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PubMed1983

Virulence and phenotypic characterization of Yersinia enterocolitica isolated from humans in the United States.

Yersinia enterocolitica was recently reclassified into Yersinia enterocolitica sensu stricto and three additional species. With this new classification, it was of interest to reexamine pathogenicity previously ascribed to Y. enterocolitica. All available clinical isolates of Y. enterocolitica sent to the Centers for Disease Control from 1970 through 1980 were selected for characterization and comparison. One-hundred such strains had been submitted, from 21 states. Most (85%) were biotype 1, and O:8 was the most common of the 24 serotypes encountered. All strains were examined by several virulence assays. Two strains caused conjunctivitis in guinea pigs, 7 were lethal for mice, 54 invaded HEp2 cells, 18 produced a heat-stable enterotoxin, 9 were calcium dependent, 20 autoagglutinated, and 34 had a distinctive colonial morphology at 37 degrees C. Ten isolates of each of the new species that had previously been grouped with Y. enterocolitica (Y. kristensenii, Y. intermedia, and Y. frederiksenii) were characterized and were generally negative in all assays. This study points out pathogenicity differences among Yersinia species, confirms the complex nature of virulence in Y. enterocolitica, and confirms that no single current assay correlates with virulence in Y. enterocolitica.

Agglutination↗

PubMed2006

Phylogenetic analysis of polyomavirus BK sequences.

Polyomavirus BK (BKV) has emerged as an important pathogen in kidney transplant patients. Existing taxonomic classifications of BKV come from conventional DNA sequence alignments based on limited data derived from the VP1 gene. We have used a phylogenetic whole-genome approach to examine the pattern of diversity and evolutionary relationships between 45 BKV strains isolated from multiple clinical settings. This analysis supports the classification of BKV into six genotypes, of which types V and VI have not been previously recognized. BKV strains hitherto classified as type I are, in fact, quite heterogeneous, and several cluster with our newly defined genotypes V and VI. The sequence information needed for assigning genotypes can be captured by VP1, VP2, VP3, or large T-gene sequencing. The most polymorphic coding region in the viral genome is VP1, but significant variation is also present in the large T-antigen gene, wherein polymorphisms are found in 11.39% of all nucleotide sites, 46.22% of which are cluster specific. Type-specific amino acid changes within the VP1 region are predicted to map to the BC and DE loops. The number of taxonomically informative amino acid changes in the large T antigen exceeds even that of the VP1 region. Viral strains isolated from healthy subjects and from patients with human immunodeficiency virus infection, Wiskott-Aldrich syndrome, and vasculopathy with capillary leak syndrome formed distinct subclusters. However, within the kidney transplant population, BKV strains derived from patients with asymptomatic viruria did not show complete separation from strains associated with allograft nephropathy.

Antigens, Viral, Tumor↗

PubMed1999

Cerebral systems in the pathogenesis of endogenous psychoses. 1974.

Mental process imply a harmonious functioning of psychic systems, assembled into larger units, psychic spheres (Table 1). Their neurophysiological representatives are brain systems of areas and pathways (Figs 1-4). Under functional and/or organic disturbances these systems originate the leading mental symptoms (Table 2) characterizing the diverse endogenous psychoses: hence, the latter's distinctive patterns. Accordingly, understanding and classification of psychoses should rest on the pathogenic dynamisms, not on clinical description. This is why Kleist's and Leonhard's conceptions of the endogenous psychoses surpass any other to exist. Kleist stands among the founders of psychiatry, by describing the "degeneration psychoses" and many single psychoses, as well as redefining, isolating and clarifying the progressive ones, later on renamed as schizophrenias (Table 3). Such pathogenic criterion may also be useful to define mental conditions other than psychoses, as hysteria, neuroses and psychopathic inferiority (Tables 4 and 5). One should consider here, besides the psychic systems and spheres involved, the way they were caught and the corresponding developmental phase. In Kleist's "degeneration psychoses"--cyclic or episodic (Table 6) the systems and spheres are disturbed by functional transient processes due to latent dispositions, while his and Leonhard's schizophrenias (Table 7) show a rather progressive, deteriorating course. The nature of the disorder is itself genetically determined, as is either its confinement to one sphere or its spreading out. The spread out pattern, while exceptional in schizophrenia, represents a rule for the "degeneration psychoses", in discussant's mind. Both groups may have symptoms alike by involvement of the same sphere (Table 8), but proper diagnosis is reached by taking pathogenesis into consideration.

