bluuebunny/crossref_metadata_2025_split huggingface dataset:
The kinetics of 111Indium distribution following injection of 111Indium labelled autologous granulocytes in man
Authors: Saverymuttu S. H. , Peters A. M. , Keshavarzian A. , Reavy H. J. , Lavender J. P. 
Published: March 2008

Summary. The kinetics of human autologous granulocytes, separated and labelled with 111In without isolation from plasma, have been studied in subjects with and without sepsis with the aim of identifying the fate and sites of destruction of granulocytes in man.In subjects without inflammatory disease, 111In granulocyte recovery in faeces, urine and saliva over 4 d was less than 1% of the dose, so that the activity visualized by the gamma camera represented almost 100% of the dose. On images taken at 24 and 48 h, this activity was distributed between spleen, bone marrow and liver, with foci of additional abnormal activity in subjects with inflammatory disease.Splenic activity fell between 40 min and 24 h, consistent with the presence of a splenic granulocyte pool, but remained constant after 24 h. Since granulocyte clearance from the blood was predominantly completed by 24 h, the residual splenic activity at that time reflected splenic granulocyte destruction. In patients with sepsis, the fall in splenic activity was greater than in those without, implying diversion of granulocytes from splenic destruction to tissue utilization when inflammation is present. Bone marrow activity increased between 40 min and 24 h and then remained stable. Granulocytes that were extensively manipulated in saline prior to labelling failed to localize in marrow, suggesting that visualization of the latter reflected destruction of intact, normal granulocytes. Although the changes in splenic and marrow activities terminated at 24 h, at which time granulocyte clearance from blood was at least 80% completed, plasma 111In remained essentially unchanged between 40 min and 48 h at less than 5% of the dose, discounting it as the source of splenic and marrow activities.
Book Reviews
Authors: Luzzatto L. , Gaffney Patrick J. , Gordon M. Y. , Weatherall D. J. , Machin S. J. , Bloom A. L. , Rampling Mike , Poller Leon , Epenetos A. A. 
Published: March 2008

Advances in Human Genetics Clinical Aspects of Fibrinolysis and Thrombolysis. Edited by T. Jespersen, C. Kluft and C. Korsgaard. Normal and Neoplastic Hematopoiesis. UCLA Symposium on Molecular and Cellular Biology, New Series Volume 9. Edited by D. W. Golde and S. A. Mares. Malaria and the Red Cell. Edited by J. W. Eaton and G. J. Brewer. Thrombosis and Cardiovascular Diseases. Advances in Experimental Medicine and Biology, Volume 164. Edited by A. Strano. Factor VIII Inhibitors. By L. W. Hoyer. Red Cell Deformability and Filtration. Edited by J. Dormandy. Thromboplastin Calibration and Oral Anticoagulant Control. Edited by A. M. H. P. van den Besselaar, H. R. Gralnick and S. M. Lewis. The Reticuloendothelial System. A Comprehensive Treatise to Cancer. Ed. Herberman & Friedman.
Thrombocytopenia in SLE and related autoimmune disorders: association with anticardiolipin antibody
Authors: Harris E. N. , Asherson R. A. , Gharavi A. E. , Morgan S. H. , Derue G. , Hughes G. R. V. 
Published: March 2008

SummaryAnticardiolipin antibody levels were determined in 116 patients with systemic lupus erythematosus and related autoimmune disorders. Forty‐three of these patients had a history of thrombocytopenia—36 of whom had SLE, three primary Sjögren's syndrome, two rheumatoid arthritis and two mixed connective tissue disease. IgG anticardiolipin antibody levels were raised in 31 (72%) of the 43 patients and IgM anticardiolipin antibody levels were raised in 19 (44%). There was a strong statistical correlation between thrombocytopenia and raised anticardiolipin antibody levels of both the IgG (P < 0.001) and IgM (P < 0.01) immunoglobulin classes. Of the 20 patients with the highest IgG anticardiolipin antibody levels 16 had a history of thrombocytopenia. We suggest that anticardiolipin antibodies may play a direct role in mediating platelet destruction in autoimmune disorders.
Heterogeneity of hereditary and acquired factor X deficiencies by combined immunochemical and functional analyses
Authors: Fair Daryl S. , Edgington Thomas S. 
Published: March 2008

