bluuebunny/crossref_metadata_2025_split huggingface dataset:
Forms of Vitamin B12 in Blood and Bone Marrow in Patients with Pernicious Anaemia
Authors: Abe Tsukasa , Gibbs Bernard , Cooper Bernard A. 
Published: March 2008

Summary.The biologically‐active forms of vitamin B12 in blood and bone marrow and changes induced in these by injections of cyanocobalamin have been measured in patients with pernicious anaemia. Bone marrow methylcobalamin was low before therapy, and increased 24 h after therapy. The largest portion of bone marrow vitamin B12 was 5′deoxyadenosylcobalamin, and this increased more than did methylcobalamin during the 24 h after injection of cyanocobalamin. A single injection of roo μ of cyanocobalamin induced about 10 times the increase of the intracellular coenzyme forms of vitamin B12 in bone marrow than followed injection of 100 μg. Plasma methylcobalamin was extremely low before therapy, and increased only moderately 24 h after therapy; the majority of plasma vitamin B12 remaining as cyanocobalamin. In contrast, only a minority of intracellular bone marrow vitamin B12 was cyanocobalamin 24 h after injection of cyanocobalamin.The degree of anaemia did not correlate with bone marrow methylcobalamin, nor did bone marrow cobalamin correlate significantly with cobalamin content of washed blood erythrocytes. Correlation was observed between intra‐erythrocyte vitamin B12 content and the degree of anaemia; the correlation being inverse with haemoglobin concentration in the peripheral blood. Inverse correlation also was observed between MCV and erythrocyte folate content.These studies suggest that megaloblastic maturation appears at different concentrations of bone marrow vitamin B12 in different patients, presumably because in vitamin B12 deficiency, eventual limitation of normoblastic maturation may be determined by factors such as folate metabolism, vitamin B12 binders, and the affinity of vitamin B12 dependent enzymes. Although the clinical response to 1000 μg of cyanocobalamin does not differ from that to 100 μg, the concentration of vitamin B12 coenzymes in bone marrow cells was proportional to the cyanocobalamin injected.
Intracellular Localization of Hepatic Propionyl‐CoA Carboxylase and Methylmalonyl‐CoA Mutase in Humans and Normal and Vitamin B12 Deficient Rats
Authors: Frenkel Eugene P. , Kitchens Richard L. 
Published: March 2008

Summary.The intracellular localization of the enzymes in the vitamin B12 dependent pathway which involves the oxidation of propionate was studied in rat liver obtained from normal and vitamin B12 deficient rats as well as from man. The subcellular site of propionyl CoA carboxylase and the vitamin B12 dependent‐methylmalonyl CoA mutase were determined. All of the activity of these two enzymes was demonstrated to be in the mitochondria and those enzymes were shown to be loosely bound to the inner membrane‐matrix portion of the mitochondria. Vitamin B12 deficiency did not alter the subcellular localization. Finally, a rapid enzymatic assay for methylmalonyl‐CoA mutase was described.
Haem Synthesis in the Diamond‐Blackfan Syndrome
Authors: Freedman Melvin H. , Amato Dominick , Saunders E. Fred 
Published: March 2008

Summary.The response of bone marrow to erythropoietin (EPO) from five children with the Diamond‐Blackfan syndrome, also known as congenital hypoplastic anaemia (CHA), was tested in tissue culture by measurement of haem synthesis. Studies of 13 control marrows indicated that the maximum EPO effect occurred at approximately 70 h incubation using an EPO concentration of 0.2–0.3 units/ml and a nucleated cell concentration of 5 × 106 per culture. Under these conditions, haem synthesis was 121% greater in EPO‐stimulated than in unstimulated cultures. Patients with CHA with anaemia and diminished marrow erythroids had reduced or absent haem synthesis. In one patient, haem production became normal after a spontaneous remission, and was not inhibited by autologous plasma drawn at the time of diagnosis. Plasma from three patients did not show inhibitory activity when cultured with control marrow. In contrast, plasma from an adult with acquired pure red cell aplasia produced striking inhibition of haem synthesis when cultured with control marrow. We conclude that, in comparison to some cases of the adult acquired condition, CHA is not due to inhibitors or antibodies. When present, erythroid precursors in children with CHA are capable of responding normally to EPO with increased haem synthesis.
Iron Absorption: Present State of the Art
Authors: Jacobs A. , Worwood M. 
Published: March 2008

