bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Pyrimidine Compounds on the Potentiation of Adenosine Inhibition of Aggregation, on Adenosine Phosphorylation and Phosphodiesterase Activity of Blood Platelets
Authors: Rozenberg M. C. , Walker C. M. 
Published: March 2008

Summary. Three pyrimidine compounds (dipyridamole, RA233 and VK 744) produced variable degrees of direct inhibition as well as potentiation of adenosineinduced inhibition of ADP aggregation of blood platelets. RA233 and VK744 were more potent direct inhibitors of platelet aggregation, whereas RA233 was a more powerful potentiator of adenosine–induced inhibition. A relation between the effect of these compounds on platelet aggregation and on adenosine phosphorylation and phosphodiesterase activity of platelets was looked for in an attempt to elucidate possible modes of action.RA233 and dipyridamole were powerful inhibitors of [14C]adenosine phosphorylation by platelets and VK744 had no effect. There was no correlation with inhibition of platelet aggregation. Adenosine‐induced inhibition of platelet aggregation in the presence of dipyridamole could be maintained for at least 10 min after the rapid clearance of the adenosine with exogenous deaminase. The presence of the pyrimidine so modified the inhibition response that there was no correlation between the concentration of adenosine in the system and the degree or rate of recovery from the inhibition.Dipyridamole, VK744 and RA233 produced 45%, 45% and 55% inhibition of phosphodiesterase activity as measured by the rate of breakdown of [3H]cyclic AMP to AMP in platelet lysates. There was possible correlation between the effect of the three pyrimidine compounds on platelet phosphodiesterase activity and their potentiatory action on adenosine‐induced inhibition of platelet aggregation. These findings suggested that adenosine might induce inhibition of platelet aggregation through the adenyl cyclase, cyclic AMP, phosphodiesterase system.
Prothrombin during Warfarin Treatment
Authors: Brozović M. , Gurd L. J. 
Published: March 2008

Summary. Prothrombin levels were studied in a group of hospital controls and a group of patients stabilized on long‐term warfarin treatment. The behaviour of prothrombin was also followed in two healthy subjects given a single oral dose of warfarin, and in four patients starting long‐term treatment with warfarin. Three techniques were employed in studying the changes in prothrombin; the measurement of prothrombin clotting activity, the estimation of total immunologically detectable prothrombin, and the detection of the structurally abnormal form of prothrombin in plasma.The mean plasma prothrombin activity for the hospital controls and the patients stabilized on long‐term warfarin was 266 (range 160–376) and 107 (range 48–192) NIH thrombin units per ml respectively. The mean total immunologically detectable prothrombin concentration was 99 (range 63–132) and 87 (range 61–135) % of the normal reference level, respectively. The differences found were statistically significant.No decrease in the immunologically detectable prothrombin levels, and a very slight fall in prothrombin activity were observed in two healthy subjects, given a single warfarin dose. The abnormal form of prothrombin was first detected 8 and 12 hr after the dose and persisted for at least 6 days in the plasma of both subjects. In patients followed from the start of the warfarin treatment, the abnormal form appeared within 12 hr of the first dose, and became the predominant form in plasma, at the latest, after 84 hr of treatment. The clotting activity fell to below 100 NIH units per ml, whereas the immunologically detectable prothrombin levels decreased after a longer time interval.These results confirm that the major changes in therapeutic anticoagulation are the fall in prothrombin clotting activity and the appearance of an abnormal form of prothrombin in plasma. The levels of the immunologically detectable prothrombin in plasma are affected later and to a lesser extent.
Gaucher‐like Cells and Congenital Dyserythropoietic Anaemia, Type II (HEMPAS)
Authors: Dorpe A. Van , Orshoven A. Broeckaert‐Van , Desmet V. , Verwilghen R. L. 
Published: March 2008

Summary. .‘Gaucher‐like cells’ were observed in the bone marrow of 18 out of 20 HEMPAS (CDA II) patients. These cells contain birefringent, PAS positive material. Further cytochemical procedures identified the inclusions as a glycoprotein or a glycopeptide but the presence of cerebrosides could not be excluded. An intralysosomal localization was suggested by electronmicroscopy.HEMPAS is characterized by inefficient erythropoiesis and it is suggested that accumulation of a catabolite of the erythroblasts gives rise to these cells. A possible relation with the cell membrane anomaly of HEMPAS erythrocytes is discussed.
The Exchangeable Splenic Platelet Pool Studied with Epinephrine Infusion in Idiopathic Thrombocytopenic Purpura and in Patients with. Splenomegaly
Authors: Branehoug Ingmar , Weinfeld Aleksander , Roos Bengt 
Published: March 2008

