bluuebunny/crossref_metadata_2025 huggingface dataset:
The Periodic Acid—Schiff Reaction of Lymphocytes in Human Malignant Disease
Authors: Crowther D. , Fairley G. Hamilton , Sewell R. L.
Published: March 2008

Increased P.A.S. scores have been found in lymphocytes from patients with untreated Hodgkin's disease whereas few patients with advanced carcinoma had high scores before treatment. Patients with Hodgkin's disease treated with radiotherapy and chemotherapy showed increased P.A.S. staining over pretreatment levels. Patients with acute lymphoblastic leukaemia in remission and patients with advanced carcinoma also had high P.A.S. scores following treatment.

Individual analysis of delayed hypersensitivity responses in patients with Hodgkin's disease and patients with advanced carcinoma revealed no correlation between this parameter of cellular immunity and the blood lymphocyte P.A.S. score. There was no correlation between the P.A.S. score and the presence of reactive hyperbasophilic lymphoid cells (plasma cells, immunoblasts and hyperbasophilic medium‐sized lymphocytes) in the lymphocyte preparations.
Serum Vitamin‐B12‐Binding Proteins in Kwashiorkor*
Authors: Grassmann R. , Retief F. P.
Published: March 2008

Summary. In contrast with plasma albumin and transport proteins such as transferrin and ceruloplasmin, vitamin B12‐binding proteins are not decreased in Cape Coloured children with kwashiorkor. Compared with normal coloured adults the mean serum vitamin B12 was increased while the unsaturated vitamin B12 binding capacity (UBBC) was markedly increased mainly due to elevation of the alpha‐1‐globulin vitamin B12 binder (alpha‐binder). In normal coloured children the UBBC was also increased with mean alpha‐binder intermediate between values found in kwashiorkor and normal coloured adults. The mean beta‐globulin‐vitamin B12‐binder (beta‐binder) was decreased in kwashiorkor. The total serum alpha‐1 and beta‐globulins, showed poor quantitative correlation with alpha‐and beta‐vitamin B12‐binders in these patients. Urinary vitamin B12‐levels were similar in kwashiorkor, normal children and adults. In the small series of adult Cape Coloured subjects studied, serum vitamin B12 and UBBC values were higher than in white adults.

The alpha‐ and beta‐binders of kwashiorkor and normal children adequately transferred 57 Co‐vitamin B12 to rat liver homogenate while the alpha‐binder of chronic myeloid leukaemia transferred less efficiently.
In‐Vitro Prediction of Clinical Response to Chemotherapy in Childhood Acute Leukaemia
Authors: Laurie H. C. , Willoughby M. L. N.
Published: March 2008

Summary. An in‐vitro test of drug sensitivity has been performed on leukaemic blast cells obtained from eight children on 11 occasions. The test depends upon the per cent survival of the leukaemic cells during short‐term culture when exposed to appropriate concentrations of Daunorubicin, Vincristine and Prednisolone, singly or in combination. The in‐vitro results showed a satisfactory correlation with the subsequent in‐vivo tumoricidal effect of Daunorubicin in combination with Vincristine, and would appear to have practical predictive value for selecting drug therapy for such patients.
A Low Km Phosphoenolpyruvate Mutant in the Amish with Red Cell Pyruvate Kinase Deficiency
Authors: Oski Frank A. , Bowman Herbert
Published: March 2008

Summary. The biochemical heterogeneity of red cell pyruvate kinase (PK)‐deficiency was demonstrated in a study of six patients with this abnormality. Three siblings of an Amish kindred were found to possess a mutant enzyme with a decreased Km phosphoenolpyruvate. In this kindred the Km PEP ranged from 0.018 to 0.024 mM (normal 0.055–0.067 mm). Two deficient patients were found to have an enzyme with a normal Km PEP, while in the sixth patient the Km PEP was increased to 0.120 mM.

In all patients the red cells possessed increased quantities of the glycolytic intermediates proximal to the PK step, reduced levels of ATP and reduced glycolysis for cell age.

When reconstituted haemolysates from these patients were supplemented with PK, a correction of the glycolytic rate was observed. No acceleration of glycolysis occurred in PK‐supplemented normal or reticulocyte‐rich haemolysates.

These studies re‐emphasize the heterogeneity of PK deficiency and demonstrate that this deficiency alone can result in an impairment in red cell glycolysis.
Immunochemical Quantitation of Human Transferrin in Pregnancy and during the Administration of Oral Contraceptives
Authors: Jacobi J. M. , Powell L. W. , Gaffney T. J.
Published: March 2008

Summary. The effects of pregnancy and oral contraceptive administration on serum transferrin levels were studied using an immunochemical method of estimation. Serum iron, total iron‐binding capacity (TIBC) measured chemically, plasma bound iodine (PBI) and serum glutamic oxalacetic transaminase (SGOT) were also estimated on the same samples. The results show that the striking elevation in TIBC produced by oral contraceptives is due to increase in the transferrin level in the serum. The increase in serum transferrin, TIBC and PBI following the administration of oral contraceptives were of the same order as the changes produced physiologically during the second half of pregnancy. SGOT values were all normal. The findings suggest that changes in transferrin and other serum proteins produced by oral contraceptives are not due to liver damage but perhaps to increased protein synthesis. However, further study is necessary to elucidate the factors regulating the serum transferrin concentration and the effect on these of synthetic hormones.
Effect of Splenic X‐Irradiation on Bone Marrow Function: Experimental Studies of a Serum Mitotic Inhibitor in Rabbit and in Patients with Chronic Myelocytic Leukaemia
Authors: Maurice P. A. , Williner B. , Gindrat J. J. , Brand A.
Published: March 2008

Summary. The effect of a selective splenic irradiation on bone marrow function was studied in rabbits given a single splenic exposure with 300 r. of X‐rays. Serum collected shortly thereafter decreased mitotic activity in suspensions of normal rabbit bone marrow. This in vitro inhibitory effect was only transiently demonstrable in the serum appearing 2 hours after irradiation and disappearing 3 hours later.

