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[Primates in the study of hepatitis viruses].

There is no a conventional tissue culture system for the propagation of the hepatitis viruses and only some of them can be maintain in continuous cell culture in particular conditions. A transmissibility of hepatitis is limited to primates. The narrow host specificity may help to establish the classification of the hepatitis viruses and their mode of transmission. Moreover, the primate animal model provided the most accessible source of viruses and for clinical reasons presents the only opportunity for the studies of pathogenic mechanisms involving cellular immunity with allogenic restriction. The marmosets and chimpanzees susceptible to the hepatitis A and B viruses, respectively are the primates of choice for the experimental models. For the studies on parenterally transmitted NANB hepatitis the chimpanzee and some rhesus monkeys may provide an animal system. At last, most of the primates seem to be susceptible to agent responsible for the water-borne non A non B hepatitis.

Animals↗

[Determination of zinc and copper in patients with liver cirrhosis of diverse clinical severity].

Zinc and copper levels in the blood and urine of 44 liver cirrhosis patients and 10 healthy volunteers are reported. The clinical severity of the liver disease (according to the Child classification system) was correlated with the levels of the two metals. An attempt was also made to break down the parameters on which the Child System in based in order to contribute to the pathogenic interpretation of changing zinc levels in liver disease patients. The results show a significant reduction in zinc in the blood but an increase in the urine in the various degrees of liver damage. A connection was also noted between low blood zinc and encephalopathy.

Copper↗

[Pneumonia in ambulatory care patients. Choice of antibiotics for therapy of community-acquired pneumonia].

According to the statistics prepared by health insurance carriers community-acquired pneumonia has an incidence of some 300,000 to 400,000 cases per year. In old age (more than 80 years), the mortality rate increases from 20 to 2000 per 100,000 head of the population, that is, by a factor of 100. The former classification into "typical" and "untypical" pneumonia has now been abandoned, the modern approach being that of "calculated antibiotic therapy" that involves the placing of patients in "risk groups". To each risk group a probable pathogen spectrum is assigned and a recommendation for the selection of an appropriate antibiotic then made. Thus, for example, for the pathogen spectrum in group 1 (ambulatory patients under 60 years of age and no major secondary diseases), the macrolides are the antibiotics of first choice. The procedure to be followed in the other risk groups and in the event of treatment failures is discussed. Criteria that identify the need for hospitalization are presented.

Aged↗

[Autosomal recessive cerebellar ataxias. Their classification, genetic features and pathophysiology].

INTRODUCTION AND DEVELOPMENT: Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs. They use to have early onset before the age of 20. Based on pathogenic mechanisms five main types may be distinguished: congenital (developmental disorder), mitochondrial ataxias, ataxias associated with metabolic disorders, ataxias with a DNA repair defect, and degenerative ataxia with unknown pathogenesis. The most frequent in Caucasian population are Friedreich ataxia and ataxia-telangiectasia. Other forms are much less common, and include abetaliproteinemia, ataxia with vitamin E deficiency (AVED), ataxia with oculomotor apraxia types 1 (AOA1) and 2 (AOA2), early onset cerebellar ataxia with retained reflexes, Charlevoix-Saguenay spastic ataxia, and Joubert syndrome. The prevalence of ARCA has been estimated to 7 in 100,000 inhabitants. These diseases are due to mutations in specific genes, some of which and its encoded proteins have been identified, such as FRDA (frataxin) in Friedreich ataxia, APTX (aprataxin) in AOA1, alphaTTP (alpha-tocopherol transfer protein) in AVED, and STX (senataxin) in AOA2. Due to autosomal recessive inheritance, previous familial history of affected individuals unlikely. CONCLUSIONS: Most of these cerebellar ataxias have no specific treatment with exception of the ataxia associated with deficiency coenzyme Q10 and abetalipoproteinemia. Clinical diagnosis must be confirmed by ancillary tests such as neuroimaging (magnetic resonance, scanning), electrophysiological examination, and mutation analysis when the causative gene has been identified. Correct clinical and genetic diagnosis is important for appropriate prognosis and genetic counseling and, in some instances, pharmacological treatment.

Age of Onset↗

Using Mapping-Profiles to Refine Strain-Level Metagenomic Classification.

