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At least 1,009 records · Page 56Linked to original sources
PubMed2005

Chronic sinusitis in children and adults: role of bacteria and antimicrobial management.

The nasopharynx serves as the reservoir for anaerobic bacteria as well as pathogenic bacteria that can cause respiratory infections including sinusitis. Some of these organisms possess the ability to interfere with the growth of potential pathogens and may play a role in preventing infections. Anaerobic bacteria emerge as pathogens as the infection becomes chronic. This may result from the selective pressure of antimicrobial agents that enable resistant anaerobic organisms to survive, and from the development of conditions appropriate for anaerobic growth, which include the reduction in oxygen tension and an increase in acidity within the sinus. Anaerobes were identified in chronic sinusitis in adults and children whenever techniques for their cultivation were employed. The predominant isolates were pigmented Prevotella, Fusobacterium, and Peptostreptococcus spp. The choice of antimicrobial agent in chronic sinusitis should provide coverage for the usual pathogens in acute sinusitis as well as beta-lactamase-producing aerobic and anaerobic organisms.

Adult↗
PubMed2004

Plant innate immunity - direct and indirect recognition of general and specific pathogen-associated molecules.

Plants have the capacity to recognise and reject pathogens at various stages of their attempted colonisation of the plant. Non-specific rejection often arises as a consequence of the potential pathogen's attempt to breach the first lines of plant defence. Pathogens able to penetrate beyond this barrier of non-host resistance may seek a subtle and persuasive relationship with the plant. For some, this may be limited to molecular signals released outside the plant cell wall, but for others it includes penetration of the cell wall and the delivery of signal molecules to the plant cytosol. Direct or indirect recognition of these signals triggers host-specific resistance. Our understanding of host-specific resistance and its possible links to non-host-specific resistance has advanced significantly as more is discovered about the nature and function of the molecules underpinning both kinds of resistance.

Carrier Proteins↗
PubMed2005

Different activation patterns of proinflammatory cytokines in melancholic and non-melancholic major depression are associated with HPA axis activity.

BACKGROUND: Recent studies showed an activation of the cytokine system and the HPA axis in major depression, although with inconsistent results. While the non-melancholic subtype displayed a proinflammatory cytokine pattern, the melancholic subtype showed signs of impaired cytokine production. In order to understand the potential pathogenic significance of these systems further, the interplay between the cytokine system and the HPA axis in depressive subtypes as well as potential changes of these systems during the course of disease were investigated. METHODS: N=37 initially unmedicated patients with acute major depression were sub-classified (melancholic vs. non-melancholic) and compared with N=37 matched healthy controls. Upon admission and after complete clinical remission, basal plasma ACTH and serum cortisol levels as well as cytokine productions (IL-1beta, IL-1 receptor antagonist (IL-1RA)) upon mitogen stimulation (PHA) were measured in a whole blood assay. RESULTS: ACTH and cortisol concentrations were significantly elevated on admission in the melancholic but not the non-melancholic subgroup. Non-melancholic patients produced significantly more IL-1beta and IL-1RA upon admission than controls or melancholic patients. The IL-1 RA/IL-1beta ratio was significantly lower in the non-melancholic compared to the melancholic subgroup and increased significantly upon remission. LIMITATIONS: Patient treatment was not standardized. No Dex/CRH test was performed. CONCLUSIONS: Melancholic patients demonstrated an activation of the HPA axis in acute stage with partial normalization upon remission but no signs of inflammation. Non-melancholic patients showed signs of inflammation in acute depression with normalization upon remission while the function of the HPA axis was normal.

Adrenocorticotropic Hormone↗
PubMed1996

Antigen presenting cells in the porcine gut.

It has long been known that mucosal responses are most effectively stimulated by local presentation of antigen but the mechanisms whereby the gut immune system is able to distinguish between potential pathogens and harmless dietary antigens are not clear. The gut immune system is capable of mounting both primary and secondary responses to potentially harmful antigens while avoiding the expression of damaging responses to harmless food proteins. Historically, most attention has focused on Peyer's patches and there is evidence of their role in the induction of both primary and secondary responses. Fed antigen can also be detected in the intestinal lamina propria (LP) and it has been shown that murine LP cells can stimulate allogenic mixed lymphocyte responses and present KLH to naive T cells. In contrast to guinea pigs, rodents and humans, pig intestinal epithelial cells do not express MHC Class II molecules, but they are present on a number of other cell types in the subepithelial LP. Amongst these are a significant proportion of non-professional APC including endothelial cells and eosinophils. Phenotypically pig LP T cells are a homogeneous population and the majority of CD4 T cells express the low molecular weight isoform of CD45. This is compatible with the suggestion that they are CD45RO-positive cells. A significant proportion of LP CD4 T cells are CD25 (IL-2R) positive, but following activation they secrete IL-4, with little or no IL-2 production. Based upon these observations, we would conclude that the lamina propria is a unique immunological microenvironment, and suggest that it may be of significance not only in surveillance and the provision of help during rapid responses to recall antigens but also in the down-regulation of local responses to food-derived peptides.

