bluuebunny/crossref_metadata_2025 huggingface dataset:
Lymphocyte Transformation in Megaloblastic Anaemia: Morphology and DNA Synthesis
Authors: Das K. C. , Hoffbrand A. V.
Published: March 2008

Summary.Lymphocytes from six patients with untreated pernicious anaemia and from one patient with folate deficient megaloblastic anaemia were cultured with phytohaemagglutinin (PHA). The mean percentage of cells undergoing transformation (78) was similar to normal. The morphology of the PHA‐stimulated transformed ‘megaloblastic’lymphocytes was distinct from that of PHA‐stimulated normal lymphocytes. Transformed ‘megaloblastic’lymphocytes tended to be larger and to show a more finely reticulated open chromatin pattern than normal transformed lymphocytes.

The incorporation of [3H]thymidine into DNA of PHA‐stimulated ‘megaloblastic’lymphocytes was significantly greater than normal. The inhibitory action of deoxyuridine (dU) on [3H]thymidine incorporation into the DNA of PHA‐stimulated lymphocytes was significantly less in ‘megaloblastic’lymphocyte cultures than in normal cultures. Both these observations suggest that there is a block in synthesis of thymine‐DNA from dU in PHA‐stimulated ‘megaloblastic’lymphocytes.

The metabolic block in vitamin B12deficiency could be partly corrected by vitamin B12and completely corrected by folic acid or folinic acid suggesting that the defect was due to lack of folate coenzyme. The abnormality of thymine‐DNA synthesis in ‘megaloblastic’lymphocytes shown here was similar to that shown by other workers in megaloblastic bone marrow cells. The present study provides cytological and biochemical evidence that deficiency of vitamin B12or folate causes a derangement of DNA synthesis in the lymphocyte.
Thiol Groups in the Blood Clotting Action of Factor VIII
Authors: Austen D. E. G.
Published: March 2008

Summary. Investigations have been carried out on the chemical groupings in factor VIII with a view to discovering the biochemical mechanisms involved, and the chemical groups responsible, for its particular blood clotting properties. Bovine factor VIII has been treated with iodine, hydrogen peroxide, iodoacetamide and the sodium salt of p‐Chloromercuribenzoic acid. Each of these reagents is known to react with thiol groups. Each inactivates factor VIII and, in the case of the mer‐ cury compound, factor‐VIII activity can be regenerated using cysteine. Preliminary results indicate that similar effects are obtained using human factor VIII.

It is concluded that factor VIII contains thiol groups situated at or near to the active sites of clotting. Possible applications of these new findings are also discussed. In particular, it may provide more insight into the storage stability of factor‐VIII concentrates.
HL‐A Antigens on Leukaemic Cells
Authors: Pegrum G. D. , Balfour I. C. , Evans Carol A. , Middleton Valerie L.
Published: March 2008

Summary. The peripheral blood leucocytes from 26 leukaemic patients have been typed using alloantisera which recognize 13 HL‐A specificities. The results show a marked increase in the incidence of HL‐A 3, some increase in certain other HL‐A antigens, and a slighty reduced frequency of HL‐A 2, as compared with a population of healthy volunteers, kidney donors and patients awaiting renal transplantation.

These findings suggest that leukaemic cells either react differently to the alloantisera or that additional tumour‐specific antigens are present on the cells. Another possibility is that persons with these antigenic configurations have a genetic predisposition to develop leukaemia.

Further studies on leucocytes from patients with various types of leukaemia and from different population groups will be needed to confirm these findings.
Maternofoetal Iron Transfer in the Rat
Authors: And Nathan Kaufman , Wyllie John C.
Published: March 2008

Summary. The distribution of 59Fe in maternal, placental and foetal tissues of the rat was determined at intervals of 8, 12, 15, 17, 19, 20 and 21 days of gestation. Large amounts of 59Fe are transferred from maternal plasma to the foetuses in late gestation when foetal development is proceeding at a rapid rate. The deposition of 59Fe in the developing foetus appears governed by erythropoiesis; liver and carcass are the principal sites. 59Fe is rapidly transported across the placenta; there is no indication of a large iron pool within it. Both the allantoic and yolk sac placentae contribute significantly to placental iron uptake during the period of maximum iron transfer. Very little iron is deposited in the uterus during gestation; hence secretions from uterine glands entering the yolk sac cavity are a minor source of foetal iron. There is diminished uptake of 59Fe by the maternal liver and spleen during the period of rapid iron accumulation by the foetuses.
Stimulation by Serotonin of Erythropoietin‐dependent Erythropoiesis in Mice
Authors: Lowy Peter H. , Keighley Geoffrey , Cohen Natalie S.
Published: March 2008

Summary. Serotonin stimulates erythropoiesis in normal mice but not in the presence of anti‐erythropoietin serum. It also stimulates erythropoiesis in adrenalectomized or hypophysectomized mice. It increases erythropoietin titres in the plasma of normal but not of nephrectomized mice. The serotonin precursor l‐5‐hydroxytryptophan stimulates, but d‐5‐hydroxytryptophan and the serotonin catabolite 5‐hydroxyindoleacetic acid do not.

As shown by ink penetration, serotonin blocks blood circulation in the kidney. Tissue hypoxia, especially of the kidney, causes the production of erythropoietin. Serotonin may cause a general hypoxia sufficient for the generation of erythropoietin. But its strong effect on kidney circulation suggests kidney hypoxia as the specific reason for its effectiveness in the mouse.
Inflammation and Haemostasis in Paraproteinaemias
Authors: Penny Ronald , Castaldi Peter A. , Whitsed Helen M.
Published: March 2008

Summary.

