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Results for “Continuous Evolution”

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At least 289 records · Page 16Linked to original sources

PubMed2002

Basic principles of flow cytometry.

Although the basic principles of flow cytometry have changed little in the past quarter century, the applications of this technology have evolved substantially. As in the past, cytometers interrogate individual cells or particles in a stream with a laser as the cells move past a set of stationary detectors. Increasingly, more colors of fluorescence are being detected by cytometers, faster analysis and sorting rates are becoming possible, cytometers capable of multidirectional sorting are being marketed, and more reagents are becoming available for a wide variety of applications. Furthermore, flow cytometry has not stopped evolving. The development of narrow spectrum flourescent probes, the integration of molecular biologic techniques with flow cytometry, and the evaluation of cell-free markers such as cytokines will be key components in the continuing evolution of flow cytometry.

Analog-Digital Conversion↗

PubMed1992

A randomized controlled trial of early surgery in Duchenne muscular dystrophy.

We performed a randomized controlled trial of early surgical treatment of contractures in 20 boys with Duchenne muscular dystrophy, age 4-6 yr. Surgery consisted of release of hip flexors, removal of iliotibial bands, and lengthening of tendo Achilles bilaterally. All patients were monitored for at least 12 months post-randomization, and assessed quantitatively for muscle strength and function. Surgery corrected the deformities, but had no beneficial effect on strength or function. Indeed, data in the second year showed more rapid deterioration of function in some of the operated boys. There appeared to be continued evolution of pathology following surgery, as assessed by sequential muscle ultrasound and muscle biopsy. We cannot recommend this type of surgery as a routine treatment.

Biopsy↗

PubMed2003

Mimicking the way to autoimmunity: an evolving theory of sequence and structural homology.

Although the etiology of autoimmune diseases remains largely unknown, a prevailing theory concerns the infection-induced activation of self-reactive lymphocytes via the process of molecular mimicry. Here, we discuss the theory of molecular mimicry and its continued evolution from the initial basic considerations of sequence similarity to the current theories of structural homology. Such findings serve to further our understanding of T-cell receptor degeneracy and might one day provide a direct link between infection and autoimmune disease.

Amino Acid Sequence↗

PubMed1993

[Characteristics and mechanisms of action of leukocyte depletion filters].

Since their creation, leukocyte depletion filters, used to prepare leukocyte-poor red cell or platelet concentrates, have been continuously evoluting: their volume has been reduced and their composition has been modified, polyester fibers have replaced cotton wool or cellulose acetate. In the same way, their capacity to remove leukocytes has increased. The mechanisms of cell separation are still unclear. Through published studies, different factors seem to be implicated, such as wetable surface of the filter, surface tension or charge density of fibers. It was also observed that removal of lymphocytes from red cell concentrates is rather based on trapping in the fiber network, and that removal of granulocytes, monocytes and platelets is partly due to activation and subsequent adhesion to the fibers. There have been few studies of the mechanism of leukocytes depletion from platelets concentrates.

Adsorption↗

PubMed2002

The evolving role of information technology in the drug discovery process.

Information technologies for chemical structure prediction, heterogeneous database access, pattern discovery, and systems and molecular modeling have evolved to become core components of the modern drug discovery process. As this evolution continues, the balance between in silico modeling and 'wet' chemistry will continue to shift and it might eventually be possible to step through the discovery pipeline without the aid of traditional laboratory techniques. Rapid advances in the industrialization of gene sequencing combined with databases of protein sequence and structure have created a target-rich but lead-poor environment. During the next decade, newer information technologies that facilitate the molecular modeling of drug-target interactions are likely to shift this balance towards molecular-based personalized medicine -- the ultimate goal of the drug discovery process.

Animals↗

PubMed2004

Therapeutic scope of modulation of non-voltage-gated cation channels.

