bluuebunny/crossref_metadata_2025 huggingface dataset:
Monosomy 7 in Childhood: a Myeloproliferative Disorder
Authors: Sieff C. A. , Chessells J. M. , Harvey B. A. M. , Pickthall V. J. , Lawler S. D.
Published: March 2008

Summary. Between 1976 and 1979 a myeloproliferative disease associated with cells monosomic for chromosome number 7 in the bone marrow was seen in six boys aged 51/2 months to 8 years (median 10 months). Presenting features included hepatosplenomegaly (5/6), respiratory infections (4/6), pallor (2/6) and skin infections (1/6). Haematological features included a leucoerythroblastic anaemia with leucocytosis and thrombocytopenia, and a hyperplastic marrow with a slight excess of blasts. Fetal haemoglobin was normal in four patients and mildly raised in the other two. Neutrophil function tests showed defective chemotaxis with reduced killing, despite a normal NBT test. Cytogenetic analysis of the marrow showed a preponderance of cells with monosomy 7; the blood lymphocytes were cytogenetically normal.

In three patients the disease progressed to acute myeloid leukaemia (AML) after 3 weeks to 23 months; the only patient who remitted did so in response to 6‐mercaptopurine and prednisolone, but relapsed 16 months later. A fourth child developed massive splenomegaly which initially responded to 6‐mercaptopurine and prednisolone, but progressed to myelofibrosis 11 months later. A fifth child died from anaemia and respiratory infection without progression to leukaemia and the sixth patient has not yet developed leukaemia.

Monosomy 7 is the diagnostic criterion of one of the more common myeloproliferative states in childhood and carries a high risk of progression to AML. The acute phase is usually resistant to chemotherapy, but even in responsive cases treatment does not result in elimination of the abnormal clone. Allogeneic bone marrow transplantation should be considered in cases with a suitable donor.
The Migratory Properties of Indium‐111 Oxine Labelled Lymphocytes in Patients with Chronic Lymphocytic Leukaemia
Authors: Wagstaff J. , Gibson C. , Thatcher N. , Crowther D.
Published: March 2008

Summary. These studies describe the application of a new method for following the migration of autologous lymphocytes in normal subjects and patients with chronic lymphocytic leukaemia (CLL). There is evidence that Indium 111 oxine is a reliable radioactive cell label for in vivo studies of lymphocyte traffic in man. In normal subjects, where 60‐70% of the lymphocytes labelled are T cells, the results are different from those of previous workers. The lymphocytes leave the blood initially but later return to it. It is believed that this is due to the reappearance of cells which at first entered the spleen. It is suggested that the difference between these data and those of Hersey (1971) is due to the failure of lymphocytes in the latter studies to return to the blood after primary migration. In CLL no such reappearance in the blood is seen and the lymphocytes do not leave the spleen in significant numbers over 48 h. This suggests that CLL B cells either do not recirculate through spleen or that their transit time is greater than 48 h. Bone marrow localization in CLL patients is greater than in the normal subjects, suggesting that either a larger proportion of the neoplastic B lympliocytes enter this compartment or their transit time through it is longer than the transit time of a normal T cell predominant population. Localization in normal‐sized lymph nodes in patients with CLL is less than that in the lymph nodes of normal subjects. This may possibly be explained by the greater propensity of T lymphocytes to enter lymph nodes than B lymphocytes, or by the altered migratory properties of CLL B lymphocytes as compared with normal B cells.
Failure to Augment Primary Rh Immunization Using a Small Dose of ‘Passive’ IgG Anti‐Rh
Authors: Contreras Marcela , Mollison P. L.
Published: March 2008

Summary. The immune response to the i.v. injection of 1 ml of D‐positive (ccDEE, presumably cDE/cDE) red cells was studied in 12 D‐negative (ccddee) subjects who received a simultaneous i.m. injection of 5 μg anti‐D (the test group) and in a further 12 D‐negative subjects who were not given anti‐D (the control group). In all cases the red cells were labelled with 51Cr. Further injections of 1 ml of red cells were given at 7 and 12 months to subjects who had not made serologically detectable anti‐D. In the test group the rate of clearance of the first injection of red cells was very variable, 99% of the cells being cleared in a period ranging from 3 to 20 d. Within 6—10 weeks of the first injection four subjects had produced anti‐D; four more subjects produced anti‐D after the second injection of red cells. In the control group Cr red cell survival following the first injection was normal in six cases and curtailed in the remaining six. Of the latter, four produced anti‐D within 4—10 weeks of the first injection and two produced anti‐D only after the second or third injection of red cells. Amongst the subjects who produced anti‐D after the first injection of red cells antibody levels were lower in the test group than in the control group, indicating that the injection of 5 μg of anti‐D with 1 ml red cells had not augmented the immune response and might have partially suppressed it.
Total Tumour Mass Score (TTM): a New Parameter in Chronic Lymphocytic Leukaemia
Authors: Jakšić Branimir , Vitale Branko
Published: March 2008

