bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thymidylate Synthesis in a Folate Deprived Cell Line
Authors: Marquet J. , Zittoun J. , Weynants C. , Zittoun R. 
Published: March 2008

Summary. Abnormalities of the de novo and salvage pathways of thymidylate synthesis have been investigated in a folate deprived lymphoblastoid cell line. Impaired DNA synthesis was observed, with an increased percentage of cells in S and G2 phase, whereas the mitotic index was decreased.Thymidylate synthesis along the salvage pathway was markedly increased, with a higher activity of thymidine kinase and higher uptake of 3H‐thymidine (3H‐TdR). The same abnormalities were observed when cells were treated with 5‐fluorodeoxyuridine or methotrexate.The de novo pathway was slightly modified with a nearly normal incorporation of 3H‐6 deoxyuridine (3H‐UdR) and a moderate decrease of thymidylate synthetase activity; in contrast, the uptake of 3H‐dU was markedly inhibited in drug‐treated cells.Preincubation with cold deoxyuridine (10−4 M) did not suppress the uptake of 3H‐TdR as efficiently as in control cells; with increasing concentration of dU to 10−2 M, this suppressive effect became almost complete. This high concentration of cold dU exerted a competitive inhibition on thymidine kinase.The deoxythymidine triphosphate (dTTP) pool was increased in deficient cells and it was only slightly increased by addition of cold dU (10−4 M) in the culture medium whereas a substantial expansion of this pool was observed in control cells treated under the same conditions.These data do not necessarily exclude a defect of thymidylate synthesis along the de novo pathway in the folate deficient cells. The normal incorporation of 3H‐dU could be explained by a decreased isotope dilution due to a reduced deoxyuridine monophosphate (dUMP) pool. This pool could be decreased by feedback inhibition by dTTP on some enzymatic activities, mainly deoxycytidylate deaminase. The enlarged dTTP pool which probably derives mainly from the salvage pathway could be poorly functional for DNA replication according to the model of compartmentation of DNA precursors.
T‐cell function in chronic lymphocytic leukaemia
Authors: Whelan C. A. , Willoughby R. , McCann S. R. 
Published: March 2008

Summary. Fifteen patients with chronic lymphocytic leukaemia (CLL) were studied. The diagnosis was made by a combination of clinical findings, peripheral blood morphology and cell surface markers. The Rai clinical staging (Rai et al, 1975) was used to classify all patients. Serum immunoglobulins, B and T cell lymphocytes, TG and TM cell populations were evaluated in all patients before commencing treatment.No correlation was found between clinical staging and the presence or absence of hypogammaglobulinaemia. The ratios of TG to TM cells were abnormal in all patients and this abnormality paralleled the stage of the disease.While there was a significant difference in the proliferative responses of highly purified T cells from patients and controls at 1 μg and 2 μg/ml of Concanavalin A (Con A) (P values =P < 0.005 and P < 0.01 respectively). There was no significant difference at dose 5 μg/ml.The ability of T cells to suppress allogeneic PBMC responses to Con A was dependent on T cell purification procedures. The significance of the results and the possible role of T cells in the pathogenesis of CLL is discussed.
‘Silent’β‐thalassaemia caused by a ‘silent’β‐chain mutant: the pathogenesis of a syndrome of thalassaemia intermedia
Authors: Fessas Phaedon , Loukopoulos Dimitris , Loutradi‐Anagnostou Aphrodite , Komis George 
Published: March 2008

Summary.In a Greek family three cases of β‐thalassaemia intermedia were diagnosed as resulting from the interaction of a typical high HbA2‐β‐thalassaemia with an atypical (silent) β‐thalassaemia gene. Following electrophoresis of globins on an acid‐urea‐Triton‐acrylamide system, an otherwise silent β‐like variant was revealed in the carriers of the atypical thalassaemia gene and in the intermediates; it amounted to 33% of the non‐α chains in the former and to c. 75% in the latter. The provisional name Hb Knossos is suggested for this abnormality.
Bone marrow reconstitution of lethally irradiated canines using autologous bone marrow fractions obtained by counterflow centrifugation‐elutriation
Authors: Jemionek J. F. , Monroy R. L. , MacVittie T. J. , Contreras T. J. , Espy S. B. 
Published: March 2008

