bluuebunny/crossref_metadata_2025 huggingface dataset:
The Cellular Basis for the Defect in Haemopoiesis in Flexed‐Tailed Mice
Authors: Gregory C. J. , Mcculloch E. A. , Till J. E.
Published: March 2008

Summary. Three assays for erythropoietic progenitor cells have been applied to mice of genotype f/f and to nearly congenic +/+ controls. When f/f mice were tested for their ability to generate transient endogenous erythroid spleen colonies 4–6 days after 800 rads and 10 units of erythropoietin, the numbers of such colonies detected were greatly reduced, although normal numbers of spleen colonies appeared at later times (9–12 days) postirradiation. In contrast, cells capable of erythropoietic colony formation in culture (CFU‐E) were present within the normal range in both f/f spleen and marrow and their sensitivity to erythropoietin in culture was the same as that found previously for CFU‐E in the marrow and spleen of +/+ mice. Transfusion‐induced plethora reduced the number of CFU‐E in marrow to a similar extent in both f/f and +/+ mice; likewise, subsequent administration of 10 units of erythropoietin induced a rapid return in the number of marrow CFU‐E in both genotypes. In the spleen, CFU‐E numbers were approximately three‐fold lower in f/f mice in each group. These results support the view that the 5 day assay for transient endogenous spleen colonies detects cells (TE‐CFU) that are different from both CFU‐E and pluripotent stem cells (CFU‐S), although possibly overlapping to some extent with the immediate progenitors of CFU‐E. The results also indicate that the generation or maturation of TE‐CFU represents a primary site of expression of the f/f defect.
Polymerized Monoclonal IgA in Two Patients with Myelomatosis and Hyperviscosity Syndrome
Authors: Virella G. , Preto R. Valadas , Graça Felicidade
Published: March 2008

Summary. Two cases of multiple myeloma with IgA gammopathy and the syndrome of serum hyperviscosity are reported. A common feature of both patients was the production of large amounts of polymeric IgA (more than 50% of the monoclonal proteins existed as dimers or larger forms). However, similar large amounts of polymeric IgA were present in sera with only slightly raised viscosity, suggesting that factors such as the molecular configuration of the polymers or their sub‐units may play a role in determining serum viscosity.

The association of plasmapheresis and chemotherapy produced remarkable improvements of the symptoms attributable to increased serum viscosity, and 16 months after diagnosis one of the patients has survived relatively free of symptoms. The hyperviscosity syndrome is being diagnosed with increasing frequency in association with IgA multiple myeloma, and should be investigated in all cases with monoclonal proteins exceeding a concentration of 3.0 g/dl.
Auto‐Anti‐Pra: a ‘Second’ Example in a Newborn
Authors: Habibi B. , Cregut R. , Brossard Y. , Veron P. , Salmon C.
Published: March 2008

Summary. A second example of anti‐Pra was recognized in a newborn infant which exhibited several signs of developmental disease. The antibody was complement‐fixing 19S IgM and showed a high thermal range but no detectable haemolytic anaemia was associated. It gave negative reactions with a panel of animal cells as well as with two samples of human En(a‐) cells. The latter, however, could absorb the antibody.
Distribution and Mobility of the A, D and c Antigens on Human Red Cell Membranes: Studies with a Gold‐labelled Antiglobulin Reagent
Authors: Romano E. L. , Stolinski C. , Hughes‐jones N. C.
Published: March 2008

Summary. Studies are presented in which a gold‐labelled anti‐IgG reagent has been used to map the distribution of A, D and c antigen sites on the human red cell membrane. Red cells were combined with IgG antibodies; ghosts were produced which were then labelled with gold‐anti‐IgG. D antigen sites were found to be single entities dispersed on the red cell membrane of lysed but otherwise untreated Rh positive cells. Following papain treatment prior to lysis, a clustered distribution was observed. Clustering of D sites was also observed on non‐enzyme‐treated red cells of the ‐D‐ phenotype. Further studies indicated that D and c antigen sites are closely associated on ccDEE red cells. The distribution of A antigen sites was found to be clustered in proportion to the amount of IgG anti‐A combined with the cells. Reasons are given for considering such distribution as indirect evidence of mobility of A sites. There was an association between agglutinability of red cells by IgG antibodies and the extent of the clustering of the antigen sites.
Foetal Erythropoiesis in Steel Mutant Mice
Authors: Chui David H. K. , Loyer Brian V.
Published: March 2008

Summary A rapid and reliable method of definitively identifying mutant (Sl/Sld) and wild type (+/+) mouse embryos in segregating litters is described, based on the mean cell volume determination of circulating foetal erythrocytes by an electronic particle counter. The mean cell volumes of yolk sac derived nucleated erythrocytes from +/+ and Sl/Sld embryos are similar, whereas the foetal liver derived non‐nucleated red blood cells are much larger in Sl/Sld than +/+ embryos. There is no significant retardation in the growth of mutant embryos in spite of the severe anaemia which is macrocytic and normochromic. Evidence is also presented that the proportion of haemopoietic stem cells among hepatic erythroblasts, assayed by the macroscopic spleen colony technique, is higher in the mutant embryos, even though the total number of these progenitor cells present in each mutant foetal liver is less than the normal. Furthermore, these stem cells undergo active proliferation in Sl/Sld foetuses during development.

