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M A Cooper

Publications and source records attributed to M A Cooper.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cutting edge: IL-15 costimulates the generalized Shwartzman reaction and innate immune IFN-gamma production in vivo.

Sequential administration of LPS to SCID mice results in the generalized Shwartzman reaction, manifesting as rapid mortality via cytokine-induced shock. Here we demonstrate that in vivo neutralization of IL-15 before LPS priming significantly reduced lethality in this reaction (p = 0.0172). We hypothesize that LPS priming induces IL-12 and IL-15 that costimulate NK cell-derived IFN-gamma. Such IFN-gamma may then in turn sensitize macrophages to elicit the Shwartzman reaction following a subsequent LPS challenge. Supporting this, IL-12 and IL-15 synergized to induce murine NK cell IFN-gamma production in vitro. LPS stimulation of SCID mouse splenocytes resulted in measurable IFN-gamma production, which was reduced when IL-15 was neutralized or IL-2/15Rbeta was blocked. Pretreatment with either anti-IL-2/15Rbeta or anti-IL-15 Abs reduced serum IFN-gamma protein following LPS administration to SCID mice. Collectively, these data provide the first in vivo evidence that IL-15 participates in LPS-induced innate immune IFN-gamma production and significantly contributes to the lethal Shwartzman reaction.

Animals↗
PubMed2000

A vesicle capture sensor chip for kinetic analysis of interactions with membrane-bound receptors.

A novel sensor chip for use in surface plasmon resonance (SPR) biosensors has been developed to capture vesicles which may contain membrane-bound receptors. Sulforhodamine-containing vesicles were shown by fluorescence microscopy to be immobilized intact on the sensor chip. Binding of cholera toxin to captured vesicles containing ganglioside GM(1) was demonstrated using SPR, and the derived kinetic and affinity constants were similar to literature values. Biotinylated vesicles captured on the sensor chip were used to bind streptavidin and then biotinylated ss-DNA. The hybridization of complementary ss-DNA to the immobilized ss-DNA was then analyzed using SPR. The values obtained were similar to those obtained for an identical interaction analyzed using a commercially available streptavidin-containing sensor chip. Binding of vancomycin-group antibiotics to captured vesicles containing a bacterial cell wall mucopeptide analogue was demonstrated. No binding of the bacterial endotoxin Cry1A(c) to captured vesicles containing its cell surface receptor could be demonstrated.

Animals↗
PubMed2000

Social grooming in assamese macaques (Macaca assamensis).

Reciprocity and social bonding hypotheses were evaluated as explanations for observed patterns of social grooming in assamese macaques (Macaca assamensis). In accordance with social bonding, females, as the long-term residents of this matrifocal group, groomed each other and juveniles more often than males groomed one another or juveniles. On the other hand, males groomed females more often and for longer durations than females groomed males and, whereas both males and females groomed juveniles more often than juveniles groomed them, juveniles groomed their elders for longer durations. Male grooming of females did not seem directly related to matings as males are single mount ejaculators and use coercive mating tactics. Male grooming of females could not be accounted for in terms of reciprocity; it was not a simple function of dominance. Although both sexes groomed subordinate females more than vice versa, males groomed dominant males more and females groomed subordinate males more than they received grooming from them. Grooming was concluded to function to establish and maintain affiliative social bonds rather than as a specific mechanism to obtain matings or any other specific reciprocation in terms of services or favors.

Age Factors↗
PubMed2000

Binding of vancomycin group antibiotics to D-alanine and D-lactate presenting self-assembled monolayers.

