bluuebunny/crossref_metadata_2025 huggingface dataset:
Hereditary Factor VII and IX Deficiencies in a Large Kindred
Authors: Hall C. A. , London A. R. , Moynihan A. C. , Dodds W. J.
Published: March 2008

Summary.A large kindred with combined deficiencies of factors VII and IX is presented. The deficiencies appeared to be independent and the data were not consistent with a diagnosis of haemophilia BM. The identification of mildly affected family members, including carriers of haemophilia B and heterozygotes for factor‐VII deficiency, was facilitated by comparison with the 95% confidence interval of an age‐ and sex‐matched control population. The bleeding patterns were those of mild to moderate haemophilia B and did not appear to have been modified by the presence of factor‐VII deficiency.
Folate Deficiency in the Alcoholic—its Relationship to Clinical and Haematological Abnormalities, Liver Disease and Folate Stores
Authors: Wu A. , Chanarin I. , Slavin G. , Levi A. J.
Published: March 2008

Summary. Clinical and laboratory observations were made on 84 patients regularly taking more than 80 g of alcohol daily. Macrocytosis was present in 84.5%, but only 13% were anaemic. Twenty‐seven of the 57 bone marrows sampled were abnormal, 20 showing megaloblastic changes, mostly mild in degree. Serum, red cell, and liver folate levels were reduced in 28%, 35% and 31% of patients respectively. Liver folate concentration showed good correlation with serum and red cell folates. The folate deficiency was more severe in those patients, more often female, who had inadequate diets or drank wine and spirits rather than beer. The amount of alcohol consumption and extent of liver damage did not affect folate status. The findings suggest that folate deficiency is common among alcoholics in this country. More frequently, however, patients had macrocytosis, sometimes with megaloblastosis, in the absence of folate deficiency emphasizing the direct toxic effect of alcohol on the developing erythroblast.
Interaction of Thrombin with Human Platelets
Authors: Ganguly P.
Published: March 2008

Summary The first step in thrombin‐induced aggregation of blood platelets is binding of thrombin to specific receptors on the platelet membrane. Elucidation of the nature of this receptor in human platelets was attempted using radioactively labelled thrombin. In disc gel electrophoresis an extract of thrombin‐treated platelets showed one peak of radioactivity near the origin. Gel filtration of the platelet extract through Sephadex G‐200 showed mainly one protein peak at the void volume which contained radioactivity. After column fractionation the final isolate reacted with antiserum to thrombosthenin but did not react with antiserum to serum, fibrinogen or soluble platelet proteins. Gel electrophoresis of the reduced isolate in the presence of sodium dodecyl sulphate showed a pattern similar to thrombosthenin. To explore the possibility that thrombosthenin might be the receptor of thrombin, attempts were made to complex the receptor sites with thrombosthenin antibody or its univalent fragment. It was observed that complexing these receptors potentiates, rather than inhibits, platelet aggregation by thrombin or by adenosine diphosphate. Univalent fragment of antibody to albumin failed to cause this potentiation. Thus, blocking of the thrombosthenin sites is necessary for sensitization of platelets.
Blood Leucocyte Enzymes: III. DIURNAL RHYTHM OF ACTIVITY IN ISOLATED LYMPHOCYTES OF NORMAL SUBJECTS AND CHRONIC LYMPHATIC LEUKAEMIA PATIENTS
Authors: Ramot Bracha , BROK‐SIMONI Frida , Chweidan Emma , Ashkenazi Yisrael E.
Published: March 2008

SUMMARY. The activities of glucose‐6‐phosphate dehydrogenase (D‐glucose‐6‐phosphate: NADP oxidoreductase, G6PD), 6 phosphate glucono dehydrogenase (6 phospho‐D‐gluconate: NADP oxido reductase, 6PGD) lactate dehydrogenase (D‐lactate: NAD oxidoreductase, LDH), glutamate oxaloacetate transaminase (L‐aspartate: 2‐oxo‐glutarate aminotransferase, GOT) and hexokinase(ATP: D‐hexo‐6‐phosphotrans‐ferase, Hx) were measured over 24 h in isolated lymphocytes of normal subjects and in white cells of patients with chronic lymphatic leukaemia (CLL). The activity patterns of all enzymes in the normal lymphocytes were similar. A computed pattern of all the results exhibited a circadian rhythm of activity with the highest level at 16.00 hours. The oscillations in the activities of the same enzymes in the CLL cells differed among the patients, although all the enzymes of the same individual showed a similar diurnal rhythmic pattern. All peaks in this group appeared between 20.00 and 08.00 hours. The possible importance of these observations in setting up therapeutic schedules was raised.
Christmas Disease (Haemophilia B) in a Girl with Deletion of the Short Arm of One X‐Chromosome (Functional Turner Syndrome)
Authors: Spinelli A. , Schmid W. , Straub P. W.
Published: March 2008

SUMMARY

A I‐year‐old girl with severe Christmas disease and a factor IX content less than 1% of normal is described. The family history was negative and coagulation studies on her relatives were normal. Genetic investigation showed an XXp‐karyotype with deletion of the short arm of one X‐chromosome, a cytogenetic variant of Turner syndrome. The transmission pathway of the haemophilia gene is discussed.
Depressed Phagocytic Function Exhibited by Polymorphonuclear Leucocytes from Chronically Iron Deficient Rabbits
Authors: Likhite Vilas , Rodvien Robert , Crosby William H.
Published: March 2008

