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PubMedDate not supplied

[Systemic inflammatory response syndrome: new concepts].

Systemic inflammatory response syndrome is secondary to several insults whose purpose is to limit and reverse the injury. The outcome and intensity of the inflammatory response is determined by injury extension and balance between inflammatory and compensatory antiinflammatory responses. The interaction of the several soluble and cellular mediators of inflammatory and antiinflammatory responses determine the next evolutive phases: a) local inflammatory response; b) systemic inflammatory response; c) massive systemic inflammatory response; d) immunologic paralysis; and e) immune dissonance. If the last three phases do not control, cell damage can be amplified and thus perpetuating the infectious process and leading the patient to multiple organ dysfunction. Gamma interferon and steroids as modulators of the inflammatory response, in stages of paralysis and immune dissonance has been studied in clinical and experimental trials with promising results, but more studies to are needed validate their usefulness.

Humans↗
PubMed1997

Compensatory effects of glutamatergic inputs to the substantia nigra pars compacta in experimental parkinsonism.

The effect of transitory blockage of substantia nigra pars compacta glutamatergic inputs by intracranial injections of kynurenic acid were evaluated in two monkey treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The MPTP protocol was designed to mimic the gradual evolution of human Parkinson's disease. No effects were observed before MPTP treatment or in the first stage of treatment. Once clinical signs appeared, however, motor abnormalities were significantly aggravated by blockage of these inputs (P < 0.001). Conversely, after full Parkinsonism was established, blockage no longer had any behavioural effect. These results confirm the postulated compensatory role of the glutamatergic pathways feeding the substantia nigra pars compacta. This added insight into the physiopathology of the basal ganglia, when compared with previous data on the presymptomatic revelation of experimental Parkinsonism, should help elucidation of the time pattern of evolution of Parkinson's disease.

Animals↗
PubMed1977

Masticatory function and post-Pleistocene evolution in Nubia.

The present research focuses on craniofacial variation in Nubia over approximately 10,000 years. Samples were grouped according to their temporal location and subsistence pattern, and represent a transition from a hunting-gathering adaptation (Mesolithic) to a transitional hunting-gathering-agricultural adaptation (A-C Group) and finally to a fully agricultural adaptation (Meroitic/X-Group/Christian). The purposes were: (1) to compare the Mesolithic sample with the later Nubian populations; and (2) to evaluate further the hypothesis that change in Nubian craniofacial morphology was due to changing functional demands associated with the progressive change in subsistence adaptation and associated behavior. The results tend to support recent views that the Nubian Mesolithic population is probably ancestral to later Nubian groups, and that the masticatory-functional hypothesis can best account for craniofacial change among the Nubians since 12,000 B.P. According to this hypothesis systematic reduction in functional demand placed on the masticatory complex from the Mesolithic led, secondarily, to an alteration of the growth of the maxillomandibular complex such that the face became progressively less robust and more inferoposteriorly located relative to the cranial vault. Both the increase in the height of the vault relative to its length, producing a more "globular" appearance, and the reduction in dental size were tertiary, compensatory responses to altered facial size and position.

Biological Evolution↗
PubMed1999

Cross-modal reorganization of horizontal connectivity in auditory cortex without altering thalamocortical projections.

The development of the different, highly specialized regions of the mammalian cerebral cortex depends in part on neural activity, either intrinsic spontaneous activity or externally driven sensory activity. To determine whether patterned sensory activity instructs the development of intrinsic cortical circuitry, we have experimentally altered the modality of sensory inputs to cerebral cortex. Neonatal diversion of retinal axons to the auditory thalamus (cross-modal rewiring) results in a primary auditory cortex (AI) that resembles visual cortex in its response properties and topography (Roe et al., 1990, 1992). To test the hypothesis that the visual response properties are created by a visually driven reorganization of auditory cortical circuitry, we investigated the effect of early visual experience on the development of intrinsic, horizontal connections within AI. Horizontal connections are likely to play an important role in the construction of visual response properties in AI as they do in visual cortex. Here we show that early visual inputs to auditory thalamus can reorganize horizontal connections in AI, causing both an increase in their extent and a change in pattern, so that projections are not restricted to the isofrequency axis, but extend in a more isotropic pattern around the injection site. Thus, changing afferent modality, without altering the source of the thalamocortical axons, can profoundly alter cortical circuitry. Similar changes may underlie cortical compensatory processes in deaf or blind humans and may also have played a role in the parcellation of neocortex during mammalian evolution.

