bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelet‐Function Studies in Patients with Glucose‐6‐Phosphate Dehydrogenase Deficiency
Authors: Schwartz Jack P. , Cooperberg Arthur A. , Rosenberg Arthur
Published: March 2008

Summary. Tests of platelet function were carried out in 17 patients with glucose‐6‐phosphate dehydrogenase (G6PD) deficiency. Despite the clinical absence of defective haemostasis impaired platelet function was observed in all patients studied. This consisted of reduced platelet‐factor 3 (PF 3) availability, a reduced prothrombin‐consumption time, and/or reduced platelet retention in a glass bead column. PF3 assay of freeze‐thawed platelets demonstrated that this reduction of PF3 availability represents a true deficiency rather than defective release. Platelet aggregation with ADP, collagen and adrenaline was normal. These findings suggest that G6PD deficiency, which leads to impaired NADPH production, may cause reduced fatty‐acid and phospholipid synthesis by the platelets resulting in PF3 deficiency. The normal platelet aggregation suggests that energy derived from the hexose‐moaophospliatc shunt is not essential for this function.
The Effect of Calcium Ions on the Properties of Factor IX and its Activated Form
Authors: Chuang Tsin F. , Sargeant Robert B. , Hougie Cecil
Published: March 2008

Summary. The activation of bovine plasma factor IX requires activated factor XI and calcium ions, but not phospholipids. It results in an apparent reduction in molecular size or shape as shown by gel filtration on Sephadex G‐200 and sucrose gradient ultracentrifugation. DEAE chromatography reveals that the surface charge may be altered upon activation. In the presence of calcium ions, both the precursor and activated form of factor IX showed reduction in sizes. Calcium ions also promote the adsorption of factor IXa on a glass surface. The significance of the change of size and surface charge in the interaction of factor IX and phospholipids is discussed.
Haemoglobin F Port Royal (α2Gγ2, 125Glu → Ala)
Authors: Brimhall B. , Vedvick T. S. , Jones R. T. , Ahern E. , Palomino E. , Ahern V.
Published: March 2008

Summary. A Gγ‐chain variant, Hb F Port Royal, with an electrophoretic mobility intermediate between Hb S and Hb C, was found in a Jamaican‐Negro infant, and made up 14–15% of the total Hb F. A glycinamidation procedure was employed to aid in determining the amino‐acid residue substitution of γ125Glu → Ala, and the presence of glycinc in position 136.
The Syndrome of Hepatitis and Aplastic Anaemia
Authors: Ajlouni Kamel , Doeblin Thomas D.
Published: March 2008

Summary. Eighty‐eight cases of severe pancytopcnia closely following the onset of apparently typical viral hepatitis have been described. We report two additional patients. Remarkable features of the syndrome are the rapid, high mortality (88%) and the fact that the age and sex distribution parallel that of hepatitis, not that of other wries of aplastic anaemia. Although viral damage to haematopoietic cells can be demonstrated in vitro, chromosonies in our patients were normal after short‐term culture of peripheral lyrnpliocytes. Therapeutically, androgens may be of some benefit despite the high mortality. No adequate explanation for the association is available, but infectious hepatitis should be accepted as a potential cause of aplastic anacmia.
The Effect of Lead on Total Globin and a‐ and P‐Chain Synthesis; in Vitro and in Vivo
Authors: Piddington Sylvia K. , White J. M.
Published: March 2008

Summary. The effect of lead in vitro and in viuo on the synthesis of total globin and a and fl chains in reticulocytes has been studied. In vitro lead at concentrations of 50–400 μg/dl of whole blood was shown to depress globin synthesis; the degree of depression being dependent on the concentration. Also a‐chain synthesis was inhibited more than β‐chain synthesis. Part of these effects could be explained by the fact that lead inhibited the incorporation of [3H]leucine into the reticulocytes. Haemin added to the incubation mixture prior to the addition of lead corrected the inhibition of total globin synthesis, but only partially corrected the imbalance of α‐ and β‐chain synthesis. Studies on the distribution of 203Pb within the red cell showed that it rapidly became bound to red‐cell stroma, ribosomes and haemglobin. In vivo it was found that in 28 lead workers there was no significant alteration in the synthesis of a and β chains when compared with normal controls. However, in six of the lead workers, the α/β ratio was greater than 1.2. The results are discussed in terms of the effect of lead upon haemoglobin synthesis.
The Mechanism of Neutropenia in Felty's Syndrome
Authors: Vincent P. C. , Levi J. A. , Macqueen Ann
Published: March 2008

Summary. Neutrophil kinetics were studied in 17 patients with Felty's syndrome using an in vitro diisopropylfluorophosphate‐32P technique. Excessive margination of neutrophils was present in all patients, and was solely responsible for the neutro‐penia in 12. Five patients had a total blood neutrophil pool which was so low that they would have been neutropenic even with a normal ratio of marginated to circulating cells; in these the production rate was subnormal. In no case was neutropenia due to shortened nueutrophil survival. There was no correlation between either the degree of marrow cellularity, or serum lysozyme levels, and the measured neutrophil production rate. Two patients studied before and after splenectomy showed improvement in kinetic abnormalities following operation. We conclude that the principal mechanism responsible for the neutropenia in Felty's syndronie is excessive margination of cells. In about one third of patients neutrophil production is subnormal in addition, but excessive neutrophil destruction is an uncommon finding. Conventional laboratory investigations are of little or no help in defining the mechanism in an individual patient. The value of splenectomy still has to be established, although short‐term improvement in kinetic parameters may occur.
Immunological Rebound after Cessation of Long‐term Chemotherapy in Acute Lymphocytic Leukaemia: Changes in Distribution of T and B Cell Populations in Bone Marrow and Peripheral Blood
Authors: Sen Luisa , Borella Luis
Published: March 2008

