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[Characteristics and classification of plasmids of conditionally pathogenic E. coli according to their conjugative and mobilization capacity].

A number of conjugative plasmids of opportunistic E. coli with molecular weights of 23.6--81.8 megadaltons have been studied. On the basis of the data thus obtained conjugative F-like R-plastmids have been subdivided into 2 groups characterized by the unsuppressed or suppressed manifestation of their functions. Individual conjugative plasmids have been found to differ in their capacity for mobilizing non-conjugative SuSm plasmid for transfer, which indicates the possibility of using this test for characterization and classification of plasmids, identified in natural bacterial population.

Animals

Primary amoebic meningoencephalitis.

As a serendipitous by-product of polio virus research, a highly fatal amoebic meningoencephalitis was recognized in animals. The causative microorganisms, contaminants of the viral cultures, were identified as small soil amoebae. These organisms, previously considered non-pathogenic, are prevalent throughout the world. Based on animal studies, the original investigators suggested the possibility of a similar disease in humans. Seven years later, human cases of amoebic meningoencephalitis were reported from widely separated areas of the world. Since 1965, a total of 79 cases have been reported. The literature of primary amoebic meningoencephalitis is presented. The history of the discovery and elucidation of this disease is reviewed. The 79 cases reported in the world literature are divided into two groups, those diagnosed retrospectively after reviewing previous deaths from meningoencephalitis, and those diagnosed at the time of the illness. The classification, morphology, pathogenicity, virulence and distribution of pathogenic soil amoebae are reviewed. The presenting clinical findings, diagnostic procedures, pathology, and management of this recently recognized, highly fatal, human disease is presented along with a report of a new case. Otolaryngologists should become familiar with this serious disorder with a transnasal portal of entry.

Amebiasis

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

[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

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

Evolutionary relationship between luteoviruses and other RNA plant viruses based on sequence motifs in their putative RNA polymerases and nucleic acid helicases.

Comparative studies of sequence motifs in the RNA polymerases and nucleic acid helicases of positive-sense RNA plant viruses have provided a new scheme for the classification of these pathogens. We propose a new luteovirus supergroup which should be added to the already described Sindbisvirus-like and picornavirus-like supergroups. Sequence motifs of nucleic acid helicases and RNA polymerases which previously were considered to be specific for each of the two supergroups now occur together within this new supergroup. We propose that this new viral supergroup provides an evolutionary link between the other two supergroups.

Amino Acid Sequence

[Effect of cyclic nucleotides on beta-lactamase production and outer membrane proteins of clinical Xanthomonas maltophilia isolates].

Resistance of clinical Xanthomonas maltophilia isolates to beta-lactam compounds is influenced considerably by the nutrient medium employed for sensitivity testing; the organisms were much more resistant to beta-lactams when susceptibility testing was performed in Mueller-Hinton broth as compared to Isosensitest broth as the nutrient medium. Consequently, the influence of cyclic nucleotides was studied on beta-lactamase expression and outer membrane proteins in more detail. The exogenous supply of 5 mmol/l c-AMP or its lipophilic derivative c-AMP-N6,O2-dioctanoyl resulted in a marked reduction of enzyme production as compared to the control assay; 0.5 mmol/l c-AMP-S or 1 mmol/l c-GMP did not exhibit any effect. The analysis of the outer membrane proteins of Xanthomonas maltophilia revealed the single band of a 40 kdal protein which was expressed independently of the experimental conditions, thus confirming the classification of this pathogen as Xanthomonas maltophilia. The reduction of beta-lactamase expression in the presence of either c-AMP or c-AMP-N6,O2-dioctanoyl cannot be explained at present. The above findings emphasize again the problem of in-vitro susceptibility testing. To avoid false sensitive results, the use of Mueller-Hinton broth is recommended.

Bacterial Outer Membrane Proteins

[New contributions to the etiology of insulin-dependent diabetes (author's transl)].

The present studies on the possible factors that can be implicated in the etiopathogenesis of diabetes are reviewed. The association between insulin-dependent diabetes and certain specifications of the HLA system are commented on, as well as the experimental studies and the clinical observations which indicate the possible relationship between this disease and some viruses. The role played by autoimmunity is thoroughly discussed, specially the significance of anti-pancreatic islet antibodies. Finally, new pathogenic theories and classifications of the disease are proposed.

Autoantibodies

Tears of the peripheral retina; pathogenesis, incidence and classification in autopsy eyes.

A pathogenic analysis of full-thickness tears of the peripheral retina and their incidence in autopsy eyes is presented. Tears were classified according to their location (ora or postora, quadrant and zone), type of traction (zonuloretinal or vitreoretinal), morphological features (flap or operculum), presence or absence of posterior vitreous detachment, and their association with other ocular lesions. Tears were present in 2% of eyes. They were postoral in 92%, uniformly distributed in the quadrants, in the equatorial zone in 95%, related to vitreoretinal traction in 94%, of the flap type in 64%, accompanied by posterior vitreous detachment in 79% and were significantly more prevalent in eyes with lattice degeneration (17%). A simple classification of postoral tears is recommended which incorporates these pathogenic principles and includes three types according to their topographical relationship to the vitreous base: intrabasal--caused by avulsion of zonular traction tufts; juxtabasal--related to traction of the posteriorly detached vitreous on irregularities in posterior border of vitreous base; extrabasal--resulting from avulsion of cystic retinal tufts.

Adult