SUMMARY. The production of chronic iron deficiency in rabbits was associated with impaired phagocytosis of opsonized Staphylococcus aureus by their polymorphonuclear leucocytes. These cells had a reduced ability to ingest the bacteria and the rate of ingestion could not be stimulated by autologous serum leucophilic γ‐globulin.
Fragmentation Haemolysis in Patients with Severe Diabetic Angiopathy
Authors: Brunning R. D. , Jacob H. S. , Brenckman W. D. , Jimenez‐pasquau F. , Goetz F. C.
Published: March 2008

Haemolytic anaemia associated with prominent red cell fragmentation is described in seven patients with long‐standing diabetes mellitus. A common feature in the patients was severe microangiopathy as detected by retinal examination and microscopic examination of the kidneys. Renal or pancreatic islet malfunction per se is not involved in the haemolytic syndrome, since red cell abnormalities persisted in one patient for over a year following successful renal and pancreatic transplantation—this, despite the maintenance of normal renal and carbohydrate homeostasis. The kinetics of fragmentation was studied by transfusing normal type O cells into this type A patient. With reisolation of these cells by the Ashby‐technique, rapid and progressive red cell fragmentation was demonstrated by: (a) membrane lipid loss; (b) osmotic fragility increase; and (c) increase in mean cell haemoglobin concentration. These studies indicate that a red‐cell‐fragmentation haemolytic anaemia may occur in long‐standing diabetes mellitus, related to the angiopathy of this disease and not to insulin deficiency or renal malfunction.
Carbon Monoxide Production in Patients with Breast Carcinoma
Authors: Cavallin‐Starhl Eva , Mercke C. , Lundh B.
Published: March 2008

Total haem catabolism has been studied through measurement of endogenous production of carbon monoxide (V co) in 19 patients treated for breast carcinoma. The subjects were divided into three groups. Group A included six patients with haemoglobin (Hb) concentration greater than 11.5 g/dl and considered free from disease. Group B consisted of seven patients with distant metastases and Hb concentration greater than 11.5 g/dl and group C of six patients with distant metastases and anaemia (Hb concentration less than 11.5 g/dl). V co in group A was 10.3 ± 3.7 (mean±1 SD) and in group B 9.0±2.5 μmol/mmol total body haem (TBH)/d. These values are not different from our normal values of 10.8 ± 2.8 μmol/mmol TBH/d. In group C V co was 21.1 ± 3.1 (an increase of 100%).

V co was compared to daily catabolism of circulating red cell haemoglobin haem (V haem‐c) in the V co/V haem‐c quotient. V haem‐c was calculated from total circulating red cell haemoglobin haem (TBHb‐c) and red cell survival. In group A and group B this quotient was 1.3 ± 0.6 and 1.1 ± 0.2, respectively, and in group C was 2.5 ± 0.9. The difference between group A and B on one side and group C on the other side was significant (P<0.001). The ‘extra’ CO produced in patients with anaemia and disseminated disease (group C) was thought to originate from increased turnover of bone marrow haem, reflecting considerable ineffective erythropoiesis with destruction of haemoglobinized immature red cells. The results confirm earlier findings of a high V co/V haem‐c quotients in patients with anaemia secondary to Hodgkin's disease.
Role of Vitamin B12 in Folate Coenzyme Synthesis
Authors: Perry Janet , Lumb M. , Laundy M. , Reynolds E. H. , CHANARIN I.
Published: March 2008

Normal red cells in man were found to contain predominantly folate pentaglutamates with smaller amounts of tetra‐ and hexapolyglutamates. There was no change in the type of polyglutamate present in red cells from patients with vitamin B12 deficiency and primary folate deficiency.

In contrast to the fall in red cell polyglutamate concentration in vitamin B12 deficiency, there was a marked fall in short‐chain folates in early folate deficiency (treated non‐anaemic epileptics) and a fall in both short chain and long chain polyglutamates in patients with severe folate deficiency and megaloblastic anaemia. These differences in folate distribution within cells exclude a primary failure to transport methylfolate into cells as the lesion in vitamin B12 deficiency.

The failure of folate polyglutamate synthesis in vitamin B12 deficiency arises either from a failure to provide the proper substrate for polyglutamate synthesis or to a direct requirement for vitamin B12 for polyglutamate synthesis.
Variable Response of Bone Marrow to Feeding DL‐5‐Formyltetrahydrofolate in Pernicious Anaemia
Authors: Cooper B. A. , Abe T.
Published: March 2008

It has been suggested that the megaloblastic anaemia in pernicious anaemia is due to inadequate intracellular concentration of monoglutamyl folates other than methyltetrahydrofolate caused by diminished conversion of methyltetrahydrofolate to tetrahydrofolate (methylfolate trap). To test this, we have increased the concentration of methyltetrahydrofolate in the plasma of six patients with pernicious anaemia by feeding DL‐5‐formyltetrahydrofolate. The effect of therapy on bone marrow morphology and routine haematologic parameters was measured. Of two patients receiving 800 μ/d of DL‐5‐formyltetrahydrofolate, one had a significant response; of four receiving 6 mg/d, one converted erythroid maturation to normoblastic, and in two others some improvement was noted in levels of neutrophils, platelets or reticulocytes although marrow morphology remained megaloblastic. Response did not correlate with the degree of elevation of plasma folate. In patients receiving this therapy, slight increase of methylcobalamin in plasma may have occurred (P<0.05).

