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PubMed1998

Sporadic inclusion-body myositis and hereditary inclusion-body myopathies: current concepts of diagnosis and pathogenesis.

We discuss the pathologic diagnostic criteria and review the major new advances related to seeking the pathogenic mechanism of sporadic inclusion-body myositis (s-IBM) and hereditary inclusion-body myopathy (h-IBM). A classification of the various h-IBM syndromes is also presented. The several forms of the h-IBMs have different genetic transmissions and probably different genetic defects. In neither s-IBM nor the h-IBMs are the sequential steps of the pathogenic cascade understood. Because s-IBM and the h-IBMs have a number of characteristic pathologic features in common, we postulate that their different causes trigger the same upstream aberration leading to a similar downstream cascade of pathologic events, which are ultimately responsible for the characteristic muscle-fiber degeneration. Muscle-biopsy and experimental evidence is given supporting our hypothesis that overexpression of beta-amyloid precursor protein within abnormal muscle fibers is an early upstream event causing the pathogenic cascade. We also present evidence supporting our concept that muscle aging and oxidative stress are important factors contributing to the s-IBM-specific muscle fiber destruction. Additionally, the intriguing parallels between the pathologic phenotype of IBM muscle fibers and Alzheimer's disease brain are summarized.

Aging↗
PubMed1978

A diagnostic key employing biological reactions for differentiating pathogenic Corynebacterium genitalium (NSU corynebacteria) from commensals of the urogenital tract.

More than 100 strains of Corynebacterium genitalium, probably responsible for coryneform urethritis and other infections, and 600 commensals of the male and female urogenital tracts have been studied and grouped into five pathogenic types numbered I to V and six saprophytic types designated C-1 to C-6 on the basis of eight biological reactions. This preliminary classification has been based on differences in requirements for oxygen, on the fermentation of fructose, dextrose, sucrose, and starch together with the production of the enzymes gelatinase, lipase, and urease. One criterion differentiated the pathogens from the commensals: All pathogens were nonfructose fermenters whereas every commensal fermented this sugar.

Bacteriological Techniques↗
PubMed2001

Urinary tract infections in women.

Urinary tract infections (UTIs) are the most common infections seen in the hospital setting, and the second most common infections seen in the general population. Due to women's anatomy, UTIs are especially problematic for them, and up to one-third of all women will experience a UTI at some point during their lifetimes. Appropriate treatment of a UTI requires accurate classification that includes infection site, complexity of the infection, and the likelihood of recurrence. The predominant pathogen in both complicated and uncomplicated UTI remains pathogenic Escherichia coli, although Klebsiella sp. and Proteus appear with increased frequency in complicated UTI. Most often, bacteria cause UTIs by ascending means through the urethra into the bladder. Bacteria must possess virulence factors to cause UTI. Host defense factors that predispose patients to UTI include urinary stasis, abnormal urinary tract anatomy, diabetes mellitus, debility, and aging. Estrogen-related issues and short urethras predispose women to UTI. Although urine culture, with >105 colony-forming units/mL (CFU/mL) in symptomatic patients, remains the diagnostic "gold standard," correlation of the patient's history and physical examination with urinalysis (including nitrite dipstick and leukocyte esterase test) results usually suffices to diagnose UTI. Three-day of antimicrobial treatment is recommended for simple cystitis. Acute pyelonephritis, an infection of the kidney parenchyma tissue, is treated with antibiotics for 7 to 14 days depending on the antimicrobial agent used and the severity of infection. In addition, patient classification determines the need for hospitalization or for urological imaging studies. Women with recurrent UTIs merit consideration for antimicrobial prophylaxis. Self-administered topical vaginal estradiol cream is an important adjunct in UTI prevention for postmenopausal women. Asymptomatic bacteruria only merits antimicrobial therapy in high-risk patients or those colonized with Proteus species.

Acute Disease↗
PubMedDate not supplied

Feature extraction from light-scatter patterns of Listeria colonies for identification and classification.

