The healthy living partnerships to prevent diabetes and the diabetes prevention program: a comparison of year 1 and 2 intervention results.

A number of research studies have attempted to translate the behavioral lifestyle intervention delivered in the Diabetes Prevention Program (DPP). To compare the active interventions of two trials, Diabetes Prevention Program DPP and Healthy Living Partnerships to Prevent Diabetes (HELP PD), after 1 and 2 years of intervention. DPP included 3234 adults with prediabetes randomized to intensive lifestyle intervention, metformin, troglitazone, or placebo.

A Modified Bacillus Calmette-Guérin (BCG) Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence.

Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses.

Mycobacterium tuberculosis RNA Expression Patterns in Sputum Bacteria Indicate Secreted Esx Factors Contributing to Growth are Highly Expressed in Active Disease.

To identify factors contributing to the ability of tubercle bacilli to grow in the lung during active infection, we analyzed RNA expression patterns in bacteria present in patient sputum. Prominent among bacterial transcripts identified were those encoding secreted peptides of the Esat-6 subfamily that includes EsxK and EsxL (Rv1197 and Rv1198). H37Rv esxKL and esxJI transcripts were differentially expressed under different growth conditions, and disruption of these genes altered growth phase kinetics in typical laboratory batch broth cultures.

Decrease in the effectiveness of Bacille Calmette-Guérin vaccine against pulmonary tuberculosis: a consequence of increased immune suppression by microbial antioxidants, not overattenuation.

Mutations that arose in bacille Calmette-Guérin (BCG) daughter strains during decades of in vitro cultivation have long been suspected of reducing the efficacy of the BCG vaccine against pulmonary tuberculosis. Although concern was raised 6 decades ago that BCG had become overattenuated, preferential use of relatively virulent BCG vaccines has not restored efficacy. The recent discovery that as BCG evolved its production of antioxidants increased as a consequence of genomic duplications and other mutations suggests the alternative hypothesis that BCG became better at suppressing oxidant-dependent immune responses.

Monitoring therapeutic efficacy by real-time detection of Mycobacterium tuberculosis mRNA in sputum.

Background: Current laboratory methods for monitoring the response to therapy for tuberculosis (TB) rely on mycobacterial culture. Their clinical usefulness is therefore limited by the slow growth rate of Mycobacterium tuberculosis. Rapid methods to reliably quantify the response to anti-TB drugs are desirable.

Reducing the activity and secretion of microbial antioxidants enhances the immunogenicity of BCG.

Background: In early clinical studies, the live tuberculosis vaccine Mycobacterium bovis BCG exhibited 80% protective efficacy against pulmonary tuberculosis (TB). Although BCG still exhibits reliable protection against TB meningitis and miliary TB in early childhood it has become less reliable in protecting against pulmonary TB. During decades of in vitro cultivation BCG not only lost some genes due to deletions of regions of the chromosome but also underwent gene duplication and other mutations resulting in increased antioxidant production.

Increasing rates of nasal carriage of methicillin-resistant Staphylococcus aureus in healthy children.

Background: Prior studies, including one from our institution performed in 2001, suggest that nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) occurs infrequently in the healthy pediatric population (0.2-2.2%).

Oral quinolones in hospitalized patients: an evaluation of a computerized decision support intervention.

Objective: To determine whether a computerized decision support system could increase the proportion of oral quinolone antibiotic orders placed for hospitalized patients.

Design: Prospective, interrupted time-series analysis.

Setting: University hospital in the south-eastern United States.

Benefits and harms of doxycycline treatment for Gulf War veterans' illnesses: a randomized, double-blind, placebo-controlled trial.

Background: It has been hypothesized that certain Mycoplasma species may cause Gulf War veterans' illnesses (GWVIs), chronic diseases characterized by pain, fatigue, and cognitive symptoms, and that affected patients may benefit from doxycycline treatment.

Objective: To determine whether a 12-month course of doxycycline improves functional status in Gulf War veterans with GWVIs.

Design: A randomized, double-blind, placebo-controlled clinical trial with 12 months of treatment and 6 additional months of follow-up.

p47phox deficiency impairs NF-kappa B activation and host defense in Pseudomonas pneumonia.

We examined the role of redox signaling generated by NADPH oxidase in activation of NF-kappaB and host defense against Pseudomonas aeruginosa pneumonia. Using mice with an NF-kappaB-driven luciferase reporter construct (HIV-LTR/luciferase (HLL)), we found that intratracheal administration of P. aeruginosa resulted in a dose-dependent neutrophilic influx and activation of NF-kappaB.