These observations support ineffective utilization of methyltetrahydrofolate as the major cause of megaloblastic anaemia in pernicious anaemia, but indicate that the degree and location of block varied in different patients, and in different precursor cells of a single patient.
Assay of Thalassaemic Messenger RNA in the Wheat Germ System
Authors: Pritchard Jon , Longley Janice , Clegg J. B. , Weatherall D. J.
Published: March 2008

Messenger RNA (mRNA) has been prepared from reticulocytes obtained from patients with different types of thalassaemia and assayed in the wheat germ system. Since normal human reticulocyte mRNA directs the synthesis of equal numbers of α‐ and β‐globin chains in this system it offers a rapid and simple technique for assaying mRNA in the thalassaemic disorders. In mRNA from β+ thalassaemics the deficiency of β‐globin synthesis mirrored that observed in intact reticulocytes while that prepared from patients with haemoglobin H disease gave α/β globin chain production ratios which showed consistently greater imbalance than was found in reticulocytes. Messenger RNA prepared from haemoglobin E‐β0 thalassaemics from Thailand directed no detectable β‐chain synthesis while that prepared from a β0 thalassaemic from Ferrara synthesized a fraction with the chromatographic characteristics of β‐globin chains.
Growth of Mouse Yolk Sac Cells Cultured in Vivo
Authors: Weinberg Sheila R. , Stohlman Frederick
Published: March 2008

The proliferation and differentiation of yolk sac cells from 10 1/2‐day‐old mouse embryos were studied in diffusion chambers implanted into syngeneic and allogeneic hosts. The most striking observation was the appearance, proliferation and predominance of immature and mature plasma cells. The data suggested that the differentiation into plasma cells and the rate of growth of yolk sac cells cultured in vivo may be dependent on the genetics of the strain of mouse and host.

This demonstration of differentiation of plasma cells from yolk sac cells cultured in vivo adds further information to the origin and ontogeny of potentially immunocompetent cells.
Lack of Association between the HL‐A System and Pernicious Anaemia
Authors: Eastmond C. J. , Woodrow J. C.
Published: March 2008

Summary.

Fifty‐two patients with pernicious anaemia have been typed for the histocompatibility antigens. No association was found with any particular antigen.
The Relationship between Total Red Cell Volume, Plasma Volume and Venous Haematocrit
Authors: Bentley S. A. , Lewis S. M.
Published: March 2008

Summary. Total red cell volume (TRCV) and plasma volume (PV) have been measured in 130 cases including 65 polycythaemic patients and 65 patients with a wide variety of disorders. Patients with gross splenomegaly were excluded from the study. The regression of TRCV on venous haematocrit (VHct) was found to be curvilinear, a single exponential function providing a good approximation (r= 0.92, P < 0.001). No significant difference was found between the mean PVs of the polycythaemic and control groups (40.97 and 42.94 ml/kg respectively) although a slight but highly significant negative correlation was observed between PV and VHct (r= 0.47, P < 0.001). This was most marked for patients with VHcts below 0.30, for whom a separate plot yielded a correlation coefficient of 0.75. Total blood volume (TBV) and VHct were found to be positively correlated (r= 0.57, P < 0.001) as would be expected from the TRCV and PV data. The significance of these findings is discussed.
Quantitative Determination of Factor‐VIII Protein by Two‐Stage Gel Electrophoresis
Authors: Weinstein Mark J. , Devkin Daniel , Davie Earl W.
Published: March 2008

Summary. A new method for the quantification of factor‐VIII protein in plasma is described which utilizes only commercially available equipment and material. The procedure involves separation of factor VIII from other plasma proteins by a two‐stage sodium dodecyl sulphate gel electrophoretic technique and quantification of the protein by scanning densitometry. The plasma from normal individuals, haemophiliacs, obligate carriers of haemophilia and patients with von Willebrand's disease have been examined by this technique. In general, the data support the earlier findings obtained by quantitative immunoelectrophoresis. In addition, some abnormalities not detected by immunoelectrophoresis are observed by the gel electrophoresis technique.
Thymidine Kinase in Megaloblastic Anaemia
Authors: Hooton J. W. L. , Hoffbrand A. V.
Published: March 2008

Summary. Thymidine kinase has been measured in phytohaemagglutinin (PHA)‐stimulated lymphocytes from 13 normal subjects and eight patients with megaloblastic anaemia. The levels in normal subjects ranged from 0.20 to 2.10 units/mg protein (mean 0.903 units/mg protein) and in megaloblastic anaemia from 2.99 to 9.97 units/mg protein (mean 5.76 units/mg protein). All the patients showed raised levels of the enzyme which were partly but not completely reduced to normal by addition of folic acid in vitro. Vitamin B12in vitro had a lowering effect in the five vitamin‐B12‐deficient patients and two patients with combined deficiencies but not in one‘pure’folate‐deficient patient.

Thymidine kinase activity was highest in the cells of the least anaemic patients, suggesting that the degree of anaemia in megaloblastic anaemia may be determined in part by the ability of the cells to utilize thymidine by the 'salvage’pathway when the de novo pathway of thymidylate synthesis is failing.

The rise in thymidine kinase activity in megaloblastic anaemia is presumably due to induction of the enzyme. Addition of methotrexate or 5‐fluorouracil, drugs known to inhibit de novo thymidylate synthesis, caused an increase in thymidine kinase activity in normal PHA‐stimulated lymphocytes after 24 h (but not after 1 h) which could be completely blocked by addition of puromycin.

