bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of Resistance of Human Acute Leukaemia Cells to Cytosine Arabinoside
Authors: Tattersall M. H. N. , Ganeshguru K. , Hoffbrand A. V. 
Published: March 2008

Summary. Biochemical differences between human acute myeloblastic leukaemia cells sensitive and resistant to cytosine arabinoside have been studied. Bone marrow cells from seven patients with leukaemia resistant to cytosine arabinoside showed deoxycytidine kinase activity either below normal or in the low normal range and the mean level of this enzyme was significantly lower in cells from resistant than sensitive cases. On the other hand, deoxycytidine deaminase activity tended to be high in resistant cells but the difference from sensitive cells was not statistically significant. Deoxycytidylate deaminase activity also did not vary significantly with degree of sensitivity to cytosine arabinoside. The free concentrations of the four deoxyribonucleoside triphosphates were, in general, lower in resistant than sensitive marrow cells. The deoxycytidine triphosphate level, however, was relatively increased in the resistant cells.We conclude that a number of biochemical changes may be present in cytosine arabinoside resistant leukaemia cells. It is likely that kinetic differences are the basis for some of these changes, and that low proliferative rate may be the major cause of cytosine arabinoside resistance. Selection of cells with raised deoxycytidine deaminase levels and relatively increased deoxycytidine triphosphte concentrations may also contribute to resistance.
A Serum Haemolytic Factor Demonstrable at Low Ionic Strength
Authors: Riedler G. F. , Straub P. W. 
Published: March 2008

Summary. In the sucrose haemolysis test incubation of patient serum with normal compatible erythrocytes led to the discovery of a new serum haemolytic factor (SHF). Normal erythrocytes in the presence of sucrose 1% haemolysis when incubated with sera of 55 normal individuals, but more than 4% haemolysis with sera of 17 of 37 patients with acute leukaemia, four of 17 with chronic leukaemia and three of eight with aplastic anaemia. Three additional patients with aplastic anaemia and a positive SHF test subsequently developed acute myeloid leukaemia. In three cases of acute myeloblastic ledtaemia the test became negative during remission. In all eight patients with Coombs‐positive haemolytic anaemia the test was negative.The SHF is active only in the presence of sucrose. Its activity is increased with rising temperature; the pH optimum is between 7.4 and 7.8. The factor is labile upon storage except at ‐ 70°C and it is inactivated at 56°C. For incubation times below go min, haemolysis is a linear function of the serum concentration.
In Vitro Spontaneous Thrombin Generation in Human Factor‐IX Concentrates
Authors: Sas Geza , Owens Rosemary E. , Smith James K. , Middleton Sarah , Cash John D. 
Published: March 2008

Summary.A series of in vitro studies designed to ascertain the potential in vivo thrombogenicity of human factor IX‐containing concentrates is described. Using concentrates obtained from several different Centres the fibrinogen clotting time with some preparations was less than 6 h and/or the recalcification time of normal plasma was shortened. In some preparations, however, the plasma recalcification time was lengthened.Further studies revealed that all diluted factor‐IX concentrates generated thrombin after recalcification, and that the rate of thrombin generation appeared to be characteristic of a particular preparation. This characteristic has been designated the TGt50, which is the incubation period in minutes, after recalcification, required to obtain a 50 s clotting time of a fibrinogen substrate. The TGt50 was found to correlate most strongly with recalcification time of celite exhausted plasma (P < 0.001), but no correlation was observed between it and the immunological antithrombin III or factor‐VIII antigen levels. Evidence is presented which suggests that the thrombin generation test and recalcification time of celite exhausted plasma may represent suitable in vitro quality control assays for factor‐IX concentrates.
Fibrin‐Blood Platelet Interaction in a Contracting Clot
Authors: Cohen Isaac , Gabbay Jacob , Glaser Tova , Oplatka Avraham 
Published: March 2008

