 111.2 days with an SD of 20.3 days.
Jaundice and Antibodies Directed against Factors VIII and IX in Patients Treated for Haemophilia or Christmas Disease in the United Kingdom
Authors: Biggs Rosemary
Published: March 2008

Summary. A study has been made of the incidence of jaundice and of antibodies directed against factors VIII and IX in patients treated for haemophilia and Christmas disease at 37 Haemophilia Centres in the United Kingdom during 1969–71. Records of 1837 patients were received and of these, 1625 (88.5%) had haemophilia and 212 (11.5%) had Christmas disease. The incidence of jaundice in all patients for the 3‐yr period was 3.48%. The average annual incidence of episodes of jaundice among patients treated in each year was 1.83%. The use of freeze dried concentrate (in comparison to cryoprecipitate) did not cause a dangerous increase in episodes of jaundice. The incidence of antibodies directed against factor VIII was 6–7%. The proportion did not increase over the 3‐yr period. There was no evidence of a familial tendency to develop antibodies directed against factor VIII.
The Influence pH, Temperature, and Calcium on Platelet Aggregation: Maintenance of Environmental pH and Platelet Function for in Vitro Studies in Plasma Stored at 37° C
Authors: Han P. , Ardlie N. G.
Published: March 2008

Summary. The threshold concentration of ADP required to induce second phase or irreversible platelet aggregation was shown to differ between individuals when certain environmental factors were controlled during platelet handling. The factors shown to be important were plasma pH, temperature, and calcium concentration. PRP exposed to air showed a rise in pH and this was initially associated with an increase in the threshold concentration of ADP required to induce second phase aggregation. When the pH rose above 8.0 a second phase could not be elicited. Plasma pH and platelet; responsiveness could be maintained for up to 4 hr by simply storing the PRP under an atmosphere of 5% CO2–95% air. The second phase of aggregation is due to fibrin polymerization (Ardlie & Han, 1974) which is calcium‐dependent, and the pH effect was shown to be due in part to a decrease in availability of calcium as a consequence of a pH‐dependent increase in binding of calcium, possibly to citrate and albumin. Alkaline pH also inhibited fibrin polymerization independently of calcium. The ADP threshold for secondary aggregation was also influenced by the citrate concentration and it was shown that 0.1 M and not 0.129 M (3.8%) citrate should be used for blood collection for preparation of plasma for studies of platelet function. Platelets stored at room temperature were much more sensitive to ADP and thrombin than when kept at 37° C and it is suggested that this sensitization at lower temperatures may obscure differences in platelet responsiveness between individuals. As the pH became more alkaline the sensitivity of platelets stored at room temperature increased and then subsequently decreased. Since the coagulation pathway is involved in the response of platelets to stimuli (Ardlie & Han, 1974) meaningful clinical studies of platelet function will have to be carried out with PRP and the present report defines some of the optimal conditions for handling and storage of plasma.
Identification of Promonocytes and Monocytoid Precursors in Acute Leukaemia of Adults: Ultrastructural and Cytochemical Observations
Authors: Glick Alan D. , Horn Robert G.
Published: March 2008

Summary. Examination of 25 cases of adult non‐lymphoid acute leukaemia by electron microscopy and esterase cytochemistry revealed that most cases contained a majority of classifiable cells, however undifferentiated they may have appeared by routine light microscopy. The major proliferating cell in most cases (72%) was found to be a promonocyte or monocytoid precursor cell, characterized by extreme nuclear convolution, large cytoplasmic bundles of microfilaments, and numerous small electron‐dense lysosomal granules, which strongly stained for alpha‐naphthyl acetate esterase. Pure granulocytic cases, representing a minority (24%), were composed of blasts and typical promyelocytes and myelocytes, staining for Naphthol‐AS‐D chloroacetate esterase. Only one case was totally composed of undifferentiated, unclassifiable blasts. These results show that electron microscopy and cytochemistry increase the accuracy of classification of leukaemia and that the true incidence of monocytic leukaemia may be much higher than generally recognized.
Platelet Antiheparin Activity
Authors: Walsh Peter N. , Biggs Rosemary , Gagnatelli Giovanna
Published: March 2008

