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PubMed1996

Pathophysiological analysis of serum troponin T release kinetics in evolving ischemic myocardial injury.

The present study measured cardiac troponin T(TnT) for the pathophysiological analysis of evolving ischemic myocardial injury in 35 patients with unstable angina (3: Class IB, 32: Class IIIB) and in 40 patients undergoing coronary reperfusion therapy for acute myocardial infarction. Serum TnT, creatine kinase (CK), CKMB, myoglobin (Mb), and myosin light chain 1 (MLC1) were measured every 2-24 h for 10 days after admission to the CCU. In patients with unstable angina, positive test results were detected in 65.7% for TnT, 20% for CK, 37.1% for CKMB, 60.9% for Mb, and 26% for MLC1. Of the 23 patients with positive TnT, 12 (52.2%) had cardiac events. Of the 12 patients with negative TnT, 11 (91.6%) were event-free. All of the patients who developed cardiac events showed a persistent (n = 10) or delayed elevation (n = 2) pattern 28-120 h beforehand. The sensitivity for predicting cardiac events was 92.3% for TnT, 80% for Mb, 53.8% for CKMB, and 50% for MLC1. In patients with acute myocardial infarction, TnT release kinetics showed 2 peaks after coronary reperfusion therapy. TnT values at the 1st peak significantly correlated with maximum CKMB (r = 0.70, p < 0.05) and early-stage left ventricular wall motion score (r = 0.60, p < 0.05), while 2nd-peak TnT values significantly correlated with maximum MLC1 (r = 0.59, p < 0.05), the T1-SPECT score (r = 0.78, p < 0.05) and left ventricular ejection fraction (r = -0.74, p < 0.05) in the convalescent stage. The 2nd/1st-peak TnT ratio significantly correlated with the nQ/nST elevation index (ratio of the number of leads developing abnormal Q-wave 1 week after the onset to the number of leads showing ST elevation of more than 1 mm at admission) (r = 0.63, p < 0.05) in patients with anterior myocardial infarction. These data indicate that persistent release of TnT reflects progressive irreversible myocardial damage in unstable angina and indicates a risk of future cardiac events. In acute myocardial infarction, the 2nd/1st-peak TnT ratio in patients undergoing coronary reperfusion therapy may be useful for the quantitative evaluation of myocardial salvage.

Acute Disease↗
PubMed2003

The Cresta Run: a uniquely evolving tradition.

The Cresta Run is a unique toboggan run and exists in only one place in the world, namely, St. Moritz, Switzerland. The height of the resort is over 6,000 feet (1828 metres). Therefore there is a diminution of oxygen content in the air. Normally it takes from three to seven days for a person from lower habitat altitudes, visiting the resort, to become fully acclimatized if they are to be involved in energetic competitive sport. The age and fitness of the toboggan rider is a factor. The Cresta Run takes place each year and has, since its inception under the auspices of the St Moritz Tobogganing Club, been built from virgin snow to a formula determined by a brilliant 22-year-old Swiss geometrician, Peter Bonorand, who devised the first Run in 1884. Using his exceptional mathematical knowledge to determine a course from St. Moritz to Celerina, he drew up plans and drawings for the first Cresta Run. The Run therefore is constructed to a known formula and it is significant that in over 115 years the times on the Run have only improved on average by a few tenths of a second progressively each year despite improvements to riding equipment. Since the Run's inception in 1885 there has always been an element of danger, but accidents have invariably occurred on the section of the Run that comprises the competition course between the start line and the finish line. During the past few seasons, an increasing number of accidents have taken place after the finish line. The problem is short-term blackout while riding (Reader, 1978). There is now a need to investigate what changes have been made or have evolved to cause this. However, certain immutable facts have remained constant and these must be identified and then considered in the context of recent changes as a result of improvements in equipment. Considerable improvements have been made over the past 25 years to safety helmets. These are the result of different materials, their suitability and ease of manufacture, particularly with regard to the full-face type helmet. The full-face helmet could be a significant contributing factor to the problem of accidents, particularly after the finish line, on the Cresta Run.

Accident Prevention↗
PubMed2006

Nucleotide sequences and organization of the genes for carotovoricin (Ctv) from Erwinia carotovora indicate that Ctv evolved from the same ancestor as Salmonella typhi prophage.

