The use of Web Services to enable programmatic access to on-line bioinformatics is becoming increasingly important in the Life Sciences. However, their number, distribution and the variable quality ...of their documentation can make their discovery and subsequent use difficult. A Web Services registry with information on available services will help to bring together service providers and their users. The BioCatalogue (http://www.biocatalogue.org/) provides a common interface for registering, browsing and annotating Web Services to the Life Science community. Services in the BioCatalogue can be described and searched in multiple ways based upon their technical types, bioinformatics categories, user tags, service providers or data inputs and outputs. They are also subject to constant monitoring, allowing the identification of service problems and changes and the filtering-out of unavailable or unreliable resources. The system is accessible via a human-readable 'Web 2.0'-style interface and a programmatic Web Service interface. The BioCatalogue follows a community approach in which all services can be registered, browsed and incrementally documented with annotations by any member of the scientific community.
Na+/H+ exchange (antiport) is a major pathway for the regulation of intracellular pH. Antiport activity is stimulated when suspended cells adhere to the substratum. In this report, immunofluorescence ...was used to study the subcellular localization of the ubiquitous NHE‐1 isoform of the antiport. NHE‐1 was not distributed homogeneously on the surface of the cells. Instead, antiports were found to accumulate along the border of lamellipodia and near the edge of finer processes. Dual immunofluorescence experiments demonstrated that vinculin, talin and F‐actin are concentrated at sites of NHE‐1 accumulation. A mutated construct of NHE‐1 lacking residues 566‐635 of the cytosolic domain also accumulated near marginal lamellae. In contrast, the focal distribution observed in adherent cells was not detectable in cells grown in suspension. Fluorescence ratio imaging was used to define the functional consequences of focal accumulation of NHE‐1. In the steady state, the pH was virtually identical throughout the cytosol. Moreover, no pH gradients were found to develop when cells recovered from an acid load by activation of Na+/H+ exchange. This is probably because of the presence of high concentrations of mobile buffers in the cytosol. The focal accumulation of antiporters near the cell margins may be involved in stimulation by adherence and/or generation of local osmotic gradients.
Several myths about drowning have developed over the years. This article has attempted to dispel some of these myths, as follows: 1. Drowning victims are unable to call or wave for help. 2. "Dry ...drownings" probably do not exist; if there is no water in the lungs at autopsy, the victim probably was not alive when he or she entered the water. 3. Do not use furosemide to treat the pulmonary edema of drowning; victims may need volume. 4. Seawater drowning does not cause hypovolemia, and freshwater drowning does not cause hypervolemia, hemolysis, or hyperkalemia. 5. Drowning victims swallow much more water than they inhale, resulting in a high risk for vomiting spontaneously or on resuscitation. No discussion of drowning would be complete without mentioning the importance of prevention. Proper pool fencing and water safety training at a young age are instrumental in reducing the risk for drowning. Not leaving an infant or young child unattended in or near water can prevent many of these deaths, especially bathtub drownings. Also crucial is the use of personal flotation devices whenever boating. Proper training in water safety is crucial for participation in water recreation and sporting activities, including SCUBA diving. The incidence of pediatric drowning deaths in the United States has decreased steadily over the past decade, perhaps as a result of increased awareness and attention to drowning-prevention measures (Box 1).
To determine if an altered expression of the Na,K-ATPase alpha isoform genes is responsible for an observed increase in cardiac glycoside sensitivity in compensatory hypertrophy, we performed ...Northern and slot blot analyses of RNA and specific immunological detection of Na,K-ATPase isoforms in rat hearts from normal and pressure overload-treated animals induced by abdominal aortic constriction. During the early phase of hypertrophy, the only alteration is a decrease in the alpha 2 mRNA isoform. In the compensated hypertrophied heart, the levels of the predominant alpha 1 isoform (mRNA and protein) and the beta 1 subunit mRNA are unchanged. In contrast, the alpha 2 isoform (mRNA and protein) is decreased by 35% and up to 61-64% in mild (< 55%) and severe (> 55%) hypertrophy, respectively. The alpha 3 isoform (mRNA and protein), which is extremely low in adult heart, is increased up to 2-fold during hypertrophy but accounts for only approximately equal to 5% of the total alpha isoform mRNA. These findings demonstrate that, in cardiac hypertrophy, the three alpha isoforms of the Na,K-ATPase are independently regulated and that regulation occurs at a pretranslational level. The pattern of expression in hypertrophied adult heart is similar to that of the neonatal heart where the inverse regulation between the alpha 2 and alpha 3 ouabain high affinity isoforms has been reported. This suggests that distinct regulatory mechanisms controlling Na,K-ATPase isoform expression may, at least in part, be involved in the sensitivity to cardiac glycosides.
