bluuebunny/crossref_metadata_2025 huggingface dataset:
Myeloid progenitor surface antigen identified by monoclonal antibody
Authors: Bradstock Kenneth F. , Favaloro Emmanuel J. , Kabral Arnold , Kerr Arna , Hughes Wilbur G. , Musgrove Elizabeth
Published: March 2008

Summary. A mouse monoclonal antibody, WM‐15, has been developed which reacts with a human myeloid lineage‐restricted cell surface antigen. WM‐15, an IgG1 antibody, reacts with a mean of 3.8% of normal bone marrow mononuclear cells, identifying predominantly promyelocytes and myeloblasts, and in fluorescence‐activated cell sorting experiments produces enrichment of bone marrow granulocyte‐macrophage progenitor cells. Normal mature monocytes and granulocytes are weakly labelled by WM‐15, but other haemopoietic cells including erythroblasts and all lymphoid cells are unreactive. The myeloid specificity of this antibody is highlighted by its reactivity with myeloid leukaemia cell lines and 65% of cases of acute myeloid leukaemia, while lymphoid cell lines and leukaemias are WM‐15 negative. WM‐15 appears to be a useful reagent for further investigation of normal and abnormal myelopoiesis.
A study of cell mediated and humoral immunity in haemophilia and related disorders
Authors: Moffat Elizabeth H. , Bloom A. L. , Jones Jennifer , Matthews N. , Newcombe R. G.
Published: March 2008

Summary. Helper (OKT4) and suppressor (OKT8) T lymphocyte populations and functional assays of cellular immunity were studied in 37 patients with haemophilia and related disorders in parallel with age matched control subjects. The study included 26 patients with factor VIII (FVIII:C) deficiency, eight patients with factor IX deficiency and three patients with severe von Willebrand's disease (vWd). In patients with factor VIII deficiency low helper T lymphocyte counts, low T helper: suppressor ratios and a diminished response to the lymphocyte mitogen phytohaemagglutinin with decreased natural killer cell activity were observed. Individuals with factor IX deficiency had low absolute T lymphocyte (OKT3) counts and T helper cell counts. Patients with severe factor VIII deficiency (FVIII:C<1 u/dl) had lower T helper suppressor ratios and lower killer cell and natural killer cell activity in comparison to mildly affected individuals and all of the severely affected factor IX deficient cases. Studies of humoral immunity revealed a generalized increase in immunoglobulin levels in patients with coagulation disorders of any type. The total haemolytic complement activity was reduced in a significant proportion of haemophilic subjects. Levels of alpha‐1‐interferon were elevated in the groups of haemophilic subjects studied. The abnormalities of cellular and humoral immunity observed did not correlate with the amount or type of coagulation factor administered to individual patients in the preceding 2 years. The most marked abnormalities of immune function occurred in the one patient diagnosed as suffering from AIDS on clinical grounds.
In vitro tests in severe aplastic anaemia (SAA): a prospective study in 46 patients treated with immunosuppression
Authors: Bacigalupo A. , Podesta M. , Frassoni F. , Piaggio G. , Van Lint M. T. , Repetto M. , Marmont A. M.
Published: March 2008

Summary Forty‐six patients with severe aplastic anaemia (SAA) were studied for CFU‐c growth on admission and 1 month post‐treatment with immunosuppression (IS). Twenty‐three patients became transfusion independent after IS, and were considered responders, and 23 did not. CFU‐c growth from unfractionated bone marrow cells was comparable in both groups on admission and 1 month post‐treatment. CFU‐c growth from E rosette depleted BM cells (E‐BM) was also comparable on admission. However, 1 month post‐treatment, responders showed a significantly higher CFU‐c growth (P = 0.02) from E‐BM cells compared to non‐responders. At the same time 7/8 responders studied showed T cell mediated suppression of autologous CFU‐c growth. T cell depletion experiments do not give predictive information on the outcome of IS therapy on admission. They may, however, be helpful to identify responders early post‐treatment.
Lactoferrin in the myeloproliferative disorders: a search for granulopoietic regulator defects
Authors: Brown Ross D. , Rickard K. A. , Kronenberg H.
Published: March 2008

Summary Evidence of a defect in the negative feedback control of granulopoiesis in the myeloproliferative disorders is presented. Neutrophil release of lactoferrin, plasma lactoferrin concentration, the number of lactoferrin receptor sites on mononuclear cells and granulocyte‐monocyte colony stimulating factor (GM‐CSF) release from peripheral blood cells were determined in patients with myeloproliferative disorders and compared with normal individuals. There was a significantly (P<0.001) decreased release of lactoferrin from the neutrophils of patients with myeloproliferative disorders which could be responsible for a reduced suppression of GM‐CSF release from mononuclear cells which in turn may be responsible for the increased myeloid proliferative activity in patients with myeloproliferative disorders.
Complete correction of Glanzmann's thrombasthenia by allogeneic bone‐marrow transplantation
Authors: Bellucci S. , Devergie A. , Gluckman E. , Tobelem G. , Lethielleux P. , Benbunan M. , Schaison G. , Boiron M.
Published: March 2008

Summary Allogeneic bone marrow transplantation (BMT) successfully corrected type I thrombasthenia in a 4‐year‐old boy. The donor was his HLA‐A, B and D identical 14‐year‐old brother who was heterozygous for thrombasthenia. A first transplant after conditioning with cyclophosphamide and thoracoabdominal irradiation was rejected, but a second transplant using CCNU, cyclophosphamide, procarbazine and horse antihuman thymocyte globulin in the preparative regimen was successful. Engraftment was proven by studies of platelet membrane antigens, PLA1 and glycoprotein IIb/IIIa complex and by platelet function studies. Haemor‐rhagic manifestations completely disappeared; platelet membrane markers and clot retraction returned promptly to normal values, and platelet aggregation tests more slowly. Twenty‐four months after bone‐marrow transplant, the patient was well with mild chronic hepatic graft versus host disease. BMT therefore appears to be a possible treatment for severe inherited platelet disorders.
Acquired autoimmune thrombocytopenia after allogeneic bone marrow transplantation
Authors: Bierling Philippe , Cordonnier Catherine , Fromont Patricia , Rodet Martine , Tanzer Joseph , Vernant Jean‐Paul , Braco Christine , Duedari Najib
Published: March 2008