Summary. The aim of this study was to compare the kinetics of recovery of B (thymus‐independent) and T (thymus‐dependent) cells in the peripheral blood and bone marrow of children with acute lymphocytic leukaemia (ALL) after long‐term immunosupprcssive therapy. B‐cells were identified by the presence of immuno‐globulins on their surface and T‐cells by spontaneous rosette formation with sheep crythrocytes. In peripheral blood of children who had been in remission for more than 3 yr, the percentage of B‐lymphocytes bearing detectable IgM and IgG increased from 2–4 mth after therapy was stopped, while the percentage of T‐lymphocytes decreased. In bone marrow the number of B‐lymphocytes bearing IgM was higher in the first month after therapy than in the following months. This early increase preceded the rise of IgM‐ and IgG‐lymphocytes in peripheral blood. The proportion of T‐lymphocytes in bone marrow was significantly lower than in peripheral blood and did not change throughout the recovery phase. No differences in the rebound of peripheral blood B‐cells were demonstrated between three children who had relapsed and those who remained in remission.

These data demonstrate that after long‐term chemotherapy, bone marrow and peripheral blood lymphocytes bearing B‐ and T‐cell surface markers recover with different kinetics. These results suggest that bone in arrow IgM‐lymphocytes may be the precursors of circulating lymphocytes bearing IgM and IgG in man.
Haemoglobin Synthesis in Human Fetal Liver Maintained in Short‐Term Tissue Culture
Authors: Shchory M. , Weatherall D. J.
Published: March 2008

Summary. Human fetal liver maintained in tissue culture has been examined as a model system for studying the factors involved in the switch from fetal to adult haemoglobin production. In erythropoietin‐treated cultures α‐, β‐ and γ‐chain synthesis remains active for up to 12 days. Globin‐chain synthesis is balanced and the α/β+γ‐chain production ratio remains constant up to about 8 days; in longer cultures γ‐chain production declines before that of β chains. It is concluded that the system may be useful for examining factors involved in the switch from γ‐ to β‐chain production provided that these are acting on cells already committed to the erythroid compartment.
Acute Leukaemia with Eosinophilia or Acute Eosinophilic Leukaemia: A Dilemma
Authors: Weinger R. S. , André‐Schwartz Janine , Desforges Jane F. , Baker Margaret
Published: March 2008

Summary. A young male patient is described with acute leukaemia whose bone marrow and peripheral blood contained abundant cells of the eosinophilic series in all stages of maturation. These cells, proven histochemically to be true eosinophils, were abnormal in both maturation and proliferation. Upon electron microscopic study of bone marrow and peripheral blood, abnormalities in the eosinophilic series were identified as early as the promyelocytic stage as well as in the most mature eosinophil seen. The clinical and morphologic picture of this patient's disease raises the possibility of this being an acute eosinophilic leukaemia.
Fibrinogen Metabolism in Acute Hepatitis and Active Chronic Hepatitis
Authors: Clark R. D. , Gazzard B. G. , Lewis M. L. , Flute P. T. , Williams Roger
Published: March 2008

Summary. Coagulation studies, including those of radioactive fibrinogen metabolism, were performed in seven patients with acute viral hepatitis and 12 patients with active chronic hepatitis. An increased fractional catabolic rate for fibrinogen was observed in four patients from the first group, and seven from the second. The catabolic rate was increased in those patients with the greatest degree of hepatic necrosis as demonstrated by the raised serum aminotransferase levels. There was no correlation between the rate of fibrinogen catabolism and the standard clotting tests, but the SDPS test (indicating the presence of fibrin monomers in the circulation) was consistently positive in those cases where the catabolic rate was increased.
Measurement of Heparin in Patients Receiving Subcutaneous Heparin Therapy
Authors: Denson K. W. E. , Bonnar J.
Published: March 2008

Summary. Heparin assays based on four different tests of clotting function have been compared with a heparin assay utilizing the potentiating effect of heparin on anti‐factor Xa in a group of patients receiving subcutaneous heparin therapy during late pregnancy. It is considered that the anti‐factor Xa method is a better indication of the antithrombotic effect of heparin. In the presence of high levels of clotting factors, heparin assays based on tests of clotting function can be misleading.
Partial Myeloperoxidase Deficiency in a Case of Preleukaemia
Authors: Breton‐Gorius J. , Houssay D. , Dreyfus B.
Published: March 2008

Summary. The ultrastructural localization of peroxidase activity has been studied in the circulating neutrophils and in a neutrophilic series of bone marrow cells from a patient with preleukaemia.

Light microscopic examination showed 36% of the polymorphonuclear leucocytes to be totally devoid of myeloperoxidase, while 50% were normally stained and 14% were slightly positive for this enzyme.

Electron microscopic studies revealed considerable heterogeneity in the promye‐locyte population, since the number of peroxidase‐deficient azurophil granules was seen to vary from o to 100% in these cells. Thus, several types of promyelocytes were identified. One cell type, which resembled that seen in normal subjects, contained myeloperoxidase within its azurophil granules and also within the cisternae of the rough endoplasmic reticulum and Golgi complex. A second type of pro‐myelocyte, which was at an early stage of development, lacked myeloperoxidase in its secretory apparatus. These cells contained two species of azurophil granules, the first of which was devoid of peroxidase activity whereas the other reacted positively.

