bluuebunny/crossref_metadata_2025_split huggingface dataset:
The distribution of CD45R, CD29 and CD45RO (UCHL1) antigens in mature CD4 positive T‐cell leukaemias
Authors: Worner Inga , Matutes Estela , Beverley Peter C. L. , Catovsky Daniel 
Published: March 2008

SummaryWe have studied the expression of antigens characterizing functional T‐cell subsets in 32 CD4 + mature T‐cell leukaemias. In this analysis we used two monoclonal antibodies (McAb) of the CD4 5R group (2H4 and GRT22) which have been shown to identify the ‘naive/virgin’ T‐cell population that functions as ‘suppressor‐inducer’ cells in vitro, and two McAb, CD29 (4B4) and CD45RO (UCHL1), which characterize non‐identical ‘memory’ cells that proliferate in response to soluble recall antigens and provide help in antigen‐specific IgG synthesis. Four groups of CD4 + cases were identified according to this reactivity: (a) 15 CD45R +, CD29 +; (b) 13 CD45R ‐, CD29 +; (c) three CD45R ‐, CD29 ‐; and (d) one case only CD45R +, CD29 ‐. The high incidence of coexpression of CD45R and CD29 (47% of cases) is a new finding which contrasts with the mutual exclusion of these antigens on normal CD4 + T‐lymphocytes. There was no correlation between subset phenotypes and pathological disease entities. None of the six cases of adult T‐cell leukaemia/lymphoma (ATLL), which is known as a disorder of activated ‘suppressor‐inducer’ cells, had the ‘expected’ CD45R +, CD29 ‐ phenotype. Reactivity with UCHL1 showed a good correlation with CD29 in the CD45R ‐ CD29 + cases which included three with ATLL. These results may help in the further characterization of T‐cell malignancies according to functional subgroups and may clarify further the role of T‐differentiation antigens in health and disease.
Expansion by folinic acid of the peripheral blood progenitor pool after chemotherapy: its use in autografting in acute leukaemia
Authors: Laporte J. P. , Douay L. , Allieri A. , Lopez M. , Montbrun M. C. Dupuy , Mary J. Y. , Giarratana M. C. , Isnard F. , Najman A. , Gorin N. C. 
Published: March 2008

SummaryWe have tested folinic acid (FA) for ability to increase peripheral blood stem cells (PBSC) after chemotherapeutic aplasia in acute leukaemia. Five adult patients (four AML, one ALL) entered the study, each patient underwent two series of three leukapheresis, the first following induction chemotherapy and the second following the first course of consolidation. The first leukapheresis of each series was done when the white blood cell count reached 109/1 with subsequent leukapheresis every other day. Folinic acid (Lederle Laboratories, France) was administered at a dose of 50 mg (i.v.) per day, 15 days from initiation of chemotherapy and continuing through the third leukapheresis of the series (days 25–30). PBSC were collected on a Haemonetics V50 cell separator.In these five cases we observed an increased yield of both colony‐forming units, granulocyte macrophage (CFU‐GM) and burst forming units‐erythroid (BFU‐E) expressed per ml of cytapheresis product: CFU‐GM × 18, BFU‐E × 3 and if expressed per 104/kg of body weight: CFU‐GM × 30, BFU‐E×3 (CFU‐GM P<0·05, BFU‐E<0·01). Long‐term blood culture (LTSC) from FA stimulated leukapheresis, in an attempt to quantitate the most primitive stem cells, demonstrated that this expansion of the PBSC was sustained in time. We found by means of LTSC that FA did not stimulate CFU‐L from patients with AML (two cases tested).Finally two AML patients were grafted with FA‐PBSC after Cytotoxan and total body irradiation (TBI). Haematopoietic reconstitution was rapid complete and sustained in time in both patients.This indication for folinic acid should be further studied with or as an alternative to haematopoietic growth factors.
Alpha interferon therapy for haematological malignancies: correlation between in vivo induction of the 2′,5′ oligoadenylate system and clinical response
Authors: Mel W. C. P. de , Hoffbrand A. V. , Giles F. J. , Goldstone A. H. , Mehta A. B. , Ganeshaguru K. 
Published: March 2008

