bluuebunny/crossref_metadata_2025 huggingface dataset:
Some Effects of Electrical Fields on Red Blood Cells with Remarks on Electronic Red Cell Sizing
Authors: Ur Amiram , Lushbaugh C. C.
Published: March 2008

Sizing normal RBC by an electronic method showed that with certain aperture currents a skewed bimodal size‐distribution curve is obtainable. In these studies some possible causes for such distributions were investigated. The experiments show that an electrical field can cause change in shape, size, and staining properties of RBC as well as lysis. Extrapolation of the results of these experiments to the conditions of the RBC sizing method indicate that these changes are not responsible for the skewed bimodal distribution. We believe, therefore, that normal RBC vary among themselves in some structural or physiologic way, not necessarily size, that was measured by this system.

The use of aperture currents within the range that displays the bimodal distribution is helpful in diagnostic practice, because the bimodal size distribution enhances the discrimination of the system for detection of simultaneously existing different red cell populations.
Peripheral Blood Eosinophilia in Guinea‐pigs following Implantation of Anaphylactic Guinea‐pig and Human Lung
Authors: Parish W. E. , Coombs R. R. A.
Published: March 2008

Summary. Samples of anaphylactic guinea‐pig lung implanted in the peritoneal cavity of normal guinea‐pigs induced an eosinophilia in the peripheral blood 24 hours later; samples of normal, non‐anaphylactic lung caused only a slight rise in the number of eosinophils. Samples of diaphragm from guinea‐pigs killed by anaphylaxis stimulated a smaller increase of eodnophils in the recipients than that caused by lung, but diaphragm taken from normal animals depressed the eosinophil count of the recipients to zero.

The eosinophil‐stimulating factor was present in cell‐free extracts of anaphylactic lungs tested by intraperitoneal injection, though it was unable to diffuse through Millipore membranes in vivo. Antigen‐antibody complexes prepared in vitro, and sensitized tissue treated with antigen, stimulated an eosinophilia in normal guinea‐pigs, and such complexes are believed to be the eosinophil‐stimulating factor in anaphylactic lung.

Intraperitoneal injections of 2 and 20 μg. histamine were followed by an eosinophilia in the peripheral blood 3–6 hours later. However, histamine does not appear to be the eosinophil‐stimulating factor in post‐mortem anaphylactic tissue.

Fresh human lung from infants dying suddenly from unexplained causes, possibly an anaphylactic cot death, implanted in the peritoneal cavity of normal guinea‐pigs depressed the eosinophil counts, though not completely and to a lesser extent than lung from infants dying of other causes, which depressed the eosinophil counts to zero.

This test in guinea‐pigs is not reliable evidence of anaphylaxis in post‐mortem tissue and therefore cannot be used to put to a crucial test the hypothesis that cot death may result from anaphylaxis. Nevertheless, there was some indirect evidence for an eosinophil‐stimulating factor in the lungs of all of four cot‐death cases, and this was absent from the lungs of all of three infants dying of other causes; this is slight evidence, more in favour of the anaphylactic hypothesis than against it.
The Ultrastructure of Bone Marrow Histiocytes in Megaloblastic Anaemia and the Anaemia of Infection
Authors: Goodman J. R. , Wallerstein R. O. , Hall S. G.
Published: March 2008

Summary. An electron‐microscopic study was made of the iron in the histiocytes in niegaloblastic anaemia and in the anaemia of infection. The particulate iron seen by Prussian Blue staining in the histiocytes in megaloblastic anaemia was demonstrated by electron microscopy to be bound in the vesicles, while the diffuse iron staining in the anaemia of infection was related to the free dispersion of iron‐containing particles in the cytoplasm of the histiocytes. The phagocytosis of erythroblasts at various stages of maturity occurred in cases of niegaloblastic anaemia and resulted in a picture showing every stage of degradation. Phagocytosis of erythroblasts by histiocytes was not seen in the marrows of patients with the anaemia of infection nor did it occur in niegaloblastic anaemia in remission.
Influence of Hyperdiploidy on Ph1 Prevalence Response to Therapy in Chronic Myelogenous Leukaemia
Authors: Pedersen Bent
Published: March 2008

Summary. In earlier investigations, evidence was found to suggest that hyperdiploid cells are less sensitive to cytostatic treatment than other Ph1‐positive cells. The object of the present paper is to test this hypothesis. In a blood culture material, two treatment groups were defined according to the extent of the cytostatic therapy of the patients in the period preceding the time of sampling. The patients in treatment group T had received cytostatics for a total of 30 days or more during the preceding 2 months or had been treated continuously for the last 14 days. Group t originated from patients not fulfilling these demands. Each treatment group was subdivided into two Ph1 prevalence classes, one with more and one with less than 50 per cent Ph1 ‐positive cells. In group T, the average frequency of hyperdiploid Ph1‐positive cells was found to be significantly higher in cultures with more than 50 percent Ph1‐positive cells than in cultures with less. Group t did not show a corresponding difference. Closer analysis of group T revealed a linear positive correlation between the Ph1 prevalences and the logarithms of the proportions of hyperdiploid Ph1‐positive cells. The best explanation of these results seems to be that hyperdiploid cells are less sensitive to cytostatic treatment than other Ph1‐positive cells. This assumption is in agreement with and supplements earlier results and seems to lead to the conclusion that development of high frequencies of hyperdiploid Ph1‐positive cells involves haematological and clinical progression of chronic myelogenous leukaemia.
Hageman Factor (Factor XII) in an Affected Kindred and in Normal Adults
Authors: Kasper C. K. , Whissell Buechy D. Y. E. , Aggeler P. M.
Published: March 2008

