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PubMed1986

Vascular malformations of the stomach and duodenum: an endoscopic classification.

Having reviewed 47 cases of vascular malformations of the stomach and duodenum, we propose an endoscopic classification for these lesions: Pattern I (flat or slightly protruded, bright red lesions with frond-like margin) is the most usual form of presentation. The "telangiectatic form" (pattern II) is an endoscopic variation, with the same clinical and, possibly, pathogenic significance. Submucosal nodular forms (pattern III) are the most difficult to diagnose and treat. Electrocoagulation is the most pertinent treatment.

Acute Disease↗
PubMed1990

The division between fast- and slow-growing species corresponds to natural relationships among the mycobacteria.

Comparative 16S rRNA sequencing was used to infer the phylogenetic relationships among selected species of mycobacteria and related organisms. The phylogeny inferred reflects the traditional classification, with major branches of the phylogenetic tree in general correspondence to the four Runyon groups and with numerical classification analyses. All the mycobacterial species compared, with the exception of M. chitae, are closely related (average similarity values greater than 95%). The slow growers form a coherent line of descent, distinct from the rapid growers, within which the overt pathogens are clustered. The distant relationship between M. chitae and the remaining mycobacteria suggests that this organism is incorrectly classified with the mycobacteria. M. paratuberculosis 18 was indistinguishable from M. avium-M. intracellulare-M. scrofulaceum serovar 1 by this analysis.

Base Sequence↗
PubMed1990

Interactions of antimicrobial combinations in vitro: the relativity of synergism.

Interactions of combinations of netilmicin, amikacin, piperacillin, imipenem, azlocillin, ceftazidime or moxalactam were studied in vitro against Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus. Microtiter checkerboard technique was compared with standard killing curve method and with killing curves obtained in kinetic in vitro models mimicking single or multiple dosing regimens according to human pharmacokinetics. Antibiotic combinations were classified as antagonistic, indifferent or synergistic. Disagreement between classification by checkerboard and by kinetic model was found in 14 of 33 combinations studied (42%). Further analysis by standard killing curve method demonstrated that synergism or antagonism is a relative, not an absolute feature of drug combinations against given pathogens. Factors contributing to disagreements included the concentrations studied relative to the bacterial sensitivity, the ratio of concentrations of the two drugs tested, the size of the bacterial inoculum and the endpoint of the interaction assessment. Standard in vitro methods do not consider changes of antibiotic concentrations over time during combination therapy. Concentrations studied are defined according to bacterial sensitivity (fractions of MIC). Therefore, they may or may not relate to those at the infected site. The observed discrepancies between standard methods for testing drug interaction and a model which more closely reflects human pharmacokinetics support the argument that standard synergy testing provides incomplete data to reliably design clinical combination therapy.

Amikacin↗
PubMed2001

The mycobacteria: an introduction to nomenclature and pathogenesis.

Tuberculosis, caused by Mycobacterium tuberculosis, and leprosy, caused by M. leprae, are diseases known since antiquity. In developing countries, tuberculosis is still the leading cause of mortality due to an infectious disease. Taxonomically, mycobacteria belong to the genus Mycobacterium, which is the single genus within the family of Mycobacteriaceae, in the order Actinomycetales. Actinomycetales include diverse micro-organisms, but mycobacteria and allied taxa are easily distinguished on the basis of the ability to synthesise mycolic acids. Mycobacterial species are traditionally differentiated on the basis of phenotypic characteristics, and the authors provide an updated list of the biochemical tests currently employed and the culture properties that help to discriminate among various species of mycobacteria. However, as the phenotypic characteristics do not allow precise identification of all species, recent molecular taxonomical approaches for mycobacterial classification and phylogeny are also described. Mycobacteria are also a leading cause of infection in various domesticated animals and wildlife. The authors briefly describe the mycobacteria involved in animal infections, the wildlife reservoirs and strategies to control bovine tuberculosis, and the use of molecular tools for diagnostics and epidemiology of mycobacterial infections in animals. The characteristic of intracellular parasitism is discussed, in addition to the fate of pathogenic mycobacteria that have the ability to grow inside phagosomes and phagolysosomes of infected host macrophages. The mycobacterial cell envelope, which is a complex tripartite structure containing a high proportion of lipids (approximately 30% to 40% of the total weight) could play a crucial role in the adaptation of mycobacteria to intracellular growth and survival, immune modulation and drug resistance.

Animals↗
PubMed2000

Genetic diversity of the fish pathogen Aeromonas salmonicida demonstrated by random amplified polymorphic DNA and pulsed-field gel electrophoresis analyses.