The data indicate that the mutant Sl genes do not affect the primitive erythroid cell lineage derived from the yolk sac blood islands, but seriously interfere with the differentiation of the definitive erythroid cell lineage of foetal liver origin. It is further suggested that the mutant foetal liver fails to support or interferes with the normal rate of differentiation from immature precursor cells into haemoglobinized erythroblasts. The reduction of total haemopoietic stem cells in mutant embryos may be secondary to this defect in cellular differentiation.
Unbalanced Globin Chain Synthesis in Erythroid Precursor Cells of Heterozygous αThalassaemia
Authors: Steinberg Martin H. , Coleman Mary , Dreiling Bernard
Published: March 2008

SUMMARY Globin biosynthesis was studied in both erythroid precursors and reticulocytes of three individuals with heterozygous αthalassaemia. In contrast to the finding of equal or nearly equal α and β chain synthesis in the marrow of patients with heterozygous β‐thalassaemia previously examined, our studies showed equal degrees of unbalanced globin synthesis in both reticulocytes and nucleated erythroid cells of αthalassaemia heterozygotes. Greater stability and less susceptibility to proteolysis of the excess β‐chain formed in αthalassaemia may explain our findings.
Defective Neutrophil Function in Chronic Granulocytic: Leukaemia
Authors: EL‐MAALEM Hilal , Fletcher John
Published: March 2008

SUMMARY. The ability of neutrophils to phagocytose, kill and digest Candida guilliermondii was investigated in twelve patients with chronic granulocytic leukaemia (CGL). Following ingestion of organisms there was considerable reduction in the ability of CGL cells to kill Candida and this was not explained by a mild impairment of phagocytosis. Histochemical staining showed that granules containing lysosomal enzymes disappear from the cytoplasm of normal neutrophils during killing and digestion of the fungus, while in CGL cells the granules remain. Quantitative measurement confirmed loss of peroxidase from normal neutrophils during Candida killing but no loss from CGL neutrophils. The primary granules of CGL neutrophils do not fuse with and discharge their contents into the phagocytic vacuole and this explains their impaired ability to kill and digest Candida.
Factor VIII and Human Platelet Aggregation
Authors: Vermylen J. , Bottecchia D. , Szpilman H.
Published: March 2008

SUMMARY When highly purified human factor VIII is submitted to agarose gel chromatography in the presence of 0.5 M CaCl2, the procoagulant activity (low molecular weight factor VIII, LMW‐F VIII) is separated from the void volume protein (Vo‐VIII). Upon incubation of human factor VIII with purified neuraminidase, a very stable platelet aggregating activity develops in the ‘Vo‐VIH’fraction, not in the ‘LMW‐F VIII’part. Evidence is provided that the generated aggregating activity is a property of the ‘carrier protein’for LMW‐F VIII.

Desialylated factor VIII retains its antigenic reactivity, its procoagulant or ristocetin cofactor properties and the capacity of its subunits to dissociate and recombine. Neuraminidase‐treated human factor VIII, in contrast to intact bovine factor VIII or intact human factor VIII in the presence of ristocetin, does not induce aggregation of EDTA‐platelet rich plasma, of congenitally afibrinogenaemic platelet rich plasma, nor of washed platelets.
Oxidation of Human and Animal Haemoglobins with Ascorbate, Acetylphenylhydrazine, Nitrite, and Hydrogen Peroxide
Authors: Harvey John W. , Kaneko J. J.
Published: March 2008

Partially purified haemoglobin solutions of man, horse, cat and dog were oxidized with ascorbate, acetylphenylhydrazine, nitrite, and H2O2 at 25°C and with ascorbate and acetylphenylhydrazine at 37°C. Haemoglobins of the carnivores were more easily oxidized with ascorbate, nitrite, and H2O2 than equine and human haemoglobins. Feline haemoglobin, in general, appeared more susceptible to oxidation, particularly oxidative denaturation, than those of the other species. In addition, results of the incubations at 37°C suggest that feline haemoglobin B might be more susceptible to oxidative denaturation than feline haemoglobin A. Equine haemoglobins appeared to be the least susceptible to oxidation with ascorbate and nitrite, but were more easily oxidized with acetylphenylhydrazine than those of the dog or man. It is apparent, therefore, that because a haemoglobin is more susceptible to oxidation with one oxidant does not mean that it will be more susceptible to oxidation with all oxidants. Results from the present study support the concept that an oxidant intermediate(s) is more important than H2O2 in drug‐mediated oxidation of haemoglobin.
Prostaglandin E2 Potentiation of Platelet Aggregation Induced by LASS Endoperoxide: Absent in Storage Pool Disease, Normal after Aspirin Ingestion
Authors: Weiss Harvey J. , Willis Anthony L. , Kuhn Douglas , Brand Harvey
Published: March 2008

Patients with storage pool disease and normal subjects who ingest aspirin show diminished collagen‐induced platelet aggregation and an absent second wave of aggregation with ADP or adrenaline. These ‘second‐phase’ aggregation responses are thought to be mediated by cyclic endoperoxide (‘labile aggregation stimulating substance’, LASS) that is derived from arachidonic acid and is the precursor of prostaglandin E2 (PGE2) and PGF2α. Furthermore, although PGE2 does not directly aggregate platelets, it markedly potentiates LASS‐induced aggregation. The platelets of six patients with storage pool disease were capable of converting arachidonic acid to LASS, but the potentiation of LASS‐induced aggregation by PGE2 was markedly diminished. In contrast, PGE2‐potentiation of LASS aggregation was not reduced after aspirin ingestion. The effects of aspirin can be attributed entirely to its ability to block the enzymatic conversion of arachidonic acid to LASS and PGE2. These findings explain why a mutual correction of the aggregation defects is often seen when aspirin‐treated platelets are mixed with storage pool‐deficient platelets. This is because ‘aspirin platelets’ aggregate to the mixture of LASS and PGE2 produced by the storage pool‐deficient platelets, which are themselves unresponsive. The findings in storage pool disease support previous conclusions that prostaglandin sensitization of platelets to the pro‐aggregatory effects of LASS is an important factor in irreversible aggregation, and could be clinically important.
Cell Proliferation and Protein Synthesis in Human Leukaemic Myeloblasts after Cytosine Arabinoside Therapy
Authors: Wantzin G. Lange , Karle H. , Killmann S.‐A.
Published: March 2008

The effect of a single intravenous bolus injection of cytosine arabinoside (ARA‐C) on the cytokinetics and 3H‐leucine uptake of leukaemic myeloblasts in bone marrow and blood was studied at intervals up to 96h after ARA‐C in five patients with previously untreated acute myelogenous leukaemia. An early decrease in mitotic index and in 3H‐thymidine labelling was observed in four of five patients and pretreatment values were reached again within the observation period. Changes suggesting synchronization were not observed.

