bluuebunny/crossref_metadata_2025 huggingface dataset:
Defective expression of T cell antigens in chronic lymphocytic leukaemia: relationship to T cell dysfunction
Authors: Kay Neil E. , Kaplan Manuel E.
Published: March 2008

Summary. In chronic lymphocytic leukaemia (CLL) peripheral blood T cells have a variety of functional abnormalities. To explore more extensively the T cell status of B‐CLL patients, surface immunoglobulin‐negative cells were isolated by sheep erythrocyte rosetting (ER) and the membrane phenotypes of the ER + cells defined by immunofluorescence utilizing monoclonal antibodies (MAb). In 11 of 18 CLL patients (CLL group I) there was excellent correlation between ER + and T3 (mature T cell marker) positivity. In the remaining patients (CLL group II), only 5–45% of ER+ cells were T3 positive, suggesting that many rosetting cells were non‐T, However, the ER+, T3 negative cells were nonreactive with OKM‐1 (MAb which detects monocytes and ‘null’ lymphocytes) or with OKT11, 9.6, and 35.1, MAb against the T cell E receptor. Moreover ER +, T3 negative cells were not stained with OKT4, OKT8, OKT6, OKT9, or OKT10. Treatment of group II ER + cells with neuraminidase increased (from 27% to 74%) the mean percentages of T3 positive cells detected, but not other membrane antigens. ER+ cells from group II patients, compared with normal and group I patients, exhibited diminished proliferative responses to PHA and Con‐A (P<0.01) and supported poorly pokeweed mitogeninduced proliferation of normal allogeneic B cells (P<0.01). Thus, in approximately one‐third of the CLL patients studied, many ER+ cells poorly express a number of membrane antigens characteristic of normal mature T cells, one of which (T3) is unmasked by neuraminidase treatment. This phenotypic abnormality appears to be associated with significant T cell dysfunction in vitro and may, at least in part, contribute to the commonly encountered immunological defects present in these patients.
Kinetic studies of the activation of factor X by factors IXa and VIII:C in the absence of thrombin
Authors: Neal Gregory G. , Esnouf M. Peter
Published: March 2008

Summary. The activation of factor X by the components of the intrinsic coagulation pathway has been studied using a preparation of bovine factor VIII which did not require ‘activation’ with thrombin prior to its participation in the reaction. Measurements of the kinetic parameters indicated that factor VIII: C stimulated the formation of factor Xa via a 170‐fold increase in the Vmax; factor VIII: C had little effect on the Km for factor X.
Malignant lymphomas with band 8q24 chromosome abnormality: a morphologic continuum extending from Burkitt's to immunoblastic lymphoma
Authors: Sigaux F. , Berger R. , Bernheim A. , Valensi F. , Daniel M. T. , Flandrin G.
Published: March 2008

Summary. Chromosome abnormality involving band 8q24 is present in the malignant cells in virtually all ‘Burkitt's’ type malignancies. t(8;14)(q24;q32) translocations have nevertheless been found in certain cases of malignant lymphomas (ML) described as ‘small non‐cleaved non‐Burkitt’, ‘immunoblastic’ or ‘histiocytic’. With a view to comparing objectively the histological picture of such lymphomas, we undertook morphometric analysis of seven cases of diffuse ML classed as ‘Burkitt's’ (three cases), ‘immunoblastic’ (two cases), ‘small non‐cleaved non‐Burkitt’ (one case) and ‘large‐cell lymphoma’ (one case), all exhibiting band 8q24 rearrangement arising from various translocations. Our study substantiates the view that the histologic picture of MLs with 8q24 anomaly fits into a morphological continuum containing ‘Burkitt's’, ‘small non‐cleaved non‐Burkitt’ and ‘immunoblastic’ lymphomas.
Two‐dimensional separation of α‐naphthyl acetate esterases in human leucocytes and platelets
Authors: Oertel Joachim , Kastner Michael
Published: March 2008

Summary. Normal human leucocytes and platelets contain esterases which hydrolyse α‐naphthyl acetate (αNA). Purified preparations from these cells were investigated by isoelectric focusing and subsequent polyacrylamide gradient gel electrophoresis at pH 9.0. Extractable αNA esterases were separated according to isoelectric point (pI) and molecular weight (MW).

Monocytes, lymphocytes, granulocytes and platelets contain a unique pattern of αNA esterases, most of which can be inhibited by diisopropyl fluorophosphate (DFP; 0.1 mM). Their activity, however, is not affected by eserine (0.1 mM) or p‐hydroxymercuribenzoate (1 mM). No protease activity of these enzymes was detected; it is likely that the majority constitute carboxylesterases (EC 3.1.1.1). Monocytes contain five αNA esterases which are additionally inhibited by bis(4‐nitrophenyl)‐phosphate (0.1 mM) and sodium fluoride (40 mM). PIs are in the range 5.7–6.2 and MWs are 145 000, 155 000, 250 000, 290 000 and 340 000. These enzymes are specific for monocytes. Platelets are characterized by a group of αNA esterases having pIs between 6.5 and 8.0, these corresponding to MWs ranging from 150 000 to 400 000.
Evaluation of the contribution of red and white cells to the flow of suspensions of washed blood cells through 3 μm Nuclepore membranes
Authors: Jones J. G. , Holland B. M. , Humphrys J. , Quew R. , Wardrop C. A.
Published: March 2008

Summary. This study was designed to investigate a method of analysis which can quantitate the contribution of white cells to the flow of washed suspensions of blood cells. Such an analysis would obviate the need to remove white cells when studying the filterability of normal and abnormal red cells.