Inflammatory and haemostatic functions were assessed simultaneously in 16 patients with serum paraproteins.

Skin window responses were severely depressed in 10; neutrophil phagocytosis was reduced in five. Platelet function was abnormal in 10 and inhibitors of blood coagulation were found in four. Whereas the changes in platelet function appeared to be more concentration‐dependent, abnormal skin window responses occurred at all concentrations of paraprotein. The effect on coagulation and neutrophil phagocytosis appears to be specific for a given paraprotein. Study of isolated γG paraproteins showed this depression of cell function to be markedly concentration‐dependent.

Haemostatic defects were corrected by plasmapheresis. Clinical infection and bleeding were prevalent only in patients with levels of paraprotein in excess of 5 g/100 ml, despite abnormal test results at lower concentrations.
The Second Variant of Human Myoglobin; 138 (H16) Arginine → Glutamine
Authors: Boulton F. E. , Huntsman R. G. , Yawson G. I. , Romero Herreka A. E. , Lorkin P. A. , Lehmann H.
Published: March 2008

Summary.

In a survey of 6000 human muscle samples, four myoglobin variants were discovered by electrophoresis. One has been previously described and this paper gives an account of the second one, which is of particular interest because it may be the same as Myoglobin Annapolis, described by Boyer, Fainer & Naughton in 1963, which at that time could not be completely characterized.
Absorption of Vitamin B12 by the Guinea‐Pig
Authors: Peters T. J. , Quinlan Angela , Hoffbrand A. V.
Published: March 2008

Summary.

The gastrointestinal distribution and subcellular localization of radioactivity in the ileum of the guinea‐pig was determined 2 hr after oral feeding of physiological doses of cyano‐, methyl‐ and 5′ desoxyadenosyl‐cobalamin. The gastrointestinal distribution of the three analogues was similar although the uptake of methyl‐ and adenosylcobalamin by the ileum was less than that of cyanocobalamin. All three analogues were significantly localized in the mitochondrial fraction of the ileal mucosa during absorption.

Guinea‐pigs were injected with sodium fluoroacetate, a drug which is thought to interfere with the conversion of cyano‐ to adenosylcobalamin. Large doses of the drug caused a marked delay in gastrointestinal transit. The subcellular distribution of radioactivity in the ileum was similar in the control group and those pretreated with a small dose (5μg/100 g) of fluoroacetate.

It is concluded that the mitochondrial localization of vitamin B12 during absorption by the ileum plays a fundamental role in the transport of the vitamin but that interconversion of cyano‐ to adenosylcobalamin is not the reason for this localization.
Measurement of the Amount of Ingested Iron Temporarily Retained in the Intestine
Authors: Jasani B. M. , Tonge J. L. , Fletcherand J. , Barnaby C. F.
Published: March 2008

Summary.

The temporary retention in the intestine of radioactive iron (59Fe) has been compared with that of a radioactive non‐absorbed marker (131BaSO4) using a large area liquid scintillation whole‐body counter. There was no temporary retention of radioactive iron when given with a meal to normal subjects. However, a proportion of the radioactive iron was temporarily retained when given as labelled haemoglobin.
THE TREATMENT OF ACUTE MYELOBLASTIC LEUKAEMIA
Authors: Fairley G. Hamilton
Published: March 2008

In a recent symposium held in Paris, Holland (1970) divided the treatment of acute leukaemia into three historical phases:

(i) Before 1947, the era of despair with no effective treatment.

(ii) From 1947 to 1963, the advent of chemotherapy, and with the failure to find a curative drug, the era of palliation.

(iii) Since 1963, the appearance of new drugs, their use in intensive regimes and in combinations, and the beginning of immunotherapy, have all made palliation too mean a goal.
The Subcellular Distribution of Orally Administered 59Fe in Rat Small Intestinal Mucosa
Authors: Worwood M. , Jacobs A.
Published: March 2008

Summary.

Rats were given 59Fe by stomach tube. Small intestinal mucosal cells were isolated and after homogenization were separated into nuclear, mitochondrial, lysosomal, microsomal and soluble fractions by differential centrifugation. From 15 min to 4 hr after administration of the dose mucosal 59Fe was concentrated in the soluble fraction but at 12 and 18 hr the mitochondrial fraction was most active. The amount of mucosal 59Fe present as ferritin increased from 31% at 15 min to 74% at 4 hr and decreased to 14% at 18 hr. Most of the 59Fe present during the early phase of absorption was in a high molecular weight non‐ferritin form.
The Influence of Glucose and Exogenous Glutathione on the Red Cell Membrane Effect of the Antimalarial Drugs 1,4‐Naphthoquinone and β‐Naphthol
Authors: Miller Aaron , Smith Hinton C.
Published: March 2008

Summary.

Glucose‐depleted red cells incubated with primaquine, primaquine degradation products, quinine and quinacrine demonstrated far less osmotic fragility than did glucose‐repleted cells. The increase in osmotic fragility in the presence of glucose could not be correlated with an effect of the drug on the levels of glutathione or methaemoglobin. The prelytic loss of cell K+ caused by these agents was unaffected by the presence or absence of glucose. In contrast to the antimalarial drugs, the osmotic fragility produced by 1,4‐naphthoquinone and β‐naphthol was not glucose‐dependent. Glutathione added to incubating cell suspensions in molar concentrations seven and one‐half times that of the drug, greatly decreased, but did not eliminate, the hypotonic haemolysis and the prelytic loss of cell K+ caused by 1,4‐naphthoquinone. It offered red cells no protection against the membrane action of antimalarial drugs and β‐naphthol. 1,4‐Naphthoquinone was the only drug capable of reacting stoichiometrically with glutathione.