Carotovoricin Er (CtvEr), which is produced by a plant soft rot disease causative agent, Erwinia carotovora subsp. carotovora Er, is a high-molecular-weight bacteriocin showing Myoviridae phage-tail-like morphology with contractile sheath and plural tail fibers. We determined the complete nucleotide sequences of CtvEr genes on the E. carotovora Er chromosome and report that CtvEr genes consist of lysis cassette, major and minor structural protein gene clusters. Four promoters were identified. The lysis gene cassette, which is composed of the genes for lysis enzyme and holin, was also identified and characterized. The nucleotide sequences and organization of the genes for CtvCGE, which is produced by E. carotovora strain CGE234-M403 with the morphology similar to CtvEr, were also determined and compared to that of CtvEr, and it was found that CtvCGE is almost identical to CtvEr except for tail fibers which are involved in the killing spectra of both bacteriocins. We also explain that the gene organization and the deduced amino acid sequences of both carotovoricins are very close to those of prophage, which is lysogenized in the chromosome on Salmonella enterica serovar Typhi CT18. These findings strongly suggest that Ctv evolved as a phage tail-like bacteriocin from a common ancestor with Salmonella typhi prophage.

Amino Acid Sequence↗
PubMed2002

Genetic evidence that two types of retroelements evolved through different pathways in ectomycorrhizal homobasidiomycetes Tricholoma spp.

We designed a polymerase chain reaction that allows us to clone two types of putative reverse transcriptase genes from 11 species of ectomycorrhizal basidiomycetes that belong to the genus Tricholoma. One corresponds to the putative gene of marY1, a long terminal repeat (LTR) retroelement from Tricholoma matsutake, and the other, marY2N, a LINE-like non-LTR (L1-like) retroelement from this fungus. Putative protein products predicted from nucleotide sequencing of cloned fragments were phylogenetically analyzed. marY1-like elements had a parallel phylogenetic relationship with no apparent correlation to a current taxonomic profile, while marY2N-like elements showed a vertical one in relation to host-plant species. Data suggest that marY1-like elements and marY2N-like elements have evolved independently, and the evolution of marY1-like elements could have occurred later than the evolution of marY2N-like elements in the species of Tricholoma.

Amino Acid Sequence↗
PubMed2000

A living framework: Evolving from traditional care to individual mastery.

Caught up in the drop-dead pace of change in the world around us, it often appears that everything in life is uncertain; yet perhaps, in healthcare, nothing is actually changing. Nonetheless, the potential role of home care, which offers the flexibility for us to do different things and respond more effectively to emerging needs of individuals and families, has always been exciting and offers such tremendous promise. There is something quite magical about the relationship with clients in their own homes. Healthcare is all about relationships, and with today s technologies and other enablers that offer incredible opportunity to foster deeper, more meaningful relationships, the potential for home care in this new, evolving world is particularly exhilarating.

Canada↗
PubMedDate not supplied

The evolving role of the clinical nurse specialist.

There is still a great deal of confusion surrounding the role of specialist nurses. These individuals are often the most confused as to the contribution they can make to nursing as a continually evolving profession of the 1990s. By clarifying the relationship between research, theory and education, their role identity is enhanced.

Humans↗
PubMed2006

Chronic myelomonocytic leukemia evolving from preexisting myelodysplasia shares many features with de novo disease.

The majority of chronic myelomonocytic leukemia (CMML) cases arise de novo; cases evolving from preexisting myelodysplasia (MDS) or myeloproliferative diseases have not been well-studied. We conducted the present study to determine the clinicopathologic features and to study possible underlying molecular and cytogenetic mechanisms involved in this evolution. Between April 1995 and November 2005, we identified 120 CMML cases, of which 20 (16.7%) had a previous diagnosis of MDS. Of the 20 patients with MDS, 6 had relative monocytosis at diagnosis. At the time of MDS to CMML evolution, mutations in JAK2 (V617F), FLT3 (ITD), K-ras-2, or N-ras were not acquired, and only 1 (6%) of 17 evaluable cases showed cytogenetic progression. The median time to evolution from MDS to CMML was 29 months, and the median survival following CMML development was 13 months. Three cases (17%) transformed to acute myeloid leukemia. These findings indicate that in some cases of otherwise typical MDS, the progenitor cells may have some capacity for monocytic proliferation at diagnosis and manifest rapid disease progression once a monocytic proliferation supervenes.

Aged↗
PubMed2003

Temperature-dependent near-infrared spectra of bovine serum albumin in aqueous solutions: spectral analysis by principal component analysis and evolving factor analysis.

