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PubMed2004

Classification of papillomaviruses.

One hundred eighteen papillomavirus (PV) types have been completely described, and a yet higher number of presumed new types have been detected by preliminary data such as subgenomic amplicons. The classification of this diverse group of viruses, which include important human pathogens, has been debated for three decades. This article describes the higher-order PV taxonomy following the general criteria established by the International Committee on the Taxonomy of Viruses (ICTV), reviews the literature of the lower order taxa, lists all known "PV types", and interprets their phylogenetic relationship. PVs are a taxonomic family of their own, Papillomaviridae, unrelated to the polyomaviruses. Higher-order phylogenetic assemblages of PV types, such as the "genital human PVs", are considered a genus, the latter group, for example, the genus "Alpha-Papillomavirus". Lower-order assemblages of PV types within each genus are treated as species because they are phylogenetically closely related, but while they have distinct genomic sequences, they have identical or very similar biological or pathological properties. The taxonomic status of PV types, subtypes, and variants remains unchanged and is based on the traditional criteria that the sequence of their L1 genes should be at least 10%, 2-10%, and maximally 2% dissimilar from one another.

Papillomaviridae↗
PubMedDate not supplied

Infections caused by nondiphtheria corynebacteria.

After decades of confusion about their microbiologic classification and clinical significance, the nondiphtheria corynebacteria have emerged as important pathogens. Although isolation of these organisms may represent contamination with skin flora, several species, including Corynebacterium ulcerans, Corynebacterium pseudotuberculosis (Corynebacterium ovis), Corynebacterium haemolyticum, Corynebacterium pseudodiptheriticum, Corynebacterium equi, Corynebacterium bovis, Corynebacterium xerosis, and corynebacteria of group JK, clearly cause disease in humans. Most of these organisms infect animals, which are the source of human infection with some species. Some nondiptheria species of Corynebacterium produce recognizable clinical syndromes such as granulomatous lymphadenitis, pneumonitis, pharyngitis, cutaneous infections, and, most commonly, endocarditis. Certain species infect healthy hosts, while others predominantly attack immunocompromised individuals. Several species produce toxins, including a diphtheria-like toxin, a dermonecrotic toxin, and a soluble hemolysin. A microbiologic scheme of identification of the genus Corynebacterium and its major defined species is presented.

Animals↗
PubMed1999

Adult posttraumatic osteomyelitis of the tibia.

Posttraumatic tibial osteomyelitis results from trauma or nosocomial infection from the treatment of trauma that allows organisms to enter bone, proliferate in traumatized tissue, and cause subsequent bone infection. The resulting infection is usually polymicrobial. The patient may be classified using the May and the Cierny-Mader classification systems. The diagnosis is based on the isolation of the pathogen(s) from the bone, or blood cultures. Appropriate therapy of posttraumatic tibial osteomyelitis includes adequate drainage, thorough debridement, obliteration of dead space, stabilization when necessary, wound protection, and specific antimicrobial therapy.

Adult↗
PubMed2006

[Pneumocystis jiroveci: a new name for an old pathogen].

Pneumonia due to Pneumocystis is an important cause of morbidity-mortality among immunodepressed patients, above all with human immunodeficiency virus infection and finally in patients with transplants, oncology patients and those subjected to drug immunodepression. Its lack of capacity to grow in the usual culture mediums has hindered knowledge on many aspects of this infection (transmission, acquisition mode, infection sources). However, the incorporation of molecular biology tools in recent years has made it possible to go deeper into the understanding of the epidemiology, biology and characteristics of the infection by this pathogen. These advances have led to the modification of the taxonomic classification of this atypical fungus and change in the name of the Pneumocystis responsible for the infection in humans, which is now called Pneumocystis jirovecii. During this article, we will show some of the most recent advances in the knowledge of the human pneumocystosis.

Humans↗
PubMed2006

Multiple sclerosis therapy monitoring based on gene expression.