Summary A 29‐year‐old man in remission from acute myeloblastic leukaemia was treated by chemoradiotherapy and transplantation of bone marrow (BMT) collected from his HLA identical brother. Engraftment was documented on D12. Transient acute GVHD (grade II) appeared from D34. No infection complicated the BMT. Nevertheless severe thrombocytopenia persisted and was unresponsive to marrow donor platelet transfusion. The platelet immunofluorescence test demonstrated the autoimmune basis of the thrombocytopenia. This study suggests that the transient immune imbalance observed in the early post graft period could facilitate the appearance of autoimmune cytopenias.

Prolonged thrombocytopenia may occur after bone marrow transplantation (BMT). This requires platelet support which could delay the discharge from hospital. Thrombocytopenia is mostly related to marrow insufficiency and/or viral infections. We report a case of severe autoimmune thrombocytopenic purpura (AITP) in a recipient of an allogeneic BMT.
The myelodysplastic syndromes: different evolution patterns based on sequential morphological and cytogenetic investigations
Authors: Tricot G. , Boogaerts M. A. , Wolf‐Peeters C. De , Van den Berghe H. , Verwilghen R. L.
Published: March 2008

Summary Serial morphological and cytogenetic investigations were performed in 46 patients with the myelodysplastic syndrome (MDS). Twenty‐one patients (45.5%) progressed to AML (> 30% blasts in bone marrow smears).

Based on sequential determinations of percentages of bone marrow blasts, three patterns of evolution were observed in MDS. Patients with evolution pattern A (48%) had an apparently stable disease with minimal or no increase in bone marrow blasts. Exceptionally they developed new or additional chromosomal anomalies during the course of their disease. Cases in this group, who showed no abnormal localization of immature myeloid precursors (ALIP) at time of diagnosis experienced prolonged survival (median: 43 months), while ALIP positive patients had shorter survival times (median: 14 months), with high probability of early death from infections and/or bleeding problems. Patients with evolution pattern B (28%) initially had a morphologically stable disease, comparable to cases with evolution pattern A, but showed an abrupt shift from MDS to AML. Most of these patients (82%) were ALIP positive and a substantial proportion (46%) showed karyotype anomalies at diagnosis. The abrupt shift to AML in these patients was frequently (61.5%) associated with additional cytogenetic anomalies. Patients with evolution pattern C (24%) showed a gradual increase in bone marrow blasts. The majority of these cases (8/11) ultimately developed acute myeloid leukaemia (gradual progression to AML), whereas some patients (3/11) died from infections and/or haemorrhagic complications before they had reached the level of clinical AML. All of these patients were ALIP positive at diagnosis and no additional cytogenetic alterations occurred during evolution.

Acquisition of new karyotypic anomalies during the course of MDS was almost invariably associated with abrupt shift to AML.
Lymphoid crisis with T‐cell phenotypes in a patient with Philadelphia chromosome negative chronic myeloid leukaemia
Authors: Soda H. , Kuriyama K. , Tomonaga M. , Yao E. , Amenomori T. , Yoshida Y. , Matsuo T. , Jinnai I. , Sadamori N. , Ichimaru M.
Published: March 2008

Summary A case of Philadelphia (Ph1) chromosome negative chronic myeloid leukaemia (CML) developed lymphoid crisis. Immunological marker studies disclosed that the lymphoid cells were sheep erythrocyte‐rosetting‐, Leu‐1+, Leu‐5+, OKT‐4+, OKT‐8+, common ALL antigen‐, HLA‐DR‐, cytoplasmic and surface immunoglobulin‐, MAS 036C(antithymocyte)+ (after in vitro culture) and terminal deoxynucleotidyl transferase‐, indicating T‐cell phenotypes, probably of common thymocytes. Cytochemical staining also demonstrated immature T‐cell characters: dot‐positivity for acid phosphatase and beta‐glucuronidase, and negative for acid alpha‐naphthyl acetate esterase. All bone marrow metaphases exhibited normal karyotypes. Our observation suggests that the neoplastic features of a common stem cell for myeloid and lymphoid cell lines are very similar in Ph1 positive and negative CMLs, and that the stem cell can differentiate towards T‐lineage.
Acute lymphoblastic leukaemia in adults: results of a ‘total‐therapy’programme in 47 patients over 15 years old
Authors: Sánchez‐Fayos J. , Outeiriño J. , Villalobos E. , Paniagua C. , Calabuig T. , Lite M. , Figuera A. , Pérez‐Rus G. , Prieto E. , Serrano J. , Escudero A.
Published: March 2008

Summary For the last 13 years, 47 patients with ALL over 15 years old (range 15–72; median 21) entered a ‘total‐therapy’ programme. All cases received a 6–8 week induction course of PRD, VCR, DRB and/or L‐ASN. Prophylaxis of CNS was done by cranial radiotherapy plus i.t. MTX in 32/45 patients who attained complete remission (CR). After CR, subsequent therapy involved a programme of maintenance with 6MP and MTX at full doses. Pulses of intermittent reinforcement (PRD, VCR and DRB) were done for 2 weeks, every 3 months, for at least 3 years. CR was achieved in 42/47 patients (89.3%). The median relapse‐free survival of the patients who attained CR was 57 months, with an 8‐year estimated disease‐free survival rate of 43% for those cases. If actuarial assumptions were to be sustained, it would indicate an encouraging cure rate of 38% of all our adult ALL patients (mainly in those cases between 15 and 30 years old).
Protoporphyrin accumulation by mitogen stimulated lymphocytes and protoporphyrinogen oxidase activity in patients with porphyria variegata and erythropoietic protoporphyria: evidence for deficiency of protoporphyrinogen oxidase and ferrochelatase in both diseases
Authors: Siepker Lydia J. , Kramer Sidney
Published: March 2008

Summary

In erythropoietic protoporphyria (EPP) and porphyria variegata (PV) excess protoporphyrin is excreted in the stool, suggesting one or more enzyme defects in the terminal steps of the haem biosynthetic pathway.