Brain Diseases↗

PubMed1984

Pathogenic mechanisms in osteochondrodysplasias.

UNLABELLED: We performed histochemical, immunohistochemical, electron-microscopic, and microchemical studies on cartilage growth plates from sixty-eight patients with nineteen different forms of human osteochondrodysplasia. Cartilage biopsies were obtained during orthopaedic procedures. Postmortem specimens were obtained within a short time after death. The combined morphological and biochemical studies revealed specific abnormalities suggestive of a particular biochemical defect in several chondrodysplasias. In pseudoachondroplasia, non-collagenous protein accumulated in the rough endoplasmic reticulum of chondrocytes and a proteoglycan species that normally is present in the extracellular matrix was not detected by gel electrophoresis. The accumulated material was stained with antibodies against the core protein of proteoglycan. This strongly suggested that in this syndrome an abnormal core protein of a proteoglycan species is not properly transferred to the Golgi system. In Kniest syndrome, intracytoplasmic accumulation of metachromatic material, dilatation of rough endoplasmic reticulum, and an abnormal gel-electrophoretic pattern of cartilage proteoglycans suggested an abnormality of cartilage proteoglycan metabolism. Abnormalities that probably are related to degradative lysosomal processes of proteoglycans in chondrocytes were found in spondylometaphyseal dysplasia of the Kozlowski type. An abnormal organization of type-II collagen was found in fibrochondrogenesis. In diastrophic dysplasia, an abnormal organization of collagen was found in areas of interterritorial matrix and around many degenerated cells, but also in the lacunae of cells without ultrastructural signs of degeneration. The segment-long-spacing form of collagen prepared from cartilage of three patients with diastrophic dysplasia showed an abnormal cross-striation pattern in a portion between bands 42 and 45, corresponding to the position of the alpha 1(II) cyanogen-bromide-derived 10,5 peptide. This suggested that in this syndrome there is a structural alteration of the type-II collagen molecule. There was an accumulation of intracellular lipid in pyknodysostosis and in hypochondrogenesis, and of glycoproteins in several atypical cases of spondyloepiphyseal dysplasia. In a pair of twins with an atypical form of spondyloepiphyseal dysplasia, the presence of many multinucleated chondrocytes suggested a primary impairment of cell division. CLINICAL RELEVANCE: A knowledge of the pathogenic mechanisms in osteochondrodysplasias might improve the classification; aid in diagnosis, prognosis, and genetic counseling; and contribute to the understanding of normal endochondral growth.(ABSTRACT TRUNCATED AT 400 WORDS)

Achondroplasia↗

PubMed1999

[Taxonomy of genus Malassezia: progress and problems].

The genus Malassezia is composed of lipophilic basidiomycetous yeasts which were recently shown to consist of seven species, one lipid-independent species, M. pachydermatis and six lipid-dependent species, M. furfur, M. sympodialis, M. globosa, M. obtusa, M. restricta and M. slooffiae. Based on this classification, we will be able to analyze pathogenicity or relationship between Malassezia-related diseases and each species.

Malassezia↗

PubMed1993

Periodontal diseases in young individuals.

The prevalence and severity of periodontal diseases in young people are significant. Recent progress in understanding the etiology and pathogenesis of periodontal diseases in this group of patients has allowed significant improvement in periodontal classifications. Actinobacillus actinomycetemcomitans characteristically is the major pathogen involved; black-pigmented anaerobic rods and other organisms can also be important. Treatment of periodontitis should focus on meticulous plaque control and eradication of periodontal pathogens, possibly by means of systemic or topical antimicrobial therapies.

Adolescent↗

PubMed1996

[Proposal of a new topographic classification of mandibular fractures].

