bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro Binding of Folates by Body Fluids
Authors: Retief F. P. , Heyns A. du P. , Oosthuizen Mariëtha , van Reenen O. R. , Badenhorst C. J. 
Published: March 2008

Summary.It is useful to differentiate between saturated folate binders in serum (carrying endogenous folate) and unsaturated binders (investigated in the present study). These two groups of binders need not necessarily be chemically identical and the unsaturated binder may even be an in vitro artifact, especially when measured with non‐physiological folates. Macromolecular binding of radio‐active N5‐methyl tetrahydrofolic acid (CH3H4PteGlu) and/or folic acid (PteGlu) by human serum and urine was assessed by means of exhaustive saline dialysis, haemoglobin‐coated charcoal adsorption, column chromatography with DEAE‐Sephadex A‐50, and sucrose gradient analysis. Binding was found to be minimal or absent. Charcoal adsorption showed a mean serum binding capacity of oμ/l. for PteGlu and 0.58 μ/1. for CH3H4PteGlu. In pregnancy the mean serum values were 0.23 μ/1. for PteGlu, 0.66 μ/1. for CH3H4PteGlu, and with folate deficiency 0.30 μ/1. for PteGlu, 0.49 μ/1. for CH3H4PteGlu. Mean urinary folate binding was minimal (<0.5 μ/1.), and red cell haemolysate similarly revealed very low binding on exhaustive dialysis. Column chromatography showed that tracer doses of [14C]PteGlu added to serum migrated distally to the protein zone; [14C]CH3H4‐PteGlu similarly showed no evidence of protein binding. On a sucrose gradient [14C]PteGlu also separated clear of the protein zone.
Inhibitors of Plasminogen Activation in Human Blood
Authors: Beattie A. G. , Ogston D. , Bennett B. , Douglas A. S. 
Published: March 2008

Summary.Plasma contained two inhibitors of plasminogen activation by urokinase when fractioned by gel filtration on Sephadex G‐200. The inhibitor in the lower molecular weight fractions was separate from the principal protease inhibitors of plasma: α1‐antitrypsin, α2‐macroglobulin, C1 inactivator and antithrombin III, and from factor XIII. This activation inhibitor was present in both plasma and serum and its recovery was not reduced by preincubating the serum for 6 h at 37°C. Its inhibitory activity was stable for several days at 4°C, and was enhanced in the presence of an increased saline concentration. Preparations of the inhibitor, active in a clot lysis system, failed to inhibit the esterase activity of urokinase on N‐α‐acetylglycyl‐L‐lysine methyl ester.
Serum ‘Uracil+Uridine’Levels Before and After Vitamin B12 Therapy in Pernicious Anaemia
Authors: PARRY T. E. , BLACKMORE J. A. 
Published: March 2008

Summary. The serum ‘uracil+uridine’levels, expressed as uracil, have been measured in 10 cases of pernicious anaemia both before and after treatment, and compared with the levels in 97 normal subjects. The mean pre‐treatment value (8.82 μmol/l., range 6.0–12.0 μmol/l.) differed significantly from that of the normal controls (15.7 μmol/l., range 5.7–40.5 μmol/1., t= 8.8, P<0.001). This confirms the low serum uracil level previously reported in pernicious anaemia in relapse. The level rose progressively after treatment, reaching a maximum on the fourth day (mean 17.85 μmol/1., range 9.3–23.4 μmol/l.). This was not significantly different from the mean of the normal control group. The difference between the pre‐ and post‐treatment levels was significant on days 3, 4 and 5 (P<0.005, P<0.001 and P<0.005 respectively) and the rise preceded the reticulocyte response by 24 h. A further case was treated with physiological doses of vitamin B12 (2 μg daily for 6 d) and a similar rise in the serum uracil level noted.These results are not explained by any of the known functions of vitamin B12. They are, however, similar to the changes in the serum methionine levels previously reported in pernicious anaemia. The latter were readily explained by the known action of vitamin B12 on ‘de novo’methionine synthesis and it is suggested that the synthesis of uracil, like that of methionine, might be influenced by vitamin B12 in man.
The Heterogeneity of Erythrocyte Antigen Distribution in Human Normal Phenotypes: an Immunoelectron Microscopy Study
Authors: REYES F. , GOURDIN M. F. , LEJONC J. L. , CARTRON J. P. , GORIUS J. BRETON , DREYFUS B. 
Published: March 2008