Thymidine mono‐ and di‐phosphate kinases were also measured in normal PHA‐stimulated lymphocytes. The activities were substantially higher than that of thymidine kinase and their activities were unaffected by methotrexate addition.
Clinical Experience with Transfusion of Cryopreserved Platelets
Authors: SCHIFFER CHARLES A. , AISNER JOSEPH , WIERNIK PETER H.
Published: March 2008

Summary. Multiple units of platelet concentrate obtained by plateletpheresis of normal, ‘random’or HL‐A matched donors were pooled and frozen in polyolefin bags using 5% dimethylsulphoxide (DMSO) as a cryoprotective agent and a controlled freezing rate of 1°/min. The platelets were stored at approximately — 120° C for as long as 201 days, thawed rapidly at 37°, washed once and resuspended in ACD plasma prior to transfusion. Two different final concentrations of platelets (˜ 2.7 and 9.0 × 1012/1.) were studied. Twenty‐three thrombocytopenic patients have received a total of 40 frozen platelet transfusions. The mean freeze‐thaw loss was 21% and was similar for both platelet concentrations. All transfusions were well tolerated and there were no side effects attributable to the small amounts of DMSO infused. Increments in platelet counts I h after transfusion ranged from 0 to 102 × 109/1. with an overall mean corrected increase in evaluable patients of 12 800 (increase × surface area (m2)/number of platelets transfused × 1011). Corrected increases tended to be greater with the low concentration of platelets. Overall, the increase in count for the frozen platelet transfusions was 65% of the increments obtained with fresh platelet transfusions administered within I week of the frozen platelets. Bleeding times were partially corrected after four out of six transfusions with post‐transfusion counts greater than 50 × 109/1., and active haemorrhage was controlled in some patients by frozen platelet transfusions. These results indicate that pooled platelets can be frozen, thawed and transfused with reasonable efficiency. The frozen platelets can circulate and function haemostatically and may eventually play an important role in supportive care.
Adaptation of Marrow Sinus Wall to Fluctuation in the Rate of Cell Delivery: Studies in Rabbits after Blood‐letting
Authors: Tavassoli Mehdi
Published: March 2008

The extent of marrow sinus wall coverage by perisinal adventitial cells was measured before and after removing 25% of the calculated blood volume in rabbits. A marked reduction in the area covered by adventitial cells was recorded coinciding with the early reticulocyte response to phlebotomy. In control animals, only scattered microfilaments were occasionally observed in the cytoplasmic process of adventitial cells. After phlebotomy, these filaments were more frequently observed and appeared as band‐like structures, raising the possibility of an active role for perisinal adventitial cells in response to fluctuations in the magnitude of cell traffic.

Perisinal adventitial cells may, therefore, translate the body's demand for cell delivery by regulating the rate of transmural cell migration from the marrow. Such an adaptive mechanism may depend on the incompleteness of the adventitial layer of the sinus wall and the absence of endothelial‐adventitial cell junctions, permitting separation of the two layers of the wall, so that the reticulocyte can gain access to more endothelial surface and the pores.
Myosin in Cultured Human Endothelial Cells
Authors: Moore Anne , Jafee Eric A. , Becker Carl G. , Nachman Ralph L.
Published: March 2008

Myosin was isolated from cultured human endothelial cells by extraction with 0.6 M KCl and chromatography on Sepharose 4B. The extracted endothelial cell protein was identified as myosin by the characteristic ATPase profile, that is, the ATPase was activated by Ca2+ and EDTA and inhibited by Mg2+. On sodium dodecyl sulphate polyacrylamide gel electrophoresis, the endothelial cell myosin heavy chain migrated with a molecular weight of 200 000 as did rabbit uterine and human platelet myosin heavy chains. A crude preparation of the endothelial cell myosin reacted immunologically with an antiserum to platelet myosin, a smooth muscle type of myosin. In indirect immunofluorescence studies, antiserum to the purified endothelial cell myosin stained cultured endothelial cells in a fibrillar pattern. The fibrillar pattern was more intense when the endothelial cells were stained with antiserum to platelet myosin. The presence of myosin in the endothelial cell provides a basis for the contractility of these cells. This contractile property may plan an important role in the physiologic function of these cells.
Membrane Changes in Human Platelets Induced by Lipopolysaccharide Endotoxin
Authors: Hawiger J. , Hawiger A. , Steckley S. , Timmons S. , Cheng C.
Published: March 2008

The unexplained occurrence of thrombocytopenia in cases of Gramnegative sepsis in man led us, in the light of animal experiments indicating the blood platelet as the target cell for endotoxin, to examine the effect of Salmonella enteritidis lipopolysaccharide B on human platelets. Human platelets were separated from a coat of plasma proteins by Sepharose 2B filtration or by a combined procedure of albumin gradient and Sepharose 2B filtration. The action of endotoxin on human platelets resulted in membrane changes manifested by dose‐dependent release of [3H]serotonin and adenine nucleotides. Cytoplasmic marker, lactic dehydrogenase, and lysosomal marker, beta glucuronidase, were retained indicating that the release reaction was selective. Release of [3H]serotonin was specific for endotoxin since other particulates, zymosan and erythrocyte stroma, were without effect. Endotoxin, added to gel‐filtered human platelets, induced a significant evolution of platelet factor 3 procoagulant activity. Preincubation of endotoxin with a membrane‐rich homogenate of human platelets inhibited its labilizing effect on human platelets thus suggesting an interaction between endotoxin and the platelet membrane itself. Other plausible factors in this interaction (fibrinogen, adenine nucleotides, thrombin, sialic acid residues, and IgG) were eliminated on the basis of a series of control experiments. From the negligible effect of aspirin and indomethacin, we may infer that the interaction of endotoxin with platelets does not depend on the platelet prostaglandin synthesis pathway.