Summary. Total tumour mass score (TTM) is introduced as a new parameter in chronic lymphocytic leukaemia (CLL) in order to assess the tumour mass within all major body compartments. TTM is the sum of: (1) the square root of the number of peripheral blood lymphocytes per nl, (2) the diameter of the largest palpable lymph node in centimetres, and (3) the enlargement of the spleen below left costal margin in centimetres. The validity of the proposed scoring system was evaluated in a prognostic study on 256 CLL patients. Patients with high TTM (>9.0) at presentation had the expected median survival (EMS) of 39 months whereas patients with low TTM (<8.9) had EMS of 101 months (P< 0.0005). TTM was a significant prognostic factor even when adjustment was performed for age, sex, lymphocyte count, response to therapy, TTM‐distribution pattern and bone marrow failure. In contrast, the lymphocyte count was not prognostically significant when adjustment was performed for TTM. This suggests that TTM is a better indicator of tumour cell burden than the lymphocyte count. TTM measurement enables the analysis of the tumour mass size independently of other factors. TTM is a simple, objective parameter that can be measured as a continuous quantitative variable allowing derivation of new factors. TTM‐doubling time and TTM‐response to therapy were significant for prognosis (P< 0.0005). The proposed scoring system can also be used for the study of the tumour mass distribution pattern.
A Double Blind Study of Prostacyclin in Cardiopulmonary Bypass Surgery
Authors: Walker Isobel D. , Davidson J. F. , Faichney A. , Wheatley D. J. , Davidson K. G.
Published: March 2008

Summary. In a double‐blind placebo‐controlled trial of 48 patients requiring open heart surgery, prostacyclin (PGI2) was infused in a dose of 20 ng/kg/min throughout cardiopulmonary bypass. When compared with the placebo group, the patients given active PGI2 were found to have significantly higher platelet counts from 30 min after commencement of bypass and in the immediate post‐operative period, and to have significantly less elevation of the platelet secretory proteins, β thromboglobulin and platelet factor 4 during bypass. The mean weight increase in the arterial line filters was significantly greater in the placebo‐treated patients than in the PGI2 group. It is suggested that infused PGI2 decreases platelet activation during cardiopulmonary bypass and that further studies are required to establish its clinical value in this situation.
Transfusion Studies in Patients with Familial Antithrombin III (ATIII) Deficiency: Half‐disappearance Time of Infused ATIII and Influence of such Infusion on Platelet Life‐span
Authors: Winter J. H. , Fenech A. , Bennett B. , Douglas A. S.
Published: March 2008

Summary. Two patients with familial ATIII deficiency received infusions of a concentrate of ATIII prepared from human plasma. Serial plasma samples were assayed for their functional and immunological content of ATIII. The rates of disappearance of ATIII activity found in this study suggest that, initially, frequent infusions are necessary to maintain normal levels of ATIII activity in patients with a severe deficiency. In one patient platelet survival did not appear to be influenced by ATIII infusions.
Bone Marrow Fibroblastoid Colony‐Forming Cells (F‐CFC) in Aplastic Anaemia: Colony Growth and Stimulation of Granulocyte‐Macrophage Colony‐Forming Cells (GM‐CFC)
Authors: Gordon M. Y. , Gordon‐Smith E. C.
Published: March 2008

Summary. Colonies of fibroblast‐like cells have been grown from the mononuclear cell fractions of bone marrow aspirated from normal individuals and patients with aplastic anaemia. Some of the characteristics of the fibroblastoid cells have been determined and their granulocyte‐macrophage colony‐stimulating activity (CSA) in semi‐solid agar culture has been used as a functional test of their influence on granulopoiesis.

The incidence and growth rates of fibroblastoid colony‐forming cells (F‐CFC) from aplastic patients’bone marrows were not markedly different from normal either before or after treatment by allogeneic bone marrow transplantation or with antilymphocyte globulin (ALG).

Confluent monolayers of fibroblastoid cells grown from normal marrow were, on the whole, poor stimulators of granulocyte‐macrophage colony‐forming cells (GM‐CFC) and CSA was not detected in the supernatant medium. Fibroblastoid monolayers derived from many of the aplastic bone marrows studied were efficient stimulators of GM‐CFC but, like the monolayers grown from normal cells, did not release CSA into the culture medium.

Addition of methylprednisolone (MP) to the cultures had little effect on fibroblastoid cell growth, induced fat‐accumulation by some of the fibroblastoid colonies comprising the monolayer and reduced the abilities of the monolayers to stimulate GM‐CFC.
THYMIDINE KINASE ISOENZYMES IN CHRONIC LYMPHOCYTIC LEUKAEMIA
Authors: Ellims Peter H. , Gan T. Eng , Van der Weyden Martin B.
Published: March 2008

Summary. The profile of thymidine kinase isoenzymes was determined in peripheral blood lymphocytes from 14 patients with chronic lymphocytic leukaemia (CLL) and 31 controls. Twelve patients with indolent disease showed TK2 isoenzyme activity, while two patients in whom the disease evolved and two patients who presented with aggressive disease exhibited TK1 isoenzyme activity. The demonstration of TK1 activity in the peripheral blood lymphocytes of clinically aggressive CLL suggests that this isoenzyme may be a useful biochemical marker of such behaviour.
Monoclonal Antibody to Human Platelet Glycoprotein I II. EFFECTS ON HUMAN PLATELET FUNCTION
Authors: Ruan C. , Tobelem G. , McMichael A. J. , Drouet L. , Legrand Y. , Degos L. , Kieffer N. , Lee H. , Caen J. P.
Published: March 2008

