bluuebunny/crossref_metadata_2025 huggingface dataset:
Variations in the Red Cells in Paroxysmal Nocturnal Haemoglobinuria
Authors: Rosse Wendell F.
Published: March 2008

Summary. The red cells of 22 patients with paroxysmal nocturnal haemoglobinuria have been evaluated by the complement lysis sensitivity test of Rosse & Dacie. Four patterns of abnormal susceptibility to complement lysis were seen. In Group 1 (10 patients), markedly abnormal complement‐sensitive cells were present and cells of a second population were not distinguishable from normal cells. In Group 2 (four patients), markedly abnormal complement‐sensitive cells were present and the second population of cells was clearly distinguishable, but not markedly different from normal. In Group 3 (five patients), three populations of cells were present: a markedly abnormal complement‐sensitive population, a population of moderately abnormal cells and a population of normal‐appearing cells. In Group 4 (three patients), no cells with marked complement sensitivity were seen; two populations were present, one was apparently normal and the other moderately abnormal (3–4 times as sensitive as normal). During the period of observation two patients in Group 4 acquired a markedly abnormal complement‐sensitive population.

The proportion of cells in each population varied during the course of the illness. In three patients the proportion of complement‐sensitive cells increased during the onset of the illness, and in two patients the proportion decreased gradually during the resolution of the disease. Increase in the total production of red cells resulted in an increased proportion of complement‐sensitive cells, as did decrease in haemolytic rate. Increase in the haemolytic rate resulted in a decreased proportion of complement‐sensitive cells.
Iron Uptake by Rabbit Reticulocytes
Authors: Lane R. S.
Published: March 2008

Summary. In keeping with present concepts of internal iron exchange, it is thought that the two iron binding sites of transferrin molecules bind and donate iron in a similar manner. Since recent data, however, have suggested that iron attached at one iron binding site may be more readily available to cells than iron bound to the other site, a further study of in vitro iron exchange between transferrin and reticulocytes has been undertaken.

Transferrin samples were first incubated with reticulocytes to reduce the transferrin iron saturation; rates of iron uptake from incubated transferrin samples and appropriate non‐incubated controls with the same iron saturation were then compared. At 24% transferrin iron saturation, iron uptake from incubated transferrin was significantly less than from the control; at 48% transferrin iron saturation, iron uptake was the same from incubated transferrin and controls.

Two transferrin samples of equal protein concentration were prepared; each was 50% iron saturated. One sample contained twice the proportion of iron saturated transferrin molecules (2Fe‐transferrin) present in the other sample. Iron uptake by reticulocytes was decreased by 22–25% from the sample with less 2Fe‐transferrin molecules. Thus iron was exchanged very rapidly between 2Fe‐transferrin and reticulocytes.

It is proposed that the preliminary incubation of transferrin samples with reticulocytes caused a marked reduction in their 2Fe‐transferrin molecules which, at low levels of transferrin iron saturation, resulted in the incubated samples containing less 2Fe‐transferrin than the controls. In these circumstances, iron uptake from incubated transferrin was decreased when compared with the control.
Factor‐Xa Inactivation by Antithrombin III
Authors: Marciniak Ewa
Published: March 2008

Summary. The inactivation of the procoagulant activity of bovine factor Xa by antiproteinase present in antithrombin III preparation follows the pseudo‐first‐order kinetics with respect to factor Xa. The rate of inactivation is devoid of the dimension of factor Xa concentration when antiproteinase in excess is held constant. In the presence of physiological concentrations of factor V, phospholipids and ionic calcium, the affinity of factor Xa for antithrombin III drastically decreases, and the half‐life of the enzyme is very significantly prolonged. This biological stabilization of factor Xa requires the presence of all three substances: factor V, phospholipid and calcium. However, it is quantitatively dictated only by factor V concentrations. Calcium ions and phospholipid required for factor Xa protection from inactivation by antithrombin III have a rather low optimum concentration range, beyond which the original fast rate of inactivation tends to be restored. A direct interaction between antithrombin III and factor V or phospholipid was not found. Thus binding of factor V mediated by phospholipid and calcium ions, which brings about the increase in factor Xa proteolytic activity, also decreases the susceptibility of this enzyme to a biological inactivator in blood.
The Effect of Pyrimidine Compounds on the Potentiation of Adenosine Inhibition of Aggregation, on Adenosine Phosphorylation and Phosphodiesterase Activity of Blood Platelets
Authors: Rozenberg M. C. , Walker C. M.
Published: March 2008

Summary. Three pyrimidine compounds (dipyridamole, RA233 and VK 744) produced variable degrees of direct inhibition as well as potentiation of adenosineinduced inhibition of ADP aggregation of blood platelets. RA233 and VK744 were more potent direct inhibitors of platelet aggregation, whereas RA233 was a more powerful potentiator of adenosine–induced inhibition. A relation between the effect of these compounds on platelet aggregation and on adenosine phosphorylation and phosphodiesterase activity of platelets was looked for in an attempt to elucidate possible modes of action.

RA233 and dipyridamole were powerful inhibitors of [14C]adenosine phosphorylation by platelets and VK744 had no effect. There was no correlation with inhibition of platelet aggregation. Adenosine‐induced inhibition of platelet aggregation in the presence of dipyridamole could be maintained for at least 10 min after the rapid clearance of the adenosine with exogenous deaminase. The presence of the pyrimidine so modified the inhibition response that there was no correlation between the concentration of adenosine in the system and the degree or rate of recovery from the inhibition.