ARA‐C induced a marked decrease in protein synthesis in the leukaemic myeloblasts as estimated from either a decrease in the 3H‐leucine labelling index or the mean grain count of 3H‐leucine labelled cells. It is suggested that ARA‐C is incorporated also by cells which are not in S‐phase and has a prolonged biochemical effect on the leukaemic cells.
The Scanning Electron Microscopy of Normal Human Peripheral Blood Lymphocytes
Authors: Newell D. G. , Roath S. , Smith J. L.
Published: March 2008

A study of the effects of various sample preparation techniques for scanning electron microscopy has been undertaken in an attempt to resolve conflicting descriptions of the surface topography of human peripheral blood lymphocytes. By fixing cells in suspension—a technique thought most likely to avoid the production of artefacts—no clearly defined morphological classification of lymphocytes could be made, and when T‐ and B‐lymphocyte enriched preparations were studied their surfaces appeared similar. Both T‐ and B‐rosetted cells showed identical morphological changes as a result of their interaction with red blood cells. The smooth cells described in other reports were found only under certain conditions of preparation. It is therefore not possible to distinguish between T‐ and B‐cell populations, using the S.E.M., on the basis of surface morphology alone.
Leucocyte Function in a Case of Chronic Benign Neutropenia of Infancy Associated with Circulating Leucoagglutinins
Authors: Kay A. B. , White A. G. , Barclay G. R. , Darg C. , Raeburn J. A. , Uttley W. S. , McCrae W. M. , Innes Elizabeth M.
Published: March 2008

A case of chronic benign neutropenia is described in association with circulating leucoagglutinins. IgG and IgM leucoagglutinins demonstrated by Sephadex G‐200 chromatography agglutinated neutrophils and monocyte enriched leucocyte preparations. Total IgG, IgA, IgM and IgE, total haemolytic complement, C3 and C4 complement components were all within normal limits. Lymphocyte populations and transformation were normal apart from a relative increase in the number of B lymphocytes. In vitro studies showed that the patient's monocytes responded in chemotaxis, phagocytosis and intracellular killing of S. aureus in a comparable fashion to that of control neutrophils. Although the patient's serum also agglutinated monocytes these findings do not exclude the possibility that leucoagglutinins may have aetiological significance in this disease. The study also emphasizes the versatility of the monocyte in benign neutropenia.
A Controlled Trial of Androgen Therapy in Experimental Chronic Hypoplastic Marrow Failure
Authors: Morley Alec , Remes Judith , Trainor Kevin
Published: March 2008

A controlled trial of an androgen, 17‐nortestosterone decanoate, was carried out to test its effect as therapy in an experimental model of chronic hypoplastic marrow failure. No effect was detected.
Radioimmunoassay Studies of the Cross‐reacting Antibody of Human Group O Sera
Authors: Holburn A. M.
Published: March 2008

Cross‐reacting antibody was obtained from three recently stimulated group O donors. The biological reactions of cross‐reacting antibody were investigated by a study of the binding characteristics of 125I‐labelled purified IgG fractions with red cells and by the reactions of whole antiserum or eluates with 125I‐labelled blood group glycoproteins.

The bulk of cross‐reacting antibody activity is restricted to the IgG fraction. Experiments with 125I‐labelled IgG and with the radioimmunoassay system revealed that cross‐reacting antibody has a higher binding constant than specific anti‐A or anti‐B.

In the radioimmunoassay system complete inhibition of cross‐reacting antibody was obtained either with D‐galactose or with N‐acetyl‐D‐galactosamine, but the same concentrations of monosaccharides gave only partial inhibition of specific anti‐A and anti‐B antibodies. The results indicate that cross‐reacting antibody binds to a smaller determinant than specific antibody. Investigations with other monosaccharides did not, however, reveal a common inhibitory structure. The ability of cross‐reacting antibody to bind to both group A and B antigens may, therefore, be a property of a ‘Polyfunctional’ antibody binding site.
Clinical and Haematological Data in 254 Cases of Beta‐Thalassaemia Trait in Italy
Authors: Mazza U. , Saglio G. , Cappio F. Caligaris , Camaschella C. , Neretto G. , Gallo E.
Published: March 2008

Summary.

The haematological and clinical data in 254 Italian subjects with β‐thalassaemia trait are reported. 46% of the patients were anaemic, 40% complained of weakness, 19% showed enlargement of the spleen and 10% enlargement of the liver. The haemoglobin levels ranged from 8 to 15.5 g/dl with a normal distribution and a mean of 12.73 for males, 10.93 for females and 11.34 for children (4–15 years). Reticulocyte counts and serum bilirubin levels were slightly increased and both showed a statistically significant relationship with haemoglobin levels. The serum iron level was increased in 27% and decreased in 6% of the cases. Haemoglobin A2 concentrations ranged from 3.5 to 8% with a normal distribution and a mean of 5.37; Hb F values were less than 1% in 36% and varied from 1 to 14% in the remainder. Red cell osmotic fragility was decreased in all but 6% of the subjects: low MCV, MCH and MCHC values were observed in 75%, 86% and 10% respectively. A comparison is made between the data and those obtained by other workers.
The Availability of Folates in Man: Effect of Orange Juice Supplement on Intestinal Conjugase
Authors: Tamura T. , Shin Y. S. , Buehring K. U. , Stokstad E. L. R.
Published: March 2008

Summary.

