bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoplastic Acute Myelogenous Leukaemia
Authors: Beard M. E. J. , Bateman C. J. T. , Crowther D. C. , Wrigley P. F. M. , Whitehouse J. M. A. , Fairley G. Hamilton , Scott Ronald Bodley
Published: March 2008

Summary.

The clinical course, diagnosis and management of nine cases of hypoplastic acute myelogenous leukaemia are described. Such cases may follow a slowly progressive course and should not receive anti‐leukaemic chemotherapy unless the disease is advancing rapidly or unless some specific complication develops. If chemotherapy has to be given, usually because of severe and recurrent infections, then prompt and prolonged remission of disease may occur.
The Significance of Abnormal Circulating Cells in Patients with Hodgkin's Disease
Authors: Schiffer Charles A. , Levi John A. , Wiernik Peter H.
Published: March 2008

Summary.

Buffy coat preparations of peripheral blood from two patients with Stage IVB Hodgkin's disease, 33 patients with Hodgkin's disease undergoing complete staging including laparotomy, 12 normal controls and eight patients with viral upper respiratory infections were examined for the presence of abnormal cells. Primitive histiocytic cells were seen in the two patients with IVB disease and in two patients with IIIB disease all of whom proved to be refractory to chemotherapy. Reed‐Sternberg cells were seen in one IVB patient. Large cells with basophilic, agranular cytoplasm and moderately convoluted nuclei often with a perinuclear halo and nucleoli were detected in 30 of 35 patients with Hodgkin's disease, five of eight patients with viral infections but in none of 12 normal controls. Other abnormal large cells with round nuclei, occasional prominent nucleoli, grey to lightly eosinophilic cytoplasm and diffuse granulation were seen almost exclusively in Hodgkin's disease. There was no correlation between histology, stage, splenic involvement, skin test positivity and response to therapy with the presence or frequency of either of these cell types. This observation suggests that these cells are more likely to be ‘reactive’rather than malignant. It is unusual for abnormal histiocytic cells to circulate in Hodgkin's disease and their presence may be a poor prognostic sign. The presence of other types of large atypical cells is not indicative of either haematogenous spread of Hodgkin's disease or of poor prognosis after treatment with radiotherapy alone.
Sodium Periodate Modification of Factor VIII Procoagulant Activity
Authors: Kaelin A. C.
Published: March 2008

Summary.

Chemical treatment of human factor VIII by sodium periodate resulted in increased levels of procoagulant activity when measured by the two‐stage assay. Increased levels of factor‐VIII activity were observed following periodate treatment of factor‐VIII concentrates and normal, haemophilic and von Willebrand's disease plasmas. However, sodium periodate treatment of haemophilic plasmas which were completely deficient in factor‐VIII activity did not cause any reduction in the clotting times of two‐stage assays. No increase in procoagulant activity following oxidation of factor VIII could be detected by the one‐stage assay method. Gel filtration of factor‐VIII concentrates before periodate treatment showed that the protein exhibiting factor‐VIII activity had an apparent molecular weight in excess of 1 000 000, whilst after periodate treatment the apparent molecular weight was reduced to 690 000.
Solid‐Phase Immunoradiometric Assay of Factor‐VIII Protein
Authors: Counts Richard B.
Published: March 2008

Summary.

A solid phase immunoradiometric assay for factor‐VIII protein has been developed using 125I‐labelled rabbit antibody made against highly purified factor VIII. Antibody specific for high molecular weight factor‐VIII protein was isolated using an immunoadsorbent consisting of highly purified factor VIII bound to diazotized m‐aminobenzyl (oxymethyl)‐cellulose. The purified anti‐factor VIII antibody was labelled with 125I while bound to the immunoadsorbent and then eluted at pH 2.9. Dilutions of plasma samples for assay were incubated for 48 h in anti‐factor VIII antibody‐coated tubes. The tubes were washed to remove unbound proteins and the 125I‐labelled, purified antibody was added. After 48 h incubation the tubes were washed to remove unbound antibody and counted. The concentration of immunoreactive factor‐VIII protein in pooled normal human plasma was determined to be 8 μg/ml. The minimum amount of factor VIII measured by the assay is less than 0.16 ng. Factor‐VIII protein was present in normal concentration in haemophilia A plasma, and in reduced concentration in von Willebrand's disease plasma. This method has the advantages of improved sensitivity, specificity, efficiency and economy as compared with previous factor‐VIII immunoassays.
Quantitative Measurement of Splenic and Hepatic Red‐Cell Destruction
Authors: Bowring C. S. , Ferrant A. E. , Glass H. I. , Lewis S. M. , Szur L.
Published: March 2008

Summary.

A method has been developed by means of which independent measurement can be made of the amount of red‐cell destruction occurring in the spleen and the liver. The technique involves a standard red‐cell survival study and surface‐counting measurements together with quantitative scanning of the spleen and liver with 113mIn colloid in order to calibrate the surface counter. The rate of destruction in each organ is obtained by fitting the measured uptake curve for the organ to a theoretical uptake curve by computer. In addition, if whole body counting is also performed, the amount of red‐cell destruction occurring in the rest of the reticulo‐endothelial system may be deduced. Results are given for measurements on a series of 11 patients.
Acquired Erythroenzymopathies in Blood Disorders: Study of 200 Cases
Authors: Boivin Pierre , Galand Colette , Hakim Jacques , Kahn Axel
Published: March 2008

Summary.

