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At least 343 records · Page 19Linked to original sources
PubMed1975

The capillary permeability of the rete mirabile of the eel, Anguilla vulgaris L.

Direct measurements of transcapillary exchange during steady-state conditions have been performed in the rete mirabile of the eel. The capillaries were found to be more than 30 times as permeable to THO (PTHO = 33.2 times 10(-5) cm sec-1), ethanol and antipyrine than to K+. The mutual relationship of the permeabilities for K+, Na+, urea and sucrose were similar to that between the corresponding free diffusion coefficients in water. The permeability characteristics did not change when the perfusate contained metabolic inhibitors. Additional of 1 mM/l of albumin lead to a significant transcapillary osmotic flow. NaCl, urea and sucrose, however, did not cause osmotic flow. Based on the quantitative values for permeability and volume flow the capillary pores should be about 1300 A and have a frequency of 1.3 times 10(6) per cm2 of the capillary surface, occupying an area of about 0.1% of the total area. The results obtained in the present investigation raise questions as to the validity of the Pappenheimer single-pore theory for transcapillary transport as well as to the fine structure of the capillary pores. As an alternative to Pappenheimer's theory a multi-pathway model is proposed in order to explain transcapillary transport.

Anguilla↗
PubMed1975

The permeability of fish gills with comments on the osmotic behaviour of cellular membranes.

The permeability of eel gills to ions, lipid-soluble and -insoluble substances has been measured under steady-state conditions. The results obtained support the multi-pathway model for transcapillary transport (Stray-Pedersen and Steen 1975). The gills are 25 times more permeable to THO than to Na+ or K+. Metabolic inhibitors do not affect the transfer of substances across the gills. Exposure to EDTA or MS-222 changes the permeability properties to resemble those of an aquous barrier. The gills are 10 times less water permeable than the capillaries of the rete mirabile.

Animals↗
PubMed2006

A systems approach to mapping DNA damage response pathways.

Failure of cells to respond to DNA damage is a primary event associated with mutagenesis and environmental toxicity. To map the transcriptional network controlling the damage response, we measured genomewide binding locations for 30 damage-related transcription factors (TFs) after exposure of yeast to methyl-methanesulfonate (MMS). The resulting 5272 TF-target interactions revealed extensive changes in the pattern of promoter binding and identified damage-specific binding motifs. As systematic functional validation, we identified interactions for which the target changed expression in wild-type cells in response to MMS but was nonresponsive in cells lacking the TF. Validated interactions were assembled into causal pathway models that provide global hypotheses of how signaling, transcription, and phenotype are integrated after damage.

DNA Damage↗
PubMed1991

Protein electron transfer rates set by the bridging secondary and tertiary structure.

The rate of long-distance electron transfer in proteins rapidly decreases with distance, which is indicative of an electron tunneling process. Calculations predict that the distance dependence of electron transfer in native proteins is controlled by the protein's structural motif. The helix and sheet content of a protein and the tertiary arrangement of these secondary structural units define the distance dependence of electronic coupling in that protein. The calculations use a tunneling pathway model applied previously with success to ruthenated proteins. The analysis ranks the average distance decay constant for electronic coupling in electron transfer proteins and identifies the amino acids that are coupled to the charge localization site more strongly or weakly than average for their distance.

Amino Acids↗
PubMed1999

Alternative oxidase inhibitors potentiate the activity of atovaquone against Plasmodium falciparum.

