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PubMedDate not supplied

The systemic vasculitides.

The systemic vasculitides include a heterogenous group of diseases, characterized by inflammatory and necrotic lesions of the vessel walls, with subsequent ischemic changes in different organs. Various factors are incriminated in the vasculitides etiology, despite the fact that, in most of the cases, the etiologic agents are unknown. The pathogenic mechanisms are generally mediated through circulant immune complexes, which induce the inflammatory reaction at the vessel wall site, accompanied by complex immune reactions. A classification of vasculitides should take into account the type of the injured vessel, the elements of the inflammatory infiltrate and the triggering pathogenic mechanisms. The definition and monitoring of the therapeutic regimen are difficult but, generally, the main elements of medication are represented by corticosteroid and cytotoxic drugs.

Humans↗

PubMed1975

A numerical taxonomic study of coryneform and related bacteria.

Two hundred and thirty-three strains of coryneform bacteria, including representatives of the genera Arthrobacter, Brevibacterium, Cellulomonas, Corynebacterium, Erysipelothrix, Jensenia, Kurthia, Listeria, Microbacterium, Mycobacterium, Nocardia and Propionibacterium and other related bacteria, were studied using 173 morphological, physiological and biochemical tests. The bacteria were grown on a soil extract medium which allowed growth of all the strains, and all were incubated at 30 degrees C. The results were subjected to computer analysis. The majority of the strains grouped into eight main clusters representing: (A) Lactobacillus, Listeria, Microbacterium thermosphactum and Streptococcus faecalis; (B) Erysipelothrix and Streptococcus pyogenes; (C) animal corynebacteria and Microbacterium flavum; (D) Cellulomonas and related bacteria; (E) Propionibacterium; (F) Arthrobacter, Brevibacterium, Kurthia and Mycobacterium rhodochrous; (G) plant pathogenic corynebacteria; (H) Nocardia. Based on these clusters, several recommendations are made regarding the classification of the coryneform area. (i) The members of clusters A and B at present placed in the Corynebacteriaceae would seem better moved to the Lactobacillaceae. (ii) The genus Corynebacterium would best be retained for the types species C. diphtheriae, closely related animal corynebacteria and Micro. flavum. (iii) Cellulomonas and Propionibacterium are distinct taxa more closely related to Corynebacterium than to either Arthrobacter or Lactobacillus. (iv) Clusters F and G are evidently heterogeneous. In particular the positions of Kurthia and the plant pathogenic corynebacteria are unclear. Arthrobacter is a large loose taxon and it is premature to decide on its taxonomic rank. The genus Brevibacterium should be retained for B. linens and closely related strains. (v) The cellulolytic forms of Nocardia should be removed from the genus; they are however quite distinct from Cellulomonas.

Actinomycetales↗

PubMed1993

A nephrological view of the classification of vasculitis.

From the nephrologic perspective, a nomenclature system has been proposed that is clinically useful for diagnosis, classification and therapy. This nomenclature allows the nephrologist to consider the best approach to ANCA positive patients with necrotizing and crescentic glomerulonephritis. It allows for better understanding of the extra-renal manifestations of disease especially those with pulmonary-renal syndrome. The classification system allows for the rapid introduction of immunosuppressive therapy in individuals without repetitive search for specific pathological features on biopsy. This classification system allows for the possibility that all of these conditions are pathogenically related. As such, it separates this group of diseases from those which are attributable to immune complex disease or direct antibody binding. For this nomenclature system to stand the test of time it must be simple, logical and clinically usefully. While not yet perfected, the working nomenclature for ANCA-associated diseases is a step forward.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed1988

Angels with wet wings won't fly: maternal sentiment in Brazil and the image of neglect.

Current theories of fatalism and neglect and current descriptions of childhood illness in impoverished Northeastern Brazil are evaluated. Findings of an ongoing multidisciplinary project indicate that neglect and fatalism theories are incomplete as applied to the Brazilian Northeast. Intensive interviews and observations with bereaved mothers and traditional healers show that mothers' failure to obtain medical care for severely ill children is due more to real-life bureaucratic and geographic barriers to access than to fatalistic or neglectful attitudes on the part of the poor, that mothers' flat affect in response to infant deaths is due more to folk Catholic beliefs than to lack of emotional attachment to infants, that fatalistic statements are often post hoc and do not indicate fatalistic behavior, and that decisions about whether to treat severely ill infants are made by mothers and families in consultation with traditional healers in accord with a folk system of classification of high risk infants. What have been described as "death accepting," "pathogenic," and "ethnoeugenic" attitudes are part of a folk ethical system developed to guide reactions to terminal childhood illness. We argue that human behavior, especially in the realm of health, cannot be understood without reference to both biomedical and psychosocial realities.

