bluuebunny/crossref_metadata_2025_split huggingface dataset:
B‐CLL cells express true endogenous E receptor after culture with T‐cells and mitogens
Authors: Worman C. P. , Cawley J. C. 
Published: March 2008

Summary. Culture studies of peripheral blood mononuclear cells from seven typical cases of B‐cell chronic lymphatic leukaemia (CLL) showed that, in the presence of PHA or Con A and ≧20% autologous or allogeneic T‐cells, CLL cells express true sheep erythrocyte (E) receptor after 2‐5 d, but fail to stain with a panel of anti‐T‐cell sera. In contrast to similarly cultured hairy cells (HCs), the cultured CLL cells continue to express light‐chain‐restricted surface immunoglobulin (SIg) and show no change in their morphology.The continued SIg positivity and staining with a panel of monoclonal antibodies indicated that the high proportion of E+ cells could not be attributed to the outgrowth of normal T‐cells or to mitogen‐induced non‐specific stickiness. Repeated addition of supernatants from cultured T‐cells caused no phenotypic changes and therefore excluded the possibility of shedding and passive acquisition of E receptor.The points of similarity and difference between the responses of CLL cells and HCs cultured in a like manner are briefly considered in relation to the possible lineages of these two cell types.
The interaction between factor VIII clotting antigen (VIIICAg) and phospholipid
Authors: Yoshioka A. , Peake I. R. , Furlong B. L. , Furlong R. A. , Giddings J. C. , Bloom A. L. 
Published: March 2008

Summary.The interaction between factor VIII clotting antigen (VIIICAg) and phospholipid (PL) was studied using a two‐site solid phase immunoradiometric assay (IRMA) for VIII CAg. Incubation (2 h, 37°C) of normal plasma, cryoprecipitate or factor VIII concentrate with Diagen PL (0·5 mg/unit VIIICAg) resulted in 80–90% loss of IRMA‐measurable VIIICAg. No loss of factor VIII related antigen (VIIIRAg) or factor VIII clotting activity (VIIIC) was seen. Treatment of factor VIII concentrate with purified PLs showed greatest VIIICAg reduction with phosphatidylserine, less with phosphatidylethanolamine, and very little with phosphatidylcholine. The action of phospholipase‐C (PL‐C) on VIIICAg–PL complexes was investigated, with enzyme activity being monitored by thin‐layer chromatography. Treatment of normal plasma, cryoprecipitate or factor VIII concentrate with PL‐C (5 u/unit VIIICAg) resulted in 25%, 25% and 30% increases in VIIICAg. No increase in VIIIC or VIIIRAg was seen. Preincubation of factor VIII concentrate with PL, followed by PL‐C incubation, resulted in 70–80% recovery of measurable VIIICAg. Incubation of ‘activated’prothrombin complex with PL‐C increased VIIICAg by 44% (Autoplex) and 80% (FEIBA), indicating VIIICAg–PL complexes are present. Incubation of factor VIII concentrate with fresh platelet lysate led to a reduction in VIIICAg (100 u/dl to 21 u/dl). In fresh platelet lysate alone low VIIICAg levels were detectable (0·71 × 10−3 u/109 plt). After PL‐C incubation VIIICAg levels increased to 9·8 × 10−3 u/109 plt) (14‐fold increase). Thus VIIICAg in platelets may be hidden by VIIICAg–PL complexes.
Isoferritins in normal leucocytes
Authors: Jones B. M. , Worwood M. , Jacobs A. 
Published: March 2008

