bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Testosterone and Oestradiol on Erythroprotein Production in Vitro
Authors: Zucali J. R. , Mirand E. A.
Published: March 2008

The effects of testosterone and oestradiol on erythropoietin production by mouse fetal liver in primary culture was studied. No stimulatory effect on in vitro erythropoietin production was observed by any of the oestradiol concentrations employed (10‐10M to 10‐6M); whereas testosterone, only over a dose range of 10‐12 M to 10‐10 M, stimulated erythropoietin production by mouse fetal liver in culture. In addition, a stimulatory effect of testosterone on fetal liver tissue was obtained by injecting testosterone (20 mg/mouse) intramuscularly into pregnant mice 4 d prior to obtaining the fetal liver tissue for culture. Therefore, it is concluded that testosterone can exert a direct stimulatory effect on erythropoietin production by mouse fetal liver.
Simultaneous Presence of Receptors for Complement and Sheep Red Blood Cells on Human Fetal Thymocytes
Authors: Stein H. , Müller‐hermelink H. K.
Published: March 2008

The cells of four thymus glands, two at 12 weeks, one at 16 weeks and one at 22 weeks gestational age, were examined cytochemically for enzymic activity and for surface markers. The reactions for chloroacetate esterase, peroxidase, and alkaline phosphatase were negative and the reaction for nonspecific esterase was only weakly positive in some of the cells. In contrast, nearly all thymocytes at the 12th gestational week showed strong focal acid phosphatase (acP) activity. The number of acP‐stainable cells and the staining intensity declined progressively. A high percentage of thymocytes in early fetal life express a complement receptor (CR); the proportion of CR‐bearing cells decreased while cells forming rosettes with sheep erythrocytes (possessing erythrocyte receptors: ER) correspondingly increased during fetal life. Using a mixed rosette assay, up to 30% of the thymocytes at 12 weeks gestation were found to bear CR and ER simultaneously. The number of CR‐and ER‐positive cells also declined progressively with fetal age.

These findings show that CR‐positive, ER‐negative thymus cells mature into CR‐negative, ER‐positive thymocytes via a CR‐positive and ER‐positive intermediate cell, indicating that mature ER‐positive thymocytes do not originate from another cell line lacking CR. The changes in surface markers during early T cell maturation is relevant to certain lymphomas whose cells also show strong focal acP activity and also express both CR and ER. These lymphoma cells may correspond to fetal thymocytes or T precursor cells present in small numbers after birth.
Studies of von Willebrand Factor: Effects of Different Kinds of Carbohydrate Oxidases, SH‐Inhibitors and some other Chemical Reagents
Authors: Fukui H. , Mikami S. , Okuda T. , Murashima N. , Takase T. , Yoshioka A.
Published: March 2008

The effects of several kinds of carbohydrate oxidase, SH‐inhibitors and some other chemical reagents on the activities of von Willebrand factor, factor VIII procoagulant and factor VIII‐related antigen were studied.

Factor VIII procoagulant and von Willebrand factor activities were both inhibited by galactose oxidase, p‐hydroxymercuribenzoic acid, 2,4,6‐trinitrobenzensulfonic acid and sodium periodate. α‐mannosidase, N‐ethylmaleimide and phospholipase C inactivated factor VIII procoagulant but not von Willebrand factor activity. Dithiothreitol had little effect on factor VIII procoagulant activity but reduced significantly that of von Willebrand factor. It is suggested that galactose and the thiol and α‐aminogroup groups of lysine may play an important role in both factor VIII procoagulant and von Willebrand factor activity. Mannose may be responsible for the factor VIII procoagulant activity but not for the von Willebrand factor activity.

The Laurell rocket heights of factor VIII‐related antigen rose with increasing concentration of galactose oxidase, 2,4,6‐trinitrobenzenesulfonic acid or sodium periodate. Gel filtration experiments showed that factor VIII‐related antigen may be dissociated into subunits by galactose oxidase but not by 2,4,6‐trinitrobenzenesulfonic acid or sodium periodate.
Activated T‐Cells in Autoimmune Haemolytic Anaemia
Authors: Parker A. C. , Stuart A. E. , Dewar A. E.
Published: March 2008

In 12 of 14 patients with clinically active autoimmune haemolytic anaemia high levels (9–78%) of homologous and autologous resetting cells were found in the peripheral blood. In 10 of these patients, who were observed over a period of 2 years, the levels bore a direct relationship to the activity of the disease. The cells so identified were T‐lymphocytes. The role of cells, identified by this method in AIHA, is discussed.
Chronic Lymphatic Leukaemia: Correlation of Immunofluorescent Characteristics and Clinical Features
Authors: Hamblin Terry , Hough David
Published: March 2008

60 patients with chronic lymphatic leukaemia (CLL) were classified according to the immunofluorescent characteristics of their lymphocytes. A group expressing surface membrane (Sm) IgM had a significantly less aggressive disease than those expressing a mixture of SmIgM and SmIgD or those without surface immunoglobulin. The patients were older than in most comparable series and had a 2:1 preponderance of women. It is suggested that especially among old ladies there is a benign variety of CLL which expresses SmIgMk, and that determination of the SmIg class in CLL has prognostic value.
The Role of Iron in the Regulation of Hepatic Transferrin Synthesis
Authors: Morton A. G. , Tavill A. S.
Published: March 2008

