bluuebunny/crossref_metadata_2025 huggingface dataset:
Congenital Heart Disease
Authors: van Dorp Francoise , Simon Chantal
Published: March 2008

Congenital heart disease simply means heart disease present at birth. It comprises genetic heart disease and structural anormalities of the heart. This article aims to describe the presentation of congenital heart disease, and outline common structural and genetic heart problems.
Prevention of Coronary Heart Disease in General Practice
Authors: Dunn Nick
Published: March 2008

Coronary heart disease in the UK is a very common problem. Coronary heart disease (CHD) causes over 117,000 deaths a year in the UK: approximately 1 in five deaths in men and one in six deaths in women. Although death rates from CHD have been falling rapidly in the UK since the late 1970s, they are still among the highest in Western Europe. There is considerable variation in death rates from CHD in the UK: death rates are higher in Scotland than in the south of England, as shown in Figure 1 , and this is typical of all age groups and both sexes. Also death rates are higher in manual workers than non-manual workers and are particularly high among Indian and Pakistani men.
Recent changes in solar outputs and the global mean surface temperature. III. Analysis of contributions to global mean air surface temperature rise
Authors: Lockwood Mike
Published: March 2008

A multivariate fit to the variation in global mean surface air temperature anomaly over the past half century is presented. The fit procedure allows for the effect of response time on the waveform, amplitude and lag of each radiative forcing input, and each is allowed to have its own time constant. It is shown that the contribution of solar variability to the temperature trend since 1987 is small and downward; the best estimate is −1.3% and the 2σconfidence level sets the uncertainty range of −0.7 to −1.9%. The result is the same if one quantifies the solar variation using galactic cosmic ray fluxes (for which the analysis can be extended back to 1953) or the most accurate total solar irradiance data composite. The rise in the global mean air surface temperatures is predominantly associated with a linear increase that represents the combined effects of changes in anthropogenic well-mixed greenhouse gases and aerosols, although, in recent decades, there is also a considerable contribution by a relative lack of major volcanic eruptions. The best estimate is that the anthropogenic factors contribute 75% of the rise since 1987, with an uncertainty range (set by the 2σconfidence level using an AR(1) noise model) of 49–160%; thus, the uncertainty is large, but we can state that at least half of the temperature trend comes from the linear term and that this term could explain the entire rise. The results are consistent with the intergovernmental panel on climate change (IPCC) estimates of the changes in radiative forcing (given for 1961–1995) and are here combined with those estimates to find the response times, equilibrium climate sensitivities and pertinent heat capacities (i.e. the depth into the oceans to which a given radiative forcing variation penetrates) of the quasi-periodic (decadal-scale) input forcing variations. As shown by previous studies, the decadal-scale variations do not penetrate as deeply into the oceans as the longer term drifts and have shorter response times. Hence, conclusions about the response to century-scale forcing changes (and hence the associated equilibrium climate sensitivity and the temperature rise commitment) cannot be made from studies of the response to shorter period forcing changes.
The AGL62 MADS Domain Protein Regulates Cellularization during Endosperm Development inArabidopsis
Authors: Kang Il-Ho , Steffen Joshua G. , Portereiko Michael F. , Lloyd Alan , Drews Gary N.
Published: March 2008

Endosperm, a storage tissue in the angiosperm seed, provides nutrients to the embryo during seed development and/or to the developing seedling during germination. A major event in endosperm development is the transition between the syncytial phase, during which the endosperm nuclei undergo many rounds of mitosis without cytokinesis, and the cellularized phase, during which cell walls form around the endosperm nuclei. The molecular processes controlling this phase transition are not understood. In agl62 seeds, the endosperm cellularizes prematurely, indicating that AGL62 is required for suppression of cellularization during the syncytial phase. AGL62 encodes a Type I MADS domain protein that likely functions as a transcription factor. During seed development, AGL62 is expressed exclusively in the endosperm. During wild-type endosperm development, AGL62 expression is strong during the syncytial phase and then declines abruptly just before cellularization. By contrast, in mutant seeds containing defects in some FERTILIZATION-INDEPENDENT SEED (FIS) class Polycomb group genes, the endosperm fails to cellularize and AGL62 expression fails to decline. Together, these data suggest that AGL62 suppresses cellularization during the syncytial phase of endosperm development and that endosperm cellularization is triggered via direct or indirect AGL62 inactivation by the FIS polycomb complex.
On the Formation of Haemosiderin and its Relation to Ferritin II. A Radioisotopic Study*
Authors: Shoden A. , Sturgeon P.
Published: March 2008

In vivo biochemical studies on rabbits have shown that, with the intravenous injection of iron dextran, the rate of liver ferritin formation limits the uptake of iron by this organ. When ferritin production reaches 25‐30 mg. Fe per day, increased rates of iron dextran injection result only in increased serum concentrations of the compound. Regardless of the rate of injection, haemosiderin (insoluble iron) forms at a rate of approximately one‐tenth that of ferritin (soluble iron) until the total liver ferritin iron reaches 150‐200 mg. Therefore, when iron dextran is injected, the rate of haemosiderin formation is limited by the liver ferritin concentration. When this concentration reaches the ‘critical’level of 150‐200 mg. of iron and loading is continued, a process begins whereby ferritin production gradually decreases until the ferritin content of the liver reaches a maximum. Simultaneously the rate of haemosiderin production increases until all subsequent iron deposition is reflected in increased haemosiderin content (Shoden and Sturgeon, 1962a).