Animals↗
PubMed2006

Induction of tolerance in arthritogenic B cells with receptors of differing affinity for self-antigen.

Multiple mechanisms of tolerance induction limit autoimmunity, but their relative contribution for lymphocytes recognizing self-antigens of differing availability is incompletely understood. The mechanisms applied to arthritogenic B cells expressing antigen-specific B cell receptors (BCRs) with different affinities for glucose-6-phosphate isomerase (GPI) were examined in the corresponding Ig gene knock-in mice. This ubiquitously expressed and blood-borne enzyme is the target autoantigen in the K/BxN model of inflammatory arthritis and perhaps in some humans with arthritis. Negative selection of B cells expressing high-affinity anti-GPI specificities, whose surface receptors were occupied by GPI, operated mainly at the transitional B cell stages in the spleen, preventing their final differentiation and entry into follicular areas. Receptor editing contributed to the purging of cells displaying anti-GPI BCRs, and significant numbers of autoreactive cells escaped through expression of an additional Ig light (L) chain, accumulating gradually in lymphoid organs. In contrast, low-affinity anti-GPI B cells, whose surface receptors did not carry GPI, matured normally. The "escaped" dual-L-chain cells and the "ignored" low-affinity cells are the likely precursors of cells that produce pathogenic autoantibodies once T cell help is provided. These studies portray, in a single system, the range of tolerance mechanisms applied to potentially pathogenic B cells, and serve as a base for dissecting where T cell help intervenes and where therapeutic agents impinge.

Alleles↗
PubMed2026

Whole-genome prediction of bacterial pathogenic capacity on novel bacteria using protein language models with PathogenFinder2.

MOTIVATION: Infectious diseases continue to be a leading cause of mortality and pose a significant global health threat. Thus, the development of tools for surveillance and early detection of emerging pathogens is needed. RESULTS: We introduce PathogenFinder2, a novel, alignment-free, taxonomy-agnostic model for predicting bacterial pathogenic capacity in humans using protein language models. It outperforms previous methods, particularly for novel taxa, and provides interpretable outputs by highlighting proteins most relevant to pathogenic potential. These insights aid the identification of virulence factors, vaccine targets, and infection-related metabolic pathways. Furthermore, we introduce the Bacterial Pathogenic Capacity Landscape, which reveals patterns linked to host condition, infection site, microbial antagonism, and environmental origin. AVAILABILITY: The model is freely available online at https://genepi.dk/pathogenfinder2, or as a standalone program (https://github.com/genomicepidemiology/PathogenFinder2).

Genome, Bacterial↗
PubMed2005

Prevalence of pathogenic Yersinia enterocolitica strains in pigs in the United States.

Yersinia enterocolitica is considered an important food-borne pathogen impacting the pork production and processing industry in the United States. Since this bacterium is a commensal of swine, the primary goal of this study was to determine the prevalence of pathogenic Y. enterocolitica in pigs in the United States using feces as the sample source. A total of 2,793 fecal samples were tested for its presence in swine. Fecal samples were collected from late finisher pigs from 77 production sites in the 15 eastern and midwestern pork-producing states over a period of 27 weeks (6 September 2000 to 20 March 2001). The prevalence of ail-positive Y. enterocolitica was determined in samples using both a fluorogenic 5' nuclease PCR assay and a culture method. The mean prevalence was 13.10% (366 of 2,793 fecal samples tested) when both PCR- and culture-positive results were combined. Forty-one of 77 premises (53.25%) contained at least one fecal sample positive for the ail sequence. The PCR assay indicated a contamination rate of 12.35% (345/2,793) compared to 4.08% (114/2,793) by the culture method. Of the 345 PCR-positive samples, 252 were culture negative, while of the 114 culture-positive samples, 21 were PCR negative. Among 77 premises, the PCR assay revealed a significantly (P < 0.05) higher percentage (46.75%, n = 36 sites) of samples positive for the pathogen (ail sequence) than the culture method (22.08%, n = 17 sites). Thus, higher sensitivity, with respect to number of samples and sites identified as positive for the PCR method compared with the culture method for detecting pathogenic Y. enterocolitica, was demonstrated in this study. The results support the hypothesis that swine are a reservoir for Y. enterocolitica strains potentially pathogenic for humans.

