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PubMed1999

Alu repeats and human disease.

Alu elements have amplified in primate genomes through a RNA-dependent mechanism, termed retroposition, and have reached a copy number in excess of 500,000 copies per human genome. These elements have been proposed to have a number of functions in the human genome, and have certainly had a major impact on genomic architecture. Alu elements continue to amplify at a rate of about one insertion every 200 new births. We have found 16 examples of diseases caused by the insertion of Alu elements, suggesting that they may contribute to about 0.1% of human genetic disorders by this mechanism. The large number of Alu elements within primate genomes also provides abundant opportunities for unequal homologous recombination events. These events often occur intrachromosomally, resulting in deletion or duplication of exons in a gene, but they also can occur interchromosomally, causing more complex chromosomal abnormalities. We have found 33 cases of germ-line genetic diseases and 16 cases of cancer caused by unequal homologous recombination between Alu repeats. We estimate that this mode of mutagenesis accounts for another 0.3% of human genetic diseases. Between these different mechanisms, Alu elements have not only contributed a great deal to the evolution of the genome but also continue to contribute to a significant portion of human genetic diseases.

Alu Elements↗

PubMed1986

Platelets and foam cells in the evolution of atherosclerosis. Histological and immunohistological studies of human lesions.

Sixty-seven coronary, aortic and other lesions (39 subjects) ranging from minor to advanced disease were studied histologically and by immunohistology for antigens of platelets, beta-lipoprotein (LpB) and fibrinogen. Collections of lipid-filled foam cells were found in nearly every lesion mainly in the thickened intima, sometimes associated with macrophages. Foam cells were also present elsewhere including, in advanced lesions, necrotic zones filled with cholesterol needles. Then they too were necrotic. Platelets were observed in many lesions as small free clusters and/or phagocytosed in foam cells and sometimes also in macrophages. Cellular and extracellular reactions for platelet derivatives and for LpB were very frequent. Reactions for fibrinogen were only extracellular. Foam cell cytoplasm reacted for platelet derivatives and for LpB whilst macrophages, endothelium and certain other cells sometimes reacted for platelet derivatives but rarely for LpB. The studies indicate that: Foam cells originate from macrophages mainly in the intima and many migrate elsewhere. Their formation and their uptake of LpB requires cellular acquisition of a platelet factor or factors. Acquisition of platelet factor(s) is by phagocytosis of intact platelets and/or uptake of extracellular soluble derivatives from disrupted platelets. These processes begin early, are likely to be continuous and are significant for the evolution of atherosclerosis including the necrotic foci of advanced lesions.

Antigens↗

PubMedDate not supplied

Michigan's fisheater cohorts: a prospective history of exposure.

Interest in environmental contaminants and their effect on human health emerged as a primary focus in the 1970s following the discovery of significant levels of mercury, dichloro diphenyl trichloroethane (DDT), and polychlorinated bihpenyls (PCBs) in recreationally caught Great Lakes fish. In response to these findings, the Michigan Department of Public Health, in 1971, initiated a series of "fisheater" cohort studies. These studies continue to be conducted today. The evolution of human exposure assessment by serum PCB determination parallels the evolution of more precise and sensitive analytical laboratory procedures over the past 25 years. Early work quantitated PCB with Aroclor 1254 standards. By 1980, the Webb and McCall packed-column method (Webb and McCall, 1972, 1973), which quantitates total PCB with Aroclor 1016 and 1260 standards, had gained the Association of Official Analytical Chemists (AOAC) approval and became the accepted method. This method was used in the 1978-1980 Michigan Great Lakes Fisheater Study, the first sizable study of this kind in the nation. The study confirmed that fisheaters had significantly more exposure (median 21.4 ppb vs 6.6 ppb) than controls. Toxicology studies have indicated the need to quantitate individual PCB congeners, in order to correlate exposure with possible toxicological and health outcomes. Today, capillary column gas chromatography and gas chromatography/mass spectrometry are used to search for trace components of the total PCB dose (Mullen et al., 1984). Because of the legacy of the earlier analytical data, Michigan also continues to conduct packed-column analysis for longitudinal comparisons. The Michigan fisheater study database and registry provide a significantly exposed and historic foundation for research testing health outcome hypotheses.

