bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunoblastic lymphadenopathy with early onset in two boys: immunohistochemical study and indication of decreased proportion of circulating T‐helper cells
Authors: Stensvold K. , Brandtzaeg P. , Kvalosy S. , And M. Seip , Lie S. O.
Published: March 2008

Summary. Two boys, 5 and 18 years old, had had frequent infections from their second month of life and had later suffered from generalized lymphadenopathy, intermittent maculopapular exanthema, anaemia, and weight loss. Histopathological features of lymph nodes were consistent with immunoblastic lymphadenopathy. Immunohistochemistry showed hyperimmune state with numerous T cells and macrophages along with selective polyclonal IgM‐producing cell response in one patient, and IgG‐and IgM‐producing cells in the other. Both had severe deficiency of serum IgA. Classification of T‐cell subsets (OKT4+ and OKT8+) in peripheral blood indicated an imbalance with a relative excess of putative suppressor cells (OKT4+/OKT8+<1; normal, 1.7). It is suggested that decreased T‐helper cell activity may explain the observed maturational defects in the B‐cell system which probably underlie a hyper‐reactive state induced by some sort of triggering, e.g. chronic infection. During steroid treatment the general condition improved remarkably and the lymphadenopathy and hepatosplenomegaly decreased, but the T‐cell subset proportions and the serum immunoglobulin levels remained unchanged.
Haematological reconstitution and severity of graft‐versus‐host disease after bone marrow transplantation for chronic granulocytic leukaemia: the influence of previous splenectomy
Authors: Baughan A. S. J. , Worsley A. M. , McCarthy D. M. , Hows J. M. , Catovsky D. , Gordon‐Smith E. C. , Galton D. A. G. , Goldman J. M.
Published: March 2008

Summary. Eighteen patients with chronic granulocytic leukaemia (CGL) were treated by chemoradiotherapy and transplantation of bone marrow (BMT) collected from their HLA‐identical sibs; engraftment with donor marrow occurred in all cases. Ten of the patients had been subjected to splenectomy before BMT; recovery after BMT of granulocyte, lymphocyte and platelet numbers in the peripheral blood was more rapid in these patients than in the eight patients who retained their spleens. Acute graft‐versus‐host disease occurred in 12 of the 15 evaluable patients and appeared to be more severe in those who lacked their spleens at the time of transplant. Of the 12 patients surviving at follow‐up times ranging from 59 to 207 weeks, six had been subjected to splenectomy before BMT and six retained their spleens. We conclude that engraftment was more rapid in the splenectomized patients and splenectomy might have increased the chance of eradicating the leukaemia, but these considerations must be balanced against the short‐term and long‐term risks associated with splenectomy.
The HbA/HbA2 ratio in newborns and its correlation with fetal maturity
Authors: Felicetti L. , Novelletto A. , Benincasa A. , Terrenato L. , Colombo B.
Published: March 2008

Summary. The relative amounts of HbF, HbA and HbA2 were determined in about 1000 newborns and their parents. In newborns the mean value of HbA2 was 0.27±0.02% and that of HbF 74.69±0.25%. The ratio HbA/HbA2 was estimated at different gestational ages and was found to range from 101 at 32 weeks gestation to 76 at 45 weeks, indicating that the relative amount of HbA2 increases with fetal maturation. The correlations between the levels of the different haemoglobins and various indexes of fetal maturation (gestational age, birth weight, crown–heel length and head circumference) are also given.
Pyrimidine 5′nucleotidase and several other red cell enzyme activities in β‐thalassaemia trait
Authors: Vives Corrons J. L. , Pujades M. A. , Aguilar i Bascompte J. L. , Jou J. M. , Rozman C. , Ester A.
Published: March 2008

Summary. The activity of 18 red blood cell (RBC) enzymes and reduced glutathione (GSH) content were measured in 70 normal subjects, in 50 heterozygous β‐thalassaemia carriers and in 50 non‐thalassaemic patients with haemolytic anaemia and high reticulocyte counts. In addition, pyrimidine 5′nucleotidase (P5N) activity was also determined in 34 patients with hypochromic, microcytic, iron deficiency anaemia.

β‐Thalassaemia trait was associated with an increase in almost all of the enzyme activities, except for 2,3‐bisphosphoglycerate synthetase (BPGS) and glutathione reductase (GR) which were normal and for acetylcholinesterase (AChE) and P5N which were slightly and markedly decreased respectively. The increases in enzyme activities were similar to those observed in patients with non‐thalassaemic reticulocytosis except for glyceraldehydephosphate dehydrogenase (GAPD), phos‐phoglyceratekinase (PGK), pyruvate kinase (PK), glutathione peroxidase (GPX) and adenylate kinase (AK) which were higher than in non‐thalassaemic group of patients with increased number of reticulocytes. No correlation was found between the severity of P5N deficiency and the intensity of basophilic stippling which was present in 46 of 50 thalassaemic carriers here studied. In addition, GSH content and UV absorption spectra of deproteinized thalassaemic RBC extracts were also found to be normal.