Multiple sclerosis (MS) is the most prevalent chronic autoimmune, neurodegenerative disorder of the central nervous system (CNS). Despite substantial progress, treatment of MS and other autoimmune diseases is only moderately effective. It is anticipated that the treatment of autoimmune diseases with single drugs or biological approaches will in the future be complemented, or even replaced, by combination therapies, which include immunomodulation, elimination of infectious triggers and tissue repair. One proclaimed goal of biomedical research and clinical practice is the discovery of sets of genes with expression that correlates with successful outcomes of drug therapy, or with unfortunate side effects. Such information has direct consequences for selection, refinement or development of treatments and will soon be translated into clinical trials. The genome-wide RNA profile of an individual represents one complement to the comprehensive determination of disease- or drug response-related elements; comparable to a 'sentinel' method, it serves as a large-scale approach to MS biology. This work reviews the state of the art in MS research at the transcriptome level applying genomewide screening methods. It discusses implications in understanding disease pathogenicity, diagnostic markers, the identification of new therapeutic targets and a classification of patients towards the advent of tailored therapies.

Biomarkers↗
PubMed2002

[Cystic periventricular leukencephalomalacia].

Cystic periventricular leukomalacia refers to necrosis of the white matter in a characteristic distribution dorsal and lateral to the external angles of the lateral ventricles in preterm infants. The pathogenesis includes either hypoxic-ischaemic lesions resulting from impaired perfusion at the vascular border zones or the role of intra-amniotic infection with toxic effects of endotoxins and cytokines on oligodendrocytes. This overview illustrates the pathogenic theories, risk factors, diagnosis by cranial ultrasonography, and the actual classification. Cystic periventricular leukomalacia is the most severe and frequent cause of cerebral palsy in preterm infants and is almost constantly associated with serious subsequent neuromotor impairments such as diplegia or tetraplegia. Dependant on site and extension of the cysts additionally visual impairments, seizure disorders, hearing impairments, mental retardation, and microcephaly are observed.

Echoencephalography↗
PubMed1996

Occupational health and safety in the biotechnology industry--a survey of practicing professionals.

A survey was created to gauge how health and safety (H&S) resources are allocated in the biotechnology industry and to help understand the concerns of industry H&S professionals. A questionnaire was distributed to "the person most responsible for health and safety" at 34 companies; 12 commercial firms responded. Nearly 68% of the work force monitored did not fall into any biohazard classification. Almost 80% of work involving biohazards was considered "exempt" or "BL-1" under the Centers for Disease Control and Prevention classification system, indicating that most work was performed involving organisms of low pathogenic potential. H&S program development and administration is mature; 100% of respondents report having written programs for chemical, biological, and physical hazards. Chemical safety programs occupied, on average, the greatest percentage of the H&S professionals' time (46%), followed by biosafety (29.6%) and physical hazards (16.4%). The person most responsible for H&S averaged 65% of work time on H&S issues, while only 25% described their full-time responsibilities as H&S related. Staffing levels for companies with more than about 100 technical workers approximated 1.0-1.5 full-time H&S staff equivalents per 100 technical workers. This figure compares favorably with levels reported in a benchmarking survey of hospitals. Investigation into accident rates as a measure of H&S program effectiveness suggests that the biotechnology industry is a relatively safe one. Lost time injury and illness rates were significantly lower for the 12 participating companies than the accident frequency rates in the Standard Industrial Classification codes selected for comparison.

Accidents, Occupational↗
PubMed2005

Dominant and opportunistic leukemic clones: proposal for a pathogenesis-oriented classification in acute myeloid leukemia.

Despite the common clinical, hematological and prognostic features that define acute myeloid leukemia (AML) there is considerable heterogeneity among individual cases, suggesting different pathogenic pathways. Based on a simple theoretical model, according to the vital characteristics of the leukemic clone (proliferative rate and resistance to apoptosis), I propose a classification of AML into two broad categories: (a) high leukemic clone vitality (HLV) AML or "dominant type" AML, corresponding roughly to the World Health Organization (WHO) classification group of entities "AML with recurrent cytogenetic abnormalities" and (b) low leukemic clone vitality (LLV) or "opportunistic type" AML corresponding to the WHO groups "AML with multilineage dysplasia" and "alkylating agent-related AML". HLV-AML leukemic clones are characterized by rate-limiting genomic mutations capable of conferring proliferation/survival advantage over a normal hematopoietic environment while in LLV-AML, the leukemic clones are not particularly proliferative or apoptosis-resistant, but are nevertheless selected against an impaired, previously damaged hematopoietic environment. Such a pathogenesis-oriented classification might have therapeutic and prognostic implications, providing a theoretical basis for a further adaptation of the current standard treatment strategies to the individual characteristics of the AML patients.