Summary2′,5′ oligoadenylate (2‐5A) synthetase mRNA and enzyme levels have been studied in peripheral blood mononuclear cells from 12 patients with chronic granulocytic leukaemia (CGL), 14 with essential thrombocythaemia (ET) and nine with chronic lymphocytic leukaemia (CLL), undergoing therapy with alpha interferon (αIFN). 2‐5A synthetase mRNA was assayed by hybridization using the dot–blot technique and the enzyme activity was measured biochemically. A statistically significant difference was observed (P<0·05) between the degree of in vivo induction of mRNA by IFNα in the total patients between the good and intermediate responders and the poor responders. There was a similar pattern in each of the CGL, ET and CLL groups although this only reached statistical significance in the CGL group. In vitro induction of either mRNA or of enzyme activity, however, did not show a difference between the responders and poor responders in any of the patient groups. Our findings are consistent with the concept that 2‐5A has an important role in the anti‐tumour activity of αIFN and suggest that measurement of in vivo induction of 2‐5A synthetase mRNA may be useful in predicting clinical response. In vitro studies, on the other hand, do not provide a reliable predictor of clinical response.
Hypercoagulability during l‐asparaginase treatment: the effect of antithrombin III supplementation in vivo
Authors: Gugliotta Luigi , D'Angelo Armando , Belmonte Monica Mattioli , Viganò‐D'Angelo Silvana , Colombo Giuseppina , Catani Lucia , Gianni Lorenzo , Lauria Francesco , Tura Sante 
Published: March 2008

SummaryTo evaluate the occurrence of hypercoagulability during treatment with l‐asparaginase (l‐ase), thrombin‐antithrombin complex (TAT) and d‐dimer levels in plasma were serially measured in 15 consecutive adult patients with acute lymphoblastic leukaemia or lymphoblastic lymphoma who had recently completed a chemotherapy cycle with cytosine arabinoside and methotrexate. The first eight patients (group A) received i.v. l‐ase alone (20000 U/m2 on alternate days over 10 d); the last seven patients (group B) received, in addition to l‐ase, bolus injection of antithrombin concentrate (2000 U) on alternate days for a total of six administrations, beginning with the second l‐ase infusion. Increased levels of TAT (P<0·05) and d‐dimer (P<0·01) were observed prior to l‐ase, possibly related to inflammation and cytolysis secondary to previous chemotherapy. In patients treated with l‐ase alone, further elevation of TAT (P<0·05) and persistence of increased d‐dimer were observed, associated with marked reduction of the anticoagulant activities of protein C, protein S and antithrombin III. At variance, in patients receiving antithrombin III supplementation there was no increase of TAT and a normalization of d‐dimer levels occurred during l‐ase treatment. In these patients, mean plasma antithrombin III activity was maintained at levels higher than 70% of normal throughout the treatment. The rate of decline of fibrinogen, factor IX, protein C and protein S was unaffected by antithrombin III supplementation, indicating that hypercoagulability has little if any relevance for the reduction of coagulation factors and inhibitors induced by l‐ase treatment. The usefulness of antithrombin III concentrates in preventing thromboembolic complications in patients submitted to l‐ase treatment remains to be determined.
Anaemia and marrow blood flow in the rat
Authors: Schoutens A. , Verhas M. , Dourov N. , Verschaeren A. , Mone M. , Heilporn A. 
Published: March 2008