Summary. Assays for Hageman‐factor (Factor‐XII) activity were performed on plasma obtained from 80 normal adults and from 39 members of an inbred kindred including a subject with severe Factor‐XII deficiency. Two normal alleles of the gene governing Factor‐XII production are postulated: Hh, associated with higher levels of Factor XII, and H1, associated with lower levels of Factor XII. In addition, the existence of two abnormal alleles is suggested: Ho, associated with almost no Factor‐XII activity, and Hm, with moderate Factor‐XII deficiency. Based on this hypothesis, the mother of the proposita (with 13 per cent Factor‐XII activity) has a probable H1Ho genotype. The father (with 58 per cent Factor‐XII activity) has a probable HhHo genotype.

As well as a plasma Factor‐XII activity of 13 per cent, the mother of the proposita had a prolonged partial thromboplastin time, but no other abnormalities were observed in non‐specific coagulation tests. The results of all these tests, including the partial thromboplastin time, were normal in subjects with Factor‐XII levels of 22 per cent or more.
Blood Fibrinolytic Activity during Arvin Therapy
Authors: Pitney W. R. , Bell W. R. , Bolton Gillian
Published: March 2008

When Arvin is administered to patients, there is a rapid fall in plasma plasminogen concentration and fibrin degradation products appear in the blood which can be detected both by their anticoagulant effect and by their reaction with anti‐fibrinogen serum. There is a minimal but inconstant increase in the concentration of plasminogen activator and circulating plasmin cannot be detected. These findings are similar to those recorded in the defibrination syndrome and are explained by the assumption that both plasminogen and activator are adsorbed onto intravascular fibrin micro‐clots. Local plasmin release would then cause lysis of fibrin with the appearance of fibrin degradation products.

There is no apparent reason why this mechanism should assist in the lysis of coexisting preformed thrombi. The apparent rapid lysis of thrombi which has been observed in some patients treated with Arvin can be explained if such thrombi are not static, but represent a balance between fibrin deposition and fibrinolysis. Therapeutic defibrination, by preventing extension of the thrombus, would allow the normal fibrinolytic mechanism to produce dissolution of the thrombus.
A Method for the Positive Identification of Erythropoietic Cells in Chromosome Preparations of Bone Marrow
Authors: Rastrick Joan M.
Published: March 2008

Chromosome preparations from the bone marrow of four patients with chronic granulocytic leukaemia were made after the cells had been cultured for 12 hours with iron isotopes in a medium with added GSH, ATP, cysteine and ascorbic acid, which permitted optimal iron uptake and incorporation. The cells were fixed for 15 minutes only in formaldehyde‐methanol‐acetic acid. Auto‐radiographs of these preparations showed that the Ph1 chromosome was present in erythroid cells. This indicates that erythroid and myeloid cell lines have a common stem cell in the bone marrow.
The Pattern of Disordered Haemoglobin Synthesis in Homozygous and Heterozygous β‐Thalassaemia*
Authors: Weatherall D. J. , Clegg J. B. , Na‐Nakorn Supa , Wasi Prawase
Published: March 2008

The rate of globin chain production has been studied in patients with homozygous β‐thalassaemia, heterozygous β‐thalassaemia, haemoglobin E‐thalassaemia, and sickle‐cell‐thalassaemia, and compared with that in non‐thalassaemic individuals. A partial or total deficit of β‐chain synthesis has been demonstrated in all forms of β‐thalassaemia. This results in the production of a large intracellular pool of α‐chains, the kinetics of which have been worked out. The α‐chains in this pool appear to contain haem and are unstable, rapidly becoming associated with the stromal fraction. These findings are examined in terms of the pathogenesis of the anaemia of thalassaemia.
The in Vitro Lysis of the Red Cells of Paroxysmal Nocturnal Haemoglobinuria by the Serum of Patients with Cirrhosis of the Liver
Authors: Sirchia G. , Ferrone S. , Mercuriali F.
Published: March 2008

The complement (c′) titre, the concentration of the third component of C’ (c′3) and the capacity of sera to lyse PNH cells in the acidified‐serum test and the sugar‐haemolysis test have been determined on the sera obtained from 100 healthy subjects and 103 patients with cirrhosis of the liver.

The lytic capacity of normal sera for PNH cells is not correlated with the serum's C'titre or c′3 concentration. With cirrhotic sera, however, a significant correlation was found between c′3 concentration and PNH haemolytic capacity, especially in the sugar‐haemolysis test. It is concluded that, under certain conditions, c′3 can be rate‐limiting in PNH cell lysis in vitro.
Further Observations on Spontaneous Blastoid Transformation of Human Small Lymphocytes in Vitro
Authors: Caron G. A.
Published: March 2008

DNA synthesis, measured by tritiated thymidine uptake during the final 1 hour in vitro, has been used as a measure of blast transformation of human peripheral small lymphocytes cultured in media containing 20 per cent autologous plasma. Control cultures from two subjects of up to 12 and 15 days duration and from eight further subjects of 3 and 6 days duration have been studied and the degree of spontaneous transformation compared to the response to known stimulants of transformation, phytohaemagglutinin and specific antigens.

Spontaneous transformation was consistently low for up to 6 days. Thereafter there was a relatively slight increase. Theoretical arguments why the increased proportion of labelled cells found in some of the older cultures may be an artifact of differential cell survival are presented.

