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At least 343 records · Page 19Linked to original sources

[Syphillis. An up-to-date physio-biological view of the main topics. II- The evolutive process of experimental syphilitic infection and a comparison with clinical symptoms in man (author's transl)].

For lack of being able to grow Treponema pallidum, the only possibility that we have to study its biological behavior is to have recourse to experimentation upon animals. The stade comprising primary and secondary syphilis is characterized by visible "warning signals" which are not serious for the patient himself. But all their importance lies in the fact that they reveal the dissemination of T. pallidum inside the whole body. Thus, the healing alone or the disappearance of the lesion does not necessarily mean that it is cured. As a matter of fact, after that phase, infection may proceed "á bas bruit", as a chronic affection, which will come to light later, 10 to 15 years or more after the primary stage, as a visceral phase involving mainly cardiovascular or central nervous system. Those impairments cannot then be cured. Now, during that long period of latency, we are totally without any absolute criterion of "bacteriological sterilization", for we do not know precisely the physio-pathological meaning of these numerous serological reactions which are at out disposal and subsequently we are obliged to interpret them through divergent opinions because these techniques are not established on scientific method but are based upon empiric knowledges.

Animals↗

[Experimental brain abscess evolution : brain edema and neuropathologic correlation (author's transl)].

In the right hemisphere of rabbits an inoculation of a mixture of agar and bouillon with Staphylococcus aureus was performed to examine brain inflammation, which always led to brain abscess with a spreading inflammatory edema. The size of the acute abcess and the concomitant edema are dependant from the degree of pathogenecity, less from the inoculated quantity of bacteria. In the acute phase, the edema had the tendency to spread towards the ventricular system. When the intracranial pressure exceeds a certain limit by the spreading edema, the mortality increased significantly. With the incipient encapsulation from the 5th day on the accumulation of extracellular fluid decreased but remained recognisable around the encapsulated abscess as long as bacteria maintain a chronic inflammation.

Acute Disease↗

Laparoscopic-assisted colon resection. Evolution from an experimental technique to a standardized surgical procedure.

Between October 1991 and November 1992, 51 patients in the mean age 63.2 years (range 19 to 91 years) underwent laparoscopic colon resection. Indications for surgery were colon carcinoma (31), adenomatous polyps (8), diverticulitis (10) and Crohn's disease (2). In right-sided lesions an extracorporeal anastomosis and in left-sided lesions an intracorporeal anastomosis was performed using the double stapling technique. The mortality rate was 1.9% and the morbidity rate 20.5% in the laparoscopic-treated group. The conversion rate was 13.7%. Except for one anastomotic leakage in a converted patient, no anastomotic problems were encountered. The percentage of infectious complications was 11.7%. Three reinterventions were necessary for treatment of two deep subfascial abscesses and one case of localized peritonitis, caused by a small small bowel injury. The mean hospital stay was 9.1 days (range 4-29 days). In the last 13 consecutive patients, except for a urinary infection, no further post-operative morbidity was encountered. Laparoscopic-assisted colon resection has evolved in to a standardized surgical technique. Initial learning problems are solved by good patient selection, better operative logistics and awareness of the dangers and pitfalls of laparoscopic surgery.

Adult↗

Response to divergent selection on meiotic recombination in Saccharomyces cerevisiae.

Meiotic recombination is a key driver of evolution in sexually reproducing species, reshaping genetic diversity by generating novel allelic combinations. The rate of recombination varies substantially across living organisms depending on cis- or trans-acting genetic elements, as seen in many species, including the yeast Saccharomyces cerevisiae. Here, we report on an experimental evolution-based study to better understand the factors shaping this natural variation. Starting with a genetically diverse population of S. cerevisiae, we have carried out recurrent divergent selection on recombination rate using a fluorescence-based sorting approach in four independent lineages. After ten generations, we observed an average response of recombination rate of +28% after positive selection and -24% after negative selection, within the interval used for selection. In the adjacent region, however, we observed a weaker response in the opposite direction, and no response in four other unlinked genomic regions. Whole-genome sequencing of individuals selected for high recombination revealed mixed outcomes in the four independently evolved lineages for high genome-wide recombination rates. However, all four lineages showed selection for high recombination locally, with particular haplotypes heavily favored and sequence- or structural variation-based heterozygosity selected against within the selection interval. Overall, this experimental evolution approach provides original and useful insights into the evolvability of the meiotic recombination rate and the associated genetic determinants.