Five patients with chronic myelocytic leukaemia in relapse receiving splenic radiotherapy in large single doses of 200–400 r. (surface dose) were studied along these lines. Serum collected 3 hours after X‐ray treatment was tested with suspensions of normal bone marrow and was found to decrease erythroblastic mitotic activity significantly below the control values observed with serum collected before irradiation. The magnitude of this in vitro effect was to some extent related to the spleen size and the radiation dose. No differences were observed between bone marrow suspensions incubated with pre‐irradiation leukaemic serum and normal control serum.
Blood Volume Changes in Splenomegaly
Authors: Donaldson G. W. K. , McArthur Marjory , Macpherson A. I. S. , Richmond J.
Published: March 2008

Summary. Blood volume changes have been measured in 65 patients with splenomegaly due to a miscellany of causes. The red‐cell mass is often normal despite the fact that anaemia is present, and the anaemia is in part due to sequestration of red cells in a splenic pool and haemodilution of the red cells in an expanded plasma volume. Both factors may be relieved by splenectomy although the ultimate prognosis is dependent on the primary disease present.
Porphyrin Metabolism in Experimental Hepatic Siderosis in the Rat
Authors: Shanley B. C. , Zail S. S. , Joubert S. M.
Published: March 2008

Summary. Experimental hepatic siderosis in the rat due to dietary iron overload produced increased urinary excretion of uro‐ and coproporphyrin which was further aggravated by concurrent drinking of alcohol. On the basis of these findings it is considered very likely that the invariable presence of hepatic siderosis in symptomatic porphyria is more than incidental and that the presence of excessive iron in the liver cells is an important factor determining the development of symptomatic porphryia. Liver ALA synthetase activity was increased in the alcohol‐consuming animals but iron overload alone had no effect on the activity of this enzyme. The mechanism whereby siderosis influences hepatic porphyrin metabolism is unknown. No effect on hepatic mitochondrial coproporphyrinogen oxidase was found. It is suggested that in the siderotic animals and in patients with symptomatic porphyria there is interference with a normal disposal route for excessive haem precursors.
Microangiopathic Haemolytic Anaemia and Mucin‐forming Adenocarcinoma
Authors: Brain M. C. , Azzopardi J. G. , Baker L. R. I. , Pineo G. F. , Roberts P. D. , Dacie J. V.
Published: March 2008

Summary. Twelve patients are described who developed well‐marked micro‐angiopathic haemolytic anaemia in association with metastatic carcinoma. The tumours originated in the stomach in six cases, in the breast in two cases, in the lung in one case and the origin was uncertain in three cases. All 11 tumours studied were found to be mucin‐secreting adenocarcinomas.

Ten out of the 12 patients were thrombocytopenic. Fibrinogen metabolism was studied in four patients and in each patient the catabolism of fibrinogen was found to be greatly increased despite normal or near normal plasma fibrinogen levels and an absence of overt fibrinolysis. Fibrin degradation products were demonstrated in the serum of five out of six patients. Hyaline thrombi were seen in the small blood vessels in the kidneys and suprarenals in one patient and in the myocardium in two patients, while changes suggestive of organized thrombi were present in the interlobular arteries of the kidneys in three patients.

It is thought likely that the microangiopathic haemolytic anaemia develops secondarily to intravascular coagulation brought about by thromboplastins derived from mucin‐forming tumour cells which have entered blood vessels, and that contact between circulating red cells and tumour emboli within blood vessels may be an additional cause of red‐cell damage.
Iron Metabolism and Absorption Studies in the X‐linked Anaemia of Mice
Authors: Pinkerton Peter H. , Bannerman Robin M. , Doeblin Thomas D. , Benisch Barry M. , Edwards John A.
Published: March 2008

Summary. The X‐linked anaemia of mice (gene symbol, sla) is hypochromic and microcytic, and the stainable iron stores are reduced. Chemical estimates of total body iron content and serum iron concentration show low values and the total serum iron binding capacity is elevated in anaemic mice. Rapid plasma iron clearance and increased iron utilization provide further confirmation of iron deficiency in anaemic animals. Alterations in activity of haem‐containing enzymes have been sought in the heart, liver and kidney of anaemic mice, and slightly decreased activity found only in kidney cytochrome oxidase.