The role of iron supply in the regulation of hepatic transferrin synthesis by the isolated perfused rat liver was studied using nutritional iron deficiency as the experimental model. The increased transferrin release encountered in iron deficiency could be equated with enhanced de novo synthesis as evidenced by the inhibitory effects of cycloheximide and measurements of intrahepatic protein pools before and after perfusion. Refeeding with iron, sufficient to restore plasma iron and hepatic ferritin iron but before correction of anaemia, promoted a reduction towards normal in the transferrin synthetic rate. This effect was not produced by transfusional correction of the anaemia, suggesting a specific response to iron supply. Phenobarbitone treatment, which produced a marked fall in hepatic ferritin iron concentration but no change in haemoglobin or plasma iron concentrations, promoted a specific enhancement of transferrin synthesis in both control and iron deficient livers. The concentration of liver iron stores appears to be a major regulatory factor in the control of hepatic transferrin synthesis.
Aspects of Folate Metabolism in Renal Failure
Authors: Retief F. P. , Heyns A. du P. , Oosthuizen Mariëtha , van Reenen O. R.
Published: March 2008

Plasma and urine folate fractions were evaluated after ingestion of radio‐active N5‐methyl‐tetrahydrofolic acid by a normal control (subject 1), a patient on maintenance haemodialysis for chronic glomerulonephritis (subject 2), and an anephric patient on haemodialysis (subject 3). In subjects 1 and 2 maximal plasma radiofolate peaks appeared within 1 h of isotope ingestion. In subject 3 the radio‐folate peak was delayed for 6 h although the total biofolate fraction reached a maximum at 0.5 h (comparable with findings in subject 2). Sephadex DEAE A50 chromatography showed the radiofolate fraction in subject 1 to be compatible with N5‐methyl‐tetrahydrofolic acid (peak 1). In subject 2 additional radiofolate peaks 2 and 3 were found. The nature of peak 2 is unknown but peak 3 may represent 10‐formyl‐tetrahydrofolate. Peak 1 was minimally present in subject 3. This limited study suggests a defect of methyl‐tetrahydrofolate metabolism in the anephric state unassociated with defective renal excretion per se.

In normal urine, peak 2 predominated while urine of subject 2 had a predominant peak 3 and lesser peaks 1 and 2. Compared with the control, uraemic subjects 2 and 3 showed greatly decreased dialysis‐resistant (bound) plasma radiofolate fractions; all urinary radiofolates were fully dialysable. The unexplained radiofolate ‘binder’detected with haemoglobin‐coated charcoal adsorption in urine (subject 2) and occasionally in plasma, probably represents an artefact. Plasma from 27 uraemic subjects showed no abnormal in vitro radiofolate binding capacity.
Heterocellular Hereditary Persistence of Fetal Haemoglobin (Heterocellular HPFH) and its Interaction with β Thalassaemia
Authors: Wood W. G. , Weatherall D. J. , Clegg J. B. , Hamblin T. J. , Edwards J. H. , Barlow A. M.
Published: March 2008

Summary. Three families have been observed in which a gene for heterocellular hereditary persistence of fetal haemoglobin (HPFH), probably identical to that previously described as Swiss type HPFH, has been inherited together with β thalassaemia. The interaction of these two genes results in β thalassaemia heterozygotes with unusually high levels of fetal haemoglobin, 6–15%, heterogeneously distributed. In four individuals with Hb S‐β thalassaemia who also inherited a heterocellular HPFH gene, Hb F levels of up to 25% were observed, resulting in an extremely mild clinical condition. Globin synthesis studies show less chain imbalance in the heterocellular HPFH‐β thalassaemia compound heterozygotes than in the heterozygous β thalassaemia members of these families. Age stratification of the red cells by centrifugation showed enrichment of Hb F and Hb F‐containing cells (F‐cells) in the older cell population. It is suggested that the effect of the heterocellular HPFH gene is to increase the size of the F‐cell population and that preferential survival of that expanded F cell population leads to the high levels of Hb F which result when heterocellular HPFH interacts with β thalassaemia or Hb S. The mild clinical condition which results from such interaction may explain part of the heterogeneity of the β thalassaemia syndromes and suggests that the induction of even relatively small increases in the production of Hb F in these conditions could be of potential therapeutic benefit.
Decreased Deformability of Erythrocytes in Haemolytic Anaemia Associated with Glucosephosphate Isomerase Deficiency
Authors: Schröter W. , Tillmann W.
Published: March 2008

Summary. Deformability of erythrocytes from four patients with different types of glucosephosphate isomerase (D‐glucose‐6‐phosphate ketoisomerase, GPI) deficiency has been determined by cell filtration. Young as well as whole erythrocyte populations had a markedly increased rigidity and an abnormally strong attachment of haemoglobin to the inner surface of isolated membranes. Acidic environment may enhance membrane rigidity in vitro and also during passage of the erythrocytes through the spleen. The decrease of deformability at a pH of 6.8 was most pronounced in the splenectomized patients, and likewise in erythrocytes from the splenic artery, which were obtained from one patient during splenectomy. It is suggested that the metabolic environment of the spleen, with its low pH, impairs the deformability of GPI‐deficient erythrocytes and predisposes them to splenic sequestration. The clinical improvement of all patients following splenectomy which is accompanied by an increase of the erythrocyte survival time and by unchanged reticulocyte counts, is in accordance with this view.
Radioimmunoassay of Human Eosinophil Cationic Protein
Authors: Venge Per , Roxin Lars‐Erik , Olsson Inge
Published: March 2008

Summary. A radioimmunosorbent assay has been developed which allows the detection in serum of a cationic protein derived from eosinophil granulocytes. In 34 healthy individuals the mean level was 31 μg/l. with a range of 5–55 μg/l. The serum concentration of ‘eosinophil’ cationic protein was correlated (P<0.001) to the number of eosinophil granulocytes in peripheral blood. Quantitation of ‘eosinophil’ cationic protein in serum might be useful in the study of eosinophil granulocyte turnover and function in vivo.
Kinetics of Erythroid and Myeloid Stem Cells in Post‐Hypoxia Polycythaemia
Authors: Peschle C. , Magli M. C. , Cillo C. , Lettieri F. , Genovese A. , Pizzella F. , Soricelli A.
Published: March 2008

Summary. The number of erythroid burst‐ (BFU‐E) and colony‐forming units (CFU‐E), as well as of myeloid‐macrophage colony‐forming units (CFU‐C), has been evaluated in tibial marrow and spleen of ex‐hypoxic polycythaemic mice, at sequential time intervals after the end of hypoxia.

