bluuebunny/crossref_metadata_2025 huggingface dataset:
Observations on the Myelocyte to Tissue Transit Time (MTT) in Acute Leukaemia and Other Proliferative Disorders
Authors: Galbbaith Peter R. , Advincula Edgardo G.
Published: March 2008

Summary

The myelocyte to tissue transit time (MTT) was determined by labelling leucocytes in vivo with radioactive diisopropylfluorophosphate (DF32P) and determining the time for labelled leucocytes to disappear from the blood. Normally this is complete in 22 days or less. Prolongation of MTT suggests that the later stages of granulopoiesis may be impaired (dysgranulopoiesis). Dysgranulo‐poiesis was found previously in patients with acute myelogenous and myelo‐monocytic leukaemia. In this study we have found that MTT was reduced during treatment of the acute leukaemia with cy to toxic drugs, suggesting that there was a defect in myelocyte maturation in this disease. In addition we have found evidence of dysgranulopoiesis in patients (a) whose acute leukaemia was in complete remission, (b) with myeloproliferative disorders, and (c) with obscure blood dyscrasias without leukaemia. These findings suggest that acute leukaemia may be antedated by a proliferative disorder more frequently than is usually apparent, and that remission of acute leukaemia does not necessarily depend upon marrow repopulation by normal cell lines.
Co‐ordinated Increase of Sodium Leak and Sodium Pump in Hereditary Spherocytosis
Authors: Wiley J. S.
Published: March 2008

Summary

The presence of an increased sodium leak into hereditary spherocytes up to three times normal has been confirmed from measurement of 22Na+ influx into red cells. 22Na+ influx was not identical to the net inward leak of Na+ but the two kept a constant relationship since influx was about double the net Na+ gain in both normal and abnormal cells incubated with ouabain. The intracellular concentration of Na+ ions in fresh cells from hereditary spherocytes was identical to that in normal red cells. Hereditary spherocytes showed increased maximal activity of a membrane ATP‐ase inhibited by ouabain and the Na+ concentration giving half‐maximal activation of this ATP‐ase was the same for spherocytes and normal cells. When the 22Na+ influx into red cells from nine patients with hereditary spherocytosis was compared with maximal activity of cation pump ATP‐ase in the same cells a significant correlation was obtained (r= 0.78, P > 0.01). The results indicate some linkage between the increase in the Na+ leak and functional number of active cation pumps in the membrane of hereditary spherocytes.
The Control of Oxygen Affinity of Red Cells with Hb‐Shepherds Bush
Authors: May A. , Huehns E. R.
Published: March 2008

Summary

The red cells of the original patient with Hb‐Shepherds Bush (Hb‐ShB 25%, Hb‐A 75%) have a physiologically significant increased oxygen affinity. This is one third due to the intrinsic raised oxygen affinity of Hb‐ShB and two‐thirds due to its diminished response to 2,3‐DPG, there being no interaction between the two haemoglobins present in the cells.
Erythrocyte Glutathione Peroxidase Content and Serum Tocopherol Levels in Newborn Infants
Authors: Emerson Pauline M. , Mason David Y. , Cuthbert Jean E.
Published: March 2008

Summary

Two methods for the determination of glutathione peroxidase (GSH‐Px) activity have been compared and the overall superiority of a linked‐enzyme system has been confirmed. The erythrocyte GSH‐Px activity was measured in 120 newborn infants and compared with older children and adults. A definite deficiency of the enzyme was found in the former group, but could not be related to evidence of haemolysis. A relationship between serum tocopherol levels and erythrocyte GSH‐Px was found and the possible implications are discussed.
The Role of Platelets in Intrinsic Factor‐Xa Formation
Authors: Walsh P. N. , Biggs Rosemary
Published: March 2008

Summary

Although the essential role of phospholipid in the interaction of factors VII and IX has been demonstrated (Lundblad & Davie, 1964), detailed studies of platelet activity in intrinsic coagulation have not previously been reported. A basic test system has been developed for studying the interaction of factors XIa, VIII, IX, and X in the formation of factor Xa. Using platelets from normal and coagulation‐factor‐deficient donors, washed by albumin density gradient separation (ADGS), a comparative study of platelets and phospholipid in intrinsic factor‐Xa formation has been done under various test conditions.

Both platelets and phospholipid (Folch) are shown here to play a part in intrinsic factor‐Xa formation, whereas neither enhances extrinsic factor‐Xa formation. Collagen promotes a platelet coagulant activity which increases the rate of factor‐Xa formation in the test system employed. The effect of collagen depends entirely on the presence on the platelet surface of factor XI, but not of factor XII. In contrast to collagen, adenosine diphosphate has no effect on this intrinsic platelet coagulant activity. In experiments carried out in the presence of naturally‐occurring inhibitors to active clotting factors (anti‐factors Ila, Xa, and XIa) it is shown here that contact product is adsorbed to the platelet surface where it is protected from destruction by antifactor XIa. Factor Xa is formed subsequently by the interaction of intrinsic clotting factors, which is presumed to occur on the platelet surface since factor Xa is found in association with the platelets, not the surrounding plasma.
Haemoglobin Synthesis in Reticulocytes of Prenatal f/f Anaemic Mice
Authors: Cole R. J. , Regan T. , Tarbutt R. G.
Published: March 2008