Dipyridamole, VK744 and RA233 produced 45%, 45% and 55% inhibition of phosphodiesterase activity as measured by the rate of breakdown of [3H]cyclic AMP to AMP in platelet lysates. There was possible correlation between the effect of the three pyrimidine compounds on platelet phosphodiesterase activity and their potentiatory action on adenosine‐induced inhibition of platelet aggregation. These findings suggested that adenosine might induce inhibition of platelet aggregation through the adenyl cyclase, cyclic AMP, phosphodiesterase system.
Increased Platelet Adhesiveness as a Familial Characteristic
Authors: Papayannis A. G. , Geary C. G. , Burn Aileen , Israëls M. C. G.
Published: March 2008

Summary. Two families are described in which many members were shown to have increased platclet adhesiveness, using a modification of the Salzman techniquc. The abnormality appears to be inherited as an autosomal dominant characteristic. In addition, one member of each family had an abnormally low level of plasma factor VIII (AHG) and a moderatcly severe haemorrhagic disorder, while two members of one of the families had factor‐VIII levels at the lower limit of normal. Several individuals showed a mild haemorrhagic disorder, but none had thrombotic manifestations. The significance of these findings and their distinction from those present in von Willebrand's disease is discussed.
The Detection of Factor‐VIII‐like Antigen in Haemophilic Carriers and in Patients with Raised Levels of Biologically Active Factor VIII
Authors: Denson K. W. E.
Published: March 2008

Summary. A rabbit antibody has been prepared against therapcutic factor VIII of intermediate purity. Using this antibody in quantitative immunoelectrophoresis, the results of Zimmerman et al (1971a, b) have been confirmed. Female carriers of haemophilia were classified with greater certainty than by the use of bioassay alone. The factor‐VIII‐like antigen was present in all haemophilic patients tested, and was reduced or absent in patients with von Willebrand's disease. The antigen was increased in all cases following physical exercise, the infusion of adrenaline and following major gynaecological surgery. Raised values of factor‐VIII‐like antigen correlated well with increase in biological activity of factor VIII. The method has been applied to whole plasma and the antigen may be quantitated directly without the necessity for initial ethanol fractionation of plasma.
The Clinical Features of Haemoglobin SC Disease in Jamaica
Authors: Serjeant G. R. , Ashcroft M. T. , Serjeant B. E.
Published: March 2008

Summary. The clinical and haematological features of 90 Jamaican patients with haemoglobin SC disease are reviewed. Mean haemoglobin levels indicated mild anaemia although individual haemoglobin levels were often within the normal range. The clinical features were qualitatively similar to those of homozygous sickle cell disease (SS disease) although they were generally less frequent and of lesser severity. Ocular pathology was an exception, occurring more frequently in SC disease than in SS disease even in age–sex‐matched groups. There is some evidence that the higher haemoglobin level in SC disease may be aetiologically related to retinal vascular disease.
Surface Immunoglobulins on Lymphocytes in Chronic Lymphocytic Leukaemia and Lymphosarcoma
Authors: Wilson J. D. , Hurdle A. D. F.
Published: March 2008

Summary. The density of surface immunoglobulins on peripheral blood lymphocytes from 10 patients with chronic lymphocytic leukaemia (CLL) and three patients with lymphosarcoma was examined using a sandwich radio‐immunolabelling technique. In healthy people two populations of lymphocytes are seen: densely labelled cells with a high surface immunoglobulin density or B cells and lightly labelled T cells. CLL lymphocytes were found to comprise a single population with labelling characteristics of B lymphocytes in eight patients and of T lymphocytes in two patients. In the three lymphosarcoma patients grain count histograms revealed two or three populations where the abnormal lymphocytes fell into the T cell type in two and into the B cell group in one patient. There were no essential clinical differences between these three patients.
Prothrombin during Warfarin Treatment
Authors: Brozović M. , Gurd L. J.
Published: March 2008

Summary. Prothrombin levels were studied in a group of hospital controls and a group of patients stabilized on long‐term warfarin treatment. The behaviour of prothrombin was also followed in two healthy subjects given a single oral dose of warfarin, and in four patients starting long‐term treatment with warfarin. Three techniques were employed in studying the changes in prothrombin; the measurement of prothrombin clotting activity, the estimation of total immunologically detectable prothrombin, and the detection of the structurally abnormal form of prothrombin in plasma.

The mean plasma prothrombin activity for the hospital controls and the patients stabilized on long‐term warfarin was 266 (range 160–376) and 107 (range 48–192) NIH thrombin units per ml respectively. The mean total immunologically detectable prothrombin concentration was 99 (range 63–132) and 87 (range 61–135) % of the normal reference level, respectively. The differences found were statistically significant.

No decrease in the immunologically detectable prothrombin levels, and a very slight fall in prothrombin activity were observed in two healthy subjects, given a single warfarin dose. The abnormal form of prothrombin was first detected 8 and 12 hr after the dose and persisted for at least 6 days in the plasma of both subjects. In patients followed from the start of the warfarin treatment, the abnormal form appeared within 12 hr of the first dose, and became the predominant form in plasma, at the latest, after 84 hr of treatment. The clotting activity fell to below 100 NIH units per ml, whereas the immunologically detectable prothrombin levels decreased after a longer time interval.

