bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new congenital defect of platelet secretion: impaired responsiveness of the platelets to cytoplasmic free calcium
Authors: Hardisty R. M. , Machin S. J. , Nokes T. J. C. , Rink T. J. , Smith Sharon W. 
Published: March 2008

Summary. A 16‐year‐old boy with a bleeding disorder since infancy has a long bleeding time, normal platelet count and morphology and normal plasma factor‐VIII activities. His platelets undergo normal shape change and primary aggregation in response to ADP but show defective 5‐hydroxytryptamine (5‐HT) secretion and aggregation in response to adrenaline, sodium arachidonate, U44069, PAF‐acether, A23187 and low concentrations of collagen. Thrombin and higher concentrations of collagen produce a normal response. Secretion of β‐thromboglobulin and platelet factor 4 parallels that of 5‐HT. Thromboxane B2 is produced normally in response to exogenous arachidonate and to stimulation by thrombin, collagen and A23187 in all concentrations tested. The patient's endoperoxides and thromboxane A2 aggregate aspirin‐treated platelets, though his platelets are themselves unresponsive. Cyclic AMP is present at normal concentration in the patient's unstimulated platelet‐rich plasma, and PGI2 inhibits platelet aggregation by ADP and thrombin in a normal dose‐related manner. Platelet ultrastructure, 5‐HT uptake and content of adenine nucleotides, platelet factor 4 and β‐thromboglobulin are all within normal limits.When the patient's platelets were loaded with the fluorescent dye quin 2, which serves as an indicator of cytoplasmic free calcium ions, their responses to thrombin, whether in the presence or virtual absence of extracellular Ca2+, were entirely normal in respect of free calcium ions, secretion, shape‐change and aggregation. In response to ionomycin, however, a normal increase in free calcium ions was accompanied by normal shape‐change but virtually no aggregation or 5‐HT secretion. The platelet calmodulin content was normal. These findings show that the defect in this patient's platelets is of utilization of cytoplasmic Caz+ for secretion and aggregation, rather than of Ca2+ uptake or mobilization of Ca2+ from intracellular storage sites. It is suggested that the most likely site of the defect is the phosphorylation of one of the proteins concerned in the secretory mechanism.
Abnormal in vitro function of a variant human transferrin
Authors: Young S. P. , Bomford A. , Madden A. D. , Garratt R. C. , Williams R. , Evans R. W. 
Published: March 2008

Summary. Normal and variant transferrins have been isolated from the plasma of an individual heterozygous for the abnormal protein. The normal and variant proteins were separated, saturated with 59Fe, labelled with 125I and then compared in their interaction with PHA‐stimulated human lymphocytes in vitro.At 4°C the variant protein bound to the transferrin receptors on these cells with an association constant (6·25±2·53×107 I mol‐1, mean ± SD; n= 4) which was an order of magnitude lower than that of the normal diferric transferrin (6·31 ± 1·82 × 108 1 mol‐1, mean±SD; n= 4). This low association constant was reflected in a much reduced rate of iron donation to the cells at 37°C (22·2±8·3 pg/106 cells/h compared with 48·1±15·6 pg/106 cells/h).As the variant transferrin has both abnormal iron‐binding properties (Evans et al, 1982) and an abnormal interaction with the transferrin receptor, it would appear that these two functions may be closely interdependent.
The effects of low‐dose vincristine on megakaryocyte colony‐forming cells and megakaryocyte ploidy
Authors: Harris R. A. , Penington D. G. 
Published: March 2008

Summary. The administration of low‐dose vincristine (VCR) (0.1 mg/kg) to mice resulted in thrombocytosis without prior thrombocytopenia. No significant changes in marrow megakaryocyte numbers were found. However, after a minor early decrease, mean megakaryocyte ploidy increased, with a peak at 3 d. The number of megakaryocyte colony‐forming cells (MEG‐CFC) in bone marrow did not change significantly. In contrast with the effects on marrow, the concentration of megakaryocytes and the content of MEG‐CFC in the spleen were significantly reduced for 1–2 d after VCR. This reduction was followed by a compensatory rise in the splenic content of MEG‐CFC (peak 3‐fold increase at 3 d), and 1–2 d later, an increase in splenic megakaryocytes which was concurrent with the increased platelet count. Culture of marrow and spleen cells in the presence of VCR resulted in inhibition of megakaryocyte colony formation at concentrations > 5 ng/ml and parallel reduction of the number of megakaryocytes per colony and the mean ploidy of colony megakaryocytes.The results suggest that the thrombocytosis induced by low‐dose VCR does not result simply from an effect on platelets, but reflects compensatory changes in megakaryopoiesis secondary to toxic suppression of megakaryocytes and their progenitors.
Megakaryoblast precursors in rodent bone marrow: specificity of acetylcholinesterase staining
Authors: Lepore D. A. , Harris R. A. , Penington D. G. 
Published: March 2008

