bluuebunny/crossref_metadata_2025 huggingface dataset:
The Behaviour of Infused Human Platelets During the First Twenty‐Four Hours After Infusion
Authors: Davey M. G. , Lander H.
Published: March 2008

When freshly collected human platelets are transfused into normal recipients, an appreciable proportion disappears extremely rapidly from the circulation and does not reappear. This proportion increases with the number of manipulations performed in the preparation of the platelet concentrate (Gardner, Howell and Hirsch, 1954), and with the period of storage before infusion (Baldini, Costea and Dameshek, 1960). Those platelets which remain in the circulation after 24 hours—so‐called ‘viable’platelets—disappear slowly from the blood in the course of a further 7–10 days (see reviews by Najean and Bernard, 1960, and Odell and Kniseley, 1962). This period of platelet survival in the circulation is similar to that determined by labelling platelets in vivo with di‐isopropylfluorophosphonate‐32 P (DF32 P) (Leeksma and Cohen, 1956; Zucker, Ley and Mayer, 1961).

Following the infusion of labelled platelets into normal recipients, it has also been shown that the platelet‐bound radioactivity in the blood increases after 30 minutes to reach a maximum within 24–48 hours of infusion (Adelson, Rheingold and Crosby, 1957; Reisner, Keating, Friesen and Loeffler, 1958; Aas and Gardner, 1958; and others). This is contrary to what might be anticipated. A delayed increase in the number of circulating platelets has also been shown to occur when unlabelled platelets are given to thrombocytopenic subjects (Aas and Gardner, 1958). No such change is observed, however, when DF32P is injected to label circulating platelets (Zucker et al., 1961); this suggests that the phenomenon is due to changes which occur during the removal of platelets from the body and/or their manipulation in vitro.

The fate of those infused platelets which are immediately and irreversibly cleared from the circulation is unknown; nor is it known where the potentially viable platelets reside before their return to the circulation, nor where they are finally destroyed. Surface‐counting procedures using platelets labelled in vitro with 51Cr have led some workers to suggest that temporary accumulation occurs in the liver, the lungs and possibly the spleen, and that the liver and spleen play some role in their final destruction (Aas and Gardner, 1958; Najean and Bernard, 1960; Najean, Larrieu and Bernard, 1961). This study is concerned particularly with the sequence of events in the brief period immediately following the infusion of 51Cr‐labelled human platelets—a period in which some of them disappear rapidly from the circulation, and later return to it. We have carried out 36 studies of these events.
Studies on Fibrinogen Fractions Isolated from Human Plasma by Precipitation with Cold Ether
Authors: Mackay Margaret , Maycock W. d'A. , Silk Elsie , Combridge B. S.
Published: March 2008

During clinical trials of a human antihaemophilic globulin concentrate (HAHG) prepared from very fresh plasma by the method of Kekwick and Wolf (1957), it was observed (Maycock, Evans, Vallet, Combridge, Wolf, MacGibbon, French, Wallett, Dacie, Biggs, Handley and Macfarlane, 1963) that the transfusion of this material into haemophiliacs was sometimes followed by reactions similar to those observed by Fox, Goldsmith, Kidd and Lewis (1961) after the intravenous injection of purified bradykinin. A chemically similar fraction (ETF), prepared from aged plasma, has been used for many years for the treatment of hypofibrino‐genaemia without any reported reactions.