The current taxonomy of Aeromonas salmonicida includes 4 subspecies. A. salmonicida subsp. salmonicida is associated with salmonid furunculosis, and A. salmonicida subsp. achromogenes, A. salmonicida subsp. masoucida, and A. salmonicida subsp. smithia are strains that show variation in some biochemical properties. This classification does not readily encompass isolates from a wide range of fish hosts currently described as atypical A. salmonicida. This study examined 17 typical strains, 39 atypical strains and 3 type A. salmonicida subspecies strains for genetic similarity using the random amplified polymophic DNA (RAPD) and pulsed-field gel electrophoresis (PFGE) techniques. On the basis of RAPD- and PFGE-derived profiles, similarity matrices and dendrograms were constructed. The results showed that species A. salmonicida constituted a genetically heterogeneous group of strains, encompassing within an homogeneous or clonal lineage comprised solely of typical strains and the A. salmonicida subsp. salmonicida type strain.

Aeromonas↗
PubMed2026

Systematic functional evaluation of CNGA1 missense variants associated with retinitis pigmentosa.

BACKGROUND: Missense variants are frequently classified as variants of uncertain significance (VUS) according to the guidelines of the American College of Medical Genetics and Genomics and the Association of Molecular Pathology (ACMG/AMP). Consequently, disease relevance remains elusive, impeding molecular genetic diagnostics, patients` and family genetic counseling, and identification of patients eligible for clinical trials. Functional studies are critical for resolving the clinical significance of VUS. CNGA1 encodes the main subunit of the rod cyclic nucleotide-gated (CNG) channel, a vital component of the phototransduction cascade. Variants in CNGA1 are a rare cause of autosomal recessive retinitis pigmentosa and a phase I/II gene augmentation trial (NCT06291935) is currently ongoing highlighting the necessity to differentiate benign from pathogenic variants. METHODS: CNGA1 missense variants compiled from retinal disease patient cohorts, public databases and literature were functionally investigated using a medium-throughput aequorin-based assay and in vitro minigene splice assays for predicted exonic spliceogenic variants. Functional data were correlated with the in silico prediction of five variant effect predictors (VEPs) and applied to support or revise variants' ACMG/AMP classification. RESULTS: Data mining revealed 86 missense CNGA1 variants - including three novel - most of them lacking functional data; 65.1% of the variants were initially classified as VUS. The aequorin-based assay showed that 72.1% of tested variants significantly impaired CNG channel function and were classified as functionally abnormal, while 23.3% were functionally normal and 5% remained functionally uncertain. Correlation of the functional data with in silico predictions identified AlphaMissense and CPT-1 to be the most suitable tools for assessing CNGA1 missense variants. Using in vitro minigene splice assays, two putative missense variants were shown to induce missplicing. Based on the functional findings, 62.1% of the variants initially classified as VUS were re-categorized as likely pathogenic or likely benign. Furthermore, 93.3% of the variants initially classified as likely pathogenic showed an effect on CNGA1 channel function, confirming their disease relevance and supporting their reclassification as pathogenic. CONCLUSION: This study represents the first comprehensive functional assessment of disease-associated CNGA1 missense variants, thus significantly advancing the understanding of their disease relevance and improving molecular genetic diagnostics in patients.

Humans↗
PubMed2004

Assessment of genetic, antigenic and pathotypic criteria for the characterization of IBDV strains.

The aim of this work was the selection and comparison of representative infectious bursal disease virus (IBDV) strains. Nine strains of IBDV, isolated at different times and from different geographic regions of Europe and China, were characterized. Batches of all strains were prepared following standardized protocols and checked for the absence of contaminating viruses. Criteria used for their characterization were: (i) the nucleotide sequence of the VP2 variable region, (ii) binding to a panel of neutralizing monoclonal antibodies in antigen capture enzyme-linked immunosorbent assays, and (iii) virulence in specific pathogen free chickens after infection with a standardized number of median embryo infective doses. Based on the first two criteria, two of nine strains were classified as classical virulent (cv) IBDV (F52/70, Cu-1wt), and five as very virulent (vv) IBDV (849VB, 96108, HK46, GX, Harbin). Remarkably, although a clear-cut difference was demonstrable between European cvIBDV (F52/70 and Cu-1wt) and vvIBDV (849VB and 96108) strains, there was a continuum in the pathogenicity of Chinese vvIBDVs. Our results indicate the probable existence of differences in virulence within IBDV lineages determined on the basis of antigenic typing using monoclonal antibodies and the alignment of the VP2 sequences. This indicates limitations in the analysis of IBDV pathotypes based on the VP2 variable region and emphasizes that these criteria may not be sufficient for the classification of IBDV strains.