Review of previous reports of spontaneous lymphocyte transformation suggests that this is minimal when the cells are cultured in autologous plasma and that heterologous sera may act as an unsuspected transformation stimulant.
The Distribution of Folates in Rabbit Tissues during Phenylhydrazine‐Induced Haemolysis
Authors: Izak G. , Rachmilewitz M. , Grossowicz N. , Galewski K. , Jablonska M.
Published: March 2008

Acute haemolysis induced in rabbits with acetylphenylhydrazine (APH) was associated with a high reticulocytosis and increased folate activity with all three bioassays (L. casei, S. faecalis and P. cerevisiae) employed, in comparison with untreated animals. The bone marrow folate activity of the APH‐treated rabbits was considerably higher than that of control marrows; activity measured with P. cerevisiae reached 50 per cent of that obtained with L. casei, indicating a high conversion into reduced forms. Administration of pteroylglutamate (PGA) together with APH resulted in higher red cell folate values than administration of APH alone. In vitro, reticulocytes from APH‐treated rabbits incorporated three times more radioactive‐PGA than those from animals given APH with PGA. The various aspects regulating the uptake and function of folates in red cells at varying degrees of maturation are discussed.
Studies on Fibrin Monomer Aggregation in Congenital Dysfibrinogenaemia (Fibrinogen ‘Zürich’): Separation of a Pathological from a Normal Fibrin Fraction
Authors: Von Felten A. , Frick P. G. , Straub P. W.
Published: March 2008

Further characterization of the delay in aggregation of fibrinogen ‘Zürich’ showed a potentiation of the defect by increasing ionic strength and an acceleration by calcium ions or protamine. A new type of paracoagulation due to soluble abnormal fibrin monomers in fresh serum is described.

Using Reptilase, it was possible to separate a fibrin fraction with normal aggregation from a pathological fraction with virtually no clot formation. Mixtures of equal parts of the abnormally aggregating fraction with normal monomers of either patient or control demonstrated a pattern of aggregation analogous to monomers of the patient's whole fibrinogen. It appears possible that certain differences between some published cases of dysfibrinogenaemia might be due to the association of variable amounts of pathological fibrinogen with normal fibrinogen.
Chromatographic Behaviour of Clotting Factors
Authors: Casillas G. , Simonetti C. , Pavlovsky A.
Published: March 2008

Through the use of DEAE‐cellulose under the conditions reported in this paper which were particularly selective for the adsorption of clotting factors, the chromatographic behaviour of Factors I, II, V, VII, VIII, IX and X was studied using different buffer systems. Human plasma, supernatant of Fraction I of Cohn and human Factor‐VIII concentrates were used as starting materials. As some of the chromatographic systems used do not perceptibly modify the physical and chemical properties of the plasma or its derivatives, they allow the techniques to be included in a general scheme of routine plasma fractionation.

The conclusions drawn from the chromatographic behaviour of the factors studied have led to the preparation of a concentrate of Factors II, IX and X for clinical use, a concentrate of Factor VII and an artificial substrate for the assay of Factor VII.
Regional Variations in the Proportion of Red Cells in the Blood in Man
Authors: Bowdler A. J.
Published: March 2008

Surface counting techniques following the intravenous injection of 51Cr labelled red cells and 131I labelled human serum albumin have been used to investigate the regional haematocrit in normal subjects, subjects with splenic enlargement and after splenectomy. Regional variations in the proportions of red cells and plasma were demonstrated, the red‐cell concentration being highest at the precordium and lowest in the hepatic region. Intermediate values were obtained for the lumbar and splenic regions in normal subjects.

The enlarged spleen has a definite but variable tendency to be associated with high local haematocrit values when compared with the venous haematocrit. Raised whole‐body to venous haematocrit ratios result from the pool of red cells in the spleen which shows delayed mixing with the cells of the extrasplenic circulation. The raised whole‐body to venous haematocrit ratio associated with splenomegaly is more dependent on the concentration of the pooled cells relative to the venous haematocrit than on the volume of pooled cells and spleen size.

The significance of variations in regional to venous haematocrit and whole‐body to venous haematocrit ratios is discussed.
Erythroid Cell Proliferation in Hypertransfused Rats
Authors: Tarbutt R. G.
Published: March 2008

Summary. 55Fe autoradiography of the circulating erythrocytes has been used to study the proliferation of erythroblasts in hypertransfused rats. The maturation time of the recognizable erythroid precursors labelled with 55Fe 6 hours before hypertransfusion is not changed by the subsequent transfusion, and the number of labelled erythrocytes produced by these precursors is also normal. The results imply that the recognizable erythroid precursors present in the marrow at the time of hypertransfusion undergo the normal number of divisions in a normal maturation time, and therefore that the proliferation rate of these precursors is unchanged by hypertransfusion. The results have been discussed in terms of the role of erythro‐poietin in the control of erythroid cell proliferation.
In‐Vitro Lysis of AET‐Treated Normal Red Cells (PNH‐like Cells) by Normal and Cirrhotic Sera
Authors: Sirchia G. , Ferrone S. , Mercuriali F.
Published: March 2008

