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Biomedical subjects

B E Roberts

Publications and source records attributed to B E Roberts.

At least 91 records · Page 5Linked to original sources
PubMed1982

Secondary treatment of polycythemia rubra vera with 6-thioguanine.

6-thioguanine, an antimetabolite not potentiated by allopurinol, has been used in the treatment of 29 patients with polycythemia vera. All but two of the patients had been treated previously by venesection and/or radioactive phosphorus (32p) and/or alkylating agents. The usual dose was 40-160 mg daily alternate weeks according to individual response. The treatment period varied from 6-66 months (mean, 31 months). Of 27 evaluable patients 24 (89%) responded to treatment and at one year there was a significant fall in all blood count parameters. Seven patients relapsed while on treatment and four were withdrawn because of side effects. 6-thioguanine merits further evaluation in the management of polycythemia vera, particularly in those patients who have received large cumulative doses of 32p and/or alkylating agents and in whom an alternative mode of therapy is desirable.

Aged↗
PubMed1982

The influence of iron-deficient indices on whole blood viscosity in polycythaemia.

The relationship of the red-cell indices, packed-cell volume (PCV) and plasma viscosity to whole-blood viscosity was examined in 18 patients with polycythaemia. Sixteen were examined again following a course of venesection. The results were analysed by multiple regression analysis which allowed the effects of individual variables to be independently assessed. A reduction of the MCH or MCV was associated with increased whole-blood viscosity especially at low-shear rates. It is concluded that the reduced size of iron-deficient cells results in increased cell-cell interaction causing an increase in whole-blood viscosity.

Adult↗
PubMed1982

Asynchronous expression of granulocyte membrane receptors in megaloblastic anaemia.

The expression of Fc(IgG) and C3b membrane receptors by granulocytes and their precursors was examined in 23 cases of megaloblastic anaemia which were graded I-III according to morphological severity. Fractionated bone marrow and peripheral blood granulocyte receptors were assessed by rosette formation with optimally sensitized ox erythrocytes and the results compared with those found in 14 normal marrows. Promyelocyte Fc and C3b receptor activities in megaloblastic anaemia did not differ from normal whilst the number of Fc receptor positive myelocytes and later cells showed a significant increase (P less than 0.05 in Grade I, P less than 0.01 in Grades II and III) proportional to the severity of megaloblastosis. An increase in the number of C3b receptor positive granulocytes was seen in early megaloblastic anaemias and, in contrast to Fc receptor expression, showed the highest receptor activities in the Grade II cases. The most significant changes in receptor expression were seen at the metamyelocyte stage and appear to be related to the numbers of these cells found in the megaloblastic marrows. It is suggested that these alterations are primarily related to asynchronous granulocyte maturation and the application of these findings to the study of granulocytic disorders is discussed.

Anemia, Macrocytic↗
PubMed1982

Glucocorticoid binding and cytolethal responsiveness of hairy-cell and chronic lymphocytic leukaemia.

The glucocorticoid binding properties and cytolethal responsiveness of leukaemic cells were studied in vitro in seven patients with hairy-cell leukaemia (HCL) and five with chronic lymphocytic leukaemia (CLL). Substantial levels of glucocorticoid binding were detected both in whole cell and cytosol preparations from all patients although the level of binding by HCL cells always exceeded that of CLL cells (P less than 0.05). In both leukaemic cell types the uptake and binding of prednisolone in vitro was significantly greater than that of dexamethasone (P less than 0.05). CLL cells showed a variable dose-related cytolethal response to methylprednisolone sodium succinate (MPSS) treatment in vitro although cytolytic effects were not marked in the usual pharmacological dose range (10(-5)-10(-6)M). Treatment of CLL patients with conventional doses of prednisone for extended periods or high intravenous infusions of MPSS over shorter periods had no consistent effect on the in-vitro level of steroid binding or the cytolethal responsiveness of CLL cells to glucocorticoid treatment. Although HCL cells proved highly resistant to the cytolethal effects of MPSS in vitro, the substantial binding of glucocorticoids by leukaemic cells from all HCL patients indicates the potential value of steroid therapy in this disease should be explored further.

Administration, Oral↗
PubMed1982

Relation of neutrophil alkaline phosphatase activity to Fc IgG receptor development in human blood and bone marrow.

A possible correlation between Fc-IgG receptor expression and neutrophil alkaline phosphatase (NAP) activity was investigated in relation to maturation of granulocytes in human peripheral blood and bone marrow. NAP activity was studied in bone marrow from patients with normal peripheral blood NAP scores (20-100) and compared with those with high NAP scores. Results indicate that NAP activity is confined to segmented neutrophils (SN) in marrow and peripheral blood except when peripheral NAP activity is abnormally high. There is a normal increase of approximately 60% in mean NAP scores of peripheral blood compared to marrow SN. Granulocyte Fc-IgG receptor activity, known to increase with maturation, was studied in relation to NAP activity. A combined assay using a rosetting technique with ox-erythrocyte (oxE) antibody-IgG and subsequent NAP cytochemistry was used. Receptor expression was found to be virtually complete in normal granulocytic maturation before the appearance of detectable NAP activity. This was supported by findings in chronic myeloid leukaemia where no cases of low Fc receptor activity were found despite NAP scores of less than 5. The significance of these findings is discussed in the light of current concepts of the control of NAP activity.

Alkaline Phosphatase↗
PubMed1982

Erythroid Fc-IgG and complement receptor expression: a study of normoblastic and megaloblastic human bone marrows.

