bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin 2 production in bone marrow of normal individuals and patients associated with B‐cell chronic lymphocytic leukaemia
Authors: Rossi Jean‐François , Klein Bernard , Commes Therese , Jourdan Michel , Janbon Charles 
Published: March 2008

SummaryT‐cells from patients with B‐cell chronic lymphocytic leukaemia (B‐CLL) have abnormal T4/T8 ratios and functions. Previously, we demonstrated that peripheral blood (PB) mononuclear cells from B‐CLL patients secrete significant amounts of interleukin 2 (IL2) with an apparent dysregulation of accessory cells controlling this production. In this study, IL2 production was investigated in PB and in bone marrow (BM) from patients with previously untreated B‐CLL, mostly in early stages of the disease, and compared to normal donors. A significant secretion was observed in both PB and BM from B‐CLL patients after stimulation by phyto‐haemagglutinin (PHA), with lower amounts in patients with nodular involvement of BM, as compared to interstitial or diffuse involvements. To explore the role of accessory cells in controlling IL2 production, we added phorbol ester or indomethacin to the culture system or irradiated the cells before culture. Phorbol ester significantly increased the IL2 secretion in both the PB and the BM of B‐CLL patients. The irradiation or the addition of indomethacin did not enhance the IL2 production in PB from B‐CLL patients. However, IL2 secretion increased in the BM cells from B‐CLL patients after addition of indomethacin or prior irradiation, in a similar way to that observed in PB and BM of normal controls, suggesting an apparent normal control of the IL2 production in BM from B‐CLL patients. In normal controls, we demonstrated that IL2 secretion per T‐cell from BM was 5·4‐fold greater than that from normal PB, suggesting a very efficient role of accessory cells controlling IL2 production in normal BM.
Platelet‐associated immunoglobulins G, A and M are secreted during platelet activation: normal levels but defective secretion in grey platelet syndrome
Authors: Pfueller Sharron L. , David Rosemary 
Published: March 2008

SummaryPlatelet‐associated (PA) IgG is known to be released from normal human platelets when they are stimulated by aggregating agents. We have studied whether PA‐IgA and PA‐IgM are also secreted during platelet activation or during blood collection and processing and whether their levels are related to those in serum. Processing of platelets from normal donors in the presence of secretion inhibitors prostaglandin E1 (PGE1) and theophylline increased levels of both surface and total PA‐immunoglobulins (Ig) in intact and lysed platelets respectively, with increases being significant for surface PA‐IgA and PA‐IgM and total PA‐IgM. About 50% of total PA‐IgM, 40% PA‐IgA and 20% PA‐IgG was detectable on intact platelets. All three PA‐Ig and PA‐albumin were secreted in response to thrombin and this release was inhibited by PGE1. The platelet: serum ratio of each Ig and albumin were similar. In grey platelets deficient in α‐granules, PA‐Ig and PA‐albumin levels were raised per platelet but when increased platelet size was taken into account PA‐Ig were normal and PA‐albumin just below normal. Although thrombin caused release of most of the small amounts of β‐thromboglobulin present, PA‐Ig and PA‐albumin were not released. This suggests that PA‐Ig and albumin from plasma may enter a pool of secretory proteins in normal platelets, but in grey platelets they remain in some other site.
Inhibition of CFU‐GM by prostaglandins in a case of chronic T‐cell lymphocytosis and neutropenia
Authors: Smith J. G. , Smith M. A. , James I. , Blundell E. , Maddison P. J. 
Published: March 2008

SummaryA 45‐year‐old Caucasian female with seropositive rheumatoid arthritis was found coincidentally to have a circulating lymphocytosis (6.4 × 109/1) and neutropenia (0.1 × 109/1). Initial presentation was with mouth ulceration and recurrent infections. A spleen scan showed no evidence of splenomegaly and serum titres against EBV, CMV and toxoplasmosis were negative. No anti‐neutrophil antibodies were found. Marrow aspiration demonstrated a lymphocytosis of 60% with reduced numbers of granular precursors. Lymphocytes in both blood and bone marrow were CD3, CD8, CD16 and HLA‐DR positive. Lymphocyte conditioned medium (LCM) generated from the patient's blood lymphocytes (without phytohaemagglutinin) was found to inhibit allogeneic colony‐forming unit, granulocyte‐macrophage (CFU‐GM) stem cells in semi‐solid culture compared with control LCM. This inhibitory activity was abrogated by the cytolytic removal of CD8 cells prior to LCM production and was significantly reduced by co‐culture with indomethacin. Culture of the patient's marrow at autostimulatory light density marrow cell concentrations showed poor spontaneous CFU‐GM colony formation until marrow CD8 lymphocytes were removed cytolytically. Prednisolone was used therapeutically (40 mg/d) and resulted in the patient's neutrophil count rising from 0.06 × 109/1 to 1.1 × 109/1 and a fall in the total lymphocyte count to 1.9 × 109/1. Re‐evaluation of the patient's LCM post steroid therapy showed loss of the previous inhibitory effect. The patient's neutrophil count is maintained on oral azathioprine and indomethacin.
Serum levels of soluble interleukin‐2 receptor in hairy cell leukaemia: a reliable marker of neoplastic bulk
Authors: Ambrosetti A. , Semenzato G. , Prior M. , Chilosi M. , Vinante F. , Vincenzi C. , Zanotti R. , Trentin L. , Portuese A. , Menestrina F. , Perona G. , Agostini C. , Todeschini G. , Pizzolo G. 
Published: March 2008