The mechanisms of the low availability of endogenous folates in orange juice and the inhibitory effects on the availability of pteroylheptaglutamate (PteGlu7) caused by orange juice supplements were investigated in man by the use of simulated orange juice (containing the principal components: citric acid, malic acid, etc.) with several different pHs.

The endogenous folates in orange juice were identified as mainly 5‐methyl reduced derivatives of pteroylpolyglutamates (40–45% pentaglutamate, 10–15% tetraglutamate, 30–40% monoglutamate, and the rest were tri‐ and diglutamates).

The availability of PteGlu7 is decreased to 54% by supplementation with 600 g concentrated orange juice (pH 3.7) and to 39% and 66% by the supplement of 24 g and 12 g citric acid (pH 3.7), respectively. Neutralization of 12 g citric acid to pH 6.4 largely reverses the inhibitory effect. On the other hand, the availability of pteroylmonoglutamate (PteGlu) is not influenced by a supplement of orange juice or citric acid.

The results suggest that the low availability of PteGlu7 is due to the inhibition of intestinal conjugase caused by the low pH. These observations suggest that pH of foodstuffs may be an important factor in the absorption of polyglutamate forms of folate.
Analysis of Treatment in Childhood Leukaemia
Authors:   Medical Research Council's Working Party on Leukaemia in Childhood, MacLennan I. C. M. , Kay H. E. M. , Festenstein M. , Smith P. G.
Published: March 2008

Summary. The first and second Medical Research Council UKALL trials have shown that alteration in the timing of methotrexate and 6‐mercaptopurine maintenance therapy for the treatment of acute lymphoblastic leukaemia can markedly change drug induced toxicity. Maintenance chemotherapy in both trials used a similar total dosage of these drugs but the timing of their administration was different in the two schedules.

Serial analysis of leucocyte count showed that the UKALL I regimen caused considerably more neutropenia than UKALL II but UKALL II was associated with prolonged lymphopenia which was not characteristic of UKALL I. Analysis of deaths in remission in these two trials showed some correlation with these findings. Deaths in complete remission were compared with the known prognostic features of age and presenting white cell count. Of the 350 patients achieving remission 63% had the good prognostic features of being less than 13 years of age and having a white cell count below 20 × 109/1. at presentation. Twelve out of the 26 deaths in this group occurred in patients in first remission. In the remaining 128 patients who lacked one or both of these good prognostic features only one out of 56 deaths recorded to date occurred during remission.
Inhibitory Effect of Eggs on Vitamin B12 Absorption: Description of a Simple Ovalbumin 57Co‐Vitamin B12 Absorption Test
Authors: Doscherholmen A. , McMahon J. , Ripley D.
Published: March 2008

Summary. Ovalbumin and egg yolks, mixed separately in vitro with radiocyanocobalamin (57Co‐vitamin B12), were served to normal volunteers in a cooked form. Ovalbumin, and to a lesser degree, egg yolks were observed to inhibit vitamin B12 absorption. This observation explains the rather poor assimilation of vitamin B12 from eggs labelled in vivo with 57Co‐vitamin B12.

The assimilation of vitamin B12 from the ovalbumin 57 Co‐vitamin B12 mixture was also measured in patients with structural alterations and functional disorders of the stomach. In contrast to the absorption test using crystalline radio‐vitamin B12, this simple food‐vitamin B12 absorption test successfully distinguished between the controls and subjects who had simple gastric achlorhydria and patients who had undergone a Billroth I or II operation or a successful vagotomy with pyloroplasty. Furthermore, this ovalbumin 57Co‐vitamin B12 test successfully separated patients with pernicious anaemia from those with simple gastric achlorhydria. The ovalbumin 57Co‐vitamin B12 test, in contrast to that using crystalline 57Co‐vitamin B12, showed a positive correlation with the serum vitamin B12 concentration. This ovalbumin57 Co‐vitamin B12 test, being more physiologic and informative than the method using crystalline radio‐vitamin B12, is the first simple model for food‐vitamin B12 absorption to be proposed for research and for clinical purposes.
Immunological Classification of Acute Lymphoblastic Leukaemias: Evaluation of its Clinical Significance in a Hundred Patients
Authors: Brouet Jean‐Claude , Valensi Françoise , Daniel Marie‐Thérèse , Flandrin Georges , Preud'homme Jean‐Louis , Seligmann Maxime
Published: March 2008

Summary. The use of T and B lymphocyte markers and of different antisera raised against malignant B cells and fetal thymocytes allowed the classification of 100 patients with acute lymphoblastic leukaemia (ALL) into three groups. (1) Patients with non‐T non‐B ALL whose cells were devoid of conventional B and T markers but characterized by a leukaemia associated antigen (69 cases). (2) Patients with T‐derived ALL (28 cases). (3) Patients with ALL of B cell origin (three cases). The search for haematological and clinical correlations showed that those patients with T‐derived ALL tended to have a higher leucocyte count (P= 0.05) and acid phosphatase positivity of blast cells (P= 0.01), a higher incidence of tumour presentation (P= 0.05) and a thymic mass. Survival curves for the two main groups of patients are similar at 36 months but meningeal relapses were more frequent in patients with T‐derived ALL (P= 0.02).
In Vivo Plasma and Urine Folate Binding after Ingestion of 3H‐Folic Acid and 14C‐Methyl‐Folate
Authors: Retief F. P. , Heyns A. du P. , Oosthuizen Mariëtha , van Reenen O. R.
Published: March 2008

