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Biomedical subjects

A Brown

Publications and source records attributed to A Brown.

At least 19 recordsLinked to original sources
PubMed2026

Addressing the dual-use of antifungals and fungal antimicrobial resistance (fAMR) through a One Health approach.

Fungal antimicrobial resistance (fAMR) is accelerating, driven in part by the dual-use of antifungal modes of action in agriculture and medicine, threatening therapy. Addressing this challenge requires a unified One Health response that balances agricultural productivity, economic stability, and human and animal health. By focusing on the United Kingdom's policy approach, we argue that current efforts are constrained by fragmented governance, surveillance and regulation. To resolve this, we propose three policy recommendations: 1. a cross-government fAMR body, 2. mandatory environmental and clinical surveillance, and 3. for fungicide approvals to look beyond crop pathogens and integrate risk assessments for potential hotspots of resistance selection in human fungal pathogens. These measures will safeguard current and future antifungals while providing much-needed regulatory clarity and will be translatable to other national and regional contexts.

Journal Article↗
PubMed1979

Effect of ammonia on the glutamate dehydrogenase catalyzed oxidative deamination of L-glutamate. The steady state.

Ammonia is known to inhibit the steady-state rate of oxidation of L-glutamate catalyzed by glutamate dehydrogenase. We reported previously [Brown, A., Colen, A. H., & Fisher, H. F. (1978) Biochemistry 17, 2031] kinetic evidence supporting the formation in the initial rapid phase of a complex which is composed of enzyme, reduced coenzyme, alpha-ketoglutarate, and ammonia. We show here that the effects of ammonia on the steady-state reaction can be correlated with transient-state kinetic effects related to the concentration of that ammonia-containing complex. These results indicate the existence of alternate reaction pathways which become important at high ammonia concentrations. These new pathways provide an additional route for the release of NADPH from the enzyme surface. The expanded mechanism shows that the noncompetitive product inhibition by ammonia can occur without the simultaneous presence of ammonia and L-glutamate on the enzyme. This mechanism also accommodates the observed substrate inhibition by L-glutamate.

Ammonia↗
PubMed1979

Antigen- and receptor-driven regulatory mechanisms. II. Induction of suppressor T cells with idiotype-coupled syngeneic spleen cells.

Anti-p-azobenzenearsonate (ABA) antibodies, coupled covalently to normal syngeneic spleen cells and then given intravenously to normal animals, were found to be potent tolerogens for delayed-type hypersensitivity (DTH) to ABA. The ability of the antibody-coupled cells to induce tolerance was determined to be a result of the cross-reactive idiotype (CRI+) fraction of the antibodies, because anti-ABA antibodies lacking the CRI+ components when coupled to spleen cells were unable to cause any significant inhibition. Furthermore, genetic analysis revealed that the ability of CRI-coupled cells to inhibit ABA-specific DTH is linked to Igh-1 heavy chain allotype, in as much animals which possess heavy chain allotypes similar to that of A/J were sensitive to this inhibition. Adoptive transfer experiments provided evidence that CRI-coupled cells induce suppressor cells, and spleen cells or thymocytes from animals received CRI-coupled cells were able to transfer suppression to naive recipients. In addition, treatment with anti-Thy1.2 serum plus complement completely abrogated their ability to transfer suppression. Thus, this active suppression is a T-cell-dependent phenomenon. In investigating the specificity of these suppressor T cells, it was found that they functioned in an antigen-specific manner and were unable to suppress the development of DTH to an unrelated hapten 2,4-dinitro-1-fluorobenzene.

Animals↗
PubMed1979

Bacteriocin typing of Serratia marcescens. A simplified system.