The studies demonstrate distinctive differences in the action of these actual or potential oxidant drugs on the red cell membrane. A possible explanation for the glucose‐dependent haemolysis produced by antimalarial drugs is presented.
Vitamin B12 Levels in Erythrocytes in Anaemia due to Folate Deficiency
Authors: Harrison R. J.
Published: March 2008

Summary.

In folate‐deficiency anaemia erythrocyte vitamin B12 levels were low before treatment began (mean = 80 ± 13.1 pg/ml). A rapid rise occurred during folic acid therapy (mean peak = 375 ± 207 pg/ml) and was followed by a slow fall towards normal (mean = 170 ± 54 pg/ml).
Haemolysis and Intravascular Coagulation due to Incompatible Red Cell Transfusion in Isoimmunized Monkeys
Authors: Lopas H. , Birndorf N. I.
Published: March 2008

Summary. Ten randomly selected cynomolgus monkeys were each given an intramuscular injection of a mixture of isologous red cells suspended in complete Freund's adjuvant. After 6 weeks a second injection of red cells in incomplete Freund's was given and thereafter intravenous booster injections of red cells in isotonic saline were used. Antibody titres were determined with serial crossmatches at 37°C, 4°C, and with rabbit antimonkey serum. All animals developed antibody to at least one and several against all four immunizing red cells. Haemolysins were seen frequently.

Transfusion reactions followed intravenous injections of incompatible 51Cr‐labelled red cells. Major reactions occurred in five of seven animals and consisted of complete destruction of infused cells within 5 min, haemoglobinuria, haemoglobinaemia, oliguria, anuria in one case, and the disseminated intravascular coagulation syndrome in three cases. The remaining two animals had mainly extravascular destruction of the transfused red cells and exhibited no coagulation changes.
Nitrogen Metabolism in Pernicious Anaemia
Authors: Heathcote J. G. , Davies D. M. , Mooney F. S.
Published: March 2008

Summary. Nitrogen metabolism has been studied in pernicious anaemia patients before, during and after treatment with vitamin B12 therapy. Before treatemnt there are high levels of amino acids and urea present in the urine while the creatinine level remains normal. At the same time there is a state of amino acidaemia, but adequate treatment brings about a rapid return of the plasma amino acid level to normal. The pattern of recovery appears to be quite different in the urine where an initial, but temporary, fall in the excretion of urea and amino acids to subnormal levels is followed by a slow return to normal on prolonged therapy. During this time the excretion of creatinine remains within the normal range.

Substiution of placebo for vitamin B12 therapy brings about an early recurrence of the abnormal excretion of urea and amino acids, even before any sign of clinical deterioration occurs in the condition of the patient; creatinine excretion again remains normal.

The findings are in full agreement with the view that vitamin B12 plays a fundamental and essential role in the general utilization of amino acids for protein biosynthesis in mammals.
Hageman Factor Activation in the Generalized Shwartzman Reaction Induced by Endotoxin
Authors: Müller‐Berghaus Gert , Schneberger Reiner
Published: March 2008

Summary. The role of Hageman factor (factor XII) in triggering intravascular coagulation was studied in rabbits injected with Thorotrast and endotoxin. Besides changes of coagulation, parameters characteristic of consumption coagulopathy (e.g. decreases in platelet counts and fibrinogen levels), a drop in Hageman factor activity was observed. However, this decrease in Hageman factor activity does not appear responsible for triggering intravascular coagulation, becuase it was found that: (1) A decrease in Hageman factor activity occurred only in those animals which developed a generalized Shwartzman reaction with a drop in fibrinogen levels. A small single dose of endotoxin did not lower Hageman factor activity. (2) Coumarin pretreatment prevented the drop in Hageman factor activity after Thorotrast and endotoxin injections, although this would not be expected if Hageman factor was the first coagulation factor to be activated. (3) Inhibition of Hageman factor activation by lysozyme infusion did not prevent the generalized Shwartzman reaction elicited by Thorotrast and endotoxin.

We conclude that endotoxin triggers intravascular coagulation by a mechanism different from that of the intrinsic pathway of coagulation.
Automated Platelet Counting
Authors: Glass Ursula H. , Wetherley‐Mein G. , Mills R. T. , Priest C. J.
Published: March 2008

Summary. Modifications of the Technicon S.M.A.4 and S.M.A.4A equipment which substitute automated platelet counting for red cell counting are described. Experimental results are presented which establish the validity and reproducibility of the method and show that the results are quantitatively comaprable to those obtained by manual and semi‐automated techniques. Experience of the method in routine use for approximately 3 yr, during which time about 150000 platelet counts have been done, indicates that the modification produces no increase in maintenance or running problems.
Erythrocyte Sensitivity to In‐Vitro Lysis in Leukaemia
Authors: Catovsky D. , Lewis S. M. , Sherman Diane
Published: March 2008

Summary. In‐vitro lysis tests with cold antibody, sucrose and acidified serum have been carried out on 139 patients suffering from leukaemia, lymphomas and other bone‐marrow malignancies. None of the patients tested showed a positive acidified‐serum test but a positive cold‐antibody lysis occurred in a significant number of patients with acute leukaemias, especially the myeloid type in whom 58% were positive with varying degrees of lysis. In some patients the positive test persisted for a long time even when the patient was in haematological remission, suggesting the possibility that the defective red cells were derived from a persistently abnormal clone. Minor degrees (less than 5%) of lysis occurred with the sucrose‐lysis test in 40% of patients with chronic granulocytic leukaemia and more than 5% lysis occurred in one patient with erythroleukaemia. Anaemia was twice as common in patients with a positive cold‐antibody lysis than in patients with no lysis. In the cases of malignant lymphomas there appeared to be a relationship between positive cold‐antibody lysis and bone‐marrow infiltration.