After simultaneous ingestion of equivalent amounts of [3H]folic acid (3H‐PteGlu) and [14C]N5‐methyl‐tetrahydrofolic acid (14C‐CH3‐H4PteGlu) we were able to demonstrate progressive macromolecular binding of radiofolate in plasma, which appeared to be near maximal at 6 h. Bound radiofolate was predominantly of 14C‐CH3H4PteGlu origin, and only at 24 h could 3H incorporation be demonstrated. The binder eluted with albumin from Sephadex DEAE‐A50 columns. In urine a smaller bound radiofolate fraction, with approximately equal amounts of 3H and 14C, appeared after 5.5 h. Plasma chromatography showed radio‐PteGlu (peak 1) to be rapidly converted to CH3‐H4PteGlu (peak 2), with subsequent appearance of two further radiofolate peaks (peaks 3 and 4) the nature of which is as yet unclear. Urine showed similarly placed fractions but their magnitude differed, and urinary peak 3 in particular was much more prominent than its plasma counterpart.
Patterns of Food Iron Absorption in Iron‐Deficient White and Indian Subjects and in Venesected Haemochromatotic Patients
Authors: Bezwoda W. R. , Disler P. B. , Lynch S. R. , Charlton R. W. , Torrance J. D. , Derman D. , Bothwell T. H. , Walker R. B. , Mayet F.
Published: March 2008

Summary. The absorption of radioactive iron from a solution of ferrous ascorbate, and from a standard meal containing intrinsically labelled haemoglobin and wheat, was measured in 12 Indian housewives, 18 white hospital patients and 12 subjects with idiopathic haemochromatosis. Eight of the latter had been fully treated by multiple venesections, so that their serum ferritin concentrations were below 25 μg/1. Since the serum ferritin concentrations of the housewives and the hospital patients were comparable, their body iron stores were considered to be depleted to a similar degree. There were no significant differences between the absorptions of ferrous ascorbate or of the haem iron in the standard meal by each group, but the housewives and the hospital patients absorbed significantly less of the non‐haem food iron. The mean non‐haem food iron absorptions were 36.4%, 5.8% and 18.9% for the treated haemochromatotic subjects, the Indian housewives and the white hospital patients respectively. The discrepancies between the absorptions of the different forms of food iron were highlighted by calculating the ratios between them. The mean non‐haem: haem food iron absorption ratio for the group of treated haemochromatotic subjects was 0.98, and for the Indian housewives only 0.18. The white hospital patients did not form a homogeneous population: the ratios of the five males and three of the females were greater than 1.0, whereas those of the remaining 10 females were less than 0.5. The results of this study suggest that mal‐absorption of non‐haem iron from a meal containing bread, presumably due to a defect at the luminal level, may be an important factor in the pathogenesis of iron deficiency in some subjects. The abnormality appears to be particularly prevalent among Indian women living in Durban.
Proposals for the Classification of the Acute Leukaemias French‐American‐British (FAB) Co‐operative Group
Authors: Bennett J. M. , Catovsky D. , Daniel Marie‐Theregse , Flandrin G. , Galton D. A. G. , Gralnick H. R. , Sultan C.
Published: March 2008

Summary. A uniform system of classification and nomenclature of the acute leukaemias, at present lacking, should permit more accurate recording of the distribution of cases entered into clinical trials, and could provide a reference standard when newly developed cell‐surface markers believed to characterize specific cell types are applied to cases of acute leukaemia. Proposals based on conventional morphological and cytochemical methods are offered following the study of peripheral blood and bone‐marrow films from some 200 cases of acute leukaemia by a group of seven French, American and British haematologists. The slides were examined first independently, and then by the group working together. Two groups of acute leukaemia,‘lymphoblastic’and myeloid are further subdivided into three and six groups. Dysmyelopoietic syndromes that may be confused with acute myeloid leukaemia are also considered. Photomicrographs of each of the named conditions are presented.
Effect of Iron Deficiency and Desferrioxamine on DNA Synthesis in Human Cells
Authors: Hoffbrand A. V. , Ganeshaguru K. , Hooton J. W. L. , Tattersall M. H. N.
Published: March 2008

Summary. Desferrioxamine (10‐3m) caused a fall in the deoxyadenosine triphosphate level after 4 h incubation in normal phytohaemagglutinin‐stimulated lymphocytes. There was a rise in the concentrations of the other three deoxyribonucleoside triphosphates (deoxythymidine‐, deoxycytidine‐ and deoxyguanosine‐triphosphate). The changes are similar to those caused by hydroxyurea, a known inhibitor of ribonucleotide reductase. Desferrioxamine (10‐3m) was found to inhibit human lymphocyte ribonucleotide reductase to a mean of 11% of control activity after 45 min incubation. Both drugs, desferrioxamine and hydroxyurea, inhibited incorporation of [3H]thymidine DNA into lymphocytes in the presence or absence of deoxyuridine, and inhibited production of lymphocytic thymidine kinase, having opposite effects to methotrexate on both [3H]thymidine incorporation and thymidine kinase activity. Phytohaemagglutinin‐stimulated lymphocytes from patients with chronic iron deficiency showed lower levels of all four deoxyribonucleoside triphosphates than normal lymphocytes. It is suggested that this may be due to reduced ribonucleotide reductase activity of the iron‐deficient cells.
Bleeding from Self‐administration of Phenindione: a Detailed Case‐study
Authors: Gover P. A. , Ingram G. I. C. , Cork M. S. , Holland L. , Hopkins R. P. , Callaghan P. , Barkhan P. , Shearer M. J.
Published: March 2008