Histochemical studies have shown that there is no appreciable deposition of stainable iron in the Kupffer cells of the liver when iron dextran is administered intravenously. When saccharated iron oxide is given, however, there is immediate and marked deposition of stainable iron in the Kupffer cells, even when relatively small amounts of iron are injected at slow rates. In contrast to the Kupffer cell insoluble iron, deposition of histochemically demonstrable iron in the parenchymal cells does not begin until the total liver ferritin iron reaches approximately the 150‐200 mg. level. At this level, regardless of the type of iron compound given, faint bluish areas or vacuoles, some of which may contain discrete blue granules, appear in the parenchymal cells. As the iron load is increased beyond this point, the number and size of the parenchymal cell granules increase. When iron dextran is given, the appearance of the blue granules is paralleled by a marked increase in the water‐insoluble iron fraction. Extraction with normal saline of small liver cubes, preceding the fixation and staining, shows that ferritin is removed, but not the haemosiderin granules (Shoden and Sturgeon, 1962b).

From the above observations, the hypothesis was advanced that liver ferritin is a precursor of the haemosiderin granules found in the parenchymal liver cells (Shoden and Sturgeon, 1961). The present study was designed to test this hypothesis. It was planned to establish in the two iron storage ‘compartments’(ferritin and parenchymal haemosiderin) known specific activities (concentrations) of radioactive iron. Then, to study the pathway taken by new iron, non‐radioactive iron in form of iron dextran was administered. The sequence in the dilution of radioactive iron in the two compartments, and the shift of radioactivity between them,
The Fate of Prothrombin and Factors VIII, IX and X Transfused to Patients Deficient in these Factors
Authors: Biggs Rosemary , Denson K. W. E.
Published: March 2008

The treatment of patients with coagulation defects consists of an attempt temporarily to replace in their blood the factor they lack. This is achieved by giving whole plasma or concentrates of the appropriate factor prepared from human or animal blood. There is now no reasonable doubt that this treatment is effective. With increasing precision of the methods used to assay the different factors it is becoming possible to relate the blood level achieved in the patient to the dose of material administered and to study the rate of disappearance of the factor from the patient's circulation. Accumulation of this information for all treated patients should improve treatment. If bleeding is related to the concentration of a particular factor in the patient's blood, it is clearly important to be able to predict what concentration is likely to be reached after a given dose and to predict how long it is likely to be maintained. If the response of patients to therapeutic material prepared by different methods is not the same, this again is important because allowances must be made for the variations in calculating the effective dose.

The purpose of the present communication is to present the results of studies recently made at Oxford during the routine treatment of patients admitted to the Oxford hospitals. Assays were made of the blood levels of the relevant factor before and after the administration of a variety of therapeutic materials. The blood levels achieved were related to the calculated amount of the factor given and the rate of its disappearance from the blood was recorded. In this study the case records are not given in detail, nor is there any discussion of the therapeutic effectiveness of treatment in any particular case.
Heparin and Thrombus Formation: Early Suppression and Late Enhancement*
Authors: Mustard J. F. , Murphy E. A. , Downie H. G. , Rowsell H. C.
Published: March 2008

It has been demonstrated in animal studies that heparin in suitable doses suppresses fibrin formation and in larger doses prevents the clumping of platelets (Best, Cowan and MacLean, 1938; Zucker, 1947). In view of this, it is surprising that in controlled studies it has not proved a more effective therapeutic agent in the management of arterial thrombosis (Carleton, Sanders and Burack, 1960). This may reflect inadequacy of dosage or too long an interval between doses, or it may indicate that treatment would only be effective if given in an earlier stage of the disease, or that the mechanism of the clinically recognized catastrophe is something other than arterial thrombosis.

While the predominant effects of heparin are antithrombotic, there are some indications that they are not unambiguous. Ashwin (1961) found that low doses of heparin produced a higher percentage of animals with thrombosis than that in the control group, and while the difference was not impressive, it is somewhat disturbing that it lay in an unexpected direction. If this effect proved not to be an artefact arising from sampling error it could be attributed to one of a variety of mechanisms of which the two most plausible seem to be that low doses of heparin are directly thrombogenic or that counteracting thrombogenic mechanisms are excited by doses of heparin too small to prevent thrombus formation.

In ordinary experiments, it is difficult to determine the time sequence of events. In vitro studies may be done, but their relationship to endogenous thrombus formation has been repeatedly called into question (Poole and French, 1962). Study of endogenous thrombus formation is handicapped by the lack of adequate methods of quantitation and by difficulty of studying tendency to thrombus formation over short periods of time.