The reactions described by Maycock et al. (1963) were sufficiently frequent and severe to warrant an investigation of the kininogenic properties of HAHG and, for comparative purposes, of ETF. For reasons not understood, but clearly associated with the adoption of a modification of the original technique (Kekwick and Walton, 1965), reactions occurring during the transfusion of recently prepared batches of HAHG into haemophiliacs are now no greater in number and severity than those occurring during the transfusion of fresh plasma. Human plasma contains prokininogenases, the precursors of enzymes which hydrolyse protein substrates (kininogens, kallidinogens) to produce kinins, polypeptides which cause vasodilation and plain muscle constriction (Lewis, 1960). Activation of two of these proenzymes, kallikrein and plasminogen (profibrinolysin), could lead to the production of kinin in HAHG either during preparation, or during transfusion, and might cause the observed reactions.
The Anaemia of Erythropoietic Porphyria with the First Description of the Disease in an Elderly Patient
Authors: Kramer S. , Viljoen E. , Meyer A. M. , Metz J.
Published: March 2008

less than 60 cases of erythropoietic porphyria have been described since the original report by Shultz in 1874. It is a congenital disease and is generally thought to be transmitted in a non sex‐linked recessive mode (Goldberg and Rimington, 1962, p. 49; Heilmeyer, Clotten, Kerp, Merker, Parra and Wetzel, 1964). All cases in whom a definitive statement was made regarding age of onset presented in childhood and no patient has survived to middle age (Goldberg and Rimington, 1962, p. 55). The first of the two cases described here is unusual in that the disease only manifested itself after the age of 50

Most patients with erythropoietic porphyria have a haemolytic anaemia (Goldberg and Rimington, 1962, p. 54). There is frequently a reticulocytosis and the serum bilirubin may be slightly raised. Urobilinogen and stercobilinogen excretion are increased. Erythrocyte survival has been studied in a few cases with equivocal results (London, West, Shemin and Rittenburg, 1950; Gray, Muir and Neuberger, 1950; Rosenthal, Lipton and Asrow, 1955; Canivet and Pernard‐Considére, 1958; Heilmeyer et al., 1964). In an attempt to elucidate the mechanism underlying the anaemia associated with this disease two cases of erythropoietic porphyria were studied using a combined radioactive iron and chromium technique to make detailed simultaneous measurements of red‐cell production and destruction.
Electron‐Microscope Studies of the Red Cell in Paroxysmal Nocturnal Haemoglobinuria
Authors: Lewis S. M. , Danon D. , Marikovsky Y.
Published: March 2008

It is generally accepted that in paroxysmal nocturnal haemoglobinuria (PNH) there is a fundamental defect in the red cell, but the nature of the defect has not been completely elucidated. The red cells show no particular abnormal morphological features when viewed by the optical microscope but several studies have been carried out on the red‐cell membrane to see if any defect might be revealed by electron microscopy. Matthes, Schubothe and Lindemann (1951) noted an abnormality in the red cell membrane consisting of a patchy appearance with many clefts. This was subsequently confirmed by Braunsteiner, Gisinger and Pakesch (1956) and by Cecchi and Conestabile (1957). However, results have been variable, possible due to the fact that the usual method of preparing red‐cell membranes (‘ghosts’) by drastic osmotic haemolysis in distilled water results in tears and other damage to the membrane (Ponder and Ponder, 1960, 1961; Danon, 1961). Thus, for example, when Douglas and Eaton (1955) used a slight variation of the usual technique they concluded that the membranes of PNH cells were not abnormal, although it should be remarked that electron‐dense ovoid structures can be seen in the illustration of their shadow‐cast preparation.

In order to avoid subjecting red cells to a very low ionic strength, Danon, Nevo and Marikovsky (1956) devised a method of dialysis of red‐cell suspensions against hypotonic NaCl, by means of which a gradual decrease in the salt concentration of the medium surrounding the red cells is achieved. By this method ghosts of red cells have been obtained practically free of haemoglobin and relatively undamaged. Electron microscope studies of PNH cells prepared by this method showed a number of abnormalities, which will be described in this paper. It was observed that many of the PNH cell membranes contained electron‐dense material of varying form, size and amount. In order to investigate the nature of this residual material electron microscopy of ultra‐thin sections of the red cells was also carried out.
A Comparative Study of Coagulation and Fibrinolysis in Blood from Normal Men and Women
Authors: Brakman P. , Albrechtsen O. K. , Astrup T.
Published: March 2008