The results obtained do not add definitive evidence to the hypothesis that PNH is related to the myeloproliferative disorders but they do demonstrate that in the conditions which were studied, notably acute myeloid leukaemia, there is dyserythropoiesis and the production of an abnormal erythrocyte with membrane defect; this may suggest that the affected red cells are derived from an abnormal stem cell common to both granulopoesis and erythropoiesis.
A Simple Routine Radioisotopic Method for the Estimatin of Serum Vitamin B12 Using DEAE Cellulose and Human Serum Binding Agent
Authors: Wagstaff M. , Broughton A.
Published: March 2008

Summary. A simplified radioisotope method for serum vitamin B12 assay has been described using pooled human serum as a binding agent and equilibrated DEAE cellulose as a separating agent. The normal range found was 185‐1020 pg/ml and a probable significant difference between males and females was discovered. There was no overlap between the normal range and the pernicious anaemia range (30–160 pg/ml). Comparison of the method with microbiological assays (Euglena and Lactobacillus leichmannii) showed good correlation although minor variations between the methods were found and are discussed. The method was precise, economical with reagents and sera, and could easily be introduced as a new procedure in any routine laboratory.
Nature of Foetal Haemoglobin in F‐Thalassaemia
Authors: Stamatoyannopoulos George , Schroeder W. A. , Huisman T. H. J. , Shelton J. Roger , Shelton Joan Balog , Apell Gerald , Bouver Nicole
Published: March 2008

Summary

The nature of Hb‐F was studied in 32 heterozygotes for F‐thalassaemia, in four homozygotes, and in four persons who have F‐thalassaemia in combination with β‐thalassaemia or Hb‐S. Analysis of the cyanogen bromide fragment γCB‐3 indicated that, in all heterozygotes, both Gγ and Aγ chains were present in Hb‐F in an average ratio of about 2:3. In the homozygotes and the double heterozygotes, both Gγ and Aγ chains were observed in an approximate ratio somewhat higher than 1:1. This pattern of γ chain synthesis is nonspecific for F‐thalassaemia but similar to that observed in the traces of Hb‐F of normal adults. In conjunctionwith existing information from other genetic studies, it may be concluded that the mutation in F‐thalassaemia is associated with a complete deficiency of β and σ chains from cis position together with an increased synthesis of γ chains that is directed by both Aγ and Gγ loci.
Variability of Sheep Red Cells in their Reaction to Agglutinins in Normal Human Sera
Authors: Hoq M. S. , Cash J. D. , Das P. C. , Cumming R. A.
Published: March 2008

Summary The interaction (agglutination) of 25 normal sera against a panel of 10 different sheep red cells was studied. There were highly significant differences in the agglutinability of different sheep cells to any one normal serum, and the cells could be divided into ‘high reactors’and ‘low reactors’. Absorption studies confirmed these observations. The significance of these findings is discussed in the light of previous studies on anti‐sheep cell haemagglutinins in disease and the selection of sheep cells for all types of haemagglutinin immunoassays.
The Use of Modified Cells to Induce an Anti‐Rh Response
Authors: Gunson H. H. , Stratton F. , Phillips P. K.
Published: March 2008

Summary Prior to their use for the primary immunization of Rh‐negative male volunteers, group O R2 R2 cells have been coated with complement and subjected to heat treatment. Eleven out of 12 men receiving complement‐coated cells developed a serologically detectable anti‐D after a single injection, but no antibodies could be detected in the sera of six volunteers receiving heated red cells. In association with doses of untreated cells and complement‐coated cells other volunteers were given small doses of anti‐D immunoglobulin. Although seven of eight men developed anti‐D when immunoglobulin was injected at the same time as the immunizing cells, there was no apparent enhancement based on the time of appearance of the antibody after immunization. In six men, anti‐D immunoglobulin was given 1 week before the injection of R2 R2 cells. None of these men developed anti‐D.