Peptides terminating in -Lys-D-Ala-D-Ala, -Lys-D-Ala-L-Ala and -Lys-D-Ala-D-Lactate were covalently coupled via an N-terminal aminohexanoic acid linker to a self-assembled monolayer of HS(CH2)15CO2H on a thin gold film. Binding of the glycopeptide antibiotics vancomycin and chloroeremomycin to these surfaces was then measured using a surface plasmon resonance biosensor. Both antibiotics bound with micromolar affinity to the D-Ala-terminating surface and with millimolar affinity to the D-Lactate-terminating surface. Increasing density of these covalently attached peptides on the surface had no effect on the resultant affinities of either antibiotic for the surface. In contrast, when the lipid-anchored peptide N-alpha-docosanoyl-epsilon-acetyl-Lys-D-Ala-D-Ala was inserted into a supported lipid monolayer, the affinity of the strongly dimerizing antibiotic chloroeremomycin for the surface showed a dependence on ligand density. This was not the case with the weakly dimerizing antibiotic vancomycin. The lipid monolayer surface, which is a more realistic model of the surface of a bacterium, was thus better suited for the study of the cooperative binding interactions that occur between dimeric glycopeptide antibiotics and surface-bound ligands.

Alanine↗
PubMed2000

Ascites syndrome and related pathologies in feed restricted broilers raised in a hypobaric chamber.

It has been demonstrated that the incidence of ascites can be significantly reduced through feed restriction. This method is thought to have an effect by slowing the growth rate of the birds. Interestingly, when birds are grown in a hypobaric chamber, ascites incidence increases while the overall growth rate of the birds is decreased. Unfortunately, the restriction programs practiced also have a detrimental effect on growth characteristics. An experiment was conducted to determine if the timing and duration of feed restriction can be used to reduce the incidence of ascites for broilers reared under high altitude and local elevation without having a negative impact on growth. A total of 600 commercial broiler males were used. Birds were divided, placing 360 birds in the hypobaric chamber at a simulated 2900 m (9,500 ft) above sea level, and 240 birds were placed at local elevation [390 m (1,300 ft) above sea level]. At each altitude there were four treatments: 1) fully fed controls; 2) feed available for 8 h/d for 6 wk (the duration of the study); 3) feed available for 8 h/d during the first 3 wk, then full feed for the remaining 3 wk; and 4) full feed for the first wk, then 3 wk of 8 h of feed availability, then 2 wk of full feed. Birds and feed were weighed weekly, and mortalities were necropsied to determine the cause of death. At the end of 6 wk, blood samples were taken, and the birds were weighed, necropsied, and scored for ascites, and organ weights were recorded. All feed restriction treatments significantly reduced ascites incidence, when compared with the fully fed controls. Treatment 2 birds were significantly lighter than any other group at both altitudes. The fully fed controls at local elevation were heavier than the fully fed controls at simulated high altitude, as seen in past experiments.

Animals↗
PubMed2000

Potential mechanisms of human natural killer cell expansion in vivo during low-dose IL-2 therapy.

The continuous, in vivo infusion of low-dose IL-2 selectively expands the absolute number of human natural killer (NK) cells after 4-6 weeks of therapy. The mechanism responsible for this expansion is unknown and was examined in this study. NK cells cultured at low concentrations of IL-2, comparable to those found during in vivo therapy, proliferate for 6 days and then exit the cell cycle. However, NK cells in vivo did not traverse the S/G(2)/M phase of the cell cycle during low-dose IL-2 therapy. Low concentrations of IL-2 delay programmed cell death of NK cells but have the same effect on resting T cells that do not expand in vivo. When CD34(+) bone marrow hematopoietic progenitor cells are cultured for 21 days with low concentrations of IL-2, they differentiate into CD56(+)CD3(-) NK cells, not T cells. Thus, the selective expansion of human NK cells during continuous in vivo infusion of low-dose IL-2 likely results from enhanced NK-cell differentiation from bone marrow progenitors, combined with an IL-2-dependent delay in NK-cell death, rather than proliferation of mature NK cells in the periphery.

Animals↗
PubMed2000

National athletic trainers' association position statement: lightning safety for athletics and recreation.

