bluuebunny/crossref_metadata_2025 huggingface dataset:
The Organ Distribution of 125I‐Fibrin in the Generalized Shwartzman Reaction and its Relation to Leucocytes
Authors: Lipinski Boguslaw , Nowak Andrzej , Gurewich Victor
Published: March 2008

Summary. A quantitative method utilizing 125I‐fibrinogen was used to study the deposition and distribution of fibrin in the generalized Shwartzman reaction (GSR). In control rabbits, intravenous injection of 125I‐fibrinogen results in the deposition of a small quantity of radioactive material uniformly distributed among the organs examined. After two doses of endotoxin 24 hr apart, the total organ radioactivity was increased eight‐fold, most of it being found in the spleen, followed in turn by the lungs, kidneys and liver. Extraction experiments showed that the radioactive material had the characteristics of stabilized fibrin. Autoradiography of kidney slices established the characteristic features of the GSR by demonstrating localization of radioactivity in the renal glomeruli. In animals treated with warfarin, heparin, streptokinase or nitrogen mustard, little or no radioactive fibrin was found in the organs. A highly significant (P<0.001) correlation was found between the fall in leucocyte count 3 hr after the second dose of endotoxin and the amount of fibrin deposited in the organs. No corresponding correlation was found with the platelet count. The association of fibrin deposition and leucocytes was supported by expcriments with 51Cr‐labelled leucocytes which were found also to accumulate predominantly in the spleen. The findings suggest that fibrin deposition in the GSR occurs as a result of the local interaction of leucocytes with circulating fibrin monomer (FM). Accumulation of fibrin deposits is attributed to inhibition of fibrinolysis. It is concluded that the development of the GSR requires the simultaneous presence of at least three factors: FM, granulocytes and inhibition of fibrinolysis. The absence of any one of these factors is sufficient to prevent fibrin deposition in endotoxin treated animals.
An Abnormal Platelet Glycoprotein Pattern in Three Cases of Glanzmann's Thrombasthenia
Authors: Nurden A. T. , Caen J. P.
Published: March 2008

Summary. A glycoprotein abnormality in membrane fractions isolated from the platelets of patients with Glanzmann's thrombasthenia is described. Glycoproteins solubilized from thrombasthenic and control human platelets have been compared by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. Whereas in a control human platelet membrane fraction three major glycoproteins of molecular weight 155 000, 135 000 and 103 000 were observed, in a similar fraction from thrombasthenic platelets a glycoprotein of 152 000 molecular weight predominated. No differences were observed in the nature of a high molecular weight acidic glycopeptide released from washed thrombasthenic and control platelet suspensions by trypsin, and the sialie acid content of thrombasthenic platelets was shown to be within the normal range.

It is suggested that the glycoprotein abnormality may be due to an altered organization within the thrombasthenic platelet membrane and that further studies are necesasry to investigate the role of membrane glycoproteins in platelet function.
The Effect of Sex Difference on Iron Exchange in the Rat
Authors: Hershko Ch. , Eilon L.
Published: March 2008

Summary.When compared with normal males, female Wistar rats have significantly higher serum iron levels, a higher rate of plasma iron turnover and a higher proportion of their plasma iron is diverted into non‐erythroid tissues. These difference are abolished by castration and reestablished by the supplementation of testosterone and oestrogen to castrated animals. The effect of sex hormones on iron handling is independent of their action on erythropoiesis, since in hypertransfused animals with complete inhibition of erythropoiesis the sex difference in serum iron levels and in hepatic iron uptake is maintained, The absolute rate of iron absorption is similar in both groups, but when the daily absorption of food iron is related to growth rate, it is considerably higher in females than in males (P< 0.001). The cumulative effect of a relatively higher iron absorption in females is the establishment of large iron stores which by virtue of their higher rate of exchange with transferrin contribute to their higher plasma iron turnover.
Erythrocytosis in Hepatocellular Carcinoma: A Compensatory Phenomenon
Authors: Tso S. C. , Hua A. S. P.
Published: March 2008

Summary. Red cells were removed by phlebotomy in nine patients having erythrocytosis associated with hepatocellular carcinoma. This resulted in an increase in the plasma levels of erythropoietin in seven; the rise was statistically significant in three. It suggests that, in the absence of systemic hypoxia, erythrwytosis develops in hepatocellular carcinoma as a compensatory response to local hypoxia in the liver. However, no rise in the 24 hr urinary output of erythropoietin was observed in any of the patients. It is postulated that this may be due to the presence in urine of inhibitors to erythropoietin.
Esterases in Human Neutrophil Granulocytes: Evidence for their Protease Nature
Authors: Rindler‐Ludwig Rothild , Schmalzl F. , Braunsteiner H.
Published: March 2008

Summary. The nature of the esterases localized in granules of human neutrophil granulocytes has been investigated. The esterases of the granule fraction were fractionated first by selective solubilization of the granule proteins with 0.15 M‐NaCl and subsequently by gel filtration of the dissolved proteins on Sephadex G‐75. The chymotrypsin‐like activity of the granule fractions was insoluble in 0.15 M‐NaCI. Part of the granule esterase activity is known to be due to this chymotrypsin‐like enzyme. The soluble esterase activity of the granule fraction could be attributed to proteases as well. Two peaks of proteolytic activity on casein at pH 8.0 were obtained by gel filtration. The peak eluted first from the Sephadex G‐75 column contained two esterase proteins with a molecular weight of about 70000. The second protease peak contained the elastase‐like activity in addition to other proteases. A molecular weight of about 33000 was estimated for these proteins. Acrylamidegel electrophoresis of this fraction revealed a pattern of esterase bands. No esterase bands were demonstrable on the gel electrophoretograms given by fractions without proteolytic activity.
Hyperviscosity Syndrome in IgA Multiple Myeloma
Authors: Tuddenham E. G. D. , Whittaker J. A. , Bradley J. , Lilleyman J. S. , James D. R.
Published: March 2008