Summary.Canine bone marrow fractionated by counterflow centrifugation‐elutriation results in three areas of nucleated cell recovery. Fraction 1 accounts for 50% of the total nucleated cells and 25‐40% of the total recovered CFU‐GM activity. Fraction 2 contains less than 2% of the total nucleated cells and less than 0‐2% of the CFU‐GM activity. Fraction 3 accounts for approximately 50% of the total nucleated cell recovery and 60‐75% of the total recovered CFU‐GM activity. Animal survival was not directly correlated with the levels of CFU‐GM activity in the transfused fractions. Autologous infusion of these fractions into irradiated canines (9 Gy, 0.1 Gy/min) resulted in distinct survival profiles. Canines receiving autologous fraction‐2 cells showed no haematological reconstitution, with death occurring on days 10‐11 post‐irradiation. Canines receiving autologous fraction‐3 cells showed limited myeloid repopulation of both the bone marrow and peripheral blood with a mean survival time for 24 d. Canines receiving autologous fraction‐1 cells showed complete haematological reconstitution after 48 d and long‐term survival. The data may indicate a separation or enrichment of pluripotential stem cells (fraction 1) from committed myeloid progenitor cells (fraction 3).
Cell lines derived from a human myelomonocytic leukaemia
Authors: Bradley T. R. , Pilkington G. , Garson M. , Hodgson G. S. , Kraft N. 
Published: March 2008

Summary.Two cell lines have been isolated from separate samples, taken at the same time, from the peripheral blood of a case of myelomonocytic leukaemia. One of these (CESS‐B) is a typical B cell line obtained after treatment of the peripheral blood white cells with Epstein‐Barr virus (EBV). The second line (RC‐2) is a monocyte‐macro‐phage type, originally isolated by 5 months continuous culture in the presence of colony stimulating factor (CSF). Subsequently, after further culture, this line has become autonomous (RC‐2A), no longer requiring CSF for maintenance of proliferation, whilst retaining the characteristics of the original line.
Sudan Black B positivity in acute lymphoblastic leukaemia
Authors: Tricot G. , Orshoven A. Broeckaert‐Van , Hoof A. Van , Verwilghen R. L. 
Published: March 2008

Summary.An adult patient with Sudan Black B (SB B) positive leukaemic lymphoblasts is described. Peroxidase and naphtol AS D chloroacetate esterase stains were negative. The diagnosis of acute lymphoblastic leukaemia (ALL) was based on morphology (FAB classification: L1), on immunological marker studies (cALL+, Tdt+, Ia+) and on electron microscopy, revealing blasts, compatible with lymphoblasts. Additional proof of the diagnosis of ALL were the diffuse lymphadenopathy and the rapid response to ALL chemotherapy.Scattered azurophilic granules were present in some lymphoblasts; ultrastructurally multiple lysosomal inclusions were detected, containing small vesicles, sometimes in association with entrapped cytoplasmic organelles. The large amounts of phospholipids in these inclusions explain the Sudan Black B positivity. This type of ALL can easily be misdiagnosed as acute myeloid leukaemia.
Influence of high molecular weight factor VIII on the measurement of low molecular weight factor VIII procoagulant in different assay systems
Authors: Muntean Wolfgang , Hathaway Wm. E. , Montgomery Robert R. 
Published: March 2008

Summary.Factor VIII procoagulant activity (VIIIC) is exerted by a low molecular weight (LMW) moiety of the factor VIII molecule that can be separated from a high molecular weight (HMW) moiety by high ionic strength buffers. In this investigation the procoagulant activity of the LWM moiety of factor VIII prepared by immuno‐adsorbent chromatography and its relationship to the HMW moiety of haemophilic plasma was studied by means of different VIIIC assay systems and using different substrates in regard to their content of the HMW VIII moiety. LMW VIIIC was prepared by immunoadsorbent chromatography; HMW VIII without VIIIC was prepared by chromatographing cryoprecipitate from a coagulant antigen negative severe haemophiliac on 4% agarose. The LMW VIIIC obtained by immunoadsorbent chromatography gave higher VIIIC values when tested in the one‐stage partial thromboplastin time (PTT) system using von Willebrand's disease plasma as substrate than using haemophilic plasma as substrate. This finding was shown to be related to the HMW VIII measured as VIII related antigen (VIII: Ag) in the substrate plasmas. When the VIIIR: Ag was removed from the haemophilic substrate plasma by immunoadsorption, the VIIIC values obtained for the LMW VIIIC were higher. Also, adding HMW VIII purified from haemophilic plasma to the von Willebrand's disease substrate plasma resulted in lower VIIIC values for the LMW VIIIC in the PTT system.
Generation of CFU‐C suppressor T cells in vitro: V. A. MULTISTEP PROCESS
Authors: Bacigalupo Andrea , Podesta' Marina , Frassoni Francesco , Piaggio Giovanna , Van Lint Maria T. , Raffo Maria R. , And Mario Repetto , Marmont Alberto 
Published: March 2008