We have recently described a standardized extracorporeal circulation for use with experimental animals which allows precise quantitation of thrombus formation in a system which allows rapid pulsatile flow to be maintained and in which the blood is repeatedly re‐circulated through the animals (Downie, Murphy, Rowsell and Mustard, 1963). This seemed to be a suitable means of exploring the relationship of heparin in thrombosis.
The Origin of ‘Burr’Erythrocytes
Authors: Bell R. E.
Published: March 2008

The term ‘burr’red cell was introduced by Schwartz and Motto (1949) to describe irregularly shaped erythrocytes ‘having one or more large spiny projections’along their periphery. These abnormal erythrocytes are found most frequently in uraemia and gastric carcinoma and less frequently in association with bleeding peptic ulcer (Aherne, 1957). They are also seen in haemolytic anaemia where they are associated with fragmented erythrocytes (schistocytes), triangular forms, or other unusual shapes (Brain, Dacie and Hourihane, 1962). Recently they have also been described in aplastic anaemia (Lewis, 1962). On rare occasions they may be seen in blood smears of normal subjects. Very little is known about how these abnormal erythrocytes are produced. Dacie (1960) suggested that burr cells were artefacts produced on the slide as the cell dries. There is evidence suggesting that mechanical injury to the cell may be a major factor (Brain et al., 1962; Sayed, Dacie, Handley, Lewis and Cleland, 1961) but they may also result from the action of unknown metabolic or ‘toxic’factors. It is the purpose of this paper to present some morphological evidence that suggests a mechanism for their development. The sequence of events ending in a burr cell appears to be the formation of a vacuole at the periphery of the cell that subsequently ruptures through the cell membrane leaving a crater and a deformed erythrocyte.
The Relative Importance of the Duodenum in the Intestinal Absorption of Iron
Authors: Duthie H. L.
Published: March 2008

It is generally believed that iron is absorbed principally in the duodenum and that absorption diminishes progressively throughout the jejunum and ileum. Much of the evidence is histological or histochemical: early studies in the guinea‐pig, after the ingestion of iron, showed iron in the bowel mucosa only near the pylorus unless the dose was large (McCallum, 1894); later the distribution of the iron‐containing protein ferritin was found to be similar (Granick, 1946 a, b; Gillman and Ivy, 1947). The significance of these findings was questioned when it was noted that after administration of radioactive iron to guinea‐pigs, the radioactivity in the mucosa did not coincide with the histochemical iron (Endicott, Gillman, Brecher, Ness, Clarke and Adamik, 1949). Support for the importance of the duodenum came from autoradiograms of the excised intestine of rats after intragastric administration of radioactive iron, which demonstrated radioactivity only at the pylorus and in the duodenum (Wack and Wyatt, 1959); when the rat was anaemic the radioactivity extended to the caecum. While these studies are suggestive of maximal absorption of iron in the duodenum, they only demonstrate iron in the bowel wall and not the amount absorbed, which may well have passed into the rest of the body.

Measurements of the absorption of iron from different areas of the bowel have led to no uniformity of opinion on the importance of the duodenum. Absorption of iron introduced into jejunal fistulae in two dogs (Hahn, Bale, Ross, Balfour and Whipple, 1943; Stewart, Yuile, Claiborne, Snowman and Whipple, 1950) was less than when the dose was given into the stomach. In man, the duodenum is by‐passed when a gastrojejunal anastomosis is performed after partial gastric resection; the absorption of inorganic iron in such patients is not significantly different from that in patients who have a gastroduodenal anastomosis after the gastric resection (Smith and Mallett, 1957; Duthie, 1959). It can thus be seen that the role of the duodenum in the intestinal absorption of iron is not fully defined: the studies to be reported here have been designed to clarify this question.
A SYMPOSIUM ON SIDEROBLASTIC ANAEMIA Held at the Postgraduate Medical School of London on Friday, March 20th, 1964, during the Annual Meeting of the British Society for Haematology. Introduction: Sideroblasts and Sideroblastic Anaemia
Authors: Mollin D. L.
Published: March 2008

The main purpose of this introductory paper is to describe the haematological features of the different varieties of sideroblastic anaemia and to discuss how these disorders may be related and classified. A number of the points made here were previously touched on in a paper read at the European Congress of Haematology, London (Mollin and Dacie, 1960).
Sideroblastic Anaemia, Mitochondria and Erythroblastic Iron
Authors: Bessis M. C. , Jensen W. N.
Published: March 2008

The variety of terms used to describe the hypersideraemic hypersiderotic anaemia associated with normoblastic bone marrow which is refractory to treatment reflects the impression that these disorders have diverse causes (Dacie, Smith, White and Mollin, 1959; Bernard, Lortholary, Levy, Bonon, Najean and Tanzer, 1963; Heilmeyer, 1963). Despite valid objections, they are often referred to as ‘sideroblastic anaemias’. The term ‘sideroblastic anaemia’ at least affords a discrete point of cytological reference which infers a pathogenetic significance of the sideroblast. It is desirable, therefore, to inquire as to the morphological nature of the sideroblast.
Experimental Sideroblastic Anaemia
Authors: Harriss Eileen B. , MacGibbon Barbara H. , Mollin D. L.
Published: March 2008

There is increasing evidence that some defect of pyridoxine metabolism is implicated in human sideroblastic anaemia. Some cases of sideroblastic anaemia respond to treatment with pyridoxine although large doses may be necessary. Pyridoxine is known to be a necessary co‐enzyme in the early stages of haem synthesis (Schulman and Richert, 1957; Kikuchi, Kumar, Talmage and Shemin, 1958) and haemoglobin synthesis is impaired in sideroblastic anaemia where hypochromasia exists in the presence of abundant iron stores. Several species of animals develop a hypochromic anaemia when deprived of pyridoxine (Fouts, Helmer and Lepkovsky, 1940; Wintrobe, Follis, Miller, Stein, Alcayaga, Humphreys, Suksta and Cartwright, 1943; Hegsted and Rao, 1945; Kornberg, Tabor and Sebrell, 1945; Luckey, Briggs, Elvehjem and Hart, 1945; Poppen, Greenberg and Rinehart, 1952; Gershoff, Faragalla, Nelson and Andrus, 1959; Mirone and Jackson, 1959; Harriss, 1963; Shen, Wong and Oguro, 1964) but it is not clear from these reports whether the animals showed ‘ring’ sideroblasts and other features characteristic of human sideroblastic anaemia. In order to investigate more fully the relationship between sideroblastic anaemia and pyridoxine metabolism, we have attempted to reproduce in experimental animals a condition similar to the anaemia seen in man.