Afferent Pathways↗
PubMed1996

Modeling marrow damage from response data: evolution from radiation biology to benzene toxicity.

Consensus principles from radiation biology were used to describe a generic set of nonlinear, first-order differential equations for modeling toxicity-induced compensatory cell kinetics in terms of sublethal injury, repair, direct killing, killing of cells with unrepaired sublethal injury, and repopulation. This cellular model was linked to a probit model of hematopoietic mortality that describes death from infection and/or hemorrhage between 5 and 30 days. Mortality data from 27 experiments with 851 dose-response groups, in which doses were protracted by rate and/or fractionation, were used to simultaneously estimate all rate constants by maximum-likelihood methods. Data used represented 18,940 test animals: 12,827 mice, 2925 rats, 1676 sheep, 829 swine, 479 dogs, and 204 burros. Although a long-term, repopulating hematopoietic stem cell is ancestral to all lineages needed to restore normal homeostasis, the dose-response data from the protracted irradiations indicate clearly that the particular lineage that is critical to hematopoietic recovery does not resemble stemlike cells with regard to radiosensitivity and repopulation rates. Instead, the weakest link in the chain of hematopoiesis was found to have an intrinsic radioresistance equal to or greater than stromal cells and to repopulate at the same rates. Model validation has been achieved by predicting the LD50 and/or fractional group mortality in 38 protracted-dose experiments (rats and mice) that were not used in fitting of model coefficients.

Animals↗
PubMed2000

Phylogenetic evidence for excision of Stowaway miniature inverted-repeat transposable elements in triticeae (Poaceae).

The mode of transposition of miniature inverted-repeat transposable elements (MITEs) is unknown, but it has been suggested that they are duplicated rather than excised at transposition. However, the present investigation demonstrates that a particular family of MITEs, Stowaway:, is excised. Mapped onto a gene tree based on partial sequences of disrupted meiotic cDNA1 (DMC1) from 30 species of the Triticeae grasses, it is evident that at least two excisions have occurred, leaving short footprints. These footprints may subsequently be reduced in length or deleted. Excision of Stowaway: elements lends strong support to the suggestion that MITEs are DNA transposons and should be classified as class II elements. The evolution of Stowaway: elements can also be traced by scrutiny of the gene tree. It appears that base substitutions are as frequent in the conserved terminal inverted repeats (TIRs) as in the core of the element. Neither substitutions nor deletions lead to compensatory changes; hence, the highly stable secondary structure of the elements may gradually be reduced.

Base Sequence↗
PubMed2000

A population genetics model for multiple quantitative traits exhibiting pleiotropy and epistasis.

We study a population genetics model of an organism with a genome of L(tot)loci that determine the values of T quantitative traits. Each trait is controlled by a subset of L loci assigned randomly from the genome. There is an optimum value for each trait, and stabilizing selection acts on the phenotype as a whole to maintain actual trait values close to their optima. The model contains pleiotropic effects (loci can affect more than one trait) and epistasis in fitness. We use adaptive walk simulations to find high-fitness genotypes and to study the way these genotypes are distributed in sequence space. We then simulate the evolution of haploid and diploid populations on these fitness landscapes and show that the genotypes of populations are able to drift through sequence space despite stabilizing selection on the phenotype. We study the way the rate of drift and the extent of the accessible region of sequence space is affected by mutation rate, selection strength, population size, recombination rate, and the parameters L and T that control the landscape shape. There are three regimes of the model. If LT< >L(tot), there are many small peaks that can be spread over a wide region of sequence space. Compensatory neutral mutations are important in the population dynamics in this case.

Animals↗
PubMed1996

Evolution of hemopoietic ligands and their receptors. Influence of positive selection on correlated replacements throughout ligand and receptor proteins.

The rates of amino acid replacement in cytokines and their receptors are high and vary considerably. To determine whether this reflects the action of positive selection, rates of nonsynonymous DNA substitution were examined and found to exceed the synonymous substitution rate in certain exons of rodent IL-3, granulocyte-macrophage stimulating factor, and IL-4. To determine the extent to which positive selection could account for correlations between the amino acid replacement rates of hemopoietins and their receptors, rates were examined in various domains: the correlation with ligand rate was not confined to the ligand-binding domain of the receptor, but extended into the transmembrane and cytoplasmic domains and even to leader peptide domains of both ligand and receptor. As the majority of these replacements are unlikely to be strongly advantageous, different levels of both positive and purifying selection contribute to the extensive variation in hemopoietin/receptor evolutionary rates. Changes in a few residues critical for ligand-receptor interaction may be followed by changes of lesser selective importance in both molecules: replacements of growth hormone residues that form hydrogen or salt bridges with the receptor occur in lineages in which there are many concurrent replacements. A ligand/receptor rate correlation is not found between the seven-transmembrane receptors and their ligands, whose mature forms are often short and completely conserved. This study predicts that a minority of concurrent evolutionary changes in hemopoietins and their receptors reflect directly compensatory changes.