Summary. A method for assaying the heparin‐neutralizing activity of platelets washed by albumin density gradient separation (ADGS) is described. Residual heparin, not neutralized by platelets, is measured by its capacity to potentiate the inactivation of factor Xa by antifactor Xa. The assay is sensitive to concentrations of heparin as low as 5 × 10−4 units (approximately 5 ng) per ml. One major advantage of the assay is that it specifically detects the heparin‐neutralizing and not the clot‐promoting effect of platelets. The calibration curve relating the logarithm of clotting time to heparin concentration is linear. Platelets washed by ADGS (original method) spontaneously released 35% of the total antiheparin activity, where as only 2.75% of the total antiheparin activity was spontaneously released from platelets washed by a modified method of ADGS. Normal platelets washed by ADGS (modified method) and solubilized with Triton X‐100 neutralized 19.08 units of heparin per 1010 platelets (mean of 19 samples). Two patients with platelet adenine nucleotide ‘storage pool deficiency’ had 16.3% and 21.4% of normal total antiheparin activity.
Fibrinogen ‘Leuven’, Another Genetic Variant
Authors: Verhaeghe R. , Verstraete M. , Vermylen J. , Vermylen C.
Published: March 2008

Summary. An in vitro coagulation defect, shown by a prolongation of the thrombin time and a discrepancy between fibrinogen determinations with different methods, is described in a young healthy female. The disturbance in the fibrinogen‐fibrin conversion, using different enzymes, persisted after purification of fibrinogen from plasma and was shown to be caused by a delayed aggregation of the patient's fibrin monomers. The presence of a delayed fibrinogen‐fibrin conversion in several members of the family indicates an inherited variant.
Investigation of the Mechanism of False Positive 125I‐Labelled Fibrinogen Scans
Authors: Kerrigan G. N. W. , Buchanan M. R. , Cade J. F. , Regoeczi E. , Hirsh J.
Published: March 2008

Summary. When 125I‐fibrinogen scanning is used for the early detection of venous thrombosis, comparison with venography has shown a small percentage of abnormal scans associated with normal venograms. The mechanism of this discrepancy was investigated in an experimental model. Venous thrombosis was produced in 56 dogs using stasis and local thrombin. The data obtained from scanning and venography were validated by direct vein examination. 125I scanning agreed in 96% with venography when thrombus was present, but when thrombus lysed or embolized scans continued to read positive even though venograms were negative. Deliberate embolization of thrombi showed that these false positive scans continued for up to 48 hr owing to activity persisting in the vein wall. This was shown on histology to be related to fibrin deposition in the sub‐endothelial and adventitial layers with inflammatory changes.
Absence of Haemoglobin A in an Individual Simultaneously Heterozygous in the Genes for Hereditary Persistence of Foetal Haemoglobin and β‐Thalassemia°
Authors: Fogarty W. M. , Vedvick T. S. , Itano H. A.
Published: March 2008

Summary. Haemoglobins F and A2 are the only haemoglobins present in an American Negro adult who is simultaneously heterozygous in the genes for hereditary persistence of foetal haemoglobin (HPFH) and β‐thalassaemia°. About 15% of the haemoglobin F in descendants who are heterozygous only for HPFH is of the Gγ‐chain type. About 73% of the haemoglobin F in the HPFH‐β‐thalassaemia° heterozygote is of the Gγ‐chain type, and the fraction attributable to control cis to the β‐thalassaemia° gene in this individual is calculated to be entirely of the Gγ‐chain type. Thus synthesis of Aγ‐chain as well as of β chain is absent under control cis to this β‐thalassaemia° gene.
Platelet‐Aggregating Activity in Neuraminidase‐Treated Human Cryoprecipitates: Its Correlation with Factor‐VIII‐Related Antigen
Authors: Vermylen J. , de Gaetano G. , Donati M. B. , Verstraete M.
Published: March 2008

Summary. Neuraminidase induced platelet‐aggregating activity in cryoprecipitates from three normal subjects and from six haemophilia A patients; the effect was not or only slightly seen in cryoprecipitate from two patients with von Willebrand's disease; development of this activity was linked to the presence of factor‐VIII‐related antigen. These findings may be of interest for the diagnosis of von Willebrand's disease and suggest a reaction sequence of major importance for human haemostasis.
A Study of Steroid‐Induced Granulocytosis in a Patient with Chronic Benign Neutropenia of Childhood
Authors: Deinard Amos S. , Page Arthur R.
Published: March 2008

Summary.