These observations suggest that the premature arrest of myeloperoxidase synthesis in the promyelocytes from a preleukaemic patient may give rise to several populations of circulating neutrophils which can exhibit varying contents of myeloperoxidase.
G6PD Hillbrow: A New Variant of Glucose‐6‐Phosphate Dehydrogenase Associated with Drug‐induced Haemolytic Anaemia
Authors: Cayanis Eftihia , Gomperts E. D. , Balinsky Doris , Disler P. , Myers A.
Published: March 2008

Summary. A new genetic variant of the red cell enzyme glucose‐6‐phosphate dehydrogenase is described. It was observed in a patient presenting with severe haemolytic anaemia and renal failure following ingestion of an overdose of Beserol (paracetamol and chlormezanone). The enzyme in the red cell had 12% of the activity of a normal B+ control, but only slightly lower activity in the kidney compared with a normal control. The red cell enzyme showed normal electrophoretic mobility and thermostability, a biphasic pH optimum curve, higher than normal utilization of the substrate analogues 2‐deoxyglucose‐6‐phosphate and deamino‐NADP, and lower than normal Michaelis constants for both substrates, glucose‐6‐phosphate and NADP. The enzyme was strongly inhibited in vitro by high concentrations of paracetamol and chlormezanone. The extent of inhibition was similar to that for the enzyme from a normal B+ individual.
Distribution of Fibrinogen, and Platelet Factors 4 and XIII in Subcellular Fractions of Human Platelets
Authors: Broekman M. Johan , Handin Robert I. , Cohen Phin
Published: March 2008

Summary.

The distribution of fibrinogen, platelet factor 4 (heparin‐neutralizing factor) and factor XIII amongst subcellular fractions of human platelets was determined. It was found that fibrinogen and platelet factor 4 peaked sharply in the region of the density gradient previously shown to be heavily enriched with α‐granules. By contrast, factor XIII, fibrin‐stabilizing factor, was found exclusively in the supernatant.
Lack of Correlation of Lymphoblast Cell Size with Presence of T‐Cell Markers or with Outcome in Childhood Acute Lymphoblastic Leukaemia
Authors: Murphy Sharon B. , Borella Luis , Sen Luisa , Mauer Alvin
Published: March 2008

Summary.

The proportion of pretreatment bone marrow macrolymphoblasts was determined in a total of 93 children with acute lymphoblastic leukaemia (ALL) in order to assess the validity of cell size as a prognostic indicator. A macrolymphoblast (MLb) was defined as having a diameter greater than 12 μm, and patient samples were divided simply on the basis of whether they had more or less than 10% MLb present at diagnosis. In a retrospective study of a sample of 47 children treated according to Total Therapy Study VII, the continuous complete remission duration, survival and incidence of CNS disease bore no relationship to the cell size distribution present at diagnosis. A second sample of 46 current patients with untreated ALL was examined both for the presence of surface markers for T‐ and B‐cells and for cell size. Bone marrow blasts from 10 of these 46 children formed rosettes with sheep erythrocytes (E)—a T‐cell marker. E‐rosette formation was associated with a constellation of adverse prognostic factors, including older age, very high initial WBC counts, organomegaly, and mediastinal enlargement; yet the presence of this T‐cell marker was unrelated to cell size. We conclude that pretreatment lymphoblast cell size is not a reliable prognostic indicator in childhood ALL.
Ultrastructural Studies of the Bone Marrow in Sickle Cell Anaemia
Authors: Grasso J. A. , Sullivan A. L. , Sullivan L. W.
Published: March 2008

Summary.

Marrow aspirates from sickle cell patients were examined without prior deoxygenation and revealed the presence of a variable proportion (10–30%) of sickled red cells and reticulocytes. The main feature of sickled red cells was the presence of 17.6 nm fibres arranged in hexagonal order, and to a lesser extent in square or rectangular array, to form bundles of varying size and compactness which occupied the entire cytoplasm. The sickling pattern in reticulocytes was more variable. Some reticulocytes contained highly‐ordered bundles of 17.6 nm fibres whose structure and distribution was identical to that in red cells from which they could be distinguished only by their content of organelles. Many reticulocytes exhibited less‐organized fibre patterns ranging from localized aggregates to poorly‐ordered regions of short fibres and filaments lacking apparent preferential orientation. In these cells, the bulk of the cytoplasm was not polymerized. Haemoglobin polymerization in reticulocytes led to entrapment of ribosomes in concentrated foci among the fibres. Frequently, iron‐laden mitochondria were associated with sickled reticulocytes. The variation in pattern of sickling seen in reticulocytes is attributed to possible differences in concentration of Hb S. Correlative studies have shown that fibres were not induced by fixation procedures. Marked phagocytic degradation of sickled cells by macrophages was observed. The results are interpreted to indicate the possible intramedullary phagocytosis of red cells and reticulocytes, predisposed to sickling in the marrow. However, the data are also consistent with the removal of sickled elements from the circulating blood.
Brain Iron: Persistent Deficiency following Short‐term Iron Deprivation in the Young Rat
Authors: Dallman P. R. , Siimes M. A. , Manies E. C.
Published: March 2008

Summary.