These results confirm that the major changes in therapeutic anticoagulation are the fall in prothrombin clotting activity and the appearance of an abnormal form of prothrombin in plasma. The levels of the immunologically detectable prothrombin in plasma are affected later and to a lesser extent.
A Genetically Determined Disorder with Features both of Thalassaemia and Congenital Dyserythropoietic Anaemia
Authors: Weatherall D. J. , Clegg J. B. , Knox‐Macaulay H. H. M. , Bunch C. , Hopkins C. R. , Temperley I. J.
Published: March 2008

Summary. What appears to be a hitherto unreported type of congenital anaemia has been found in six members of an Irish family. It is inherited in an autosomal dominant manner and is characterized by moderate anaemia, lifelong jaundice, cholelithiasis and splenomegaly, marked morphological abnormalities of the red cells (which are, however, well haemoglobinized), erythroid hyperplasia of the bone marrow with increased numbers of multinucleate red cell precursors, and the presence of large inclusion bodies in the normoblasts, both in the marrow, and in the peripheral blood after splenectomy. Potassium flux across the red cell membranes is increased and there is imbalanced globin chain synthesis with α‐chain production exceeding that of β‐chains by a factor of 2/1. Excess α‐chains in the bone marrow form a pool of similar magnitude to that observed in β‐thalassaemia heterozygotcs but the latter do not have red cell precursor inclusion bodies or the degree of ineffective erythropoiesis seen in the present cases. The most likely molecular mechanisms for this disorder are either an ‘overproduction abnormality’ of α‐chain synthesis, or a defect in cell division leading to increased amounts of genetic material per cell, a mechanism postulated recently as a basis for the unusual distribution of red cell enzyme levels in congenital dyserythropoietic anaemia.
Haematological Data in 312 Cases of β‐Thalassaemia Trait in Thailand
Authors: Pootrakui P. , Wasi P. , Na‐Nakorn S.
Published: March 2008

Summary. The haematological data are presented in 312 individuals of Thai or Chinese extraction with the high A2β‐thalassaemia trait. The mean haemoglobin concentrations were 12.1 g% among males and 10.8 g% among eemalcs; 54% of the subjects were not anaemic and all were asymptomatic. Low MCV, MCH and MCHC values were found in 67%, 81% and 6% respectively; erythrocytosis was detected in 34%. Variable hypochromia and microcytosis were usually present, but leptocytosis and red cell basophilic stippling were often absent. Decreased red cell osmotic fragility was always detected. Fifteen cases were found to have normal red cell morphology and 17 normal red cell osmotic fragility. The reticulocyte counts, although ranged up to 12%, were normal in the majority. The serum iron levels and unsaturated iron binding capacity were normal except in 11% of the cases where the scrum iron levels were lower than 50 μg%. Haemoglobin A2 levels varied from 3.4 to 7.8% with a normal distribution and a mean of 5.2%. Haemoglobin F levels varied from o to 7.8% with 58% elevated values. Analysis of variance revealed intrafamilial segregation of both haemoglobin A2 and haemoglobin F levels. The literature is reviewed and findings are compared.
Gaucher‐like Cells and Congenital Dyserythropoietic Anaemia, Type II (HEMPAS)
Authors: Dorpe A. Van , Orshoven A. Broeckaert‐Van , Desmet V. , Verwilghen R. L.
Published: March 2008

Summary. .‘Gaucher‐like cells’ were observed in the bone marrow of 18 out of 20 HEMPAS (CDA II) patients. These cells contain birefringent, PAS positive material. Further cytochemical procedures identified the inclusions as a glycoprotein or a glycopeptide but the presence of cerebrosides could not be excluded. An intralysosomal localization was suggested by electronmicroscopy.

HEMPAS is characterized by inefficient erythropoiesis and it is suggested that accumulation of a catabolite of the erythroblasts gives rise to these cells. A possible relation with the cell membrane anomaly of HEMPAS erythrocytes is discussed.
Sustained Erythropoietin Production in Nephrectomized Rats Subjected to Severe Hypoxia
Authors: Peschle Cesare , Rappaport Ira A. , Jori Gian P. , Chiariello Massimo , Gordon Albert S. , Condorelli Mario
Published: March 2008

Summary. The present studies indicate that rats of both sexes subjected to a hypoxic stimulus of severe degree (0.35 atmospheres of air) show sustained production of erythropoietin (Ep) up to 30 hr after bilateral nephrectomy. In contrast to this phenomenon, the Ep response to relatively mild hypoxia (0.45 atmospheres of air) declines rapidly and is totally abolished within either 12 hr (females) or 24 hr (males) after nephrectomy. In this regard, since orchidectomized rats and intact female animals show a similar decline of the Ep response curve, it seems likely that androgens play a major role in the above sex difference. The sustained Ep production in both anephric rodents exposed to severe hypoxia and ureter‐ligated rats subjected to mild hypoxic stimuli suggest that extrarenal Ep production is largely independent of the development of uraemia. It is postulated that the biogenesis of Ep in anephric rodents is mediated by either the triggering of extrarenal sources of Ep and/or erythrogenin (Eg) induced by severe hypoxia or activation of residual renal Eg following relatively mild hypoxic stimuli.
Effect of Isopropyl Methane Sulphonate (IMS) on Haemopoietic Colony‐Forming Cells
Authors: Schofield R. , Lajtha L. G.
Published: March 2008

Summary. A dose of isopropyl methane sulphonate (IMS) has been selected which depletes the population of CFU in the femur to 30–50%. During the subsequent 5–7 days the surviving population declines to between 0.5% and 2% of controls. It is shown that the IMS‐treated host is a satisfactory environment for growth of CFU in grafts from either normal or IMS‐treated donors although the grafts themselves behave differently from each other. The colonies produced from marrow from IMS‐treated donors are virtually devoid of CFU, whereas 70% of those from control donors contain CFU. It is proposed that IMS, at the dose selected, kills primary, self‐maintaining CFC but does not kill the derived non‐self‐maintaining cells which, nevertheless, are also capable of spleen colony formation. It is suggested that the chemical provides a useful tool for the study of the haemopoietic stem cell complex.
Quantitative Haemagglutination
Authors: Greenwalt T. J. , Steane E. A.
Published: March 2008