Amino Acid Sequence↗
PubMed2005

Mayaro virus: complete nucleotide sequence and phylogenetic relationships with other alphaviruses.

Mayaro (MAY) virus is a member of the genus Alphavirus in the family Togaviridae. Alphaviruses are distributed throughout the world and cause a wide range of diseases in humans and animals. Here, we determined the complete nucleotide sequence of MAY from a viral strain isolated from a French Guianese patient. The deduced MAY genome was 11,429 nucleotides in length, excluding the 5' cap nucleotide and 3' poly(A) tail. Nucleotide and amino acid homologies, as well as phylogenetic analyses of the obtained sequence confirmed that MAY is not a recombinant virus and belongs to the Semliki Forest complex according to the antigenic complex classification. Furthermore, analyses based on the E1 region revealed that MAY is closely related to Una virus, the only other South American virus clustering with the Old World viruses. On the basis of our results and of the alphaviruses diversity and pathogenicity, we suggest that alphaviruses may have an Old World origin.

Alphavirus↗
PubMed2003

Priapism pathophysiology: clues to prevention.

Priapism, in which penile erection persists in the absence of sexual excitation, is an enigmatic yet devastating erectile disorder. Current endeavors to manage the disorder suffer from a poor fundamental knowledge of the etiology and pathogenesis of priapism. These endeavors have remained essentially reactive, which commonly fail to avert its pathological consequences of erectile tissue damage and erectile disability, not to mention its psychological toll. The role of preventative management seems paramount with respect to priapism. As a prerequisite to formulating prevention strategies, gaining understanding of its pathogenic features and likely pathophysiologic mechanisms is viewed to be quite important. This review combined an analysis of clinicopathologic reports as well as a summary of clinical and basic science investigations on the subject to date. These assessments support the basic classification of priapism into low-flow (ischemic) and high-flow (nonischemic) hemodynamic categories, resulting from venous outflow occlusion and unregulated arterial overflow of the penis, respectively. In addition, consistent with the hypothesis that dysregulative physiology of penile erection accounts for some presentations of priapism, several plausible molecular mechanisms influencing the functional state of the erectile tissue are discussed. Current progress in the field suggests prevention possibilities using androgenic suppressive therapy, adrenergic agonist therapies, and effectors of the nitric oxide-dependent erection regulatory pathway in the penis. New ideas for prevention may emerge from targeting molecular mechanisms involved in regulating erectile tissue function.

Humans↗
PubMed2004

Serum levels of tumor necrosis factor-alpha, interleukin-6 and interleukin-8 are not increased in dyspeptic patients with Helicobacter pylori-associated gastritis.

INTRODUCTION: Helicobacter pylori (H. pylori) is a non-invasive microorganism causing intense gastric mucosal inflammatory and immune reaction. H. pylori-induced gastric mucosal cytokine overproduction has been clearly documented previously. The stomach has a large surface area and continuous spill-over of locally produced cytokines into the blood stream is a possibility. There are few and conflicting data on circulatory proinflammatory cytokine levels in patients with H. pylori infection. MATERIALS AND METHODS: Forty-two dyspeptic patients were enrolled into the study. The presence of H. pylori infection was diagnosed with antral histopathologic examination. After overnight fasting; serum samples were obtained from each patient to determine circulating interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) levels. RESULTS: H. pylori was shown in 30 cases using Giemsa stain in antral histopathologic evaluation. Twelve cases were negative for H. pylori staining. Both the age and sex distribution had an insignificant difference in both H pylori-positive and H. pylori-negative groups. The mean circulatory levels of IL-6, IL-8 and TNF-a in both groups were not different. The situation was same in respect to the serum levels of these cytokines and the degree of inflammation, H. pylori density and activation scores according to Sydney classification. CONCLUSION: We could not show elevated circulatory levels of IL-6, IL-8 and TNF-alpha in H. pylori-infected cases. We believe that H. pylori-related cytokine activation become concentrated on gastric mucosa and this pathogen-induced local inflammatory cascade does not cause changes in circulatory levels of these cytokines. Moreover, there is no correlation between the levels of serum cytokines and Sydney parameters.

Adult↗
PubMed2006

Development and application of reference antisera against 15 hemagglutinin subtypes of influenza virus by DNA vaccination of chickens.