In both marrow and spleen, the kinetics of the CFU‐E pool is characterized by a sharp fall from above normal to lower than normal values. BFU‐E and CFU‐C however rise from below normal to higher than normal levels. These results have been correlated with both the erythropoietin (Ep) and the erythropoietic activity curves.

It is apparent that Ep levels largely control both the differentiation and the amplification of the CFU‐E pool and it is suggested that Ep may act as a ‘survival factor’ at the CFU‐E level and/or increase the flow of cells from BFU‐E to CFU‐E.

The difference in response between CFU‐E and BFU‐E favours a clearcut distinction between these populations, whereas the similarity between the BFU‐E and CFU‐C response suggests a close relationship between these two cell populations.

It is also of interest that the murine spleen functions as a large reservoir of erythroid microenvironment for hypoxia‐induced stress erythropoiesis.
Membrane Proteins of Incubated Erythrocytes: Effects of Sulphydryl Inhibition
Authors: Zail S. S. , van den Hoek A. K.
Published: March 2008

Summary. Incubation of erythrocytes with various sulphydryl inhibitors for 24 h leads to an accumulation in isolated membranes of globin as well as an unidentified polypeptide of apparent molecular weight 24 000 on polyacrylamide gel electrophoresis. Accumulation of both these components does not appear to be directly related to erythrocyte adenosine triphosphate and reduced glutathione levels. The 24 000 molecular weight polypeptide is probably derived from the erythrocyte cytosol, as determined by polyacrylamide gel electrophoresis of the non‐haemoglobin proteins of the cytosol. Together with globin it forms an integral part of the ‘spectrin‐actin lattice’ of sulphydryl‐inhibited erythrocytes, as both these components can be detected, together with spectrin and actin, after extraction of such membranes by Triton X‐100. We postulate that this leads to inherent damage and distortion to the membranes of such erythrocytes.
Absorption of Inorganic and Haemoglobin Iron in Coeliac Disease
Authors: Anand B. S. , Callender Sheila T. , Warner G. T.
Published: March 2008

Summary.Absorption from a 5 mg dose of iron as Fe++or haemoglobin iron was studied using a Total Body Counter in control subjects and patients with coeliac disease. In both groups the majority of subjects were iron deficient. Thirteen control subjects, 13 patients with untreated coeliac disease and 14 on treatment with gluten‐free diet had both absorption tests. Absorption of Fe++iron was reduced in untreated coeliac disease. This was particularly significant in iron deficient patients. Absorption was improved on treatment with gluten‐free diet. In contrast, the absorption of haemoglobin iron was not affected in coeliac disease, indicating that absorption of iron in this form is not dependent on the integrity of the mucosa of the proximal small bowel.
Erythroid Colony Forming Cells in Aplastic Anaemia
Authors: Hansi W. , Rich I. , Heimpel H. , Heit W. , Kubanek B.
Published: March 2008

Summary. The concentration and erythropoietin dependence of erythropoietic progenitor cells (CFU‐E) were examined in 13 patients with aplastic anaemia at different stages of their disease. The CFU‐E incidence was shown to be quantitatively diminished in aplastic anaemia but tended to recover to normal values if the disease recovered. In addition the CFU‐E showed a qualitatively different response to stimulation by erythropoietin, being resistant to low concentrations but responsive to concentrations greater than 0.2 U/ml whereas there was a linear response in the controls up to 0.5 U/ml.
Cytochemical Profile of Human Haematopoietic Biopsy Cells and Derived Cell Lines
Authors: Sundström C. , Nilsson K.
Published: March 2008

Summary. Twenty‐three human haematopoietic cell lines, normal and mitogen stimulated peripheral blood lymphocytes and tumour material from fresh leukaemias, myelomas and lymphomas were investigated with a panel of cytochemical reactions. Normal and mitogen stimulated lymphocytes, non‐neoplastic lympho‐blastoid cell lines (LCL), lymphoma lines with B‐lymphocyte characteristics, chronic lymphocytic leukaemia and fresh lymphocytic lymphomas reacted weakly or negatively with all stains. T‐lymphocyte acute leukaemia lines were PAS and α‐naphtyl acetate esterase positive. Myeloma lines and fresh myelomas were strongly β‐glucoronidase positive. A histiocytic lymphoma cell line was strongly esterase positive with naphtol AS‐D acetate esterase inhibited by NaF. The three fresh histiocytic lymphomas, however, reacted as the lymphocytic lymphomas suggesting a lymphoid origin. A myeloid leukaemia line was strongly positive for acid phosphatase. No major disagreement was noted between the reactivity of established neoplastic lines and the corresponding fresh biopsy cells indicating an unaltered qualitative expression of enzyme production after prolonged in vitro culture.
Characteristics of Various Factor VIII Concentrates used in Treatment of Haemophilia A
Authors: Nilsson I. M. , Hedner U.
Published: March 2008