Summary.The availability of food iron is one of the major factors determining the total amount of iron absorbed. Iron is released from food in the stomach in an ionizable form or as haem. These forms are affected differently by both the composition of the diet and gastrointestinal secretions. Iron is taken up by the epithelial cells of the small intestine and is released from haem in the same cells. This uptake may be related to the iron status of the cells. Iron transport within these cells has been studied by both subcellular fractionation and electron microscopy with autoradiography. The biochemical studies have shown that much of the mucosal iron is associated with the mitochondria whereas absorbed radioiron is largely bound to ferritin in iron replete rats and to a transferrin‐like protein in iron deficient animals. It has been suggested that this latter protein is the intracellular ‘carrier’of iron. Serosal transport to the plasma is influenced by a number of factors and is not clearly understood. A review of the major problems in this area reveals more questions than answers.
Intestinal Absorption of Folic Acid Monoglutamates and Polyglutamates: a Brief Review of Some Recent Developments
Authors: Butterworth C. E. , Krumdieck C. L. 
Published: March 2008

Summary.Recent evidence indicates that there are important species differences in the digestion and intestinal absorption of pteroylpolyglutamates, the predominant form of the folate vitamin(s) in food. Birds appear to possess a pteroylpolyglutamyl hydrolase, or conjugase, in extracts of pancreas and intestinal mucosa, that acts as an endopeptidase and produces pteroyldiglutamate as a major end product. The precise anatomical site of pteroylpolyglutamate cleavage (whether intraluminal, intracellular, or at the cell surface) has not been established with certainty in the chick, although it has been assumed to occur in the lumen. Several lines of current investigation indicate that in mammalian systems conjugase is primarily an intracellular, lysosomal enzyme, and that it is not localized in brush‐border fractions of intestinal epithelium. There appears to be relatively little conjugase activity in the proximal small bowel lumen of humans or dogs. Human liver conjugase appears to act as an exopeptidase, cleaving terminal glutamate residues from the gamma‐glutamyl chain one at a time, with pteroylmonoglutamate as the end product. These and other observations are compatible with the view that (at least in some mammalian systems) pteroylpolyglutamates are absorbed intact by intestinal epithelial cells and cleaved to monoglutamates at an intracellular site.
Haemoglobin Tak: a β‐Chain Elongation
Authors: Lehmann H. , Casey R. , Lang A. , Stathopoulou R. , Imai K. , Tuchinda S. , Vinai P. , Flatz G. 
Published: March 2008

Summary.In Haemoglobin Tak two normal α‐chains are combined with two β‐chains elongated by 11 residues beyond the C‐terminus. Unlike in the α‐chain abnormal Hb Constant Spring, the elongation cannot result from a point mutation of a stop codon. It is probably due to an unequal crossing‐over near the 3′ end of the β‐chain structural gene. This could cause either a deletion of the normal stop codon or a shift in the reading frame. Oxygen dissociation of purified Hb Tak shows no cooperativity but in Hb A + Tak haemolysates there is no interaction between the two above 40% O2 saturation. Heterozygotes for Hbs A and Tak show an imbalance of globin chain synthesis (α/non α= 1.5), the synthesis of β Tak resembles that of the β‐chain in β+ thalassaemia.
Platelet Kinetics in Idiopathic Thrombocytopenic Purpura (ITP) before and at Different Times after Splenectomy
Authors: Branehög Ingmar 
Published: March 2008

Summary. Platelet kinetics were studied in 18 patients with idiopathic thrombocytopenic purpura (ITP) before splenectomy, 1 month and 8 months after splenectomy. A gamma function was used for the calculation of platelet mean life span (MLS).Before splenectomy platelet MLS was greatly reduced and platelet production was 2.8 times normal. The peripheral platelet count and platelet recovery were significantly related to platelet MLS. One month after splenectomy platelet MLS increased appreciably while platelet production decreased but continued to be significantly above normal. These changes together with the removal of the splenic platelet pool resulted in a peripheral platelet count significantly higher than normal and a total platelet mass not differing from normal. Eight months after splenectomy platelet MLS increased slightly but was not significantly different from that found 1 month after splenectomy. Platelet production, however, decreased significantly and became normal. This resulted in a normal peripheral platelet count and a decreased total platelet mass which was significantly lower than in non‐splenectomized control subjects. The results suggest that platelet production is regulated by a feed‐back mechanism that is governed by the peripheral platelet count. The high platelet count encountered 1 month after splenectomy is due to a sluggishness of this regulatory mechanism.
Skin Window Studies in Polycythaemia Rubra Vera
Authors: Ghosh M. L. , Hudson G. , Blackburn E. K. 
Published: March 2008

