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At least 217 records · Page 12Linked to original sources
PubMed2006

Origin of mutations under selection: the adaptive mutation controversy.

Growth under selection causes new genotypes to predominate in a population. It is difficult to determine whether selection stimulates formation of new mutations or merely allows faster growth of mutants that arise independent of selection. In the practice of microbial genetics, selection is used to detect and enumerate pre-existing mutants; stringent conditions prevent growth of the parent and allow only the pre-existing mutants to grow. Used in this way, selection detects rare mutations that cause large, easily observable phenotypic changes. In natural populations, selection is imposed on growing cells and can detect the more common mutations that cause small growth improvements. As slightly improved clones expand, they can acquire additional mutational improvements. Selected sequential clonal expansions have huge power to produce new genotypes and have been suggested to underlie tumor progression. We suggest that the adaptive mutation controversy has persisted because the distinction between these two uses of selection has not been appreciated.

Adaptation, Physiological↗
PubMed2006

Anti-neutrophil cytoplasmic autoantibodies: a renewed paradigm in periodontal disease pathogenesis?

In the past, various models including the autoimmunity model have been proposed to explain the pathogenesis of periodontal diseases. The aim of this review is to introduce the pathogenic role of anti-neutrophil cytoplasmic autoantibodies (ANCAs) in various autoimmune diseases and compare these conditions with periodontal disease to elucidate common pathogenic mechanisms. Also, a novel model to explain the pathogenesis of periodontal disease based on the concept of ANCA-associated autoimmunity is proposed. This encompasses a wide array of biochemical mediators that range from direct and indirect initiators of ANCA production and eventual release of proinflammatory mediators and free radicals, all of which have been implicated in periodontal tissue destruction in the past. In addition, specific links between the typical ANCA-associated diseases and periodontal disease are discussed. Finally, a new paradigm in the periodontal disease-associated destruction is proposed that includes the currently accepted mechanism, namely, the genetic-microbial-host interactions.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1995

Cancer risk among workers in biomedical research.

OBJECTIVE: This epidemiologic study was undertaken after a cluster of five cases of rare forms of cancer (bone sarcoma, non-Hodgkin's lymphoma) had been observed among biomedical research workers at the Pasteur Institute in Paris to ascertain whether their disease was connected with exposure during this research. METHODS: A mortality study included 3765 people who worked at the Pasteur Institute between 1971 and 1986 and were followed until the end of 1987. Within this cohort a nested case-referent study included 23 cases of cancer [non-Hodgkin's lymphoma (6), multiple myeloma (1), leukemia (3), pancreatic cancer (7), bone cancer (3), brain tumor (3)], and four referents per case, matched for gender and year of birth. RESULTS: Total mortality from cancer was less than expected, the standardized mortality ratio (SMR) being 72 for the men and 82 for the women. Among the women the proportion of pancreatic cancer cases was larger than expected [SMR 490, 95% confidence interval (95% CI) 158-1144], as was the number of brain cancer cases (SMR 239, 95% CI 48-696). Among the men, mortality from bone cancer was greater than expected (SMR 553, 95% CI 62-2006). In the nested case-referent study, more cases than referents had worked in the areas of molecular biology [odds ratio (OR) 7.1, 95% CI 1.5-33] and microbial genetics (OR 6.7, 95% CI 1.3-35). These cases especially included non-Hodgkin's lymphoma and bone cancer. Associated with this finding was the fact that more cases had used certain chemicals, including ethidium bromide, acrylamide, methylnitronitrosoguanidine and ethylmethanesulfonate, and radioactive compounds (essentially 32phosphorus). CONCLUSIONS: As the products used are potent genotoxicants, the present findings suggest that work in biomedical research might well involve an increased risk of certain types of cancer; this conclusion should be balanced by the fact that two of the five index cases were included in the mortality study and four in the nested case-referent study.