SummaryLimited information is available regarding molecular abnormalities associated with derived factor X deficiencies. In order to assess the types of molecular aberrations that may occur in this group of haemostatic diseases we have analysed plasmas of 33 individuals from 28 kindred exhibiting factor X deficiency. These included those of hereditary type, transiently acquired deficiency as well as factor X deficiency associated with amyloidosis. Plasmas were analysed by one‐stage assays for factor X activation by the extrinsic coagulation pathway, intrinsic coagulation pathway and Russell's viper venom. Selected plasmas were analysed in two‐stage assays. Normal factor X concentration by specific radioimmunoassay was 6.38 ± 1.29 μg/ml. Factor X associated with factor X deficiency were grouped by their specific activities measured for the three activation pathways and antigen concentration. The results suggest that a broad spectrum of molecular aberrations exist in the factor X deficiency states. The most common group of factor X deficiency was associated with abnormal activation of factor X by all three pathways. Variants of factor X associated with primary amyloidosis and transient acquired deficiency appeared to be abnormal molecules and not just reduced factor X concentration. Hereditary abnormal factor X molecules include the spectrum of potential defective molecules. The relationship of factor X structure to function and the heterogeneity of these defective molecules is discussed.
The sequence of the Aγ globin gene in a Gγβ+ type of hereditary persistence of fetal haemoglobin
Authors: Jones R. W. , Goodbourn S. E. Y. , Old J. M. , Weatherall D. J. 
Published: March 2008

SummaryThe sequence of the Aγ globin gene from the affected chromosome of an individual heterozygous for the Gγβ+ type of hereditary persistence of fetal haemoglobin (Gγβ+ HPFH) is reported. With two exceptions, it is identical to one of the two allelic Aγ globin genes already sequenced and there is therefore no change which could explain the absence of its expression in the face of the persistent Gγ globin expression which is a feature of this condition.
The haematology of steady state homozygous sickle cell disease: frequency distributions, variation with age and sex, longitudinal observations
Authors: Hayes R. J. , Beckford M. , Grandison Y. , Mason K. , Serjeant B. E. , Serjeant G. R. 
Published: March 2008

SummaryThe steady state haematological characteristics observed in 1071 patients with homozygous sickle cell (SS) disease aged 5–66 years are presented.Cross sectional studies indicated that HbA2 levels were consistently higher in males but no age related change was apparent. Fetal haemoglobin levels were consistently higher in females and fell significantly in males between the 5–9 and 10–14 year age groups. Total haemoglobin was significantly higher in females before age 15 and higher in males after 20 years, a dramatic age related rise occurring in males between the 10–14 and 25–29 year age groups, and a fall in patients aged 40 years and over. The mean cell volume was consistently greater in females after 15 years and a marked age related rise occurred in both sexes between the 5–9 and 25–29 year age groups. Counts of irreversibly sickled cells were consistently higher in males. Reticulocytes fell significantly with age, while platelets and total bilirubin fell significantly after the age of 15 years.Longitudinal studies confirmed the increase in total haemoglobin levels in males over the ages 10–14 years, and a significant fall in males after the age of 30 years. Such studies also confirmed the fall in HbF in males aged 5–14 years, the increase in MCV in both sexes aged 5–29 years, and the fall in platelet counts in both sexes over the age of 20 years.These observations provide ‘normal’values for patients seen elsewhere and also contribute to an understanding of factors determining the haemoglobin indices in SS disease.
Acquired autoimmune thrombocytopenia after allogeneic bone marrow transplantation
Authors: Bierling Philippe , Cordonnier Catherine , Fromont Patricia , Rodet Martine , Tanzer Joseph , Vernant Jean‐Paul , Braco Christine , Duedari Najib 
Published: March 2008