Enzyme abnormalities are frequently found in the red cells of patients with various acquired blood disorders. In leukaemias, preleukaemic states and bone marrow insufficiencies with or without sideroblastosis, changes in enzyme activity are usually characterized by the coexistence of deficiency of some enzymes and an increased activity of others.

The most frequently decreased activities are those of pyruvate kinase, phosphofructokinase,2,3‐diphosphoglycerate mutase and adenylate kinase; the most frequently increased activities are those of hexokinase, aldolase, enolase, 6‐phosphogluconate dehydrogenase and glucose‐6‐phosphate dehydrogenase.

In primary myelofibrosis and in polycythaemia rubra vera, enzyme deficiencies are infrequent and differ from those observed in leukaemias and related disorders. Phosphohexose isomerase and phosphoglucomutase deficiencies seem relatively specific for polycythaemia rubra vera.

Explanations for the acquired enzymopathies are still at the stage of hypothesis. The theory of multiple genetic damage may explain some findings but has not yet been proved right. The possibility of post‐translational molecular modification is suggested as a working hypothesis.
Molecular Basis of Thalassaemia
Authors: Weatherall D. J. , Clegg J. B.
Published: March 2008

Summary.

The thalassaemias are a heterogeneous group of conditions characterized by imbalanced globin chain production. In some forms there is a total absence of globin chain synthesis while in others globin chains are synthesized but at a reduced rate. There is increasing evidence that inefficiently synthesized structural haemoglobin variants can produce an identical clinical picture to thalassaemia.

The molecular defect in the β thalassaemias is not yet worked out but in all forms studied, except the Ferrara type, there is an absolute reduction in the amount of β‐chain messenger RNA. In the Ferrara type there appears to be messenger RNA present but β‐chain synthesis does not occur unless induced by a soluble fraction from normal cells. The molecular pathology of the α thalassaemias is understood better. The severe type, α‐thalassaemia 1, results from a deletion of all or most of the α‐chain genes. There is good circumstantial evidence that the milder form, α‐thalassaemia 2, results from a loss of one of a pair of linked α‐chain genes. About half of the individuals with the haematological picture of α‐thalassaemia 2 are heterozygous for Hb Constant Spring, a chain‐termination mutant which is synthesized inefficiently. The chain‐termination mutants form a class of disorders which can produce the clinical picture of thalassaemia due to inefficient production of elongated α chains.
Nucleic Acid Studies on the Pathogenesis of Leukaemia
Authors: Polli Elio E. , Corneo Gianmarco
Published: March 2008

Summary.

Recent work has lent strong support for the viral hypothesis of pathogenesis of human leukaemia. In laboratory animals both horizontal transmission from one individual to another by inoculation of leukaemia virus in the newborn, and vertical transmission through subsequent generation, have been shown to occur. With some animal leukaemias, and in general in human leukaemia, virus‐like particles cannot be detected by the electron microscope. It is generally accepted, however, that oncogenic virus infection can be transmitted through viral nucleic acids alone. Although oncogenic DNA viruses such as the Ebstein‐Barr virus might be the agent of Burkitt's lymphoma, tumour viruses which cause leukaemia in animals are usually RNA, and RNA viruses are the more likely candidates as viral agents for human leukaemia.

RNA molecules with nucleotide sequences related to those of animal RNA tumour viruses have been found in human leukaemia, lymphoma, sarcoma and carcinoma cells. Such RNA molecules have the size of 70S RNA and are contained in a complex with reverse transcriptase. Nucleotide sequences, related to sequences of known RNA tumour viruses, have also been detected in human leukaemic cell DNA.

Viral DNA sequences appear to be integrated into the genome mainly in the DNA fraction having an intermediate repetition frequency. They are not enriched in the satellite DNAs, which are the most highly repeated sequence of the cellular genome.

Normal cell genomes may contain endogenous viral sequences which are inactive and might have been transmitted vertically through many generations. Recent work indicates that inherited endogenous tumour virus nucleotide sequences are related in evolutionary related species. Therefore, it appears likely that a possible human leukaemia virus might be related to primate leukaemia viruses.
Factor VIII‐Related Antigen and von Willebrand's Disease
Authors: Rizza C. R.
Published: March 2008

Summary.

Immunological methods for the detection and assay of factor VIII‐related antigen have proved to be valuable tools in the study of factor VIII, haemophilia and von Willebrand's disease. The antibody neutralization tests, with their inherent difficulties and variability, have been largely replaced by the electroimmunoassay based on the method of Laurell. Using this latter method, it has been convincingly shown that whereas normal individuals and haemophiliacs have an antigen which precipitates with the rabbit anti‐factor VIII antibody, patients with von Willebrand's disease have a reduced amount of the antigen.