Summary. A and A1 antigen were detected on human blood erythrocytes by immunoelectron microscopy using peroxidase‐conjugated antibodies. Cells were obtained from various normal A subgroups, including rare weak A phenotypes and infant (cord blood) samples. Erythrocytes were fixed prior to incubation with specific reagents. The detection of surface antigens was carried out by an indirect method involving anti‐A and anti‐A1 antibodies and conjugated anti‐immunoglobulin antibodies. The surface labelling was seen as a diffuse dense layer. Haem peroxidase‐like activity resulted in a faint background which did not interfere at the level of ultrathin sections, with surface staining due to exogeneous peroxidase.The most significant finding was the existence, in a given sample, of several populations of cells as revealed by their antibody‐binding capacity. The distribution of the various populations varied from one sample to another according to its subgroup. The progressive weakening of phenotype expression which characterizes the various subgroups from A1 to A weak was paralleled by a decreasing number of ‘antigen rich’cells, which were still detectable in weak phenotypes as a minor population.This study confirms that a given normal phenotype in fact represents a mixture of antigenically different populations of erythrocytes.
The Immunotherapy of Acute Myelogenous Leukaemia using Intravenous BCG
Authors: Whittaker J. A. , Slater A. J. 
Published: March 2008

In a 2‐year period, 37 of 81 adults with acute myelogenous leukaemia achieved complete remission after repeated courses of Daunorubicin (DNR) and Cytosine Arabinoside (ARAC). They were randomized to maintenance treatment with monthly DNR/ARAC, or to identical chemotherapy plus intravenous BCG. Eighteen BCG treated patients had significantly longer survival times than 19 patients treated with chemotherapy only although no statistically significant difference can be seen in the remission duration of the two groups. Eleven patients in the BCG treated group who have relapsed, have received DNR/ARAC reinduction and five second and two third remissions have been obtained. Twelve control group patients have relapsed and 10 have received further reinduction treatment with DNR/ARAC but only one patient has entered a complete remission. Seven patients in the BCG treated group who survived for 75 weeks or more (76, 76, 96, 124, 125, 138 and 145 weeks) were either PPD positive before treatment or converted to PPD positivity after BCG treatment. Using a battery of skin tests it may be possible to define a good prognostic group of patients and design future treatment accordingly.The BCG group had a total of 198 intravenous treatments. All patients had pyrexia 6‐12 h after injection lasting 12‐72 h and occasionally headaches and muscle pains. Two patients had non‐fatal anaphylactic reactions which did not recur when BCG was subsequently re‐administered. Other complications of BCG therapy were not a problem and we have not needed to withdraw treatment for any patient.
Inherited Sialoglycoprotein Deficiencies in Human Erythrocytes of Type En(a ‐)
Authors: Anstee D. J. , Barker Diana M. , Judson P. A. , Tanner M. J. A. 
Published: March 2008

We have investigated the membranes of erythrocytes from a family in which there is a genetic defect (previously described as the En(a ‐) condition) resulting in the loss of the major erythrocyte sialoglycoprotein (PAS‐1). The results show that two different types of sialoglycoprotein deficiency can be distinguished within this family. We suggest that the En(a ‐) group of variants is more appropriately described as a class of sialoglycoprotein deficient erythrocytes.Using a new technique it is shown that the blood group M antigen of normal erythrocytes is found only on the erythrocyte sialoglycoprotein while in this family the M antigen is found on membrane components other than the sialoglycoprotein. Our results suggest that the amino acid sequence of the sialoglycoprotein is important in defining the difference between the blood group M and N antigens in normal erythrocytes.
Abnormal Folate Polyglutamate Ratios in Untreated Pernicious Anaemia Corrected by Therapy
Authors: Perry Janet , Chanarin I. 
Published: March 2008