The present findings provide further information on the metabolic status of RBC in β‐thalassaemia trait and suggest a possible molecular explanation for the frequently observed basophilic stippling in this disease.
Systemic irradiation in multiple myeloma: a report on nineteen cases
Authors: Rostom A. Y. , O'Cathail S. M. , Folkes Anne
Published: March 2008

Summary. Nineteen patients with relapsed or resistant multiple myeloma were treated with sequential half‐body irradiation (12) and half‐body irradiation only (seven). This treatment proved acceptable to the majority of patients and required one night's stay in hospital. Gastro‐intestinal toxicity was transient and self limiting. Haematological toxicity was acceptable and recovery was complete in all but two of the 19 patients following half‐body irradiation. However, only six of the 12 patients who subsequently had the remaining half irradiated completely recovered. Blood transfusions were required to correct anaemia in six patients, a platelet transfusion was given to one and a further patient required both platelet and blood transfusions. We observed no serious haematological complications. Six of the 13 patients who received upper half‐body irradiation of probable chest infection, while one patient of the six who received lower half‐body irradiation died of this complication. Some of the seven deaths may have been due to radiation pneumonitis. Two patients developed brain secondaries, which is a very rare occurrence in this disease. This may indicate a change in the natural history of myeloma produced by this new treatment. Subjective improvement was observed in 17 patients and relief of pain usually occurred within the first 24 h. Objective responses were noted in six patients. The median survival for all patients was 6 months with five patients alive 11‐28 months at the time of this report. This treatment compares favourably to second line chemotherapy. It is perhaps more economical and better tolerated by patients. Further assessment in a larger number of patients with either untreated or relapsed disease is warranted.
CM Affi‐Gel Blue chromatography of human urine: a simple one‐step procedure for obtaining erythropoietin suitable for in vitro erythropoietic progenitor assays
Authors: Krystal Gerald , Eaves Connie J. , Eaves Allen C.
Published: March 2008

Summary. A method for both concentrating and purifying human urinary erythropoietin (Ep) using CM Affi‐Gel Blue is described. We have found that up to 40 litres of urine can be processed on a 1 litre gel bed of this material. This gives a 25‐50‐fold purification of Ep with an apparent Ep recovery in excess of 100%. The high recovery of Ep is probably due, in part, to the removal of inhibitors present in the initial urine. By selecting urine that contains high levels of Ep (>0.5 units/ml), it is possible with this method routinely to obtain preparations with specific activities of 100‐300 units of Ep per mg protein. Such preparations are noninhibitory when assayed in either short‐term suspension cultures or in longer‐term methylcellulose cultures at concentrations up to 5‐10 units/ml. Similar tests with these same bioassay systems have shown that other non‐Ep stimulating factors (i.e. erythroblast enhancing factor (EEF), granulocyte/macrophage colony stimulating factor (GM‐CSF) and burst promoting activity (BPA)) are also not present at detectable levels. In this study we also show that the loss of biological activity which often occurs when partially purified Ep preparations are stored in solution is markedly reduced in the presence of either 1% bovine serum albumin or 0‐1% sodium dodecyl sulphate.
Serous effusions in monocytic leukaemias
Authors: Mufti G. J. , Oscier D. G. , Hamblin T. J. , Nightingale Anne , Darlow S.
Published: March 2008

Summary. We report four patients who either presented with or developed serous effusions during the course of monocytic leukaemia. This finding has not been documented previously. All the patients had very high peripheral blood monocyte counts when effusions developed. The effusions resolved after the patients were treated with anti‐leukaemic therapy. It is therefore likely that the effusions were disease related. Two of the patients have been treated with raxoxane, one with eptoposide and the other with cytarabine.

Monocytic leukaemias comprise a spectrum of disorders ranging from acute monoblastic leukaemias (AMOL) and acute myelomonocytic leukaemia (AMML) to chronic myelomono‐cytic leukaemias (CMML) (Shaw, 1980). Whereas leukaemic infiltration of the gums, central nervous system and skin is well recognized in AMOL and AMML, it is uncommon in CMML (Shaw, 19 78). In contrast to the lymphoid malignancies, leukaemic infiltration of the serosal surfaces giving rise to effusions is rare in both myeloid and monocytic leukaemias and has not been previously documented in CMML. We report four patients with monocytic leukaemia who developed either pleural and/or pericardial effusions or ascites which responded to anti‐leukaemic therapy.
Bone marrow transplantation for acute lymphoblastic leukaemia: a survey of the European Group for Bone Marrow Transplantation (E.G.B.M.T.)
Authors: Zwaan F. E. , Hermans J. , Barrett A. J. , Speck B.
Published: March 2008

Between 1979 and 1982, 192 patients with acute lymphoblastic leukaemia were given allogenic bone marrow transplants from HLA‐identical siblings. Data on 5 7 patients transplanted in first remission were compared with the results in 96 patients transplanted in second remission, and 39 in third or subsequent remission. The majority of these patients were of the non‐B non‐T‐ALL and T‐ALL subtypes. The 2‐year actuarial survival for non‐B non‐T‐ALL was 58% for patients transplanted in first remission, 34% for second remission patients and 33% for patients transplanted in third or subsequent remission (P= O60). For patients with T‐ALL, the survivals at 2 years for first and second remission transplant patients were 61% and 10%, respectively (P=0‐04). Multifactorial analysis demonstrated a significantly higher probability of survival for patients grafted in first remission (compared with more advanced remission states) and with bone marrow from young (age ≤ 20 years) donors. The 2‐year actuarial risk of relapse for patients with non‐B non‐T‐ALL transplanted in first remission was 0%, 32% and 69% for second and third or subsequent remission patients, respectively (P= 0‐04). For T‐ALL the actuarial risk of relapse at 2 years is 10% for first remission grafts and 48% for second remission grafts (P= 0‐07). Only patients (with both non‐B non‐T‐/and T‐ALL) transplanted in first remission have a high and stable probability of remaining in remission.
Fibronectin C in acute leukaemia
Authors: Reilly J. T. , Galloway M. J. , Mackie M. J. , McVerry B. A.
Published: March 2008

