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PubMed1998

The course of post-traumatic amnesia: three little words.

OBJECTIVE: To provide a simple means of "real time" recognition of emergence from post-traumatic amnesia (PTA). METHODS: Ninety-one patients with traumatic brain injury (PBI); 53 minor (GCS 13-15), 19 moderate (GCS 9-12), 18 severe (GCS 3-8). Twenty-seven control subjects treated at two regional trauma units for their acute phase and followed in a hospital-based research institute were studied prospectively. Subjects were examined repeatedly following injury with the Galveston Orientation and Amnesia Test (GOAT) and tests of their ability to learn and retain new information. Word triplets balanced for concreteness and frequency were presented. Immediate and 24-hour recall were tested. If 24-hour recall was imperfect, recognition was tested by presenting the 3 target words and 6 distracters. The target words were then re-presented and recall was tested the next day. The time intervals to first perfect recognition and first free perfect recall were compared with the patients' first GOAT score of 75 or greater on 2 successive days. Simple line drawings of common objects were also presented to the subjects using an identical paradigm. The outcome measures were GOAT, 3-word recognition and recall, 3 picture recognition and recall. RESULTS: For all categories of head injury severity, the median interval to perfect free recall of words followed the achievement GOAT criterion by a significant interval. The mean GOAT scores for perfect 3-word recall and recognition corresponding to minor, moderate and severe injuries were 97, 90 and 88, and 97, 76 and 68 respectively. The recognition and recall of pictures preceded the recognition and recall of words by approximately 1 day. CONCLUSIONS: The orientation measures of the GOAT that contain material that the patient knew prior to injury obscure the determination of recovery of continuous memory and should be tested separately. Three-word recall which is simpler to administer than the GOAT is a more reliable measure of emergence from PTA. For patients who are dysphasic or who do not share a common language with the examiner, 3-picture recognition and recall may substitute for word recognition and recall.

Adolescent↗

PubMed2006

Lessons learned from clustering of fluorinated glycolipids on selectin ligand function in cell rolling.

Selectin-induced leukocyte rolling along the endothelium is an essential step in the cellular immune response. Since clustering of binding epitopes is thought to be crucial for selectin-ligand interaction, we focused on requirements of ligand clusters in a flow chamber study. Neoglycolipids bearing the binding epitope sialyl Lewis X (sLeX) were used as artificial ligands in model membranes. sLeX ligands or matrix lipids or both were applied with partially fluorinated alkyl chains to increase the ligand cluster separation tendency. Cluster size, their inner structure, and separation distance were evaluated with high resolution by scanning force microscopy (SFM) and correlated with binding or rolling of E-selectin-expressing cells. Fluorination of only one component, sLeX ligand or matrix lipid, leads to a very high separation tendency and impeded cell rolling, although firm cell adhesion could be observed down to 0.005 mol % ligand concentration. As a sign of total immiscibility, cluster size increased with ligand concentration, and resulting excessive ligand densities within the clusters prevent cell rolling. Fluorination of both sLeX ligands and matrix created small clusters which could serve as rolling patches. Our results confirmed that cluster size and separation distance controlled by a certain miscibility of ligand and matrix as well as a sufficiently diluted ligand concentration within the clusters are necessary for cell rolling. Within this work, selectin ligand clustering and its ability to mediate cell rolling are presented as a balance between multivalency of binding and sufficient flexibility of the single epitopes. This might be helpful for better understanding the function of the natural selectin ligands.

Animals↗

PubMed1976

The effect of active immunization against aldosterone on the colonic potential response and sodium excretion in rabbits.