Summary. A young woman presented with a 2 year history of a severe bleeding disorder and marked deficiencies in all four vitamin‐K‐dependent factors. Metabolic studies with tracer doses of tritium‐labelled vitamin K1 suggested that the patient might be taking an oral anticoagulant; and subsequently her plasma was found to contain a substance identical to phenindione in its spectrophotometric and chromatographic properties. The half‐disappearance times of factors II, IX, X were measured after the administration of a concentrate of these factors and were found to conform with published figures. The concentrate controlled the patient's excessive bruising and prolonged skin and gingival bleeding. It would therefore seem that factor VII may not be essential in reversal of the bleeding disorder induced by anticoagulant overdose.
Abnormal Fibrin Polymerization in Liver Disease
Authors: GREEN G. , THOMSON JEAN M. , DYMOCK I. W. , POLLER L.
Published: March 2008

Summary. Although there have been isolated reports of an acquired abnormal fibrinogen in patients with liver disease, its frequency and clinical significance is not known. In this study 121 consecutive patients with a wide spectrum of hepatic disorders were screened for abnormal fibrin polymerization. A simple colorimetric method using Reptilase was employed. Of 32 patients with proven cirrhosis, 16 (50%) showed abnormal fibrin polymerization. The incidence in decompensated alcoholic cirrhosis was particularly high. The abnormality was also detected in all patients with acute liver failure and seven of 15 with chronic active liver disease. Clinical improvement often correlated with its disappearance. Two patients with primary liver cell tumours demonstrated the abnormal polymerization. In patients with bleeding oesophageal varices the detection of abnormal fibrin polymerization was associated with a poor prognosis. None of the patients with surgical obstructive jaundice (26) or miscellaneous liver disorders (37) had abnormal fibrin polymerization. The occurrence of abnormal fibrin polymerization in liver disease is more frequent than previously suspected and usually signifies severe primary hepatocellular dysfunction. Evidence is presented to support the presence of a primary abnormality of fibrinogen as the cause of impaired fibrin monomer polymerization.
An Inhibitor of Stem Cell Proliferation in Normal Bone Marrow
Authors: LORD B. I. , MORI K. J. , WRIGHT E. G. , LAJTHA L. G.
Published: March 2008

Summary. A saline extract from normal bone marrow cells having a molecular weight in the range 50 000–100 000 daltons has been found to protect rapidly proliferating haemopoietic spleen colony forming cells (CFUs) from the lethal effects of large doses of tritiated thymidine. This extract is non‐toxic to the cells. It is not found in regenerating marrow where the CFUs population is rapidly proliferating. Its effect appears to be specific for the CFUs since it has no effect on the proliferation of its close descendant, the granulocytic precursor cell (CFUc), and no effect on the average cytoplasmic structuredness of the whole bone marrow cell population. The active material is probably protein since it is degraded by trypsin.
Globin Synthesis in Normal Human Bone Marrow
Authors: CHALEVELAKIS G. , CLEGG J. B. , WEATHERALL D. J.
Published: March 2008

Summary. Globin synthesis has been studied by in vitro labelling with radioactive amino acids in 60 normal human bone‐marrow samples. Under the conditions routinely used to fractionate α and β chains by chromatography α/β production ratios ranging from 0.5 to 1.0 were obtained, depending on the method of sample treatment. This variation was due entirely to the presence of non‐haem proteins derived from white cells which chromatograph with globin on CM‐cellulose. Purification of globin on Sephadex G100 and fractionation of α and β globin chains by a modified chromatographic system resulted in α/β ratios of unity. The relevance of these findings to the study of marrows in which there is unbalanced globin chain production is discussed.
Relationship of Factor VIII‐like Antigen (VIII AGN) and Clot Promoting Activity (VIII AHF) as Measured by One‐and Two‐Stage Assays in Patients with Liver Disease
Authors: ROGERS J. S. , EYSTER M. ELAINE
Published: March 2008

Summary. We recently observed an increase in factor‐VIII clot promoting activity as measured by a one‐stage assay (VIII AHF1) in a haemophiliac with hepatitis. However, VIII AHF as measured by a two‐stage assay (VIII AHF2) was 0.013 u/ml at a time when VIII AHF1 measured 0.38 u/ml.

We then studied seven non‐haemophiliacs with liver disease, and attempted to correlate the levels of VIII AHF1 and VIII AHF2 with factor VIII‐like antigen (VIII AGN) as measured by quantitative immunoelectrophoresis. In four of the seven patients, disproportionate elevations of VIII AHF2 compared to VIII AHF1 were found. Furthermore, VIII AHF2 values correlated well with VIII AGN values. No such discrepancy was apparent in four normal control subjects.

These findings emphasize the necessity for performing two‐stage assays in haemophiliacs as well as non‐haemophiliacs with liver disease to assess factor‐VIII levels. In addition, they suggest that confirmation of the diagnosis of haemophilia may not be possible in the haemophiliac with hepatitis unless VIII AHF2 determinations are performed. The reason for the disparity between VIII AHF1 and VIII AHF2 levels is not apparent. However, the correlation of VIII AGN and VIII AHF2 levels in the non‐haemophiliacs with liver disease provides further support for the concept that VIII AGN and VIII AHF are closely related or identical molecular entities.
Studies of the Influence of Cyclic Nucleotides on in Vitro Haemoglobin Synthesis
Authors: Brown James E. , Adamson John W.
Published: March 2008