Fibronectin C (FN: C) is thought to represent fibronectin complexed with other plasma proteins and can be detected by a crossed two‐dimensional immuno‐electrophoretic technique. While we have not detected this on examination of normal plasma, FN: C was found in 26 of 33 patients (79%) with acute leukaemia at diagnosis. FN:C persisted throughout the induction phase of chemotherapy and disappeared only when a complete remission was obtained in 16 of 17 FN:C+ patients. FN:C has reappeared in the only patient whose leukaemia has relapsed to date. FN:C was present in both acute non‐lymphoblastic (85%) and acute lymphoblastic leukaemia (50%). Leukaemia remission rates were similar in patients who were FN: C+ or FN: C∼ (69% and 57%). Evidence is presented to suggest that the composition of FN:C is partially related to the binding of fibrinogen/fibrin to fibronectin in plasma. No significant difference in in vivo activation of coagulation was detected between FN: C+ and FN: C∼ patients. There was no correlation between the presence of FN: C and plasma fibronectin levels.
Acute myelogenous leukaemia modulated by B12deficiency: a case with bone marrow blast cell assay corroboration
Authors: Ahmann Frederick R. , Durie Brian G. M.
Published: March 2008

A patient is described who appeared to demonstrate modulation of acute myelogenous leukaemia with vitamin B12deprivation. Support for this observation was obtained via anin vitrobone marrow blast cell assay. The addition of B12to this patient's bone marrowin vitrosignificantly stimulated the colony forming ability of the blast cells. Patients with B12deficiency have an increased incidence of haematopoietic malignancies and excessive replacement of B12may in some cases have the potential of accelerating such disorders. Intensive B12replacement in refractory megaloblastic anaemias should be done with caution.
Pure red cell aplasia: relationship between inhibitory activity of T cells to CFU‐E and erythropoiesis
Authors: Hanada Takashi , Abe Tsukasa , Nakamura Haruo , Aoki Yasuko
Published: March 2008

T cell‐mediated inhibition of autologous late erythroid colony formation was found in two patients with PRCA. Each patient was treated separately with immunosuppressive agents, ALG, bolus methylprednisolone or cyclophosphamide. Cyclophosphamide was the most effective among these immunosuppressive therapies. Peripheral blood T cells, which were taken serially from the patients during the course of the disease, were cryopreserved until use. The inhibitory activity of T cells was assayed after remission using autologous bone marrow. It was found that the decrease of inhibitory activity was closely correlated with clinical improvement and that the effectiveness of the immunosuppressive therapy on inhibitory activities of T cells differed between therapies. These findings suggest that T cell‐mediated inhibition of erythropoiesis may be pathogenetic for PRCA in some patients.
Monocytes direct T lymphocyte stimulation of human peripheral blood granulocyte‐macrophage colony formation
Authors: Harvey. Andrew R. , Kaiser Jutta , Clarke Bryan J.
Published: March 2008

The committed granulocyte‐macrophage progenitor cell (or colony‐forming unit, CFU‐GM) differentiates in vitro under the influence of the soluble glycoprotein factor(s) termed colony stimulating activity (GM‐CSA), which can be derived from several cellular sources, including normal human peripheral blood mononuclear cells (PBMNC). We have investigated the respective roles of the monocyte and T lymphocyte components of PBMNC in generating GM‐CSA using as an assay CFU‐GM colony formation by purified peripheral blood null cells. Highly purified unstimulated T‐lymphocytes did not themselves stimulate null cell CFU‐GM colony formation, but when monocytes were also included, large numbers of colonies were observed, far greater than those stimulated by monocytes alone. This synergism was independent of HLA phenotype, occurring with T‐lymphocyte and monocyte fractions from unrelated donors. Media conditioned by unstimulated purified monocytes promoted CFU‐GM colonies from null cells only in the presence of T‐Iymphocytes, suggesting that monocytes produce a factor directing the synthesis and/or release of GM‐CSA by T cells.
A and B blood group antigen expression on mixed colony cells and erythroid precursors: relevance for human allogeneic bone marrow transplantation
Authors: Blacklock. H. A. , Katz F. , Michalevicz. R. , Hazlehurst. G. R. P. , Davies L. , Prentice H. G. , Hoffbrand A. V.
Published: March 2008

Using anti‐A and anti‐B blood group monoclonal antibodies and fluorescent activated cell sorting of human bone marrow, A (or B) blood group antigen was shown to be on 5.2 ± 5.9 (meanfSD) % of CFU‐GEMM and 12 ± 5 ± 19.6% of the erythroid burst forming cells (designated BFU‐GEMM) as defined by the mixed colony assay, and 49.5±20% of the BFU‐E and 83.5±9.9% of the CFU‐E as defined by the erythroid colony assay. This antigen expression on the BFU‐GEMM is consistent with the concept that erythroid bursts stimulated by leucocyte conditioned medium are less mature, and are closer in development to the pluripotent stem cell than the BFU‐E. These results help to explain the delayed erythropoiesis, and perhaps impaired engraftment of all cell lineages, that may occur in some recipients of ABO incompatible bone marrow transplants, with persistent and high anti‐A titres.
Alteration of platelet responses to metabolites of arachidonic acid by oral contraceptives
Authors: Pan Jia‐Qi , Hall E. R. , Wu K. K.
Published: March 2008