Summary. Small cells staining diffusely for acetylcholinesterase, corresponding closely to the description of Jackson (19 73,19 74), have been quantitated in the bone marrow of mouse and rat. These cells fulfil the requirements of megakaryoblast precursors, showing elevation in numbers prior to megakaryocytes in response to thrombocytopenia, and carrying platelet‐specific antigens demonstrated by immunofluorescence. Some show a clearly defined nucleus whilst in others the nucleus is obscured; the femoral content of both types follows the same time course after acute thrombocytopenia and the latter can be distinguished from megakaryocyte cytoplasmic fragments.Other small cells present in rodent bone marrow contain granular positivity after acetylcholinesterase staining but also granules staining with Luxol‐Fast‐Blue, suggesting that these cells are eosinophils. These cells are greatly increased in number with stimulation of eosinophilia by parasite infestation but show no response to acute thrombocytopenia. Peripheral blood eosinophils exhibit both acetylcholinesterase and Luxol‐Fast‐Blue staining.A number of properties ascribed to granular‐staining small acetylcholinesterase‐positive cells previously presumed to be megakaryoblast precursors will need to be reassessed.
Myelokathexis: a rare form of chronic benign granulocytopenia
Authors: Bassan Renato , Viero Piera , Minetti Bruno , Comotti Benedetto , Barbui Tiziano 
Published: March 2008

SUMMARYA case of childhood chronic neutropenia due to myelokathexis is reported. This extremely rare condition (the fourth case in the literature) has been diagnosed from the characteristic bone marrow abnormalities in the neutrophils.Myelokathexis (kathexis‐retention) is a form of childhood granulocytopenia characterized by marked degenerative changes in mature neutrophils and considerable hyperplasia of the bone marrow myeloid cell series. The disease is rare and, since the first description by Zuelzer in 1964, only two additional cases have been reported (Krill et ah 1964; O'Regan et al 1977). We wish to describe the first case observed in Italy which is also the first reported outside U.S.A.
Preferential phagocytosis of in vivo aged murine red blood cells by a macrophage‐like cell line
Authors: Walker William S. , Singer Judith A. , Morrison Martin , Jackson Carl W. 
Published: March 2008

SummaryThe ability of an established line of mouse macrophages (IC‐21) to ingest red blood cells (RBC) aged in vivo was assessed. RBC populations of increasing age were prepared in mice by serial hypertransfusion, a procedure that inhibits erythropoiesis. Mouse RBC with a mean age of about 58 d (normal RBC life span, 60 d) had a circulating half‐life of less than 1 d when transfused into normal mice. IC‐21 macrophages ingested the in vivo aged RBC in preference to RBC from normal mice (mean RBC age, 30 d). RBC isolated from mice 10 d after being released from one red blood cell lifespan (60 d) of inhibited erythropoiesis (mean RBC age 5 d) were ingested significantly less than RBC from normal mice. The IC‐21 macrophage line used with in vivo aged RBC affords a highly defined model system for identifying the mechanism(s) of macrophage‐mediated homeostasis.
Plasmodium falciparum takes up iron from transferrin
Authors: Pollack Simeon , Fleming John 
Published: March 2008

SUMMARY Plasmodium falciparum, cultured in vitro, is inhibited by desferrioxamine, a specific iron chelating agent, despite the abundant haem iron which surrounds the parasite. In this report we show that the intraerythrocytic parasite obtains iron from transferrin. The parasite may therefore be freed of a requirement to catabolize haem to obtain iron thus minimizing haem toxicity.
The effects of therapeutic dialysis and renal transplantation on uraemic serum inhibitors of erythropoiesis in vitro
Authors: Summerfield Geoffrey P. , Bellingham Alastair J. 
Published: March 2008