Oxidized LDL stimulates the expression of TGF-β and fibronectin in human glomerular epithelial cells. Abnormal lipid accumulation in glomeruli is a recognized early event in the development of ...glomerulosclerosis. The presence of LDL and scavenger receptors has recently been demonstrated in glomerular cells, including the visceral epithelial cells. To explore the possible molecular mechanisms of lipid-induced glomerular injury, the present investigation was conducted to examine the effects of oxidized LDL (ox-LDL) on the expression of transforming growth factor (TGF)-β and fibronectin by cultured human glomerular epithelial cells (GEC). Cultured GEC were exposed to human ox-LDL (0 to 100 µg/ml) for various time points. Ox-LDL induced a dose- and time-dependent increase in the expression of TGF-β mRNA. Actinomycin D, a transcriptional inhibitor, but not cycloheximide, a protein synthesis inhibitor, inhibited the response. GEC exposed to ox-LDL also demonstrated elevated levels of fibronectin mRNA. In addition, treatment of GEC with ox-LDL resulted in increased TGF-β and fibronectin protein expression as detected by immunocytochemistry. Addition of anti-TGF-β antibody significantly inhibited the increase in fibronectin message level induced by ox-LDL. These data suggest that ox-LDL stimulates matrix protein fibronectin in GEC by a mechanism involving expression of TGF-β. Thus, accumulation of lipids in human glomerular epithelial cells may contribute to the pathogenesis of glomerulosclerosis through TGF-β mediated mechanism(s).
Aspiration of bile is an underpublicized aspiration syndrome. Using a porcine lung model, the physiologic response and the histopathology of lung tissue were evaluated after the intratracheal ...instillation of sublethal doses of bile. Twenty-one domestic swine (11 to 19 kg) were the studied population. Three groups of five swine were evaluated: a control group received intratracheal physiologic saline (pH 7.45); study group 1 received strained gastric contents (pH 2.24); and study group 2 received strained bile (pH 7.19). All animals received the solutions at 0.5 ml/kg intratracheally. Lungs of six additional animals were studied (two gastric, two bile, and two physiologic saline) after aspiration by scanning electron microscopy (SEM). A seventh untreated animal was used as the SEM control. The physiologic data were analyzed using analysis of variance for repeated measures. The SEM and histopathologic results were graded by an observer blinded to the groups and were analyzed using the analysis of variance (ANOVA) and Scheffe tests. The group with bile aspiration was consistently characterized by significant deterioration of PaO2, the alveolar-arterial (A-a) gradient, shunt fraction, and static compliance (p<0.01); and the light histopathologic and SEM findings demonstrated pathologic changes in the bile-exposed lung (p<0.05) greater than the gastric- or salineexposed lungs. It is concluded that bile aspiration produces a severe chemical pneumonitis leading to noncardiac pulmonary edema.
The association of actin filaments with the plasma membrane maintains cell shape and adhesion. Here, we show that the plasma membrane ion exchanger NHE1 acts as an anchor for actin filaments to ...control the integrity of the cortical cytoskeleton. This occurs through a previously unrecognized structural link between NHE1 and the actin binding proteins ezrin, radixin, and moesin (ERM). NHE1 and ERM proteins associate directly and colocalize in lamellipodia. Fibroblasts expressing NHE1 with mutations that disrupt ERM binding, but not ion translocation, have impaired organization of focal adhesions and actin stress fibers, and an irregular cell shape. We propose a structural role for NHE1 in regulating the cortical cytoskeleton that is independent of its function as an ion exchanger.
Difficulties and delays in establishing intravenous access are not uncommon in emergency situations in pediatrics. Alternatives to venous cannulation exist, including intraosseous access, ...intratracheal drug administration, sublingual and intralingual injection, the intrapenile route, and intracardiac injection. Each of these emergency alternatives to intravenous access is discussed from the historical, technical, utilitarian, and risk-benefit aspects. It is concluded that the intraosseous effective alternative to intravenous access in emergency situations.
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