Amino Acids↗
PubMed1990

Pressor responsiveness to endothelin is not attenuated in gravid rats.

The aim of this study was to evaluate the effect of synthetic human/porcine endothelin (ET-1) on mean arterial blood pressure (MAP) in pregnant and non-pregnant rats and to compare this to the effects of two well characterized agonists, angiotensin II (AII), and vasopressin (VP). On day 14 of gestation (parturition day 22) polyethylene catheters were chronically implanted in the abdominal aorta for monitoring of MAP and in the vena cava for administration of drugs. Pressor responsiveness was measured in conscious freely moving animals on day 20 and again on the 7th day post-partum. All three agonists increased MAP in a dose related manner. However, whereas the sensitivity of pregnant rats (P) to AII and VP was significantly blunted compared to postpartal (PP) measurements, the MAP responses to ET-1 were the same in both groups. Moreover, the combined administration of ET-1 at a subpressor dose (0.05 pmol/100 g bw) and AII or VP at effective doses significantly potentiated (particularly in P) the pressor effects of AII and VP. These results demonstrate that ET-1 and possibly other vasoactive substances of endothelial origin, override the compensatory mechanism of normal pregnancy with respect to the blunted responsiveness to AII and VP. Such a mechanism may be of particular relevance in the evolution of pregnancy-induced hypertension.

Angiotensin II↗
PubMed1975

Alteration of hepatocytes by subcarcinogenic exposure to n-2-fluorenylacetamide.

These experiments examined the effects of a single, subcarcinogenic dose of dimethylnitrosamine or N-hydroxyfluorenylacetamide when administered after a subcarcinogenic dietary regimen of N-2-fluorenylacetamide. Control rats that received either carcinogen diet alone or a single dose of carcinogen demonstrated neither hepatic nodules nor hepatocellular carcinomas. Those animals that received dimethylnitrosamine subsequent to carcinogen diet demonstrated many persistent hepatic nodules and 100% hepato-cellular carcinomas. These data support the concept that the nodules produced by subcarcinogenic ingestion of N-2-fluorenylacetamide are not composed simply of normal hepatocytes undergoing compensatory regeneration but consist of cells that have been altered by the carcinogen. One manifestation of this alteration is an increased susceptibility to further carcinogenic evolution.

Animals↗
PubMed1996

[The patterns of the karyotypic evolution of cells in culture].

Numerous personal and literary data on the karyotypic variation of cell lines during their establishing and long-term culturing have been reviewed. A new notion about karyotypic evolutionary pathways of cells in culture is presented. A detailed original approach to cytogenetic study of permanent cell lines is given, which allows, via karyotype reconstruction, to obtain finally a new karyotypic characteristics-the generalized reconstructed karyotype (GRK). Application of the cytogenetic approach as a criterion for the control of authenticity, purity and stability of cell lines is discussed. The cell line analysis by means of GRK elicited that the cell line evolution in vitro passes through two stages: a stage of establishment, and a stage of stabilization, both differing in karyotypic variability of cell populations and clonal selection in culture. The data indicate that it is important in experiments to utilize cell lines being in the stage of stabilization and to characterize chromosomally the cell line at the same passage when it is used. Above all, a comparison of karyotypic variations of tumor and leukemic cells in vitro and in vivo has revealed their common karyotypic evolution regularities (a nonrandom character of numerical and structural chromosome changes and the loss of one of the sex chromosomes) and the karyotypic evolutionary regularities characteristic solely of cells in culture. The main of these being a balanced chromosome set in the cell population as a whole and obligatory retention of diploidy in all chromosomes of the normal set by the majority of human and animal cell lines. It has been revealed that no less than two homologs of each autosome are present in cells of at least 85% of examined lines. Other cell lines (at least 15%) of a generally neurogenic origin are shown to be notable by keeping partial or complete monosomies on autosomes throughout the long-term culturing. Peculiarities of the karyotypic evolution of the latter are regarded in detail in addition to the data on the expression of oncogenes and other growth-associated genes in their cells. It is suggested that there are three main compensatory mechanisms through which cell lines with autosomal monosomies may maintain the vitality in culture: polyploidization of initial cell clones, oncogene amplification, mainly of the myc-family oncogenes, and fragmentary or complete extracopying of several autosomes. In summary, perspective of cell line cytogenetics as a field of biology of the cell in culture is discussed.