The relationship of the antigen to factor VIII activity is not yet clear; nevertheless the assay of factor VIII‐related antigen is proving of some value in the diagnosis of von Willebrand's disease and in the detection of carriers of haemophilia. In von Willebrand's disease the test for the antigen along with the ristocetin test for platelet aggregation has thrown new light on the condition and has helped to define several variants of the disease.
The Effect of Various Cytotoxic Agents on Bone Marrow Progenitor Cells as Measured by Diffusion Chamber Assays
Authors: Squires D. J. P. , Lamerton L. F.
Published: March 2008

Summary. TWO diffusion chamber assays, termed the ‘Full’ chamber technique and the ‘Empty’ chamber technique, have been used to determine the effect of various doses of cyclophosphamide, vinblastine and busulphan on the population of diffusion chamber progenitor cells (DCPC). The diffusion chamber dose‐response curves were compared to the progenitor cell survivals estimated by the spleen colony technique. The in vitro agar colony assay was also performed on the busulphan‐treated marrow. The diffusion chamber and spleen colony techniques estimated similar survivals after cyclophosphamide and vinblastine treatment. However, with busulphan, the chamber, spleen colony and agar colony methods estimated different survivals. The indication is that the diffusion chamber techniques assay the same population of cells as the spleen colony technique, and that busulphan alters the capacity of surviving DCPC to generate granulocytes and macrophages.
The Growth of Human Bone Marrow in Diffusion Chambers
Authors: Squires D. J. P.
Published: March 2008

Summary. Diffusion chambers containing normal human bone marrow were implanted intraperitoneally into normal and irradiated mice and cultured for various periods. Granulocytes, macrophages and lymphocytes comprised the majority of the cells harvested in all cultures. The most impressive cell growth occurred when the chambers were implanted into primary hosts irradiated with 840 R and then retransplanted on Day 8 of the culture into secondary hosts irradiated with the same dose. Linear relationships were found between the number of nucleated cells inoculated into the chambers and the number of cells harvested after 8 or 10 days of culture in heavily irradiated hosts.
Chamber Centrifugation: A Harvesting Technique for Estimation of the Growth of Human Haemopoietic Cells in Diffusion Chambers
Authors: Jacobsen Niels
Published: March 2008

Summary. A harvesting technique which gives information about the spatial relationships between cells grown in diffusion chambers in mice has been designed. The principle is that cells are centrifuged directly from the chamber clot onto a slide during pronase treatment.

The technique has been applied to normal human bone marrow cells grown in diffusion chambers. The slides show that the cells are situated in clusters. A limiting dilution assay of progenitor cells based on the presence of granulopoietic clusters in the chambers demonstrates the use of the method for quantitation of progenitor cells.
A Form of Hereditary Persistence of Fetal Haemoglobin Characterized by Uneven Cellular Distribution of Haemoglobin F and the Production of Haemoglobins A and A2 in Homozygotes
Authors: Weatherall D. J. , Cartner R. , Clegg J. B. , Wood W. G. , Macrae I. A. , Mackenzie A.
Published: March 2008

Summary. Thirteen members of a British family were found to have elevated levels of haemoglobin F (Hb F) which segregated into two groups with mean values of 19.8±0.52% and 8.9±3.1% respectively. Genetic data indicate that the individuals in the former group are probably homozygous, and those in the latter group heterozygous, for the gene causing persistent Hb‐F production. There is a significant reduction in the level of Hb A2 in the homozygotes. The Hb F is hcterogeneously distributed among the red cells of each of the affected family members. In each case the haematological findings are normal and biosynthetic studies indicate balanced globin‐chain synthesis. Chemical studies indicate that the Hb F consists mainly of the Ay type together with a small (c 10%) but significant amount of the Gy type in both homozygotes and heterozygotes. The other red‐cell proteins and antigens are of the adult variety in all affected family members. The condition differs from previously described forms of hereditary persistence of fetal haemoglobin by virtue of the heterogeneous distribution of the Hb F and the presence of β and δ‐chain synthesis in homozygotes. Its possible basis as a controller‐gene mutation is discussed.
Effect of Human Erythrocyte Stromata on Complement Activation
Authors: Corrocher R. , Tedesco F. , Rabusin P. , De Sandre G.
Published: March 2008

Summary. Stroma from either normal or PNH‐likc red cells is capable of inhibiting, to some extent, lysis in the sucrose test and enhancing lysis in the acidified‐serum test. The same opposing effects are displayed by the exclusion peaks from Sephadcx G‐200 obtained from each stroma preparation, suggesting that the same factor could be responsible for both activities. Stromata and peaks also induce lysis of PNH‐likc cells in unacidified serum, indicating activation of complement through the alternate pathway. This is confirmed by immunoelcctrophorctic observation. When serum previously activated through the alternate pathway is used in the sucrose test the amount of lysis is markedly reduced. This would indicate that the classical pathway activation can be controlled by the alternate pathway. The possible clinical significance of these factors in determining the hacinolytic crisis in PNH patients is discussed.
The Value of Age‐ and Sex‐Matched Controls for Coagulation Studies
Authors: Dodds W. J. , Moynihan A. C. , Benson R. E. , Hall C. A.
Published: March 2008

Summary. Several coagulation parameters and plasminogen levels were studied in 80 normal people divided into eight paired and sex‐matched age groups: prepubertal children, postpuberal children, young adults, and adults over 50. The data indicate that factor‐VII and ‐IX activities increase with age, with a cluster of lower activity for children and higher activity for adults. Factor‐VIII levels appear to decrease with age, although this effect could be due to greater anxiety in the pre‐ and postpubertal children at the time of venipuncture. The adults showed no significant change in factor‐VIII activity with age, but partial data indicate that factor‐VIII levels are higher in adults with blood group A than those with blood group O. The age‐related changes in factor‐VII, ‐IX, and possibly ‐VIII activities did not vary between sexes. By contrast, plasminogen increased strikingly with age in males and decreased with age in females. With fibrinogen, a similar effect was found for adults, though not for the entire population. These findings indicate the importance of using appropriate age‐ and sex‐matched controls for coagulation and plasminogen assays, especially in patients with mild inherited or acquired coagulation disorders.
Coagulation Studies as a Prognostic Index in Acute Liver Failure
Authors: Dymock I. W. , Tucker J. S. , Woolf I. L. , Poller L. , Thomson J. M.
Published: March 2008

Summary. A coagulation screen has been performed on 12 patients with acute liver failure. Six died and six recovered. All six fatal cases developed a haemorrhagic state with haemostatic failure. An attempt has been made to delineate the various mechanisms for the production of the coagulation defect. The significance of the different haematological parameters in assessing prognosis has been assessed.