There has been a certain amount of confusion in publications concerning fractures of the mandible due to the lack of consensus on classification. Starting with the embryological, anatomic, biomechanical, pathogenic and epidemiological features of these fractures, we propose a new terminology and a new distribution of the units and subunits of the mandible in traumatology. The main point is to incorporate the angle subunit into the ramus unit.

Adult↗

PubMedDate not supplied

Characterization and serological classification of a collection of Proteus penneri clinical strains.

INTRODUCTION: Bacteria of the genus Proteus, which are a common cause of urinary tract infections, are divided into four species: P. mirabilis, P. vulgaris, P. penneri, and P. hauseri, and three unnamed genomospecies, Proteus 4, 5, and 6 (single-strain species P. myxofaciens was isolated from the gypsy moth). Establishing the serological classification of these species would aid in completing the classification scheme of the whole genus Proteus and in applying serological methods in diagnostic procedures and epidemiological investigations for these opportunistic pathogens. The aim of this research was a serological characterization and classification of 57 Proteus penneri clinical strains, isolated from patients from different countries all over the world, into Proteus O serogroups. MATERIAL/METHODS: Purified lipopolysaccharides (LPSs) extracted from 57 P. penneri strains were used as antigens in enzyme immunosorbent assay (EIA), SDS/PAGE, and Western blot techniques, and alkali treated LPSs in passive immunohemolysis test (PIH), inhibition of PIH, and absorption of rabbit polyclonal O-antisera. RESULTS: That result confirms the serological distinction of this species within the genus Proteus, and may have diagnostic significance. CONCLUSIONS: As a result of serological studies of LPSs extracted from the P. penneri strains, one new Proteus serogroup, represented by the P. penneri 97 strain, was established. Three further strains were classified into the Proteus serogroup O8, which had not contained any P. penneri strains before. All the remaining strains were classified into 11 already existing Proteus O serogroups. It is important to emphasize that 72% of studied strains were classified into serogroups that contain P. penneri strains only.

Antigens, Bacterial↗

PubMed1991

Protein pI alteration related to strain variation of infectious bronchitis virus, an avian Coronavirus.

Viral proteins of two strains of infectious bronchitis virus (IBV), which have different tissue trophism and serology, were separated on the basis of their isoelectric points (pI). The viruses have four structural proteins; the protein of greatest serological importance is found at the peplomer tip. The viral structural proteins separated by isoelectric focusing were identified by comparison to SDS-PAGE separations. Three protein bands were identical in pI and one protein band showed a difference in pI between strains. When the renatured viral proteins were Western blotted and reacted with strain-specific antiserum, antigen-antibody complexing was seen only at points corresponding to the strain-specific variant bands. For IBV strain Mass-41, antigen-antibody complexing occurred at a pI of 6.8, and, for IBV strain Ark-99, at 7.2. No cross reaction of antisera was observed for either strain. Since tissue affinities are a function of the viral peplomer-mediated attachment of virus to cells and are often directly related to pathogenicity, it appears that altered pathogenicity of strains of IBV may be detected by alteration of pI of the proteins. Classification by pI of proteins of at least the smaller viruses allows untypeable, highly pathogenic or persistent strains of these viruses to be characterized on the basis of variant proteins.

Antibodies, Viral↗

PubMed2003

[The Ljubljana classification of epithelial hyperplastic laryngeal lesions].

Epithelial hyperplastic laryngeal lesions caused by pathogenic factors injuring the mucosa may contain reactive and/or preneoplastic histological changes. The grading system devised and tested in Ljubljana comprises simple hyperplasia (benign spinous layer augmentation), abnormal hyperplasia (benign basal and parabasal layer augmentation), atypical hyperplasia (risky for malignancy) and carcinoma in situ (actually malignant, but without invasion). In addition to making the diagnosis this classification is appropriate to evaluate the potential of any particular abnormality for progression into carcinoma. So it helps the clinician not only in planning the therapy and follow-up, but to assess the prognosis as well.

Carcinoma in Situ↗

PubMed2025

Distinct rates of VUS reclassification are observed when subclassifying VUS by evidence level.

