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L M Henderson

Publications and source records attributed to L M Henderson.

At least 19 recordsLinked to original sources
PubMed1992

The NADPH-oxidase-associated H+ channel is opened by arachidonate.

The H+ channel associated with the generation of O2.- by NADPH oxidase and the oxidase itself must both be activated in response to stimuli (e.g. phorbol esters, chemotactic peptides, certain fatty acids). We have investigated the effects of membrane potential, an imposed pH gradient and a combination of the two (the protonmotive force) on the H+ conductivity of the cytoplast membrane. H+ conductivity was observed only in the presence of arachidonate and not in its absence. In the presence of arachidonate, H+ movement was determined by the protonmotive force. The effect of arachidonate was probably on a channel, since this fatty acid did not significantly increase the H+ permeability of artificial phospholipid membranes. It appears, therefore, that arachidonate is required both for the activation of O2.- production and the associated H(+)-channel-mediated efflux.

Arachidonic Acid↗
PubMed1992

Immunovisualization of high (HK) and low (LK) molecular weight kininogens on isolated human neutrophils.

An immunocytochemical study was performed to examine the cellular localization and the subcellular distribution of kininogens in human blood cells. Kininogens were visualised using the immunogold-silver staining method and confocal scanning laser microscopy. We confirmed the existence of high molecular weight kininogen in human neutrophils and describe for the first time the presence of low molecular weight kininogen on these cells. Both high and low molecular weight kininogens were restricted to the neutrophils where they localized as clusters of immunogold particles on the cell membrane. No labeling was observed intracellularly in organelles such as mitochondria, endoplasmic reticulum, and azurophilic or specific granules after permeabilization of the neutrophils with Triton X-100, a procedure that permitted the visualization of elastase in the azurophilic granules. Clusters of high molecular weight kininogen molecules attached to the neutrophil surface could serve as receptors for plasma kallikrein and/or be the source of substrate for a discrete and circumscribed formation of kinins that may in turn facilitate the local diapedesis of neutrophils and the transudation of plasma constituents during acute inflammation.

Antibodies, Monoclonal↗
PubMed1992

Immunovisualisation of plasma prekallikrein and H-kininogen on human neutrophils and in human hepatocytes.

Both plasma prekallikrein and H-kininogen were immunolocalised in human hepatocytes by the use of immunocytochemical techniques in conjunction with the confocal optical scanning microscopy. In contrast, both proteins were demonstrated on the external surface of human blood neutrophils. However, detection of H-kininogen on non-fixed but not on fixed neutrophils with the anti-domain 6 antibody (directed at the prekallikrein binding site on H-kininogen), suggested that access to the epitope was blocked by the presence of the bound plasma prekallikrein. Therefore, we prepose that H-kininogen provides the binding site for plasma prekallikrein on circulating neutrophils.

Adult↗
PubMed1991

Recombination of pseudorabies virus vaccine strains in swine.

We report here genetic recombination between 2 USDA-licensed vaccine strains of pseudorabies virus co-inoculated into swine. The vaccine strains, one of which was a conventionally attenuated strain and the other, a genetically engineered deleted strain containing a negative immunologic marker, had complementary genomes. Co-inoculation resulted in the creation of novel strains of pseudorabies virus containing negative immunologic markers with restored virulence genes. Plaque-purified recombinant progeny viruses were found in 2 litters of pigs in which both strains were co-inoculated IM, a litter in which both strains were co-inoculated oronasally, and a litter in which the conventionally attenuated strain was inoculated oronasally and the genetically engineered strain was inoculated IM. Recombinant phenotypes and recombinant restriction fragment patterns were observed. The creation, spread, and potential misdiagnosis of these types of recombinant strains could disrupt control and eradication programs that are based on the serologic identification of swine infected with potentially virulent strains of pseudorabies virus.

Animals↗
PubMed1990

Recombination in vivo of pseudorabies vaccine strains to produce new virus strains.

Herpesvirus suis (pseudorabies virus, PRV) has been the focus of intensive genetic engineering efforts and several effective genetically recombinant modified live virus PRV vaccines have resulted. The likelihood and consequences of complementation and/or genetic recombination in vivo between genetically engineered and conventionally derived vaccine strains of PRV are essentially unknown. In this study, two vaccine strains of PRV with complementary gene deletions were co-inoculated into sheep. It reports that avirulent vaccine strains of PRV (genetically engineered and conventionally attenuated) recombined in vivo, resulting in the production of a new and undesirable strain of PRV. The present study exemplifies the need for thorough assessment of genetically engineered micro-organisms in the animal environment.

Animals↗
PubMed1990

Long-term double masked trial of early treatment with L-dopa plus bromocriptine versus L-dopa alone in Parkinson's disease. Interim results.

The quality and duration of control in two groups of parkinsonian patients under treatment with an L-dopa-based drug alone or L-dopa-based drug which has been partially substituted with bromocriptine are being compared over a 5-year period using a double-blind placebo-controlled study design. The aim is to establish whether early addition of bromocriptine will minimise late L-dopa complications. Results are presented after 1 year. Of 31 patients randomised, 13 were treated with combined L-dopa/bromocriptine and 14 with L-dopa/placebo. 4 patients were withdrawn for various reasons. In both groups any dose adjustments were aimed at maintaining the pre-entry clinical condition. In the group receiving bromocriptine combination therapy, progressive reduction of L-dopa was possible without deterioration of the patients' condition. In patients receiving L-dopa alone, the dose of L-dopa at 12 months was almost similar to that recorded on entry to the study. The total number of patients reporting adverse events in the L-dopa/bromocriptine combination and L-dopa alone groups were 8 and 7, respectively. At the present interim stage of the study it is not possible to compare the incidence of L-dopa long-term complications in either group.