The study emphasizes the importance of the synthetic ability of the liver in determining survival prospects. A good correlation between the factor‐VII level, which is a guide to liver synthesis, and recovery has been shown. The value of a specific factor‐VII assay in acute liver failure appears considerable. Where this assay cannot be performed the clot opacity fibrinogen technique provides a reasonable guide to the prognosis.

The presence or absence of DIG was not a determinant factor in survival in this series.
Observations on a Factor‐V Inhibitor
Authors: Crowell E. B.
Published: March 2008

Summary. A 67‐year‐old man developed a potent inhibitor of factor V shortly after undergoing blood transfusions and surgery. The inhibitor reacted in a time‐dependent manner with factor V and gave a non‐linear concentration graph. Studies with specific antisera indicated that it contained γ and μ heavy chains and both κ and λ light chains. The plasma from two patients with congenital factor‐V deficiency did not neutralize the inhibitor.
Endogenous Production of Carbon Monoxide as Measured Simultaneously in Blood and Gas Phase
Authors: Bensinger T. A. , Brouillard R. P. , Conrad M. E.
Published: March 2008

Summary.Endogenous carbon monoxide (CO) production rates and total body haemoglobin content were determined simultaneously in blood and gas phase in 15 individuals. At 24% oxygen (O2) concentration in the closed rebreathing system, a correlation was obtained which revealed that a 1 μmole rise in CO in the gas phase of the system was the result of 48.94± 5.3 (SE) μmoles of CO rise in the body. Three individuals had heat‐damaged red cells reinjected intravenously to determine if the recovery rate of the subsequently produced CO was proportionate in both the gas phase and blood phase. Changes in blood CO concentration were not consistently detected by gas phase analysis. Prediction of CO production rates utilizing gas phase data alone did not reflect accurately CO production rates determined from blood carboxyhaemoglobin rises.
Ferritin Synthesis in Lymphocytes, Polymorphs and Monocytes
Authors: Summers M. , White G. , Jacobs A.
Published: March 2008

Summary. A rapid two‐stage method has been devised for the separation of different leucocyte populations from human blood. Different cell types can be obtained in an undamaged state and with little contamination. Ferritin and total protein synthesis has been determined by measuring [14C]leucine incorporation in culture media which contain varying amounts of added ferric iron or desferrioxamine. Both ferritin and total protein synthesis is greater in monocytes than in lymphocytes or polymorphs when the basal medium is used. Only monocytes show a consistent increase in ferritin production due to iron stimulation. Ferritin synthesis by monocytes, polymorphs and lymphocytes is inhibited in the presence of desferrioxamine.
The Role of Thrombin in ADP‐Induced Platelet Aggregation and Release: a Critical Evaluation
Authors: Macfarlane Donald E. , Walsh Peter N. , Mills David C. B. , Holmsen Holm , Day H. James
Published: March 2008

Summary. The role of thrombin in ADP‐induced aggregation and release in vitro was critically examined. The addition of heparin or hirudin to citrated platelet rich plasma did not prevent aggregation or release. The addition of citrate to heparinized plasma restored secondary aggregation and release. Hirudin did not prevent irreversible aggregation. These results are incompatible with the hypothesis that thrombin is a primary and necessary mediator of platelet aggregation (Ardlie & Han, 1974; Han & Ardlie, 1974a, b, c). This hypothesis is based in part on the assumption that EDTA enhances the elution of clotting factors from platelets; we found no enhanced elution of factors II, V, X, VIII, IX or XI when platelets were washed in EDTA.
Alternative Pathways for the Activation of Factor XIII
Authors: Mcdonagh Jan , Mcdonagh R. P.
Published: March 2008

Summary. Factor XIII is present in plasma as a proenzyme, which when activated catalyses the formation of ε(γ‐glutamyl)lysyl bonds in fibrin. In this study the activation of purified plasma factor XIII was examined quantitatively with the fluorescent amine incorporation assay. Activation products were examined by polyacrylamide gel electrophoresis. The serine proteases, thrombin, trypsin, chymotrypsin, and factor Xa, and also Reptilase were tested for their ability to activate factor XIII. Highly purified thrombins activated purified factor XIII; this reaction was not calcium dependent. Trypsin was also a potent activator, but no transglutaminase activity was found with chymotrypsin. The most highly purified preparations of Reptilase had no effect on factor XIII activity. Less purified Reptilase preparations activated factor XIII, which suggests the presence of another enzyme in these Reptilase preparations. Highly purified factor Xa was found to be an effective activator of purified factor XIII, In contrast to thrombin activation, this reaction required calcium. It may be that under certain circumstances factor XIIIa could be formed in vivo directly by the alternative pathway of factor Xa. Factor XIIIa could then crosslink fibrinogen, which would also provide an alternative pathway for thrombus formation. Also, the activation of factor XIII by both factor Xa and thrombin provides a further point of control in the blood coagulation process.
Leukaemia in Children and. their Grandparents: Studies of Immune Function in Six Families
Authors: Till Morwenna M. , Jones Lindsay H. , HARDISTY R. M. , Lawler Sylvia D. , Harvey Betty A. M. , Soothill J. F.
Published: March 2008