Fourier transform near-infrared (FT-NIR) spectra have been measured for bovine serum albumin (BSA) in an aqueous solution (pH 6.8) with a concentration of 5.0 wt% over a temperature range of 45-85 degrees C. Not only conventional spectral analysis methods, such as second-derivative spectra and difference spectra, but also chemometrics, such as principal component analysis (PCA) and evolving factor analysis (EFA), have been employed to analyze the temperature-dependent NIR spectra in the 7500-5500 and 4900-4200 cm-1 regions of the BSA aqueous solution. Intensity changes of bands in the 7200-6600 cm-1 and 4650-4500 cm-1 regions in the difference spectra indicate variations of the hydration and secondary structure of BSA in the aqueous solution, respectively. The plot of a band intensity at 7080 cm-1 in the different spectra shows a clear turning point at 63 degrees C, revealing that a significant change in the hydration occurs at about 63 degrees C. The forward and backward eigenvalues (EVs) from EFA suggest that marked changes in the hydration and secondary structure of BSA take place in the temperature ranges of 61-65 degrees C and 59-63 degrees C, respectively. In addition, the temperature of 71 degrees C marked in the EFA plots may correspond to the onset temperature of increase in the intermolecular beta-sheet structure.

Animals↗
PubMed2004

Cobalamin-independent methionine synthase (MetE): a face-to-face double barrel that evolved by gene duplication.

Cobalamin-independent methionine synthase (MetE) catalyzes the transfer of a methyl group from methyltetrahydrofolate to L-homocysteine (Hcy) without using an intermediate methyl carrier. Although MetE displays no detectable sequence homology with cobalamin-dependent methionine synthase (MetH), both enzymes require zinc for activation and binding of Hcy. Crystallographic analyses of MetE from T. maritima reveal an unusual dual-barrel structure in which the active site lies between the tops of the two (betaalpha)(8) barrels. The fold of the N-terminal barrel confirms that it has evolved from the C-terminal polypeptide by gene duplication; comparisons of the barrels provide an intriguing example of homologous domain evolution in which binding sites are obliterated. The C-terminal barrel incorporates the zinc ion that binds and activates Hcy. The zinc-binding site in MetE is distinguished from the (Cys)(3)Zn site in the related enzymes, MetH and betaine-homocysteine methyltransferase, by its position in the barrel and by the metal ligands, which are histidine, cysteine, glutamate, and cysteine in the resting form of MetE. Hcy associates at the face of the metal opposite glutamate, which moves away from the zinc in the binary E.Hcy complex. The folate substrate is not intimately associated with the N-terminal barrel; instead, elements from both barrels contribute binding determinants in a binary complex in which the folate substrate is incorrectly oriented for methyl transfer. Atypical locations of the Hcy and folate sites in the C-terminal barrel presumably permit direct interaction of the substrates in a ternary complex. Structures of the binary substrate complexes imply that rearrangement of folate, perhaps accompanied by domain rearrangement, must occur before formation of a ternary complex that is competent for methyl transfer.

Amino Acid Sequence↗
PubMed2006

Forces shaping the fastest evolving regions in the human genome.

Comparative genomics allow us to search the human genome for segments that were extensively changed in the last approximately 5 million years since divergence from our common ancestor with chimpanzee, but are highly conserved in other species and thus are likely to be functional. We found 202 genomic elements that are highly conserved in vertebrates but show evidence of significantly accelerated substitution rates in human. These are mostly in non-coding DNA, often near genes associated with transcription and DNA binding. Resequencing confirmed that the five most accelerated elements are dramatically changed in human but not in other primates, with seven times more substitutions in human than in chimp. The accelerated elements, and in particular the top five, show a strong bias for adenine and thymine to guanine and cytosine nucleotide changes and are disproportionately located in high recombination and high guanine and cytosine content environments near telomeres, suggesting either biased gene conversion or isochore selection. In addition, there is some evidence of directional selection in the regions containing the two most accelerated regions. A combination of evolutionary forces has contributed to accelerated evolution of the fastest evolving elements in the human genome.

Animals↗
PubMed2003

Evolved regulation of gonadotropin-releasing hormone receptor cell surface expression.