The relative amounts of folate compounds having 1–3‐, 4–, 5– and 6–glutamic acid residues in the molecule were measured in red blood cells. The results were expressed in relation to methyltetrahydrofolate pentaglutamate (5‐glutamic acid residues) which is the analogue present in highest concentration. When the concentration of pentaglutamate is given a value of 100 the relative concentration of folates with 1–3‐, 4‐, 5‐ and 6‐glutamic acid residues in control subjects are 48, 48, 100 and 58 respectively.In folate deficiency there is a fall in the relative amount of the short chain glutamic acid chain compounds in addition to having an overall fall in the amount of folate present, the values for 1–3, 4, 5 and 6 chain folates being 16, 14, 100 and 39. By contrast, in untreated pernicious anaemia there is an accumulation of the short chain folates as well as an overall fall in polyglutamate concentration and the relative concentrations were 72, 44, 100 and 30.Folate polyglutamate appears to be the active coenzyme and the relative amounts of glutamic acid residues may serve to regulate the rate of enzyme activity. In pernicious anaemia the amount of enzyme is reduced and on this hypothesis the regulatory function impaired.
Thromboxane Synthesis and the Platelet Release Reaction in Bernard‐Soulier Syndrome, Thrombasthenia Glanzmann and Hermansky‐Pudlak Syndrome
Authors: Malmsten C. , Kindahl H. , Samuelsson B. , Levy‐toledano S. , Tobelem G. , Caen J. P. 
Published: March 2008

Thromboxane (TX) synthesis was investigated in some characterized platelet disorders and correlated with release of ADP or [14C]serotonin and platelet aggregation. In a case with Bernard‐Soulier syndrome TX‐synthesis as well as ADP‐[14C]serotonin release and platelet aggregation were found to be essentially normal when platelets were incubated with collagen, ADP, arachidonic acid or prostaglandin G2 (PGG2). In a case with Hermansky‐Pudlak syndrome aggregation was normal with ADP, whereas aggregation with collagen and PGG2 was markedly decreased. Release of ADP and [14C]serotonin was found to be decreased with all investigated inducers in this platelet disorder, whereas TX‐synthesis was normal with arachidonic acid and PGG2. In three cases with Glanzmann's thrombasthenia almost no aggregation was observed with any of these compounds. However, in this disorder platelet TX‐formation from arachidonic acid or PGG2 was also normal whereas ADP and collagen both induced less TX‐formation than in normal platelets.These results indicate that none of the investigated platelet disorders was associated with abnormal TX‐synthesis from arachidonic acid as found in platelet cyclo‐oxygenase deficiency. These observations provide further evidence for the hypothesis that the Bernard‐Soulier syndrome and Glanzmann's thrombasthenia are primarily associated with glycoprotein abnormalities at receptor level (Nurden & Caen, 1974, 1975, 1976). A hypothetical model for the interrelationship of two specific glycoproteins and thromboxane‐synthesis is discussed.
Cobalamin Dependent Methionine Synthesis and Methyl‐Folate‐Trap in Human Vitamin B12 Deficiency
Authors: Sauer Hansjörg , Wilmanns Wolfgang 
Published: March 2008

The activity of methionine synthetase (MS) is important for the rapid growth of human haematopoietic cells and cultured lymphoblastoid cells. The MS reaction is the only known metabolic step in which both vitamin B12 and folate are essential in a single enzyme reaction. In vitamin B12 deficiency the MS activity in bone marrow cells is significantly lower than that in normal bone marrow.Free tetrahydrofolic acid (H4PteGlu) is normally liberated from its metabolically inactive storage form, 5‐methyl‐H4PteGlu (CH3H4PteGlu), in the cobalamindependent MS reaction. Thus, in vitamin B12 deficiency H4PteGlu is not available in sufficient concentration to maintain the de novo synthesis of thymidylate and purines, and accords with the methyl‐folate‐trap hypothesis.After treatment with amethopterin (MethotrexateTM), the incorporation of 3Hdeoxyuridine into cellular DNA is reduced. In proliferating normal cells this effect of methotrexate can be prevented (and the cells rescued) with CH3‐H4PteGlu or with CHO‐H4PteGlu (5‐formyl‐H4PteGlu; LeucovorinTM). On the other hand, in vitamin B12 deficient bone marrow cells this so‐called rescue‐effect could only be achieved with CHO‐H4PteGlu and not with CH3‐H4PteGlu. These observations also support the hypothesis of the methyl‐folate‐trap in vitamin B12 deficiency.Decreased MS activity in vitamin B12 deficiency seems to be the essential metabolic fault, which is responsible for secondary alterations of folate metabolism. Thus, measurement of MS activity may allow direct functional assessment of vitamin B12 deficiency, at least with regard to DNA metabolism.
Impaired Neutrophil Function and Myeloperoxidase Deficiency in Myeloid Metaplasia
Authors: El‐Maallem Hilal , Fletcher John 
Published: March 2008