The effects of oral contraceptive (OC) usage on platelet responsiveness to arachidonic acid metabolites was investigated. Platelets obtained from women who had been taking oral contraceptives for at least 3 months were compared with those of age‐matched controls. Both the basal and prostacyclin (PGI2)‐stimulated platelet cAMP levels were significantly lower in OC users than in non‐users. There was no significant difference in the PGD2‐stimulated cAMP levels between the two groups. Furthermore, platelet aggregability to U46619, a TXA2 agonist, was greatly enhanced by OCs. Our data suggests that OC usage can specifically enhance platelet responsiveness to TXA2 while suppressing platelet responsiveness to PGI2. Thus their overall effect would be a disruption of normal platelet responses in favour of thrombus formation.
Neonatal antithrombin III
Authors: Peters Marjolein , Jansen Ed , Cate Jan W. ten , Kahle Laurens H. , Ockelford Paul , Breederveld Cees
Published: March 2008

Antithrombin III (AT‐III) heparin cofactor activity and its antigen levels have been determined in 106 plasma samples from 42 term and preterm neonates. In contrast to healthy adult controls, a reduced activity/antigen (act/ag) ratio (ranging from 0‐26 to 0‐86) was observed in 90% of the samples and was independent of the state of health of the infant. By modifying the routine assay techniques, laboratory artefacts were excluded as the cause of the observed discrepancy. The relative increase in antigenic AT‐III could not be accounted for by circulating AT‐III‐thrombin complexes, or by increased heparin cofactor II plasma levels in neonates.
Quantitation of prothrombin activation products in human urine
Authors: Bezeaud Annie , Guillin Marie‐Claude
Published: March 2008

Urine samples obtained from 37 normal individuals have been screened for the presence of prothrombin activation products using radioimmunoassays developed for fragment 1, fragment 2 and prothrombin derivatives bearing the thrombin region. The cross‐reacting materials detected in urine were isolated by affinity chromatography on insolubilized antibodies, and analysed by SDS polyacry‐lamide gel electrophoresis. The only prothrombin derivatives detected were fragment 1 (37/3 7) and fragment 2 (22/3 7). The mean values of daily urinary fragment 1 and fragment 2 excretion were respectively 13‐4 nM and 1‐5 nM.

The excretion of prothrombin derivatives has been quantitated in 14 normal pregnant women, during the third trimester of gestation. The mean values of urinary excretion were 47‐2 nM per day for fragment 1 (P<0‐005) and 6‐4 nM per day for fragment 2 (P<0‐05). The significant increase in fragment 1 and fragment 2 excretion observed in a condition known to be associated with the so‐called hypercoagulable state suggest that the measurement of prothrombin derivatives in urine could be a useful tool for the non‐invasive detection of thromboembolic diseases or prethrombotic states.
Allogeneic bone marrow transplantation in man: in vitro activity of FTS‐Zn on T‐cell markers and functions
Authors: BORDIGONI P. , BÉNÉ M. C. , FAURE G. , DONNER M. , Janot C. , Dardenne M. , Duheille J. , Olive D.
Published: March 2008

Thymulin (FFTS‐Zn) is a synthetic metallo‐nonapeptide similar to the serum factor of thymic origin FTS, which induces the maturation of lymphoid cells. The activity of this compound on peripheral blood mononuclear cells from 12 bone marrow recipients was studied in vitro. It was demonstrated that thymulin was able to induce or modulate the expression of T‐cell membrane markers, to enhance the proliferative responsiveness of lymphocytes to mitogens or allogeneic cells, and to increase mononuclear cells’ natural killer activity. This in vitro responsiveness was contemporary to a transient decrease of FTS levels in the patients’ serum, documented by sequential assays.

These results suggest that thymulin could be of interest as a prophylactic therapy to speed up the immunological reconstitution of bone marrow recipients.
A model for erythropoiesis in experimental chronic renal failure
Authors: Mason C. , Thomas T. H.
Published: March 2008

Chronic renal failure (CRF) in rats was induced by various subtotal nephrectomy procedures. Plasma creatinine concentrations ([Creat]p) were consistently elevated in partially nephrectomized (PNX) rats (P& 0.001) and renal function ([Creat]p−1) was correlated with the amount of intact renal tissue (r= 0.624, P < 0.001). Red blood cell (RBC) production in uraemic and non‐uraemic rats was assessed using the recovery of packed cell volume (PCV) and the production of reticulocytes in response to acute blood loss (5, 10, 15 and 20 ml kg−1 body wt). PCV recovery was significantly delayed and failed to reach pre‐bleed values for up to 28 d in PNX rats compared with full recovery within 8 d in controls. Linear relationships between the index of reticulocyte production (RP1) and blood loss induced falls in PCV were found in PNX (r=−0.679, P<0.001) and control rats (r=−0.696, P < 0.001). The index of RBC production was lower in PNX rats compared with controls. This was attributed to a reduced erythropoietin (Ep) mediated reticulocyte response to acute blood loss in PNX rats. PNX rats developed a normocytic, normochromic form of anaemia in which the red blood cell volume (RBCV) and plasma volume (PV) were both appropriate for measured PCVs. The reduced RBC production response in experimental CRF may explain the development of anaemia in PNX rats, even though steady state erythropoiesis may eventually be established at a reduced level of PCV. Furthermore, the quantitative evaluation of RBC production in response to acute blood loss provides a further model for the assessment of agents which may stimulate erythropoiesis in CRF.
Extramedullary presentation of the blast crisis of chronic myelogenous leukaemia
Authors: Jacknow Gerald , Frizzera Glauco , Gajl‐Peczalska Kazimiera , Banks Peter M. , Arthur Diane C. , McGlave Philip B. , Hurd David D.
Published: March 2008