Recent evidence suggests that the malaria parasite Plasmodium falciparum utilizes a branched respiratory pathway including both a cytochrome chain and an alternative oxidase. This branched respiratory pathway model has been used as a basis for examining the mechanism of action of two antimalarial agents, atovaquone and proguanil. In polarographic assays, atovaquone immediately reduced the parasite oxygen consumption rate in a concentration-dependent manner. This is consistent with its previously described role as an inhibitor of the cytochrome bc1 complex. Atovaquone maximally inhibited the rate of P. falciparum oxygen consumption by 73% +/- 10%. At all atovaquone concentrations tested, the addition of the alternative oxidase inhibitor, salicylhydroxamic acid, resulted in a further decrease in the rate of parasite oxygen consumption. At the highest concentrations of atovaquone tested, the activities of salicylhydroxamic acid and atovaquone appear to overlap, suggesting that at these concentrations, atovaquone partially inhibits the alternative oxidase as well as the cytochrome chain. Drug interaction studies with atovaquone and salicylhydroxamic acid indicate atovaquone's activity against P. falciparum in vitro is potentiated by this alternative oxidase inhibitor, with a sum fractional inhibitory concentration of 0.6. Propyl gallate, another alternative oxidase inhibitor, also potentiated atovaquone's activity, with a sum fractional inhibitory concentration of 0.7. Proguanil, which potentiates atovaquone activity in vitro and in vivo, had a small effect on parasite oxygen consumption in polarographic assays when used alone or in the presence of atovaquone or salicylhydroxamic acid. This suggests that proguanil does not potentiate atovaquone by direct inhibition of either branch of the parasite respiratory chain.

Animals↗
PubMed2002

The Ralstonia eutropha PhaR protein couples synthesis of the PhaP phasin to the presence of polyhydroxybutyrate in cells and promotes polyhydroxybutyrate production.

Polyhydroxyalkanoates (PHAs) are polyoxoesters that are produced by many bacteria and that accumulate as intracellular granules. Phasins (PhaP) are proteins that accumulate during PHA synthesis, bind PHA granules, and promote further PHA synthesis. Interestingly, PhaP accumulation seems to be strictly dependent on PHA synthesis, which is catalyzed by the PhaC PHA synthase. Here we have tested the effect of the Ralstonia eutropha PhaR protein on the regulation of PhaP accumulation. R. eutropha strains with phaR, phaC, and/or phaP deletions were constructed, and PhaP accumulation was measured by immunoblotting. The wild-type strain accumulated PhaP in a manner dependent on PHA production, and the phaC deletion strain accumulated no PhaP, as expected. In contrast, both the phaR and the phaR phaC deletion strains accumulated PhaP to higher levels than did the wild type. This result implies that PhaR is a negative regulator of PhaP accumulation and that PhaR specifically prevents PhaP from accumulating in cells that are not producing PHA. Transfer of the R. eutropha phaR, phaP, and PHA biosynthesis (phaCAB) genes into a heterologous system, Escherichia coli, was sufficient to reconstitute the PhaR/PhaP regulatory system, implying that PhaR both regulates PhaP accumulation and responds to PHA directly. Deletion of phaR caused a decrease in PHA yields, and a phaR phaP deletion strain exhibited a more severe PHA defect than a phaP deletion strain, implying that PhaR promotes PHA production and does this at least partially through a PhaP-independent pathway. Models for regulatory roles of PhaR in regulating PhaP and promoting PHA production are presented.

Bacterial Proteins↗
PubMed1982

Membrane permeability of isolated lung cells to nonelectrolytes at different temperatures.

Membrane permeability coefficients (P0) of rabbit lung cells consisting primarily of alveolar epithelial and endothelial cells and of alveolar macrophages from dog lungs were determined for tritiated water, n-[14C]alcohols, and [14C]antipyrine over the temperature range 10 to 37 degrees C with the series-parallel pathway model. In the mixed cell preparation both the diffusional permeability to water (755 X 10(-5) cm.s-1 at 37 degrees C) and the response to temperature change (apparent activation energy, Ea, 10 kcal.mol-1) are greater than the corresponding values in the macrophages (110 X 10(-5) cm.s-1 and 4.8 kcal.mol-1, respectively). The permeability coefficients for the small alcohols (C1-C3) are similar and considerably higher than for water in both cellular preparations. The values of the permeability coefficients and the temperature dependence for antipyrine and the larger alcohols in the mixed lung cells differ from the values obtained in the macrophages. Comparison of our results with those obtained in erythrocytes and Novikoff hepatoma cells demonstrates the differences in water permeability in each cell preparation and the similarity in permeation for the more lipophilic solutes in the cell preparations. These differences may be important in the comparison of results obtained in isolated cellular systems and in intact tissues and organs.