Summary A 29‐year‐old man in remission from acute myeloblastic leukaemia was treated by chemoradiotherapy and transplantation of bone marrow (BMT) collected from his HLA identical brother. Engraftment was documented on D12. Transient acute GVHD (grade II) appeared from D34. No infection complicated the BMT. Nevertheless severe thrombocytopenia persisted and was unresponsive to marrow donor platelet transfusion. The platelet immunofluorescence test demonstrated the autoimmune basis of the thrombocytopenia. This study suggests that the transient immune imbalance observed in the early post graft period could facilitate the appearance of autoimmune cytopenias.Prolonged thrombocytopenia may occur after bone marrow transplantation (BMT). This requires platelet support which could delay the discharge from hospital. Thrombocytopenia is mostly related to marrow insufficiency and/or viral infections. We report a case of severe autoimmune thrombocytopenic purpura (AITP) in a recipient of an allogeneic BMT.
The myelodysplastic syndromes: different evolution patterns based on sequential morphological and cytogenetic investigations
Authors: Tricot G. , Boogaerts M. A. , Wolf‐Peeters C. De , Van den Berghe H. , Verwilghen R. L. 
Published: March 2008

Summary Serial morphological and cytogenetic investigations were performed in 46 patients with the myelodysplastic syndrome (MDS). Twenty‐one patients (45.5%) progressed to AML (> 30% blasts in bone marrow smears).Based on sequential determinations of percentages of bone marrow blasts, three patterns of evolution were observed in MDS. Patients with evolution pattern A (48%) had an apparently stable disease with minimal or no increase in bone marrow blasts. Exceptionally they developed new or additional chromosomal anomalies during the course of their disease. Cases in this group, who showed no abnormal localization of immature myeloid precursors (ALIP) at time of diagnosis experienced prolonged survival (median: 43 months), while ALIP positive patients had shorter survival times (median: 14 months), with high probability of early death from infections and/or bleeding problems. Patients with evolution pattern B (28%) initially had a morphologically stable disease, comparable to cases with evolution pattern A, but showed an abrupt shift from MDS to AML. Most of these patients (82%) were ALIP positive and a substantial proportion (46%) showed karyotype anomalies at diagnosis. The abrupt shift to AML in these patients was frequently (61.5%) associated with additional cytogenetic anomalies. Patients with evolution pattern C (24%) showed a gradual increase in bone marrow blasts. The majority of these cases (8/11) ultimately developed acute myeloid leukaemia (gradual progression to AML), whereas some patients (3/11) died from infections and/or haemorrhagic complications before they had reached the level of clinical AML. All of these patients were ALIP positive at diagnosis and no additional cytogenetic alterations occurred during evolution.Acquisition of new karyotypic anomalies during the course of MDS was almost invariably associated with abrupt shift to AML.
Protoporphyrin accumulation by mitogen stimulated lymphocytes and protoporphyrinogen oxidase activity in patients with porphyria variegata and erythropoietic protoporphyria: evidence for deficiency of protoporphyrinogen oxidase and ferrochelatase in both diseases
Authors: Siepker Lydia J. , Kramer Sidney 
Published: March 2008