Reference antisera were produced against 15 influenza hemagglutinin (HA) subtypes using DNA vaccination to produce a high-quality polyclonal serum to the HA protein without antibodies to other influenza viral proteins. The HA gene from each of 15 different HA subtypes of influenza virus was cloned into a eukaryotic expression vector and injected intramuscularly, together with a cationic lipid, into 3- to 4-week-old specific-pathogen-free chickens. Birds were boostered twice at 4-week intervals after the initial injection, and in general, antibody titers increased after each boost. The antisera were successfully applied in the hemagglutination inhibition test, which is the standard method for the classification of the HA subtypes of influenza virus. We also demonstrated the HA specificity of the antisera by Western blot and immunodot blot analysis. DNA vaccination also provides a safer alternative for the production of HA-specific antibodies, since it is produced without the use of live virus.

Animals↗
PubMed2002

[Treatment of pneumonia acquired in the community].

The community-acquired pneumonia is a common and serious illness. Pneumonia is said to be community acquired if it is contracted outside of hospital environment or if it is diagnosed within the first 48 hours of hospitalisation. The pathogen remains unknown after investigations in around 50%. The patient should initially be treated empirically, based on the likely pathogens according to the patient's risk-factors, underlying diseases, severity of pneumonia and place of therapy. If recent guidelines are compared (American Thoracic Society, British Thoracic Society and the Infectious Disease Advisory Board) there are differences concerning epidemiology, patients classification and the empiric antibiotic treatment. The appearance of resistances and the recent availability of new antibiotics account partially for these differences. In order to avoid further resistances but still achieving an efficient treatment, coherent antibiotic schemes considering local microbiological epidemiology and patients classifications must be applied as proposed by different guidelines.

Anti-Bacterial Agents↗
PubMed2003

[Decompensation of a cirsoid aneurysm: a case report].

We report a case of a 27-year-old woman with a cirsoid aneurysm, also called congenital arteriovenous communication of the retina. The cirsoid aneurysm, stage I according to Archer's classification, was revealed by a serous retinal detachment. The exudation resolved, and acuity was recovered after a short time, but exudation recurred during the 5 years of follow-up. Exudation of type I cirsoid aneurysm is rare. The clinical and pathogenic features are discussed.

Adult↗
PubMed1992

[New views on the pathogenesis and diagnosis of toxoplasmosis].

T. gondii is one of the most occurring human pathogenic parasites in Europe. While the majority of immunocompetent individuals with T. gondii infection do not present clinical symptoms, congenital toxoplasmosis and reactivation of a latent infection in immunocompromised patients (i. e. patients with AIDS) are of high clinical relevance. A classification of T. gondii isolates is not available so far, although it was possible to demonstrate strain differences by the use of several methods, i. e. by using monoclonal antibodies. T. gondii seems to be able to infect any mammalian cell. Host cell-derived as well as parasite-derived factors seem to be important for the contact between host cell and parasite and the subsequent internalization. Following invasion, T. gondii is located within a parasitophorous vacuole that does not fuse with lysosomes. The multiplication rate of these obligately intracellular growing parasites decreases during conversion from the tachyzoite stage to the bradyzoite stage. Finally, the bradyzoites-harbouring cysts persist for the lifetime of the host. Reconversion from bradyzoites to tachyzoites may occur in immunocompromised patients. Probably, IFN-gamma is involved in this process. In addition to serological methods, direct detection of T. gondii using PCR or demonstration of circulating antigens might be routinely used as diagnostical tools in the future. Determination of specific IgA antibodies, which can be evaluated using the immunoblot technique, seem to be important for early serological diagnosis. The use of recombinant antigens might be helpful in future diagnosis to circumvent discrepancies between serological test results which could have resulted from strain-specific differences.

Animals↗
PubMed1991

[The role of microbial toxic substances in the pathogenesis of acute intestinal infections].

The authors suggest a syndromal approach to the acute intestinal infection pathogenesis provoked by gram-negative bacteria. A brief review of the achievements in the field of pathogenicity of infectious agents is given on the basis of which a conclusion is drawn about the main role of toxins in the clinical manifestation determining the principal syndromes in acute intestinal infections, i. e. diarrhea and inflammation. A pathogenetic syndromal classification of acute intestinal infections is forwarded which allows a practitioner to choose a pathogenetic therapy. The classification is useful for the pharmacologists as well searching for the methods of detoxification.

Acute Disease↗
PubMed1978

[Pathogenicity of E. coli: biological aspects and problems related to laboratory diagnosis (author's transl)].