Summary.Five different factor VIII concentrates, AHF‐Kabi (fraction I‐o), Krynativ‐Kabi (freeze‐dried cryoprecipitate), Hemofil‐Hyland, AHF‐profilate‐Abbott, Kryobulin‐Immuno, available in Sweden for treatment of haemophiliacs were compared with respect toin vivorecovery, half‐life of factor VIII clotting activity (VIII:C) andin vitroproperties. The parameters studied were VIII:C, factor VIII related antigen (VIIIR:AG), crossed immunoelectrophoresis, ristocetin co‐factor activity (VIII: Rcof), fibrinogen content and factor XIII activity. AHF‐Kabi had the lowest concentration of VIII:C. All the preparations had higher values for VIIIR:AG than for VIII:C. The quotient was highest for Hemofil, Krynativ‐Kabi and Kryobulin and varied between 4 and 7. The lowest quotient, 1.3 to 4, was that of AHF‐Kabi. The number of units of VIII: Rcof was almost the same as that of VIII:C. AHF‐Kabi had the highest fibrinogen concentration and was the only preparation with high amounts of F XIII. In crossed immunoelectrophoresis AHF‐Kabi showed a similar pattern to that of normal plasma. The other preparations had a different pattern suggesting less heterogenicity of the molecule. Thein vivorecovery was about the same for all the concentrates. The disappearance rate of VIII:C after infusion of corresponding doses of the different concentrates was studied in six patients with severe haemophilia A who were not bleeding. AHF‐Kabi had a half‐life between 18 and 26 h which was substantially longer than any of the other preparations. The half‐life of Hemofil, Krynativ‐Kabi, AHF‐Profilate and Kryobulin varied between 8 and 16 h. The concentrates were given to three patients with severe classical von Willebrand's disease. All the preparations caused an increase of VIII:C and VIIIR:AG as well as of VIII:Rcof, but only AHF‐Kabi corrected the prolonged bleeding time.

Knowledge of the properties of various VIII concentrates is of importance for the choice of treatment in haemophilia and von Willebrand's disease.
The Effect of Thiamphenicol on the Production of Immature Red Blood Cells under Anaemic Conditions
Authors: Nijhof W. , Wierenga P. K. , Kardaun S.
Published: March 2008

Summary. The toxic action of thiamphenicol was demonstrated in normal and phlebotomized rabbits. Thiamphenicol administration to normal rabbits resulted in a reduction of the number of reticulocytes and eventually to a decrease in the total red cell count. In rabbits made anaemic thiamphenicol did not prevent a reticulocyte crisis. The rate of synthesis of haemoglobin and the total amount of ribosomes in these reticulocytes were low. The disome was the most abundant polysome. This was in contrast with the findings of reticulocytes from control rabbits. Shortly after the thiamphenicol administration reticulocytes appeared with propcrties comparable with those from control rabbits.

Besides the impairment of reticulocyte production a decrease in the total cellularity of the marrow was shown. The erythroid, granuloid and lymphoid cell lines appeared to be all affected. However, only the red cells showed a distinct shift from young to old erythroblasts. The inhibition of red cell production was not caused by a deficiency of erythropoietin since the levels were extremely high during thiamphenicol administration. From these findings it is concluded that one of the major effects of thiamphenicol is the inhibition of the conversion of the committed stem cell to proerythroblasts.
Adenosine Deaminase (ADA) Activity in Lymphocytes of Normal Individuals and Patients with Chronic Lymphatic Leukaemia
Authors: Ramot B. , Brok‐Simoni F. , Barnea N. , And I. Bank , Holtzmann F.
Published: March 2008

Summary. Adenosine dcamiiiase (adenosine aminohydrolase, ADA) activity was found to be low in lymphocytes of chronic lymphatic leukaemia (CLL) patients compared to normal lymphocytes. This was determined on 42 controls and 49 CLL patients. The mean activity in normal lymphocytes was found to be 4.35±3.34 μmol/h/108 cells while in CLL cells it was 2.45±2.54 μmol/h/108 cells.

The association of red cell adenosine deaininase (ADA) deficiency with the autosomal recessive form of combined immune deficiency syndrome has been well established (Giblett & Anderson, 1972; Knudsen & Dissing, 1973; Meuwissen et al, 1975). Low levels of ADA were also described in children with acute lymphatic leukaemia in relapse and remission as well as in their parents (Zimmer et al, 1974). Since an immunologic handicap frequently evolves during the course of chronic lymphatic leukaemia (CLL), it is of special interest to determine the activity of this enzyme in lymphocytes of such patients as compared to normals.
New Evidence Relating to the Nature and Origin of the Hairy Cell of Leukaemic Reticuloendotheliosis
Authors: Burns G. F. , Cawley J. C. , Barker C. R. , Goldstone A. H. , Hayhoe F. G. J.
Published: March 2008

Summary. New evidence is presented concerning the nature and origin of the pathognomonic cell of leukaemic reticuloendotheliosis (LRE). A specific receptor for IgM was demonstrated by an EAIgM rosette test in all seven cases of LRE studied. This marker was absent from the pathological cells of a wide variety of haematological proliferative disorders, and from cells of the normal myeloid and monocyte‐histiocyte series. A small percentage of circulating mononuclear cells which did not resemble monocytes morphologically, did possess the receptor for IgM. The LRE cells were found to show variable phagocytic activity for IgG opsonized erythro‐cytes and latex particles. Studies of differences in the kinetics of the rosette test in the seven cases together with the range of phagocytic activity and cytological maturity observed, suggested that the diagnosis of LRE may encompass a broader spectrum of clinical and cytological features than has previously been recognized. Evidence presented suggests that the cells of LRE are not related to either B‐lymphocytes or the monocyte‐histiocyte series. It is proposed that LRE represents a leukaemic proliferation of the newly identified small population of EAIgM receptor bearing normal circulating mononuclear cells.
Evidence that Stimulation of Megakaryocytopoiesis by Low Dose Vincristine Results from an Effect on Platelets
Authors: Jackson Carl W. , Edwards Carol C.
Published: March 2008