Adult↗

PubMed1991

Species identification and characterization of an Acanthamoeba strain from human cornea.

The isoenzyme pattern of an Acanthamoeba, stock H-1, isolated from a patient with keratitis (Krankenhaus Heidberg, Hamburg) was compared with that of two strains of A. quina-A. lugdunensis (302-2, 312-1), two stocks of A. lenticulata (45, 89-1) and one strain of A. rhysodes (302-1). The isolated stock showed glucose-6-phosphate dehydrogenase (G-6-PDH), beta-hydroxybutyric dehydrogenase (beta-HBDH), alcohol dehydrogenase (ADH) and superoxide dismutase (SOD) isoenzyme patterns similar to those of A. quina-A. lugdunensis but their acid phosphatase (AP) patterns differed. Furthermore, cyst morphology showed that the patient-isolated stock belongs to group II of the taxonomic classification of Acanthamoeba. This stock was not thermophilic and exhibited non-pathogenic properties after its intranasal instillation into NMRI mice, whereas it killed BALB/c mice. Immunofluorescent studies revealed the presence of antibodies against Acanthamoeba in the patient's serum. Immunoblotting experiments showed that a 45-kDa protein reacted with this serum. Such an antigen was also detected in A. quina-A. lugdunensis and A. lenticulata. Lectin reactions with Canavalia ensiformis, Ricinus communis-120, Lotus tetragonolobus, Ulex europaeus I, Helix pomatia, Arachis hypogaea, Triticum vulgaris, Glycine maxima, Bauhinia purpurea and Mycoplasma gallisepticum demonstrated that only the A. lenticulata stocks could not be distinguished and that the H-1 stock was more similar to the A. lugdunensis 302-2 strain than to the other acanthamoebae.

Acanthamoeba↗

PubMed2006

Genetic variability of Blastocystis hominis isolates in China.

To determine if genetic diversity of Blastocystis hominis exists in China, 35 B. hominis isolates obtained from 19 asymptomatic infected individuals and 16 patients with gastrointestinal symptoms were genotyped by PCR using seven pairs of known sequenced-tagged site (STS) primers. Out of the 35 isolates, 29 were identified as one of the known genotypes, while five isolates showed two distinct genotypes, and one isolate was an unknown genotype as this was negative with all the STS primers. In this study, none of the isolates was classified as subtypes 4-7. Compared with the spectrum of human B. hominis subtypes obtained from five geographically different countries (Japan, Pakistan, Bangladesh, Germany, and Thailand), these results showed that subtype 1 was more a popular genotype (18/35) in China. In addition, two groups of the isolates from 19 asymptomatic infected individuals and those from 16 patients with intestinal symptoms were compared with the PCR-based subtype classification. The results suggest a possible relationship between subtype 1 and a pathogenic potential of this parasite.

Animals↗

PubMed1994

Long-bone osteomyelitis diagnosis and management.

The pathogen may proliferate years after seemingly successful treatment. The authors describe a classification system to evaluate both the disease and the patient's capacity to undergo the rigors of therapy. Two cases illustrate the clinical issues.

Adolescent↗

PubMed2001

[Chromosome replication in mycobacteria].

Variation in growth rate has provided a basis for the broad classification of Mycobacterium: (i) the slow-growing class includes the human pathogens Mycobacterium tuberculosis and M. leprae, and (ii) the fast-growing class includes saprophytic nonpathogens, such as M. smegmatis. An intimate association between DNA chromosomal replication and growth rate have been suggested. However, the molecular basis of this relation is unknown. In this article, we summarise our recent work on the study of the origin replication region of some species of mycobacteria, determination of the factors regulating the initiation of DNA replication and the characterisation of the main factor of the replicative machinery, the DnaA protein.

Bacterial Proteins↗

PubMedDate not supplied

[Secreted pathogenicity factors of enterobacteria].

Data on the secreted pathogenicity factors of different enterobacterial species are reviewed. Update information on toxin classification is presented. The main cytotoxic and cytotonic enterotoxins, transient pore forming toxins (RTX), cytotoxic necrotizing factor and injection toxins have been analyzed. Problems connected with the mechanism of action and genetic control of known enterobacterial toxins are discussed.