Bacterial contamination by Listeria monocytogenes not only puts the public at risk, but also is costly for the food-processing industry. Traditional biochemical methods for pathogen identification require complicated sample preparation for reliable results. Optical scattering technology has been used for identification of bacterial cells in suspension, but with only limited success. Therefore, to improve the efficacy of the identification process using our novel imaging approach, we analyze bacterial colonies grown on solid surfaces. The work presented here demonstrates an application of computer-vision and pattern-recognition techniques to classify scatter patterns formed by Listeria colonies. Bacterial colonies are analyzed with a laser scatterometer. Features of circular scatter patterns formed by bacterial colonies illuminated by laser light are characterized using Zernike moment invariants. Principal component analysis and hierarchical clustering are performed on the results of feature extraction. Classification using linear discriminant analysis, partial least squares, and neural networks is capable of separating different strains of Listeria with a low error rate. The demonstrated system is also able to determine automatically the pathogenicity of bacteria on the basis of colony scatter patterns. We conclude that the obtained results are encouraging, and strongly suggest the feasibility of image-based biodetection systems.

Algorithms↗
PubMed2025

A functional assay to classify RB1 variants of uncertain significance.

PURPOSE: The RB1 gene encodes the retinoblastoma protein (pRB) playing a major role in cell cycle control, particularly by its interaction with E2F transcription factors. Familial forms of retinoblastoma are caused by germline pathogenic variants in the RB1 gene predisposing to retinoblastoma and other tumors. By analyzing the RB1 gene in patients with retinoblastoma, we found that missense variants often remain variants of uncertain significance (VUS). METHODS: To classify RB1 VUS, we developed a functional assay evaluating their impact on the ability of pRB to inhibit the activity of the E2F1 promoter, with a luciferase reporter gene. A set of 14 pathogenic/likely pathogenic and benign/likely benign RB1 variants was used for validation. RESULTS: We tested 16 VUS detected in patients with retinoblastoma and found that 9 VUS reduced the ability of pRB to inhibit E2F1 promoter. Among them, the (RB1) c.2263T>G p.(Phe755Val) variant showed a reduced level of pRB on Western blot, suggesting a defect in pRB stability. By applying the criterion PS3_moderate of the American College of Medical Genetics and Genomics/Association for Molecular Pathology classification to this functional assay, 5 of the 9 VUS with functional impact could be classified as likely pathogenic. CONCLUSION: This functional assay can improve the molecular diagnosis of retinoblastoma predisposition by a better determination of pathogenic/likely pathogenic RB1 variants.

Humans↗
PubMed2005

Cutaneous vasculitis update: diagnostic criteria, classification, epidemiology, etiology, pathogenesis, evaluation and prognosis.

Vasculitis, inflammation of the vessel wall, can result in mural destruction with hemorrhage, aneurysm formation, and infarction, or intimal-medial hyperplasia and subsequent stenosis leading to tissue ischemia. The skin, in part due to its large vascular bed, exposure to cold temperatures, and frequent presence of stasis, is involved in many distinct as well as un-named vasculitic syndromes that vary from localized and self-limited to generalized and life-threatening with multi-organ disease. To exclude mimics of vasculitis, diagnosis of cutaneous vasculitis requires biopsy confirmation where its acute signs (fibrinoid necrosis), chronic signs (endarteritis obliterans), or past signs (acellular scar of healed arteritis) must be recognized and presence of extravascular findings such as patterned fibrosis or collagenolytic granulomas noted. Although vasculitis can be classified by etiology, many cases have no identifiable cause, and a single etiologic agent can elicit several distinct clinicopathologic expressions of vasculitis. Therefore, the classification of cutaneous vasculitis is best approached morphologically by determining vessel size and principal inflammatory response. These histologic patterns roughly correlate with pathogenic mechanisms that, when coupled with direct immunofluorescent examination, anti-neutrophil cytoplasmic antibody (ANCA) status, and findings from work-up for systemic disease, allow for specific diagnosis, and ultimately, more effective therapy. Herein, we review cutaneous vasculitis focusing on diagnostic criteria, classification, epidemiology, etiology, pathogenesis, and evaluation of the cutaneous vasculitis patient.

Humans↗
PubMed2004

Analysis of phenetic trees based on metabolic capabilites across the three domains of life.