PURPOSE: Genetic testing commonly yields a plethora of variants of uncertain significance (VUS) that can lead to ongoing uncertainty for patients and their caregivers. Although all VUS hold uncertainty, some VUS have more evidence in support of pathogenicity, whereas others have more evidence of a benign role. Sharing these nuances can help guide the investment in follow-up clinical and research investigations and may, at times, influence medical decision making despite appreciated uncertainty. METHODS: Four clinical laboratories have been subclassifying VUS to help prioritize investigation and guide reporting decisions. Each laboratory developed a distinct approach for how these subclasses are used in their laboratories and, in some cases, displayed on reports. We examined the composition of each laboratory's VUS subclasses and the likelihood variants from each subclass were reclassified toward pathogenic or benign. RESULTS: We found that variants in the lowest subclass of VUS were never reclassified as likely pathogenic or pathogenic, whereas those in the highest subclass were much more likely to be reclassified as pathogenic or likely pathogenic. CONCLUSION: Given that forthcoming professional guidance in variant classification will advise the use of VUS subclasses, the experience of our laboratories in using VUS subclasses can inform future practices.

Humans↗

PubMedDate not supplied

Subgenus systematics of Acanthamoeba: four nuclear 18S rDNA sequence types.

Classification of Acanthamoeba at the subgenus level has been problematic, but increasing reports of Acanthamoeba as an opportunistic human pathogen have generated an interest in finding a more consistent basis for classification. Thus, we are developing a classification scheme based on RNA gene sequences. This first report is based on analysis of complete sequences of nuclear small ribosomal subunit RNA genes (Rns) from 18 strains. Sequence variation was localized in 12 highly variable regions. Four distinct sequence types were identified based on parsimony and distance analyses. Three were obtained from single strains: Type T1 from Acanthamoeba castellanii V006, T2 from Acanthamoeba palestinensis Reich, and T3 from Acanthamoeba griffini S-7. T4, the fourth sequence type, included 15 isolates classified as A. castellanii, Acanthamoeba polyphaga, Acanthamoeba rhysodes or Acanthamoeba sp., and included all 10 Acanthamoeba keratitis isolates. Interstrain sequence differences within T4 were 0%-4.3%, whereas differences among sequence types were 6%-12%. Branching orders obtained by parsimony and distance analyses were inconsistent with the current classification of T4 strains and provided further evidence of a need to reevaluate criteria for classification in this genus. Based on this report and others in preparation, we propose that Rns sequence types provide the consistent quantititive basis for classification that is needed.

Acanthamoeba↗

PubMed1985

Classification and pathogenesis of vulvovaginal candidiasis.

Although candidiasis of the female genital tract is one of the most common of the vaginitides, it is a poorly understood disease entity. Vulvovaginal candidiasis is a monoetiologic disease, but the pathways by which pathogenic expression is attained are sufficiently divergent to constitute a classification schema that influences therapy. For selection of appropriate therapy, the following three broad categories are proposed: (1) primary candidiasis, (2) antibiotic-induced candidiasis, and (3) systemically induced candidiasis.

Anti-Bacterial Agents↗

PubMed2006

The EUHPID Health Development Model for the classification of public health indicators.

The European Community Health Promotion Indicator Development Model has been developed as the basis for establishing a European set of indicators for monitoring health promotion interventions. This paper offers the model more generally as a common frame of reference for broader public health practice and indicator development. The model builds around the physical, mental and social health of individuals and shows how health develops by interaction between individual and environmental health determinants. It demonstrates that health development can be analysed from a salutogenic and a pathogenic perspective and explains how the differing starting points of different intervention approaches such as health promotion and health care are related to these two perspectives. Finally, a classification system for pathogenic and salutogenic public health outcome indicators is derived from the model and has been applied to the current core list of the European Community Health Indicator system. The model and its application highlight the need for systematic salutogenic indicator development in the field of public health and for strengthening the health promotion perspective in the future.

Community Participation↗

PubMed1980

Persistent hog cholera infection detected during virulence typing of 135 field isolates.