Summary. The exchangeable splenic platelet pool (ESPP) was studied with epinephrine infusion and platelet labelling with 51Cr in five healthy students, 10 patients with idiopathic thrombocytopenic purpura (ITP) and 10 patients with splenomegaly. Five of the ITP‐patients were studied after splenectomy. Platelet recovery of infused labelled platelets was calculated in all subjects and also in nine healthy volunteers who had been splenectomized for traumatic rupture of the spleen. Spleen size was determined by gamma camera scintigraphy. It was shown that the spleen is the only site of an exchangeable platelet pool in ITP and that this pool was of the same size in ITP‐patients as in the normal controls, viz ∼30% of the total body platelet mass.In patients with splenomegaly the ESPP was larger than that in controls and ITP‐patients. A highly significant correlation was found between the ESPP and the spleen volume. In splenectomized and in non‐splenectomized ITP‐patients platelet recovery was significantly less than in their respective control groups, indicating that a proportion of the labelled platelets was immediately removed from the circulation after infusion into an ITP recipient and that the recovery of labelled platelets cannot be used as a measure of the ESPP in ITP.It is suggested that the early destruction of platelets may be due to slight damage to the platelets during the labelling procedure. These damaged platelets can survive in a normal recipient, but are destroyed when infused into the‘milieu’ of an ITP‐patient.
The Erythropoietic Response to Pregnancy in β‐Thalassaemia Minor
Authors: Schuman John E. , Tanser Catherine L. , Pealoquin Robert , de Leeuw Nannie K. M. 
Published: March 2008

Summary. In 15 women with β‐thalassaemia minor, the haemoglobin concentration fell to a greater extent during pregnancy than in normal women. The lower haemoglobin level in the thalassaemics was caused by limited expansion of their red‐cell mass.Although the increase in red‐cell mass in iron‐sufficient thalassaemics was not influenced by iron supplementation, two of the unsupplemented women were in negative iron balance. Ideally, each thalassaemic patient should receive individual assessment prior to iron therapy. Iron supplementation is recommended, when there is evidence of a negative iron balance.There was great variability in the rise of red‐cell mass observed in the thalassaemic women. The rise correlated inversely with the morphological abnormality of the red cells, suggesting that the underlying disorder in haemoglobin synthesis was the main limiting factor.In the thalassaemic women foetal haemoglobin was significantly greater in the first half of pregnancy than in the puerperium. This raises the possibility that the increased production of γ‐chains could favourably influence haemoglobin synthesis in pregnant women with thalassaemia minor.
Ouabain‐Sensitive and Oligomycin‐Sensitive Adenosine‐triphosphatase Activities of Normal Human Lymphocytes
Authors: Ellegaard Josrgen , Dimitrov Nikolay V. 
Published: March 2008

Summary. Homogenates of highly purified normal human lymphocytes contained two different adenosinetriphosphatase (ATPase) activities. One of these activities was present in a supernatant fraction of the lymphocyte homogenates, possibly related to mitochondria. This activity was independent of the presence of monovalent cations, was insensitive to ouabain, but was inhibited by oligomycin and stimulated by 2,4 dinitrophenol. Exchange of Mg++ with Ca++, or addition of sodium fluoride completely inhibited this ATPase activity. A Km‐value for the substrate ATP was determined to be 0.83 mm. The specific activity of the oligomycin‐sensitive, supernatant ATPase was 0.31 ± 0.13 (SD) μmoles Pi per mg protein per 30 min.The other ATPase activity was activated by Na+ and K+ and was inhibited by ouabain. This ATPase activity was only found in the pellet fraction after centrifugation, possibly associated with the cell membranes. The specific activity of this ATPase was 0.25 ± 0.09 (SD) μmoles Pi per mg protein per 30 min. The effect of ouabain in various cation combinations of the assay is reported. Optimal ouabain‐sensitive ATPase activity was found at 100 mm Na+, 15 mm K+ and 6 mm Mg++.Only the oligomycin‐sensitive ATPase activity increased after short time stimulation of the lymphocytes by phytohaemagglutinin (PHA), and this could be inhibited by puromycin.The increased ATPase activity of normal lymphocytes caused by the non‐specific mitogen PHA suggest the possibility that the increased ATPase activity of lymphocytes from patients with malignant tumours could be due to a stimulation of the lymphocytes by tumour specific antigens in vivo.
Transport of Methotrexate into Normal Haemopoietic Cells and into Leukaemic Cells and its Effects on DNA Synthesis
Authors: Hoffbrand A. V. , Tripp Edith , Catovsky D. , Das K. C. 
Published: March 2008

