Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “evolvability”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,081 records · Page 60Linked to original sources

Emergency coronary artery bypass surgery after intracoronary thrombolysis for evolving myocardial infarction.

Sixteen patients underwent emergency coronary artery bypass surgery immediately after intracoronary streptokinase infusion for acute evolving myocardial infarction. Of these, 11 patients had 70% residual stenosis in the recanalised vessel, and in five thrombolysis was unsuccessful. There were no hospital deaths. All the patients sustained myocardial necrosis, the peak activity of creatine phosphokinase correlating with the time to reperfusion. Chest tube drainage (mean 960 ml) was significantly higher than for control patients but did not correlate with the total dosage of streptokinase. No patients had further myocardial infarction or developed recurrent angina. Selected patients may benefit from coronary bypass surgery after intracoronary streptokinase infusion. If necessary this may be performed immediately with low mortality and morbidity.

Adult↗

Outpatient clinics for adults with congenital heart disease: increasing workload and evolving patterns of referral.

OBJECTIVE: To examine the evolving role of specialised outpatient services for adult patients with congenital heart disease. DESIGN: A retrospective analysis of all patients attending the Toronto Congenital Cardiac Centre for Adults over three corresponding three month periods in 1987, 1992, and 1997. SETTING: A tertiary referral centre. MAIN OUTCOME MEASURES: Patient demographics, residence, medical and surgical history, type and source of referral, and investigations performed. RESULTS: In all, 570 patients were seen at the clinic during these three periods. There was a 44% and a 269% increase in workload between 1987 to 1992 and 1992 to 1997, respectively. There was a steady fall in mean age of patients seen at the clinic with time (38.5, 33.6, and 31.7 years in 1987, 1992, and 1997, respectively, p < 0.001). New referrals from community cardiologists and family physicians increased more in relative terms than did referrals from the Hospital for Sick Children, Toronto (6.7%, 15%, and 37.5%, p = 0.02). There was a steady increase in patients with previous reparative surgery (48.9%, 59.2%, and 69.2%, p < 0.002). The proportion of patients with previous reoperations also increased (2.3%, 10%, and 9.2%, p < 0.01). Echocardiography remained the predominant method of diagnosis. The diagnostic mix did not change with time. CONCLUSIONS: Over the past 10 years there has been a large increase in adults with congenital heart disease requiring and seeking specialised care in a tertiary health centre, with a concomitant evolution of referral patterns. These data may be helpful in planning of similar paediatric and adult cardiac services for this expanding population.

Adult↗

Do Toxoplasma gondii RH strain tachyzoites evolve during continuous passage?

AIM: To examine three lineages of Toxoplasma gondii RH strain in terms of performance in the dye test, culture, and gene expression. METHODS: Historical data (culture growth and performance in the dye test) from three lineages of RH strain tachyzoites (B, J, and Q) that had been continuously cultured in HeLa cells was assessed. Tachyzoite harvests obtained during continuous cell culture were retrieved from liquid nitrogen and cultured in HeLa cells, providing mRNA that was extracted and used to study gene expression using random amplified polymorphic DNA analysis at different stages of lineage adaptation to continuous culture. RESULTS: The B and Q lineages consistently produced tachyzoites that were successfully used in the dye test and their gene expression was stable after multiple passages. The J lineage had unpredictable growth, tachyzoites unsuitable for use in the dye test, and changing gene expression with multiple passage. CONCLUSION: This study has explained some anomalies in the performance of different stocks of T gondii, and suggests that lineages that are still evolving in cell culture should be avoided.

Animals↗

Primary choriocarcinoma of the bladder evolving from a transitional cell carcinoma.

A 67 year old man presented with haematuria, which on investigation was shown to be derived from a bladder tumour. The tumour initially was a typical transitional cell carcinoma except for rare trophoblastic cells. Over the next year and a half it gradually evolved into a choriocarcinoma. Postmortem examination confirmed that this was a primary choriocarcinoma of the bladder with no other sites of derivation shown.

Aged↗

The need for risk management to evolve to assure a culture of safety.