The flow of suspensions of washed blood cells through a 3 μm Nuclepore membrane declines continually due to the occlusion of pores and the degree of pore occlusion is reduced significantly by the removal of the ‘buffy coat’ during the preparation of the suspension. These findings are in complete agreement with many other reports. However, a detailed kinetic analysis of the results suggests strongly that the white cell population makes a small contribution to the degree of pore occlusion which is caused largely by approximately 1% of the total red cell population.

Despite the phenomenon and extent of pore occlusion, a kinetic analysis of the complete non‐linear flow profile allows a measure of the deformability of red cells from filtration studies of washed but unfractionated blood cells.
Differentiation antigens on mouse eosinophils and neutrophils identified by monoclonal antibodies
Authors: Lopez Angel F. , Strath Malcolm , Sanderson Colin J.
Published: March 2008

Summary. A panel of hybridomas secreting monoclonal antibodies (mAb) reacting with antigens on mouse eosinophils and neutrophils has been selected. It is shown that four mAb bind preferentially to eosinophils, recognizing antigens expressed between 5 and 25 times more densely on these cells than on neutrophils. One mAb reacts preferentially with neutrophils, binding an antigen about 12 times more common on these cells than on eosinophils. Four mAb are shown to react with both eosinophils and neutrophils, and also macrophages. These mAb confirm the presence of different differentiation antigens on both eosinophils and neutrophils, and show that the myeloid series express antigens not expressed on lymphocytes.
Separation of diploid from aneuploid cells in acute lymphoblastic leukaemia
Authors: Walle A. J. , Niedermayer W.
Published: March 2008

Summary. A new method for the separation of diploid and aneuploid cells from blood of patients with leukaemia is described. Density gradient separation using a modified silica particle gradient was combined with analysis of cellular DNA content by flow cytometry. Submicroscopic levels of diploid or aneuploid cells were enriched up to 90% purity. Three patients with acute lymphoblastic leukaemia and no evidence of aneuploid cells after separation are in continuing complete remission after 24.5–47 months. Two patients with aneuploid cells detected after separation expired in relapse 0.5 and 3 months later. Cell separation prior to flow cytometric analysis might be a useful tool to detect submicroscopic levels of aneuploid leukaemic cells in blood and bone marrow, and to predict impending relapse.
Prolymphocytic leukaemia: surface morphology in 21 cases as seen by scanning electron microscopy and comparison with B‐type CLL and CLL in ‘prolymphocytoid’ transformation
Authors: Polliack Aaron , Leizerowitz Rachel , Berrebi Alain , Gamliel Haim , Galili Naomi , Gurfel Dorit , Catovsky Daniel
Published: March 2008

Summary. The surface architecture of leukaemic cells obtained from 21 cases of proven prolymphocytic leukaemia (PLL) and eight cases of chronic lymphocytic leukaemia (CLL) with ‘prolymphocytoid’ transformation (PL‐CLL) was compared with the cell surface morphology of leukaemic cells obtained from 46 cases of B‐type CLL, using the scanning electron microscope (SEM). All cases were defined by cytochemistry, immunological markers and transmission electron microscopy prior to SEM examination. B‐CLL cells showed the well‐recognized spectrum of surface architecture described in earlier studies. The majority of cells had moderate numbers of short microvilli, although in a minority, cells with relatively smooth surfaces predominated. In seven of the eight cases of PL‐CLL, cells were villous in nature and in this respect similar to CLL cells; however, more cells with dense microvilli were seen. The prolymphocytic cells were recognized by their larger size and in 18 of the 19 cases of B‐derived PLL, villous cells predominated. Two cases of T‐derived PLL showed variable cell surface morphology ranging from smooth to moderately villous. It appears that B‐PLL cells are most frequently villous and display more surface microvilli than B‐CLL cells. B‐prolymphocytes display the surface features regarded as characteristic for neoplastic B‐cells as seen in patients with B‐type lymphoma and leukaemia.
Chloroquine stripping of HLA antigens from neutrophils without removal of neutrophil specific antigens
Authors: Minchinton R. M. , Waters A. H.
Published: March 2008

Summary. Chloroquine stripping removes HLA antigens from neutrophils without damage to neutrophil specific antigens. This offers, for the first time, a simple procedure for the demonstration of neutrophil specific antibodies in sera that also contain HLA antibodies.
The significance of fibrinogen derivatives in plasma in human renal failure
Authors: Lane D. A. , Ireland H. , Knight I. , Wolff S. , And P. Kyle , Curtis J. R.
Published: March 2008

Summary. The concentrations in plasma of fibrinogen derivatives fibrinopeptide A (FPA), β 15–42 antigen and fragment E (FgE) antigen have been determined in patients with renal failure and compared to the concentrations of the platelet release products, β‐thromboglobulin (βTG) and platelet factor 4 (PF4). In ‘partial renal failure’(51Cr‐EDTA clearance rate 4–60 ml/min) FPA, β 15–42 antigen, FgE antigen and βTG levels were significantly raised above a normal laboratory control group. These levels were further raised in a group of patients whose disease required regular maintenance haemodialysis (51Cr‐EDTA clearance rate < 4 ml/min). PF4 levels were not significantly raised in either group. A statistical analysis of all patient results revealed that FPA, β 15–42 antigen and FgE antigen levels all correlated with βTG levels but not with PF4 levels. It is known that βTG is catabolized by the kidney but PF4 is not and that elevated βTG levels in renal failure are caused by impaired elimination rather than increased production. These results suggest that the plasma levels of these three fibrinogen derivatives are elevated in renal disease at least in part by decreased elimination rather than by increased thrombin and plasmin activities alone.
The HLA‐system in immune thrombocytopenic purpura: its relation to the outcome of therapy
Authors: Gratama J. W. , D'Amaro J. , Koning J. de , Den Ottolander G. J.
Published: March 2008