SummaryIn hairy cell leukaemia (HCL), the strong membrane expression of the Tac antigen, corresponding to the p55 chain of the interleukin‐2 receptor (IL‐2R), is associated with the presence in the serum of high levels of a soluble form of the same molecule (sIL‐2R). Previous observations that therapy‐induced clinical and haematologic improvement in HCL is accompanied by a progressive decrease of sIL‐2R suggest a possible correlation between sIL‐2R levels and tumour burden. To verify this hypothesis, we monitored the variation of sIL‐2R values in 13 non‐splenectomized HCL patients admitted for treatment with recombinant interferon alpha‐2. The data were correlated with the estimated weight of bone marrow (BM) and spleen infiltrations, which in these patients almost entirely account for the tumour mass. The regression analysis test showed a direct correlation between sIL‐2R values and both BM neoplastic involvement (r= 0.63) and spleen tumour mass (r= 0.76). In addition, the correlation was further improved (r= 0.86) when sIL‐2R values were correlated with the total neoplastic mass, as calculated by the sum of spleen and BM neoplastic tissue weight. These data indicate that the detection of sIL‐2R in HCL is a reliable non‐invasive marker of tumour burden, which can be regarded as an additional useful tool for monitoring treatment response.
Study of three patients with monoclonal gammopathies and ‘lupus‐like’ anticoagulants
Authors: Bellotti V. , Gamba G. , Merlini G. , Montani N. , Bucciarelli E. , Stoppini M. , Ascari E. 
Published: March 2008

SummaryIn three patients with monoclonal gammopathies: a case of multiple myeloma, a case of monoclonal gammopathy of uncertain significance (MGUS) and a case of monoclonal gammopathy associated with lymphocytic lymphoma, we found the presence of a circulating lupus‐like anticoagulant. Coagulative studies showed that the paraproteins: an IgG3k, an IgG1k and an IgMλ, were responsible for the anticoagulant activity by interacting with the thromboplastin phospholipids. Using isoelectrofocusing we demonstrated that the three monoclonal immunoglobulins had a strong basic charge which may have contributed to determining their interaction with the acidic thromboplastin phospholipids. The binding of various phospholipids to the monoclonal proteins was assessed by the fluorescence quenching method which showed heterogeneous specificity. In order to establish whether the electrical charge is also relevant in cases with polyclonal lupus anticoagulant, the polyclonal immunoglobulins were fractionated according to their charge. The strongest inhibitor activity was found in the most basic immunoglobulins. Monoclonal lupus‐like anticoagulants represent useful tools for investigating the heterogeneous world of polyclonal lupus‐like anticoagulants.
Studies on the sensitivity to complement‐mediated lysis of erythrocytes (Inab phenotype) with a deficiency of DAF (decay accelerating factor)
Authors: Merry Anthony H. , Rawlinson Violet I. , Uchikawa Makoto , Daha Mohamed R. , Sim Robert B. 
Published: March 2008