There is a need for the traditional risk management model, which focuses on department based risk assessment, loss management and risk financing, to evolve to enable it to become more responsive to the increasing demands for safety and accountability imposed on the current US healthcare system. The risk management focus must become more strategic and systems based, and less crisis orientated and individual provider based, in order to provide its greatest value to the organization and the patients those organizations serve.

Efficiency, Organizational↗

Continuous non-invasive monitoring of evolving acute severe asthma during sleep.

A spontaneous acute severe asthmatic attack was monitored non-invasively in a 27 year old sleeping female asthmatic subject. As the attack evolved there was a switch from predominant abdominal breathing (associated with inspiratory indrawing of the rib cage) to gradually increasing rib cage excursion (associated with inspiratory paradox of the abdominal wall with respect to the rib cage). Abdominal paradox increased progressively until it appeared to fill the whole of the inspiratory period of the rib cage, at which point rapid oxygen desaturation developed.

Acute Disease↗

Fructosyltransferase and invertase genes evolved by gene duplication and rearrangements: rice, perennial ryegrass, and wheat gene families.

The invertase enzyme family is responsible for carbohydrate metabolism in rice, perennial ryegrass, and wheat. Fructan molecules accumulate in cell vacuoles of perennial ryegrass and wheat and are associated with abiotic stress tolerance. High levels of amino acid similarity between the fructosyltransferases responsible for fructan accumulation indicates that they may have evolved from invertase-like ancestral genes. In this study, we have applied comparative genomics to determine the mechanisms that lead to the evolution of fructosytransferase and invertase genes in rice, perennial ryegrass, and wheat. Duplications and rearrangements have been inferred to generate variant forms of the rice invertases since divergence from a common grass progenitor. The occurrence of multiple copies of fructosyltransferase genes indicated that duplication events continued during evolution of the wheat and perennial ryegrass lineages. Further gene rearrangements were evident in perennial ryegrass genes, albeit at a reduced level compared with the rice invertases. Gene orthologs were largely static after duplication during evolution of the wheat lineage. This study details evolutionary events that contribute to fructosyltransferase and invertase gene variation in grasses.

Amino Acid Sequence↗

A rapid radiometric technique used to trap and quantitate 14CO2 evolved by slow-growing microorganisms.

An apparatus to trap and quantitate 14CO2 is described. When used to measure antibiotic effects on Histoplasma capsulatum and Mycobacterium bovis (BCG), there was an inverse quantitative relationship between 14CO2 evolved and antibiotic concentration. The technique should prove useful for analyses that require trapping and quantitation of 14CO2, including antimicrobial sensitivities of slow-growing organisms.

Amphotericin B↗

KIR: diverse, rapidly evolving receptors of innate and adaptive immunity.

KIR genes have evolved in primates to generate a diverse family of receptors with unique structures that enable them to recognize MHC-class I molecules with locus and allele-specificity. Their combinatorial expression creates a repertoire of NK cells that surveys the expression of almost every MHC molecule independently, thus antagonizing the spread of pathogens and tumors that subvert innate and adaptive defense by selectively downregulating certain MHC class I molecules. The genes encoding KIR that recognize classical MHC molecules have diversified rapidly in human and primates; this contrasts with conservation of immunoglobulin- and lectin-like receptors for nonclassical MHC molecules. As a result of the variable KIR-gene content in the genome and the polymorphism of the HLA system, dissimilar numbers and qualities of KIR:HLA pairs function in different humans. This diversity likely contributes variability to the function of NK cells and T-lymphocytes by modulating innate and adaptive immune responses to specific challenges.

Alleles↗

The importance of strategy for the evolving field of radiology.

During the 20th century, the field of radiology experienced extraordinary growth and became an essential component of the practice of clinical medicine. In the 21st century, it is likely that radiology will continue to grow by interfacing with new and important domains such as information technology and molecular biology and by playing a more central role in general medical education, biomedical research, and noninvasive therapeutic interventions. To sustain such wide-ranging growth and yet remain intact as a medical specialty, the profession will require many radiologists who can provide leadership to bridge the many gaps between the various frontiers and the traditional core of radiology. These radiologists will need skills and background in two critical management areas: leadership and strategy. This article approaches the broad topic of strategy in several ways. First, it provides the radiologist with a basic framework for strategy development. Second, it summarizes central ideas from the evolving field of strategic thinking. Finally, it outlines a strategy-based method for dealing with uncertainty about the future and identifies situations where specific strategic tools and techniques are likely to be helpful.