Animals↗
PubMed2001

Evolution of AZT resistance in HIV-1: the 41-70 intermediate that is not observed in vivo has a replication defect.

The human immunodeficiency virus type 1 (HIV-1) is notorious for its ability to evolve drug-resistance in patients treated with potent antivirals. Resistance to inhibitors of the viral reverse transcriptase (RT) enzyme is frequently mediated by a single amino acid substitution within RT. Resistance against the nucleoside analogue AZT is remarkable in that multiple amino acid changes accumulate over time to yield virus variants with high-level drug resistance. We now report that in addition to drug-resistance properties, the relative replication capacity of the virus variants affects the evolution of AZT resistance. Some of the typical AZT-resistance mutations have a negative impact on virus replication, and the 41-70 double mutant was found to represent a particularly poor virus. Furthermore, introduction of additional AZT-resistance mutations (41-70-215) leads to nearly complete restoration of virus replication. These results may explain the absence of the 41-70 double mutant in clinical samples and indicate that the evolution of AZT resistance is also influenced by virus replication parameters. Prolonged passage of the replication-impaired 41-70 virus in the absence of AZT yielded several fast-replicating variants. These revertants have compensatory changes in the RT polymerase, some of which have been observed previously in AZT-treated patients. Because we could select for these changes without drug pressure, these changes are likely to improve the RT enzyme function and the HIV-1 replication capacity.

Anti-HIV Agents↗
PubMed1991

Secondary structure as a constraint on the evolution of a plant viral satellite RNA.

The genetic variability and evolution of the satellite RNA (satRNA) of cucumber mosaic virus (CMV) was analyzed. Twenty-five CMV-satRNAs compared clustered into three main groups, and no correlation was found between genetic proximity and other characteristics (pathogenicity, geographical origin) of the satRNAs. Values for the number of nucleotide substitutions per site between any two satRNAs suggest that divergence is checked by functional constraints. The analysis of mutations relative to an ancestral sequence, and the number of substitutions per site at first, second and third positions of codons in putative open reading frames, show that the variation of CMV-satRNAs does not follow a pattern typical of coding sequences, and indicates that preservation of the sequence of encoded products is not a constraint to evolution. On the other hand, when the observed variation was analyzed relative to a secondary structure model proposed for CMV-satRNAs, several lines of evidence indicated that the maintenance of the secondary structure is a constraint to evolution: the number of substitutions per site, the number of point insertions and deletions and the number of base substitutions that would disrupt base-pairing were significantly higher for unpaired than for base-paired positions. Also, compensatory mutations at base-paired positions occurred more frequently than expected from random. The results suggest that CMV-satRNAs are non-coding, functional RNAs whose biology would be determined by their direct interaction with components of the host and/or the helper virus.

Base Composition↗
PubMed2000

Effects of environment on compensatory mutations to ameliorate costs of antibiotic resistance.

Most types of antibiotic resistance impose a biological cost on bacterial fitness. These costs can be compensated, usually without loss of resistance, by second-site mutations during the evolution of the resistant bacteria in an experimental host or in a laboratory medium. Different fitness-compensating mutations were selected depending on whether the bacteria evolved through serial passage in mice or in a laboratory medium. This difference in mutation spectra was caused by either a growth condition-specific formation or selection of the compensated mutants. These results suggest that bacterial evolution to reduce the costs of antibiotic resistance can take different trajectories within and outside a host.

Adaptation, Physiological↗
PubMed1996

A simplified T2-T3 thoracoscopic sympathicolysis technique for the treatment of essential hyperhidrosis: short-term results in 100 patients.

A simplified one-time bilateral thoracoscopic T2-T3 sympathicolysis technique using single-lumen endotracheal intubation with high frequency jet ventilation and electrocautery destruction ("sympathicolysis") of the sympathetic ganglia was applied in 100 consecutive patients with severe essential hyperhidrosis (EH). Providing a pleural space can be created, this technique was proven simple and safe, and short-term clinical results were excellent: palmar hyperhidrosis was cured in 98% of patients, and axillar and plantar improvement was achieved in 62 and 65% of patients, respectively. Side-effects and complications were minor (compensatory hyperhidrosis) or self-limiting (pain). These data confirm the safety and efficacy of thoracoscopic sympathetic interventions for the treatment of EH, and support the evolution toward simplified methodologies.