Pyridoxine deficiency was produced in animals by feeding a diet deficient in pyridoxine or by giving drugs known to interfere with pyridoxine metabolism. The use of antituberculous drugs was suggested by the observation of Verwilghen, Lahaye, van Orshoven and Reybrouck (1963) that sideroblastic anaemia occurred in tuberculous patients treated with isoniazid, cycloserine, pyrazinamide and p‐aminosalicylic acid (PAS).
Familial Haemolytic Anaemia with Erythrocyte Inclusion Bodies, Bilifuscinuria and Abnormal Haemoglobin (Haemoglobin Galliera Genova)
Authors: Sansone G. , Pik C.
Published: March 2008

From the heterogeneous group of the non‐spherocytic haemolytic anaemias a new clinical and haematological entity has been isolated in recent years in which the presence of red‐cell inclusion bodies and the excretion of dark brown urine are associated with the characteristics commonly observed in all chronic haemolytic processes.

In 1952 Cathie described what may be the first case in medical literature. He noted the remarkable finding of apparently spontaneous Heinz bodies in the erythrocytes of an infant after splenectomy. Later on a new characteristic was added to the pattern of the disease, the identification of dipyrrolic mesobilifuscin in the urine (Schmid, Brecher and Clemens, 1959), and more recently an abnormal haemoglobin fraction was detected (Scott, Haut, Cartwright and Wintrobe, 1960).

Up to now less than ten cases have been reported. The subject has been briefly and clearly reviewed by Schmid (1961).

We had the opportunity of studying an Italian family in which the mother and the only daughter were affected by the disease. It was fortunate for our study that only the mother had been splenectomized; we could, therefore, compare the haematological findings in a splenectomized and in a non‐splenectomized case. The finding of an abnormal haemoglobin component makes our observation similar to those of Scott et al. (1960), Pribilla (1962) and Hutchison, Pinkerton, Waters, Douglas, Lehmann and Beale (1964).
Haemopoietic Changes in the Rat during Growth and during Continuous Gamma Irradiation of the Adult Animal
Authors: Lord B. I.
Published: March 2008

In this report, the changing patterns of cell proliferation in the various haemopoietic tissues (in particular the bone marrow and the spleen of the rat) are studied in relation to one another and to the changing requirements for blood production during growth. Particular attention is given to the erythropoietic system.

In addition, haemopoiesis during growth involves maintaining the cellular content of an expanding blood volume and previous work (Lamerton, Pontifex, Blackett and Adams, 1960; Lord, 1964) has shown that the cellular content of the blood can be maintained in spite of a greatly depleted marrow cell population. Therefore, changes in cell proliferation in the bone marrow and spleen of adult rats following doses of continuous whole‐body γ‐irradiation are also studied. These changes are compared with those taking place during growth.
Persistent Post‐Splenectomy Thrombocytosis and Thrombo‐embolism: A Consequence of Continuing Anaemia
Authors: Hirsh J. , Dacie J. V.
Published: March 2008

splenectomy is usually followed by a mild, symptomless thrombocytosis which reaches a peak at about the end of the second week and gradually subsides within 3 months (Evans, 1928; Doan, Curtis and Wiseman, 1935; Wollstein and Kreidel, 1936; Ek and Rayner, 1950; Welch and Dameshek, 1950; Sedgwick and Hume, 1960). Occasionally, however, post‐splenectomy thrombocytosis persists (Rosenthal, 1925; Chesner, 1946; Mills and Lucia, 1949; Green, Conley, Ashburn and Peters, 1953; Merskey and Budtz‐Olsen, 1953; Gelpi and Ende, 1958; Byrd and Cooper, 1961; Barry and Day, 1962; Hayes, Spurr, Hutaff and Sheets, 1963; Dacie, Grimes, Meisler, Steingold, Hemsted, Beaven and White, 1964; Grimes, Meisler and Dacie, 1964; Losowsky and Hall, 1965) and may be associated with thrombo‐embolic complications (Rosenthal, 1925; Chesner, 1946; Mills and Lucia, 1949; Gelpi and Ende, 1958; Byrd and Cooper, 1961; Barry and Day, 1962; Hayes et al., 1963). However, although per‐sistent post‐splenectomy thrombocytosis has thus been recognized for many years, the underlying cause is poorly understood and has seldom been discussed. A consideration of the mechanism of post‐splenectomy thrombocytosis and its possible bearing on post‐splenectomy thrombo‐embolism forms the basis of this report.