Using these cells, the frequency of the immune response appears to be higher than in other studies on the primary immunization of male volunteers. However, not all the volunteers immunized in this series produced high titres of anti‐D after successive injections of Rh positive cells and the significance of this is discussed.
Studies on Hyposideraemia and Altered Iron Storage in the Rat following Thermal Injury
Authors: Elek S. J. , Schäfer I.
Published: March 2008

Summary. Hyposideraemia with concomitant accumulation of non‐haem iron in the liver and spleen was found following thermal injury by scalding in the rat. It is supposed that the changes may be due to failure to reutilize iron for haemoglobin synthesis.
The Removal of Heat‐damaged and 51Cr‐labelled Red Cells in Haemoglobinopathies
Authors: Ringelhann Bela , Konotey‐Ahulu F. I. D.
Published: March 2008

Summary. Fifty‐seven individuals, all living in Ghana, and having Hb types AA (controls), AS, S‐thalassaemia, CC, SC, and SS, were studied using 51Cr‐labelled heatdamaged red cells. Investigations were designed to show the effect of heating on red cell morphology, G6PD activity, osmotic and mechanical fragility, ESR, sickling, and the clearance of the cells from the circulation after injection. In transfusion experiments, damaged cells were given to recipients with differing haemoglobin types and the cell disappearance and radioactive uptake by the liver and spleen were measured. In AS, S‐thalassaemia and CC patients the clearance and splenic uptake were similar to those of the AA subjects. In some of the SC and in all of the SS patients, the spleen did not sequester damaged cells, although they were cleared fairly rapidly from the circulation in a few cases. It was concluded that intracorpuscular factors cannot be ignored in the removal of heat damaged cells from the circulation, even though extracorpuscular mechanisms play the major part.
Experimental Achylia Gastrica and Iron Absorption
Authors: Murray M. J. , Stein Nell
Published: March 2008

Summary. Achylia gastrica with lowered iron stores was produced in rats by direct X‐irradiation of the exposed stomach. Absorption of 59Fe as a ferrous salt was measured in these and in normal and iron‐deficient control rats to study the effect of various components of gastric juice on iron absorption. Hydrochloric acid had no effect in rats with achylia gastrica, but neutralized rat gastric juice, pernicious anaemia gastric juice, and intrinsic factor increased absorption two‐fold. Untreated rat and human gastric juice increased absorption four‐fold while antigastric mucosal serum reduced absorption four‐fold. This reduction was corrected by adding rat gastric juice. Gastric juice appears to play a significant role in iron absorption.
Structural and Compositional Changes in the Red Cell Membrane during Clostridium welchii Infection
Authors: Simpkins H. , Kahlenberg A. , Rosenberg A. , Tay S. , Panko E.
Published: March 2008

Summary. The RBC haemolysis resulting from Clostridium welchii septicaemia is generally thought to be caused by the lecithinase (α toxin) produced by that bacterium. A woman admitted to this hospital suffering from a Clostridium septicaemia presented us with the opportunity to study whether structural and compositional changes in her RBC membrane could account for the observed haemolysis. Previous studies showed that treatment of RBC membranes with phospholipase C (α toxin), obtained from Clostridium welchii, produces vast changes in both the phospholipid structure and composition, without any detectable alteration in the protein composition or structure. The RBC membranes, prepared from the patient's blood, exhibited little or no change in phospholipid composition and structure, when compared with normal cells; however, both the protein composition and structure appeared drastically altered. These results, therefore, suggest that the haemolysis observed during Clostridium welchii septicaemia is not the result of a lecithinase (α toxin), but may be due to the proteolytic action of one or more of the other toxins secreted by this bacterium.
Four Cases of Acquired von Willebrand's Syndrome
Authors: Ingram G. I. C. , Kingston P. J. , Leslie J. , Bowie E. J. W.
Published: March 2008

Summary. Four cases are reported in which a bleeding disorder associated with a long bleeding time and a low factor‐VIII level, like von Willebrand's disease, appears to have developed in adult life. In each there were abnormalities of plasma proteins, similar to but in some instances more extreme than patterns found in haemophilia and ‘classical’ von Willebrand's disease. One patient's bleeding tendency developed in association with a generalized illness, probably systemic lupus erythematosus, and improved rapidly on steroid treatment. The other three patients, with no symptoms of underlying disease, were not treated with steroids. Two patients, infused with plasma, showed rather more than the predicted rise in factor VIII.
Factor X in Freeze‐dried Factor‐VIII Reference Plasma
Authors: Brozović M. , Gurd L. J. , Robertson I. , Bangham D. R.
Published: March 2008

Summary. The activity and stability of factors X and VIII were studied in three ampouled preparations of freeze‐dried pooled human plasma.

Factor‐X activity in all three preparations decreased on storage. It was calculated that after 10 yr at – 20°C, between 3% and 8% of the original factor‐X activity would be lost. If stored for the same period at 4°C and 20°C the loss could be up to 54% and 90% respectively of the initial activity. If, however, factor VIII was added to restore the concentration of this factor to approximately normal level, the proportion of factor X available for activation via the intrinsic pathway remained the same irrespective of the temperature and length of storage.

Factor‐VIII activity was lost more readily. It was estimated that between 20% and 30% of the activity would be lost in each of the preparations kept at ‐ 20°C in 10 years. This is in good agreement with the results of the international collaborative study carried out to establish the international standard for factor VIII.
Interference of Lysed Fibrin with Coagulation: a Quantifying Approach Using Isotopic Techniques
Authors: Regoeczi E.
Published: March 2008

Summary. Coagulation of plasma fibrinogen in the presence of fibrin degradation products was studied in rabbits treated with ancrod (Arvin), Two techniques were employed: the first, based on trace‐labelling of plasma samples with labelled fibrinogen in vitro, was to measure the degree to which solubilized fibrin inhibited coagulation; in the second, two differently labelled fibrinogens were used, one injected intravenously and the other added in vitro, by which estimation of fibrinogen in serum relative to the amount of circulating breakdown products was attempted.

The first technique is considered to provide reliable information about the extent of defective coagulation, and hence the proportion of masked fibrinogen present in serum. Because of the difficulty in obtaining resolution between fibrinogen and its breakdown products in clots, the second technique is thought to be more suitable for comparative studies rather than for measurements in absolute terms.

