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A shift in the optimum pH of pospholipase D produced by activating long-chain anions.

1. The activity of phospholipase D (phosphatidylcholine phosphatidohydrolase, EC 3.1.4.4) towards ultrasonically treated phosphatidylcholine or large phosphatidylcholine particles activated with ether was maximal near pH5, and there was little activity above pH6. 2. When the enzyme was activated by the addition of phosphatidic acid to large phosphatidylcholine particles the pH optimum was shifted to pH6.5 irrespective of the amount of activator added. 3. When the enzyme was activated with low concentrations of dodecyl sulphate the pH optimum was 5.5 with little activity above pH6. With higher concentrations of dodecyl sulphate the pH-activity profile was shifted upwards towards a pH optimum of 6.5-6.6, the magnitude of the shift depending on the extent of the hydrolysis. 4. The shifts in the pH-activity profiles cannot be correlated with changes in the ;surface pH' of the substrate particles calculated from the measurement of their zeta-potentials (electrophoretic mobilities).

Calcium Chloride↗

The gastroenterology fellowship Match: how it failed and why it could succeed once again.

The market for gastroenterology (GI) fellows adopted a centralized Match in 1986, and abandoned it in the late 1990s. We discuss why the Match initially was adopted, how and why it broke down, what differences this has made in the market for fellows, and what would be needed to restart the Match successfully. We assess the effects of the Match by comparing the GI fellows market now with when the Match was operating, and with the fellowship markets for internal medicine subspecialties that continue to use a Match. The breakdown of a well-functioning Match is rare, but may be caused by unusual shifts in market conditions, such as those experienced by gastroenterology in the late 1990s. The problems the gastroenterology Match originally was designed to solve re-emerged with the demise of the Match. The market has become more local and less national, than when there was a Match in place, and program recruitment of fellows occurs earlier and is more dispersed in time than internal medicine subspecialties that continue to use a Match. There is no evidence that the demise of the Match has had any effect on wages. The evidence strongly suggests that the Match could be reintroduced successfully, which would increase the mobility of potential GI fellows, allow potential fellows to compete for the widest range of programs, and allow programs to compete for the widest range of fellows.

Antitrust Laws↗

Nitrogen cycling by wood decomposing soft-rot fungi in the "King Midas tomb," Gordion, Turkey.

Archaeological wood in ancient tombs is found usually with extensive degradation, limiting what can be learned about the diet, environment, health, and cultural practices of the tomb builders and occupants. Within Tumulus Midas Mound at Gordion, Turkey, thought to be the tomb of the Phrygian King Midas of the 8th century B.C., we applied a stable nitrogen isotope test to infer the paleodiet of the king and determine the nitrogen sources for the fungal community that decomposed the wooden tomb, cultural objects, and human remains. Here we show through analysis of the coffin, furniture, and wooden tomb structure that the principal degrader, a soft-rot fungus, mobilized the king's highly (15)N-enriched nutrients, values indicative of a diet rich in meat, to decay wood throughout the tomb. It is also evident from the delta(15)N values of the degraded wood that the nitrogen needed for the decay of many of the artifacts in the tomb came from multiple sources, mobilized at potentially different episodes of decay. The redistribution of nutrients by the fungus was restricted by constraints imposed by the cellular structure of the different wood materials that apparently were used intentionally in the construction to minimize decay.

Archaeology↗

Microglia in diseases of the central nervous system.

Microglia (MG) are enigmatic cells of the central nervous system (CNS). MG are morphologically, antigenically and functionally flexible, and have the potential for mobility and proliferation. MG are professional antigen-presenting cells and constitute part of the local CNS innate immune system, communicating with other immune cells via chemokines, cytokines and growth factors. MG contain several antigenic and functional markers similar to macrophages and dendritic cells (DCs), but also present several differences from DCs. The exact role(s) played by MG in the normal human CNS is the topic of lively debate. MG participate in many reactive processes in the CNS and are therefore an integral part of lesions in a variety of pathologic conditions. It is thought that MG may exacerbate diverse neurological conditions, including viral encephalitis, AIDS, Multiple Sclerosis (MS) and Alzheimer's disease. A recurrent theme is the perpetuation by MG of pathological cycles of monocyte recruitment, activation and cytopathic secretions, and/or auto antigen presentation.

Acquired Immunodeficiency Syndrome↗

Macrophage plasma membrane and secretory properties in murine malaria. Effects of Plasmodium yoelii blood-stage infection on macrophages in liver, spleen, and blood.