Apoptosis↗
PubMed2006

MAMPs and MIMPs: proposed classifications for inducers of innate immunity.

Plants encode a sophisticated innate immune system. Resistance against potential pathogens often relies on active responses. Prerequisite to the induction of defences is recognition of the pathogenic threat. Significant advances have been made in our understanding of the non-self molecules that are recognized by plants and the means by which plants perceive them. Established terms describing these recognition events, including microbe-associated molecular pattern (MAMP), MAMP-receptor, effector, and resistance (R) protein, need clarification to represent our current knowledge adequately. In this review we propose criteria to classify inducers of plant defence as either MAMPs or microbe-induced molecular patterns (MIMPs). We refine the definition of MAMP to mean a molecular sequence or structure in ANY pathogen-derived molecule that is perceived via direct interaction with a host defence receptor. MIMPs are modifications of host-derived molecules that are induced by an intrinsic activity of a pathogen-derived effector and are perceived by a host defence receptor. MAMP-receptors have previously been classified separately from R-proteins as a discrete class of surveillance molecules. However, MAMP-receptors and R-proteins cannot be distinguished on the basis of their protein structures or their induced responses. We propose that MAMP-receptors and MIMP-receptors are each a subset of R-proteins. Although our review is based on examples from plant pathogens and plants, the principles discussed might prove applicable to other organisms.

Immunity, Innate↗
PubMed1985

Experience with cefotaxime in infections caused by gram-positive pathogens, especially Staphylococcus aureus.

Cefotaxime (CTX) was the first third-generation cephalosporin to be launched. According to my classification of cephalosporins for practitioners, in contrast to old beta-lactamase-labile cephalosporins (Group I-III), CTX is beta-lactamase-stable and belongs to Group V with anti-pseudomonas activity. A critical review of about 90 patients with Staphylococcus aureus infections, found among analyzable subjects treated with CTX for gram-positive infections, demonstrates that CTX can be expected to be bacteriologically and clinically effective against this pathogen. Moreover, CTX had excellent efficacy against gram-positive organisms compared with other so-called third-generation cephalosporins. CTX is comparable to or more effective than conventional antibiotics in the treatment of respiratory tract infections, soft tissue infections, and neonatal and pediatric infections caused by gram-positive organisms, S. aureus included, if used after taking the susceptibility of the pathogen into account.

Bacterial Infections↗
PubMed2026

Biallelic pathogenic variants in FLNB are associated with paediatric steroid-resistant nephrotic syndrome via podocyte cytoskeletal dysfunction.

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is a severe paediatric kidney disease and a leading cause of end-stage kidney disease in children, with a high genetic contribution. While over 80 monogenic causes of SRNS have been identified, a significant proportion of affected patients still lack a clear genetic diagnosis, indicating that additional causative genes remain to be discovered. METHODS: Through whole-exome sequencing of a paediatric SRNS cohort, we identified three probands carrying biallelic FLNB pathogenic variants. Sanger sequencing was performed for familial cosegregation verification and ACMG classification. Expression of Filamin B, Nephrin and Synaptopodin in renal tissues was assessed by immunohistochemistry/immunofluorescence. Wild-type and patient-derived variant FLNB plasmids were constructed and transfected into HEK293T cells and immortalised human podocytes (HPCs). The effects of these variants on protein expression, localisation and cytoskeletal organisation were assessed by western blotting and immunofluorescence. FLNB expression in HPCs was silenced using shRNA to evaluate the impact on podocyte marker proteins, cytoskeletal integrity and migratory capacity. A zebrafish flnb knockdown model was employed to validate its effects on renal development. RESULTS: All three probands presented with isolated SRNS without skeletal developmental abnormalities, and renal tissues showed significantly reduced Filamin B protein expression. In vitro, p.L117P and p.M1803L variants led to markedly reduced protein expression, while p.R470L and p.K2586R induced perinuclear aggregation of Filamin B accompanied by F-actin rearrangement. FLNB silencing led to downregulation of Nephrin and Synaptopodin, cytoskeletal disorganisation and impaired cell migration. Zebrafish flnb knockdown exhibited pericardial oedema, defective nephron development and abnormal podocyte foot processes. CONCLUSION: We report for the first time that biallelic FLNB pathogenic variants are associated with paediatric SRNS by disrupting Filamin B expression, cytoskeletal integrity and podocyte function, providing evidence that FLNB is a novel monogenic cause of SRNS.