Summary. The total complement (C′) titre, the concentration of the third component of C (C′3) and the haemolytic activity against AET‐treated cells (PNH‐like cells) of normal and cirrhotic sera have been investigated. Serum haemolytic activity has been judged by the amount of haemolysis obtained in two in‐vitro tests, the acidified‐serum test and the sugar‐haemolysis test. A significant correlation has been found between total C’ titre and C′3 concentration of cirrhotic sera and the serum haemolytic activity against AET cells in the sugar‐haemolysis test.
The Role of Puberty in Red‐Cell Production in Hereditary: Haemolytic Anaemias
Authors: Shahidi N. T. , Clatanoff D. V.
Published: March 2008

Summary. Long‐term follow‐up of two male siblings with hereditary non‐spherocytic haemolytic anaemia revealed marked haematological improvement leading to normal haemoglobin concentration in the older boy undergoing puberty, whereas the younger brother who was prepubescent remained anaemic. While the erythrocyte life‐span was the same in both patients, the total nucleated erythron, red‐cell volume, and consequently the rate of red‐cell production, was significantly higher in the older sibling. This finding suggested that puberty in males may play an important role in the compensation of haemolytic process. This hypothesis was further substantiated by analysis of data in 119 patients with hereditary spherocytic and non‐spherocytic haemolytic anaemia. In comparing the haemoglobin concentration it was found that affected adult males had significantly higher haemoglobin concentration than affected children. This haematological discrepancy is thought to be the result of erythroid stimulation by androgens produced endogenously.
Erythropoiesis, Red‐Cell Creatine and Plasma Aldolase Activity in Anaemia in the Rabbit and Man
Authors: Griffiths W. J. , Lothian Elizabeth J.
Published: March 2008

Summary. It has been shown that in the rabbit plasma aldolase was not increased by phlebotomy whereas in haemolytic anaemia produced by acctylphenylhydrazine there was a marked rise in plasma aldolase which was not, however, sustained throughout the period of falling haemoglobin. It is suggested that because of this dissociation of enzyme activity and haemoglobin the increased plasma aldolase activity in haeniolytic anaemia is not due to release of enzyme from the haemolysed red cells but that it is derived from immature precursor cells destroyed during transient ineffective erythropoiesis in the bone marrow.

The data obtained from these animal experiments have been used to elucidate the cause of the raised plasma aldolase which is a feature of some types of human anaemia. In iron‐deficiency anaemia the plasma aldolase was not increased. In megaloblastic anacinia the plasma aldolase was increased in some but not in all patients. Evidence is adduced to support the hypothesis that the increase in plasma aldolase activity, when it is present, is due to release of enzyme from precursor cells destroyed in the marrow during ineffective erythropoiesis.

The creatine content of the red cell has been used as an index of the mean age of the cells in the peripheral circulation. Increased red‐cell creatine in iron‐deficiency anaemia is considered to be the result of a shortened survival of the cells in this condition.
Haemoglobin Synthesis in β‐Thalassaemia
Authors: Modell C. B. , Latter A. , Steadman J. H. , Huehns E. R.
Published: March 2008

Summary. The incorporation of radioactive amino acids into the polypeptide chains of haemoglobin has been studied in reticulocyte preparations from five patients with β‐thalassaemia and four control patients. In both groups of patients an intracellular pool of free α‐chains has been found, but the pool is much larger in patients with β‐thalassaeniia major. The α‐chains exist in two forms: α‐dimers and α‐monomers, but the results suggest that they are released as dimers from the ribosomes and that the α‐chains for Hb‐A and Hb‐F synthesis are derived from the α‐dimer pool. The α‐dimers are also gradually converted to the monomers, and this may be the first stage in the denaturation of this protein. The results also show that the α‐dimer can exchange with the α‐chains of Hb‐A and that this exchange is more rapid in the presence of in vivo aged Hb‐A. In one patient with thalassaemia it was shown that there was no pool of unreleased β‐chains on the ribosomes. There is also no evidence for the release of incompleted β‐chains in our patients.
A Random Sample from Wales
Authors: Jacobs A. , Waters W. E. , Campbell H. , Barrow A.
Published: March 2008

Summary. The serum iron, iron binding capacity and transferrin saturation has been estimated in a random sample of the Welsh population. The results indicate that iron deficient erythropoiesis is not uncommon, being present in 22 per cent of women and 6 per cent of men. Iron deficiency has only a low correlation with haemoglobin concentration and it is commonly found in subjects with a normal haemoglobin concentration by conventional standards.
2,3‐Diphosphoglycerate Metabolism in Hereditary Spherocytosis
Authors: Palek J. , Mirčevová L. , Brabec V.
Published: March 2008

Summary.

The red cell 2,3‐DPG content of unsplenectomized patients with hereditary spherocytosis (HS) was found to be markedly lower than that of other haemolytic disorders with similar reticulocyte values. However, there were no differences in 2,3‐DPG between splenectomized HS patients and healthy subjects.

The cause of this decreased 2,3‐DPG in unsplenectomized patients was studied. When heparinized blood both of unsplenectomized and splectomized HS individuals was incubated with excess of glucose, there was a significantly higher splitting of 2,3‐DPG than in the normal subjects.

Since the activity of the 2,3‐DPG splitting enzyme, 2,3‐DPGase, was shown to be increased by decreasing pH, the increased 2,3‐DPG splitting during incubation of HS blood could be explained by the increased fall in pH during incubation of the blood, presumably due to increased lactate formation. This assumption was further supported by the finding that 2,3‐DPG splitting both in normal and HS blood was completely inhibited when the pH of blood was raised to 7.8–7.9 and maintained in this range during the incubation.