Summary. Different cell fractions obtained from five patients with immune severe aplastic anaemia (SAA) in complete autologous haematologic reconstitution were tested for CFU‐c suppression. Bone marrow mononuclear cells (BMMC), but not peripheral blood mononuclear cells (PBMC), showed definite CFU‐c inhibitory activity. On the contrary, both peripheral blood and marrow E rosetting cells (E+) suppressed CFU‐c growth. The suppressor activity of PBE+ cells could not be rescued by adding back PBE‐ cells and/or PB adherent cells (AC). In addition, unfractionated PBMC exposed to sheep red blood cells (SRBC) suppressed CFU‐c growth. PBMC from normal donors exposed to SRBC had no suppressor activity.This study suggests that CFU‐c suppressor T cells in the peripheral blood of SAA patients are in different activation state as compared to BM cells from the same patients, and also differ from normal PB cells. The identification of T cells with different requirements for in vitro activation in order to exhibit a suppressor activity, suggests that generation of suppressor cells is a multistep process, and this may have practical implications for in vitro assays designed to test for immune suppression of haematopoiesis.
Antithymocyte globulin treatment of severe aplastic anaemia
Authors: Miller Wesley J. , Branda Richard F. , Flynn Patrick J. , Howe Robert B. , Ramsay Norma K. C. , Condie Richard M. , Jacob Harry S. 
Published: March 2008

Summary.Nineteen patients with severe aplastic anaemia were treated with antithymocyte globulin. Ten patients obtained remissions (transfusion independent, at least 45000 platelets and 2000 PMN/mm3) within 2–3 months and continue in remission 5–35 months after antithymocyte globulin. Ages of responders ranged from 17 to 71. Complications of antithymocyte globulin included arthralgias, rash, serum sickness, angioedema and fever. Two patients died during, two shortly after, and one 10 months after therapy. One patient with a previous remission following antithymocyte globulin relapsed and achieved a second remission with retreatment. Previous androgen therapy did not affect outcome since two of four patients with and eight of 15 patients without previous androgen therapy achieved remission with ATG. Treatment with antithymocyte globulin is a promising alternative to bone marrow transplantation in the treatment of severe aplastic anaemia.
The effect of stasis on the venous endothelium: an ultrastructural study
Authors: Thomas D. P. , Merton R. E. , Hockley D. J. 
Published: March 2008

Summary.In carefully dissected neck veins, no evidence was found of platelet adherence to the vessel wall or leucocyte migration. However, 30–60 min of total stasis led to polymorphonuclear leucocytes sticking to the endothelium and their subsequent migration. This migration across the vessel wall resulted from stasis and not the trauma of dissection. Adherence and migration of leucocytes did not cause gross endothelial cell damage or desquamation within the observed period of stasis and there was no associated platelet adherence following restoration of blood flow. Thus leucocyte migration does not impair the non‐thrombogenicity of the endothelium in acute experiments.
Blood neutrophil function in primary myelodysplastic syndromes
Authors: Boogaerts M. A. , Nelissen V. , Roelant C. , Goossens W. 
Published: March 2008

Summary.Ten different tests of blood neutrophil function were studied in 20 patients with primary myelodysplastic syndromes (PMDS). The patients were selected according to the new diagnostic criteria for PMDS of the FAB‐cooperation group. Impairments of granulocyte functions were found in all patients. Moreover, several steps in the mobilization of granulocytes at the site of injury seemed to be affected: decreased adhesion (P < 0–05), deficient chemotaxis (P < 0.05), decreased enzyme content (P < 0.001), ‘slower’chemiluminescence (P < 0005), decreased phagocytosis (P < 0.05) and impaired microbicidal capacity (P < 0.025). No significant correlation between disease category and severity of granulocyte dysfunction was discerned, though an increasing number of blasts was associated with more severe granulocytic disability. Results in seven patients with abnormal karotypes were not significantly different from 13 others with normal karyotypes. Our results indicate that defects in blood neutrophil function are a common feature in PMDS and might account for the increased frequency of infection in these patients.
T‐lymphocytes escape membrane defect in paroxysmal nocturnal haemoglobinuria
Authors: Cooper Michael R. , Currie Mark S. , Rustagi Pradip K. , Logue Gerald L. 
Published: March 2008