SummaryNo episodes of clinically significant in vivo haemolysis have been reported in individuals with a novel form of decay accelerating factor (DAF) deficiency (Inab phenotype), nor do functional in vitro assays for complement‐mediated haemolysis show the extreme sensitivity to lysis characteristic of paroxysmal nocturnal haemoglobinuria (PNH) erythrocytes. DAF appears to be totally deficient in the Inab erythrocytes as judged by immunochemical and functional assays. Unlike PNH, the only other described DAF deficiency (where several other phosphatidylinositol (PI)‐linked membrane proteins are also absent), the only protein lacking from Inab erythrocytes appears to be DAF. The Inab phenotype seems to be an inherited specific defect in DAF whereas PNH is an acquired defect in the mechanism of insertion of PI‐linked proteins into cell membranes. These findings support the view that susceptibility of PNH erythrocytes to in vivo and in vitro complement‐mediated haemolysis is not due simply to DAF deficiency but to either the combined lack of several membrane proteins or to deficiency of other regulatory proteins such as the membrane attack complex inhibitor/homologous restriction factor (MIP/HRF). The findings also raise questions as to the role of erythrocyte DAF.
Mechanism of action of α interferon in chronic granulocytic leukaemia: evidence for preferential inhibition of late progenitors
Authors: Galvani D. W. , Cawley J. C. 
Published: March 2008

SummaryThe effect of α interferon (α IFN) on colony forming unit, granulocyte‐macrophage (CFU‐GM) formation by normal bone marrow (BM) as compared with chronic granulocytic leukaemia (CGL) BM and peripheral blood (PB) was tested in semi‐solid assay systems employing either 5637CM or recombinant granulocyte‐macrophage colony stimulating factor (GM‐CSF) to support growth. αIFN (> 125 U/ml) caused consistent inhibition (P=0.02) of day‐7(late progenitor) colonies, but had little or no effect on either day‐7 clusters or day‐14 colonies/clusters. This selective effect on day‐7 colonies was quantitatively similar for both normal and CGL (P < 0.5). Similar results were obtained whether or not the mononuclear preparations were depleted of potential accessory cells, suggesting that the αIFN‐suppression is directly mediated. Morphological examination of colonies and clusters showed that IFN had no effect on cell maturation and that colony inhibition is not, therefore, a consequence of blocked maturation. Since the late‐progenitor compartment is preferentially expanded in CGL, we suggest that our demonstration that αIFN selectively inhibits this compartment is relevant to the clinical effects of the cytokine in the disease.
No preferential use of the VH(V) family in human multiple myeloma
Authors: Clofent G. , Brockly F. , Commes T. , Lefranc M. P. , Bataille R. , Klein B. 
Published: March 2008

SummaryA recently described immunoglobulin VH family (the VH(V) family) close to the DH and JH genes is preferentially rearranged in immature B‐cell tumours. The question of the emergence of multiple myeloma (MM) from a tumorous pre‐B cell is not yet resolved. To draw a comparison with chronic lymphocytic leukaemia (CLL), we studied the VH(V) rearrangements in 28 MM patients. A rearranged Hind III‐Bam HI fragment of 9.5 kb was detected in only one patient instead of the rearranged fragment of 8.5 kb described in CLL. Rearrangements of a member of the VH(V) family in a 9.5 kb fragment were also observed in two out of 20 lymphoblastoid cell lines obtained from peripheral blood of MM patients. We report here that the VH(V) family is not preferentially involved in this pathology and that the size of the only rearrangement obtained is larger than the 8.5 kb fragment observed in CLL. These results do not favour the hypothesis of a pre‐B cell involvement in MM.
A new case of ‘type II’ inherited protein S deficiency
Authors: Chafa O. , Fischer A. M. , Meriane F. , Chellali F. , Rahal S. , Sternberg C. , Benabadji M. 
Published: March 2008

SummaryProtein S inherited deficiency is associated with high risk of recurrent venous thrombotic disease (Broekmans et al, 1985a, b). Protein S exists as two forms in plasma, either free and functionally active or complexed with C4b‐binding protein (C4b BP) and inactive (Dahibäck & Stenflo, 1981). We report here the case of a 26‐year‐old woman and her brother, 28 years old, both suffering from recurrent venous thrombosis since the age of 20, diagnosed as severe protein S deficiency according to the following data: free protein S: 2.5–3% by ELISA, undetectable by electroimmunodiffusion (BID); total protein S: 13–16% by ELISA, 21–18% by EID, C4b BP: normal levels. Crossed immunoelectrophoresis using anti‐protein S antibodies revealed only traces of protein S associated with C4b BP and no free protein S. All these assays were performed in the absence of any anticoagulant therapy. Among the investigated relatives, less severe protein S deficiency was observed in three children of the propositus: total protein S levels ranging from 41% to 50% (EID), 40–53% (ELISA); free protein S levels ranging from 16% to 18% (EID), 10–12% (ELISA); normal C4b BP levels. Crossed immunoelectrophoresis revealed traces of free protein S but a significant amount of protein S associated with C4b BP. From these results, we consider, according to Comp's classification (Comp et al, 1986a), that the propositus and her brother are the second case of protein S deficiency type II to be reported in the literature while her children belong to the type I category.
Detection of Rh D‐associated epitopes in human and animal tissues using human monoclonal anti‐D antibodies
Authors: Thorpe Susan J. 
Published: March 2008