Summary. Appropriate low dosages of vincristine stimulate megakaryocytopoiesis and produce thrombocytosis. In this study of the thrombocytotic action of vincristine, administration of a single dose of 0.1 mg/kg to rats produced an increase in megakaryocyte concentration, diameter and 24 h [3H]thymidine labelling index. Transfusion of one body equivalent of platelets from normal donors prevented stimulation of megakaryocytopoiesis by vincristine whereas platelets from vincristine‐treated donors did not. These results suggest that vincristine stimulates megakaryocytopoiesis by altering the functional role of circulating platelets in the regulation of thrombopoiesis.
Immunological Studies in Combined Factor V and Factor VIII Deficiency
Authors: Giddings J. C. , Seligsohn U. , Bloom A. L.
Published: March 2008

Plasma samples from patients with inherited combined factor V and factor VIII deficiency were examined by immunological methods for the presence of factor V and factor VIII‐related antigens. A factor V‐related antigen was consistently demonstrated in all plasma samples by inhibitor neutralization assay using a non‐precipitating rabbit antibody. Factor VIII‐related antigens were detected by inhibitor neutralization using human antibody and by electroimmunoassay using a precipitating rabbit antibody. The amounts of factor V and factor VIII‐related antigens present in the patient's samples were similar to those found in normal human plasma. The findings confirm the presence of normal levels of factor VHI‐related antigen in the plasma of these patients and suggest that inactive antigenic determinants of procoagulant factor V and procoagulant factor VIII are also present. The results are consistent with the possibility that a common precursor of procoagulant factor V and factor VIII is defective in these patients.
Assay of Ristocetin Co‐factor using Fixed Platelets and a Platelet Counting Technique
Authors: Evans R. J. , Austen D. E. G.
Published: March 2008

A new assay of ristocetin co‐factor has been developed which is based on platelet counting using a Coulter Counter. A modified method of washing and fixing platelets has also been devised to provide a suitable platelet preparation which can be used in this assay. These fixed platelets have consistently proved to be satisfactory and have given high levels of maximum percentage aggregation. They have been stored for periods up to 6 months without significant deterioration. The method of platelet counting is simple in operation and sensitive to relatively low levels of platelet aggregation. It is precise and seems to offer distinct advantages over existing methods.
Effect of Treatment on T‐Cell Function in Chronic Lymphocytic Leukaemia
Authors: Fernandez L. A. , MacSween J. M. , Langley G. R.
Published: March 2008

T‐cell functions were studied in vitro on enriched T‐lymphocyte populations obtained from three groups of patients with chronic lymphocytic leukaemia (CLL): (a) untreated, (b) treated with chlorambucil, and (c) treated with chlorambucil and prednisone. The results were compared to age‐matched controls and patients without CLL on comparable doses of prednisone. T cells obtained from untreated and chlorambucil‐treated patients showed significantly decreased responses to phytohaemagglutinin (PHA) at short‐term cultures (4 d) and in the mixed lymphocyte response (MLR). The lymphocyte responses to PHA, after 8 d in culture, were not significantly decreased. T cells obtained from CLL patients treated with chlorambucil and prednisone showed markedly reduced responses to MLR and to PHA at both time intervals. These responses were significantly less than those of cells obtained in the same manner from untreated or chlorambucil‐treated patients with CLL or from patients with bronchial asthma treated with equivalent doses of prednisone. These results suggest that T cells from patients with CLL are particularly susceptible to inhibitory effects of corticosteroids. An increased susceptibility to infection has been reported in patients with CLL treated with chlorambucil and prednisone. The marked suppression of lymphocyte responses to PHA and in MLR demonstrated in this group of patients may play a role in increasing susceptibility to infections.
Characterization of Marrow Granulocyte Development: Enzyme‐Specific Activity Profiles in Response to Inflammatory Reactions
Authors: Eanes Robert Z. , Scott Robert B. , Swenson Betty , Cooper LaVerne W.
Published: March 2008

Isopycnic sedimentation has been used to separate granulocytes of varying stages of maturity from the bone marrows of normal rabbits and rabbits stimulated to undergo an intense inflammatory response. The separated cell populations were in turn utilized to study the specific activities of six intracellular enzymes. The study revealed an increase with cell maturation in the specific activities of myeloperoxidase, NADPH oxidase, alkaline phosphatase and acid phosphatase in normal animals; in stimulated animals only myeloperoxidase and NADPH oxidase increased significantly with cell maturation. Glucose‐6‐phosphate dehydrogenase showed no change in specific activity in all animals studied. Malate dehydrogenase tended to show a specific activity decrease in the maturing cells of normal but not in those of stimulated animals.
Cytochemical, Ultrastructural and Immunological Studies of Circulating Reed–Sternberg Cells
Authors: Hayhoe F. G. J. , Burns G. F. , Cawley J. C. , Stewart J. W.
Published: March 2008