The blood volume of mice with X‐linked anaemia is increased in spite of decreased red cell mass, and thus the anaemia is in part due to dilution. The cause of the increased blood volume has not been elucidated, but it may be related to splenic enlargement. In contrast to iron depleted humans and experimental animals, mice with X‐linked anaemia show impaired rather than increased intestinal iron absorption, indicating that the anaemia is a consequence of iron malabsorption. The defect in iron absorption may be an isolated one, since evidence of impaired retention of orally administered radio‐iodinated triolein, radio‐zinc, radio‐copper and radio‐cobalt has not been found. It is suggested that the genetically‐determined defect in the intestinal mucosa of mice with X‐linked anaemia may be due to deficiency of either an enzyme or a carrier substance necessary for the normal transfer of iron from the intestinal mucosal cell to the plasma.
Fletcher Factor Deficiency: A Report of Three Unrelated Cases
Authors: Hattersley Paul G. , Hayse Dorothy
Published: March 2008

Summary. The authors report three unrelated patients who apparently have a severe deficiency of the ‘Fletcher factor’. None had a haemorrhagic tendency, and all had normal bleeding times, prothrombin times and thrombin times. All three showed defective intrinsic thromboplastin production, as evidenced by much prolonged kaolin activated partial thromboplastin time (PTT). None had deficiencies of factors VIII, IX, XI or XII. The prolonged PTT of each failed to shorten when his plasma was mixed with proven Fletcher deficient plasma. The plasma of one was assayed with plasma from a reference case of Fletcher deficiency and found to contain less than 1% of the normal activity. The prolonged PTT of each came down into or near the normal range on longer kaolin activation.
Haematological Changes in Heat‐Acclimated Golden Hamsters
Authors: Meyerstein Naomi , Cassuto Yair
Published: March 2008

Summary. Haematological changes were investigated in heat‐acclimated hamsters. Haemoglobin, packed‐cell volume, and red‐cell counts were not affected by heat acclimation. Glucose uptake and osmotic fragility in the red blood cells of these animals were increased. The red cell ATP level was lower in heat‐acclimated than in control hamsters. No change was observed in the density distribution of the red cell population in heat‐acclimated hamsters. The resemblance of these cells to the red cells of hereditary spherocytosis and pyruvate‐kinase deficiency is discussed.
Pernicious Anaemia in Indian Immigrants in the London Area
Authors: Britt R. P. , Stranc W. , Harper C.
Published: March 2008

Two out of 15 cases of megaloblastic anaemia in Punjabi immigrants in the Southall area of Middlesex, studied in one year, were found to have all the features of Addisonian pernicious anaemia. This unexpected finding in Asiatics calls for a reappraisal of the previously accepted rarity of this disease in dark‐skinned races and draws attention to the need for consideration of pernicious anaemia as a cause of megaloblastic anaemia in the Indian immigrant.
The Extraction and Separation of Activators and Inhibitors of Fibrinolysis from Bovine Endothelium and Mesothelium
Authors: Pugatch E. M. J. , Foster E. A. , Macfarlane D. E. , Poole J. C. F.
Published: March 2008

Extracts of endothelial cells and of mesothelial cells have been shown to contain both an activator and an inhibitor of fibrinolysis. While activator predominates in material obtained from endothelium, the converse is true for mesothelium. Electrophoretic fractionation on acrylamide gel showed that samples could be obtained showing each type of activity without the other. In terms of the current concepts of the mechanism of fibrinolysis, these two substances seem to be a plasminogen activator and an anti‐plasmin respectively.
Differences between Rh(D) Negative Subjects in Response to Rh(D) Antigen
Authors: Mollison P. L. , Frame Marion , Ross Margaret E.
Published: March 2008

Summary Further evidence is produced of the existence of two kinds of Rh negative subject: the first forms anti‐Rh after a single injection although sometimes in such a low concentration that a clearance study with a small dose of Rh positive red cells is required to detect it; antibody usually becomes detectable serologically after a second, spaced injection; the second kind of Rh negative subject fails to form anti‐Rh even after several injections and has a repeatedly normal survival of Rh positive red cells and may be incapable of becoming immunized to the Rh antigen. In the present series of 34 Rh negative subjects, approximately 50% became immunized following injections of Rh positive red cells; the number is not significantly different from the incidence of approximately 60% reported in other published series. Some further evidence is provided that the rate of clearance of Rh positive red cells is more sensitive than any serological test in indicating the presence of a low concentration of anti‐Rh and that different examples of anti‐Rh in presumably similar concentrations in the plasma produce very different rates of red cell clearance. Of seven subjects given at least two injections of D positive Bua‐positive red cells, four formed anti‐D, but only one formed anti‐Bua.
Method to Determine the Degree of ADP‐Induced Platelet Aggregation in Circulating Rat Blood (‘Filter‐loop Technique’)
Authors: Hornstra G.
Published: March 2008

Summary.

A technique to determine experimentally induced thrombocyte aggregation continuously in circulating rat blood is described. The blood pressure is measured before and behind a microfilter which has been placed in continuity with the arterial circulation. Aggregation is induced by infusing adenosine diphosphate (ADP). The aggregates partly obstruct the filter, thus causing the blood pressure before and behind the filter to change. The degree of aggregation is calculated from these changes.

On administration of ADP‐doses between 0.0175 and 0.2 μg/30 s the relationship between log ADP and the aggregation does not deviate from a straight line.