Summary. The distribution of HLA‐A, ‐B, ‐C and ‐DR antigens was investigated in 154 patients with immune thrombocytopenia (99 adults and 55 children). An increased frequency of HLA‐Bw56 (a split of HLA‐Bw22) was found both in the adults (RR = 4.30) as well as in the children (RR =7.91). Differences in HLA antigen distributions have also been analysed in patient subgroups with a good and a bad response to corticosteroids and splenectomy. The frequency of HLA‐DR4 was low in those patients with a good response to prednisone as compared with those with a poor response. The opposite was found in splenectomized patients. In 22 patients who did not respond to splenectomy, LB4 (a local split of HLA‐DR4) was completely absent. These results suggest that HLA‐DR4 (LB4) may be a predictive marker for therapy in ITP patients, i.e. a bad response to corticosteroids and a favourable outcome of splenectomy. However, none of the differences were significant after correction was made for the number of antigens tested.
Adrenergic modulation of erythropoiesis: in vitro studies of colony‐forming cells in normal and polycythaemic man
Authors: And J. Mladenovic , Adamson J. W.
Published: March 2008

Summary. The effect of hormonal interactions on human erythroid colony growth has been studied using the β adrenergic agonist, isoproterenol. The growth of colonies derived from both erythroid burst‐forming cells (BFU‐E) and erythroid colony‐forming cells (CFU‐E) was enhanced in the presence of isoproterenol. While isoproterenol was effective at all concentrations of erythropoietin (Ep) in cultures of marrow cells, an increase in BFU‐E‐derived colonies in peripheral blood cultures could be detected only at suboptimal levels of Ep concentrations. The isoproterenol effect was blocked by an agent with β2 receptor specificity (butoxamine), and L‐isomeric configuration (L‐propranolol). The stimulatory effect appeared to be mediated by a receptor different from that for Ep or for phytohaemagglutinin‐stimulated leucocyte conditioned medium. Circulating BFU‐E from eight patients with polycythaemia vera were also studied. Those colonies which grew in the absence of added Ep increased with isoproterenol; in cultures from normal subjects and in patients with secondary erythrocytosis, agonist stimulation was seen only in the presence of Ep. These studies provide evidence that the growth of both normal and neoplastic erythroid progenitors may be modulated by hormonal interactions.
Cytogenetic studies on recipients of allogeneic bone marrow using the sex chromosomes as markers of cellular origin
Authors: Lawler Sylvia D. , Baker Marion C. , And Helen Harris , Morgenstern G. R.
Published: March 2008

Summary. In 45 patients whose donor was of unlike sex, the sex chromosomes were used as markers of the cellular origin of myeloid and lymphoid tissues after allogeneic bone marrow transplantation (BMT). Successful engraftment was characterized by the appearance of dividing donor cells in marrow within 2 weeks of grafting and in mitogen stimulated blood cultures by 3 weeks. Leukaemic relapse was identified in eight cases and was associated with different patterns of cellular origin of the myeloid and lymphoid tissues. At the time of relapse the marrow contained either a mixed population of normal donor and leukaemic recipient cells, or only recipient cells. Thus, in this series, leukaemic relapse was not found occurring in donor cells. The importance of defining the origin of cells in interphase as well as in metaphase was demonstrated. In all but one case, the dividing lymphoid population remained of donor origin during relapse.
Cytochemical and immunological characteristics of acute monocytic leukaemia
Authors: Milligan D. W. , Roberts B. E. , Limbert H. J. , Jalihal S. , Scott C. S.
Published: March 2008

Summary. Immunological and cytochemical findings are presented from 12 cases of morphologically unequivocal acute monocytic leukaemia (AMoL). The results indicate considerable heterogeneity and three main non‐morphological subgroups were identified. The blast cells from half the patients were positive for the presence of both cytoplasmic alpha naphthyl acetate esterase (ANAE) and monocyte‐associated membrane determinants whereas the cells from three cases lacked detectable monocytic antigens despite the presence of strong cytochemical ANAE activity. A further three cases expressed monocytic antigens but were cytochemically unreac‐tive for ANAE. These cytochemical results, which were extended by electrophoretic studies of ANAE isoenzymes, suggest that the absence of significant cytoplasmic ANAE activity does not preclude the diagnosis of AMoL and that serum lysozyme estimations may be of value in the recognition of irnmunocytochemically‐atypical cases.
High levels of circulating haemopoietic stem cells in very early remission from acute non‐lymphoblastic leukaemia and their collection and cryopreservation
Authors: To L. B. , Haylock D. N. , Kimber R. J. , Juttner C. A.
Published: March 2008