The influence of various cyclic nucleotides on in vitro haemoglobin synthesis has been examined in suspension cultures of mammalian marrow cells. Over a wide range of concentrations, dibutyryl cyclic AMP (db‐cAMP) was either ineffective or inhibited haemoglobin synthesis by marrow cells from rat, mouse and guinea‐pig. However, 10‐3 M db‐cAMP consistently stimulated haemoglobin synthesis in cultures of human, sheep, rabbit and canine cells, with the latter being most responsive. This effect, which approached in magnitude that of erythropoietin (ESF) itself, was specific for cAMP and its mono‐ and dibutyryl derivatives and was not inhibited by anti‐ESF. Adenosine, AMP, ADP, ATP, cGMP, db‐cGMP, cCMP, cIMP and sodium butyrate were either inactive or inhibitory at similar concentrations. Enhancement of haemoglobin synthesis was also observed with the phosphodiesterase inhibitor, RO‐20‐1724. The susceptibility to ionizing radiation of the response to ESF and db‐cAMP was marked, indicating that the increased haemoglobin synthesis in this system was proliferation dependent, although the response to db‐cAMP was less radiosensitive. Studies with tritiated thymidine showed that about 50% of the cells which were responding to either db‐cAMP or ESF were actively engaged in DNA synthesis. However, the physical characteristics of db‐cAMP‐ and ESF‐responsive cells were dissimilar as analysed by their velocity sedimentation properties. These studies demonstrate that cAMP has a major stimulatory effect on haemoglobin synthesis with cells from selected mammalian species with activity approaching that of ESF, but the target cells most responsive to these agents appear different. The results suggest that cyclic nucleotiderelated mechanisms may modulate in vitro erythropoiesis.
Neutrophil Function in Bone Marrow Transplant Recipients
Authors: Territo Mary C. , Gale Robert P. , Cline Martin J. ,   The UCLA Bone Marrow Transplantation Team
Published: March 2008

The neutrophil function of seven patients receiving allogeneic bone marrow transplantation was studied. Five of the patients had been transplanted for aplastic anaemia and two for acute leukaemia. Determinations were made of neutrophil phagocytosis, chemotaxis, random migration, and microbicidal activity for Candida albicans and Staphylococcus aureus. One patient showed a decreased ability to kill C. albicans at a time when she had active pneumonia due to Pneumocystis carinii. The remainder of the studies showed normal neutrophil functions. No differences were observed in the patients who had graft versus host disease (GvH) from those without GvH.

These studies suggest that defects in phagocytic neutrophil function do not contribute significantly to the impaired host defenses in recipients of bone marrow transplantation.
Splenic Red Cell Pooling in Hairy Cell Leukaemia
Authors: Lewis S. M. , Catovsky D. , Hows J. M. , Ardalan B.
Published: March 2008

The splenic red cell volume has been measured directly by an isotope method with quantitative scanning in 10 patients with leukaemic reticuloendotheliosis (hairy cell leukaemia). The volume ranged between 211 and 726 ml (mean 410 ml, SD 158) and this constituted 15–48% (mean 28.1%, SD 9.5) of the total circulating red cell volume. This is an exceptionally large pool when compared with that found in myeloproliferative and lymphoproliferative disorders with the same degree of splenomegaly. It is consistent with the histological features which show marked red cell accumulation in the splenic cord areas. The red cell pooling in the spleen thus appears to be a significant factor in the anaemia and there was fairly good correlation between the percentage of improvement in the anaemia and the percentage of red cell volume contained in the spleen. By direct measurement of the splenic red cell pool, it is possible to predict the extent to which splenectomy will benefit the anaemia and this may also provide an indirect measure of the extent of bone marrow dysfunction in the causation of the anaemia.
Altered Haem—Haem Interaction and Tissue‐Oxygen Supply: A Theoretical Analysis
Authors: Neville J. Ryan
Published: March 2008

On the basis of its assumed invariance, the haem‐haem interaction or shape of the oxyhaemoglobin dissociation curve is frequently ignored when considering the potential effect of haemoglobin‐oxygen affinity (as characterized by the P50) on oxygen transport. This report reviews some experimental evidence with respect to this assumption and demonstrates the potential effect of altered haem‐haem interaction on tissue‐oxygen supply as distinguished from the effect of P50 or position change. Theoretically, haem‐haem interaction values in the range that has been reported for apparently healthy human subjects can substantially modify oxygen transport to tissues, in some cases equalling or exceeding the effect from a similar range of P50 values. It is not presently clear to what extent this range may represent true variation as opposed to random technical error, but the possible implications for oxygen transport indicate that a more systematic evaluation of the problem is desirable.
Factor XI and Platelets: Evidence that Platelets Contain only Minimal Factor XI Activity and Antigen
Authors: Schiffman Sandra , Rimon Abraham , Rapaport Samuel I.
Published: March 2008

Factor‐XI activity of platelets has been studied in platelet‐rich plasmas and isolated platelet suspensions. Fresh platelets in both environments had little or no measurable factor‐XI activity. Frozen and thawed platelet‐rich normal plasma had markedly elevated apparent factor‐XI activity and factor‐IX activity as compared to platelet‐poor plasma. Frozen and thawed platelet‐rich and platelet‐poor normal plasmas had equivalent factor‐XI antigen. Platelets isolated from normal blood and from factor‐XI deficient blood had the same small amounts of apparent factor‐XI activity, which increased slightly on freezing and thawing. The data indicates that minimal factor XI is associated with the platelet. The markedly elevated apparent factor‐XI activity of frozen and thawed platelet‐rich plasma is shown to reflect the interaction of a platelet activator with plasma clotting factors to produce a later activated‐clotting‐intermediate.
Specific Interaction of HLA Antibodies (Eluates) with Washed Platelets
Authors: Heinrich D. , Stephinger U. , Mueller‐eckhardt C.
Published: March 2008