Summary. The inflammatory response was studied in patients with primary polycythaemia by means of a modified skin window technique. In untreated patients, the overall cellularity was a prominent feature and, as compared with the controls, the 48 h preparations showed a significantly greater percentage of granulocytes with a corresponding decreased percentage of macrophages. In the peripheral blood of these patients, both total white cells and granulocyte counts were significantly higher than in the control subjects. A highly significant relationship between the blood and skin window neutrophils was demonstrated. In polycythaemia patients in remission, the results were generally similar to the controls, except that there was still a highly significant increase in the percentage of skin window basophils.The results provided no evidence of a defect in cell migration or in the phagocytic activity of macrophages in polycythaemia vera. Possible mechanisms of the cutaneous basophilia and its relevance to the manifestation of this disorder are discussed.
Blast Crisis of Chronic Myeloid Leukaemia (CML): II. CELL SURFACE MARKER ANALYSIS OF ‘LYMPHOID’AND MYELOID CASES
Authors: Janossy G. , Greaves M. F. , Revesz T. , Lister T. A. , Roberts Marion , Durrant Jill , Kirk Barbara , Catovsky D. , Beard M. E. J. 
Published: March 2008

SUMMARY. Fourteen cases of Philadelphia chromosome (Ph1) positive chronic myeloid leukaemia in blast transformation have been investigated using cell surface markers. Morphologically eight cases were lymphoid and the remainder myeloid in appearance. All cases were negative with surface markers for thymocytes and T and B lymphocytes. Five of the lymphoid cases reacted with an antiserum specific for acute lymphoid leukaemia (ALL) of non‐T non‐B type and were also weakly reactive with a lymphocyte reactive antiserum. A sixth patient, whose blast cells were anti‐ALL negative (ALL‐) at presentation, subsequently developed central nervous system leukaemia with anti‐ALL positive (ALL+) blast cells in the CSF. In all cases the leukaemic blast cells showed greatly diminished expression of cholera toxin receptors when compared to granulocytic cells from the chronic phase of CML. This parallels weak or negligible expression of the cholera toxin receptor in ALL and AML.These results suggest that the blastic phase of CML may involve different cellular derivatives of a pluripotential stem cell in which the primary malignant/genetic changes reside. The blast crisis of CML can therefore be heterogeneous with respect to cellular expression and in a significant proportion of patients involves a cell which is by membrane markers and morphological criteria indistinguishable from that seen in the common form of ALL. In these cases the Philadelphia chromosome may be the only distinguishing cellular characteristic.
Sodium Pertechnetate as a Red Cell Label: In Vitro and In Vivo Studies
Authors: Schmidt Peter , Lohrmann Hans‐Peter , Heimpel Hermann 
Published: March 2008

In vitro investigations were performed to re‐examine the variables that influence the binding of sodium 99Tcm‐pertechnetate to human red blood cells. Irreversible binding of the radioisotope was observed only when red cells were incubated with tin chloride after their incubation with pertechnetate; binding of pertechnetate is completed within 10 min after its addition to red cells. Composition, temperature and possibly the oxygen saturation of the incubation medium affect the fraction of the isotope that becomes red cell‐bound.Using a labelling method derived from these in vitro studies, the usefulness of pertechnetate‐labelled autologous red cells for the determination of red cell volumes was studied. Elution of pertechnetate occurred in vivo in an exponential fashion. Using the specific red cell activity, corrected for elution, of blood samples drawn 30 miu after injection of 99Tcm‐labelled red cells, calculated red cell volumes were almost identical to those determined simultaneously with radiochromate‐labelled cells. It is concluded that 99Tcm‐pertechnetate is a useful label for red cell volume determination; it may be less reliable when delayed mixing of the labelled red cell tracer in the patient's circulation is expected.
A Hypothesis for the Increased Oxygen Affinity in Haemoglobin Malmö
Authors: Zak Solomon J. , Geller Gary R. , Rrivit William , Tukey David , Brimhall Bernadine , Jones Richard T. , Bunn H. Franklin , McCormack Michael 
Published: March 2008

