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The theory of the pathogenetic basic types renders possible a clinical basic classification of the infectious diseases. The essential qualities and characteristics of the cyclic infectious diseases, of the local infections and of sepsis are again represented in a survey and explained in the light of more recent knowledge.
The authors present a survey of medically important microscopic fungi whose classification were critically revised and correctly named in the last few years. The list was adopted from a paper of American mycologists trying to make the nomenclature of mycotic agents more precise and stable. The authors divided the adopted list according to diseases the individual fungi produce and explained less known terms describing mostly non-european mycoses. Notes giving reasons for nomenclature changes supplement the list of names.
Despite an apparent stabilizing of nomenclature and concepts involved in fungal conidiogenesis during the past decade, there is now evidence that a much more complex and demanding approach to the descriptive study of processes involved in conidial formation would allow a more phylogenetically realistic classification of anamorphic fungi. The present review attempts to evaluate data on the human pathogenic molds in light of this new approach and to relate conidiogenesis to the known teleomorph connections of the fungi concerned. It is hoped that by treating the species in groups corresponding to their sexual affinities, it may be possible to infer homologous forms of conidiogenesis by comparative morphology and development.
IMPORTANCE: To date, no environmental factors and few therapeutic options are known for uveal melanoma (UM), the most common malignant intraocular primary tumor in adults. Identification of new predisposition factors could lead to better monitoring and possibly improved treatments of patients with UM. OBJECTIVE: To identify new genetic alterations predisposing for UM. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study conducted at Institut Curie in Paris, France, among 381 consecutive patients diagnosed with UM between July 2021 and February 2023. UM was diagnosed clinically by ophthalmologists, and a senior pathologist confirmed the diagnosis when tumor or biopsy was available. All participants received genetic counseling and consented to extended genetic testing. A panel of 122 genes predisposing to cancer were analyzed by targeted sequencing on germline DNA from these patients. MAIN OUTCOMES AND MEASURES: Frequency of pathogenic variants (PVs) in genes from a targeted panel, with classification of germline PVs done according to the American College of Medical Genetics and Genomics guidelines and the French Unicancer Genetics Group. RESULTS: A total of 79 PVs were identified in 70 participants (41 female and 29 male; mean [SD] age, 60.6 [15.3] years). Among them, 21 were found in clinically relevant genes, with an enrichment in the mismatch repair (MMR) genes, involved in Lynch syndrome, a frequent predisposition to colon and endometrial cancers. This finding suggested MMR germline PVs could also predispose to UM. One tumor was available from a participant carrying a MLH1 germline PV. The tumor exhibited a monosomy 3 with loss of the wild-type allele of MLH1, located on chromosome 3. Loss of expression of MLH1 was observed by immunohistochemistry, and MMR variant signatures SBS6, ID1, and ID2 were identified from the whole-genome sequencing of this tumor, supporting the possibility that MLH1 contributes to the oncogenesis of this UM. CONCLUSIONS AND RELEVANCE: This prospective germline study on patients with UM provided evidence supporting the notion that MMR germline alterations are enriched among patients with UM and may contribute to oncogenesis of UM, and that UM may therefore be a rare tumor manifestation of Lynch syndrome.
The recent discovery of mutations in the uromodulin gene ( UMOD ) in patients with medullary cystic kidney disease type 2 (MCKD2), familial juvenile hyperuricemic nephropathy (FJHN), and glomerulocystic kidney disease (GCKD) provides the opportunity for a revision of pathogenic aspects and puts forth the basis for a renewed classification. This review focuses on clinical, pathological, and cell biology advances in UMOD -related pathological states, including a review of the associated clinical conditions described to date in the literature. Overall, 31 UMOD mutations associated with MCKD2 and FJHN (205 patients) and 1 mutation associated with GCKD (3 patients) have been described, with a cluster at exons 4 and 5. Most are missense mutations causing a cysteine change in uromodulin sequence. No differences in clinical symptoms between carriers of cysteine versus polar residue changes have been observed; clinical phenotypes invariably are linked to classic MCKD2/FJHN. A common motif among all reports is that many overlapping symptoms between MCKD2 and FJHN are present, and a separation between these 2 entities seems unwarranted or redundant. Cell experiments with mutant variants indicated a delay in intracellular maturation and export dynamics, with consequent uromodulin storage within the endoplasmic reticulum (ER). Patchy uromodulin deposits in tubule cells were found by means of immunohistochemistry, and electron microscopy showed dense fibrillar material in the ER. Mass spectrometry showed only unmodified uromodulin in urine of patients with UMOD mutations. Lack of uromodulin function(s) is associated with impairments in tubular function, particularly the urine-concentrating process, determining water depletion and hyperuricemia. Intracellular uromodulin trapping within the ER probably has a major role in determining tubulointerstitial fibrosis and renal failure. We propose the definition of uromodulin storage diseases for conditions with proven UMOD mutations.