When two aggregation measurements are carried out using the same ADP‐dose on the same animal, the values obtained do not differ. However, when the number of measurements on the same animal is extended further, a significant, rectilinear downward course of the aggregation is observed.
The Formation of Foetal and Adult Haemoglobin in Cell Cultures of Neonatal Calf Marrow
Authors: Gabuzda Thomas G. , Silver Ruth K. , Chui Lily Cheung , Lewis Hugh B.
Published: March 2008

Summary Neonatal erythroid cells in the bovine respond to erythropoietin in vitro with a pari passu increase in the synthesis of both foetal and adult haemoglobins. With marked stimulation the effect upon the latter predominates. The conditions of cell culture, however, promote the formation of a protein with chromatographic characteristics of foetal gamma‐globin subunits, quite independently of the presence of erythropoietin or of haem synthesis. The results suggest that erythropoietin might be assigned a significant although indirect role in the gradual switchover of haemoglobin types during development.
Acute Complement‐mediated Haemolysis in the Rabbit: Relationship between the Thrombocytopenia and Neutropenia and Complement Consumption
Authors: Brown D. L.
Published: March 2008

Summary. There appears to be a direct relationship between complement consumption in the rabbit (demonstrated by a fall in CH50 and plasma C3 concentration) and the temporary disappearance of platelets and neutrophils from the circulation during IgM cold antibody induced intravascular haemolysis. Studies with 51Cr‐labelled platelets showed that although the platelet counts returned to initial values following the thrombocytopenia, 18–38% of the labelled platelets failed to return, suggesting platelet loss at the site of sequestration (mainly the lungs) and dilution of the recirculating platelets with unlabelled platelets from another pool. There is no evidence that these events trigger intravascular coagulation. Complement‐depleted rabbits are totally refractory to further attempts to produce lysis, thrombocytopenia and neutropenia by cold antibody, though, even when complement activity in the plasma is allowed to recover, the lytic response to doses of cold antibody similar to those originally given, is reduced. The surviving circulating red cells are coated with C3 following an acute lytic episode and the immune‐adherence of neutrophils and platelets to fixed‐C3 on red‐cell membranes in the pulmonary circulation provides one possible mechanism for the thrombocytopenia and neutropenia.
Factor V: An Activator of Factor Xa in the Absence of Prothrombin
Authors: Colman Robert W.
Published: March 2008

Summary. Purified factor V accelerates the rate of conversion of prothrombin to thrombin by activated factor X (factor Xa) in the presence of phospholipid and calcium. Factor V potentiates the arginine esterase activity of factor Xa more than three‐fold in the presence of phospholipid and calcium but in the absence of prothrombin.

The increase of factor Xa esterase activity as a function of factor‐V concentration demonstrated signoidal kinetics and a linear Hill plot, suggesting cooperative binding of factor V to multiple sites on the phospholipid micellar surface.

An increase in both Km and Vm of factor Xa for tosyl l‐arginine methyl ester occurs in the presence of factor V, suggesting that factor V enhances the dissociation of the factor‐Xa substrate complex. In addition, factor V alters the catalytic efficiency of factor Xa toward various substituted basic amino acid esters.

Based on these observations, a model is suggested in which factor V interacts with factor Xa on the surface of a phospholipid micelle to alter the affinity of factor Xa for certain susceptible bonds on the prothrombin molecule.
A Comparative Study of Hypersplenism in Reactive and Congestive Splenomegaly
Authors: Bagshawe A.
Published: March 2008

Summary. Anaemia, leucopenia, and thrombocytopenia due to hypersplenism have been compared in 75 patients. Forty‐six patients had congestive splenomegaly due to portal hypertension. Twenty‐nine patients had reactive splenomegaly due in 27 to idiopathic tropical splenomegaly, and in two to visceral leishmaniasis. The only definite difference between the two groups was a lesser degree of lymphopenia in patients with reactive splenomegaly. It is suggested that this difference may be explained by an increase in production of lymphocytes in idiopathic tropical splenomegaly and that manifestations of hypersplenism are not directly influenced by histological or haemodynamic differences within the enlarged spleen.
Saline Agglutinating Anti‐K and Anti‐k in the Apparent Absence of IgM Antibody
Authors: Hopkins D. F.
Published: March 2008

Summary. Eighteen anti‐K and three anti‐k sera were studied; each was serologically active at 37°C, with a saline agglutinating antibody titre of 1 and a higher indirect anti‐globulin titre. It is shown that saline agglutination at a titre of 1 can occur in the absence of saline agglutinating IgM anti‐K or anti‐k. No IgA anti‐K or anti‐k was found.
Erythrokinetic Studies in Thalassaemia
Authors: Shahid M. J. , Sahli I. T.
Published: March 2008

Summary.

Erythrocyte survival studies were performed in a group of thalassaemic patients. The survival and sites of destruction of autologous and normal donor cells were determined. These studies were repeated in patients who had undergone splenectomy. The life span of the autologous red cells was found to be invariably shortened with some evidence of splenic sequestration. On the other hand, the life span of the donor cells was normal or decreased after repeated blood transfusions.

Following surgery, there was no noticeable improvement in the survival of the patient's abnormal cells, while transfused red cells now survived normally.
Immunological Studies of the Renal Erythropoietic Factor (Erythrogenin)
Authors: McDonald Ted P. , Zanjani Esmail D. , Lange Robert D. , Gordon Albert S.
Published: March 2008

Summary.