Summary. Methotrexate uptake by, and action on normal and leukaemic haemopoietic cells has been studied. Peak uptake occurred just prior to peak DNA synthesis, at 48 hr for normal, and at 6–7 days for chronic lymphocytic leukaemic lymphocytes stimulated by phytohaemagglutinin (PHA). Uptake of methotrexate into these cells and into normal bone marrow cells was consistently inhibited by dibutyryl cyclic 3′,5’adenosine monophosphate (dibutyryl cyclic AMP) at concentrations of 10−3 to 10−5m and by inhibitors of phosphodiesterase (theophylline, puromycin aminonucleoside and puromycin). Lower external concentrations of dibutyryl cyclic AMP (10−5 to 10−6m), however, slightly increased the uptake of methotrexate.Dibutyryl cyclic AMP and the phosphodiesterase inhibitors at high concentrations also inhibited cellular uptake of 5‐methyltetrahydrofolate and of thymidine into DNA. Conversely, none of these compounds inhibited uptake of pteroylglutamic acid (folic acid). These results suggest that the rate of entry of methotrexate and reduced folates (but not of folic acid) into haemopoietic cells may be governed by the intracellular concentration of cyclic AMP and that uptake of methotrexate by cells is related to uptake of natural folates but not to that of folic acid. Methotrexate uptake was also rapidly inhibited by actinomycin D suggesting that it is closely coupled to DNA synthesis.Rate of entry of methotrexate into acute leukaemic blast cells was roughly proportional to their rate of proliferation, measured by 3H‐thymidine (3H‐TdR) incorporated into DNA. Resistant cells were not found to show a defect in methotrexate transport in relation to their degree of proliferation.Methotrexate was found to inhibit mitosis, but not transformation of PHA‐stimulated lymphocytes and this was presumably due to blocking of de novo thymidylate synthesis from deoxyuridylate, as shown by inhibition of incorporation of tritiated deoxyuridine (3H‐dU) into DNA.Studies on human leukaemic blast cells showed differences between sensitive and resistant cases in the effect of methotrexate in vitro on 3H‐dU and 3H‐TdR incorporation into DNA and on dU blocking of 3H‐TdR incorporation into DNA but none of these tests gave reliable prediction of resistance or sensitivity to methotrexate.
Plasma Clearance of 125I‐labelled Haemopexin in Normal and Haem‐loaded Rabbits
Authors: Lane R. S. , Rangeley D. M. , Liem H. H. , Wormsley S. , Muller‐Eberhard U. 
Published: March 2008

Summary. Plasma clearance of 125I‐labelled rabbit haemopexin has been studied in six normal control rabbits and in a test group of rabbits haem‐loaded with 25 mg of haem.Following intravenous injection, equilibration of 125I‐haemopexin between intravascular and extravascular compartments appeared to be complete within 24 hr and the decline in plasma activity then became constant in rate. The plasma activity curve was resolved into two exponential functions of time and from the data, fractional catabolic rate, intravascular:extravascular distribution of haemopexin and total haem binding capacity were calculated. Control group. Mean plasma half‐clearance time of haemopexin was 20.3 hr; fractional catabolic rate was 1.8 (SD 0.19) times the intravascular haemopexin pool per day. Extravascular haemopexin was 0.6 (SD 0.11) times the mass of haemopexin in the intravascular pool. Test group. 90–95% of injected 125I‐activity was eliminated from the plasma with a mean half‐clearance time of 1.57 hr and was associated with a significant urinary excretion of labelled iodine. Fractional catabolic rate was 5.84 (SD 0.3) times the intravascular haemopexin pool per day and extravascular haemopexin was 3.38 (SD 1.03) times the mass of haemopexin in the intravascular pool.Haemopexin concentration in normal rabbit plasma was 31–52 mg/100 ml; intravascular plus extravascular haemopexin was 54.5 mg (mean value) and total haem binding capacity of haemopexin was 0.53 mg (mean value).Intravascular haem rapidly complexed with haemopexin and the data suggested that this complex was promptly eliminated from the plasma and the haemopexin catabolized.
Effect of Repeated Treatment of Rabbit Platelets with Low Concentrations of Thrombin on their Function, Metabolism and Survival
Authors: Reimers H. J. , Packham M. A. , Kinlough‐Rathbone R. L. , Mustard J. F. 
Published: March 2008

