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subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens.toll-like receptors (tlrs) are ancient microbial pattern recognition receptors highly conserved from drosophila to humans. to investigate if subsets of human dendritic cell precursors (pre-dc), including monocytes (pre-dc1), plasmacytoid dc precursors (pre-dc2), and cd11c(+) immature dcs (imdcs) are developed to recognize different microbes or microbial antigens, we studied their tlr expression and responses to microbial antigens. we demonstrate that whereas monocytes preferentially express tlr ...200111561001
survival of potentially pathogenic human-associated bacteria in the rhizosphere of hydroponically grown wheat.plants may serve as reservoirs for human-associated bacteria (h-ab) in long-term space missions containing bioregenerative life support systems. the current study examined the abilities of five human-associated potential pathogens, pseudomonas aeruginosa, pseudomonas cepacia, staphylococcus aureus, streptococcus pyogenes and escherichia coli, to colonize and grow in the rhizosphere of hydroponically grown wheat, a candidate crop for life support. all of these bacteria have been recovered from pa ...199611539850
a simple model host for identifying gram-positive virulence factors.we demonstrate the use of the nematode caenorhabditis elegans as a facile and inexpensive model host for several gram-positive human bacterial pathogens. enterococcus faecalis, streptococcus pneumoniae, and staphylococcus aureus, but not bacillus subtilis, enterococcus faecium, or streptococcus pyogenes, kill adult c. elegans. focusing our studies on the enterococcal species, we found that both e. faecalis and e. faecium kill c. elegans eggs and hatchlings, although only e. faecalis kills the ad ...200111535834
antiviral and antimicrobial activities of colombian medicinal plants.strong antiviral and antimicrobial activities were detected in methanolic extracts of 24 plants used medicinally in the treatment of skin infections in four different regions of colombia. thirteen extracts displayed activity against herpes simplex virus (hsv) whereas none was active against poliovirus. the antiviral activity was indicated by a total inhibition of viral cytopathic effects (cpe) at a non-cytotoxic concentration of the extract. the most potent extract was obtained from byrsonima ve ...200111535363
structural requirements of muramylpeptides for induction of toll-like receptor 2-mediated nf-kappab activation in cho cells.we previously demonstrated that gram-positive bacteria activated immune cells via cd14 and toll-like receptor 2 (tlr2). although peptidoglycan, a major constituent of the bacterial cell wall, substituted for whole organisms, the essential structure of muramylpeptides required to stimulate the cells is not clear. we further investigated the critical determinant for recognition by cd14 and tlr2. chinese hamster ovary (cho) fibroblasts, which do not express a functional tlr2 transcript, were transf ...200011521064
human milk anti-inflammatory component contents during acute mastitis.mastitis is a common complication of human lactation. we examined milk specimens from eight women with clinical mastitis to determine their content of anti-inflammatory components. antioxidant activity (spontaneous cytochrome c reducing activity), selected pro-inflammatory cytokines (il-6, il-1beta), selected endogenous cytokine control molecules (sil-6r, sil-1rii, and stnfri), lactoferrin, na(+):k(+) ratios, and milk bioactivities that cause shedding of sil-1rii from human polymorphonuclear leu ...200111520075
filarial antigens impair the function of human dendritic cells during differentiation.the antigen-specific t-cell unresponsiveness seen in lymphatic filariasis is mediated, in part, by diminished antigen-presenting cell function and is most specific for microfilariae (mf), the parasite stage found in large numbers in the peripheral circulation. we investigated the effect of mf antigen (mfag) on dendritic cells (dc) in both their differentiation process from monocyte precursors and also after they have developed into dc. when mfag was added to cultures of monocytes during their di ...200111500459
oral clearance and pathogenic oropharyngeal colonization in the elderly.the elderly have an increased incidence of oropharyngeal colonization with respiratory pathogens, a well-known risk factor for the development of pneumonia. changes in the oral milieu may occur secondary to decreased salivary production and abnormalities in swallowing. these abnormalities, common in the elderly, may result in impaired clearance of organisms, allowing pathogenic colonization. to test this hypothesis, we performed a prospective cross-sectional analysis of 75 elderly institutionali ...200111500351
expression of human beta-defensin-1 promotes differentiation of keratinocytes.epithelial cells have been shown to express the antibiotic peptides human beta-defensins-1 and 2. while beta-defensin-2 is known to be up-regulated by bacterial factors and proinflammatory mediators, the expression of beta-defensin-1 does not appear to be affected by these mediators. to determine the regulation and function of beta-defensin-1 we analyzed its expression upon stimulation of inflammatory mediators in vitro and ex vivo. in immortalized human cell lines (hacat) and nasal polyps beta- ...200111485020
enterotoxin production and dna fingerprinting in staphylococcus aureus isolated from human and food samples. relations between genetic types and enterotoxins.a total of 224 staphylococcus aureus strains from human carriers (110 strains) and manually handled foods (114 strains) collected in the principality of asturias, spain over 1995-1999 were analysed for the production of enterotoxins (ses) a, b, c, and d by a reversed passive latex agglutination test and by amplification of ent genes (a, b, c, d, e, and j) using pcr. sixty-two strains were enterotoxigenic and a good relation between detection of ses and their ent genes was found. no strain carrie ...200111482562
survey of staphylococcal enterotoxin genes, exfoliative toxin genes, and toxic shock syndrome toxin 1 gene in non-staphylococcus aureus species.the aim of this study was to analyze the presence of staphylococcal exotoxin genes in staphylococci other than staphylococcus aureus. whereas for staphylococcus aureus a large spectrum of different exotoxins responsible for toxin-mediated diseases has been described, only few and conflicting data are available regarding toxin production in all other staphylococcal species. a collection of clinical non-staphylococcus aureus staphylococcal isolates were systematically screened for the presence of ...200111476441
the two-component system arls-arlr is a regulator of virulence gene expression in staphylococcus aureus.staphylococcus aureus is a major human pathogen that produces many virulence factors in a temporally regulated manner controlled by at least two global virulence regulatory loci (agr and sara). we identified previously a two-component system, arls-arlr, that modifies the activity of extracellular serine protease and may be involved in virulence regulation. here, we show that mutations in either arlr or arls increase the production of secreted proteins [alpha-toxin (hla), beta-haemolysin, lipase, ...200111454217