An infant with chronic benign neutropenia of childhood was found to respond to a sudden, transient, stress‐induced rise in plasma corticoid level with a pronounced rise in peripheral neutrophil count. Neutrophil survival studies were performed following this stress‐induced neutrophilia and during and following hydrocortisone stimulation. Measurement of the decline in total neutrophil‐associated radioactivity showed that neurophils were removed from the circulation at a normal rate while measurement of neutrophil specific activity indicated that the observed steroid‐induced granulocytosis was a result of marrow released of neurtrophils.
Transfusion and Gel Filtration Studies in von Willebrand's Disease
Authors: Kernoff P. B. A. , Rizza C. R. , Kaelin A. C.
Published: March 2008

Summary.

A study has been made of the plasma levels of factor‐VIII clotting activity and factor‐VIII related antigen following transfusion in five patients with von Willebrand's disease and one patient with severe haemophilia. All of the patients were transfused with cryoprecipitate or an AHG concentrate and their plasma levels of factor‐VIII clotting activity and factor‐VIII related antigen assayed at intervals after transfusion. In the case of the patients with von Willebrand's disease there was the expected post transfusion rise of factor‐VIII activity followed by a fall of activity and then a secondary rise of activity. During this same period there was a rapid fall of the factor‐VIII related antigen from the high levels attained immediately after transfusion but at about the same time as the secondary increase of factor‐VIII clotting activity took place there was a slowing down of the rate of disappearance of factor‐VIII related antigen. Indeed in several patients there was a secondary rise of factor‐VIII related antigen which coincided with the secondary peak of factor‐VIII activity.

Throughout the post‐transfusion period all plasma samples containing factor‐VIII clotting activity also contained measurable amounts of factor‐VIII related antigen.

Gel filtration studies carried out on plasma obtained from the von Willebrand's patients after transfusion failed to show any small molecular weight factor VIII. The possible implications of those findings are discussed.
Factor VII in an Industrial Population
Authors: Brozović Milica , Stirling Yvonne , Harricks Christine , North W. R. S. , Meade T. W.
Published: March 2008

Summary.

Factor‐VII levels were measured in members of an industrial population participating in a long‐term prospective study of arterial disease. A modified semi‐automated method with an artificially prepared factor‐VII deficient plasma, one batch of freeze‐dried thromboplastin and one freeze‐dried pooled reference plasma was used throughout. All calculations were carried out on a programmable desk calculator.

Mean factor‐VII levels in men and in women never on oral contraceptives were similar (age‐adjusted means 95.0% and 92.4% respectively). A very highly significant increase in factor VII was found in women on the low oestrogen contraceptive pill (age‐adjusted mean 134.8% compared to 92.4% in women never on oral contraceptives).

There was a highly significant rise in factor‐VII activity with age in both men and women. In men, factor VII rose 0.45% per year, whereas in women it increased at the rate of 1.1% per year. The difference in the slopes of these regression lines for men and women was significant. At younger ages, the mean levels for women were lower than for men, while at older ages the reverse was true.

No relationship with ABO blood groups or secretor status were found. Venepunctures noted as difficult appeared to have no effect on factor‐VII levels.
Ferritin in Normal Erythrocytes, Lymphocytes, Polymorphs, and Monocytes
Authors: Summers M. , Worwood M. , Jacobs A.
Published: March 2008

Summary. A method has been devised for the separation of red cells, polymorphs, lymphocytes, and monocytes from the peripheral blood. The fractions give a large yield of cells with a high degree of purity, and cells appear to be undamaged.

The ferritin concentration in cell extracts has been determined in 10 normal men and 10 normal women. There is no sex difference in any of the cell types. The mean ferritin concentration in monocytes is approximately 7.5 times the concentration in other leucocytes.
Cytochemical Demonstration of Dihydrofolate Reductase Activity
Authors: Tzortzatou Fotini , Hayhoe F. G. J.
Published: March 2008