The present findings, based on a study of patients with a variety of anaemias and haematologically normal controls, suggest that persistence of thrombosytosis after splenectomy can usually be predicted: this happens when anaemia continues after splenectomy in association with active haemopoiesis.
The Nature of the Vitamin B12 Binding Protein in Human Serum*
Authors: Hardwicke J. , Jones J. Howel
Published: March 2008

It has been known for some years that the vitamin B12 circulating in the plasma is bound to protein. When this plasma binding capacity is exceeded, by the oral or intravenous administration of large doses of the vitamin, the excess unbound vitamin is rapidly excreted in the urine (Mollin and Ross, 1953). The exact nature of this binding protein has yet to be identified. In normal subjects and in patients with myeloproliferative disorders it migrates electrophoretically with the speed of an α1‐globulin, and is present in that fraction of the serum proteins which is not precipitated by 0.6 M‐perchloric acid, the seromucoid fraction (Weinstein, Weissman and Watkin, 1959). This serum fraction contains a number of antigenically distinct proteins (Burtin, 1964), two of which have been identified respectively as Orosomucoid and the α1‐acid–glycoprotein of Schultze (Hardwicke and St. Cyr, 1961).

In this paper the binding of vitamin B12 to the constituent fractions of a seromucoid, obtained by (NH4)2 SO4 fractionation of serum, has been investigated by chromatography on DEAE‐cellulose. Binding into this seromucoid fraction of the serum proteins is confirmed, in normals and in myeloproliferative disorders, but this binding appears to be onto two separable serum proteins which are neither the Orosomucoid nor any other recognized α1‐glycoprotein.
Studies on Neutrophil Function. II. PATHOLOGICAL ASPECTS
Authors: Penny R. , Galton D. A. G.
Published: March 2008

The functional capacities of mature neutrophils in disease have been less studied than their biochemical, cytogenetic and cytochemical characteristics. It is surprising that the biochemical and other abnormalities revealed in recent years have not been related to functional capacity. In the present study two features of neutrophil function have been examined: they are first, the capacity of the neutrophils to adhere to glass, as shown by the reduction in the proportion of cells emerging after the passage of blood through a column of minute glass beads; and second, the capacity of the neutrophils to phagocytose heat‐killed yeast cells. By these simple means, applied to the blood of normal subjects and of patients, it has been possible to examine the relationship between the adhesiveness of the neutrophils and their capacity for phagocytosis, and the dependence of each activity on factors intrinsic to the neutrophils and on extrinsic factors. The physiological aspects of the work have been reported in the preceding paper (Penny, Galton, Scott and Eisen, 1966).
Involvement of the Erythroid Series in Blastic Crisis of Chronic Myeloid Leukaemia. FURTHER EVIDENCE FOR THE PRESENCE OF PHILADELPHIA CHROMOSOME IN ERYTHROBLASTS
Authors: Clein G. P. , Flemans R. J.
Published: March 2008

Involvement of the erythroid series in chronic myeloid leukaemia may be evidenced haematologically by a normochromic anaemia with anisocytosis, the presence of circulating normoblasts, the presence of bizarre normoblasts in the marrow and peripheral blood, and rarely the presence of sideroblasts. The Philadelphia (Ph1) chromosome has been assumed to be present in the erythrocyte as well as the granulocyte series on good but circumstantial evidence and it is generally agreed that the leukaemic process probably affects the basic stem cell of the red cells, granulocytes and platelets.

When blastic crisis occurs there is an increase in the percentage of blast cells in marrow and peripheral blood, and anaemia, thrombocytopenia and resistance to therapy accompany the apparently irreversible downward clinical course. Aneuploid cell lines emerge (Hammouda, Quaglino and Hayhoe, 1964). We are here presenting evidence that aneuploid Ph1‐positive cell lines are also found in the erythroid cells in blastic crisis and therefore that when this occurs the essential change may also affect the basic stem cell. In a case of chronic myeloid leukaemia seen recently, a sideroblastic phase was found terminally and it was possible to combine standard cytogenetic methods with Perls's prussian blue stain for iron and demonstrate siderotic granules in the cytoplasm surrounding Ph1‐positive aneuploid chromosome spreads. We thus prove the erythroid nature of these spreads, and incidentally provide more direct evidence than offered hitherto, for the presence of the Ph1 chromosome in the erythroid cells.
Red Cell Life Span in Iron Deficiency Anaemia
Authors: Loría Alvar , Sánchez‐Medal Luis , Lisker Rubén , Rodríguez Elisa de , Labardini Juan
Published: March 2008

Ashby survival studies were performed with hypochromic red cells of six patients with iron deficiency anaemia in the circulation of normal subjects and with normal red cells in two patients with iron deficiency anaemia. Three of the anaemic donors were professional donors with anaemia due to excessive blood donations as the only abnormality.

The life span of the hypochromic cells was decreased (46–85 days) whereas the normal cells survived normally or near normally in the patients with iron deficiency anaemia. Simultaneous 51Cr survival studies made with the hypochromic cells gave normal results in one instance and abnormal results in three. These findings suggest that hypochromic cells have a shortened life span due to an intracorpuscular defect.

In a complementary study, it was observed that hypochromic cells showing a decreased survival in two normal individuals, had a normal survival in a splenectomized subject.
The Fibrinolytic Response to Moderate Exercise and Intravenous Adrenaline in the Same Subjects
Authors: Cash J. D. , Allan A. G. E.
Published: March 2008

The fibrinolytic response, as measured by the euglobulin lysis time, to exercise and intravenous adrenaline was studied in 25 normal young subjects. A good correlation was demonstrated between the individual response to the two stimulants. These findings are regarded as further proof of the existence of a small group of apparently healthy young persons whose mechanisms for generating plasminogen activator to stress are defective.
Köln Haemoglobinopathy: FURTHER DATA AND A COMPARISON WITH OTHER HEREDITARY HEINZ BODY ANAEMIAS
Authors: Jones R. Vaughan , Grimes A. J. , Carrell R. W. , Lehmann H.
Published: March 2008

Five patients with haemolytic anaemia from one family were studied; three had splenomegaly and one who had been splenectomized had numerous inclusions in his fresh red cells. An abnormal haemoglobin was found by electrophoresis. This was isolated and identified as α2β2 98 Valine → Methionine, i.e. Haemoglobin Köln.