SummaryIn erythropoietic protoporphyria (EPP) and porphyria variegata (PV) excess protoporphyrin is excreted in the stool, suggesting one or more enzyme defects in the terminal steps of the haem biosynthetic pathway.We measured protoporphyrinogen oxidase (PPO), which catalyses the oxidation of protoporphyrinogen to protoporphyrin, in both EPP and PV patients and in the offspring of PV patients. In the same subjects we measured protoporphyrin formation by mitogen stimulated lymphocytes, with delta aminolaevulinic acid (ALA) as substrate and with the addition of chelators or iron, an indirect measure of ferrochelatase activity. PPO activity was reduced by 41% (P<0.001) in PV patients and in 50%0 of their offspring, and by 36% (P<0.001) in EPP patients. Protoporphyrin accumulation in stimulated lymphocytes was increased by 1.3‐fold (P<0.001) in EPP and 1.5‐fold (P<0.001) in PV patients compared to normal subjects. There was a significant difference in protoporphyrin accumulation between iron deficient and iron replete cells from PV patients as compared to normals but not as marked as for EPP cells treated similarly. Stimulated lymphocytes from prepubertal PV offspring with reduced PPO activity accumulated normal amounts of protoporphyrin. We have interpreted our findings as follows: PPO is significantly reduced in both diseases. Ferrochelatase becomes defective in PV patients after puberty. This could explain why PV is clinically and biochemically manifest only after puberty. As it has been repeatedly shown that ferrochelatase is markedly
Ultrastructural localization of transferrin, transferrin receptor, and iron‐binding sites on human placental and duodenal microvilli
Authors: Parmley Richard T. , Barton James C. , Conrad Marcel E. 
Published: March 2008

SummaryUltrastructural methods were used to determine the subcellular location of the transferrin receptor, transferrin and iron‐binding sites on human term placenta and human duodenum microvillus surfaces. The transferrin receptor and transferrin were localized by immunocytochemical methods employing either OKT9, a human transferrin receptor monoclonal antibody, or mouse anti‐human transferrin (ATfn), both followed by a horseradish peroxidase (HRP)‐conjugated goat anti‐mouse IgG (GAM‐HRP) and diaminobenzidine (DAB) sequence. Iron‐binding sites were localized by acid ferrocyanide (AF) staining after saturation of tissue specimens with iron, accomplished with iron nitrilotriacetate (FeNTA), a known transferrin iron donor. Placental microvillus surfaces demonstrated staining for the OKT9‐GAM‐HRP‐DAB‐reactive transferrin receptor, ATfn‐GAM‐HRP‐DAB‐reactive transferrin, and FeNTA‐AF‐reactive iron acceptor, whereas enterocyte microvillus surfaces lacked significant staining with each of these methods. FeNTA‐AF stained iron‐binding substance in placental and enterocyte microvilli and cytoplasmic matrix. Thus using the same ultrastructural immunostaining and cytochemical methods transferrin receptor, transferrin, and nitrilotriacetate iron acceptor sites can be demonstrated on the microvillus surface of human placenta but not on the microvillus surface of human duodena.
The kinetics of unmatched and HLA‐matched 111In‐labelled homologous platelets in recipients with chronic marrow hypoplasia and anti‐platelet immunity
Authors: Peters A. M. , Porter J. B. , Saverymuttu S. H. , Malik F. , Zuiable A. , Lavender J. P. , Schwarz G. , Lewis S. M. , Gordon‐Smith E. C. 
Published: March 2008

SummaryThe kinetics of homologous platelets, labelled in plasma with 111In‐tropolonate, have been studied in five recipients with chronic marrow hypoplasia and severe thrombocytopenia, who were refractory to platelet transfusions as a result of alloimmunization. Mean platelet life span (MPLS), recovery, plasma 111In level and splenic and hepatic uptake kinetics were studied on two occasions, one using HLA‐matched platelets and the other unmatched platelets. In each case, recovery of labelled platelets at 1 h post‐injection and MPLS improved with HLA matching, although this improvement was highly variable. Only two of the five subjects would have derived any significant benefit from HLA‐matched as compared with unmatched platelet transfusions. It was concluded that the need exists for additional cross‐matching procedures, possibly related to platelet specific antigens, in patients who remain refractory to platelet transfusion.
Graft‐versus‐host disease prophylaxis with anti‐T‐cell monoclonal antibody OKT3, prednisone and methotrexate in allogeneic bone‐marrow transplantation
Authors: Filipovich A. H. , Krawczak C. L. , Kersey J. H. , McGlave P. , Ramsay N. K. C. , Goldman A. , Goldstein G. 
Published: March 2008