Summary. SUMMARY. Prenatal reticulocytes of f/f mice utilize less than half as much exogenous iron for haem synthesis as normal prenatal reticulocytes. The intracellular pool of iron available for haem synthesis is less in f/f prenatal reticulocytes than in normal cells (0.2 μg/107 f/f reticulocytes and 0.5 μg/107 f/+ reticulocytes, on Day 18). Uptake of iron by f/f prenatal reticulocytes is normal, but incorporation of bound iron into haem is reduced. Incorporation of glycine into porphyrins relative to that into protein is reduced in f/f prenatal reticulocytes. Addition of haemin to cultured f/f and f/+ prenatal reticulocytes stimulates protein synthesis similarly in both genotypes. Reticulocytes produced by phenylhydrazine treatment of adult f/f mice have normal intracellular iron pools, normal utilization of exogenous iron, and normal incorporation of glycine into porphyrin and protein.
Combined Deficiency of Factor V and Factor VIII: Report of a Family and Genetic Analysis
Authors: Sibinga C. Th. Smit , Gökemeyer J. D. M. , ten Kate L. P. , Zwol F. Bos‐van
Published: March 2008

Summary. A family, in which the combined deficiency of factor V and factor VIII is segregating, is described. It is the first family reported which was detected through routine coagulation studies and the first one in which paternal relatives are found to be affected as well as maternal relatives. Over 40 family members have been studied. A review of the genetic hypotheses in the literature is presented. The data from this family and from the previously reported ones are analysed as to the mode of inheritance. An autosomal recessive mode of inheritance with a marked degree of penetrance (27.2–72.8%) and varying expressivity in heterozygotes seems to be the most likely explanation. The aims for further studies are outlined.
The Absence of Lipid Peroxidation in Human Red Cells Exposed to Acetylphenylhydrazine
Authors: Winterbourn Christine C. , Carrell R. W.
Published: March 2008

Summary. The membrane lipids from human red cells which had been treated with acetylphenylhydrazine were examined for evidence of autoxidation. Malonyldialdehyde production was measured and the lipids were extracted and examined by thin‐layer chromatography. No lipid autoxidation was detected by either method, even when the cellular haemoglobin was considerably oxidized. In addition, the susceptibility of red‐cell lipids to autoxidation by hydrogen peroxide did not increase if the cells were prcincubated with APH. The significance of these results is discussed in relation to the mechanism of haemolysis in Heinz‐body haemolytic anaemias.
The Metabolism of Maturing Reticulocytes
Authors: Gasko O. , Danon D.
Published: March 2008

Summary

A functional Krebs tricarboxylic acid cycle was demonstrated to exist in rabbit reticulocytes by the following methods:

Measurement of the rate of oxygen consumption of the cells, using acetate and succinate as substrates.

Demonstration of the Crabtree effect exerted by glucose on cellular respiration.

Following the metabolic pathway of [2‐14 C]acetate, [3‐14 C]pyruvate and [6‐14 C]glucose and measuring the formation of labelled CO2 by the cells. The effects of some inhibitors of mitochondrial activity on this pathway were also studied.

Demonstration of the conversion of labelled acetate into various intermediates of the Krebs cycle by chromatography and autoradiography.
Iron Transport by Rat Small Intestine in Vitro: Effect of Body Iron Status
Authors: Howard J. , Jacobs A.
Published: March 2008

Summary. Both mucosal uptake and serosal transfer of iron by everted sacs of rat small intestine were maximal in the duodenum and decreased progressively towards the ileum. Transport of iron against a concentration gradient did not occur in any part of the intestine. When the iron concentration in the bathing medium was varied over the range 10–500 μM a saturable transport process was revealed in the proximal small intestine. In iron‐deficient rats mucosal uptake of iron was increased but in iron‐loaded rats it remained normal. The results suggest that iron transport across the proximal small intestine of the rat in vitro involves a carrier mechanism which responds adaptively to iron deficiency but not to overload.
Osmotic Resistance of Abnormal Red Cells Exposed to Lead in Vitro
Authors: Qazi Qutub H. , Go Suat Cheng , Smithwick Elizabeth M. , Madahar D. P.
Published: March 2008

Summary. Exposure of normal red cells to lead in vitro is known to result in decreased osmotic fragility. Red cells from a normal individual and from two children with genetically determined red‐cell abnormalities (spherocytosis and elliptospherocytosis) were exposed to lead acetate solution. Osmotic fragility curves were determined for treated and untreated red cells. Exposure to lead was found to increase the osmotic resistance of normal as well as abnormal red cells.
Intestinal Conversion of Folinic Acid to 5‐Methyltetrahydrofolate in Man
Authors: Whitehead V. Michael , Pratt Roy , Viallet André , Cooper Bernard A.
Published: March 2008

Summary. In three adult subjects undergoing diagnostic umbilical vein catheteriza‐tion, the active stereoisomer of folinic acid (dl,‐5‐formyltetrahydrofolate) was metabolized during absorption and appeared in hepatic portal venous plasma as 5‐methyltetrahydrofolate. A small amount of 5‐formyltetrahydrofolate and probably of 10‐formylfolate was detected in hepatic portal venous plasma early during absorption as well.

Peripheral venous plasma folate changes in these subjects and in two achlorhydric subjects fed folinic acid were similar, suggesting that isomerization of 5‐formyl‐ to 10‐formyltetrahydrofolate by gastric acid was not necessary for its subsequent metabolism by the intestinal cell.