SummaryThe distribution of Rh D‐associated epitopes in human and animal tissues has been assessed by immunochemical techniques using six human monoclonal anti‐D antibodies. The IgM antibody MAD‐2 reacted predominantly with endothelial cells lining blood vessels and with animal leucocytes and human leucocytes from both Rh D‐positive and Rh D‐negative donors. Immunoblotting revealed reactivity with a 55 kDa tissue component which was most prominent in homogenates of heart, lung and spleen. In contrast, the IgG antibodies UCHD4 and FOG‐1 stained smooth muscle, and UCHD4 in addition weakly stained cardiac and skeletal muscle and the glomeruli of kidney. Immunoblotting with UCHD4 revealed reactivity with a 27 kDa tissue component which was most prominent in heart homogenates. The results show that the six monoclonal anti‐D antibodies recognize at least four different epitopes and that Rh D‐associated epitopes may occur in non‐erythroid cell types.
Effect of antilymphocyte globulin (ALG) on bone marrow T/non‐T cells from aplastic anaemia patients and normal controls
Authors: Tong Jie , Bacigalupo Andrea , Piaggio Giovanna , Figari Osvaldo , Marmont Alberto 
Published: March 2008

SummaryThe aim of this study was twofold: (a) to test the effect of antilymphocyte globulin (ALG) on bone marrow (BM) T/non‐T cells, and (b) to look for a possible differential response of cells from severe aplastic anaemia (SAA) patients and controls. For this purpose bone marrow T/non‐T cells from normal individuals (n=7) or aplastic patients (SAA, n=13) were kept in liquid culture with or without ALG. Supernatants were then tested for enhancement/suppression on colony forming unit, granulocyte‐macrophage (CFU‐GM) growth (in the he presence of exogenous recombinant granulocyte‐macrophage colony stimulating factor (rGM‐CSF)), or for their ability to support CFU‐GM growth (in the absence of exogenous rGM‐CSF). Supernatants from SAA T cells suppressed CFU‐GM growth of normal bone marrow cells in 5/12 patients (mean expected growth (EG) 71 ± 16%), but not after incubation with ALG (mean 110±29% EG, P=0.03). No inhibition could be obtained with the supernatants from untreated normal T cells. Significant enhancement was seen with ALG treated versus untreated SAA T cells (142±28%EG v. 105±61%EG, P=0.01) and with ALG treated versus untreated SAA non‐T cells (165±26%EG v. 105±23%EG, P=0.01), but not in controls.Supernatants from SAA and control T/non‐T cells were capable of promoting colony formation in the absence of rGM‐CSF (colony‐stimulating activity (CSA) production): 16±14% for SAA‐T cells and 19±18%EG for non‐T cells 100%= 30 ng rGM‐CSF/ml). The addition of ALG increased CSA production in T cells to 37±23%EG (P=0.04) and in non‐T cells to 40±13% EG (P=0.04). Similar results could be obtained in controls.In conclusion: (a) ALG interacts in vitro with bone marrow T and non‐T cells from SAA patients, down‐regulating the production of negative lymphokines and enhancing the release of haemopoietins; (b) the latter, but not the former effect, can be shown also with cells from normal controls. The two effects are not mutually exclusive, and are likely to provide maximal benefit in vivo.
Pre‐B and ‘common’lymphoblastic leukaemia of childhood compared
Authors: Lilleyman and J. S. , Hinchliffe R. F. 
Published: March 2008

Summary Consecutive children suffering from pre‐B lymphoblastic leukaemia (pre‐B ALL) were compared with those who had ‘common’ALL (C‐ALL) to assess any clinical and pathological differences between the two groups.Over 101 months 27 pre‐B children were seen—an incidence in the population served of around 0.8/100 000 per year. There was some time‐clustering and 12 of the 27 presented in one year (1987). The 51 patients with C‐ALL who presented for comparison were distributed more evenly over the study period. Pre‐B children had more basophilic blast cells with less periodic acid‐Schiff positivity. They had higher presenting white cell counts and serum concentrations of lactic dehydrogenase; two variables which were correlated with each other. There was a trend towards pre‐B children being younger and fewer had hyperdiploid blasts, but these differences were not statistically significant. No difference from ‘common’ALL in response to therapy was apparent for the pre‐B patients at a median follow up time of 17 months—too short a period for any conclusion to be drawn.Other than immunophenotype, pre‐B ALL has no pathognomonic features, but there are differences from C‐ALL in the distribution of some disease characteristics known to be associated with a worse prognosis.
Amodiaquine‐induced immune agranulocytosis
Authors: Rouveix B. , Coulombel L. , Aymard J. P. , Chau F. , Abel L. 
Published: March 2008