Animals↗

PubMed1998

[New classification and diagnostic criteria for diabetes mellitus].

The new Classification and Diagnostic Criteria for Diabetes Mellitus (DM), prepared by a group of experts from the American Diabetes Association is presented and analyzed. On an etiopathogenic basis, it designates Insulin Dependent and Non Insulin Dependent as Type 1 and Type 2 respectively. It specifies DM having specific known causes. It maintains Gestational Diabetes and Glucose Intolerance and adds the Impaired Fasting Glucose Condition. It recommends fasting plasma glucose for search and diagnosis, and lowers the level to > or = 126 mg/dl instead of > or = 140 mg/dl, due to its association with chronical complications of DM. It maintains the diagnostic criteria of random and post charge glycemia > or 200 mg/dl. It does not alter the glucose intolerance figure (140-200 mg/dl in OGTT) and introduces fasting abnormality > or = 110 and < 126 mg/dl. It encourages the search with fasting glucose every 3 years in individuals aged over 45, and at more frequent intervals in younger individuals with high risk factors. Analysis of the report allows to conclude that, although the classification does not introduce any significant change in daily clinical use, its pathogenic orientation makes future innovations possible. The preferential use of fasting glucose > or = 126 mg/dl for diagnosis of DM has theoretical basis and practical advantages. Identification of individuals with impaired fasting glucose allows to detect, in a simple manner, a high risk group in which to start preventive measures. However, there is a percentage of cases which are not diagnosed by fasting glycemia, but are diagnosed by OGTT, therefore the latter should not be discarded.

Blood Glucose↗

PubMed2004

Genomics and microarray for detection and diagnostics.

Genomics provided biomedical scientists an inventory of all genes and sequences present in a living being. This provides an unique opportunity to the scientists to predict and study biological functions of these genes. The changes in the gene expression regulated by genomic sequences therefore reflect changes in the molecular processes working in a cell or tissue in response to external factors including exposure to toxic compounds and pathogens. Microarray offers a biotechnological revolution with the help of DNA chemistry, silicon chip technology and optics to be used to monitor gene expression for thousands of genes in one single experiment. Briefly, 20,000 to 100,000 unique DNA molecules get applied by a robot to the surface of silicon wafers (approximately the size of a microscope slide). Using a single microarray experiment, the expression level of 20,000 to 100,000 genes will be examined in one single experiment. Genomics and microarray have a significant role and impact on the design and development of modern detection and diagnostic tools in several different ways. Microarray tools are now used on regular basis for monitoring gene expression of large number of genes and also frequently applied to DNA sequence analysis, immunology, genotyping, and molecular diagnosing. For diagnostics, these tools can be used to distinguish and differentiate between different DNA fragments that differ by as little as a single nucleotide polymorphism (SNP). These microarrays can be divided based on the gene density spots that will be high density (>10,000 spots) per slide, medium (< 1000 > 100) and low density (< 100). High-density arrays have proven to be very useful in disease diagnosis especially in diagnosis and classification of different types of cancers. These microarray tools hold tremendous potential for pathogen detection, which will be comprised, of unique sets of genes (also referred to as "signatures") able to unambiguously identify the species and strain of pathogens of interest.

Drug Design↗

PubMed2004

In vitro investigation of voriconazole susceptibility for keratitis and endophthalmitis fungal pathogens.

PURPOSE: To update the spectrum of ocular fungal isolates and investigate the in vitro efficacy of voriconazole and other antifungals. DESIGN: Experimental study. METHODS: Microbiology database was scanned and fungal isolates associated with keratitis (419) and endophthalmitis (122) were analyzed for classification and isolate frequency. The Sensititre YeastOne microdilution antifungal susceptibility test was used to evaluate susceptibility (MICs) of 34 common fungal pathogens against amphotericin B, fluconazole, ketoconazole, 5-flucytosine, itraconazole, and voriconazole. Ten of the test isolates were sent to a reference laboratory to validate the Sensititre results. RESULTS: Fusarium species remains the most frequent corneal fungal pathogen (60.1%). Colletotrichum species (4.1%) has emerged as the fifth most common mold in keratitis. Top yeast isolates from cornea included Candida albicans (52.3%) and Candida parapsilosis (37.3%). Half of the intraocular pathogens were Candida species. Paecilomyces (2.9%) and Philophora (1.9) were unusual pathogens. In vitro susceptibility profiles were voriconazole (100%), ketoconazole (82.4%), amphotericin (76.5%), itraconazole (67%), fluconazole (60%), and 5-FC (60%). Voriconazole MIC(90) were lowest for Candida species (0.016 microg/ml) and highest for Fusarium species (2 microg/ml). Reference laboratory MICs correlated 100% for yeast isolates (0.016 microg/ml) but were fourfold higher for Fusarium species (8 microg/ml). MIC(90) for Aspergillus species was 0.5 microg/ml. CONCLUSIONS: Candida, Fusarium, and Aspergillus species remain frequent fungal pathogens. Voriconazole may have a role in the therapeutic management of Candida and Aspergillus ocular infections. Clinical efficacy must determine the role for other fungal pathogens. Human use and animal models will determine its use in the clinical setting.