The direct interaction of endotoxin with the human platelet membrane comprises a new mechanism which may help to clarify the pathogenesis of vascular and haemostatic disorders accompanying bloodstream infections due to Gram‐negative bacteria.
The Early Detection of Remission in Acute Myelogenous Leukaemia by in Vitro Cultures
Authors: Spitzer G. , Dicke K. A. , Mccredie K. B. , Barlogie B.
Published: March 2008

Twenty‐eight cases of acute myeloid leukaemia without normal myeloid colony growth in vitro were serially cultured by an in vitro agar culture method during remission induction therapy. Colony formation frequently returned before morphological evidence of remission. Without early return of colony formation drug induced aplasia was prolonged and fatal. Analysis of the pattern of return of in vitro colony forming cells may be of value in designing the chemotherapy schedule.
Clinical Course and Survival after Elective Splenectomy in 19 Patients with Primary Myelofibrosis
Authors: Mulder H. , Steenbergen J. , Haanen C.
Published: March 2008

Nineteen patients with primary myelofibrosis and myeloid metaplasia (MMM), who fulfilled well‐defined criteria, underwent elective splenectomy as soon as the diagnosis was confirmed. Nine patients developed postoperative complications such as intra‐abdominal bleeding (three), rupture of the inferior vena cava (one), ascites (two), Australia antigen‐positive hepatitis (three), mesenteric artery thrombosis (one) and pneumonia (one). One patient died within a month of the operation due to secondary intra‐abdominal infection. The mean age of the patients at splenectomy was 56 years and the mean duration of their disease 2.4 years. The median actuarial survival after operation was 51 months. Although the series of patients is small, it seems that splenectomy did not have an adverse effect on life expectancy. The haematological status and the quality of life improved after splenectomy in 17 of 19 patients. The results warrant a further trial with elective splenectomy in an early stage of MMM.
Granulocytic Progenitor Cells in Aplastic Anaemia
Authors: Kern P. , Heimpel H. , Heit W. , Kubanek B.
Published: March 2008

The characteristics and the concentration of granulopoietic colony forming cells (CFC) were examined in 22 patients with aplastic anaemia at different stages of their disease. Additionally the ability of the patients’peripheral leucocytes to elaborate factors necessary for colony stimulation in vitro (CSA) was studied. The ability of the patients’cells to generate CSA was shown to be unaffected. However, the incidence of CFC within the marrow and peripheral blood suspensions was significantly reduced in all patients. The results suggest a reduced compartment size of CFC even in those patients who have recovered from aplastic anaemia. This may indicate that the disturbances in the preceding compartments of the haemopoietic cell renewal system still persist after recovery from the acute bone marrow failure.
The Effect of Anticonvulsant Drugs on Thymidine and Deoxyribosenucleic Acid Synthesis by Human Marrow Cells
Authors: Taguchi H. , Laundy M. , Reid C. , Reynolds E. H. , Chanarin I.
Published: March 2008

An abnormal deoxyuridine suppression test was found in treated epileptic patients that did not correlate with other evidence of abnormal folate metabolism. Diphenylhydantoin at a level of 100 μg/ml interfered with the incorporation of [3H]thymidine into DNA. It is suggested that anticonvulsants may exert their effect at a stage of DNA synthesis beyond that at which folate coenzymes operate. Folate deficiency may then arise as a result of death of cells in vivo causing an increased folate requirement.
The Duffy Blood Group Determinants: Their Role in the Susceptibility of Human and Animal Erythrocytes toPlasmodium knowlesiMalaria
Authors: Mason Steven J. , Miller Louis H. , Shiroishi Tsugiye , Dvorak James A. , Mcginniss Mary H.
Published: March 2008

Duffy blood group negative erythrocytes from blacks are refractory to invasion byPlasmodium knowlesimerozoitesin vitro, and blacks with this genotype are resistant to infection byP. vivax in vivo. In order to evaluate in a direct manner the role of Duffy blood group determinants in invasion byP. knowlesimerozoites, we studied erythrocytes from three rare non‐black Duffy negative individuals, Fy(a–b–), in whom the Duffy negative phenotype probably represents a mutation and not the introduction of the blackFygene. These cells were resistant to invasion byP. knowlesi in vitroindicating that resistance to invasion is mediated by theFyFygenotype and not another closely linked factor. The erythrocyte receptors for invasion, however, may not be the Fyaor FybDuffy antigens themselves, or at least not restricted to these determinants, since refractory Duffy negative human erythrocytes were invaded after treatment with trypsin or neuraminidase although these enzyme‐treated cells still lacked Fyaand Fybdeterminants. Furthermore, new world monkey erythrocytes and chymotrypsinized chimpanzee and kra monkey erythrocytes were invaded, although there was no serologic evidence of Fyaor Fybdeterminants on these cells.
Intraerythrocyte pH, pCO2 and the Hexose Monophosphate Shunt
Authors: Warth James A. , Desforges Jane F. , Stolberg Sherry
Published: March 2008

Summary. We have documented a rise in pCO2 when erythrocytes are haemolysed by freeze‐thaw using solid CO2 and methanol. This is partially corrected by preventing leakage of CO2 into the system. The remaining increment is partially explained by stimulation of the hexose monophosphate shunt when erythrocytes are haemolysed by this technique.
Procoagulant Specificity of Factor VIII Inhibitor
Authors: Yang Henry C. , Kuzur Michel
Published: March 2008

Summary. Nine haemophilia A patients with an inhibitor to factor VIII procoagulant and eight without an inhibitor were studied for the presence of an inhibitor to von Willebrand factor (vWf) in a quantitative ristocetin‐induced platelet aggregation system. The mean vWf, factor VIII related antigen (FVIII Ag) and vWf:FVIII Ag ratio were not significantly different in the two groups (P > 0.6). The inhibitor plasmas did not reduce the vWf level in normal plasma after a 2 h incubation. The factor VIII inhibitor is highly specific for the procoagulant function of the factor VIII complex.
Inhibition of Platelet Function with 2,3‐Dihydroxybenzoic Acid
Authors: Greenberg M. , Grady R. W. , Peterson C. M.
Published: March 2008