The authors describe a simplified system for the detection of bacteriocin production by Serratia marcescens with the use of six indicator strains, which include Escherichia coli, Klebsiella pneumoniae, Citrobacter diversus, Enterobacter aerogenes (two strains), and Serratia rubidaea grown on arabinose minimal medium plates. Of the 64 possible bacteriocin types, 11 were observed; 66% of the isolates tested were found to be one of three types. Occasionally more than one bacteriocin type was observed in an individual specimen; however, serotyping or antibiograms, or both, also indicated this was a different strain. The marcescin types were stable markers. With the use of this technic, different endemic strains of Serratia were shown to predominate in various areas of the hospital. In addition, when urinary tract isolates were compared with respiratory tract isolates, significant differences were found in the predominate types. The typing of these isolates by bacteriocin production was supported by serotype and antibiotype findings. The results suggest that this simple system may be a useful tool in a general hospital.

Bacteriocins↗
PubMed1979

Definitive control of bleeding from severe pelvic fractures.

Forty patients with severe pelvic fracture and extraperitoneal hemorrhage were reviewed. Eighteen patients seen prior to 1975 (group I) were clinically similar to 22 patients seen subsequently (group II). Major pelvic fracture hemorrhage was defined as bleeding in excess of 2,000 ml over and above initial resuscitation volumes. Ten of 22 group II patients met the criteria for continued extraperitioneal bleeding and were immobilized in an inflatable G-suit after surgically remediable lesions had been excluded. Ventilator support and hemodynamic monitoring were instituted and clinical response recorded. Prompt cessation of bleeding was observed in nine of ten patients. One patient required selective catheterization of a bleeding artery with subsequent embolic occlusion. Significant reductions in overall mortality and the frequency of shock related death were observed in group II patients. Sepsis was the leading cause of late death in survivors. Immobilization of pelvic fracture patients in the G-suit is recommended as a means of controlling continuing retroperitoneal hemorrhage when surgically correctable bleeding points have been dealt with. Failure of patients to respond promptly to the G-suit strongly suggests arterial bleeding amenable to selective catheterization and embolic occlusion.

Adolescent↗
PubMed1979

Cross protection among togaviruses in nude mice and littermates.

After immunization with Sindbis virus, T-cell deficient nude mice, compared to normal littermates, were equally protected against challenge with Sindbis virus. However, the nude mice showed about one-tenth the protection observed with normal littermates after challenge with Semliki Forest virus at a dose of 100 LD50. This consistent with our previous interpretation that sensitized T-cell populations play a major role in cross protection between the two togaviruses. The remaining low level of specific cross protection in nude mice (detectable only at a challenge dose of 10 LD50) could not be attributed to an anamnestic response of neutralizing antibody to the challenge virus or to an effective antibody-dependent, complement-mediated cytolysis of infected cells in vivo. Other possible compensatory mechanisms to explain the low level of specific cross protection in nude mice are discussed.

Animals↗
PubMed1979

Adoptive transfer of cross-protection among alphaviruses in mice requires allogeneic stimulation.

Cell-mediated (T-effector cell) immunity is proposed as playing the major role in cross-protection between Sindbis and Semliki Forest viruses, which are alphaviruses that do not elicit cross-neutralizing antibodies. In adoptive transfer experiments, T-cells from spleens of Sindbis virus-immunized mice were found to confer specific cross-protection to Semliki Forest virus upon recipient mice. This cross-protection was observed in the outbred ICR strain of mice and when transfers were made between several combinations of inbred and hybrid strains. Cross-protection was substantially reduced if syngeneic rather than allogeneic cell transfers of one spleen equivalent per mouse were made. The results suggest that allogeneic stimulation (mixed lymphocyte reaction in vivo) is necessary to increase the number of effector cells (donor) in the recipient. This was supported by the observation that blastogenic stimulation of donor cells in vitro by concanavalin A induces cross-protection in syngeneic animals. Conversion of recipient cells to specific effector cells also appears to play a role in protecting mice against Semliki Forest virus. This was concluded from the experiments described above, a time course study, and the results of experiments that involved serial passages of transferred cells across histocompatibility barriers. Thus, we propose that both donor and recipient cells are active in protecting recipient mice against challenge with Semliki Forest virus after adoptive transfer.

Animals↗