We have studied the effect of infection with the blood-stage of Plasmodium yoelii 17X, a nonlethal parasite, on plasma membrane antigens, receptors, and secretory properties of macrophages (M phi) in murine liver, spleen, and blood. mAb F4/80 (M phi specific), F7/4 (a marker for immature and immunologically activated M phi, as well as neutrophils), and Mac-1, which binds to the type 3 complement receptor, were used to measure the distribution and total content of antigens in situ and to assay surface expression of antigens on M phi isolated by collagenase perfusion-digestion and adherence. We also examined respiratory burst activity after stimulation with PMA, FcR activity, Ia antigen expression, and binding of 125I-mannose-BSA and unopsonized sheep erythrocytes by isolated M phi. In the normal animal, spleen M phi expressed Mac-1 and F7/4 antigens and relatively high levels of respiratory burst activity, in contrast to Kupffer cells in liver, where all three features were virtually absent. The introduction of parasitized erythrocytes into the circulation resulted in a large influx of F4/80+ M phi into the blood, liver, and spleen, where local M phi proliferation could also contribute. Liver M phi during malaria infection showed increased Mac-1 and 7/4 antigen and an increased respiratory burst potential compared with uninfected controls. Increases in total, but not specific activity of FcR, Ia antigen, and binding of unopsonized sheep erythrocytes were found in spleen and liver M phi populations after infection. In both populations, there was an early but persistent marked reduction in specific binding and uptake of 125I-mannose-BSA. These results confirm and extend observations that normal Kupffer cells are relatively homogeneous in morphology, surface markers, and anatomical location, in contrast to M phi in normal spleen, and that both of these populations differ from resident M phi elsewhere, including the peritoneal cavity. In the course of infection by P. yoelii, M phi with high levels of opsonic receptors (CR3, FcR) and respiratory burst potential are mobilized in large numbers at specific sites such as liver and spleen, in accordance with an important role for M phi in the clearance of parasitized erythrocytes from blood.

Animals↗

Contribution of the putative heparan sulfate-binding motif BBXB of RANTES to transendothelial migration.

The chemokines are a family of small chemoattractant proteins that have a range of functions, including activation and promotion of vectorial migration of leukocytes. Regulation on activation, normal T cell expressed and secreted (RANTES; CCL5), a member of the CC-chemokine subfamily, has been implicated in a variety of immune responses. In addition to the interaction of CC-chemokines with their cognate cell-surface receptors, it is known that they also bind to glycosaminoglycans (GAGs), including heparan sulfate. This potential for binding to GAG components of proteoglycans on the cell surface or within the extracellular matrix might allow formation of the stable chemokine concentration gradients necessary for leukocyte chemotaxis. In this study, we created a panel of mutant RANTES molecules containing neutral amino acid substitutions within putative, basic GAG-binding domains. Despite showing reduced binding to GAGs, it was found that each mutant containing a single amino acid substitution induced a similar leukocyte chemotactic response within a concentration gradient generated by free solute diffusion. However, we found that the mutant K45A had a significantly reduced potential to stimulate chemotaxis across a monolayer of microvascular endothelial cells. Significantly, this mutant bound to the CCR5 receptor and showed a potential to mobilize Ca(2+) with an affinity similar to the wild-type protein. These results show that the interaction between RANTES and GAGs is not necessary for specific receptor engagement, signal transduction, or leukocyte migration. However, this interaction is required for the induction of efficient chemotaxis through the extracellular matrix between confluent endothelial cells.

Amino Acid Motifs↗

Regional fasciocutaneous flaps for the burned axilla.

The conventional approach for secondary correction of unstable axillary scars or contractures with skin grafting commonly risks failure of adherence and early recurrence of the problem, even in highly motivated patients. Potential early mobilization and the avoidance of postoperative splinting may be advantages of reconstruction with vascularized tissues instead. The local fasciocutaneous flap is advocated as a simple, rapidly elevated, single-staged option that preserves function while correcting these deformities. Although the dorsal thoracic fascial flaps are the most versatile in the axillary region, if they are unavailable or unsuitable, other unspecified but equally robust alternatives from the upper arm or anterolateral chest are similarly efficacious.

Adolescent↗

Feasibility issues in reproductive biomonitoring of female flight attendants and teachers.

Flight attendants (FAs) may be at risk of adverse reproductive outcomes. We investigated the feasibility of biomonitoring studies in this mobile workforce. Forty-five female FAs and 26 female teachers (referents) collected daily urine and saliva samples for one menstrual cycle, provided daily diary data for approximately three months, and wore a wrist monitor to measure sleep disruption. A transport system enabled FAs to store samples while traveling. Overall, participation rates were low (37%) but of those recruited, over 90% of FAs and teachers completed the biomonitoring cycle. Data collection and sample integrity were not diminished by travel. Study methods resulted in good compliance and high quality data. It is possible to conduct studies of menstrual cycle function, sleep disruption, and circadian rhythm disruption in a mobile workforce potentially exposed to reproductive hazards.