In vitro incubation of blood simulates in some ways in vivo erythrostasis in the spleen and it is suggested that the decreased 2,3‐DPG content found in the fresh red cells of unsplenectomized HS patients is due to increased 2,3‐DPG splitting in these cells during their erythrostasis in the spleen.
Activation Characteristics of Bovine Prothrombin Preparations
Authors: Landaburu R. H. , Lima F. , Albado E.
Published: March 2008

Summary.

Chromatographic fractionation of purified bovine prothrombin, obtained by the method of adsorption and elution on magnesium hydroxide, yields fractions which restore to the product the properties lost during the procedure. Cellulose chromatography separates fractions without which prothrombin is not activated by 25 per cent sodium citrate. On the other hand, the fractions separated during chromatography on amberlite AG3‐X4 catalyse further the activation of the product in that medium. C‐terminal amino acid analyses confirm that both chromatographic exchangers selectively adsorb each of the two active substances which contaminate prothrombin preparations. Changes introduced by chromatography in the activation characteristics of prothrombin are due to the presence or absence of these contaminants.
Immunological and Chromosomal Studies in First‐Degree Relatives of Children with Acute Lymphoblastic Leukaemia
Authors: Sutton R. N. P. , Bishun N. P. , Soothill J. F.
Published: March 2008

Summary

. Immunoglobulins (IgG, IgM and IgA) were estimated in sera from mothers and siblings of children with acute lymphoblastic leukaemia (ALL) and in sera from appropriate controls. The distribution of IgA titres was significantly lower in the siblings of leukaemic children than in control children and that of IgM was significantly higher in mothers of leukaemic children than in control mothers.
On the Mechanism of the In Vitro Production of Ham‐positive Red Cells by Sulphydryl Compounds: Role of pH and Free ‐SH Groups
Authors: Sandre G. De , Cortesi S. , Corrocher R. , Falezza G. , Perona G.
Published: March 2008

Experiments were carried out in order to obtain high percentages of Ham‐positive red cells (HPRC) from normal human red cells incubated with various ‐SH containing compounds and to evaluate the role of the free ‐SH groups in these sulphydryl compounds and of the red cells themselves in the HPRC‐producing process.

The sulphydryl compounds producing HPRC were all far more effective at pH 9 than at lower pH values; they became ineffective if their ‐SH groups were blocked. Sulphydryl‐inhibited red cells maintained their susceptibility to become HPRC suggesting that sulphydryl compounds display their damaging activity other than upon the free ‐SH groups of the red cell membrane. HPRC have been obtained using 2‐mercaptoethylamine, 2‐mercaptoethanol or 3‐mercaptopropionic acid.
Haemolysis in Cold Agglutinin Disease: The Role of C’and Cell Age in Red Cell Destruction
Authors: DE Wit C. Dudok , Gastel C. Van
Published: March 2008

The mechanism of red‐cell destruction was studied in a patient with cold‐agglutinin disease. It was confirmed that the patient's red cells were abnormally resistant to lysis by the anti‐I cold agglutinin in the serum. This increased resistance is probably due to the accumulation of C’on the red‐cell membrane. It was found that red cells were only protected if C’was brought on to the red cell by anti‐I antibodies and not if this was the result of treatment with normal serum at low ionic strength. The resistance was also found only to apply to lysis by anti‐I antibodies and not to a haemolytic rabbit anti‐human‐red‐cell serum. These results can be explained by assuming that inactive C’complexes around the I‐antigen were blocking receptor sites for new haemolytic C’factors.

It was shown in normal individuals that red‐cell age does not effect the susceptibility of the cells to lysis by anti‐I serum. In the patient with cold‐agglutinin disease, however, the young cells were preferentially lysed, probably because these cells had not yet accumulated C’to the same extent as the more mature cells and were, as a result, less resistant to haemolysis.
Studies on Protein Fractions Isolated from Human Plasma
Authors: MACKAY MARGARET , SILK ELSIE , MASON BRENDA , COMBRIDGE B. S.
Published: March 2008

Summary. Fractions of human plasma separated by precipitation with cold ether and ethanol were examined for a number of protease and esterase activities. Plasminogen, kallikrein, increased vascular permeability, thrombin and TAMe esterase were concentrated in fraction G2/iR, a lipo‐protein fraction containing a mixture of alpha and beta globulins and a gamma‐M globulin, which also contained activated coagulation contact factors. ATEe esterase was concentrated in G2/iR and fibrinogen. Kinin‐ase and TAMe esterase were also found in G2/2 a mixture of alpha, beta and gamma globulins.

Tests of fractions of G2/iR separated by chromatography confirmed the findings of Kagen et al, (1963) and showed that kallikrein was a gamma‐M globulin. Vascular permeability activity, but not kininogenase activity was removed by high‐speed centrifugation from this fraction.

Fractions G2/iR, G2/2 and to a lesser extent G3 contained a substance which induced kininogenase activation in intact plasma, but was not identified as PF, plasmin or activated contact factor and had no esterase activity.