Summary. Circulating myeloid progenitor cells (PB CFU‐GM) were measured in the peripheral blood of 13 patients with acute non‐lymphoblastic leukaemia (ANLL) as they entered first remission. The mean of the recorded peak levels was 2796 × 105 CFU‐GM/1, representing a 2 5‐fold increase above the mean value in normal subjects. These elevated levels of PB CFU‐GM occurred regularly during the very early remission phase when platelet counts rose rapidly. Five of the patients had PB mononuclear cells collected by continuous‐flow leukapheresis during this early recovery phase. CFU‐GM were assayed as a measure of the number of haemopoietic stem cells in each collection. The cells were concentrated and then cryopreserved in liquid nitrogen. Leukapheresis was also performed on five normal subjects for comparison. Low numbers of CFU‐GM were harvested from normal subjects, mean 033 ± 0‐06 × 104 CFU‐GM/kg body weight for each leukapheresis. In ANLL patients entering remission, however, very large numbers of CFU‐GM were regularly harvested. A mean of 11 ± 2 × 104 CFU‐GM/kg body weight were cryopreserved after each leukapheresis, representing 5 times the number of CFU‐GM considered necessary for successful autologous haemopoietic reconstitution. Haemopoietic stem cell viability was assessed after varying periods of cryopreservation. There was no significant stem cell loss after up to 24 months storage. Thus, it is possible to collect and cryopreserve large numbers of CFU‐GM and by inference pluripotent haemopoietic stem cells from the peripheral blood of patients with ANLL during very early remission. The possible biological and therapeutic implications are discussed.
Light chain isotype associated suppression of surface immunoglobulin expression on peripheral blood lymphocytes in myeloma during plateau phase
Authors: Wearne Alaine , Joshua D. E. , Kronenberg Harry
Published: March 2008

Summary. Light chain isotype suppression in multiple myeloma has been reported in the plasma cells of the lamina propria of the gut (Leonard et ah 1979). In this paper we present further evidence of systemic suppresssion of the light chain isotype of the paraprotein expressed on normal peripheral blood lymphocytes in myeloma. Twenty patients with myeloma in plateau phase were monitored over 6 months for the expression of either kappa or lambda light chains on the surface of peripheral blood lymphocytes using monoclonal antibodies. The surface markers were analysed on an Ortho Spectrum III flow cytometer. Results of these studies indicate a selective suppression of the cells expressing the light chain isotype of the paraprotein in stable myeloma. Thus, in kappa myeloma there is a low kappa/lambda ratio and in lambda myeloma there is a high kappa/lambda ratio, and this suppression is lost with progressive disease.
The anaemia of chronic renal failure in sheep: studies in vitro
Authors: Mladenovic Jeanette , Eschbach Joseph W. , Garcia Joseph F. , Adamson John W.
Published: March 2008

Summary. The presence of inhibitors which accumulate during uraemia has been postulated as a significant factor in the development of anaemia in chronic renal failure (CRF). To determine whether factors in uraemic serum depress erythropoiesis, samples were obtained from sheep prior to and after surgical induction of CRF. The sera were tested in vitro for their effect on erythroid colony growth. The sheep sera were substituted for fetal calf serum (30% concentration) in cultures of serotype‐matched or autologous sheep marrow cells at optimal doses of erythropoietin (Ep). Forty‐two paired sera from five animals were tested against normal (22) and uraemic marrow (20). In 7/42 random pairs, erythroid colony growth was decreased by 20% in the presence of uraemic serum when compared to a normal sample from the same animal. In the remainder of the cultures, uraemic sera stimulated or supported erythroid colony growth as well as normal sera. When the results were analysed individually, serum from only one of five animals showed minimal (10%) in vitro inhibition of erythroid colony growth. This study, performed in a prospective manner utilizing compatible target cells, disputes the hypothesis that uraemic toxins significantly inhibit in vitro erythropoiesis. These data correlate with the in vivo response to Ep in this sheep model, and suggest Ep would be effective in treating the anaemia of CRF.
Conversion of endogenous cobalamins into microbiologically‐inactive cobalamin analogues in rats by exposure to nitrous oxide
Authors: Muir M. , Chanarin I.
Published: March 2008

Summary. Rats were exposed to a mixture of oxygen and nitrous oxide (1/1) for up to 18 d. There was a marked fall in both the serum and liver cobalamin levels. There was a significant rise in the concentration of microbiologically‐inactive cobalamins in serum 24 h after exposure to N20. The proportion of microbiologically‐inactive cobalamin in liver increased throughout the period of exposure. We were unable to show a similar effect in sera from patients inhaling N20 for 24 h, nor by exposing rat plasma to N2O for 24 h. It was concluded that microbiologically‐inactive cobalamins are produced in vivo from endogenous cobalamins and that one form appears to be a product of cobalamin oxidation.
Therapy‐induced preleukaemia in patients treated for Hodgkin's lymphoma: clinical and therapeutic relevance of sequential chromosome banding studies
Authors: Gyger Martin , Forest Lorraine , Vuong T. E. , Perreault Claude , Lavallee Rene , Lacombe Michel , Boileau Jacques , D'Angelo Giovanni
Published: March 2008

Between January 1978 and December 1982 successful sequential chromosome analyses were carried out on bone marrow cells of five patients previously treated for Hodgkin's lymphoma (HL) presenting unexplained cytopenia or pancytopenia during follow‐up. All patients had concurrent morphological examination of bone marrow specimens showing signs of dysplasia and/or hypoplasia, without leukaemic infiltrate. Six other patients treated for HL who had normal haematological parameters served as controls. All the patients with unexplained cytopenias had clonal chromosome abnormalities; monosomy for chromosome No. 5 was the most frequent. No abnormalities were detected in the control group. Two patients have evolved to resistant leukaemia, one died of sepsis before leukaemic conversion while severely neutropenic, and two are in full marrow and cytogenetic recovery after aggressive anti‐leukaemic treatment in the pre‐leuk‐aemic phase. Our data suggest that cytogenetic studies may be of crucial value in detecting therapy‐induced preleukaemia (t‐PL) at an early stage of its evolution and in planning appropriate therapy before the establishment of overt leukaemia.
Inhibition of normal human macrophage progenitors by retinoic acid
Authors: Januszewicz E. , Cooper I. A.
Published: March 2008

