bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Diurnal Variation of Plasma Iron Turnover and Erythropoiesis in Healthy Subjects and Cancer Patients
Authors: Lockner D. 
Published: March 2008

The amount of plasma iron transported per time unit (PIT) is usually calculated from values obtained in the morning. It is known, however, that one of the key parameters necessary for the calculation of PIT, namely serum iron concentration, shows pronounced diurnal variations (Vahlquist, 1941; Hemmeler, 1944; Höyer, 1944a, b; Waldenström, 1946; Schlaphoff, Johnston, and Boroughs, 1950; Hamilton, Gubler, Cartwright and Wintrobe, 1950; Paterson, Marrack and Wiggins, 1952). It remains uncertain whether these serum iron variations are accompanied by changes in the half time of serum iron disappearance, whether PIT is constant throughout the day and, if not, whether a constant relation between PIT determined in the morning and that measured at other times of the day exists. It is also not known whether such possible relations change under pathological conditions and if PIT fluctuations indicate variation in erythropoiesis.Recently erythropoietic models have been proposed developed from plasma 59Fe disappearance data determined in the morning and partly also from radio‐iron appearance in erythrocytes and changes in organ activity (Pollycove and Mortimer, 1961; Sharney, Wasserman, Schwartz and Tendler, 1963; Garby, Schneider, Sundquist and Vuille, 1963; Najean, Ardaillou, Dresch and Mulmann, 1964; Vuille, 1965, Sharney, Gevirtz, Wasserman, Schwartz, Levitan, Mittleman and Tendler, 1965). Some of these models include proposed compartments, not all of which could be proved to exist (Noyes, Hosain and Finch, 1964; Najean et al., 1964; Lockner, 1966). The influence of possible diurnal variations of PIT on such models is not established, although the model proposed by Garby et al. (1963) and recently refined by Vuille (1965) was shown to be relatively independent of such diurnal variations.Two studies only have been published investigating the diurnal variation of PIT. In the first (Bothwell and Mallett, 1955) in which 20 patients were studied, 59Fe bound to purified β1‐globulin was used, a technique which the same author later demonstrated to give false results (Bothwell, Hurtado, Donohue and Finch, 1957). The second study (Paterson, 1957) was on five subjects including three normals, a material which did not allow far reaching conclusions.For these reasons and to answer the question whether changes observed when studying the PIT of patients with cancer could be explained by the diurnal variation of PIT further studies of these variations and their relation to erythropoiesis have been carried out. A preliminary account of part of this work has already been published (Lockner, 1963, 1964).
Lactate Dehydrogenase in the Diagnosis and Assessment of Response to Treatment of Megaloblastic Anaemia
Authors: Emerson Pauline M. , Wilkinson J. H. 
Published: March 2008

Gross elevation of the serum lactate dehydrogenase (S.L.D.) in megaloblastic anaemia was first reported by Hess and Gehm (1955) who found values from 5 to 21 times the upper limit of normal in 16 cases of pernicious anaemia. They also noted an inverse correlation between the serum enzyme activity and the peripheral red blood cell count. The rise in the S.L.D. has since been confirmed by Lührs and Negelein (1955), Cintrön‐Rivera, Acosta‐Martienzo and Diaz‐Rivera (1956), Zimmerman, West and Heller (1958), Heller, West and Zimmerman (1959), Gordin and Enari (1959), Levitan, Wasserman and Wróblewski (1959), Amelung (1960), Grönvail (1961), Elliott and Wilkinson (1963) and Goldfarb and Papp (1963), but there are conflicting reports concerning the relation between the degree of S.L.D. elevation and the severity of the anaemia.While Gordin and Enari (1959) reported that the S.L.D. activity correlated inversely with the serum vitamin B12 level, but not with either the blood haemoglobin concentration or the peripheral red cell count, in patients with pernicious anaemia or Diphyllobothrium latum infections, Levitan et al. (1959) found S.L.D. elevations in Addisonian anaemia only and not in megaloblastosis due to other causes. However, Amelung (1960) and Grönvall (1961) have suggested that the occurrence of extremely high S.L.D. activities might be diagnostic of megaloblastosis, and Fleming and Elliott (1964) have recently reported high levels of S.L.D. and of serum 2‐hydroxybutyrate dehydrogenase (S.H.B.D.) in folic acid‐deficient Nigerian patients with macrocytic anaemia of pregnancy. Similar elevation of the S.H.B.D. in pernicious anaemia had previously been reported by Elliott and Wilkinson (1963) who also observed a rise in the S.H.B.D./S.L.D. ratio during specific therapy.The present investigation was carried out to assess the reliability of S.L.D. and S.H.B.D. determinations in the diagnosis of megaloblastic anaemia and as indicators of the response to treatment. The enzyme levels have also been compared with the results of haematological investigations.
Incidence of Gastric Parietal Cell Antibody in Families of Patients with Iron Deficiency Anaemia
Authors: McFadyen I. J. , Goldberg A. , Dagg J. H. , Anderson J. R. 
Published: March 2008