Meiotic recombination↗

Evolution of female remating behaviour following experimental removal of sexual selection.

The relatively small number of ova produced by a female can be fertilized by a single ejaculate in most species. Why females of many species mate with multiple males is therefore enigmatic, especially given that costs associated with remating have been well documented. Recently, it has been argued that females may remate at a maladaptive rate as an outcome of sexually antagonistic coevolution: the evolutionary tug-of-war between manipulation by one sex and resistance to being manipulated by the other sex. We tested this hypothesis experimentally for the evolution of the female remating interval in a naturally promiscuous species, Drosophila melanogaster. In two replicate populations, sexual selection was removed through enforced monogamous mating with random mate assignment, or retained in polyandrous controls. Monogamy constrains the reproductive success of mates to be identical, thereby converting prior conflicts between mates into opportunities for mutualism. Under these experimental conditions, the sexually antagonistic coevolution hypothesis generates explicit predictions regarding the direction of evolutionary change in female remating behaviour. These predictions are contingent upon the mechanism of male manipulation, which may be mediated biochemically by seminal fluids or behaviourally by courtship. Levels of divergence in female remating interval across lines, and in male ejaculatory and courtship effects on female remating, were quantified after 84 generations of selection. Data refute the hypothesis that the evolutionary change in female remating behaviour was due to sexually antagonistic coevolution of courtship signal and receiver traits. The data were, however, consistent with a hypothesis of sexual conflict mediated through ejaculate manipulation. Monogamy-line males evolved ejaculates that were less effective in inducing female non-receptivity and monogamy-line females evolved to remate less frequently, symptomatic of lowered resistance to ejaculate manipulation. The consistency of the results with alternative hypotheses to explain female promiscuity are discussed.

Animals↗

Serum sickness-like syndrome associated with minocycline therapy.

A 19 year-old youth was taking oral minocycline and after 8 days he presented all four cardinal symptoms of serum sickness (urticaria, fever, lymphadenopathy and joint symptoms). C3, C4 and CH50 evolution imitate experimental serum sickness complement evolution. We exclude other causes of this syndrome. Although other hypersensitivity reactions have occurred with minocycline usage, to our knowledge serum sickness-like syndrome has not been previously reported with this drug.

Adult↗

Aneurysm formation in experimental atherosclerosis: relationship to plaque evolution.

To determine whether aneurysms form in experimental diet-induced atherosclerosis, we reviewed our experience with cynomolgus monkeys (n = 268) and rhesus monkeys (n = 175) fed an atherogenic diet for various lengths of time. Many animals in long-term experiments were fed "regression" diets and cholestyramine to lower cholesterol levels after lesions were established. No aneurysms were found in animals on normal diet. There were no aneurysms in 252 animals fed an atherogenic diet with or without regression for 12 months or less. However, aneurysms formed in 13% of cynomolgus monkeys (4 of 31) and 1% (1 of 107) rhesus monkeys on an atherogenic regimen for 16 to 24 months. Four of the five animals with aneurysms were on a regression diet and cholestyramine for 4 to 12 months. The fifth was fed the atherogenic diet for 20 months without subsequent regression. Aneurysms were prominent and involved the thoracic and abdominal aorta, innominate artery, carotid arteries, iliac and femoral arteries, and formed in areas most involved with plaque formation in both species. Histologic evidence was found of thinning of the media and atrophy with loss of normal architecture. The higher incidence of aneurysms in cynomolgus monkeys was associated with greater media destruction than was noted in the rhesus. These data support the thesis that aneurysm formation is a manifestation of atherosclerosis. In primate atherosclerosis, aneurysms form only after prolonged exposure to the atherogenic regimen, even in the presence of declining serum cholesterol levels. Matrix fibers in plaques may provide structural support to the aortic wall where there is underlying atrophy of the media. With time or declining serum cholesterol levels or both, plaques may atrophy leaving an aortic wall too thin to support increasing mural tension, leading to aneurysmal enlargement.