1. A group of rabbits was actively immunized against aldosterone and their subsequent response to infused aldosterone and to dietary sodium restriction was compared with that of a control group. 2. Colonic electrical potential difference (CP) was used as an index of relative mineralocorticoid activity in both groups of animals. 3. Infusion of aldosterone produced a rise in CP to a maximum of -50 to -70 mV at rates of infusion of 55-270 pmol min-1 kg-1. In contrast, the immune group showed no change until infusion dose rates of 2700 pmol min-1 kg-1 were used. 4. During dietary sodium restriction, CP increased in normal rabbits to a significantly greater degree than in immune animals although cumulative urinary sodium losses were the same in both groups. 5. The ability of the immune animals to remain in sodium balance despite physiological aldosterone blockade suggests that aldosterone is not an essential component of their sodium-conservation mechanisms.

Aldosterone↗

PubMed1989

A comparative cephalometric investigation of the Greek craniofacial pattern through 4,000 years.

A comparative cephalometric investigation was conducted between modern and ancient Greeks to determine craniofacial characteristics and to examine the significance of ethnic heritage. The modern sample was composed of 54 individuals chosen on the basis of ethnic background, normal occlusion and facial harmony. The ancient sample consisted of 40 skulls with normal occlusion dated back to the Minoan civilization (ca. 1,800-1,200 B.C.). A remarkable similarity in craniofacial morphology was revealed between the two groups, suggesting a close genetic affinity between modern and ancient Greeks. The ability of the craniofacial complex to make compensatory or balancing changes was noted. The craniofacial complex was seen to function as an integrated biological entity. Moreover, the cranial base showed a definite influence on skeletal profile configuration. These results provide a more comprehensive understanding of how craniofacial variables interact and contribute to the morphology of the dentofacial skeleton.

Adolescent↗

PubMed2002

Children's rights: a decade of dispute.

AIM: This paper attempts to raise issues surrounding children's rights against a backdrop of ethical principles and their subsequent interpretation and application in practice. METHOD: Key words have been used to search a selection of electronic databases and a range of 'grey' literature has been reviewed. BACKGROUND: Over a decade ago the United Nations (1989) Convention on the Rights of the Child was ratified, with the exception of two member states (UNICEF 2000). The Human Rights Act (Department of Health 1998) became law in October 2000 in the United Kingdom (UK). Despite a decade of recommendations, guidelines and legislation, children's rights, particularly consent to health care, remain complex and inconsistent. As we move into a new era of human rights involving all members of society, it is timely for nurses in the UK to reflect on the challenges created in attempting to interpret the philosophy of such legislation because such complexity surrounds the interpretation of human rights for many other vulnerable clients within health care. FINDINGS: The interpretation of children's rights continues to be influenced by the evolution of the meanings of childhood. Adults view children's rights from multiple perspectives of best interest, which are determined by their beliefs about children's ability to understand and consent to health care and treatment. An ability and right to consent appears not to be balanced by the right to withhold consent. Inconsistency and ambiguity persist in the law and its interpretation. Adults need to develop a more pragmatic approach to children's rights. This requires better understanding of children and their experiences of health care. CONCLUSION: Until adults develop a more pragmatic ideology in relation to children's rights then a true respect for children's autonomy will not be achieved. Consent will therefore remain an adult and legal prerogative.

Child↗

PubMed1996

Alkali cation selectivity of the wheat root high-affinity potassium transporter HKT1.

The wheat root high-affinity K+ transporter HKT1 functions as a sodium-coupled potassium co-uptake transporter. At toxic millimolar levels of sodium (Na+), HKT1 mediates low-affinity Na+ uptake while potassium (K+) uptake is blocked. In roots, low-affinity Na+ uptake and inhibition of K+ uptake contribute to Na+ toxicity. In the present study, the selectivity among alkali cations of HKT1 expressed in Xenopus oocytes and yeast was investigated under various ionic conditions at steady state. The data show that HKT1 is highly selective for uptake of the two physiologically significant alkali cations, K+ and Na+ over Rb+, Cs+ and Li+. In addition, Rb+ and Cs+, and an excess of extracellular K+ over Na+, are shown to partially reduce or block HKT1-mediated K(+)-Na+ uptake. Furthermore, K+, Rb+ and Cs+ also effectively reduce outward currents mediated by HKT1, thereby causing depolarizations. In yeast, HKT1 can produce high-affinity Rb+ uptake at approximately 15-fold lower rates than for K+. Rb+ influx in yeast can be mediated by the ability of the yeast plasma membrane proton pump to balance the >or= 35-fold lower HKT1 conductance for Rb+. A model for HKT1 activity is presented involving a high-affinity K+ binding site and a high-affinity Na+ binding site, and competitive interactions of K+, Na+ and other alkali cations for binding to these two sites. Possible implications of the presented results for physiological K+ and Na+ uptake in plants are discussed.