Summary. The enzyme dihydrofolate reductase plays an important role in the conversion of dietary folate to the active coenzymatic form, tetrahydrofolate, and during the synthesis of thymidylate from deoxyuridylate, when tetrahydrofolate is oxidized to dihydrofolate and the reductase re‐converts dihydro‐ to tetrahydrofolate. The enzyme may be an important target for the action of folic acid antagonists. A method has been devised for the cytochemical demonstration of dihydrofolate reductase activity which uses dihydrofolate as substrate, blocks diaphorase and cytochrome oxidase activity, and permits the non‐enzymatic reduction of nitro‐blue tetrazolium by tetrahydrofolate formed by the action of the reductase on the substrate, thus revealing intracellular sites of enzyme activity. The method appears to be specific and shows only intracellular localization of the blue formazan deposits of reduced tetrazolium. The distribution of positivity in cells of human blood and bone marrow, in cultured fibroblasts and in cells of marrow, lymph nodes, spleen, liver, kidney and brain of normal AKR mice is described.
Metabolic and Functional Studies of Monocytes in Congenital Neutropenia
Authors: Biggar W. D. , Holmes B. , Page A. R. , Deinard A. S. , And P. L'Esperance , Good R. A.
Published: March 2008

Summary. Children with the severe form of congenital neutropenia usually die from infection by 2 yr of age. Metabolic and functional studies of monocytes from three patients with this disease were undertaken to understand further the role of monocytes in the host's defences against bacterial infection. The bactericidal capacity of monocytes compared favourably to the bactericidal capacity of control neutrophils (PMN). Metabolic studies of monocytes and control leucocytes showed similar stimulation of oxygen consumption, hexose monophosphate pathway activity arid 125iodide fixation during phagocytosis. Further, myeloperoxidase (MPO) activity of patients’monocytes was comparable to the activity of control leucocytes. Using the Rebuck skin window, very few of the patients’mononuclcar cells were seen to migrate during the initial 2–4 hr of observation. During this time, the PMN migration of controls was maximal. Following the relatively acellular period observed in patients, a brisk mononuclear cell infiltration occurred apparently independent of the presence of neutrophils. Epinephrine injection into patients stimulated a marked increase of blood monocytes, suggesting the existence of a marginal monocyte pool. An injection of hydrocortisone caused an unexplained 3–8‐fold decrease in circulating monocytes. The delay of phagocytic cell migration to an inflammatory site, and the apparent sensitivity of monocytes to hydrocortisone may account in part for the increased susceptibility to infection in patients with severe congenital neutropenia.
The Sheep‐Cell Rosette Test on Human Peripheral Blood Lymphocytes: An Analysis of Some Variable Factors in the Technique
Authors: Steel C. M. , Evans Judith , Smith Marilyn A.
Published: March 2008

Summary. Results obtained in the sheep cell‐rosette test for identification of human T lymphocytes are strongly dependant on the origin of the sheep erythrocytes. Other factors which influence rosette formation are the duration of incubation of the lymphocyte erythrocyte mixture and the concentration of serum used. The most reproducible results, giving a range of 55–75% RFC among the peripheral blood lymphocytes of healthy adults, are obtained by leaving the cell mixture overnight at room temperature in the presence of 10–25% serum.

The spontaneous sheepcell rosette test appears to be a useful means of identifying human T lymphocytes (Jondal et al, 1972; Papamichail et al, 1972; Wortis et al, 1973; Yata et al, 1973); there are, however, striking discrepancies in the percentage of rosette‐forming cells (RFC) reported among the peripheral blood lymphocytes of healthy donors for the figures quoted range from under 5% (Bach et al, 1969) to almost 80% (Bentwich et al, 1973). There are many points of variation between the techniques employed (Bach et al, 1969; Coombs et al. 1970; Brain et al, 1970; Lay et al, 1971; Jondal et al, 1972; Papamichail et al, 1972; Wybran et al, 1973; Yata et al, 1973; Bentwich et al, 1973) but the importance of such technical variations is largely unknown (Urbaniak et al, 1973). In the present study, several of the points of variance between published techniques have been analysed.
Iron Deficiency: Impaired Liver Growth and DNA Synthesis in the Rat
Authors: Snms M. A. , Dallman P. R.
Published: March 2008