Kininogenase activity was associated with contaminants of fibrinogen and gamma globulin concentrates and absent from albumin. In fractions prepared by large‐scale methods, only those made from G2 are likely to contain sufficient kininogenase to cause a clinical reaction. Kininogenase was not adsorbed by Al(OH)3 gel or Ca3(PO4)2 and would not contaminate clotting factors prepared from G2.
The Incidence of Glucose‐6‐Phosphate Dehydrogenase Deficiency and Thalassaemia in Malta
Authors: Cauchi M. N.
Published: March 2008

Summary. A survey of G6PD deficiency in Malta including 1145 males and 369 females has shown that 2.7% of the males and 1.9% of the females have enzyme deficiency. More than 60% of the enzyme‐deficient males but none of the females had decolorization times between 90 min and 24 hr. Using quantitative estimation of Hb A2 as a measure of β‐thalassaemia, an incidence of 3.4–3.6% was found. A raised Hb F was found in 2.3% of cases. The incidence of G6PD deficiency and thalassaemia does not seem to be correlated with intermarriage.
Increased Prothrombin Conversion: A New Activity of Lysed Fibrinogen*
Authors: Triantaphyllopoulos Demetrios C. , Brunetti Andrée J. , Triantaphyllopoulos Eugenie
Published: March 2008

Summary. Derivatives of lysed fibrinogen added to mixtures of ‘prothrombin complex’, brain phospholipids and calcium chloride increased significantly the amount of thrombin which was generated. This augmentation was not destroyed by heating at 60°C for 15 min and was shared by all the chromatographic fractions of lysed fibrinogen (A, D and E) which were tested, even by derivatives prepared from haemophilia A plasma. Contamination with factor VIII cannot therefore be responsible. Addition of fibrinogen derivatives to normal blood or haemophilic plasma at low concentrations increased the prothrombin consumption, although the partial thromboplastin times of normal and haemophilic plasma were not shortened.
Coagulation Factor IX in Normal and Haemophilia B Plasma
Authors: Somer J. B. , Castaldi P. A.
Published: March 2008

Summary. Coagulation factor IX has been isolated in a partially purified form from normal human plasma. Studies have been performed of the coagulant properties of this factor, of its activation by contact product and subsequent reaction with factor VIII. A similar chromatographic procedure with DE AE cellulose has been used to study the plasma of a patient with haemophilia B. A fraction has been isolated with similar physico‐chemical properties to normal factor IX but lacking coagulant activity.
The Relation of ‘Fletcher Factor’ to Factors XI and XII
Authors: Hathaway William E. , Alsever Judith
Published: March 2008

Summary. Further evidence is presented for the existence of a new coagulation factor which is closely related to Hageman factor (XII) and plasma thromboplastin antecedent, PTA (XI). This factor has been tentatively designated ‘Fletcher factor’. Coagulant activity of Fletcher factor was separated from the clotting activity of factors XI and XII by C‐M Sephadex column chromatography of intact normal plasma. Other studies showed that the prolonged partial thromboplastin time or plasma recalcification time of Fletcher‐deficient plasma could be ‘corrected’ by prolonged contact with celite, glass, kaolin, or ellagic acid; all are known activators of factor XII. Cytochrome c, known to inhibit the contact activation of factor XII, completely abolished this contact ‘correction’ of Fletcher‐deficient plasma. Thus, the clotting times of plasmas deficient in Fletcher factor (presently found in seven individuals from four unrelated families) are readily corrected by activated factors XII and XI. None of these individuals has any bleeding tendencies.

Fletcher factor activity is deficient in the plasma of newborn infants; the factor is probably produced in the liver and not dependent on vitamin K for its synthesis.
The Osmotic Fragility of Human Leucocytes in Normal and in Some Pathological Conditions
Authors: Nir Emanuel , Efrati Pinhas , Danon David
Published: March 2008

Summary. Leucocytes were separated from blood specimens by centrifugation and their osmotic fragility was automatically recorded using the Fragiligraph Model D‐2.

As the salt concentration of the surrounding medium was gradually reduced changes in the leucocytes were studied by phase microscopy. These changes, which are automatically recorded by the Fragiligraph, result in increased light transmission. The results are reproducible and the range for leucocytes of normal individuals is relatively narrow.

Leucocytes in acute leukaemia are very fragile. In chronic lymphatic leukaemia they are either more fragile or more resistant than the normal cells.
Effects of Sulphydryl Inhibition on the Erythrocyte in Paroxysmal Nocturnal Haemoglobinuria
Authors: Canellos G. P. , Brain M. C. , Dacie J. V.
Published: March 2008

Summary. Normal erythrocytes exposed to high concentrations of sulphydryl‐containing compounds such as reduced glutathione, cysteine, and 2‐aminoethyliso‐thiouronium bromide (AET) acquire some in‐vitro properties of the PNH erythro‐cyte with increased sensitivity to acidified serum and cold‐antibody lysis. These findings suggested the possibility that an abnormality of membrane sulphydryl metabolism is a feature of PNH. Investigations were undertaken in five patients with PNH and a group of normals. Quantitative determination of measurable SH groups in haemoglobin‐free erythrocyte membranes failed to reveal a difference between PNH and normal. Normal erythrocytes exposed to AET had a marked reduction in measurable SH groups. The functional status of the membrane SH groups was studied by the in‐vitro effect of sulphydryl‐binding compounds, p‐chloromercuribenzoate (PMB) and p‐chloromercuribenzene sulphonate (PMBS).