SummaryThe methyl cellulose culture system using human bone marrow and erythropoietin (Ep) at different concentrations was used to examine the effects of uraemic sera on erythropoiesis in vitro.Sera from undialysed patients with advanced uraemia (plasma creatinine ± 900 μmol/l) when added to cultures at 10% with Ep at 2‐0 u/ml were consistently inhibitory to the growth of erythroid burst‐forming units (BFU‐E). No inhibition of erythroid colony‐forming units (CFU‐E) was observed at this Ep concentration but inhibition was consistently demonstrated with Ep at 0‐2 u/ml. Sera from undialysed patients with less severe uraemia (plasma creatinine < 900 μmiol/1) were not inhibitory to BFU‐E or CFU‐E at Ep 2‐0 u/ml.Sera from patients with stable, functioning renal transplants were stimulatory to erythropoiesis in vitro with Ep at 2 ‐0 u/ml. This finding is consistent with the normal or increased haematocrits often found following renal transplantation. Sera from patients on maintenance haemodialysis and continuous ambulatory peritoneal dialysis (CAPD) were not significantly different from normal in their effect on BFU‐E growth in vitro and were slightly but significantly stimulatory to the growth of CFU‐E. This suggests that these two forms of dialysis are equally effective in reducing the activity of uraemic inhibitors in serum and that inhibition of the marrow response to Ep and/or burst‐promoting activity (BPA) is unlikely to be a major factor in the continued anaemia of dialysis patients.
Characterization of an Indian (δβ)° thalassaemia
Authors: Wainscoat J. S. , Old J. M. , Wood W. G. , Trent R. J. , Weatherall D. J. 
Published: March 2008

SummaryThe molecular basis of δβ thalassaemia in an Indian family is shown here to be due to a previously undescribed deletion within the β globin gene complex. Starting 3 kilobases from the 3’ end of the Aγ gene, the deletion removes the δ and β globin genes and continues to an unknown extent in the 3’ direction. Heterozygotes for this deletion have about 25% Hb F with a Gγ: Aγ ratio of 70:30 while interaction with β+ thalassaemia results in the clinical picture of thalassaemia intermedia.
Prognostic significance of chromosome abnormalities in chronic lymphocytic leukaemia
Authors: Pittman Sally , Catovsky D. 
Published: March 2008

SummaryLymphocytes from 33 out of 63 patients with B‐cell chronic lymphocytic leukaemia (B‐CLL) were successfully stimulated for cytogenetic analysis by means of two B‐cell mitogens: pokeweed mitogen and lipopolysaccharide‐B, used after pretreatment of the cells with neuraminidase and galactose oxidase. All patients had abnormal clones in 30‐100% of the cells analysed. Chromosomes more frequently involved were Nos. 1,3, 6,11,12,13 and 14. The most common abnormality was a marker 14q+ (breakpoint 14q32) seen in 17 cases; trisomy 12 was observed in seven cases. A clinical scoring system was used to investigate the correlation of chromosome abnormalities with prognosis. The group with 14q+ was often associated with features of progressive disease, namely; prolymphocytoid or Richter transformation, refractoriness to therapy, high WBC and advanced staging. A significant difference in survival was observed between patients with 14q+ and the rest: median survival from diagnosis being 45 months and over 64 months, respectively (P<0‐05); when survival was calculated from the time of chromosome analysis the values were 8 months and more than 41 months, respectively (P < 0 01). It is suggested that 14q + is acquired during the evolution of CLL and that this development may be a key event in the clinical progression of B‐CLL. Other abnormalities, including trisomy 12, were not found to be associated with a worse prognosis.
Chemotherapy and autografting for chronic granulocytic leukaemia in transformation: probable prolongation of survival for some patients
Authors: Haines M. E. , Goldman J. M. , Worsley A. M. , McCarthy D. M. , Wyatt S. E. , Dowding C , Kearney L. , Th'ng K. H. , Wareham N. J. , Pollock A. , Galvin M. C. , Samson D. , Geary C G. , Catovsky D. , Galton D. A. G. 
Published: March 2008

SummaryBetween June 1977 and July 1983 51 patients with Ph1‐positive chronic granulocytic leukaemia (CGL) in transformation were treated either by chemotherapy or by chemoradiotherapy followed by autografting with haemopoietic stem cells collected from their peripheral blood at the time of diagnosis. Forty‐eight patients were restored to a second chronic phase. The median duration of survival after autografting was 26 weeks (range 2‐152 weeks). Twenty‐one patients with relatively long durations of second chronic phase were treated again by autografting as consolidation or when transformation recurred; this selected group of patients survived longer than the 30 patients treated by autografting only once (medians 52 v. 13 weeks respectively, P<0‐01). There was no significant influence of the patients’ age, splenectomy status, type of transformation, treatment pre‐autograft or number of nucleated cells autografted on the duration of survival. Three patients treated in myeloid blastic transformation were restored to partially Phnegative haemopoiesis. We conclude that this approach to the management of CGL in transformation can offer benefit for a minority of patients and that further chemotherapy and autografting for patients still in second chronic phase may be valuable.
Evaluation of serum deoxythymidine kinase as a marker in multiple myeloma
Authors: Simonsson B. , Källander C. F. R. , Brenning G. , Killander A. , Åhre A. , Gronowitz J. S. 
Published: March 2008