Summary. This study deals with liver growth and DNA synthesis in young, rapidly growing rats weaned to an iron deficient diet. Shortly after the development of anaemia there was a depression in the rate of liver growth that was more profound than that of body growth. The rate of increase in total liver DNA was similarly depressed, in comparison with iron‐supplemented animals. Paradoxically, in the deficient rats, two normally sensitive indices of DNA synthesis, incorporation of [3H]thymidine into DNA and activity of thymidine kinase, were unaffected. This was also the case in animals acclimated to a 4 hr/day restricted feeding regimen in order to control for possible variations in feeding patterns. Although [3H]thymidine incorporation was normal throughout a 24 hr period, incorporation of 32P into liver DNA was depressed in the iron deficient rats. The results indicate changes in liver DNA synthesis due to iron deficiency that are distinct from those seen in starvation and protein‐calorie malnutrition. Probably DNA synthesis in iron deficiency is modified through a depression of de novo synthesis, in the presence of normal salvage pathway activity.
Endocytosis and Exocytosis in Membrane Remodelling during Reticdocyte Maturation
Authors: Gasko O. , Danon D.
Published: March 2008

Summary. Young reticulocytes have a greater surface area and surface charge density than mature reticulocytes. Membrane remodelling of maturing reticulocytes was investigated by electron microscopic methods. Endocytosis was demonstrated in reticulocytes by a‘two stage labelling’technique in which colloidal gold particles were used as a substrate for pinocytosis; after fixation, cationized ferritin served as a marker for the membrane connected with the outer cell surface. Incubation of reticulocytes in agar semi‐solid media, which prevents subcellular elements from migrating, demonstrated exocytosis and shedding of membranous structures and cell fragments. Membrane remodelling of the reticulocyte appears to occur by internali‐zation of the plasmalemma. This is followed either by intracellular digestion or by exocytosis with previously existing vesicles, as well as by fragmentation and detachment of microspheres containing haemoglobin.
The Fortification of Common Salt with Ascorbic Acid and Iron
Authors: Sayers M. H. , Lynch S. R. , Charlton R. W. , Bothwell T. H. , Walker R. B. , Mayet†‐ F.
Published: March 2008

Summary. Common salt fortified with ascorbic acid or iron compounds became discoloured on storage, the reaction being accelerated by heat and humidity. Soluble iron compounds such as FeSO4 caused discoloration more readily than insoluble compounds such as ferric orthophosphate (FePO4). Fortification with both ascorbic acid and iron led to more rapid discoloration than fortification with either alone. Colour developed more rapidly in coarse salt than in refined commercial salt, while chemical NaCk developed a faint discoloration only under very hot and humid conditions. Discoloration was inhibited if starch was mixed with the salt: coarse salt mixed with 2.5% starch, 1.25% ascorbic acid and 0.1% iron as FePOI retained an acceptable appearance during storage under subtropical conditions (Durban) for more than I yr. A double isotope red cell utilization method was employed to assess the absorption of iron from maize porridge and from a standard rice meal cooked with fortified salt. The absorption of both the intrinsic food iron and the iron in the fortified salt was increased threefold if the salt contained 50 mg ascorbic acid as well as FePO4. The amount of iron absorbed was similar whether the salt contained 50 mg ascorbic acid and 4 mg iron as FePO4 or 50 mg ascorbic acid and 4 mg iron as FeSO4. It was concluded that crude common salt could be fortified with 0.1% iron as FePO, and 1.25% ascorbic acid and stored under all but the most extreme tropical conditions, provided that 2.5% starch was added to prevent the development of discoloration, and that such fortification would significantly improve the iron nutrition in countries where the staple food is rice or maize.
Genetic Haemoglobin Abnormalities in about 9000 Black and 7000 White Newborns; Haemoglobin F Dickinson (Aγ97 HisÅg), a New Variant
Authors: Schneider R. G. , Haggard M. E. , Gustavson L. P. , Brimhall B. , Jones R. T.
Published: March 2008

Summary. Electrophoretically detectable haemoglobin abnormalities are readily identified in umbilical cord blood haemolysates by cellulose acetate electrophoresis, followed by citrate agar electrophoresis of those samples exhibiting an abnormality, and, if necessary, by globin electrophoresis. In samples from 9224 Black newborns, the prevalence of all such abnormalities was about 13%, with 12 cases of sickle‐cell anaemia, seven of Hb‐SC disease and five of Hb‐S β thalassaemia. Clinical and haematologic manifestations of these conditions usually appeared in the first few years of life. The prevalence of sickle‐cell trait was about 7%, Hb‐C trait 2%, and Hb Bart's 5%. Several new or rare haemoglobins, both adult and foetal, were found in individual families.