Adolescent↗

Impact of hydrophobic pollutants' behavior on occupational and environmental health.

This paper reviews the influence of hydrophobic pollutant behavior on environmental hazards and risks. The definition and examples of hydrophobic pollutants are given as a guide to better understand the sources of release and the media of dispersion in the environment. The properties and behavior of hydrophobic pollutants are described and their influence on environmental hazard and risk is reviewed and evaluated. The overall outcome of the assessment and evaluation showed that all hydrophobic pollutants are hazardous and risky to all organisms, including man. Their risk effects are due to their inherent persistence, bioaccumulation potential, environmental mobility, and reactivity. Their hazardous effects on organisms occur at varying spatial and temporal degrees of emissions, toxicities, exposures, and concentrations.

Adsorption↗

Endogenous serum levels of thrombopoietic cytokines in healthy whole-blood and platelet donors: implications for plateletpheresis.

Serum concentrations of the thrombopoiesis-enhancing cytokines thrombopoietin (TPO), erythropoietin (EPO), interleukin (IL)-6 and IL-11 were determined in 119 healthy whole-blood (WBD) and 101 platelet donors (PD) prior to donation. The 90% TPO reference interval in WBD of 64-867 pg/ml (median 163, 100% range 45-7572) was significantly higher than in PD of 56-524 (median 122, range 44-801, P = 0.004), whereas their platelet counts were lower (P < 0.001). EPO levels were not different (WBD 7.7 +/- 3.8, PD 8.0 +/- 4.9 IU/l), IL-6 and IL-11 were below the detection limit in >/=90% of cases (IL-6 < 3.2 pg/ml, IL-11 < 31.2 pg/ml). None of the cytokines correlated with platelet counts, other blood parameters, or in the PD group with the frequency of platelet donations within the last 6 months. We conclude that plateletpheresis does not lead to a lasting increase of thrombopoietic cytokines and provide reference data for potential platelet mobilization strategies with recombinant growth factors.

Adult↗

Dose-dependent effects of zinc supplementation during chelation of lead in rats.

Dose-dependent effects of zinc supplementation in order to enhance the efficacy of calcium disodium EDTA in lead intoxicated rats was investigated in rats. The results suggest simultaneous supplementation of zinc at a lower concentration i.e. 10 mg/kg (orally, once during chelation treatment), 25 mg/kg zinc (Flora & Tandon 1990) potentiates the mobilization of lead from blood and soft tissues. However, at a higher dose level (50 mg/kg once orally) it has deleterious and much reduced ability to deplete tissue lead contents and restore altered lead sensitive biochemical variables.

Animals↗

The congruence of nursing diagnoses and supporting clinical evidence.

In this secondary analysis, 890 patients 40 years of age and older were assessed within 24 hours of transfer from intensive care to medical/surgical units. Nursing diagnoses documented in the hospital record were compared to supporting clinical evidence obtained from subjects, the hospital record, and interviews with subjects and nurse caregivers. The congruence, based on the kappa statistic, between the nursing diagnosis and clinical evidence ranged from 0.1% for altered thought processes to 10% for impaired gas exchange, impaired physical mobility, and potential for injury, while no diagnoses were made for self-care deficits or sensory alterations, visual, when clinical evidence for them was available.

Adult↗

Genetics of intracisternal-A-particle-related envelope-encoding proviral elements in mice.

Intracisternal-A-particle-related envelope-encoding (IAPE) proviral elements in the mouse genome encode and express an envelope-like protein that may allow transmission of IAPEs as infectious agents. To test IAPE mobility and potential transmission in mice, we have analyzed the distribution of IAPE elements in the genomes of Mus spretus and Mus musculus inbred strains and wild-caught animals. Potential full-length (IAPE-A) proviral elements are present as repetitive copies in DNA from male but not female animals of M. musculus inbred strains and Mus musculus castaneus. Analysis of IAPE-cellular junction fragments indicates that fixation of most IAPEs in the germ line occurred in M. musculus and M. spretus after speciation but before M. musculus inbred strains were derived.

Animals↗

Integrated self-inactivating lentiviral vectors produce full-length genomic transcripts competent for encapsidation and integration.