Bromocriptine↗
PubMed1990

Superoxide generation by EBV-transformed B lymphocytes. Activation by IL-1 beta, TNF-alpha and receptor independent stimuli.

The generation of superoxide by Epstein-Barr virus (EBV)-transformed human B lymphocytes can be stimulated by a range of compounds; receptor-dependent stimuli include tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and lipopolysaccharides (LPS), and independent stimuli include AlF3, A21387 and ionomycin. The stimuli suggest that the activation pathway for the lymphocyte oxidase is similar to that proposed for the neutrophil oxidase. Although the rate of superoxide production was lower than that by neutrophils, the respiratory burst was much prolonged. It is possible that this superoxide generation by lymphocytes may have a biological function.

B-Lymphocytes↗
PubMed1990

In vivo and in vitro genetic recombination between conventional and gene-deleted vaccine strains of pseudorabies virus.

Pseudorabies virus (PRV), an alpha-herpesvirus, causes substantial economic losses in the swine industry and is currently the focus of eradication and control programs. Some of these programs rely on the ability of veterinarians to differentiate animals exposed to virulent strains of PRV from animals exposed to avirulent vaccine strains of PRV on the basis of a serologic response to nonessential glycoproteins that are deleted in some vaccine strains of PRV. Genetic recombination resulting in the creation of virulent strains of PRV with the same negative immunologic markers as vaccine strains could disrupt these programs. Two strains of PRV were coinoculated either into tissue culture or into sheep to facilitate recombination. Progeny viruses were selected to detect a specific recombinant phenotype. We were able to detect genetic recombination between vaccine strains of PRV following in vitro or in vivo coinoculation of 2 strains of PRV. The selected recombinants had marker-deleted phenotypes in strains with restored virulence genes. Increased virulence was observed in sheep after coinoculation of 2 avirulent vaccine strains of PRV.

Animals↗
PubMed1989

Superoxide generation is inhibited by phospholipase A2 inhibitors. Role for phospholipase A2 in the activation of the NADPH oxidase.

The stimulation of O2.- generation by phorbol 12-myristate 13-acetate (PMA) in human neutrophil-derived cytoplasts was inhibited by a variety of phospholipase A2 inhibitors in a concentration-dependent manner. Inhibition was found to be independent of the order of addition of the inhibitor and PMA. The most potent inhibitor, RO 31-4639, inhibited O2.- generation with an IC50 value (concentration causing 50% inhibition) of 1.5 microM. The addition of either arachidonic acid or SDS, in the presence of the inhibitors, was able to restore O2.- generation. The results suggest that arachidonic acid, released by phospholipase A2, is necessary for both the activation and the maintenance of O2.- generation by the NADPH oxidase.

Acetophenones↗
PubMed1988

Superoxide generation by the electrogenic NADPH oxidase of human neutrophils is limited by the movement of a compensating charge.

The ability of the NADPH oxidase of human neutrophil-derived cytoplasts to generate O2.-anions on the addition of phorbol 12-myristate 13-acetate is severely reduced in the presence of valinomycin and Zn2+ ions. The addition of NH4Cl or carbonyl cyanide m-chlorophenylhydrazone (K+ medium only) to these cytoplasts results in a restoration of O2.- generation. At an elevated pHo CCCP restores a greater rate of O2.- generation. Increasing the concentration of Zn2+ ions reduces the extent of the generation of O2.- on the addition of PMA. The restoration of O2.- generation by NH4Cl or CCCP requires the presence of valinomycin. The restoration of O2.- generation appears to be dependent on the movement of NH4+ ions or the anionic form of the uncoupler across the plasma membrane. The activity of the electrogenic NADPH oxidase of cytoplasts is limited by the movement of an ion to act as a compensator. The NADPH oxidase therefore exhibits respiratory control.

Ammonium Chloride↗
PubMed1988

Internal pH changes associated with the activity of NADPH oxidase of human neutrophils. Further evidence for the presence of an H+ conducting channel.

The internal pH (pHi) of cytoplasts, derived from human neutrophils, falls 0.05 pH units upon activation of the superoxide-generating NADPH oxidase. The decrease in pHi is absent in diphenyleneiodonium-treated cytoplasts and therefore it is likely to arise directly from the activity of the oxidase. The addition of amiloride, to diminish the Na+/H+ exchanger, enhanced the extent of the internal acidification but not the initial rate. However the electroneutral Na+/H+ exchanger cannot be a contributor to H+ efflux to compensate for charge translocated by the oxidase. In the presence of Cd ions or valinomycin, phorbol-induced acidification of the cytosol was greatly increased, suggesting an inability to translocate the cytosolic H+ generated by an electrogenic oxidase. In the presence of both Cd and valinomycin the cytoplasts retained 0.8 H+ per O2-. generated. The rate of acidification of the external medium by stimulated cytoplasts is greatly reduced in the presence of Zn and valinomycin. Our results support the view that the plasma membrane of neutrophils contains Zn2+- or Cd2+-sensitive proton-conducting channels which maintain a stable membrane potential and pHi during the activity of the electrogenic NADPH oxidase.

Cadmium↗