Reed–Sternberg (R–S) cells in the circulating blood of a patient with Hodgkin's disease were cytochemically peroxidase and Sudan black negative, devoid of alkaline phosphatase and non‐specific esterase, mostly PAS negative but occasionally showing positivity, and nearly always showing moderately strong granular positivity for acid phosphatase. Electron microscopy showed irregular nuclear profiles, conspicuous nucleoli, a moderate development of cytoplasmic organelles but absence of structures resembling monocytic granules. The R–S cells frequently possessed receptors for the Fc region of IgG and were mostly positive for SmIg, but did not form rosettes with sheep or mouse erythrocytes nor have receptors for the Fc region of IgM or the C3 component of complement. The combined results suggest that R–S cells are of B‐cell lineage.
Erythropoietin Dependent Erythropoiesis during the Erythroblastic Phase of Juvenile Chronic Granulocytic Leukaemia
Authors: Hoffman Ronald , Zanjani Esmail D.
Published: March 2008

A child aged 3 1/2 years with typical juvenile chronic granulocytic leukaemia whose course terminated in an erythroblastic phase is described. Both in‐vivo transfusion studies and in‐vitro bone marrow culture studies indicate that red cell production remains erythropoietin dependent in this situation. The relationship of erythropoietin to the reversion to fetal haematopoiesis which characterizes juvenile chronic granulocytic leukaemia is discussed.
Intensive Plasma Exchange on the Cell Separator: Effects on Serum Immunoglobulins and Complement Components
Authors: Keller A. J. , Urbaniak S. J.
Published: March 2008

Six patients with IgG myeloma and four patients with glomerulonephritis underwent a course of intensive plasma exchange on a continuous flow cell separator. Immunoglobulin‐free and complement‐free replacement fluids were used in each 4.0 or 5.2 l. exchange. The concentrations of the serum immunoglobulins IgG, IgA and IgM, total haemolytic complement (CH50) and the complement components C3 and C4 were measured immediately before and after each exchange. The efficiency of an individual plasma exchange varied from a mean reduction in CH50 and IgA to 47.5% and 47.8% respectively of their initial level to a corresponding reduction of C3 concentration to 37.2%. Consecutive daily plasma exchange further decreased the serum levels of all these factors. All factors except CH50 were reduced to less than 30% after the fifth and less than 10% after the tenth exchange. Although daily exchanges were necessary to maintain reductions in serum C3 and C4 concentrations, subnormal immunoglobulin concentrations could be maintained with alternate daily exchanges. The effect of concurrent immunosuppressive therapy could be assessed in one patient. A significant reduction in the rate of recovery of serum IgG and IgA concentrations was demonstrated during immuno‐suppressive therapy. Although the therapeutic effectiveness of sustained reduction of these proteins is unproven, our data have important implications for the organization, cost and workload involved in programmes of intensive plasma exchange.
Immunologic Studies of Factor IX (Christmas Factor)
Authors: Yang Henry C.
Published: March 2008

A solid‐phase two‐site immunoradiometric assay has been developed which measures factor IX antigen levels as low as 0.0004 u per ml of plasma. In normal individuals, the factor IX antigen level correlated with the factor IX procoagulant level. In haemophilia B, 14 patients had markedly reduced antigen levels (<0.06 u/ml) and five had normal levels (>0.60 u/ml).
Haemoglobin Vanderbilt (α2β289Ser→Arg): a New Haemoglobin with High Oxygen Affinity and Compensatory Erythrocytosis
Authors: Paniker N. V. , Lin Kuang‐Tzu Davis , Krantz S. B. , Flexner J. M. , Wasserman B. K. , Puett D.
Published: March 2008

Haemolysates of family members from three generations, all of whom had polycythaemia, were analysed by polyacrylamide gel electrophoresis at pH 8.8. Two closely spaced major bands were observed, one of which corresponded to Hb A and the other to a new mutant designated Hb Vanderbilt. Whole blood from a heterozygote for Hb Vanderbilt was analysed for oxygen affinity which was found to be much higher than that of normal subjects. Haemoglobin Vanderbilt was separated from Hb A using anion exchange chromatography. Cation exchange chromatography yielded a variant β chain from which a mutant peptide was identified with a structure corresponding to residues β83–89 with a Ser→Arg replacement at position 89. The oxygen affinity of ‘stripped’ haemolysates from the heterozygote was found to be much less sensitive to added organic phosphates than haemolysates from normal subjects. In whole blood, the decreased sensitivity to 2,3‐diphosphoglycerate results in an increased oxygen affinity, thus explaining the clinical observations of tissue hypoxia and compensatory polycythaemia.
The Development of Haemoglobin A2 in Normal Negro Infants and in Sickle Cell Disease
Authors: Serjeant B. E. , Mason K. P. , Serjeant G. R.
Published: March 2008

The development of haemoglobin A2 levels from birth to 3 years has been compared in normal, β‐thalassaemia trait, sickle cell (SS) disease, and S‐β‐thalassaemia genotypes. Hb A2 levels were almost identical in normals and in children with SS disease at 1, 2 and 3 years. The most rapid increases in Hb A2 levels occurred before 6 months but levels were still rising at the end of the third year. Sickle cell‐β+ thalassaemia could be differentiated from SS disease by the higher Hb A2 levels between 6 months and 1 year. Insufficient data were available on S‐β° thalassaemia but since Hb A2 levels in this condition are generally higher than those in S‐β+ thalassaemia, differentiation from SS disease may also be possible from the age of 6 months.
Leucocyte Alkaline Phosphatase Activity during High Risk Pregnancies
Authors: Louis D. , Creatsas G. , Psomadakis C. , Kaskarelis D.
Published: March 2008