Of 7006 White newborns, 76 or 1.1% had electrophoretically detectable haemoglobin abnormalities, all in the simple trait condition. Sixty‐one of these (0.8% of the total) had Hb‐Bart's and 10 had adult variants—four Hb S, four Hb C, one Hasharon and one unidentified α chain variant. Five samples contained structural γ chain abnormalities. One new variant—Hb‐F Dickinson (Aγ97 HisÅg), was found in two siblings.
Willebrand Factor and Ristocetin I. MECHANISM OF RISTOCETIN‐INDUCED PLATELET AGGREGATION
Authors: Jenkins C. S. P. , Meyer D. , Dreyfus M. D. , Larreu M.‐J.
Published: March 2008

Summary. Ristocetin induces aggregation of normal platelet‐rich plasma over a wide range of concentrations. Low doses induce a biphasic response of which the first wave is not mediated by ADP and proceeds without the initial platelet shape change. The absence of aggregation in von Willebrand's disease results from the lack of a component, Willebrand factor, which is eluted together with platelets, factor VIII activity and Willebrand (or factor VIII related) antigen in the void volume fraction when platelet‐rich plasma is gel filtered (Sepharose 2B). Twice washed normal platelets aggregate to ristocetin whereas four times washed platelets only aggregate when low volumes of normal haemophilia A plasma or serum are added. The interaction of ristocetin with platelets and plasmatic components has been investigated. A mechanism is proposed for ristocetin‐induced aggregation.
The Variability of Measurements of the Prothrombin Time Ratio in the National Quality Control Trials: a Follow‐up Study
Authors: Leck Ian , Gowland E. , Poller L.
Published: March 2008

Summary. British hospitals which use the one‐stage prothrombin time tat my participatc in one of two schemes. Those in the Routine Supply Scheme use a standardized tissue thromboplastin, the Manchester Comparative Reagent (MCR). Those in the National Referencc Scheme use other reagents routinely, but calibrate thcm against the British Comparative Thromboplastin (BCT) which consists of batches of thc MCR which have been checked for accuracy by a group of expert Monitoring Centrcs selected from the hospitals in each scheme. The performance of hospitals in both schemes is monitored by trials in which they are asked to measure prothrombin time ratios, using BCT, on lyophilized plasma preparations which are sent to them.

Four trials are reported here. In one, a single plasma preparation was used. In each of thc other three, samples of three plasmas were sent. There was considerable variation in the ratios reported by different hospitals for each plasma. In the trials involving three plasma samples, a marked tendency was demonstrated for hospitals which obtained a particularly high or low reading for one plasma to deviate in the same direction when measuring other plasmas in the same trial, but this was not found when readings from different trials (separated by several months) were compared.

A breakdown of the results by type of hospital suggested that those obtained by the participants in the Routine Supply Scheme, and especially by the Monitoring Centres m this group, were more accurate than those of the National Reference Scheme hospitals, but within each group no persistent differences in accuracy between hospitals and no general improvement between the earlier and later trials could be demonstrated. Confidence limits estimated com the results of all mals suggest that even in Routine Supply Scheme hospitals, the chances of having a true prothrombin time ratio outside what is usually quoted as the therapeutic range (1.8‐3.0) should be regarded as higher than I in 20 for every patient whose reported ratio @ad on duplicate readings) is below 2.1 or above 2.45.

It is concluded that the National Reference Scheme should be phased Out in favour of the Routine supply Scheme, and that even among most of the hosPimls in the latter scheme there is scope for greater accuracy, which the experience Of the Correspondence: Dr L. Poller, National Reference Laboratory for Anticoagulant Control Reagents, Withington Hospital. Manchester M20 8LR.
Prolymphocytic Leukaemia
Authors: Galton D. A. G. , Goldman J. M. , Wiltshaw E. , Catovsky D. , Henry K. , Goldenberg G. J.
Published: March 2008

Summary. The clinical and haematological features of 15 patients with a rare variant of chronic lymphocytic leukaemia (CLL) are described. The disease predominantly affects males in the sixth and seventh decades of life and presenting symptoms include fatigue, weakness, weight loss, sweats and fevers. Massive enlargement of the spleen (mean weight at autopsy 1383 g, range 227–3500 g) and to a lesser extent of the liver (mean weight 2445 g, range 2030–3079 g) are regular findings. In contrast, peripheral lymphadenopathy is inconspicuous or absent. The characteristic cell in the peripheral blood is a relatively large lymphoid cell with a large vesicular nucleolus, relatively well‐condensed nuclear chromatin and moderate amount of cytoplasm. The counts of these cells in the peripheral blood at the time of diagnosis are very high (mean 355 000/μl, range 26000–1 11 000/μl). The clinical response to methods of treatment that are usually effective in classical CLL (particularly alkylating agents and corticosteroid drugs) is uniformly poor and the patients’survival after diagnosis is in most cases quite short.