SummaryThis report describes two patients who developed agranulocytosis while receiving prophylactic amodiaquine treatment. The neutrophil counts returned to normal in one after stopping the drug while the other died of sepsis. Amodiaquine‐dependent circulating neutrophil IgG antibodies were demonstrated in both patients using the indirect granulocyte immunofluorescence test. The antineutrophil antibody activity was enhanced with the use of the major amodiaquine metabolite, mono‐desethyl amodiaquine. Additional studies showed the activity of the sera to be nondialysable, heat stable, active against autologous as well as allogenic cells, and absent from the convalescent sera. There was no growth inhibition of allogenic myeloid committed progenitor cells (CFU‐GM) following incubation with the patients’ sera, complement and amodiaquine. These results indicate that agranulocytosis can be mediated by a drug‐dependent antibody which affects mature blood cells.
Characterization of deletions of chromosome 7 short arm occurring as primary karyotypic anomaly in acute myeloid leukaemia
Authors: Mecucci Cristina , Van Orshoven Angeline , Boogaerts Marc , Michaux Jean‐Louis , Van den Berghe Herman 
Published: March 2008

SummaryThree patients with an acute myeloid leukaemia (AML) showed a deletion of the short arm of chromosome 7 with loss of the deleted material. The 7p — anomaly originated from either a terminal or an interstitial deletion and it represented the only karyotypic aberration in all the three cases. According to the clinical, morphological and immunological features of this series of patients, a 7p — chromosome appears to be associated with a group of AML with myelodysplastic features in the bone marrow, including secondary disorders in patients treated for a previous malignancy.
VAD chemotherapy for refractory multiple myeloma
Authors: Lokhorst H. M. , Meuwissen O. J. A. Th. , Bast E. J. E. G. , Dekker A. W. 
Published: March 2008

SummaryThirty‐four patients with refractory multiple myeloma were treated with 4‐d continuous infusions of vincristine and adriamycin in combination with 4‐d pulsed high‐dose dexamethasone (VAD). Of 31 evaluable patients, 16 entered a complete remission (50%) and three a partial remission (10%). No difference in response rate was observed between primary refractory and relapsed patients. The median response duration was 9 months and the median survival of the responding patients was 12 months versus 4 months for the non‐responders. Ten patients have currently survived longer than 360 d, of which six are stable in complete remission without therapy. All responding patients showed a remarkable improvement of their performance status and 70% of these patients became pain‐free. Bacterial infection was the major complication and was probably due to the intensive corticosteroid programme. Severe myelosuppression was rarely observed. Irrespective of the response to VAD, a high β‐microglobulin of 4 μg/ml or more was a bad prognostic parameter. As early relapses were seen especially in this group of patients, in the patients with a plasma‐cell LI% of 3 or more, and in patients with previous anthracyclin treatment, early consolidation, with, for instance, high dose melphalan, might improve the prognosis for these patients.
Children in long‐term remission after treatment for acute lymphoblastic leukaemia show persisting haemopoietic injury in clonal and long‐term cultures
Authors: Bhavnani M. , Jones P. H. Morris , Testa N. G. 
Published: March 2008

SummaryTwenty children who were in unmaintained full haematological remission after treatment for acute lymphoblastic leukaemia (ALL) showed a significantly lower incidence of granulocyte‐macrophage progenitor cells (GM‐CFC) in the bone marrow compared to controls. This low incidence lasted for up to at least 3 years after the cessation of chemotherapy. There was no tendency to higher values with longer times after treatment, and the low incidence was not predictive of relapse.Long‐term cultures from ALL bone marrows and from controls achieved similar levels of production of mature cells through the whole period of culture (6 weeks). However, cultures from patients’ bone marrow had on average about 5 times lower numbers of GM‐CFC, indicating that the level of mature cell production was achieved by a higher level of post‐GM‐CFC amplification than needed in the controls. This is taken to be due to compensatory mechanisms operative during stressed haemopoiesis which appears to be a long‐lasting effect after current chemotherapy of ALL.