142 determinations of leucocyte alkaline phosphatase (LAP) activity have been done in 103 cases of high risk pregnancy. A statistically significant elevation of LAP score has been found in high risk pregnancies due to diabetes mellitus, toxaemia, renal diseases and third trimester haemorrhage, but not in pregnancies complicated by cardiac disease, chronic hypertension, Rh sensitization or anaemia.
Auto Analyzer Determination of Red Cell Kell Phenotypes in Patients with Chronic Granulomatous Disease (CGD) and Heterozygous Carriers
Authors: Bowell P.J. , Hill F. G. H.
Published: March 2008

One of six boys with chronic granulomatous disease was shown to have the rare Kell phenotype, McLeod, by both manual and AutoAnalyzer techniques. Using the AutoAnalyzer, the red cells of this boy's mother were clearly shown to have weaker expression of k and Kpb antigens than those of the controls, whereas the Kell groups on the father's red cells appeared normal.
Heterogeneity of Rabbit Platelets
Authors: Karpatkin S.
Published: March 2008

Rabbits were injected intravenously with a cohort platelet label, 75Se‐selenomethionine. Platelet‐rich plasma was separated into five different platelet density fractions on each of seven days by repetitively centrifuging the same sample of platelet‐rich plasma at increasing gravitational force. The heaviest platelet sediment fraction was enriched with larger platelets. The lightest platelet sediment fraction was enriched with smaller platelets. Incorporation of isotope into the heaviest platelet fraction was considerably greater than incorporation into the lightest platelet fraction, i.e. heavy‐light specific activity ratio was 9.63, on day 1. The ratio of the heaviest platelet fraction specific activity to the specific activities of the platelets sedimented at higher g forces (lighter‐smaller platelets), generally decreased on each day for 4–6 d by a factor of 2.8–7.0‐fold. Whereas incorporation of isotope into the heaviest platelet fraction declined on days 3–4, incorporation into the lightest three fractions remained the same. Cohort platelet survival curves revealed a significant lag period of 1–2 d for the incorporation of isotope into the lightest three platelet fractions compared to the heaviest two platelet fractions. The mean platelet survival of the lightest two fractions was significantly shorter than the mean platelet survival of the heaviest three fractions.

SDS‐polyacrylamide gel electrophoresis of the platelet cell sap of the five platelet fractions generally revealed 10 prominent protein bands for the heaviest platelet fractions. The lightest platelet fraction, which comprised 16% of the harvested platelet population, had six absent to markedly diminished platelet proteins of modecular weights between 142 000 and 46 000 daltons.

The data are compatible with two models: (1) Heavy‐large platelets are, on average, young platelets which become lighter‐smaller platelets while losing platelet membrane and cell sap components with time. (2) Heavy‐large platelets and light‐small platelets are produced independently by specific megakarocytes. The heavy‐large platelets incorporate more isotope than lighter‐smaller platelets (possibly because of their megakarocyte precursor). However, they are released earlier into the circulation than lighter‐smaller platelets and are therefore younger platelets.
Mutant Mouse L‐Cells: A Model for Megaloblastic Anaemia
Authors: Dardick Irving , Sheinin Rose , Setterfield George
Published: March 2008

Summary. When temperature‐sensitive (ts) mutant lines of mouse L‐cells, ts A1S9 and ts C1, are shifted from 34°C to 38.5°C, a rapid inhibition of DNA synthesis and mitosis occurs. During this phase, cell and nuclear growth continues and results in a substantial increase in cell and nuclear volume. Such cellular modifications are also associated with a marked dispersal of the condensed chromatin masses of interphase nuclei, so that after 48–72 h of incubation at 38.5°C, nuclear profiles of both ts cell lines bear a striking resemblance to the nuclear features characteristic of megaloblastic anaemia. Despite these marked alterations in nuclear chromatin organization, morphometric analysis indicates that the volume of condensed chromatin does not decrease. Current biochemical, cytological and morphometric data on the two ts lines of mutant mouse L‐cells during expression of the mutation, suggest that they might provide a useful model to further elucidate cytological features of megaloblastic anaemia.
The Control of Hepatic Iron Uptake: Correlation with Transferrin Synthesis
Authors: Morton A. G. , Tavill A. S.
Published: March 2008

Summary. The control of hepatic iron uptake was studied in the perfused liver isolated from rats subjected to nutritional iron deficiency. The total hepatic iron uptake and incorporation into ferritin was found to be higher in iron deficiency and during the 48 h of oral refeeding with iron than in the normal state. Specific incorporation of iron into ferritin from a perfusate of normal transferrin iron saturation was enhanced in nutritional iron deficiency as compared to controls after 5 h of perfusion but not after 1 h, suggesting that increased uptake of iron from the perfusate may play a role in stimulating hepatic ferritin synthesis and assembly. This promotion of uptake into ferritin was inhibited by cycloheximide suggesting that enhanced incorporation of iron is dependent upon de novo synthesis of apoferritin. In control, nutritionally iron deficient and iron‐refed rats there was a significant, direct correlation between the transferrin‐iron saturation of the perfusate at physiological transferrin concentrations and total hepatic iron uptake after 5 h perfusion.

