Genotype variation and capsular serotypes of Porphyromonas gingivalis from chronic periodontitis and periodontal abscesses

Porphyromonas gingivalis is considered an important pathogen in periodontal disease. While this organism expresses a number of virulence factors, no study combining different virulence polymorphisms has, so far, been conducted. The occurrence of combined virulence (Cv) genotypes in 62 isolates of P. gingivalis was investigated from subjects displaying either chronic periodontitis or periodontal abscess. The Cv genotypes, based on gene variation of fimbriae (fimA), Lys-specific cystein proteinase (kgp) and Arg-specific cystein proteinase (prpR1/rgpA), were evaluated by PCR. The isolates were also subjected to capsular polysaccharide K-serotyping. A total of 18 Cv genotype variants based on fimA: kgp: rgpA were identified, of which II:I:A and II:II:A Cv genotypes (53.3%) were the two most frequently detected combinations. Moreover, 36% of the isolates were K-typeable, with the K6 serotype being the most prevalent (23%). Two isolates had the same genotype as the virulent strain W83. The results indicate that chronic periodontitis is not associated with a particularly virulent clonal type. A highly virulent genotype (e.g. strain W83) of P. gingivalis can be found in certain periodontitis patients.     

Understanding the natural biology of kidney cancer: implications for targeted cancer therapy

During the past several decades, there has been a significant increase in the understanding of the biology, clinical behavior, and prognostic factors of renal cell carcinoma (RCC). Such progress has led to greater sophistication in the diagnosis and classification of RCC. Here, we review recent advances in our knowledge of the biologic characteristics of RCC that have resulted in notable achievements in staging, prognosis, patient selection, and treatment.     

Toxicity,behavior impairment,and repellence of essential oils from pepper‐rosmarin and patchouli to termites

Plant essential oils are potential sources of insecticidal compounds, but have rarely been explored for their effect on termites. In the present study, we assessed the chemical composition of essential oils of Lippia sidoides Cham. (pepper‐rosmarin; Verbenaceae) and Pogostemon cablin (Blanco) Benth. (patchouli; Lamiacaeae) and evaluated their toxicity, behavioral impairment, and repellence to termite species of the genera Amitermes and Microcerotermes (Isoptera: Termitidae: Termitinae). The main components of essential oils of L. sidoides and P. cablin were thymol (44.6%) and patchouli alcohol (36.6%), respectively. The essential oil of P. cablin was most potent against Amitermes cf. amifer Silvestri and had the lowest LD₅₀ (0.63 μg mg^?1). There was no difference in toxicity for Microcerotermes indistinctus Mathews between the essential oils of L. sidoides (LD₅₀ = 1.49 μg mg^?1) and P. cablin (LD₅₀ = 1.67 μg mg^?1). Pogostemon cablin essential oil was the most toxic to M. indistinctus (LC₅₀ = 0.32 μl ml^?1) and A. cf. amifer (LC₅₀ = 0.29 μl ml^?1). The essential oils analyzed exhibited high toxicity and repellence to the termites, in addition to reducing behavioral interactions among individuals, thus constituting potential termiticides.     

Rheumatoid arthritis–associated autoantibodies in non–rheumatoid arthritis patients with mucosal inflammation: a case–control study

IntroductionRheumatoid arthritis–associated autoantibodies (RA-AAB) can be present in serum years before clinical onset of rheumatoid arthritis (RA). It has been hypothesized that initiation of RA-AAB generation occurs at inflamed mucosal surfaces, such as in the oral cavity or lungs. The aim of this study was to assess systemic presence of RA-AAB in patients without RA who had oral or lung mucosal inflammation.MethodsThe presence of RA-AAB (immunoglobulin A [IgA] and IgG anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2), IgM and IgA rheumatoid factor (RF), IgG anti-carbamylated protein antibodies and IgG and IgA anti-citrullinated peptide antibodies against fibrinogen, vimentin and enolase) were determined in sera of non-RA patients with periodontitis (PD, n = 114), bronchiectasis (BR, n = 80) or cystic fibrosis (CF, n = 41). Serum RA-AAB levels were compared with those of periodontally healthy controls (n = 36). Patients with established RA (n = 86) served as a reference group. Association of the diseases with RA-AAB seropositivity was assessed with a logistic regression model, adjusted for age, sex and smoking.ResultsLogistic regression analysis revealed that IgG anti-CCP seropositivity was associated with BR and RA, whereas the association with PD was borderline significant. IgA anti-CCP seropositivity was associated with CF and RA. IgM RF seropositivity was associated with RA, whereas the association with BR was borderline significant. IgA RF seropositivity was associated with CF and RA. Apart from an influence of smoking on IgA RF in patients with RA, there was no influence of age, sex or smoking on the association of RA-AAB seropositivity with the diseases. Anti-CarP levels were increased only in patients with RA. The same held for IgG reactivity against all investigated citrullinated peptides.ConclusionAlthough overall levels were low, RA-AAB seropositivity was associated with lung mucosal inflammation (BR and CF) and may be associated with oral mucosal inflammation (PD). To further determine whether mucosal inflammation functions as a site for induction of RA-AAB and precedes RA, longitudinal studies are necessary in which RA-AAB of specifically the IgA isotype should be assessed in inflamed mucosal tissues and/or in their inflammatory exudates.     

The Human Immunopeptidome Project, a suggestion for yet another postgenome next big thing

The time is ripe for staging the Human Immunopeptidome Project, whose goal is to analyze the full repertoires of peptides bound to the HLA molecules, in both health and disease. Mass spectrometry technologies have matured to enable comprehensive analyses of both the membrane-bound and the plasma soluble immunopeptidomes associated with each of the HLA allomorphs and the different diseases. The expected outcomes of such project will include basic understanding of the molecular mechanisms involved with formation of immunopeptidomes, correlating them with their source cellular proteomes, definition of both the consensus motifs and the scope of each allomorphs-specific immunopeptidomes, and most importantly, identification of disease-related HLA peptides, which may eventually serve as biomarkers or immunotherapeutics. Ideally, the Human Immunopeptidome Project will become public and the gathered data will be shared, as soon as possible. Other immunopeptidome projects, of other animals, will follow suit.     

Kinase activity profiling of pneumococcal pneumonia

Background

Pneumonia represents a major health burden. Previous work demonstrated that although the induction of inflammation is important for adequate host defense against pneumonia, an inability to regulate the host''s inflammatory response within the lung later during infection can be detrimental. Intracellular signaling pathways commonly rely on activation of kinases, and kinases play an essential role in the regulation of the inflammatory response of immune cells.

Methodology/Principal Findings

Pneumonia was induced in mice via intranasal instillation of Streptococcus (S.) pneumoniae. Kinomics peptide arrays, exhibiting 1024 specific consensus sequences for protein kinases, were used to produce a systems biology analysis of cellular kinase activity during the course of pneumonia. Several differences in kinase activity revealed by the arrays were validated in lung homogenates of individual mice using western blot. We identified cascades of activated kinases showing that chemotoxic stress and a T helper 1 response were induced during the course of pneumococcal pneumonia. In addition, our data point to a reduction in WNT activity in lungs of S. pneumoniae infected mice. Moreover, this study demonstrated a reduction in overall CDK activity implying alterations in cell cycle biology.

Conclusions/Significance

This study utilizes systems biology to provide insight into the signaling events occurring during lung infection with the common cause of community acquired pneumonia, and may assist in identifying novel therapeutic targets in the treatment of bacterial pneumonia.