Summary. 2,3‐Dihydroxybenzoic acid (2,3‐DHB) inhibits the second wave of platelet aggregation, release of serotonin, and malonaldehyde production. The effect is concentration dependent and reversible in vitro and in vivo. 50% inhibition of platelet aggregation induced in vitro with 70 μM adrenaline was obtained with 1.5 mM 2,3‐DHB. Malonaldehyde production was inhibited by 50% with 0.4 mM 2,3‐DHB. Serotonin release was 50% inhibited by 50% with 0.08 mM 2,3‐DHB. Neither desferrioxamine nor various benzoic acid derivatives with iron‐chelating properties showed the effect. Only benzoic acid derivatives with the potential to terminate free radical reactions through the formation of an ortho‐ or paraquinone structure inhibit the second wave of platelet aggregation. These studies support the concept that the second wave of platelet aggregation is mediated through free radical reactions.
Reversible C3 Hypocomplementaemia in Megaloblastic Anaemia due to Vitamin B12 Deficiency
Authors: Horton M. A. , Burman J. F.
Published: March 2008

Summary. Serum C3 and C4 levels have been determined in patients with Addisonian pernicious anaemia (PA) and megaloblastic anaemia due to vitamin B12 deficiency from other causes, before and after treatment, in order to study the interaction between vitamin B12 deficiency and Complement and the role of complement in the pathogenesis of the gastric lesion of PA. C3 levels are significantly reduced in vitamin B12 deficiency and return to normal on treatment; C3 levels correlate with the degree of anaemia but not with serum vitamin B12 levels at diagnosis. C4 levels are normal. These observations suggest that the observed C3 hypocomplementaenlia is not a consequence of immune mechanisms, but may be due to altered synthesis of C3 complement component.
Inhibition of Leukaemia Blast Cell Motility as a Test for Specific Antibody in Acute Adult Myelogenous Leukaemia
Authors: Katz J. , Currie G. A. , Oliver R. T. D.
Published: March 2008

Summary. Migration studies of acute myelogenous leukaemia blast cells in autologous diagnostic and remission sera from a series of I I patients have demonstrated two factors.

A factor of less than 70 000 molecular weight appears to potentiate blast cell migration whereas the other of molecular weights 100 000–250 000 inhibits blast cell migration relative to a standard non‐immune AB serum. The low molecular weight fraction was found in the serum of patients prior to relapse while the greater molecular weight fraction was possibly an IgG antibody that increased in concentration with length of remission. The inhibitory factor was found in patients following immunotherapy and in one patient who received chemotherapy alone.

An inhibitory factor was also consistently found in patients in overt clinical relapse following on remission induction and maintenance therapy.
The Biosynthesis and Characterization of Unreleased IgM in a Case of CLL
Authors: Smith J. L. , Gordon J. , Newell D. G. , Whisson M.
Published: March 2008

Intracellular IgM K is described in a case of CLL. The intracellular immunoglobulin occurred as amorphous spherical globules enclosed by rough endoplastic reticulum in the cytoplasm of the neoplastic lymphocytes. No abnormal IgM paraprotein could be found in the serum nor was there any Bence Jones protein detectable in concentrated urine. Biosynthetic studies confirmed the cells were able to synthesize IgM K immunoglobulin. On sizing gel analysis the intracellular IgM occurred as 7S monomer. The biosynthesis studies did not indicate secretion of IgM and was consistent with the serological findings. However, cells in culture secreted K light chain into the supernatant medium. It appears in this case that the secretory block is operating against heavy chain and not against free light chain. Some explanations for these findings are discussed.
Comparison of Heparin and a Semi‐synthetic Heparin Analogue, A73025
Authors: Michalski R. , Lane D. A. , Kakkar V. V.
Published: March 2008

A comparison has been made of some effects of a semi‐synthetic heparin analogue, A73025, and heparin upon platelet function. In several of the in vitro tests performed, such as their potentiating effects on ADP and adrenaline induced aggregation and their effects on the aggregation of washed platelets by activated factor X, heparin proved to be more potent than A73025. Following intravenous injection of twice the quantity of A73025, an equivalent anti‐factor Xa activity was obtained, in agreement with our previous studies. However, it was found that PRP containing heparin and A73025 with comparable anti‐Factor Xa activity responded differently to the addition of thrombin, as A73025 barely inhibited thrombin induced aggregation. Similarly, A73025 had little effect on the dilute thrombin clotting time of plasma, following intravenous injection. Heparin and A73025 were neutralized to approximately the same degree by a crude PF4 preparation.
Hairy Cell Leukaemia: Evidence for the Existence of a Spectrum of Functional Characteristics
Authors: Golomb Harvey M. , Vardiman James , Sweet Donald L. , Simon Deberah , Variakojis Daina
Published: March 2008

Functional markers of malignant cells from 14 patients with hairy cell leukaemia were evaluated during a 10 month period to assess the possible existence of sub‐types of the disease. Surface immunoglobulin on the hairy cells from the peripheral blood was studied initially, and again either after trypsinization and culture or after culture alone. Resynthesis of surface immunoglobulin occurred in all 12 patients studied; in four it was clearly monoclonal. Hairy cells from 11 patients were evaluated for their capacity to phagocytose zymosan; in five patients, 25% or more of the hairy cells demonstrated phagocytosis; in five others, less than 10%. One patient had only 13% zymosan phagocytosis initially, but when the study was repeated at a later date, 31% of the hairy cells phagocytosed. There was no phagocytosis of zymosan by malignant cells in 12 patients with a variety of other lymphoproliferative diseases. The percentage of E‐rosettes was correlated inversely with the percentage of circulating hairy cells. EAC‐rosettes were very low in three patients tested, all of whom had a high percentage of hairy cells. The number of tartrate‐resistant acid‐phosphatase‐positive cells varied from patient to patient, and within the same patient at different times. Platelet function was abnormal in six of 11 patients tested, who had a decreased, but not absent, epinephrine response. The significance of these findings in regard to the origin of the hairy cells in hairy cell leukaemia and in regard to the variable clinical course remains to be established.
The Identification of the Products of Folate Catabolism in the Rat
Authors: Murphy Mary , Boyle Peter H. , Weir Donald G. , Scott John M.
Published: March 2008