This study was designed to determine the content of non‐haem iron in the brain as iron deficiency develops in the rapidly growing rat. Rats were provided with either an iron‐deficient diet or an identical control diet with added ferrous sulphate starting at 10 d of age and continuing after weaning at 21 d. At 28 or 48 d of age the deficient animals received 5 mg of iron (iron dextran) i.m. and were placed on the control diet regimen. The deficient animals had a concentration of non‐haem iron in the brain that was 27% below the control value at 28 d and 22% below at 48 d. After 14–45 d of iron treatment, the non‐haem iron remained depressed, 19–29% below the control means (P<0.05 to 0.001). Ferritin iron in brain also remained depressed, 33–42% below the control means (P<0.01). In contrast, haematocrit, liver non‐haem iron, and liver ferritin iron, although they were more profoundly depressed in the iron‐deficient animals, promptly returned to control values after treatment with iron. Thus, a brief period of severe iron deficiency in the young rat resulted in a deficit of brain iron that persisted in the adult animal despite an adequate intake of iron.
Functional and Metabolic Studies of Platelets from Patients with Lesch‐Nyhan Syndrome
Authors: Rivard Georges E. , Izadi Parvin , Lazerson Jack , McLaren John D. , Parker Charles , Fish Charles H.
Published: March 2008

Summary.

Platelet function was investigated in three patients with the Lesch‐Nyhan syndrome. Platelet count, morphology and size distribution was normal in all patients. Platelet turnover was normal. Electron microscopy did not reveal any ultrastructural abnormality. Template bleeding times were normal and prolonged after aspirin ingestion in two out of the three patients: the patient that failed to respond to the aspirin challenge also had decreased retention of platelets on a glass bead column.

Biochemical studies revealed that total platelet ATP was reduced by 34% in the presence of a normal level of ADP in the storage pool. These platelets failed to incorporate radioactive hypoxanthine but did incorporate radioactive adenine to produce adenine nucleotides and a trace amount of guanine nucleotides.

The results indicate that normal platelets have a functionally intact pathway for utilizing hypoxanthine as a source of preformed purine, and that the failure to salvage this purine, as in the Lesch‐Nyhan syndrome, results in a decreased level of total platelet ATP. These findings suggest that platelets can function normally despite a one third reduction in total ATP content.
The Anti‐Folate Effect of Methionine on Bone Marrow of Normal and Vitamin B12 Deficient Rats
Authors: Cheng F. W. , Shane B. , Stokstad E. L. R.
Published: March 2008

Summary.

The effects of dietary vitamin B12 and methionine deficiency, and the in vitro addition of methionine, homocysteine, or folic acid on the methylation of dUMP to dTMP were studied in rat bone marrow culture. Vitamin B12 or methionine deficiency had no effect on the methylation reaction or on bone marrow folate levels although the vitamin B12 content in bone marrow was reduced in vitamin B12 deficiency. In vitro addition of vitamin B12 or folic acid also had no effect on the methylation of dUMP. In vitro addition of methionine reduced the methylation of dUMP and increased the proportion of 5‐methyltetrahydrofolate at the expense of other folate coenzymes. The reason for this‘anti‐folate’effect of methionine, which is the opposite to that found in liver, was not clear. The presence of 5,10‐methylenetetrahydrofolate reductase and 5‐methyltetrahydrofolate‐homocysteine methyltransferase were confirmed in rat bone marrow and they were inhibited by S‐adenosylmethionine and methionine, respectively, in a similar fashion to that found with the liver enzymes. Homocysteine had no effect on the proportions of the various folate coenzymes in bone marrow but did inhibit the incorporation of deoxyuridine and deoxythymidine into DNA. It appeared that homocysteine exerted its effect at a non‐folate dependent step beyond the formation of dTMP.
Stimulation of Erythrocyte Glutathione Reductase Activity by Flavin Adenine Dinucleotide (FAD) in Malaysian Adults and Newborns and their Parents
Authors: Eng Lie‐Injo Luan , Ng T. , Wan Wong Pui , Ganesan J.
Published: March 2008

Summary.

A study of glutathione reductase (GR) activity and its stimulation by flavin adenine dinucleotide (FAD) in erythrocytes of Malaysian newborns and adults of different racial groups showed that GR stimulation by FAD was greater than 20% in 50% of 866 newborns (57% of Malays, 55% of Indians and 41% of Chinese) and 54% of 274 adults (46% of Malays, 65% of Indians and 45% of Chinese). There was a significant negative correlation between GR activity and percentage FAD stimulation in both newborns and adults in all racial groups. Low GR activity and a high percentage FAD stimulation were more prevalent among parents of newborns with low GR activity than among parents of newborns with higher GR activity. Administration of riboflavin to mothers with low GR activity resulted in increased GR activity and a decreased percentage of FAD stimulation. None of the individuals examined had clear clinical manifestations of riboflavin deficiency. It is concluded that subclinical riboflavin deficiency leading to low GR activity is prevalent in Malaysia among adults and newborns, especially among Malays and Indians.
The Detection of Intracellular Antigens in Human Leucocytes by Immunoperoxidase Staining
Authors: Mason D. Y. , Farrell Caroline , Taylor C. R.
Published: March 2008

Summary.

An immunoperoxidase procedure is described for staining intracellular leucocyte antigens in peripheral blood and bone marrow smears. Brief exposure of cell smears to a buffered formol acetone mixture was found to give optimal fixation, combining good cellular morphology with preservation of antigenic reactivity. The immunoperoxidase method is superior to immunofluorescence in that it provides a permanent preparation which can be counterstained with orthodox reagents and viewed by conventional light microscopy. In addition the technique is considerably more sensitive than immunofluorescence procedures.

Immunoglobulin was demonstrated in plasma cells, Türk cells and a minority of peripheral blood lymphocytes. Lysozyme was found in cells of the neutrophil series from promyelocytes to mature granulocytes. Monocytes stained for lysozyme but the reaction was less intense than in neutrophils and some monocytes were devoid of activity. Lactoferrin stained strongly in mature neutrophil polymorphs and metamyelocytes, but was weak or absent in earlier myeloid cells.

