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Escherichia coli serogroup O111 includes several clones of diarrheagenic strains with different virulence properties.

Genetic variation among isolates of Escherichia coli O111 obtained mostly from patients with diarrhea in Brazil was assessed by multilocus enzyme electrophoresis to characterize chromosomal genotypes and by gene probes and adherence assays to characterize virulence properties. Among the 152 isolates, we resolved 16 distinct electrophoretic types (ETs), which differed on average at 40% of the enzyme loci. We identified four major bacterial O111 clones of different disease classes: ET 12, which includes the bulk of the enteropathogenic E. coli strains, typically showing localized adherence and intimate attachment in tissue culture assays; ET 1, which includes strains with a different set of virulence markers; ET 9, which includes strains that show intimate attachment but lack localized adherence and Shiga-like toxin genes; and ET 8, which includes strains that are Shiga-like toxin producers and have the corresponding traits of enterohemorrhagic E. coli. Enteroaggregative strains constituted ET 10 and also occurred in ET 1. Isolates of the major clones were found in South and North America and matched in ET and virulence factors to previously described diarrheagenic clones that are widely disseminated in the human population. Because the major clones are genetically distantly related and exhibit different combinations of virulence factors, we hypothesize that they have distinct mechanisms of pathogenesis. The results indicate that genetic divergence of bacteria with the O111 antigen, as measured by allelic variation in enzyme loci, is accompanied by divergence in virulence properties of clones so that identification and classification of pathogenic E. coli strains cannot be based solely on serotyping or a single virulence factor.

Bacterial Adhesion

Large-scale functional annotation establishes a reference framework for human LRRK2 variants.

Pathogenic variants in leucine-rich repeat kinase 2 (LRRK2)1are among the most frequent monogenic causes of Parkinson's disease (PD)2 and act through a gain-of-function mechanism of increased kinase activity. LRRK2-targeted therapies are in clinical development, but interpretation of the rapidly expanding catalogue of rare LRRK2 variants remains a barrier to translation. Here, we present functionally annotated data on >350 LRRK2 coding variants using a standardized cellular assay with Rab10 phosphorylation as a readout of kinase activity and integrated these data with curated genetic and clinical annotations from the Movement Disorders Society Genetic Mutation Database (MDSGene). Variants differed in activation magnitude, ranging from modest increases (e.g., p.G2019S) to strongly activating substitutions such as p.Y1699C or p.L1795F. Activating variants occurred across the full length of LRRK2, although the largest effects clustered within the ROC-COR regulatory hub, where structural analysis identified subdomains forming an allosteric scaffold controlling kinase output. All known/established pathogenic variants showed increased activity, whereas benign and likely benign variants remained within the wild-type range. Functional effect sizes correlated with pathway activation in patient-derived immune cells, altogether providing a framework for ACMG-based variant interpretation in which kinase activation can support PS3 functional evidence for reclassification of variants.

Protein phosphorylation

[Teeth extractions on diabetics patients].

In this paper the writer primarily mentions the temporary theories on the classification and pathogenic origin of diabetes. Furthermore, he describes the most important etiological factors of the appearance of the disease and its clinical picture. He specially extends to mentioning the probability of appearance of acute complications during dental help to a diabetic patient. He also underlines that the degree the reformatory functions of the organism are influenced by the interference of chronic complications which he describes. After maintaining the basic precautionary lines during the extraction of teeth in diabetic patients he describes the basic approach necessary in case of acute complications of diabetes. In the paper are also mentioned the latest methods of direct calculation of the level of glucose both to blood and the urine of the patient.

Blood Glucose

X-ray microanalysis as applied to fungal tissues.

Analytical electron microscopy combines the techniques of high-resolution electron microscopy and high-sensitivity X-ray microanalysis of samples. Spectrometry of the elements (characteristic X-rays produced by a scanning electron microprobe) was employed to detect some elements of Mendeleev's classification in pathogenic fungi for humans. X-ray microanalysis applied in wavelength dispersive spectrometry was used to study Coccidioïdes immitis, Paracoccidioïdes brasiliensis and Trichosporum cutaneum.

Coccidioides

[Urethro-adnexitis in the man and acute urethral syndrome in the woman. Microbiological and immunologic studies of etiologic classification].

Both common pathogens and unconventional, fastidious bacteria, viruses, parasites, and fungi are causative agents in male urethro-adnexitis and in female acute urethral syndrome. Uropathogens, Neisseria gonorrhoeae, Treponema pallidum, Mycobacterium tuberculosis, Chlamydia trachomatis, Mycoplasma spp., Haemophilus ducreyi, Calymmatobacterium granulomatis, Gardnerella vaginalis, anaerobic bacteria, Herpes simplex virus type II (HSV II), papillomaviruses (HPV), Trichomonas vaginalis and Candida spp. must be considered. The various diagnostic procedures and criteria applied for aetiological classification in cases of balanitis, urethritis, prostatitis, epididymitis, orchitis, and acute urethral syndrome are reviewed and evaluated.