Forecasting↗

Left ventricular shape changes during the course of evolving heart failure.

The temporal relationship between left ventricular (LV) shape changes and the development of LV dysfunction, dilation, and sympathoadrenergic hyperactivity was examined in 10 dogs with chronic heart failure produced by multiple sequential intracoronary microembolizations. LV shape was quantitated from serial ventriculograms based on the ratio of the major to minor axis at end systole and end diastole. Measurements were made at baseline (before embolizations) and were repeated at 2, 8, and 16 wk after the last embolization. A significant increase of LV sphericity was present at 2 wk, with only minimal changes occurring thereafter. Despite the tendency for LV shape changes to plateau between 2 and 16 wk, LV ejection fraction continued to decline (31 +/- 1 vs. 20 +/- 2%; P less than 0.001), and LV end-diastolic volume continued to increase (86 +/- 6 vs. 103 +/- 9 ml; P less than 0.01) as did plasma norepinephrine concentration (456 +/- 30 vs. 868 +/- 172 pg/ml; P less than 0.02). These data indicate that in the course of evolving heart failure, LV shape abnormalities precede the development of profound LV dysfunction, dilation, and overt activation of the sympathetic nervous system.

Adrenal Glands↗

Dynamics of interstitial and intracellular pH in evolving brain infarct.

We examined the relationships between intracellular pH (pHi) and interstitial pH (pHe) in a rat model of focal ischemia. Interstitial pH was measured with pH-sensitive microelectrodes, and the average tissue pH was measured with the [14C]dimethadione method in rats subjected to occlusion of the right middle cerebral and common carotid arteries (MCA-CCAO). In normal cortex, pHe and pHi were 7.24 +/- 0.97 and 7.01 +/- 0.13 (means +/- SD, n = 6), respectively. In the ischemic cortex, pHe fell to 6.43 +/- 0.13, whereas pHi decreased only to 6.86 +/- 0.11 (n = 5) 1 h after MCA-CCAO. After 4 h of ischemia, the pHe was 6.61 +/- 0.09 and pHi was 6.62 +/- 0.20 (n = 4). Treatment with glucose before ischemia markedly lowered the pHe (5.88 +/- 0.17) but not pHi (6.83 +/- 0.03, n = 4) measured 1 h after ischemia. In the ischemic cortex of animals made hypoglycemic by pretreatment with insulin, neither pHe (7.25 +/- 0.06) nor pHi (6.99 +/- 0.13, n = 4) decreased. The demonstrated difference in pHi and pHe indicates that some cells remained sufficiently functional to maintain a plasma membrane gradient of protons within the evolving infarct. If the calculated pHi values accurately reflect the true pHi of cells within zones of severe focal ischemia, then cerebral infarction can proceed at pHi levels not greatly altered from normal.

Animals↗

Transthyretin gene expression in choroid plexus first evolved in reptiles.

The presence of transthyretin in mammals and birds, but not amphibia, suggested that transthyretin expression first appeared in stem reptiles. Therefore, transthyretin synthesis was studied in a lizard. Transthyretin synthesis in choroid plexus pieces from Tiliqua rugosa was demonstrated by incorporation of radiactive amino acids. Oligonucleotides corresponding to conserved regions of transthyretin were used as primers in polymerase chain reaction with lizard choroid plexus cDNA. Amplified DNA was used to screen a lizard choroid plexus cDNA library. A full-length transthyretin cDNA clone was isolated and sequenced. A three-dimensional model of lizard transthyretin was obtained by homology modeling. The central channel of transthyretin, containing the thyroxine-binding site, was found to be completely conserved between reptiles and mammals. Transthyretin expression was not detected in lizard liver. These data suggest that transthyretin first evolved in the choroid plexus of the brain. Due to a change in tissue distribution of gene expression, occurring much later during evolution, transthyretin also became a plasma protein, synthesized in the liver.