Abnormal red cell GSH and methaemoglobin values were found in fresh and incubated blood. The presence of a heat‐labile haemoglobin fraction and the formation of inclusion bodies in red cells incubated in vitro was confirmed. Red‐cell morphology and the benefit of splenectomy are discussed.

The findings in patients with Haemoglobin Köln are compared with those reported in other hereditary Heinz‐body anaemias. It appears that at present Köln haemoglobinopathy is the commonest member of this group of disorders.
The Erythrocythaemic Effects of Androgen
Authors: Gardner Frank H. , Nathan David G. , Piomelli Sergio , Cummins James F.
Published: March 2008

Summary. Pharmacological doses of androgens increased the total red‐cell mass as well as the plasma volume in fifteen elderly normal male subjects. The changes in peripheral erythropoietic measurements are related to total red‐cell mass increments rather than alterations of the plasma volume.
Effect of Vincristine on Synthesis of Ribonucleic Acid and Protein in Leukaemic Leucocytes
Authors: Cline M. J.
Published: March 2008

Summary

Vincristine, 7 × 10−5 m in vitro, inhibits the incorporation of 3H‐uridine into RNA and of amino acids into protein by neoplastic human leucocytes within 15–45 minutes. Normal granulocytes are resistant to this inhibitory action.

The inhibition of 3H‐uridine incorporation into RNA of malignant leucocytes is time‐ and dose‐dependent and at 24 hours is observed at concentrations as low as 7× 10−9 M.

The synthesis of all the classes of RNA discriminated by density gradient centrifugation is inhibited by vincristine.

The production of lactate and of 14CO2 from glucose‐1‐14C and cell viability are unaffected by vincristine, 7×10−5 m, for periods up to 7.5 hours.

Plasma obtained within 60 minutes of vincristine administration had an inhibitory effect on 3H‐uridine incorporation by myeloblasts from one patient.

Because RNA and protein synthesis in human leucocytes were closely linked it could not be determined which process was inhibited first by the alkaloid.

Vincristine, 7×10−5 m, was without effect on the incorporation of 14C‐phenylalanine by a cell‐free bacterial system containing artificial polyribonucleotide or viral RNA as messenger.
The Effect of Enteral and Parenteral Iron on Ferritin Synthesis in the Intestinal Mucosa of the Rat
Authors: Smith J. A. , Drysdale J. W. , Goldberg A. , Munro H. N.
Published: March 2008

Summary It has been suggested that the iron incorporated into ferritin of intestinal mucosa provides a means for the excretion of unrequired iron. In iron deficiency there is little mucosal ferritin but in states of iron repletion there is ample.

In the present study oral and parenteral administration of iron in the rat caused a three‐ and ten‐fold increase, respectively, in ferritin synthesis in intestinal mucosa, assayed by the rate of incorporation of 1–14C‐dl‐leucine into ferritin. Small‐scale isolation of mucosal ferritin was achieved by using a specific antiserum prepared by injection of horse spleen ferritin into rabbits.

These results help to explain how iron absorption and excretion may be controlled by the iron content of the body.
Pyridoxine and Riboflavin Status in the Paterson — Kelly Syndrome
Authors: Jacobs A. , Cavill I. A. J.
Published: March 2008

Summary A study of 25 patients with the Paterson‐Kelly syndrome shows them to have a normal red cell total riboflavin content. This suggests that riboflavin deficiency is not an important factor in this condition. There is a reduction of red cell transaminase activity which can be stimulated in vitro by pyridoxal phosphate. In three cases the administration of pyridoxine resulted in an in viva rise in red cell transaminase activity. Some degree of pyridoxine deficiency appears to be common in the Paterson‐Kelly syndrome.
Antihaemophilic Globulin (AHG) in Multiple Myeloma and Macroglobulinaemia
Authors: Weiss Harvey J. , Kochwa Shaul
Published: March 2008

SummaryAnti‐haemophilic globulin (AHG) was markedly increased in eight out of 11 untreated patients with γG myeloma, two out of eight patients with γA myeloma and two out of six patients with macroglobulinaemia.

Among patients with γG myeloma, increase in AHG did not correlate with the Gmgroup, H‐chain subtype, γG concentration or starch gel pattern.

There was no correlation between AHG and either the fibrinogen concentration, platelet count or percentage of plasma cells in the bone marrow. Thrombotic complications were not observed in patients with increased AHG.

The increase in AHG cannot be attributed to a binding of active AHG by myeloma protein or,in vitro, to a stimulatory effect on AHG activity.

In some patients, therapy produced a striking change in their AHG concentration.
Infusion of Marrow and Spleen Cells in Irradiated NZB/Bl Mice: Amelioration of Autoimmune Disease
Authors: Lindsey Edward S. , Woodruff M. F. A.
Published: March 2008

Summary Adult NZB/Bl mice which showed a positive Coombs' test and other evidence of abnormal haemolysis were exposed to 800 r. whole body irradiation. They were then given an intravenous injection of bone marrow or a mixture of bone marrow and spleen cells from either young (Coombs negative) NZB/Bl mice or Coombs negative (NZB/Bl × T6) F1 hybrids.

