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Reduced Susceptibility (reduced + susceptibility)
Selected AbstractsAssociation of aldose reductase gene Z+2 polymorphism with reduced susceptibility to diabetic nephropathy in Caucasian Type 1 diabetic patientsDIABETIC MEDICINE, Issue 8 2004M. Lajer Abstract Aims The Z,2 allele of the (AC)n polymorphism in the aldose reductase gene (ALR2) confers increased risk of microvascular diabetic complications, whereas the Z+2 allele has been proposed to be a marker of protection. However data are conflicting. Therefore, we investigated whether this polymorphism is associated with diabetic nephropathy and retinopathy in Type 1 diabetes mellitus in a large case,control study and a family-based analysis. Methods A total of 431 Type 1 diabetic patients with diabetic nephropathy and 468 patients with longstanding Type 1 diabetes and persistent normoalbuminuria were genotyped for the case,control study. In addition, 102 case trios and 98 control trios were genotyped for a family-based study. Results Thirteen different alleles were identified. In the case,control study, the Z+2 allele frequency was significantly higher in the normoalbuminuric diabetic than in patients with diabetic nephropathy (0.17 vs. 0.11, P = 0.008), suggesting a protective function of the Z+2 allele. No significant increase in the frequency of the putative risk allele Z,2 was found in patients with diabetic nephropathy vs. controls (0.39 vs. 0.36). No association with diabetic retinopathy was found. Although the results of the transmission of the Z,2 and Z+2 alleles in the independent family-based study were consistent with the association study, the number of informative families was limited and thus differences were not statistically significant. Conclusions The Z+2 allele of the ALR2 promoter polymorphism is associated with a reduced susceptibility to diabetic nephropathy in Danish Type 1 diabetic patients, suggesting a minor role for the polyol pathway in the pathogenesis of diabetic kidney disease. No association of the ALR2 polymorphism with diabetic retinopathy was found. [source] Dental plaque: biological significance of a biofilm and community life-styleJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 2005P. D. Marsh Abstract Background: Most microorganisms in nature attach to surfaces and form matrix-embedded biofilms. Biofilms are highly structured and spatially organized, and are often composed of consortia of interacting microorganisms, termed microbial communities, the properties of which are more than the sum of the component species. Microbial gene expression alters markedly in biofilms; organisms communicate by gene transfer and by secretion of diffusible signalling molecules. Cells in biofilms are less susceptible to antimicrobial agents. Aim and Materials & Methods: To comprehensively review the literature to determine whether dental plaque displays properties consistent with those of a typical biofilm and microbial community. Results: Novel microscopic and molecular techniques have demonstrated that plaque has a structured architecture with an extracellular matrix, and a diverse composition (around 50% of cells are unculturable). The constituent species communicate by gene transfer, by secreted peptides (Gram-positive bacteria) and autoinducer-2 (Gram-positive and Gram-negative bacteria). These organisms are functionally organized for increased metabolic efficiency, greater resistance to stress and for enhanced virulence. Plaque formation has direct and indirect effects on gene expression. Conclusion: Dental plaque displays properties that are typical of biofilms and microbial communities in general, a clinical consequence of which is a reduced susceptibility to antimicrobial agents as well as pathogenic synergism. [source] Bacterial enteritis and the development of the larval digestive tract in olive flounder, Paralichthys olivaceus (Temminck & Schlegel)JOURNAL OF FISH DISEASES, Issue 9 2004D-H Kim Abstract Three bacterial isolates obtained from diseased olive flounder larvae, Paralichthys olivaceus, were identified as Vibrio ichthyoenteri based on the results of phenotypic characterization and 16S rRNA gene sequencing studies. Bacterial enteritis was reproduced in 16 and 22 days post-hatch (dph) larvae by administering brine shrimp nauplii, Artemia salina, dosed with the environmental isolates and reference strains of V. ichthyoenteri. To investigate the effect of the disease on development of the stomach, a pepsin activity assay and reverse transcription-polymerase chain reaction (RT-PCR) analysis of the expression of the pepsinogen gene were performed. Expression of olive flounder pepsinogen was detected from 30-dph larvae and the increased level of pepsin activity coincided with reduced susceptibility to the disease. Growth rates of V. ichthyoenteri, V. anguillarum and Edwardsiella tarda were tested in artificial stomach conditions using HCl and porcine pepsin. All the strains of V. ichthyoenteri were inhibited by low pH conditions which corresponded with an increase in pepsin levels. This suggests that differentiation of the stomach in olive flounder larvae and juveniles, an essential physiological development, also provides the host with a non-immunological defence mechanism. [source] Impact of unreported HIV-1 reverse transcriptase mutations on phenotypic resistance to nucleoside and non-nucleoside inhibitorsJOURNAL OF MEDICAL VIROLOGY, Issue 1 2006A. Saracino Abstract An extended spectrum of HIV-1 reverse-transcriptase (RT) mutations in HAART-treated patients has been recently described. To verify the possible association of previously unreported RT mutations with a decrease of phenotypic susceptibility to nucleoside (NRTIs) and non-nucleoside (NNRTIs) RT inhibitors, the RT sequence of 328 HIV-1-positive patients (102 naïve and 226 treated with HAART participating in either the PhenGen or Genpherex study) was analyzed. All treated patients were tested at the time of therapeutic failure with both phenotypic (Antivirogram®, Virco) and genotypic analyses (VircoGenÔ); the frequency of RT substitutions (positions 1,240) with respect to consensus B was compared to that of naïve patients using a Chi-square test. Amino acid changes at 13 positions not included in the IAS list of resistance-associated mutations were detected more frequently in treated than in naïve subjects. The mutations involving 10 of these positions were associated with a reduced susceptibility to antiretroviral drugs; K20R, T39A, K43EQN, E203KD, H208Y, and D218E were correlated with NRTI resistance while mutations K101EQP, H221Y, K223EQ, L228HR were associated to NNRTI resistance. A correlation was found between K20R and lamivudine resistance (P,=,0.006) while T39A (P,=,0.005), K43EQN (<0.001), E203KD (P,=,0.010), and H208Y (P,=, <,0.001) seemed to be associated with a previous use of zidovudine and stavudine and with the development of thymidine analog resistance. For H208Y, an association with use/resistance to abacavir (P,=,0.004) was also noted. D218E showed a weak association to didanosine resistance (P,=,0.013). The data confirm that previously unreported mutations are associated with antiretroviral drug experience and, more importantly, with a reduced susceptibility to NRTIs and NNRTIs. J. Med. Virol. 78:9,17, 2006. © 2005 Wiley-Liss, inc. [source] Barrier requirements as the evolutionary "driver" of epidermal pigmentation in humansAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 4 2010Peter M. Elias Current explanations for the development of epidermal pigmentation during human evolution are not tenable as stand-alone hypotheses. Accordingly, we assessed instead whether xeric- and UV-B-induced stress to the epidermal permeability barrier, critical to survival in a terrestrial environment, could have "driven" the development of epidermal pigmentation. (1) Megadroughts prevailed in central Africa when hominids expanded into open savannahs [,1.5,0.8 million years ago], resulting in sustained exposure to both extreme aridity and erythemogenic UV-B, correlating with genetic evidence that pigment developed ,1.2 million years ago. (2) Pigmented skin is endowed with enhanced permeability barrier function, stratum corneum integrity/cohesion, and a reduced susceptibility to infections. The enhanced function of pigmented skin can be attributed to the lower pH of the outer epidermis, likely due to the persistence of (more-acidic) melanosomes into the outer epidermis, as well as the conservation of genes associated with eumelanin synthesis and melanosome acidification (e.g., TYR, OCA2 [p protein], SLC24A5, SLC45A2, MATP) in pigmented populations. Five keratinocyte-derived signals (stem cell factor,KIT; FOXn1,FGF2; IL-1,, NGF, and p53) are potential candidates to have stimulated the sequential development of epidermal pigmentation in response to stress to the barrier. We summarize evidence here that epidermal interfollicular pigmentation in early hominids likely evolved in response to stress to the permeability barrier. Am. J. Hum. Biol., 2010. © 2010 Wiley-Liss, Inc. [source] Enzymatic and structural analysis of the I47A mutation contributing to the reduced susceptibility to HIV protease inhibitor lopinavirPROTEIN SCIENCE, Issue 9 2008Klára Grantz, ková Abstract Lopinavir (LPV) is a second-generation HIV protease inhibitor (PI) designed to overcome resistance development in patients undergoing long-term antiviral therapy. The mutation of isoleucine at position 47 of the HIV protease (PR) to alanine is associated with a high level of resistance to LPV. In this study, we show that recombinant PR containing a single I47A substitution has the inhibition constant (Ki) value for lopinavir by two orders of magnitude higher than for the wild-type PR. The addition of the I47A substitution to the background of a multiply mutated PR species from an AIDS patient showed a three-order-of-magnitude increase in Ki in vitro relative to the patient PR without the I47A mutation. The crystal structure of I47A PR in complex with LPV showed the loss of van der Waals interactions in the S2/S2, subsites. This is caused by the loss of three side-chain methyl groups due to the I47A substitution and by structural changes in the A47 main chain that lead to structural changes in the flap antiparallel ,-strand. Furthermore, we analyzed possible interaction of the I47A mutation with secondary mutations V32I and I54V. We show that both mutations in combination with I47A synergistically increase the relative resistance to LPV in vitro. The crystal structure of the I47A/I54V PR double mutant in complex with LPV shows that the I54V mutation leads to a compaction of the flap, and molecular modeling suggests that the introduction of the I54V mutation indirectly affects the strain of the bound inhibitor in the PR binding cleft. [source] Hypoxia modulates phenotype, inflammatory response, and leishmanial infection of human dendritic cellsAPMIS, Issue 2 2010MAIRA CEGATTI BOSSETO Bosseto MC, Palma PVB, Covas DT, Giorgio S. Hypoxia modulates phenotype, inflammatory