During the hog cholera (HC) eradication program in the United States, 135 field isolates were characterized by inoculation into specific-pathogen-free pigs. This gave origin to the classification of 61 (45%) as high virulent, 37 (27%) as low virulent, 29 (22%) as avirulent or immunizing, and 8 (6%) as capable of causing persistent infection. The persistent infections caused by the eight isolates were of long durtion, lasting in one instance to 152 days. The persistently infected pigs remained relatively free of clinical signs of HC but had high concentrations of HC virus (HCV) in their blood. When 6 of these pigs were given a second inoculation (with the virulent Ames strain of HCV), 2 died while the health status of 4 remained unchanged.

Animals↗

PubMed2025

NextVir: Enabling classification of tumor-causing viruses with genomic foundation models.

MOTIVATION: Oncoviruses, pathogens known to cause or increase the risk of cancer, include both common viruses such as human papillomaviruses and rarer pathogens such as human T-lymphotropic viruses. Computational methods for detecting viral DNA from data acquired by modern DNA sequencing technologies have enabled studies of the association between oncoviruses and cancers. Those studies are rendered particularly challenging when multiple species of oncovirus are present in a tumor sample. In such scenarios, merely detecting the presence of a sequencing read of viral origin is insufficiently informative-instead, a more precise characterization of the viral content in the sample is required. RESULTS: We address this need with NextVir, to our knowledge the first multi-class viral classification framework that adapts genomic foundation models to detecting and classifying sequencing reads of oncoviral origin. Specifically, NextVir explores several foundation models-DNABERT-S, Nucelotide Transformer, and HyenaDNA-and efficiently fine-tunes them to enable accurate identification of the sequencing reads' origin. The results demonstrate superior performance of the proposed framework over existing deep learning methods and suggest downstream potential for foundational models in genomics.

Humans↗

PubMed1994

DNA probe-based classification of Simulium damnosum s. l.-borne and human-derived filarial parasites in the onchocerciasis control program area.

The development of polymerase chain reaction-based methods using strain- and species-specific DNA probes for Onchocerca volvulus has permitted classification of individual parasites from every stage of the parasite's life cycle. This technology has been applied on a large scale basis by Onchocerciasis Control Program (OCP) in West Africa. The primary objective of the OCP in using the DNA probes was to obtain accurate estimates of the annual transmission potential of the blinding strain of O. volvulus. The DNA probe classification of larvae collected throughout the OCP area demonstrated that larvae of less pathogenic strains of O. volvulus and other filarial parasites carried by Simulium damnosum s.l. have resulted in a significant overestimation of the annual transmission potential for blinding onchocerciasis. This effect is particularly pronounced along the southern border of the OCP, where the blinding and less pathogenic strains of O. volvulus coexist, and in the north of the control area, where animal parasites, particularly O. ochengi, may even predominate. A second objective of the OCP in applying the DNA probe technology was to determine the distribution of blinding and less pathogenic O. volvulus in infected individuals along the southern border of the control area. Results obtained from these studies have generally confirmed the distribution pattern established by previous epidemiologic studies. In addition, DNA probe classifications have demonstrated that in areas where the blinding and less pathogenic strains of O. volvulus coexist, a single individual may simultaneously be infected with both strains of the parasite.

Africa, Western↗

PubMed1994

From shaman to human clinical trials: the role of industry in ethnobotany, conservation and community reciprocity.

Shaman Pharmaceuticals is a development-stage company engaged in developing traditional pharmaceuticals identified through a discovery process focused on isolating active compounds from tropical plants with a history of medicinal use. This process has resulted in two products in clinical trials: Provir, an oral product for the treatment of respiratory viral infections, and Virend, a topical antiviral product for the treatment of herpes. Shaman's drug-discovery process targets specific plants that have been used for medicinal purposes by native peoples. By integrating the sciences of ethnobotany, medicine and plant natural product chemistry, Shaman has been able to achieve time and cost savings for the identification of active compounds and preclinical development of its initial products. Numerous drugs have entered the international pharmacopoeia via the study of ethnobotany and traditional medicine. Two important elements of this approach to drug discovery are the percentage of plants that show activity against specific viral pathogens and the correlation between the folk therapeutic classification of plants used and the percentage of those plants that have shown activity in our antiviral screens. Conservation and direct reciprocity to indigenous communities are important features of Shaman Pharmaceuticals' drug-discovery process.

Clinical Trials as Topic↗