Similar increments in peripheral venous plasma folate followed feeding of comparable doses of folinic acid and folic acid, evidence that folinic acid may be effectively administered by mouth. When so administered, the effect in respect of all tissues except the intestine is essentially equivalent to the feeding of 5‐methyltetra‐hydrofolate itself.
Plasmin Lysis of Fibrinogen and Fibrin and the Antigenic Properties of their Degradation Products
Authors: Ekert H. , Muntz R. H.
Published: March 2008

Summary. Purified fibrinogen was lysed by plasmin and the degradation products identified by gel filtration, immunoelectrophoresis and the tanned red cell haem‐agglutination inhibition (TRCHI) test. After 15 min of lysis, fractions with molecular weight (mol wt) 270 000 (fragment X), 110 000 (containing both fragments D and E) and 15 000 were present. After 6 hr lysis, only fractions of mol wt 80 000 (fragments D and E) and 15 000 were present. Fibrin was lysed by plasmin for 30 min, 4, 8 and 24 hr. In each case fractions of mol wt 150 000 (fragment Y), 80 000 (fragments D and E) and 15 000 were produced. It was shown that early and late products of fibrin lysis are similar to those of fibrinogen, and that the tanned red cell haemagglutination inhibition test using anti‐fibrinogen antibody provides a reliable estimate of fibrin lysis both in vitro and in vivo.
Preparation of Suspensions of Washed Platelets from Humans
Authors: Mustard J. F. , Perry D. W. , Ardlie N. G. , Packham M. A.
Published: March 2008

Summary: Methods have been developed for the preparation of suspensions of washed platelets from humans. Heparin is used in the washing fluids to prevent: thrombin generation and apyrase is used to prevent adenine nucleotide accumulation. Platelets suspended in Eagle's tissue culture medium containing albumin were more responsive to ADP than platelets in Tyrode's‐albumin solution. Addition of fibrinogen is required for maximum sensitivity to ADP‐induced aggregation. These platelets can be stored for 4 hr or more at 37°C in the presence of apyrase and maintain their ability to aggregate upon the addition of low concentrations of ADP.

Without apyrase the platelets gradually become insensitive to ADP upon storage at 37°C; this is presumably caused by the accumulation of ADP in the suspending fluid because sensitivity can be partially restored by the addition of apyrase and further incubation.
The Role of Platelets in the Contact Phase of Blood Coagulation
Authors: Walsh P.N.
Published: March 2008

Summary: Freshly collected intact platelets were shown to have an activity important in the initiation of intrinsic coagulation. They enhance the reactions involving factors XII and XI to form contact activation product in the absence of calcium. This activity, termed contact product forming activity (CPFA), is specifically and rapidly stimulated by‘physiological’concentrations of ADP in platelet suspensions not stirred and not undergoing platelet aggregation. The stimulation of CPFA by ADP was shown to be reversible. A phospholipid mixture (Folch) with PF3 activity was inactive in all test systems for CPFA. Although independent of platelet aggregation, the stimulation of CPFA by ADP was accompanied by a reversible change in platelet shape characteristic of the response of platelets to ADP. The possible significance of CPFA is discussed.
Polysomes of Cultured Normal and Leukaemic Lymphocytes: Response to Phytohaemagglutinin
Authors: Rabinowitz Y. , Justice P. , Wong Polly , Hsia D. Y. Y.
Published: March 2008

Summary. Polysome OD260 profiles of glass column separated normal and leukaemic lymphocytes were studied. Contaminating RBC were haemolysed with NH4Cl prior to culture. Post‐mitochondrial supernatants from lymphocytes ruptured by nitrogen cavitation were analysed in a scaled‐down sucrose gradient procedure. Normal lymphocytes responded to phytohaemagglutinin stimulation in a few hours with increases in all classes of polysome OD260 absorbances from the low levels found in both normal and leukaemic unstimulated lymphocytes. Leukaemic lymphocytes which responded to PHA showed delays in both polysome formation and blast‐cell production. With leukaemic lymphocytes the degree of responsiveness to PHA and the amount of polysome OD260 produced were inversely related to the level of the peripheral WBC counts. Incorporation of [14C]‐amino acids at polysomes in both intact cells and in cell free reactions increased with PHA stimulation and blast‐cell production. With both normal and leukaemic lymphocytes increased [14C]amino acid incorporation was related to increase in polysome OD260. There was no evidence that leukaemic polysomes when formed were defective.
Comparison of the Kinetics of Colony Forming Units in Spleen (CFUs) and Culture (CFUc)
Authors: Testa N. G. , Lajtha L. G.
Published: March 2008

Summary. A comparative study of the in vitro kinetics of CFUs and CFUc indicated that: (a) there is a five‐ to seven‐fold increase in CFUc numbers under conditions which result in a progressive depletion of CFUs; (b) refeeding the cultures delayed the late decline in CFUc numbers without affecting CFUs; (c) using cycling CFUs or adding erythrocytes to the culture markedly improved CFUs survival without affecting that of CFUc; (d) the CFUc/CFUs ratio changes during marrow regeneration, but in the opposite direction which would be expected if CFUc were a part of the cycling CFUs population. It is concluded from these that the two operational definitions, CFUs and CFUc, do not denote the same cell type under the culture conditions described.
Globin Synthesis in Sideroblastic Anaemia
Authors: White J. M. , Ali M. A. M.
Published: March 2008

Summary. The effect of pyridoxal‐5‐phosphate, δ‐aminolaevulinic acid and haematin hydrochloride on the in‐vitro synthesis of globin by reticulocytes has been examined in sideroblastic anaemia. In each of the seven patients studied, haematin consistently stimulated globin synthesis. In two siblings suffering from congenital sideroblastic anaemia δ‐ALA also stimulated globin synthesis. It was, however, ineffective in another patient with the same disorder with different clinical and haematological features. This evidence strongly supports our earlier conclusions that sideroblastic anaemia is brought about by a deficiency of haem. It also demonstrates biochemical heterogenity in the congenital type of sideroblastic anaemia.
Copper and Zinc Concentration in the Plasma of Leukaemic Children
Authors: Delves H. T. , Alexander F. W. , Lay Helen
Published: March 2008

Summary. The concentrations of copper and zinc have been measured in the plasma of children with acute lymphoblastic leukaemia before and after treatment, and compared with healthy controls.