Metagenomic classification at the strain level remains challenging due to high sequence similarity among closely related genomes, which leads to ambiguous read mappings and frequent false-positive strain detections. Reducing such errors improves the reliability of strain-level analyses, which is critical for applications such as pathogen detection. We introduce StrainRefine, a post-mapping refinement method that analyzes read-reference mapping profiles to resolve ambiguous assignments among highly similar genomes. The method represents candidate reference genomes using binary profiles that capture read-support patterns and measures similarity between references based on profile overlap. The method clusters references based on similar mapping profiles, filters weakly supported genomes, and reassigns reads to representative references, reducing redundant reporting of near-identical strains. StrainRefine substantially reduces false-positive strain detections while preserving recall and improving agreement between predicted and true abundance profiles. On large-scale metagenomic datasets, it achieves a substantially improved precision-recall balance compared with existing mapping-based approaches, with the standalone method obtaining the highest read-level classification accuracy on the most complex evaluated dataset. Unlike many strain-level tools designed for individual species, StrainRefine operates without prior assumptions about sample composition or curated species-specific reference collections, while still achieving comparable performance in single-species settings on species-specific reference databases. These results highlight mapping-profile similarity as an effective signal for improving strain-level metagenomic classification.

false-positive reduction↗

Development of a nosocomial outbreak investigation database.

A pilot web-based database was created to facilitate epidemiological investigation of nosocomial outbreaks. The database provides highly structured abstracts in a case study format to serve as a guide for investigations. Problems encountered in abstracting over 330 published reports included missing information and classification of study methods. The database offers a new way to review outbreaks, for example, in terms of their impact measured by various combinations of database fields, such as the number of cases, attack rate, pathogens, service/ward and mode of transmission. Feedback from users of the database suggests its usefulness. Creation of a large web-based database seems to be both desirable and feasible.

Abstracting and Indexing↗

Phylogenetic analysis by rRNA comparison of the highly pathogenic sheep-infecting parasites Theileria lestoquardi and a Theileria species identified in China.

In the Northwestern part of China there have been reports of clinical cases in small ruminants of a haemoparasite with the characteristics of Theileria hirci (T. lestoquardi). However, some properties of this parasites argue against its classification as T. lestoquardi. In this paper, we present evidence that T. lestoquardi and the Chinese Theileria isolate are distinct parasite species. Phylogenetic analysis of determined nucleotide sequences of small subunit ribosomal RNA (srRNA) genes of T. lestoquardi and the Chinese Theileria parasite show that they belong to different clades within the phylogenetic tree of piroplasms. The srRNA sequence of the Chinese parasite was found to be most closely related to T. buffeli, which, with T. sergenti, belongs to an evolutionary lineage of non-lymphoproliferative Theileria species. On the other hand, it was clearly divergent to a lineage of lymphoproliferative Theileria species; T. annulata, T. parva, T. taurotragi, and T. lestoquardi, the latter being most closely related to T. annulata.

Animals↗

Transcriptomic analysis of the cardiac left ventricle in a rodent model of diabetic cardiomyopathy: molecular snapshot of a severe myocardial disease.

Heart disease is the major cause of death in diabetes, a disorder characterized by chronic hyperglycemia and cardiovascular complications. Diabetic cardiomyopathy (DCM) is increasingly recognized as a major contributor to diastolic dysfunction and heart failure in diabetes, but its molecular basis has remained obscure, in part because of its multifactorial origins. Here we employed comparative transcriptomic methods with quantitative verification of selected transcripts by reverse transcriptase quantitative PCR to characterize the molecular basis of DCM in rats with streptozotocin-induced diabetes of 16-wk duration. Diabetes caused left ventricular disease that was accompanied by significant changes in the expression of 1,614 genes, 749 of which had functions assignable by Gene Ontology classification. Genes corresponding to proteins expressed in mitochondria accounted for a disproportionate number of those whose expression was significantly modified in DCM, consistent with the idea that the mitochondrion is a key target of the pathogenic processes that cause myocardial disease in diabetes. Diabetes also induced global perturbations in the expression of genes regulating cardiac fatty acid metabolism, whose dysfunction is likely to play a key role in the promotion of oxidative stress, thereby contributing to the pathogenesis of diabetic myocardial disease. In particular, these data point to impaired regulation of mitochondrial beta-oxidation as central in the mechanisms that generate DCM pathogenesis. This study provides a comprehensive molecular snapshot of the processes leading to myocardial disease in diabetes.