Summary. The ability of neutrophils to phagocytose and kill Candida guilliermondii was investigated in 12 patients with myeloid metaplasia (MM). Following ingestion there was a considerable impairment in the ability of MM neutrophils to kill and digest Candida which was not explained by the very mild impairment in phagocytosis. Quantitative myeloperoxidase measurement revealed an overall deficiency of this enzyme in MM neutrophils and a highly significant correlation between low myeloperoxidase levels and impaired candidacidal activity. Neutrophils from patients with myeloid metaplasia show a pattern of defective microbial killing, high alkaline phosphatase activity and low myeloperoxidase activity which is similar to that seen in severe infections and distinct from chronic granulocytic leukaemia.The cells of one patient with particularly low myeloperoxidase and defective microbial killing were further studied both cytochemically and by electron microscopy. The azurophilic granules of his neutrophils were present in normal numbers and contained normal amounts of acid phosphatase but they lacked myeloperoxidase.
Blood Lymphocyte Surface Markers and Clinical Findings in Chronic Lymphoproliferative Disorders
Authors: Jayaswal U. , Roath S. , Hyde R. D. , Chisholm D. M. , Smith J. L. 
Published: March 2008

SUMMARY.Surface receptors on peripheral blood lymphocytes have been studied in 43 cases with chronic lymphocytic leukaemia (CLL), and five cases with lymphoma and overspill. One quarter of the cases with CLL had lymphocytes with no detectable surface immunoglobulin (SIg) by direct fluorescent antibody staining. The remainder had SIgM, which was associated with SIgD in one third of the cases. 70% of the SIg negative group had extensive extramedullary involvement (EMI) compared with 3 5 % of the SIg positive group at presentation; correspondingly more of the SIg negative group were treated. 46% of the SIg negative group were CLL patients of more than 3 years standing compared with 9% of the SlgM + D group and 32% of the SIgM group. Some explanations for this pattern are discussed.
Drug Uptake and Ribonucleotide Profiles of Blast‐enriched and Blast‐depleted Human Bone Marrow Cell Populations
Authors: Preisler H. D. , Rustum Y. , Walczak IRENE 
Published: March 2008

SUMMARY.A density cut method was used to prepare two subpopulations of bone marrow cells which were enriched (BE) and depleted (BD) respectively of blast cells. Marrow aspirates were obtained from 32 patients, 26 of whom had acute leukaemia. The uptake of a variety of chemotherapeutic agents by these two subpopulations and the acid‐soluble ribonucleotide profiles of the populations were compared and significant differences were found in drug uptake by BE and BD subpopulations. For some drugs such as cytosine arabinoside, uptake was greatest by the BE cells, while for 5‐azacytidine the BD subpopulation took up the greatest amount of the drug. The preparation of the BE subpopulation also permitted the recognition of several patients with acute leukaemia whose blast cells possess nondetectable levels of ATP, UTP, and GTP components, in their acid‐soluble fractions. The studies presented demonstrate the necessity of using purified cell populations when characterizing the drug uptake patterns and the soluble ribonucleotide profiles of the leukaemic cells. A simple method for enriching bone marrow aspirates for leukaemic cells is also presented.
Comparison of Heparin and a Semi‐synthetic Heparin Analogue, A73025
Authors: Lane D. A. , Michalski R. , Van Ross Maureen E. , Kakkar V. V. 
Published: March 2008

SUMMARY.A study has been made of a low molecular weight semi‐synthetic heparin analogue, A73025, that may be clinically useful as an antithrombotic agent because of its reported high specificity for antithrombin III. The clearance from the circulation of both heparin and the analogue has been studied in man following intravenous injection. Heparin obeyed almost first order kinetics when assayed using a specific anti‐Xa assay and first order kinetics when measured with KCCT. At high concentrations the heparin analogue was cleared with first order kinetics when assayed both with the anti‐Xa assay and with KCCT. At low concentrations the analogue produced between one half and two‐thirds of the anti‐Xa activity of an equal dose of heparin, producing only a small prolongation of KCCT. With increasing dose, the more specific anti‐Xa potentiating effect of A73025 decreased because of a flattening of its anti‐Xa dose‐response curve. These results suggest that the analogue might be useful as an antithrombotic agent when it is used as a prophylactic agent.
A Sex Difference in the Platelet Count
Authors: Stevens R. F. , Alexander M. K. 
Published: March 2008