evolutionary genomics of staphylococcus aureus: insights into the origin of methicillin-resistant strains and the toxic shock syndrome epidemic.an emerging theme in medical microbiology is that extensive variation exists in gene content among strains of many pathogenic bacterial species. however, this topic has not been investigated on a genome scale with strains recovered from patients with well-defined clinical conditions. staphylococcus aureus is a major human pathogen and also causes economically important infections in cows and sheep. a dna microarray representing >90% of the s. aureus genome was used to characterize genomic divers ...200111447287
recent developments in staphylococcal scalded skin syndrome.staphylococcal scalded skin syndrome describes a spectrum of superficial blistering skin disorders caused by the exfoliative toxins of staphylococcus aureus. in its severe form, the exfoliation can spread to cover the entire body surface area. two s. aureus exfoliative toxin serotypes affecting humans have been identified, but their purpose and mechanism of action have remained elusive. based on their interaction with human and mouse epidermis, their three-dimensional structure and site-directed ...200111442563
model systems: modeling human staphylococcal arthritis and sepsis in the mouse.the staphylococci have been recognized as serious pathogens for over a century and are the etiological agent of a variety of diseases ranging from mild cutaneous infections to often fatal forms of septic arthritis, endocarditis, toxic shock syndrome and sepsis. despite intensive efforts to halt their spread, they remain the most common cause of community- and nosocomially acquired bacteremia. murine models of staphylocococus aureus-mediated arthritis and sepsis exist and are being used to gain a ...200111435106
crystal structure of a superantigen bound to mhc class ii displays zinc and peptide dependence.the three-dimensional structure of a bacterial superantigen, staphylococcus aureus enterotoxin h (seh), bound to human major histocompatibility complex (mhc) class ii (hla-dr1) has been determined by x-ray crystallography to 2.6 a resolution (1hxy). the superantigen binds on top of hla-dr1 in a completely different way from earlier co-crystallized superantigens from s.aureus. seh interacts with high affinity through a zinc ion with the beta1 chain of hla-dr1 and also with the peptide presented b ...200111432818
potential impact of the vitek 2 system and the advanced expert system on the clinical laboratory of a university-based hospital.a study was designed to assess the impact of the vitek 2 automated system and the advanced expert system (aes) on the clinical laboratory of a typical university-based hospital. a total of 259 consecutive, nonduplicate isolates of enterobacteriaceae members, pseudomonas aeruginosa, and staphylococcus aureus were collected and tested by the vitek 2 system for identification and antimicrobial susceptibility testing, and the results were analyzed by the aes. the results were also analyzed by a huma ...200111427542
adjunctive rifampin therapy for central nervous system staphylococcal infections.to review the published clinical data assessing the role of adjunctive rifampin therapy for the treatment of staphylococcal central nervous system (cns) infections.200111408996
superantigen antagonist blocks th1 cytokine gene induction and lethal shock.bacterial superantigens trigger an excessive, th1-cytokine response leading to toxic shock. we designed a peptide antagonist that inhibits seb-induced expression of human genes for il-2, ifn-gamma, and tnf-beta, cytokines that mediate shock. the peptide antagonist shows homology to a beta-strand-hinge-alpha-helix domain that is conserved structurally in superantigens produced by staphylococcus aureus and streptococcus pyogenes yet remote from known binding sites for the major histocompatibility ...200111404377
gram-positive and gram-negative bacteria do not trigger monocytic cytokine production through similar intracellular pathways.toll-like receptors (tlrs) are involved in human monocyte activation by lipopolysaccharide (lps) and staphylococcus aureus cowan (sac), suggesting that gram-positive and gram-negative bacteria may trigger similar intracellular events. treatment with specific kinase inhibitors prior to cell stimulation dramatically decreased lps-induced cytokine production. blocking of the p38 pathway prior to lps stimulation decreased interleukin-1alpha (il-1alpha), il-1ra, and tumor necrosis factor alpha (tnf-a ...200111402003
adherence properties of staphylococcus aureus under static and flow conditions: roles of agr and sar loci, platelets, and plasma ligands.global regulatory genes in staphylococcus aureus, including agr and sar, are known to regulate the expression of multiple virulence factors, including cell wall adhesins. in the present study, the adherence of s. aureus rn6390 (wild type), rn6911 (agr), alc136 (sar), and alc135 (agr sar) to immobilized fibrinogen, fibronectin, von willebrand factor (vwf), extracellular matrix (ecm), and human endothelial cells (ec) eahy.926 was studied. bacteria grown to postexponential phase were subjected to l ...200111401988
influenza pneumonia: a descriptive study.to describe the clinical features and complications of patients hospitalized with influenza during the 1999-2000 influenza season.200111399696
effects of helichrysum italicum extract on growth and enzymatic activity of staphylococcus aureus.helichrysum italicum g. don (compositae) is a shrub commonly found in dry, sandy and stony areas of mediterranean regions. this plant is known for its anti-inflammatory, anti-allergic and antimicrobial activity. the aim of this study was to evaluate the effect of the diethyl ether extract on growth of staphylococcus aureus (atcc 6538p, mrsa and mssa isolates) and the influence of subminimum inhibitory concentrations (submics) on some enzymes which are considered virulence factors. the results in ...200111397624
venous access port--related bacteremia in patients with acquired immunodeficiency syndrome or cancer: the reservoir as a diagnostic and therapeutic tool.to describe the rate of response to an antibiotic-lock technique (alt) in the treatment of venous access port (vap)--related bacteremia and to analyze the role of the reservoir in the persistence of infection, we reported the data from 12 human immunodeficiency virus--infected and 8 oncologic patients with vap-related bacteremia. the alt consisted of intracatheter delivery of antibiotics and was associated with a systemic antibiotic infusion. we monitored clinical manifestations and performed qu ...200111360220
characterization of a novel proapoptotic caspase-2- and caspase-9-binding protein.caspases play important roles in regulating apoptotic signaling pathways. here we report the cloning, by the yeast two hybrid system with dominant negative caspase-2 as "bait," of a proapoptotic molecule named proapoptotic caspase adaptor protein (pacap), encoded by a 372-base pair open reading frame. binding of this novel protein to caspase-2 (casp-2) was confirmed in yeast two hybrid, in vitro, and in vivo assays. the deduced amino acid sequence revealed homology to functional motifs, includin ...200111350957