Animals↗

Is closer linkage between systemic lupus erythematosus and anti-double-stranded DNA antibodies a desirable and attainable goal?

The anti-double-stranded DNA (anti-dsDNA) antibody test incorporated in the 1982 revised American College of Rheumatology criteria for the classification of systemic lupus erythematosus needs updating to reflect current insights and technical achievements, including allowance for the presence of nonpathogenic anti-dsDNA antibodies. As we need to develop at least some measure of pathogenicity of anti-dsDNA antibodies, we propose that initial anti-dsDNA antibody screening is done by sensitive ELISA and supplemented by more stringent assays. Simultaneously the relevance of anti-dsDNA antibody presence needs to be restricted to clinical manifestations, thought to be caused by anti-dsDNA antibody and within an appropriate time frame.

Antibodies, Antinuclear↗

[Determination of serum Fe in prostatic pathology].

We have determined serum Fe concentrations in 75 patients whose post-surgical anatomo-pathological diagnostic was: 25 cases with prostate benign hyperplasia, 25 cases where besides hyperplasia there was also an associated chronic prostatitis and 25 cases of moderately differentiated prostatic adenocarcinoma stage D according to the Jewett classification. No patient had received prior medication nor had associated metabolic pathology. Serum Fe concentration was significantly decreased in the cases with prostatic adenocarcinoma. The methodology used for these determinations is presented, discussing the possible pathogenic hypothesis explaining this finding together with the clinical consequences.

Adenocarcinoma↗

Variability versus heterogeneity in syndromal hypothalamic hamartoblastoma and related disorders: review and delineation of the cerebro-acro-visceral early lethality (CAVE) multiplex syndrome.

We report on a case of neonatal hypothalamic hamartoblastoma with holoprosencephaly, Hirschsprung disease, and tetramelic postaxial polydactyly. Twenty-seven previous cases of congenital hypothalamic embryonic tumours with associated congenital defects are reviewed. A classification in isolated, associated, and syndromal forms is proposed. The difficulties encountered in differential diagnosis between the syndromal form (mainly represented by the Pallister-Hall syndrome) and related diseases as Smith-Lemli-Opitz type II, holoprosencephaly-polydactyly, orofaciodigital type VI and hydrolethalus syndromes are outlined. Two pathogenic mechanisms are discussed: a classical pleiotropic model and single sequence model. The latter is sufficient to delineate syndromal hypothalamic hamartoblastoma. With the former, syndromal hypothalamic hamartoblastoma cannot be clearly recognized in the absence of a CNS tumour, a child with syndromal hypothalamic hamartoblastoma cannot be reliably diagnosed as Pallister-Hall rather than another MCA syndrome, and, ultimately, the existence of Pallister-Hall syndrome could be questioned, as it could only be the extreme expression of one or several other syndromes. As this hypothesis cannot be proven or disproven at this point, the authors suggest creating the concept of multiplex phenotype. "Cerebro-Acro-Visceral Early lethality multiplex syndrome" is suggested to encompass all the ambiguous cases. Within this complex, an operative classification key is proposed.

Abnormalities, Multiple↗

Diagnostic, prognostic and pathogenic value of the direct immunofluorescence test in cutaneous leukocytoclastic vasculitis.

BACKGROUND: No precise studies have been performed on cutaneous leukocytoclastic vasculitis (LV) to establish whether it is better to obtain a skin biopsy from lesional or from perilesional skin for direct immunofluorescence (DIF). There is no agreement on the immunoglobulins most frequently detected and the value of DIF for the classification of cutaneous vasculitis. METHODS: A prospective study of DIF in lesional and perilesional skin was performed in 50 leukocytoclastic vasculitis patients and 15 nonvasculitis patients. RESULTS: We detected a higher level of positivity in involved skin than in uninvolved skin for IgG, IgA, IgM, C3 and fibrinogen but not for C1q. In vasculitic patients, IgA was the immunoglobulin most frequently detected in lesional (82%) and perilesional skin (68%), followed by IgM (56 and 34%, respectively) and IgG (20 and 8%, respectively). Only IgA deposits were associated with the diagnosis of vasculitis, with a sensitivity of 82% in lesional and 68% in perilesional skin, and with a specificity of 73 and 66.7%, respectively. The presence of IgA in lesional skin was associated with renal involvement but there was no association with severity. The presence of IgG or IgM, or the absence of IgA in perilesional skin was related to the presence of cryoglobulins. The absence of IgA in lesional and perilesional skin was also related to hepatitis C virus infection. CONCLUSIONS: DIF findings in involved skin are more closely related to the diagnosis of vasculitis and can give more information about overall renal involvement than findings in uninvolved skin. However, findings in uninvolved skin are more closely related to the pathogenic factors that trigger the development of vasculitis.