We measured protoporphyrinogen oxidase (PPO), which catalyses the oxidation of protoporphyrinogen to protoporphyrin, in both EPP and PV patients and in the offspring of PV patients. In the same subjects we measured protoporphyrin formation by mitogen stimulated lymphocytes, with delta aminolaevulinic acid (ALA) as substrate and with the addition of chelators or iron, an indirect measure of ferrochelatase activity. PPO activity was reduced by 41% (P<0.001) in PV patients and in 50%0 of their offspring, and by 36% (P<0.001) in EPP patients. Protoporphyrin accumulation in stimulated lymphocytes was increased by 1.3‐fold (P<0.001) in EPP and 1.5‐fold (P<0.001) in PV patients compared to normal subjects. There was a significant difference in protoporphyrin accumulation between iron deficient and iron replete cells from PV patients as compared to normals but not as marked as for EPP cells treated similarly. Stimulated lymphocytes from prepubertal PV offspring with reduced PPO activity accumulated normal amounts of protoporphyrin. We have interpreted our findings as follows: PPO is significantly reduced in both diseases. Ferrochelatase becomes defective in PV patients after puberty. This could explain why PV is clinically and biochemically manifest only after puberty. As it has been repeatedly shown that ferrochelatase is markedly
Ultrastructural localization of transferrin, transferrin receptor, and iron‐binding sites on human placental and duodenal microvilli
Authors: Parmley Richard T. , Barton James C. , Conrad Marcel E.
Published: March 2008

Summary

Ultrastructural methods were used to determine the subcellular location of the transferrin receptor, transferrin and iron‐binding sites on human term placenta and human duodenum microvillus surfaces. The transferrin receptor and transferrin were localized by immunocytochemical methods employing either OKT9, a human transferrin receptor monoclonal antibody, or mouse anti‐human transferrin (ATfn), both followed by a horseradish peroxidase (HRP)‐conjugated goat anti‐mouse IgG (GAM‐HRP) and diaminobenzidine (DAB) sequence. Iron‐binding sites were localized by acid ferrocyanide (AF) staining after saturation of tissue specimens with iron, accomplished with iron nitrilotriacetate (FeNTA), a known transferrin iron donor. Placental microvillus surfaces demonstrated staining for the OKT9‐GAM‐HRP‐DAB‐reactive transferrin receptor, ATfn‐GAM‐HRP‐DAB‐reactive transferrin, and FeNTA‐AF‐reactive iron acceptor, whereas enterocyte microvillus surfaces lacked significant staining with each of these methods. FeNTA‐AF stained iron‐binding substance in placental and enterocyte microvilli and cytoplasmic matrix. Thus using the same ultrastructural immunostaining and cytochemical methods transferrin receptor, transferrin, and nitrilotriacetate iron acceptor sites can be demonstrated on the microvillus surface of human placenta but not on the microvillus surface of human duodena.
The kinetics of unmatched and HLA‐matched 111In‐labelled homologous platelets in recipients with chronic marrow hypoplasia and anti‐platelet immunity
Authors: Peters A. M. , Porter J. B. , Saverymuttu S. H. , Malik F. , Zuiable A. , Lavender J. P. , Schwarz G. , Lewis S. M. , Gordon‐Smith E. C.
Published: March 2008

Summary

The kinetics of homologous platelets, labelled in plasma with 111In‐tropolonate, have been studied in five recipients with chronic marrow hypoplasia and severe thrombocytopenia, who were refractory to platelet transfusions as a result of alloimmunization. Mean platelet life span (MPLS), recovery, plasma 111In level and splenic and hepatic uptake kinetics were studied on two occasions, one using HLA‐matched platelets and the other unmatched platelets. In each case, recovery of labelled platelets at 1 h post‐injection and MPLS improved with HLA matching, although this improvement was highly variable. Only two of the five subjects would have derived any significant benefit from HLA‐matched as compared with unmatched platelet transfusions. It was concluded that the need exists for additional cross‐matching procedures, possibly related to platelet specific antigens, in patients who remain refractory to platelet transfusion.
Graft‐versus‐host disease prophylaxis with anti‐T‐cell monoclonal antibody OKT3, prednisone and methotrexate in allogeneic bone‐marrow transplantation
Authors: Filipovich A. H. , Krawczak C. L. , Kersey J. H. , McGlave P. , Ramsay N. K. C. , Goldman A. , Goldstein G.
Published: March 2008