Summary. The polycations Polybrene®, protamine and polylysine aggregate red cell suspensions. Mild neuraminidase treatment abolishes aggregation by Polybrene® and protamine, but not by polylysine. Blood samples, separated into old and young populations on the basis of density, aggregate to the same degree despite the decreased total NANA of older cells. Aggregation appears to be mainly dependent upon the degree to which the polycation disturbs the vicinal water of the erythrocyte. Desialated red cells are probably less hydrated and do not compete as vigorously with Polybrene® and protamine for the available water. Polylysine may act by cross‐linking red cells, but more Polybrene® and protamine is required to cause aggregation than would completely saturate surface NANA. Protamine may bind to some NANA molecules preferentially since it prevents total desialation by neuraminidase, but neither Polybrene® nor polylysine significantly affects neuraminidase action.
The Exchangeable Splenic Platelet Pool Studied with Epinephrine Infusion in Idiopathic Thrombocytopenic Purpura and in Patients with. Splenomegaly
Authors: Branehoug Ingmar , Weinfeld Aleksander , Roos Bengt
Published: March 2008

Summary. The exchangeable splenic platelet pool (ESPP) was studied with epinephrine infusion and platelet labelling with 51Cr in five healthy students, 10 patients with idiopathic thrombocytopenic purpura (ITP) and 10 patients with splenomegaly. Five of the ITP‐patients were studied after splenectomy. Platelet recovery of infused labelled platelets was calculated in all subjects and also in nine healthy volunteers who had been splenectomized for traumatic rupture of the spleen. Spleen size was determined by gamma camera scintigraphy. It was shown that the spleen is the only site of an exchangeable platelet pool in ITP and that this pool was of the same size in ITP‐patients as in the normal controls, viz ∼30% of the total body platelet mass.

In patients with splenomegaly the ESPP was larger than that in controls and ITP‐patients. A highly significant correlation was found between the ESPP and the spleen volume. In splenectomized and in non‐splenectomized ITP‐patients platelet recovery was significantly less than in their respective control groups, indicating that a proportion of the labelled platelets was immediately removed from the circulation after infusion into an ITP recipient and that the recovery of labelled platelets cannot be used as a measure of the ESPP in ITP.

It is suggested that the early destruction of platelets may be due to slight damage to the platelets during the labelling procedure. These damaged platelets can survive in a normal recipient, but are destroyed when infused into the‘milieu’ of an ITP‐patient.
The Erythropoietic Response to Pregnancy in β‐Thalassaemia Minor
Authors: Schuman John E. , Tanser Catherine L. , Pealoquin Robert , de Leeuw Nannie K. M.
Published: March 2008

Summary. In 15 women with β‐thalassaemia minor, the haemoglobin concentration fell to a greater extent during pregnancy than in normal women. The lower haemoglobin level in the thalassaemics was caused by limited expansion of their red‐cell mass.

Although the increase in red‐cell mass in iron‐sufficient thalassaemics was not influenced by iron supplementation, two of the unsupplemented women were in negative iron balance. Ideally, each thalassaemic patient should receive individual assessment prior to iron therapy. Iron supplementation is recommended, when there is evidence of a negative iron balance.

There was great variability in the rise of red‐cell mass observed in the thalassaemic women. The rise correlated inversely with the morphological abnormality of the red cells, suggesting that the underlying disorder in haemoglobin synthesis was the main limiting factor.

In the thalassaemic women foetal haemoglobin was significantly greater in the first half of pregnancy than in the puerperium. This raises the possibility that the increased production of γ‐chains could favourably influence haemoglobin synthesis in pregnant women with thalassaemia minor.
Ouabain‐Sensitive and Oligomycin‐Sensitive Adenosine‐triphosphatase Activities of Normal Human Lymphocytes
Authors: Ellegaard Josrgen , Dimitrov Nikolay V.
Published: March 2008

Summary. Homogenates of highly purified normal human lymphocytes contained two different adenosinetriphosphatase (ATPase) activities. One of these activities was present in a supernatant fraction of the lymphocyte homogenates, possibly related to mitochondria. This activity was independent of the presence of monovalent cations, was insensitive to ouabain, but was inhibited by oligomycin and stimulated by 2,4 dinitrophenol. Exchange of Mg++ with Ca++, or addition of sodium fluoride completely inhibited this ATPase activity. A Km‐value for the substrate ATP was determined to be 0.83 mm. The specific activity of the oligomycin‐sensitive, supernatant ATPase was 0.31 ± 0.13 (SD) μmoles Pi per mg protein per 30 min.

The other ATPase activity was activated by Na+ and K+ and was inhibited by ouabain. This ATPase activity was only found in the pellet fraction after centrifugation, possibly associated with the cell membranes. The specific activity of this ATPase was 0.25 ± 0.09 (SD) μmoles Pi per mg protein per 30 min. The effect of ouabain in various cation combinations of the assay is reported. Optimal ouabain‐sensitive ATPase activity was found at 100 mm Na+, 15 mm K+ and 6 mm Mg++.