Humans↗
PubMed1989

Blastocystis hominis: phylogenetic affinities determined by rRNA sequence comparison.

In 1912 Blastocystis hominis was identified as a new species and classified as a yeast (Brumpt 1912). In the early 1920s several groups confirmed its classification as a yeast, specifically a member of the genus Schizosaccharomyces (discussed by Zierdt et al. 1967). Apart from an occasional case report, the classification of B. hominis and its role as a harmless intestinal yeast was not questioned for another 50 years. Then, Zierdt (1967) suggested that it should be classified in the phylum Protozoa, subphylum Sporozoa, and that it should be considered as a potential pathogen. The likely role of B. hominis as a human pathogen has recently become more firmly established (Garcia et al. 1984; Sheehan et al. 1986) and its classification has been changed. Although the classification of B. hominis as a protozoon was assumed widely, classification as a sporozoon was not accepted, and the most recent definitive classification of the Protozoa did not even list B. hominis (Lee et al. 1985). Then, based essentially on a review of the known characteristics of the organism, it was recently reclassified into the subphylum Sarcodina (Zierdt 1988). Clearly, the phylogeny of this emerging human pathogen needs definitive analysis (Mehlhorn 1988).

Animals↗
PubMed2000

Fusobacterium nucleatum involvement in adult periodontitis and possible modification of strain classification.

BACKGROUND: This investigation was designed to evaluate the involvement of Fusobacterium nucleatum clinical strains in adult periodontitis by subspecies and expression of hemagglutination activity. METHODS: Forty-nine Fusobacterium strains were isolated from 40 sites in 40 subjects presenting with adult periodontitis. F. nucleatum subspecies identification was based on the electrophoretic migration of glutamate dehydrogenase and 2-oxoglutarate reductase. Hemagglutination activity and inhibition by galactose were tested on sheep erythrocytes. RESULTS: The 49 isolates belonged to the F. nucleatum species with a predominance of the nucleatum (34.7%) followed by the vincentii (26.5%) subspecies. In parallel, 71% of the strains belonging to the nucleatum subspecies were preferentially associated with Porphyromonas gingivalis. Prevotella intermedia/nigrescens detection was essentially correlated with identification of Fusobacterium nucleatum subspecies vincentii. No correlation was established between any particular subspecies and the pathogenicity factors tested (hemagglutination and production of short-chain fatty acids). On the other hand, significant predominance (65%, P= 0.017) of strongly hemagglutinating strains (titre > or =8 U) was observed in the sites where Porphyromonas gingivalis, Prevotella intermedia/nigrescens and/or Campylobacter rectus were not detected. These strains also showed higher butyric acid production. CONCLUSION: The importance of the adherence factors for Fusobacterium nucleatum strains and their multimodal aspect may indicate a higher pathogenicity or a higher involvement of certain strains and could lead to a classification of these strains, which is more closely related to their implication in the development of periodontal disease.

Adult↗
PubMed2001

Karl Bonhoeffer and the concept of symptomatic psychoses.

With the description and classification of Symptomatic psychoses in 1908, Karl Bonhoeffer laid the foundation for a categorization into exogenous and endogenous psychoses. This opened new pathogenic and psychopathologic horizons in connection with the aetiology of psychoses, as was particularly exemplified by Bonhoeffer in the 'catatonic psychoses'. Later, his concept of Symptomatic psychoses was further developed. Especially the symptom of an impaired consciousness as a diagnostic criterion in delirium underwent a critical discussion. However, Bonhoeffer's basic positions have not even now lost their significance. They find their representation in a modified form in all of the recent classification systems ICD-10 and DSM-IV. The study of pathogenic, clinic-psychopathologic, classificatory and therapeutic perspectives in detail, following Bonhoeffer's example, remains an important task for neuropsychiatry in the present as well as the future.

Classification↗
PubMed2026

LDLR Variant Classification Through Activity-Normalized Prime Editing Screening.