The proteins of the cell envelope of Neisseria sicca strain ATCC 9913 have been examined by SDS - polyacrylamide gel electrophoresis. Some 20 proteins were resolved from the total envelope fraction, and nearly all of these were found to be localized in the outer membrane. Preparations of the "free-endotoxin" fraction differ from the outer membrane only in lacking a few minor proteins. The behavior of several of the envelope proteins on electrophoresis can be modified by changing the temperature of sample solubilization, and also by alteration of the growth medium. Experiments with phosphate-limited cultures showed that certain periplasmic proteins are closely associated with free endotoxin. Mutations which result in altered outer membrane permeability to antibiotics were found to cause changes in cell envelope protein composition. A comparison of the envelope proteins of eight species of non-pathogenic Neisseria showed that each had a characteristic composition. A classification of the organisms based on the relatedness of the protein patterns seen on SDS-polyacrylamide gels was in close agreement with classifications based on more usual methods.
Antibiotic pharmacodynamics is an evolving science that focuses on the relationship between drug concentration and pharmacologic effect, which is an antibiotic-induced bacterial death that also can manifest as an adverse drug reaction. The pharmacologic action of antibiotics usually can be described as concentration dependent or independent, although such classifications are highly reliant on the specific antibiotic and bacterial pathogen being studied. Quantitative pharmacodynamic parameters, such as ratio of the area under the concentration-time curve during a 24-hour dosing period to minimum inhibitory concentration (AUC0-24:MIC), ratio of maximum serum antibiotic concentration to MIC (Cmax:MIC), and duration of time that antibiotic concentrations exceed MIC (T>MIC), have been proposed as likely predictors of clinical and microbiologic success or failure for different pairings of antibiotic and bacteria. Thus far, most pharmacodynamic data reported have focused on fluoroquinolones, but work has been conducted on vancomycin, beta-lactams, macrolides, aminoglycosides, and other antibiotics. Despite the development of a number of different pharmacodynamic modeling systems, remarkable agreement exists between in vitro, animal, and limited human data. Although still somewhat premature and requiring additional clinical validation, antibiotic pharmacodynamics will likely advance on four fronts: the science should prove to be extremely useful and represent a cost-effective and efficient method to help develop new antibiotics; formulary committees will likely use pharmacodynamic parameters to assist in differentiating antibiotics of the same chemical class in making antibiotic formulary selections; pharmacodynamic principles will likely be used to design optimal antibiotic strategies for patients with severe infections; and limited data to date suggest that the application of pharmacodynamic concepts may limit or prevent the development of antibiotic resistance. The study of antibiotic pharmacodynamics appears to hold great promise and will likely become a routine part of our daily clinical practices.
In December 1994, a highly pathogenic (HP) avian influenza (AI) outbreak occurred in Mexico, caused by the subtype H5N2, affecting two main regions of egg and poultry-meat production. At that time, governmental actions included immediate stamping out of the affected flocks, disinfection of affected premises, quarantine measures in the region, strict movement controls on poultry and their products and vaccination. With these policies, the disease was eradicated in a relatively short time. The last case of HPAI was detected in June 1995 and the country was declared as free of HPAI virus in January 1996 to the World Animal Health Organisation (OIE). Since then, Mexico has maintained a control programme against low pathogenic (LP) AI virus that is based on a zoning classification, movement controls and other strategies.
Twenty-three children with idiopathic hypercalciuria and 7 control children were studied. Patients were classified into three groups according to the response to an oral calcium load. Five children displayed absorptive hypercalciuria (UCa/Cr 0.14 +/- 0.04 mg/mg with poor calcium diet and 0.33 +/- 0.16 after loading, p less than 0.01); 10 were classified renal hypercalciuria (UCa/Cr during the fasting state of 0.28 +/- 0.09 and 0.31 +/- 0.11 after loading) and 8 were classified as alimentary hypercalciuria (UCa/Cr 0.14 +/- 0.07 during the fasting state and 0.15 +/- 0.04 after loading). The urinary cAMP showed no significant differences in any of the three groups compared to the control. Magnesiuria did not show significant differences between the two forms of hypercalciuria and the control; a significant increase was observed after the loading and a positive correlation between magnesiuria and calciuria in the absorptive form. Our study supports the validity of the test for the classification of the different forms of hypercalciuria in children. The urinary cAMP is not a valid approach for classification. The difference observed in the magnesiuria suggests a different pathogenic mechanism between the two types of idiopathic hypercalciuria.
