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PubMed2001

Il-17 mobilizes peripheral blood stem cells with short- and long-term repopulating ability in mice.

Autologous and allogeneic bone marrow transplantations have evolved as important cancer therapy modalities. For both indications, peripheral blood has been shown to have distinct advantages over bone marrow as the stem cell source. Cytokine combinations for mobilization have enhanced stem cell yield and accelerated engraftment. However, novel mobilizing agents and strategies are needed to further improve clinical outcomes. Within the donor graft, the dynamic equilibrium between T cells and stem cells critically influences engraftment and transplantation results. IL-17 is a cytokine produced almost exclusively from activated T cells. IL-17 was expressed in vivo with adenovirus technology. Here, proof-of-principle studies demonstrate that IL-17 effectively mobilizes hemopoietic precursor cells (CFU-granulocyte-erythrocyte-macrophage-monocyte, CFU-high proliferative potential) and primitive hemopoietic stem cells (Lin(-/low)c-kit(+)Sca1(+)). Moreover, mouse IL-17 adenovirus-mobilized peripheral blood stem cells rescued lethally irradiated mice. Bone marrow was found to be 45-75% of donor origin at 1 year. In secondary recipients, donor-derived bone marrow cells ranged from 45 to 95%. These data show that IL-17 mobilizes stem cells in mice with short- and long-term reconstituting capacity. Additional comparative studies are needed as well as studies in tumor models to refine distinct potential clinical applications for IL-17-mobilized peripheral blood stem cells.

Animals↗
PubMed2006

The application of sub-2-microm particle liquid chromatography-operated high mobile linear velocities coupled to orthogonal accelerated time-of-flight mass spectrometry for the analysis of ranitidine and its impurities.

Impurity profiling of pharmaceutical drug substances or dosage formulations require methods involving high sensitivity and resolution from LC and MS alike as well as an acceptable analysis time. While throughput can be increased, it is usually at the expense of chromatographic resolution. The application of sub-2-microm stationary phases and high mobile linear velocities has been combined with orthogonal acceleration (oa)-TOF MS for the impurity structural characterization analysis of small-molecule pharmaceutics. A pharmaceutical drug substance was forcefully degraded and used to test the proof of concept of developing an impurity profile method by ultra performance liquid chromatography (UPLC). Optimum conditions were identified by use of method development simulation software as well as traditional approaches of method scouting with columns and a varied range of pH. Further analysis illustrated the effectiveness of applying oa-TOF MS techniques to assist in achieving exact mass coupled with MS/MS to define the structural characterization of the related substances relative to the pharmaceutical active ingredient and identification of any unknown impurity substances. The barriers with trade-offs between resolution and speed are overcome by the application of UPLC, whereas the increased sensitivity provides for superior exact mass oa-TOF MS.

Chemistry Techniques, Analytical↗
PubMed1988

Theory of relaxation of mobile water protons induced by protein NH moieties, with application to rat heart muscle and calf lens homogenates.

Kimmich and co-workers (cf., Winter, F., and R. Kimmich. 1982. Biochim. Biophys. Acta. 719:292-298) discovered peaks in the magnetic field-dependent longitudinal relaxation rate (1/T1) of water protons of muscle tissue, cells, and dehydrated protein in the field range 0.5-5 MHz (proton Larmor frequency), and argued that the peaks resulted from cross relaxation associated with quadrupolar splittings of the 14N nuclei of protein NH groups. More recently, analogous peaks were found in homogenates of calf eye lens (Beaulieu, C.F., J.I. Clark, R.D. Brown III, M. Spiller, and S. H. Koenig, 1987. Abstr. Soc. Magn. Res. Med., 6th, New York. 598-599), which are essentially concentrated protein solutions, and were measured with sufficient precision to allow resolution of the relaxation spectra into several peaks and the intrinsic linewidths to be determined. Here, we analyze these relaxation spectra, as well as earlier data on rat heart (Koenig, S. H., R. D. Brown III, D. Adams, D. Emerson, and C. G. Harrison. 1984. Invest. Radiol. 19:76-81) in some detail, and suggest a specific pathway for the cross relaxation to which we apply the theory of relaxation quantitatively. The view that emerges is that, at fields such that the proton Zeeman energy of the NH protons matches an 14N quadrupolar splitting, relaxation of these protons is by cross relaxation to the 14N nuclei which in turn transfer excess energy to the protein. The correlation time for the NH proton interaction is the T2 of the 14N nuclei, approximately 10(-6) s, whereas T1 of the NH protons is approximately 1.25 ms. At these energy level crossings, the NH protons become relaxation sinks for protons of rapidly exchanging (-3 x 109 s-1) water molecules hydrogen bonded to the same backbone carbonyl oxygens as the NH protons. The lifetime of this hydrogen bond (-3 x 10-10 s) then becomes the correlation time for the water proton-NH proton interaction which, though short, is much longer than the analogous correlation time (-5 x 10-12 s) in pure water; the enhanced interaction results in peaks in the field-dependent 1/ T, of the solvent protons. There are few data on the lifetime of such bonds, but the results here conform with the recent considerations of Bennett, H. F., R. D. Brown III, S. H. Koenig, and H. M. Swartz. 1987. Magn. Reson. Med. 4:93-111, regarding hydrogen bond lifetimes for water molecules bound to macromolecules. The recent precise field-dependent relaxation data, here combined with both a quantitative theory and the fact that the magnitude of the 14N peaks is very concentration sensitive, allow, at least for lens proteins, a study of protein-protein interactions difficult to investigate by other methods.