Summary

A new regimen for prevention of acute graft‐versus‐host disease (GvHD)—OKT3 (murine monoclonal anti‐pan‐T antibody), prednisone and methotrexate (OKT3‐pred‐MTX)—was compared with the Minnesota standard regimen—antithymocyte globulin, prednisone and methotrexate (ATG‐pred‐MTX)—for adverse effects, effect on incidence of acute GvHD, and survival at 1 year post‐transplant. Twenty patients (aged 25 ± 9 years) had bone‐marrow transplantation (BMT) from their HLA‐MLC identical sibling donors for treatment of aplastic anaemia (four), acute leukaemia in remission (13) or chronic myelogenous leukaemia (three). These 20 patients received (OKT3‐pred‐MTX) on days 8‐22 post‐transplant. Results of this group are compared to those of 19 concurrent patients (aged 26 ± 12 years) who received ATG‐pred‐MTX on days 8‐22 post‐transplant. On the first day of treatment, 20/20 OKT3 patients and 18/19 ATG patients were febrile, Within 24 h of the first dose of OKT3, 6/20 patients experienced dyspnoea or chest pain and 3/20 patients developed diarrhoea. No further adverse effects were seen after the second dose of OKT3 and no late adverse effects were attributed to this drug. Time to engraftment (x̄ 25 d) was not statistically significantly different in the two prophylactic groups. Acute GvHD was diagnosed in 14 of 20 patients who received OKT3‐pred‐MTX and in eight of 19 patients who received ATG‐pred‐MTX (P= 0.06). The incidence of hepatic or gastrointestinal GVHD (≥ grade 2) was similar in the two groups: 4/20 OKT3‐pred‐MTX, 6/19 ATG‐pred‐MTX. Characteristics of post‐transplant infections were also similar for the two prophylactic groups. Survival at 1 year post‐transplant was 65% for patients
Activation of neutrophil phagocytosis of complement coated and IgG coated sheep erythrocytes by platelet release products
Authors: Sakamoto H. , Ooshima A.
Published: March 2008

Summary

Phagocytosis by human neutrophils of opsonized sheep erythrocytes with rabbit immunoglobulin M and human complement (IgM‐EACh) and those with rabbit immunoglobulin G (IgG‐EA) increased 2‐3 times of control neutrophils after treatment with released products from activated platelets (PRPr). The factors in PRPr which augmented IgM‐EAChphagocytosis were suggested to be adenosine diphosphate (ADP) and triphosphate (ATP) by experiments using apyrase treated PRPr and by direct exposures of neutrophils with these nucleotides. The presence of two other stimulators for phagocytosis of IgG‐EA were suggested. One was a macromolecular substance of molecular weight greater than 100 000 and the other was a substance of molecular weight less than 500. The latter may be a prostaglandin because the activity was easily removed by acid‐extraction with ethylacetate from the water phase, and because prior incubation of platelets with 10μg per ml indomethacin deprived PRPr of its low molecular weight activity. Exposure of neutrophils to thromboxane B2, prostaglandin F2α and prostaglandin E2at the concentration of 10−6–10−7mg/ml actually increased the phagocytosis of IgG‐EA. The activity in the macromolecular fraction was not affected by prior incubation of platelets with indomethacin.
A regulatory role of activated T‐lymphocytes on human megakaryocytopoiesis in vitro
Authors: Geissler D. , Konwalinka G. , Peschel C. , Grünewald K. , Odavic R. , Braunsteiner H.
Published: March 2008

Summary

Cellular interactions responsible for regulating in vitro megakaryocytopoiesis were studied using a microagar culture system which permits the simultaneous proliferation of human megakaryocytic progenitor cells (CFU‐M) and T‐lymphocytic colonies (CFU‐TL). The proliferation of these colony types depends mainly on two factors: phytohaemagglutinin (PHA) and erythropoietin (EP). The direct addition of increasing PHA concentrations to the liquid overlayer resulted in a parallel increase of CFU‐M and CFU‐TL. If the T‐lymphocytes were removed by an E‐rosetting technique a marked diminution of CFU‐M and CFU‐TL numbers was observed. However, monocyte depletion resulted in a marked augmentation of CFU‐M proliferation compared to unfractionated mononuclear cells. In order to confirm that the reduction of CFU‐M proliferation observed after T‐depletion was primarily mediated by the absence of T‐lymphocytes, we have co‐cultured different concentrations of previously removed autologous T‐lymphocytes with a constant number of T‐depleted bone marrow cells. A parallel increase of CFU‐TL and CFU‐M was found if 0.75‐7.5 × 104 T‐lymphocytes were added to the culture. In conclusion, our results indicate that activated T‐lymphocytes augment proliferation of human bone marrow CFU‐M and that monocytes are less important for the growth of megakaryocytic colonies.
Suppressor cell function after intravenous gammaglobulin treatment in adult chronic idiopathic thrombocytopenic purpura
Authors: Delfraissy J. F. , Tchernia G. , Laurian Y. , Wallon C. , Galanaud P. , Dormont J.
Published: March 2008

Summary

Intravenous gammaglobulin (IVIgG) was given to seven adults with chronic idiopathic thrombocytopenic purpura (ITP). In parallel with platelet count, we studied Con A induced suppressor cell function for the autologous in vitro B cell response, T cell subsets and PAIgG levels, immediately before and 3–4 d after completion of treatment. Before treatment all patients had normal T cell subsets, decreased T suppressor cell function and increased levels of PAIgG. After IVIgG infusions, two patients were unresponsive and neither suppressor cell function nor PAIgG levels varied. In contrast, in the five responding patients we found an improvement in suppressor cell function and a decrease in PAIgG levels, while T cell subsets remained unmodified. Such results were reproducible in three patients after a second series of gammaglobulin infusions. Our results support the hypothesis that IVIgG infusion, apart from its effects on the reticuloendothelial system, may modulate the immune response by enhancing suppressor T cell function.
A myelodysplastic syndrome preceding acute lymphoblastic leukaemia
Authors: Berneman Z. N. , Bockstaele D. Van , Meyer P. De , der Planken M. Van , Vertessen F. , Bock R. De , Peetermans M. E.
Published: March 2008

Summary

The bone marrow of a patient with pancytopenia showed dyserythro‐poiesis, dysmegakaryocytopoiesis and 13% blasts. The patient was hypertransfused and the pancytopenia resolved completely for 1 month, while the blastic infiltration in the bone marrow remained. Three months later a frank acute lymphoblastic leukaemia developed.
The effect of indomethacin treatment on lymphocyte PHA reactivity in healthy controls and patients with lymphoma and sarcoidosis
Authors: Underhill G. , Valdimarsson H.
Published: March 2008

Summary

Lymphocytes from healthy volunteers who took indomethacin orally for 3 d showed an enhanced in vitro response to phytohaemagglutinin (PHA). When indomethacin was added in vitro, lymphocytes from healthy controls showed similar but more consistent increases of PHA responses than lymphocytes from patients with sarcoidosis or lymphoma. Moreover, the enhancing effect of indomethacin was by and large more pronounced in those patients who had relatively normal PHA lymphocyte responses in the absence of indomethacin, and the presence of indomethacin failed in most instances to increase subnormal responses to normal control levels.