Summary.Monocytes, lymphocytes and polymorphs were separated from the peripheral blood of normal human subjects. Ferritin concentrations were determined with antibodies to both human spleen and heart ferritins. The heart type ferritin concentration in monocytes was 38·4±21·6 fg/cell (mean ±SD), in lymphocytes 8·6±6·6 fg/cell and in polymorphs 3·2±2·4 fg/cell. Spleen type ferritin concentrations (fg/cell) were 15·6±7·0 in monocytes, 6·6±5·7 in lymphocytes and 7·0±4·6 in polymorphs. The mean heart/spleen ferritin ratios were 2·8/1 for monocytes, 2·0/1 for lymphocytes and 0·6/1 for polymorphs. The cell extracts were also subjected to anion exchange chromatography. Heart type ferritin eluted at a higher chloride ion concentration than spleen type ferritin. Both H and L subunits were synthesized by mononuclear cells when incubated with 3H‐leucine. Human leucocytes contain a wide range of isoferritins and ferritin concentrations may be considerably underestimated in conventional assays for serum ferritin which employ antibodies to liver or spleen ferritin.
Demonstration of an immune‐mediated mechanism of penicillin‐induced neutropenia and thrombocytopenia
Authors: Murphy M. F. , Riordan T. , Minchinton R. M. , Chapman J. F. , Amess J. A. L. , Shaw E. J. , Waters A. H. 
Published: March 2008

Summary.Severe neutropenia may be a more common complication of high‐dose penicillin therapy than previously recognized. This report describes five such patients, one of whom also had thrombocytopenia. The neutrophil and platelet counts rapidly increased on stopping penicillin, and the bone‐marrow, which was hypocellular in some cases, became normal. Further studies on one of these patients, using a fluorescent antiglobulin technique with paraformaldehyde‐fixed cells, demonstrated a complement‐fixing IgG penicillin antibody reacting with the patient's granulocytes and platelets in the presence of the drug. This suggested an immune mechanism similar to the well‐recognized penicillin‐induced immune haemolytic anaemia. The associated bone‐marrow hypoplasia may also be due to antibody‐mediated suppression of penicillin‐coated precursor cells.
Oxygenation alters red cell folate levels
Authors: Nelson Nancy L. , Klausner Jeffrey S. , Branda Richard F. 
Published: March 2008

Summary.Folate activity is consistently higher in deoxygenated than oxygenated human blood as measured by both radioassay and Lactobacillus casei growth. Red cell, but not serum, folate levels are rapidly mutable: when fully oxygenated, the mean red cell folate level of 15 samples was 489 ng/ml; after deoxygenation the mean rose to 553 ng/ml; following re‐oxygenation the mean returned to 488 ng/ml. Transport of folate across the red cell membrane apparently does not contribute to these changes in folate levels, since agents known to inhibit permeation (N‐ethyl‐maleimide, p‐chlormercuriphenyl sulfonic acid and ethacrynic acid) do not affect the rise with deoxygenation. Moreover, new synthesis of folate compounds seems unlikely, since the changes are observed in energy‐depleted cells. Instead, direct binding of folate to haemoglobin is suggested by experiments in which the rise with deoxygenation was not seen in red cells exposed to carbon monoxide or treated with cyanate. Similar changes also occur in vivo: canine red cell, but not serum folate levels are significantly higher (P < 0.05) in samples collected from five different veins compared with blood from the paired artery (carotid‐jugular, renal, mesenteric, splenic, femoral) of four animals. Thus red cell folate levels are predictably influenced by the levels of oxygenation of the erythrocyte both in vitro and in vivo, possibly by reversibly binding to haemoglobin.
Incomplete glycosylation of erythrocyte membrane proteins in congenital dyserythropoietic anaemia Type II (CDA II)
Authors: Mawby W. J. , Tanner M. J. A. , Anstee D. J. , Clamp J. R. 
Published: March 2008