Using a standardized rosetting technique with IgG-coated ox erythrocytes, avid IgG (Fc) receptors were demonstrated on red cell precursors. The proportion of receptor-positive cells in normal marrows was highest in early precursors and appeared to be lost with maturation. In megaloblastosis, the absolute percentage of early precursors increase, but there is an even greater increase in the proportion of receptor-positive cells. It is proposed that this reflects the degree of maturation arrest. The specificity of the receptor was confirmed by inhibition studies with aggregated human IgG. In contrast, the expression of the C3b "immune adherence" receptor, assessed by IgM-C3b-coated ox erythrocytes, was seen to increase with erythroid maturation. Early megaloblasts, especially in severe megaloblastosis, showed a marked decrease in C3b receptor activity, again in proportion to the level of maturation arrest. The significance and possible function of these receptors is discussed.

Anemia, Megaloblastic↗
PubMed1981

Expression of early adenovirus genes requires a viral encoded acidic polypeptide.

Host-range mutants of adenovirus 5 that contain a defect in region E1A (0-4.5 units) fail to replicate in HeLa cells and to transform rodent cells. In HeLa cells, these mutants synthesize only the two RNAs from E1A that share the same 5' and 3' termini but differ in length by the amount of internal sequence removed by splicing. RNA from wild-type virus, selected by hybridization to DNA from region E1A, translates into polypeptides of Mr 51,000 and 48,000 that are highly acidic in isoelectric focusing gels. These acidic Mr 51,000 and Mr 48,000 polypeptides are encoded by the longer and shorter E1A RNAs, respectively. Two of the host-range mutants, H5hr1 and H5hr2, fail to synthesize the Mr 51,000 polypeptide but do produce the Mr 48,000 polypeptide and a novel polypeptide thought to be a truncated portion of the Mr 51,000 polypeptide. H5hr1 and H5hr2 are hypothesized to have termination codons in sequences found only in RNA encoding the Mr 51,000 polypeptide. This prediction is verified for H5hr1 by DNA sequence analysis. The other three host-range mutants (H5hr3-5) synthesize both acidic polypeptides and are predicted to be missense. These results strongly imply that the Mr 51,000 polypeptide, alone or in combination with the Mr 48,000 polypeptide, is needed to regulate expression of adjacent viral genes during the early phase of adenovirus infection.

Adenoviruses, Human↗
PubMed1981

Abnormalities of T-cell subsets in patients with neutropenia and an excess of lymphocytes in the bone marrow.

Morphological, surface-marker and culture studies were performed in three patients who had in common neutropenia and an excess of lymphocytes in the bone marrow, but who differed from each other in certain regards such as age and peripheral lymphocyte numbers. All three patients had an increased proportion of E-rosetting cells bearing Fc receptors for IgG. These cells were shown to be T lymphocytes by staining with monoclonal anti-T-cell sera and their subset phenotype was established as OKT4- OKT8+; in addition, a variable proportion of the cells was Ia+. The functional significance of this expanded subpopulation of T cells was not clear, but it was shown that they did not inhibit colony formation in vitro.

Adult↗
PubMed1980

Translation and developmental regulation of RNA encoded by the eukaryotic transposable element copia.

copia-specific RNA was isolated from Drosophila melanogaster tissue culture cells by hybridization of cytoplasmic polyadenylylated RNA to copia DNA immobilized on cellulose. The purified RNA was translated in reticulocyte lysates. One major polypeptide of approximately 51,000 daltons was synthesized in addition to several others between 18,000 and 38,000 daltons. The 51,000-dalton polypeptide and several of the others are encoded by mRNAs of about 2000 nucleotides. The approximate locations on the copia element of the coding sequences for the 51,000-dalton polypeptide and several other proteins were determined by hybrid-arrested translation with copia restriction fragments. The relative abundance of copia-specific RNA was determined at various stages of the Drosophila life cycle. The level of copia-specific RNA is modulated during development of the organism, with the highest level occurring during the larval stages.

Animals↗
PubMed1980

Platelet production time in surgery.

A study of platelet production time in major surgery is described. This was equated to the time taken for renewal of maximum malondialdehyde (MDA) activity in blood platelets following suppression by a single dose of aspirin (Stuart et al 1975). The method was simplified by using EDTA disodium salt as an anticoagulant instead of citrate, resuspending platelets with small bar magnets, and reducing time of incubation with thiobarbituric acid reagent from 1 h to 15 min. Results for maximum platelet renewal taken to be the time to achieve a pre-aspirin baseline level were median in surgery 6.3 (3.8-9.2) d and controls 7.0 (6.2-12.5) d. Using the modified method, average baseline malondialdehyde (MDA) levels were 6.2 +/- 1.4 nmol/10(9) platelets in surgical patients and 6.34 +/- 1.2 nmol/10(9) platelets in controls. Platelet production time determination using this method is not strictly analogous compared with survival of 51Cr-labelled platelets and it however warrants further study.

Adult↗
PubMed1980

Determination of the identity and organization of messenger RNAs within DNA.

We outline methods for identifying DNAs containing sequences complementary to specific mRNAs, and provide a number of complementary approaches for mapping the arrangement of mRNAs along the DNA. These methods, together with S1 nuclease mapping and the direct visualization of R-loops with the electron microscope, provide a comprehensive approach to defining the architecture of mRNAs coding for specific polypeptides and the arrangement of RNA transcripts along the genome. This detailed cartographic information can then be used to study the steps in the processing of mature mRNAs and determine the modes by which the expression of specific genes is regulated.

DNA↗