High doses of hydrocortisone administered to rabbits for several days prior to ancrod significantly reduced the speed of the dissolution of microclots. The data obtained are consistent with the hypothesis that the hormone interfered with fibrinolysis at the plasminogen activator level.
Studies on Christmas Disease: Investigation and Treatment of a Familial Acquired Inhibitor of Factor IX
Authors: George J. N. , Miller G. M. , Breckenridge R. T.
Published: March 2008

Summary. A family is reported in which three of four members with Christmas disease have developed an inhibitor to factor IX. Studies of this inhibitor have demonstrated that it is an IgG antibody directed against the activated form of factor IX (IXa).

There was no immunologically detectable factor‐IX‐like material in the affected family member without an inhibitor. This is consistent with previous postulates that inhibitors to factor IX would only develop in patients with Christmas disease who lack the factor‐IX antigen.

One member of this family who had developed an inhibitor has been successfully managed through two dental procedures after transfusion with a factor‐IX concentrate.
Nervous Regulation of Factor‐VIII Levels in Man
Authors: Mannucci P. M. , Ruggeri Z. M. , Gagnatelli Giovanna
Published: March 2008

Summary. Neurological procedures such as pneumoencephalography (PE), electro‐shock (ES), electrocoagulation (EC) of the ventrolateral thalamic nucleus, cerebral arteriography and myelography have been studied as experimental models in which to investigate in man the effect on plasma factor‐VIII levels of stresses applied to the CNS. A marked elevation of factor VIII followed PE and ES; the factor‐VIII levels showed some fluctuations over the period of experimental observation. The other coagulation factors were unchanged. A three‐fold increase of factor VIII was also observed after PE in a subject with mild haemophilia A. EC was followed by a significant rise of factor VIII, which was however much lower than after PE and ES. No significant change was produced by the other procedures.

A number of experiments have been carried out to investigate the possibility that the observed increase might be artefactual.

No evidence has been obtained that the rise measured with the bioassay results from some sort of activation or potentiation of the factor‐VIII molecule, rather than from a true molecular increase. It is suggested that the phenomenon is related to the stimulation by PE and ES of discrete neuronal structures regulating the plasma levels of factor VIII through a mechanism at present unknown.
The Assay of a Plasma Component Necessary for the Generation of a Plasminogen Activator in the Presence of Hageman Factor (Hageman Factor Co‐factor)
Authors: Ogston D. , Bennett N. B. , Ogston C. M. , Ratnoff O. D.
Published: March 2008

Summary. Kaolin‐induced generation of fibrinolytic activity requires, in addition to factor XII (Hageman factor) and plasminogen, at least one further plasma factor which has been termed Hageman factor co‐factor (HF co‐factor). A technique for the assay of HF co‐factor in plasma is described using plasma specifically depleted of HF co‐factor by treatment with glass. The kaolin‐induced lysis time bears log:log relationship to the concentration of untreated test plasma diluted glass‐adsorbed plasma. The influence of the plasma fibrinogen concentration is small, and the assay is not affected by exercise‐induced changes in the plasma plasminogen‐activator level. Using this technique the range of HF co‐factor in the plasma of 20 healthy subjects was found to lie between 76 and 150% of pooled normal plasma.
In‐Vitro Studies with Ancrod (‘Arvin’)
Authors: Turpie A. G. G. , Prentice C. R. M. , McNicol G. P. , Douglas A. S.
Published: March 2008

Summary. The effect of ancrod on the fibrinolytic enzyme system in vitro and on artificial thrombi in the Chandler tube system has been studied. Ancrod has no direct lytic activity and does not influence the rate of lysis of artificial thrombi in the Chandler tube. Clots formed by the action of ancrod are more susceptible to the lytic action of urokinase compared to those formed by thrombin but are equally as susceptible to spontaneous lysis as comparable thrombin clots. The rapidity with which the fibrin formed in vivo by ancrod is removed must be attributed to some process other than the generalized activity of the plasminogen–plasmin system.
Ultrastructural Studies on Monocytic Leukaemia
Authors: Freeman Arnold I. , Journey L. J.
Published: March 2008

Summary. Bone marrdw specimens from four cases of pure monocytic leukaemia. (Schilling type) and three cases of myelo‐monocytic leukaemia (Naegeli type) were examined by electron microscopy. The hallmark of the monoblasts and more mature monocytoid forms was the extreme nuclear irregularity with frequent nuclear bridges and blebs. Abundant cytoplasm with a serrated margin, dense granules, numerous pinocytic vesicles and vacuoles, frequent peri‐nuclear fibrillar bands and a well‐developed Golgi zone served as additional criteria for identifying monoblasts. Various stages in the maturation of monoblasts were observed. Stem cells possessed a large round nucleus which became extremely folded with increasing maturity. The graduai appearance of condensed chromatin paralleled this nuclear polymorphism. The fine structure of these monoblasts was compared with that of myeloblasts to point out distinguishing features. It is felt that ultrastructural analysis can be of value in separating pure monocytic leukaemia from myelo‐monocytic leukaemia.
Kinetics of Haemopoietic Colony Growth
Authors: Lajtha L. G. , Gilbert C. W. , Guzman E.
Published: March 2008