OBJECTIVE: To educate athletic trainers and others about the dangers of lightning, provide lightning-safety guidelines, define safe structures and locations, and advocate prehospital care for lightning-strike victims. BACKGROUND: Lightning may be the most frequently encountered severe-storm hazard endangering physically active people each year. Millions of lightning flashes strike the ground annually in the United States, causing nearly 100 deaths and 400 injuries. Three quarters of all lightning casualties occur between May and September, and nearly four fifths occur between 10:00 AM and 7:00 PM, which coincides with the hours for most athletic or recreational activities. Additionally, lightning casualties from sports and recreational activities have risen alarmingly in recent decades. RECOMMENDATIONS: The National Athletic Trainers' Association recommends a proactive approach to lightning safety, including the implementation of a lightning-safety policy that identifies safe locations for shelter from the lightning hazard. Further components of this policy are monitoring local weather forecasts, designating a weather watcher, and establishing a chain of command. Additionally, a flash-to-bang count of 30 seconds or more should be used as a minimal determinant of when to suspend activities. Waiting 30 minutes or longer after the last flash of lightning or sound of thunder is recommended before athletic or recreational activities are resumed. Lightning- safety strategies include avoiding shelter under trees, avoiding open fields and spaces, and suspending the use of land-line telephones during thunderstorms. Also outlined in this document are the prehospital care guidelines for triaging and treating lightning-strike victims. It is important to evaluate victims quickly for apnea, asystole, hypothermia, shock, fractures, and burns. Cardiopulmonary resuscitation is effective in resuscitating pulseless victims of lightning strike. Maintenance of cardiopulmonary resuscitation and first-aid certification should be required of all persons involved in sports and recreational activities.

Journal Article↗
PubMed1999

Kinetic analysis of antibody-antigen interactions at a supported lipid monolayer.

Modified phospholipids possessing carboxyl head groups synthesized from phosphatidylethanolamine were incorporated into supported lipid monolayers on top of a thin gold film. A monoclonal antibody was chemically coupled to the modified lipids in these monolayers and the kinetics of antigen binding were determined by surface plasmon resonance. The binding could be analyzed using a conventional 1:1 binding algorithm and the derived kinetic and affinity constants were almost identical to those reported for the same interaction on a dextran hydrogel-based sensor chip. When an antigen was chemically coupled to a modified lipid monolayer, the binding of a monoclonal antibody to this surface was biphasic. A two-step algorithm describing the formation of a 1:2 antibody:antigen complex was developed which accurately described the data and enabled differentiation of the two binding steps. The binding was assayed varying both the concentration of antibody in solution and the density of antigen on the surface. The affinities determined by Scatchard analysis of equilibrium binding levels were similar to those values obtained from an ELISA.

Animals↗
PubMed1999

Differential cytokine and chemokine gene expression by human NK cells following activation with IL-18 or IL-15 in combination with IL-12: implications for the innate immune response.

NK cells constitutively express monocyte-derived cytokine (monokine) receptors and secrete cytokines and chemokines following monokine stimulation, and are therefore a critical component of the innate immune response to infection. Here we compared the effects of three monokines (IL-18, IL-15, and IL-12) on human NK cell cytokine and chemokine production. IL-18, IL-15, or IL-12 alone did not stimulate significant cytokine or chemokine production in resting NK cells. The combination of IL-18 and IL-12 induced extremely high amounts of IFN-gamma protein (225 +/- 52 ng/ml) and a 1393 +/- 643-fold increase in IFN-gamma gene expression over those in resting NK cells. IL-15 and IL-12 induced less IFN-gamma protein (24 +/- 10 ng/ml; p < 0.007) and only a 45 +/- 19-fold increase in IFN-gamma gene expression over those in resting NK cells. The CD56bright NK cell subset produced significantly more IFN-gamma following IL-18 and IL-12 compared with CD56dim NK cells (p < 0.008). However, the combination of IL-15 and IL-12 was significantly more potent than that of IL-18 and IL-12 for NK cell production of IL-10, macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta, and TNF-alpha at the protein and transcript levels. Granulocyte-macrophage CSF was optimally induced by IL-15 and IL-18. Resting CD56+ NK cells expressed IL-18R transcript that was up-regulated by IL-12 or IL-15. Our results show that distinct cytokine and chemokine patterns are induced in NK cells in response to different costimulatory signals from these three monokines. This suggests that NK cell cytokine production may be governed in part by the monokine milieu induced during the early proinflammatory response to infection and by the subset of NK cells present at the site of inflammation.