SummaryAn increase in bone marrow blood flow has been previously described in anaemic rabbits and dogs. We examined the effect of haemorrhage and haemolysis in female Sprague‐Dawley rats, with the hypothesis that high blood flow was related to hyperplasia of bone marrow tissue and that the increase would affect bone as well. Blood flow was measured in tibia and femur by the microspheres trapping method. Chronic anaemia was accompanied at day 32 by a marked increase (factor of 1·7–1·9) in blood flow to bone marrow and to bone. On the other hand, no increase in blood flow was observed in chronic compensated anaemia, showing that anaemia per se and not stimulation of erythropoiesis was responsible for the increase. We then explored the effect on blood flow of two factors associated with anaemia. Erythropoietin 4 U/d for 4 d failed to induce any increase in bone and marrow blood flow. Systemic hypoxia (76 mmHg for 3 d) reduced the fraction of cardiac output conveyed to bone and marrow by 40–50%, but this decrease was more than compensated by an increase in cardiac output. We conclude that neither erythropoietin nor low tissue pO2 is the direct cause for the increase in bone and marrow blood flow observed in anaemia.
Unrestricted growth of Plasmodium falciparum in microcytic erythrocytes in iron deficiency and thalassaemia
Authors: Luzzi G. A. , Torii M. , Aikawa M. , Pasvol G. 
Published: March 2008

SummaryThe mechanism(s) underlying the apparent resistance to malaria in certain inherited red cell disorders and iron deficiency anaemia remain poorly understood. The possibility that microcytic erythrocytes might inhibit parasite development, by physical restriction or reduced supply of nutrients, has been considered for many years, and never formally investigated. We sought to determine whether in vitro growth studies of P. falciparum could provide evidence to suggest that small red cell size contributes to malaria resistance in those red cell disorders in which microcytosis is a characteristic feature.Invasion and development of P. falciparum in iron deficient red cells (mean values for mean cell volume [MCV] 66 fl, mean cell haemoglobin [MCH] 19 pg) and in the red cells of two gene deletion forms of α‐thalassaemia (mean MCV 71 fl, MCH 22 pg) were normal, assessed both morphologically, and by 3H‐hypoxanthine incorporation. Although parasite appearances were normal in all cell types, morphological abnormalities were noted in iron deficient and thalassaemic cells parasitized by mature stages of P. falciparum, notably cellular ballooning and extreme hypochromia of the red cell cytoplasm. Using electron microscopy, the red cell cytoplasm in parasitized thalassaemic cells showed reduced electron density and abnormal reticulation. Normal invasion rates were observed following schizogony in microcytic cells of both types.Our findings indicate that whilst minor morphological abnormalities may be detected in parasitized iron deficiency and thalassaemic erythrocytes, development of P. falciparum in these conditions is not limited by small erythrocyte size.
Haemoglobin α2β223Val → Ile produced in Escherichia coli facilitates Hb S polymerization
Authors: Pagnier J. , Baudin‐Chich V. , Lacaze N. , Bohn B. , Poyart C. 
Published: March 2008

SummaryThe doubly substituted variant Hb S‐Antilles (β6 Glu → Val, β3 Val → Ile) produces sickling in heterozygous carriers. The Csat value for pure deoxyHb S‐Antilles is nearly half that of deoxyHb S. Dilute solutions of pure Hb S‐Antilles have a lower oxygen affinity than those of Hb A or Hb S. The mutant Hb α2β223 Val → Ile was synthesized in E. coli. It exhibits a decreased oxygen affinity compared to Hb A and does not polymerize in 1·8 m phosphate buffer. Mixtures of equal amounts of Hb S +Hb β23 Val → Ile have a decreased Csat value compared to mixtures of Hb S + Hb A. The β23 Val in Hb S contributes to the axial contact joining molecules in each single filament. Substituting Ile for Val at this site increases the strength of this contact through hydrophobic interactions, allowing increased stability of the lateral contact between filaments in pair, which is the specific unit structure of polymers in deoxyHb S.
Expression of integrins in human bone marrow
Authors: Soligo Davide , Schiró Raffaella , Luksch Roberto , Manara Giancarlo , Quirici Nadia , Parravicini Carlo , Dellliers Giorgio Lambertenghi 
Published: March 2008