Only the oligomycin‐sensitive ATPase activity increased after short time stimulation of the lymphocytes by phytohaemagglutinin (PHA), and this could be inhibited by puromycin.

The increased ATPase activity of normal lymphocytes caused by the non‐specific mitogen PHA suggest the possibility that the increased ATPase activity of lymphocytes from patients with malignant tumours could be due to a stimulation of the lymphocytes by tumour specific antigens in vivo.
Transport of Methotrexate into Normal Haemopoietic Cells and into Leukaemic Cells and its Effects on DNA Synthesis
Authors: Hoffbrand A. V. , Tripp Edith , Catovsky D. , Das K. C.
Published: March 2008

Summary. Methotrexate uptake by, and action on normal and leukaemic haemopoietic cells has been studied. Peak uptake occurred just prior to peak DNA synthesis, at 48 hr for normal, and at 6–7 days for chronic lymphocytic leukaemic lymphocytes stimulated by phytohaemagglutinin (PHA). Uptake of methotrexate into these cells and into normal bone marrow cells was consistently inhibited by dibutyryl cyclic 3′,5’adenosine monophosphate (dibutyryl cyclic AMP) at concentrations of 10−3 to 10−5m and by inhibitors of phosphodiesterase (theophylline, puromycin aminonucleoside and puromycin). Lower external concentrations of dibutyryl cyclic AMP (10−5 to 10−6m), however, slightly increased the uptake of methotrexate.

Dibutyryl cyclic AMP and the phosphodiesterase inhibitors at high concentrations also inhibited cellular uptake of 5‐methyltetrahydrofolate and of thymidine into DNA. Conversely, none of these compounds inhibited uptake of pteroylglutamic acid (folic acid). These results suggest that the rate of entry of methotrexate and reduced folates (but not of folic acid) into haemopoietic cells may be governed by the intracellular concentration of cyclic AMP and that uptake of methotrexate by cells is related to uptake of natural folates but not to that of folic acid. Methotrexate uptake was also rapidly inhibited by actinomycin D suggesting that it is closely coupled to DNA synthesis.

Rate of entry of methotrexate into acute leukaemic blast cells was roughly proportional to their rate of proliferation, measured by 3H‐thymidine (3H‐TdR) incorporated into DNA. Resistant cells were not found to show a defect in methotrexate transport in relation to their degree of proliferation.

Methotrexate was found to inhibit mitosis, but not transformation of PHA‐stimulated lymphocytes and this was presumably due to blocking of de novo thymidylate synthesis from deoxyuridylate, as shown by inhibition of incorporation of tritiated deoxyuridine (3H‐dU) into DNA.

Studies on human leukaemic blast cells showed differences between sensitive and resistant cases in the effect of methotrexate in vitro on 3H‐dU and 3H‐TdR incorporation into DNA and on dU blocking of 3H‐TdR incorporation into DNA but none of these tests gave reliable prediction of resistance or sensitivity to methotrexate.
Plasma Clearance of 125I‐labelled Haemopexin in Normal and Haem‐loaded Rabbits
Authors: Lane R. S. , Rangeley D. M. , Liem H. H. , Wormsley S. , Muller‐Eberhard U.
Published: March 2008

Summary. Plasma clearance of 125I‐labelled rabbit haemopexin has been studied in six normal control rabbits and in a test group of rabbits haem‐loaded with 25 mg of haem.

Following intravenous injection, equilibration of 125I‐haemopexin between intravascular and extravascular compartments appeared to be complete within 24 hr and the decline in plasma activity then became constant in rate. The plasma activity curve was resolved into two exponential functions of time and from the data, fractional catabolic rate, intravascular:extravascular distribution of haemopexin and total haem binding capacity were calculated.

Control group. Mean plasma half‐clearance time of haemopexin was 20.3 hr; fractional catabolic rate was 1.8 (SD 0.19) times the intravascular haemopexin pool per day. Extravascular haemopexin was 0.6 (SD 0.11) times the mass of haemopexin in the intravascular pool.

Test group. 90–95% of injected 125I‐activity was eliminated from the plasma with a mean half‐clearance time of 1.57 hr and was associated with a significant urinary excretion of labelled iodine. Fractional catabolic rate was 5.84 (SD 0.3) times the intravascular haemopexin pool per day and extravascular haemopexin was 3.38 (SD 1.03) times the mass of haemopexin in the intravascular pool.

Haemopexin concentration in normal rabbit plasma was 31–52 mg/100 ml; intravascular plus extravascular haemopexin was 54.5 mg (mean value) and total haem binding capacity of haemopexin was 0.53 mg (mean value).

Intravascular haem rapidly complexed with haemopexin and the data suggested that this complex was promptly eliminated from the plasma and the haemopexin catabolized.
Reduced Glutathione, Glutathione Reductase, Glutathione Peroxidase, and Pyruvate Kinase in Erythrocytes of Human Newborns and Adults in Malaysia
Authors: Eng Lie‐Injo Luan , Wan Wong Pui , Ng T.
Published: March 2008

Summary. The mean level of glutathione, and activities of glutathione reductase, glutathione peroxidase and pyruvate kinase in human newborns showed highly significant differences from those in adults. Except for glutathione peroxidase, the mean activity of which was significantly lower in neonates, the values were significantly higher in neonates than in adults. Among neonates, Chinese had a higher mean glutathione reductase activity than Malays or Indians, but lower than that of Caucasians; these racial differences are probably due to a different dietary intake of riboflavin. Such racial differences were not seen in the activity of glutathione peroxidase and pyruvate kinase, but the mean level of reduced glutathione was significantly higher in Chinese than in Indian neonates although not than in Malayan neonates. The levels of glutathione, glutathione peroxidase and pyruvate kinase were significantly higher in female than in male newborns.
Bone Marrow and Bone Mineral Scintigraphic Studies in Sickle Cell Disease
Authors: Hammel C. F. , DeNardo S. J. , De Nardo G. L. , Lewis J. P.
Published: March 2008