Summary.Erythrocytes, granulocytes and platelets from patients with paroxysmal nocturnal haemoglobinuria (PNH) are abnormally sensitive to lysis by complement. We studied T‐lymphocytes from PNH patients for abnormal complement lysis sensitivity. T‐lymphocytes free of other contaminating blood cells were prepared by sedimentation, nylon wool filtration, and density gradient centrifugation. The lymphocytes were then labelled with 51Cr and lysis induced by antithymocyte globulin and rabbit complement. PNH lymphocytes were no more susceptible to complement‐mediated lysis than lymphocytes from normal individuals. The unusual sensitivity of PNH erythrocytes could still be demonstrated when rabbit serum was a source of complement so the lack of any difference in the sensitivity of normal and PNH lymphocytes was probably not attributable to the inability of rabbit serum to elicit the membrane defect. PNH erythrocytes and granulocytes also acquire more membrane‐bound C3 when human complement is activated. Therefore we also searched for increased membrane C3 binding on PNH lymphocytes using anti‐I antibody and human serum as a complement source. C3 binding was measured using 125I labelled monoclonal mouse anti‐human C3. While we verified increased membrane C3 binding on PNH granulocytes during complement activation we were unable to show similar differences between PNH and normal T‐lymphocytes. Thus PNH T‐lymphocytes do not share the membrane abnormalities of PNH erythrocytes and granulocytes.
Normalized natural killer (NK) cell activity in long‐term remission of acute leukaemia
Authors: Yoda Yasuhiro , Abe Tsukasa , Tashiro Akio , Hirosawa Shinsaku , Kawada Kenichi , Onozawa Yasusuke , Adachi Yamao , Shishido Hideo , Nomura Takeo 
Published: March 2008

Summary.NK cell activity was studied in 28 cases of acute leukaemia in remission. It was found that patients in long‐term remission for 5 years or more had normal NK cell activity but those in remission for less than 5 years had significantly lowered activity. This suggests that patients with acute leukaemia had not been constitutionally deficient in NK cell activity. Low activity was augmented but not fully restored by interferon pretreatment in vitro. Therefore, the low NK cell activity observed during remission is not solely attributable to inadequate secretion of interferon in the host. It is suggested that the production of NK cells in bone marrow is impaired, or the function of NK cells is suppressed, by the leukaemia itself or by chemotherapeutic agents. Increased consumption of NK cells is also a possibility.
Bone marrow fibroblast function in relation to granulopoiesis in aplastic anaemia
Authors: Gordon M. Y. , Gordon‐Smith E. C. 
Published: March 2008

Summary. Fibroblasts grown from the bone marrow of normal individuals and incubated with colony‐stimulating factor (CSF) enhance the stimulating activity of this CSF on granulocyte‐macrophage colony‐forming cell (GM‐CFC) proliferation.For this study, the ability of fibroblast monolayers grown from the marrows of six patients with severe aplastic anaemia to increase the activity of CSF has been compared with the activity of normal fibroblasts. Tests of this function showed subnormal CSF‐enhancing activity by fibroblasts grown from the marrows of three of the six aplastic patients.Since cultured bone marrow fibroblasts are thought to represent an important component of the haemopoietic microenvironment, the results suggest that some of the patients had a microenvironmental abnormality at the time of study.One of the patients whose fibroblasts were abnormal was reinvestigated after he had been given a graft of allogeneic bone marrow cells. His post‐graft fibroblast function was normal, showing that the abnormality was reversible.
Acute leukaemia in patients treated for Hodgkin's disease
Authors: PAPA G. , Mauro F. R. , Anselmo A. P. , Cimino G. , Alimena G. , Amadori S. , D'Arcangelo E. , Giannarelli D. , Bosi A. , Bellesi G. , Fiacchini M. , Mazza P. , Babini L. , Emiliani E. , Enrici R. Maurizi , Biagini C. 
Published: March 2008