SUMMARY.A study of the platelet counts of 868 blood donors aged 18‐65 showed a higher mean count in women than in men, the difference in the premenopausal age groups being highly significant (P<o.ooI) and of the order of 40‐70 × 109/l. The mean counts of women taking a contraceptive pill did not differ significantly from those who were not.Values for the normal platelet count in man quoted in most standard haematological texts are derived from studies made on relatively small numbers of individuals using visual counting techniques. The advent of automatic counting and data processing has made practicable the examination and evaluation of larger bodies of data with a relatively higher degree of precision than previously. This communication reports the results of such a study made on blood donors. The work was suggested by the finding of a significantly higher mean platelet count for women in the routine counts made selectively on a hospital population.
Further Evidence for the Role of Thrombin in the Platelet Release Reaction Caused by Various Agents, and the Nature of Biphasic Platelet Aggregation
Authors: Huzoor‐Akbar  , Ardlie Neville G. 
Published: March 2008

Studies were undertaken to resolve conflicting reports about the possible involvement of thrombin in the release reaction and second phase aggregation caused by ADP.Washed human platelets suspended in a buffered solution responded poorly to ADP, with no second phase aggregation or release of [3H]5HT. In contrast, washed platelets suspended in dialysed plasma containing all intrinsic pathway clotting factors responded to ADP with second phase aggregation and release of radioactivity. This response depended on an optimum calcium concentration above which aggregation was impaired. Biphasic aggregation and release of platelet contents by ADP, epinephrine and collagen in dialysed plasma was inhibited by hirudin and heparin. The inhibitory effects of hirudin and heparin were not observed when citrate was present.These observations provide further evidence for the central role of thrombin in the release reaction and biphasic aggregation caused by various agents and indicate that these platelet reactions are not artifacts due to a citrate. Since the effect of citrate on aggregation and the inhibitory actions of hirudin and heparin were produced by another chelating agent, viz EGTA, it is suggested that the citrate effect is due to reduction of cation concentration.
Cell Membrane Enzymes: L‐γ‐Glutamyl Transpeptidase, Leucine Aminopeptidase, Maltase and Trehalase in Normal and Leukaemic Lymphocytes
Authors: Kramers Mary T. C. , Catovsky D. 
Published: March 2008

Several cell‐membrane enzymes, which serve functions in amino acid and sugar transport, were measured in peripheral blood lymphocytes from chronic B and T lymphocytic disorders, blast cells in acute leukaemias, and in normal lymphocytes from cord blood, peripheral blood of adults, tonsils and bone‐marrow plasma cells in myelomatosis.The specific activities of l‐γ‐glutamyl transpeptidase, maltase and trehalase were low, as compared with those measured in normal blood lymphocytes, in the acute leukaemias and in the chronic B‐cell disorders. In myelomatosis and in the chronic T‐cell disorders, the specific activity of these three enzymes was in the normal range or above normal. The specific activity of leucine aminopeptidase was low in all the chronic B‐cell disorders and in some of the lymphoblastic leukaemias. It was elevated in Sézary syndrome cells but low in T‐chronic lymphocytic leukaemia. All four enzymes were lower than normal in cord blood lymphocytes and higher than normal in tonsils. These findings are discussed in relation to the patterns of lymphoid cell differentiation and maturation in normal tissues and in leukaemic states.
Myelomatosis and the Hyperviscosity Syndrome
Authors: Preston F. E. , Cooke K. B. , Foster Margaret E. , Winfiel D. A. , Lee D. 
Published: March 2008

Eleven patients are described in whom myelomatosis was complicated by the laboratory and clinical features of the hyperviscosity syndrome (HVS). The myeloma type was IgA in nine and IgG3 in two. In those patients with IgA myeloma the HVS was related to the presence of high molecular weight complexes in the serum. Remission of clinical features was obtained in all patients by plasma exchange. Clinical improvement coincided with reduction of whole blood viscosity and in those patients with IgA myeloma, with a parallel reduction of the high molecular weight complexes.The relationship between the IgA complexes and blood viscosity has been examined by physicochemical analysis of purified IgA monomer and polymers and evidence is presented to show that the IgA polymer has a higher intrinsic viscosity and axial ratio than the larger IgM molecule. The significance of these observations is discussed.