Role of the Phagocyte in Host-Parasite Interactions XXIV. Aldehyde Generation by the Myeloperoxidase-H(2)O(2)-Chloride Antimicrobial System: a Possible In Vivo Mechanism of Action

Myeloperoxidase (MPO), H₂O₂, and chloride ions in the presence of bacteria form aldehydes and are bactericidal. The use of heat-inactivated MPO prevented both killing and aldehyde generation. Decarboxylation and deamination of carboxyl and amino group substrates arising from the bacterial surface may participate in the reaction which yields aldehydes. Bacterial contact was essential for killing. Decarboxylation and bactericidal activities were noted when physiological concentrations of chloride were used. When MPO was replaced with horseradish peroxidase (HPO) in the chloride medium, decarboxylation and bactericidal activities were no longer noted. In contrast, iodide functioned in the antimicrobial system with either MPO or HPO. The iodide concentrations required were at least sixfold greater than circulating blood iodide levels. Moreover, decarboxylation did not occur in the presence of iodide with either enzyme. Thus, both halides function in the MPO-H₂O₂ system but by different mechanisms. It is likely that in vivo under most conditions chloride is the functional halide and that generation of aldehydes is the mechanism responsible for the antimicrobial activity of the MPO-H₂O₂-chloride system.     

In vitro anti-anaerobic activity of the cephalosporin derivative RWJ 54428, compared to seven other compounds

Agar dilution MIC was used to test the activity of RWJ 54428, a new cephalosporin derivative, compared to imipenem, meropenem, ceftriaxone, piperacillin, piperacillin–tazobactam, clindamycin and metronidazole against 363 anaerobes isolated from clinical specimens. RWJ 54428 had low MICs against most β -lactamase-negative Gram-negative rods, and all Gram-positive strains except Clostridium difficile . Imipenem and meropenem had the lowest MICs (MIC₅₀s of 0.125 mg/L and MIC₉₀s of 1.0 mg/L). Piperacillin–tazobactam, clindamycin and metronidazole were active against most strains, and ceftriaxone was active mainly against β -lactamase-negative organisms.     

Cholesterol screening in general practice

Serum cholesterol levels were measured in 250 men and 250 women aged 25-60 years attending a general practice. Seventy three per cent of the sample had levels above 5.2 mM and of these 98 patients agreed to follow a low cholesterol/low saturated fat diet for six months. The overall reduction in serum cholesterol level among these patients was 13%, suggesting that lipid screening in general practice could be worthwhile.     

Virtual patient simulator for distributed collaborative medical education

Project TOUCH (Telehealth Outreach for Unified Community Health; http://hsc.unm.edu/touch) investigates the feasibility of using advanced technologies to enhance education in an innovative problem-based learning format currently being used in medical school curricula, applying specific clinical case models, and deploying to remote sites/workstations. The University of New Mexico's School of Medicine and the John A. Burns School of Medicine at the University of Hawai'i face similar health care challenges in providing and delivering services and training to remote and rural areas. Recognizing that health care needs are local and require local solutions, both states are committed to improving health care delivery to their unique populations by sharing information and experiences through emerging telehealth technologies by using high-performance computing and communications resources. The purpose of this study is to describe the deployment of a problem-based learning case distributed over the National Computational Science Alliance's Access Grid. Emphasis is placed on the underlying technical components of the TOUCH project, including the virtual reality development tool Flatland, the artificial intelligence-based simulation engine, the Access Grid, high-performance computing platforms, and the software that connects them all. In addition, educational and technical challenges for Project TOUCH are identified.     

Interleukin-1 beta regulation of islet and thyroid autoimmunity in the BB rat.

Daily injections of high dose human recombinant interleukin-1 beta (IL-1 beta) accelerated the onset of both insulin-dependent diabetes mellitus and lymphocytic thyroiditis in genetically prone BB rats. In diabetes-resistant BB rats, high dose IL-1 beta failed to induce diabetes. Additionally, the presence of neutralizing IL-1 beta antibodies in these rats strongly correlated with inhibition of lymphocytic thyroiditis. Since low dose IL-1 beta protects diabetes-prone rats from IDDM, we conclude that IL-1 beta is a potent modulator of autoimmune diabetes and thyroid disease in genetically susceptible rats.     

Human mtDNA sublimons resemble rearranged mitochondrial genoms found in pathological states

Sublimons, originally identified in plant mitochondria, are defined as rearranged mtDNA molecules present at very low levels. We have analysed the primary structures of sublimons found in human cells and tissues and estimated their abundance. Each tissue of a given individual contains a wide range of different sublimons and the most abundant species differ between tissues in a substantially systematic manner. Sublimons are undetectable in rho(0) cells, indicating that they are bona fide derivatives of mtDNA. They are most prominent in post-mitotic tissue subject to oxidative stress. Rearrangement break-points, often defined by short direct repeats, are scattered, but hotspot regions are clearly identifiable, notably near the end of the D-loop. The region between the replication origins is therefore frequently eliminated. One other hotspot region is located adjacent to a known site of protein binding, suggesting that recombination may be facilitated by protein-protein interactions. For a given primary rearrangement, both deleted and partially duplicated species can be detected. Although each sublimon is typically present at a low level, at most a few copies per cell, sublimon abundance in a given tissue can vary over three orders of magnitude between healthy individuals. Collectively, therefore, they can represent a non-negligible fraction of total mtDNA. Their structures are very similar to those of the rearranged molecules found in pathological states, such as adPEO and MNGIE; therefore, we propose that, as in plants, human mtDNA sublimons represent a pool of variant molecules that can become amplified under pathological conditions, thus contributing to cellular dysfunction.     

An MMPI sign to separate organic from functional psychiatric patients

Evaluated the utilities of all 90 possible unweighted additive/subtractive two-scale MMPI combinations as indices to separate brain-damaged from functional patient groups in a Veterans Administration psychiatric hospital. One index, Hs-PT, showed more promise than any of the other 89. Hs-PT mean scores were significantly higher among organics than among alcoholics, neurotics, affective psychoses, character disorders, process schizophrenics or reactive schizophrenics. Interpretative information on the Hs-PT index was presented.