We believe that the clinical and haematological features of this condition justify its recognition separately from classical CLL, from lymphosarcoma cell leukaemia and from acute lymphoblastic leukaemia. We have therefore designated it ‘prolymphocytic leukaemia’. On the basis of a single case we suggest that further trials of splenectomy are indicated.
Heparin, Platelets and Blood Coagulation: Implications for Low‐Dose Heparin Prophylactic Regimens in Venous Thrombosis
Authors: Han P. , Ardlie N. G.
Published: March 2008

Summary. Heparin has been shown to inhibit the second phase of aggregation and the platelet release reaction induced by ADP. These platelet responses to ADP are mediated by thrombin, generated through the coagulation pathways, on the platelet membrane (Ardlie & Han, 1974), and evidence was obtained that the inhibitory action of heparin is due to inactivation of coagulation factor Xa in the presence of XaI. In contrast, it has been shown that thrombin adsorbed to the platelet surface is protected from destruction by its natural inhibitor and heparin. Since trace amounts of heparin were able to augment the inhibitory action of XaI on factor Xa, this phenomenon has relevance to low‐dose heparin regimens for prophylaxis of venous thrombosis. It is proposed that postoperative thrombosis is due to abnormal platelet function caused by accelerated coagulation, and that heparin prevents thrombosis through its anticoagulant action on factor Xa. It is also suggested that trace amounts of heparin which may be present normally in the circulation may act as a natural anticoagulant.

One of two commercial preparations of heparin caused washed platelets, prepared by some, but not all, of the methods used, to aggregate and release their constituents. However, it was shown that these effects of heparin on washed platelets are simply a consequence of storage of platelets at 4°C, emphasizing the need to keep platelets at 37°C for in vitro studies. Heparin failed to inhibit the release reaction of platelets in citrated‐plasma, and it is suggested that this may be due to interference by citrate. These observations with washed platelets and citrated plasma are considered to be artefacts and thus have no relevance to heparin action in vivo.
Alpha Thalassaemia in Adults with Sickle‐Cell Trait
Authors: Steinberg M. H. , Adams J. G. , Dreiling B. J.
Published: March 2008

Summary. Mild forms of α thalassaemia are difficult to detect in adults. Since α thalassaemia existing with structural defects of the β chain of haemoglobin may lead to decreased levels of the abnormal haemoglobin, we examined individuals having sickle‐cell trait for the possible coexistence of α thalassaemia. Patients with sickle‐cell trait having haemoglobin‐S (Hb‐S) levels less than commonly expected were compared to two control groups—one with sickle‐cell trait and the usual levels of Hb S and one with normal haemoglobin. Twenty‐one patients with sickle‐cell trait having Hb‐S concentrations below 35% had 65.8% Hb A, 31.8% Hb S, and a mean corpuscular volume of 81.6 fl. Studies of the relative rates of α‐, βs‐ and βA‐chain synthesis in 14 of these individuals showed a mean α:β ratio of 0.76. In patients with normal haemoglobin as well as in sickle‐cell trait with Hb‐S levels above 35%, this ratio was unity. These findings are consistent with the presence of α thalassaemia in patients with sickle‐cell trait who have lower than usual levels of Hb S and micro‐cytosis.
Mechanism of Plasminogen Activator and Factor VIII Increase after Vasoactive Drugs
Authors: Mannucci P. M. , ÅBerg M. , Nilsson I. M. , Robertson B.
Published: March 2008