Summary. We report the clinical histories and a multiparameter pathological study of the extramedullary lesions of seven patients with chronic myelogenous leukaemia in whom the initial clinical presentation of blast crisis (BC) was in an extramedullary site (lymph nodes in six, mandibular mass in one). Bone marrow BC was demonstrated simultaneously or within a few months in four patients. Three patients received chemotherapy only, four underwent bone marrow transplant. Six patients died within 1 year from diagnosis of extramedullary BC, one is alive without disease. The longest survivals (12 +, 12, 11 months) were those of patients who never developed bone marrow BC and were recipients of bone marrow transplant.

Studies of extramedullary disease included: histology; histochemistry for chloracetate esterase (CAE) and lysozyme; assays for TdT; electron microscopy; immunofluorescence for Fc‐receptors, immunoglobulins and lymphoid and myeloid antigens by a panel of monoclonal antibodies; and cytogenetics. Three cases were classified as myeloid BC based on histochemistry and/or ultrastructure and immunology (OKM1+, MCS2+, IG10+); two as lymphoid BC (CAE‐, lysozyme‐, TdT+), one of them expressing a T‐cell phenotype. Cytogenetic analysis of extramedullary lesions and simultaneous or subsequent bone marrows demonstrated identical karyotypes in three patients and significantly different karyotypes in one.
Profound alterations of the multimeric structure of von Willebrand factor in a patient with malignant lymphoma
Authors: Tran‐Thang C. , Mannucci P. M. , Schneider Ph. , Federici A. , Bachmann F.
Published: March 2008

Summary. Laboratory investigation of an acquired haemorrhagic diathesis in a 63‐year‐old man with malignant lymphoma revealed the classical haemostatic defects found in von Willebrand's disease (vWD). In addition, SDS–agarose gel electrophoresis demonstrated alterations of the von Willebrand factor (vWF) multimeric structure. A profound defect of large and intermediate size multimers was observed which was different from those seen in variants of congenital vWD. In vitro, weak inhibitory activity against factor VIII procoagulant activity and ristocetin cofactor activity was present in the patient's plasma. When patient's plasma was incubated with normal plasma, followed by centrifugation, vWF antigen (vWF:Ag) was precipitated. In vivo, after transfusion of cryoprecipitate, there was rapid plasma clearance of vWF:Ag and ristocetin cofactor and of FVIII coagulant activities.
Factor VIII antibody in a patient with mild haemophilia
Authors: Bovill Edwin G. , Burns S. L. , Golden Elizabeth A.
Published: March 2008

Summary. We present the rare occurrence of an inhibitor of factor VIII procoagulant arising in a patient with mild haemophilia A and rheumatoid arthritis. The inhibitor was transient and behaved like a low titre, type II factor VIII procoagulant inhibitor similar to previously reported cases (Biggs et al, 1972b). In vitro studies confirmed the type II‐like interaction of this inhibitor with the factor VIII procoagulant molecule. Factor VIII procoagulant antigen level was equal to the factor VIII procoagulant activity, which excluded dysproteinaemia as the cause. This patient's HLA type has no known association with abnormal immune responsiveness or autoimmune disease, and his clinical course as well as in vitro studies were similar to the eight previously reported cases of factor VIII procoagulant inhibitors arising in mild haemophilia A.
Demonstration of haemoglobin associated with isolated, purified spectrin from senescent human red cells
Authors: Snyder L. Michael , Garver Fred , Liu S. C. , Leb Laszlo , Trainor Jane , Fortier Normand L.
Published: March 2008

Summary. Employing a direct and sensitive radioimmunoassay (RIA) we have confirmed the presence of haemoglobin associated with isolated, purified spectrin from senescent red cells. Haemoglobin associated with spectrin occurs in the highest amount in cells with an MCHC greater than 36 g/dl and is approximately 3% of the total spectrin extract. Spectrin from the young cells had the least haemoglobin, while an intermediate amount was found in unfractionated, whole red cells. The RIA results were in close approximation with estimation of the haemoglobin–spectrin complex obtained by carefully integrating the Coomassie blue stain profiles from 4% SDS PAGE in densitometric scans from isolated spectrin.
Rapid correction of red‐cell nucleotide abnormalities following successful renal transplantation
Authors: Rejman A. S. M. , Mansell M. A. , Grimes A. J. , Joekes A. M.
Published: March 2008

Summary. Erythrocyte levels of 5’mono‐, di‐ and triphosphates of adenosine, inosine and guanosine, together with NAD+ (H) and NADP+ (H) were measured before and serially after renal transplantation. The high levels of ATP and guanosine triphosphate (GTP) fell to normal within 3 d of achieving a normal plasma creatinine. The decline in ATP and GTP levels paralleled the fall in plasma creatinine. Acute graft rejection was accompanied by a rise in ATP and GTP, both of which returned rapidly to normal with resolution of the rejection episode. Radiolabelling of red cells confirmed that the metabolism of the existing red‐cell population was corrected so that observed changes in nucleotide concentrations were not due to a new cohort of cells.
Stimulatory serum factors in aplastic anaemia
Authors: Nissen C. , Moser Y. , Weis J. , Speck B.
Published: March 2008

Summary. Human serum contains an activity which enhances the release of colony stimulating and burst promoting activity (CSA and BPA). It is low in the majority of normal sera and was found elevated in patients with aplastic anaemia.