Summary Seven of 500 children with acute leukaemia seen over a 15‐year period were known to have a close relative with leukaemia or lymphoma. In each case the affected relative was a grandparent of the child, six of the seven being paternal grandparents. Investigation of these six families showed that the fathers, who had two affected first‐degree relatives, had lower lymphocyte counts and higher serum IgA concentrations than paired controls. Atopy, repeated infections and rheumatic disease were common amongst the parents and their sibs. The findings suggest a possible immunodeficiency basis for leukaemia in these families and perhaps also for acute lymphoblastic leukaemia of childhood in general. In the only family in which three generations, including both leukaemic patients, were available for HL‐A typing, the affected grandson had not inherited either of his affected grandmother's haplotypes.
Karyotypic Abnormalities in Transformed Chronic Granulocytic Leukaemia
Authors: Sharp J. C. , Potter A. M. , Guyer R. J.
Published: March 2008

Summary Chromosomal abnormalities in three cases of chronic granulocytic leukaemia are presented. The relative importance of ‘specific’ chromosomal abnormalities, additional to the Ph1 in the karyotypic evolution of chronic granulocytic leukaemia is discussed. A new abnormal metacentric chromosome is described.
Hereditary Giant Platelet Syndrome
Authors: Walsh P. N. , Mills D. C. B. , Pareti Francesco I. , Stewart Gwendolyn J. , Margaret D. E. Macfarlane , Johnson M. , Egan J. J.
Published: March 2008

Summary The platelets from two related patients with the hereditary giant platelet syndrome were examined. They were larger than normal but otherwise ultra‐structurally normal; they contained increased storage pools of adenine nucleotides and heparin‐neutralizing activity and took up serotonin at an increased rate. They aggregated normally with ADP and collagen but failed to aggregate with bovine factor VIII and Ristocetin. Some change in shape occurred with ADP, and the reduction in adenylate energy change after addition of ADP to platelet‐rich plasma was smaller than normal.

Platelet coagulant activities including contact product forming activity, intrinsic factor‐Xa forming activity and platelet factor 3 activity were normal or increased, but collagen‐induced coagulant activity was absent whether tested in washed platelet suspensions or platelet‐rich plasma. Platelet washing experiments showed decreased binding of factors V and VIII to hereditary giant platelets and no detectable factor XI in washed platelet suspensions. It is concluded that (1) the hereditary giant platelets studied lacked a binding mechanism for factors V, VIII and XI; (2) the normal development of collagen‐induced coagulant activity apparently depends upon the binding of factor XI to the platelet membrane; and (3) the defective prothrombin consumption observed in these patients may have resulted from the failure of their platelets to bind factor XI.
Another Example of an Antibody Reacting Optimally with p Red Cells
Authors: Issitt C. H. , Duckett J. B. , Osborne B. M. , Gut J. B. , Beasley J.
Published: March 2008

SUMMARY An antibody is described that reacted strongly with red cells of the p(Tj(a —)) phenotype and moderately to strongly with cord red cells of the P2 phenotype. The antibody failed to react, or reacted very weakly, with red cells of the P1k and P1 phenotypes and with the red cells of five children of a p individual, and reacted weakly with occasional red cell samples from adults of the P2 phenotype. These results suggest that the antibody does not detect a product of the p, gene but instead detects a P system precursor substance. In p individuals this P system precursor substance is not altered by the p, genes. In individuals of the P1 or P2 phenotype this precursor substance is apparently converted to P1 and/or P antigens by the P1 or P2 genes,
Remission Maintenance Therapy for Meningeal Leukaemia: Intrathecal Methotrexate and Dexamethasone versus Intrathecal Craniospinal Irradiation with a Radiocolloid
Authors: Muriel F. Sackmann , Schere D. , Barengols A. , EPPINGER‐HELFT M. , Braier J. L. , Pavlovsky S. , Macchi G. H. , Guman L.
Published: March 2008

SUMMARY. Thirty‐two patients with meningeal leukaemia who achieved meningeal remission with intrathecal methotrexate (MTX) plus dexamethasone (DMT) were entered in a randomized study of two maintenance treatments: (a) 16 patients received intermittent intrathecal doses of MTX plus DMT, and (b) 16 patients received intermittent intrathecal doses of radioactive chromic phosphate (CROP). The population and clinical characteristics of the cases assigned to each maintenance regimen were similar. The duration of meningeal remission was 55–600+ d (median 550 d) for the MTX and DMT group and 56–555 d (median 360 d) for the CROP group. There was no statistical difference (P0.05) between the curves of the two groups. Intrathecal CROP seems to be as effective as intrathecal MTX plus DMT as maintenance treatment for intrathecal MTX plus DMT induced meningeal remission. Further uses of this compound should be explored but it seems to be dangerous to administer it by lumbar puncture.
Iron Absorption in the Rat: The Search for Possible Intestinal Mucosal Carriers
Authors: Halliday June W. , Powell Lawrie W. , Mack Ulrich
Published: March 2008