Adolescent↗
PubMed1996

Radiological parameters associated with the evolution of degenerative scoliosis.

The risk factors related to the evolution of the degenerative adult scoliosis are investigated. A review was conducted of the the radiographs of 162 women (mean age 65 years) with degenerative scoliosis who were examined at the Research Center for Diseases of the Musculoskeletal System "Th. Garofalidis" Orthopaedic Department, at the Medical School of Athens University, during the period of 1985 through 1994. Only patients with degenerative lumbar curves greater than 10 degrees and only patients with no previous history of scoliosis were included in the study. The mean follow-up was 8 years (range 5-30 years) and for 30 patients the follow-up period was more than 10 years. The research demonstrated that the degenerative changes of the spine may relate to appearance and evolution of scoliotic curves in adults. Additionally, it was found that the risk factors that are associated with the evolution of the degenerative adult scoliosis are: curves over 30 degrees; curves having Grade II and III rotation; curves that are imbalanced and have a secondary compensatory curve that is sharp and angular at the L4-S1 level; curves in which the apex is at the L2-L3 and L3-L4 area; an intercrest line through the L5 vertebra; and vertebral translation equivalent to or more than 6 mm.

Aged↗
PubMed1999

A molecular description of the evolution of resistance.

BACKGROUND: In vitro evolution has been used to obtain nucleic acid molecules with interesting functional properties. The evolution process usually is carried out in a stepwise manner, involving successive rounds of selection, amplification and mutation. Recently, a continuous in vitro evolution system was devised for RNAs that catalyze the ligation of oligonucleotide substrates, allowing the evolution of catalytic function to be studied in real time. RESULTS: Continuous in vitro evolution of an RNA ligase ribozyme was carried out in the presence of a DNA enzyme that was capable of cleaving, and thereby inactivating, the ribozyme. The DNA concentration was increased steadily over 33.5 hours of evolution, reaching a final concentration that would have been sufficient to inactivate the starting population in one second. The evolved population of ribozymes developed resistance to the DNA enzyme, reducing their vulnerability to cleavage by 2000-fold but retaining their own catalytic function. Based on sequencing and kinetic analysis of the ribozymes, two mechanisms are proposed for this resistance. One involves three nucleotide substitutions, together with two compensatory mutations, that alter the site at which the DNA enzyme binds the ribozyme. The other involves enhancement of the ribozyme's ability to bind its own substrate in a way that protects it from cleavage by the DNA enzyme. CONCLUSIONS: The ability to direct the evolution of an enzyme's biochemical properties in response to the behavior of another macromolecule provides insight into the evolution of resistance and may be useful in developing enzymes with novel or enhanced function.

Base Sequence↗
PubMed1997

Site-directed mutations reveal long-range compensatory interactions in the Adh gene of Drosophila melanogaster.

Long-range interactions between the 5' and 3' ends of mRNA molecules have been suggested to play a role in the initiation of translation and the regulation of gene expression. To identify such interactions and to study their molecular evolution, we used phylogenetic analysis to generate a model of mRNA higher-order structure in the Adh transcript of Drosophila melanogaster. This model predicts long-range, tertiary contacts between a region of the protein-encoding sequence just downstream of the start codon and a conserved sequence in the 3' untranslated region (UTR). To further examine the proposed structure, site-directed mutations were generated in vitro in a cloned D. melanogaster Adh gene, and the mutant constructs were introduced into the Drosophila germ line through P-element mediated transformation. Transformants were spectrophotometrically assayed for alcohol dehydrogenase activity. Our results indicate that transformants containing a silent mutation near the start of the protein-encoding sequence show an approximately 15% reduction in alcohol dehydrogenase activity relative to wild-type transformants. This activity can be restored to wild-type levels by a second, compensatory mutation in the 3' UTR. These observations are consistent with a higher-order structure model that includes long-range interactions between the 5' and 3' ends of the Adh mRNA. However, our results do not fit the classical compensatory substitution model because the second mutation by itself (in the 3' UTR) did not show a measurable reduction in gene expression.

Alcohol Dehydrogenase↗