The potential utilisation of monthly cell counts per cow to determine their infection status was studied for 30 months on 62 cows from an experimental herd, and by simulation, on different herd models with defined epidemiological characteristics. During this period, the cows of the experimental herd were regularly submitted to bacteriological tests for intramammary infections and individual cell counts. The cows which were not chronically infected by a major pathogen were characterised by cell counts of less than 300 000 cells/ml throughout lactation. The chronically infected cows were characterised by at least two peaks over 300 000 with at least one beyond 800 000, but cell counts could be, at other time intervals, below 300 000 cells/ml. Provided that at least two monthly cell counts were available for each cow, it was possible to discriminate strongly the cows not chronically infected and the cows chronically infected by a major pathogen which are reservoirs of infection. The percentage of correct classifications varied between 74 and 87% in relation with the chosen threshold and the infection status of the herd in which this threshold was used. With the same threshold, there were higher percentages of false negative diagnosis in a herd model where staphylococcal like long-term infections were prevalent and of false positive when there was a high incidence of clinical short-term infections. Monthly cell counts per cow did not correctly reveal short-term clinical infections which are particularly prevalent in herds affected mainly by environmental mastitis. The precision and practical importance of this individual diagnosis was discussed for different herd models.
Over 500,000 workers in the USA alone are employed in laboratories that range from small physician offices to large clinical laboratories handling microbes for comprehensive research and/or diagnostic work. These workers are exposed to a variety of potential occupational health risks such as exposure to infectious clinical materials, environmental specimens, cultures, complex and inflammable chemicals, radiation, and electrical and mechanical hazards. As members of the International Society for Human and Animal Mycology, we have no policy statement on biosafety standards for handling medically important fungi. The intent of the symposium is to cover some of the important aspects of biosafety; (1) standards in handling dimorphic fungal pathogens; (2) the principles and criteria of biosafety levels and classification of known medically important fungi, aerobic actinomycetes, environmental fungi according to their biosafety levels; (3) medically important fungal waste and its safe disposal; and (4) biosafety and regulatory considerations in handling and mailing medically important fungi in a culture collection.
Most current classifications of lymphoid neoplasms define the tumors based on the cell of origin, phenotype, genetic abnormalities, and clinical features. Here it is proposed that human lymphocytic tumors can be categorized based on the propensity and capacity of the tumor cells to undergo apoptosis. The first category is defined by malignant cells that are resistant to apoptosis due to expression of anti-apoptotic factors such as bcl-2 and cellular inhibitors of apoptosis (IAPs). These tumors would include CLL and follicular lymphomas, as well as some malignancies in which the tumor cells are infected by viruses that co-opt cell survival pathways, such as human T-cell leukemia/lymphoma virus (HTLV)-1. The second category, in which the malignant cells are apoptosis-prone, would include tumors arising in the context of impaired cytotoxic T-cell function. These neoplasms would include some human immunodeficiency virus (HIV)-related lymphomas such as Burkitt's lymphoma, and post-transplantation lymphomas. The third category would include neoplasms of intermediate sensitivity to apoptosis, some of which are associated with infection such as mucosa-associated lymphoid tissue (MALT) lymphomas of the stomach. Although this classification is tentative, it should evolve in parallel with our understanding of pathogenic mechanisms in lymphoid neoplasia, and provides a novel framework with which to consider the appropriateness of specific therapeutic strategies. Distinctions among lymphocytic tumors in terms of the likelihood of response to therapies such as antisense to bcl-2 related proteins, inhibitors of NF-kappa B activity, and new approaches aimed at bolstering the host's immune response, would cross standard classifications based on the T or B-cell origin of the tumor cells.
Page, L. A. (Biological Research Institute, San Diego, and University of California, Davis). Acetylmethylcarbinol production and the classification of aeromonads associated with ulcerative diseases of ectothermic vertebrates. J. Bacteriol. 84:772-777. 1962.-Quantitative colorimetric tests were made for acetylmethylcarbinol (AMC) production by 14 Aeromonas isolates from ulcerous lesions of snakes, lizards, frogs, and other animals, and by 27 cultures of "identified" aeromonads. The tests revealed that: (i) some strains failed to produce AMC, while the other strains produced AMC in amounts of 5 to > 100 mug/ml of culture; (ii) the reagents employed in the standard method of Barritt failed to detect AMC in concentrations below 35 mug/ml; and (iii) certain strains reported as producing AMC at 23 C and not at 37 C (or vice versa) produced AMC at both temperatures, but at one temperature produced AMC at a level below the sensitivity of the qualitative test. The strains representing the two biotypes could not be distinguished on the basis of their morphology, habitat, pathogenicity for mice or snakes, or serological specificity. Therefore, the Aeromonas classification proposed by Ewing, Hugh, and Johnson, who incorporated the two biotypes into one species, was followed, and the new isolates were designated A. hydrophila.