The effects of retinoic acid on the clonal growth in nutrient agar of neutrophil and macrophage progenitors from normal bone marrow and fetal liver were studied. The technique of whole plate fixation and staining with luxol fast blue and haematoxylin was employed to distinguish colonies and clusters into morphological groups. Retinoic acid at a concentration of 3 × 10−7 M resulted in 97% inhibition of macrophage clonal growth and a mean increase in neutrophil clonal growth from bone marrow of 150 ±14%. These effects of retinoic acid were most obvious on bone marrow cluster forming cells. The inhibition of macrophage cluster growth was independent of exogenous colony stimulating factor. This dual action of retinoic acid is likely to be a direct effect on the progenitor cells since it is (1) independent of cell concentration, (2) not mediated by phagocytic cells or other bone marrow cells, and (3) was maximal in the first 2 d of incubation before the appearance of clusters.
Differentiation and cytokinetic analyses of normal and neoplastic lymphoid cells in B and T cell malignancies of childhood
Authors: Hirt A. , Baumgartner C. , Imbach P. , Luethy A. , Wagner H. P.
Published: March 2008

The labelling index (LI) of untreated B cell non‐Hodgkin's lymphoma (B NHL) in children was significantly higher (P< 0.002) than the LI of untreated T cell malignancies (median LI 27‐7% and 10 3%, respectively). In B NHL abdominal tumour material showed a significantly higher in vitro incorporation of tritiated thymidine (3H‐dT) than extra‐abdominal tumour material (P±0 01). Sequential immunological, cytochemical and cytokinetic studies revealed tumour cells in up to three marker‐defined subpopulations of lymphoid cells. In all 14 patients examined the LI of E−Ia+sIgM+ cells was higher than the LI of E+Ia+/‐ sIgM− cells; in all eight patients with Ia+ and la− tumour cells the former had a higher LI than the latter (P<0‐002).

In all T cell neoplasia (T ALL/NHL) investigated malignant cells were found in two of the three marker‐defined subsets of lymphoid cells. In 10/13 patients the E‐rosette positive blast cells had a higher LI than the E‐rosette negative T blast cells. For the small group of patients with T cell malignancies no significant difference in the overall LI between OKT9+ stage I (early thymocyte) and OKT9− stage II (cortical thymocyte) neoplasias could be found. However, within the malignant clone of a T cell malignancy the expression of the OKT9 (transferrin receptor) but not the cortical thymocyte (HTA‐1) antigen was related to the in vitro3H‐dT incorporation.
Identification of plasminogen activator releasing activity in the neurohypophysis
Authors: Colucci M. , Stassen J. M. , Salwa J. , Collen D.
Published: March 2008

Vasopressin (AVP) and some of its synthetic analogues, for example 1 desamino 8‐D‐AVP (DDAVP), induce plasminogen activator (PA) release in vivo. It has been proposed that this occurs via the release from the central nervous system of a plasminogen activator releasing hormone (PARH). The present study shows that a crude extract of bovine posterior pituitary, but not of the anterior pituitary or of the hypothalamus, induces a marked increase of circulating PA in anaesthetized rats. PA release appears to be caused by AVP because no other PA releasing activities could be identified in or isolated from the extract. In addition, no PA‐releasing activity was found in extracts of pituitary glands of rats congenitally deficient in vasopressin. The following experiments did not reveal central nervous system involvement in the PA‐release caused by AVP or DDAVP. Perfusion of isolated organs (rat heart and rat liver) with AVP resulted in PA‐release. In squirrel monkeys, comparable PA levels were found in the venous return following intrafemoral or intracarotid injection of AVP. Moreover, when plasma obtained 2 min following AVP or DDAVP injection was transfused to a receiving animal no PA release was observed. Thus our present findings do not support the hypothesis that the fibrinolytic response to AVP is mediated by the release of a specific peptide hormone from the central nervous system.
Falsely prolonged prothrombin time due to an inhibitor to human thromboplastin
Authors: Tinegate H. N. , McArdle B. , Qureshi M.
Published: March 2008

A patient with nephrotic syndrome of unknown aetiology was found to have a grossly prolonged prothrombin time in the absence of any other coagulation abnormality and with no clinical bleeding problem. Subsequent investigations showed his plasma contained an inhibitor‐like substance, directed against human but not animal thromboplastin.

Estimation of prothrombin time using either human or rabbit brain thromboplastin is a simple and reproducible test. The standard method which has been in routine use for many years has rarely been reported to give falsely prolonged results in a properly collected blood sample, tested in parallel with a control plasma. A molecular variant of factor VII has been reported to give misleading results with animal thromboplastin (Girolami et al, 1979). We report a patient who had no clinical evidence of a bleeding tendency, and whose plasma gave grossly abnormal and inconsistent prothrombin times due to the presence of a species specific inhibitor of human thromboplastin in the plasma.
Alpha thalassaemia in Sardinian newborns
Authors: Galanello R. , Maccioni L. , Ruggeri R. , Perseu L. , Cao A.
Published: March 2008

In this study we describe the correlation between the haematological parameters (red cell indices and Hb Bart's levels) and the α‐globin genotype in Sardinian newborns. Increased Hb Bart's levels at birth always indicates α‐thalassaemia, either of the deletion or non‐deletion variety. Infants with two α‐globin genes deleted (‐α/ ‐α and ‐ ‐/act genotypes) had microcytosis, low MCH and Hb Bart's in the 2.0‐7.1% range. A minority (38.9%) of infants with the (‐α/αα) globin genotype had detectable Hb Bart's, in the 0.78‐2 '5% range, frequently associated with minimal microcytosis while the remainder (61 e l %) were completely silent. Infants carriers of a non‐deletion type of α‐thalassaemia showed Hb Bart's levels within the range found in the (‐ α/αα) genotype. The association of heterozygous Po‐thalassemia seems to have no effect on the expression of any of these α‐thalassaemia lesions at birth.
Delay in primary haemostasis produced by a fish diet without change in local thromboxane A2
Authors: Thorngren Margareta , Shafi Shahida , Born G. V. R.
Published: March 2008