Amino Acid Sequence↗

Pulmonary compliance: early assessment of evolving lung injury after onset of sepsis.

We compared the sensitivity of dynamic (Cdyn) and static lung compliance (CL) with indicators of permeability injury in a model of septic porcine adult respiratory distress syndrome. Two groups of anesthetized ventilated swine (15-25 kg) were studied. Septic animals (Ps, n = 13) received Pseudomonas aeruginosa intravenously for 1 h, which resulted in severe adult respiratory distress syndrome. Controls (C, n = 13) received 0.9% NaCl. Cdyn, CL, bronchoalveolar lavage for protein estimation, and thermal cardiogreen extravascular lung water (EVLW) measurements were performed in seven C and eight Ps animals. Six C and five Ps animals underwent gamma camera measurement of lung-to-heart ratio (slope index) of 99Tc-labeled human serum albumin. Both Cdyn and CL decreased significantly (P less than 0.01) at 30 min and thereafter in Ps vs. C. EVLW, slope index, and bronchoalveolar protein content increased significantly (P less than 0.05) in Ps vs. C at 120, 150, and 300 min, respectively. Cdyn and CL decreased well before onset of permeability injury. These early changes may be due to release of vasoactive mediators and sequestration of neutrophils in the pulmonary capillaries and later to increases in EVLW. Measurement of Cdyn and CL represents an early means of assessing evolving lung injury in this acute septic porcine model.

Animals↗

Simultaneous reorganization in thalamocortical ensembles evolves over several hours after perioral capsaicin injections.

Reorganization of the somatosensory system was quantified by simultaneously recording from single-unit neural ensembles in the whisker regions of the ventral posterior medial (VPM) nucleus of the thalamus and the primary somatosensory (SI) cortex in anesthetized rats before, during, and after injecting capsaicin under the skin of the lip. Capsaicin, a compound that excites and then inactivates a subset of peripheral C and Adelta fibers, triggered increases in spontaneous firing of thalamocortical neurons (10-15 min after injection), as well as rapid reorganization of the whisker representations in both the VPM and SI. During the first hour after capsaicin injection, 57% of the 139 recorded neurons either gained or lost at least one whisker response in their receptive fields (RFs). Capsaicin-related changes continued to emerge for >/=6 h after the injection: Fifty percent of the single-neuron RFs changed between 1-2 and 5-6 h after capsaicin injection. Most (79%) of these late changes represented neural responses that had remained unchanged in the first postcapsaicin mapping; just under 20% of these late changes appeared in neurons that had previously shown no plasticity of response. The majority of the changes (55% immediately after injection, 66% 6 h later) involved "unmasking" of new tactile responses. RF change rates were comparable in SI and VPM (57-49%). Population analysis indicated that the reorganization was associated with a lessening of the "spatial coupling" between cortical neurons-a significant reduction in firing covariance that could be related to distances between neurons. This general loss of spatial coupling, in conjunction with increases in spontaneous firing, may create a situation that is favorable for the induction of synaptic plasticity. Our results indicate that the selective inactivation of a peripheral nociceptor subpopulation can induce rapid and long-evolving (>/=6 h) shifts in the balance of inhibition and excitation in the somatosensory system. The time course of these processes suggest that thalamic and cortical plasticity is not a linear reflection of spinal and brainstem changes that occur following the application of capsaicin.

Analysis of Variance↗

The evolving role of endoscopic retrograde cholangiography before and after cholecystectomy.

Laparoscopy is the preferred approach for cholecystectomy; however the indications for pre- versus postoperative endoscopic retrograde cholangiography (ERC) are still evolving. The records of patients who had ERC performed one month before (n = 119) or after (n = 35) laparoscopic or open cholecystectomy from January 1990 to August 1992 (period 1), and 66 patients who had preoperative ERC from November 1995 to October 1996 (period 2) are reviewed, ERC indications, findings and outcomes were reviewed, and trends in the use of preoperative ERC from 1990 to 1996 were sought. Between periods 1 and 2 the yield of preoperative ERC increased from 36% to 58% (P < 0.01). The use of preoperative ERC for the indication of abnormal liver enzymes declined (P < 0.05), while the yield increased (25% versus 61%, P < 0.01). Both the use of ERC and the yield remained stable for other indications. ERC was felt to have changed the surgical approach in 5% of patients. Primary indications for postoperative ERC (n = 35) included abnormal intraoperative cholangiography (43%), liver function test abnormalities (23%) and recurrence of preoperative symptoms (14%); stones were found in 60%, 50% and 20% of patients with these indications, respectively. Overall, 46% of postoperative studies revealed duct stones. The roles for pre- and postoperative ERC are changing and depend greatly on the relative laparoscopic and endoscopic expertise at a given institution.