Animals↗
PubMed2003

Characterization of avian influenza virus isolates submitted to the National Centre for Foreign Animal Disease between 1997 and 2001.

The National Centre for Foreign Animal Disease (NCFAD) in Winnipeg, Manitoba, is the Canadian Food Inspection Agency's (CFIA) newest high biocontainment laboratory. One of the functions of the NCFAD is to serve as a national reference laboratory for avian influenza. Between 1997 and 2001, 15 avian influenza virus isolates were characterized. These isolates originated from domestic poultry, imported caged birds held in quarantine, and wild birds. Diagnostic specimens were submitted to the NCFAD by CFIA field veterinarians, provincial veterinary diagnostic laboratories, and veterinary colleges. Characterization of isolates included the determination of H and N subtypes: H1, H6, H7, and H10 subtypes were isolated from domestic poultry; H3, H4, and three H13 viruses were isolated from water fowl, and six H3 viruses were isolated from caged birds being held in import quarantine. Selected isolates were characterized with respect to their pathogenic potential by intravenous inoculation of 4-to-6-wk-old chickens. A molecular-based protocol was used to assess the pathogenicity of one H7 isolate. During this period, work was also carried out toward validating our molecular pathotyping protocol for avian influenza viruses with H5 and H7 hemagglutinin subtypes.

Amino Acid Sequence↗
PubMed2006

Contamination of multiple-dose vials in a veterinary hospital.

Bacterial contamination of multiple-dose saline bottles and medication vials in a veterinary teaching hospital was evaluated. Bacterial contamination was identified in 16/88 (18%) containers, with no difference in contamination between the large animal clinic, small animal clinic, and ruminant ambulatory clinic. Contamination of multiple-dose containers containing substances for injection was common, and potential pathogens were present in many situations. While the clinical significance is not resolved at this point, infection control practices should address this potential source of nosocomial infection.

Animals↗
PubMed1987

Clearance kinetics and immunochemistry in rabbits of soluble antibody/DNA immune complexes. Effects of antibody class and DNA conformation.

We examined the clearance kinetics in rabbits of soluble antibody/DNA immune complexes (IC) containing either IgG or IgM anti-DNA antibodies. Differences in the complement-mediated binding of these IC to rabbit blood cells (platelets) were also studied. Complexation of either double-stranded (ds) or single-stranded (ss) DNA with IgG anti-DNA tends to preclude in vivo DNA recognition mechanisms; the DNA is cleared as part of an IC at a rate slower than that of free DNA. Binding of ds- or ssDNA by IgM anti-DNA antibodies leads to formation of IC which are cleared more like free DNA, and this effect is most evident for ssDNA. However, although both IgG- and IgM-containing IC bound rapidly to blood cells in vivo, significant differences in their immunochemistry were apparent. For example, the DNA in IgM-containing IC was more susceptible to both in vivo and in vitro degradation. In addition, the binding of IgM-containing IC to rabbit platelets and human red blood cells was considerably more labile. Based on this systematic investigation of the soluble antibody/DNA IC that can potentially form in the circulation of a patient with systemic lupus erythematosus, it should be possible to formulate predictions regarding the relative pathogenic potential of these IC.

Animals↗
PubMed1999

Antimicrobial phytoprotectants and fungal pathogens: a commentary.

Many plants produce antifungal secondary metabolites. These may be preformed compounds which are found in healthy plants and which may represent in-built chemical barriers to infection by potential pathogens (preformed antimicrobial compounds or phytoanticipins). Alternatively they may be synthesized in response to pathogen attack as part of the plant defence response (phytoalexins). If these molecules do play a role in protecting plants against pathogen attack, then successful pathogens are presumably able to circumvent or tolerate these defences. Strategies may include avoidance, enzymatic degradation, and/or nondegradative mechanisms. This review outlines the different ways in which fungal pathogens may counter the antifungal compounds produced by their host plants and summarizes the evidence for and against these compounds as antimicrobial phytoprotectants.

Antifungal Agents↗
PubMed2003

Should we change the definition of avian influenza for eradication purposes?