These findings are not consistent with the notion that increased prostaglandin synthesis is the principal cause of subnormal PHA reactivity of lymphocytes from patients with sarcoidosis or lymphoma.
Studies on the locomotory behaviour and adhesive properties of mononuclear phagocytes from blood
Authors: Lackie J. M. , Urquhart C. M. , Brown A. F. , Forrester J. V.
Published: March 2008

Summary

Mononuclear phagocytes isolated from peripheral blood move slowly on albumin‐, collagen‐ and fibronectin‐coated glass, as judged by analysis of time‐lapse film, although their movement is stimulated somewhat by serum. When a differential‐adhesion method is used to purify monocytes from a crude mononuclear cell fraction it appears to select a particularly slow‐moving sub‐group. Despite their slow rate of movement (especially in comparison with neutrophils) monocytes move over and penetrate monolayers of endothelial cells, apparently without difficulty; they are, however, restricted to the upper surface of a fibroblast monolayer. Penetration of reconstituted collagen gels by freshly isolated monocytes was not observed but cultured monocytes, which spontaneously detached from the culture substratum over a 48 h period, did invade collagen gels. The adhesive properties of these cultured cells, measured in a flow‐chamber assay, did not differ from freshly isolated monocytes purified on serum‐coated dishes and detached with EDTA, and their invasive capacity does not seem to be a consequence of altered adhesive properties. The behavioural differences between monocytes and neutrophils are considerable, although both cell types have to leave the circulation and penetrate tissues in vivo.
Massive chemotherapy with autologous bone marrow transplantation in 50 cases of bad prognosis non‐Hodgkin's lymphoma
Authors: Philip T. , Biron P. , Maraninchi D. , Goldstone A. H. , Herve P. , Souillet G. , Gastaut J. L. , Plouvier E. , Flesh Y. , Philip I. , Harousseau J. L. , Mevel A. Le , Rebattu P. , Linch D. C. , Freycon F. , Milan J. J. , Souhami R. L.
Published: March 2008

Summary

50 cases of advanced, intermediate (18) and high grade (32) non‐Hodgkin's lymphoma (NHL) including 16 with Burkitt lymphoma have been treated with very high dose chemotherapy and autologous bone marrow transplantation (ABMT). These cases represent a retrospective analysis of the combined experience of a recently established collaborative group. 31 patients were treated with a protocol used in Lyon, 12 with that used in Marseille and seven with that used in London. Although the details of drug administration differed, each protocol was based on high dose alkylating agent (cyclophosphamide or melphalan), BCNU and cytosine arabinoside. 16 patients had drug resistant progressive NHL. Of these 11 responded to high dose treatment (nine CR, two PR). The duration of CR in this group was short (median 104d) and only one patient was in CR at 1 year. 19 patients had relapsed on previous therapy but were still responding to conventional rescue therapy. Following high dose therapy 47% of these patients are in continuous CR with a median time of observation of 300 d (73–962 d). Seven patients were partial responders to conventional induction therapy. Of these, six had a CR with high dose treatment and are still in CR (range 39–1230 d, median 200 d). Eight patients received high dose therapy as intensification after a long delay to CR with conventional treatment. Of these, four are alive and in remission 124–763 d after
The influence of the polyphenols of cider on plasmin and plasminogen activators
Authors: Ogston D. , Lea A. G. H. , L anghorne P. , Wilson S. B.
Published: March 2008

Summary

Preliminary findings suggested that the inhibitory activity on fibrinolysis produced by most varieties of cider is due to their content of polyphenols. In particular, the inhibitory activity co‐eluted with the brown coloration on gel filtration, was removed by adsorption with polyvinylpyrrolidine, and was greatly reduced in a type of cider with a low concentration of phenolic compounds.

The individual polyphenols of apple juice and ciders were examined for their ability to inhibit tissue activator, urokinase and plasmin. Neither phloridzin nor chlorogenic acid had any inhibitory activity at concentrations of 500 μg/ml while epicatechin had only a slight inhibitory effect at this concentration. The procyanidin fractions were markedly inhibitory on urokinase‐induced clot lysis, the amidolytic activity of plasmin and on the fibrinolytic activities of plasmin, urokinase and tissue activator on fibrin plates: inhibition was noted at concentrations as low as 0.25 μg/ml. The order of inhibition was polymer > oligomer > trimer > dimer.
Platelet‐associated complement in chronic ITP
Authors: Kurata Y. , Curd J. G. , Tamerius J. D. , McMillan R.
Published: March 2008