bone marrow-derived macrophages grown in gm-csf or m-csf differ in their ability to produce il-12 and to induce ifn-gamma production after stimulation with trypanosoma cruzi antigens.trypanosoma cruzi is the etiological agent of chagas' disease in man. control of parasitism at the beginning of experimental infection depends on cytokine-activated macrophages that synthesize nitric oxide (no). we investigated macrophage populations derived in the presence of m-csf (m-mø) or gm-csf (gm-mø) regarding their ability to control intracellular parasitism by t. cruzi and to synthesize il-12 and no. both macrophage populations supported intracellular multiplication of the parasite; whe ...200111348667
csf oligoclonal bands in ms include antibodies against chlamydophila antigens.considerable evidence suggests the role of an infectious agent in ms. the presence of chlamydophila pneumoniae in csf from patients with ms was shown earlier; to further examine this association the reactivity of the oligoclonal antibody response in the csf of patients with ms to c pneumoniae antigens was determined and compared with other antigens.200111342681
staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor mprf is based on modification of membrane lipids with l-lysine.defensins, antimicrobial peptides of the innate immune system, protect human mucosal epithelia and skin against microbial infections and are produced in large amounts by neutrophils. the bacterial pathogen staphylococcus aureus is insensitive to defensins by virtue of an unknown resistance mechanism. we describe a novel staphylococcal gene, mprf, which determines resistance to several host defense peptides such as defensins and protegrins. an mprf mutant strain was killed considerably faster by ...200111342591
effect of pinealectomy on immune parameters in rats with staphylococcus aureus infection.it is generally accepted that the pineal gland is a neuroendocrine organ. several recent experiments have shown that the pineal gland has functional and anatomical connections, particularly with the immune system, and therefore the gland is now recognized as an important immunoneuroendocrine organ in both man and animals. the present study investigates the effect of pinealectomy on some immune parameters, including hematological alterations, and the response of the brain tissue against infection ...200111339464
99mtc-labeled antimicrobial peptides for detection of bacterial and candida albicans infections.this study compared the possibilities and limitations of 99mtc-labeled synthetic peptides derived from two human antimicrobial peptides, namely, ubiquicidin (ubi) and lactoferrin (hlf), for the scintigraphic detection of bacterial and fungal infections in mice and rabbits. the rationale of our approach was that selected peptides accumulate in infected areas but not in sterile inflammatory lesions, because they bind preferentially to microorganisms. 99mtc-labeled human neutrophil peptides (defens ...200111337578
cutaneous leucocytoclastic vasculitis associated with oxacillin.a 67-year-old man who was treated with oxacillin for one week because of staphylococcus aureus bacteremia, developed renal failure and diffuse, symmetric, palpable purpuric lesions on his feet. necrotic blisters were noted on his fingers. skin biopsies showed findings diagnostic of leucocytoclastic vasculitis. oxacillin was discontinued and patient was treated with corticosteroids. the rash disappeared after three weeks and renal function returned to normal. leucocytoclastic vasculitis presents ...200111337188
acute gastric dilatation accompanied by diabetes mellitus.a 72-year-old man with diabetic triopathy was hospitalized with methicillin resistant staphylococcus aureus pneumonia. six hours after the admission, his abdomen was fully expanded. an abdominal x-ray showed gastric dilatation. after insertion of a gastric tube to extract gastric air, his abdomen was flat and gastric dilatation improved. a positive schellong test and decreased coefficient of rr interval in electrocardiogram variation indicated autonomic neuropathy, which may explain the reason f ...200111334392
polylysine-porphycene conjugates as efficient photosensitizers for the inactivation of microbial pathogens.porphycenes are electronic isomers of porphyrins which, when neutral, display no appreciable photosensitizing action towards gram-negative bacteria. the covalent binding of oligomeric polylysine moieties, which are cationic at physiological ph values, endows porphycenes with a significant phototoxic activity against gram-negative bacteria while retaining their photoefficiency against a variety of microbial pathogens, including gram-positive bacteria, fungi and mycoplasmas. the effect of the poly ...200011332884
trem-1 amplifies inflammation and is a crucial mediator of septic shock.host innate responses to bacterial infections are primarily mediated by neutrophils and monocytes/macrophages. these cells express pattern recognition receptors (prrs) that bind conserved molecular structures shared by groups of microorganisms. stimulation of prr signalling pathways initiates secretion of proinflammatory mediators, which promote the elimination of infectious agents and the induction of tissue repair. excessive inflammation owing to bacterial infections can lead to tissue damage ...200111323674
synergistic interactions between mammalian antimicrobial defense peptides.a single animal can express several cationic antimicrobial peptides with different sequences and structures. we demonstrate that mammalian peptides from different structural classes frequently show synergy with each other and selectively show synergy with human lysozyme.200111302828
clumping factor a mediates binding of staphylococcus aureus to human platelets.the direct binding of bacteria to platelets may be an important virulence mechanism in the pathogenesis of infective endocarditis. we have previously described staphylococcus aureus strain ps12, a tn551-derived mutant of strain isp479, with reduced ability to bind human platelets in vitro. when tested in an animal model of endocarditis, the ps12 strain was less virulent than its parental strain, as measured by bacterial densities in endocardial vegetations and incidence of systemic embolization. ...200111292731
monocytes augment bacterial species- and strain-dependent induction of tissue factor activity in bacterium-infected human vascular endothelial cells.in bacterial endocarditis (be), intravascular infection with staphylococcus aureus, streptococcus sanguis, or staphylococcus epidermidis can lead to formation of a fibrin clot on the inner surface of the heart and cause heart dysfunction. the events that start the coagulation in the early stage of the disease are largely unknown. we have recently shown that human endothelial cells (ec) upon binding and internalization of s. aureus, but not s. sanguis or s. epidermidis, express tissue factor (tf) ...200111292691
fibronectin binding protein a of staphylococcus aureus can mediate human t lymphocyte adhesion and coactivation.the extracellular matrix protein fibronectin (fn) mediates the adhesion of bacteria as well as t lymphocytes. mammalian cells express integrins alpha(4)beta(1) and alpha(5)beta(1) as the major fn-binding cell surface receptors. bacteria such as staphylococcus aureus, also express fn-binding receptors that are important for adherence to host tissue and initiation of infection. the s. aureus fn-binding protein, fnbpa, has been previously identified, and recombinant proteins that correspond to dist ...200111290795