Alcohols↗
PubMed2003

A tripeptidyl ensemble perspective of interactive control of growth hormone secretion.

Current investigational tools in molecular biology, biochemistry and integrative physiology have revealed an increasing array of signals that influence growth hormone (GH) secretion. The present perspective combines these factors under a simplified final-common pathway model of threefold joint control by GH-releasing hormone, GH-releasing peptide/ghrelin and somatostatin. This concept is highlighted from the viewpoint of sex steroid- and age-dependent modulation of the peptide trilogy listed above.

Aging↗
PubMed2026

Proteomic Profiling of Pulmonary Function and Cardiovascular Disease Risk in the Atherosclerosis Risk in Communities Study.

BACKGROUND: Pulmonary function is linked to cardiovascular disease risk; however, the underlying mechanisms remain unclear. We aimed to identify protein biomarkers associated with pulmonary function and examine their impact on incident chronic obstructive pulmonary disease, coronary heart disease, heart failure, and all-cause mortality. METHODS: Data from White and Black Americans in the Atherosclerosis Risk in Communities study (visit 2: N=11&#x2009;354, mean age=57 years; visit 5: N=3517, mean age=75 years), a prospective cohort, were analyzed. Linear regression assessed associations between protein levels and pulmonary function measures, including forced expiratory volume in 1 second and forced vital capacity. The impact of the identified proteins on incident chronic obstructive pulmonary disease, coronary heart disease, heart failure, and mortality was estimated using logistic regression and Cox proportional hazards models. Pathway enrichment and Mendelian randomization explored underlying biological functions and causal effects. RESULTS: Of 4766 proteins analyzed, 364 were cross-sectionally associated with forced expiratory volume in 1 second (and forced vital capacity (false discovery rate<0.05). Ninety-four and 270 proteins had concordant positive and negative effects, respectively. Five pathways related to pulmonary and cardiac function were enriched. Of the 364 proteins, 112 were linked to all 4 outcomes, where 86 were associated with increased risk (odds ratio/hazard ratio [OR/HR], 1.05-1.42) and 26 with reduced risk (OR/HR, 0.69-0.96). Six proteins (STAT3 [signal transducer and activator of transcription 3], MIC-1 [growth differentiation factor 15], apoA-II [apolipoprotein A-II], TPST1 [protein-tyrosine sulfotransferase 1], integrin a1b1 [integrin alpha-I: beta-1 complex], and BLC [C-X-C motif chemokine 13]) showed potential inverse causal effects on with forced expiratory volume in 1 second and forced vital capacity, and integrin a1b1 demonstrated consistent inverse associations with chronic obstructive pulmonary disease, coronary heart disease, and heart failure risks. CONCLUSIONS: Proteins associated with pulmonary function may influence CVD risk. Six proteins, including integrin a1b1, represent promising targets for future interventions.

Aged↗
PubMed2004

Current challenges and issues facing nursing in Australia.

This column is a discussion of nursing in Australia. The authors present current challenges and issues related to recruitment and retention, an aging workforce, violence and bullying, diversity, undergraduate and graduate education, professional development, information technology, clinical pathways, models of care delivery, and funding models. They also present what is happening in Australia in relation to nursing's scope of practice, development of the nurse practitioner role, nursing leadership, and nursing research.

Australia↗
PubMed2005

Executive and motivational processes in adolescents with Attention-Deficit-Hyperactivity Disorder (ADHD).