These reaction patterns are in keeping with previous reports on the distribution of these antigens in human leucocytes. In the case of immunoglobulin and lysozyme it was possible to abolish leucocyte staining by incubation of the specific antisera with the appropriate purified antigen, providing additional proof of the specificity of the reactions. Anti‐ferritin antisera stained granulocytes and myeloid precursors strongly, and reacted weakly with a minority of monocytes. These latter observations are not entirely in accordance with published data on the leucocyte distribution of ferritin and may be attributed to antibody activity of unknown specificity in the anti‐ferritin antiserum.
Regeneration of Intact Spleen in a Heterotopic Site in Splenectomized Mice
Authors: Warner T. F. C. S. , Krueger R. G.
Published: March 2008

Summary.

The regeneration of intact spleens implanted in the sacrospinal areas of splenectomized mice was studied by light microscopy. The weight of the implanted tissue was not fully regenerated 50 days after implantation. The pattern of embryonic development of the spleen was investigated and the histologic appearance of the implant 46 days after implantation resembled that of normal spleen. The appearance of primitive myelopoietic stem cells in the early phases of regeneration makes this an attractive model in which to study the biologic effects of tumour viruses.
Red Cell 2,3‐Diphosphoglycerate Levels in Children with Hereditary Haemolytic Anaemias
Authors: Haidas S. , Zannos‐Mariolea L. , Matsaniotis N.
Published: March 2008

Summary.

The role of red cell 2,3‐diphosphoglycerate (2,3‐DPG) in increasing the availability of haemoglobin oxygen in neonatal jaundice and hereditary haemolytic anaemias was investigated. Measurements of 2,3‐DPG were carried out on 58 normal children and six normal adults, 18 full‐term newborns with neonatal jaundice and 57 cases (51 children and six adults) with hereditary haemolytic anaemias. In normal children and adults, with a mean haemoglobin of 12.69 g/dl, mean 2,3‐DPG was 14.90 μmol/g Hb. In jaundiced newborns with a mean haemoglobin of 16.04 g/dl mean 2,3‐DPG levels were 14.51 μmol/g Hb, i.e. normal. 2,3‐DPG levels were increased in patients with β‐thalassaemia major, α‐thalassaemia, sickle‐cell disease, favism, hereditary spherocytosis and in heterozygotes for β‐thalassaemia with increased haemoglobin F. In heterozygotes for β‐thalassaemia with increased haemoglobin A2 only and in sickle cell trait 2,3‐DPG levels were normal.
The Sézary Syndrome Lymphoid Cell: Abnormal Surface Properties and Mitogen Responsiveness
Authors: Braylan Raul , Variakojis Daina , Yachnin Stanley
Published: March 2008

Summary.

The peripheral blood lymphoid cells of five patients with Sézary syndrome (SS) were examined with respect to their surface membrane characteristics and their response to mitogens. These cells showed markedly defective mitogenic responses to a broad dose range of phytohaemagglutinin (PHA), pokeweed mitogen, concanavalin A, and a rabbit antihuman lymphocyte antiserum (ATS), when compared with normal human lymphocytes. SS lymphoid cells (three patients studied) also displayed diminished or nearly absent capacity to form rosettes with unsensitized sheep erythrocytes (E‐rosettes), and lacked surface immunoglobulin determinants. Despite their poor mitogenic response to ATS, they were as susceptible as normal lymphocytes to ATS‐induced, complement mediated cytotoxicity. By comparison with lymphocytes from patients with chronic lymphocytic leukaemia, however, SS lymphoid cells showed decreased susceptibility to leukoagglutination by PHA. By way of contrast, three patients with mycosis fungoides having normal‐appearing peripheral blood lymphocytes showed normal lymphocyte responses to mitogens, as well as normal proportions of E‐rosette forming and surface immuno‐globulin‐bearing lymphocytes. These studies demonstrate that the SS lymphoid cell may, in some cases, lack surface properties and mitogen response characteristics of both B‐ and T‐lymphocytes.
Red Cell Structure, Shapes and Deformability
Authors: Bessis Marcel , Mohandas Narla
Published: March 2008

Summary.

Recent information on factors inducing form changes in human red cells are reviewed. A new diffractometric technique for the measurement of red cell deformability is discussed. Preliminary results on changes in red cell deformability during the form changes and in pathological cases are presented.
Pathophysiology of Aplastic Anaemia
Authors: Heimpel H. , Kubanek B.
Published: March 2008

Summary.

Aplastic anaemia is the clinical expression of reduced influx into the compartments of morphologically identifiable proliferating and maturing haemo‐poietic cells from the stem cell compartment. The bulk of evidence, especially the results of bone marrow transplantation, favours a primary alteration of the proliferation and/or differentiation of pluripotent haemopoietic stem cells. Experimental and clinical data suggest that a stem cell compartment which is reduced in size may compensate its output by adaptation of kinetics for a limited period of time; this could explain the well‐known time lag between exposure to potentially harmful drugs or viruses and manifestation of aplastic anaemia. Humoral regulating factors, as far as have been examined, show normal reactivity. A primary alteration of bone marrow stroma is less likely. However, the basic mechanism of aplastic anaemia may be heterogenous and some cases may be due to alteration in the micro‐environment of haemopoietic cells. In many, and maybe in all cases, haemopoietic insufficiency is induced by external factors on the basis of individual hypersensitivity. Chemical, physical and viral factors are known. Direct toxicity of these factors on stem cells is more likely than mediation through immune mechanisms.
Antenatal Diagnosis of the Haemoglobinopathies
Authors: Nathan David G. , Alter Blanche P.
Published: March 2008

Summary.