Antifungal Agents↗

PubMed2006

Exogenous nitric oxide inhibits Crimean Congo hemorrhagic fever virus.

Crimean Congo hemorrhagic fever virus (CCHFV) is a geographically widespread pathogen that causes severe hemorrhagic fever with high mortality. Even though one of the main objectives focuses on the progress of antiviral agents, the research on CCHFV is strongly hampered due to its BSL-4 classification. Nitric oxide (NO), a mediator with broad biological effects, has been shown to possess inhibitory properties against various pathogens. The molecule constitutes a component of the innate immunity and serves to assist in the early immunological events where it contributes to clearance of microorganisms. In this study, we investigated the inhibitory properties of exogenous NO on CCHFV. We found that NO had a significant antiviral activity against CCHFV replication. By using the NO-donor S-nitroso-N-acetylpenicillamine (SNAP) we were able to show up to 99% reduction in virion progeny yield. In contrast, 3-morpholinosydnonimine hydrochloride (SIN-1), a peroxynitrite donor, had no significant antiviral activity against CCHFV. Furthermore the expression of viral proteins; the nucleocapsid protein and the glycoprotein, were clearly reduced with increasing concentrations of SNAP. We have also shown that the amount of total vRNA in SNAP-treated cells was reduced by about 50% compared to the controls.

Dose-Response Relationship, Drug↗

PubMed1996

[Molecular biology of enteroviruses].

Molecular biological methods offer new approaches to the study of RNA viruses. On the example of enteroviruses we tried to give an account, of recent progress in the knowledge and understanding of these important human pathogens. Firstly concerning their structural and genomic organisation; secondly as regards understanding of their pathology and pathogenicity; thirdly the impact of such methods on rapid, sensitive and specific diagnosis, treatment, on epidemiology and finally on evolution and classification of the large picornavirus family where the enterovirus genus belongs. We believe that molecular biology will elucidate still unknown features of enteroviruses, which are not yet correctly evaluated human pathogens.

Enterovirus↗

PubMed2026

Molecular clusters and precision medicine in pheochromocytomas and paragangliomas.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors derived from chromaffin cells of the adrenal medulla and extra-adrenal paraganglia. Over the past two decades, the genomic characterization of PPGLs has profoundly transformed their diagnosis, classification, risk stratification, and therapeutic management. Up to 40% of PPGLs harbor germline pathogenic variants, the highest proportion among human neoplasms, and somatic driver events are identified in a substantial fraction of the remaining cases. Integrative multi-omic studies have established three main molecular clusters: a pseudohypoxic cluster driven by Krebs-cycle alterations (SDHx, FH, MDH2, DLST) and HIF-2α pathway alterations (VHL, EPAS1, EGLN1/2); a kinase-signaling cluster driven by activation of RAS/MAPK and PI3K/AKT pathways (RET, NF1, HRAS, TMEM127, MAX); and a Wnt-signaling cluster characterized primarily by MAML3 fusions. This review summarizes progress in PPGL genomics, highlighting geographic and sex-related particularities. Using EPAS1/HIF-2α and RET as paradigmatic examples, we illustrate how diverse germline, somatic, mosaic, and fusion events converge on common core signaling hubs that can be therapeutically exploited with FDA-approved selective inhibitors for relevant targets (e.g. belzutifan for HIF-2α; selpercatinib and pralsetinib for RET). We further review the genomic determinants of metastatic risk (SDHB, ATRX, TERT, and MAML3 fusions), the immune microenvironment of metastatic disease, and emerging radionuclide theranostics, liquid biopsy biomarkers, and integrative multi-omic approaches that are reshaping precision medicine for PPGLs.