SummaryExpression of integrins, a superfamily of glycoprotein α/β heterodimers which integrate the cytoskeleton with the extracellular matrix and/or mediate cell‐cell adhesive interactions, was examined on normal and leukaemic bone marrow cells by immunohistochemistry and immunotransmission electron microscopy (immuno‐TEM). Among the β1/VLA molecules studied, VLA‐2 and 6 were expressed on megakaryocytes and platelets, while VLA‐4 was present on 40% of haemopoietic cells, including monocytes, erythroblasts and immature cells; this molecule was typically localized at sites of intercellular contact, as seen by immuno‐TEM, suggesting it may be involved in interactions among haemopoietic cells during differentiation. In human longterm bone marrow cultures (LTBMC), VLA‐1 and 3 were present respectively on 35% and 40% of the adherent cells which included flbroblasts and endothelial cells, as shown by double‐labelling experiments; VLA‐2 was expressed only on a subpopulation of flbroblasts. β2/LeuCAM molecules were absent from platelets, megakaryocytes and HLA‐DR+/myelo‐peroxidase− early myeloid precursors, and appeared progressively during maturation in both lymphoid and myeloid cells. Expression of β3/cytoadhesin molecules was restricted to megakaryocytes and platelets and, in the adherent layer of LTBMC, to endothelial cells. The regulated expression and specific localization of integrins in the bone marrow suggest that these molecules may have a role in normal haemopoiesis.
Prognostic factors in stage AO B‐cell chronic lymphocytic leukaemia
Authors: Oscier D. G. , Stevens J. , Hamblin T. J. , Pickering R. M. , Fitchett M. 
Published: March 2008

Summary85 patients presenting to a single centre with stage AO B‐cell chronic lymphocytic leukaemia (B‐CLL) have been studied. The duration of follow‐up has ranged from a minimum of 1 year to a maximum of 18 years with a mean of 6 years.14 patients have had progressive disease and 23 patients have died, of whom nine had CLL‐related deaths. We assessed the prognostic significance of the following parameters: age at presentation, sex, haemoglobin concentration, initial lymphocyte count, surface membrane phenotype. serum immunoglobulin levels at presentation and karyotype.None of these factors were predictive of survival, but there was a correlation between initial lymphocyte count, surface immunoglobulin MDλ phenotype, and complex karyotypic abnormalities and disease progression.Two patients with a complex karyotype have been followed for more than 5 years without evidence of progression.
Studies of natural anticoagulant proteins and anticardiolipin antibodies in patients with the lupus anticoagulant
Authors: Lo Samuel C. L. , Salem Hatem H. , Howard Margaret A. , Oldmeadow Michael J. , Firkin Barry G. 
Published: March 2008

SummaryComponents of the natural anticoagulant system (NAS) and anticardiolipin antibodies were examined in 21 patients with lupus anticoagulant (LA), 13 of whom had past histories of thrombotic episodes. No relationship could be shown between the antigenic levels of protein C and S (PC, PS) and a history of thrombosis. Inhibition of the anticoagulant activity of activated protein C (APC) was observed using plasma from 20/21 patients when phospholipid vesicles were used as the surface for the coagulation reaction. This effect was not affected by the addition of PS. When platelet membranes were employed only 2/21 patients demonstrated inhibition of APC. Under the latter condition, PS functional activity was inhibited in 7/21 patients, six of whom had a past history of thrombosis.Reduced antithrombin III or heparin cofactor II levels were observed in a total of 4/21 patients and may have contributed to the development of thrombosis in three of these patients. Antibodies specifically directed against these proteins were not detected suggesting the possibility of an associated constitutional deficiency. Anticardiolipin antibodies, though elevated in 17/21 patients, did not serve as a useful marker for an increased risk of thrombosis, and the level did not correlate with inhibition of the activity of APC or PS.We conclude that the mechanism of thrombosis in patients with LA is multi‐factorial. A subset of patients in whom LA specifically inhibits PS function may represent patients who are at significant risk from thrombosis.
Demonstration of the heterogeneity of epitopes of the platelet‐specific alloantigen, Baka
Authors: Take Hironori , Tomiyama Yoshiaki , Shibata Yoichi , Furubayashi Takayasu , Honda Shigenori , Mizutani Hajime , Nishiura Tetsuo , Tsubakio Tadahiro , Kurata Yoshiyuki , Yonezawa Takeshi , Tarui Seiichiro 
Published: March 2008

