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Biomedical subjects

M Evans

Publications and source records attributed to M Evans.

At least 271 records · Page 15Linked to original sources
PubMed1990

Specificity and function of monoclonal antibodies reactive with discrete structural elements of bacterial lipopolysaccharide.

We examined the binding and functional activities of monoclonal antibodies (mAbs) reactive with different structural elements of Escherichia coli and Salmonella minnesota LPS. O-side chain-reactive mAbs were highly specific for homologous, smooth LPS, bound avidly to intact bacteria, mediated complement-dependent bactericidal and/or opsonic activity, and protected against live, homologous IP challenges in mice. Core- and lipid A-specific mAbs, on the other hand, were more cross-reactive, although this cross-reactivity was severely restricted by the relative inaccessibility of epitopes in the core/lipid A region. This was reflected in the general inability of these mAbs to react with isolated smooth LPS or wild type bacteria, or to mediate bactericidal or opsonic functions. No LPS-reactive mAbs, regardless of molecular specificity, was able to block LPS- or lipid A-induced TNF production by RAW 264.7 macrophages, thus raising doubts concerning the putative endotoxin-neutralizing properties of mAbs reactive with the core/lipid A complex. Bacterial lipopolysaccharides (LPS) exhibit a complex identity. They represent an essential structural element of the outer membrane of all Gramnegative bacteria (7); they are toxins (5); they mediate a variety of immunomodulatory activities; and they are important bacterial surface antigens (2). In general, LPS macromolecules consist of three genetically, biochemically, and antigenetically distinct regions or domains: the O-side chain, core oligosaccharide, and lipid A moiety (15). Of these three regions, the O-side chain is the most phylogenetically diverse. It also represents the most antigenetically exposed element on isolated or cell-associated, native LPS. The core and lipid A structures, in contrast, are relatively conserved among different bacteria and are less accessible to antibody attack by virtue of overlying sugars contained in the O-side chain or outer core (8). In this study, we investigated selected functional activities of monoclonal antibodies (mAbs) specific for different epitopes within the three major structural domains of Escherichia coli and Salmonella minnesota LPS. The possible endotoxin-neutralizing and antibacterial properties of these mAbs were our particular focus.

Animals↗
PubMed1990

Natural killer cell-mediated lysis of Mycobacterium-avium complex-infected monocytes.

Since the precise mechanism of host responses to infection with Mycobacterium-avium complex (MAC) is unclear and since cytotoxic lymphocytes may be involved in the destruction of cells infected with intracellular pathogens, we investigated the ability of normal peripheral blood lymphocytes to kill MAC-infected monocytes in a short-term isotope release assay. Nylon wool-passed lymphocytes lysed MAC-infected but not uninfected monocytes during a 4-hr assay. Infected monocytes were less sensitive to cell-mediated killing than the standard natural killer (NK) cell-sensitive cell line K562, although the kinetics of lysis were similar. The release of lymphocyte-derived mediators such as tumor necrosis factor, interleukin-2 (IL-2), and interferon-alpha and -gamma could not be implicated as a cause of monocyte death. Through the use of cell-specific monoclonal antibodies plus complement, the phenotype of the effector cell was that of an NK cell (CD3 negative, partially CD8 negative, and CD16 positive). The use of highly purified, negatively selected NK cells confirmed these results. NK cell-mediated lysis of infected monocytes decreased MAC viability, indicating that this cytotoxic activity would not favor dissemination of the organism. The killing of MAC-infected monocytes was reduced by K562 cells, suggesting that these targets shared common recognition/binding structures. These results suggest that NK-cell function may be important in the prevention of or response to MAC infection and may help explain the predilection of AIDS patients to develop widespread disease.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Modulation of suppression of mitogen-induced T cell-dependent B cell responses by natural killer cells.

We examined the ability of human natural killer (NK) cells to modualte pokeweed mitogen (PWM)-induced polyclonal antibody production. Highly purified NK cells inhibited plaque-forming cell (PFC) responses and this suppression could be substantially increased by preincubation of NK cells with the known enhancers of NK cell lytic activity, interferon (IFN)-alpha, IFN-gamma, and interleukin-2. Additionally, costimulation of NK cells with two anti-CD2 antibodies (9-1 and 9.6), which recognize different epitopes on the CD2 molecule, also augmented the inhibitory effect. When subpopulations of NK cells were assayed for suppressor cell activity, this activity was primarily mediated by NK cells bearing Leu-7 but not Leu-2 (CD8) antigens. Thus, alteration of NK cell lytic activity may have significant effects on the immunoregulatory functions of these cells, which may have important implications for the in vivo manipulation of cytotoxic responses.

Antibodies, Monoclonal↗
PubMed1990

Design and testing of external fixator bone screws.

In external fixation, bone screw loosening still presents a major clinical problem. For this study, the design factors influencing the mechanics of the bone-screw interface were analysed and various experimental screws designed with the intention of maximizing the strength and stiffness of the inserted screw. Push-in, pull-out and bending tests were then carried out on the three experimental screws, and on two commercially available screws in both a synthetic material and in cadaveric bone; photoelastic tests on different screw threadforms were also performed. The results of the push-in and pull-out tests indicate that both the screw threadform and cutting head have a significant effect on the holding strength of the screw. The photoelastic tests show that most of the applied load is distributed over the first few threads closest to the load, and that the area between the thread crests is subjected to high shear stresses.