response, and leishmanial infection of human dendritic cells. APMIS 2010; 118: 108,14. Development of hypoxic areas occurs during infectious and inflammatory processes and dendritic cells (DCs) are involved in both innate and adaptive immunity in diseased tissues. Our group previously reported that macrophages exposed to hypoxia were infected with the intracellular parasite Leishmania amazonensis, but showed reduced susceptibility to the parasite. This study shows that although hypoxia did not alter human DC viability, it significantly altered phenotypic and functional characteristics. The expression of CD1a, CD80, and CD86 was significantly reduced in DCs exposed to hypoxia, whereas CD11c, CD14, CD123, CD49 and HLA-DR expression remained unaltered in DCs cultured in hypoxia or normoxia. DC secretion of IL-12p70, the bioactive interleukin-12 (IL-12), a cytokine produced in response to inflammatory mediators, was enhanced under hypoxia. In addition, phagocytic activity (Leishmania uptake) was not impaired under hypoxia, although this microenviroment induced infected DCs to reduce parasite survival, consequently controlling the infection rate. All these data support the notion that a hypoxic microenvironment promotes selective pressure on DCs to assume a phenotype characterized by pro-inflammatory and microbial activities in injured or inflamed tissues and contribute to the innate immune response. [source] The first major extended-spectrum ,-lactamase outbreak in Scandinavia was caused by clonal spread of a multiresistant Klebsiella pneumoniae producing CTX-M-15,APMIS, Issue 4 2008BIRGITTA LYTSY Between May and December 2005, 64 multidrug-resistant isolates of Klebsiella pneumoniae were detected from patients admitted to Uppsala University Hospital. This represented a dramatic increase in ESBL-producing K. pneumoniae compared to previous years. To investigate the epidemiology and to characterize the resistance mechanisms of the isolates, a study was initiated. Antibiotic susceptibility was determined by means of the Etest and the disc diffusion method. Extended-spectrum beta-lactamase (ESBL) production was identified by clavulanic acid synergy test and confirmed with PCR amplification followed by DNA sequencing. DNA profiles of the isolates were examined with pulsed-field gel electrophoresis (PFGE). All isolates were resistant or exhibited reduced susceptibility to cefadroxil, cefuroxime, cefotaxime, ceftazidime, aztreonam, piperacillin/tazobactam, ciprofloxacin, tobramycin, and trimethoprim-sulfamethoxazole. They produced ESBL of the CTX-M-15 type, and the involvement of a single K. pneumoniae clone was shown. This is the first major clonal outbreak of multiresistant ESBL-producing K. pneumoniae in Scandinavia. The outbreak demonstrates the epidemic potential of enterobacteria containing ESBLs of the CTX-M type, even in a country with a relatively low selective pressure and a low prevalence of multiresistant bacteria. [source] Pyrosequencing of the DNA gyrase gene in Neisseria species: effective indicator of ciprofloxacin resistance in Neisseria gonorrhoeae,APMIS, Issue 12 2006EMMA LINDBÄCK The quinolone resistance determining region (QRDR) of the gyrA gene in ciprofloxacin-susceptible strains (n=53) and strains of Neisseria spp. with reduced susceptibility (n=70) was determined by the pyrosequencing method. Results showed that the QRDR of the gyrA gene is an effective molecular indicator of resistance to ciprofloxacin in Neisseria gonorrhoeae, and presumably in Neisseria meningitidis, but not in all other Neisseria spp. This sequence was not unique for N. gonorrhoeae and seems unsuitable for species verification of N. gonorrhoeae. However, whether it is also possible to use this region for verification depends on the specificity of the primary screening method used. [source] Invasive Streptococcus pneumoniae from Portugal: implications for vaccination and antimicrobial therapyCLINICAL MICROBIOLOGY AND INFECTION, Issue 7 2004I. Serrano Abstract The distribution of pneumococcal serotypes among 465 invasive isolates recovered from 1999 to 2002 in Portugal was analysed by age group. Serotype 14 was either the most prevalent or the second most prevalent in all age groups. Among children aged <,2 years, serotypes 6B and 23F, which are usually associated with children, together with serotypes 19A and 14, accounted for more than half of the isolates. In contrast, in older adults (, 60 years), serotypes 3, 14, 1, 8 and 4 were the most prevalent. The potential coverage of the seven-valent conjugate vaccine is 63.2% among infants, and does not change significantly if children aged <,6 years are considered, which is a lower coverage than in other European countries. The potential coverage of the 23-valent polysaccharide vaccine is high in all age groups, particularly among older adults (80.7%). All isolates were tested for their susceptibility to penicillin, cefuroxime, cefotaxime, vancomycin, erythromycin, clindamycin, levofloxacin, gatifloxacin, moxifloxacin, linezolid, quinupristin,dalfopristin, tetracycline, chloramphenicol and trimethoprim,sulphamethoxazole. Most isolates collected from children aged <,6 years had decreased susceptibility to at least one antibiotic class, whereas isolates from patients aged ,,6 years were mostly susceptible to all antimicrobial agents tested. Overall, 23% of isolates showed reduced susceptibility to penicillin. Most (98.5%) isolates remained fully susceptible to cefotaxime, and a single isolate was resistant to quinolones. [source] | |||||||||||||