Summary. A recently developed deoxythymidine kinase assay utilizing 125I‐iododeoxyuridine as substrate was used in an investigation of sera from 122 untreated patients with multiple myeloma. Most patients had slightly elevated or normal serum deoxythymidine kinase activity (S‐TK), although in some patients values increased by more than forty‐fold were found. S‐TK correlated with the haemoglobin level but did not correlate with sex, age, erythrocyte sedimentation rate, nor with the serum concentrations of creatinine, β2‐microglobulin, Ca or M‐component. The distribution of S‐TK values in IgG, IgA and pure Bence‐Jones myeloma did not differ significantly.Patients with IgG and IgA myeloma excreting light‐chain immunoglobulin in the urine had significantly higher S‐TK than non‐excreters. There was a significant correlation between S‐TK values and tumour cell mass as determined by clinical staging. A high pretreatment S‐TK (> 5·1 units) also distinguished a group of patients with a significantly shorter survival time. Patients with no response to initial therapy had significantly higher S‐TK values than those who did respond. In longitudinal studies of 11 patients, S‐TK was found to increase when the disease became more aggressive.The possibility of diagnosing disease progression at an early stage by an elevation of S‐TK is discussed.
Endogenous origin of microbiologically‐inactive cobalamins (cobalamin analogues) in the human fetus
Authors: Muir M. , Landon M. 
Published: March 2008

Summary. The cobalamin content of placenta, maternal and fetal sera was assayed by methods which measure microbiologically‐active and microbiologically‐inactive cobalamins. Only microbiologically‐active cobalamins were present in the placenta but both types were present in both maternal and fetal circulations.We conclude that only microbiologically‐active cobalamins cross the placenta and that the microbiologically inactive cobalamins in the fetus must arise by metabolism in situ.
Degradation of factor VIII coagulant antigen by proteolytic enzymes
Authors: Rick Margaret E. , Popovsky Mark A. , Krizek Dennis M. 
Published: March 2008

Summary.The factors responsible for the lability of factor VIII coagulant activity (VIII:C) and factor VIII coagulant antigen (VIII:CAg) are poorly understood. In this study the VIII:C and VIII:CAg are studied after incubation with plasmin, trypsin or α‐chymotrypsin. Both isolated human VIII:CAg and VIII:CAg associated with factor VIII‐related antigen (VIII R:Ag) are evaluated. The antigenic sites of the VIII:CAg are somewhat more stable to the action of these enzymes than the functional activity, although both follow a generally parallel degradation. A biphasic decay curve is seen in the initial time points. No stabilization of the functional or antigenic reactivity is observed in the presence of the VIII R:Ag.Lower concentrations of each enzyme cause an initial rise in the factor VIII:C in the presence of VIII R:Ag, but not in the isolated VIII:CAg. Higher concentrations of α‐chymotrypsin cause activation of VIII:C and a slight decrease in the VIII:CAg values in both preparations. These enzymes may play a modulating role in the coagulation cascade through the activation and degradation of VIII:C and VIII:CAg.
Platelet associated immunoglobulins (PAIgG and PAIgM) in autoimmune thrombocytopenia
Authors: Hegde U. M. , Ball S. , Zuiable A. , Roter B. L. T. 
Published: March 2008

SummaryAn enzyme linked assay system was used to quantitate platelet associated IgM (PAIgM) in addition to platelet associated IgG (PAIgG) in normal subjects and in 145 patients with autoimmune thrombocytopenia (AITP). The mean PAIgM level in normals was 1.17 ng/106 platelets with a range of 0.01–2.45 ng (mean ± 2 SD). The corresponding PAIgG values as follows: mean 6.0 ng, range 2.0–10 ng/106 platelets. Elevated PAIgG was seen in 67.6% and abnormally raised PAIgM in 79.3% of patients. Both values were raised together in 57.2% and either elevated PAIgG or PAIgM in 89.7%. All patients with PAIgG values greater than 4 times upper limit of normality were found to have abnormal PAIgM. The relevance of elevated PAIgM, the possible interaction between PAIgG and PAIgM and the implication of our results in patients with autoimmune thrombocytopenia are discussed.
Assay of factor VII activity by two techniques: evidence for increased conversion of VII to αVIIain hyperlipidaemia, with possible implications for ischaemic heart disease
Authors: Miller G. J. , Walter S. J. , Stirling Y. , Thompson S. G. , Esnouf M. P. , Meade T. W. 
Published: March 2008