Calcium↗

PubMed2002

The bioartificial kidney in the treatment of acute renal failure.

The application of cell therapy to the successful substitution process of hemofiltration may improve the poor prognosis of patients with acute renal failure (ARF) in the intensive care unit. An extracorporeal bioartificial kidney consisting of a conventional hemofilter followed in series with a renal tubule assist device (RAD) has been developed. The RAD is a hemofiltration cartridge containing 109 human renal tubule cells grown as monolayers along the inner surface of the hollow fibers. The fibers provide a porous scaffold that is immunoprotective. The ultrafiltrate from the hemofilter is delivered to the luminal compartment of the RAD, and the postfiltered blood is delivered to the extracapillary space of the RAD. The RAD has been shown to possess multiple differentiated transport, metabolic, and endocrinologic activities of renal epithelium. These activities have been demonstrated to occur when the RAD is placed in the extracorporeal circuit of the bioartificial kidney in uremic animals. This approach may improve the current therapies used to treat patients with ARF because of the RAD's ability to restore lost metabolic renal function and cytokine balance in these desperately ill patients. In this regard, the RAD was able to ameliorate endotoxin and bacteremic shock in uremic animals by altering cytokine levels, improve mean arterial blood pressure, and maintain better cardiac output. With these supportive preclinical data, an FDA-approved phase I/II clinical trial has been initiated and early results are encouraging.

Acute Kidney Injury↗

PubMed2006

Migration of tumor cells in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis.

Cell migration on 2D surfaces is governed by a balance between counteracting tractile and adhesion forces. Although biochemical factors such as adhesion receptor and ligand concentration and binding, signaling through cell adhesion complexes, and cytoskeletal structure assembly/disassembly have been studied in detail in a 2D context, the critical biochemical and biophysical parameters that affect cell migration in 3D matrices have not been quantitatively investigated. We demonstrate that, in addition to adhesion and tractile forces, matrix stiffness is a key factor that influences cell movement in 3D. Cell migration assays in which Matrigel density, fibronectin concentration, and beta1 integrin binding are systematically varied show that at a specific Matrigel density the migration speed of DU-145 human prostate carcinoma cells is a balance between tractile and adhesion forces. However, when biochemical parameters such as matrix ligand and cell integrin receptor levels are held constant, maximal cell movement shifts to matrices exhibiting lesser stiffness. This behavior contradicts current 2D models but is predicted by a recent force-based computational model of cell movement in a 3D matrix. As expected, this 3D motility through an extracellular environment of pore size much smaller than cellular dimensions does depend on proteolytic activity as broad-spectrum matrix metalloproteinase (MMP) inhibitors limit the migration of DU-145 cells and also HT-1080 fibrosarcoma cells. Our experimental findings here represent, to our knowledge, discovery of a previously undescribed set of balances of cell and matrix properties that govern the ability of tumor cells to migration in 3D environments.

Cell Adhesion↗

PubMed1996

Epstein-Barr virus vectors for gene delivery to B lymphocytes.