Although widely regarded as attractive drug targets, less than a tenth of known ion channels are currently commercially exploited as therapeutic targets. Historically, drug discovery efforts on ion channel targets have been encumbered by a lack of molecular and structural information, sub-optimal screening technologies and a paucity of discriminating pharmacological tools. Although challenges remain, recent scientific and technological advances in the area of ion channel research and screening offer the exciting prospect of a new, more-predictive era of ion channel drug discovery. In this article, focusing primarily on non-voltage-gated cation channels, we describe the continuing evolution of approaches to ion channel drug discovery, highlight recent developments in the ion channel field and consider their potential impact on discovering and ascribing function to ion channel targets. We discuss the renaissance of known ion channel targets, such as nicotinic acetylcholine receptors and calcium-activated potassium channels, as well as the emergence of the transient receptor potential (TRP) channels as a gene family of cation channels with broad therapeutic potential.

Animals↗

PubMed2005

Therapeutic scope of modulation of non-voltage-gated cation channels.

Although widely regarded as attractive drug targets, less than a tenth of known ion channels are currently commercially exploited as therapeutic targets. Historically, drug discovery efforts on ion channel targets have been encumbered by a lack of molecular and structural information, sub-optimal screening technologies and a paucity of discriminating pharmacological tools. Although challenges remain, recent scientific and technological advances in the area of ion channel research and screening offer the exciting prospect of a new, more-predictive era of ion channel drug discovery. In this article, focusing primarily on non voltage gated cation channels, we describe the continuing evolution of approaches to ion channel drug discovery, highlight recent developments in the ion channel field and consider their potential impact on discovering and ascribing function to ion channel targets. We discuss the renaissance of known ion channel targets, such as nicotinic acetylcholine receptors and calcium-activated potassium channels, as well as the emergence of the transient receptor potential (TRP) channels as a gene family of cation channels with broad therapeutic potential.

Animals↗

PubMed2002

Hughes syndrome crosses boundaries.

Hughes (antiphospholipid) syndrome is a condition in continuous evolution. Since it was first described almost 20 years ago, significant advances in its diagnosis and management have been made. Recently, classification criteria for definite antiphospholipid syndrome have been proposed and validated. However, there is still controversy regarding issues such as the utility of new diagnostic tests (detecting antibodies to beta(2)-glycoprotein I, phospholipids other than cardiolipin or phospholipid mixtures), the role of antiphospholipid antibodies in neurological conditions such as demyelinating disease, cognitive impairment or migraine and the optimal management of thrombosis and obstetric manifestations. These are all briefly discussed in this review.

Abortion, Spontaneous↗

PubMed1995

Orthoses and prostheses.

Orthoses and prostheses include a wide range of devices and strategies for correcting and alleviating dysfunction and disability. Features in these areas of technology include continuing evolution of new devices, further development of well-established approaches, a need for critical assessment, requirements for support from technical and health care workers, and the need to identify funding to achieve efficient programs.

Persons with Disabilities↗

PubMed1994

Geminate recombination of diatomic ligands CO, O2, and NO with myoglobin.

The kinetics of geminate recombination of horse heart myoglobin with the diatomic ligands carbon monoxide, dioxygen, and nitric oxide have been reexamined. The new measurements are distinguished from previous studies by (1) consideration of the complete time range longer than 1 ps, (2) inclusion of the effect of temperature changes near ambient, (3) attention to the relation between recombination kinetics and the yield of dissociated partners on the millisecond time scale, and (4) use of singular value decomposition in the analysis. These picosecond results, together with earlier nanosecond data, for O2 prove that models incorporating one, two, or even three discrete intermediates are not sufficient to account for all features of geminate recombination kinetics. Instead, a continuous evolution of the geminate pair distribution is preferred.

Animals↗

PubMed2006

Rational design of a beta-lactamase inhibitor achieved via stabilization of the trans-enamine intermediate: 1.28 A crystal structure of wt SHV-1 complex with a penam sulfone.

beta-Lactamases are one of the major causes of antibiotic resistance in Gram negative bacteria. The continuing evolution of beta-lactamases that are capable of hydrolyzing our most potent beta-lactams presents a vexing clinical problem, in particular since a number of them are resistant to inhibitors. The efficient inhibition of these enzymes is therefore of great clinical importance. Building upon our previous structural studies that examined tazobactam trapped as a trans-enamine intermediate in a deacylation deficient SHV variant, we designed a novel penam sulfone derivative that forms a more stable trans-enamine intermediate. We report here the 1.28 A resolution crystal structure of wt SHV-1 in complex with a rationally designed penam sulfone, SA2-13. The compound is covalently bound to the active site of wt SHV-1 similar to tazobactam yet forms an additional salt-bridge with K234 and hydrogen bonds with S130 and T235 to stabilize the trans-enamine intermediate. Kinetic measurements show that SA2-13, once reacted with SHV-1 beta-lactamase, is about 10-fold slower at being released from the enzyme compared to tazobactam. Stabilizing the trans-enamine intermediate represents a novel strategy for the rational design of mechanism-based class A beta-lactamase inhibitors.