Summary. Four cases of IgA multiple myeloma with raised serum or Plasma viscosity and clinical features of the hyperviscosity syndrome (HVS) are described. Plasmapheresis was effective in reducing blood viscosity and improving the clinical condition in all four patients. In three of four cases plasma viscosity studies showed an increase in viscosity at low temperature which in one patient was attributable to excess chylomicrons. Although rarely reported in the past, IgA myeloma has been the commonest cause of HVS in Cardiff and should be looked for in all cases of myeloma whatever the paraprotein type. Measurement of serum viscosity is essential for rational clinical management. Whole blood viscosity measurements, although technically more difficult, are also of great help in patient management.
Kinetic Evaluation of Haemostasis during Surgery and Wound Healing
Authors: Slichter Sherrill J. , Funk Donald D. , Leandoer Lennart E. , Harker Laurence A.
Published: March 2008

Summary. This study indicates that platelets and fibrinogen are utilized following surgery as a physiological response to tissue injury. The amount and duration of the consumption of haemostatic components is related to the extent of the surgical injury. In vivo counting demonstrates localized accumulation of radioactively tagged platelets and fibrinogen in the surgical wound that proceeds for several days. It is concluded that this consumption reflects the participation of the haemostatic apparatus in wound healing.
Chemical Heterogeneity of Foetal Haemoglobin in the Lepore Haemoglobinopathy
Authors: Efremov G. D. , Sadikario A. , Stojmirovic E. , Schroeder W. A. , Roger Shelton J. , Balog Shelton Joan , Apell Gerald , Wilson J. B. , Brodie AnneR. , Huisman T. H. J.
Published: March 2008

Summary. The glycine/alanine composition of the γCB‐3 peptide of haemoglobin F obtained from persons heterozygous and homozygous for haemoglobin Lepore has been determined. The mean glycine value for heterozygotes was 0.34 ± 0.1 residues which is similar to that observed in the haemoglobin F of normal adults. A higher glycine value was found in a homozygous individual. These findings are discussed with regard to the light which they shed on the molecular basis for the haemoglobin‐Lepore disorders and related types of δβ and β thalassaemia.
Cation Content and Membrane Deformability of Heterozygous P‐Thalassaemic Red Blood Cells
Authors: Vettore L. , Falezza G. C. , Cetto G. L. , De Matteis M. C.
Published: March 2008

Summary. The red blood cells of patients heterozygous for 8‐thalassaemia contain less sodium, potassium and water than do normal red cells. Incubation of red cells in plasma at 37°C for 24 hr in the absence of glucose produced the following changes: (1) An increase in the red‐cell sodium content of both normal and thalas‐saemic cells. (2) A decrease in the red cell potassium content which was much more pronounced in thalassaemic than in normal cells. (3) A reduction in the total cation content of the red cells from patients heterozygous for β‐thalassaemia; this reduction seemed to be related to the clinical severity of the disease, as well as the reduction in mean corpuscular volume and osmotic fragility. (4) The trapped plasma values, which reflect the deformability of red cells, were initially greater for thalassaemic red cells than normal cells and in both groups increased after incubation.

The addition of glucose to the incubation medium largely prevented the changes produced by incubation. The changes induced by incubation in vitro may be relevant to changes in vivo, where a local lack of glucose might lead to a loss of potassium and water from thalassaemic cells. This could give rise to shrinking of the red cells and a reduction in their deformability which may play a role in the haemolysis of heterozygous β‐thalassaemia.
Observations on the Ultrastructure of Platelets in Glanzmann's Disease
Authors: Firkin Barry G. , Howard Margaret A. , Farmer Sue J.
Published: March 2008

Summary. The platelets from six patients with congenital thrombasthenia (Glanzmann's disease) have been studied with respect to their ultrastructure and to the changes which occur following incubation with 4% sodium EDTA and uptake of particulate matter in the form of thorotrast and latex following incubation at timed intervals. Platelets from all patients behaved abnormally on incubation with EDTA. Thorotrast uptake was greatly increased in three and possibly reduced in the remaining three patients. Latex uptake was normal to increased in four of the patients and greatly reduced or absent in two. These differences must reflect abnormalities in membrane properties and/or cell metabolism. These findings suggested that there are at least two varieties of Glanzmann's disease.
The Effect of Urea on Sickling
Authors: May A. , Huehns E. R.
Published: March 2008