SummaryFourteen acute non‐Iymphoid leukaemias (ANIL) were identified among 947 consecutive patients with Hodgkin's disease (HD) treated in five collaborating centres in Italy between January 1969 and December 1979.Leukaemia developed 12‐118 months after the diagnosis of HD and was always preceded by a pre‐leukaemic phase. The karyotype of the leukaemic cells was studied in nine of the 14 patients and was abnormal in seven cases. Bone marrow agar cultures were performed in five of the 14 patients and were abnormal in every case.The actuarial risk of developing ANLL at 10 years was 6.2% for combined therapy, 4.8% for salvage therapy and 2.2% for chemotherapy alone. No case of ANLL was documented among 136 patients treated with radiotherapy alone. One patient developed acute promyelocytic leukaemia following treatment with ABVD and radiotherapy. Both univariate and multivariate analyses seem to demonstrate that the induction therapy modality is a significant variable in development of secondary acute leukaemia. The recognition of a significant risk of ANLL in patients treated for HD should create changes in treatment policy.
Mechanism and characteristics of platelet activation by haematin
Authors: Neely Sara M. , Gardner Diane V. , Reynolds Nancy , Green David , Tšao Chung‐hsin 
Published: March 2008

SummaryThe mechanism as well as some characteristics of haematin‐induced human platelet aggregation were investigated. Haematin‐induced platelet aggregation required the presence of devalent cations; Mg2+, and to a lesser extent, Co2+, were just as effective as Ca2+ in supporting the aggregation. Mono‐ and trivalent cations were ineffective. Verapamil inhibited the aggregation. The aggregation was accompanied by thromboxane formation which could be abolished by aspirin. The release of adenine nucleotides was only slightly inhibited by aspirin. The rate of aggregation and the ultrastructure of the aggregated platelets were comparable between control and aspirin‐treated samples. It is concluded therefore that haematin‐induced aggregation is not dependent on platelet prosta‐glandin synthesis. Haematin induced binding of fibrinogen to platelets, and failed to aggregate thrombasthenic platelets. These findings indicate that haematin may induce platelet aggregation by promoting influx of divalent cations in association with increased fibrinogen binding and release of adenine nucleotides.
Cigarette smoking and platelet adhesion
Authors: Pittilo R. M. , Clarke J. M. F. , Harris D. , Mackie I. J. , Rowles P. M. , MACHIN S. J. , Woolf N. 
Published: March 2008

SummaryNon‐abraded rabbit endothelium has been exposed to human blood taken from male non‐smoking volunteers before and after the smoking of two medium tar cigarettes, in an in vitro system using a Baumgartner chamber. In each case the blood was allowed to circulate for 10 min at a constant flow rate. Blood from 10 volunteers has been tested in this way. Scanning electron microscopy of the endothelial surfaces demonstrates large numbers of adherent platelets when ‘post‐smoking blood’ is used, but very few and in some cases none with the ‘pre‐smoking’ blood. As a further control to ensure that this phenomenon did not occur as a result from changes in the vessel related to the time during which it had been removed from its normal physiological environment, blood from further non‐smoking volunteers was passed over seven of the remaining pieces of vessel at the completion of these runs. Platelets were either absent or very few in number, as with the pre‐smoking samples.
Efficacy of porcine factor VIII in the management of haemophiliacs with inhibitors
Authors: Ciavarella N. , Antoncecchi S. , Ranieri P. 
Published: March 2008

SUMMARYWe report our experience with polyelectrolyte‐fractionated highly purified porcine factor VIII concentrate (Hyate:C). Porcine factor VIII concentrate was used to treat 14 haemorrhagic episodes including seven severe haemarthroses, three severe haematomata, two episodes of oral bleeding, one traumatic and the other after multiple dental extractions and two life‐threatening intestinal haemorrhages. Altogether 60 infusions of Hyate:C were given to five haemophiliacs with inhibitors. At the time of the first infusion with porcine factor VIII the anti‐human inhibitor level ranged from 60 to 2‐5 modified Bethesda units/ml (MBU 4 h incubation). The porcine cross‐reactivity of these inhibitors was 25‐6% and 5‐4% of the human inhibitor level in two patients and scarcely measurable in the other three patients. We injected an amount of porcine factor VIII concentrate corresponding to the calculated porcine neutralizing units plus the units required for haemostasis. The clinical efficacy was excellent and no adverse effects were encountered, apart from two episodes of mild pyrogenic reactions well controlled by hydrocortisone. The anamnestic antibody response against human factor VIII was of slight degree in all cases, while the porcine cross‐reactivity showed no significant variation. Our results emphasize the role of porcine factor VIII in the treatment of haemophiliacs with inhibitors.