SUMMARY. The biological relevance of four iron‐containing fractions previously detected in rat intestinal mucosal cells has been studied. The distribution of iron in these fractions obtained by chromatography on Sepharose 6B has been examined after in vivo and in vitro incubation of mucosal cells with 59Fe. In addition, the effects of phenobarbitone, cycloheximide, iron‐deficiency and iron‐loading on the uptake and distribution of iron within the four mucosal cell fractions was studied. The iron in fraction I was mostly bound to intracellular membrane particles. Fraction II was shown to be ferritin. Fraction III contained some transferrin and also a protein of molecular weight similar to transferrin but which was not precipitable by antitransferrin antiserum. Quantitative differences between the in vivo and in vitro studies combined with the results of ‘chaser’experiments suggested that, in addition to ferritin, at least two of the fractions (I and III) were involved in the process of iron absorption by the mucosal cell.
Factor VIII and Human Platelet Aggregation
Authors: Bottecchia D. , Vermylen J.
Published: March 2008

SUMMARY Bovine factor VIII is a potent inducer of aggregation of human platelets. Upon gel filtration of five‐thousand‐fold purified material in 0.5 M CaCl2, bovine factor VIII is separated into high and low molecular weight components: the former contains both a ‘carrier protein’and platelet aggregating activity, the latter theproco‐agulant activity (low molecular weight factor VHI, LMW‐F VIII). Upon removal of Ca2+ ions, LMW‐F VIII recombines with the ‘carrier protein’. LMW‐F VIII modifies aggregation by ‘carrier protein’, but not aggregation by undissociated bovine factor VIII, adenosine‐5′‐diphosphate or adrenaline. This finding indicates that the platelet aggregating activity is indeed a property of the ‘carrier protein’.
The Effect of Trimethoprim on Cellular Transport of Methotrexate and its Cytotoxicity to Human Lymphoblastoid Cells in Vitro
Authors: Niethammer D. , Jackson R. C.
Published: March 2008

A study has been made of the effects of the antifolate drug trimethoprim (2,4‐diamino‐5‐(3′,4′,5′‐trimethoxybenzyl)pyrimidine) on the cellular transport of natural folates and of methotrexate in a human lymphoblastoid cell line grown in culture. The results indicated that cellular uptake of 5‐methyltetrahydrofolate, folic acid and methotrexate could be inhibited by trimethoprim; the inhibition, for methotrexate at least, was competitive, but it was in every case rather weak. Calculations showed that under conditions used during therapy with methotrexate, trimethoprim could be employed as an antibacterial agent without the cellular uptake of methotrexate being impaired by more than 1%. The cytotoxic effect of trimethoprim against the cell line used was 2000 times less, on a molar basis, than that of methotrexate. However, the degree of growth inhibition caused by the two agents in combination was greater than the sum of the individual toxicities. Again, this effect was not large at clinically useful concentrations of trimethoprim.
The Anti‐Rh0(D) Responses of Immunized Volunteers following Repeated Antigenic Stimuli
Authors: Gunson H. H. , Stratton F. , Phillips P. K.
Published: March 2008

Twenty‐nine Rh0(D) negative male volunteers previously immunized with D‐positive red cells have received series of antigenic stimuli repeated at intervals of 2 or 4 weeks. Although there is an individual variation in the magnitude of the anti‐D responses, the levels of anti‐D achieved are, in general, higher than those obtained after stimuli spaced at intervals of several months. Moreover, certain volunteers whose plasma was not suitable for inclusion into pools for the preparation of anti‐D immunoglobulin after spaced stimuli could donate regularly following the repeated stimuli.

Whilst untoward clinical reactions did not occur as a result of the repeated stimuli five volunteers developed unwanted antibodies outside the Rh system and this may be related to the total dose of red cells injected.
The Effect of pH upon Human Transferrin: Selective Labelling of the Two Iron‐binding Sites
Authors: Lestas A. N.
Published: March 2008

The influence of pH changes upon the iron‐binding properties of transferrin was investigated in the absence of chelating agents. The effects were demonstrated by spectrophotometry, gel filtration, and by studies of the intermolecular transfer of 59Fe from transferrin to conalbumin.

At pH values below 6.7, diferric transferrin readily loses iron. The monoferric molecule, which is relatively resistant to acid dissociation, is preferentially formed. A temporary reduction of pH provides a simple method for selectively attaching iron to one metal‐binding site, and allows double isotopic labelling of the transferrin molecule. This technique may permit further investigation of the physiological properties of the two iron‐binding sites.
Variations in Globin Chain Synthesis in Hereditary Persistence of Fetal Haemoglobin
Authors: Friedman Shlomo , Schwartz Elias , Ahern Edgar , Ahern Valda
Published: March 2008

Globin synthesis was studied in four Negro families including 10 members with Hb A‐HPFH and four with Hb S‐HPFH. The β/α specific activity ratios in 10 of these HPFH heterozygotes were similar to those of the control group. In two patients with Hb A‐HPFH, the β/α ratio was slightly decreased in one (0.84) and clearly decreased in another (0.78). In two of the patients with Hb S‐HPFH the ratios were clearly decreased (0.71 and 0.75). The extended range of β/α ratios in these 14 patients is similar to that of Negro patients with β‐thalassaemia trait. These studies indicate that a decreased β/α ratio may be found in HPFH, as well as in β‐thalassaemia.