Summary.The alterations in the erythrocyte membrane proteins of individuals with congenital dyserythropoietic anaemia (CDA II) were studied. Alterations were observed in both the erythrocyte sialoglycoproteins and erythrocyte anion transport protein (Band 3). There was a decrease in the apparent molecular weight of the major sialoglycoprotein α (glycophorin A) as well as a general reduction in the intensity of staining of all the sialoglycoproteins by the PAS stain. Sialoglycoprotein α isolated from CDA II erythrocytes contained 30% less sialic acid than normal α. The anion transport protein of CDA II erythrocytes migrated as a band with a lower molecular weight than the normal protein on SDS‐gel electrophoresis. The CDA II anion transport protein had a substantially reduced content of N‐acetylglucosamine and galactose, which probably reflects a reduction in the number of N‐acetyl‐lactosamine units carried by the protein. Our results suggest that there is a general defect in glycosylation of the major membrane glycoproteins of CDA II erythrocytes. We suggest that this glycosylation defect is a consequence of bone marrow stress.
Cellular cooperation in endothelial cell thromboplastin synthesis
Authors: Lyberg T. , Galdal K. S. , Evensen S. A. , Prydz H. 
Published: March 2008

Summary. Endothelial cells from human umbilical veins produce a procoagulant identified as thromboplastin (tissue factor, factor III) when stimulated with the phorbol ester 12‐0‐tetradecanoyl‐phorbol‐13‐acetate (TPA), phytohaemagglutinin (PHA) or endotoxin. Inducible thromboplastin synthesis (i.e. synthesis of the protein component of thromboplastin, apoprotein III) was totally inhibited by cycloheximide and actinomycin D, indicating that de novo protein and RNA syntheses are necessary. Serum enhanced the induced apoprotein synthesis.Of the total thromboplastin activity in homogenates of stimulated endothelial cells, about 50–70% was available on the cell surface for interaction with other coagulation factors, inactivation by trypsin and neutralization with antiserum against apoprotein III.Induced synthesis of thromboplastin in endothelial cells was 2–7‐fold enhanced by the presence of several other cell types in optimal ratio 4–10 cells per endothelial cell. Some of these cell types were themselves thromboplastin producers (U‐937, U‐937‐4), some were not inducible (lymphocytes, granulocytes and the lymphoblast lines Daudi and Molt 4). This enhancing effect was also seen with cell‐free culture supernatants, but these were generally somewhat less effective than the intact cells. Supernatants derived from cells cultured in the presence of TPA, PHA or endotoxin were in most cases more effective than supernatants from unstimulated cells.
Influence of the tumour promoter TPA upon erythroid burst formation in vitro
Authors: Brockbank K. G. M. 
Published: March 2008

Summary. A dose dependent effect of the tumour promoter TPA on burst formation by rabbit erythroid progenitors (BFU‐e) was demonstrated in cultures deficient in the early erythroid regulator burst‐promoting activity (BPA). In these culture conditions the burst number was highest (193% of controls) at 10 9m TPA and concentrations higher than 3 × 10 9m TPA were inhibitory. The degree of burst enhancement by TPA and bone marrow conditioned medium as a source of BPA was similar. The addition of optimal concentrations of both TPA and BPA simultaneously to cultures resulted in no further increase in burst number. Short‐term incubation of bone marrow cells with TPA failed to enhance the percentage of S‐phase BFU‐e under conditions in which BPA significantly increases the number of BFU‐e in the cell cycle.These results indicate that the same population of BFU‐e responds to TPA and BPA, but TPA does not mimic the mitogenic effect of BPA upon BFU‐e.
Haematological reconstitution following high dose and supralethal chemo‐radiotherapy using stored, non‐cryopreserved autologous bone marrow
Authors: Burnett A. K. , Tansey P. , Hills C. , Alcorn M. J. , Sheehan T. , McDonald G. A. , Banham S. W. 
Published: March 2008