The patient's ‘response’ to autologous serum releaser activity was measured by comparing CSA and BPA release by patient cells in percentage of release by normal cells. This ‘response’ was negatively correlated with serum releaser activity (P=0·0035 for CSA‐release, P <0·0001 for BPA‐release), i.e. releaser activity was high, when factor release was low.

This inverse relationship between releaser activity and the patient's response was also observed in four patients with pancytopenia of causes other than aplastic anaemia. We conclude that elevated serum releaser activity reflects a repair mechanisms which operates when CSA‐ and BPA‐production is inadequate. Thus, releaser activity is likely to be a haemopoietic regulator.
Stimulatory serum factors in aplastic anaemia II
Authors: Nissen C. , Moser Y. , Speck B. , Gratwohland A. , Weis J.
Published: March 2008

Summary. Serum from patients with aplastic anaemia contains two distinct stimulatory activities on haemopoiesis in culture. The first is a highly unstable enhancing activity, which mainly stimulates colony formation from BFU‐E and macrophage precursors, and only acts when added directly to target bone marrow cultures. It is destroyed by Sephadex G‐150 chromatography, and thus differs from colony stimulating activity (CSA) and burst promoting activity (BPA). Its mode of action is unknown. It was elevated in 70/97 patients with severe aplastic anaemia (SAA). 71 of these 97 patients were treated with high dose immunosuppression. 55/71 who achieved self‐sustaining haemopoiesis had higher serum stimulating activity on BFU‐E than 16/71 who never achieved remission (P= 0·0004). It was predictive of response as an all or none phenomenon, independent of the time required for recovery. It was, however, unsatisfactory as a single prognostic test. Bone marrow reconstitution also occurred in 4/71 patients whose serum inhibited BFU‐E in direct culture.

The second stimulator acts via enhancement of CSA‐ and BPA‐release by accessory cells and is therefore termed ‘releaser’ activity. It was elevated in 27 of 51 aplastic anaemia patients and did not correlate with direct stimulatory activity. High ‘releaser’ activity was not predictive of response in 42 patients treated with high dose immunosuppression. However, the ability of patient cells to respond to autologous ‘releaser’ activity was a positive risk factor. Patients whose cells released an excess of CSA in the presence of autologous serum had a significantly higher chance of autologous recovery within 3 months than patients who produced little or no CSA in the presence of normal or excess releaser activity (P <0·0001).

A scoring system which includes these two good risk factors is proposed for estimation of a patient's probability to recover autologous bone marrow reconstitution.
Heterogeneous distribution of antigens on human platelets demonstrated by fluorescence flow cytometry
Authors: Dunstan Robert A. , Simpson Marcus B.
Published: March 2008

Summary. We have used fluorescence flow cytometry to analyse cell‐to‐cell variability in the density of platelet ABH, Ii, Lewis, P, P1A1, Bak,a and HLA class I antigens. Human IgG and IgM antibodies were used in a two‐stage assay with goat FITC‐conjugated antihuman IgG (H&L) antibody as the label, followed by single cell analysis of 10 000 platelets per sample using a 256‐channel fluorescence flow cytometer (Becton‐Dickinson FACS Analyser). Computer analysis of fluorescence intensity histograms for mean and peak channel and coefficient of variation shows that the degree of heterogeneity in platelet antigen density varies with each particular blood group. The broad fluorescence distribution curves with oligosaccharide antigens (CVs: A = 53, B = 40, I = 44, Lea= 40, P = 40) indicate that these antigens possess a greater variability in the number of sites per cell compared to the more homogeneous distribution of P1,A1 BaK,a and HLA (CVs: P1A1= 24, HLA = 30). These findings may partly account for the mechanism by which transfusion of ABO‐incompatible platelets results in a biphasic survival curve, with a period of early rapid removal of those platelets with a high density of antigen sites, followed by a relatively normal survival curve for those platelets that possess only a few or no antigen sites. In contrast, P1A1 and HLA sites are less variable in number from one platelet to another in a given donor, and immune‐mediated removal would be more likely to approximate a single exponential curve.
Low haematocrit and prolonged bleeding time in uraemic patients: effect of red cell transfusions
Authors: Fernandez F. , Goudable C. , Sie P. , Ton‐That H. , Durand D. , Suc J. M. , Boneu B.
Published: March 2008