Bone marrow globin synthesis was measured in two patients with Hb S‐HPFH and decreased peripheral blood β/α ratios, and in one with Hb A‐HPFH and a normal peripheral blood β/α ratio. In each patient the (β+γ)/α ratio of radioactivities as well as the β/α specific activity ratio was close to 1 and therefore balanced, indicating more rapid decay of β‐chain synthesis relative to α‐chain during red cell maturation or extremely rapid destruction of newly synthesized excess α‐chains in the bone marrow.
The Relationship of Platelet Coagulant Activities to Venous Thrombosis following Hip Surgery*
Authors: Walsh P. N. , Rogers P. H. , Marder V. J. , Gagnatelli G. , Escovitz E. S. , Sherry S.
Published: March 2008

Platelets have recently been shown to trigger intrinsic coagulation by two alternative pathways, protect active clotting factors from inactivation by plasma inhibitors and catalyse intrinsic coagulation reactions on the platelet surface to form fibrin. To determine whether these platelet coagulant activities (PCA) might have a role in the pathogenesis of DVT, 29 patients have been studied before and after arthroplasty or other surgery for fractured hip or degenerative hip disease. The occurrence of DVT was detected by [125I]fibrinogen uptake in the legs and confirmed by venography. In patients who developed DVT, all PCA increased progressively and significantly on day 1 (mean rise, 146% of baseline), day 3 (228%) and day 5 (298%) after surgery before isotopic evidence of DVT appeared (mean 3.27 days postoperatively). In patients without DVT no changes in PCA were observed. Plasma coagulation factor assays were no different in patients with and without DVT. Platelet counts and total platelet antiheparin activity increased during the early postoperative period in DVT patients but not in patients without DVT. It is suggested that progressive increases in PCA concerned with triggering and catalysing intrinsic coagulation reactions may play a pathogenetic role in DVT after hip surgery.
Platelet Dysfunction in Vincristine Treated Patients
Authors: Steinherz P. G. , Miller D. R. , Hilgartner M. W. , Schmalzer E. A.
Published: March 2008

Recent revival of interest in the use of vincristine (VCR) for the treatment of idiopathic thrombocytopenic purpura prompted us to evaluate the platelet function of our patients on VCR. Eighteen patients with acute lymphoblastic leukaemia (ALL) in remission, and nine children with solid tumours were studied on 80 occasions at different time intervals after their last VCR dose. A mildly elevated threshold for epinephrine‐induced second phase aggregation and a delay in the onset of collagen‐induced aggregation was found in patients with ALL not on VCR. Vincristine induced unobtainable second phase aggregation to epinephrine in 67%, 38%, 30% and to ADP in 53%, 13%, 33% of the patients 1 week, 2–3 weeks and 4 weeks respectively after administration. The thrombocytopathy was relative, not absolute, since collagen induced aggregation at all times. Platelet counts, uptake and release of serotonin, bleeding times, clot retractions and release of platelet factor 3 were normal. Platelet adhesion was abnormal in five of 12 patients tested. In vitro platelets are a hundred‐fold less sensitive to VCR than in vivo. Cyclic adenosine monophosphate, cyclic guanosine monophosphate and dimethylsulfoxide do not protect platelets from VCR. The exact mechanism by which VCR abolishes second phase aggregation in patients is uncertain. Because of VCR's narrow therapeutic index between thrombocytopenia and thrombocythaemia, the use of VCR should be reserved for life‐threatening haematologic disorders when treating non‐malignant conditions.
Chemotaxis for Human Monocytes by Fibrinogen‐derived Peptides
Authors: Richardson D. L. , Pepper D. S. , Kay A. B.
Published: March 2008

Chemotactic activity for human peripheral blood monocytes was generated by the action of thrombin on human fibrinogen, a reaction known to release low molecular fibrinopeptides. Supernatants prepared by incubating Contortrix venom with fibrinogen, which cleaves the B peptide, were also chemotactic, whereas no activity was present in supernatants from Arvin venom, which cleaves peptides A, AP and AY. Thus fibrinopeptide B was chemotactic for the monocyte in addition to the neutrophil, as previously reported.

Monocyte chemotactic activity was also generated by the action of plasmin on human fibrinogen and shown to be associated with the D and E fragments but not with a mixture of fragments X and Y. When plasmin digestion was stopped at time intervals up to 24 h, monocyte chemotactic activity corresponded with the appearance of the D and E fragments. The monocyte chemotactic activity, contained in a 24 h digest, eluted from Sephadex G‐75 at V0, corresponding to the expected position of the D and E fragments whereas neutrophil chemotactic activity eluted with molecules of molecular size of approximately 30 000 daltons. Thus fragments D and E derived from plasmin digestion of fibrinogen attract the monocyte whereas only the small uncharacterized peptides were chemotactic for the neutrophil. These different profiles of chemotactic activity for the neutrophil and the monocyte in terms of plasmin digestion products of fibrinogen may be of significance in the events leading to the accumulation of these cells in vivo during fibrin deposition.
Fine Structural Studies of Peripheral Blood Leucocytes from Children with Kwashiorkor: Morphological and Functional Properties
Authors: Schopfer Kurt , Douglas Steven D.
Published: March 2008

This is the first report of electron microscopic observation on circulating leucocytes from children with kwashiorkor. Neutrophils showed evidence of immaturity, prominent Golgi zones, granule pleomorphism; strands of endoplasmic reticulum and Döhle bodies were frequent. Although an in vitro microbicidal defect occurs with S. aureus, E. coli and C. albicans, the postphagocytic morphological events, including vacuole formation and degranulation, were normal. In mononuclear cell pellets plasmacytoid cells were frequently observed, and rare lymphoblasts occurred. The findings suggest activation of the phagocytic system and stimulation of humoral immunity in children with kwashiorkor. These fine structural observations are comparable to those which occur in trauma or thermal injury, both conditions associated with tissue breakdown and extensive antigenic stimulation.
Comparison of the Coagulant Activities of Platelets and Phospholipids
Authors: Walsh Peter N. , Lipscomb Myatt S.
Published: March 2008

Summary.