Here, we used data of complete genomes to study comparatively the metabolism of different species. We built phenetic trees based on the enzymatic functions present in different parts of metabolism. Seven broad metabolic classes, comprising a total of 69 metabolic pathways, were comparatively analyzed for 27 fully sequenced organisms of the domains Eukarya, Bacteria and Archaea. Phylogenetic profiles based on the presence/absence of enzymatic functions for each metabolic class were determined and distance matrices for all the organisms were then derived from the profiles. Unrooted phenetic trees based upon the matrices revealed the distribution of the organisms according to their metabolic capabilities, reflecting the ecological pressures and adaptations that those species underwent during their evolution. We found that organisms that are closely related in phylogenetic terms could be distantly related metabolically and that the opposite is also true. For example, obligate bacterial pathogens were usually grouped together in our metabolic trees, demonstrating that obligate pathogens share common metabolic features regardless of their diverse phylogenetic origins. The branching order of proteobacteria often did not match their classical phylogenetic classification and Gram-positive bacteria showed diverse metabolic affinities. Archaea were found to be metabolically as distant from free-living bacteria as from eukaryotes, and sometimes were placed close to the metabolically highly specialized group of obligate bacterial pathogens. Metabolic trees represent an integrative approach for the comparison of the evolution of the metabolism and its correlation with the evolution of the genome, helping to find new relationships in the tree of life.

Animals↗
PubMed2001

Identification and classification of consumer food-handling behaviors for food safety education.

OBJECTIVE: To identify key behaviors associated with major food safety pathogen control factors. DESIGN: World Wide Web-based descriptive study with 4 tasks: compile a list of food-handling behaviors from the literature; use Delphi process to build consensus, rank order, and edit lists of behaviors; assess content and construct validity; and review results of Delphi process at a summit meeting of selected experts to make final recommendations for a food safety behavior list. SUBJECTS/SETTING: A convenience sample of 10 epidemiologists, 11 food microbiologists, 10 food safety educators, and 10 food safety policy makers was recruited from lists of nationally known experts. Twenty-four experts completed 4 rounds of surveys presented to them via a Web site. Six experts attended a face-to-face meeting to finalize behavior lists. Statistical analyses performed Descriptive statistics and sum of observation data were used to determine rank order and validity. RESULTS: Twenty-nine key food-handling behaviors for maintaining the safety of food and reducing the number of cases and outbreaks of foodborne illness were identified. These were rank-ordered within 5 pathogen control factors: practice personal hygiene, cook foods adequately, avoid cross-contamination, keep foods at safe temperatures, and avoid foods from unsafe sources. APPLICATIONS/CONCLUSIONS: This list of rank-ordered behaviors grouped by pathogen control factor should help dietitians and educators confidently teach food safety guidance that will be most effective in preventing illness.

Consumer Product Safety↗
PubMed2002

Possible pathogenic mechanisms in inflammatory myopathies.

The limitations associated with the different approaches into the pathogenesis of the IIM have resulted in incomplete knowledge of disease mechanisms in myositis. In most research, in which muscle tissue was used to study the different aspects of disease, biopsies with inflammatory infiltrates have been selected. Although inflammatory cell infiltrates are a characteristic feature of myositis, selecting patients with inflammatory cell infiltrates for investigations naturally introduces a selection bias. Only a few studies have been published on patients without inflammatory infiltrates but with muscle weakness, and few studies have included follow-up biopsies after different therapies. The heterogeneity of the population of patients with myositis is another limitation of the studies of pathogenic mechanisms. Although most studies classify patients according to the Bohan and Peter criteria [118, 119], some studies used histopathologic criteria [6], and only a few studies included characterization with myositis-specific autoantibodies. Because myositis-specific autoantibodies are often associated with certain clinical profiles, classification according to autoantibody profiles could be important to define differences in the pathogenesis of different phenotypes [3]. From available data on pathogenic mechanisms it is evident that cellular and humoral immune responses are involved in disease mechanisms of myositis, but whether there is a muscle-specific immune response cannot be answered by current studies. It is likely that other mechanisms are important for development of muscle weakness, including metabolic disturbances, and muscle weakness could be caused by different mechanisms in different IIM subsets or in patients in different phases of the disease. There could be early changes, which reversibly affect the metabolism, and later, irreversible changes, that could be dependent on muscle fiber damage and replacement of muscle tissue by connective tissue and fat. Current findings suggest that cytokines, which are produced in muscle tissue from different cell sources including inflammatory cells, endothelial cells, and muscle fibers, could affect muscle function. Careful follow-up studies, including the effect of therapies targeting different molecules on molecular expression in muscle tissue, are likely to increase our knowledge on disease mechanisms. A better understanding of which molecules and mechanisms affect muscle function is likely to lead to improved, less toxic therapies in patients with myositis. Many possible target molecules for blocking therapies, especially the proinflammatory cytokines IL-1 and TNF-alpha, have been identified and should be studied in appropriate clinical settings given the currently poor outcomes of many patients with IIM.