Cohort Studies↗

PubMed2025

Phylogenetic and Genetic Evolution Analysis of Complete SFTSV Genome Sequences in Shandong Province, China.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS virus (SFTSV). Shandong province is one of the epidemic regions with high incidence rate of SFTS. To investigate phylogenetical and genetic evolution characteristics of SFTSV in Shandong province, we isolated SFTSV from suspected patients between April 2023 and October 2024, and then whole SFTSV genomes were amplified and sequenced in this study. A total of 25 new strains were analyzed together 56 strains submitted in Genbank from Shandong province. Phylogenetical and genetic analyses of the data set revealed that four genotypes were co-circulating in Shandong province. C3 genotype was the most common genotype in each year with lower genetic divergence. 298 amino acid substitutions were detected in the four proteins of SFTSV, but only two substitutions (Arg624Lys and Arg962Ser) had been proven to have potential impacts on biological functions. In addition, one reassortment strain (C3/C4/C4 for L, M and S segments) and three recombinant strains were identified. Analysis of selection pressure at the level of amino acid substitutions indicated genes within the four ORFs of SFTSV were all subjected to negative selection. In conclusion, the genetic characteristics and evolutionary mechanism of SFTSV was complex in Shandong province. It is necessary to conduct continuous surveillance to grasp the genetic evolution patterns, and to discover novel prevalent variants in a timely manner.

China↗

PubMed1999

[Does continuing medical education improve the way physicians conduct their practice?].

OBJECTIVES: Physicians practicing in France are required to participate in continuing education programs in accordance with the code of deontology and the official decree on controlling medical expenditures. We reviewed the literature to analyze the efficacy of such training on the way physicians conduct their practice. METHODS: We examined the following educational methodologies: diffusion of educational documents or guidelines, conferences and presentations, interventions by opinion leaders, direct visits at the physician's office. The analysis was based solely on publications issuing from work considered to be valid in accordance with the Cochrane collaboration: intervention trials, chronological series, before-after studies with control group. RESULTS: The diffusion of educational material or more formal continuing education programs do not appear to have an effect on the way physicians conduct their practice. Interventions by opinion leaders have a demonstrated impact but are rarely judged clinically significant. Visits to the physician's office by specially trained health care workers have an effect but this mode of education is costly. CONCLUSIONS: The conventional strategies, such as simple information diffusion and continuing education programs, developed to promote an evolution of clinical practices appear to be the least effective methodologies.

Education, Medical, Continuing↗

PubMed1999

Evolution of bacterial pathogenesis.

The evolution of bacteria is associated with continuous generation of novel genetic variants. The major driving forces in this process are point mutations, genetic rearrangements, and horizontal gene transfer. A large number of human and animal bacterial pathogens have evolved the capacity to produce virulence factors that are directly involved in infection and disease. Additionally, many bacteria express resistance traits against antibiotics. Both virulence factors and resistance determinants are subject to intrastrain genetic and phenotypic variation. They are often encoded on unstable DNA regions. Thus, they can be readily transferred to bacteria of the same species or even to non-related prokaryotes. This review article focuses on the main mechanisms of bacterial microevolution responsible for the rapid emergence of variants with novel virulence and resistance properties. In addition, processes of macroevolution are described with special emphasis on gene transfer and fixation of adaptive mutations in the genome of pathogens.

Animals↗

PubMed1999

Phylogeny and evolution of Orchis and allied genera based on ITS DNA variation: morphological gaps and molecular continuity.

Phylogenetic relationships among members of genus Orchis and allied genera Aceras, Anacamptis, Barlia, Dactylorhiza, Gymnadenia, Himantoglossum, Neotinea, Ophrys, Platanthera, and Serapias were inferred from nucleotide sequence variation in the internal transcribed spacer (ITS) regions of nuclear ribosomal DNA. Sequences were subjected to various alignments by changing the gap opening and extension parameters. After a preliminary parsimony analysis, the alignment with the lowest homoplasy indicators was chosen as optimal. The phylogenetic analysis, carried out on the optimal alignment by using Gennaria as an outgroup and a total of 31 taxa, showed that all the genera considered in this study are nested in Orchis despite their distinct morphological features. Genus Orchis is divided into two major clades, each of which includes one or more of the other genera in this study. The resulting phylogenetic hypothesis does not match previous conclusions based on vegetative and floral morphology of the taxa involved but is congruent with isoenzyme, karyological, and chloroplast DNA restriction data. Our results indicate that floral morphology is highly flexible and current generic and infrageneric limits are artificial. Even if some floral characters closely correspond to the molecular data, most are highly homoplastic and thus unsuitable for phylogenetic reconstruction. Various traits pertaining to floral morphology may be interpreted as a result of ecological convergence related to pollinator-mediated selection; such characters can undergo drastic modifications without correspondingly dramatic genetic changes.