Summary. Eighteen patients with small cell carcinoma of the lung received high dose cyclophosphamide (180–200 mg/kg) intensification following five pulses of ‘CHOP’ chemotherapy (cyclophosphamide 750 mg/m2 i.v., adriamycin 50 mg/m2 i.v., vincristine 1·4 mg/m2 i.v., prednisolone 40 mg orally for 5 d). They received infusions of autologous bone marrow which had been stored at 4°C for 34 h. Pancytopenia was predictable in onset and its duration acceptable. Recovery of neutrophils to greater than 1·0 × 109/l was achieved in 17·5 ± 0·9 d (mean ± SEM) and platelets to greater than 100 × 109/l in 17·5 ± 0·8 d. Four patients with acute myeloid leukaemia in complete remission received intensification with the supralethal combination of cyclophosphamide and total body irradiation followed by infusion of autologous marrow which had been stored at 4°C for 54 h. Haematological reconstitution in these patients was acceptable but slower (greater than 1·0 × 109/l neutrophils between days 26 and 40; greater than 20 × 109/l platelets between days 23 and 77). Except in one case, normal peripheral counts were attained in all patients.It is concluded that bone marrow stored at 4°C for up to 54 h is a simple and practical source of viable stem cells which have the capacity for acceptable haematological reconstitution.
Sickle cell disease: the proportion of liganded haemoglobin needed to prevent crises
Authors: Franklin I. M. , Rosemeyer M. A. , Huehns E. R. 
Published: March 2008

Summary. In an attempt to predict the likelihood of successfully treating sickle cell disease by increasing haemoglobin S (Hb S) oxygen affinity, two liganded derivatives of Hb S have been studied in an in vitro system that measures deoxy‐Hb S polymerization. The participation of these liganded forms in the polymers has been quantitated in terms of an exclusion factor that relates their behaviour to that of deoxy‐Hb S.Carbonmonoxy‐Hb S has an oxy‐Hb‐like conformation and did not participate significantly in the polymerization. It was calculated that 30% carbonmonoxy‐Hb S would have to be maintained in vivo to prevent sickling. Met‐Hb S has a conformational equilibrium intermediate between oxy‐ (or carbonmonoxy‐) and deoxy‐Hb S and behaved in a similarly intermediate manner with regard to deoxy‐Hb S polymerization. 60% met‐Hb S would be needed to prevent in vivo sickling.It is concluded that stabilizing the oxy(R)‐conformation is a potentially useful way of preventing sickling, and that a level of 30% R‐state Hb S would have to be maintained for this to be successful.
A trial of folate supplementation in children with homozygous sickle cell disease
Authors: Rabb L. M. , Grandison Yvonne , Mason Karlene , Hayes R. J. , Serjeant Beryl , Serjeant G. R. 
Published: March 2008

Summary. A double blind controlled trial of supplementation with folic acid has been performed in 117 children with homozygous sickle cell (SS) disease aged 6 months to 4 years over a 1 year period. No megaloblastic change was observed in either group. At the end of the study period the folate supplemented group showed no significant differences in haemoglobin, growth characteristics, or in the proportion of children affected by major or minor infections, acute splenic sequestration, dactylitis or episodes of bone or abdominal pain. However, the folate supplemented group showed a significantly lower mean cell volume and the placebo group contained a significant excess of children experiencing multiple episodes of dactylitis.The results are compatible with mild folate deficiency in some patients in the placebo group but the absence of striking effects on haematology or growth suggest that the policy of regular folate supplementation in children with SS disease should be critically reviewed.
Normal glutathione content and some related enzyme activities in the fetal erythrocytes
Authors: Lestas A. N. , Rodeck C. H. 
Published: March 2008