Summary. The effect on platelet function of a monoclonal platelet antibody to platelet membrane glycoprotein I was tested. This antibody, AN51, inhibited ristocetin or bovine factor VIII‐induced aggregation but did not modify ADP, collagen type I or type III, thrombin or arachidonic acid induced aggregations. Furthermore, the adhesion‐aggregation of platelets induced by microfibrils was also inhibited by the antibody. Platelet adhesion to rabbit aorta subendothelium was impaired by the antibody. The persistent adhesion of platelets to collagenase‐treated subendothelium was also inhibited. These findings strongly suggested that platelet membrane glycoprotein I could interact with a non‐collagenic microfibrillar component of subendothelium. The binding of factor VIII/von Willebrand factor to platelet membrane in the presence of ristocetin was decreased in the presence of the antibody. Platelet membrane glycoprotein I could, thus, be a binding site for factor VIII/von Willebrand factor to allow platelet adhesion to subendothelium.
Heparin‐induced Thrombocytopenia: Effect of Heparin Platelet Antibody on Platelets
Authors: Chong B. H. , Grace C. S. , Rozenberg M. C.
Published: March 2008

Summary. The plasma of two patients with heparin‐induced thrombocytopenia has been shown to cause platelet aggregation in the presence of heparin. The platelet aggregating factor was isolated in the IgG fraction of the patients’sera suggesting that it was an antibody. This heparin anti‐platelet antibody (HAP‐Ab) induced platelet aggregation and release but did not cause platelet lysis, although it fixed complement. Platelet aggregation was inhibited by EDTA and by inactivation of complement. There was a significant production of malondialdehyde (MDA) and thromboxane B2 (TXB2) implying a role of the prostaglandin synthesis pathway in HAP‐Ab induced aggregation. ADP release also appeared to be involved as apyrase blocked aggregation while hirudin, a thrombin inhibitor, had no effect. The thrombotic complications that have recently been reported in patients with heparin‐induced thrombocytopenia may be explained by some effects of HAP‐Ab on platelets, namely: the antibody mediated platelet factor 3 release, prostaglandin endoperoxides and thromboxane A2 (TXA2) production and platelet aggregation in vivo. These HAP‐Ab mediated effects could be inhibited by anti‐platelet drugs such as aspirin, indomethacin and dipyridamole and thus may have therapeutic implications.
Megaloblastic Change is a Feature of Colonies Derived from an Early Erythroid Progenitor (BFU‐E) Stimulated by Monocytes in Culture
Authors: Reid C. D. L. , Baptista Luisa C. , Deacon R. , Chanarin I.
Published: March 2008

Summary. The morphology of stained preparations of cells from human bone marrow and peripheral blood erythroid colonies cultured in methylcellulose, were examined by light microscopy. Although the morphology of 7 d erythroid colonies (CFU‐E) was largely normoblastic, bone marrow and peripheral blood erythroid bursts (BFU‐E) showed a variable degree of megaloblastic and dyserythropoietic change. This was not due to nutritional deficiencies of the culture system and the deoxyuridine suppression test demonstrated active thymidine synthesis.

Megaloblastic morphology was correlated with the growth induced by the addition of monocytes to erythroid progenitors. It was concluded that megalo‐blastosis was a feature of the erythroblasts derived from an early BFU‐E which required monocytes for their development.
Chronic Myelocytic Leukaemia: a Pluripotent Haemopoietic Cell is Involved in the Malignant Clone
Authors: Douer Dan , Levin Alexandra M. , Sparkes Robert S. , Fabian Ina , Sparkes Maryellen , Cline Martin J. , Koeffler H. Phillip
Published: March 2008

Summary. Haemopoietic cells with pluripotent capabilities, were grown in soft‐gel cultures from the peripheral blood of a glucose‐6‐phosphate dehydrogenase (G6PD) electrophoretic A,B heterozygous female with chronic myelocytic leukaemia (CML). The cells produced mixed colonies composed of erythrocytic and granulocytic progeny. Only type B isoenzyme of G6PD was found in mixed colonies, in mature neutrophils, erythrocytes, and committed granulocyte and erythrocyte stem cells. The fibroblasts of the patient contained both A and B isoenzymes of G6PD. This study provides direct evidence that a pluripotent haemopoietic stem cell is involved in the malignant clone in CML.
Expression of Receptors for IgA in Hairy‐Cell and Other B‐Cell Leukaemias
Authors: Lydyard Peter M. , Powell Robert G. , Fanger Michael W. , Worman Colin P. , Cawley John C.
Published: March 2008

Summary. In six cases of both hairy‐cell leukaemia (HCL) and chronic lymphocytic leukaemia (CLL) it was shown that the pathological cells express receptors for the Fc portion of IgA (RFcα). Many of the cells simultaneously expressed receptors for IgA, IgM and IgG, and blocking studies showed that these are distinct receptors. In contrast, the malignant cells of most of the various other B‐cell leukaemias studied showed low levels of RFcα expression. The significance of the results is briefly discussed and it is suggested that receptor expression may be a marker of certain stages of B‐cell development.
Iron Uptake and Ferritin Synthesis by Peripheral Blood Leucocytes in Patients with Primary Idiopathic Haemochromatosis
Authors: Jacobs A. , Summers M. R.
Published: March 2008

Summary. Iron uptake and storage in peripheral blood leucocytes has been studied to test the hypothesis that the basic lesion in idiopathic haemochromatosis resides in a failure of mononuclear phagocytic cells to store iron. In seven fully treated cases of this disease there was no evidence of any abnormality in iron uptake, synthesis of the storage protein ferritin or its ability to incorporate iron. The ferritin content of leucocytes was found to be increased.
Haematological factors associated with avascular necrosis of the femoral head in homozygous sickle cell disease
Authors: Hhawker H. , Neilson H. , Hayes R. J. , Serjeant G. R.
Published: March 2008