Further analysis of rat urine containing labelled catabolites derived from administered 3H‐ or 14C‐labelled folic acid is described. The results support previously described studies, and show that folate catabolism in the rat takes place by cleavage of the C9‐N10 bond, and not by excretion of inactive forms of the vitamin which still contain the intact folate skeleton.
Evidence that ‘Activated’ Prothrombin Concentrates Enhance Platelet Coagulant Activity
Authors: Vermylen J. , Schetz J. , Sermeraro N. , Mertens F. , Verstraete M.
Published: March 2008

The infusion of an ‘activated’ prothrombin concentrate in five haemophilic patients with factor VIII inhibitors and two haemophilic patients without inhibitors resulted in all cases in a shortening of the whole blood clotting time and improvement of the thromboelastographic indices of blood coagnlation. In only three of the patients was a definite shortening of the activated partial thromboplastin time observed. In all seven patients an enhancement of the platelet coagulant activity was found using a recently described method. Similarly, platelets isolated from PRP to which the ‘activated’ prothrombin concentrate was added at a concentration approaching the maximal concentration achieved following in vivo infusion, showed an increase in platelet coagulant activity. This enhanced platelet coagulant activity could neither be explained by an increase of the factor V level or platelet factor 3 availability on the platelets nor by adsorption of an active clotting enzyme present in ‘activated’ prothrombin concentrate onto the platelet surface. These findings indicate that ‘activated’ prothrombin concentrate enhances platelet coagulant activity by increasing the activity of the platelet factor X activator recently described. This mechanism may explain how ‘activated’ prothrombin concentrates by‐pass factor VIII or IX inhibitors.
Fetal Haemoglobin in Early Malignant Osteopetrosis
Authors: Schilirò G. , Musumeci S. , Pizzarelli G. , Russo A. , Marinucci M. , Tentori L. , Russo G.
Published: March 2008

The characteristics of the fetal haemoglobin (Hb F) in two children with osteopetrosis and high levels of Hb F have been studied. The structural analysis of the γ chains demonstrated a fetal Gγ/Aγ ratio. Hb F was distributed inside only 30% of the peripheral red blood cells. In vitro globin chain synthesis studies showed that there was balanced globin chain production, despite the increased level of Hb F.
Acute Myeloid Leukaemia with Monosomy‐7 Follows Acute Lymphoblastic Leukaemia
Authors: Walker Lorna M. Secker , Sandler R. M.
Published: March 2008

A case report of an 8‐year‐old girl who developed acute myeloid leukaemia (AML) following the successful treatment of acute lymphoblastic leukaemia (ALL) is presented. Haematological and cytochemical evidence for the two types of leukaemia is given. This is reinforced by the cytogenetic findings. After 2 years' treatment for ALL the patient became pancytopenic and marrow depression continued even when all treatment was stopped. Marrow cells monosomic for chromosome‐7 (45 XX ‐7) were first seen 2 months before the onset of progressive pancytopenia when blood parameters were normal. Both during the pre‐leukaemic and frankly leukaemic stages of the myeloid neoplasm, cells with monosomy‐7 constituted the dominant cell line in the marrow. This suggests that in this case the preceding pancytopenia was part of the malignant change and that the chromosomal change was one of the earliest events in the neoplastic process. Other reports of AML following cytotoxic therapy for treatment of malignant diseases as well as for non‐malignant conditions are briefly reviewed and the neoplastic mechanisms under these conditions are discussed. There is some evidence that in the case reported here genetic factors may have been at least as important as environmental conditions in triggering off the second malignant change.
Abnormal Platelet Aggregation in Severe Combined Immunodeficiency Disease with Adenosine Deaminase Deficiency
Authors: Schwartz A. L. , Polmar S. H. , Stern R. C. , Cowan D. H.
Published: March 2008

The platelets from a boy with adenosine deaminase deficiency‐severe combined immunodeficiency disease (ADA‐SCID) showed markedly subnormal aggregation in response to collagen and ADP. In contrast with normal platelets, ATP, AMP and adenosine had little effect in inhibiting ADP‐induced aggregation of ADA‐SCID platelets. These observations suggest that altered adenosine metabolism exists in ADA‐SCID platelets.
Abnormal Membrane Lipid‐Related Properties during Maturation of Reticulocytes from Severely Anaemic Rats as Measured by Partition in Two‐Polymer Aqueous Phases
Authors: Walter Harry , Krob Eugene J. , Ascher Galli S.
Published: March 2008

Aqueous solutions of dextran and of polyethylene glycol when mixed give rise to immiscible, liquid two‐phase systems. Such systems are suitable for separating cells by partition and for tracing subtle changes in the cells’membrane surface properties as a function of differentiation, maturation and age. By appropriate manipulation of polymer concentration and ionic composition and concentration one can select certain membrane properties (e.g. charge‐associated, lipid‐related) that will determine the cells’partition coefficient (i.e. the cells’relative affinity for the top or bottom phase or adsorption to the interface). Combining radioisotopic labelling and cell countercurrent distribution techniques we have examined the partition behaviour of reticulocytes from severely anaemic rats (made so through phenylhydrazine‐injection) in two‐polymer phase systems which reflect membrane lipid‐related properties. It was found that such stress reticulocytes are abnormal with respect to their membrane lipid which does not produce the changes in partition coefficients observed with normal reticulocytes during maturation. The mature erythrocytes derived from such stress reticulocytes also have abnormal lipid‐related membrane properties. Together with our earlier results it is clear that red blood cells produced in severe anaemia have and retain abnormal charge‐associated and lipid‐related membrane surface properties during their life‐span and do not undergo the membrane surface changes associated with normal maturation and ageing as discerned by partition in two‐polymer aqueous phase systems.
An Immunoradiometric Assay for Factor III (Tissue Thromboplastin)
Authors: Bjørklid Eirik , Giercksky Karl E. , Prydz Hans
Published: March 2008