Dominant negative effects of mutant gonadotropin-releasing hormone (GnRH) receptors (GnRHR; isolated from patients with idiopathic hypogonadotropic hypogonadism) on plasma membrane expression (PME) and function of the wt GnRHR were examined. In addition, we assessed the effect of mutants on wt GnRHR with receptor modifications that, by themselves, diminished PME. Among such mechanisms that restrict PME of GnRHR in primates are: (a) addition of the primate-specific K191 and (b) deletion of the carboxyl tail ("Ctail") found in pre-mammalian species (fish, birds) of GnRHR. We prepared rat (r) and human (h) GnRHR plasmids (88% homologous), each with or without the K191; chimeras were then made with C-tail or each of four truncated fragments (selected to isolate consensus sites for palmitoylation or phosphorylation) of the 51-amino-acid Ser-rich piscine GnRHR C-tail and then expressed in COS-7 cells. The data suggest that the dominant negative effect of the mutants on the hGnRHR requires intrinsic low PME that co-evolved with the dominant-negative effect. The data further reveal that additional modifications must have occurred in primates that are important for both the diminution of the PME and the development of the dominant negative effect of the mutants.

Amino Acid Sequence↗
PubMed1999

How the licensure process will evolve.

BACKGROUND AND OVERVIEW: All aspects of dental licensure are continuing to evolve. This article describes the changes that are occurring in the licensure process and projects the direction and magnitude of future changes. CONCLUSIONS: The author predicts that national board examinations will continue to move away from recall of facts and toward assessment of basic science and clinical principles as they apply to clinical decision making and delivery of care. Clinical examinations will continue their evolution to become even more reliable and valid. Licensure by credentials will be adopted by more states, thus addressing concerns about mobility that are expressed by many practitioners. PRACTICE IMPLICATIONS: Despite all of this projected progress, the dental profession should expect elevated public pressure for greater accountability unless it takes a proactive position to ensure the continued competency of all practitioners.

Clinical Competence↗
PubMed2004

The standard of care in dentistry: Where did it come from? How has it evolved?

BACKGROUND: The author explores the topic of the standard of care. He reviews the initial application of the standard to health care professionals, as well as its evolution from an 1898 legal case in which 10 elements of the standard of care were stated. CONCLUSIONS: The standard of care continually evolves with the advent of new materials, new procedures and new court rulings. Before applying the standard of care, dentists should consider new available treatments, as well as their state's current interpretation of the standard of care. PRACTICE IMPLICATIONS: The standard of care should be applied to all dentists when patients claim alleged malpractice. It should be tempered by changes in the practice of dentistry, which dentists should be aware of.

Dental Care↗
PubMed2004

Bone marrow angiogenesis: methods of quantification and changes evolving in chronic myeloproliferative disorders.

Until now little information is available about bone marrow (BM) angiogenesis in chronic myeloproliferative disorders (CMPDs). Amongst the various immunohistochemical markers for endothelial cells CD34 and CD105 have proven to be most reliable since they exhibit no relevant co-staining. Determination of vascularity has to include pathophysiological aspects of perfusion. Therefore, quantification of the microvascular density (MVD) by the so-called hot spot method has to be improved by parameters that characterize blood flow more properly like microvessel area (luminal distension), shape (form factor), tortuosity, and branching (maximal vessel length). In comparison to the normal BM chronic myeloid leukemia (CML) revealed a significant increase in MVD which was functionally associated with elevated levels of angiogenic cytokines. Structure of vessels was significantly altered by showing an enhanced irregularity of shape and tortuosity and increase in fibers was conspicuously accompanied by a higher degree of MVD. Contrasting the group of patients with Imatinib (STI571) therapy interferon failed to reduce the number of vessels. Following bone marrow transplantation a significant enhancement of the MVD was found in the early post-transplant period, but after about 6 months normalization occurred. Anomalies of microvascular architecture were easily demonstrable by three-dimensional reconstruction and consisted of a complex branching network of irregular shaped sinuses. Chronic idiopathic myelofibrosis displayed a significant increase in the MVD only in the advanced fibrosclerotic stages. This feature was accompanied by an enhanced luminal distension and tortuosity, thus contrasting the prefibrotic and early fibrotic phases of this disorder. Similar to CML a relationship between evolving myelofibrosis and change in vascular architecture was encountered. This feature may present a possible target for future anti-angiogenic therapy. In essential thrombocythemia there is only a mild increase in MVD detectable while in polycythemia vera besides an enlarged number, a luminal dilation due to the densely packed erythrocytes is recognizable. In conclusion, contrasting the usually applied quantification technique more elaborate morphometrical methods are warranted to obtain a better insight into the vascular architecture of the BM. In CMPDs angiogenesis is significantly associated with the evolution of myelofibrosis and may be altered by therapeutic regimens probably due to changes in cytokine release.