The plasma copper concentrations were higher and the plasma zinc concentrations lower for the untreated leukaemic children than for the other two groups. The concentrations of both metals were altered after treatment to values approaching the normal range.

The plasma copper: zinc ratio discriminated well between the untreated leukaemic children and the other two groups. This ratio might prove useful in monitoring the response to treatment.
A Three‐Year Study of Adolescent Boys Suffering from Haemophilia and Allied Disorders
Authors: Rainsford S. G. , Hall Angela
Published: March 2008

Summary. Details concerning the frequency of bleeding in haemophilia, Christmas disease and von Willebrand's disease in adolescent boys are given. The results show that the frequency of bleeding remained constant throughout eight academic terms. There was no seasonal variation. Severity, as judged by frequency of bleeding, cannot be correlated entirely with factor‐VIII activity, there being evidence that there is some other factor in addition to factor VIII concerned with bleeding in haemophilia.

Of 61 haemophilic boys treated, only one developed an inhibitor to factor VIII. A higher incidence of haematuria was observed among boys with factor‐VIII inhibitors. The advent of replacement therapy has increased the role of orthopaedic surgery. The requirements for the care of 50 boys suffering from serious coagulation defects are discussed, and indications for further research are suggested.
Lysozyme Activity in Human Neutrophilic Granulocytes
Authors: Hansen Niels Ebbe , Andersen Vagn
Published: March 2008

Summary. Among five different methods for the extraction of lysozyme from human neutrophilic granulocytes (mechanical disruption, freezing‐thawing, sonication, solubilization with saponin and with n‐butanol), extraction with n‐butanol was found to give the highest lysozyme yield per cell. With this method the lysozyme content of neutrophilic granulocytes was measured in a control group with no haematological, renal or infectious disease, and in patients with bacterial infection, severe uraemia, and myeloproliferative disorders.

It was found that the lysozyme concentration in normal human adults was 2.7 μg per 106 neutrophils. Intraneutrophilic lysozyme in patients with bacterial infection was reduced by 50% whereas the activity in patients with severe uraemia was reduced by 25%. The content in patients with myeloproliferative disorders was normal. The intraneutrophilic lysozyme content varied inversely with the severity of the infection as judged by the degree of neutrophil leucocytosis. Taking all patients examined, the intraneutrophilic lysozyme activity varied inversely with the degree of toxic granulation. A negative correlation was also demonstrated between neutrophilic lysozyme and the serum creatinine level.

It is suggested that bacterial infection and uraemia suppress lysozyme synthesis in the bone marrow, although other mechanisms cannot be excluded. The consequences for neutrophil function are unknown.
Platelets and Initiation of Intrinsic Clotting
Authors: Schiffman Sandra , Rapaport Samuel I. , Chong May M. Y.
Published: March 2008

Summary. Comparison of activities in platelet rich and platelet poor plasmas from normal donors and patients deficient in either factor VIII, IX, XI or XII indicates that platelets contain activities which can partially substitute for plasma factors XI and XII. The factor‐XI‐like activity is expressed in a one‐stage activated partial thromboplastin assay and in an intact prothrombin consumption system. The factor‐XII‐like activity is scarcely detectable in a one‐stage assay but markedly enhances the defective prothrombin consumption of factor XII deficient plasma. Intact prothrombin consumption tests with platelet poor plasmas fortified with cephalin show that in the presence of high concentrations of platelet factor 3 activity only trace contact activation is required to promote good prothrombin consumption. The platelet, by supplying both platelet factor 3 and activities bypassing plasma contact activation factors XI and XII, may provide an important route for activating intrinsic clotting.
Paroxysmal Nocturnal Haemoglobinuria and Refractory Marrow Failure Treated by Marrow Transplantation
Authors: Storb Rainer , Evans Robert S. , Thomas E. Donnall , Buckner C. Dean , Clift Reginald A. , Fefer Alexander , Neiman Paul , Wright Stephen E.
Published: March 2008

Summary. A patient with pancytopenia and paroxysmal nocturnal haemoglobinuria (PNH) following exposure to insecticide spray developed complete marrow failure after inhalation of vapours containing benzol. There was no sign of spontaneous recovery after more than 6 mth of conventional and supportive therapy. The patient was treated with the immunosuppressive agent cyclophosphamide, 50 mg/kg on each of four days, followed in 36 hr by transplantation of marrow from a sibling compatible at the major human histocompatibility locus (HL‐A). Intermittent methotrexate therapy was given for 102 days after grafting to prevent graft‐versushost disease. The patient showed prompt haemopoietic engraftment indicated by restoration of marrow cellularity and a rise in peripheral blood cell counts beginning on day 11 after the graft. The patient is alive and well with normal haemopoietic function and continued absence of PNH more than 1 yr and 4 mth after transplantation.
The Hermansky‐Pudlak Syndrome: Inclusions in Circulating Leucocytes
Authors: White James G. , Witkop Carl J. , Gerritsen Sybrand M.
Published: March 2008

Summary. Electron microscopy of circulating leucocytes from a patient with the Hermansky‐Pudlak syndrome revealed two different types of inclusions in a small percentage of monocytic cells. One of the inclusions closely resembled the large masses of lipopigment which fill the bone marrow macrophages in this disorder. The second type was unlike any inclusion previously reported in human leucocytes.
Relationship of the Pre‐treatment Peripheral Lymphocyte Count to Histology in Hodgkin's Disease
Authors: Henry L. , Knowelden J. , Swan H. T.
Published: March 2008