A significant positive correlation was found between the hepatic total and ferritin iron uptake and the transferrin synthetic rate measured in the same liver. It is proposed that in the liver the negative feedback of iron supply on transferrin synthesis may be linked with a positive feedback on ferritin synthesis. The timecourse of these reciprocal responses suggests a role for hepatic ferritin and/or a component of the non‐haem, non‐ferritin iron pool in the regulation of transferrin synthesis.
Changes in the Ca2+‐Transport Processes of Red Cells during Cold Storage in ACD
Authors: Szász I. , Sarkadi B. , Gárdos G.
Published: March 2008

In order to characterize Ca2+‐transport in red cells stored in ACD Ca2+‐loading and Mg2+‐depletion by the ionophore A23187, CaATPase activity determination in intact cells and an accurate Ca2+‐influx technique were adapted to preserved blood. Active Ca2+‐efflux (pump) was measured in rejuvenated cells loaded by Ca2+ with A23187. The rate of Ca2+‐pump declined only slightly during 3 weeks of storage (from 80 ± 15 to 66 ± 17 μmoles Ca2+/l. cells/min) and a marginal trend of decrease in the Ca:ATP ratio was observed (from 1.96 ± 0.15 to 1.88±0.11). Passive Ca2+‐influx (leak) was studied in regenerated cells in which the Ca2+‐pump was blocked with 0.2 mm lanthanum. Ca2+‐influx showed a slow increase during the first 3 weeks of storage (from 0.4±0.16 to 1.25±0.4 μmoles Ca2+/l. cells/min), later it increased rapidly. Passive Ca2+ leak and exchange transport were studied in unregenerated, phosphate ester‐depleted cells. In this case passive Ca2+‐influx increased 2–3‐fold as early as 1–2 d after storage in ACD. This initial increase was followed by a continuous slow enhancement that reached a flux of 3.5±0.7 μmoles Ca2+/l. cells/min after 3 weeks of storage. The passive Ca2+‐permeability increase that occurred during storage could be readily compensated by the Ca2+‐pump without causing metabolic imbalance. The Ca2+‐transport, of unregenerated stored cells, however, showed impairment under certain conditions (A23187+EDTA and lanthanum treatments, ghost preparation). The Ca2+‐induced shape changes were reversible and ran parallel with the cell Ca2+ level during Ca2+‐pumping up to 5 weeks of storage. This finding indicates a direct relationship between cell Ca2+ and shape.
Hodgkin's Disease: Ultrastructural Localization of Intra‐cytoplasmic Immunoglobulins within Malignant Cells
Authors: Bernuau D. , Feldmann G. , Vorhauer W.
Published: March 2008

SUMMARY An immunoperoxidase technique has been applied to the detection of intracellular immunoglobulins at the light and ultrastructural levels in three untreated cases of Hodgkin's disease. The results are compared with those obtained in three treated cases. In both groups, 20–90%) of malignant cells had intra‐cytoplasmic immunoglobulins. There was no correlation between the percentage of imniuno‐globulin‐containing cells and the histological type or the stage of the disease. At the ultrastructural level, imniunoglobulins were constantly localized on cytoplasmic ribosomes, the later being either free in the cytoplasm or bound to the endoplasmic reticulum and to the external envelope of the perinuclear space. In addition, a very few malignant cells exhibited imrnunnglobulins within their perinuclear space and their endoplasmic reticulum. These results demonstrate that immunoglobulins in Hodgkin's malignant cells are present on the cellular sites of protein synthesis. They appear to be retained in their cytoplasm, and to be secreted only very occasionally. The significance of these findings as to the cellular origin of malignant cells in Hodgkin's disease is briefly discussed.
Malignant Histiocytosis: A Clinico‐pathological Study of 12 Cases
Authors: Lampert I. A. , Catovsky D. , Bergier N.
Published: March 2008

SUMMARY The clinico‐pathological features of 12 cases of inalignant histiocytosis (histiocytic medullary reticulosis), aged 12–60 years, were studied. Special emphasis wx put on the analysis of the hacmatological, cytological and histopathological findings of the disease.

Bone marrow aspirates and biopsies from involved tissues (liver, lymph node, spleen and skin) were found best suited for establishing the diagnosis. Cytochemical and ultrastructural data support the concept that the neoplastic cells belong to the mononuclear‐phagocyte system.

Three untreated patients died in less than 6 months. Median survival of the nine treated patients was 1 year. Seven patients were treated with the combination chemotherapy CHOP and four achieved a complete remission. Three of them are alive and continue in unmaintained remission for more than 1 year, surviving so far for 18+ to 31+ months. Two cases showed evidence of CNS involvement, one during life and the other as a post‐mortem finding.

The differential diagnosis from other related or unrelated disorders and the possible aetiological factors responsible for the disease are discussed in detail.
Platelet and Plasma β Thromboglobulin in Mycloproliferative Syndromes and Secondary Thrombocytosis
Authors: Boughton U. J. , Aliington M. J. , King A.
Published: March 2008

SUMMARY Elevated plasma β thromboglobulin (βtg) and decreased intracellular platelet βtg were found in patients with various myeloproliferative disorders. In secondary thrombocytosis, similar, but less marked changes were found. The abnormalities were increased during episodes of clinical thrombosis and could be suppressed in two‐thirds of cases by aspirin therapy.
Stimulation of in Vitro Granulocyte‐Macrophage Colony Formation by Mouse Heart Conditioned Medium
Authors: Byrne Peter V. , Heit Wolfgang , Kubanek Bernhard
Published: March 2008

Summary. Medium conditioned by mosue heart tissue was found to contain colony‐stimulating factor(s) (CSF) which prodduced in vitro colonies of granulocytes and/or macrophages with bone marrow cells of CBA mice. The action of this CSF type (CSFMHCM) was compared with that of post‐endotoxin mouse serum (CSFES) on colony formation by density subpopulations of colony‐forming cells (CFU‐c), separated by isopycnic centrifugation in a continous albumin density gradient. The number, size and morphology of colonies were examined.

Mouse heart conditioned medium produced slightly more colonies adn of larger size than endotoxin serum but the density distribution of their CFU‐c were similar. Low density CFU‐c produced predominatly pure granulocytic colonies and high density ones predominately pure macrophage colonies with both types of CSF. There was no apparent relationship between colony size and CFU‐c density.