Summary.The interaction of fibrin and blood platelets was studied by measuring tension development in clots containing different ratios of these two components. Isometric tension attained a saturating value (MT) when plotted as a function of the concentration of either component at a constant concentration of the other. The value of MT increases linearly with the minimal platelet concentration (Ps) required in order to reach saturation at various different fibrin concentrations. A linear relationship also holds in a plot of Ps versus the logarithm of the corresponding fibrin concentration. When the cylindrical clots contracted isotonically, the velocity, normalized with respect to the momentary length, was found to be constant. This velocity decreased in an hyperbolic manner with increasing fibrin concentration at a constant concentration of blood platelets. The results are interpreted in terms of a three‐dimensional network in which the blood platelets serve as contractile cross‐bridges connecting fibrin fibres. Tension development is assumed to be accompanied by the reduction of the angle between fibrin fibres. An attempt was made to calculate the isometric tension developed by a platelet.
Abnormal Membrane Surface Properties during Maturation of Rat Reticulocytes Elicited by Bleeding as Measured by Partition in Two‐Polymer Aqueous Phases
Authors: Walter Harry , Krob Eugene J. , Ascher Galli S. 
Published: March 2008

Summary.Partition of cells in two‐polymer aqueous phases is an extremely sensitive method for the separation of cells and for tracing subtle changes in the cells' membrane surface properties (primarily surface charge) as a function of in vivo processes (e.g. differentiation, maturation, ageing). Combining isotope labelling and cell countercurrent distribution techniques we have examined the membrane surface properties of rat reticulocytes produced in response to erythroid stress by bleeding. It was found that the rapid increase in the partition coefficient of normal reticulocytes subsequent to release into the peripheral blood (which reflects a rapid increase in membrane surface charge) is absent in reticulocytes produced in response to bleeding. In this way the reticulocytes behave like those produced in response to repeated phenylhydrazine injections. ‘Stress reticulocytes’ never mature to erythrocytes having normal membrane surface properties as judged by partition. The experiments show that our previous results are not due to phenylhydrazine per se but rather to the production of ‘stress reticulocytes’. Further, if remodelling of the phlebotomy‐induced reticulocyte cell membrane occurs in the circulation as has been suggested it does not lead to a cell with normal membrane surface properties. Whether the abnormal membrane surface properties of ‘stress reticulocytes’ and of the erythrocytes to which they give rise affect the cells' life‐span is not clear since phenylhydrazine‐induced ‘stress reticulocytes’ have been reported to have at least a component of short‐lived cells while the phlebotomy‐induced cells are said to have a virtually normal life‐span. It is likely that reticulocytes produced in severe anaemias, in general, mature to erythrocytes having abnormal surface properties (i.e. lower membrane surface charge).
The Effect of Diet and Alcohol on the Development of Folate Deficiency in the Rat
Authors: McGuffin Robert , Goff Paul , Hillman R. S. 
Published: March 2008

Summary.Studies of the rate of depletion of serum and tissue methylated and nonmethylated folates were carried out in rats maintained for long periods on either a folate deficient (sucrose‐water/sulphathiazole) diet or a deficient diet plus high alcohol intake. By means of implantation of a feeding gastrostomy tube, it was possible to sustain constant blood ethanol levels of between 50 and 300 mg/dl for 3–4 weeks with relatively normal calorie intake and without death of the animal. Using this animal model, which closely resembles severe alcoholism in man, a very rapid depression in serum 5‐methyl tetrahydrofolate was observed similar to that reported in alcoholic man. At the same time, release of folates from liver stores was unimpaired by alcohol ingestion. Liver folate store depletion rates were identical for alcoholic and folate starved animals. The explanation for the sudden alcohol suppression of serum folate levels must, therefore, be sought at a point in the internal metabolic sequences of folate other than the delivery of folate stores to plasma.
Stimulation by Propylthiouracil of the Hexose Monophosphate Shunt in Human Polymorphonuclear Leucocytes during Phagocytosis
Authors: Tsan Min‐Fu , McIntyre Patricia A. 
Published: March 2008

Summary.The effect of propylthiouracil on glucose metabolism in human polymorphonuclear leucocytes was studied. At a therapeutically achievable concentration (0.1 mm), propylthiouracil stimulated hexose monophosphate shunt activity in normal leucocytes during phagocytosis but not in resting cells. However, in the presence of hydrogen peroxide it stimulated hexose monophosphate shunt activity in resting cells, and in the soluble fraction when reduced glutathione and reduced nictotinamide adenine dinucleotide phosphate (NADPH) were also present. Propylthiouracil had no effect on glucose‐1‐C oxidation in either phagocytosing or resting leucocytes obtained from two male patients with chronic granulomatous disease. Stimulation of the hexose monophosphate shunt activity in normal leucocytes during phagocytosis also was demonstrated with methimazole, thiouracil and thiourea, but not with adenine, uracil or urea. There was an apparent minimal common structure requirement in thiourea. Propylthiouracil had no effect on phagocytosis, formate oxidation, glucose‐6‐phosphate dehydrogenase, 6‐phosphogluconate dehydrogenase or catalase activities. Thus, the stimulation of the hexose monophosphate shunt activity by propylthiouracil is dependent on hydrogen peroxide and is best explained by its stimulation or participation in the glutathione cycle.
Christmas Disease (Haemophilia B) in a Girl with Deletion of the Short Arm of One X‐Chromosome (Functional Turner Syndrome)
Authors: Spinelli A. , Schmid W. , Straub P. W. 
Published: March 2008