Bone Marrow↗
PubMed1998

Isolation of erythropoietin receptor agonist peptides using evolved phage libraries.

Cyclic peptides capable of activating the erythropoietin receptor (EPOR) were isolated from phage display libraries by screening with a novel EPOR-IgG fusion protein reagent. A parental clone ERB1 (EPO Receptor Binder 1) was first isolated from a phage display library displaying 38 random amino acids as an N-terminal fusion with the M13 minor capsid protein, pill. An evolved library was then produced from the parental sequence using an oligonucleotide saturation mutagenesis strategy which yielded EPOR binding sequences with 20 times the relative affinity of ERB1. Two synthetic peptides were constructed from these sequences both of which bind the EPO receptor in specific ELISA, and act as full agonists in EPO dependent cell proliferation assays. These peptides are 18 amino acids in length, disulfide-bonded, and have a minimum consensus sequence of CXXGWVGXCXXW, where X represents positions tolerant of several amino acids.

Amino Acid Sequence↗
PubMed2003

The human amygdala: an evolved system for relevance detection.

Evidence from pioneering animal research has suggested that the amygdala is involved in the processing of aversive stimuli, particularly fear-related information. Fear is central in the evolution of the mammalian brain: it is automatically and rapidly elicited by potentially dangerous and deadly events. The view that the amygdala shares the main characteristics of modular systems, e.g. domain specificity, automaticity, and cognitive impenetrability, has become popular in neuroscience. Because of its computational properties, it has been proposed to implement a rapid-response 'fear module'. In this article, we review recent patient and neuroimaging data of the human brain and argue that the fundamental criteria for the amygdala to be a modular system are not met. We propose a different computational view and suggest the notion of a specific involvement of the human amygdala in the appraisal of relevant events that include, but are not restricted to, fear-related stimuli. Considering the amygdala as a 'relevance detector' would integrate the 'fear module' hypothesis with the concept of an evolved neural system devoted to the processing of a broader category of biologically relevant stimuli. In primates, socially relevant events appear to have become, through evolution, the dominant elements of the amygdala's domain of specificity.

Amygdala↗
PubMed2006

In silico evolved lac operons exhibit bistability for artificial inducers, but not for lactose.

Bistability in the lac operon of Escherichia coli has been widely studied, both experimentally and theoretically. Experimentally, bistability has been observed when E. coli is induced by an artificial, nonmetabolizable, inducer. However, if the lac operon is induced with lactose, the natural inducer, bistability has not been demonstrated. We derive an analytical expression that can predict the occurrence of bistability both for artificial inducers and lactose. We find very different conditions for bistability in the two cases. Indeed, for artificial inducers bistability is predicted, but for lactose the condition for bistability is much more difficult to satisfy. Moreover, we demonstrate that in silico evolution of the lac operon generates an operon that avoids bistability with respect to lactose, but does exhibit bistability with respect to artificial inducers. The activity of this evolved operon strikingly resembles the experimentally observed activity of the operon. Thus our computational experiments suggest that the wild-type lac operon, which regulates lactose metabolism, is not a bistable switch. Nevertheless, for engineering purposes, this operon can be used as a bistable switch with artificial inducers.

Computer Simulation↗
PubMed2004

The Bacillus subtilis sin operon: an evolvable network motif.

The strategy of combining genes from a regulatory protein and its antagonist within the same operon, but controlling their activities differentially, can lead to diverse regulatory functions. This protein-antagonist motif is ubiquitous and present in evolutionarily unrelated regulatory pathways. Using the sin operon from the Bacillus subtilis sporulation pathway as a model system, we built a theoretical model, parameterized it using data from the literature, and used bifurcation analyses to determine the circuit functions it could encode. The model demonstrated that this motif can generate a bistable switch with tunable control over the switching threshold and the degree of population heterogeneity. Further, the model predicted that a small perturbation of a single critical parameter can bias this architecture into functioning like a graded response, a bistable switch, an oscillator, or a pulse generator. By mapping the parameters of the model to specific DNA regions and comparing the genomic sequences of Bacillus species, we showed that phylogenetic variation tends to occur in those regions that tune the switch threshold without disturbing the circuit function. The dynamical plasticity of the protein-antagonist operon motif suggests that it is an evolutionarily convergent design selected not only for particular immediate function but also for its evolvability.

Bacillus subtilis↗