SummaryA new regimen for prevention of acute graft‐versus‐host disease (GvHD)—OKT3 (murine monoclonal anti‐pan‐T antibody), prednisone and methotrexate (OKT3‐pred‐MTX)—was compared with the Minnesota standard regimen—antithymocyte globulin, prednisone and methotrexate (ATG‐pred‐MTX)—for adverse effects, effect on incidence of acute GvHD, and survival at 1 year post‐transplant. Twenty patients (aged 25 ± 9 years) had bone‐marrow transplantation (BMT) from their HLA‐MLC identical sibling donors for treatment of aplastic anaemia (four), acute leukaemia in remission (13) or chronic myelogenous leukaemia (three). These 20 patients received (OKT3‐pred‐MTX) on days 8‐22 post‐transplant. Results of this group are compared to those of 19 concurrent patients (aged 26 ± 12 years) who received ATG‐pred‐MTX on days 8‐22 post‐transplant. On the first day of treatment, 20/20 OKT3 patients and 18/19 ATG patients were febrile, Within 24 h of the first dose of OKT3, 6/20 patients experienced dyspnoea or chest pain and 3/20 patients developed diarrhoea. No further adverse effects were seen after the second dose of OKT3 and no late adverse effects were attributed to this drug. Time to engraftment (x̄ 25 d) was not statistically significantly different in the two prophylactic groups. Acute GvHD was diagnosed in 14 of 20 patients who received OKT3‐pred‐MTX and in eight of 19 patients who received ATG‐pred‐MTX (P= 0.06). The incidence of hepatic or gastrointestinal GVHD (≥ grade 2) was similar in the two groups: 4/20 OKT3‐pred‐MTX, 6/19 ATG‐pred‐MTX. Characteristics of post‐transplant infections were also similar for the two prophylactic groups. Survival at 1 year post‐transplant was 65% for patients
Activation of neutrophil phagocytosis of complement coated and IgG coated sheep erythrocytes by platelet release products
Authors: Sakamoto H. , Ooshima A. 
Published: March 2008

SummaryPhagocytosis by human neutrophils of opsonized sheep erythrocytes with rabbit immunoglobulin M and human complement (IgM‐EACh) and those with rabbit immunoglobulin G (IgG‐EA) increased 2‐3 times of control neutrophils after treatment with released products from activated platelets (PRPr). The factors in PRPr which augmented IgM‐EAChphagocytosis were suggested to be adenosine diphosphate (ADP) and triphosphate (ATP) by experiments using apyrase treated PRPr and by direct exposures of neutrophils with these nucleotides. The presence of two other stimulators for phagocytosis of IgG‐EA were suggested. One was a macromolecular substance of molecular weight greater than 100 000 and the other was a substance of molecular weight less than 500. The latter may be a prostaglandin because the activity was easily removed by acid‐extraction with ethylacetate from the water phase, and because prior incubation of platelets with 10μg per ml indomethacin deprived PRPr of its low molecular weight activity. Exposure of neutrophils to thromboxane B2, prostaglandin F2α and prostaglandin E2at the concentration of 10−6–10−7mg/ml actually increased the phagocytosis of IgG‐EA. The activity in the macromolecular fraction was not affected by prior incubation of platelets with indomethacin.
A regulatory role of activated T‐lymphocytes on human megakaryocytopoiesis in vitro
Authors: Geissler D. , Konwalinka G. , Peschel C. , Grünewald K. , Odavic R. , Braunsteiner H. 
Published: March 2008