Acute Disease

Emended description of Herbaspirillum; inclusion of [Pseudomonas] rubrisubalbicans, a milk plant pathogen, as Herbaspirillum rubrisubalbicans comb. nov.; and classification of a group of clinical isolates (EF group 1) as Herbaspirillum species 3.

[Pseudomonas] rubrisubalbicans, a mild plant pathogen. Herbaspirillum seropedicae, and EF group 1 strains (clustered by an immunological method) were investigated by a polyphasic approach with DNA-rRNA and DNA-DNA hybridizations and auxanography on 147 substrates. Our results show that they all belong to the genus Herbaspirillum. In addition to H. seropedicae, two other species are described: Herbaspirillum rubrisubalbicans and a new unnamed species, Herbaspirillum species 3, containing mainly strains of clinical origin. The three species can be differentiated on the basis of their auxanographic features and DNA-DNA similarities. The type strain of H. rubrisubalbicans is NCPPB 1027 (=LMG 2286); representative strains of the third Herbaspirillum species are strains CCUG 189 (=LMG 5523), CCUG 10263 (=LMG 5934), and CCUG 11060 (=LMG 5321). It has been confirmed that H. rubrisubalbicans is an endophytic diazotroph. It colonizes the roots, the stems, and predominantly the leaves of sugarcane (Saccharum spp.), while Herbaspirillum seropedicae colonizes in large numbers many different species of the Gramineae. Both diazotrophic Herbaspirillum species could be differentiated with meso-erythritol and N-acetylglucosamine. Oligonucleotide probes based on partial sequences of the 23S rRNA of H. seropedicae and H. rubrisubalbicans (HS and HR probes, respectively), were constructed and used as diagnostic probes.

Base Sequence

[Classification of septicemias. A clinical and pathogenic approach].

Classic sepsis is characterized by the presence of bacteria in blood originating from a primary infection site with secondary location at other sites. Some infectious diseases like typhoid and paratyphoid fever, brucellosis an others share this pathogenetic mechanism but have a characteristic clinical course and usually a good prognosis. After analyzing the differences between the 2 types the author proposes the terms "non specific" and "specific" for each type of sepsis, respectively. The differences between the 2, the organism involved and different reaction of the host in types, may be related to different pathogenetic effects of each case.

Brucellosis

Numerical classification and identification of Bacillus sphaericus including some strains pathogenic for mosquito larvae.

Ninety-one strains of Bacillus sphaericus, including representatives of all the established DNA homology groups, related round-spored and oval-spored species, and six strains pathogenic for mosquito larvae, were examined for 155 characters. Numerical analyses (Jaccard coefficient/average linkage clustering) based on the 88 variable features revealed 14 clusters at the 79% similarity level that contained more than one strain and 17 single member clusters. All insect pathogenic strains were recovered in a single cluster and the classification was in accord with an established classification based on DNA sequence homology. Two frequency matrices for probabilistic identification were constructed and tested. A comprehensive matrix comprising 14 mesophilic, round-spored taxa and 27 tests gave good results for identification of hypothetical median organisms, cluster overlap and identifications of representative strains (based on data generated in the classification study). Reference strains for the 14 taxa and eight additional insect pathogenic strains were examined for the 27 tests and were correctly identified with high scores using this matrix. A second matrix comprising seven taxa and 13 tests also performed well in the theoretical evaluation and correctly identified the reference strains and insect pathogenic strains.

Animals

Classifying extraintestinal non-typhoid Salmonella infections.

Non-typhoid Salmonella infection in man has been divided into five clinical groups: gastroenteritis, enteric fever, bacteraemia, chronic carrier state and localized infection. This classification has neither pathogenic nor prognostic significance. We retrospectively reviewed the charts of 183 patients with extraintestinal salmonellosis who presented to our institution during a period of 32 years. Patients were classified into four groups: primary bacteraemia (PB), enteritis-associated bacteraemia (secondary bacteraemia) (SB), digestive focal infection (DI) and non-digestive focal infection (NDI). Sex, age, acquisition, underlying disease and outcome were compared between patients with bacteraemia and diseases with focal infection. The differences found between PB and SB were: community acquisition (66% in PB and 85% in SB, p = 0.06) severe immunosuppression (53% in PB and 15% in SB, p < 0.001) and mortality (37% in PB and 3% in SB, p < 0.001). The differences found between NDI and DI were: age over 60 years (45% in NDI and 18% in DI, p < 0.05), severe immunosuppression (51% in NDI and 12% DI, p < 0.001) and associated bacteraemia (38% in NDI and 6% in DI, p < 0.001). This classification of extraintestinal salmonellosis may have pathogenic and prognostic implications, and could help us to understand the clinical significance of this disease.

Aged

Inoculation of pigs with Streptococcus spp. isolated from arthritic porcine joints.