Humans↗

PubMed1993

[Chromobacterium violaceum, opportunist pathogenic bacteria in tropical and subtropical regions].

Chromobacterium violaceum is isolated from soil and waters in tropical and subtropical areas. This Gram negative bacillus is considered as a saprophyte, but occasionally it can act as an opportunistic pathogen for animals and man, and cause fatal septicaemia from skin lesion with many liver and lung abscesses. Classification, nomenclature, media used to isolation, characters useful to identification (morphology, cultural and biochemical traits, violacein pigmentation), differentiation from related violet-pigmented species and from Vibrionaceae (when C. violaceum cultures are not pigmented), antibiotics resistance and susceptibility, experimental and natural pathogenicity are emphasized.

Animals↗

PubMed1995

A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association.

This report is the continuation of two earlier reports that defined human arterial intima and precursors of advanced atherosclerotic lesions in humans. This report describes the characteristic components and pathogenic mechanisms of the various advanced atherosclerotic lesions. These, with the earlier definitions of precursor lesions, led to the histological classification of human atherosclerotic lesions found in the second part of this report. The Committee on Vascular Lesions also attempted to correlate the appearance of lesions noted in clinical imaging studies with histological lesion types and corresponding clinical syndromes. In the histological classification, lesions are designated by Roman numerals, which indicate the usual sequence of lesion progression. The initial (type 1) lesion contains enough atherogenic lipoprotein to elicit an increase in macrophages and formation of scattered macrophage foam cells. As in subsequent lesion types, the changes are more marked in locations of arteries with adaptive intimal thickening. (Adaptive thickenings, which are present at constant locations in everyone from birth, do not obstruct the lumen and represent adaptations to local mechanical forces). Type II lesions consist primarily of layers of macrophage foam cells and lipid-laden smooth muscle cells and include lesions grossly designated as fatty streaks. Type III is the intermediate stage between type II and type IV (atheroma, a lesion that is potentially symptom-producing). In addition to the lipid-laden cells of type II, type III lesions contain scattered collections of extracellular lipid droplets and particles that disrupt the coherence of some intimal smooth muscle cells. This extracellular lipid is the immediate precursor of the larger, confluent, and more disruptive core of extracellular lipid that characterizes type IV lesions. Beginning around the fourth decade of life, lesions that usually have a lipid core may also contain thick layers of fibrous connective tissue (type V lesion) and/or fissure, hematoma, and thrombus (type VI lesion). Some type V lesions are largely calcified (type Vb), and some consist mainly of fibrous connective tissue and little or no accumulated lipid or calcium (type Vc).

Aneurysm↗

PubMed1995

A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association.

This report is the continuation of two earlier reports that defined human arterial intima and precursors of advanced atherosclerotic lesions in humans. This report describes the characteristic components and pathogenic mechanisms of the various advanced atherosclerotic lesions. These, with the earlier definitions of precursor lesions, led to the histological classification of human atherosclerotic lesions found in the second part of this report. The Committee on Vascular Lesions also attempted to correlate the appearance of lesions noted in clinical imaging studies with histological lesion types and corresponding clinical syndromes. In the histological classification, lesions are designated by Roman numerals, which indicate the usual sequence of lesions progression. The initial (type I) lesion contains enough atherogenic lipoprotein to elicit an increase in macrophages and formation of scattered macrophage foam cells. As in subsequent lesion types, the changes are more marked in locations of arteries with adaptive intimal thickening. (Adaptive thickenings, which are present at constant locations in everyone from birth, do not obstruct the lumen and represent adaptations to local mechanical forces). Type II lesions consist primarily of layers of macrophage foam cells and lipid-laden smooth muscle cells and include lesions grossly designated as fatty streaks. Type III is the intermediate stage between type II and type IV (atheroma, a lesion that is potentially symptom-producing). In addition to the lipid-laden cells of type II, type III lesions contain scattered collections of extracellular lipid droplets and particles that disrupt the coherence of some intimal smooth muscle cells. This extracellular lipid is the immediate precursor of the larger, confluent, and more disruptive core of extracellular lipid that characterizes type IV lesions. Beginning around the fourth decade of life, lesions that usually have a lipid core may also contain thick layers of fibrous connective tissue (type V lesion) and/or fissure, hematoma, and thrombus (type VI lesion). Some type V lesions are largely calcified (type Vb), and some consist mainly of fibrous connective tissue and little or no accumulated lipid or calcium (type Vc).

Aneurysm↗