[evaluation of methicillin-resistance in staphylococcus aureus by the agar disk diffusion method and pcr].staphylococcus aureus is a widespread human pathogen. one the most striking characteritics of this bacterium is resistance to methicillin and all beta-lactam antibiotics. the agar disk diffusion method is the most widely used in vitro susceptibility test, but recently molecular methods, e.g. polymerase chain reaction, have been also introduced. we compared the detection of methicillin resistant coagulase positive staphylococcus aureus isolated from clinical materials in silesian microbiological ...200011286174
the mechanism of a bacterial plasminogen activator intermediate between streptokinase and staphylokinase.the therapeutic properties of plasminogen activators are dictated by their mechanism of action. unlike staphylokinase, a single domain protein, streptokinase, a 3-domain (alpha, beta, and gamma) molecule, nonproteolytically activates human (h)-plasminogen and protects plasmin from inactivation by alpha(2)-antiplasmin. because a streptokinase-like mechanism was hypothesized to require the streptokinase gamma-domain, we examined the mechanism of action of a novel two-domain (alpha,beta) streptococ ...200111278483
cystic fibrosis pathogens activate ca2+-dependent mitogen-activated protein kinase signaling pathways in airway epithelial cells.much of the pulmonary disease in cystic fibrosis is associated with polymorphonuclear leukocyte-dominated airway inflammation caused by bacterial infection. respiratory epithelial cells express the polymorphonuclear chemokine interleukin-8 (il-8) in response to ligation of asialylated glycolipid receptors, which are increased on damaged or regenerating cells and those with cystic fibrosis transmembrane conductance regulator mutations. because both pseudomonas aeruginosa and staphylococcus aureus ...200111278360
heat-killed microorganisms induce pai-1 expression in human peritoneal mesothelial cells: role of interleukin-1alpha.human peritoneal mesothelial cells (hmcs) have a critical role in maintaining the intraperitoneal balance between fibrinolysis and coagulation by expressing the fibrinolytic enzyme, tissue-type plasminogen activator (tpa), as well as a specific plasminogen activator inhibitor (type 1; pai-1). during bacterial peritonitis, the balance between intraperitoneal generation and degradation of fibrin is disturbed. as a consequence, severe peritoneal damage occurs, which is one of the leading causes of ...200111273882
neonatal fungemia caused by hansenula anomala: a case report.hansenula anomala, an ascosporogenous yeast of the class ascomycetes, is a free-living organism isolated from the environment. it is also a part of the normal or transient flora of the human throat and alimentary tract. it has been recognized as an opportunistic pathogen and its infection is very rare. a premature infant, a victim of right femoral osteomyelitis and right hip arthritis caused by oxacillin-resistant staphylococcus aureus, was found to have developed h. anomala fungemia just before ...200011269374
[age determination using peptide mapping of non-collagenous proteins in human dentin].the submitted paper deals with possibilities of assessment of human age based on findings of stereospecific breakdown of proteins containing d-forms of aspartic acid. the stereospecificity of enzymatic breakdown assumes that after enzymatic hydrolysis peptide breakdown products with different molecular weights--the so-called peptide map--will be formed, depending how many d-aspartyl residues the protein contains. the authors proved in the submitted preliminary study in subjects of different age ...200111269023
suppression of superantigen-induced lung injury and vasculitis by preadministration of human urinary trypsin inhibitor.we examined whether the lung injury produced in rats by intraperitoneal injection of the superantigen, staphylococcal enterotoxin b (seb), could be inhibited by intravenous preadministration of human urinary trypsin inhibitor (uti), which exhibits multipotent inhibitory effects on serine proteinases such as plasmin, chymotrypsin, or human leukocyte elastase or cathepsin g, since preliminary experiments showed the ability of uti to bind lipopolysaccharides and bacterial toxins. for ligand blottin ...200111264657
methicillin-resistant staphylococcus aureus keratitis after laser in situ keratomileusis.a 50-year-old man had uneventful bilateral laser in situ keratomileusis (lasik) for moderate myopia (-4.50 diopters sphere, both eyes). twelve days postoperatively, he developed unilateral bacterial keratitis. cultures revealed methicillin-resistant staphylococcus aureus. the antibiotic regimen was adjusted, and he regained an uncorrected visual acuity of 20/40 and a best spectacle-corrected visual acuity (bscva) of 20/15. bacterial keratitis after lasik is a rare occurrence. aggressive use of c ...200111255063
comparison of methods for the determination of antimicrobial resistance in staphylococcus aureus from bovine mastitis.the results of three standard methods (broth dilution, agar dilution, disk diffusion) and an experimental modification of the microdilution method for determination of resistance to ampicillin, cephalotin, cloxacillin, neomycin, novobiocin, penicillin and streptomycin were compared using 151 staphylococcus aureus isolates obtained from cases of mastitis. the accuracy of the dilution methods was compared by determination of minimum inhibition concentrations (mic, mic50, mic90 and modal mic) and b ...200111254096
comparative in vitro and in vivo activity of the c-8 methoxy quinolone moxifloxacin and the c-8 chlorine quinolone bay y 3118.the c-8 methoxy quinolone moxifloxacin is highly bactericidal against wild-type and first-step gyrase- and topoisomerase iv-resistant mutants. this finding led to the hypothesis that the c-8 methoxy group may lower the propensity for resistance development compared with quinolones possessing different substituents at the c-8 position. therefore, resistance development of the c-8 methoxy quinolone moxifloxacin was compared with that of its structural analogue bay y 3118 (chlorine moiety at the c- ...200111249824
broad-spectrum antimicrobial activity of hemoglobin.while hemoglobin is one of the most well characterized proteins due to its function in oxygen transport, few additional properties of hemoglobin have been described. while screening serum samples for novel antimicrobial factors, it was found that intact hemoglobin tetramers, including that from human, exhibited considerable activity against gram-positive and gram-negative bacteria, and fungi. to further characterize this surprising activity, the antimicrobial potency of sections of human hemoglo ...200111249130
thermodynamic stability and functional activity of tumor-associated antibodies.tumor-associated antibodies of human igg1 subclass were eluted from cell-surface antigens of human carcinoma cells and studied by differential scanning calorimetry and binding to local conformational probes, protein a from staphylococcus aureus and a monoclonal antibody targeted to the ch2 domain of the fc fragment. at ph 2.0-7.0, we observed virtually identical enthalpies of thermal unfolding for igg1 from normal human sera and tumor-associated igg1. the exact values of calorimetric enthalpy (d ...200111240389
