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Biomedical subjects

A Kerr

Publications and source records attributed to A Kerr.

At least 37 records · Page 2Linked to original sources
PubMed1987

Transplantation of monoclonal antibody-purged autologous bone marrow for treatment of poor risk common acute lymphoblastic leukemia.

Two murine monoclonal antibodies, FMC-8 and WM-21, reactive with the human leucocyte differentiation antigens CD-9 (p-24) and CD-10 (CALLA), respectively, have been used for purging leukemic cells from remission bone marrow. Nine patients with the common variant of acute lymphoblastic leukemia (c-ALL) in second or subsequent remission underwent bone marrow harvesting. Bone marrow mononuclear cells underwent lytic incubation in vitro with antibodies FMC-8 and WM-21, and rabbit serum as a source of complement, and were then cryopreserved. A mean of 0.90 +/- 0.50 x 10(8) nucleated cells per kilogram of recipient body weight remained after treatment, with 0.38 +/- 0.24 x 10(8) nucleated cells and 8.3 +/- 10.3 x 10(4) CFUGM per kg being recovered on thawing. Seven patients subsequently received marrow-ablative treatment with high dose cyclophosphamide (120 mg/kg) and fractionated total body irradiation (12 Gy), followed by infusion of antibody-purged autologous bone marrow. Three deaths due to sepsis occurred within the first 35 days, compounded in one patient by poor marrow engraftment. All other patients engrafted promptly, and four remain in continuous complete remission at 2, 6, 9, and 28 months after transplantation. The procedure carries a substantial risk of early toxicity, but offers a significant chance of prolonged unmaintained remission to selected patients with poor prognosis acute lymphoblastic leukemia.

Adolescent↗
PubMed1986

Coexpression of p165 myeloid surface antigen and terminal deoxynucleotidyl transferase: a comparison of acute myeloid leukaemia and normal bone marrow cells.

A double immunofluorescence technique, using antibodies to terminal transferase (TdT) and a 165-kilodalton myeloid differentiation antigen (p165), has been used to investigate the phenomenon of TdT expression in cases of acute myeloid leukaemia (AML). Five cases of AML were shown to have significant (18-90%) numbers of leukaemic cells that concurrently expressed both TdT and p165 myeloid surface antigen. Examination of nonleukaemic bone marrow cells showed that the vast majority of normal TdT+ cells are p165 negative. However, in 5 of the 11 samples analyzed, rare cells staining for both p165 and TdT were found. These results suggest that some cases of TdT+ AML may arise from the clonal expansion of rare "biphenotypic" precursor cells existing in normal bone marrow.

Adult↗
PubMed1986

Standardization of monoclonal antibodies for use in autologous bone marrow transplantation for common acute lymphoblastic leukemia.

Two monoclonal antibodies suitable for leukemia cell purging of remission bone marrow from patients with common acute lymphoblastic leukemia (common-ALL) are described. WM-21, reacting with the gp 100 common-ALL associated antigen (CALLA), and FMC-8, reactive with a p24 surface antigen, both bind to the majority of leukemic blast cells from cases of common ALL, and promote complement-mediated lysis of CALLA+ leukemias and cell lines. After initial dye exclusion studies to standardize antibody and rabbit complement concentrations and incubation times, an in vitro plating assay using CALLA+ p24+ cell lines was used to investigate the lytic ability of monoclonal antibody treatment. Incubation with WM-21, FMC-8, and complement produced up to 5 logs inhibition of growth in this system. Under similar conditions, no inhibition of in vitro growth of normal bone marrow myeloid progenitor cells was seen. These antibodies therefore appear to be useful therapeutic reagents for removing residual common ALL blast cells from bone marrow prior to autologous marrow transplantation.

Antibodies, Monoclonal↗
PubMed1986

Characterizing "difficult" acute leukemias. A combined electron microscopic and immunological marker study.

The techniques of transmission electron microscopy (TEM), including ultrastructural myeloperoxidase cytochemistry (MPO), and immunological marker analysis, have been used to classify 58 "difficult" cases of acute leukemia where a precise diagnosis could not be made on the basis of conventional light microscopy and cytochemistry. TEM with MPO proved most valuable in characterizing 15 cases of acute myeloid leukemia and its variants, as well as defining complex cellular subpopulations in 11 cases of chronic myeloid leukemia in blast crisis. Immunological marker studies provided conclusive evidence of lymphoid differentiation in 18 cases of acute lymphoblastic leukemia and related disorders. In addition, the combined techniques were used to document 14 cases of terminal transferase-positive acute myeloid leukemia. This study demonstrates that these 2 techniques provide overlapping and complementary information for accurate diagnosis and classification of morphologically difficult hematological malignancies.