It is well known that several coagulation factors increase in concentration in the blood during pregnancy (Pechet and Alexander, 1961; Kasper, Hogg, Aggeler and Stone, 1964), and changes in the fibrinolytic system have also been described (Brakman and Astrup, 1963). Some coagulation factors and components of the fibrinolytic system are reported to be influenced by male and female hormones (Tagnon, Schulman, Whitmore and Leons, 1953). Mixtures of progestational and oestrogenic hormones influence coagulation and fibrinolysis in blood (Brakman and Astrup, 1964a; Hougie, Rutherford, Banks and Coburn, 1965). An increase in fibrinolytic activity of the circulating blood during menstruation has been reported by some authors, though others have been unable to confirm this. It is often difficult to evaluate these results because inaccurate or insensitive assay methods have been used. The present paper attempts to establish carefully assayed, normal values of certain parameters of blood coagulation and fibrinolysis in peripheral blood from men and women in order to compare them and to elucidate their possible fluctuations during menstruation. Such data are needed for establishing the normal patterns of coagulation and fibrinolysis, and in order to evaluate the possible influence of male and female hormones on these patterns. The present report provides a baseline for further studies of coagulation and fibrinolysis in blood.
Changes in Iron Mobilization and Utilization Induced by Acute Haemorrhage
Authors: Meital V. , Izak G. , Rachmilewitz M.
Published: March 2008

The measurement of the rate of appearance in the circulating blood of radioactive iron that has been previously injected is one of the most convenient techniques in the study of red‐cell production. Using this isotope, Dubach, Moore and Minnich (1946), Dubach, Callender and Moore (1948), Saylor and Finch (1953) and Dubach, Moore and Callender (1955) reported observations on the mechanism of the absorption of iron and its deposition in the storage organs. Jandl, Inman, Simmons and Allen (1959) and Morgan and Laurell (1963) described the competition between the reticulocytes and the iron‐binding protein of plasma for iron. Lamerton, Belcher and Harris (1959), Stohlman (1959), Donohue, Gabrio and Finch (1958), Bothwell, Pribilla, Mebust and Finch (1958) and others examined the uptake of iron by the early erythroid precursors in human and animal bone marrow. Stohlman (1959), Alpen and Cranmore (1959) and others examined the relationship between the incorporation of 59Fe into erythroid precursors and the release of mature red cells into the circulation. Information concerning iron absorption, utilization, storage and mobilization in iron‐deficiency anaemia due to chronic blood loss is also abundant.

The present paper deals with the erythropoietic response as measured by ferrokinetic studies in the rat following acute haemorrhage. Evidence will be presented to show that this response is different from that produced by erythropoietin administration to the rat.
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

1. 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

Two 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

The 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

Rat 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

Cyanocobalamin, 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

A 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.
A Family Study of Pernicious Anaemia: I. AUTOANTIBODIES, ACHLORHYDRIA, SERUM PEPSINOGEN AND VITAMIN B12
Authors: Wangel A. G. , Callender S. T. , Spray G. H. , Wright R.
Published: March 2008

Summary Anaemia was not a common finding in a study of 386 relatives and 46 spouses of patients with pernicious anaemia. When present, it was more often hypochromic than macrocytic in nature and affected women more frequently than men.

The serum levels of vitamin B12 decreased with age in first‐degree relatives and were significantly lower in relatives over the age of 70 than in control subjects matched for age and sex. The serum pepsinogen also decreased with age in first‐degree relatives with achlorhydria but increased with age in relatives who secreted acid and in control subjects. The difference between relatives with and without achlorhydria was significant. Achlorhydria, which became increasingly common with age in first‐degree relatives, preceded the fill in the serum pepsinogen.

The prevalence of gastric parietal cell antibodies increased with age in both first‐degree relatives and matched control subjects. It was significantly higher in the former than in the latter but of the same order in second‐degree relatives and spouses as in control subjects. Antibody to intrinsic factor was rare in the relatives and not found in spouses or control subjects. Most of the relatives with the antibody had overt or latent pernicious anaemia. Antibodies to thyroid antigens were not significantly more common in first‐degree relatives than in control subjects.