Summary. The haematological indices in 50 patients with homozygous sickle cell (SS) disease and avascular necrosis of the femoral head and in 180 patients with SS disease without this complication have been compared. Avascular necrosis of the femoral head was significantly associated with high total haemoglobin levels and with low fetal haemoglobin levels. Low fetal haemoglobin levels are associated with increased intravascular sickling. These results suggest that both intravascular sickling and the increased viscosity associated with high haemoglobin levels are related to the development of avascular necrosis of the femoral head in SS disease.
Erythrocyte membrane proteins in an unusual case of congenital dyserythropoietic anaemia type II (CDA II)
Authors: Harlow Roger W. H. , Lowenthal Ray M.
Published: March 2008

Summary. Analysis of the erythrocyte membrane protein of an atypical case of congenital dyserythropoietic anaemia type II (CDA II) by electrophoresis on polyacrylamide gels revealed marked abnormalities. One‐dimensional analysis showed a pronounced decrease in levels of B1.1 components, an increase in the level of B1.4 and the appearance of new components in the A region as well as in the C region of the gel. There were no artefacts due either to the presence of early red cells or to abnormally high levels of proteolytic enzyme activity in the CDA II preparations. Two‐dimensional analysis confirmed the alterations in membrane components showing two novel A region species not reported in other studies of this disease. Abnormalities in components of such large molecular size may explain the greater degree of membrane perturbation seen in the present case and support the idea that CDA II may embrace more than one disease entity.
Comparison of antithrombin III assays using biological and chromogenic substrates
Authors: Philo R. D. , Gaffney P. J.
Published: March 2008

Summary. Antithrombin III (At III) levels in plasma samples were determined by incubation of diluted plasma with thrombin, either with or without heparin, followed by measurement of residual thrombin using clotting and amidolytic methods. All assays were of multidose bioassay design suitable for parallel line analysis. Assays without heparin showed only a small difference between amidolytic and clotting methods, which was not significant at the 95% level. Assays with heparin showed a much larger difference between clotting and amidolytic methods which is shown to be attributable to the heat defibrination step used in the clotting assay. Heat defibrination and ancrod defibrination methods are compared using the amidolytic heparin cofactor assay and it is shown that heat defibrination can cause the loss of nearly 50% of the functional At III in a reconstituted freeze‐dried plasma which was used as a standard. No loss occurs when ancrod is used for defibrination. It is an advantage of the amidolytic heparin cofactor assay that defibrination is not required.
Atypical T lymphoproliferative disorder demonstrating in vitro suppressor and helper characteristics
Authors: Proctor S. J. , McGregor A. M. , Clark Jane , McLachlan Sandra , Dickinson Anne
Published: March 2008

A patient initially diagnosed on surface marker status as having T cell chronic lymphatic leukaemia (T‐CLL) was found to have arthropathy and recurrent pulmonary infarction associated with a high anti‐DNA antibody titre. The T cells from this patient, on assessment in an in vitro pokeweed mitogen driven B cell system, demonstrated suppressor and helper characteristics but lacked antibody dependent cellular cytotoxicity (ADCC) activity and natural killer (NK) activity. Using peripheral blood mononuclear cells (PBM) from patients with Hashimoto's thyroiditis and normals, it was shown that the patient's T cells suppressed both IgG and thyroid autoantibody production. Irradiation of the patient's PBM inhibited the suppressor effect and a residual helper effect remained. The patient was treated with systemic steroids for exacerbations of arthropathy which caused a fall in lymphocyte count. After 36 months the DNA binding activity spontaneously improved and the lymphocytosis disappeared. It is indicated that T‐cell proliferations demonstrating functional activity must be assessed within the context of any underlying non‐haematological clinical and laboratory findings.
Haemostatic and rheological changes in normal pregnancy and pre‐eclampsia
Authors: Inglis T. C. M. , Stuart J. , George A. J. , Davies A. J.
Published: March 2008

Platelet activity (microaggregate formation, ADP‐aggregation and β‐thromboglobulin release), coagulation activity (fibrinogen level and factor VIII related antigen/coagulant activity), and rheological factors (plasma viscosity, whole‐blood viscosity and erythrocyte deformability) were studied serially in 14 healthy pregnancies to determine the effect of gestational age. Fourteen patients with pre‐eclampsia, each matched for stage of gestation with a normal pregnancy, showed normal rheology of circulating blood and normal aggregability of circulating platelets, but there was a significant increase in platelet release of β‐thromboglobulin and a shorter platelet production time, indicating a shorter life‐span. The results suggest that localized platelet activation within the utero‐placental microvasculature, rather than a rheological abnormality, is a likely contributory factor to the occlusive vascular lesion of pre‐eclampsia and fetal growth retardation.
The influence of iron‐deficient indices on whole blood viscosity in polycythaemia
Authors: Milligan D. W. , MacNamee Rosanne , Roberts B. E. , Davies J. A.
Published: March 2008

The relationship of the red‐cell indices, packed‐cell volume (PCV) and plasma viscosity to whole‐blood viscosity was examined in 18 patients with polycythaemia. Sixteen were examined again following a course of venesection. The results were analysed by multiple regression analysis which allowed the effects of individual variables to be independently assessed. A reduction of the MCH or MCV was associated with increased whole‐blood viscosity especially at low‐shear rates. It is concluded that the reduced size of iron‐deficient cells results in increased cell‐cell interaction causing an increase in whole‐blood viscosity.
Red cell membrane protein anomalies in congenital dyserythropoietic anaemia, type II (HEMPAS)
Authors: Baines A. J. , Banga J. P. S. , Gratzer W. B. , Linch D. C. , Huehns E. R.
Published: March 2008