Adolescent↗
PubMed1985

Antigenic phenotype of TdT-positive cells in human peripheral blood.

Double immunofluorescence studies for terminal deoxynucleotidyl transferase (TdT) and leucocyte surface membrane antigens have been used to characterize the small subpopulation of TdT-positive cells in human peripheral blood. The predominant antigens demonstrated were those coded for by the major histocompatibility complex, namely HLA-A,B and Ia-like antigens. A small proportion of TdT+ cells expressed antigens restricted to B lymphocytes and their precursors (BA-1+ CALLA+). In contrast, antigens associated with T-lymphocyte differentiation were not detected using a panel of T-cell-specific monoclonal antibodies. These results preclude the possibility that circulating TdT+ cells are immature cortical thymocytes that have "leaked" into the bloodstream. Although bone marrow-derived prothymocytes, which have not yet acquired T-cell lineage markers, may be included amongst this subset, the expression of B-cell related antigens by some TdT+ cells indicates the likely existence of lineage heterogeneity amongst this population of lymphoid cells. The relevance of these findings to the monitoring of human acute lymphoblastic leukaemia is discussed.

Adult↗
PubMed1985

Immunological detection of covert leukaemic spread in mediastinal T-cell lymphoblastic lymphoma.

A double immunofluorescence assay for terminal transferase (TdT) and surface membrane T-cell differentiation markers, defined by monoclonal antibodies, was used to analyse peripheral blood and bone marrow from patients with mediastinal T-cell lymphoma with clinically localized disease. In 2 patients, at diagnosis and during two subsequent relapses, cells with abnormal immunological phenotype were detected in low numbers in the peripheral blood, which contained no morphologically abnormal cells on any occasion. Bone marrow was uninvolved by immunological criteria on 3 of 4 examinations. The findings suggest that morphologically undectable T-lymphoblasts escape from the site of disease origin in the thymus in patients with lymphoblastic lymphoma, leading to "seeding" of sites such as bone marrow and central nervous system. Furthermore, the techniques described appear to be potentially very useful for the monitoring of lymphoblastic lymphoma patients for early prediction of disease relapse.

Adolescent↗
PubMed1985

Tn5 insertions in the agrocin 84 plasmid: the conjugal nature of pAgK84 and the locations of determinants for transfer and agrocin 84 production.

The kanamycin-resistance transposon Tn5 was randomly introduced into pAgK84, a 47.7-kb plasmid coding for agrocin 84 production in Agrobacterium. Using such marked plasmids, pAgK84 was found to be conjugal. It could be transferred to several Agrobacterium strains including those harboring octopine- or nopaline-type Ti plasmids. Its presence has no effect on Ti plasmid functions such as opine utilization and tumorigenicity, but it does confer agrocin 84 immunity upon previously sensitive strains. The plasmid could also be conjugally transferred to a Nod+ Fix+ strain of Rhizobium meliloti. The production of agrocin 84 is expressed in all Agrobacterium and Rhizobium transconjugants tested. The agrocin plasmid could not be introduced into restrictionless Escherichia coli or Pseudomonas aeruginosa recipients by conjugation or transformation. The sites of 92 independent Tn5 insertions were mapped on pAgK84. These insertions are dispersed over the entire length of the plasmid. Analysis of the sites and effects of the Tn5 insertions has allowed us to construct a functional map of pAgK84. Forty-three of these insertions, spanning a 20-kb segment of the plasmid, abolished or greatly reduced the production of agrocin 84. The presence of two insertions within this segment having an effect on agrocin production suggests that at least three regions of the plasmid are involved in agrocin 84 biosynthesis. Fourteen of the Tn5 insertion derivatives are no longer conjugally transferable. These insertions all map to a single region of the plasmid and define about 3.5-kb as being associated with transfer functions.

Adenine Nucleotides↗
PubMed1985

Myeloid progenitor surface antigen identified by monoclonal antibody.

A mouse monoclonal antibody, WM-15, has been developed which reacts with a human myeloid lineage-restricted cell surface antigen. WM-15, an IgG1 antibody, reacts with a mean of 3.8% of normal bone marrow mononuclear cells, identifying predominantly promyelocytes and myeloblasts, and in fluorescence-activated cell sorting experiments produces enrichment of bone marrow granulocyte-macrophage progenitor cells. Normal mature monocytes and granulocytes are weakly labelled by WM-15, but other haemopoietic cells including erythroblasts and all lymphoid cells are unreactive. The myeloid specificity of this antibody is highlighted by its reactivity with myeloid leukaemia cell lines and 65% of cases of acute myeloid leukaemia, while lymphoid cell lines and leukaemias are WM-15 negative. WM-15 appears to be a useful reagent for further investigation of normal and abnormal myelopoiesis.