Base Sequence↗

PubMed1997

Classification of endometriosis.

The evolution of classification schemes for endometriosis has continued since the 1920s, when initial attempts were made to describe endometriosis. The cause, pathophysiology, and natural history of endometriosis remain difficult to characterize. As knowledge about endometriosis increases, classification schemes will change to incorporate new ideas. Evolution of the current American Fertility Society's revised classification of endometriosis is reviewed, as well as evaluation of its use with respect to prediction of fertility and management of pelvic pain. Possible directions for classification in the future are also discussed in this article.

Endometriosis↗

PubMed1992

The role of oxygen radicals in the pathobiology of traumatic brain injury.

This manuscript considers some of the most prominent consequences of traumatic brain injury (TBI), namely vascular and axonal change, and evaluates the role of damaging oxygen radicals in their pathogenesis. To this end, existing as well as new data derived from traumatically injured experimental animals and humans was employed. Experimental animals were subjected to fluid-percussion brain injury. Some animals were equipped with cranial windows to allow for the functional assessment of the pial vasculature, while others received various exogenous tracers to assess blood-brain barrier status. In order to identify traumatically induced axonal change, some animals were also processed for the light and electron microscopic visualization of antibodies targeted to the neurofilament subunits. Similar immunocytochemical strategies were employed in the postmortem study of humans who had sustained severe TBI. Through these approaches, TBI was recognized to result in vascular abnormalities ranging from impaired vascular responsiveness to altered blood-brain barrier status. Typically, these vascular abnormalities continued for several hours postinjury and showed evolution which correlated with the production of damaging oxygen radicals. Importantly, the use of radical scavengers reversed these vascular abnormalities and provided protection. Traumatically induced axonal damage was also associated with evolving posttraumatic change. This involved the continued posttraumatic disassembly and misalignment of the intra-axonal neurofilament subunits which caused impaired axoplasmic transport leading to axonal swelling and detachment. Although these intra-axonal changes did not appear to be directly caused by oxygen radicals, it is suggested that the presence of oxygen radicals may exacerbate the progression of these reactive events.

Animals↗

PubMed2004

[Clinical significance of continuous karyotyping in myelodysplastic syndromes].

OBJECTIVE: To explore the relationship between evolution of karyotype and clinical progress in myelodysplastic syndromes (MDS) and estimate the clinical outcomes of high risk patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Continuous karyotyping were performed using short-term culture of bone marrow cells and G-banding technique to follow up 41 cases of MDS patients. RESULTS: Karyotype analysis showed that 24 cases (58.5%) had clonal karyotypic abnormalities. In a median follow up of 34 months (7 approximately 72 months), 6 cases had karyotype evolution in 12 cases with clinical deterioration, while only one had karyotype evolution in 18 cases without clinical progression. The involved chromosomes included No. 2, 4, 7, 8, 10, 11, 17 and 21. Six out of 7 patients who received allo-HSCT attained complete remission and their abnormal karyotypes returned to normal. Four patients with clinical remission after therapy attained cytogenetic remission too. CONCLUSION: Karyotype evolution showed a strong relationship with clinical progress in MDS patients, and indicated a very poor prognosis. Patients with clinical progress had much higher incidence of clonal evolution than those with relatively stable clinical course. Allo-HSCT should be considered the first choice of therapy for MDS patients with clonal karyotypic abnormalities.

Adolescent↗

PubMed2002

Origin of multicellular organisms as an inevitable consequence of dynamical systems.

The origin of multicellular organisms is studied by considering a cell system that satisfies minimal conditions, that is, a system of interacting cells with intracellular biochemical dynamics, and potentiality in reproduction. Three basic features in multicellular organisms-cellular diversification, robust developmental process, and emergence of germ-line cells-are found to be general properties of such a system. Irrespective of the details of the model, such features appear when there are complex oscillatory dynamics of intracellular chemical concentrations. Cells differentiate from totipotent stem cells into other cell types due to instability in the intracellular dynamics with cell-cell interactions, as explained by our isologous diversification theory (Furusawa and Kaneko, 1998a; Kaneko and Yomo, 1997). This developmental process is shown to be stable with respect to perturbations, such as molecular fluctuations and removal of some cells. By further imposing an adequate cell-type-dependent adhesion force, some cells are released, from which the next generation cell colony is formed, and a multicellular organism life-cycle emerges without any finely tuned mechanisms. This recursive production of multicellular units is stabilized if released cells are few in number, implying the separation of germ cell lines. Furthermore, such an organism with a variety of cellular states and robust development is found to maintain a larger growth speed as an ensemble by achieving a cooperative use of resources, compared to simple cells without differentiation. Our results suggest that the emergence of multicellular organisms is not a "difficult problem" in evolution, but rather is a natural consequence of a cell colony that can grow continuously.