SUMMARYA I‐year‐old girl with severe Christmas disease and a factor IX content less than 1% of normal is described. The family history was negative and coagulation studies on her relatives were normal. Genetic investigation showed an XXp‐karyotype with deletion of the short arm of one X‐chromosome, a cytogenetic variant of Turner syndrome. The transmission pathway of the haemophilia gene is discussed.
Carbon Monoxide Production in Patients with Breast Carcinoma
Authors: Cavallin‐Starhl Eva , Mercke C. , Lundh B. 
Published: March 2008

Total haem catabolism has been studied through measurement of endogenous production of carbon monoxide (V co) in 19 patients treated for breast carcinoma. The subjects were divided into three groups. Group A included six patients with haemoglobin (Hb) concentration greater than 11.5 g/dl and considered free from disease. Group B consisted of seven patients with distant metastases and Hb concentration greater than 11.5 g/dl and group C of six patients with distant metastases and anaemia (Hb concentration less than 11.5 g/dl). V co in group A was 10.3 ± 3.7 (mean±1 SD) and in group B 9.0±2.5 μmol/mmol total body haem (TBH)/d. These values are not different from our normal values of 10.8 ± 2.8 μmol/mmol TBH/d. In group C V co was 21.1 ± 3.1 (an increase of 100%). V co was compared to daily catabolism of circulating red cell haemoglobin haem (V haem‐c) in the V co/V haem‐c quotient. V haem‐c was calculated from total circulating red cell haemoglobin haem (TBHb‐c) and red cell survival. In group A and group B this quotient was 1.3 ± 0.6 and 1.1 ± 0.2, respectively, and in group C was 2.5 ± 0.9. The difference between group A and B on one side and group C on the other side was significant (P<0.001). The ‘extra’ CO produced in patients with anaemia and disseminated disease (group C) was thought to originate from increased turnover of bone marrow haem, reflecting considerable ineffective erythropoiesis with destruction of haemoglobinized immature red cells. The results confirm earlier findings of a high V co/V haem‐c quotients in patients with anaemia secondary to Hodgkin's disease.
Role of Vitamin B12 in Folate Coenzyme Synthesis
Authors: Perry Janet , Lumb M. , Laundy M. , Reynolds E. H. , CHANARIN I. 
Published: March 2008

Normal red cells in man were found to contain predominantly folate pentaglutamates with smaller amounts of tetra‐ and hexapolyglutamates. There was no change in the type of polyglutamate present in red cells from patients with vitamin B12 deficiency and primary folate deficiency.In contrast to the fall in red cell polyglutamate concentration in vitamin B12 deficiency, there was a marked fall in short‐chain folates in early folate deficiency (treated non‐anaemic epileptics) and a fall in both short chain and long chain polyglutamates in patients with severe folate deficiency and megaloblastic anaemia. These differences in folate distribution within cells exclude a primary failure to transport methylfolate into cells as the lesion in vitamin B12 deficiency.The failure of folate polyglutamate synthesis in vitamin B12 deficiency arises either from a failure to provide the proper substrate for polyglutamate synthesis or to a direct requirement for vitamin B12 for polyglutamate synthesis.
Variable Response of Bone Marrow to Feeding DL‐5‐Formyltetrahydrofolate in Pernicious Anaemia
Authors: Cooper B. A. , Abe T. 
Published: March 2008