In all of six cases of congenital dyserythropoietic anaemia, type II (HEMPAS), gel electrophoresis in the presence of SDS revealed abnormally rapid migration of the preponderant integral membrane protein, band 3. After proteolysis of intact cells, the remaining part of the band 3, comprising the intramembrane segment and the cytoplasmic domain, migrated electrophoretically as a single band, identical in mobility to that from normal cells treated in the same manner. The anomaly thus resides in the extracellular domain of the protein, which is the glycosylated part of the chain. Peptide digests of the band 3 showed no evidence of a missing protein segment in the abnormal cells and the amino acid composition of the peptides derived from proteolysis of the extracellular protein of intact cells was also normal. We infer that the anomaly is one of glycosylation. The major glycoproteins, detected by carbohydrate‐specific (PAS) stain appear normal in SDS gels. However, when the more sensitive procedure of reacting after electrophoresis with radio‐iodinated lentil lectin is employed, some additional minor protein components are revealed. In particular one species of apparent subunit molecular weight about 150 000 appeared in all cases of HEMPAS examined and in no normals. This component is not accessible to proteolysis by chymotrypsin or Streptomyces griseus protease, and may be associated with the inner membrane patches, characteristic of the HEMPAS condition. Overall cell shape and microviscosity of the membrane bilayer, as measured by fluorescence polarization of a lipid‐soluble fluorophore, were substantially normal in HEMPAS cells.
Erythrocyte hemighosts: a hallmark of severe oxidative injury in vivo
Authors: Chan T. K. , Chan W. C. , Weed R. I.
Published: March 2008

Erythrocyte hemighosts and ghosts were found in five patients: two with severe oxidant haemolysis caused by chemicals or drugs, and three G6PD deficient subjects with haemolysis triggered by infection and/or drugs. Scanning and transmission electron‐microscopy showed that the hemighost consisted of a thinned‐out part with antero‐posterior apposition of the membrane and a thicker spheroidal part containing most of the haemoglobin. Heinz bodies were found in both parts of the cell close to the membrane. Large number of hemighosts (30‐90%) is an ominous sign as three of our five affected patients died. The removal of these cells by exchange transfusion or the induction of forced diuresis probably saved the life of the other two patients. Experiments in rabbits showed that hemighosts were found only with severe oxidative injury induced by a large dose of acetylphenylhydrazine (50 mg/kg) and the spleen was not required for their formation. The marked congestion in the splenic sinusoids and other microcirculation results from sludging of these damaged rigid cells and is an important pathophysiological mechanism in severe oxidant injury.
Differentiation of human bone marrow‐derived fibroblastoid colony forming cells (CFU‐F) and their roles in haemopoiesis in vitro
Authors: Kaneko Shushi , Motomura Seiji , Ibayashi Hiroshi
Published: March 2008

Summary. Human bone marrow‐derived fibroblastoid colonies have been quantitatively developed in a liquid culture. A linear relationship between cell number plated and colony number formed supports their clonal origin and hydroxyurea killing indicates that the fibroblastoid colony forming cell (CFU‐F) is not in cell cycle in normal bone marrow. Adipose cells were induced in the fibroblastoid colonies by the addition of hydrocortisone (optimal concentration: 10−6 M). Furthermore, adherent layers with adipocytes provided a more favourable condition for maintaining haemopoiesis in Dexter‐system cultures. These results indicate that CFU‐F belongs to stromal precursor cells intimately involved in the formation of the haemopoietic microenvironment. Colony incidence of CFU‐F was almost normal in most patients with aplastic anaemia, haemopoietic dysplasia and chronic myelogenous leukaemia. However, in acute myelogenous leukaemia, it varied with the stage of the disease. It is concluded that the colony assay is useful for investigating stroma/haemopoietic cell interactions.
Erythrocytic calmodulin correlates with red cell age
Authors: Monzon Carlos M. , Penniston John T. , Fairbanks Virgil F. , Burgert E. Omer
Published: March 2008

Summary. Red blood cells from normal persons and from patients with reticulocytosis were tested for their calmodulin content. Elevated calmodulin correlated with high reticulocyte counts, rather than with any specific disorder. The correlation between reticulocyte content and elevated calmodulin was further tested by fractionating the erythrocytes from 12 patients into reticulocyte‐rich and reticulocyte‐poor fractions. In the samples from each patient, erythrocytic calmodulin increased with increasing reticulocyte count.
Haemoglobin Constant Spring has an unstable α chain messenger RNA
Authors: Hunt D. M. , Higgs D. R. , Winichagoon P. , Clegg J. B. , Weatherall D. J.
Published: March 2008

Summary.

Haemoglobin Constant Spring (Hb CS) is a variant with an elongated α‐chain associated with an α+ thalassaemia phenotype. The amount of α mRNA relative to β mRNA in reticulocytes was reduced in carriers of Hb CS by an amount equivalent to the reduction observed in carriers of α+ thalassaemia. In a patient with Hb CS‐H disease there was greater α/β mRNA ratio in bone marrow nuclear RNA than in the peripheral blood. Furthermore, all the α mRNA in the patient's peripheral blood was derived from the α1 (αA) gene. The data suggest that αCS mRNA is unstable and degraded in the cytoplasm. This instability may be due to destabilization of a specific sequence in the 3’non‐coding region during translation.
Decreased glycosylation of band 3 and band 4‐5 glycoproteins of erythrocyte membrane in congenital dyserythropoietic anaemia type II
Authors: Scartezzini P. , Forni G. L. , Baldi M. , Izzo C. , Sansone G.
Published: March 2008

Summary.