An immunological study of the renal erythropoietic factor (REF or erythrogenin) has been described. The experiments indicate that the erythropoietic activity of REF, as assayed in the polycythaemic mouse, is neutralized in vitro by addition of serum obtained from a rabbit previously immunized with a REF preparation. These anti‐REF sera had no effect on the biological activity of ESF; however, a depression in erythropoiesis was observed after injection of anti‐REF into normal mice. It is concluded that the injection of an antibody developed against the REF into normal mice interrupts normal erythropoiesis by reducing REF levels; the reduced REF levels lead to decreased amounts of ESF.
Methaemoglobin Formation by Ethyl N‐Hydroxycarbamate and Related Compounds
Authors: Nery R.
Published: March 2008

Summary. Methyl, ethyl and n‐propyl N‐hydroxycarbamates and hydroxyurea catalysed the conversion of haemoglobin into methaemoglobin in the presence of oxygen. The rate of the reaction with ethyl N‐hydroxycarbamate increased with increasing hydroxamic acid concentration. The conversion also occurred when urethane was incubated with oxyhaemoglobin in the presence, but not in the absence, of an in vitro metabolizing system.
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 R2R2 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 R2R2 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.
Assay of Megakaryocytopoiesis in Thrombocytopenic Rats
Authors: Odell T. T. , Jackson C.W. , Friday T.J. , Du K. Y.
Published: March 2008

Summary. Rats were given exchange transfusions with different volumes of platelet‐poor blood, injected 24 hr later with tritiated thymidine, and killed after another 24 or 36 hr. Autoradiograms of bone marrow smears were made and the labelling index of megakaryocytes was determined. The labelling index was proportional to the degree of thrombocytopenia induced by exchange transfusion. The results therefore demonstrate that the number of circulating platelets exerts a rather delicate control over megakaryocytopoiesis. In addition, the potential of this procedure for studying megakaryocytopoiesis, its regulation, and its abnormalities is indicated.
Blood and Bone‐Marrow Lysozyme in Neutropenia: An Attempt towards Pathogenetic Classification
Authors: Hansen Niels Ebbe , Karle Hans
Published: March 2008

Summary. Thirty‐four consecutive patients with neutropenic disorders of various aetiologies were examined with determinations of lysozyme (muramidase) activity in plasma from peripheral blood and bone‐marrow. Based on these activities the patients were tentatively grouped in three classes in terms of decreased production, increased destruction, and combinations of these. Lysozyme activities closely followed changes in the clinical states of the patients.
The Influence of Fibrin Crosslinking on the Kinetics of Urokinase‐Induced Clot Lysis*
Authors: McDonagh R. P. , McDonagh Jan , Duckert F.
Published: March 2008

Summary. The effect of fibrin crosslinking on the lysis of plasma clots was investigated with plasma from a patient congenitally deficient in plasma factor XIII (fibrin stabilizing factor). The thrombin‐activated plasma factor XIII was found to render clots more resistant to fibrinolysis when urokinase (UK) was used to induce plasminogen activation. Incorporation of UK in the clot by addition to plasma immediately before clotting resulted in a log‐log relationship when lysis time was plotted against UK concentration, with greater differences between normal and factor‐XIII deficient clots at lower UK concentrations. Addition of UK to the clot externally, after preincubation of the clot, gave linear plots on rectangular coordinates when either plasma or euglobulin fraction was used; and the difference in lysis time between factor‐XIII deficient and normal clots was nearly constant over the range of UK concentrations tested. When the fluorescent amine, dansylcadaverine, was used to measure factor‐XIII activity quantitatively, plasma clot lysis times were found to be directly proportional to amine‐incorporating activity over a wide range of activities at low UK concentrations. The range of proportionality was reduced when UK concentration was increased. Addition of purified factor XIII to the patient's plasma restored the resistance of these clots to within the normal range.
IRON REQUIREMENTS IN INFANCY
Authors: Burman David
Published: March 2008

Iron deficiency is the commonest nutritional deficiency in paediatric practice, particularly in the first 2 yr of life. This review of iron requirements in full‐term normal infants includes the findings of a survey carried out in Bristol from 1965 to 1968 on infants aged 3–24 mth (Burman, 1970). The much more severe problems of the premature are not considered here.
Fibrinogen Amsterdam, Another Hereditary Abnormality of Fibrinogen
Authors: Janssen Catherine L. , Vreeken J.
Published: March 2008

Summary. A coagulation defect, characterized by a prolonged thrombin and pro‐thrombin time, was discovered in a family without haemorrhagic diathesis. The disorder is caused by a delayed aggregation of fibrin monomers. Patient's and normal purified fibrin monomers showed the same aggregation properties, but the patient's fibrin monomers aggregated abnormally in the presence of the α2‐globulin fraction of plasma. The presence of an abnormal fibrinogen is postulated. The inheritance of this fibrinogen is compatible with an autosomal dominant trait.
Polyploidization of Megakaryocytes in Normal Humans, in Patients with Idiopathic Thrombocytopenia and with Pernicious Anaemia
Authors: Queisser U. , Queisser W. , Spiertz B.
Published: March 2008

Summary. Polyploidization of human megakaryocytes was studied in bone marrow aspirates from three normal individuals, three patients with idiopathic thrombocytopenic purpura (ITP) and three patients with pernicious anaemia (PA). The cells were labelled in vitro with tritiated thymidine and analysed by a combined cytophotometric and autoradiographic method. Cells were divided into types I, II and III.