Twelve apparently healthy male volunteers were maintained for 6 weeks on a fish diet, the haemostatic effects of which were determined as standardized skin bleeding times; thromboxane A2 formation in vivo in the bleeding time blood and in vitro in clotting venous blood; platelet aggregability; and platelet phospholipids. Within 1 week the fish diet changed the fatty acid composition of platelet membrane phospholipids, with increases in ω‐3 and decreases in ω‐6 fatty acids; decreased platelet aggregability by ADP and collagen; but the bleeding time was unchanged. Not until 6 weeks on the diet did the bleeding time increase (by 3 7%: P < 0‐01) and it was still increased 3 weeks after the end of the diet, when the fatty acid composition of the platelets had returned to normal. The effect of the diet on decreased aggregability of platelets also failed to follow the changes in their fatty acid composition and in the bleeding time. Aggregation by ADP and by the highest dose of collagen was decreased throughout the diet and for several weeks thereafter, i.e. even when the fatty acid composition had reverted to the pre‐dietary pattern and long after the normalization of the bleeding time. The diet caused no change in the in vivo appearance of thromboxane A2 in the bleeding time blood, contrasting with its effect in decreasing the in vitro formation of thromboxane A2 in clotting venous blood. These observations suggest that such fish diets do not delay haemostasis by diminishing the formation of thromboxane A2 locally nor directly by decreasing the aggregability of platelets or directly by the induced changes in their to‐3 fatty acids.
The mechanism of the anaemia in rheumatoid arthritis: effects of bone marrow adherent cells and of serum on in‐vitro erythropoiesis
Authors: Reid C. D. L. , Prouse P. J. , Baptista L. C. , GUMPEL J. M. , Chanarin I.
Published: March 2008

Clonal assays for erythroid progenitors (BFU‐e and CFU‐e) were used to study 20 patients with rheumatoid arthritis, 15 of whom had anaemia of chronic disease and five of whom were haematologically normal. The numbers of bone marrow BFU‐e and CFU‐e in the anaemic patients did not differ significantly from those in normal controls.

Macrophages were removed from the bone marrow by a combination of adherence and buoyant density centrifugation over a sucrose gradient and the resulting fractions were cultured alone or together with autologous adherent cells in BFU‐e assays. Co‐culture with adherent cells significantly increased colony growth in both the controls and in seven of eight anaemic patients studied.

Serum from 14 anaemic patients and from five non‐anaemic patients was added to cultures of bone marrow or to control peripheral blood ‘null’ cells. Anaemic serum uniformly either inhibited or failed to stimulate BFU‐e growth under these conditions. Serum from non‐anaemic patients and from 10 healthy controls stimulated BFU‐e growth from ‘null’ cells to an equal degree.
Assessment of the drug sensitivity of acute nonlymphocytic leukaemia using the in vitro clonogenic assay
Authors: Preisler H. D. , Azarnia N.
Published: March 2008

The ability of an in vitro clonogenic drug sensitivity assay to predict the outcome of therapy for acute nonlymphocytic leukaemia was evaluated using marrow cells obtained from previously untreated or first relapsed patients treated with either cytosine arabinoside/anthracycline antibiotic or high dose cytosine arabinoside remission induction therapy. While the per cent of leukaemic cells killed in vitro was correlated with the outcome of therapy, this drug sensitivity assay provided little or no clinically useful information.

In 1980 we reported the results of our initial studies of an in vitro drug sensitivity assay designed to predict the response of patients with acute nonlymphocytic leukaemia (ANLL) to chemotherapy (Preisler, 198Oa). The studies described here extend our initial report and relate in vitro drug sensitivity to the biological characteristics of the leukaemic cells and to response to remission induction therapy with conventional dose cytosine arabinosidelanthracycline antibiotic therapy or ‘high dose’ cytosine arabinoside therapy.
The haemostatic plug in haemophilia A: a morphological study of haemostatic plug formation in bleeding time skin wounds of patients with severe haemophilia A
Authors: Sixma Jan J. , Van Den Berg Agnes
Published: March 2008

Haemostatic plug formation in four patients with severe haemophilia A (VIII:C < 1%) was studied in skin biopsies taken at 3, 10 and 30 min and 2 h after a template bleeding time wound had been made. The primary haemostatic plug showed relatively minor changes, consisting of a delay in platelet degranulation and interdigitation. Some platelet aggregates not attached to vessels were encountered in the wound. Subsequently the primary haemostatic plug changed into a firm stable degranulated mass of interdigitated platelets.