Summary. Pure fetal blood was obtained by direct‐vision fetoscopy from 66 fetuses at 17–24 weeks gestation. The concentration of GSH and the activities of the enzymes γ‐glutamylcysteine synthetase (GCS), glutathione synthetase (GS), glutathione reductase (GR) and glutathione peroxidase (GPx) were analysed by established techniques to find the normal ranges for this gestational age. The ranges were relatively narrow and could serve as reference values for the prenatal diagnosis of defects in the GSH metabolism of erythrocytes. The results were compared with those obtained from 38 normal adults and with published values on neonatal blood. In the case of GR a comparison was also made with maternal blood.In comparison with adults, fetal erythrocytes showed higher GSH concentration and GCS activity and lower GS and GPx activities. This pattern resembled that found in neonatal erythrocytes except for the GCS activity, which was higher in the fetal cells. Furthermore the differences between fetal and adult erythrocytes were more pronounced than those between neonatal and adult cells. The GR activity of fetal erythrocytes was also higher than that of either normal adult or maternal blood. This difference, however, was reduced to an insignificant level when the enzyme was activated in vitro by flavin adenine dinucleotide (FAD) because of a relatively low per cent activation of the GR in the fetal erythrocytes.
Bone marrow transplantation from identical twins in the treatment of aplastic anaemia: implication for the pathogenesis of the disease
Authors: Champlin Richard E. , Feig Stephen A. , Sparkes Robert S. , Gale Robert Peter 
Published: March 2008

Summary. Treatment of aplastic anaemia by bone marrow transplantation from a syngeneic (identical twin) donor has provided insights into the pathophysiology of the disease.We report from patients with severe anaemia who were treated by syngeneic bone marrow transplantation. None of the patients had sustained recovery of peripheral blood counts. All four received second transplants from the same twin donor after immunosuppressive conditioning treatment. Each had prompt recovery of haematopoiesis. A review of the literature indicates that failure of syngeneic bone marrow transplantation in patients with aplastic anaemia is not uncommon. These data indicate that aplastic anaemia may be caused by a mechanism other than an absence or intrinsic abnormality of haematopoietic stem cells in many patients.
Natural killer‐interferon system in patients with preleukaemic states
Authors: Takagi Shojiro , Kitagawa Seiichi , Takeda Akira , Minato Nagahiro , Takaku Fuminaro , Miura Yasusada 
Published: March 2008

SummaryThe natural killer (NK)‐interferon (IFN) system was investigated in patients with preleukaemic states. Endogenous NK cell activity was markedly reduced in all 12 patients studied. No significant correlation was observed between the activity of NK cells and the percentage of blast cells in the peripheral blood or bone marrow. The frequency of large granular lymphocytes (LGL) in lymphocytes of the peripheral blood was not reduced in most patients. The percentage of target binding cells in patients was essentially the same as that in normal controls, and the activity of NK cells from normal donors was not affected by the coexistence of mononuclear cells obtained from the peripheral blood of patients.Furthermore, the α‐IFN production in response to HeLa cells persistently infected with measles virus was reduced in all patients studied, except for one case with acquired idiopathic sideroblastic anaemia. The augmented activity of NK cells induced by α‐IFN was variable, but remained at lower levels than the endogenous activity of NK cells in normal controls.These findings suggest that not only the intrinsic defect and reduced number of NK cells but also the dysfunction of the NK‐IFN system may be responsible for the reduced activity of NK cells in patients with preleukaemic states.
Analysis of lymphocyte subsets in patients with aplastic anaemia
Authors: Zoumbos Nicholas C. , Ferris Warren O. , Hsu Su‐Ming , Goodman Steven , Griffith Patricia , Sharrow Susan O. , Humphries R. Keith , Nienhuis Arthur W. , Young Neal 
Published: March 2008

SummaryLymphocyte subsets have been measured in the blood of 28 patients with aplastic anaemia. The mean helper/inducer:suppressor/cytotoxic T lymphocyte ratio (1.24 ± 0.74) was significantly decreased in the total population in comparison to mean ratios in a normal population (1.78±0‐57) and in patients with other haematological diseases (l‐82±0‐92). A reversed ratio (< 1) was present in a large proportion (53%) of aplastic patients, due both to an absolute deficiency of helper/inducer lymphocytes and an increase in suppressor/cytotoxic lymphocytes. Increased HLA‐DR expression, evidence of lymphocyte activation, was present in seven of 12 patients evaluated and was confined to the suppressor/cytotoxic lymphocyte population. In the bone marrow, the percentage of lymphocytes was increased two‐fold compared to normal bone marrow but the ratio of T cell subsets was not abnormal. Two of four patients evaluated after haematopoietic recovery following ATG treatment showed a return to normal of the T4/T8 ratio; in two others a low T4/T8 ratio persisted despite recovery. These results indicate that lymphocyte subset imbalance and lymphocyte activation are present in many patients with aplastic anaemia, either as a contributing factor or as a result of bone marrow failure.
Arachidonic acid and leukotriene B4 induce aggregation of human peripheral blood mononuclear leucocytes in vitro
Authors: Villa Silvia , Colotta Francesco , Gaetano Giovanni DE , Semeraro Nicola 
Published: March 2008