Basic research in Epstein-Barr virus (EBV) molecular genetics has provided means to maintain episomes in human cells, to efficiently deliver episomes with up to 150 kbp of heterologous DNA to human B lymphocytes, and to immortalize human B lymphocytes with EBV recombinants that can maintain up to 120 kbp of heterologous DNA. Episome maintenance requires an EBV nuclear protein, EBNA1, whereas immortalization of cells with EBV recombinants requires EBNA1, EBNA2, EBNA3A, EBNA3C, EBNALP, and LMP1. EBV-derived vectors are useful for experimental genetic reconstitution in B lymphocytes, a cell type frequently used in establishing repositories of human genetic deficiencies. The ability of EBV-infected cells to establish a balanced state of persistence in normal humans raises the possibility that cells infected with EBV recombinants could be useful for genetic reconstitution, in vivo.

B-Lymphocytes↗

PubMed2001

p53 associates with and targets Delta Np63 into a protein degradation pathway.

A human p53 homologue, p63 (p40/p51/p73L/CUSP) that maps to the chromosomal region 3q27-29 was found to produce a variety of transcripts that encode DNA-binding proteins with and without a trans-activation domain (TA- or Delta N-, respectively). The p63 gene locus was found to be amplified in squamous cell carcinoma, and overexpression of Delta Np63 (p40) led to increased growth of transformed cells in vitro and in vivo. Moreover, p63-null mice displayed abnormal epithelial development and germ-line human mutations were found to cause ectodermal dysplasia. We now demonstrate that certain p63 isotypes form complexes with p53. p53 mutations R175H or R248W abolish the association of p53 with p63, whereas V143A or R273H has no effect. Deletion studies suggest that the DNA-binding domains of both p53 and p63 mediate the association. Overexpression of wild type but not mutant (R175H) p53 results in the caspase-dependent degradation of certain Delta Np63 proteins (p40 and Delta Np63 alpha). The association between p53 and Delta Np63 supports a previously unrecognized role for p53 in regulation of Delta Np63 stability. The ability of p53 to mediate Delta Np63 degradation may balance the capacity of Delta Np63 to accelerate tumorigenesis or to induce epithelial proliferation.

Animals↗

PubMed2000

Lipid oxidation enhances the function of activated protein C.

Although lipid oxidation products are usually associated with tissue injury, it is now recognized that they can also contribute to cell activation and elicit anti-inflammatory lipid mediators. In this study, we report that membrane phospholipid oxidation can modulate the hemostatic balance. Oxidation of natural phospholipids results in an increased ability of the membrane surface to support the function of the natural anticoagulant, activated protein C (APC), without significantly altering the ability to support thrombin generation. Lipid oxidation also potentiated the ability of protein S to enhance APC-mediated factor Va inactivation. Phosphatidylethanolamine, phosphatidylserine, and polyunsaturation of the fatty acids were all required for the oxidation-dependent enhancement of APC function. A subgroup of thrombotic patients with anti-phospholipid antibodies specifically blocked the oxidation-dependent enhancement of APC function. Since leukocytes are recruited and activated at the thrombus or sites of vessel injury, our findings suggest that after the initial thrombus formation, lipid oxidation can remodel the membrane surface resulting in increased anticoagulant function, thereby reducing the thrombogenicity of the thrombus or injured vessel surface. Anti-phospholipid antibodies that block this process would therefore be expected to contribute to thrombus growth and disease.

Humans↗

PubMed2003

The role of oxidative stress in diabetic vascular and neural disease.

This review will focus on the impact of hyperglycemia-induced oxidative stress in the development of diabetes-induced vascular and neural dysfunction. Oxidative stress occurs when the balance between the production of oxidation products and the ability of antioxidant mechanisms to neutralize these products is tilted in the favor of the former. The production of reactive oxygen species has been shown to be increased in patients with diabetes. The possible sources for the overproduction of reactive oxygen species is widespread and include enzymatic pathways, autoxidation of glucose and the mitochondria. Increase in oxidative stress has clearly been shown to contribute to the pathology of vascular disease not only in diabetes but also in hypertension, stroke and ischemia. Since the etiology of diabetic neuropathy is considered to have a large vascular component, prevention of oxidative stress in diabetes is considered by many investigators to be a primary defense against the development of diabetic vascular disease. Potential therapies for preventing increased oxidative stress in diabetes and the neural vasculature will be discussed.