The major abnormality occurred during the fibrinous transformation. At 2 h many haemostatic plugs consisted of a thin peripheral layer of fibrin and platelet remnants around a central area containing red and white blood cells with a varying amount of plasma and only relatively few fibrin fibres. These observations suggest that fibrin formation in the periphery of the plug is less dependent of factor VIII than in central areas. The lack of fibrin formation in the centre of the plug compensating for the platelet lysis at 2 h may have caused the central erosion of the plug.
Platelet autoantibodies in septicaemia
Authors: Van Der Lelie J. , Dalen C. M. van der Plas‐Van , Von Dem Borne A. E. G. Kr.
Published: March 2008

Thirty‐three patients, 16 of whom had a platelet count below 100 × 109/1, were studied for the presence of platelet antibodies using the platelet suspension immunofluorescence test (PSIFT). In the acute phase platelet‐bound immunoglobulins (PBIg) were found in 62% of the thrombocytopenic patients, but also in 65% of the patients with a normal platelet count. Fourteen patients were re‐examined after successful treatment of their infection. At that time all had a normal platelet count, yet PBIg were found in 71%. In all but four patients the PBIg could be eluted with ether and were shown to bind to normal platelets but not to Glanzmann type I platelets in 11 of 12 patients tested, indicating the platelet‐specific autoantibody nature of the PBIg. Platelet autoantibodies were also demonstrated in the sera: in 38% in the acute phase and in 43% after treatment. In those patients in whom this could be tested the antibodies appeared to be strictly or partially EDTA‐dependent. It is postulated that the antibodies are mainly directed against cryptantigens, exposed in vivo only on platelets damaged by the septicaemia and in vitro in the presence of EDTA. This would also explain the lack of relationship between the platelet count and the serological findings.
Cyclosporin A in the treatment of severe acute aplastic anaemia
Authors: Jacobs Peter , Wood Lucille , Martell Robert W.
Published: March 2008

Summary. Twelve consecutive adults with severe acute aplastic anaemia, not having a bone marrow transplantation option, were prospectively randomized to receive either cyclosporin A alone or an equivalent amount of this immunosuppressive agent in combination with antilymphocyte serum. The minimum follow‐up is 36 months, with half the patients developing nephrotoxicity, which was easily reversible in all but one. No response could be attributed to either regimen. Cyclosporin A does not appear to have a place as primary form of treatment for adults with severe acute aplastic anaemia, either on its own or in combination with antilymphocyte serum.
Characterization of an occult inhibitor to factor IX in a haemophilia B patient
Authors: Miller Connie H. , Orstavik Karen H. , Hilgartner Margaret W.
Published: March 2008

Summary. Six haemophilia B patients were studied while undergoing infusion with factor IX concentrate. All were negative for factor IX antigen (IX:AG) and inhibitor to factor IX coagulant activity (IX:C). One patient showed an atypical response pattern, with prolonged survival of IX:C and IX:Ag. This patient remained under prophylactic treatment and more than 1 year later developed an inhibitor to IX:C of clinical significance. Retrospective study revealed that this patient had significantly higher levels of circulating immune complexes than other haemophilia B patients and in vivo formation of immune complexes containing IX:Ag prior to detection of his inhibitor in conventional clotting assays, suggesting long‐term persistence of an occult inhibitor. The inhibitor was shown to be an IgG antibody with both kappa and lambda light chains.
Idiopathic combined immunocytopenia
Authors: Wiesneth M. , Pflieger H. , Frickhofen N. , Heimpel H.
Published: March 2008

Summary. Four patients with combined immunocytopenia of unknown origin were investigated. Two patients with pancytopenia had allo‐ and autoantibodies against erythrocytes, granulocytes and thrombocytes. Two other patients with granulocytopenia and thrombocytopenia showed allo‐ and autoantibodies against granulocytes and thrombocytes. All patients went into a transient or persistent remission under immunosuppressive therapy. The normalization of peripheral blood correlated with the disappearance of antibodies suggesting that the cytopenia was caused by an antibody mediated autoimmune mechanism.
Autoimmune disease in hairy‐cell leukaemia: clinical syndromes and treatment
Authors: Westbrook Carol A. , Golde David W.
Published: March 2008

Summary. Thirty‐seven patients with hairy‐cell leukaemia were retrospectively reviewed for the presence of autoimmune disease. Ten definite and two probable cases were identified; these patients had positive serologies (immune complexes, antinuclear antibodies or rheumatoid factor) or biopsy‐proven vasculitis. Clinically, two distinct syndromes were recognized. Six patients had joint symptoms, usually associated with nodular skin lesions; all responded promptly to therapy. Four additional cases had a more severe disease consisting of fevers, malaise, weight loss, skin rash, and variable visceral involvement; there was one death in this group. There appeared to be no relationship between presence of vasculitis and the severity or progression of the underlying malignant disease. We conclude that autoimmune disease is much more frequent in hairy‐cell leukaemia than has previously been recognized, and that the outcome in these syndromes is usually good. Although the autoimmune syndrome generally responds promptly to splenectomy, corticosteroids, or cytotoxic therapy, failure to recognize this complication may lead to increased morbidity and occasional mortality.
Classification of anaemia on the basis of ferrokinetic parameters
Authors: Barosi G. , Cazzola M. , Berzuini C. , Quaglini S. , Stefanelli M.
Published: March 2008

Summary. Quantitative information on abnormalities of erythropoiesis and mechanisms of anaemia has been obtained in 136 anaemic patients by means of ferrokinetic studies. To derive a functional classification of anaemia based on ferrokinetic parameters, agglomerative hierarchical cluster analysis and principal coordinate analysis were utilized as techniques for unsupervised classification. Two main clusters were found and named anaemia with low potential erythropoiesis and with high potential erythropoiesis, since the most discriminant parameter between them was total erythroid iron turnover, a measure of total erythropoietic activity. A value of total erythropoiesis equal to 4 times the normal was found to discriminate these two types of anaemia in 94% of cases. Within the group with low potential erythropoiesis, three clusters showing different qualitative disturbances of erythropoiesis were singled out. Among patients with high potential erythropoiesis, two clusters were found. A value of effective erythropoiesis equal to 2·5 times the normal was shown to have a high discriminant power between these clusters. This threshold level distinguished between patients having ineffective erythropoiesis or peripheral haemolysis as the major mechanism of anaemia. The present functional classification of anaemia provides a complete picture of the different pathogenetic mechanisms and may represent the basis for a more rational diagnostic approach to erythroid disorders.
Iron overload in subjects with beta‐thalassaemia trait: role of idiopathic haemochromatosis gene
Authors: Fargion Silvia , Piperno Alberto , Panaiotopoulos Nikos , Taddei Maria Teresa , Fiorelli Gemino
Published: March 2008