Summary. The effect of urea on the oxygen affinity of sickle cells and normal cells was studied up to a concentration of about 1.0 M. Besides the increase in oxygen affinity found in both normal and sickle cells there was a further increase found only in the sickle cells. This specific increase was caused by the direct inhibition of the polymerization of deoxygenated Hb‐S by the urea and was used to measure the extent of this inhibition. Even at concentrations of 1.0 M the urea did not fully inhibit the polymerization. At the urea concentrations recommended for treatment of sickle cell crises and for the oral treatment of the disease there was only a very slight inhibition of polymerization. The small increase in oxygen affinity brought about by these concentrations of urea (equivalent to a log P50 change of 0.016) will cause some additional minimal inhibition of sickling at physiological partial pressures of oxygen. Oxygen dissociation measurements of Hb‐A in dilute solution showed that 0.95 M urea had no effect on the interaction of 2, 3‐DPG and chloride with haemoglobin nor on the haem‐haem interactions. This implies that the quaternary ‘deoxy’ form of the haemoglobin may still form and that the action of urea in inhibiting the polymerization is through interference with the intermolecular bonds rather than by inducing a conformational change which disrupts the bonding. Unless urea at the concentrations recommended for treatment inhibits the sickling of the cells by some mechanism other than its effect on the haemoglobin (such as by an effect on the membrane), these results suggest that it is of little use for the treatment of sickle cell disease.
A Rapid Method for Obtaining the Half Saturation Tension of Small Blood Samples Using a Standard Clark Electrode System
Authors: Scott G. E.
Published: March 2008

Summary. A method is described which allows the half saturation tension (T50 value) of blood to be obtained within 5 min on samples of 100 μl volume, using a standard Clark Po2 electrode. A Po2‐time trace is recorded on a blood/buffer suspension from which the oxygen is removed at a constant rate using yeast cells. The T50 value is then derived graphically. The values taken for 210 traces show the graphical solutions to lie within ± 0.5 mmHg of the tensions calculated from complete dissociation curves. Values from a further 590 traces show the T50 estimates are also reproducible with a standard error of less than 0.3 mmHg.
Quantitation of the ABO System Antigens by Means of Isoprecipitating Antisera
Authors: Pintera J. , Vacl J. , Hrnčířová D. , Kurtinová J. , Zelená E.
Published: March 2008

Summary. A quantitative method for the determination of blood group specific substances A and B on red blood cells was developed, using them to absorb isoprecipitating antisera anti‐A and anti‐B, followed by estimation of the residual antibody by means of a counterimmunoelectrophoretic technique with standard solutions of A and B substances prepared from saliva. The method was tested on a population of A2B donors.

The mean amount of A substance in A2B RBC was 131 × 10−12±217 × 10−12 u/cell in the population of 95 donors. The A substance thus determined agreed significantly with values obtained by classical haemagglutinating titration. The mean amount of B substance in A2B RBC was 222 × 10−12±178 × 10−12 u/cell. The amounts of both the A and B substances were not correlated on the same RBC. Several peaks of the distribution curve of both substances confirmed the nonhomogeneity of the populations, there being a wide standard deviation presumably due to differences in the antigen content of different subgroups.
Coagulation Changes during the Steady State in Homozygous Sickle‐Cell Disease in Jamaica
Authors: Leslie J. , Langler D. , Serjeant G. R. , Serjeant B. E. , Desai P. , Gordon Y. B.
Published: March 2008

Summary. Coagulation studies were carried out in 117 Jamaicans with homo‐zygous sickle‐cell disease in the steady state, and 40 local controls. The patients had significantly higher factor‐VIII levels, higher platelet counts, lower factor‐V and plasminogen levels, shorter thrombin times and higher serum fibrinogen degradation products (FDP) than the control group. The low factor‐V and plasminogen levels, and high FDP levels, might be explained by activation of the coagulation system and continuous clot lysis even in the absence of painful crisis. The high factor‐VIII levels and short thrombin times found in these patients could not be explained.
Erythraemia due to Haemoglobin San Diego
Authors: Chanarin I. , Samson D. , Lang A. , Casey R. , Lorkin P. A. , Lehmann H.
Published: March 2008

Summary. A 63‐year‐old man with erythraemia was found to have a high affinity haemoglobin which was subsequently identified as Hb San Diego β 109 (G11) Val→Met, recently described in a Filipino family (Nute et al, 1974). The oxygen affinity of the haemolysates was increased approximately two‐fold at pH values between 6.04 and 7.90. The n value was nearly normal (2.5–2.9) in the upper range of saturation (70–95% oxygenation) but was somewhat diminished (1.9–2.1) below this range. In vitro biosynthesis of globin by reticulocytes showed that there was balanced synthesis of α and β chains (α:β ratio = 1).
Investigations on Antithrombin III in Normal Plasma and Serum
Authors: Sas Géza , Pepper Duncan S. , Cash John D.
Published: March 2008

Summary. Studies on antithrombin III (AT‐III) were made by a modification of the two dimensional crossed immunoelectrophoresis technique and gel filtration. Mixing various quantities of heparin with agarose in the first phase of electro‐phoresis, AT‐III from normal human plasma and serum revealed a heterogeneity which depended on the heparin concentration in the agarose gel. At heparin concentrations higher than 16 u/ml, AT‐III displayed three components with different electrophoretic mobilities. The component with the highest mobility (designated immunoantithrombin III1: IAT‐III1) dominated in plasma. In normal serum, however, the quantity of this component was decreased and the two other peaks with a slower electrophoretic mobility (IAT‐III2 and IAT‐III3) became more evident.