A solid‐phase immunoradiometric assay for tissue thromboplastin (factor III) has been established based on its displacing effect on the binding of 125I‐labelled factor III‐antibodies to polyvinyl tubes coated with the purified protein component of factor III (apoprotein III). By this method circulating tissue thromboplastin can be detected in experimental animals receiving infusions of crude or purified tissue thromboplastin and in patients undergoing major orthopaedic surgery.
Decrease of Alpha‐Hasharon Globin in Beta‐Thalassaemia
Authors: Conconi F. , Alberti R. , Mariuzzi G. M. , Guglielmini C. , Vullo C. , Senno L. del
Published: March 2008

In time course experiments performed in subjects carrying haemoglobin Hasharon and β‐thalassaemia the synthesis of αA‐, αHasharon‐, β‐ and γ‐globin has been determined. The α‐globin molecules synthesized in excess were found to be removed from the red cell cytoplasm (phenomenon characteristic of β‐thalassaemia, described by Bargellesi et al, 1968a); in addition the αHasharon‐globin molecules were removed at a faster rate than normal α‐globin. The preferential removal of the mutant α‐globin explains the reduced level of haemoglobin Hasharon found in subjects carrying the gene for β‐thalassaemia (Alberti et al, 1975).

Reductions below normal levels of other haemoglobin variants occurring in the presence of the counterpart‐globin thalassaemia are probably determined through a similar mechanism.
The Effect of Deoxyuridine, Vitamin B12, Folate and Alcohol on the Uptake of Thymidine and on the Deoxynucleoside Triphosphate Concentrations in Normal and Megaloblastic Cells
Authors: Ganeshaguru K. , Hoffbrand A.V.
Published: March 2008

SUMMARY Deoxyuridine suppression of labelled thymidine uptake tests were performed in the bone marrows of 58 patients with megaloblastic anaemia (haemoglobin less than 10.0 g/dl) and invariably gave values (range ro.3–58.8%) above the range in 16 control marrows (range 1.0–9.0%). Folinic acid corrected the test equally well in either folate or vitamin B12 deficiency, even at concentrations as low as 60 ng/ml. Folic acid also corrected the test equally well in either deficiency but was only effective at concentrations down to 5 μg/ml. Vitamin B12 (100 μug/ml) only corrected the test in vitamin B12 deficiency and 5‐methyltetrahydrofolate only corrected the test in folate deficiency at the concentrations tested between 60 and 1.2 μg/ml.

Among 16 patients with subnormal serum levels of both vitamin B12 and folate, vitamin B12 partially corrected the test in eight, including all five with pernicious anaemia, but had no effect in the other eight.

Despite the clear‐cut results of the dU suppression test, measurement of the deoxythymidine triphosphate (dTTP) concentration in normal and megaloblastic pliytohaemagglutinin stimulated lymphocyte cultures or short‐term bone marrow cultures gave no clear‐cut differences between normal and megaloblastic cells after addition of deoxyuridine nor did the addition of vitamin B12 folic acid or folinic acid either alone or with deoxyuridine produce consistent changes in the dTTP concentration in lymphocytes or bone marrow cells in megaloblastic anaemia.

Alcohol caused a rise in deoxyadenosine triphosphate concentration in normal PHA‐stimulated lymphocytes which was concentration dependent but caused no consistent change in any of the other three deoxynucleoside triphosphate (dNTP) concentrations. Diphenylhydantoin (10‐3 m, 10‐4 m) had no consistent effect on any of the four dNTP concentrations.
Remission Induction in Chronic Granulocytic Leukaemia using Intermittent High‐Dose Busulphan
Authors: Douglas I. D. C. , Wiltshaw E.
Published: March 2008

SUMMARY In a series of 19 patients, the pre‐blastic phase of chronic granulocytic leukaemia was controlled with busulphan given as single doses of 50–100 mg at 2‐weekly intervals. Although there was no significant increase in the incidence of Ph1‐negative cells in the bone marrow, remissions of a better haematological quality were attained more rapidly than with conventional therapy.
Correction of the Bleeding Time in Patients with Storage Pool Deficiency by Infusion of Cryoprecipitate
Authors: Gerritsen Sijbrand W. , Akkerman Jan‐Willem N. , Sixma Jan J.
Published: March 2008

SUMMARY Five patients with Hermansky‐Pudlak syndrome: storage pool deficiency, albinism and ceroid containing bone marrow macrophages and three patients with uncomplicated storage pool deficiency were treated with cryoprecipitate from 16 donors. Within 2 h of transfusion, bleeding times decreased towards a third of initial values. This effect lasted for at least 4 h but had disappeared after 24 h. Six of these eight patients were also treated with an equal volume of human albumin solution. Infusion of albumin had no effect on the bleeding times, The abnormal platelet function tests and biochemical abnormalities (decreased values of platelet total adenosine diphosphate (ADP), adenosine triphosphate (ATP(1) and serotonin) remained unchanged. On four occasions infusion of cryoprecipitate twice daily protected patients with Hermansky‐Pudlak syndrome and storage pool deficiency from bleeding during surgery. The mechanism of action of cryoprecipitate in this clinical situation is obscure.