It has been suggested that the megaloblastic anaemia in pernicious anaemia is due to inadequate intracellular concentration of monoglutamyl folates other than methyltetrahydrofolate caused by diminished conversion of methyltetrahydrofolate to tetrahydrofolate (methylfolate trap). To test this, we have increased the concentration of methyltetrahydrofolate in the plasma of six patients with pernicious anaemia by feeding DL‐5‐formyltetrahydrofolate. The effect of therapy on bone marrow morphology and routine haematologic parameters was measured. Of two patients receiving 800 μ/d of DL‐5‐formyltetrahydrofolate, one had a significant response; of four receiving 6 mg/d, one converted erythroid maturation to normoblastic, and in two others some improvement was noted in levels of neutrophils, platelets or reticulocytes although marrow morphology remained megaloblastic. Response did not correlate with the degree of elevation of plasma folate. In patients receiving this therapy, slight increase of methylcobalamin in plasma may have occurred (P<0.05).These observations support ineffective utilization of methyltetrahydrofolate as the major cause of megaloblastic anaemia in pernicious anaemia, but indicate that the degree and location of block varied in different patients, and in different precursor cells of a single patient.
Growth of Mouse Yolk Sac Cells Cultured in Vivo
Authors: Weinberg Sheila R. , Stohlman Frederick 
Published: March 2008

The proliferation and differentiation of yolk sac cells from 10 1/2‐day‐old mouse embryos were studied in diffusion chambers implanted into syngeneic and allogeneic hosts. The most striking observation was the appearance, proliferation and predominance of immature and mature plasma cells. The data suggested that the differentiation into plasma cells and the rate of growth of yolk sac cells cultured in vivo may be dependent on the genetics of the strain of mouse and host.This demonstration of differentiation of plasma cells from yolk sac cells cultured in vivo adds further information to the origin and ontogeny of potentially immunocompetent cells.
Thymidine Kinase in Megaloblastic Anaemia
Authors: Hooton J. W. L. , Hoffbrand A. V. 
Published: March 2008

Summary. Thymidine kinase has been measured in phytohaemagglutinin (PHA)‐stimulated lymphocytes from 13 normal subjects and eight patients with megaloblastic anaemia. The levels in normal subjects ranged from 0.20 to 2.10 units/mg protein (mean 0.903 units/mg protein) and in megaloblastic anaemia from 2.99 to 9.97 units/mg protein (mean 5.76 units/mg protein). All the patients showed raised levels of the enzyme which were partly but not completely reduced to normal by addition of folic acid in vitro. Vitamin B12in vitro had a lowering effect in the five vitamin‐B12‐deficient patients and two patients with combined deficiencies but not in one‘pure’folate‐deficient patient.Thymidine kinase activity was highest in the cells of the least anaemic patients, suggesting that the degree of anaemia in megaloblastic anaemia may be determined in part by the ability of the cells to utilize thymidine by the 'salvage’pathway when the de novo pathway of thymidylate synthesis is failing.The rise in thymidine kinase activity in megaloblastic anaemia is presumably due to induction of the enzyme. Addition of methotrexate or 5‐fluorouracil, drugs known to inhibit de novo thymidylate synthesis, caused an increase in thymidine kinase activity in normal PHA‐stimulated lymphocytes after 24 h (but not after 1 h) which could be completely blocked by addition of puromycin.Thymidine mono‐ and di‐phosphate kinases were also measured in normal PHA‐stimulated lymphocytes. The activities were substantially higher than that of thymidine kinase and their activities were unaffected by methotrexate addition.
Adaptation of Marrow Sinus Wall to Fluctuation in the Rate of Cell Delivery: Studies in Rabbits after Blood‐letting
Authors: Tavassoli Mehdi 
Published: March 2008

The extent of marrow sinus wall coverage by perisinal adventitial cells was measured before and after removing 25% of the calculated blood volume in rabbits. A marked reduction in the area covered by adventitial cells was recorded coinciding with the early reticulocyte response to phlebotomy. In control animals, only scattered microfilaments were occasionally observed in the cytoplasmic process of adventitial cells. After phlebotomy, these filaments were more frequently observed and appeared as band‐like structures, raising the possibility of an active role for perisinal adventitial cells in response to fluctuations in the magnitude of cell traffic.Perisinal adventitial cells may, therefore, translate the body's demand for cell delivery by regulating the rate of transmural cell migration from the marrow. Such an adaptive mechanism may depend on the incompleteness of the adventitial layer of the sinus wall and the absence of endothelial‐adventitial cell junctions, permitting separation of the two layers of the wall, so that the reticulocyte can gain access to more endothelial surface and the pores.
Membrane Changes in Human Platelets Induced by Lipopolysaccharide Endotoxin
Authors: Hawiger J. , Hawiger A. , Steckley S. , Timmons S. , Cheng C. 
Published: March 2008