Normal human plasma and serum were filtered on Sephadex G‐200 and the AT‐III concentration measured in the fractions by rocket immunoelectrophoresis. The peaks of AT‐III were found in the same fractions for both plasma and serum and were coincident with the albumin peak of the plasma proteins. However, in the case of serum the AT‐III concentration decreased less sharply in those fractions with higher molecular weight than in the corresponding plasma fractions. Analysis of these fractions by crossed immunoelectrophoresis revealed that the two components with slower electrophoretic mobility (IAT‐III2 and IAT‐III3) had higher molecular size than IAT‐III1, that the concentration of IAT‐III2 and IAT‐III3 was significantly higher in serum, and that the high molecular weight components in plasma and serum were qualitatively identical. It is concluded that high molecular weight complexes between AT‐III and activated coagulation factors may be present in normally circulating blood and that their detection and possibly quantitation can be achieved using the heparin/agarose crossed immunoelectrophoresis system.
The Concentration Dependence of the Oxygen Affinity of Haemoglobin S
Authors: May A. , Huehns E. R.
Published: March 2008

Summary. The effect of the concentration of haemoglobin S (Hb S) on its oxygen‐dissociation properties was studied using either reconstituted Hb‐S cells of different mean corpuscular haemoglobin concentrations (MCHCs) prepared by osmotic lysis, or cells in which Hb S is diluted by the presence of another haemoglobin.

Only 4% (phosphate buffer) and 21%(bis Tris) of the low oxygen affinity of fresh Hb‐S cells was found to be due to their slightly elevated intracellular 2, 3‐DPG concentrations since when the cells were depleted of 2, 3‐DPG most of the low affinity remained. The low affinity showed a marked dependence upon haemoglobin concentration which was absent for 2, 3‐DPG‐depleted Hb‐A cells and, by extrapolation, the MCHC at which the oxygen affinities of the Hb‐S cells became identical to that of the Hb‐A cells was 14.5 g/dl in phosphate buffer and 13.1 g/dl in bis Tris.

Both fresh and 2, 3‐DPG‐depleted cells containing another haemoglobin as well as Hb S (Hb‐SA, Hb‐SC and Hb‐SF cells) were also found to have low oxygen affinities provided that the intracellular Hb‐S concentration (MC(Hb‐S)C) was above a certain level. These also showed a strong dependence upon the MC(Hb‐S)C. The mean MC(Hb‐S)C at which the low oxygen affinities of the DPG‐depleted cells were abolished were 8.3 g/dl (phosphate) and 11.2 g/dl (bis Tris). Hb F in fresh Hb‐SF cells brought about a much greater increase in oxygen affinity than the same amount of either Hb A or Hb C. In 2, 3‐DPG depleted cells Hb A showed a greater ability to ‘dilute’ the Hb S than did Hb C.

The conditions for the low oxygen affinity of Hb S were therefore found to be very similar to those required for the gelling of both pure Hb S, and Hb S in haemoglobin mixtures. It was concluded therefore that the low oxygen affinity of the Hb S was caused by the polymerization and that the difference between the oxygen affinities of Hb‐S and Hb‐A cells may be used as a measure of the polymerization process.
Ethanol Inhibition of Reticulocyte Protein Synthesis: The Role of Haem
Authors: Freedman Michael L. , Cohen Howard S. , Rosman Judith , Forte Frank J.
Published: March 2008

Summary. Ethanol, in concentrations of 0.05–0.8 M, inhibited intact human and rabbit reticulocyte protein synthesis in the presence of iron‐transferrin for endogenous haem synthesis. Associated with this effect there was a conversion of polyribosomes to monoribosomes and a decreased incorporation of radioactive leucine into nascent globin chains. When physiological levels of ethanol (0.05–0.1 M) were used, these effects were prevented by incubation with 50 μM haemin and reversed by removing the alcohol and reincubating with iron‐transferrin or haemin. The polyribosomal disaggregation was also prevented by stopping ribosomal movement with 5 mM cycloheximide. Neither ATP nor GSH levels were altered in the presence of ethanol. When non‐physiological levels of 0.8 M ethanol were used, haemin did not prevent the inhibition of protein synthesis. Likewise, in the rabbit reticulocyte cell‐free lysate system containing haemin inhibition was noted at concentrations greater than 0.05 M ethanol. The polyribosomal disaggregation in reticulocytes incubated with 0.8 M ethanol was associated with decreased dissociation of monoribosomes into subunits. Similarly, when ribosomes were directly suspended cell‐free in 0.1 or 0.8 M ethanol there was a decreased percentage of subunits.

These results indicate that physiological concentrations of ethanol inhibit initiation of reticulocyte protein synthesis secondary to a block in haem synthesis. When intact cells are exposed to high non‐physiological concentrations of ethanol the inhibition is secondary to decreased ribosomal dissociation. The cell‐free lysate inhibition is also through this effect on ribosomal dissociation. This study supports the view that alcohol is a direct toxin to developing red cell precursors via its effect on mitochondrial haem synthesis. The physiological role of the decreased dissociation of monoribosomes into subunits is not yet clear.
Liver Transplantation in Pigs with von Willebrand's Disease
Authors: Bowie E. J. Walter , Woods John E. , Fass David N. , Zollman Paul E. , Owen Charles A.
Published: March 2008

Summary.