Normal megakaryocytes showed ploidy stages from 4c to 32c, the 4c stage occurring only in type I. The labelling indices showed that in normal megakaryocytes polyploidization takes place in type I and II and not in type III cells. This study provided evidence for alternation of DNA synthesis and rest periods. It is postulated that rhythmical polyploidization in megakaryocytopoiesis takes place. The progressive increase in the proportion of cells in successive resting periods (G‐phases) suggests that high ploidy cells have longer resting periods than low ploidy cells.

In ITP, megakaryocyte morphology, labelling indices and distribution of DNA content were normal. Assuming a normal ploidy composition in ITP, the megakaryocytic hyperplasia observed in typical cases may be explained by an increased influx from the unrecognizable progenitor cell.

In PA, an arrest of megakaryocytic DNA synthesis was observed comparable to that found in megaloblastic erythropoiesis.
Deduction of Mean Red‐Cell Life‐Span from 51Cr Survival Curves*
Authors: Garby L. , Mollison P. L.
Published: March 2008

Summary. Twenty‐two estimates of Cr red‐cell survival in normal subjects, using the ‘citrate‐wash’ method of labelling, are described; results obtained with this method are shown to have given closely similar results in three different laboratories. By contrast, methods in which 51Cr is added to ACD blood have given a much wider range of normal values.

In 14 patients red‐cell survival was estimated simultaneously with DF32P and 51Cr, the latter results being corrected for Cr elution using empirical factors. Estimates of mean red‐cell life‐span by the two methods agreed fairly closely. It is concluded that when 51Cr is used as a red‐cell label, the citrate‐wash method, or some other method which has also been shown to give reproducible results in different laboratories, should be used and the results should then be corrected so as to obtain an estimate of mean life‐span. Such estimates should be more useful in clinical practice than uncorrected Cr survival data.
Serum Half Life in Mice of Colony Stimulating Factor Prepared from Human Urine
Authors: Metcalf D. , Stanley E. R.
Published: March 2008

Summary. Partially purified preparations of the colony stimulating factor (CSF) from human urine were given as a single intravenous injection to adult C57BL mice. Assays for human CSF in the sera of these mice were performed in cultures of C57BL bone marrow cells using a discriminatory rabbit anti‐human CSF antibody preparation, incapable of blocking the action of mouse serum CSF. The half life of injected CSF varied from 1.7 to 3.7 hr (mean 2.9 hr). The injection of these human urine preparations caused a temporary elevation of mouse CSF levels in the serum of recipient mice, which prolonged the effective period of elevated CSF levels in the serum following injection.
The Effects of Phenothiazines on Human Erythrocytes: An Ultrastructural Study
Authors: Preston F. E. , Lee D.
Published: March 2008

Summary. The in vitro effects of two phenothiazine derivatives on human erythrocytes have been studied by scanning electron microscopy.

The induced changes were identical for both compounds and consisted of cup‐shaped deformities of the erythrocytes, sphering and membrane defects. The type and degree of alteration was a function of the concentration of the phenothiazine derivative.

The demonstration of multiple surface membrane defects affords a satisfactory explanation of the haemolysis of red cells which have been exposed to chlorpromazine concentrations greater than 2.5 × 10−4m.
Re‐assessment of the Reliability of the Haematocrit
Authors: England J. M. , Walford D. M. , Waters D. A. W.
Published: March 2008

Summary. Significant quantities of plasma are trapped between the centrifuged red cells in the microhaematocrit. This produces a falsely high haematocrit and mean corpuscular volume, and a falsely low mean corpuscular haemoglobin concentration. Trapped plasma accounts for approximately 3% of the normal red‐cell column. Slightly higher values are found in macrocytic anaemias, but values as high as 5–6% may be found in the hypochromic anaemias, and even over 20% in sickled samples of blood.

It is suggested that automatic blood counters of the Coulter S type be set to record a true haematocrit without trapped plasma. This value is 1 1/2% less than the microhaematocrit value with normal blood. Absolute values in normal subjects under these conditions are reported.
The Prevalence of Iron Deficient Erythropoiesis and Anaemia in a Rural Jamaican Community
Authors: Ahern E. J. , Swan A. V. , Ahern V. N.
Published: March 2008

Summary

Serum iron, iron binding capacity and transferrin saturation were measured in 389 predominantly Negro adults from an agricultural community in Jamaica. The relationships between iron measurements and several other red cell characteristics were investigated and the possible influence of common inherited red cell defects was examined. Iron deficient erythropoiesis (transferrin saturation ± 15%) occurred in only a third of anaemic subjects. Values for total iron binding capacity were considerably lower than those found in a large random sample from Wales (Jacobs et al., 1969). These findings are considered in relation to the nutritional status of the population.
Heterogeneous Metabolism of Marrow Ferritins during Erythroid Cell Maturation
Authors: Shepp M. , Toff H. , Yamada H. , Gabuzda T. G.
Published: March 2008