Summary.Haemoglobin Malmöβ97HisGln, a high oxygen affinity haemoglobin which causes secondary erythrocytosis, is transmitted in an autosomal dominant manner. A hypothesis accounting for the high oxygen affinity, hyperbolic oxy‐haemoglobin dissociation curve, and the relatively normal Bohr effect is presented. The purified abnormal haemoglobin from the present family provided biochemical and functional data for this hypothesis based on the allosteric model proposed by Perutz. Experimental results support the formation of a chemical bond between the ‐SH proton of the β93 cysteine and the amide of oxygen of the substituted β97 glutamine as an explanation for the high oxygen affinity of haemoglobin Malmö.
Relationship between Paraprotein Polymerization and Clinical Features in IgA Myeloma
Authors: Roberts‐Thomson P. J. , Mason D. Y. , MacLennan I. C. M. 
Published: March 2008

Summary.The clinical manifestations of IgA multiple myeloma are usually not considered distinguishable from those of IgG myeloma despite the fact that IgA differs from IgG in several characteristics, particularly molecular size heterogeneity. The clinical and laboratory features of 25 patients with IgA myeloma seen during a 5 year period are presented. The degree of paraprotein polymerization was observed to vary greatly in these patients but remained chronologically constant in six individuals studied on several occasions over this period. The patients were divided into two groups on the basis of the degree of paraprotein polymerization. The first group comprised those patients in whom the IgA paraprotein was greater than 50% polymerized, whilst in the second group the paraprotein was predominantly monomeric. No clinical or pathological differences were seen between the ‘polymeric’ and ‘monomeric’ groups of myeloma apart from that directly attributable to the physicochemical effect of the paraprotein polymerization. Thus, five patients out of 11 of the ‘polymeric’ group had developed the hyperviscosity syndrome, whilst no patients in the ‘monomeric’ group had developed this complication. The concentration of the paraprotein during the course of the disease was comparable in both groups.This syndrome is considered to be relatively common in IgA myeloma and adds to the morbidity and mortality of the disease. Its anticipation and treatment may improve the quality and survival of patients likely to develop this complication.
The Effect of Transfer Factor on Neutrophil Function in Chronic Mucocutaneous Candidiasis
Authors: Lawton J. W. M. , Costello Christine , Barclay G. R. , Urbaniak S. J. , Darg C. , Raeburn J. A. , Uttley W. S. , Kay A. B. 
Published: March 2008

Summary.Chronic mucocutaneous candidiasis with hypoparathyroidism in a 6‐year‐old boy is described. In addition to defects of in vivo and in vitro correlates of delayed‐type hypersensitivity to Candida albicans the child also had abnormalities of neutrophil function in terms of their capacity to respond by chemotaxis to a known attractant and to kill suspensions of C. albicans. Dialysable transfer factor was given on six occasions at intervals of between 26 and 45 days. Neutrophil chemotaxis (optimal conditions) was restored following each of the six injections, neutrophil chemotaxis (sub‐optimal conditions) following five of the six injections and candidicidal capacity following four of the six injections. The effects of transfer factor were transient requiring repeated injections. The Candida delayed‐type hypersensitivity skin test was restored to normal but lymphocyte transformation to Candida extract was not consistently positive following treatment. There was a slight clinical improvement following therapy. These abnormalities of neutrophil and lymphocyte function point to the complexity of chronic mucocutaneous candidiasis. The improvement in neutrophil chemotaxis and candidicidal capacity following treatment suggests that transfer factor may be a heterogeneous group of molecules, some of which affect granulocytes and restore defects in their function.
The Effect of Cytotoxic Drugs on Neutrophil Phagocytosis in Vitro and in Patients with Acute Myelogenous Leukaemia
Authors: Davies J. E. , Whittaker J. A. , Khurshid M. 
Published: March 2008

Summary.The in vitro effects of a range of concentrations of cyclophosphamide, doxorubicin, actinomycin D, cytarabine and methotrexate on neutrophil phagocytosis of C. albicans was studied. The reduction in phagocytic index (PI) was inversely proportional to the dilution of the drug and there was some inhibition of phagocytosis at all dilutions of all drugs. In patients with acute myelogenous leukaemia (AML), in vivo experiments showed that remission chemotherapy of doxorubicin or daunorubicin together with cytosine arabinoside increasingly inhibited phagocytosis over the period studied. The importance of these findings in the chemotherapy of malignant disease and the possible mode of action of cytotoxic drugs are discussed.
The Kenya Form of Hereditary Persistence of Fetal Haemoglobin: Structural Studies and Evidence for Homogeneous Distribution of Haemoglobin F using Fluorescent Anti‐haemoglobin F Antibodies
Authors: Nute P. E. , Wood W. G. , Stamatoyannopoulos G. , Olweny C. , Failkow P. J. 
Published: March 2008