Summary. A survey was made of 249 cases of Hodgkin's disease. The pre‐treatment lymphocyte count in the peripheral blood was correlated with the histological appearance of the tumour classified into ‘lymphocytic’, ‘mixed’, ‘lymphoid depletion’ and ‘nodular sclerosing’ groups. The peripheral lymphocyte count was significantly higher in the ‘lymphocytic’ than in the ‘lymphoid depletion’ varieties. The two remaining groups occupied an intermediate position. The prognostic and immunological implications of this observation are discussed.
Non‐immunoglobulin‐bearing‘B’ Lymphocytes in Chronic Lymphatic Leukaemia?
Authors: McLaughlin H. , Wetherly‐Mein G. , Pitcher C. , Hobbs J. R.
Published: March 2008

Summary. Log‐normal ranges for the incidence of immunoglobulin‐bearing lymphocytes in human peripheral blood are described. Twenty‐five cases of chronic lymphatic leukaemia have been investigated and absolute numbers of cells have been ascertained and related to clinical details. It is suggested that most CLL patients suffer from a disorder of the B cell population, including many in which non‐immunoglobulin‐bearing cells predominate.
Haemophilia and Allied Disorders in the Sudan
Authors: Omer A. , Ziada M.
Published: March 2008

Summary. During the last 4 years 36 Sudanese patients with various hereditary bleeding disorders have been seen in the University Pathology Department. The ratio of von Willebrand's disease to haemophilia (10:18) is higher than expected. The report includes also a family with factor‐V deficiency and three patients with functional platelet defect. The results suggest a higher incidence of these diseases in subjects of Arab as compared to Negroid ancestry.
A Method of Antithrombin Estimation using Plasma Defibrinated with Ancrod
Authors: Howie P. W. , Prentice C. R. M. , McNicol G. P.
Published: March 2008

Summary. A method for the measurement of progressive antithrombin activity is described. Higher levels of antithrombin activity are found in plasma defibrinated with ancrod than in plasma defibrinated by heating to 56°C or by thrombin. As ancrod itself has no antithrombin activity, it is recommended as the best agent for defibrinating plasma prior to antithrombin estimation.

The relationship between plasma and serum antithrombin concentration was studied in patients during oral contraceptive therapy. There was a fall in both plasma and serum antithrombin during this therapy but the fall in serum antithrombin was significantly greater than that seen in plasma; this reflects the fact that the serum antithrombin concentration is dependent on the degree of thrombin generation which has taken place during clotting.
Low Factor‐VIII‐like Antigen in Acquired Von Willebrand's Syndrome and Response to Treatment
Authors: Ingram G. I. C. , Prentice C. R. M. , Forbes C. D. , Leslie J.
Published: March 2008

Summary. Measurements of factor‐VIII‐like antigen have been made in three previously reported cases of acquired von Willebrand's syndrome. Antigen levels correlated well with biological activity of factor VIII over a wide range, providing a further similarity between the acquired and classical forms of the disorder.
Quantitative Haemagglutination
Authors: Greenwalt T. J. , Steane E. A.
Published: March 2008

Summary. As sialic acid is removed from red cells by neuraminidase treatment agglutinability measured by the sensitive AutoAnalyzer continuous flow technique increases with anti‐A, ‐B, ‐H, ‐D and ‐c. The increase in agglutinability is related to the amount of sialic acid removed, but the relationship is different for different antibodies. Rather than a simple non‐specific reduction in zeta potential, these results suggest a more complex explanation, probably involving the decrease of ordered water near the surface of the desialated cells.
Phagocytic Function of Leucocytes from Patients with Acute Myeloid and Chronic Granulocytic Leukaemia
Authors: Goldman J. M. , Th'ng K. H.
Published: March 2008

Summary. The capacity of peripheral blood leucocytes from 11 patients with acute myeloid leukaemia (AML) and 10 patients with chronic granulocytic leukaemia (CGL) to ingest and kill Candida albicans was tested in vitro. The patients with CGL were, for the most part, receiving chemotherapy and had peripheral leucocyte counts in the normal range, whereas none of the patients with AML had received therapy within the preceding 7 days and none had entered complete remission. Ingestion of Candida organisms was found to be normal in both groups of patients, but the killing activity (candidacidal index) of leucocytes from patients with AML was significantly impaired. Leucocytes from CGL patients killed engulfed Candida normally. It is postulated that the candidacidal defect in leucocytes from patients with AML has two components, one intrinsic to the leucocyte and the other due to a deficient (or inhibitory) factor in the patient's plasma.
52Fe Studies of the Effects of Treatment on Erythropoiesis in Megaloblastic Anaemia
Authors: Bruce‐Tagoe A. A. , Hoffbrand A. V. , Short M. D. , Szur L.
Published: March 2008

Summary. 52Fe has been used to study iron turnover and the extent of haemopoietic tissue in five patients (age range 13–74 yr) with severe megaloblastic anaemia, before and after treatment. All the untreated patients showed extension of haemopoietic marrow, and this was most marked in the youngest subjects. One patient (aged 60) showed a considerable degree of extramedullary haemopoiesis in the spleen. The extent of haemopoietic tissue decreased after therapy in all cases and appeared to reach normal by about 4–5 mth.