The unexplained occurrence of thrombocytopenia in cases of Gramnegative sepsis in man led us, in the light of animal experiments indicating the blood platelet as the target cell for endotoxin, to examine the effect of Salmonella enteritidis lipopolysaccharide B on human platelets. Human platelets were separated from a coat of plasma proteins by Sepharose 2B filtration or by a combined procedure of albumin gradient and Sepharose 2B filtration. The action of endotoxin on human platelets resulted in membrane changes manifested by dose‐dependent release of [3H]serotonin and adenine nucleotides. Cytoplasmic marker, lactic dehydrogenase, and lysosomal marker, beta glucuronidase, were retained indicating that the release reaction was selective. Release of [3H]serotonin was specific for endotoxin since other particulates, zymosan and erythrocyte stroma, were without effect. Endotoxin, added to gel‐filtered human platelets, induced a significant evolution of platelet factor 3 procoagulant activity. Preincubation of endotoxin with a membrane‐rich homogenate of human platelets inhibited its labilizing effect on human platelets thus suggesting an interaction between endotoxin and the platelet membrane itself. Other plausible factors in this interaction (fibrinogen, adenine nucleotides, thrombin, sialic acid residues, and IgG) were eliminated on the basis of a series of control experiments. From the negligible effect of aspirin and indomethacin, we may infer that the interaction of endotoxin with platelets does not depend on the platelet prostaglandin synthesis pathway.The direct interaction of endotoxin with the human platelet membrane comprises a new mechanism which may help to clarify the pathogenesis of vascular and haemostatic disorders accompanying bloodstream infections due to Gram‐negative bacteria.
Inhibition of Leukaemia Blast Cell Motility as a Test for Specific Antibody in Acute Adult Myelogenous Leukaemia
Authors: Katz J. , Currie G. A. , Oliver R. T. D. 
Published: March 2008

Summary. Migration studies of acute myelogenous leukaemia blast cells in autologous diagnostic and remission sera from a series of I I patients have demonstrated two factors.A factor of less than 70 000 molecular weight appears to potentiate blast cell migration whereas the other of molecular weights 100 000–250 000 inhibits blast cell migration relative to a standard non‐immune AB serum. The low molecular weight fraction was found in the serum of patients prior to relapse while the greater molecular weight fraction was possibly an IgG antibody that increased in concentration with length of remission. The inhibitory factor was found in patients following immunotherapy and in one patient who received chemotherapy alone.An inhibitory factor was also consistently found in patients in overt clinical relapse following on remission induction and maintenance therapy.
The Biosynthesis and Characterization of Unreleased IgM in a Case of CLL
Authors: Smith J. L. , Gordon J. , Newell D. G. , Whisson M. 
Published: March 2008

SUMMARY.Intracellular IgM K is described in a case of CLL. The intracellular immunoglobulin occurred as amorphous spherical globules enclosed by rough endoplastic reticulum in the cytoplasm of the neoplastic lymphocytes. No abnormal IgM paraprotein could be found in the serum nor was there any Bence Jones protein detectable in concentrated urine. Biosynthetic studies confirmed the cells were able to synthesize IgM K immunoglobulin. On sizing gel analysis the intracellular IgM occurred as 7S monomer. The biosynthesis studies did not indicate secretion of IgM and was consistent with the serological findings. However, cells in culture secreted K light chain into the supernatant medium. It appears in this case that the secretory block is operating against heavy chain and not against free light chain. Some explanations for these findings are discussed.
Comparison of Heparin and a Semi‐synthetic Heparin Analogue, A73025
Authors: Michalski R. , Lane D. A. , Kakkar V. V. 
Published: March 2008

SUMMARY.A comparison has been made of some effects of a semi‐synthetic heparin analogue, A73025, and heparin upon platelet function. In several of the in vitro tests performed, such as their potentiating effects on ADP and adrenaline induced aggregation and their effects on the aggregation of washed platelets by activated factor X, heparin proved to be more potent than A73025. Following intravenous injection of twice the quantity of A73025, an equivalent anti‐factor Xa activity was obtained, in agreement with our previous studies. However, it was found that PRP containing heparin and A73025 with comparable anti‐Factor Xa activity responded differently to the addition of thrombin, as A73025 barely inhibited thrombin induced aggregation. Similarly, A73025 had little effect on the dilute thrombin clotting time of plasma, following intravenous injection. Heparin and A73025 were neutralized to approximately the same degree by a crude PF4 preparation.