Adolescent↗

Infections in patients requiring ventilation in intensive care: application of a new classification.

OBJECTIVE: To classify infections according to the carrier state determined by surveillance cultures of throat and rectum, rather than by the traditional criterion of the time of onset after admission. METHODS: An observational cohort study of 3 months' duration was performed in a mixed medical---surgical intensive care unit (ICU) in a district general hospital of a subset of patients requiring mechanical ventilation for 3 days. Surveillance cultures from throat and rectum were obtained on admission to the ICU and then twice weekly to distinguish carriage of potentially pathogenic microorganisms (PPM) brought in by the patient from microorganisms acquired during the ICU stay. RESULTS: Out of the total population of 104 patients, 21 patients were enrolled over 3 months. Eight patients (38%) developed 12 infections, half of which were of primary endogenous pathogenesis and caused by Haemophilus influenzae, Candida albicans and Pseudomonas aeruginosa carried by the patients on admission. The remaining six were of secondary endogenous pathogenesis and caused by Acinetobacter baumannii and Pseudomonas aeruginosa acquired in the unit. CONCLUSIONS: Traditional classifications of hospital infection are challenged. If the traditional 48-h cut-off point was used, then 9 of 12 cases (75%) of infection would have been classified as nosocomial, whereas using the method based on the carrier state, 50% of all infections were caused by microorganisms carried by the patient on admission to the ICU. Moreover, we believe that the distinction between primary endogenous, secondary endogenous and exogenous is valid because these three types of infection each require different control methods.

Journal Article↗

[Occurrence of fungal pathogens in the delivery rooms of a hospital obstetrics department].

OBJECTIVES: Assessment of the incidence of fungal pathogens in air of the operating rooms from one of the hospitals in Białystok. MATERIAL AND METHODS: Investigations were conducted in selected rooms of obstetrics department. Material for mycological studies was air sampled at the entrance of hospital building, the entrance to operating room, hall and selected rooms of the department. Fungi were identified using the standard microbial procedures: The monitoring of airborne fungi pollution was done using SAS SUPER 100 (pbi international). Classification of the isolated fungi was done with an accordance to the current procedures. RESULTS: In the air of 16 rooms of obstetrics department different numbers of fungal colonies from 0 to 560 CFU/1000L of air were isolated. Fungi were not isolated from the air samples of preparing, septic, operating and family deliveries rooms. The highest number of fungi colonies were isolated at the entrance the hospital. The following fungal pathogens isolated from the air were: Candida albicans. non-Candida albicans, Penicillium species, Cladosporium species and Aspergillus species. CONCLUSIONS: 1. The different number of fungal colonies was found depending on type of the hospital room. 2. The highest number of fungal colonies was isolated from the air samples of patients rooms 3. No fungal colonies were isolated from the septic, operating and family deliveries rooms 4. The main fungal pathogen isolated from the air samples was Candida albicans.

Air Microbiology↗

Surgical resection for cancer of the cardia.