Biomechanical Phenomena↗
PubMed1990

Effects of beta-carotene repletion on beta-carotene absorption, lipid peroxidation, and neutrophil superoxide formation in young men.

The chemopreventive effects of beta-carotene are usually attributed to its antioxidant properties. To determine the effects of beta-carotene supplementation on different parameters of oxidative metabolism, 15 normal young male subjects (18-30 yrs) were placed on a carotenoid-free liquid diet for two weeks prior to entry into the study. Blood was then measured for five carotenoids, retinol, retinyl palmitate, retinol-binding protein, alpha-tocopherol, vitamin C, zinc, lipid peroxides, and neutrophil superoxide production. Absorption tests were performed with 15 mg of beta-carotene to determine absorption curves for each subject. Subjects were then divided into two groups and given either 15 (n = 7) or 120 (n = 8) mg of beta-carotene daily for four weeks along with the same carotenoid-free liquid diet. The absorption test and the blood measurements were repeated. After repletion with beta-carotene, serum lipid peroxide levels decreased in both groups (p less than 0.05), but no other changes were noted in either the neutrophil superoxide production or in the levels of any of the vitamins measured. In contrast to vitamin E, the superoxide scavenging ability of beta-carotene apparently does not contribute to its effects in lowering serum lipid peroxide levels.

Absorption↗
PubMed1990

Death in Denmark.

Does it matter that the hearts of 'brainstem dead' patients may persist in beating spontaneously? Hostile reactions, to the Danish inclusion of cardiac criteria in the determination of death, betray reductionist views of human life at the core of 'brainstem' conceptions of death. Such views (whether centred on neurological function or on abstractions concerning 'personhood') supplant the richness of human life and death with the poverty of essentialism: and mask the lethal nature of beating-heart organ retrieval. The affirmation of cardiac criteria for death is not an alternative form of essentialism as some critics suppose, but part of an understanding of human life and death which rejects essentialism altogether. The spontaneously persistent heartbeat does not constitute human life, but most certainly counts for it.

Advisory Committees↗
PubMed1990

Post-mortem biochemistry of beagle dog lenses after treatment with Fluvastatin (Sandoz) for 2 years at different dose levels.

Post-mortem biochemical analyses of dog lenses and of aqueous humour of a 2 year oral toxicity study in the dog with Fluvastatin (control, 1, 8 and 16 mg/kg/day) did not show any relationship to the observed lens opacities (3 animals out of 8 at 16 mg/kg/day). With respect to lens transparency, a daily dosage of 8 mg/kg/day Fluvastatin to dogs over a period of 2 years is non-cataractogenic. Mean data on lenticular enzyme activities (GPX, G6PH, GAPDH, ALD, AR, LDH, PFK and SDH) as well as measurements of GSH/GSSG, ATP, ADP, AMP, Gluc, Fruc, Sorb, G6P and F6P do not indicate changes which may directly lead to lens opacifications. Conformational changes of lens proteins (heat lability of PFK-activity), a shift in the albumin/IgG ratio of aqueous humour and equatorial lens protein composition changes (after isoelectrofocusing) were observed. The biological significance of these changes is unknown as the non-cataractogenic dose for lens opacities in beagle dogs is 8 mg/kg/day.

Animals↗
PubMed1990

Investiture.

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Career Choice↗
PubMed1990

DNA content as a prognostic factor in endometrial carcinoma.

Two hundred thirty-three cases of endometrial carcinoma were analyzed for DNA content using flow cytometry of cell nuclei extracted from archival paraffin blocks. The median follow-up time for the cases was 8.7 years. Aneuploidy, present in 18% of tumors overall, was associated with adverse histologic type, high grade, and depth of invasion in the uterus. Aneuploidy was not detected in low-grade carcinomas. A DNA index greater than 1.5 strongly predicted death from disease. For endometrial adenocarcinoma and papillary serous carcinoma, this finding appeared independent of stage or tumor grade. The percentage of cells in S phase or G2 + M of the cell cycle did not predict clinical outcome in diploid tumors. Application of DNA analysis to low-stage endometrial cancers of high grade or of papillary serous type may be useful for selecting a subgroup of patients for adjuvant therapy.

Adenocarcinoma↗
PubMed1989

Natural killer cells can enhance the proliferative responses of B lymphocytes.

In addition to lytic activity against malignant and virally transformed target cells, recent evidence has suggested that natural killer (NK) cells can modulate immune activities such as the suppression of B cell responses through noncytotoxic means. Using human B cells and highly purified autologous NK cells, we have demonstrated that NK cells can substantially augment the proliferative responses of B cells stimulated with the surface immunoglobulin crosslinking agents anti-IgM or Staphylococcus aureus Cowan strain I (SAC). This "enhancer" activity of NK cells was quite potent and was observed at an NK:B cell ratio as low as 0.05. Peak blastogenic responses of B cells cocultured with NK cells in the presence of B cell activators were observed at 2-3 days, similar to the responses of B cells in the absence of NK cells. Using the inhibitor of DNA synthesis mitomycin C, we determined that B cells and not NK cells were proliferating in cocultures of these lymphocytes stimulated with SAC. Activated B cells neither prevented the lysis of the isotope-labeled NK-sensitive target cell line K562 nor formed conjugates with NK cells, suggesting that cell contact was not a prerequisite for the effect. These studies have further expanded the functional repertoire of NK cells to include enhancer as well as suppressor and lytic activities.

Antibodies, Anti-Idiotypic↗