Summary.Several members of a Ugandan family were heterozygous for the γβ fusion gene of Haemoglobin Kenya. Levels of Hb Kenya were significantly higher than those in subjects of previous reports, ranging from 20.68 to 23.35% of the total haemoglobin. The individuals had also 5–8% Hb F, consisting solely of α and Gγ chains. Investigation of the distribution of Hb F among the red cells of Hb Kenya heterozygotes, using monospecific antibodies absorbed against pure Hb Kenya and rendered fluorescent by conjugation with fluorescein isothiocyanate, showed the presence of fetal haemoglobin in all red cells. The data suggest that the phenotype of the Hb Kenya trait resembles that of the Gγ form of hereditary persistence of fetal haemoglobin rather than that of thalassaemia.
Heterozygous Beta Thalassaemia of Unusual Severity
Authors: Friedman Sh. , ÖZsoylu S. , Luddy R. , Schwartz E. 
Published: March 2008

Summary.The proband of each of three families of Northern European or Italian extraction had an unusual form of heterozygous β‐thalassaemia, confirmed by haem‐atological, genetic and peripheral blood globin synthesis studies. The unusual severity of this disorder was indicated by chronic haemolysis leading to splenectomy and cholecystectomy, by numerous nucleated red cells and reticulocytes in the peripheral blood, and by leg ulcers in one family. The diversity of clinical expression in many family members with heterozygous β‐thalassaemia was striking. Bone marrow examination in the probands showed numerous large inclusion bodies of the type usually found only in thalassaemia major. In addition, there was unbalanced globin synthesis in the bone marrow, in contrast to the more balanced synthesis found in asymptomatic β‐thalassaemia trait. The amount of newly synthesized α‐chain found in the free δ‐chain pool was markedly elevated. The unbalanced globin synthesis and δ‐chain inclusions in the bone marrow cells suggest that the severity of the disorder in these patients may be due to the inability of their red cell precursors to fully compensate for the thalassaemic defect or to remove excess δ‐chains. The diversity of clinical expression suggests the influence of undefined acquired or genetic factors on the expression of β‐thalassaemia in these families.
The Pattern of Fetal Haemoglobin Disappearance after Birth
Authors: Colombo B. , Kim B. , Atencio R. Perez , Molina C. , Terrenato L. 
Published: March 2008

Summary.Haemoglobin F (Hb F) levels were determined in 209 full‐term newborn babies or infants of different ages ranging from birth to 11 months. A follow‐up study of the disappearance of Hb F after birth was carried out on 25 premature babies; they were followed periodically from birth until 8 months. The results obtained in both samples show that Hb F levels remain constant after birth for periods varying from about 15 d in at term babies to about 40 d in premature babies; a linear decrease follows in both cases. The initial plateau is a finding contrary to what has been reported. A possible model for the phenomenon is discussed in terms of haemoglobin genes and ontogenetic differentiation.
A Familial Abnormality of Circulating Vitamin B12 Binding Proteins: Occurrence in a Family of High Serum Concentrations of Transcobalamin II
Authors: Kane S. P. , Hoffbrand A. V. , Allen R. H. , Neale G. 
Published: March 2008

Summary. A family is described in which two members (a father and daughter), both with quiescent ulcerative colitis, had abnormally high serum concentrations of a vitamin B12 binding protein. This protein had the molecular weight of transcobalamin II on gel filtration, and behaved like transcobalamin II with respect to its elution from DE‐23 cellulose, its inhibition at acid pH, its absorption by uncoated charcoal, its binding by anti‐TC II antibodies, and its ability to transfer vitamin B12 to transformed lymphocytes. Its plasma clearance and tissue distribution when injected into rabbits was indistinguishable from that of transcobalamin II from normal subjects. It migrated on electrophoresis in the βγ region.This is the first case report of related subjects in whom high serum concentrations of transcobalamin II have been observed.