In the first‐degree relatives the gastric parietal cell antibody was associated with significant reductions in the serum levels of vitamin B12 and pepsinogen and with a significant increase in the prevalence of achlorhydria. The sequence of the changes was suggestive of the gradual onset and evolution of autoimmune gastritis in a proportion of the relatives.

In view of the known familial coexistence of pernicious anaemia and iron‐deficiency anaemia, and in view of the association between the latter and gastric autoimmunity, a correlation was sought between hypochromia and parietal cell antibodies in the relatives. Although a positive correlation was found further analysis suggested that it was an effect of age and did not imply a causal relationship.
Human Bone Marrow Sulphydryl Levels
Authors: Calcutt G. , Bromley Anne
Published: March 2008

Summary The acid soluble, protein and total —SH values for 101 samples of bone marrow from hospital patients have been measured. The results have been considered in terms of age, sex, clinical status and the susceptibility of bone marrow to drugs and radiation.
The Metabolism of Phytohaemagglutinin during Incubation with Human Peripheral Lymphocytes
Authors: Naspitz Charles K. , Richter Maxwell
Published: March 2008

The mechanism of action of PHA in in vitro leucocyte cultures was investigated with respect to the fate of the mitogen during the 3‐day blastogenic response. It was demonstrated that incubation of the leucocytes with PHA for only 5 minutes followed by incubation for 72 hours in medium devoid of PHA was sufficient to initiate mitosis and blastogenesis. However, the minimum incubation time with PHA required to induce maximum blastogenesis was 6 hours. Furthermore, it was demonstrated that the mitogen is bound to cells in culture but the experimental findings suggest that this cell‐bound mitogen is not degraded during the 3‐day incubation period.
A Splenunculus in Hereditary Spherocytosis
Authors: Westerman M. P. , Jenkins J. L. , Bron K. M.
Published: March 2008

Studies on a patient with hereditary spherocytosis and a functioning splenunculus are reported. An inverse relationship between splenic size and red cell survival was observed. Evidence was obtained which further verified that red cell survival in hereditary spherocytosis is not related to the shape or to the osmotic sensitivity of the cell and that more than one type of hereditary spherocytosis exists.
Solubilization and Structural Integrity of the Human Red Cell Membrane
Authors: Lauf P. K. , Poulik M. D.
Published: March 2008

Solubilization of structural protein components of red‐cell ghosts and alterations of their biological activities by treatment with various solvents was attempted. Ghosts were suspended in the solvents and then separated into supernates and residues by high‐speed ultracentrifugation. Treatment with 8 M urea yielded the highest degree of solubilization (60 per cent) and approximately 80 per cent of the protein‐bound sialic acid was found in the supernate. Non‐urea solvents yielded supernates rich in proteins but low in phosphorus and carbohydrates. Urea starch gel electrophoresis demonstrated the heterogeneity of the solubilized material. Serological studies showed high sensitivity of the Rh0(D)‐antigen to treatment with urea, mercaptoethanol and iodoacetamide. The M‐antigen was present in all residues and some M activity was found in the urea supernate. No acetylcholin‐esterase (AChE) activity was detected in the residue and supernate of stroma treated with 8 M urea. To ascertain the critical molarity, red blood cells and ghosts were incubated at increasing urea concentrations (0.5–6.0 M) and complete loss of AChE activity was observed with 4 M urea. Considerable reduction of AChE (70 per cent) was found after mild reduction and alkylation of stroma. When mercaptans and iodoacetamide were tested separately, no significant effect on AChE activity was observed except with high concentrations of cysteine.
Fibrinogenolysis: the Micromolecular Derivatives
Authors: Triantaphyllopoulos E. , Triantaphyllopoulos D. C.
Published: March 2008