Summary

Two metabolically distinct pools of ferritin exist side by side in the bone marrow. One has been designated‘anabolic’ since it accepts iron from transferrin and is presumably an isoferritin characteristic of erythroid cells. The other is primarily‘catabolic’, since it accepts iron from degraded haemoglobin and is considered an isoferritin of reticuloendothelial cells. Both of these isoferritins, however, incorporate iron during the period of erythroid cell maturation in the marrow, although the incorporation proceeds at markedly different rates. The incorporation of iron into both isoferritins can be demonstrated regardless of the route of administration of iron, i.e., whether by transferrin or by degraded haemoglobin. The results support the hypothesis that storage iron moves directly or indirectly from the ferritin pool of the developing erythroid cell to that of the reticuloendothelial cell. They also show that reticulothelial cell ferritin iron undergoes rapid reutilization to re‐enter the iron storage pool of erythroblasts.
The Relation between Erythropoiesis and Plasma Erythropoietin Levels in Normal and Genetically Anaemic Mice during Prolonged Hypoxia or after Whole‐Body Irradiation
Authors: Russell Elizabeth S. , Keighley Geoffrey
Published: March 2008

Summary

When normal mice (B6D2F1, WBB6F1‐ +/+ and WCB6F1‐ +/+) are exposed to constant hypoxia, they respond with a steady increase of PCV for about 3 weeks. Plasma erythropoietin increases sharply for the first 1 or 2 days only, then falls to control levels, with occasional temporary increases through the next 30–40 days. Genetically anaemic mice (WBB6F1‐W/Wv and WCB6F1‐Sl/Sld) respond differently. The W/W mice show an increase of PCV, and Sl/Sld mice do not, but both respond with large increases of plasma erythropoietin levels which persist, except for some temporary falls, through 16–40 days. The response to hypoxia of chimeric W/W mice, their anaemia cured by implantation of +/+ marrow cells, resembles that of normal +/+ mice much more than that of anaemic W/W mice. Although normal WBB6F1‐ +/+ mice recover after 200 R whole‐body irradiation at rates similar to those of other normal mice, anaemic WBB6F1‐W/W mice show delayed onset of haemopoietic recovery in spite of significant production of erythropoietin. Exogenous erythropoietin injected into mice disappears more slowly from the plasma of anaemic W/W mice than from the plasma of normal +/+ mice, and erythropoietin which has been passed through WBB6F1‐ +/+ normal mice is not thereby made as effective in anaemic W/W mice as it is in normal mice. These findings are consistent with the view that although both W/W and Sl/Sld anaemic mice can produce large amounts of erythropoietin over prolonged periods, W/W mice remain anaemic because of a genetic defect in RBC precursors, and Sl/Sld mice remain anaemic because of a genetic defect in some part of the internal environment in which the RBC must develop.

WBB6F1‐W/W anaemic mice, when exposed to hypoxia, excrete erythropoietin in their urine. When these mice have their kidneys removed and they are exposed to hypoxia for a short time there is no significant production of erythropoietin.

The suggestion is made that some genetically anaemic large domestic animals, if they could be found, might be useful and needed sources of erythropoietin.
Urokinase Therapy: Dosage Schedules and Coagulant Side Effects
Authors: Prentice C. R. M. , Turpie A. G. G. , McNicol G. P. , Douglas A. S.
Published: March 2008

Summary

The effect of a new preparation of urokinase (Roche) has been studied, in the laboratory and in 10 patients and three volunteers. It is a non‐toxic and active fibrinolytic agent if given in adequate dosage, but it was found that a small initial infusion gave rise to a paradoxical coagulant effect in the recipient. This effect was associated with the formation of‘cryofibrinogen’ and an increase in factor‐VIII activity. The coagulant effect was probably mediated by a low‐grade process of plasminogen activation rather than due to the preparation of urokinase itself. The preparation did have minor intrinsic thromboplastic activity similar to that described in other preparations of urokinase, but it is unlikely that this would produce a significant effect in vivo. The coagulant effect could be overcome by increasing the initial dose of urokinase to produce rapidly the haemostatic defect normally associated with fibrinolytic therapy.
Effect of Vincristine on Platelet Production in Mice
Authors: Rak K.
Published: March 2008

Summary

Platelet production was investigated using [75Se]selenomethionine bio‐assay in C57BL mice after a single injection of vincristine within the dose range 0.2–3.2 mg/kg. The changes in the circulating platelet count were also followed. There was an immediate, not strictly dose‐dependent, fall in the number of platelets, a quick recovery with an overshoot after small doses, delayed recovery with a moderate overshoot after intermediate doses and a slow recovery returning to normal levels after large doses. The drug caused an overproduction of platelets with every dose used, but this was not necessarily reflected in the peripheral platelet count. It seems unlikely, at least after the smaller doses, that the early fall in platelets plays a role in the increased platelet production. Platelet precursors are resistant to a single dose of vincristine and the drug may have a primary stimulatory effect on the megakaryocytopoietic system.
Comparative Effects of Fibrinogen Degradation Fragments D and E on Coagulation
Authors: Larrieu M. J. , Rigollot C. , Marder V. J.
Published: March 2008

Summary

The mechanism of anticoagulant action of the fibrinogen degradation products (fragments D and E) has been investigated using purified products in selected esterolytic, proteolytic and coagulation systems. Their modes of action were distinctly different. Fragment D acted primarily by inhibiting fibrin monomer polymerization, while fragment E did not significantly alter this process. The latter product appeared to be a competitive inhibitor of the clotting action of thrombin on fibrinogen. Its comparative effect in thrombin proteolytic and esterolytic systems indicated that fragment E did not irreversibly inactivate the enzyme centre of thrombin. Rather, it appeared to block a thrombin binding site essential for proper alignment with the fibrinogen substrate. This competitive inhibition suggests that fragment E may derive from and share physical structures with the thrombin‐susceptible, N‐terminal portion of the fibrinogen molecule.
Observations on the Survival of Circulating Reticulocytes
Authors: Zervas J. D. , Delamore I. W. , Cunliffe D. J. , Israëls M. C. G.
Published: March 2008