[toxic shock syndrome complicating influenza].in january 1999, an outbreak of type a(h3n2) influenza occurred in a psychiatric hospital. among 273 inpatients, 59 male and 40 female patients, age between 24-84 year old, developed high fever(38 degrees c), joint pain, cough and nasal discharge, and eleven male and one female patients died. in that hospital, methicillin-resistant staphylococcus aureus(mrsa), with production of toxic shock syndrome toxin-1 (tsst-1) and staphylococcal enterotoxin(se) type c(sec), were isolated from inpatients, m ...200011225327
[microbial biocenosis of the nasal mucosa in healthy persons and in staphylococcus carriers].the normal microflora of the nasal mucosa in man is differentiated into main, complementary and casual microflora, taking into account its isolation rate and characteristics of microbial contamination. the main microflora of adults, in contrast to children, is represented, in addition to coagulaso-negative (cn) staphylococci, by bacteria of the genus corynebacterium. in staphylococcal carrier state a decrease in the isolation rate and the amount of bacteria belonging to the main and complementar ...200011220970
disinfection efficacy of contact lens care solutions against ocular pathogens.three commercially available products labeled as multi-purpose contact lens solutions, one multi-purpose disinfecting solution, and a hydrogen peroxide system were evaluated for antimicrobial activity according to the current international organization for standardization (iso) and the u.s. food and drug administration (fda) stand-alone procedure for disinfecting products. one multi-purpose solution was selected to assess its antimicrobial activity against two human corneal isolates of pseudomon ...200111215601
deep wound infection after vagus nerve stimulator implantation: treatment without removal of the device.effective treatment of deep wound infection without removal of a previously implanted foreign body is difficult. the neurocybernetic prosthesis (ncp) system (cyberonics inc., webster, tx, u.s.a.), implanted for vagus nerve stimulation in patients with medically refractory epilepsy, uses coil-like electrodes placed around the left vagus nerve after exposure of the nerve in the carotid sheath. infection within this compartment endangers the contained structures and makes removal of the system haza ...200111207797
fibronectin-binding protein acts as staphylococcus aureus invasin via fibronectin bridging to integrin alpha5beta1.the ability of staphylococcus aureus to invade mammalian cells may explain its capacity to colonize mucosa and to persist in tissues after bacteraemia. to date, the underlying molecular mechanisms of cellular invasion by s. aureus are unknown, despite its high prevalence and difficulties in treatment. here, we show cellular invasion as a novel function for an s. aureus adhesin, previously implicated solely in attachment. s. aureus, but not s. epidermidis, invaded epithelial 293 cells in a temper ...199911207545
common infections in older adults.infectious diseases account for one third of all deaths in people 65 years and older. early detection is more difficult in the elderly because the typical signs and symptoms, such as fever and leukocytosis, are frequently absent. a change in mental status or decline in function may be the only presenting problem in an older patient with an infection. an estimated 90 percent of deaths resulting from pneumonia occur in people 65 years and older. mortality resulting from influenza also occurs prima ...200111201692
crystal structures of sara, a pleiotropic regulator of virulence genes in s. aureus.staphylococcus aureus is a major human pathogen, the potency of which can be attributed to the regulated expression of an impressive array of virulence determinants. a key pleiotropic transcriptional regulator of these virulence factors is sara, which is encoded by the sar (staphylococcal accessory regulator) locus. sara was characterized initially as an activator of a second virulence regulatory locus, agr, through its interaction with a series of heptad repeats (agttaag) within the agr promote ...200111196648
epidemic spread of a single clone of methicillin-resistant staphylococcus aureus among injection drug users in zurich, switzerland.we describe an outbreak of methicillin-resistant staphylococcus aureus (mrsa) among injection drug users (idus). from august 1994 through december 1999, we registered 31 idus with mrsa infections (12 with soft-tissue infection, 7 with pneumonia [fatal in 1], 7 with endocarditis [fatal in 1], 2 with osteomyelitis, 2 with septic arthritis, and 1 with ulcerative tonsillitis), with a marked increase in the number of idus registered during 1998 and 1999. of 31 patients, 15 (48%) were infected with hu ...200111181121
simultaneous cytofluorometric measurement of phagocytosis, burst production and killing of human phagocytes using candida albicans and staphylococcus aureus as target organisms.polymorphonuclear leukocytes (pmn) play a central role in the elimination of most extracellular pathogens, and an impairment of their functions predisposes an individual towards local and systemic bacterial and fungal infections. here we describe a rapid and easy-to-perform cytofluorometric assay for investigation of pmn activity using candida albicans and staphylococcus aureus as target organisms.200011168121
molecular cloning and functional characterization of a human scavenger receptor with c-type lectin (srcl), a novel member of a scavenger receptor family.using a human placenta cdna library, we cloned a novel member belonging to the scavenger receptor family. complementary dna of this clone encodes a type ii transmembranous glycoprotein containing a collagen-like domain, which are typical structural characteristics of scavenger receptor class a. this protein also contains a c-type lectin/carbohydrate recognition domain (c-type crd) located at the c-terminus. we designated this as scavenger receptor with c-type lectin (srcl) type i. we also isolat ...200111162630
breast milk transmission of a panton-valentine leukocidin-producing staphylococcus aureus strain causing infantile pneumonia.we report on a 38-day-old infant who developed pleuropneumonia due to a staphylococcus aureus strain responsible for familial furunculosis, which was acquired by maternal breast-feeding. all isolates from the infant and parents were genetically related by randomly amplified polymorphic dna analysis and produced panton-valentine leukocidin.200111158136
antibacterial effect of the culture fluid of lentinus edodes mycelium grown in submerged liquid culture.the antimicrobial activity of the culture fluid of lentinus edodes mycelium grown in submerged liquid culture was tested against some common bacterial species and candida albicans. the mycelium-free culture fluid was bacteriostatic against streptococcus pyogenes, staphylococcus aureus and bacillus megaterium. the substance responsible for the activity was heat-stable, could be extracted with chloroform and had a molecular weight under 10000. these characteristics suggested that the component mig ...200111137653