The biological properties which may contribute to the pathogenicity of E. coli are reviewed in this article. Specifically the following topics are discussed in detail: 1) adhesion to the intestinal epithelial cells, 2) production of enterotoxins, 3) invasiveness of and ability to multiply within the epithelial cells, 4) insensitivity to complement lysis or inability to activate the alternative pathway of complement, 5) resistance to phagocytic killing. The various techniques which might be of potential usefulness in the clinical laboratory to test the parameters of the pathogenicity of E. coli are briefly outlined. The dissociation between the definition of pathogenicity, as established on the basis of the results of E. coli serotyping, and the criteria of pathogenicity listed above is brought to the attention of the reader. As specificity regards the toxinogenicity, what emerged from a survey of the literature, was that only one of the so called "enteropathogenic" strains of E. coli, according to the serotype classification, was found to produce an enterotoxin.

Clinical Laboratory Techniques↗
PubMed2025

Hidden diversity in Enterococcus faecalis revealed by CRISPR2 screening: eco-evolutionary insights into a novel subspecies.

Enterococcus faecalis is a commensal bacterium that colonizes the gut of humans and animals and is a major opportunistic pathogen, known for causing multidrug-resistant healthcare-associated infections (HAIs). Its ability to thrive in diverse environments and disseminate antimicrobial resistance genes (ARGs) across ecological niches highlights the importance of understanding its ecological, evolutionary, and epidemiological dynamics. The CRISPR2 locus has been used as a valuable marker for assessing clonality and phylogenetic relationships in E. faecalis. In this study, we identified a group of E. faecalis strains lacking CRISPR2, forming a distinct, well-supported clade. We demonstrate that this clade meets the genomic criteria for classification as a novel subspecies, here referred to as "subspecies B." Through a comprehensive pangenome analysis and comparative genomics, we explored the adaptive ecological traits underlying this diversification process, identifying clade-specific features and their predicted functional roles. Our findings suggest that the frequent isolation of subspecies B from meat products and processing facilities may reflect dissemination routes involving environmental contamination (e.g., water, plants, soil) from avian species. The absence of key virulence traits required for pathogenicity in mammals, particularly humans, and the lack of clinically relevant resistance determinants indicate that subspecies B currently poses minimal threat to public health compared with the broadly disseminated "subspecies A." Nevertheless, the unclear potential for genetic exchange between these subspecies and the frequent association of subspecies B with food sources calls for continued genomic surveillance of E. faecalis from a One Health perspective to detect and mitigate the emergence of high-risk variants in advance.IMPORTANCEExploring intraspecific genetic variability in generalist bacteria with pathogenic potential, such as Enterococcus faecalis, is a key to uncovering stable evolutionary trends. By screening the CRISPR2 locus across a representative set of genomes from diverse sources, this study reveals a previously unrecognized lineage within the population structure of E. faecalis, associated with underexplored nonhuman and nonhospital reservoirs. These findings broaden our knowledge of the species' genetic landscape and shed light on its adaptive strategies and patterns of ecological dissemination. By bridging phylogenetic patterns with variation in genetic defense systems and accessory traits, the study generates testable hypotheses about the genomic determinants and corresponding selective pressures that shape the species' behavior and long-term dissemination. This work offers new perspectives on the eco-evolutionary dynamics of E. faecalis and highlights the value of genomic surveillance beyond clinical settings, in alignment with One Health principles.

Enterococcus faecalis↗
PubMed2001

Listeria monocytogenes lineage group classification by MAMA-PCR of the listeriolysin gene.

Nucleotide sequence differences within several virulence genes, including the listeriolysin O (hly) gene, are associated with three evolutionary lineage groups of Listeria monocytogenes. Because the ability of L. monocytogenes to cause disease may vary by evolutionary lineage group, rapid discrimination among the three lineage types may be important for estimating pathogenic potential. A Mismatch Amplification Mutation Assay (MAMA) was developed and used to rapidly screen and characterize L. monocytogenes isolates with regard to lineage type. A standard PCR amplified a 446-bp region within the hly gene with all three L. monocytogenes lineage genotypes. MAMA primers to four different sites within this region of the hly gene were designed to amplify under the same PCR conditions and generated amplicons, the size of which depended on the isolate genotype. Ninety-seven L. monocytogenes isolates were screened. All isolates, except ATCC 19116, could be classified by MAMA PCR as one of the three hly genotypes. Overall, 56, 36, and 4 of the 97 isolates tested were type 1, 2, or 3 respectively. Among the 26 patient isolates, 85%, 15%, and 0% were type 1, 2, or 3 respectively; for the 60 food isolates, 54% were type 1, 43% were type 2, and 3% were type 3. The combination of these MAMA PCR analyses provides a rapid method to screen and categorize L. monocytogenes isolates because of conserved nucleotide differences within the hly gene.

Bacterial Toxins↗