The current definitions of high-pathogenicity avian influenza (HPAI), formulated over 10 years ago, were aimed at including viruses that were overtly virulent in in vivo tests and those that had the potential to become virulent. At that time the only virus known to have mutated to virulence was the one responsible for the 1983-84 Pennsylvania epizootic. The mechanism involved has not been seen in other viruses, but the definition set a precedent for statutory control of potentially pathogenic as well as overtly virulent viruses. The accumulating evidence is that HPAI viruses arise from low-pathogenicity avian influenza (LPAI) H5 or H7 viruses infecting chickens and turkeys after spread from free-living birds. At present it can only be assumed that all H5 and H7 viruses have this potential and mutation to virulence is a random event. Therefore, the longer the presence and greater the spread in poultry the more likely it is that HPAI virus will emerge. The outbreaks in Pennsylvania, Mexico, and Italy are demonstrations of the consequences of failing to control the spread of LPAI viruses of H5 and H7 subtypes. It therefore seems desirable to control LPAI viruses of H5 and H7 subtype in poultry to limit the probability of a mutation to HPAI occurring. This in turn may require redefining statutory AI. There appear to be three options: 1) retain the current definition with a recommendation that countries impose restrictions to limit the spread of LPAI of H5 and H7 subtypes; 2) define statutory AI as an infection of birds/poultry with any AI virus of H5 or H7 subtype; 3) define statutory AI as any infection with AI virus of H5 or H7 subtype, but modify the control measures imposed for different categories of virus and/or different types of host.

Animals↗
PubMed2000

Characterization of the pathogenicity of members of the newly established H9N2 influenza virus lineages in Asia.

The reported transmission of avian H9N2 influenza viruses to humans and the isolation of these viruses from Hong Kong poultry markets lend urgency to studies of their ecology and pathogenicity. We found that H9N2 viruses from North America differ from those of Asia. The North American viruses, which infect primarily domestic turkeys, replicated poorly in inoculated chickens. Phylogenetic analysis of the hemagglutinin and nucleoprotein genes indicated that the Asian H9N2 influenza viruses could be divided into three sublineages. Initial biological characterization of at least one virus from each lineage was done in animals. Early isolates of one lineage (A/Chicken/Beijing/1/94, H9N2) caused as high as 80% mortality rates in inoculated chickens, whereas all other strains were nonpathogenic. Sequence analysis showed that some isolates, including the pathogenic isolate, had one additional basic amino acid (A-R/K-S-S-R-) at the hemagglutinin cleavage site. Later isolates of the same lineage (A/Chicken/Hong Kong/G9/97, H9N2) that contains the PB1 and PB2 genes similar to Hong Kong/97 H5N1 viruses replicated in chickens, ducks, mice, and pigs but were pathogenic only in mice. A/Quail/Hong Kong/G1/97 (H9N2), from a second lineage that possesses the replicative complex similar to Hong Kong/97 H5N1 virus, replicated in chickens and ducks without producing disease signs, was pathogenic in mice, and spread to the brain without adaptation. Examples of the third Asian H9N2 sublineage (A/Chicken/Korea/323/96, Duck/Hong Kong/Y439/97) replicated in chickens, ducks, and mice without producing disease signs. The available evidence supports the notion of differences in pathogenicity of H9N2 viruses in the different lineages and suggests that viruses possessing genome segments similar to 1997 H5N1-like viruses are potentially pathogenic in mammals.

Animals↗
PubMed2001

Evolutionary trends in the genus Bordetella.

The genus Bordetella comprises seven species with pathogenic potential for different host organisms. This article attempts to review our current knowledge about the systematics and evolution of this important group of pathogens, their relationship to environmental microorganisms and about molecular mechanisms of host adaptation.

Animals↗
PubMed2005

Bench meets bedside: a 10-year-old girl and amino acid residue glycine 75 of the facilitative glucose transporter GLUT1.

In 2000, amino acid residue G75 of the facilitative glucose transporter GLUT1 was identified by mutagenesis as being essential for transport function [Olsowski, A., et al. (2000) Biochemistry 39, 2469-74]. In 2002, we identified a heterozygous missense mutation substituting glycine at residue 75 for tryptophan in a 10-year-old girl with intractable seizures and low glucose concentrations in the cerebrospinal fluid indicative of GLUT1 deficiency. Glucose uptake into erythrocytes of the patient was 36% of controls, and GLUT1-specific immunoreactivity was normal, indicating a functional GLUT1 defect. In silico three-dimensional modeling of the G75W mutant provided a smaller gyration radius for transmembrane segment 2 as the potential pathogenic mechanism in this patient. This case illustrates a GLUT1 mutation characterized in vitro and later confirmed by disease itself and highlights the potential of basic science and clinical medicine to collaborate for the benefit of patients.

3-O-Methylglucose↗
PubMed1997

Selective inhibition of cytosolic phospholipase A2 in activated human monocytes. Regulation of superoxide anion production and low density lipoprotein oxidation.