Summary

Chronic ITP is due to antibody‐induced destruction of platelets by the reticuloendothelial (RE) system. The role of complement in this process is unclear. We measured platelet‐associated complement (PAC) components C3, C3bi, C4 and C9 in 16 patients with chronic ITP, in two of these patients prior to and after splenectomy. Competitive solid‐phase radioimmunoassays using monoclonal antibody (anti‐C3d, anti‐C3bi neoantigen or anti‐C9) or affinity‐purified heterologous antibody (anti‐C4) were used. Mean values (±SD) of normal subjects (ng/107 plts) were: PAC3d 17.6 ± 6.8; PAC3bi 11.6 ± 2.3; PAC4 1.6 ± 0.5; PAC9 9.9 ± 2.6. Significantly elevated (< 2 SD) PAC3, PAC3bi, PAC4 and PAC9 levels occurred in 12/16, 11/14, 10/14 and 5/9 chronic ITP patients. The PAC3, PAC3bi and PAC9 values correlated inversely with the patients’platelet counts (P < 0.001); PAC4 levels did not. A positive correlation was also noted between PAC3, PAC3bi and PAC9 while PAC4 values showed no correlation. Two patients with preoperative elevation of all four PAC proteins showed normalization of PAC3, PAC3bi and PAC9 values after a splenectomy‐induced remission; PAC4 levels remained elevated for up to 5 months after surgery. We conclude that in vivo C activation occurs in most chronic ITP patients with binding of C3 and C9 to the platelet surface. This in vivo C activation may promote more efficient phagocytosis (C3b) and possibly platelet lysis (C5‐9) in some ITP patients.
Interferon is effective in hairy‐cell leukaemia
Authors: Worman C. P. , Catovsky D. , Bevan P. C. , Camba L. , Joyner M. , Green P. J. , Williams H. J. H. , Bottomley J. M. , Gordon‐Smith E. C. , Cawley J. C.
Published: March 2008

Summary

Seventeen patients with hairy‐cell leukaemia (HCL) and peripheral cytopenias were given human lymphoblastoid interferon (Wellferon), 3 megaunits daily or 6 megaunits on alternate days intramuscularly, for 4–24 weeks. Twelve of the patients had undergone splenectomy, three had no palpable spleen and had therefore not been offered surgery, and two patients with substantial splenomegaly were given interferon (IFN) as treatment of first choice.

Toxic effects were minor except in one patient who experienced a severe form of somnolence syndrome. In all patients hairy cells (HCs) were cleared from the blood and platelet and Hb levels improved in 2–14 weeks. Neutrophils were improved in 14/17 of the patients. In the two patients with splenomegaly, the spleen became impalpable after 5–8 weeks therapy, and haematological improvement occurred at 12–14 weeks. HC infiltration of the marrow was reduced in all patients, but was complete (< 5%) in only two, both of whom had impalpable spleens.

Immunological surface‐marker studies confirmed that light‐chain‐restricted B cells disappeared from the blood in parallel with the clearance of morphological HCs. There was no evidence of HC maturation and no increase in phenotypic NK cells. T cells were moderately reduced and the relatively greater reduction of Leu 2a+ suppressor cells resulted in increased Leu 3a+/2a+ helper/suppressor ratios in 11/17 of the patients.

Early experience in the six patients who have stopped IFN suggests that, after an initial further increase in Hb and neutrophil levels, HCs gradually return with slow deterioration of haematological parameters.
Two types of nomifensine‐induced immune haemolytic anaemias: drug‐dependent sensitization and/or autoimmunization
Authors: Salama A. , Mueller‐Eckhardt C.
Published: March 2008

Summary. Thirty‐one patients who developed immune haemoiytic anaemia while receiving nomifensine were studied. We provide evidence that nomifen‐sine can cause two forms of immune haemolytic anaemia: one that is associated with an abrupt haemolytic episode due to drug‐dependent antibodies, and a less acute form associated with IgG autoantibodies. The majority of patients' serum samples (23 cases) contained IgG and/or IgM antibodies reacting to a highly variable extent with red blood cells (RBC) only in the presence of the drug and/ or its metabolites. Sera of six patients contained IgG autoantibodies which reacted, like those in warm autoimmune haemolytic anaemia, with RBC in the absence of drugs. Three patients had developed both types of antibodies. From a diagnostic viewpoint, nine of the drug‐dependent antibodies could not be identified by using the drug itself, but by its known (three cases) or unknown urine‐born metabolites (ex vivo antigens). We conclude that nomifensine can induce in vivo the production of RBC drug‐ and/or metabolite‐dependent antibodies, autoantibodies, or both in the same patient.
Clinical significance of positive platelet immunofluorescence test in thrombocytopenia
Authors: von dem Borne A. E. G. Kr. , Vos J. J. E. , van der Lelie J. , Bossers B. , van Dalen C. M.
Published: March 2008

Summary. The sensitivity and specificity of the platelet immunofluorescence test for the diagnosis of idiopathic thrombocytopenia (ITP) was studied in a series of 255 patients. Patients' platelets were tested directly. Diethyl‐ether eluates of these platelets and patients' sera were tested indirectly with normal donor platelets. When all three tests were considered, positive results were obtained for 92.0% of the ITP patients with a platelet count of < 150 × 109/1 and for 98.4% of the patients with a count of < 100 × 109/1. However, for many patients rather weak test results were obtained, with a score of ½‐1 in 59.8% of the patients. Most patients (94.1%) with a positive direct test had a positive indirect test on the eluate. Thus, platelet‐bound antibodies but not platelet‐bound immune complexes were present in most, if not all, patients. Positive immunofluorescence tests were obtained for many patients with a diagnosis other than ITP. This resulted in a low specificity of the test for the diagnosis of ITP, evidently because autoimmune thrombocytopenia occurred together with many other diseases and also because antibodies against platelet cryptantigens (expressed by the action of EDTA or by platelet fixation) were present in many patients.
K‐cell lymphocytosis/neutropenia syndrome: the neutropenia is not caused by autoimmunity
Authors: van der Veen J. P. W. , Goldschmeding R. , Miedema F. , Smit J. W. , Melief C. J. M. , von dem Borne A. E. G. Kr.
Published: March 2008