From the pathogenic and therapeutic point of view, adenocarcinomas of the esophagogastric junction (AEG) should be classified into adenocarcinoma of the distal esophagus (Type I), true carcinoma of the cardia (Type II), and subcardial carcinoma (Type III). This classification can be easily performed by summarizing the information available from contrast radiography, endoscopy, and intra-operative findings; it allows comparison of data between various centers and facilitates the choice of surgical therapy. A complete removal of the primary tumor and its lymphatic drainage has to be the primary goal of any surgical approach to adenocarcinoma of the esophagogastric junction. In patients with potentially resectable, true carcinoma of the cardia (AEG Type II), this can be achieved by a total gastrectomy with transhiatal resection of the distal esophagus and en bloc removal of the lymphatic drainage in the lower posterior mediastinum and along the celiac axis and superior border of the pancreas. This approach is associated with lower morbidity and provides equal long-term survival as compared to the more radical transmediastinal or abdominothoracic esophagogastrectomy. Whether a routine splenectomy for lymphadenectomy in the splenic hilus offers a survival benefit in these patients is questionable. In patients with early tumors staged as uT1 on pre-operative endosonography, a limited resection of the proximal stomach, cardia, and distal esophagus with interposition of a pedicled isoperistaltic jejunal segment appears justified since this procedure allows a complete tumor removal with adequate lymphadenctomy and offers excellent functional results. Multimodal therapy with pre-operative polychemotherapy or combined radio-chemotherapy appears to offer a significant survival benefit in patients with locally advanced tumors. With this tailored approach, extensive pre-operative staging becomes mandatory for an adequate selection of the appropriate therapeutic concept.

Adenocarcinoma↗

Tubulointerstitial nephritis.

Tubulointerstitial nephritis (TIN) describes a range of pathological processes that are at least partly responsible for the progression of renal disease of nearly all aetiologies. TIN is frequently the most important pathological manifestation of progressive glomerulonephritis, obstructive uropathy, reflux nephropathy and cystic diseases, although it may also present as a primary disease process associated with infection, drug use or other immunologically mediated disease. Recent clinical and laboratory research has increased our knowledge of tubulointerstitial structure, physiological function and tubulointerstitial response to injury. This review presents a classification of TIN in which acute and chronic tubulointerstitial diseases are recognized as forming a continuum. Primary TIN and TIN associated with glomerulonephritis, obstructive nephropathy and chronic progressive renal disease are discussed from both clinical and pathogenic aspects. It is argued that chronic TIN is a disease process in which inflammation is accompanied by a destructive tubulopathy and fibrogenesis. In acute TIN there is a cessation and reversal of this process. It is suggested that most forms of TIN have an immunological basis because of the presence of immune cell infiltrates, the occurrence of TIN in several immune diseases and immunological animal models of TIN. However, to date TIN has not been convincingly modified in patients by immune manipulation. Experimental evidence suggesting an important pathogenic role for proteinuria and antigenuria, and the renal tubule cell acting as an antigen-presenting cell is discussed.

Acute Disease↗

[Clinical genetics of neuroendocrine tumors].

Neuroendocrine tumors (NETs) are a heterogeneous group of benign and malignant neoplasias, detectable in the context of hereditary tumor syndromes in up to 30% of cases. The pathogenic understanding of NETs has increased considerably during the last decade, mainly due to the identification of underlying genetic defects and the availability of genetically modified animal models. These developments are reflected in a revised WHO classification of gastrointestinal NETs. In contrast to a variety of rare neuroendocrine tumor syndromes, multiple endocrine neoplasia syndrome type 1 (MEN1) and type 2 (MEN2) play clinically significant roles due to their common incidence. MEN1 and MEN2 are classic autosomal-dominant familial tumor diseases with a high penetrance and variable clinical expression, caused by germ line mutations of the MEN1 tumor suppressor gene and the RET protooncogene, respectively. The clinical management of patients with NETs has changed significantly after the introduction of clinical genetic screening. The detection of MEN1 mutations allows for risk-adapted treatment and follow-up. RET gene analysis can identify individuals with a very high risk to develop familial medullary cancer (MEN2), who may be successfully treated by prophylactic thyroidectomy. NETs thus represent a paradigmatic example of the successful link between basic genetic science and clinical care in molecular medicine.

Adolescent↗

Malassezia Baillon, emerging clinical yeasts.

The human and animal pathogenic yeast genus Malassezia has received considerable attention in recent years from dermatologists, other clinicians, veterinarians and mycologists. Some points highlighted in this review include recent advances in the technological developments related to detection, identification, and classification of Malassezia species. The clinical association of Malassezia species with a number of mammalian dermatological diseases including dandruff, seborrhoeic dermatitis, pityriasis versicolor, psoriasis, folliculitis and otitis is also discussed.

Animals↗