BACKGROUND: The objective of the current study was to examine performance and correlates of performance on a decision-making card task involving risky choices (Iowa Gambling Task) in adolescents with ADHD and comparison controls. Forty-four participants with ADHD and 34 controls were administered measures of estimated intellectual ability, working memory, and the card task. Also, behavioural ratings were obtained from parents and teachers. RESULTS: Adolescents with ADHD scored lower on the measures of intellectual ability, working memory, and made less advantageous selections on the card task compared to controls. Performance on measures of intellectual ability and working memory were unrelated to card task performance in both the ADHD and control samples. Parent ratings of hyperactivity/impulsivity were significantly associated with card task performance in the adolescents with ADHD, but not in controls. CONCLUSION: These findings demonstrate impaired decision-making in adolescents with ADHD, and the separability of motivational and executive function processes, supporting current dual pathway models of ADHD.

Journal Article↗
PubMed2004

Cascade pathway of filopodia formation downstream of SCAR.

The protrusion of two distinct actin-containing organelles, lamellipodia and filopodia, is thought to be regulated by two parallel pathways: from Rac1 through Scar/WAVEs to lamellipodia, and from Cdc42 through N-WASP to filopodia. We tested this hypothesis in Drosophila, which contains a single gene for each WASP subfamilies, SCAR and WASp. We performed targeted depletion of SCAR or WASp by dsRNA-mediated interference in two Drosophila cultured cell lines expressing lamellipodial and filopodial protrusion. Knockdown was verified by laser capture microdissection and RT-PCR, as well as western blotting. Morphometrical, kinetic and electron microscopy analyses of the SCAR-depleted phenotype in both cell types revealed strong inhibition of lamellipodial formation and cell spreading, as expected. More importantly, filopodia formation was also strongly inhibited, which is not consistent with the parallel pathway hypothesis. By contrast, depletion of WASp did not produce any significant phenotype, except for a slight inhibition of spreading, showing that both lamellipodia and filopodia in Drosophila cells are regulated predominantly by SCAR. We propose a new, cascade pathway model of filopodia regulation in which SCAR signals to lamellipodia and then filopodia arise from lamellipodia in response to additional signal(s).

Animals↗
PubMed1984

State of research: environmental pathways and food chain transfer.

Data on the chemistry of biologically active components of petroleum, synthetic fuel oils, certain metal elements and pesticides provide valuable generic information needed for predicting the long-term fate of buried waste constituents and their likelihood of entering food chains. Components of such complex mixtures partition between solid and solution phases, influencing their mobility, volatility and susceptibility to microbial transformation. Estimating health hazards from indirect exposures to organic chemicals involves an ecosystem's approach to understanding the unique behavior of complex mixtures. Metabolism by microbial organisms fundamentally alters these complex mixtures as they move through food chains. Pathway modeling of organic chemicals must consider the nature and magnitude of food chain transfers to predict biological risk where metabolites may become more toxic than the parent compound. To obtain predictions, major areas are identified where data acquisition is essential to extend our radiological modeling experience to the field of organic chemical contamination.

Air Pollutants↗
PubMed2003

Hypotonicity-induced ATP release is potentiated by intracellular Ca2+ and cyclic AMP in cultured human bronchial cells.

We have examined the cultured human bronchial epithelial cells (16HBE) to learn if changes in Cl(-) concentration or osmolality stimulate the cells to release ATP and to determine whether its release is cyclic AMP (cAMP)- and/or Ca(2+)-dependent by using the luciferin-luciferase luminometric assay. In a control solution (290 mosmol kg H(2)O(-1)), the external ATP concentration and the rate of ATP release were 0.52 +/- 0.20 nM and 0.036 +/- 0.034 pmol min(-1), respectively. Upon hypotonicity (205 mosmol kg H(2)O(-1)), they increased to 7.0 +/- 1.3 nM and 3.1 +/- 0.6 pmol min(-1), respectively, at 6 min, then decreased. At the peak, the rate of ATP release is estimated to be 6.2x10(4) ATP molecules s(-1) per cell. An accumulation of the released ATP for the initial 10 min increased significantly (p < 0.005) by 71.5% in the presence of forskolin (10 microM), adenylyl cyclase activator, however, it was abolished (p < 0.001) by pretreatment with BAPTA-AM (25 microM), a membrane permeable Ca(2+) chelator. On the other hand, neither low Cl(2-) (75 mM, isotonic) nor hypertonicity (+NaCl or +mannitol, 500 mosmol kg H(2)O(-1)) could significantly increase the ATP release. Further, forskolin or ionomycin (a Ca(2+) ionophore) or, both, failed to stimulate ATP release under the isotonic condition. In conclusion, first, hypertonicity and changes in Cl(-) concentrations are not effective signals for the ATP release; second, hypotonicity-induced ATP release is potentiated by the level of intracellular Ca(2+) and cAMP; and third, a biphasic increase in ATP release and its low rate at the peak support the hypothesis that ATP is released through a non-conducting pathway model, such as exocytosis, or through a volume-dependent, ATP-conductive anion channel.