production of il-12 by human monocyte-derived dendritic cells is optimal when the stimulus is given at the onset of maturation, and is further enhanced by il-4.dendritic cells produce il-12 both in response to microbial stimuli and to t cells, and can thus skew t cell reactivity toward a th1 pattern. we investigated the capacity of dendritic cells to elaborate il-12 with special regard to their state of maturation, different maturation stimuli, and its regulation by th1/th2-influencing cytokines. monocyte-derived dendritic cells were generated with gm-csf and il-4 for 7 days, followed by another 3 days +/- monocyte-conditioned media, yielding mature (c ...200111123347
expression and function of il-12 and il-18 receptors on human tonsillar b cells.il-12 activates murine and human b cells, but little information is available as to the expression and function of il-12r on human b lymphocytes. here we show that the latter cells, freshly isolated from human tonsils, expressed the transcripts of both beta1 and beta2 chains of il-12r and that beta2 chain mrna was selectively increased (4- to 5-fold) by incubation with staphylococcus aureus cowan i bacteria or il-12. b cell stimulation with il-12 induced de novo expression of the transcripts of ...200011120812
biochemical and biological properties of staphylococcal enterotoxin k.staphylococcus aureus is an important human pathogen which is implicated in a wide variety of diseases. major determinants of the virulence of this organism include extracellular virulence factors. staphylococcal enterotoxins (ses) are important causative agents in staphylococcal toxic shock syndrome and food poisoning. our study identified a novel enterotoxin, sek, and examined its biochemical and biological properties. sek had a molecular weight of 26,000 and an experimentally determined pi of ...200111119525
inactivation of the srta gene in streptococcus gordonii inhibits cell wall anchoring of surface proteins and decreases in vitro and in vivo adhesion.the srta gene product, srta, has been shown to be required for cell wall anchoring of protein a as well as virulence in the pathogenic bacterium staphylococcus aureus. there are five major mechanisms for displaying proteins at the surface of gram-positive bacteria (p. cossart and r. jonquieres, proc. natl. acad. sci. usa 97:5013-5015, 2000). however, since many of the known surface proteins of gram-positive bacteria are believed to be exported and anchored via the sortase pathway, it was of inte ...200111119491
evaluation of the antibacterial and hemolytic activities of latvian herbal preparation.three extracts originating from a combination of various latvian plant species were tested for their antibacterial activities by evaluating growth delays using a fully automated microturbidimetric method. ten different human and bovine strains of the genera staphylococcus and micrococcus were used as test microorganisms. the inhibitory effect in vitro was defined as the difference between the growth rate without herbs and the growth rate in the presence of an extract. among the tested strains, s ...200011111939
toll-like receptor 2-mediated nf-kappa b activation requires a rac1-dependent pathway.mammalian toll-like receptors (tlrs) are expressed on innate immune cells and respond to the membrane components of gram-positive or gram-negative bacteria. when activated, they convey signals to transcription factors that orchestrate the inflammatory response. however, the intracellular signaling events following tlr activation are largely unknown. here we show that tlr2 stimulation by staphylococcus aureus induces a fast and transient activation of the rho gtpases rac1 and cdc42 in the human m ...200011101877
bacterial pathogens induce abscess formation by cd4(+) t-cell activation via the cd28-b7-2 costimulatory pathway.abscesses are a classic host response to infection by many pathogenic bacteria. the immunopathogenesis of this tissue response to infection has not been fully elucidated. previous studies have suggested that t cells are involved in the pathologic process, but the role of these cells remains unclear. to delineate the mechanism by which t cells mediate abscess formation associated with intra-abdominal sepsis, the role of t-cell activation and the contribution of antigen-presenting cells via cd28-b ...200011083777
split stories converge at desmoglein 1. 200011062527
low sensitivity of listeria monocytogenes to quaternary ammonium compounds.ninety-seven epidemiologically unrelated strains of listeria monocytogenes were investigated for their sensitivities to quaternary ammonium compounds (benzalkonium chloride and cetrimide). the mics for seven serogroup 1/2 strains were high. three came from the environment and four came from food; none were isolated from human or animal samples. all 97 strains carried the mdrl gene, which encodes a multidrug efflux pump, and the orfa gene, a putative transcriptional repressor of mdrl. the absence ...200011055967
superantigen immune stimulation activates epithelial stat-1 and pi 3-k: pi 3-k regulation of permeability.signal transducers and activators of transcription (stats) are critical intracellular signaling molecules for many cytokines. we compared the ability of t84 epithelial cells to activate stats in response to cytokines [interferon-gamma (ifn-gamma), interleukin (il)-4, il-10, and tumor necrosis factor-alpha (10 ng/ml)] and conditioned medium from superantigen [staphylococcus aureus enterotoxin b (seb)]-activated peripheral blood mononuclear cells (pbmc) using electrophoretic mobility shift assays ...200011053007
[influenza a pneumonia].the majority of influenza cases are not associated with complications. secondary bacterial pneumonia, commonly caused by streptococcus pneumoniae or staphylococcus aureus, is well known to most clinicians. primary influenza viral pneumonia, characterized by rapidly progressive hypoxia and respiratory insufficiency together with non-consolidating pulmonary infiltrates, has a high mortality rate. in 3 patients, a man aged 74 years, and two neonates aged 11 months and 4 weeks respectively, primary ...200011048555
rapid dna fingerprinting of pathogens by flow cytometry.a new method for rapid discrimination among bacterial strains based on dna fragment sizing by flow cytometry is presented. this revolutionary approach combines the reproducibility and reliability of restriction fragment length polymorphism (rflp) analysis with the speed and sensitivity of flow cytometry.200011042617
staphylococcal fibronectin binding protein interacts with heat shock protein 60 and integrins: role in internalization by epithelial cells.we reported previously that internalization of staphylococcus aureus by nonprofessional phagocytes involves an interaction between fibronectin (fn) binding protein (fnbp) and the host cell, resulting in signal transduction, tyrosine kinase activity, and cytoskeletal rearrangement (k. dziewanowska, j. m. patti, c. f. deobald, k. w. bayles, w. r. trumble, and g. a. bohach, infect. immun. 67:4673-4678, 1999). the goal of the present study was to identify the host molecules responsible for uptake of ...200011035741