Summary. The role of humoral immune mechanisms in the pathogenesis of the neutropenia in five patients with chronic killer (K)‐cell lymphocytosis was studied. For the detection of neutrophil antibodies in the patient's biood, immunofluorescence, cytotoxicity and agglutination tests and a sensitive antibody‐dependent cellular cytotoxicity (ADCC) assay were applied. An assay for bone‐marrow colony growth (CFU‐GM, BFU‐E) inhibition was applied as well. A Clq‐binding test was used to detect immune complexes. The lymphocytes of all five patients had the capacity to lyse alloantibody sensitized neutrophils. Neutrophil‐bound IgG was found only in one patient. Two patients had neutrophil‐reactive antibodies in their serum; in one patient these antibodies were only detectable in the ADCC using the patient's serum to sensitize target cells. However, these antibodies reacted also with lymphocytes, were absorbable with platelets and thus probably were HLA antibodies. The serum of one of these two patients showed complement‐dependent CFU‐GM and BFU‐E inhibition, but the observed inhibition was probably also due to the anti‐HLA antibodies present in his serum, as the inhibiting effect disappeared after absorption of the serum with platelets. The serum of only one patient contained low amounts of immune complexes, as measured in the Clq‐binding test. Our data suggest that humoral autoimmune mechanisms, such as autoantibodies against neutrophils or neutrophil precursors or circulating immune complexes, do not seem to play an important role in the K‐cell lymphocytosis/neutropenia
Megaloblastic anaemia due to vitamin B12 deficiency caused by small intestinal bacterial overgrowth: possible role of vitamin B12 analogues
Authors: Murphy M. F. , Sourial N. A. , Burman J. F. , Doyle D. V. , Tabaqchali S. , Mollin D. L.
Published: March 2008

Summary. Megaloblastic anaemia due to bacterial overgrowth of the small intestine is due to vitamin B12 malabsorption. This report describes a patient with bacterial overgrowth of the small intestine who had megaloblastic anaemia and malabsorption of vitamin B12, but persistently normal levels of serum vitamin B12 and normal serum and red cell folate levels. However, there was evidence of vitamin B12 deficiency as shown by an abnormal deoxyuridine suppression test and by the response to treatment with physiological doses of vitamin B12. A relative increase in biologically inactive vitamin B12 analogues may be the explanation for the normal vitamin B12 level in this patient.
Bone lesions in chronic granulocytic leukaemia
Authors: Martell Robert W. , Myers H. S. , Jacobs Peter
Published: March 2008

Summary. Radiographic abnormalities in bone are unusual during the stable phase of chronic granulocytic leukaemia (CGL). A rare situation is reported in which a patient developed three distinctive skeletal lesions simultaneously in different anatomical sites. Firstly, in both fibulae symmetrical punched out and permeative lesions were present throughout much of the shafts, being most prominent in the mid‐diaphyseal regions. Secondly, the tibiae were slightly porotic and showed localized periosteal reactions, whereas in the fibulae there was extensive cloaking by a similar but much more intensive reaction. Thirdly, multiple osteosclerotic lesions were present in the pubic bones and in the proximal ends of the femora and humeri. Concurrently, fluctuant, culture negative swellings were present on the extremities. Histological examination of the material from the subcutaneous and lytic lesions showed only areas of fibrosis with islands of haematopoietic tissue, including scanty megakaryocytes. Bone marrow trephine biopsy showed the presence of myelofibrosis with islands of haematopoietic tissue typical of CGL without any evidence of blastic transformation.
Immunological phenotype of neoplasms involving the B cell in the last step of differentiation
Authors: San Miguel J. F. , Caballero M. D. , Gonzalez M. , Zola H. , Borrasca A. Lopez
Published: March 2008

Summary. The immunological phenotype of diseases involving the last step of B cell differentiation—multiple myeloma (MM, 38 patients) and Waldenström's macroglobulinaemia (WM, 12 patients)—was analysed with a panel of monoclonal antibodies (McAb) as well as conventional markers.

Most of the bone marrow plasma cells (80%) from MM patients reacted with the McAb OKT10, FMC8 and FMC48. Plasma cells were consistently negative with FMC7, Leu‐1 and mouse rosettes. Ia, B1 and SIg were expressed in a minority of plasma cells (<30%) in half of the cases. The circulating neoplastic cells from five MM patients showed a more immature phenotype, with a higher reactivity for OKIa, B1 and increased SIg and a lower expression of CIg, than bone marrow plasma cells.

The malignant cells of WM patients differed from those of MM in the reactivity with FMC7, being positive in 10 out of 11 cases, and in their high expression of B1, Ia and SIg with a predominant μ+ phenotype. Mouse rosettes and Leu‐1 were positive in one case; OKT10 was positive in three out of five WM patients studied. This phenotype indicates that WM cells correspond to an earlier stage of B cell differentiation than MM plasma cells. The McAb J5 was positive in three out of six MM and two out of four WM analysed. The antigenic differences observed in MM and WM patients support the notion that the cells of the neoplastic clone are able to undergo a certain degree of differentiation.
Pretreatment serum β2‐microglobulin in multiple myeloma
Authors: Brenning Gunilla , Simonsson Bengt , Källander Claes , Åhre Anders
Published: March 2008

Summary. Serum beta2‐microglobuline (S‐β2m) was evaluated in 121 untreated patients with multiple myeloma. Values > 3 mg/l were found in 82% of the patients. Mean S‐β2m values of the total group of patients correlated with clinical stage. However, there was no correlation if values were corrected for S‐creatinine. Seventy‐nine patients had normal (106 μmol/l) and 52 patients abnormal S‐creatinine. Patients with S‐β2m values below 7·6 mg/l had an estimated median survival of 44 months compared to 12 months for patients with levels above 7·6 mg/l. If S‐β2m values in patients with normal S‐creatinine were combined with values corrected for S‐creatinine from patients with elevated S‐creatinine a β2m cut off level of 6·6 mg/l gave a median probable survival of 43 months compared to 14 months. We conclude that pretreatment S‐β2 microglobulin is a useful marker for predicting survival in multiple myeloma. The problem of the relationship between S‐β2m and S‐creatinine is discussed.
Low protein C in the neonatal period
Authors: Karpatkin Margaret , Mannucci Pier Mannuccio , Bhogal Mhadu , Vigano Silvana , Nardi Michael
Published: March 2008