Summary. On continuous whole‐body γ irradiation at a dose rate of 70 rad/day the colony forming haemopoietic stem cells (CFU) show a biphasic dose–response curve where the first steeper phase is indistinguishable from the acute dose–response curve, indicating a lack of dose‐rate effect. The response of growing CFU to chronic irradiation gives a quantitative indication of the rate of differentiation of the CFU, and the growth of the individual splenic colonies indicates an age structure (process of maturation) in the erythropoietin responsive cell (ERC) population. A model is constructed illustrating the interrelationship between the pluripotent CFU and its descendants in the ‘committed’ ERC population.
A Method for Production of Antibody to Hepatitis‐Associated Antigen in Rabbits
Authors: Das P. C. , Cash J. D. , Cumming R. A.
Published: March 2008

Summary. Details are given of the production of an antibody to hepatitis‐associated antigen (HAA). Rabbits were injected with unfractionated serum obtained from patients known to have circulating HAA. Using a double diffusion agarose gel technique the absorbed rabbit serum was shown to contain a precipitating antibody against sera known to be HAA positive whereas a large selection of normal human sera was consistently negative. Further studies demonstrated reaction patterns of identity when compared with anti‐HAA obtained from human sources.
The Site of Action of Desferrioxamine
Authors: Lipschitz D. A. , Dugard J. , Simon M. O. , Bothwell T. H. , Charlton R. W.
Published: March 2008

Summary. Repeated injections of desferrioxamine significantly depleted the hepatic and splenic iron stores in normal rats, but not in rats which had been hyper‐transfused so as to reduce the rate of release of iron into the plasma. These observations indicate that the storage compounds ferritin and haemosiderin are not important direct donors of iron to desferrioxamine. Since plasma iron is not bound by the chelate, some compound or compounds on the pathway between the stores and the plasma is probably the major immediate source. By differentially labelling the iron in hepatic parenchymal cells and reticulo‐endothelial cells with 59Fe, evidence was obtained that desferrioxamine chelates iron in both cell types.
The Effect of Injected Iron on the Absorption of Iron in Iron Deficiency
Authors: Murray M. John , Stein Nell
Published: March 2008

Summary. The effects of injected iron on the absorption of iron by iron deficient animals have been studied. When iron deficiency is partly or fully corrected by injection of iron dextran, prolonged and marked depression of iron absorption follows despite the persistence of iron deficiency. Although total absorption increases with decreasing size of parenteral replacement dose, the depression of absorption per unit of iron injected increases.
Haemorrhagic Syndrome of Autoimmune Origin with a Specific Inhibitor against Fibrin Stabilizing Factor (Factor XIII)*
Authors: Lorand L. , Maldonado N. , Fradera J. , Atencio A. C. , Robertson B. , Urayama T.
Published: March 2008

Summary. The biochemical defect in a patient suffering from very severe bleeding episodes was shown to be related to the presence of an inhibitor which specifically interfered only with the thrombin‐catalysed conversion of the fibrin stabilizing factor zymogen (factor XIII) into fibrinoligase, but had no effect on the transamidase activity of the latter enzyme. As such, it differed from other known inhibitors of the fibrin stabilizing factor system. Inhibition could be demonstrated against both human and bovine factor XIII.

In terms of neutralizing equivalents, the patient's plasma contained about a tenfold excess of the inhibitor over the factor‐XIII content found in average normal plasma. This high potency was thought to be the reason for the patient's unresponsiveness to transfusions.

Precipitation with ammonium sulphate, followed by chromatographic purification on DEAE‐cellulose, allowed recovery of the inhibitor in good yield in the ‘IgG immunoglobulin’ fraction. Since, prior to the onset of bleeding episodes at about 50 yr of age the patient received no transfusions, it could be assumed that the inhibitor was of autoimmune origin.

Though the cause of the disease remains unknown, the question is raised whether previous treatment with isoniazid could be involved. Accidental modification of fibrin stabilizing factor by isoniazid could have provoked a breakdown of immunological tolerance against this component in the patient's plasma. Lorand et al (1972) have recently demonstrated the modification of proteins with isoniazid in enzymatic reactions.
Blood Clotting Activity of Reptilase and Bovine Thrombin in Vitro: A Comparative Study on Seven Different Species
Authors: Wik K. Ove , Tangen Oddvar , Mckenzie F. Neil
Published: March 2008

Summary. The clotting activities of Reptilase and purified bovine thrombin towards platelet poor plasma from seven species and purified human and rabbit fibrinogen were studied. Bovine thrombin exhibited particularly low activity towards plasma from rat, guinea‐pig and cow compared with the other species tested. Reptilase showed a relatively larger species dependent variation in activity than thrombin, and rabbit plasma was particularly resistant to Reptilase action. This was due to a low activity of Reptilase towards rabbit fibrinogen and not to inhibition of Reptilase in rabbit plasma.