Summary. Low concentrations of thrombin (< 0.05 u/ml) cause reversible aggregation of washed rabbit platelets in Tyrode‐albumin solution containing apyrase. The same platelets were aggregated several times by addition of the same concentration of thrombin with washing and resuspension after each aggregation step. Deaggregation of rabbit platelets aggregated by thrombin was enhanced by the addition of prostaglandin E1.In three successive aggregations, rabbit platelets prelabelled with [3H]serotonin released approximately 70% of their radioactivity. Platelet granule nucleotides were labelled by in vivo administration of 32P‐labelled orthophosphate: repeated thrombin stimulation caused release of 60–65% of the labelled nucleotides. The release of 3H from [3H]serotonin labelled platelets paralleled the release of 32P‐labelled adenine nucleotides and magnesium. The concentration of platelet calcium did not change significantly during repeated thrombin stimulation. Electron microscopy showed nearly complete degranulation of platelets after three thrombin treatments.The thrice thrombin‐treated platelets were more sensitive to ADP‐induced aggregation than the control platelets. They did not aggregate upon the addition of low concentrations of thrombin but showed the same extent of aggregation as the control platelets when they were exposed to high concentrations of thrombin.Rabbit platelets labelled in vitro by incubation with [14C]adenosine showed a decrease in their metabolic nucleotides ([14C]ATP, [14C]ADP)as a result of repeated thrombin treatment. These platelets showed increased glucose uptake and increased lactate production. The thrombin‐treated platelets (labelled with [3H]DFP in vitro) survived in the circulation of rabbits for the same time as control platelets.
The Haemolytic Action of Dapsone: Changes in the Red‐Cell Membrane
Authors: Rasbridge Marian R. , Scott G. L. 
Published: March 2008

Summary.Some aspects of red‐cell membrane structure and function have been investigated in patients with haemolysis due to dapsone (4,4′ diaminodiphenylsulphone). Osmotic fragility and potassium flux were not increased but red‐cell membrane changes occurred which suggested instability. These included loss of phospholipid, decrease in acetylcholinesterase activity and increased autohaemolysis. In addition, there was evidence for lipid peroxidation, which might have been the primary lesion. Red‐cell membrane sulphydryl group activity was either reduced or altered because these cells were abnormally sensitive to the action of the sulphydryl group inhibitor p‐chloromercuribenzoate, as measured by increased potassium leakage aiid haemolysis. Dapsone also caused abnormal peroxide lysis in the presence of normal hydrogen peroxide detoxification mechanisms and in the absence of vitamin E deficiency. This was prevented by excess vitamin E but not by the sulphydryl compounds, reduced glutathione or cysteine, and it was increased by previous treatment with p‐chloromercuribenzoate.It is suggested that reduced membrane sulphydryl group activity, probably due to the formation of mixed disulphides with precipitated haemoglobin, and lipid peroxidation may be responsible for in vitro and, possibly, in vivo dapsone‐induced haemolysis.
Leukaemic Reticuloendotheliosis (‘Hairy’ Cell Leukaemia): A Distinct Clinico‐Pathological Entity
Authors: Catovsky D. , Pettit J. E. , Galton D. A. G. , Spiers A. S. D. , Harrison C. V. 
Published: March 2008

Summary. The main diagnostic features of leukaemic reticuloendotheliosis (LRE) are discussed in the light of six patients studied in recent years. A detailed study of the clinical, cytological, cytochemical and histological findings in four cases is presented. Pancytopenia and the presence of mononuclear ‘hairy’ cells in the circulation were the main haematological features. Bone marrow was difficult to aspirate and contained 50–80% of the same abnormal cells as the blood; the reticulin pattern showed increased fibre density. The cytology of the LRE cells was very characteristic, particularly because of their irregular ‘hairy’ edges. Cytochemically they were positive for acid phosphatase (tartrate‐resistant) and PAS and they did not contain lysozyme. Electron‐microscopy demonstrated the irregular cytoplasmic edges and a large ‘ribosome‐lamellae’ complex in 25–30% of cells of the two cases studied. The differential diagnosis of LRE from other lymphocytic and histiocytic proliferative disorders is discussed. It is suggested that LRE should be included in the lymphoproliferative group of disorders.Splenectomy seems to have a definitive place in the management of this condition; three patients out of six did not have splenectomy and died in less than 2 yr of sepsis or haemorrhage; in the other three cases splenectomy was followed by a prolonged improvement in the pancytopenia and a better survival (3 +, 7 and 10+ yr).
Serum Vitamin E Levels with Beta‐Thalassaemia Major: Preliminary Report
Authors: Zannos‐Mariolea L. , Tzortzatou F. , Dendaki‐Svolaki K. , Katerellos CH. , Kavallari M. , Matsaniotis N. 
Published: March 2008