There is an association of pernicious anaemia with iron deficiency anaemia (Faber and Gram, 1924). There is also a high incidence (85 per cent) of gastric parietal cell antibody in the sera of patients with pernicious anaemia (Taylor, Roitt, Doniach, Couchman and Shapland, 1962) and a less marked, but significantly increased incidence (33 per cent) in patients with iron deficiency anaemia who have a histamine fast achlorhydria (Dagg, Goldberg, Anderson, Beck and Gray, 1964). Pernicious anaemia has a familial incidence (Askey, 1940; Callender and Denborough, 1957) and there is also an increased frequency of achlorhydria in relatives of patients with pernicious anaemia (Askey, 1940; Neel, 1947). In addition te Velde, Abels, Anders, Arends, Hoedemaeker and Nieweg (1964) have found the gastric parietal cell antibody in 20 per cent of relatives of patients with pernicious anaemia, compared with 6 per cent in a control series. Because of the association of iron deficiency anaemia with pernicious anaemia and the increased incidence of histamine fast achlorhydria and parietal cell antibody in both diseases, the occurrence of the antibody has been assessed in the families of patients with iron deficiency anaemia, histamine fast achlorhydria and gastric parietal cell antibody.In a group of 22 patients with iron deficiency anaemia, histamine fast achlorhydria and gastric parietal cell antibody, Dagg, Goldberg, Gibbs and Anderson (1966) found that seven had a 58Co vitamin B12 absorption test (Schilling, 1953) characteristic of pernicious anaemia, and six of these had reduced serum vitamin B12 levels; that is these patients had latent pernicious anaemia. In 10 of the 22 patients the serum vitamin B12 levels and the Schilling test were normal, and in the remaining five patients the serum vitamin B12 was low but the Schilling test was normal. Since it appeared possible that the familial incidence of gastric parietal cell antibody would be higher in relatives of the patients with latent pernicious anaemia than in relatives of those without latent pernicious anaemia, 11 families from these 22 patients were investigated, six of which had propositi with latent pernicious anaemia and five of which had propositi without latent pernicious anaemia (Table I). The relatives of the remaining 11 patients were unwilling to co‐operate in these investigations.
Kinetics of Rapidly Labelled RNA in Human Leukaemia Cells
Authors: Sinks L. F. , Hayhoe F. G. J. 
Published: March 2008

The kinetics of rapidly labelled RNA have been studied autoradiographically in several mammalian cell types, including, among cells of human origin, Hela cells (Feinendegen, Bond, Shreeve and Painter, 1960), PHA (phytohaemagglutinin)‐induced blast cells (Hayhoe and Quaglino, 1965) and various mononuclear cells of peripheral blood (Storti and Torelli, 1965). Early work with labelled RNA precursors in leukaemic cells (Gavosto, Maraini and Pileri, 1960) showed that uptake was much diminished as compared with that of normal immature cells of the haemopoietic system, and later chase studies of movement of label from nucleus to cytoplasm, while confirming the generally low percentage of uptake, suggested that the nuclear‐cytoplasmic shift was sometimes delayed (Quaglino and Hayhoe, 1965). Again, Storti and Torelli (1965) have presented evidence that in at least some cases of acute leukaemia the labile, rapidly degraded, fraction of RNA, which may well have messenger function, is either absent or metabolically different from that of normal leucoblasts.It is clearly of great importance to explore the patterns of RNA kinetics in leukaemic cells and to determine whether the time sequence of movement of label from nucleus and nucleolus to cytoplasm and the types of RNA formed do in fact differ substantially from those of normal haemopoietic precursors or such a model cell system as is provided by PHA‐induced blast cells.As a first step we have therefore carried out a series of chase experiments in ten leukaemic cases to study the intracellular movement of a potential RNA label and to establish whether a constant pattern exists.
Red‐Cell Metabolism in Hereditary Spherocytosis
Authors: Loder P. Bronwen , Babarczy Gabriella , Gruchy G. C. de 
Published: March 2008