Algorithms↗

PubMed2001

Metabolic engineering of indene bioconversion in Rhodococcus sp.

We have applied the methodology of metabolic engineering in the investigation of the enzymatic bioreaction network in Rhodococcus sp. that catalyzes the bioconversion of indene to (2R)-indandiol suitable for the synthesis of cis-1-amino-2-indanol, a precursor of the HIV protease inhibitor, Crixivan. A chemostat with a novel indene air delivery system was developed to facilitate the study of steady state physiology of Rhodococcus sp. 124. Prolonged cultivation of this organism in a continuous flow system led to the evolution of a mutant strain, designated KY1, with improved bioconversion properties, in particular a twofold increase in yield of (2R)-indandiol relative to 124. Induction studies with both strains indicated that KY1 lacked a toluene-inducible dioxygenase activity present in 124 and responsible for the formation of undesired byproducts. Flux analysis of indene bioconversion in KY1 performed using steady state metabolite balancing and labeling with [14C]-tracers revealed that at least 94% of the indene is oxidized by a monooxygenase to indan oxide that is subsequently hydrolyzed to trans-(1R,2R)-indandiol and cis-(1S,2R)-indandiol. This analysis identified several targets in KY1 for increasing (2R)-indandiol product yield. Most promising among them is the selective hydrolysis of indan oxide to trans-(1R,2R)-indandiol through expression of an epoxide hydrolase or modification of culture conditions.

Catalysis↗

PubMed1994

On some formulas in a partnership model from the perspective of a semi-Markov process.

Many deterministic models of sexually transmitted diseases, as well as population models in general, contain elements of stochastic or statistical reasoning. An example of such a model is that of Dietz and Hadeler (1988) concerning sexually transmitted diseases in which there is partnership formation and dissolution. Among the interesting formulas in this paper, which enter into the analysis of the model, are those for the expected number of partners a male or female has during a lifetime. To a probabilist such formulas suggest the possibility that some stochastic process may be constructed so as to yield these formulas as well as others that may be of interest. The principal purpose of this paper is to demonstrate that such a stochastic process does indeed exist in the form of a three state semi-Markov process in continuous time with stationary laws of evolution and with a one-step density matrix determined by four parameters which were interpreted as constant latent risk functions in the classical theory of competing risks. This construction of a semi-Markov process not only provides a framework for the systematic derivation of the formulas of Dietz and Hadeler but also suggests pathways for extensions to the age-dependent case.

Female↗

PubMed1989

First and second moments and the mean Hamming distance in a stochastic replication-mutation model for biological macromolecules.

In this work first and second moments for a many species Moran model are calculated. The model describes by means of a time-continuous birth- and death process the evolution of an ensemble of N macromolecules out of n possible species. The molecules may replicate (correct or erroneous, in the latter case producing mutants) and may undergo elimination. Replication and elimination will be coupled in order to keep population size constant. In the case of arbitrary replication rates an expansion of the moments in powers of 1/N is found. For equal replication rates exact calculation of the moments is possible. In the case of a v-cube model (binary macromolecules) the second moments may be used to find a simple expression for the mean Hamming distance in the system. This quantity provides a measure for the localization of the ensemble.

Biopolymers↗

PubMed1990

The mutating preconscious archetype in present-day ecological conditions.

Competition is an important force behind evolution in present-day ecological conditions, its intensity varying according to the organisms' expectations vis-à-vis resources available. On the other hand, the role of mutation in the evolutionary process can hardly be underestimated: Leading to the change of the preconsciously functioning archetype, mutation makes it impossible for the ego to realize its image. This is a consequence of the clash between the mutated, preconsciously functioning archetype and the system of ethical and moral norms functioning in the collective superego of a given population group. The type of mutation that results from the accelerated pace of evolution can be viewed as a continuity in the development of an organism's behavior. The preconsciously functioning archetype, resulting from these mutations, contains impulses and predispositions that differ markedly from the impulses and predispositions functioning in the genetically determined "pattern of behavior." In a situation where anxiety results from the inhibition of impulses and dispositions, hostility reactions are likely to occur. In its turn, reactive hostility can induce anxiety, thus creating a reaction cycle. Underlying this mechanism is the mutated, preconsciously functioning archetype, which itself is a result of the development of civilization in our contemporary world.