Autoimmunity↗
PubMed2002

The sequential failure of osseointegrated submerged implants.

This report presents a case of sequential failure of nonrestored implants that were osseointegrated and submerged for 3 years. The suspected causes of failure were investigated and analyzed. These included anatomic, physiologic, traumatic, and pathogenic factors. The findings of this report compliment other literature and contribute to the comprehensive classification of implant failure based on osseointegration criteria.

Dental Implantation, Endosseous↗
PubMed2003

Mapping epitopes in equine rhinitis A virus VP1 recognized by antibodies elicited in response to infection of the natural host.

Equine rhinitis A virus (ERAV) is an important respiratory pathogen of horses and is of additional interest because of its close relationship and common classification with foot-and-mouth disease virus (FMDV). As is the case with FMDV, the VP1 capsid protein of ERAV has been shown to be a target of neutralizing antibodies. In FMDV VP1, such antibodies commonly recognize linear epitopes present in the betaG-betaH loop region. To map linear B cell epitopes in ERAV VP1, overlapping fragments spanning its length were expressed in Escherichia coli as glutathione S-transferase (GST) fusion proteins. These fusion proteins were tested for reactivity with sera from ERAV-infected horses and with polyclonal sera from ERAV-immunized rabbits and mice. Regions at the N- and C-termini as well as the betaE-betaF and the betaG-betaH loop regions contained B cell epitopes that elicited antibodies in the natural host. GST fusion proteins of these regions also elicited antibodies following immunization of rabbits and mice, which, in general, strongly recognized native ERAV VP1 but which were non-neutralizing. It is concluded that the N-terminal region of ERAV VP1, in particular, contains strong B cell epitopes.

Amino Acid Sequence↗
PubMed1990

Toxigenic clostridia.

Toxigenic clostridia belonging to 13 recognized species are discussed in this review. Each species or group of organisms is, in general, introduced by presenting the historical aspects of its discovery by early investigators of human and animal diseases. The diseases caused by each species or group are described and usually discussed in relation to the toxins involved in the pathology. Morphological and physiological characteristics of the organisms are described. Finally, the toxins produced by each organism are listed, with a presentation of their biological activities and physical and biochemical characteristics. The complete amino acid sequences for some are known, and some of the genes have been cloned. The term toxin is used loosely to include the various antigenic protein products of these organisms with biological and serological activities which have served as distinguishing characteristics for differentiation and classification. Some of these factors are not truly toxic and have no known role in pathogenicity. Some of the interesting factors common to more than one species or group are the following: neurotoxins, lethal toxins, lecithinases, oxygen-labile hemolysins, binary toxins, and ADP-ribosyltransferases. Problems in bacterial nomenclature and designation of biologically active factors are noted.

Animals↗
PubMed2000

[Acquired peeling skin syndrome in an adult].

BACKGROUND: Peeling skin syndrome is a rare form of congenital ichthyosis. The term was coined in 1982 by Levy and Goldsmith and the syndrome is clinically characterized by generalized scaling. Histologically, there is an epidermal separation in the stratum corneum. CASE REPORT: We report the case of a 73-year-old woman who had ichthyosis without cicatricial progressive alopecia since her first pregnancy. An ultrastructural study was performed confirming the clinical diagnosis of peeling skin syndrome. DISCUSSION: The peeling skin syndrome designates several different clinical entities classed by Traupe in type A and type B. Mevorah and al. expanded this classification with a type C. This classification has remained valid after additional information provided by ultrastructural studies and may suggest different pathogenic mechanisms underlying the dermatosis. A critical review of the literature shows that the case reported here is exceptional and had a late clinical onset.

Adult↗
PubMed2000

[Pneumonia in HIV-infected patients: clinical observations].