Nine pigs with von Willebrand's disease (vWd pigs) received normal auxiliary livers; in the immediate postoperative period, three pigs died, three survived from 3 days to 3 weeks, and three were killed 5–13 weeks postoperatively. There was an increase in factor VIII (up to 90 u/dl) but with a type of factor VIII that was more labile than normal and that decreased after 2 weeks, probably as a result of liver rejection. There was a slight increase in the levels of the ristocetin‐Willebrand factor postoperatively (up to 11%) but this activity was undetectable after 2 weeks. There was no correction of the abnormal bleeding time and platelet retention. When a vWd liver was transplanted orthotopically into a normal pig, the factor‐VIII coagulant activity and the ristocetin‐Willebrand factor remained normal. The abnormality in porcine von Willebrand's disease is only partially corrected by liver transplantation, which suggests that there also is extrahepatic synthesis of the missing or abnormal plasmatic activity or activities.
Changes in Erythroblast Morphology as an Index of Response to Cyanocobalamin in Patients with Megaloblastic Anaemia
Authors: Dawson D. W. , Lewis M. J. , Wadsworth L. D.
Published: March 2008

Summary.

Fifty‐three patients with megaloblastic anaemia treated with cyanocobalamin and folic acid have been studied. Repeat marrow examination was found to be of value in assessing response to treatment. The early improvement in marrow morphology in patients with pernicious anaemia was greater with 1000 μg than with 5 μg doses of cyanocobalamin. The effect of folate deficiency in delaying marrow response to cyanocobalamin in patients with pernicious anaemia is described and combined cyanocobalamin and folic acid treatment was found to be more effective than either alone. The response to large doses of cyanocobalamin in folate deficient patients was unrelated to the initial serum vitamin B12 level.
The Three Transcobalamins in Myeloproliferative Disorders and Acute Leukaemia
Authors: Zittoun J. , Zittoun R. , Marquet J. , Sultan C.
Published: March 2008

Summary.

The unsaturated vitamin B12 binding capacity of whole serum (UBBC) and of the three transcobalamins (TC) has been studied in patients with various haematological diseases including myeloproliferative disorders (MPD) and acute leukaemia. The binding capacity of TC I and TC III was increased in MPD; TC I being particularly high in chronic granulocytic leukaemia (CGL) and TC III especially raised in polycythaemia rubra vera (PRV) and in infectious leucocytosis. The binding capacity of both TC I and TC III correlated with blood neutrophil count and the ratio TC III/TC I was low in CGL and increased in PRV. TC II was increased in acute myelogenous leukaemia, during remission and blast cell crisis of CGL and in refractory anaemia with excess of myeloblasts but not in acute lymphoblastic leukaemia (ALL). TC II correlated inversely with blood neutrophil count. There is an inverse ratio between TC II and TC I at least in myelogenous leukaemia. These abnormalities are discussed in relation to granulocyte kinetics. TC III and TC I reflect probably the total body granulocyte pool and share some biochemical and immunological properties supporting the view that they have a common origin in the more mature stages of the granulocyte cell line while TC II probably originates partly in more primitive granulocytes.
Effects of ADP and ATP on Bovine Fibrinogen‐ and Ristocetin‐Induced Platelet Aggregation in Glanzmann's Thrombasthenia
Authors: Cohen Isaac , Glaser Tova , Seligsohn Uri
Published: March 2008

Summary.

With thrombasthenic platelets, aggregation induced by ristocetin (R) and bovine fibrinogen (BF) is reversible, provided ATP is not added to the system. ADP inhibits BF and R induced aggregation, and when added after the onset of aggregation causes rapid disaggregation. ATP prevents these inhibitory and disaggregation effects of ADP. A mechanism is suggested whereby co‐operative effects occur between receptors in the membranes of thrombasthenic platelets.
Leucocyte Alkaline Phosphatase as a Marker of Cell Maturity: a Quantitative Cytochemical and Autoradiographic Study
Authors: Williams D. M.
Published: March 2008

Summary.

A sensitive and reproducible cytochemical technique for the demonstration of leucocyte alkaline phosphatase (LAP) has been evaluated. It produces a stable reaction product which can be readily quantified microphotometrically. In the circulating neutrophil polymorphonuclear leucocytes of rats the mean LAP levels measured in this way fluctuated only slightly from day to day. A highly significant correlation was demonstrated between LAP levels of neutrophils and their age, determined by isotope labelling with tritiated thymidine and by nuclear morphology. The correlation between the age of neutrophils and the complexity of their nuclear morphology has also been confirmed. The technique provides a useful tool for the study of leucocyte kinetics in disease states.
Procoagulant Activity of Platelets in Recalcified Plasma
Authors: Vecchione Jack , Zucker Marjorie B.
Published: March 2008

Summary.

High‐spun platelet‐poor plasma (HSPPP) and platelet‐rich plasma (PRP), prepared with minimal contact activation and pH shifts, were recalcified with little dilution in the presence of phospholipid prepared from chloroform‐extracted, acetone‐dried brain tissue. The clotting times of HSPPP and PRP were the same whether or not the platelets in PRP were first incubated or aggregated with ADP or with collagen. This suggests that platelet procoagulant activity in normal recalcified plasma derives only from provision of platelet phospholipid.
T and B Cells in Myelomatosis
Authors: Jones Susan V. , McFarlane H.
Published: March 2008

Summary.

The majority of treated patients with myelomatosis had a significantly decreased number of T cells as measured by both lymphocyte stimulation to phytohaemagglutinin (PHA) and by their ability to form spontaneous rosettes with sheep red blood cells (SRBC). Seven untreated patients also had markedly depressed T cells. On the other hand, B‐cell numbers were significantly increased in the majority of the patients as judged by increased lymphocyte stimulation to pokeweed mitogen (PWM) and the markedly increased numbers of rosettes that were formed with antibody‐coated complement activated SRBC, as well as by immunofluo‐rescence cell markers to monospecific immunoglobulin antiserum.
Enzyme Abnormalities in Red Cells
Authors: Valentine William N.
Published: March 2008

Summary.