Summary. Adrenaline, nicotinic acid (NA), vasopressin (LVP) and other drugs affecting vascular motility are known to increase plasminogen activator (PA) and factor‐VIII plasma levels in man. To evaluate the hypothesis that NA, LVP and adrenaline release PA from the endothelial cells of the vessel wall through their common effect on vascular motility, PA has been characterized by means of a histochemical technique on vein biopsies obtained from human volunteers after infusion of the compounds. Furthermore, the effect of single and repeated administration has been compared in order to investigate whether the pattern of PA and factor‐VIII variations in plasma is similar with the three drugs. There was no major difference in the PA content of the veins following the marked and sustained increase of the corresponding plasma activities. A simple explanation is that the intensity and duration of the stimulus may not be sufficient to deplete the large stores of the vessel walls. The magnitude, time course and duration of the plasmatic response after single and repeated infusions was on the whole different and peculiar for each drug. A derivative of LVP which is free of vasoactive actions was more effective than LVP in inducing the responses, which could also be elicited in two anephric subjects. These findings suggest that vasoactivity is unlikely to provide the clue to a common pathway for the fibrinolysis and coagulation response after the compounds, and support the existence of different specific receptors.
Chronic Myelomonocytic Leukaemia
Authors: Geary C. G. , Catovsky D. , Wiltshaw Eve , Milner Gillian R. , Scholes Muriel C. , van Noorden Susan , Wadsworth L. D. , Muldal S. , Maciver J. E. , Galton D. A. G.
Published: March 2008

Summary. The natural history and haematological features of 18 patients with a chronic form of myelomonocytic leukaemia are described. The majority were elderly and, in this series, females predominated. Haematological prodomata, such as unexplained monocytosis, leucopenia, or thrombocytopenia were common, and the clinical onset was insidious. Splenomegaly was variable but tended to increase as the disease progressed.

Anaemia was usually less than in the acute disease, unless compounded by iron deficiency. The blood film typically showed a mixed monocytosis and granulo‐cytosis, cells in both lines showing abnormalities. ‘Paramyeloid’ cells, appearing in Romanowsky stained films intermediate between myelocytes and monocytes, were characteristic, although cytochemical and electron microscopical analysis suggests that these cells may be allotted to one or other cell line. The marrow aspirate was characteristically hypercellular, showed granulocytic hyperplasia, and, in contrast to the well‐differentiated blood picture, the proportion of poorly differentiated cells, including blasts, was high. Serum lysozyme levels were usually raised. Five of the 18 cases survived more than 5 years, while 10 lived 2 years or longer.

The morphological and clinical features form part of a spectrum including acute myelomonocytic leukaemia, into which several of the patients transformed. Recognition of the syndrome is important because the patients are probably best managed without intensive chemotherapy.
Dyserythropoiesis and Annulate Lamellae
Authors: Verwilghen R. L. , Orshoven A. Broeckaert‐Van , Heynen M. J.
Published: March 2008

Summary. Cytoplasmic and intranuclear annulate lamellae in the erythroblasts from patients with dyserythropoietic anaemia (megaloblastic anaemia, dysplastic anaemia and erythroleukaemia) are described. Annulate lamellae have mainly been observed in oocytes, in embryonic tissues and in malignant cells. Their occurrence in dyserythropoietic anaemia may be related to the reappearance of fetal characteristics in the erythroblasts and erythrocytes.
Hypocholesterolaemia and Anaemia
Authors: Westerman M. P.
Published: March 2008

Summary.

The present study has examined the relationship and significance of hypocholesterolaemia to anaemia and to the red cell. The level of plasma cholesterol is closely related to haematocrit levels both initially and throughout the course of the anaemias associated with hypocholesterolaemia. The association is maintained, regardless of the cause of the haematocrit change, i.e. transfusion or response to treatment. Hypocholesterolaemia does not affect the red cell, i.e. its survival, cholesterol concentration or osmotic fragility and occurs in a diverse group of anaemias. As such, it is not causally related to anaemia. The changes in plasma cholesterol are most likely related to its ‘redistribution’ or to plasma ‘dilution’, with contributory factors occurring. The presence of anaemia, even to a modest degree, would be important to consider when comparing cholesterol levels between groups of individuals.
Chromosomal Abnormalities and Dyserythropoiesis in the Preleukaemic Phase of Multiple Myeloma
Authors: Dahlke Miriam B. , Nowell Peter C.
Published: March 2008

Summary.

Two patients with multiple myeloma and one patient with a plasmacytoma are reported in whom acute leukaemia developed following long‐term treatment with melphalan. Each patient had a complete remission of the plasma cell disorder during which time the bone marrow was moderately to severely hypplastic. The end of the clinical remission was heralded by a dyserythropoietic anaemia which persisted several months before the emergence of the terminal acute leukaemia. Marked chromosomal abnormalities were observed in marrow cells during the dyserythropoietic phase.