SummaryCellular interactions responsible for regulating in vitro megakaryocytopoiesis were studied using a microagar culture system which permits the simultaneous proliferation of human megakaryocytic progenitor cells (CFU‐M) and T‐lymphocytic colonies (CFU‐TL). The proliferation of these colony types depends mainly on two factors: phytohaemagglutinin (PHA) and erythropoietin (EP). The direct addition of increasing PHA concentrations to the liquid overlayer resulted in a parallel increase of CFU‐M and CFU‐TL. If the T‐lymphocytes were removed by an E‐rosetting technique a marked diminution of CFU‐M and CFU‐TL numbers was observed. However, monocyte depletion resulted in a marked augmentation of CFU‐M proliferation compared to unfractionated mononuclear cells. In order to confirm that the reduction of CFU‐M proliferation observed after T‐depletion was primarily mediated by the absence of T‐lymphocytes, we have co‐cultured different concentrations of previously removed autologous T‐lymphocytes with a constant number of T‐depleted bone marrow cells. A parallel increase of CFU‐TL and CFU‐M was found if 0.75‐7.5 × 104 T‐lymphocytes were added to the culture. In conclusion, our results indicate that activated T‐lymphocytes augment proliferation of human bone marrow CFU‐M and that monocytes are less important for the growth of megakaryocytic colonies.
Suppressor cell function after intravenous gammaglobulin treatment in adult chronic idiopathic thrombocytopenic purpura
Authors: Delfraissy J. F. , Tchernia G. , Laurian Y. , Wallon C. , Galanaud P. , Dormont J. 
Published: March 2008

SummaryIntravenous gammaglobulin (IVIgG) was given to seven adults with chronic idiopathic thrombocytopenic purpura (ITP). In parallel with platelet count, we studied Con A induced suppressor cell function for the autologous in vitro B cell response, T cell subsets and PAIgG levels, immediately before and 3–4 d after completion of treatment. Before treatment all patients had normal T cell subsets, decreased T suppressor cell function and increased levels of PAIgG. After IVIgG infusions, two patients were unresponsive and neither suppressor cell function nor PAIgG levels varied. In contrast, in the five responding patients we found an improvement in suppressor cell function and a decrease in PAIgG levels, while T cell subsets remained unmodified. Such results were reproducible in three patients after a second series of gammaglobulin infusions. Our results support the hypothesis that IVIgG infusion, apart from its effects on the reticuloendothelial system, may modulate the immune response by enhancing suppressor T cell function.
A myelodysplastic syndrome preceding acute lymphoblastic leukaemia
Authors: Berneman Z. N. , Bockstaele D. Van , Meyer P. De , der Planken M. Van , Vertessen F. , Bock R. De , Peetermans M. E. 
Published: March 2008

SummaryThe bone marrow of a patient with pancytopenia showed dyserythro‐poiesis, dysmegakaryocytopoiesis and 13% blasts. The patient was hypertransfused and the pancytopenia resolved completely for 1 month, while the blastic infiltration in the bone marrow remained. Three months later a frank acute lymphoblastic leukaemia developed.
The effect of indomethacin treatment on lymphocyte PHA reactivity in healthy controls and patients with lymphoma and sarcoidosis
Authors: Underhill G. , Valdimarsson H. 
Published: March 2008

SummaryLymphocytes from healthy volunteers who took indomethacin orally for 3 d showed an enhanced in vitro response to phytohaemagglutinin (PHA). When indomethacin was added in vitro, lymphocytes from healthy controls showed similar but more consistent increases of PHA responses than lymphocytes from patients with sarcoidosis or lymphoma. Moreover, the enhancing effect of indomethacin was by and large more pronounced in those patients who had relatively normal PHA lymphocyte responses in the absence of indomethacin, and the presence of indomethacin failed in most instances to increase subnormal responses to normal control levels.These findings are not consistent with the notion that increased prostaglandin synthesis is the principal cause of subnormal PHA reactivity of lymphocytes from patients with sarcoidosis or lymphoma.