Adaptation, Psychological↗

PubMed2005

Selective conservatism in trauma management: a South African contribution.

Trauma in South Africa has been termed the malignant epidemic. This heritage was the result of a violent colonial legacy which spawned the apartheid system of injustice and the struggle against it The Apartheid regime created overcrowding, unemployment, social stagnation, and the disruption of normal family life. These were the catalysts for the incredible amount of criminal and interpersonal conflict in South Africa over the last 50 years. African townships such as Soweto in Johannesburg and Umlazi in Durban were crime-ridden ghettoes where the apartheid police were more interested in fueling the "black on black" violence rather than trying to curb it. Baragwanath (Chris Hani-Baragwanath) and King Edward the VIII Hospital in Durban were the "trauma care epicenters" on the fringes of these huge urban conurbations. Both were designated black hospitals and both were underfunded and dilapidated. Even the architecture was similar, with prefabricated, poorly ventilated structures serving as wards and clinics in both institutions. Trauma volumes consisted of between 10 and 20 laparotomies on weekend nights at the height of political unrest. This led to vast individual experience in several areas of trauma typified by Demetriades' experience with 70 penetrating cardiac injuries. In this setting of limited resources and an overwhelming volume of trauma, selective conservatism as a surgical philosophy took root and has profoundly influenced the way the world manages trauma. We detail and illustrate the evolution of this approach and its continued application.

Humans↗

PubMed2001

Blood purification in the intensive care unit: evolving concepts.

Until relatively recently surgeons were familiar with the concept that some of their patients admitted to the intensive care unit require dialysis to deal with the development of severe acute renal failure. Under such circumstances the nephrology team would then attend the patient and take over that aspect of management. More recently, however, this situation has undergone a significant evolution because of the advent of continuous renal replacement therapy (CRRT). First introduced as "last ditch" therapy in the most critically ill patients who were hemodynamically intolerant of hemodialysis, CRRT has become more and more widely used. It is now the dominant form of artificial renal support in Australia and close to being the dominant treatment of the severe acute renal failure of critical illness in most European countries. The use of CRRT in the United States is rapidly growing. The arrival of CRRT has also renewed interest in the wider concept of blood purification during critical illness. Experimental and preliminary human data suggest that such blood purification therapies may indeed have beneficial immunomodulatory effects. Accordingly, CRRT is now being considered as a potential adjuvant treatment of septic shock and has even moved into the operating room as a tool for antiinflammatory therapy and volume control. The intensivist-surgeon and the general surgeon need to be aware of and understand these developments in extracorporeal therapy if they wish to make the full armamentarium of modern treatment available to their sickest patients.

Blood Component Removal↗

PubMed2004

Dynamic surface tension measurements with submillisecond resolution using a capillary-jet instability technique.

An oscillating capillary jet method is implemented to measure surface tension of aqueous nonionic surfactant solutions as a function of surface age from the jet orifice. The experimental technique captures the evolution of jet swells and necks continuously along the jet propagation axis and is used in conjunction with an existing linear, axisymmetric, constant-property model to determine surface tension of liquids. The method is first validated using deionized water and isopropyl alcohol (constant surface tension test fluids) and a procedure is described to identify the optimum wavelength from the breakup point, which produces the smallest error in surface tension measurements. Dynamic surface tension data of concentrated aqueous Tergitol NP-8 surfactant solutions is then presented. The measurements are performed over a spatial length of approximately 1.5 wavelengths, a span corresponding to 0.6-4.2 ms time window from the jet orifice. Submillisecond surface age measurements are made possible by decreasing the jet diameter. Increased surfactant concentrations make the liquid jet more stable and allow measurements at higher surface ages. The correlation of Hua and Rosen fits well the dynamic surface tension data, which includes submillisecond surface ages. Finally, the time required for surface tension to reach equilibrium levels is estimated using a simple adsorption kinetics theory of surfactant molecules on the liquid/air interface.

Journal Article↗