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Biomedical subjects

B E Roberts

Publications and source records attributed to B E Roberts.

At least 55 records · Page 3Linked to original sources

Serum enzyme and ferritin concentrations in acute leukaemia.

Serum ferritin concentrations were determined in 142 untreated cases of acute leukaemia. No correlation between type of leukaemia as defined by morphology and immunology and the level of serum ferritin was found. Samples were also tested for lactate dehydrogenase (LDH), phosphohexose isomerase (PHI), B-glucuronidase (B-gluc), leucine aminopeptidase (LAP), and C-reactive protein (CRP) levels. Serum ferritin was significantly correlated with serum PHI, LAP, and LDH concentrations but not with leukaemic mass as assessed by total white blood cell count (WBC). Ferritin and CRP levels were also significantly correlated suggesting that ferritin may behave to some extent like an acute phase reactant in acute leukaemia.

Enzymes↗

Prolymphocytoid transformation of CLL: a clinical and immunological study of 22 cases.

The clinical, morphological and immunological features of 22 cases of chronic lymphocytic leukaemia in 'prolymphocytoid' transformation (CLL-Pro) are reported. Immunophenotypic patterns in CLL-Pro differ from CLL by the appearance of significant (greater than 15%) FMC7-positive components and/or increased SIg densities in most cases. Membrane TU1 and MRBC receptor expression was similar to that found in typical CLL. Morphologically, all cases showed a mixture of small lymphocytes and larger nucleolated 'prolymphocytes' although the degree of prolymphocytoid change was unrelated to immunological patterns. Clinically, the cases behaved in a very heterogeneous fashion, with some patients dying rapidly following transformation despite treatment, while others even if untreated had a long, stable and relatively benign course. It was not possible to predict which patients would do badly from immunological or morphological features but the presence of more than one involved lymph node site and the occurrence of B-symptoms appeared to identify a group that did badly. Immunological assessments were however important in therapeutic terms, drawing distinction between CLL-Pro variants and prolymphocytic leukaemia (PLL).

Humans↗

Myelodysplastic syndrome coexisting with acute lymphoblastic leukaemia.

A 55 year old woman developed chronic myelomonocytic leukaemia (CMML) one year after she had been successfully treated for acute lymphoblastic leukaemia (ALL). When the ALL relapsed the CMML remitted only to return with further remission of the ALL. A consistent chromosomal abnormality, t(4;11), was present during both CMML and ALL phases.

Chromosome Aberrations↗

Association between Bell's palsy and lymphoid malignancies.

Eight cases of lymphoid malignancy preceded by Bell's palsy are reported. There was a disproportionate number of ALL cases, two of which were of T-cell type. The possible pathogenic association of these conditions is discussed.

Facial Paralysis↗

Cytochemical, immunological and ANAE-isoenzyme studies in acute myelomonocytic leukaemia: a study of 39 cases.

This study reports the cytochemical, electrophoretic and immunological characteristics of blasts cells from 39 cases of acute myelomonocytic leukaemia (M4). The results indicate considerable cytochemical heterogeneity, particularly with respect to esterase (alpha naphthyl acetate and chloroacetate) activities and suggest that an increased serum lysozyme concentration is a more consistent feature. Investigations with a range of monoclonal antibodies also revealed some differences in expression of monocyte-associated determinants although it is considered that immunological assessments are more consistent than cytochemistry in the detection of monocytic blast cell components. Analysis of ANAE isoenzymes by isoelectric focusing was found to be of particular value in cases where interpretation of ANAE cytochemistry was difficult.

Antibodies, Monoclonal↗

E1a regions of the human adenoviruses and of the highly oncogenic simian adenovirus 7 are closely related.

Simian adenovirus 7 (SA7) is a highly oncogenic virus, capable of causing tumors in hamsters upon the direct injection of viral DNA. We determined the transcriptional organization of the transforming region and compared it with that of the human adenoviruses. This analysis demonstrated that there are two independently promoted transcription units similar to the E1a and E1b regions of the human adenoviruses. The nucleotide sequence of the SA7 E1a region demonstrated considerable homology with the human adenoviruses, both in the sequences that regulate E1a expression and in the encoded polypeptides. The amino acid homology was reflected in the ability of SA7 to complement the growth of human adenoviruses mutant in the E1a region. Furthermore, we found two regions of amino acid homology unique to SA7 and the highly oncogenic human adenovirus 12.