Summary. Serum vitamin E levels were found to be below normal (<0.5 mg/100 ml) in 46% of 56 children with β‐thalassaemia major receiving inadequate treatment with blood transfusions. The difference between the mean vitamin E levels in the children with β‐thalassaemia as compared to that of normal children was highly significant (P <0.001).The hydrogen peroxide lysis test was highly abnormal in all 21 children with β‐thalassaemia major in whom it was carried out; only 11 of them had vitamin E serum levels below normal (<0.5 mg/100 ml). Parenteral administration of 200 mg α‐tocopherol in six of the 21 children resulted in a normal hydrogen peroxide lysis test. It is noteworthy that two of the six children had normal vitamin E levels.
Rapid Stem Cell Differentiation Induced by 19‐Nortestosterone Decanoate
Authors: Gorshein D. , Hait W. N. , Besa E. C. , Jepson Joanne H. , Gardner F. H. 
Published: March 2008

Summary. Erythropoiesis was suppressed in mice by hyperoxia (HOX) and/or post‐hypoxic plethora (PCT), the cytocidal effects of actinomycin‐D (ACT), or by a combination of these techniques.When 19‐nortestosterone decanoate (19‐ND) was injected during HOX and 24 hr 59Fe incorporation was measured during and following HOX, the increment in androgen‐induced erythropoiesis compared to vehicle‐treated controls was significantly greater in the post‐HOX assay system, where erythropoietin (ESF) titres were increased as compared to the response seen in the ESF suppressed mouse maintained in HOX. When erythropoiesis was suppressed by HOX and ACT, erythropoiesis was sustained in the 19‐ND‐treated mouse for a longer period than in the vehicle‐treated controls. In addition, when these mice were removed from HOX to ambient conditions and all injections were terminated, erythropoiesis recovered more rapidly in the groups previously treated with the androgen. When ESF was injected to PCT‐HOX mice only 24 hr after they received a single 19‐ND injection, it was observed that these mice had significantly greater levels of 59Fe incorporation than identical mice injected with ESF alone. In addition, it was found that HOX was capable of significantly decreasing the already minimal levels of erythropoiesis found in the plethoric mouse and that this PCT‐HOX animal did not respond as markedly to androgen administration as the plethoric animal maintained at ambient conditions. It was concluded that the data presented in this report are compatible with the concept that the androgenic steroid, 19‐ND, has a direct affect on the haematopoietic stem cell pool by increasing the size of a stem cell population capable of responding to ESF and that further differentiation of these elements is dependent on the availability of ESF to the target tissue.
Haematopoiesis Measured by Spleen Colony and Diffusion Chamber Techniques in Mice Treated with One or Two Injections of Cyclophosphamide
Authors: Bøyum A. , Carsten A. L. , Laerum O. D. 
Published: March 2008

Summary. The effect of cyclophosphamide (CY) on haematopoiesis in mice was observed by the techniques of the spleen colony and the diffusion chamber. Two hours after injection of CY, the number of spleen colony‐forming units (CFU) was reduced to 11% of control, whereas diffusion‐chamber progenitor cells (DCPC) were less affected and 30% survived initially. Histological examination showed that erythroid CFU were significantly more reduced than granuloid CFU, most likely because CY selectively impairs the ability of surviving multipotent stem cells to erythroid differentiation. This defect was repaired within a few days.A second injection of CY 4 days after the first had similar effects, indicating that the selective effect on erythroid CFU was independent of proliferative rate. DCPC were less affected by the second CY injection than by the first, possibly because a higher proliferative rate increased their resistance towards CY.The pattern of depletion and regeneration after one or two injections of CY indicates that the two techniques do not assay identical cell populations. Whereas the spleen colony technique predominantly measures multipotent stem cells, the diffusion chamber technique most probably to a larger extent measures unipotent (committed) stem cells.