BACKGROUND: Inherited variants in the LDL (low-density lipoprotein) receptor (LDLR) gene are the most common cause of familial hypercholesterolemia, significantly increasing coronary artery disease risk. Early identification of pathogenic LDLR variants enables prompt lipid-lowering therapy and cascade testing of at-risk relatives; however, most LDLR variants observed in the population have uncertain or absent clinical classifications, leaving many patients without actionable information. METHODS: We developed the first activity-normalized prime editing screening pipeline to measure the impact of 5184 LDLR coding variants on LDL-cholesterol (LDL-C) uptake. Each prime editing guide RNA is paired with a genotypic outcome reporter to correct for variable editing efficiency, overcoming a key limitation of previous pooled genome editing screens. A statistical framework further improves variant effect estimates by jointly analyzing all missense variants at each amino acid position. RESULTS: We show that prime editing of the reporter construct correlates with endogenous variant installation frequency, validating the activity normalization approach. The resulting scores capture a continuous spectrum of functional effects, robustly separate pathogenic versus benign ClinVar variants, and show concordance with LDL-C levels in UK Biobank participants. We calibrate functional evidence strengths to the ACMG/AMP variant interpretation framework, enabling integration into a clinical variant classification workflow. By combining functional, computational, population, and contextual evidence, 322 of 434 LDLR variants currently classified as variants of uncertain significance, conflicting, or absent from ClinVar appear to meet evidence thresholds for reclassification and can be prioritized for expert review, substantially expanding the pool of actionable variant classifications. The screen also reveals a cluster of gain-of-function variants in LDLR class A repeat 5, at least some of which enhance LDL-C uptake through increased apolipoprotein B interaction, with implications for therapeutic genome editing. Last, prime editing uniquely detects splice-altering coding variants missed by cDNA-based screens and pathogenicity predictors, revealing an advantage of endogenous variant installation. CONCLUSIONS: Altogether, activity-normalized prime editing provides a scalable framework for LDLR variant classification that substantially expands the proportion of variants with evidence for genetic diagnosis and reveals novel biology with therapeutic relevance.

CRISPR screening↗
PubMed2005

Enterobacter sakazakii: a coliform of increased concern to infant health.

The first cases of neonatal meningitis believed to have been caused by Enterobacter sakazakii were reported in 1961. Prompted by several subsequent outbreaks of E. sakazakii infections in neonates and an increasing number of neonates in intensive care units being fed rehydrated powdered infant formula, considered to be a source of the pathogen, public health authorities and researchers are exploring ways to eliminate the bacterium or control its growth in dry infant formula, processing environments and formula preparation areas in hospitals. Reviewed here are advances in taxonomy and classification of E. sakazakii, methods of detecting, isolating and typing the bacterium, antibiotic resistance, clinical etiology and pathogenicity. Outbreaks of E. sakazakii infections in neonates and adults are summarized. Reports on the presence of E. sakazakii in clinical settings, the environment and foods and food processing facilities are reviewed. Tolerance of the pathogen to environmental stresses, its behavior in powdered and rehydrated infant formulae and hazard analysis and risk management are discussed. Research needs are presented.

Cronobacter sakazakii↗
PubMed1981

Characteristics of listeria strains, isolated from micromammalia in Bulgaria.

56 Listeria strains isolated from the intestine contents of 13 species of micromammalia in Bulgaria were studied. 10 of the strains belong to the serovars 1/2a, 4A, 4b and 5 of Listeria monocytogenes and 44 of the strains belong to 10 antigenic variants of Listeria innocua. According to their characteristics these strains could hardly cause diseases in humans or domestic animals. Two strains have antigenic formulae O-V, VII, XIV and O-V, XIV and cannot be included in the existing classification. Prevalent are the strains antigen O-XV. They are more often isolated from synanthropic rodents. The hemolytic properties of the studied strains have the best correlation with the pathogenicity. The decomposition of rhamnose and xylose and the production of lysozyme could be a suitable basis for their classification in biotypes.

Animals↗
PubMed2004

Fluoroquinolones: mechanism of action, classification, and development of resistance.

The fluoroquinolones represent an evolving class of broad-spectrum antimicrobial agents used in the prevention and treatment of a variety of ocular infections; however, resistance to currently available agents in the class has been emerging among ocular pathogens. This article reviews the mechanism of action of existing and new fluoroquinolones and discusses the structure-activity relationship of the fluoroquinolones as it relates to the classification of these compounds. This article also highlights the mechanism of resistance among common ocular pathogens and discusses the potential need for newer fluoroquinolones in ophthalmology.

Anti-Infective Agents↗