Adolescent↗

Tumorigenic heterogeneity in cancer stem cells evolved from long-term cultures of telomerase-immortalized human mesenchymal stem cells.

Long-term cultures of telomerase-transduced adult human mesenchymal stem cells (hMSC) may evolve spontaneous genetic changes leading to tumorigenicity in immunodeficient mice (e.g., hMSC-TERT20). We wished to clarify whether this unusual phenotype reflected a rare but dominant subpopulation or if the stem cell origin allowed most cells to behave as cancer stem cells. Cultures of the hMSC-TERT20 strain at population doubling 440 were highly clonogenic (94%). From 110 single-cell clones expanded by 20 population doublings, 6 underwent detailed comparison. Like the parental population, each clone had approximately 1.2 days doubling time with loss of contact inhibition. All retained 1,25-(OH)(2) vitamin D(3)-induced expression of osteoblastic markers: collagen type I, alkaline phosphatase, and osteocalcin. All shared INK4a/ARF gene locus deletion and epigenetic silencing of the DBCCR1 tumor suppressor gene. Despite in vitro commonality, only four of six clones shared the growth kinetics and 100% tumorigenicity of the parental population. In contrast, one clone consistently formed latent tumors and the other established tumors with only 30% penetrance. Changing the in vitro microenvironment to mimic in vivo growth aspects revealed concordant clonal heterogeneity. Latent tumor growth correlated with extracellular matrix entrapment of multicellular spheroids and high procollagen type III expression. Poor tumorigenicity correlated with in vitro serum dependence and high p27(Kip1) expression. Aggressive tumorigenicity correlated with good viability plus capillary morphogenesis on serum starvation and high cyclin D1 expression. Thus, hMSC-TERT20 clones represent cancer stem cells with hierarchical tumorigenicity, providing new models to explore the stem cell hypothesis for cancer.

Adult↗

Did auditory sensitivity and vocalization evolve independently in otophysan fishes?

Otophysine fishes have a series of bones, the Weberian ossicles, which acoustically couple the swimbladder to the inner ear. These fishes have evolved a diversity of sound-generating organs and acoustic signals, although some species, such as the goldfish, are not known to be vocal. Utilizing a recently developed auditory brainstem response (ABR)-recording technique, the auditory sensitivities of representatives of seven families from all four otophysine orders were investigated and compared to the spectral content of their vocalizations. All species examined detect tone bursts from 100 Hz to 5 kHz, but ABR-audiograms revealed major differences in auditory sensitivities, especially at higher frequencies (>1 kHz) where thresholds differed by up to 50 dB. These differences showed no apparent correspondence to the ability to produce sounds (vocal versus non-vocal species) or to the spectral content of species-specific sounds. All fishes have maximum sensitivity between 400 Hz and 1,500 Hz, whereas the major portion of the energy of acoustic signals was in the frequency range of 100-400 Hz (swimbladder drumming sounds) and of 1-3 kHz (stridulatory sounds). Species producing stridulatory sounds exhibited better high-frequency hearing sensitivity (pimelodids, doradids), except for callichthyids, which had poorest hearing ability in this range. Furthermore, fishes emitting both low- and high-frequency sounds, such as pimelodid and doradid catfishes, did not possess two corresponding auditory sensitivity maxima. Based on these results it is concluded that selective pressures involved in the evolution of the Weberian apparatus and the design of vocal signals in otophysines were others (primarily predator or prey detection in quiet freshwater habitats) than those serving to optimize acoustical communication.

Animals↗