SUMMARY1. Studies relating to red‐cell glycolysis in hereditary spherocytosis have been made by: (a) analysis of the phosphate compounds of fresh and incubated cells, (b) estimation of the activities of enzymes associated with glycolysis, and (c) estimation of the co‐enzymes NAD and NADH2 and of reduced glutathione.2. The results do not support the theory that the basic abnormality in the hereditary spherocytic cell is due to a defect of glycolysis or phosphorylation.3. It seems probable that the relatively minor changes in the phosphate compounds of the glycolytic pathway described by other authors and in this paper are secondary to a more basic defect, probably in the red‐cell membrane.
Developmental and Acquired Variations in Erythrocyte Carbonic Anhydrase Isozymes
Authors: Weatherall D. J. , McIntyre Patricia A. 
Published: March 2008

SUMMARYTwo carbonic anhydrase fractions, designated B and C, can be seen readily on starch‐gel electrophoretic patterns of human red‐cell lysates stained for protein. Both isozymes are low in infancy and reach their adult intensity at the second to third year of life. Enzyme 13 is markedly reduced in patients with thyrotoxicosis and elevated in hypothyroidism, returning to normal after treatment. These findings are associated with appropriate changes in total red‐cell enzyme activity. Carbonic anhydrase activity is markedly elevated in red cells from patients with megaloblastic anaemia secondary to vitamin B12 deficiency and is probably elevated in folic acid deficiency. These findings, their diagnostic possibilities, and the light which they throw on enzyme induction in human red cells, are discussed.
Alterations in Cellular Sodium, Potassium, Calcium, Magnesium, Copper and Zinc Levels during the Development and Maturation of Erythrocytes in the Rabbit
Authors: Valberg L. S. , Card R. T. , Paulson Eleanor J. , Szivek J. 
Published: March 2008

SUMMARYThe levels of water, haemoglobin, sodium, potassium, calcium, magnesium, copper and zinc were estimated in a young population of macrocytic erythrocytes produced following the administration of phenylhydrazine, in a young population of normocytic erythrocytes, produced in response to repeated bleeding, and in a normal mixed population of erythrocytes in the rabbit.Compared with the normal mixed population of erythrocytes the average macrocytic erythrocyte contained, per cell, increased amounts of haemoglobin, water, potassium, magnesium, zinc, calcium, copper and a similar amount of sodium; per cu.μ of cell, increased amounts of water, potassium and calcium, reduced levels of haemoglobin and sodium, and similar levels of magnesium, zinc and copper; and per μl. of cell water, a decreased concentration of sodium which was accompanied by a reciprocal increase in the concentration of potassium.Compared with the normal mixed population of erythrocytes the average young normocytic erythrocyte contained, per cell, increased amounts of water, potassium and calcium, a decreased amount of sodium and similar amounts of magnesium, zinc, copper and haemoglobin; per cu.μ of cell, decreased amounts of haemoglobin and sodium, increased amounts of water and potassium and normal concentrations of magnesium, zinc and copper; and per μl. of cell water, a diminution in the concentration of sodium which was accompanied by a reciprocal increase in potassium.These results are discussed and it is postulated that these findings can be used to assess, indirectly, the chemical events that occur during the maturation of the erythrocyte precursors.
Diffusion Chamber Studies of Rat Peripheral Leucocytes in the Presence of Phytohaemagglutinin
Authors: Johnson L. Ione , Sullivan Patricia A. , Siegel Charles D. , Chan Po‐Cheun , Gordon Albert S. 
Published: March 2008