The β‐chain of adult haemoglobin is expressed in fetal red cells during the first to mid‐trimester of human pregnancy. The rate of β‐chain production is approximately 8% of γ‐chain production during this period of gestation. The production of βs‐chains is readily detectable and the reduction of βA‐chain production in thalassaemia may also be observed.

Acquisition of fetal cells by means of placentocentesis or placental venipuncture via a fetoscope are current sampling methods which have been shown to be useful. Thus far five attempts at such antenatal diagnosis have been made, four for β‐thalassaemia and one for sickle cell anaemia. In three of these attempts (all for β‐thalassaemia), a sample of fetal blood was obtained. In one, the correct diagnosis of a normal fetus was made. In a second fetus, the diagnosis of β‐thalassaemia trait was made; the infant was normal. In a third, the diagnosis of a normal fetus was made; the infant had β‐thalassaemia trait.

These early results indicate that attempts at antenatal diagnosis of the common β‐chain abnormalities do not necessarily disturb pregnancy and can yield important information which encourages mothers at risk to retain pregnancies.
The Histopathology of Malignant Lymphoma
Authors: Lennert K. , Mohri N. , Stein H. , Kaiserling E.
Published: March 2008

Summary.

It has been possible to reinterpret non‐Hodgkin's lymphomas by applying subtle histological, cytological, and cytochemical techniques and electron microscopy as well as by using modern immunological methods and immune chemical analyses. This has led to the differentiation of four main groups of low‐grade and three main groups of high‐grade malignant lymphomas. Most non‐Hodgkin's lymphomas are derived from the B‐lymphocyte system. Only some of the lymphocytic, a small fraction of the lymphoblastic, and very few immunoblastic lymphomas originate from the T‐lymphocyte system. True reticulosarcomas are very rare and will have to be redefined.
Physiological Experiments in Haemostasis and Thrombosis
Authors: Tschopp Th. B. , Baumgartner H. R.
Published: March 2008

Summary.

An in vitro perfusion system has been developed which allows morphometric measurement of platelet adhesion and surface‐induced aggregation after exposure of subendothelium and other surfaces to flowing blood. Recent results are briefly reviewed and compared with results obtained using other methods.

A number of rheologic and blood‐borne factors including flow velocity, vessel geometry, presence of red blood cells and divalent cations, affect both platelet adhesion and surface‐induced aggregation.

Diminished adhesion of platelets to subendothelium of rabbit aorta but normal surface‐induced aggregation was found after exposure to blood of patients with von Willebrand's disease and the Bernard‐Soulier syndrome at blood flow rates similar to those found in arteries. In contrast, surface‐induced aggregation was defective in patients with thrombasthenia and in an inbred strain of rats with a haemorrhagic diathesis, similar to the platelet ‘storage pool disease’in patients. Similarly, normal adhesion and strikingly diminished aggregation were found with blood of rabbits after aspirin ingestion. These findings may explain the defective haemostasis in the patients and animals, and suggest a new way to study platelet function in a physiological system.
The Use of Factor IX Concentrates for Patients with Conditions other than Factor IX Deficiency
Authors: Ménaché Doris , Gunllin Marie Claude
Published: March 2008

Summary.

The increasing availability of factor IX concentrates have extended their use in conditions other than factor IX deficiency and especially in combined acquired deficiencies of vitamin K dependent clotting factors.

The occurrence of complications such as post‐transfusion hepatitis type B and thromboembolic episodes have prompted the International Committee on Thrombosis and Hemostasis to constitute a Task Force on the clinical use of factor IX concentrates.

The various concentrates available and the basis for their method of preparation are listed. Their use in various pathological conditions other than factor IX deficiency and also the occurrence of complications in such conditions are reviewed.

The conclusions and the recommendations on the indications and contraindications formulated by the Task Force on the clinical use of factor IX concentrates as issued following the 1974 Basel Meeting are summarized.
Kinetic Studies of 51Cr and DF32P Labelled Granulocytes
Authors: Dresch C. , Najean Y. , Bauchet J.
Published: March 2008

Summary. In vivo kinetic studies of granulocytes labelled in vitro with 51 Cr and DF32P were carried out in nine haematologically normal subjects by isolation of the cells in the blood samples by the Ficoll‐Isopaque flotation method. 51 Cr and 32P specific activity of blood samples made of 93–98% granulocytes was studied. Distribution between marginated and circulating granulocyte pools was identical for both labelled cells and the marginated pool was similar to the circulating pool, except that it was lower in one subject who had a previous splenectomy.

The half‐disappearance time (T 1/2) was 16.1 ± 2.2 h for 51 Cr‐labelled and 5.4±2.1 hr for DF32P‐labelled granulocytes. In one case of a normal subject who previously received multiple transfusion homologous 51 Cr‐labelled granulocytes had a T1/2 of less than I h.
Heterogeneity in Biological Activity of Human Factor VIII Antibodies
Authors: Koutts J. , Meyer D. , Rickard K. , Stott L. , Firkin B. G.
Published: March 2008

Summary. Antibodies against factor VIII collected from six patients were studied for their effect on factor‐VIII coagulant activity, Willebrand factor activity (WF) and factor‐VIII‐related antigen. The results demonstrate differences between individual antibodies; some acting primarily as anti factor VIII, others inhibiting both factor VIII and WF. Differences in effect between plasma and serum indicate that the process of coagulation alters the interaction of these antibodies.
The Subcellular Localization of the Erythrostimulant Factors Present in the Kidney and Spleen of the Rabbit
Authors: Giovannini Elvio , Rosi Gabriella
Published: March 2008

Summary. The subcellular localization of erythrostimulant factors contained in the kidney and spleen of the rabbit have been studied. This was done by subjecting homogenates to fractionation by centrifugation and assessing the erythrostimulant capacity of the hypotonic extracts prepared from the various fractions thus obtained.