We report a study of HEMPAS erythrocyte membrane glycoproteins in relation to proteolytic digestion and surface labelling with galactose‐oxidase/NaB[3H]4. The proteolytic digestion of band 3, the major intrinsic glycoprotein of the human erythrocyte membrane, reveals an abnormality in the outer glycosylated segment of this protein. 3H incorporation in band 3 and band 4‐5 glycoproteins after treatment with galactose‐oxidase/NaB[3H]4 is reduced in HEMPAS red cells suggesting a defective glycosylation of these proteins. These findings together with the persistence of i antigen and the normal presence of I antigen lead us to conclude that erythroblastic membrane features may persist in HEMPAS erythrocytes.
Synthesis of thromboplastin by U‐937 cells
Authors: Lyberg T. , Nilsson K. , Prydz H.
Published: March 2008

Summary.

A human monocytoid cell line (U‐937) produces a procoagulant identified as thromboplastin when stimulated with phytohaemagglutinin (PHA), endotoxin, immune complexes, the phorbol ester 12‐O‐tetradecanoyl‐phorbol 13‐acetate (TPA) or the divalent ionophore A 23187. The basal thromboplastin expression of these cells and the increased activity induced by the stimulants were dependent on supply of fresh medium suggesting that the synthetic rate was highest when the cells were in logarithmic growth. Inducible thromboplastin synthesis was inhibited by actinomycin D or cycloheximide, indicating dependence on messenger RNA and protein synthesis. Differentiation of the cells in the macrophage direction by TPA did not make the cells more responsive to PHA. Thromboplastin induction in U‐937 cells was potentiated by the presence of lymphocytes, especially when stimulated with PHA or endotoxin. This supporting effect was also obtained by conditioned medium from lymphocyte cultures, suggesting a role for a soluble lymphocyte product.
Effect of frequent factor VIII replacement on the level of factor VIII antibodies in haemophiliacs
Authors: Rizza C. R. , Matthews J. M.
Published: March 2008

Summary. 24 haemophiliacs with factor VIII antibodies were treated with factor VIII replacement therapy for haemorrhagic episodes. In seven patients with low level of antibody the antibody disappeared over 1–5 years. In six patients with high levels of antibody the titre of antibody has fallen to low levels. In the remaining 11 patients, some of whom were frequently and others infrequently treated, the level of antibody has changed very little except in one patient who showed a dramatic fall in antibody titre while receiving 1500 units of factor VIII weekly over an 8 month period.
Platelet associated IgG, platelet survival, and platelet sequestration in thrombocytopenic states
Authors: Mueller‐Eckhardt C. , Mueller‐Eckhardt G. , Kayser W. , Voss R.M. , And J. Wegner , Küenzlen E.
Published: March 2008

Summary. Platelet‐associated IgG (PAIgG), platelet mean life span (MLS), and platelet sequestration sites were studied in 69 patients with immune (ITP) and presumed nonimmune thrombocytopenias (NTP). A shortened MLS was associated with elevated PAIgG (N=46), and with normal PAIgG (N=15), Four patients had a normal MLS, but elevated PAIgG, four patients were normal for both parameters. The highest PAIgG values occurred in ITP patients with a very short MLS. Nine NTP patients had also elevated PAIgG, but a normal or slightly shortened MLS. There was a significant double log correlation between PAIgG and MLS for ITP, but not for NTP patients. Judged from the coefficient of determination, only 10% of PAIgG were directly related to a shortened MLS.

70% of patients (N= 63) had exclusively splenic and 30% hepatosplenic sequestration. PAIgG was elevated in 29/44 patients with splenic (66%) and in 16/19 patients with hepatosplenic sequestration (84%). In ITP, PAIgG‐positive cases were observed in 69% of splenic v82% of hepatosplenic sequestration, while in NTP the corresponding figures were 6/11 and 2/2. No significant correlation between PAIgG and either sequestration type was demonstrable.

We conclude that in immunologically mediated thrombocytopenia only a small portion of PAIgG accounts for a decreased MLS, and that the concentration of PAIgG per se does not determine the platelet sequestration type.
Purine pathway enzymes in the circulating malignant cells of patients with cutaneous T‐cell lymphoma
Authors: Blatt Julie , Bunn Paul A. , Carney Desmond D. , Reaman Gregory , Soprey Pandu , Poplack David G.
Published: March 2008

Summary. The activities of three purine pathway enzymes—adenosine deaminase (ADA), 5′‐nucleotidase (5′N) and purine nucleoside phosphorylase (PNP)—were examined in the circulating malignant cells (Sezary cells) of eight patients with cutaneous T‐cell lymphoma (CTCL). Cell lines derived from two other patients with CTCL were also studied. These were compared with enzyme activities in peripheral blood T‐lymphocytes from 11 normal donors and six samples of human thymocytes. ADA activities were similar in the Sezary cells and peripheral blood T‐cells (medians 7 U and 15 U, P=0.14), and both of these groups demonstrated significantly lower activity than did the thymocytes (median 100 U, P=0.002). 5′N activity in the Sezary cells was also similar to that of the T‐lymphocytes (median 0.022 U and 0.030 U, P>0.05) and both of these groups had significantly greater activity than did the thymocytes (median 0.002 U, P=0.001). Median PNP activity in the Sezary cell population was also comparable to that measured in normal T‐cells. These findings suggest there is a characteristic purine pathway enzyme pattern in Sezary cells that is similar to that seen in normal T‐lymphocytes. This pattern is clearly distinguishable from that of thymocytes and from that previously described in lymphoblasts from patients with T‐cell acute lymphoblastic leukaemia. These results support the concept that Sezary cells are well‐differentiated with respect to the T‐cell axis. Quantitation of purine pathway enzymes may be useful in defining subsets of T‐cell malignancy.
GΓ and AΓ globin chain synthesis in bone marrow and peripheral blood of β‐thalassaemia homozygotes
Authors: Saglio G. , Camaschella C. , Guerrasio A. , Cambrin G. Rege , Capaldi A. , Pich P. G. , Trento M. , Mazza U.
Published: March 2008