Summary. Protein C was measured by electroimmunoassay in 47 infants within 24 h of delivery. Gestational age ranged from 28 to 43 weeks. The mean level was 27% (range < 10–67%) of the normal adult mean. In the 22 infants who had no clinical problems, protein C levels correlated significantly with gestational age. In the 25 who were sick there was no correlation, and the mean level was significantly lower than that of the healthy infants. Postnatal rise was slow; on day 7 the mean was 32% and on day 28, 31%. Levels of protein C correlated significantly with prothrombin in both the healthy and sick infants. Crossed immunoelectrophoresis in the presence of calcium ions gave one protein C peak of the same electrophoretic mobility as is seen in plasma of healthy adults, indicating that the infants’ protein C is gamma carboxylated. It is concluded that: (1) Protein C in neonates is in or below the range associated with thromboembolism in patients congenitally deficient in this protein; (2) protein C levels correlate with gestational age; and (3) the low levels during the neonatal period are not due to decreased gamma carboxylation but may reflect decreased synthesis when compared to the older child or the adult.
Fluorescence probe measurement of the pH of the transferrin microenvironment during iron uptake by rat bone marrow erythroid cells
Authors: Veldman A. , Van der Heul C. , Kroos M. J. , Van Eijk H. G.
Published: March 2008

Summary. Fluorescence probe measurements of the transferrin micro‐environment during iron uptake by rat erythroid cells revealed that part of the transferrin is taken up in an acidic environment. The pH of this intracellular transferrin environment is 5·7. When rat erythroid cell precursors are incubated with diferric transferrin then in the incubation medium monoferric transferrins TfNFe and TfFec appear. In view of the known instability of TfNFe at acidic pH, TfNFe cannot arise after endocytosis of Tf2Fe in acid vesicles at pH below 6·0. The results support the existence of a mechanism other than endocytosis in the iron uptake process in rat erythroid cells.
Enumeration of absolute numbers of T lymphocyte subsets in B‐chronic lymphocytic leukaemia using an immunoperoxidase technique: relation to clinical stage
Authors: Markey Geraldine M. , Alexander H. D. , Agnew A. N. D. , Mcconnell Robyn E. , Morris T. C. M. , Robertson J. H. , Crockard A. D. , Bridges J. M.
Published: March 2008

Summary. An immunoperoxidase technique has been used to identify and enumerate helper and suppressor T‐cell subsets, as defined by reactivity with Coulter T4 and OKT8 monoclonal antibodies in 54 patients with B chronic lymphocytic leukaemia (B‐CLL) and in the same number of matched controls. The ratio of T4+ to T8+ cells was significantly reduced in the B‐CLL group as a whole (P<0.001) and in each stage of the three clinical staging systems. There was an increase in the median absolute level of T8+ cells in the whole CLL group (P<0.001). However, subdivision of the CLL group by clinical staging systems revealed a large group (28 patients) in which median T8+ cell levels were not raised and median T4+ cell levels were low (P<0.001). There was no significant decrease in T4:T8+ ratio, increase in T8+ cells or decrease in T4+ cells with progression of clinical stage. Absolute numbers of E+ cells were significantly raised in all staging systems as were E+ T4− T8− cells (P< 0.001). A significant alteration in either of these populations with progression of clinical stage was not present.
Interaction of transferrin with iron‐loaded rat peritoneal macrophages
Authors: Saito Kainosuke , Nishisato Takuji , Grasso Joseph A. , Aisen Philip
Published: March 2008

Summary, Rat peritoneal macrophages are capable, in vitro, of processing and releasing iron derived from phagocytosed, immunosensitized red cells, From 20% to 60% of the red cell iron can be returned to the culture medium in 24 h, with resident macrophages more active than inflammatory, peptone‐induced macrophages. When apotransferrin is present in the culture medium, from 39% to 72% of iron released from macrophages is bound to the protein, with most of the remainder in a ferritin‐like form. No distinct preference of released iron for either site of transferrin could be observed. The absence of apotransferrin depresses iron release only slightly, with much of the iron then released in a form readily available to the protein in vitro. Pronase treatment of macrophages, which abolishes their ability to bind transferrin, depresses iron release no more than 10–15%. It appears, therefore, that binding of apotransferrin to macrophages may not be essential for iron excretion by the cells.
Natural killer cell activity following T‐cell depleted allogeneic bone marrow transplantation
Authors: Rooney C. M. , Wimperis J. Z. , Brenner M. K. , Patterson J. , Hoffbrand A. V. , Prentice H. G.
Published: March 2008

Summary. We have examined the recovery of natural killer (NK) cell function in seven recipients of MHC matched T cell depleted bone marrow allografts. NK cell activity against the erythroblastoid line K562 recovers 2–3 weeks after transplantation. Recipients also show a high level of killing of the T cell target HSB2 and of EBV transformed lymphoblastoid cell lines (B‐LCL). This activity peaks at 4–6 weeks and declines towards normal by 12–14 weeks after transplantation. Although killing of HSB2 and B‐LCL is usually the property of activated NK cells, few of these patients had any obvious ‘trigger’ of such activation: none had CMV infection, there were no episodes of graft rejection, and only two patients had mild and transient grade I graft versus host disease (GvHD). We conclude that T cell depletion does not affect the reconstitution of NK cell function and that NK cell activation occurs after T depleted bone marrow transplantation even in the absence of clinically detectable GvHD, graft rejection or CMV infection.