The mechanism of complement‐independent action of HLA‐A2 antibodies (eluates) on washed platelets was investigated. HLA‐specific alteration was confirmed by serological (platelet micro‐complement fixation), morphological (platelet spreading) and functional parameters (platelet aggregation, inhibition of collagen‐induced platelet aggregation, [14C]serotonin release). In the presence of fibrinogen and calcium ions, HLA antibodies induced instantaneous platelet aggregation and release. Although no morphological (spreading) and functional changes (collagen‐induced aggregation) were seen, these platelets did not aggregate or release when fibrinogen was subsequently added. When platelets—in the presence of fibrinogen—were incubated with antibody concentrations too low to induce platelet aggregation or release, specific reduction of platelet reactivity was observed by subsequent collagen aggregation. HLA‐specific action of antibodies on washed platelets was inhibited by apyrase and acetyl‐salicylic acid, indicating an active participation of platelets in HLA antibody‐induced platelet alteration.
Haemophilia Treatment in the United Kingdom from 1969 to 1974
Authors: Biggs Rosemary
Published: March 2008

A study has been made by the Haemophilia Centre Directors of the United Kingdom and Northern Ireland. From 1969 to 1974 2600 patients with haemophilia A and 388 with haemophilia B attended Haemophilia Centres for treatment.

Of these patients, 71 are known to have died in the survey period. A record is presented of the amounts and types of therapeutic materials used each year during this time. The incidence of jaundice and anti‐factor VIII and anti‐factor IX antibodies was recorded.
Defibrination of Normal Human Blood in Vitro: a Method giving a High Recovery of Untraumatized Cells
Authors: Bray Penelope J. , Ford D. , Gledhill R. M. , Grimes A. J.
Published: March 2008

A new automatic apparatus is described for the defibrination of blood in vitro at laboratory temperature which results in only small (<10%) losses of white cells. Freshly‐drawn blood is mixed smoothly at high speed (>1200 rpm) and fibrin is removed rapidly as formed. The apparatus is designed to produce minimum mechanical trauma to the blood. Subsequent in vitro incubation of red cells, granulocytes and lymphocytes demonstrated their viability to be comparable with cells obtained by other methods of defibrination.
Immune Haemolytic Anaemia and Renal Failure Induced by Streptomycin
Authors: Letona J. Martinez‐L. , Barbolla L. , Frieyro E. , Bouza E. , Gilsanz F. , Fernández M. N.
Published: March 2008

A case of acute immune haemolytic anaemia and renal failure induced by streptomycin, is reported. The clinical features are similar to those in a case previously reported in which no in vitro proof of antibodies was obtained. In this case, streptomycin‐specific IgG antibodies, with both k and λ light chains, could be demonstrated. The streptomycin bound strongly to the red cell membrane, apparently through chemical groups related to the M antigen and possibly also to the D antigen. Complement‐fixation by the drug‐specific IgG antibodies, after reaction with the streptomycin‐coated red cells, could also be demonstrated. On the basis of these findings, our conclusion is that a complement‐fixing hapten‐cell mechanism was the main cause of the intravascular haemolytic episode suffered by the patient on exposure to streptomycin. This drug had been prescribed 15 years earlier for pulmonary tuberculosis and he had since injected himself with it whenever he felt ‘flu’symptoms, without harmful effects, until now.
Red Cell Metabolic and Membrane Features in Haemolytic Anaemia of Alcoholic Liver Disease (Zieve's Syndrome)
Authors: Goebel Klaus M. , Goebel Frank D. , Schubotz Rolf , Schneider Jürgen
Published: March 2008

Zieve's syndrome (ZS), which consists of transient haemolytic anaemia, jaundice, hyperlipoproteinaemia, and alcohol‐induced liver disease, was studied in male patients during the acute (n= 20) and the remittent (n= 10) phase. Chronic alcoholics (n= 10) without haemolysis and healthy male persons (n= 10) served as controls.

Erythrocytes were separated into old and young cells by means of density‐layer centrifugation. Those fractions which contained older red cells disclosed a pyruvate‐kinase instability which resulted in impaired metabolism. Changes in membrane lipid composition as indicated by increased cholesterol and polyunsaturated fatty acids (PUFA) were also detected in patients during the acute phase of ZS. Alcohol‐induced red‐cell vitamin‐E deficiency with a decrease in PUFA levels may provoke an oxidation of reduced red‐cell glutathione which in turn results in the enzyme instability. This study lends further support to the hypothesis that the putative role of the red‐cell metabolic injury in the origin of haemolysis in ZS cannot be envisaged without introducing membrane‐linked and extracellular cofactors.
Characterization of Serum Ferritin in Iron Overload: Possible Identity to Natural Apoferritin
Authors: Arosio P. , Yokota M. , Drysdale J. W.
Published: March 2008

Serum ferritins from a patient with haemochromatosis and from a patient with transfusional siderosis were compared with tissue isoferritins on the basis of their iron content, isoferritin spectrum and immunological properties. Both serum ferritins had a low iron content and corresponded to only the most basic isoferritins in liver. The serum ferritins were very similar to the natural apoferritin from liver in all respects.
Intracellular Iron Transport in Rat Intestinal Epithelium: Biochemical and Ultrastructural Observations
Authors: Humphrys J. , Walpole B. , Worwood M.
Published: March 2008

Iron absorption by the rat intestinal epithelial cell has been studied by differential centrifugation of mucosal homogenates and by electron microscopic autoradiography. Autoradiography of both subcellular pellets and whole gut confirmed the biochemical findings. Mitochondria play a quantitatively significant role in iron metabolism within the epithelial cell but do not take part in the transport of iron across the cell during iron absorption.