Summary. The survival of reticulocytes carrying HL‐A antigens is reduced in patients with circulating cytotoxic HL‐A antibodies. The survival of mature red cells is also reduced in these patients but to a lesser degree. Both mature red cells and reticulocytes survive longer in patients without circulating cytotoxic antibodies than reticulocytes (but not mature red cells) in a cytotoxic environment. The significance of these findings is discussed.
The Effect of Some Erythropoietic Agents on the ‘Tissue’ Tension of Oxygen
Authors: Thorling E. B. , Erslev A. J.
Published: March 2008

Summary. The effect was measured of four known erythropoietic agents (erythropoietin, haemolysate, cobalt chloride and testosterone propionate) on the 24‐hr iron utilization of hypertransfused male rats and on the oxygen tension in a subcutaneous air pocket. Only testosterone propionate failed to increase the 24‐hr iron utilization of hypertransfused rats. On the other hand, only cobalt chloride altered the oxygen tension in the gas pockets. A striking increase in PO2 was observed with cobalt chloride suggesting a block in oxygen utilization with intracellular hypoxia. Using more intense treatment of female hypertransfused rats with various androgen preparations, namely, testosterone propionate, norethandrolone and nandrolone decanoate, only the latter had significant erythropoietic effect. However, this was apparently not mediated by tissue hypoxia, since the oxygen tension in subcutaneous air pockets did not change.
The Metabolism of Maturing Reticulocytes
Authors: Gasko O. , Danon D.
Published: March 2008

Summary

The aerobic metabolism of populations of rabbit reticulocytes separated into age groups by differential flotation was measured by manometric techniques. The activity of the Krebs tricarboxylic acid cycle was studied by following the metabolism of substrates such as [2‐14C]acetate, [3‐14C]pyruvate and [6‐14C]glucose. These mitochondrial activities were found to decline with maturation of the reticulocytes. The mode of decline was studied and its significance is discussed.
The Iron Content of Intestinal Epithelial Cells and Its Subcellular Distribution: Studies on Normal, Iron‐Overloaded and Iron‐Deficient Rats
Authors: Richmond Veronica S. , Worwood Mark , Jacobs Allan
Published: March 2008

Summary. Small intestinal epithelial cells from normal, iron‐loaded and iron‐deficient rats were homogenized and fractionated by differential centrifugation. The iron content of the fractions was measured together with the activities of two iron containing enzymes, succinic dehydrogenase and cytochrome oxidase. A comparison of the values obtained from the iron‐overloaded rats with controls showed no significant increase in either the iron content or the enzyme activities. However, the iron‐deficient rats showed a marked decrease in both. In all three cases the concentration of iron was particularly high in the mitochondrial fraction. In irondeficient epithelial cells mitochondrial enzyme activity appeared in the soluble fraction suggesting mitochondrial damage.

It is suggested that body iron is reflected by mitochondrial iron status and function in the intestinal epithelial cells and that this is a factor determining cell uptake of iron from the gut lumen.
Identification of a New Vitamin B12 Binder (Transcobalamin III) in Normal Human Serum
Authors: Bloomfield F. J. , Scott J. M.
Published: March 2008

Summary. Fractionation of vitamin B12 binders in a normal human serum pool showed a distribution of 92% Transcobalamin II (TCII) and 8% Transcobalamin I (TCI) on DEAE‐cellulose chromatography. Separation of the same serum pool using gel filtration gave 74% TCII and 26% TCI. This 18% discrepancy could be due either to massive contamination of the DEAE‐cellulose TCII peak with TCI, or to the presence of a high molecular weight binder which elutes with TCII on DEAE‐cellulose, and with TCI on gel filtration.

Refractionation of the TCII peak showed it to be relatively uncontaminated with TCI. Removal of the low molecular weight binders with charcoal consistently gave a peak in the TCII area on DEAE, which subsequent gel filtration analysis showed to be of high molecular weight. This new binder is further distinguished from TCI by the observation that its vitamin B12 binding capacity does not increase to the same extent as TCI on fasting.

Since this binder could be demonstrated in 50 different normal sera, it is clearly not a pathological binder, and should be called Transcobalamin III (TCIII).
Haemoglobin Bart's in Newborn Nigerians
Authors: Folayan Esan G. J.
Published: March 2008

Summary. Using starch gel electrophoresis as a screening procedure, haemoglobin Bart's was detected in 5.1% of 1866 cord blood samples from newborn Nigerians. Studies on the babies including red cell osmotic fragility, haematological values and search for inclusion bodies of haemoglobin H and comparison with other babies without haemoglobin Bart's do not suggest alpha‐thalassaemia. The parents and sibs of the babies do not constitute a separate group within the population and do not show evidence of alpha‐thalassaemia. It is postulated that a developmental abnormality, i.e. asynchronism of the neonatal ‘switch off’ of gamma chains and activation of beta chain production, is responsible for the finding. This hypothesis is supported by the results of the frequency of, and concordance rate for haemoglobin Bart's in twins.