Animals↗

Biomimicry as a basis for drug discovery.

Selected works are discussed which clearly demonstrate that mimicking various aspects of the process by which natural products evolved is becoming a powerful tool in contemporary drug discovery. Natural products are an established and rich source of drugs. The term "natural product" is often used synonymously with "secondary metabolite." Knowledge of genetics and molecular evolution helps us understand how biosynthesis of many classes of secondary metabolites evolved. One proposed hypothesis is termed "inventive evolution." It invokes duplication of genes, and mutation of the gene copies, among other genetic events. The modified duplicate genes, per se or in conjunction with other genetic events, may give rise to new enzymes, which, in turn, may generate new products, some of which may be selected for. Steps of the inventive evolution can be mimicked in several ways for purpose of drug discovery. For example, libraries of chemical compounds of any imaginable structure may be produced by combinatorial synthesis. Out of these libraries new active compounds can be selected. In another example, genetic system can be manipulated to produce modified natural products ("unnatural natural products"), from which new drugs can be selected. In some instances, similar natural products turn up in species that are not direct descendants of each other. This is presumably due to a horizontal gene transfer. The mechanism of this inter-species gene transfer can be mimicked in therapeutic gene delivery. Mimicking specifics or principles of chemical evolution including experimental and test-tube evolution also provides leads for new drug discovery.

Algorithms↗

Manipulating lek size and composition using decoys: an experimental investigation of lek evolution models.

Four theoretical models have been proposed to account for the origin and maintenance of leks: hotspot, female preference, hotshot, and black hole models. Each has been validated in particular cases, and most are not mutually exclusive; therefore, it has been difficult to contrast and separate them, empirically and experimentally. By using decoys to mimic natural leks in the little bustard, artificial leks attracted wild birds. Then, by manipulating artificial lek size and structure (sex ratio, male phenotype), the study of responses of wild males and females allowed us to test specific predictions derived from the four classical models of lek evolution. The hotspot model was not supported because female decoys did not attract wild males. Conversely, hotshot males do exist in this species (attracting both wild females and males), as does a female preference for a particular lek size (four males). Finally, males aggressive toward decoys attracted fewer females, consistent with one of the mechanisms by which the black hole model may work. Therefore, three models of lek evolution were partly or fully supported by our experimental results: hotshot, female preference, and black hole models. We suggest that these models actually fit within each other, ensuring the evolution, functioning, and long-term maintenance of leks.

Aggression↗

Morphogenesis and pathogenesis of chronic lung diseases. IX. Development of reticulinic fibrillogenesis during the evolution of an associated experimental silicosis and tuberculosis.

Well developed silicotic nodules of rabbit lungs were infected with tuberculosis and treated with tuberculostatics. The spatial evolution of lesions, as well as the density of intralesional and perilesional reticulinic fibrils were quantitatively analysed, measured by planimetric and target methods, and statistically analysed. Under tuberculostatics, the size of lesions, expressed in the dynamics of the SL/ST % ratio, rapidly diminished to half after three months. In the some period, the density of reticulinic fibrils expressed by the PA of the target method, increased, with significant differences between treated silicotuberculotic lesions and tuberculotic ones. The correlation analysis between these two divergent changes showed the interfering with other factors.

Animals↗