Adenosine Triphosphate↗
PubMed1988

Outflow facility studies in the perfused bovine aqueous outflow pathways.

We have recently developed a technique for constant pressure perfusion of the aqueous outflow pathway of the eye. Our preliminary studies, conducted in the calf eye, show surprisingly that the manipulations necessary for preparing the outflow pathways and attached corneoscleral shell for perfusion do not greatly disrupt normal aqueous outflow physiology and anatomy according to the following criteria: 1. facility of outflow is similar before and during outflow pathway perfusion 2. as in the intact eye, facility of outflow decreases with increased IOP 3. removal of outflow resistance tissue greatly increases facility of outflow 4. morphology of outflow tissues remains normal Use of the perfused outflow pathway model may enable the creation of valuable in vitro preparations which may provide much needed information about the pathogenesis of primary open-angle glaucoma.

Animals↗
PubMed2000

[Use of bone densitometry in the framework of prevention and therapy of osteoporosis. Example of a systematic evaluation (health technology assessment)].

There is an ongoing controversy concerning the use of bone density measurements within therapeutic and preventive strategies of osteoporosis. Since there are no randomized controlled trials evaluating the effectiveness of bone density measurement with subsequent therapy we used a "critical pathway" model to determine possible benefit of tertiary, secondary and primary preventive strategies utilizing bone density measurement. In a first step data for fracture risk in each group are extracted from the literature. The second step outlines possible benefit from therapeutic studies. It may be estimated that in groups of patients with prevalent fractures use of bone density measurement and therapy according to bone density values may reduce fracture rates up to 30%. Bone density measurements performed with secondary preventive intent, however will probably lead to a reduction of fracture rates markedly below 10%. A set of risk factors that allows identification of a high risk group that may benefit from bone density measurement and subsequent therapy to a relevant extent remains to be developed. Primary preventive strategies do not require bone density measurements.

Absorptiometry, Photon↗
PubMedDate not supplied

[Import risk analysis in animal disease control].

At the Swiss Federal Veterinary Office risk analyses are conducted according to international standards. A risk analysis contains the elements risk management, risk assessment and risk communication. A risk assessment is based on risk profile, hazard identification and a pathway model. All available information is gathered, documented and assessed and the risk estimated. The question. "What is the probability that unprocessed wild boar meat imported to Switzerland from the federal state Mecklenburg Western Pommerania is contaminated with classical swine fever virus?" was answered by a release assessment. The hazard identification recognized classical swine fever virus and attenuated live virus vaccine used for oral immunization as hazards. The probability of contamination was estimated to be small. The question: "What is the likelihood to introduce Aujeszky's disease to Switzerland and infect the indigenous pig population with the disease, by means of importing pork and meat products?" was answered by assessing the release, exposure and resulting consequences. The risk of an infection of the indigenous pig population was estimated to be very small, as 80% of the imported products derive from countries or zones free from Aujeszky's disease. Furthermore the majority of the imported products are processed. The strict implementation of the regulations governing feeding of food wastes to pigs reduces the probability of exposure. In all assessments the risk management decides on a strategy to deal with the risk, taking into consideration the results and recommendations derived from the risk assessment as well as other relevant factors.

Animal Diseases↗