The results of these studies show that the erythrostimulant factors are present in the light mitochondrial and microsomal fractions of the normal kidney. In conditions of anaemia they are to be found not only in the above‐mentioned fractions but also in the mitochondrial fraction. By contrast, in the spleen such factors are present only in the mitochondrial fraction.

It is likely that the different localization of the erythrostimulant factors in the kidney and in the spleen of the rabbit may be closely connected with the different functions performed by these organs in the humoral regulation of erythropoiesis.
The Effect of Cytotoxic and Anti‐inflammatory Drugs on the Phagocytosis of Neutrophil Leucocytes
Authors: Whittaker J. A. , Hughes H. R. , Khurshid M.
Published: March 2008

Summary. The phagocytosis of heat‐killed Candida albicans by neutrophil leucocytes was inhibited in vitro by phenylbutazone and acctylsalicylic acid and by the cytotoxic drugs vincristine, vinblastine, cytosinc arabinoside, daunorubicin and busulphan, but not by mustinc hydrochloride or procarbazine. In vivo studies in man have shown a significant reduction in phagocytosis after phenylbutazone ingestion, but not following an oral dose of aspirin. Possible explanatory mechanisms of drug action on neutrophil phagocytosis are discussed.
Blood Leucocyte Enzymes
Authors: Brok‐Simoni F. , Ashkenazi Y. E. , Holtzman. F. , Ramot B.
Published: March 2008

The activities of glucose‐6‐phosphate dehydrogenase (D‐glucose‐6‐phosphate: NADP oxidoreductase, G6PD), 6‐phosphogluconatc dehydrogenase (6‐phospho‐D‐gluconate: NADP oxidoreductase, 6PGD), hexokinase (ATP: D‐hexose 6‐phosphotransferase, Hx), lactate dehydrogenase (D‐lactate: NAD oxidoreductase, LDH). glutamate oxaloacetate transaminase (L‐aspartatc: 2 oxoglutarate aminotransferase, GOT) and dihydrofolatc reductase (DHFR) were measured at 8 a.m. in leucocytes of healthy individuals and patients with chronic myeloid leukaemia (CML), chronic lymphatic leukaemia (CLL), myelofibrosis with myeloid metaplasia and polycythaemia vera. In view of the heterogeneity of the leucocyte populations in these conditions, the enzyme activities were correlated to the number of immature cells in CML and to the percentage of lymphocytes in CLL. No differences in the enzyme activities were found between the white cells of healthy individuals, myelofibrosis with myeloid metaplasia and polycythaemia vera. In CML the activities of all enzymes except GOT correlated directly with the number of immature cells; an inverse correlation with the number of lymphocytes was observed in CLL. GOT was the only enzyme whose activity correlated with the number of lymphocytes in the cell suspension. Furthermore, a significantly higher activity of this enzyme was found in Ficoll‐isolated CLL lymphocytes as compared to normal lymphocytes.
Dissociation of Clot Retraction from Platelet Granule Fusion and Degranulation: an Ultrastructural Study of Reptilase—Human Platelet‐rich Plasma Clots
Authors: De Clerck F. , Borgers M. , de Gaetano G. , Vermylen J.
Published: March 2008

Summary. Human platelet‐rich plasma clots, formed with Reptilase, do not retract. Electron microscopy of such a clot reveals platelets of normal shape and ultrastructural features surrounded by fibrin. When ADP is added before Reptilase, the clot strongly retracts. A sequential ultrastructural study of this process shows that, before visible fibrin formation, the platelets form small clusters and show shape change, granule centralization and pseudopod formation. Upon immobilization of the platelets by fibrin, the pseudopods develop into large cytoplasmatic protrusions, which allow cell contact. During the retraction process, the platelet granules remain intact; some granule fusion only becomes apparent in fully retracted clots. When Thrombofax is added to platelet‐rich plasma before Reptilase, the clots formed also retract. With this aggregation inducer, granule fusion occurs earlier and in more platelets. Platelet pseudopod enlargement and fibrin concentration around the platelet mass arc similar to that in ADP‐trcated samples. Inhibitors of granule fusion and secretion (suprofen, indomethacin) do not modify ADP‐Rcptilase nor Thrombofax‐Reptilase clot retraction but reduce the incidence of granule fusion in Thrombofax‐Reptilase clots. Retraction of Thrombofax‐Reptilase clots is unaffected by concentrations of apyrase which completely block ADP‐Reptilase clot retraction. Prostaglandin E1; papaverine and amitryptiline inhibit both ADP‐and Thrombofax‐Reptilase clot retraction, platelet pseudopod formation and cell‐to‐cell adhesion. These findings suggest that interaction of fibrin with the mass of fused granules (granulomere) or platelet secretion are not responsible for clot retraction. Rather, contraction around adhesion sites formed by cytoplasmic protrusions from adjacent platelets would seem to be involved.
Granulocyte Function in Chronic Granulocytic Leukaemia
Authors: Odeberg H. , Olofsson T. , Olsson I.
Published: March 2008