Academies and Institutes↗
PubMed1976

[Pleiotropic effect of the mutation of streptomycin resistance in Micromonospora purpurea var. violacea].

Variation of different features of populations of streptomycin-sensitive and streptomycin-resistant forms of M. purpurea var. violacea, an organism producing gentamicin was studied. The population of the initial streptomycin-sensitive culture was characterized by high homogeneity with respect to the cultural, morphological and some physiological properties. The variation of the features, such as the colony size, pigment formation, auxotrophic mutations, antibiotic production significantly increased in populations grown on media with streptomycin. Mutants differing from the initial strain by a complex of cultural, morphological and physiological features and in particular the antibiotic production were isolated from populations of the streptomycin-resistant variants.

Culture Media↗
PubMed1976

[Murine model for experimental studies on attenuated mutants of a Pasteurella multocida strain with pathogenicity for the calf. 2. Primary immunization against lethal infection, using fully attenuated streptomycin-dependent (Sm-d) mutant and booster immunization with partially attenuated streptomycin-dependent (Sm-id) revertants].

An experimental study was conducted into the immunisation of mice to a strain of Pasteurella multocida with pathogenicity for calf. Here are the findings: (a) The attenuation of Sm-id revertants was measured with reference to the order of extinction and compared to the wild strain. (b) A selected range of Sm-id revertants with differentiated attenuation is presented. (c) Single immunisation, using fully attenuatted Sm-d mutant does prevent lethal infection with partially attenuated Sm-id revertants, although it is ineffective against wild strain infection. (d) Immunity against 100 times the lethal dose of the wild strain can be achieved by two immunisations, that is primary antigen application, using fully attenuated Sm-d mutant, and booster immunisation, using partially attenuated Sm-id revertant.

Animals↗
PubMed1998

The renaissance of microbiology.

Microbiology is finally occupying its true position as the pre-eminent field in life sciences. This is due to advances in molecular techniques that confirm the evolutionary significance of the biology of microbes. It is anticipated that the use of comparative genomics will provide information that will advance the understanding of mechanisms of pathogenesis and the importance of secondary metabolism in social microbiology. More emphasis on studies of microbial diversity will increase its value in both fundamental microbiology and its industrial applications.

Biological Evolution↗
PubMed1997

Nucleic acid technology and infectious diseases.

The past decade has witnessed an explosion in the knowledge of microbial genetics, pathogenesis, and antimicrobial resistance as a result of advances in molecular technology. This has brought important breakthroughs in the management of patients with infectious diseases, as organisms that had previously been difficult to demonstrate in vitro can now be detected by molecular techniques such as the polymerase chain reaction. Not only is rapid diagnosis now possible, but old diseases of uncertain aetiology have been found to have an infective origin, for instance, Whipple's disease. Molecular technology has also contributed greatly to epidemiological studies of outbreaks, understanding antimicrobial resistance, developing new antimicrobial agents, the in vitro synthesis of immunomodulators, production of vaccines, and gene therapy. The limitations of these latest technologies, however, need to be remembered so that they yield meaningful information for patient care.

Journal Article↗
PubMed2004

Inflammatory bowel disease. Part II: Crohn's disease--pathophysiology and conventional and alternative treatment options.

Crohn's disease, a subcategory of inflammatory bowel disease, contributes to significant morbidity, particularly in industrialized nations. It can affect people of any age, but is more commonly diagnosed in adolescence and young adulthood. Inflammation and ulceration occurs primarily in the terminal ileum and colon, although any portion of the intestinal tract can be affected. No etiology has been identified for Crohn's disease, although a number of factors contribute to its etiopathogenesis, including genetic, microbial, inflammatory, immune, and permeability abnormalities. Conventional medications are not curative but can contribute to resolution of acute flare-ups and help maintain remission. Because significant side effects are associated with many these medications, more natural interventions to help maintain remission should be considered. Associated nutrient deficiencies, dietary interventions, and nutrient and botanical supplementation are discussed.

Crohn Disease↗