Amines↗
PubMed2002

Effect of external electrical field on mobile water fraction and physiological processes in wheat (Triticum aestivum) leaves.

Experiments were conducted to study the effect of external electric field on physiological processes, moisture content and mobile water fraction in wheat leaves. Application of electric field increased the stomatal resistance immediately and it continued to increase upto 10 min. Photosynthesis and respiration of leaves decreased with the application of external electric field. Leaf moisture content and mobile fraction of water measured as relaxation times were marginally increased with electric field. Closure of stomata, in spite of maintaining higher leaf moisture content of the leaf with external electric field, suggested that electric field might have regulated stomatal movement through hormones or ion flux across the cells.

Electric Stimulation↗
PubMed1989

Application of free-solution capillary electrophoresis to the analytical scale separation of proteins and peptides.

The application of free solution capillary electrophoresis (FSCE) to the separation of protein and peptide mixtures is presented. Both qualitative and quantitative aspects of FSCE separations are considered. In addition, a brief introduction describing the separation principle behind FSCE separations and a discussion of electrophoretic mobility are included. The applications were chosen in order to highlight the selectivity of FSCE separations and to demonstrate applications of potential practical interest to the bioanalytical chemist. Comparison of FSCE relative to traditional analytical separation alternatives is stressed throughout. The examples are presented in three broad categories: protein separations, peptide separations, and the application of both to the analysis of recombinant protein products. In the first section, FSCE separations of peptide mixtures are presented which demonstrate the suitability of FSCE for the analysis of the purity of peptide samples, the homogeneity of peptide samples prior to sequencing, the identity of peptides by using electrophoretic mobility values, and the reduction of an intrachain disulfide bridge. In the second section, protein separations are presented that show the resolution of glycoproteins having the same primary structure and the separation of immune complexes from free unreacted antibody and antigen. In the final section, highly purified and well-characterized samples of biosynthetic human insulin (BHI), biosynthetic human growth hormone (hGH), and their derivatives were used to evaluate FSCE as a complement and/or alternative to conventional analytical separation techniques for the determination of purity and identity of biosynthetic human proteins. In addition, the quantitative aspects of FSCE analysis such as linearity of response, precision, and limit of detection were examined.

Chromatography, High Pressure Liquid↗
PubMed2006

[Minimally invasive implantation of a unicondylar knee system].

OBJECTIVE: Unicondylar medial surface replacement of the knee joint by arthrotomy with short incision and in bone-sparing resection technique. INDICATIONS: Unicompartmental medial arthritis of the joint knee. Unilateral osteonecrosis. Posttraumatic unicompartmental gonarthrosis. CONTRAINDICATIONS: Pangonarthrosis. Rheumatoid arthritis. Knee joint instability. Status following osteotomy of the tibial head. SURGICAL TECHNIQUE: The patient should be placed in the supine position with the knee joint uncovered and freely mobile. Short anteromedial skin incision and arthrotomy. Bone-sparing resection at the tibia and femur. Axial malalignment (varus deformity) is not completely corrected. The implants are centered perpendicular to one another. POSTOPERATIVE MANAGEMENT: Early functional postoperative management adapted to the symptoms with pain therapy, local application of ice, passive mobilization on an electric exercise splint and physiotherapy. Full weight bearing is usually possible from the 2nd postoperative day. RESULTS: 28 Accuris unicondylar knee systems were implanted medially in 26 patients (14 women, twelve men) in minimally invasive technique from March 2003 to July 2004. One patient was not included in the evaluation because the operation was changed to a bicondylar surface replacement due to a deep-seated infection. The patients' average age at the time of the operation was 73.8 years. On average, the operation scar was 8.2 cm long. The average quantity of secretion in the Redon drain was 155 ml. The hemoglobin value fell from 13.3 to 12.3 g/dl. The total HSS (Hospital for Special Surgery) Score increased significantly from 55.5 (34-75) to 87.4 (71-95) points. In the follow-up examination, 21 unicondylar knee systems (77.8%) were evaluated as excellent and six (22.2%) as good.