SUMMARYRat peripheral leucocytes have been cultured in diffusion chambers in an effort to achieve greater consistency in the response of lymphocytes to phytohaemagglutinin. The diffusion chamber was found to provide an in vivo environment which obviates drastic changes in pH and eliminates other factors that act as major deterrents to successful and optimal responses of lymphocytes to this mitogen in vifro. The system shows reliability and consistency in maintaining excellent cytologic and morphologic integrity of the cells in culture.
Patient Variation in Pernicious Anaemia, as Shown in a Clinical Trial of Cyanocobalamin, Hydroxocobalamin and Cyanocobalamin–Zinc Tannate
Authors: Tudhope G. R. , Swan H. T. , Spray G. H. 
Published: March 2008

SUMMARYCyanocobalamin, hydroxocobalamin and cyanocobalamin‐zinc tannate were given in turn, as a single dose equivalent to 500 μg. of vitamin B12, to twelve patients who had untreated Addisonian pemicious anaemia. The order in which the drugs were given to each patient was determined by a series of random numbers. Following the first injection, frequent measurements were made of serum vitamin B12 activity until this was reduced to 100 pg./ml. Then the second drug was given with the same follow‐up, and ultimately the third drug.In every case, serum concentrations of vitamin B12 greater than 140 and 100 pg./ml. persisted after hydroxocobalamin and cyanocobalamin‐zinc tannate for twice as long as after cyanocobalamin. However, differences between patients were very great, such that the entire trial with the three drugs was completed in 11 months in one case but lasted more than 4 years in another. Variation between patients makes it impossible to anticipate the duration of effect of a single injection of one of these drugs in any patient.Studies were made of clearance from injection sites using radioisotopically labelled drugs. Cyanocobalamin and hydroxocobalamin were both cleared with a half‐time of 30–100 minutes, whereas that of cyanocobalamin‐zinc tannate was 48–130 hours.Urinary excretion of radioactivity was measured in parallel with microbiological assay of urinary vitamin B12. Good agreement was found between the two methods in almost all cases tested. Following injections of cyanocobalamin and hydroxocobalamin most of the excretion occurred in the first 24 hours; with hydroxocobalamin the excretion was less than with cyanocobalamin. The urinary excretion following injection of the zinc tannate complex was very much less than with the other two drugs and most of the excretion occurred after the first 24 hours.
Haemoglobin F Texas I (α2γ25Glu→Lys): a Variant of Haemoglobin F
Authors: Jenkins G. C. , Beale D. , Black A.J. , Huntsman G. R. , Lehmann H. 
Published: March 2008

SUMMARYA survey of 3000 cord bloods in Great Britain yielded one electrophoretically abnormal variant of Haemoglobin F in an infant of West Indian parentage. This haemoglobin resembled Haemoglobin F Texas. Haemoglobin F Texas might either be α2γ25Glu→Lys or α2γ26Glu→Lys. The present variant F has its substitution in the fifth residue of the γ‐chain, and is designated Haemoglobin F Texas I.
Microangiopathic Haemolytic Anaemia: the Experimental Production of Haemolysis and Red‐Cell Fragmentation by Defibrination in Vivo
Authors: Rubenberg M. L. , Regoeczi E. , Bull B. S. , Dace J. V. , Brain M. C. 
Published: March 2008

Summary. In rabbits transient haemoglobinaemia accompanied rapid defibrination produced by the purified coagulant fraction of the venom of the Malayan pit‐viper, Agkistrodon rhodostoma. The degree of haemoglobinaemia was dependent upon the rate of defibrination.Inhibition of fibrinolysis resulted in the persistence of the haemoglobinaemia after venom defibrination. Irradiation to produce thrombocytopenia or anticoagulation enabled these rabbits to survive more rapid rates of defibrination and resulted in prolonged haemoglobinaemia (due to continuing haemolysis) and the appearance of fragmented red cells.Haemoglobinaemia was associated with the occurrence and persistence of a network of loose fibrin to which red cells were adherent both free in the circulation and fixed in blood vessels.It is suggested that haemolysis and red‐cell fragmentation result from the interaction of red cells with porous fibrin thrombi, and that this interaction occurs in human disease and is the causal mechanism of microangiopathic haemolytic anaemia.
Microangiopathic Haemolytic Anaemia: Mechanisms of Red‐Cell Fragmentation: in Vitro Studies
Authors: Bull B. S. , Rubenberg M. L. , Dacie J. V. , Brain M. C. 
Published: March 2008