Summary. Gγ, Aγ and β globin chain synthesis has been investigated in the peripheral blood and bone marrow from eight β‐thalassaemia homozygotes. In five out of eight cases total γ chain synthesis was higher in the peripheral blood than in the bone marrow; in seven out of eight cases Aγ chain synthesis was markedly higher in the marrow than in the peripheral blood. These data suggest that ineffective erythropoiesis selects F‐cells synthesizing the largest amounts of Gγ chains, while Aγ producing cells are preferentially destroyed in the marrow.
Graft‐versus‐host disease after treatment for chronic granulocytic leukaemia in transformation
Authors: Starke I. D. , Thein S. L. , Goldman J. M. , Galton D. A. G.
Published: March 2008

Summary. Two patients with chronic granulocytic leukaemia in blast cell transformation treated with high‐dose cytotoxic drugs and transfusion of cryoperserved chronic phase buffy coat stem cells developed a clinical and pathological syndrome that closely resembled graft‐versus‐host disease (GVHD). It was possible (1) that both patients had true GVHD resulting from transfusion of HLA‐identical blood products, or (2) that both cases were examples of the ‘pseudo‐GVHD’ seen by others following syngeneic transplants. The laboratory findings did not support one postulatd pathogenetic mechanism for ‘pseudo‐GVHD’—namely a lack of supresor T‐lymphocytes.
Haematological aspects of life with an ileostomy
Authors: Kennedy H. J. , Callender Sheila T. , Truelove S. C. , Warner G. T.
Published: March 2008

Summary. The haematological aspects of life with an ileostomy have been studied in 51 patients, of whom 39 had had ulcerative colitis and 12 had Crohn's dissease. The findings in these patients have been compared with those in 39 healthy volunteers who were matched for age and sex with the 39 patients who had had ulcerative colitis.

There was evidence of a mild degree of iron deficiency in the patients with an ileostomy. This was partly due to a pre‐existing iron deficiency resulting from their preceding illness and operation, as the abnormality was less pronounced in the patients in whom the ileostomy had been established for more than 3 years. There was some evidence of excessive iron loss and a controlled trial of ferrous fumurate showed that the iron deficiency was largely corrected by this means. Circulating levels of vitamin B12 were normal, but it is relevant that some of the Crohn's disease group were receiving parenteral supplements. The absorption of vitamin B12 was low in the patients with Crohn's disease who had had an ileal resection of more than 17 cm. The absorption of vitamin B12 in the patients who had had ulcerative colitis was increased and possible mechanisms are discussed. All but one of the patients had normal levels of plasma folate and in all the red cell blood folate was normal, which can be taken as an indication of a good dietary intake and adequate absorption.
The interaction of α thalassaemia with heterozygous β thalassaemia
Authors: Kanavakis E. , Wainscoat J. S. , Wood W. G. , Weatherall D. J. , Cao A. , Furbetta M. , Galanello R. , Georgiou D. , Sophocleous T.
Published: March 2008

Summary. The α globin genotypes of 55 β thalassaemia heterozygotes have been determined by restriction endonuclease analysis to identify those with interacting α thalassaemia genes. A comparison of the haematological and haemoglobin synthesis findings of individuals with normal α genotypes (αα/αα) with those with one (‐ α/αα) or two (‐α/‐α) α genes deleted shows that the latter two groups have more balanced globin chain synthesis ratios, higher haemoglobin levels, and larger, better haemoglobinized red cells. This suggests that the degree of globin chain imbalance is a significant factor in determining the red cell characteristics in heterozygous β thalassaemia. Screening programmes for thalassaemia, based on the detection of low MCVs, could miss cases of the interaction of α and β thalassaemia.
Studies on the partition of transferrin‐donated iron in rabbit reticulocytes: I. THE KINETICS OF IRON DISTRIBUTION BETWEEN STROMA AND CYTOSOL
Authors: Egyed A.
Published: March 2008

Summary. The distribution of transferrin‐donated iron between the stroma and cytosol compartments of rabbit reticulocytes was studied. In cells with inhibited haem synthesis iron accumulates in the stroma fraction. The stromal accumulation of iron was found to be reversible and dependent on the coupled state of mitochondrial respiration. Iron in cytosol, however, proved to be more available for haem synthesis than iron accumulated in stroma.

A hypothesis concerning mitochondrial iron uptake is proposed, by which the experimental and pathological changes in the intracellular distribution of iron can be explained.
Heterogeneity of haemophilia A: a study with three different antisera
Authors: Muller Hein P. , Van Tilburg Nico H. , Bertina Rogier M. , Veltkamp Jan J.
Published: March 2008

Summary. One human and one rabbit antibody against VIII:C—in a fluid‐phase, inhibitor neutralization assay (INA)—and one human antibody—in a solid‐phase, immunoradiometric assay (IRMA)—were used to investigate a group of 59 patients with severe, moderate and mild haemophilia A.