OBJECTIVES: To determine the occurrence of pneumonias in HIV-infected patients in our hospital during 1990-1999; to evaluate the clinical significance of pneumonias in HIV-seropositive patients; to estimate the ethiology of pulmonary infection. MATERIALS AND METHODS: One hundred and two HIV-infected patients, 17 (16.6%) female and 85 (83.3%) male with mean age of 29 +/- 4.5 yrs, were retrospectively analysed. All patients had a physical examination particularly concerning the clinical symptoms of pulmonary infection, X-ray exam and tuberculin skin test (PPD). The stage of HIV infection according to the 1993 CDC classification was determined. All patients had the microbiology test of sputum (Pc, TB, fungi, other pathogen). In some cases the bronchofiberoskopy with bronchoalveolar lavage (BAL) was performed. RESULTS: One hundred and two HIV-positive patients had 129 episodes of pneumonia. We determine the bacterial ethiology in 94/129 (72.9%) cases--TB in 11/129 (8.5%) cases. Fourteen patients had 23 episodes of Pneumocystis carinii pneumonia (PcP). Three patients had CMV--pneumonitis, detected post mortem. In seven cases the ethiology of pulmonary infection was unknown. In summary the ethiology of pneumonia was determined in 58/129 (44.9%) cases. Thirty three patients were died. The pulmonary infections were main cause of death in 23 (67.7%) persons. CONCLUSIONS: In the era of high active antiretroviral therapy (HAART) the pulmonary infections in HIV-positive patients are the main cause of death as before. The PPD test is useless in HIV-positive patients. We make a note the increase cases of TB in HIV-infected patients during the time of observations.

Adult↗
PubMedDate not supplied

Autoinflammatory syndromes.

The autoinflammatory disorders are a new and expanding classification of inflammatory diseases characterized by recurrent episodes of systemic inflammation in the absence of pathogens, autoantibodies or antigen specific T cells. These disorders are caused by primary dysfunction of the innate immune system, without evidence of adaptive immune dysregulation. Innate immune abnormalities include aberrant responses to pathogen associated molecular patterns (PAMPs) like lipopolysaccharide and peptidoglycan, prominent neutrophilia in blood and tissues, and dysregulation of inflammatory cytokines (IL-1beta, TNF-alpha) or their receptors. The autoinflammatory diseases comprise both hereditary (Familial Mediterranean Fever, FMF; Mevalonate Kinase Deficiency, MKD; TNF Receptor Associated Periodic Syndrome, TRAPS; Cryopyrin Associated Periodic Syndrome, CAPS; Blau syndrome; Pyogenic sterile Arthritis, Pyoderma gangrenosum and Acne syndrome, PAPA; Chronic Recurrent Multifocal Osteomyelitis, CRMO) and multifactorial (Crohn's and Behçet's diseases) disorders. Mutations responsible for FMF, TRAPS, CAPS, PAPA are in proteins involved in modulation of inflammation and apoptosis.

Autoimmune Diseases↗
PubMed1990

[Urine osmotic pressure and deficiency-excess syndrome of renal disease: analysis of 428 cases].

By means of TCM differentiation of symptom-complexes, the authors tested and analysed the urine osmotic pressure (UOP) and the urine and plasma osmotic ratio (UPOR) for 428 cases of renal disease, with the conclusion that the UOP and the UPOR were within the normal value range for not only the 36 cases lack of clinical symptoms so as to be unable to have TCM classification identified, but also for 24 cases of Wind edema excess syndrome mainly caused by pathogenic Wind's invasion to the Lung. But for 74 cases of damp-heat Kidney impairment and 294 cases with the main symptom being Kidney deficiency [including weakness of Qi of Kidney, Yang deficiency of Spleen and Kidney, Yin deficiency of Liver and Kidney], the value of their UOP and the UPOR had the tendency of reduction (P less than 0.01), among which the value of the patients of Kidney Yang deficiency reduced most obviously. The further observation showed that, for the nocturia patients caused by renal disease, the value of UOP and the UPOR reduced more obviously than usual. Therefore the authors assert that the test on UOP and UPOR will offer an objective index to patients' nocturia and Kidney-Qi weakness. 60 cases with renal disease of Kidney deficiency syndrome and 27 cases of damp-heat Kidney impairment syndrome under the diagnosis and treatment based on an overall analysis of symptoms and signs leads to the following conclusion: With the elimination of pathogenic factors and recovery of kidney, the damp-heat Kidney impairment patients' UOP will be increased. The low UOP of patients caused simply by Kidney deficiency, however, will recover slower.

Adult↗