Bovine fibrinogen was broken down by a streptokinase‐activated human fibrinolysin. The large protein fragments were precipitated by picric acid and the supernatant was passed through a column of Dowex 2‐X8 in order to remove the picrate. The colourless supernatant was concentrated by rotary evaporation and then chromatographed on aminex AG 50W‐X2 using gradient elution with ammonium acetate buffers. Eleven main fractions were obtained. Rechromatography of the five larger fractions on aminex 15A and 150A showed that fraction I contained at least five peptides and fraction II another eight. Fraction V contained free lysine, traces of tryptophan and histidine, and two peptides, fraction VII free arginine and three peptides and fraction VIII nine peptides. The total number of acid‐soluble peptides must be greater than 27, since six of the fractions of the supernatant were not examined.
The Absorption, Distribution and Utilization of Intramuscularly Administered Iron—Dextran: A Radio‐isotope Study
Authors: Will George
Published: March 2008

Summary. The rate and completeness of absorption of iron from the injection site were studied after intramuscular administration of 59Fe‐labelled iron‐dextran and the pattern of radio‐iron distribution and utilization followed in normal subjects and patients with iron‐deficiency anaemia. In both normal and anaemic subjects the major part of iron absorption took place within 72 hours of injection; absorption continued at a slower rate for 28 days but little further iron clearance occurred thereafter.

Rate and completeness of absorption were not related to the presence or absence of iron deficiency or to the haemoglobin level. In both normal and anaemic subjects there was marked individual variation in iron clearance. Active exercise was not found to lead to increased iron absorption but both rate and completeness of iron clearance were shown to be influenced by the site of injection. A study was made of iron clearance after multiple injections of iron‐dextran into the same site.

Serial surface scintillation counting was carried out in both normal and anaemic subjects; in smaller numbers of subjects, serial estimations of serum‐iron levels were made and percentage incorporation of radio‐iron into haemoglobin measured.

There was no evidence of significant excretion of radio‐iron in urine and faeces, and no toxic manifestations were observed.
The Effect of Administered Oestrogens and Androgens on the Absorption of Iron by Rats
Authors: Murray M. John , Stein Nell
Published: March 2008

Summary. The effects of injected oestrogens and androgens on the absorption of iron by mature female rats have been studied. Whereas there was no significant change with oestrogen despite falling haemoglobin levels, there was a slight but significant increase with androgen. These changes probably result from changes in iron stores secondary to changes in erythropoiesis.
The Effect of Small Doses of Iron on Desferrioxamine Chelation in Iron‐Deficiency Anaemia: Evidence for Ineffective Erythropoiesis
Authors: Brunström G. M. , Karabus C. , Fielding J.
Published: March 2008

Summary. We confirm that in many patients with iron‐deficiency anaemia, desferrioxamine chelates body iron in amounts similar to normal healthy men.

A short course of iron therapy (200 mg. ferrous sulphate once a day for 7 days) reduces chelation in such cases to below the normal range, i.e. into the ‘expected’ iron deficiency range.

We suggest that this effect of iron is due to a reduction of intramedullary haemolysis during the transformation of ineffective erythropoiesis to normal maturation, in the same way as vitamin B12 reduces desferrioxamine iron chelation in pernicious anaemia.

Sideropenia may be characterized by the differential ferrioxamine test as an Fv value below 110μg./kg. when the haemoglobin concentration is not less than 12 g. per 100ml.
Experimental Study of Aldomet‐Induced Positive Antiglobulin Reaction. I
Authors: Vyas G. N. , Sassetti R. J. , Petz L. D. , Fudenberg H. H.
Published: March 2008