Animals↗

PubMed1994

A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission.

BACKGROUND: A short battery of physical performance tests was used to assess lower extremity function in more than 5,000 persons age 71 years and older in three communities. METHODS: Balance, gait, strength, and endurance were evaluated by examining ability to stand with the feet together in the side-by-side, semi-tandem, and tandem positions, time to walk 8 feet, and time to rise from a chair and return to the seated position 5 times. RESULTS: A wide distribution of performance was observed for each test. Each test and a summary performance scale, created by summing categorical rankings of performance on each test, were strongly associated with self-report of disability. Both self-report items and performance tests were independent predictors of short-term mortality and nursing home admission in multivariate analyses. However, evidence is presented that the performance tests provide information not available from self-report items. Of particular importance is the finding that in those at the high end of the functional spectrum, who reported almost no disability, the performance test scores distinguished a gradient of risk for mortality and nursing home admission. Additionally, within subgroups with identical self-report profiles, there were systematic differences in physical performance related to age and sex. CONCLUSION: This study provides evidence that performance measures can validly characterize older persons across a broad spectrum of lower extremity function. Performance and self-report measures may complement each other in providing useful information about functional status.

Activities of Daily Living↗

PubMed2004

Kv3 K+ channels enable burst output in rat cerebellar Purkinje cells.

The ability of cells to generate an appropriate spike output depends on a balance between membrane depolarizations and the repolarizing actions of K(+) currents. The high-voltage-activated Kv3 class of K(+) channels repolarizes Na(+) spikes to maintain high frequencies of discharge. However, little is known of the ability for these K(+) channels to shape Ca(2+) spike discharge or their ability to regulate Ca(2+) spike-dependent burst output. Here we identify the role of Kv3 K(+) channels in the regulation of Na(+) and Ca(2+) spike discharge, as well as burst output, using somatic and dendritic recordings in rat cerebellar Purkinje cells. Kv3 currents pharmacologically isolated in outside-out somatic membrane patches accounted for approximately 40% of the total K(+) current, were very fast and high voltage activating, and required more than 1 s to fully inactivate. Kv3 currents were differentiated from other tetraethylammonium-sensitive currents to establish their role in Purkinje cells under physiological conditions with current-clamp recordings. Dual somatic-dendritic recordings indicated that Kv3 channels repolarize Na(+) and Ca(2+) spikes, enabling high-frequency discharge for both types of cell output. We further show that during burst output Kv3 channels act together with large-conductance Ca(2+)-activated K(+) channels to ensure an effective coupling between Ca(2+) and Na(+) spike discharge by preventing Na(+) spike inactivation. By contributing significantly to the repolarization of Na(+) and especially Ca(2+) spikes, our data reveal a novel function for Kv3 K(+) channels in the maintenance of high-frequency burst output for cerebellar Purkinje cells.

Action Potentials↗

PubMed2002

A long terminal repeat retrotransposon of fission yeast has strong preferences for specific sites of insertion.

The successful dispersal of transposons depends on the critical balance between the fitness of the host and the ability of the transposon to insert into the host genome. One method transposons may use to avoid the disruption of coding sequences is to target integration into safe havens. We explored the interaction between the long terminal repeat retrotransposon Tf1 and the genome of the yeast Schizosaccharomyces pombe. Using techniques that were specifically designed to detect integration of Tf1 throughout the genome and to avoid bias in this detection, we generated 51 insertion events. Although 60.2% of the genome of S. pombe is coding sequence, all but one of the insertions occurred in intergenic regions. We also found that Tf1 was significantly more likely to insert into intergenic regions that included polymerase II promoters than into regions between convergent gene pairs. Interestingly, 8 of the 51 insertion sites were isolated multiple times from genetically independent cultures. This result suggests that specific sites in intergenic regions are targeted by Tf1. Perhaps the most surprising observation was that per kilobase of nonrepetitive sequence, Tf1 was significantly more likely to insert into chromosome 3 than into one of the other two chromosomes. This preference was found not to be due to differences in the distribution or composition of intergenic sequences within the three chromosomes.