Adenoviridae↗

Individual adenovirus type 5 early region 1A gene products elicit distinct alterations of cellular morphology and gene expression.

Adenovirus early region 1A (E1A), which gives rise to three overlapping transcripts, was inserted into a murine leukemia virus-derived vector, and recombinant viruses were used to prepare permanent cell lines of NIH 3T3 cells containing DNA copies of the individual 13S, 12S, and 9S mRNAs. Integrated proviral copies of the recombinant genomes were rescued as bacterial plasmids from each of the cell lines, and the DNA sequence of E1A was demonstrated to be a precise copy of the individual transcripts. The DNA copies were shown to be expressed as part of the full-length retroviral transcript by S1 nuclease analysis, and the synthesis of their encoded polypeptides was demonstrated by immunoprecipitation. Those cell lines expressing the polypeptide encoded by the 13S transcript were shown to contain that function required for regulating the accumulation of mRNAs from adenovirus early genes by their ability to complement the adenovirus type 5 E1A deletion mutant dl312. Cell lines expressing polypeptides encoded by the 13S, 12S, and 9S transcripts showed characteristic alterations in morphology. Two-dimensional gel electrophoresis of total cellular protein derived from the three cell lines demonstrated that each E1A gene product elicits specific alterations in the patterns of proteins expressed. Studies of the expression of two specific genes, those encoding fibronectin and collagen type 1, indicated that the observed alteration in levels of the two proteins results from a reduction in RNA levels induced by E1A functions.

Adenoviruses, Human↗

Biphenotypic leukaemia: a case of mixed T lymphoblastic and myeloblastic leukaemia.

A case of mixed acute leukaemia with T lymphoblastic, myeloblastic, and monocytic components is described. The use of immunological markers, ultrastructural morphology, cytochemistry, immunochemistry, and combined techniques, simultaneously detecting two markers in individual cells, made it possible to define the different blast cell populations.

Aged↗

Membrane phenotypic studies in B cell lymphoproliferative disorders.

A total of 398 cases of B cell lymphoproliferative disease were phenotypically characterised by membrane mouse red blood cell (MRBC) receptor, surface immunoglobulin, common acute lymphoblastic leukaemia (CALLA), and FMC7 and T1 monoclonal antibody studies. Relations between chronic lymphocytic leukaemia (CLL), prolymphocytic leukaemia (PLL), and "prolymphocytoid" CLL variants were examined with particular reference to the expression of FMC7. In addition, the reactivity of TU1 monoclonal antibody with B cell disorders was established. The results suggest that despite some heterogeneity most cases may be characterised by their phenotypic patterns and that these investigations provide a reproducible basis for classification.

Antibodies, Monoclonal↗

Prednisolone levels in plasma and leukemia cells during therapy of chronic lymphocytic leukemia.

The capacity of chronic lymphocytic leukemia cells to concentrate prednisolone has been evaluated in vivo and in vitro employing a radioimmunoassay for prednisolone. No evidence to suggest that leukemia cells are capable of selectively concentrating glucocorticoid was found. The relative uptake of glucocorticoid by leukemia cells was found to be greater in vitro than in vivo. This may be attributable to differences in steroid bioavailability to cells. Substantially lower levels than previously reported of free prednisolone were found in plasma of patients receiving oral treatment with prednisolone. This may result from the failure in previous studies to remove derivatives of prednisolone and other steroids prior to assay for hormones.

Humans↗

Cytochemical and electrophoretic characterisation of alpha naphthyl acetate esterases (ANAE) in acute myeloblastic leukaemia.

The alpha naphthyl acetate esterase (ANAE) cytochemical staining patterns were examined in 40 cases of acute myeloblastic leukaemia (AML: FAB groups M1 and M2) classified by morphological and immunological criteria. The blast cells in most cases (62%) were ANAE-negative with the remainder showing diffuse, granular or focal reactions of varying intensity. The nature of cytoplasmic ANAE enzymes was further characterised in 20 cases by isoelectrophoretic analysis of ANAE isoenzymes. The results suggest that the presence of significant cytoplasmic ANAE reactivity in leukaemic myeloblasts is not due to the presence of monocyte-associated isoenzymes, in otherwise well-defined myeloblasts, but may reflect abnormally increased synthesis or atypical localisation of normally-occurring ANAE isoenzymes. In particular, the results of this study indicate the lack of discriminatory value of ANAE cytochemistry in the differentiation of AML from other acute leukaemias of non-monocytic type.