To make human immunodeficiency virus type 1 (HIV-1)-based vectors safer for use in the research and clinical setting, a significant modification to the HIV-1 genome has been the deletion of promoter and enhancer elements from the U3 region of the long terminal repeat (LTR). Vectors containing this deletion are thought to have no LTR-directed transcription and are called self-inactivating (SIN) lentivectors. Using four distinct approaches, we show that SIN lentivectors continue to have promoter activity near the 5' LTR, which is responsible for the production of full-length vector transcripts. To verify that transcripts derived from the LTR in SIN lentivectors are competent for encapsidation and integration, we transduced a lentiviral packaging cell line with a SIN lentivector and then observed the production of viable vector particles containing full-length SIN lentivector genomes. We have also attempted to identify sequences in the SIN lentivector which are responsible for transcriptional activation at the 5' LTR. Using different segments of the vector LTR and leader region in a promoter assay, we have determined that the residual promoter activity is contained entirely within the leader region and that, although this element is downstream of the transcription initiation site, it is capable of initiating transcription from the 5' end of R in the LTR. Mutation of leader region binding sites for the transcriptional activators downstream binding factor 1 (DBF1) and SP1 reduces transcription from the SIN LTR by up to 80%. Knowledge of the potential for mobilization of HIV-1-derived SIN lentivectors will be important for the design of future gene therapy trials with such vectors.

Base Sequence↗

N-methyl-D-aspartate increases cytosolic Ca2+ via G proteins in cultured hippocampal neurons.

The changes of the cytosolic Ca2+ concentrations ([Ca2+]i) induced by N-methyl-D-aspartate (NMDA) in fura-2-loaded cultured hippocampal neurons from rat embryos were investigated by the fast application method, using a fine pipe under extracellular Mg(2+)-free conditions. In the presence of Ca2+, NMDA, at concentrations in excess of 3 microM, induced a biphasic increase of [Ca2+]i, which consisted of an initial increase with a second rise that occurred after cessation of drug application. Under Ca(2+)-free conditions, NMDA (greater than 100 microM) in the absence of glycine or NMDA (greater than 50 microM) in the presence of glycine (greater than 10 microM) induced intracellular Ca2+ mobilization, which was blocked by 30 microM 2-amino-5-phosphonovaleric acid (APV) and reduced by islet-activating protein. When the neurons were superfused with Ca(2+)-free solution, the application of 3-10 microM NMDA, which had been dissolved in Ca(2+)-containing solution, induced the second phase [Ca2+]i increase, whereas application of kainate, quisqualate, or stimulation by 50 mM K+ did not. Islet-activating protein, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), and D-sphingosine reduced the second phase [Ca2+]i increase. These results suggest that NMDA-induced intracellular Ca2+ mobilization is potentiated by the initial entry of Ca2+ into the cells and is regulated in an islet-activating protein-sensitive manner.

Animals↗

Intravenous catheter for intracorporeal plasma filtration.

Future advances in dialysis of end-stage renal disease patients may include improvements in therapeutic continuity and patient mobility. Continuous renal replacement therapies could lead to self-contained, mobile and potentially wearable dialysis units. We investigated an experimental, intravenous slow-continuous plasma separation system (IPSS) as a precursor to direct intravenous hemofiltration. An intracorporeal catheter employs asymmetric hollow fibers to separate blood cells from plasma in vivo. The fibers possess a sieving coefficient of 0.7 microm and remove 99.99% of all platelets. In vivo, catheters sustain an average plasma separation flow rate of 3 ml/min over 22 h, sufficient to remove 2 net liters of water from pigs through an extracorporeal hemofilter. Used catheter fibers are relatively free of protein deposition or clots in situ. In vitro studies suggest that human catheters may perform at 3-4 times the rate of porcine catheters. IPSS is proposed for acute fluid removal in CHF patients refractory to diuretics.

Animals↗

Ifosfamide in hematological malignancies of adults.

Ifosfamide is an alkylating agent with a broad spectrum of activity in solid tumors and hematological malignancies. In this review we will illustrate its use in the treatment of lymphomas and Hodgkin's disease and the results of the principal studies which have investigated ifosfamide-containing regimens. Ifosfamide has been mainly used, in combination with other drugs, as a component of salvage regimens for relapsed or primarily refractory lymphoma. These regimens induced a variable clinical response rate (complete remissions ranging from 6 up to 73% and overall response rate from 24 to 72%). High-dose ifosfamide, in combination with etoposide or mitoxantrone, showed a good potential for mobilization of peripheral stem cells while reducing the tumor burden. Ifosfamide-based regimens are also being evaluated in the treatment of newly diagnosed patients in sequential, response-based protocols, using many non-cross-resistant drugs.

Adult↗