Hereditary deficiencies involving eight enzymes of the Embden‐Meyer‐hof pathway, at least five involving the hexosemonophosphate shunt, and GSH metabolism, and at least two involving nucleotide metabolism, are known to be associated with haemolytic syndromes in man. Lactate dehydrogenase deficiency is also recognized, but is not associated with haemolysis. In addition, markedly aberrant enzyme activity ratios characterize a variety of dyserythropoietic disorders, both hereditary and acquired. In some disorders, haemolysis is the sole clinical manifestation; in others, dysfunction of the nervous system, the heart, the skeletal muscle, and the leucocytes may occur. The red cell may also mirror enzymopathies having expression in non‐haematopoietic tissues without a haemolytic syndrome being present. While double heterozygosity for two separate enzymopathies or for an enzymopathy and hereditary spherocytosis or elliptocytosis is recognized in a number of cases, clinical manifestations have thus far appeared minimal or non‐existent. In a recently described haemolytic syndrome uniquely large accumulations of cytidine and uridine nucleotides have been noted secondary to a severe deficiency of a pyrimidine specific 5’nucleotidase.
Autoimmune Haemolytic Anaemia in New Zealand Black Mice
Authors: East June , Harvey Jennifer J.
Published: March 2008

Summary.

Mice of the NZB strain spontaneously develop autoimmune haemolytic anaemia and reticulum cell neoplasms, and they harbour murine leukaemia virus. This triad of autoimmunity, malignancy, and virus infection is explored in experiments designed to show how the autoimmune haemolytic disease and/or the virus are transmitted to NZB hybrids derived naturally, by ovum transplantation, and from allophenic parents. Possible cellular mechanisms for the autoimmune process are reviewed, and evidence for a genetic, hormonal, or viral aetiology of autoimmune haemolytic anaemia is discussed.
Regulation of Erythropoiesis and its Defects
Authors: Peschle C.
Published: March 2008

Summary.

A concise review of recent advances in studies of mechanisms controlling the rate of erythropoiesis, including some original results, is presented. The first and second sections are focused on erythropoietin (Ep) and the erythroid stem cell respectively. In the third one, clinical conditions caused by a defect in the regulation of erythropoiesis are discussed.
Immunopathology of Immunocytomas
Authors: Drivsholm Aage
Published: March 2008

Summary.

Immunocytomas are defined as disorders in the B‐lymphocyte series, characterized by production of an M‐component. After a basic description of the immunoglobulin molecule and the development of the cellular immune system by which it is built up, the production of M‐components is discussed in relation to possible aetiology and pathogenesis. The turn‐over of M‐components is mentioned, especially on the basis of the studies of Salmon and colleagues (Salmon, 1973) with reference to the different types of M‐components and to cellular aspects. The production of interferon and osteoclast activating factor is touched on, and a brief review is given of the most common clinical features of malignant immunocytomas. Finally, the interrelationship of the different manifestations of immunocytomas is described on the basis of the hypothesis put forward by Salmon & Seligmann (1974).
Red Cell Destruction in Vivo by Low Concentrations of IgG Anti‐A
Authors: Romano E. L. , Mollison P. L.
Published: March 2008

Summary. Red cells coated with as little as 0.3–0.5 μg anti‐A/ml cells were found to agglutinate if mixed with plasma and rocked on a tile, whereas the minimum amount of IgG anti‐Rh required for agglutination under these conditions was about 50 μg antibody/ml cells. Complement binding by red cells coated with IgG anti‐A could be demonstrated only when the amount of antibody on the cells was at least 14 μg antibody/ml cells. Since in ABO haemolytic disease the amount of antibody on the cells is frequently less than 0.6 μg/ml cells, it seems that red cell destruction in this syndrome is not due to the activation of complement but may be due to the sequestration of agglutinated cells.

A few experiments are described in which the survival in vivo of small amounts of agglutinated cells was studied. Reasons are given for considering that such experiments fail to mimic the conditions prevailing in ABO haemolytic disease.
Chronic Granulomatous Disease and the Kell Blood Groups
Authors: Marsh W. L. , ØYen Ragnhild , Nichols Margaret E. , Allen F. H.
Published: March 2008

Summary. Fifteen antigenic determinants are known to be related to the Kell blood group. Some boys with X‐linked chronic granulomatous disease have the very rare McLeod or K0 phenotype on their red cells. Serological studies of the McLeod type suggest that the weak Kell antigens that are present differ qualitatively and quantitatively from those on red cells of common Kell type. A new antigen, Kx, has been characterized and shown to be present on red cells and neutrophil leucocytes. Lack of red‐cell Kx is associated with the McLeod phenotype, lack of leucocyte Kx is associated with chronic granulomatous disease.
Phagocytes and C4 in Paraproteinaemia
Authors: Spitler L. E. , Spath P. , Petz L. , Cooper N. , Fudenberg H. H.
Published: March 2008