Summary. Using discriminating radioisotopic techniques, a consistent pattern of abnormalities of both bone marrow and mineral was demonstrated in a series of patients with acute bone pain of sickle cell disease in which no roentgenographic evidence of infarction or infection was present. Bone scans utilizing reticulo‐endothelial uptake of 99mTc sulphur colloid showed discrete lesions of decreased radioisotopic localization in regions of acute pain suggesting decreased marrow blood flow. In these same areas, 85Sr bone scans showed markedly increased uptake whereas 18F bone scans showed little or no alteration. The strontium findings are consistent with accelerated calcium turnover while the fluorine studies suggest that bone blood flow, in contrast to marrow blood flow, remains nearly normal. In one patient, 52Fe positron scans confirmed an absence of effective erythropoiesis in those areas of involvement demonstrated by 99mTc and 85Sr. Marrow aspiration from one such area demonstrated sterile necrotic bone. These studies demonstrate that acute bone pain of sickle cell disease is associated with bone marrow death and increased bone mineral turnover.
Oxygen Transport in Anaemia
Authors: Pollock A. , Cotter K. P.
Published: March 2008

Summary. In three groups of anaemic patients, the haemoglobin‐oxygen (Hb‐O2) dissociation curves were shifted to the right. The red cells of these patients contained increased amounts of 2,3‐diphosphoglycerate (2,3‐DPG). In iron‐deficiency anaemia and in megaloblastic anaemia there was a direct relationship between the degree of anaemia and the red cell 2,3‐DPG concentration, but this did not hold for the miscellaneous group, and no direct relationship could be demonstrated between the degree of change in the Hb‐O2 dissociation curves and the degree of anaemia in any of the groups. The greatest increase in the red cell 2,3‐DPG concentration occurred in iron deficiency.
The Metabolism of Intravenously Administered Iron‐Dextran
Authors: Kanakakorn K. , Cavill I. , Jacobs A.
Published: March 2008

Summary. A method is described for the separation of transferrin iron and iron‐dextran in plasma samples. Estimation of plasma levels following the intravenous administration of labelled iron‐dextran showed that the mean half clearance time was 5.9 hr. About 40% of the injected dose of iron in circulation was bound to transferrin 11 hr later and there was no difference between normal and iron deficient subjects in the rate of iron release by the reticuloendothelial system. The results indicate a need to re‐evaluate present concepts of reticuloendothelial iron metabolism.
Energy Metabolism in Washed Human Platelets Responsive to ADP: Comparison with Platelets in Plasma
Authors: Doery J. C. G. , Hirsh J. , Mustard J. F.
Published: March 2008

Summary. The effect of the presence of albumin and apyrase on the metabolic rate of suspensions of washed platelets was examined. Albumin and apyrase reduced platelet glycolytic rate and oxidation of [6‐14C]glucose. Albumin significantly reduced the leakage of platelet LDH, β‐glucuronidase, serotonin and nucleotide which occurred during the resuspension procedures. This indicates that albumin provides a degree of protection to the platelets during resuspension. Apyrase produced a slight reduction in the accumulation of total nucleotide in the medium during incubation and its effect on metabolism was considered to be due to its ADPase activity. Assay of levels of key glycolytic intermediates indicated that the washing procedure stimulated metabolism. Recovery of resting metabolic rates was more rapid and more complete in the presence of albumin and apyrase. It was concluded that the inclusion of these agents in the suspending medium of washed platelets is an effective way of obtaining washed platelets with a metabolic rate similar to that of unwashed platelets in plasma.
Effect of Repeated Treatment of Rabbit Platelets with Low Concentrations of Thrombin on their Function, Metabolism and Survival
Authors: Reimers H. J. , Packham M. A. , Kinlough‐Rathbone R. L. , Mustard J. F.
Published: March 2008

Summary. Low concentrations of thrombin (< 0.05 u/ml) cause reversible aggregation of washed rabbit platelets in Tyrode‐albumin solution containing apyrase. The same platelets were aggregated several times by addition of the same concentration of thrombin with washing and resuspension after each aggregation step. Deaggregation of rabbit platelets aggregated by thrombin was enhanced by the addition of prostaglandin E1.

In three successive aggregations, rabbit platelets prelabelled with [3H]serotonin released approximately 70% of their radioactivity. Platelet granule nucleotides were labelled by in vivo administration of 32P‐labelled orthophosphate: repeated thrombin stimulation caused release of 60–65% of the labelled nucleotides. The release of 3H from [3H]serotonin labelled platelets paralleled the release of 32P‐labelled adenine nucleotides and magnesium. The concentration of platelet calcium did not change significantly during repeated thrombin stimulation. Electron microscopy showed nearly complete degranulation of platelets after three thrombin treatments.

The thrice thrombin‐treated platelets were more sensitive to ADP‐induced aggregation than the control platelets. They did not aggregate upon the addition of low concentrations of thrombin but showed the same extent of aggregation as the control platelets when they were exposed to high concentrations of thrombin.