SummaryIt is well known that the platelet‐specific alloantigen, Baka is carried on glycoprotein (GP) IIb, but little is known about the biochemical characteristics of its epitopes. To clarify the characteristics of the epitopes, we examined the interaction of four anti‐Baka sera (Yam, Lin, Kl and MO) with their epitopes, either with or without modifications by sodium dodecyl sulphate (SDS) and/or neuraminidase. By immunoprecipitation, all four antisera bound to the intact GP IIb/IIIa complex from a Baka‐positive subject. In contrast, immunoblotting demonstrated that Yam, Lin and Kl bound to SDS‐denatured GP IIb, while MO did not. When blotted GP IIb was treated with neuraminidase, Yam and Lin did not bind to desialylated GP IIb, while Kl still did. When the purified GP IIb/IIIa complex or washed platelets were treated first with neuraminidase followed by immunoblotting, the molecular weight of GP IIb decreased from 145 kD to 138 kD; Yam did not bind to desialylated GP IIb, but Kl did. Furthermore, to eliminate the effect of SDS, we examined the interaction of Yam and Lin with neuraminidase‐treated platelets using flow cytometry. The results were the same as those obtained using immunoblotting. Our results thus demonstrate that the expression of the Baka epitopes is not uniform and that sialic acid contributes to the expression of some actual allogenic epitopes.
Abnormal tryptic peptide from the spectrin α‐chain resulting from α‐ or β‐chain mutations: two genetically distinct forms of the Sp αI/74 variant
Authors: Lecomte M. C. , Gautero H. , Garbarz M. , Boivin P. , Dhermy D. 
Published: March 2008

SummaryLimited tryptic digestion of native spectrin (Sp) has revealed several variants in hereditary pyropoikilocytosis (HPP) and in a subset of patients with hereditary elliptocytosis (HE). In most cases, tryptic peptide corresponding to the αI (N‐terminal) 80 kD domain is wholly or partially replaced by smaller fragments. These variants are provisionally designated according to the molecular weight of the most prominent new peptide. Partial amino acid sequences of the abnormal peptides and DNA analysis of the α‐spectrin gene have shown that most variants result from substitution or insertion of an amino acid in the αI‐domain. However, similar investigations did not detect any such abnormality in the spectrin αI‐domain of an HE black kindred with one of the spectrin variants called Sp αI/74. In this kindred, restriction fragment length polymorphism studies and transmission of the genetic polymorphism relative to the αII‐domain excluded the involvement of the α‐chain in the pathological process. To ascertain whether the abnormal αI 74 kD peptide might be caused by a β‐chain mutation, we reconstituted hybrid dimers combining normal and HE Sp‐chains. The tryptic peptide patterns of spectrin hybrid dimers containing HE α‐chain and control β‐chain showed a normal 80 kD tryptic product. In contrast, the hybrid dimer containing normal α‐chain and HE β‐chain gave rise to increased 74 kD peptide at the expense of the 80 kD, demonstrating that the mutation in this family resides in the β‐chain. The same method was used to show that in two other unrelated white kindreds, the elevated 74 kD peptide arised from a Sp α‐chain defect. Thus an alteration in tryptic susceptibility within the N‐terminal domain of the spectrin α‐chain can be directed by a mutation in the β‐chain. The hybridization technique affords a definitive means of distinguishing between α‐ and β‐chain mutants.
Increased serum levels of soluble IL‐2 receptor, CD30 and CD8 molecules, and gamma‐interferon in angioimmunoblastic lymphadenopathy: possible pathogenetic role of immunoactivation mechanisms
Authors: Pizzolo G. , Stein H. , Josimovic‐Alasevic O. , Vinante F. , Zanotti R. , Chilosi M. , Feller A. C. , Diamantstein T. 
Published: March 2008