In all PNH cases an increased sensitivity to the haemolytic effects of SH blockade as compared to normal erythrocytes was noted. Studies with the inhibitor, PMBS, which acts only on the outermost surface of the membrane, revealed two types of erythrocytes in PNH, one highly vulnerable and the other behaving similarly to normal. Haemolysis occurred without inhibition of glycolytic activity as measured by lactate production or interference with the intracellular SH status. It appears that the PNH membrane defect is associated with an abnormality in the functional activity of membrane SH groups.
Haemoglobin F Jamaica (α2γ261 Lys→Glu; 136 Ala)
Authors: Ahern Edgar J. , Jones Richard T. , Brimhall Bernadine , Gray Robert H.
Published: March 2008

Summary. Two siblings of mixed Negro, East Indian and Caucasian parentage showed an abnormal haemoglobin component in infancy which had electrophoretic characteristics similar to Hb F Roma (Silvestroni & Bianco, 1963). The amino‐acid substitution responsible for the peculiar electrophoretic mobility was found to be in the gamma polypeptide chain (γ— 61(E5) Lys→Glu). The finding of an alanyl residue at position 136 of the γ‐chain of the abnormal component in the first born of these infants was repeated in the abnormal γ‐chain of the second infant. No functional abnormalities were found to be associated with this abnormal haemoglobin, which is designated Hb F Jamaica.
Lysis by Anti‐I in Dyserythropoietic Anaemias: Role of Increased Uptake of Antibody
Authors: Lewis S. M. , Grammaticos P. , Dacie J. V.
Published: March 2008

Summary. Antibody lysis has been studied in PNH, in congenital dyserythropoietic anaemia and in other blood diseases with abnormal erythropoiesis. This last group of acquired dyserythropoietic anaemias included, especially, aplastic anaemia, megaloblastic anaemias, myelosclerosis and leukaemia. Cold‐antibody lysis, complement sensitivity and anti‐I antibody uptake by red cells were measured.

In both congenital dyserythropoietic anaemia and the acquired dyserythropoietic anaemias of all types there was increased cold‐antibody lysis which was mainly or entirely due to increased antibody binding, without increased complement sensitivity. In PNH, on the other hand, there was slightly increased antibody uptake but lysis was much greater than could be accounted for by this alone and was mainly due to increased complement sensitivity. PNH thus appears to be uniquely different from the dyserythropoietic anaemias. Also, whereas in PNH complement sensitivity curves indicated the presence of two populations of red cells, in the dyserythropoietic anaemias the curves suggested that only one cell population was present.
Shortened Red Cell Survival in Chronic Posthaemorrhagic Anaemia: Effect of Iron and Prednisone
Authors: Dyrkorn K. , Magnus E. M.
Published: March 2008

A shortened red‐cell survival time has been found in patients with prolonged external bleeding. Ten patients have been studied, seven of whom had markedly increased erythropoiesis. Prednisone therapy rapidly lengthened the red‐cell survival time, which became almost or completely normal, whereas iron therapy had no obvious effect on red‐cell life span during the first 7 weeks of therapy. The return of the red‐cell life span to normal after bleeding had ceased, occurred at a time compatible with that required for a new red‐cell population to be produced.

The effect of prednisone in producing a change of red‐cell life span toward normality seemed to be most pronounced in those patients who showed most active erythropoiesis. The effect is probably mediated via some form of red‐cell membrane stabilization.
The Lysosomal Nature of the Anomalous Granules and Chromosome Aberrations in Cultures of Peripheral Blood in Chediak‐Higashi Syndrome
Authors: Rozenszajn Leon Arie , Radnay Judith
Published: March 2008

In Chediak‐Higashi syndrome (C.H.) the lysosomal nature of the giant granules in white blood cells was demonstrated by their strong fluorescence with acridine orange and by their strong acid phosphatase and esterase activities.

Cytochemical observations on normal peripheral blood stained for esterase activity in the presence of Triton X‐100 showed an increased activity equal to that found in leucocytes from C.H. cases. This may be due to a modification of a lipid component of the lysosomal membrane.

Cultured lymphocytes from C.H. are capable of transformation like normal lymphocytes. The transformation was found not to change the appearance of the inclusion bodies. Although the chromosome number was normal, morphological abnormalities were observed, of which chromatid and chromosome breakages were the most prevalent.
Platelets and the Triggering Mechanism of Intravascular Coagulation
Authors: Evensen Stein A. , Jeremic Michael
Published: March 2008

Summary The ability of platelets to trigger intravascular coagulation was studied by infusing a suspension of frozen‐thawn homologous platelets into rabbits pretreated with either saline or Thorotrast. Each animal received during a period of 30 min an amount of platelets at least equivalent to the number of circulating platelets in a normal animal of the same weight. The infusion of platelet material did not trigger fibrinogen consumption in saline‐pretreated animals. In Thorotrast‐pretreated animals, however, the platelet suspension produced significantly increased disappearance of [125I]fibrinogen, moderate decreases in the fibrinogen level, significant falls in factors V and VIII, but no increase in fibrinolytic split products. None of the animals developed the generalized Shwartzman reaction. We conclude that platelets contain weak procoagulant activity which was effectively cleared by the reticuloendothelial system in the normal animal. Depression of the phagocytic capacity by Thorotrast prior to the infusion unmasked moderate intravascular coagulation.
Defibrination in Normal and Abnormal Parturition
Authors: Kleiner G. J. , Merskey C. , Johnson A. J. , Markus W. B.
Published: March 2008