Summary. We have characterized HLA antigens in subjects with beta‐thalassaemia trait with and without iron overload. 50% of the cases with iron overload (v 18% of those without iron overload, P <0·01) are carriers of HLA‐A3, the HLA antigen tightly linked to the IH allele. Thus, in a considerable number of these subjects, beta‐thalassaemia and IH coexist. This association exerts a synergistic effect in inducing iron overload.
Monosomy 7 and multipotential stem cell transformation
Authors: Chan L. C. , Sheer D. , Drysdale H. C. , Bevan D. , Greaves M. F.
Published: March 2008

Summary. Monosomy 7 was the sole karyotypic abnormality seen in a case of biphenotypic leukaemia involving both the myeloid and lymphoid lineages and in a case of de novo ALL undergoing a phenotypic shift to acute myeloid leukaemia at relapse. These observations suggest that monosomy 7 can be associated with transformation of a common lymphoid‐myeloid progenitor cell.
Serum beta2‐microglobulin: a real improvement in the management of multiple myeloma?
Authors: Van Dobbenburgh O. A. , Rodenhuis S. , Ockhuizen Th. , Weltevreden E. , Houwen B. , Fidler V. , Meijer S. , Marrink J.
Published: March 2008

Summary.Beta2‐microglobulin (B2‐m) determinations in serum have recently been introduced as a method of stratifying patients suffering from multiple myeloma. Conflicting results from several studies prompted us to study retrospectively the correlation of B2‐m with presenting features and disease stage, as well as the prognostic value of B2‐m, in 87 myeloma patients. Significant correlations were found between B2‐m and presenting features such as haemoglobin level, serum calcium level and total body myeloma cell mass. The strongest correlation existed between B2‐m and serum creatinine (r= 0·68). B2‐m did not discriminate between the different disease stages as defined by Durie and Salmon, nor between myeloma Stage IA and monoclonal gammopathy of undetermined significance (MGUS). Considered alone, B2‐m was found to have prognostic value in terms of survival. This correlation disappeared after correction for serum creatinine level and tumour load (multivariate analysis). Furthermore, changes in tumour load during therapy were not reflected in changes in B2‐m levels, thereby rendering B2‐m levels invalid as tumour marker. Our findings indicate no value for B2‐m determinations in the staging and follow‐up of myeloma patients.
Basophil function in patients with chronic myelogenous leukaemia
Authors: Lett‐Brown Michael A. , Juneja Harinder S.
Published: March 2008

Summary. We have compared the release of histamine from basophils isolated from six patients with chronic myelogenous leukaemia (CML) and seven normal controls. No differences were noted in the release induced by rabbit anti‐human IgE. However, basophils from CML patients released <20% of their intracellular histamine when challenged with the anaphylatoxin C5a at a concentration that caused >50% release from normal basophils. Furthermore, basophils from CML donors showed a significantly lower release in the presence of the calcium ionophore A23187. These results suggest that basophils from CML patients have an inherent defect.
Monoclonal antibody OKT17 recognizes most cases of T‐cell malignancy
Authors: Matutes E. , Parreira A. , Foa R. , Catovsky D.
Published: March 2008

Summary. Membrane phenotype analysis with monoclonal antibodies (McAb) has demonstrated great heterogeneity within the T‐cell malignancies. We describe here the reactivity with an anti‐T cell McAb, OKT17, in 80 leukaemia samples. Cells from all types of T‐cell leukaemia (48 cases), except from the small group of pre‐T‐ALL, strongly expressed the antigen identified by OKT17 whereas none of the 32 non‐T leukaemias were OKT17 positive. When the reactivity of OKT17 was compared with that of other pan‐T markers, OKT17 was positive in a larger number of T‐cell leukaemias: 87% of cases compared with 74% with E‐rosettes and 73% with the McAb 3A1. In the mature or post‐thymic proliferations OKT17 was positive in 96% of cases, compared with 77% with E‐rosettes and 61% with 3A1. The latter reagent, on the other hand, was better than OKT17 for detecting leukaemias with a thymic phenotype, 100% and 68% of positive cases respectively. The combined use of OKT17, 3A1 and terminal transferase permits a more precise classification of all the T‐cell leukaemias according to the main stages of T‐cell differentiation.
Acute megakaryoblastic leukaemia with 3q inversion and elevated thrombopoietin (TSF): an autocrine role for TSF?
Authors: Pinto M. R. , King M. A. , Goss G. D. , Bezwoda W. R. , Fernandes‐Costa F. , Mendelow B. , McDonald T. P. , Dowdle E. , Bernstein R.
Published: March 2008

Summary. A patient with acute megakaryoblastic leukaemia is described in whom exactly the same paracentric inversion of 3q was detected as in three previously documented cases. The patient's serum thrombopoietin (TSF) was significantly raised. Based on these findings we postulate a role for a gene (? oncogene) on chromosome 3q in thrombopoietin production. Abnormalities of 3q may assist in delineating a subgroup of acute nonlymphocytic leukaemia, namely acute megakaryoblastic leukaemia.