Summary. This study demonstrates that a low haematocrit is the main determining factor of the prolonged bleeding time often encountered in uraemic haemodialysed patients. Thirty‐three patients submitted to regular haemodialysis and having a platelet count > 100x109/l were investigated with the following tests: simplate bleeding time, blood cell count, platelet aggregation induced by ADP, collagen and sodium arachidonate, arachidonate induced MDA synthesis, tests for detection of an acquired storage pool disease, and factor VIII complex level. The results were compared to two other groups; one of uraemic patients not yet subjected to haemodialysis and another of healthy volunteers. The results were basically identical in the two groups of uraemic patients. The only consistent abnormality was a 30–35% reduction in the platelet MDA synthesis in comparison with control subjects. There was a negative correlation between the log bleeding time and the haematocrit (r = 0.78, P<0.01). Fourteen uraemic patients having a prolonged bleeding time were submitted to a red cell transfusion programme and were investigated a second time under identical conditions. There was no change in any of the platelet function tests or in the factor VIII complex level, but the bleeding time was normalized when the post‐transfusion haematocrit was over 26% (nine patients). This study emphasizes the role of anaemia in the pathogenesis of the prolonged bleeding time in uraemia and suggests that red cell transfusion can be a long‐term efficient therapeutic measure to stop bleeding in these patients.
(Aγδβ)°‐Thalassaemia in Blacks is due to a deletion of 34 kbp of DNA
Authors: Henthorn P. S. , Smithies O. , Nakatsuji T. , Felice A. E. , Gardiner M. B. , Reese A. L. , Huisman T. H. J.
Published: March 2008

Summary

DNA from members of 10 Black families with conditions considered to be Gγδβ)°‐thalassaemia or Gγδβ)°‐HPFH were studied by using restriction enzyme analysis. One or more affected members from each family were shown to have the same deletion of 34 kbp of DNA in the human β‐globin gene cluster. A clone spanning the deletion was isolated from the DNA of one such person and studied in detail. The deletion removed part of the Aγ and all of the Ψβ, δ and β‐globin genes and is different from the four previously identified deletions which caused a condition presently known as (Aγδβ)°‐thalassaemia.
AIDS surveillance in haemophilia
Authors: Daly Helena M. , Palmer R. , Scott G. L. , Lee G.
Published: March 2008

Summary

We suspected a patient attending our Haemophilia Centre had developed Acquired Immunodeficiency Syndrome (AIDS) and therefore immunological evaluation was performed on 43 patients with haemophilia and von Willebrand's disease attending the Centre. The index patient died of Pneumocytis carinii pneumonia. Thirty‐one patients had either abnormal T cell subsets or helper/suppressor ratios. Thirty‐two patients had hypergammaglobulinaemia. There was no direct correlation between these immunological abnormalities and the total amount or type of treatment received. T cell abnormalities were not confined to the 13 patients who had received the same batches of concentrate as the index case.

The index case simultaneously contracted hepatitis B. He was the only patient to receive a large amount of the suspect batches of concentrate, not previously immune to hepatitis B.
A case of elliptocytosis associated with a truncated spectrin chain
Authors: Ohanian V. , Evans Jane P. , Gratzer W. B.
Published: March 2008

Summary. A case of haemolytic anaemia with elliptocytosis is described, in which a large part of the smaller (β) subunit of the spectrin is truncated, and has an apparent molecular weight of about 214 000 compared with about 230 000 for the normal chain. It is shown that this is not a product of adventitious proteolysis during lysis or extraction. At the same time about 35% of the total spectrin in the cells is liberated from the membrane as the dimer (which is present in normal cells to the extent of less than 10%). The truncated (β') chain appears exclusively in this dimer fraction. The β'‐chain is incapable of phosphorylation by the endogenous cAMP‐independent membrane kinase, and it may be inferred that the deleted segment of the chain contains both the spectrin self‐association site and the residues normally phosphorylated. The αβ'‐dimer is active with respect to participation in a ternary complex with its partnering proteins in the membrane cytoskeleton, F‐actin and 4.1, confirming that the phosphorylation sites are not involved in the primary interaction with the other cytoskeletal proteins at the network junctions. The spectrin α‐chain generates the terminal tryptic fragment of molecular weight 80 000 characteristic of normal spectrin, rather than the 74 000 molecular weight peptide derived from the α‐chain in cases of hereditary elliptocytosis and pyropoikilocytosis, associated with anomalous self‐association of spectrin dimer. Membrane cytoskeletons, extracted from the patient's red cells, undergo normal gelation on incubation with cAMP‐independent kinase and ATP, and thus do not resemble those derived from hereditary spherocytosis cells. The properties of the anomalous spectrin resemble in most respects that described in a French family by Dhermy et al(1982).
Production of human active BPA from TCGF independent T cell lines that do not excrete HTLV: proof of direct action of MLA‐144 derived BPA using purified BFU‐E
Authors: Linch D. C. , Donahue R. E.
Published: March 2008

Summary. Burst promoting activity (BPA) and colony stimulating activity (CSA) were measured in the supernatants from six T‐cell lines which are IL‐2 independent and do not excrete human T‐cell leukaemia virus. Two cell lines were shown to produce high levels of BPA, namely MLA‐144 and the Jurkat cell line. MLA‐144 is a gibbon T‐cell line which can proliferate and produce BPA in serum free HB101TM medium. The BPA from this line was shown to act directly on BFU‐E by studies using highly purified peripheral blood derived BFU‐E. The Jurkat CM had far less activity against purified progenitors. These cells lines will be of value in the study of erythropoietic regulation.
The (4;11) translocation in acute leukaemia of childhood: the importance of additional chromosomal aberrations
Authors: Secker‐Walker Lorna M. , Stewart Elizabeth L. , Chan Li , O'Callaghan Una , Chessells Judith M.
Published: March 2008