One of the 14 mice which received isogeneic cells died before being retested. Nine of the remaining 13 became Coombs negative; five of these remained negative and four reverted to Coombs positive 1–8 months after cell injection.

Four of the II mice which received F1 cells died before being retested; six of the remaining seven became Coombs negative and remained so until they died or were killed 1–12 months after cell injection. Chromosome studies in the animal which survived longest in this group revealed that all dividing cells in the spleen and lymph nodes, and 90 per cent of the dividing cells in the bone marrow, were of donor origin.
The Oral Lesions of Iron Deficiency Anaemia: Pyridoxine and Riboflavin Status
Authors: Jacobs A. , Cavill I.
Published: March 2008

Summary Erythrocyte glutamic pyruvic transaminase activity is reduced in patients with iron deficiency anaemia and can be restored in vitro by the pyridoxal phosphate co‐enzyme. This abnormality is related to the presence of oral epithelial lesions rather than to the degree of anaemia. It is suggested that pyridoxine deficiency may be associated with the occurrence of oral lesions in anaemic patients.
The Effect of pH on the Volume, Density and Shape of Erythrocytes and Thymic Lymphocytes*
Authors: Legge D. G. , Shortman Ken
Published: March 2008

Summary Erythrocytes increase in volume, decrease in density and become more spherical as the pH of isotonic media decreases over the range 9.4–4.8. Swelling is rapid, reversible, occurs in a wide range of media and is independent of gas exchange; there is strong indirect evidence that it is independent of metabolic activity. The swelling is largely the result of entry of anions in the cell as the pH falls, in accordance with the degree of ionization of haemoglobin and Gibbs‐Donnan equilibria. Human erythrocytes show a complex response to the anion uptake, fail to act as perfect osmometers and ‘resist’ swelling in isotonic solutions. Rat erythrocytes differ, and swell to the extent predicted from their anion uptake.

By contrast, the volume of thymic lymphocytes does not normally vary with pH. Small changes in volume are observed in acid media containing acetate or phthalate, but no change occurs in albumin solutions used for density gradient analysis.

The results emphasize the need for control of pH as well as tonicity when using erythrocytes to calibrate Coulter Counter apertures, or when performing size range or density distribution analyses of erythrocyte populations.
Bone Marrow Colony Stimulating Activity in Human Sera. RESULTS OF TWO INDEPENDENT SURVEYS IN BUFFALO AND MELBOURNE*
Authors: Foster R. , Metcalf D. , Robinson W. A. , Bradley T. R.
Published: March 2008

In two independent surveys, 1188 sera from 947 normal persons or patients with various diseases were tested for their capacity to stimulate mouse bone marrow cells to proliferate in vitro and form cell colonies. Ninety‐eight per cent of sera from normal persons had no colony stimulating activity.

Colony stimulating activity was detected in sera from 15 to 70 per cent of patients with: (1) leukaemia and allied diseases, particularly in the advanced stages and active phases of the diseases, (2) proliferative diseases of leukopoiesis, and (3) non‐bacterial infections.

Regardless of the source of the active serum, all colonies stimulated initially contained granulocytic cells and later contained phagocytic mononuclear cells.
Immunological Studies of Proteins Associated with the Subcellular Fractions of Thrombasthenic and Afibrinogenaemic Platelets
Authors: Nachman R. L. , Marcus A. J.
Published: March 2008

Immunological studies of proteins associated with subcellular fractions of normal, thrombasthenic, and afibrinogenaemic platelets are reported. Thrombosthenin, the contractile protein of platelets, was present in afibrinogenaemic and thrombasthenic platelets in approximately normal amounts as determined by fluorescent antibody staining. Thrombasthenic and afibrinogenaemic platelets were markedly deficient in cell‐bound fibrinogen. One hundred per cent of afibrinogenaemic platelet fibrinogen was present in the intracellular granule fraction compared to 10 per cent in thrombasthenic and 27 per cent in normal platelets. An abnormal protein pattern was observed in the thrombasthenic granule preparation, while proteins derived from thrombasthenic membranes were deficient in one of the normal membrane components. The soluble ‘cell sap’fractions of the afibrinogenaemic and thrombasthenic platelets contained normal amounts of albumin, γ‐globulin and Factor XIII. The results suggest that decreased platelet fibrinogen in thrombasthenia may be a secondary phenomenon, perhaps related to an underlying membrane defect. The presence of platelet fibrinogen in the granule fraction of afibrinogenaemic platelets supports the concept of two separate pools of fibrinogen—intracellular and extracellular.
Significance of Red Cell Age to Red Cell Destruction during Experimental Pyrexia
Authors: Karle Hans
Published: March 2008

By the use of cohort labelling with 59Fe and double‐generation labelling, either with DF32P and 59Fe or with 59Fe and 55Fe, it was demonstrated that the increased haemolysis occurring during experimental pyrexia in rabbits affects predominantly the older red cells.
Erythraemia in Experimental Nephritis *
Authors: Davies Sylvia W.
Published: March 2008

Seven out of 30 rabbits with experimental nephritis developed erythraemia; all seven animals developed persistently high values for the haemoglobin and the packed cell volume. Radioactive isotope investigations were done in five of these animals and in all there was an increase in the red cell mass. There was no particular relationship between the blood picture and the biochemical and histological changes. Changes in blood volume were assessed according to alterations in weight. The renal lesions involved the glomerular capillary basement membrane; there were no arterial changes.