The intricacies of the serological grouping of streptococci are discussed. The pathogenicity and accurate classification of streptococci isolated from arthritic porcine joints were in doubt. Pure cultures of these isolates were inoculated intravenously into healthy pigs to ascertain their pathogenicity and in an attempt to fulfil Koch's postulates. The pathogenesis of streptococcal arthritis in swine is discussed. On intravenous inoculation into experimental pigs the streptococcal isolates showed varying degrees of pathogenicity and arthritogenesis.

Animals

A statistical test for classification, with applications to the characterization of pathogens according to antibiotic susceptibility patterns.

If n different analytical procedures are applied to a culture of a pathogen, then that pathogen is characterized by an ordered sequence or vector of length n. A group of such sequences (or 'susceptibility patterns' as they are called in this context) can be generated by applying this process to cultures taken from infected individuals in an epidemic. This paper introduced statistical tests that can be used to determine whether a pattern obtained from the culture of a single case differs from those patterns obtained from cultures of a group of infected individuals. The methods are applied to come nosocomial epidemics. These taxonomic techniques extend beyond the present application to other classification problems in the biological and medical sciences.

Anti-Bacterial Agents

Pathogenicity assessment of genetic variants identified in patients with severe hypertriglyceridemia: Novel cases of familial chylomicronemia syndrome from the Dyslipidemia Registry of the Spanish Atherosclerosis Society.

PURPOSE: Genetic testing is required to confirm a diagnosis of familial chylomicronemia syndrome (FCS). We assessed the pathogenicity of variants identified in the FCS canonical genes to diagnose FCS cases. METHODS: 245 patients with severe hypertriglyceridemia underwent next-generation sequencing. Preliminary variant pathogenicity criteria and classification, based on the American College of Medical Genetics and Genomics guidelines, were obtained online and verified. Phenotype evaluation was based on lipoprotein lipase activity deficiency, a clinical score, and/or type I hyperlipoproteinemia determined in 25 patients. RESULTS: Twenty-four biallelic variants were analyzed. Evidence-based criteria allowed the reclassification of 8 likely pathogenic (LP) variants in the LPL, APOA5, and LMF1 genes into pathogenic (P) and the change of 2 variants of uncertain significance (VUS) to LP. Conversely, 2 variations in LMF1 remained as VUS. Additionally, 1 variant in LPL and 2 in GPIHBP1 were likely benign. Twenty FCS cases had biallelic P/LP variants and 1 patient, with an FCS phenotype, harbored biallelic VUS. FCS was excluded from 4 patients with pathogenic/likely benign combinations. CONCLUSION: The analysis of the clinical and biochemical features of patients with variants in the FCS canonical genes allowed a confident variant classification that helped in the diagnosis of novel FCS cases.

Humans

Proteolytic enzymes of pathogenic and non-pathogenic strains of Acanthamoeba spp.

The aim of this work was biochemical characterization and classification of proteinases in pathogenic and non-pathogenic strains of Acanthamoeba spp. The authors showed two proteinase (acid 35 kDa and alkaline 65 kDa) which could be separated electrophoretically. Acid proteinase was inhibited by serine proteinase inhibitors such as DIFP. The second enzyme which was active at alkaline pH, was enhanced by EDTA and inhibited by iodoacetate (IAA) and (p-CMB) p-chloromercuribenzoate. These substances are known to inhibit cysteine type proteinases. The alkaline proteinase was more distinctively active in pathogenic strains and belongs to cysteine class (EC 3.4.22), whereas the acid proteinase was similar active in pathogenic and non-pathogenic strains and belong to serine class (EC 3.4.21).

Acanthamoeba

Interpretive criteria for antimicrobial susceptibility testing of ceftiofur against bacteria associated with swine respiratory disease.

Ceftiofur, an extended-spectrum cephalosporin, is active against a variety of animal pathogens, including organisms associated with swine respiratory disease. However, minimum inhibitory concentration (MIC) breakpoint and disk diffusion interpretive criteria have not been established for swine pathogens. Susceptibility tests were performed by broth microdilution MIC and disk diffusion methods on 246 bacterial species that cause swine respiratory disease. Ceftiofur was active against Salmonella sp., Pasteurella multocida, Actinobacillus pleuropneumoniae, Streptococcus suis, and Escherichia coli but was not active against Bordetella bronchiseptica measured by MIC. Based on pharmacokinetic studies of ceftiofur in swine after a single intramuscular injection of 3 or 5 mg/kg body weight of ceftiofur and on the MIC and disk diffusion data, we recommend MIC breakpoints and disk diffusion distances, respectively, of < or = 2 micrograms/ml and > or = 21 mm for susceptible, 4 micrograms/ml and 18-20 mm for intermediate, and > or = 8 micrograms/ml and > or = 17 mm for resistant classification for swine pathogens. When these breakpoints were applied to data from a previous study using bovine pathogens, only 1 minor interpretive error occurred.

Actinobacillus pleuropneumoniae