Plasma iron turnover was considerably increased before therapy in three patients and after 48 hr of therapy in the remaining two. Repeat studies after 5 weeks to 8 mth therapy showed a decrease in iron turnover in all five, but this was still raised at 5 weeks and 4 mth in two patients.
Sialic Acid Deficiency of Human Red Blood Cells Associated with Persistent Red Cell, Leucocyte, and Platelet Polyagglutinability
Authors: Lalezari Parviz , Al‐Mondhiry Hamid
Published: March 2008

Summary. This study reports, for the first time, a persistent polyagglutinability involving all blood cells of a patient. The phenomenon is shown to be an immunological reaction due to an antibody present in sera of all normal adults, whereas the antigen, tentatively designated ‘Tcr’, is unique to the patient. It is shown that Tcr is related to Tn, an antigen previously described in association with red cell polyagglutinability. A partial deficiency of red cell sialic acid is also found to be associated with this abnormality. It is suggested that this sialic acid deficiency may be a manifestation of a primary underlying muco‐protein abnormality.
Glutathione Peroxidase in Human Red Cells in Health and Disease
Authors: Hopkins J. , Tudhope G. R.
Published: March 2008

Summary. Red‐cell glutathione peroxidase (GSH‐Px) activity has been assayed in 62 normal subjects and in 163 patients with various diseases. In nine cases of iron deficiency anaemia, the mean GSH‐Px activity per cell or per volume of cells was low; during the first 2–4 weeks of treatment with iron, red‐cell GSH‐Px increased in parallel with haemoglobin. High enzyme activities, above the normal range, were found in 11 cases of megaloblastic anaemia due to deficiency of vitamin B12; rapid and marked fall in GSH‐Px activity followed the start of vitamin B12 therapy. Abnormally high values for red‐cell GSH‐Px were found in acute myeloblastic leukaemia and in myelofibrosis whereas the enzyme activity tended to be low in chronic lymphocytic and in chronic myeloid leukaemia. In two cases of chronic myeloid leukaemia, red‐cell GSH‐Px increased to normal during the early stage of remission produced by cytotoxic therapy. Normal red‐cell GSH‐Px was found in six cases of polycythaemia vera. In patients with carcinoma, there was a wide variation in red‐cell GSH‐Px but the mean value was significantly less than normal.
A Tanned Cell Haemagglutination Test for the Detection of Hepatitis‐Associated‐Antigen (Au‐Ag) and Antibody (Anti‐Au)
Authors: Hopkins R. , Das P. C.
Published: March 2008

Summary. A tanned cell haemagglutination technique using inactivated Au‐Ag to sensitize human ‘O’ Rh negative crythrocytes is described. The method may be used to detect Au‐Ag by haemagglutination inhibition (HI) and anti‐Au by direct haemagglutination (HA). Sensitivity and specificity arc demonstrated and its application to mass donor screening is considered.
Factor‐VIII Antigen and Platelet Retention in a Glass Bead Column
Authors: Bouma B. N. , Sixma J. J. , de Graaf S. , Wiegerinck Y. , van Mourik J. A. , Mochtar I. A.
Published: March 2008

Summary. Platelet retention by the method of Bowie et al (1969a, b) was investigated and its diagnostic value in von Willebrand's disease (VWD) confirmed. Platelet retention was not affected by variations of heparin concentration, by inverting the blood or by a delay of up to 2 hr in performing the tests. Cryoprecipitate prepared from normal and from haemophilic plasma with normal factor‐VIII antigen levels corrected the abnormal platelet retention in VWD in vitro, whereas cryoprecipitate prepared from VWD plasma with reduced factor‐VIII antigen concentration was ineffective. This suggested, in agreement with our previous findings (Bouma et al, 1972), that factor‐VHI‐related antigen is responsible for the in vitro correction of the abnormal platelet retention in VWD. Circulating inhibitors of factor VIII activity had no effect on the platelet retention of normal blood, suggesting that the site on the factor‐VIII molecule which potentiates platelet retention is not affected by blocking the molecular site which is responsible for the factor‐VIII activity. A normal factor‐VIII antigen level was found in four patients with VWD. Cryoprecipitate prepared from plasma of these patients corrected the abnormal platelet retention of patients with VWD who had reduced factor‐VIII antigen concentration. These results suggest that VWD is heterogeneous.
Application of Time Series Analysis to Serial Blood Neutrophil Counts in Normal Individuals and Patients Receiving Cyclophosphamide
Authors: Dale David C. , Alling David W. , Wolff Sheldon M.
Published: March 2008

Summary.

For periods of time ranging from 1 to 3 mth white blood cell and differential counts were made daily on eight normal volunteers and two patients receiving cyclophosphamide. The patients tended to have lower mean neutrophil (PMN) counts than the volunteers; moreover, there was a corresponding decrease in the variability of the counts around the means.

The PMN counts appear to follow a lognormal distribution which would arise if the mechanism stabilizing the PMN counts adjusts the number of circulating cells in a multiplicative manner.

Periodogram analysis of the log PMN counts showed evidence of regular periodic variation in only one of the subjects, a patient undergoing treatment with cyclophosphamide. The sequences of daily log PMN counts appeared to represent first‐order autoregressions with an average serial correlation coefficient of 0.125. These findings indicate that a typical series of daily PMN counts does not show cyclic variation.
Studies of the Procoagulant and Fibrinolytic Activity of Promyelocytes in Acute Promyelocytic Leukaemia
Authors: Gralnick Harvey R. , Abrell Elinor
Published: March 2008

Summary.