Summary. Several of the disease states in which red‐cell fragments appear in the peripheral blood have features suggestive of intravascular coagulation with fibrin deposition in vessels. As this process might be a cause of red‐cell fragmentation the interaction of rapidly moving red cells with fibrin strands was investigated.Red cells arrested on fibrin strands while moving through a loose fibrin clot at the velocity of arterial blood flow were bent over the strands by the force of blood flow and eventually fragmented. The shape of the fragments which resulted depended upon the position and plane in which the red cells were arrested, the point at which the membrane ruptured, the distribution of haemoglobin and membrane between the resulting fragments and finally on whether or not crenation of the fragments supervened.Systems in which red cells perfused artificial ‘clots’ of glass fibre and nylon also caused the red cells to fragment. The fragmentation process seems to depend, therefore, on a rapid blood flow and the arrest of individual red cells by any obstruction of small dimensions, e. g. by strands or spikes less than I p in diameter. It was concluded that these conditions were most likely to obtain in vivo as the result of intravascular deposits of fibrin in the lumen of small arterioles.
An Erythrocyte Defect in Splenectomized X‐Irradiated Mice Restored with Spleen Colony Cells
Authors: Schofield Raymond , Cole Leonard J. 
Published: March 2008

Summary The profound anaemia previously seen in splenectomized irradiated LAF1 mice injected with isogenic spleen nodule cells, has been confirmed in two other mouse strains. The anaemia does not invariably cause death, but a slow recovery to normal haematocrit levels occurs in about 80 days.By splenectomy at various times after irradiation, some modification of the severity of the anaemia was achieved, but recovery was not accelerated.Implantation of normal splenic tissues in Millipore filter chambers intraperitoneally failed to modify the severity of the anaemia, but an improvement in the rate of recovery was observed. 59Fe 5‐hour uptake data indicate that spleen nodule cells do not help in the re‐population of erythroid elements of bone marrow, though there is some acceleration of re‐population of spleen as a result of injection of these cells. Both bone marrow cells and normal spleen cells are seen to be more effective than spleen nodule cells in the re‐populating bone marrow.Spontaneous recovery of the bone marrow erythroid population occurs in mice irradiated and injected with spleen nodule cells but an anaemia persists unless the spleen is present.It is concluded that an erythrocyte defect occurs in splenectomized, irradiated, spleen nodule cell‐injected mice — a defect which only slowly recovers.
Relationship between Membrane Function and Permeability: III. FURTHER EVIDENCE LINKING MEMBRANE TRANSPORT AND THROMBOPLASTIN AVAILABILITY OF THE INTACT ERYTHROCYTE
Authors: Cohen Phin 
Published: March 2008

Summary Within a series of short straight‐chain compounds resembling glycerol in structure, the pattern of unmasking of erythrocyte ‘platelet factor 3’ (PF‐3) activity appeared to be related to a combination of cell penetrability, molecular weight and complement of hydroxyl groups. The same relationship held in a series of low molecular weight polymers of ethylene glycol. Moreover, propylene glycol and ethylene glycol monomethylether, at very low concentrations, were shown to delay glycerol‐induced erythrocyte PF‐3 enhancement. Among penetrating non‐electrolytes not having a structural similarity to glycerol, dimethylsulphoxide was the only compound that had a family of PF‐3 enhancement curves of the glycerol type.The glycerol induced PF‐3 enhancement curves with cow and sheep erythrocytes were similar to those of erythritol with human erythrocytes. Furthermore, the attainment of equilibrium of 14C erythritol between human erythrocyte and plasma compartments correlated temporally with unmasking of PF‐3 activity by erythritol solutions.The discussion attempts to relate these findings to new theoretical views which emphasize a close link between membrane transport and thromboplastin availability in the intact erythrocyte.