Institution
Public Health Research Institute
Healthcare•
About: Public Health Research Institute is a based out in . It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 4889 authors who have published 8149 publications receiving 276945 citations.
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TL;DR: It is reported that the antidiabetic drug metformin (MET) reduces the intracellular growth of Mycobacterium tuberculosis (Mtb) in an AMPK (adenosine monophosphate–activated protein kinase)–dependent manner, and controls the growth of drug-resistant Mtb strains.
Abstract: The global burden of tuberculosis (TB) morbidity and mortality remains immense. A potential new approach to TB therapy is to augment protective host immune responses. We report that the antidiabetic drug metformin (MET) reduces the intracellular growth of Mycobacterium tuberculosis (Mtb) in an AMPK (adenosine monophosphate-activated protein kinase)-dependent manner. MET controls the growth of drug-resistant Mtb strains, increases production of mitochondrial reactive oxygen species, and facilitates phagosome-lysosome fusion. In Mtb-infected mice, use of MET ameliorated lung pathology, reduced chronic inflammation, and enhanced the specific immune response and the efficacy of conventional TB drugs. Moreover, in two separate human cohorts, MET treatment was associated with improved control of Mtb infection and decreased disease severity. Collectively, these data indicate that MET is a promising candidate host-adjunctive therapy for improving the effective treatment of TB.
389 citations
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TL;DR: It is reported that CA-MRSA strain MW2, which was previously limited to the midwestern United States, has spread to the northeastern United States and has become a health care-associated pathogen.
Abstract: Infections caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) are being increasingly observed in patients who lack traditional risk factors. We described 8 postpartum women who developed skin and soft-tissue infections caused by MRSA at a mean time of 23 days (range, 4-73 days) after delivery. Infections included 4 cases of mastitis (3 of which progressed to breast abscess), a postoperative wound infection, cellulitis, and pustulosis. The outbreak strains were compared with the prototype CA-MRSA strain MW2 and found to be indistinguishable by pulsed-field gel electrophoresis. All were spa type 131, all contained the staphylococcal chromosomal cassette mec type IV, and all expressed Panton-Valentine leukocidin and staphylococcal enterotoxins C and H. The route of transmission was not discovered: the results of surveillance cultures of samples obtained from employees of the hospital, the hospital environment, and newborns were negative for the outbreak strain. We report that MW2, which was previously limited to the midwestern United States, has spread to the northeastern United States and has become a health care-associated pathogen.
384 citations
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TL;DR: A general method for restricting the selection of antibiotic-resistant mutants based on the use of antibiotic concentrations that require cells to obtain 2 concurrent resistance mutations for growth is proposed.
Abstract: Studies with fluoroquinolones have led to a general method for restricting the selection of antibiotic-resistant mutants. The strategy is based on the use of antibiotic concentrations that require cells to obtain 2 concurrent resistance mutations for growth. That concentration has been called the mutant prevention concentration (MPC) because no resistant colony is recovered even when >10 10 cells are plated. Resistant mutants are selected exclusively within a concentration range (mutant selection window) that extends from the point where growth inhibition begins, approximated by the minimal inhibitory concentration, up to the MPC. The dimensions of the mutant selection window can be reduced in a variety of ways, including adjustment of antibiotic structure and dosage regimens. The window can be closed to prevent mutant selection through combination therapy with ≥2 antimicrobial agents if their normalized pharmacokinetic profiles superimpose at concentrations that inhibit growth. Application of these principles could drastically restrict the selection of drug-resistant pathogens.
381 citations
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381 citations
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TL;DR: The results are discussed in terms of a possible mechanism of antibody production in which an RNAse-sensitive substance resulting from the interaction of macrophages and antigen is capable of stimulating antibody synthesis in lymphocytic cells.
Abstract: Neutralizing activity against T2 bacteriophage appeared in cultures of lymph node cells from normal rats in response to their in vitro stimulation with a cell-free filtrate derived from homogenized rat macrophages which had been incubated with T2 bacteriophage. This activity was specifically directed against T2 bacteriophage. It resided in a fraction of the culture fluid which had the salting-out properties of serum globulin. Phage neutralization was inhibited by antibody specific for rat serum gamma globulin. Antibody production against T2 bacteriophage in cultures of lymph node cells from normal animals failed to occur if (a) T2 bacteriophage alone was added, (b) if the incubation period of macrophages and T2 phage was unduly shortened, (c) if the cell-free filtrate was heated at 80–100°C for 15 minutes, (d) if more than an optimal amount of T2 bacteriophage was added to the macrophages. Additional factors which prevented the formation of antibody were the heat inactivation of the lymph node cells or the addition to the culture medium of either streptomycin or ribonuclease. Finally, it was found that macrophages and lymph node cells had to be obtained from animals of one and the same species. All essential findings on the production of antibody to T2 bacteriophage in vitro could be confirmed by substitution of the chick embryo for the tissue culture medium. The results are discussed in terms of a possible mechanism of antibody production in which an RNAse-sensitive substance resulting from the interaction of macrophages and antigen is capable of stimulating antibody synthesis in lymphocytic cells.
380 citations
Authors
Showing all 4916 results
Name | H-index | Papers | Citations |
---|---|---|---|
Dorret I. Boomsma | 176 | 1507 | 136353 |
Brenda W.J.H. Penninx | 170 | 1139 | 119082 |
Michael Snyder | 169 | 840 | 130225 |
Lex M. Bouter | 158 | 767 | 103034 |
David Eisenberg | 156 | 697 | 112460 |
Philip Scheltens | 140 | 1175 | 107312 |
Pim Cuijpers | 136 | 982 | 69370 |
Gonneke Willemsen | 129 | 575 | 76976 |
Britton Chance | 128 | 1112 | 76591 |
Coen D.A. Stehouwer | 122 | 970 | 59701 |
Peter J. Anderson | 120 | 966 | 63635 |
Jouke-Jan Hottenga | 120 | 389 | 63039 |
Eco J. C. de Geus | 119 | 522 | 61085 |
Johannes Brug | 109 | 620 | 44832 |
Paul Lips | 109 | 491 | 50403 |