In man erythraemia has been described in association with the nephrotic syndrome and with membranous nephritis. Other ischaemic lesions of the kidney have resulted in erythraemia both in animals and in man. It is proposed that the primary erythropoietic stimulus is provided by moderate glomerular ischaemia.
Prednisolone‐Induced Granulocytosis
Authors: Cream J. J.
Published: March 2008

A neutrophil granulocytosis with peak response at 5 hours develops after the administration of 40 mg. prednisolone tablets. In normal people the increment is greater than 2000 granulocytes per cu.mm. The response declines with advancing age, but is unrelated to sex, height, weight, surface area and initial neutrophil count. The largest responses are seen in young splenectomized people. Of 21 subjects with abnormal marrows only two gave normal responses.

The results of this preliminary study suggest that the granulocyte increment following a single oral dose of prednisolone may prove to be a useful index of marrow function. Further studies, particularly serial observations in selected patients, are necessary to establish its validity and to define the role of age and the spleen.
The Coagulant Activity of Platelets
Authors: Biggs Rosemary , Denson K. W. E. , Riesenberg D. , McIntyre Carolyn
Published: March 2008

When platelet‐rich plasma is incubated for 16–20 hours at 37° C. and the platelets are then separated and washed, tissue‐factor activity develops in these platelets. The active platelets accellerate the clotting of plasma samples deficient in Factor XII, XI, IX or VIII, and of normal plasma; the coagulant activity for samples deficient in Factors V, VII and X is much less marked. The activity developed will cause activation of Factor X in a serum eluate, whereas no such activity is evident in platelets separated from plasma immediately after collection from the donor.

The development of tissue‐factor activity of platelets depends on the presence of Factor XII but not on the presence of any of the other factors tested. The relationship of tissue‐factor activity to platelet factor 3 is discussed.
Familial Thrombopathic Thrombocytopenia
Authors: Kurstjens R. , Bolt C. , Vossen M. , Haanen C.
Published: March 2008

A family with hereditary thrombopathic thrombocytopenia is described, with eight affected members in three generations. The haemorrhagic diathesis manifests itself by bleeding from mucous membranes and after operative procedures. The platelet count varies from 20,000 to 80,000 per cu.mm. The number of megakaryocytes in the bone marrow has been examined in two affected members, and the platelet survival in one, and both are normal.

The thrombopathy consists in a deficiency of platelet factor 3 and in morphological anomalies. Electron microscopy has revealed a low content of α‐granules in platelets from two cases. The heredity shows an autosomal dominant pattern. A linkage of this genetic defect with blood group O seems probable.
Red Cell Survival in Experimental Cholestatic Jaundice
Authors: Powell L. W. , Dunnicliff Margaret A. , Billing Barbara H.
Published: March 2008

Red cell survival was estimated in Sprague‐Dawley and Gunn rats following bile duct ligation. A significant difference in the values for red cell survival was found between bile‐duct‐ligated Sprague‐Dawley rats and their sham‐operated controls using both the 51Cr and DF23P techniques, but no significant difference was observed between bile duct ligated homozygous Gunn rats and their sham‐operated controls. Heterozygous Gunn rats behaved similarly to Sprague‐Dawley rats with respect to haemolysis after bile duct ligation. These findings suggested that the haemolytic process accompanying cholestatic jaundice may be related to the increased levels of conjugated bilirubin in the plasma but not to the accumulation of conjugated bile acids, phospholipids and cholesterol.

A significant difference in red cell survival was observed between sham‐operated controls and non‐operated controls in both Sprague‐Dawley and Gunn rats; this was probably due to activation, by the operation, of Haemobartonella muris infection, which was subsequently found to be endemic in the colony.
Mechanism of Endotoxin Interaction with Human Leucocytes
Authors: Cline M. J. , Melmon K. L. , Davis W. C. , Williams H. E.
Published: March 2008

An investigation to define the mechanism of the interaction between endotoxin and human leucocytes is reported. Endotoxin produces the following changes in human leucocytes suspended in vitro in normal plasma or serum: leak of kininase and lysozyme from the cell into the medium, decreased cellular α‐glucosidase and phosphorylase activity, increased production of lactate and of 14CO2 from glucose‐1‐14C and increased incorporation of tritiated uridine into RNA and acid‐soluble nucleotide. The metabolic changes induced by endotoxin and the uptake of radioactive endotoxin by granulocytes are diminished if the suspending medium is depleted of complement components.

The thesis is presented that endotoxin in the presence of complement is ingested by or adheres to the human granulocyte and induces a series of metabolic changes resembling those associated with phagocytosis.
Concentrative Uptake of Glycine‐1‐14C by Erythrocytes in Iron‐Deficiency Anaemia
Authors: Iyer G. Y. N.
Published: March 2008

In iron‐deficiency anaemia erythrocytes concentrate added glycine‐1‐14C establishing cellular: extracellular distribution ratios distinctly higher than normal. This uphill transport is abolished at low temperature and by substitution of a potassium rich, sodium poor medium. lodoacetamide is inhibitory. Added glycine and sarcosine also reduce the distribution ratio. The uptake of glycine is considered in the light of known changes in erythrocyte metabolism and age in iron‐deficiency anaemia.