Animals↗
PubMed1985

Human myeloid differentiation antigens identified by monoclonal antibodies: expression on leukemic cells.

Six murine monoclonal antibodies reactive with human myeloid lineage differentiation antigens are described. These antibodies, designated WM-12, WM-14, WM-15, WM-16, WM-19, and WM-20, react with normal peripheral blood neutrophils and monocytes, as well as a proportion of myeloid precursor cells in bone marrow, but fail to react with the majority of normal lymphoid cells. Immunoprecipitation studies have demonstrated binding of WM-12, -14, -16, -19, and -20, to elements of a protein multimer with sub-units of 50, 105, and 170 kilodalton molecular weight under reducing conditions. WM-15 antibody, however, reacts with a separate protein of 165 kilodaltons. These 6 antibodies reacted with 89% of cases of acute myeloid leukemia, but showed significant binding with only occasional cases of acute lymphoblastic leukemia. Cases of AML (FAB M1 and M2) were more frequently positive with WM-15 (60% of cases positive) than with the other 5 antibodies, whereas the converse was true for leukemias with monocytic differentiation (FAB M4 and M5; 82-100% of cases positive with WM-12, -14, -16, -19, -20). These antibodies appear useful for diagnosis and classification of acute leukemia.

Antibodies, Monoclonal↗
PubMed1984

Defibrillators in general practice.

After a successful pilot scheme introduced in 1975, when six portable defibrillators were provided for health centres, an additional 50 defibrillators were provided in February 1982 for general practitioners to use. Between December 1975 and February 1984 defibrillation was attempted in 54 patients who collapsed with clinical cardiac arrest in the presence of general practitioners or less than five minutes before their arrival. A cardiac output was achieved in 32 patients, 28 survived to reach hospital via a mobile coronary care unit, and 22 were discharged alive. Of the 28 admitted to hospital, 24 were found to have myocardial infarction. If all general practitioners carried defibrillators they might make an important dent in the early mortality from myocardial infarction in addition to that achieved by a mobile coronary care unit.

Adult↗
PubMed1984

Agrocins and the biological control of crown gall.

Agrocin 84 is a plasmid-encoded, fraudulent adenine nucleotide antibiotic responsible for the preventative biological control of the plant cancer, crown gall. It has bacteriocin-like selectivity which is dependent on a Ti-plasmid-encoded permease in pathogenic agrobacteria. Other nucleotide agrocins have been described and partially characterized; more may be confidently predicted.

Adenine Nucleotides↗
PubMed1983

Distribution of extractable mutagenic activity in steel foundry air particulates of different sizes.

An Andersen 2000 sampler was used to collect different size classes of airborne particulate matter in a large steel foundry. When extracts of these particles were assayed for mutagenicity using the Ames Salmonella/S-9 assay, much of the mutagenic activity was found in particles of respirable size. Furthermore, mutagens requiring activation were distributed among the various size classes roughly in proportion to the total surface area of the particles with the smallest class (less than 1.1 micron) containing by far the largest amount of mutagenic activity. The distribution of direct-acting mutagenic activity was more variable and in some samples the bulk of this activity was in the largest size class (greater than 7.0 micron).

Air Pollutants, Occupational↗
PubMed1983

Expression of terminal deoxynucleotidyl transferase in malignant myeloblasts.

Blast cells from untreated cases of acute leukemia were examined for expression of terminal transferase enzyme (TdT) by immunofluorescence and for myeloid lineage commitment as demonstrated by the presence of myeloperoxidase enzyme at the ultrastructural level. In three cases, an overlapping expression of the "lymphoid-specific" marker TdT was found on peroxidase-positive myeloblasts. These results indicate either the clonal expansion of a rare TdT-positive myeloid precursor or inappropriate expression of TdT by malignant myeloblasts, and further illustrate that TdT expression must be interpreted with caution when distinguishing between lymphoid and myeloid leukemias.

Adult↗
PubMed1983

Two cases of ring chromosome 11.

Two cases of ring chromosome 11 are reported. Both had mental retardation, microcephaly, and short stature. High resolution G banding in case 1 showed no visible loss of chromatin, the karyotype being assessed as 46,XX,r(11) (p15 X 4q2 X 5). In case 2, a Wilm's tumour developed at 8 months and the child died at 18 months. Cytogenetic analysis by Q banding demonstrated minimal chromosome deletion and the karyotype was considered to be 46,XY,r(11) (p15q25).

Abnormalities, Multiple↗