CD56 Antigen↗
PubMed1999

The salt dependence of DNA recognition by NF-kappaB p50: a detailed kinetic analysis of the effects on affinityand specificity.

The binding kinetics of NF-kappaB p50 to the Ig-kappaB site and to a DNA duplex with no specific binding site were determined under varying conditions of potassium chloride concentration using a surface plasmonresonance biosensor. Association and dissociation rate constants were measured enabling calculation of the dissociation constants. Under previously established high affinity buffer conditions, the k a for both sequences was in the order of 10(7) M-1s-1whilst the k d values varied 600-fold in a sequence-dependent manner between 10(-1) and 10(-4 )s-1, suggesting that the selectivity of p50 for different sequences is mediated primarily through sequence-dependent dissociation rates. The calculated K D value for the Ig-kappaB sequence was 16 pM, whilst the K D for the non-specific sequence was 9.9 nM. As the ionic strength increased to levels which are closer to that of the cellular environment, the binding of p50 to the non-specific sequence was abolished whilst the specific affinity dropped to nanomolar levels. From these results, a mechanism is proposed in which p50 binds specific sequences with high affinity whilst binding non-specific sequences weakly enough to allow efficient searching of the DNA.

DNA↗
PubMed1999

Dominance in assamese macaques (Macaca assamensis).

A field study of 64 assamese macaques (Macaca assamensis) was conducted at a temple site in Assam, India. Focal and all occurrence scan techniques were used to collect data on agonistic, grooming, and sexual behavior. More than 1,000 hr of data were summarized into agonistic dominance, grooming, and mounting matrices. Rank hierarchies were constructed for all three and compared. We also directly compared each cell in each matrix with the corresponding cells in the other matrices. A nearly linear agonistic dominance hierarchy was found, but it did not correlate with the directionality of mounting or grooming. Adult males mounted females, generally were dominant to females and groomed females more often than they were groomed by females. Younger males groomed older males and were also generally subordinate to older males. These age and sex effects produced some inter-correlations among grooming, mounting, and dominance but only for specific age-sex classes. Theoretical models of social exchange were not considered useful in predicting the complex patterns of grooming, mounting, and dominance seen in the present group. Whereas such models may "explain" existing data for some groups and have gained widespread acceptance, they must be empirically tested.

Animals↗
PubMed1999

Binding of glycopeptide antibiotics to a model of a vancomycin-resistant bacterium.

BACKGROUND: The vancomycin group of glycopeptide antibiotics is active against a wide range of gram-positive bacteria. The increasing resistance to vancomycin is the result of a change of an amide linkage (D-Ala-D-Ala) to an ester linkage (D-Ala-D-Lactate) in the bacterial cell-wall precursors. RESULTS: We have used a peptide terminating in the sequence -Lys-D-Ala-D-Lactate linked by its amino terminus to a docosanoyl (C22) acyl chain and anchored in a supported lipid monolayer to mimic the surface of vancomycin-resistant enterococci. Surface plasmon resonance analysis was then used to investigate the binding of glycopeptide group antibiotics to this surface. Vancomycin, which dimerises weakly, bound with low affinity, whereas strongly dimerising antibiotics, such as chloroeremomycin, bound with higher affinities. Antibiotics that have attached hydrophobic groups, such as teicoplanin and biphenylchloroeremomycin (LY307599), bound to the lipid monolayer. This resulted in an enhanced affinity for the lipid-anchored peptide at the surface relative to affinities for an analogous non-anchored peptide in solution. CONCLUSIONS: We have shown that the affinities of glycopeptide antibiotics for a model of the surface of a vancomycin-resistant bacterium are enhanced relative to affinities determined in free solution. We have also shown that antibiotics that have membrane anchors bind tightly to the model surface and that this feature is an important determinant of the ability of an antibiotic to kill vancomycin-resistant enterococci.