Amines↗

PubMedDate not supplied

Transsphenoidal and transcranial surgery for pituitary adenomas.

This paper reviews the progress made over the first century of pituitary surgery. The goals of surgery for pituitary tumors are to eliminate tumor mass effect and perform as complete a removal as possible, retain pituitary function, and normalize any hormonal hypersecretion. Since the initial transsphenoidal approach performed in Austria by Schloffer, the transsphenoidal approach has become the preferred surgical approach to most pituitary tumors. The history and development of the transsphenoidal approach to the sella is discussed, as are the contemporary techniques of microscopic and endoscopic pituitary surgery. The continued evolution of the variations and extension of the transsphenoidal approach to other lesions are reviewed. The indications and use of a transcranial approach to remove pituitary tumors are discussed. More recently, stereotactic radiosurgery (SRS) has become an important adjuvant management technique in the management of difficult pituitary adenomas, especially with cavernous sinus invasion.

Adenoma↗

PubMed2005

Hsp70 overexpression sequesters AIF and reduces neonatal hypoxic/ischemic brain injury.

Apoptosis is implicated in neonatal hypoxic/ischemic (H/I) brain injury among various forms of cell death. Here we investigate whether overexpression of heat shock protein (Hsp) 70, an antiapoptotic protein, protects the neonatal brain from H/I injury and the pathways involved in the protection. Postnatal day 7 (P7) transgenic mice overexpressing rat Hsp70 (Tg) and their wild-type littermates (Wt) underwent unilateral common carotid artery ligation followed by 30 mins exposure to 8% O(2). Significant neuroprotection was observed in Tg versus Wt mice on both P12 and P21, correlating with a high level of constitutive but not inducible Hsp70 in the Tg. More prominent injury was observed in Wt and Tg mice on P21, suggesting its continuous evolution after P12. Western blot analysis showed that translocation of cytochrome c, but not the second mitochondria-derived activator of caspase (Smac)/DIABLO and apoptosis-inducing factor (AIF), from mitochondria into cytosol was significantly reduced in Tg 24 h after H/I compared with Wt mice. Coimmunoprecipitation detected more Hsp70 bound to AIF in Tg than Wt mice 24 h after H/I, inversely correlating with the amount of nuclear, but not cytosolic, AIF translocation. Our results suggest that interaction between Hsp70 and AIF might have reduced downstream events leading to cell death, including the reduction of nuclear AIF translocation in the neonatal brains of Hsp70 Tg mice after H/I.

Animals↗

PubMed2005

On the theory of aggregation and micellization: PEO-PVP copolymer in water.

We develop a theoretical approach to micellization of the PEO-PVP block-copolymer in water. This copolymer is a weak polyelectrolyte due to protonation of VP blocks. The theory accounts for non-linear ion screening, and predicts strong position dependence of both ion concentration and the effective Debye length. We consider both the case when the local Debye length is small compared to the core radius and the case when it is large. We found that the effective (local) pH is not uniform even inside one micellar core, hence non-uniform protonation of the core with higher charge density near the surface. In many cases the core charge is concentrated in a relatively thin surface layer. Considering statistical weights of non-equilibrium micelles and their continuous evolution we show that kinetics of both formation and dissociation of typical block-copolymer or surfactant micelles can be extremely slow. Thus micelle formation at the genuine (equilibrium) critical micelle concentration (c.m.c.) is totally suppressed (involves astronomical time scales) if the micelles are big enough. An 'apparent' critical micelle concentration (c.m.c.*) is introduced to account for this effect. The apparent c.m.c.* could be much higher than the genuine equilibrium c.m.c., i.e. a significant hysteresis is inherent in these systems. We also determine the ranges of meta-stability of micelles depending on the experimental time-scales.