staphylococcal enterotoxins.staphylococcus aureus is a major human pathogen that produces a wide array of toxins, thus causing various types of disease symptoms. staphylococcal enterotoxins (ses), a family of nine major serological types of heat stable enterotoxins, are a leading cause of gastroenteritis resulting from consumption of contaminated food. in addition, ses are powerful superantigens that stimulate non-specific t-cell proliferation. ses share close phylogenetic relationships, with similar structures and activit ...200011028954
human antibody response during sepsis against targets expressed by methicillin resistant staphylococcus aureus.the identification of target structures is a prerequisite for the development of new treatment options, like antibody based therapy, against methicillin resistant staphylococcus aureus (mrsa). in this study we identified immunodominant structures which were expressed in vivo during sepsis caused by mrsa. using human sera we compared the immune response of humans with mrsa sepsis with the immune response of normal individuals and asymptomatically colonized individuals. we identified and character ...200011024354
tropical pyomyositis and human toxocariasis: a clinical and experimental study. 200011020398
musculoskeletal manifestations of bacterial endocarditis.context: the incidence of staphylococcal infection has been increasing during the last 20 years. objective: report a case of staphylococcal endocarditis preceded by musculoskeletal manifestations, which is a rare form of clinical presentation. design: case report. case report: a 45-year-old-man, without addictions and without known previous cardiopathy, was diagnosed as having definitive acute bacterial endocarditis due to staphylococcus aureus. its etiology was community-acquired, arising from ...200011018851
sphingolipids and cholesterol modulate membrane susceptibility to cytosolic phospholipase a(2).modulation of cytosolic phospholipase a(2) (cpla(2)) activity by sphingomyelin (sph), ceramide (cer), and cholesterol (chol) was investigated in cho-2b cells activated by the calcium ionophore a23187 and epinephrine. chol depletion of cho-2b cells by treatment with methyl-beta-cyclodextrin (5 mm) resulted in the inhibition of the release of arachidonic acid whereas the restoration of the level by chol-loaded cyclodextrin relieved inhibition. conversion of cho-2b cellular sph to cer by staphyloco ...200011013311
neutrophil response of transgenic mice expressing human group iia phospholipase a2 in bacterial infections.group iia phospholipase a2 (pla2) is a newly recognized acute phase protein with marked antibacterial properties. we have shown previously that transgenic c57bl/6 j mice expressing human group iia pla2 (pla2+ mice) are more resistant to bacterial infections than nontransgenic c57bl/6 j mice that, among mice, are unusual in that they lack the mouse analogue of group iia pla2 (pla2- mice). to elucidate the possible mechanisms involved in the host response of these mice in bacterial infection, peri ...200011013007
surgical irrigation with pooled human immunoglobulin g to reduce post-operative spinal implant infection.a multiple-site, nonlethal rabbit surgical model of spinal implant infection was used to assess the efficacy of a spinal wound lavage to reduce post-operative infection from methicillinresistant staphylococcus aureus (mrsa). multiple aqueous lavages of isotonic saline were compared to the same procedure using 1wt% pooled human immunoglobulin g (igg) applied directly to the surgical implant sites. visually observed clinically relevant signs of infection (e.g. , swelling, erythema, pus) were suppo ...200010992435
in vitro antimicrobial properties of recombinant asabf, an antimicrobial peptide isolated from the nematode ascaris suum.asabf is a csalphabeta-type antimicrobial peptide that contains four intramolecular disulfide bridges (y. kato and s. komatsu, j. biol. chem. 271:30493-30498, 1996). in the present study, a recombinant asabf was produced by using a yeast expression system, and its antimicrobial activity was characterized in detail. the recombinant asabf was active against all gram-positive bacteria tested (7 of 7; minimum bactericidal concentration [mbc], 0.03 to 1 microg/ml) except leuconostoc mesenteroides, so ...200010991847
new antimicrobial mono- and sesquiterpenes from soroseris hookeriana subsp. erysimoides.a new monoterpene and a new guaianolide were isolated from the aerial parts of the tibetan medicinal plant soroseris hookeriana subsp. erysimoides (asteraceae), in addition to (1r,4r,5r)-5-hydroxybornan-2-one 5-o-beta-d-glucopyranoside, beta-sitosterol, daucosterol, diosmetin, isoluteolin, p-methoxybenzoic acid, isovanillic acid, two phenylmethanol derivatives (vanilioloside and phenylmethanol glucopyranoside), and five guaianolides [3 beta,8 beta-dihyroxyguaia-4(15),10(14),11(13)-triene-12,6 al ...200010985081
preseptal abscess formation following ocular cryotherapy for behçet's uveitis.a 42-year-old man with behçet's disease developed a rapidly growing mass under his right lower eyelid a week after transconjunctival cryotherapy. he underwent surgical drainage of the mass following imaging studies. magnetic resonance imaging scans demonstrated the abscess, which did not violate the orbital septum. cultures from drained material yielded staphylococcus aureus. he recovered completely with systemic antibiotics. preseptal abscess may occur as a complication of intense transconjunct ...200010976565
cd4 t lymphocyte activation in blv-induced persistent b lymphocytosis in cattle.bovine leukemia virus (blv) is an oncogenic retrovirus in the human t cell leukemia virus family. blv infects b lymphocytes and induces a nonmalignant persistent lymphocytosis (pl) and leukemia/lymphoma in cattle. there is evidence that cd4 t lymphocytes are activated during blv infection and promote the development of pl. how cd4 t lymphocytes are activated by blv infection is not known. we observed that cd4 t lymphocytes from pl cattle proliferated in the presence of autologous, irradiated per ...200010964547
comparative in vitro activities of abt-773 against aerobic and anaerobic pathogens isolated from skin and soft-tissue animal and human bite wound infections.we studied the comparative in vitro activities of abt-773, a new ketolide, against 268 aerobic and 148 anaerobic recent isolates from clinical bites using an agar dilution method and inocula of 10(4) cfu/spot for aerobes and 10(5) cfu for anaerobes. the following are the mic ranges and mics at which 90% of isolates are inhibited (mic(90)s) of abt-773 for various isolates, respectively: pasteurella multocida and pasteurella septica, 0.125 to 2 and 1 microg/ml; other pasteurella species, 0.125 to ...200010952607
induction of colony-stimulating factor expression following staphylococcus or salmonella interaction with mouse or human osteoblasts.staphylococcus aureus and salmonella spp. are common causes of bone diseases; however, the immune response during such infections is not well understood. colony-stimulating factors (csf) have a profound influence on osteoclastogenesis, as well as the development of immune responses following infection. therefore, we questioned whether interaction of osteoblasts with two very different bacterial pathogens could affect csf expression by these cells. cultured mouse and human osteoblasts were expose ...200010948128