Malignant cells from four patients with acute promyelocytic leukaemia (APL) were analysed for coagulant and fibrinolytic activity. For comparison polymorphonuclear leucocytes from normal donors and myeloblasts from patients with acute myelogenous leukaemia (AML) were also tested. The APL cells compared to the other cells consistently shortened the recalcification time and partial thromboplastin time of normal, factor VIII deficient and factor IX deficient plasma, but had no effect on factor X deficient or factor VII‐X deficient plasma. APL cells demonstrated increased (250–1500%) tissue factor activity when tested in a two‐stage assay in which tissue factor is the rate limiting component. The increased tissue factor activity was primarily found in the granular fraction of APL cells. Fibrinolytic and proteolytic activity of the APL cells was variable. Cells from three of the APL patients demonstrated a slight increase (150–400%), while the cells from one APL patient had markedly diminished proteolytic activity. The increased fibrinolytic activity was associated primarily with the granular fraction. Although the fibrinolytic activity is increased, it does not parallel the increase in tissue factor activity. This imbalance of coagulation and fibrinolysis in the cellular composition of promyelocytes could explain the high incidence of clinical thrombo‐haemorrhagic disorders related to intravascular coagulation in APL.
Effects of Ancrod (Arvin) in Mice: Studies of Plasma Fibrinogen and Fibrinolytic Activity
Authors: Silberman Simone , Bernik Maria B. , Potter Elizabeth V. , Kwaan Hau C.
Published: March 2008

Summary.

Plasma fibrinogen and its degradation products (FDP) were examined in mice given single injections of Ancrod, the purified coagulative fraction of Malayan pit viper venom previously called Arvin. Clottable fibrinogen had disappeared completely 5 min after the injection and slowly reappeared 12 hr later. At least 2 FDP appeared in the plasma 30 min after the injections while 5 hr later only one FDP was present which corresponded to human fragment E. This was in contrast to in vitro lysis of mouse fibrinogen which yielded two late FDP corresponding to human fragments D and E.

The fibrinolytic system also was examined in the plasma of these animals. 30 min after the injection, plasminogen was decreased in amount but increased in susceptibility to activation by urokinase. Transient, modest increases in fibrinolytic activity were evident in diluted plasma samples 1 hr and again 8 hr after the injections. Inhibitors of fibrinolysis did not differ from those in normal mice.

These observations are correlated with our previous immunofluorescent and histochemical studies on these and other animals. The present data support our earlier conclusion that fibrinolysis within small vessels of the tissues is of major importance in the reaction to Ancrod.
Antiplasmin Activity of Rat Serum Slow α‐Globulins
Authors: Horne C. H. W. , Forbes C. D. , Prentice C. R. M.
Published: March 2008

Summary.

The antiplasmin activity of serum slow α1‐ and α2‐globulins has been studied in rats injected with streptokinase/human serum and human or rat plasmin. Highly significant falls in serum slow α1 ‐globulin were noted soon after administration of streptokinase and human or rat plasmin; this suggested a reaction between plasmin and slow α1‐globulin with rapid removal of the resultant complexes. Rats with immune complex nephritis (ICN) given streptokinase showed a highly significant increase in slow α2‐globulin, but no change in slow α2‐globulin was noted following injection of human plasmin. Using fibrin agar plates additional evidence was obtained that rat slow α1‐globulin inhibited digestion of fibrin by plasmin. We conclude that of the two globulins in the rat only slow α1‐globulin shows antiplasmin activity and we believe that this represents the functional analogue of α1‐macroglobulin in the human.
Nonspherocytic Haemolytic Anaemia with Increased Red Cell Adenine Nucleotides, Glutathione and Basophilic Stippling and Ribosephosphate Pyrophosphokinase (RPK) Deficiency: Studies on Two New Kindreds
Authors: Valentine William N. , Bennett John M. , Krivit William , Konrad Patricia N. , Lowman James T. , Paglia Donald E. , Wakem Christopher J.
Published: March 2008

Summary.

The second and third kindreds with hereditary haemolytic anaemia characterized by marked basophilic stippling of the erythrocytes, increased red‐cell GSH and adenine nucleotides, and ribosephosphate pyrophosphokinase (RPK, PRPP synthetase) deficiency are reported. In each affected subject increased auto‐haemolysis was not corrected by glucose additives in the autohaemolysis test. Despite the clearly hereditary nature of the syndrome, a heterozygous ‘carrier’ state could not be demonstrated in any family members. While autosomal recessive transmission is likely, the genetics remain obscure. The roles of substantial RPK deficiency as either a causative factor or an epiphenomenon is likewise not firmly established.
Pregnancy and Idiopathic Autoimmune Haemolytic Anaemia: A Prospective Study during 6 Months Gestation and 3 Months Post‐Partum
Authors: Jr Chaplin, Hugh , Cohen Robert , Bloomberg Gordon , Kaplan Harold J. , Moore Joy A. , Dorner Irene
Published: March 2008

Summary.

A 31‐yr‐old woman with a 12 yr history of relapsing idiopathic autoimmune haemolytic anaemia was studied prospectively during her first pregnancy. Her serum contained a warm incomplete autoantibody as well as an elevated cold agglutinin; her red blood cells were strongly coated with IgG and complement (chiefly α2D). Haemolysis was active throughout pregnancy, accelerating from the 34th to 40th week, with developing thrombocytopenia. Amniocentesis in the 8th and 9th months suggested minimal foetal haemolysis. The maternal haemolytic process went into complete clinical remission following delivery of a healthy appearing infant whose red cells were coated with IgG. The infant developed mild hyperbilirubinaemia within 48 hr and experienced a fall in haemoglobin to 50% of the cord level by the 8th week. Abnormalities of maternal and infant C4 levels were observed. Review of 19 reported instances of presumed autoimmune haemolysis during pregnancy revealed life‐threatening anaemia in nearly 50% of mothers, with four still‐births, one neonatal death, and three seriously affected infants. A programme for prospective management of this serious clinical problem is discussed.
Production of Paroxysmal Nocturnal Haemoglobinuria‐like Red Cells by Reducing and Oxidizing Agents
Authors: Goldstein Bernard D.
Published: March 2008

Summary. Normal red cells incubated with high concentrations of compounds containing sulphydryl groups are known to develop several characteristics of red cells obtained from patients with paroxysmal nocturnal haemoglobinuria (PNH). These include positive acid and sucrose haemolysis tests and a decline in acetylcholinesterase (AChE) activity. The present studies demonstrate that incubation of normal red cells with the non‐sulphydryl reducing agent sodium borohydride also results in the production of PNH‐like characteristics. Evaluation of this phenomenon utilizing the sulphydryl agents glutathione (GSH) and dithiothreitol (DTT) reveals that the transformation is not dependent upon the presence of oxygen, is not associated with a significant decline in red cell vitamin E levels, and is not observed when GSH is rapidly oxidized by azoester. It appears that the most likely mechanism for the formation of PNH‐like red cells under these conditions is through the reduction of cell membrane disulphide groups.