SummaryFactor VII was assayed in healthy adults and pregnant women by a coagulation method (VIIc) and a procedure (VIIt) based upon activation of factor X. Although VIIcand VIItwere highly correlated (r0.8) they apparently measured different aspects of VII activity. This difference was related to plasma lipid concentrations. Plasma VIIcshowed independent positive associationsin vivowith VIIt, cholesterol and triglyceride concentrations, but was unaffected byin vitroadjustment of plasma lipoprotein concentrations. The difference between assays might be due to differing reactivities of VII. The VIIcassay measures VII in itsin vivoproportions as the single‐chain protein and fully active double‐chain form (αVIIa). In VIIt, all VII is converted to αVIIabefore measurement. Thus an increase in VIIcbut not VIItwith increasing lipid concentrations reflects an increased proportion of VII as αVIIa, possibly secondary to activation of the contact system. This effect may explain at least part of the increased VIIcand normal VIItin pregnancy, and the increased VIIcof hyperlipidaemias in general. The relative values of VIIcand VIItare proposed as a measure of flux within the coagulation system, and as a measure of coagulability in hyperlipidaemia and other states.
Five haplotypes in Black β‐thalassaemia heterozygotes: three are associated with high and two with low Gγ values in fetal haemoglobin
Authors: Harano T. , Reese A. L. , Ryan R. , Abraham B. L. , Huisman T. H. J. 
Published: March 2008

SummaryGenotypes at seven different polymorphic restriction sites (5’to the ° gene, at the Gγ, at the Aγ, at the Ψβ, 3’to the Ψβ, at the β, and 3’to the β genes) were analysed by restriction endonuclease mapping of the DNA from 66 Black β‐thalassaemia heterozygotes from Georgia and several of their normal relatives. Five different haplotypes were observed. Three of these were associated with high Gγ values in the small amount of Hb F (0.8‐8.3%) present in the blood of these patients and two with low Gγ values. One haplotype [‐ + ‐ ++++] that occurred on two of every three β thalassaemia chromosomes was associated with high Gγ levels, and is the same as that found in some Black SS patients also having high Gγ values (Gilman & Huisman, 1984). Two others [‐ ++ ‐ + ‐ +] and [−+−−+++] were also associated with high Gγ, while two [−−−−+++] and [+−−−−++] were associated with low Gγ. Variation in haematological data, mainly MCV and MCH values, was found to be caused in part by the type of β‐thalassaemia (defined by its haplotype) and by the presence of an additional α‐thalassaemia‐2 heterozygosity or homozygosity.
Fluctuating deformability of oxygenated sickle erythrocytes in the asymptomatic state and in painful crisis
Authors: Lucas G. S. , Caldwell N. M. , Stuart J. 
Published: March 2008

SummaryA new gravity filtration technique for the study of sickle cell deformability has shown a significant loss of filterability of oxygenated erythrocytes on day 2 of painful crisis in eight patients with homozygous sickle cell anaemia; there was no increase in irreversibly sickled cell (ISC) count. Serial study (mean of 5.2 occasions) in six out‐patients when asymptomatic also showed considerable fluctuation in sickle cell filterability with time; this was again independent of ISC count. Erythrocyte filtration methods demonstrate fluctuations in the rheology of sickle cells that are not detected by ISC counts and which are probably secondary to clinically occult, as well as overt, vaso‐occlusive events in the microcirculation.
Differential effect of isolated placental isoferritins on in vitro T‐lymphocyte function
Authors: Matzner Y. , Konijn A. M. , Shlomai Z. , Ben‐Bassat H. 
Published: March 2008

Summary The effect of isoferritins isolated from human term placenta on certain T‐lymphocyte parameters was studied in vitro using normal human lymphocytes. These isoferritins differed in ion exchange affinity, isoelectric point, and subunit composition. Only the acidic isoferritins caused a marked suppression of phytohaem‐agglutinin (PHA) blastogenesis and the most acidic isoferritin (‘Acid I’) was suppressive at a concentration as low as 0.25 μg/ml. All four isoferritins suppressed concanavalin A (Con A) blastogenesis in a similar concentration dependent manner, with maximum effect at an isoferritin concentration of 1 μg/ml.Both basic and acidic isoferritins reduced the Con‐A‐capping phenomenon in normal lymphocytes at concentrations higher than 0.5 μg/ml, but at 0.25 μg/ml only the acidic isoferritin was effective. The above findings support our previous report concerning the suppressive effect of splenic ferritin on T‐lymphocyte function in vitro and indicate that acidic isoferritins, which often predominate in malignancy, demonstrate a higher degree of immunosuppressive activity. Thus, acidic isoferritins may play a role in the development of abnormal lymphocyte function encountered in certain proliferative disorders.