Summary. Case reports of four girls and one boy with acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML) and t(4;11) are presented. The incidence of t(4;11) ascertained at diagnosis in ALL was 2.6% and in AML 5.3%. Four of the children were under 2 years and one was 11 years at diagnosis. Leucocyte counts above 71 × 109/1 and liver, spleen and node enlargement were found in all cases. Blasts of the four cases tested at diagnosis were negative to the c‐ALL antigen and either TdT+ (ALL) or TdT‐ (AML M1). Maximum survival was less than 8 months. Additional chromosomal change was found at diagnosis in two cases and in relapse in a third. In the case of AML t(4;11) (q21;p15) was present as a second translocation. Additional numerical changes, in these and other reported cases, included +6, commonly found in ALL, +8, +19, more often reported in AML. It is suggested that additional chromosomal changes in these cases support cytochemical and surface marker evidence that t(4;11) has a pluripotent target cell, similar to that of the Philadelphia translocation.
Drug induced red blood cell autoantibodies co‐developed with drug specific antibodies causing haemolytic anaemias
Authors: Habibi Bahman
Published: March 2008

Summary. Four individuals with anti‐glafenine, anti‐latamoxef and anti‐teniposide antibodies were found to have an associated red blood cell autoantibody. The two components could be separated by selective absorption and showed distinct time course patterns. In three patients a well‐defined blood group antigen was recognized as the receptor for both auto‐ and drug specific antibodies. Similarities between this type of immune response to drugs and the well‐known hapten and carrier specificities developed in animals immunized by hapten–carrier conjugates are discussed.
The use of danazol in the management of chronic immune thrombocytopenic purpura
Authors: McVerry B. A. , Auger M. , Bellingham A. J.
Published: March 2008

Summary. Danazol has recently been reported to be an effective mode of treatment for patients with refractory immune thrombocytopenic purpura. Following a 3 month trial of danazol, only one of 10 patients experienced a sustained increase in platelet counts and two other patients had a transient improvement. While the drug was well tolerated, it does not appear to be particularly helpful in the management of these patients.
Inherited haemorrhagic disease with abnormal prothrombin consumption
Authors: Rocha E. , Páramo J. A. , Cuesta B. , Fernandez J.
Published: March 2008

Summary.The propositus is a 4‐year‐old boy who presented with a history of excessive bleeding after surgical procedures as well as haematomas and epistaxis. The defect in haemostasis consisted in an anomaly of the prothrombin consumption tests as the only abnormality while all the other conventional coagulation and fibrinolysis tests as well as platelet function tests were normal. The father of the propositus had no previous history of excessive bleeding but was found to have an abnormal prothrombin consumption index. The reaction to prothrombin conversion, normal at onset, slowed down to less than normal and did not reach completion until 24 h. Thein vivostudies suggest that the effect does not act on the interaction between platelet phospholipid and plasma. The factor II dosage and the electrophoretic mobility of prothrombin of the plasma were normal; nevertheless when studying the purified prothrombin by means of crossed immunoelectrofocusing there appeared an anomaly of pI. This result suggests the possible existence of an abnormal prothrombin molecule responsible for a slow prothrombin conversion.
Cell lineage heterogeneity in blast crisis of chronic myeloid leukaemia
Authors: Bettelheim P. , Lutz D. , Majdic O. , Paietta E. , Haas O. , Linkesch W. , Neumann E. , Lechner K. , Knapp W.
Published: March 2008

Summary Blast cells from 45 patients with chronic myeloid leukaemia in blast crisis (CML‐BC) were immunologically phenotyped with a panel of 26 monoclonal antibodies and studied for terminal deoxynucleotidyl transferase (TdT) content. Out of 45 blast‐populations, 28 showed a myeloid, 14 a lymphoid, two a mixed and one an unclassifiable marker profile.

In contrast to acute myeloid leukaemia (AML), we found frequent involvement of the thrombopoietic and erythropoietic systems in myeloid CML‐BC. Furthermore, the marker profile on blast cells in myeloid CML‐BC was different from that seen in AML. The blast cells in lymphoid blast crises of CML displayed the same lymphoid marker profile as those in acute lymphoblastic leukaemia.

In three of 16 patients who were serially tested, we observed phenotypic changes in the blast cell populations. In one patient the blasts changed from lymphoid to myeloid type while remaining TdT‐positive; in another case the blasts switched from granulomonocytic TdT‐negative to granulomonocytic TdT‐positive. In the third patient erythroid precursor cells appeared as the disease progressed.

The results indicate the capacity of blast populations in CML‐patients during blast crisis to differentiate along several pathways.
Phylogenetically more conservative epitopes among monoclonal antibody‐defined antigenic sites of human transferrin are involved in receptor binding
Authors: Bártek Jiří , Viklický Vladimír , Stratil Antonín
Published: March 2008

Summary Of eight monoclonal antibodies raised against human transferrin, one (H.TF‐14) cross reacted with pig and rabbit transferrins and one (H.TF‐1) showed cross‐reactivity with horse and dog transferrins. While rabbit and pig transferrins exhibited the same patterns of binding to MOLT‐3 cell receptors as human and horse transferrins, binding of mouse and dog transferrins was weaker and bovine and carp transferrins gave entirely negative results. The results of these competitive binding experiments were confirmed by a biological test in which bovine transferrin had no effect on the growth of MOLT‐3 cells when added to a serum‐free medium. The observed correlation between cross‐reactivity of anti‐transferrin monoclonal antibodies and the binding abilities of transferrins to the MOLT‐3 cell receptors may be associated with the conservatism of the part of the transferrin molecule recognized by the cell receptor.