Methyldopa polymer binds to red cells. Autologous red cells coated with polymer and polymer mixed with complete Freund's adjuvant induced heterospecific immune responses in rabbits resulting in the production of antibodies against human γ‐globulin and other plasma proteins. Therefore methyldopa polymer possibly is a heterospecific hapten. The γG bound to red cells of patients on methyldopa therapy differs from native γG and shows immunologic cross‐reactivity with rabbit γG. Two possible mechanisms for producing positive antiglobulin reaction in a large number of patients (10–20 per cent) on methyldopa and infrequent haemolytic anaemia in such patients are discussed.
Alcohol Induced Alterations of Red Cell Morphology in Carriers of the Sickle Cell Trait
Authors: Rubler Shirley , Fleischer Renee Altman , Roth Eleanor
Published: March 2008

Ten informed volunteers with SC, SA, SS and AA haemoglobin ingested 6 oz. of whiskey or its equivalent and the morphology of their circulating red cells was studied at intervals after alcohol ingestion. Unlike non‐alcoholic patients, alcoholic patients had abnormal circulating red cell forms before acute alcohol ingestion. However, only in individuals with S haemoglobin did acute alcohol ingestion induce burring as well as sickling. This effect appeared to be independent of previous alcoholic history. These changes could be reversed or prevented in vitro by the addition of Tween 80 to the incubation medium used to enhance the observed changes. The implications of these findings are discussed and the terminology of types of sickle cells interpreted according to recent knowledge relating to the evolution of these forms and their role in the production of haemolysis.
The Effects of Phenothiazines on the Sickling Phenomenon in Vitro
Authors: McFadzean J. A. , Pugh Irene M. , Squires S. L.
Published: March 2008

This paper describes some observations on the inhibition of sickling in vitro by desmethylchlorpromazine (5185 R.P.). It was found that a final concentration of 125 μg/ml. of the drug consistently inhibited the sickling of SS blood regardless of the reducing agent employed. The same concentration inhibited the sickling of red deer blood.

A concentration of 250 μg./ml. caused sickled cells to revert to a normal shape. The compound had no influence on the solubility of reduced SS haemoglobin, but influenced markedly the fragility of SS and AA red blood cells in hypotonic saline solutions.

The compound influenced the rate of oxygenation of AA haemoglobin but not of SS haemoglobin.

These findings are discussed in relationship to the possible mode of action of the phenothiazines in inhibiting sickling in vitro and it is suggested that 5185 R.P. acts on the cell membrane and prevents cell distortion.
A Double‐Blind Trial of a Phenothiazine Compound in the Treatment of Clinical Crisis of Sickle Cell Anaemia
Authors: MAHMOOD A.
Published: March 2008

A double‐blind trial of 5I85 R.P. (desmethylchlorpromazine, May & Baker, Ltd) in the treatment of clinical crisis of sickle cell anaemia is reported. The compound was not found to be more effective than a placebo.
The Action of Russell's Viper Venom on Factor V and the Prothrombin‐Converting Principle
Authors: Prentice C. R. M. , Ratnoff Oscar D.
Published: March 2008

The effect of Russell's viper venom on Factor V was studied. It was found that the venom greatly increased the activity of Factor V and that the reaction was not dependent on the presence of calcium ions. This action appeared to be responsible for the time‐consuming reaction between activated Factor X and Factor V noted previously. When the venom was neutralized with a specific antiserum after Factor X had been activated, this time‐consuming reaction was no longer noted.

Factor V, treated with Russell's viper venom, was not able by itself to convert pro‐thrombin to thrombin, and could not therefore be regarded as the final prothrom‐bin‐converting principle.

The prothrombin‐converting principle, containing activated Factor X, Factor V, phospholipid and calcium was able to generate thrombin from prothrombin more rapidly when Factor V had been treated with venom than when it was untreated. The explanation for this was that, in the presence of untreated Factor V, there was a lag period before detectable thrombin appeared when the principle was added to prothrombin. When Factor V had been pre‐treated with venom, thrombin generation started immediately. In this respect, there was a similarity in action between thrombin and Russell's viper venom on Factor V.

It was concluded that the venom has an action on at least two clotting factors, namely X and V, and for this reason caution must be used in interpreting the results of laboratory tests involving its use.