Our previous studies have shown that monocyte activation and release of O-2 are required for monocyte-mediated low density lipoprotein (LDL) lipid oxidation. We have also found that intracellular Ca2+ levels and protein kinase C activity are requisite participants in this potentially pathogenic process. In these studies, we further investigated the mechanisms involved in the oxidation of LDL lipids by activated human monocytes, particularly the potential contributions of the cytosolic phospholipase A2 (cPLA2) signaling pathway. The most well-studied cPLA2, has a molecular mass of 85 kDa and has been reported to be regulated by both Ca2+ and phosphorylation. We found that cPLA2 protein levels and cPLA2 enzymatic activity were induced upon activation of human monocytes by opsonized zymosan. Pharmacologic inhibition of cPLA2 activity by AACOCF3, which has been reported to be a specific inhibitor of cPLA2 as compared with sPLA2, caused a dose-dependent inhibition of cPLA2 enzymatic activity and LDL lipid oxidation by activated human monocytes, whereas sPLA2 activity was not affected. To corroborate these findings, we used specific antisense oligonucleotides to inhibit cPLA2. We observed that treatment with antisense oligonucleotides caused suppression of both cPLA2 protein expression and enzymatic activity as well as monocyte-mediated LDL lipid oxidation. Furthermore, antisense oligonucleotide treatment caused a substantial inhibition of O-2 production by activated human monocytes. In parallel experimental groups, cPLA2 sense oligonucleotides did not affect cPLA2 protein expression, cPLA2 enzymatic activity, O-2 production, or monocyte-mediated LDL lipid oxidation. These studies support the proposal that cPLA2 activity is required for activated monocytes to oxidize LDL lipids.

Cytosol↗
PubMed2026

Calcium release channel deficiency syndrome in patients diagnosed with idiopathic ventricular fibrillation and decedents classified as sudden unexplained death in the young.

AIMS: Calcium release channel deficiency syndrome (CRCDS) results from loss-of-function (LOF) variants in the RYR2-encoded type 2 ryanodine receptor (RyR2), predisposing patients to sudden cardiac arrest/death (SCA/SCD) without abnormalities on a stress electrocardiogram (ECG). Undetected CRCDS may underlie idiopathic ventricular fibrillation (IVF) and sudden unexplained death in the young (SUDY). We aimed to determine the prevalence of potential CRCDS-causative RYR2 variants in IVF and SUDY. METHODS AND RESULTS: We reviewed clinical evaluation and RYR2 genetic analysis of 169 IVF patients and 279 SUDY victims. Only ultra-rare (<0.005% in gnomAD) nonsynonymous RYR2 variants were considered potentially pathogenic. Among IVF patients, 6/169 (3%) overall-and 6/67 (9%) with exertion-related SCA-harboured an RYR2 variant and represent potential CRCDS cases. All exhibited normal resting and stress ECGs. Genetic analysis revealed six distinct RYR2 variants, two previously characterized as LOF. In SUDY, 31/279 victims (11%) had a RYR2 variant (30 unique variants), predominantly observed in exertion-related SCD 20/83 (24%) vs. rest-related 11/196 (6%). Of the 14 SUDY victims with functionally characterized RYR2 variants, five (2% of total cohort) had a LOF variant; among the 56 exertion-related SUDY cases, four (7%) had a LOF variant. CONCLUSION: CRCDS may account for 3% of IVF overall and 9% of exertion-related SCA in IVF. Ultra-rare RYR2 variants may underlie up to 11% of SUDY, with 65% of RYR2-positive cases occurring during exertion. LOF-RYR2 variants may contribute to &#x2265;7% of exercise-associated SUDY. Accurate identification of the underlying ryanodinopathy is essential for clinical management of affected patients.

Humans↗
PubMedDate not supplied

Time course of radiometric detection of positive blood cultures in childhood.

We have determined the time course of radiometric detection of microbial growth in 2348 positive blood culture specimens obtained at Wyler Children's Hospital during a 5-year interval. Overall 72 and 88% of isolates were detected within 48 and 72 hours after sampling, respectively. For pathogenic organisms aerobic detection was generally more rapid and more inclusive than anaerobic detection. At 48 hours of incubation the detection of six potential pathogens (Salmonella sp., Haemophilus influenzae, Group D streptococci, Neisseria meningitidis, coagulase-negative staphylococci, Candida sp.) was significantly delayed compared with detection of other pathogenic organisms recovered from blood. At 72 hours of incubation the detection rates remained less than 95% for H. influenzae, Staphylococcus aureus, Klebsiella sp., coagulase-negative staphylococci, Group D streptococci and Candida sp. These data should assist clinical decisions regarding duration of antibiotic therapy for the presumptive diagnosis of bacteremia in children.

Anti-Bacterial Agents↗