Base Sequence↗

PubMed1992

Mechanisms of fibrin formation and lysis by human lung fibroblasts: influence of TGF-beta and TNF-alpha.

Fibrin gels form within the alveolar and interstitial compartments of the injured lung, and fibroblasts invade and facilitate organization of these transitional gels. We studied the effects of transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) on fibrinolytic and procoagulant activities of human lung fibroblasts (HLF) to determine their capacity to regulate pulmonary fibrin deposition. Fibrinolytic activity of cell lysates and media (n = 6 HLF cultures) were uniformly depressed by TGF-beta or TNF-alpha. In dose and time-course studies, HLF plasminogen activator inhibitor-1 (PAI-1) was increased by TGF-beta, whereas TNF-alpha induced release of PAI-1 into the media. HLF and media urokinase concentrations were depressed by TGF-beta, whereas urokinase was unchanged or increased by TNF-alpha. Tissue plasminogen activator was mainly cell associated and unchanged by TGF-beta or TNF-alpha. HLF antiplasmin activity was not detected. Plasma recalcification times of HLF media were decreased by TNF-alpha but unchanged by TGF-beta. These studies suggest that TGF-beta and TNF-alpha impair the ability of HLF to degrade fibrin by disturbing the balance of HLF plasminogen activators and PAI and that these cytokines concurrently leave unchanged or increase the capacity of HLF to initiate fibrin formation. Cytokines likely to occur in the injured lung induce abnormalities of fibrinolysis in HLF from adults; such abnormalities favor extravascular fibrin deposition, a characteristic feature of alveolitis.

Base Sequence↗

PubMed1999

Comparing AMI mortality among hospitals in patients 65 years of age and older: evaluating methods of risk adjustment.

BACKGROUND: Interest in the reporting of risk-adjusted outcomes for patients with acute myocardial infarction is growing. A useful risk-adjustment model must balance parsimony and ease of data collection with predictive ability. METHODS AND RESULTS: From our analysis of 82 359 patients >/=65 years of age admitted with acute myocardial infarction to 2401 hospitals, we derived a parsimonious model that predicts 30-day mortality. The model was validated on a similar group of 78 699 patients from 2386 hospitals. Of the 73 candidate predictor variables examined, 7 variables describing patient characteristics on arrival were selected for inclusion in the final model: age, cardiac arrest, anterior or lateral location of myocardial infarction, systolic blood pressure, white blood cell count, serum creatinine, and congestive heart failure. The area under the receiver-operating characteristic curve for the final model was 0.77 in the derivation cohort and 0.77 in the validation cohort. The rankings of hospitals by performance (in deciles) with this model were most similar to a comprehensive 27-variable model based on medical chart review and least similar to models based on administrative billing codes. CONCLUSIONS: A simple 7-variable risk model performs as well as more complex models in comparing hospital outcomes for acute myocardial infarction. Although there is a continuing need to improve methods of risk adjustment, our results provide a basis for hospitals to develop a simple approach to compare outcomes.

Age Factors↗

PubMedDate not supplied

Staging of maxillary cancer. Which classification?

Of the many proposed classifications for staging maxillary sinus cancer, none has been adopted universally and none is known to be superior to the others. This study identified the best of six currently used classifications using data from 53 previously untreated patients with squamous cell carcinoma of the maxillary sinus. Analysis of each classification's ability to stage the majority of patients, produce a balanced distribution of T stages, and correlate T stage with treatment and prognosis revealed Harrison's classification to be the best. Harrison's classification should be adopted worldwide as the classification of choice for staging squamous cell carcinoma of the maxillary sinus.

Algorithms↗