Summary. Immunological studies were performed on patients with multiple myeloma. A defect in polymorphonuclear leucocyte (PMN) function as evidenced by diminished adherence of these cells to nylon fibre columns was detected in 16, and low levels of the fourth component of complement (C4) were observed in 14, of the 26 patients studied. Twelve of the patients with low C4 exhibited the defect in PMN adhesiveness whereas only four of the 12 patients with normal C4 showed the defect. The PMN defect was not caused solely by the low C4, since PMNs from seven patients with hereditary angioedema, which is associated with low levels of C4, did not show the defect. The low C4 and defect in PMN adhesiveness occurred primarily in patients with IgG myeloma; all but one of the patients with IgA myeloma, macroglobulinaemia, or light chain disease were normal in both parameters. Results of skin window studies indicated that patients with the PMN defect also had a defect in the early PMN inflammatory response. The defect in PMN adhesiveness could be completely corrected by incubating the cells in normal plasma. Binding of the C4 to paraprotein could not be demonstrated, and C1 activation was found to be caused only by one of 10 isolated paraproteins studied. These studies indicate that patients with paraproteinaemia have immunological abnormalities in addition to low immunoglobulin levels and suggest that these abnormalities may be involved in the pathogenesis of the recurrent infections commonly associated with this disease.
Factor‐V Activation by Thrombin and its Role in Prothrombin Conversion
Authors: Giddings J. C. , Bloom A. L.
Published: March 2008

Summary. Purified coagulation factors and specific antibodies to factor V and factor X were used to investigate the action of thrombin on factor V and the mechanism by which thrombin‐treated factor V influences prothrombin activation. The formation of a complex or complexes between phospholipid, factor V, factor Xa and calcium was demonstrated by column chromatography on Sephadex gel, and by immunological analysis of the column fractions including the use of solid‐phase antibodies. Kinetic experiments demonstrated that generation of thrombin from purified prothrombin was accomplished by this complex. Pre‐treatment of factor V with trace quantities of thrombin resulted in increased yield and rate of thrombin generation. It was shown that phospholipid became saturated when incubated with increasing concentrations of factor V and that the initial saturating concentration of the latter was reduced by pre‐treatment with thrombin. The findings confirm that optimum conversion of prothrombin to thrombin is accomplished by a complex or complexes of phospholipid, factor V, factor Xa and calcium and it is suggested that thrombin plays an autocatalytic role in these reactions.
Changes in Blood Catecholamine Levels and. Blood Coagulation and Fibrinolytic Activity in Response to Graded Exercise in Man
Authors: Hawkey C. M. , Britton B. J. , Wood W. G. , Peele M. , Irving M. H.
Published: March 2008

Summary. Measurements of catecholamines, fibrinogen, factor VIII, thrombelastography, cuglobulin lysis time and platelet adhesiveness have been carried out on venous blood obtained from normal males exposed to exercise on a bicycle ergometer at various work loads.

Significant increases in adrenaline, factor VIII and fibrinogen were found only after exercise to exhaustion at 1500 kpm min−1 whereas the euglobulin lysis time was inversely proportional to the exercise load. There was no change in platelet adhesiveness. These findings support the results of studies using adrenaline infusions or adrenergic blockade which suggest that stress‐induced increases in factor VIII are mediated via adrenergic stimulation but that activation of fibrinolysis is not dependent on adrenaline.
‘Hairy’ Cell Leukaemia (Leukaemic Reticuloendotheliosis): a Scanning Electron Microscopic Study of Eight Cases
Authors: Golomb H. M. , Braylan R. , Polliack A.
Published: March 2008

Summary. Eight cases of ‘hairy’ cell leukaemia (leukaemic reticuloendotheliosis) were evaluated by scanning electron microscopy. The surface of critical‐point‐dried ‘hairy’ cells was characterized by prominent and exaggerated broad‐based, ruffled membranes and scattered small clusters of stub‐like microvilli. The surface morphology resembled that of normal and leukaemic monocytes, but differed from that of normal and leukaemic lymphocytes. Some cells with features of both lymphocytes and monocytes were difficult to categorize; the overall impression of the surface architecture of most ‘hairy’ cells suggests, however, that they are related to the monocytic series. From the examination of these cases it is evident that scanning electron microscopy may be used as a means of distinguishing chronic lymphocytic leukaemia from ‘hairy’ cell leukaemia on the basis of surface ultrastructure.
Methods of Evaluating the Sequestration Site of Red Cells Labelled with 5ICr: a Review of 96 Cases
Authors: Najean Y. , Cacchione R. , Dresch C. , Rain J. D.
Published: March 2008

Summary. The technical conditions for surface counting and the methods for calculating splenic and liver sequestration after injection of51 Cr‐labelled cells were studied in 96 patients. A comparative study of different sites of positioning of the detection probes leads us to recommend the mid‐line at the third intercostal space for the precordial area, the point of maximum count‐rate obtained at each measurement for the splenic area, with the patient in right lateral decubitus position and the probe vertical, and a point situated on the midclavicular line 4 cm above the right costal margin for the liver area.

A comparative study of different methods of calculation leads us to recommend the method known as ‘excess counts’, but with a correction of the gross values based on the evolution of circulating radioactivity and not of the count‐rate measured over the precordial area. Measurement of urinary excretion of radioactivity showed that only a minor part was due to the loss of the tracer from the sequestration sites, and that the level varied only slightly between subjects. Thus the loss of tracer does not interfere with the interpretation of external counting data.