The presence of 1% (w/v) dextran (70 000 mol wt) in the clotting mixtures significantly decreased both the thrombin and Reptilase clotting times in plasmas from all species.
A Study of Platelet Retention by Glass Bead Columns (‘Platelet Adhesiveness’ in Normal Subjects)
Authors: Rossi Ennio C. , Green David
Published: March 2008

Summary. Platelet adhesiveness tests using glass bead columns were performed in 54 normal subjects. Native blood was forced through the columns by a syringe pump at a flow rate of 6 ml/min, and effluent blood was collected in four aliquots of 2 ml each. The first two aliquots demonstrated a progressive increase in per cent platelet adhesiveness with maximum adhesiveness achieved in the second aliquot. The third and fourth aliquots showed decreased adhesiveness with a progressive broadening of the range of normal. In 11 of the 54 normal subjects the fourth aliquot of effluent blood contained more platelets than the original whole blood and indicated that platelets previously retained by the column were being returned to the effluent. The per cent platelet adhesiveness in the first aliquot did not vary with the platelet count. However, the absolute number of platelets retained by the column increased as the platelet count increased. Moreover, the number of platelets retained from a given aliquot was directly proportional to the number of platelets retained from previous aliquots. The return of platelets to the effluent in the fourth aliquot was associated with the smallest number of platelets retained from the first three aliquots. Adenosine inhibited the retention of platelets by glass bead columns. Retention of platelets by glass bead columns appears to be determined by platelet adhesion to glass surfaces, platelet to platelet aggregation due to released ADP, and spontaneous platelet disaggregation which becomes evident when the initial number of retained platelets provides an insufficient amount of ADP to sustain aggregation.
Hereditary Factor‐VII Deficiency in the Beagle
Authors: Spurling N. W. , Burton Linda K. , Peacock R. , Pilling T.
Published: March 2008

Summary. Hereditary factor‐VII deficiency is identified in another large colony of beagles. Evidence is presented to suggest that this trait may be relatively widespread in colonies in Great Britain.
Active and Inactive Factor VII in Dubin‐Johnson Syndrome with Factor‐VII Deficiency, Hereditary Factor‐VII Deficiency and on Coumadin Administration
Authors: Levanon M. , Rimon Sarah , Shani M. , Ramot B. , Goldberg Eugenie
Published: March 2008

Summary. Factor VII was purified from a lyophilized powder of PTC complex (Hemoplex, Cutter Laboratories) and an antiserum was prepared in rabbits to the partially‐purified fraction. The antiserum was found to inhibit specifically factor VII of normal plasma and the activity of the purified factor‐VII preparation.

Inactive factor‐VII‐like material was detected in the plasma of one out of nine patients with factor‐VII deficiency and the Dubin‐Johnson syndrome (DJS), as well as in the plasma of patients on short‐term Coumadin therapy.

No inactive factor VII could be detected in the plasma of patients on prolonged Coumadin therapy or in the plasma of two patients with hereditary factor‐VII deficiency.

The methodological problems are discussed.
The Platelet Defect Associated with Albinism
Authors: Hardisty R. M. , Mills D. C. B. , Ketsa‐ard Kanchana
Published: March 2008

Summary. Investigations on the blood of two albino women with a haemostatic defect have revealed a specific abnormality of their platelets. This consists of an inability of the platelets to store adenine nucleotides in a metabolically inert form, and consequently of an impairment of the release reaction whereby normal platelets are induced to aggregate by agents, including collagen and thrombin, that act indirectly through the release of adenosine diphosphate (ADP). These patients' platelets also have a greatly impaired ability to take up and store 5‐hydroxytryptamine (5HT) and adrenaline. It is suggested that the haemostatic failure previously observed in association with albinism is a result of such a defect of storage and release of adenine nucleotides by the platelets. Investigations on seven other albinos without haemorrhagic symptoms have shown no abnormality of platelet aggregation or nucleotide storage.
The Haematology of Anorexia Nervosa
Authors: Mant M. J. , Faragher B. S.
Published: March 2008

Summary. The haematological features of six patients with anorexia nervosa have been studied in a prospective fashion. Hypocellularity and the presence of large amounts of gelatinous acid mucopolysaccharide in the bone marrow has been confirmed and appears to be a common feature of this disorder. Rapid reversal occurred with clinical improvement in one patient. It is suggested that this represents a physiological response to starvation and evidence is presented that these changes are of minimal functional significance in most patients. Although mild subclinical deficiency of iron and folic acid, a slightly reduced red‐cell lifespan and a relative increase in plasma volume may also occur, anaemia is not universal and is usually mild. Plasma volume changes are probably the major mechanism. Neutropenia was common and is probably due to redistribution of granulocytes within the various granulocyte compartments. Lymphopenia and thrombocytopenia were also found. Morphological abnormalities of the red cells were a frequent finding, particularly the presence of spur cells. These were not associated with abetalipoproteinaemia nor with biochemical evidence of liver disease and did not appear to be subject to significant haemolysis. These haematological changes are also reversible with improvement in nutritional status. Blue‐green granules, probably representing ceroid, were observed in marrow histiocytes. The various abnormalities are discussed in relation to current concepts of the role of nutrition in haematopoiesis in man and haematopoietic roles for dietary factors other than protein are tentatively proposed.
Cell Proliferation and the Action of Cytotoxic Agents on Haemopoietic Tissue
Authors: Blackett N. M. , Adams K.
Published: March 2008

Summary. The effect of several cytotoxic agents on maturing erythroid cells and repopulating stem cells has been investigated. The results demonstrate the extent to which the effect of these agents depend on the rate at which the cells are proliferating. They also show the need to consider damage to the maturing cells as a possible critical factor when proliferation‐dependent agents are administered repeatedly.
Tk: A New Form of Red Cell Polyagglutination
Authors: Bird G. W. G. , Wingham June
Published: March 2008

Summary. A hitherto undescribed from of transient red cell polyagglutinability is described. It was shown to be different from T‐, Tn‐ and Cad‐polyagglutinability. The value of reagents obtained from plant seeds in the elucidation of polyagglutinability is again demonstrated.