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Biomedical subjects

F Stevenson

Publications and source records attributed to F Stevenson.

24 records · Page 2Linked to original sources

Comparison of two cochlear implant speech processors in better versus poorer performers.

The performance and subjective preferences for two different speech-processing strategies, the Speak strategy in the Cochlear Spectra 22 speech processor and the Multipeak (Mpeak) strategy in the Mini Speech Processor (MSP), are compared within two adult patient groups. Ten experienced cochlear implant (CI) users were selected for this study. One group of 5 CI users have significant open-set speech recognition, and the second group consisted of experienced CI users who have little or no open-set speech recognition on standardized tests (< 30% on sentence tests; < 10% on monosyllabic word tests). While only 4 of the 5 users in each group were available to complete this evaluation, suitable comparisons on the Speak and Mpeak strategies on test performance were possible within each patient group. The performance tests were necessarily different to suit each patient group; however, general trends of test scores and subjective evaluations of each speech processor are compared between these two groups. While the performance scores and subjective ratings consistently favored the Speak strategy in the first group of users, with good open-set speech recognition, the results within the second group were more variable. These findings have significant implications for individual patient and processor selection.

Cochlear Implants↗

Expression of conformationally constrained adhesion peptide in an antibody CDR loop and inhibition of natural killer cell cytotoxic activity by an antibody antigenized with the RGD motif.

We report that an antibody engineered to express three Arg-Gly-Asp (RGD) repeats in the third complementarity-determining region of the heavy chain (antigenized antibody) efficiently inhibits the lysis of human erythroleukemia K-562 cells by natural killer (NK) cells. Synthetic peptides containing RGD did not inhibit. Inhibition was specific for the (RGD)3-containing loop and required simultaneous occupancy of the Fc receptor (CD16) on effector cells. The antigenized antibody inhibited other forms of cytotoxicity mediated by NK cells but not cytotoxicity mediated by major histocompatibility complex-restricted cytotoxic T lymphocytes (CTL). A three-dimensional model of the engineered antibody loop shows the structure and physicochemical characteristics probably required for the ligand activity. The results indicate that an RGD motif is involved in the productive interaction between NK and target cells. Moreover, they show that peptide expression in the hypervariable loops of an antibody molecule is an efficient procedure for stabilizing oligopeptides within a limited spectrum of tertiary structures. This is a new approach towards imparting ligand properties to antibody molecules and can be used to study the biological function and specificity of short peptide motifs, including those involved in cell adhesion.

Amino Acid Sequence↗

Identification of the 9G4 idiotope in systemic lupus erythematosus.

An idiotope designated 9G4 (9G4Id) is known to be a marker for immunoglobulins which utilize a particular VH gene, VH4-21. The idiotope has been found to be present on anti-DNA antibodies, and have been identified in 45% of sera from patients with SLE. This idiotope is strongly associated with lupus being very uncommon amongst the other autoimmune rheumatic diseases tested. This distinction is unlike virtually any of the other DNA antibody idiotypes described which are much more widely distributed. 9G4Id levels were found to fluctuate with disease activity in some lupus patients and this idiotope was detected in 3/11 SLE renal biopsies tested. Its presence is associated with the HLA markers A1 and B8 and raised 9G4Id levels are not simply a reflection of hypergammaglobulinaemia. Thus a new DNA antibody associated idiotope has been identified. Expression of the idiotope indicates that a notable proportion of anti-DNA antibodies have VH segments encoded by the same, or closely related genes, and that these restricted immunoglobulins are involved in the renal pathology found in SLE.

Humans↗

Mesangial cell activation by bacterial endotoxin. Induction of rapid cytoskeletal reorganization and gene expression.

Cultured glomerular mesangial cells (MC) respond to low concentrations of bacterial endotoxin (ET) by secreting prostaglandins and interleukin-1. To evaluate further the nature of ET-induced mesangial cell activation, the authors evaluated the effects of this agent on MC morphology and cytoskeletal organization. Bacterial ET, in concentrations as low as I ng/ml, induced reversible membrane ruffling, cellular rounding, and extension of many filopodia and lamellopodia. Augmented fluid-phase pinocytosis occurred in parallel, as determined by transmission electron microscopy and tritiated sucrose uptake. These cellular morphologic and functional changes were associated with an extensive, but reversible, depolymerization of actin microfilaments. Actin gene expression was also modified by ET. At 4 to 6 hours after ET exposure, Northern blot analysis showed a twofold to fourfold increase in actin mRNA levels. In situ hybridizations of ET-stimulated cells at the light and electron microscopic levels demonstrated a markedly asymmetric distribution of actin mRNA, which was localized in the cellular periphery at filopodial and lamellopodial extensions, presumably sites of new actin protein synthesis. It is concluded that ET effects on MC are distinct from the nonspecific lytic or 'toxic' actions described for other cell types. Endotoxin induces a global activation of this cell type associated with major changes in membrane structure, cytoskeletal organization, and gene expression, which resemble in many respects the responses to peptide mitogens.

Actins↗

Heterogeneity in neoplastic cell populations in chronic lymphocytic leukaemia defined by immunoglobulin expression and secretion in vitro.

Neoplastic cell populations were prepared from peripheral blood and bone marrow samples of four patients with typical B-cell chronic lymphocytic leukaemia (CLL). Lymph node biopsies were also performed and used as a source of neoplastic cells for two of these patients. Using sensitive ELISA systems to determine unstimulated immunoglobulin (Ig) secretion of these tissue-derived populations in culture, a discrepancy between the nature of the secreted Ig products was found. Peripheral blood and lymph node-derived populations from each patient secreted both whole molecules of Ig and a large molar excess of Ig light chains (free LC), whereas all bone marrow-derived population secreted only free LC. The isotypic expression of intrinsic, cell-surface immunoglobulin (sIg), determined using immunofluorescence microscopy and flow cytometry, was, however, indistinguishable between different tissue-derived populations for any one patient. The absolute amounts of LC secretion were not markedly different between the tissue-derived populations (blood = 5.3 +/- 1.7; marrow = 3.5 +/- 1.3; lymph node = 11.5 ng per 2 X 10(7) cells per h) and thus failure of detection could not account for this discrepancy. Furthermore, the presence of sIgM and sIgD on each tissue-derived population indicated that all were at least capable of synthesizing whole Ig for membrane insertion. These results suggest that the assessment of a B-cell function, Ig secretion, is a valuable technique for determining small differences within neoplastic populations from individual patients. These functional differences may be related to the maturity of different cells within clonal populations.

B-Lymphocytes↗