Journal Article↗

PubMed2001

Clinical and economic evaluation of surgical treatments for faecal incontinence.

BACKGROUND: Faecal incontinence affects 1-2 per cent of the adult population. While many patients can be managed successfully with conservative therapy, a small proportion require surgery. Improved imaging techniques and technological advances have led to the availability of a wide range of surgical treatments. Decision-makers increasingly require clinical and cost-effectiveness studies of surgical treatments for faecal incontinence. This review examines the practical aspects of undertaking such studies. METHODS: The practical issues related to different aetiologies, different types of treatment, defining outcomes, the hidden costs of the condition and its treatment, the rapid changes in technology and issues of patient choice were all considered. A Medline search was undertaken to identify relevant publications, and the reference lists of identified papers were scanned manually. RESULTS: There are few randomized controlled studies and those that have been performed have been limited in their scope. There has also been very limited health economic analysis undertaken. Strategies for conducting such studies, and the criteria they use, have been outlined. CONCLUSION: Randomized trials have a limited role in this setting because of variations in aetiology, difficulty in standardizing procedures, continuing evolution of devices, small patient numbers, concerns for patient choice and the need for long-term follow-up. Issues to be addressed when evaluating interventions for faecal incontinence include choosing appropriate measures of surgical outcome, using new continence scoring systems and tools for quality-of-life assessment, and choosing appropriate cost perspectives and time horizons for economic evaluation.

Colorectal Surgery↗

PubMed2005

Stool screening for colorectal cancer: molecular approaches.

Assay of molecular markers in stool represents a promising noninvasive approach to screen colorectal cancer. Given that neoplasms exfoliate abundantly into the lumen and that DNA recovered from stool can be assayed with sensitive techniques, there is a strong biologic rationale to pursue this emerging technology. A challenge with DNA-based testing relates to the selection of markers. Because of the molecular heterogeneity of cancer, no single marker has yielded perfect sensitivity. Several combinations of markers in early stool assays have produced high detection rates of both colorectal cancer and advanced adenomas in selected patient groups, but observations from large representative populations are lacking at present. Potential expanded applications of stool DNA testing include detection of supracolonic aerodigestive cancers and of dysplasia in inflammatory bowel disease. Further marker discovery and technologic refinements should translate into improved test performance and fuel a continued evolution with this screening approach.

Colorectal Neoplasms↗

PubMed2004

Neurodevelopmental outcomes in hypoplastic left heart syndrome.

Infants with hypoplastic left heart syndrome (HLHS) are now surviving to school age and early adulthood because of surgical palliation with either staged reconstruction or transplantation. Although in some respects these patients are doing remarkably well, recent investigations have shown that they are at risk for cognitive, neuromotor, and psychosocial problems. This article examines the neurodevelopmental outcome for children and adolescents with HLHS. In addition, hemodynamic and genetic factors unique to this patient population that may impact longer-term outcome are explored. The continued evolution of the pre-, intra- and post-operative care of the patient with HLHS has significantly improved early survival. Concomitant changes in care, such as selective cerebral perfusion and neurologic monitoring, aimed at reducing neurologic insult may also favorably impact later neurodevelopmental status.

Adolescent↗

PubMed2001

The state of ambulatory surgery and perianesthesia nursing.

The continued success of the ambulatory surgery environment of care has been achieved through patient, physician, and nursing staff satisfaction. The growth in this industry has been greatly influenced by advances in technology, as well as the development and administration of newer anesthetic agents. The implications delineated in this article provide an overview of what is in store for the specialty of perianesthesia nursing. Issues of competency, professional excellence, patient expectations, continuous quality improvement, research, and ethics have become part of the daily lexicon. Never before has the professional nurse been counted on for so much, and future expectations of the nurse continue to grow. To survive, the nurse needs to expand the boundaries of nursing practice as they have been defined. Nurses are the backbone of the delivery of patient care, nurses are on the front line guiding the patient through every care decision, and nurses are positioned to influence the continued evolution of ambulatory surgery and perianesthesia nursing care.

Ambulatory Surgical Procedures↗