Inhibition of staphylococcal wound infection and potentiation of antibiotic prophylaxis by a recombinant fragment of the fibronectin-binding protein of Staphylococcus aureus.

Adherence of Staphylococcus aureus to host tissues is a critical step for colonization and initiation of infection. The fibronectin-binding proteins (FnBPs) of S. aureus have been implicated in adherence and internalization in nonprofessional phagocytes.

Iron-cofactored superoxide dismutase inhibits host responses to Mycobacterium tuberculosis.

Superoxide dismutase (SOD) is a ubiquitous metalloenzyme in aerobic organisms that catalyzes the conversion of superoxide anion to hydrogen peroxide. Mycobacterium tuberculosis is unusual in that it secretes large quantities of iron-cofactored SOD. To determine the role of SOD in pathogenesis, we constructed mutants of M.

Naive human T cells develop into Th1 effectors after stimulation with Mycobacterium tuberculosis-infected macrophages or recombinant Ag85 proteins.

Most studies of human T-cell responses in tuberculosis have focused on persons with either active disease or latent infection. Although this work has been critical in defining T-cell correlates of successful versus failed host containment, little is known about the development of Mycobacterium-specific T-cell responses in uninfected persons. To explore this issue, naive T cells from uninfected donors were sensitized in vitro with avirulent Mycobacterium tuberculosis-infected autologous macrophages.

Enhanced production of recombinant Mycobacterium tuberculosis antigens in Escherichia coli by replacement of low-usage codons.

A major obstacle to development of subunit vaccines and diagnostic reagents for tuberculosis is the inability to produce large quantities of these proteins. To test the hypothesis that poor expression of some mycobacterial genes in Escherichia coli is due, in part, to the presence of low-usage E. coli codons, we used site-directed mutagenesis to convert low-usage codons to high-usage codons for the same amino acid in the Mycobacterium tuberculosis genes for antigens 85A and 85B and superoxide dismutase.

Characterization of a chromosomal gene encoding type B beta-lactamase in phage group II isolates of Staphylococcus aureus.

In contrast to most Staphylococcus aureus isolates in which the gene for staphylococcal beta-lactamase (blaZ) is plasmid borne, isolates typeable by group II bacteriophages frequently carry blaZ on the chromosome. Furthermore, the chromosomal gene encodes the type B variant of staphylococcal beta-lactamase for which the nucleotide and deduced amino acid sequences have not yet been reported. To better understand beta-lactamase production among phage group II staphylococci and the nature of the type B beta-lactamase, we determined the type and amount of enzyme produced by 24 phage group II isolates.

Synergism between poly-(1-6)-beta-D-glucopyranosyl-(1-3)-beta-D-glucopyranose glucan and cefazolin in prophylaxis of staphylococcal wound infection in a guinea pig model.

To determine whether the infection-preventing capability of the neutrophil-activating agent poly-(1-6)-beta-D-glucopyranosyl-(1-3)-beta-D-glucopyranose glucan (PGG-glucan) can be enhanced with antibiotic prophylaxis, we administered PGG-glucan and cefazolin, alone and in combination, to guinea pigs inoculated with isolates of staphylococci. Guinea pigs receiving both PGG-glucan and cefazolin had 50% infective doses that were 8- to 20-fold higher than those obtained with cefazolin alone and 100- to 200-fold higher than those obtained with PGG-glucan alone. PGG-glucan and cefazolin are synergistic in their ability to prevent staphylococcal wound infection.

Recombinant expression and characterization of the major beta-lactamase of Mycobacterium tuberculosis.

New antibiotic regimens are needed for the treatment of multidrug-resistant tuberculosis. Mycobacterium tuberculosis has a thick peptidoglycan layer, and the penicillin-binding proteins involved in its biosynthesis are inhibited by clinically relevant concentrations of beta-lactam antibiotics. beta-Lactamase production appears to be the major mechanism by which M.

Prophylactic anti-infective activity of poly-[1-6]-beta-D-glucopyranosyl-[1-3]-beta-D-glucopryanose glucan in a guinea pig model of staphylococcal wound infection.

The judicious use of perioperative antibiotic prophylaxis reduces the infectious complications of surgery. However, increased bacterial resistance within hospitals may make antibiotic prophylaxis less effective in the future and alternative strategies are needed. New immunomodulatory agents might prevent wound infections by stimulation of the host immune system.