SummaryPeripheral human blood mononuclear leucocytes (MNL) aggregated in response to arachidonic acid (AA) in vitro. This phenomenon was similar to that already described for polymorphonuclear cells (PMN). The effect of AA was concentration‐dependent and was shared only by the structurally related di‐homo‐y‐linolenic acid among the other fatty acids tested. A number of agents able to induce platelet aggregation such as ADP, collagen, serotonin and a stable prostaglandin analogue all failed to stimulate MNL or PMN aggregation. Inhibitors of cyclo‐oxy‐genase activity such as acetylsalicylic acid and indomethacin not only did not prevent AA‐induced aggregation, but even potentiated it. In contrast, both nordihydroguaiaretic acid and BW 755C, two inhibitors of cyclo‐oxygenase and lipoxygenase, strongly prevented MNL aggregation. Thus AA seems to aggregate MNL through the mediation of lipoxygenase products. This is supported by the observation that leukotriene B4 (LTB4) also induced MNL aggregation. When highly purified lymphocyte and monocyte preparations were assessed separately, the latter responded to AA similarly to mixed MNL whereas lymphocyte aggregation was inconsistent, small and reversible even at high concentrations of AA. Although the pathophysiological significance of the MNL aggregation described here is still obscure, assembly of these cells‐particularly monocytes‐at the site of injury might be a crucial event.
GM 58/8: a monoclonal antibody that identifies a new lineage‐specific determinant expressed by myeloid progenitors (CFU‐GM) and their progeny
Authors: Gupta Amar Das , Brice Martha , Yokochi Takashi , Papayannopoulou Thalia , Stamatoyannopoulos George 
Published: March 2008

SUMMARYA cytotoxic (IgM) monoclonal antibody (McAb) raised against human erythroleukaemia cell line HEL appears specific for the myelomonocytic lineage. Indirect immunofluorescence and fluorescence‐activated cell sorter analyses of peripheral blood and bone marrow cells showed that this McAb (designated GM 58/8) reacts exclusively with more than 90% of the granulocytes, monocytes and myeloid precursors. The positive (fluorescent) fraction sorted from McAb‐treated bone marrow buffy coat cells showed a marked enrichment of myeloid precursors, while nonmyeloid cells were recovered in the negative fraction. GM 58/8 specifically inhibited the growth of 90‐100% of the committed myelomonocytic progenitors (CFU‐GM) in five complement‐mediated cytotoxicity experiments. GM 58/8 had virtually no effect on the erythroid progenitor (BFU‐E and CFU‐E) growth. Cell sorting experiments using this McAb resulted in recovery of 84% of CFU‐GM among the fluorescent fractions. Comparisons with other anti‐myelomonocytic McAbs reported so far suggest that GM 58/8 has more restricted reactivity and shows more efficient CFU‐GM cytotoxicity. Patterns of reactivity with normal cells and established lines indicate that the antigenic determinant identified by GM 58/8 is different from that recognized by previously described anti‐myelomonocytic McAbs. McAb GM 58/8 could be used to isolate or remove pure populations of progenitors and/or more differentiated cells of the myelomonocytic lineage for in vitro studies. This study also provides evidence that the HEL cell line, derived originally from an erythroleukaemia patient, expresses an antigenic determinant shared by the normal cells of myelomonocytic lineage.