Histocytochemistry↗

Construction and applications of a highly transmissible murine retrovirus shuttle vector.

We develop a murine retrovirus shuttle vector system for the efficient introduction of selectable and nonselectable DNA sequences into mammalian cells and recovery of the inserted sequences as molecular clones. Three protocols allow rapid recovery of vector DNA sequences from mammalian cells. Two of the methods rely on SV40 T-antigen-mediated replication of the vector sequences and yield thousands of bacterial transformants per 5 X 10(6) mammalian cells. The majority of plasmids recovered by all three protocols exhibited the proper structure and were as active as the parental vector in the generation of transmissible retrovirus genomes upon transfection of mammalian cells. One of the rescue methods, which relies on "onion skin" replication and excision of an integrated provirus from the host chromosome, enables facile recovery of the chromosomal site of proviral integration. The system was also used to generate, and then efficiently recover, a cDNA version of a genomic insert from the adenovirus E1A region.

Cell Transformation, Viral↗

Aetiologic factors in lymphoid malignancies: a case-control epidemiological study.

A prospective case-control study of the aetiologic factors involved in the production of lymphoid malignancies has been conducted within a defined geographical area covering six health districts in the Yorkshire Region. Among the aspects investigated were past medical events, occupations and certain social factors. A number of possible causal relationships have been identified including Jewish religion, past solvent exposure and ingestion of amphetamines, although the latter did not achieve statistical significance in this study. In addition several new associations have been identified, most notably with the occurrence of adult eczema/dermatitis and with treatment by radiation or steroids. The feasibility of conducting such a broadly based epidemiological investigation has been established.

Adrenal Cortex Hormones↗

Identification and mapping of polypeptides encoded by the P3HR-1 strain of Epstein-Barr virus.

The Epstein-Barr virus (EBV)-specified polypeptides induced upon viral replication in the P3HR-1 cell line have been examined by immunoprecipitation with a high-titer human anti-EBV serum. Twenty-five predominant polypeptides were identified in cell extracts, whereas 18 polypeptides were precipitated from cell-free translation reactions directed by total mRNA. Hybrid selection of mRNA to the BamHI DNA clones of the EBV genome and immunoprecipitation of the corresponding cell-free translation products revealed 98 EBV-specified polypeptides and their coding location along the viral genome. In addition, the viral polypeptides that bind reversibly to DNA-cellulose have been characterized and the deduced map locations of this functional group of EBV-specified polypeptides is presented.

Cell Line↗

Cytochemical and immunological characteristics of acute monocytic leukaemia.

Immunological and cytochemical findings are presented from 12 cases of morphologically unequivocal acute monocytic leukaemia (AMoL). The results indicate considerable heterogeneity and three main non-morphological subgroups were identified. The blast cells from half the patients were positive for the presence of both cytoplasmic alpha naphthyl acetate esterase (ANAE) and monocyte-associated membrane determinants whereas the cells from three cases lacked detectable monocytic antigens despite the presence of strong cytochemical ANAE activity. A further three cases expressed monocytic antigens but were cytochemically unreactive for ANAE. These cytochemical results, which were extended by electrophoretic studies of ANAE isoenzymes, suggest that the absence of significant cytoplasmic ANAE activity does not preclude the diagnosis of AMoL and that serum lysozyme estimations may be of value in the recognition of immunocytochemically-atypical cases.

Adult↗

The myelodysplastic syndromes--a study of haemostatic function and platelet ultrastructure.

The myelodysplastic syndromes (MDS) are characterised by dysplastic marrow and cytopenia. Clinically detectable bleeding is uncommon and usually attributed to thrombocytopenia. We have investigated some aspects of haemostatic function in 17 patients with MDS and compared the results with findings from 17 control patients matched for age and sex. No specific disorder of blood coagulation or fibrinolysis was identified. The main abnormalities observed in the patients were: prolongation of the bleeding time which was greater than could be explained on the basis of thrombocytopenia in 13 patients; absent, or severely impaired platelet aggregation in response to collagen in 7 patients; impaired platelet production of malondialydehyde when stimulated with collagen and abnormal release of 14C-5 hydroxytryptamine in 5 patients; and abnormalities of ultrastructure in all 5 patients whose platelets were viewed by electron microscopy.

Aged↗