The inflammatory myopathies - myositis - encompass a heterogeneous group of chronic muscle disorders of unknown origin and with varying prognoses. New clinical phenotypes of myositis have been identified since the most widely used classification criteria were proposed in 1975. Based on clinical and histopathological features, inclusion body myositis was identified. Furthermore, the myositis-specific autoantibodies may also identify different clinical phenotypes and serve as prognostic markers. The different classifications and inclusion criteria that have been used in different studies make some epidemiological data uncertain. In order to improve our knowledge of causative factors, as well as of pathogenic mechanisms, there is a need for revision and also for an international acceptance of the classification criteria. During recent years, our knowledge has increased regarding the role of some genetic and environmental factors that could affect susceptibility for developing myositis as well as the prognosis. Whether there is an association between myositis and malignancies has been a subject of controversy for many years and recent epidemiological data have brought some clarification on this issue.
The genus Acanthamoeba includes more than 20 morphological species, but classification is problematical. Recently, the discovery of substantial interstrain differences in ribosomal DNA (rDNA) sequences has prompted questions about the relatedness of strains of the same species. In this study, therefore, we have investigated relationships between two isolates of A. polyphaga, CCAP 1501/3c and ATCC 30871, using morphological, biochemical, physiological, molecular and cytotoxicity assays. We observed that A. polyphaga ATCC 30871 exhibited up to six arms in endocyst while A. polyphaga CCAP 1501/3c exhibited a maximum of 5 arms thus indicating their position in group 2 and 3, respectively. Acanthamoeba polyphaga ATCC 30871 exhibited growth at 37 degrees C and growth on 1M mannitol plates while A. polyphaga CCAP 1501/3c did not. In addition, both isolates exhibited differences in isoenzyme banding patterns and rDNA restriction fragment polymorphisms. More importantly, A. polyphaga ATCC 30871 produced cytotoxicity on corneal epithelial cells while A. polyphaga CCAP 1501/3c had no effects, suggesting differences in pathogenicity. Thus, all the results provide evidence for significant differences between the strains and further provided the basis for reclassification of the isolates. Implications of these results in the clinical diagnosis of pathogenic Acanthamoeba are discussed.
The current systems for classifying human pathogens on the basis of hazard are well developed and their basic criteria are in general agreement one with another. Of more importance, the safety practices based on these classifications have generally been successful. They have enabled extensive research activities, medical practice and industrial production to be conducted on an ever-increasing scale, involving dangerous microorganisms (e.g. in vaccine production and treatment of infected patients) with a very low incidence of adverse effects on the workers involved and the general public. Although the EU has adopted a harmonised list of agents in groups 1-4 there is as yet no complete agreement among member states and individual microbiologists. The purpose of this paper is to present a historical survey and to discuss the current processes for identifying and classifying the hazards posed by the use of microorganisms in research and technology. This is essential in the design of appropriate methods of counteracting potential risks.
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The two main classifications of mood disorders currently used are the American system, DSM, the fourth edition of which came out in 1994, and the International Classification of Diseases, the tenth edition of which was published in 1993. These classifications are based on the following broad principles: simple description with no hypothetical aetio-pathogenic discussion, distinction between the various clinical forms in accordance with variety and intensity of symptoms, co-existence of other more or less serious somatic disorders, individual identification of bipolar forms, etc. The key changes made in the classification of mood disorders between the revised version of DSMIII published in 1987 and DSM-IV published in 1994 suggest that a greater degree of concordance in diagnosis between different practitioners may be expected in future. In addition, certain changes such as the therapeutic decision-trees will most likely have an impact on practice. In this way, further details are added to the clinical criteria of duration or description of the clinical features seen, thereby allowing a clearer distinction to be made between normality and the onset of the pathology in question. Regarding bipolar disorders, the general organisation of the classification and the terminology used have been extensively revised, with the distinction between types I and II becoming official. Furthermore, differentiation between certain aspects of depression emphasises the frequency of certain clinical particularities, either in the onset or during the course of these disorders. This is true of melancholic, catatonic and atypical features specifiers (i.e. with mood reactivity and interpersonal rejection sensitivity), post-partum onset specifier, seasonal pattern specifier and rapid-cycling specifier. Finally, a certain number of specifications are proposed allowing the postulation of notions of complete or partial cure between episodes in case of recurrence.