The coagulant activities of various phospholipid preparations were compared with those of platelets. Folch phospholipid with maximal platelet factor 3 (PF3) activity produced long recalcified clotting times of relatively undiluted plasma in plastic tubes whereas untreated or ADP‐treated platelets with minimal PF3 activity produced short clotting times in the same test system which is sensitive to activators of the contact system of intrinsic coagulation. Bell and Alton phospholipids with maximal PF3 activity produced recalcified clotting times similar to those in the presence of platelets. Bell and Alton phospholipids had tissue factor activity, but Folch phospholipid and platelets did not. Bell and Alton phospholipids and gum acacia (used as a vehicle in one of the preparations) activated factor XII as did platelets, but Folch phospholipid did not. The multiple coagulant activies of Bell and Alton phospholipids (i.e. PF3, tissue factor and contact activating) may account for the absence of coagulant superiority of platelets in the undiluted system in plastic tubes. The coagulant activities of platelets are also complex but different from Bell and Alton phospholipids whereas Folch phospholipid would appear to possess only PF3 activity.
Chloramphenicol Induced Inhibition of Platelet Protein Synthesis: in Vitro and in Vivo Studies
Authors: Agam Galila , Gasner S. , Bessler Hana , Fishman Pnina , Djaldetti M.
Published: March 2008

Summary.

Chloramphenicol (CAP), an antibiotic which causes various blood dyscrasias, was shown to inhibit in vitro protein synthesis of human blood platelets. The effect is dose‐ and time‐dependent, it is reversible after incubation for 2 h, and is comparable with the suppression achieved by cycloheximide (CXM). Electron microscopic examination revealed swelling and destruction of mitochondria.

Administration of CAP to dogs produced a progressive inhibition of platelet protein synthesis as shown by a reduction in the rate of [3H]leucine incorporation into protein. The maximal inhibitory effect of the antibiotic was reached 0.5–4.0 h after its administration, when minimal leucine incorporation values of 9–40% of the control were measured. The suppressive effect of CAP was followed by an overshoot in the incorporation of [3H]leucine, up to a maximum of 602% of the value at zero time of the experiment.
Lack of Prognostic Value of Lymphoblast Size in Acute Lymphoblastic Leukaemia
Authors: Oster Martin W. , Margileth David A. , Simon Richard , Leventhal Brigid G.
Published: March 2008

Summary.

There are conflicting reports about the relationship of cell size and type to prognosis in acute lymphoblastic leukaemia (ALL). For this reason, bone marrows at diagnosis and first relapse were studied in 56 children with ALL treated on the same protocol. Lymphoblasts greater than 12 mμ in diameter were called macrolym‐phoblasts (MLB). Forty‐one of 56 initial bone marrows had less than 20% MLB (group A), and 15 had greater than 20% MLB (group B). Median survival, complete remission rate, first remission duration, and the distribution of CNS leukaemia were similar in both groups. First relapse marrows were examined from 50 patients and a significant increase in MLB compared to initial pre‐treatment bone marrows (18%vs 8%) was found.
Manipulation of the Mitotic Cycle in the Treatment of Acute Myelogenous Leukaemia
Authors: Lampkin B. C. , McWilliams N. B. , Mauer A. M. , Flessa H. C. , Hake D. A. , Fisher V.
Published: March 2008

Summary.

A priming dose of cytosine arabinoside (Ara C) was given to 16 children and five adults with acute myelogenous leukaemia (AML) to synchronize leukaemia cells in the DNA synthesis (S) phase of the mitotic cycle. An infusion of this drug, which was continued for 12 h, was started at the time of partial synchronization and was repeated every 6–12 h until the bone marrow was very hypocellular. Complete remission was achieved in 12 of 16 children and in all adults. Two of the four children went into complete remission with the addition of two doses of daunorubicin or adriamycin. These results suggest that partial synchronization of cells in the S phase results in a therapeutic advantage in the use of Ara C for induction of a remission of AML and that manipulation of the mitotic cycle, as monitored by kinetic studies, may be helpful in planning optimal schedules for drug administration.
Significance of Haematological Parameters in the Non‐Hodgkin's Malignant Lymphomas
Authors: Bloomfield C. D. , Mckenna R. W. , Brunning R. D.
Published: March 2008

Summary.

Blood findings at diagnosis, in 140 adults with lymphoma, were correlated with bone marrow involvement and survival. An abnormal haemoglobin, leucocyte count or platelet count was found in 57% of patients. Lymphocytopenia occurred in 46%. All patients with thrombocytopenia or neutropenia, 69% with leucopenia and 63% with anaemia had marrow involvement with lymphoma. Marrow involvement in histiocytic and stem cell lymphoma was always associated with anaemia. Marrow involvement in poorly differentiated lymphocytic lymphoma (PDL) was associated with anaemia, thrombocytopenia, leucopenia, lymphocytopenia or lymphoma cells in the blood in 93% of patients. Bone marrow involvement was found in only 13% of patients with normal haematological parameters. In the absence of marrow involvement blood abnormalities at diagnosis did not generally correlate with survival. However, among patients with diffuse PDL who had marrow involvement, anaemia, thrombocytopenia and leucopenia adversely affected survival. Lymphocytopenia did not correlate with survival.