Summary Studies of blood coagulation and fibrinolysis in women undergoing uncomplicated single delivery showed a significant fall in plasma fibrinogen and factor VIII. The levels were lowest 1–4 hr postpartum and returned to pre‐existing or higher levels within 24 hr. A significant fall in fibrinogen also occurred in women with twin delivery or caesarean section without labour. Similar changes were noted in factors V and VIII. Fibrinolytic activity was markedly decreased during delivery but increased rapidly thereafter in women with a single birth or caesarean section without labour. In women with twin delivery, it remained low. No consistent changes in the level of fibrinolytic inhibitors or plasminogen were noted. Mean levels of fibrinolytic degradation products (FDP) were in the upper level of the normal range and increased in the first 1–4 hr postpartum. These changes were even more marked in twin delivery. In women with abruptio placentae or prolonged intrauterine death (IUD), levels of fibrinogen, factors V and VIII and blood platelets were markedly reduced and generally dropped even lower during the first 4 hr after delivery, returning within 24 hr to the levels found in nonpregnant women. Levels of plasminogen and factor X were also reduced. High levels of FDP were found during labour, returning within 24 or 48 hr to the range observed in women 24 hr after normal delivery. Immunodiffusion and immunoelectrophoresis of serum in agar gel disclosed abnormal double or split precipitin lines. Sequential changes in these precipitin lines pointed to a continuing process which started before delivery, reached a maximum shortly thereafter, disappearing within the next 10–24 hr. The changes found in early (vs. late) labour, or during uterine surgery not associated with pregnancy, did not uphold the supposition that similar changes observed during normal or abnormal parturition might be due to the stresses of labour or surgery. The findings reported herein suggest that a minor degree of physiological defibrination develops during normal labour which is qualitatively similar to, but of much lesser magnitude than, the pathological defibrination syndrome (with local lysis of fibrin) commonly associated with abruptio placentae or prolonged intrauterine death.
Antithrombin III, Antifactor Xa and Heparin
Authors: Biggs Rosemary , Denson K. W. E. , Akman N. , Borrett R. , Hadden M.
Published: March 2008

Summary.

Methods have been devised for the measurement of antithrombin and of the natural inhibitor of activated factor X.

The relation between heparin and its plasma cofactor and the destruction of thrombin and activated factor X were studied. As observed by other workers, heparin has more effect on the speed of thrombin neutralized than on the amount neutralized after 1 hr of incubation. When the neutralization of activated factor X was studied it was found that heparin at very low concentrations, with a plasma cofactor, promoted the progressive destruction of activated factor X.
The Effect of Vincristine on the Platelet Count in Rats
Authors: Robertson J. H. , Crozier E. H. , Woodend Bertha E.
Published: March 2008

Summary.

The effect of vincristine on the platelet count of rats is described. It was found that, depending upon dosage, the drug can cause either a thrombocytosis or marrow hypoplasia with thrombocytopenia in normal rats. Thrombocytosis was found even after prolonged treatment with vincristine when this was given at appropriate dosage.

The thrombocytosis promoting effect of the drug was not enhanced by an increase in the splenic platelet pool or decreased by splenectomy. However, it was abolished when prior treatment was given to suppress marrow thrombopoiesis.
Free Amino Acids and Proteins in Plasma of Pregnant Patients with Megaloblastic Anaemia
Authors: Jacobs S. , Fleming A. F.
Published: March 2008

Summary.

Plasma proteins and free amino acids were estimated in 18 non‐anaemic pregnant and 16 severely anaemic pregnant or recently delivered Nigerians. The mean concentration of all plasma free amino acids, except arginine, was raised in 15 women with megaloblastic anaemia secondary to folate deficiency. Some amino acid levels in individual patients were over 5 times the highest concentration recorded in the non‐anaemic. All plasma free amino acids were within the normal range in one patient with iron deficiency anaemia and heavy hookworm infestation. The mean albumin, α2 globulin and total protein concentrations were slightly but significantly lower in the anaemic patients.

These findings have been discussed in support of a hypothesis that folate‐ or vitamin B12‐deficiency leads to a failure of methylation and formylation of tRNA and rRNA, so that coding is interrupted and cells are unable to form mature ribosomes. This results in an accumulation of free amino acids in cellular and extracellular pools with overflow amino aciduria. Haemoglobinopathies, haemolysis, malaria and liver failure were unlikely to have been causes of the high plasma amino acid concentrations observed in these women.

It is probable that this disturbance of amino acid metabolism affects adversely uterine hypertrophy, placental development and foetal growth.
Cellular Growth in Specific Nutritional Deficiency States in Rats I. IRON DEFICIENCY ANAEMIA IN POST‐WEANLING PERIOD
Authors: Canale Virginia , Lanzkowsky Philip
Published: March 2008

Summary The effect of iron deficiency anaemia on cellular growth and protein accretion in rats was studied using the parameters of organ weight, protein, DNA and RNA content. Three groups of rats were fed the same synthetic iron‐deficient diet for a period of 143 days. Group I received the diet ad libitum, Group II was pair‐fed with Group I but received supplemented iron and Group III received the diet ad libitum with supplemented iron. The following are the mean results obtained in Groups I, II and III: weight gain, 87 g, 86 g and 121 g respectively; haemoglobin 7.8 g% (w/v), 14.7 g% (w/v) and 15.2 g% (w/v) respectively; albumin 3.1 g% (w/v), 3.4 g% (w/v) respectively.

Iron deficiency anaemia per se resulted in hypoplasia (total DNA decreased) and hypertrophy (protein: DNA ratio increased) of liver cells, hypertrophy of renal cells, and increased total DNA and reduced protein: DNA ratio in spleen. Iron deficiency anaemia also induced anorexia with resultant calorie malnutrition and this caused hypertrophy of cardiac and renal cells and hypertrophy (protein: DNA ratio decreased) in brain.