genetic and serologic evaluation of capsule production by bovine mammary isolates of staphylococcus aureus and other staphylococcus spp. from europe and the united states.bovine mastitis caused by staphylococcus aureus is responsible for major economic losses to the dairy industry, and more-effective therapeutic or preventive approaches are sorely needed. the predominance of staphylococcal capsular polysaccharide types 5 and 8 among human isolates from many sources is well documented, but there seems to be a greater variation in the distribution of capsular serotypes among isolates from cows. a total of 636 isolates of s. aureus from cases of bovine mastitis in s ...200010921967
identification of a novel gene cluster encoding staphylococcal exotoxin-like proteins: characterization of the prototypic gene and its protein product, set1.we report the discovery of a novel genetic locus within staphylococcus aureus that encodes a cluster of at least five exotoxin-like proteins. designated the staphylococcal exotoxin-like genes 1 to 5 (set1 to set5), these open reading frames have between 38 and 53% homology to each other. all five proteins contain consensus sequences that are found in staphylococcal and streptococcal exotoxins and toxic shock syndrome toxin 1 (tsst-1). however, the sets have only limited overall sequence homology ...200010899837
interferon-alpha and -beta inhibit the in vitro differentiation of immunocompetent human dendritic cells from cd14(+) precursors.dendritic cell (dc) precursors and immature dc reside in epithelium where they encounter pathogens and cytokines, which stimulate their differentiation. we hypothesized that type-i interferons (ifn-alpha and -beta), cytokines that are produced early in the innate immune response against viruses and some bacteria, may influence dc differentiation and function. to examine this possibility, we used an in vitro model of dc differentiation in which initial culture of human cd14(+) monocytes with gran ...200010891453
b-cell function in canine x-linked severe combined immunodeficiency.canine x-linked severe combined immunodeficiency (xscid) is due to mutations in the common gamma (gammac) subunit of the il-2, il-4, il-7, il-9 and il-15 receptors and has a similar clinical phenotype to human xscid. we have previously shown that the block in t-cell development is more profound in xscid dogs than in genetically engineered gamma c-deficient mice. in this study we evaluated the b-cell function in xscid dogs. in contrast to the marked decrease in peripheral b-cells in gamma c-defic ...200010889304
a case of myiasis in man due to wohlfahrtia magnifica (schiner) recorded near rome.in this report the case of a 14-year-old italian boy is described in whom scratching wounds of the scalp were invaded by maggots of the dipterous wohlfahrtia magnifica (schiner).199910870566
characterization of staphylococcus aureus beta-toxin induced leukotoxicity.one virulence determinant of staphylococcus aureus is beta-toxin, a 37 kd magnesium-dependent sphingomyelinase c. this toxin lyses erythrocytes (rbcs) containing sphingomyelin in the outer lipid layer of their plasma membrane. although membranes of both human polymorphonuclear leukocytes (pmns) and lymphocytes (mnls) contain small amounts of sphingomyelin, the effect of beta-toxin on these cells remains controversial. the purpose of this study was to investigate the hemolytic activity of this to ...200010868340
expression of staphylococcal protein sbi is induced by human igg.protein sbi is an igg- and beta(2) glycoprotein i-binding protein on the surface of staphylococcus aureus. in most strains, the amount of protein sbi on the cell surface is very low under normal growth conditions. however, here we show that after growth in the presence of human serum, the amount is significantly increased. in s. aureus strain 8325-4, the observed increase is concentration-dependent and the highest level is found approximately 2 h after serum addition. the active molecule in seru ...200010865173
ifn-beta-1b inhibits il-12 production in peripheral blood mononuclear cells in an il-10-dependent mechanism: relevance to ifn-beta-1b therapeutic effects in multiple sclerosis.il-12 is a proinflammatory cytokine secreted by dendritic cells in response to microbial ags and mitogens. il-12 is thought to contribute to the pathogenesis of autoimmune diseases such as multiple sclerosis (ms). this is based on studies in experimental allergic encephalomyelitis and the demonstration that pbmc il-12 production correlates with disease progression in ms. ifn-beta-1b is an effective treatment for ms, which is thought to involve in part inhibition of proinflammatory cytokines. in ...200010861095
conservation and variation in superantigen structure and activity highlighted by the three-dimensional structures of two new superantigens from streptococcus pyogenes.bacterial superantigens (sags) are a structurally related group of protein toxins secreted by staphylococcus aureus and streptococcus pyogenes. they are implicated in a range of human pathologies associated with bacterial infection whose symptoms result from sag-mediated stimulation of a large number (2-20%) of t-cells. at the molecular level, bacterial sags bind to major histocompatability class ii (mhc-ii) molecules and disrupt the normal interaction between mhc-ii and t-cell receptors (tcrs). ...200010860729
dexamethasone promotes phagocytosis and bacterial killing by human monocytes/macrophages in vitro.one of the actions of glucocorticoids (gc) in multiple sclerosis (ms) is an inhibitory effect on demyelination. this can be caused by a reduction in the number of infiltrating macrophages and/or by an effect on the phagocytosis of myelin. here we investigate the effect of gc on the phagocytosis of myelin. contrary to what was expected, we found that incubation of human monocytes with dexamethasone (dex) for 48 h augmented (approximately threefold) the phagocytosis of myelin. this enhancement of ...200010857852
microbicidal activity of mdi-p against candida albicans, staphylococcus aureus, pseudomonas aeruginosa, and legionella pneumophila.mdi-p (medical discoveries, inc-pharmaceutical, layton, utah) is a clear, colorless liquid generated by electrolysis of preservative-free and endotoxin-free, nonpyrogenic, sterile, injection saline (0.9% nacl, wt/vol). it contains numerous highly reactive chlorine and oxygen species, including hocl(-1,) ocl-(1), cl(-1), cl(2), o(2-)(1), and o(3). this report presents data on the in vitro microbicidal activity of mdi-p against 4 clinically relevant microbial pathogens that are often difficult to ...200010840346
genotype-phenotype correlations in cystic fibrosis: clinical severity of mutation s549r(t-->g).with a view to assessing genotype-to-phenotype correlations in cystic fibrosis (cf), the clinical presentation of cf children from the united arab emirates (uae) who were homozygous for cystic fibrosis transmembrane conductance regulator (cftr) mutation s549r(t-->g was investigated. this mutation is localized in intron 11 (nucleotide binding domain 1 of the cftr protein) and had so far been described as a private mutation only. the associations between the r549/r549 genotype and 20 outcome varia ...199910836331
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