Aged↗
PubMed1999

Sensory feedback in artificial control of human mobility.

Artificial motor control systems may reduce the handicap of motor impaired individuals. Sensors are essential components in feedback control of these systems and in the information exchange with the user. The objective of this paper is to give an overview of the applications of sensors in the artificial control of human mobility. These applications may either require an accurate estimate of the measured physical quantities or can be based on learning the relation between sensory information and control actions by example. Actual use of sensors in artificial motor control systems requires that the user experienced complexity of the system is not increased, while improving the repeatable and flexible functioning of the system. Therefore, the sensors need to be integrated with the mechanical part of the artificial support system or implanted, the information exchange between sensor and controller should be wireless and automatic in-use calibration is a desired feature.

Artificial Intelligence↗
PubMed2005

Pulmonary surfactant protein A activates a phosphatidylinositol 3-kinase/calcium signal transduction pathway in human macrophages: participation in the up-regulation of mannose receptor activity.

Surfactant protein A (SP-A), a major component of lung surfactant, binds to macrophages and has been shown to alter several macrophage biological functions, including up-regulation of macrophage mannose receptor (MR) activity. In the present study, we show that SP-A induces signal transduction pathway(s) that impact on MR expression. The addition of human, rat, or recombinant rat SP-A to human monocyte-derived macrophages significantly raised the level of cytosolic Ca2+ above baseline within 10 s of SP-A addition, as measured by spectrofluorometric analysis. SP-A induced a refractory state specific for SP-A consistent with homologous desensitization of a receptor(s) linked to calcium mobilization because a second application of SP-A did not induce a rise in cytosolic Ca2+ whereas the addition of platelet-activating factor did. Using site-directed mutations in SP-A, we determined that both the attached sugars and the collagen-like domain of SP-A are necessary to optimize Ca2+ mobilization. SP-A triggered the increase in cytosolic Ca2+ by inducing activation of phospholipase C, which leads to the hydrolysis of membrane phospholipids, yielding inositol 1,4,5-trisphosphate and mobilizing intracellularly stored Ca2+ by inositol triphosphate-sensitive channels. Finally, inhibition of PI3Ks, which appear to act upstream of phospholipase C in Ca2+ mobilization, decreased the SP-A-induced rise in MR expression, providing evidence that SP-A induction of MR activity involves the activation of a pathway in which PI3K is a component. These studies provide further evidence that SP-A produced in the lung plays a role in modulating macrophage biology, thereby contributing to the alternative activation state of the alveolar macrophage.

Adult↗
PubMed1992

Video imaging of cytosolic Ca2+ in pancreatic beta-cells stimulated by glucose, carbachol, and ATP.

In order to define the differences in the distribution of cytosolic free Ca2+ ([Ca2+]i) in pancreatic beta-cells stimulated with the fuel secretagogue glucose or the Ca(2+)-mobilizing agents carbachol and ATP, we applied digital video imaging to beta-cells loaded with fura-2.83% of the cells responded to glucose with an increase in [Ca2+]i after a latency of 117 +/- 24 s (mean +/- S.E., 85 cells). Of these cells, 16% showed slow wave oscillations (frequency 0.35/min). In order to assess the relationship between membrane potential and the distribution of the [Ca2+]i rise, digital image analysis and perforated patch-clamp methods were applied simultaneously. The system used allowed sufficient temporal resolution to visualize a subplasmalemmal Ca2+ transient due to a single glucose-induced action potential. Glucose could also elicit a slow depolarization which did not cause Ca2+ influx until the appearance of the first of a train of action potentials. [Ca2+]i rose progressively during spike firing. Inhibition of Ca2+ influx by EGTA abolished the glucose-induced rise in [Ca2+]i. In contrast, the peak amplitude of the [Ca2+]i response to carbachol was not significantly different in normal or in Ca(2+)-deprived medium. Occasionally, the increase of the [Ca2+]i rise was polarized to one area of the cell different from the subplasmalemmal rise caused by glucose. The amplitude of the response and the number of responding cells were significantly increased when carbachol was applied after the addition of high glucose (11.2 mM). ATP also raised [Ca2+]i and promoted both Ca2+ mobilization and Ca2+ influx. The intracellular distribution of [Ca2+]i was homogeneous during the onset of the response. A polarity in the [Ca2+]i distribution could be detected either in the descending phase of the peak or in subsequent peaks during [Ca2+]i oscillations caused by ATP. In the absence of extracellular Ca2+, the sequential application of ATP and carbachol revealed that carbachol was still able to raise [Ca2+]i after exhaustion of the ATP response. This may be due to desensitization to the former agonist, since the response occurred in the same area of the cell. These results reveal subtle differences in [Ca2+]i distribution following membrane depolarization with glucose or the application of Ca(2+)-mobilizing agonists.