Production of a positive sucrose and acid haemolysis test as well as a decline in AChE activity was also observed in two experimental systems which produce oxidative free radical damage to the red cell membrane: gassing of normal red cells with ozone, and irradiation of red cells from patients with erythropoietic protoporphyria with 400 nm light.
Immunological Responsiveness in Idiopathic and Drug‐induced Panmyelopathy: Discrepancy between Sensitization with DNCB and Haemocyanin
Authors: Samsom J. P. , de Gast G. C. , Nieweg H. O.
Published: March 2008

Summary. Immunological responsiveness to two primary antigens, haemocyanin and dinitrochlorobenzene, was tested in seven patients with idiopathic or drug‐induced panmyelopathy. Humoral immunity was quite normal, but cell‐mediated immunity was partially deficient. Six patients showed in vitro lymphocyte reactivity to haemocyanin and positive intracutaneous tests with haemocyanin after immunization. The one patient in whom sensitization to haemocyanin did not develop had received prednisone during immunization because of overt bleeding tendency. In contrast to the successful immunization with haemocyanin, sensitization with DNCB did not succeed in any of the seven patients. PHA reactivity of the lymphocytes was not significantly lowered.
Thrombin Stimulated Release of Platelet Microfibrils
Authors: Webber A. J. , Budtz‐olsen O. E.
Published: March 2008

Summary. Platelets, separated from plasma by gel filtration, were exposed to a low level of thrombin prior to negative staining and examination by electron microscopy. Microfibrils with dimensions consistent with the contractile protein of platelets, thrombosthenin, were observed to radiate from the platelet surface.
Platelet Aggregation and Release by ADP and Thrombin: Evidence for Two Separate Effects of ADP on Platelets, Involvement of Fibrinogen in Release, and Mechanism of Inhibitory Action of Acetylsalicylic Acid
Authors: Han P. , Ardlie N. G.
Published: March 2008

Summary. The previously demonstrated roles of thrombin and fibrinogen in platelet interaction (Ardlie & Han, 1974) suggested a possible relationship between platelet aggregation and the release reaction. The present results show that a product of the action of thrombin on fibrinogen induced the release of platelet constituents. This activity was not inhibited by heparin. The thrombin‐fibrinogen reaction which occurs when platelets come into contact could be the cause of the subsequent release reaction. ADP was shown to be essential for the thrombin‐induced aggregation, but not the alteration in platelet morphology. Evidence of involvement of ADP in cell contact was obtained and it is possible that its role may be to facilitate aggregation through an effect on platelet surface charge. Thus, ADP induces aggregation through two distinct actions: (1) alteration of platelet morphology; and (2) reduction in net negative surface charge of platelets. Incubation of thrombin with aspirin inhibited its action on platelets and it is suggested that acetylation of thrombin (or prothrombin) by aspirin may account for the action of this compound on platelets. The significance of these observations and a possible mechanism for the release reaction is discussed.
Trisomy‐9 in the Bone Marrow of a Patient with Acute Myelomonoblastic Leukaemia
Authors: Rutten F. J. , Hustinx T. W. J. , Scheres J. M. J. C. , Wagener D. J. T.
Published: March 2008

Summary. The case history of an adult patient with acute myelomonoblastic leukaemia is presented. The leukaemia developed 4 yr after the first irradiation for a Wilms' tumour. Approximately 35% of the bone marrow cells had 47 chromosomes and were trisomic for chromosome 9.
A Vitamin B12 Binder with Transcobalamin I Characteristics Synthesized and Released by Human Granulocytes in Vitro
Authors: Rachmilewitz B. , Rachmilewitz M. , Gross J.
Published: March 2008

Summary. In‐vitro synthesis and release of a vitamin‐B12 binding protein by peripheral leucocytes derived from healthy subjects and patients with chronic myeloid leukaemia (CML), acute promyelocytic leukaemia (APL) and acute myeloblastic leukaemia (AML) were investigated.

Myeloid cells, incubated in a nutrient medium containing [3H]leucine, incorporated labelled amino‐acid into the vitamin‐B12 binding protein with an increase of the unsaturated vitamin‐B12 binding capacity (UBBC) of the cells.

The increase in the UBBC of the medium was due to the presence of the newly produced leucocyte binder which was released into the medium by the cells during incubation. On chromatography the newly synthesized binder was similar to transcobalamin I.

The incorporation of [3H]leucine into the leucocyte binder by mature granulo‐cytes and undifferentiated myeloblasts was very limited and reached a maximum after 60 min of incubation. Cells from CML and APL patients showed a higher rate of incorporation of the labelled amino‐acid which reached a plateau after 40 hr. The increase in the UBBC of the leucocyte binder was paralleled by the incorporation of [3H]leucine.

The percentage of immature myeloid cells in the incubation mixture (promyelocytes to stab forms) was correlated with both the incorporation of [3H]leucine and with the increase in UBBC.