Anti-Bacterial Agents↗
PubMed1998

Surface plasmon resonance analysis at a supported lipid monolayer.

Methods for the formation of supported lipid monolayers on top of a hydrophobic self assembled monolayer in a surface plasmon resonance instrument are described. Small unilamellar vesicles absorb spontaneously to the surface of the hydrophobic self-assembled monolayer to form a surface which resembles the surface of a cellular membrane. Lipophilic ligands, such as small acylated peptides or glycosylphosphatidylinositol-anchored proteins, were inserted into the absorbed lipid and binding of analytes to these ligands was analysed by surface plasmon resonance. Conditions for the formation of lipid monolayers have been optimised with respect to lipid type, chemical and buffer compatibility, ligand stability and reproducibility.

Anti-Bacterial Agents↗
PubMed1998

Bacillus thuringiensis Cry1Ac toxin interaction with Manduca sexta aminopeptidase N in a model membrane environment.

The Bacillus thuringiensis Cry1Ac delta-endotoxin was shown to bind in a biphasic manner to Manduca sexta aminopeptidase N (APN) present in a novel model membrane. Surface plasmon resonance analysis allowed the quantification of toxin binding to M. sexta APN in a supported lipid monolayer. The initial binding was rapid and reversible, with an affinity constant of 110 nM. The second phase was slower and resulted in an overall affinity constant of 3.0 nM. Reagents used to disrupt protein-protein interactions did not dissociate the toxin after high-affinity binding was attained. The initial association between Cry1Ac and APN was inhibited by the sugar GalNAc, but the higher-affinity state was resistant to GalNAc-induced dissociation. The results suggest that after binding to M. sexta APN, the Cry1Ac toxin undergoes a rate-limiting step leading to a high-affinity state. A site-directed Cry1Ac mutant, N135Q, exhibited a similar initial binding affinity for APN but did not show the second slower phase. This inability to form an irreversible association with the APN-lipid monolayer helps explain the lack of toxicity of this protein towards M. sexta larvae and its deficient membrane-permeabilizing activity on M. sexta midgut brush border membrane vesicles.

Animals↗
PubMed1998

19F NMR in the measurement of binding affinities of chloroeremomycin to model bacterial cell-wall surfaces that mimic VanA and VanB resistance.

BACKGROUND: The emergence of bacteria that are resistant to vancomycin, the drug of choice against methicillin-resistant Staphylococcus aureus, has made the study of the binding characteristics of glycopeptides to biologically relevant depsipeptides important. These depsipeptides, terminating in D-alanyl-D-lactate, mimic the cell-wall precursors of resistant bacteria. RESULTS: The use of 19F-labelled ligands in the study of the therapeutically important vancomycin series of antibiotics is demonstrated. The substantial simplification of spectra that occurs when such labelled ligands are employed is used in the measurement of binding affinities of depsipeptides to chloroeremomycin (CE). Large enhancements of binding affinities are found at a model bacterial cell-wall surface (constituted from depsipeptides that are anchored into vesicles) relative to those measured in free solution. CONCLUSIONS: Surface-enhanced binding, previously shown for strongly dimerizing glycopeptide antibiotics to normal -D-alanyl-D-alanine-terminating cell-wall precursors, is now demonstrated for CE to the surface of models of VanA- and VanB-resistant bacteria. The effect of depsipeptide chain length is shown to be critically important in producing and maximizing this enhancement.

Anti-Bacterial Agents↗