Summary. Abnormal immunoreaction associated with increased cell activation phenomena might play a role in the pathogenetic events leading to the development of angioimmunoblastic lymphadenopathy (AILD). In the present study we investigated the serum levels of some soluble molecules related to cell activation in 24 patients with AILD at presentation. In particular, we measured by immunoenzymatic or immunoradiometric techniques the levels of the Tac peptide (sIL‐2R), soluble CD30 (sCD30) and CD8 (sCD8) antigens, and gamma‐IFN (gIFN). The results show that all the above molecules are increased as compared to normal controls, with a different pattern of increase for the different molecules. The sIL‐2R levels were very high in all cases with no overlap between AILD and control samples (mean 6315±3374 U/ml, controls 271±112 U/ml, P<0.001). Very high values of the sCD30 antigen (722±895 U/ml) were detected in all cases but five, as opposed to the lack of detectable levels in controls. A significant increase of sCD8 (978±646 U/ml, controls 334±95 U/ml, P<0.01) and gIFN (329±236 U/ml, controls 97±43 U/ml, P<0.01) was also observed with some overlap between AILD samples and controls.The above findings further support the view that a condition of abnormally enhanced cell activation is likely to play a central role in the pathogenetic events leading to the composite clinicopathological picture of AILD.
Inhibition of the enzyme purine nucleoside phosphorylase (PNP) reduces refractoriness to transfused platelets in a dog model
Authors: Slichter Sherrill J. , Deeg H. Joachim , Osborn William R. A. 
Published: March 2008

Summary. To better define the role of T‐cells in alloimmunization, we induced purine nucleoside phosphorylase (PNP) deficiency in a dog platelet transfusion model. Short‐term administration of eight different drug schedules using several combinations of the PNP inhibitor 8‐aminoguanosine and/or deoxyguanosine did not induce significant toxicity in four treated animals as demonstrated by blood chemistries, cell counts, and autologous platelet recovery and survival measurements. However, continuous long‐term daily administration of these agents produced significant renal and/or hepatic toxicity leading to death in five of six animals. Modification of the drug schedule to early short‐term administration of both deoxyguanosine and 8‐aminoguanosine, followed by long‐term intermittent doses of only 8‐aminoguanosine, was not only well tolerated by all the animals but also resulted in significant immunosuppression. Overall, six of nine evaluable dogs (67%) treated with some combination of PNP inhibitors did not become refractory to eight weekly transfusions of platelets from a single random donor dog, P<0.005, compared to untreated controls, only 3/21 (14%) not immunized.Furthermore, in four evaluable recipients, discontinuation of the 8‐aminoguanosine while continuing platelet transfusions from their original donors did not result in refractoriness. In addition, these four recipients were also unable to recognize platelets from two other random donors. This suggests that both specific and non‐specific tolerance to foreign platelet antigens had been induced by PNP‐inhibitor therapy. Other evidence for the efficacy of this immunosuppressive treatment was the almost normal post‐transfusion recovery and survival of donor platelets, both during and after treatment. This suggests failure to form even low levels of platelet alloantibodies in the immunosuppressed recipients. In contrast, B‐cell immunity to soluble antigens was intact as demonstrated by a normal antibody response to keyhole limpet haemocyanin (KLH) antigen.