Summary. The ingestion, bactericidal activity and metabolism of isolated mature neutrophil leucocytes during phagocytosis was studied in 17 patients with chronic granulocytic leukaemia (CGL) with the simultaneous use of normal controls. Seven patients had received no treatment and the others had been treated previously with Busulphan. The phagocytic indices for killed yeast cells did not differ from those of the controls. A diminished bactericidal activity against E. coli was found in nine CGL cases. The bactericidal capacity closely correlated with the degree of leuco‐cytosis since patients with a WBC count of 90 ooo/tl or higher with one exception showed decreased bactericidal activities while patients with WBC counts below 90 000/μl with two exceptions showed normal bactericidal activities. The [i‐14C]‐glucose oxidation during phagocytosis was increased in four patients and decreased in three patients. Some correlation was found between abnormally high or low [i‐14C]glucose oxidation and diminished bactericidal activity. The intracellular iodination reaction during phagocytosis was decreased in 10 cases while the extracellular iodination was increased in six cases and decreased in one case. The data for granulocyte iodination did not correlate with WBC count, bactericidal capacity or [i‐14C]glucose oxidation. The time course for the bactericidal activity and granulocyte iodination seemed to deviate from the controls indicating a slow initial ingestion and/or degranulation phase. The CGL granulocyte content of myeloperoxidase was normal or increased, the lysozyme content was decreased in half of the cases while the amount of antibacterial cationic proteins was increased, normal or low. The present findings indicate a variety of abnormalities in the mature CGL granulocyte, which are not closely interrelated.
Thymoma Associated with Pure Red Cell Aplasia, Immunoglobulin Deficiency and an Inhibitor of Antigen‐induced Lymphocyte Transformation
Authors: Geary C. G. , Byron P. R. , Taylor G. , Maciver J. E. , Zervas J.
Published: March 2008

Summary. A case of thymoma associated with pure red cell aplasia and hypogammaglobulinemia is described in which the anaemia was of abrupt onset, following removal of the tumour. Tests of immunological function showed abnormalities of both humoral and cellular immunity. The patient was found to have a serum inhibitor of antigen‐induced lymphocyte transformation which disappeared after immunosuppressive therapy at the same time that erythroblasts reappeared in the marrow.

It is suggested that the triad of thymoma, pure red cell aplasia and immunoglobulin deficiency are manifestations of ‘pluripotent’ stem cell failure; in this case the inhibitor of lymphocyte transformation may have been related to the factor which also inhibited red cell maturation.
The Abnormal Surface Characteristics of the Red Blood Cell Membrane in Congenital Dyserythropoietic Anaemia Type II (HEMPAS)
Authors: Gockerman Jon P. , Durocher John R. , Conrad Marcel E.
Published: March 2008

Summary. The red blood cell membranes of patients with congenital dyserythro‐poietic anaemia Type II (CDA‐II) were found to be abnormal. They had altered antigenic characteristics, decreased electrophoretic mobility, decreased sialic acid content, and abnormal filtration through polycarbonate filters. Proteins extracted from the CDA‐II erythrocytes showed a different banding pattern on polyacrylamide gels compared to normal erythrocytes. Erythrocytes from clinically unaffected siblings and parents showed similar but less striking abnormalities of antigenic surface characteristics and banding patterns on polyacrylamide gels with nearly normal surface charge, sialic acid content, and filtration properties. These studies suggest a correlation between the degree of membrane abnormality and the clinical state of the CDA‐II family member, demonstrate the erythrocyte in the heterozygote state is not normal, and support the concept of CDA‐II as an autosomal recessive disease.
Pure Red Cell Aplasia: Studies on an IgG Serum Inhibitor Neutralizing Erythropoietin
Authors: Peschle Cesare , Marmont Alberto M. , Marone Gianni , Genovese Arturo , Sasso Guido F. , Condorelli Mario
Published: March 2008

Summary. A new type of IgG serum inhibitor in adult pure red cell aplasia (PRCA) has been investigated. This inhibitor is directed against circulating erythropoietin (Ep) (PRCA type B), rather than the erythroid marrow (PRCA type A). Thus, the IgG inhibitor, after interaction with Ep in solution, is precipitated together with Ep by addition of goat anti‐human gamma‐globulins. Pre‐therapy PRCA serum, although apparently devoid of Ep, shows considerable Ep activity following acidification and boiling. The inhibitor is absent from post‐therapy serum, while Ep levels are elevated. An experimental model for PRCA type B has been established in normal mice after prolonged administration of pre‐remission serum IgG.
Detection of Carriers of Haemophilia: a ‘Blind’ Study
Authors: Rizza C. R. , Rhymes I. L. , Austen D. E. G. , Kernoff P. B. A. , Aroni S. A.
Published: March 2008

Summary. A ‘blind’ study has been made to try to find out if it is possible to diagnose carriers of haemophilia. A group of 34 obligatory carriers of haemophilia were compared with 34 normal women. Levels of factor VIII activity, factor VIII‐related antigen, factor V and ratio of factor VIII activity to factor VIII‐related antigen were measured. In the carrier group the mean level of factor VIII activity and the mean level of the ratio of activity to antigen were each approximately half of those found in the normal women. The mean level of factor V was the same in both groups of women. By setting the lower limit of normal at the lowest level of the different factors found in the normal women, 12 out of 34 (35%) carriers could be distinguished on the basis of their factor VIII level alone; 24 out of 34 (71%) could be detected on the basis of the ratio of factor VIII activity to factor VIII related antigen and 25 out of 34 (73%) could be detected if both factor VIII activity and the ratio were taken into account. It is concluded that consideration of both the level of factor VIII activity and the ratio of factor VIII activity to factor VIII‐related antigen is of some value in detecting carriers of haemophilia. The number of carriers detected (73%) in the present study is not as high as that found by other workers.