Much of the disagreement regarding interpretation of the results of external counting in clinical practice is due to technical problems. Standardization of techniques of measurement and interpretation of results, selecting those which this study indicates as the most reliable, would permit better exchange of information between laboratories and clearer conclusions as to the practical use of surface counting.
Utilization of Iron Dextran in Recurrent Iron Deficiency Anaemia
Authors: Kernoff Leslie M. , Dommisse Johannes , du Toit Ernette D.
Published: March 2008

Summary. Previously published studies have documented a reduction in the rate at which iron stores laid down by iron dextran therapy can be utilized for haemoglobin synthesis after the acute demands of haemorrhage and phlebotomy. In order to determine if a defect in the mobilization of these stores exists in the face of a chronic stimulus to red cell production, 93 patients who had previously received a total dose infusion of iron dextran were examined for a recurrence of iron deficiency anaemia, and in those in whom anaemia had recurred, iron stores were assessed by marrow aspiration. Twenty of the 93 patients were found to have recurrent iron deficiency anaemia, and marrow aspiration in all failed to demonstrate stainable iron stores. Although the rate at which iron dextran can be mobilized from storage sites is reduced, the present study demonstrates that ultimately these stores are fully utilizable.
A Five Year Experience of the Use of Factor IX Type DE(I) Concentrate for the Treatment of Christmas Disease at Oxford
Authors: Lane Janet L. , Rizza C. R. , Snape T. J.
Published: March 2008

Summary. A survey is presented of the use of the Oxford type DE(1) II‐IX‐X concentrate in the treatment of Christmas disease in Oxford from January 1970 to September 1974. 72 different patients were treated with a total of 2436 bottles of this concentrate from 143 different batches (each bottle containing 800–1000 units of factor IX). Although most doses were given for the treatment of minor haemorrhages into joints and muscles, 717 bottles of concentrate were used to treat 11 patients who underwent 14 major surgical operations. No episode of intravascular clotting or pulmonary embolism was seen in any patient receiving the concentrate. A detailed study of the plasma levels of factor V, VIII, total progressive antithrombin, platelets and fibrinogen degradation products was carried out before and after transfusion of type DE(1) concentrate in 14 patients. No significant alteration in those factors was found after the transfusion.
The Blood Group I and i Antigens of Amniotic Fluid
Authors: Feizi Ten , Cederqvist Lars L. , Childs Robert
Published: March 2008

Summary. Human amniotic fluid has been shown to contain blood group i as well as I antigens. Crude extracts of amniotic fluids at 16–23 weeks of gestation were in general more active than those obtained at term. A pool of amniotic fluids which had A, B, H as well as I and i activity was fractionated with an insolubilized anti‐I (Group 3 type) immunoadsorbent column. There was evidence for the occurrence of I and i determinants on macromolecules carrying A, B and H determinants, for the fraction specifically retained by the column was enriched by 50–60‐fold in I and i activity and by at least 10‐fold in A, B and H activity. In the fraction not retained by the column there remained the bulk of the A, B, H activity in addition to I activity of Group 1 type which is known to be distinct from the Group 3 determinant. With the aid of specific immunochemical fractionation procedures, human amniotic fluid should prove useful in structural studies of the several I and i determinants and of their relationship to other blood group determinants.
The von Willebrand Syndrome
Authors: Stableforth Penelope , Hughes Jane , Wilson Elaine , Dormandy Katharine M.
Published: March 2008

Summary. Five patients with an original diagnosis of von Willebrand's disease are described because their levels of factor VIII related protein, Ristocetin‐induced platelet aggregation and/or family studies differed from the main group of patients with classical von Willebrand's disease. Two had normal levels of factor VIII related protein with reduced Ristocetin aggregation when this was tested in platelet rich plasma. In one, however, this was due to a plasma defect and in the other to a platelet abnormality. After cryoprecipitate infusion all abnormal tests were corrected in both these patients. The first patient, however, failed to show a secondary rise of factor VIII whereas the second showed a secondary rise of both factor VIII and of factor VIII related protein. The other three cases, who were all very severely affected, have been separated from the main group as none of their families was segregating for classical von Willebrand's disease.

It is suggested that the term von Willebrand's disease should be confined to those patients who have reduced factor VIII related protein and Ristocetin aggregation, and that von Willebrand's syndrome should be used for the various sub‐groups that are emerging.
Quantitation of Ineffective Erythropoiesis from the Incorporation of [15N]Delta‐aminolaevulinic Acid and [15N]Glycine into Early Labelled Bilirubin: I. NORMAL SUBJECTS
Authors: SAMSON Diana , HALLIDAY D. , Nicholson D. C. , Chanarin I.
Published: March 2008

SUMMARY The incorporation of [15N]glycine into early labelled bilirubin and haemoglobin haem was measured in four haematologically normal subjects, using the clearance of [14C] bilirubin to measure total bilirubin production rate. Hepatic haem turnover was calculated from the incorporation of [15N]δ‐aminolaevulinic acid into early labelled bilirubin. From the experimental data and previously published data in normal subjects a method is derived for the quantitation of ineffective erythropoiesis which can be applied to similar studies in patients with haemato‐logical disorders.
Primary Leucocyte Alkaline Phosphatase Deficiency in an Adult with Repeated Infections
Authors: Repine John E. , Clawson C. C. , BRUNNING Richard D.
Published: March 2008

SUMMARY. An individual with repeated bacterial infections, eczema, hyperimmuno‐globulin E, and a primary deficiency of leucocyte alkaline phosphatase is described. The LAP‐deficient neutrophils from this patient had marginally deficient bactericidal activity particularly when challenged with high ratios of bacteria per neutrophil. Leucotactic, metabolic and morphologic features of the neutrophils from the patient were normal. Evidence is presented which contrasts this patient's condition with previously described primary or secondary deficiencies of LAP.