Patients were classified as haemophilia A+ when the VIII:C/VIIICAG ratio was less than 0.4 while the absolute VIII:C antigen (VIIICAG) value exceeded 0.25 u/ml. Three haemophiliacs (from two pedigrees) were classified as A+ in all three assay systems. 50% of the patients were classified as haemophilia A+ on the basis of at least one assay. The other 50%, including 66% of the patients with severe haemophilia, were shown to be A‐ by all three assay systems. Combining the data obtained with the three different antibodies four different categories could be distinguished, in addition to the classification based on severity.
Significance of plasma fibrinopeptide A and high molecular weight fibrinogen in patients with liver cirrhosis
Authors: Coccheri S. , Mannucci P. M. , Palareti G. , Gervasoni W. , Poggi M. , Viganog S.
Published: March 2008

Summary. Plasma fibrinopeptide A (FPA) was measured in 50 patients with liver cirrhosis divided into‘moderate’or 'severe’cirrhotics according to standard clinical and laboratory criteria. FPA was significantly higher than in normal controls although no relation to the severity of disease was found. After a single intravenous administration of heparin there was a significant decrease in FPA levels in the patients. High molecular weight fibrinogen (HMWF) was also determined for some of the patients and was significantly greater than in the normal controls. However, there was no correlation between FPA and HMWF. The greater values of FPA and their responses to heparin indicate that there is increased thrombin formation in a number of patients with liver cirrhosis, with no apparent relation to the severity of the disease.
Regeneration of peripheral blood cells following allogeneic bone marrow transplantation for severe aplastic anaemia
Authors: Hows J. M. , Kaffaf S. , Palmer S. , Harris R. , Fairhead S. , Gordon‐Smith E. C.
Published: March 2008

Summary. We have studied the pattern of regeneration of peripheral blood cells following ABO compatible bone marrow transplantation for severe aplastic anaemia. 18 patients were treated with cyclosporin A and six with methotrexate for post graft immunosuppression. The number of days taken for the neutrophil count to reach 0.5 × 109/l, the lymphocyte count to reach 1.0 x 109/l, the platelet count to reach 100 × 109/l and the reticulocytes to reach 1% was shorter in the CyA treated patients. This finding reached statistical significance for all types of cells except the platelets (neutrophils, P < 0.001; lymphocytes, P < 0.02; platelets, P > 0.05; reticulocytes, P < 0.001).
The effect of reduced oxygen tension on colony formation of erythropoietic cells in vitro
Authors: Rich Ivan N. , Kubanek Bernhard
Published: March 2008

Summary. The effect of reduced oxygen tension and the role of cellular components known to protect the cell against oxygen toxicity has been studied with respect to erythropoietic colony formation in vitro. Alphathioglycerol can be partially replaced by vitamin E and completely replaced by reduced glutathione (GSH) at physiological concentrations. Incubation of bone marrow and fetal Iiver early (BFU‐E) and late (CFU‐E) erythropoietic progenitor cells, in the presence of GSH, in an atmosphere containing 5% oxygen, 5% carbon dioxide and 90% nitrogen, as opposed to air supplemented with 5% carbon dioxide, resulted in an increase in colony numbers and response to erythropoietin (Epo). The number of colonies derived from bone marrow and fetal liver CFU‐E increased by 1.2‐2.8‐fold with a relative Epo sensitivity increase of 3.5‐4‐fold. Bursts obtained from bone marrow and fetal liver BFU‐E increased from 2.6‐ to 3.8‐fold with an increased response to Epo of 2‐3‐fold. The effects of GSH and low oxygen tension are interpreted as causing a reduction in oxygen toxicity of the cells, thereby increasing the life span in vitro and so increasing the number of cells capable of forming colonies. The heightened response of BFU‐E to Epo, analogous to the effect seen for CFU‐E, implies that BFU‐E may be responsive to physiological Epo concentrations at physiological oxygen tensions.
Erythroblast iron metabolism in sideroblastic marrows
Authors: May A. , Souza P. de , Barnes K. , Kaaba S. , Jacobs A.
Published: March 2008

Summary. The uptake of iron by bone marrow erythroblasts and its intracellular distribution have been studied in 23 patients with primary sideroblastic anaemia (SA), five patients with secondary SA and one patient with only non‐ringed sideroblasts. EM of erythroblasts from 18 cases showed both mitochondrial iron deposits and cytoplasmic ferritin aggregates in all cases except the patient with only non‐ringed sideroblasts.

Iron uptake by erythroblasts in whole bone marrow was normal but there was a decreased incorporation into haem and an increased incorporation into cell stroma. Age matching of erythroblasts using Percoll density gradient centrifugation indicated that stromal iron incorporation was high at all stages of erythroblast development even before haem synthesis had become a major metabolic activity and in intermediate and late erythroblasts a real decrease in haem synthesis appeared less certain. These observations, together with the inability to correct the abnormality in vitro with either pyridoxal phosphate or amino‐laevulinic acid suggest that the primary defect in SA may be an abnormality of mitochondrial iron metabolism rather than an abnormality of haem synthesis.
DEMONSTRATION OF UROKINASE‐RELATED FIBRINOLYTIC ACTIVITY IN HUMAN PLASMA
Authors: Wijngaards G. , Kluft C. , Groeneveld E.
Published: March 2008

Various preparations of anti‐urokinase antibodies were found to quench a part of the plasma fibrinolytic activity. This part was also inhibited by a specific, urokinase inhibitor isolated from placenta. These observations indicate that plasma contains a urokinase‐related immuno‐reactivity. This activity was found to belong to the factor XII‐independent proactivator system.