Rabbit platelets labelled in vitro by incubation with [14C]adenosine showed a decrease in their metabolic nucleotides ([14C]ATP, [14C]ADP)as a result of repeated thrombin treatment. These platelets showed increased glucose uptake and increased lactate production. The thrombin‐treated platelets (labelled with [3H]DFP in vitro) survived in the circulation of rabbits for the same time as control platelets.
Storage Iron Kinetics
Authors: Cook James D. , Hershko Chaim , Finch Clement A.
Published: March 2008

Summary.Iron metabolism in the rat has been examined by chemical and isotopic measurements. Iron stores were larger in the female than the male, but in neither sex did stores play a dominant role in meeting increased iron needs. A nearly two‐fold higher plasma iron turnover in growing rats as compared with adult animals was accounted for largely by growth requirements. In both sexes and in both young and adult rats, the erythroid marrow assimilated more than two‐thirds of the plasma iron turnover. The source and distribution of transferrin iron was assessed in relation to the erythroid marrow, gastrointestinal tract, hepatic parenchyma and remaining body tissues. Absorption from the gastrointestinal tract provided about one‐third of the iron entering the plasma in adult rats and more than half in growing or phlebotomized rats. Iron absorption was closely related to the erythroid marrow requirements, but did not correlate with either the plasma iron level or tissue iron stores. The rat depends on dietary iron rather than iron stores to meet increased requirements and shows a much greater capacity to absorb iron than does man.
The Relationship between the Turnover Rate of Neutrophilic Granulocytes and. Plasma Lysozyme Levels
Authors: Hansen Niels Ebbe
Published: March 2008

Summary. Thirty‐six kinetic studies with radioactive diisopropylfluoro‐phosphate (DF32P) labelled neutrophilic granulocytes were carried out in 33 patients with a wide range of neutrophil counts, and the kinetic data compared with plasma lysozyme levels. A highly significant correlation was found between the neutrophil turnover rate and plasma lysozyme, which suggests that plasma lysozyme is mainly derived from disintegrating neutrophilic granulocytes. Recovery calculations showed, however, that in patients with normal and increased neutrophil counts at least 40% of the neutrophils passing through the blood did not deliver their lysozyme content back to the plasma, probably due to either lysozyme degradation in the tissues and/or due to loss of intact neutrophils from the organism, e.g. to the alimentary tract. The high degree of correlation between the neutrophil turnover rate and plasma lysozyme levels makes it possible, with certain provisos, to use plasma lysozyme levels in the clinical assessment of the neutrophil turnover rate.
Instantaneous and Continuous Measurement of Phagocytosis‐Stimulated Glucose Oxidation in Human Granulocytes by an Ionization Chamber Method
Authors: Davidson Warren D. , Tanaka Kouichi R.
Published: March 2008

Summary. A new and simple technique has been devised which allows, for the first time, the instantaneous and continuous measurement of phagocytosis‐stimulated glucose oxidation (PSGO) in granulocytes. This technique, employing the vibrating reed electrometer and ionization chamber, measures the oxidation of 14C‐labelled substrates to 14CO2. Substrate oxidation curves are described for glucose‐1‐14C, glucose‐2‐14C, and glucose‐6‐14C in normal human granulocytes before and after stimulation with latex particles. Ambient glucose concentration in the range of 50–1000 mg% did not alter the rate of PSGO. The magnitude of PSGO was shown to be directly related to the ambient oxygen concentration and to the number of added latex particles. This technique should prove useful in future studies of phagocyte metabolism.
The Haemolytic Action of Dapsone: Changes in the Red‐Cell Membrane
Authors: Rasbridge Marian R. , Scott G. L.
Published: March 2008

Summary.

Some aspects of red‐cell membrane structure and function have been investigated in patients with haemolysis due to dapsone (4,4′ diaminodiphenylsulphone). Osmotic fragility and potassium flux were not increased but red‐cell membrane changes occurred which suggested instability. These included loss of phospholipid, decrease in acetylcholinesterase activity and increased autohaemolysis. In addition, there was evidence for lipid peroxidation, which might have been the primary lesion. Red‐cell membrane sulphydryl group activity was either reduced or altered because these cells were abnormally sensitive to the action of the sulphydryl group inhibitor p‐chloromercuribenzoate, as measured by increased potassium leakage aiid haemolysis. Dapsone also caused abnormal peroxide lysis in the presence of normal hydrogen peroxide detoxification mechanisms and in the absence of vitamin E deficiency. This was prevented by excess vitamin E but not by the sulphydryl compounds, reduced glutathione or cysteine, and it was increased by previous treatment with p‐chloromercuribenzoate.

It is suggested that reduced membrane sulphydryl group activity, probably due to the formation of mixed disulphides with precipitated haemoglobin, and lipid peroxidation may be responsible for in vitro and, possibly, in vivo dapsone‐induced haemolysis.
Leukaemic Reticuloendotheliosis (‘Hairy’ Cell Leukaemia): A Distinct Clinico‐Pathological Entity
Authors: Catovsky D. , Pettit J. E. , Galton D. A. G. , Spiers A. S. D. , Harrison C. V.
Published: March 2008

Summary. The main diagnostic features of leukaemic reticuloendotheliosis (LRE) are discussed in the light of six patients studied in recent years. A detailed study of the clinical, cytological, cytochemical and histological findings in four cases is presented. Pancytopenia and the presence of mononuclear ‘hairy’ cells in the circulation were the main haematological features. Bone marrow was difficult to aspirate and contained 50–80% of the same abnormal cells as the blood; the reticulin pattern showed increased fibre density. The cytology of the LRE cells was very characteristic, particularly because of their irregular ‘hairy’ edges. Cytochemically they were positive for acid phosphatase (tartrate‐resistant) and PAS and they did not contain lysozyme. Electron‐microscopy demonstrated the irregular cytoplasmic edges and a large ‘ribosome‐lamellae’ complex in 25–30% of cells of the two cases studied. The differential diagnosis of LRE from other lymphocytic and histiocytic proliferative disorders is discussed. It is suggested that LRE should be included in the lymphoproliferative group of disorders.

