bluuebunny/crossref_metadata_2025_split huggingface dataset:
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 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.
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.
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

SUMMARYAshby 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

SUMMARYThe 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

SUMMARYFive 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.
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.
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 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.