Splenectomy seems to have a definitive place in the management of this condition; three patients out of six did not have splenectomy and died in less than 2 yr of sepsis or haemorrhage; in the other three cases splenectomy was followed by a prolonged improvement in the pancytopenia and a better survival (3 +, 7 and 10+ yr).
Studies of the Role of Red Cell Membrane Peroxidation in Paroxysmal Nocturnal Haemoglobinuria (PNH)*
Authors: Paniker N. V. , Arnold A. B. , Hartmann R. C.
Published: March 2008

Summary. No evidence was found to support the claimed role of lipid peroxidation in the pathogenesis and haemolysis in paroxysmal nocturnal haemoglobinuria (PNH) including iron‐induced episodes of gross haemoglobinuria. Therapy with the antioxidant vitamin E failed to influence the course of two patients with PNH. Three separate techniques for inducing lipid peroxidation failed to lower AChE of normal and PNH red cells and to induce susceptibility to in vitro PNH haemolytic tests in normal cells whether iron was added to the test system or not. Under peroxidatic stress, PNH cells did not generate abnormally high amounts of lipid peroxides as measured by malonaldehyde formation. Similar results were obtained with human red cells with induced high concentrations of protoporphyrin IX. Such studies do not, however, vitiate the concept that lipid peroxidation may play an important role in biologic ageing and cell destruction.
Effect of Chloramphenicol on Reticulocyte Δ‐Aminolaevulinic Acid Synthetase in Rabbits
Authors: Rosenberg Arthur , Marcus O.
Published: March 2008

Summary. Δ‐aminolaevulinic acid (ALA) synthetase activity was determined in reticulocyte mitochondria of rabbits before and while receiving 30–40 mg of chloramphenicol per kilogram per day. Maintenance of chloramphenicol at this dosage caused a 50–60% decrease in ALA synthetase activity; this enzymic activity returned to a normal level 8 days after discontinuation of the drug. Accompanying the decrease in ALA synthetase activity was a 16% reduction in haematocrit and a 30% decrease in reticulocyte count. No significant alterations in the white cell and platelet values were observed. It is hypothesized that chloramphenicol suppresses mitochondrial ALA synthetase, the rate‐limiting step in haem synthesis, and this accounts for the vulnerability of erythroid cells to the drug.
Serum Vitamin E Levels with Beta‐Thalassaemia Major: Preliminary Report
Authors: Zannos‐Mariolea L. , Tzortzatou F. , Dendaki‐Svolaki K. , Katerellos CH. , Kavallari M. , Matsaniotis N.
Published: March 2008

Summary. Serum vitamin E levels were found to be below normal (<0.5 mg/100 ml) in 46% of 56 children with β‐thalassaemia major receiving inadequate treatment with blood transfusions. The difference between the mean vitamin E levels in the children with β‐thalassaemia as compared to that of normal children was highly significant (P <0.001).

The hydrogen peroxide lysis test was highly abnormal in all 21 children with β‐thalassaemia major in whom it was carried out; only 11 of them had vitamin E serum levels below normal (<0.5 mg/100 ml). Parenteral administration of 200 mg α‐tocopherol in six of the 21 children resulted in a normal hydrogen peroxide lysis test. It is noteworthy that two of the six children had normal vitamin E levels.
Rapid Stem Cell Differentiation Induced by 19‐Nortestosterone Decanoate
Authors: Gorshein D. , Hait W. N. , Besa E. C. , Jepson Joanne H. , Gardner F. H.
Published: March 2008

Summary. Erythropoiesis was suppressed in mice by hyperoxia (HOX) and/or post‐hypoxic plethora (PCT), the cytocidal effects of actinomycin‐D (ACT), or by a combination of these techniques.

When 19‐nortestosterone decanoate (19‐ND) was injected during HOX and 24 hr 59Fe incorporation was measured during and following HOX, the increment in androgen‐induced erythropoiesis compared to vehicle‐treated controls was significantly greater in the post‐HOX assay system, where erythropoietin (ESF) titres were increased as compared to the response seen in the ESF suppressed mouse maintained in HOX. When erythropoiesis was suppressed by HOX and ACT, erythropoiesis was sustained in the 19‐ND‐treated mouse for a longer period than in the vehicle‐treated controls. In addition, when these mice were removed from HOX to ambient conditions and all injections were terminated, erythropoiesis recovered more rapidly in the groups previously treated with the androgen. When ESF was injected to PCT‐HOX mice only 24 hr after they received a single 19‐ND injection, it was observed that these mice had significantly greater levels of 59Fe incorporation than identical mice injected with ESF alone. In addition, it was found that HOX was capable of significantly decreasing the already minimal levels of erythropoiesis found in the plethoric mouse and that this PCT‐HOX animal did not respond as markedly to androgen administration as the plethoric animal maintained at ambient conditions. It was concluded that the data presented in this report are compatible with the concept that the androgenic steroid, 19‐ND, has a direct affect on the haematopoietic stem cell pool by increasing the size of a stem cell population capable of responding to ESF and that further differentiation of these elements is dependent on the availability of ESF to the target tissue.