Adenosine Triphosphate↗
PubMed2003

In-field labeling of western corn rootworm adults (Coleoptera: Chrysomelidae) with rubidium.

Field and laboratory studies were conducted in 2000 and 2001 to determine the feasibility of mass marking western corn rootworm adults, Diabrotica virgifera virgifera LeConte, with RbCl in the field. Results showed that application of rubidium (Rb) in solution to both the soil (1 g Rb/plant) and whorl (1 g Rb/plant) of corn plants was optimal for labeling western corn rootworm adults during larval development. Development of larvae on Rb-enriched corn with this technique did not significantly influence adult dry weight or survival. Rb was also highly mobile in the plant. Application of Rb to both the soil and the whorl resulted in median Rb concentrations in the roots (5,860 ppm) that were 150-fold greater than concentrations in untreated roots (38 ppm) 5 wk after treatment. Additionally, at least 90% of the beetles that emerged during the first 3 wk were labeled above the baseline Rb concentration (5 ppm dry weight) determined from untreated beetles. Because emergence was 72% complete at this time, a significant proportion of the population had been labeled. Results from laboratory experiments showed that labeled beetles remained distinguishable from unlabeled beetles for up to 4 d postemergence. The ability to efficiently label large numbers of beetles under field conditions and for a defined period with virtually no disruption of the population provides an unparalleled opportunity to conduct mark-recapture experiments for quantifying the short-range, intrafield movement of adult corn rootworms.

Animals↗
PubMed2004

Gingival necrosis following the use of a paraformaldehyde-containing paste: a case report.

AIM: To report on an unusual case of gingival necrosis following the use of a paraformaldehyde-containing paste in root canal treatment. SUMMARY: Paraformaldehyde preparations are toxic to hard and soft tissues. In an era of effective local anaesthesia, toxic devitalizing preparations have few applications. However, in a mobile world population, severe tissue injury may occasionally be encountered after the use of paraformaldehyde or other toxic agents in some parts of the world. Dentists should avoid such preparations and be alert of the features and management of local toxicity if they encounter it in practice. KEY LEARNING POINTS: Paraformaldehyde-containing pastes have no application in contemporary dentistry. Dentists should avoid toxic preparations for pulp devitalization. Dentists should be aware of the features and management of tissue necrosis resulting from the use of toxic dressing materials.

Adult↗
PubMed2005

Intermediate-conductance Ca2+-activated K+ channel is expressed in C2C12 myoblasts and is downregulated during myogenesis.

We report here the expression in C2C12 myoblasts of the intermediate-conductance Ca2+-activated K+ (IK(Ca)) channel. The IK(Ca) current, recorded under perforated-patch configuration, had a transient time course when activated by ionomycin (0.5 microM; peak current density 26.2 +/- 3.7 pA/pF; n = 10), but ionomycin (0.5 microM) + 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one (100 microM) evoked a stable outward current (28.4 +/- 8.2 pA/pF; n = 11). The current was fully inhibited by charybdotoxin (200 nM), clotrimazole (2 microM), and 5-nitro-2-(3-phenylpropylamino)benzoic acid (300 microM), but not by tetraethylammonium (1 mM) or D-tubocurarine (300 microM). Congruent with the IK(Ca) channel, elevation of intracellular Ca2+ in inside-out patches resulted in the activation of a voltage-insensitive K+ channel with weak inward rectification, a unitary conductance of 38 +/- 6 pS (at negative voltages), and an IC50 for Ca2+ of 530 nM. The IK(Ca) channel was activated metabotropically by external application of ATP (100 microM), an intracellular Ca2+ mobilizer. Under current-clamp conditions, ATP application resulted in a membrane hyperpolarization of approximately 35 mV. The IK(Ca) current downregulated during myogenesis, ceasing to be detectable 4 days after the myoblasts were placed in differentiating medium. Downregulation was prevented by the myogenic suppressor agent basic FGF (bFGF). We also found that block of the IK(Ca) channel by charybdotoxin did not inhibit bFGF-sustained myoblast proliferation. These observations show that in C2C12 myoblasts the IK(Ca) channel expression correlates inversely with differentiation, yet it does not appear to have a role in myoblast proliferation.

Adenosine Triphosphate↗
PubMed2006

Removal of PCB-DNAPL from a rough-walled fracture using alcohol/polymer flooding.

Phase behaviour experiments employing PCB (Aroclor 1242)/alcohol/water systems were conducted with ethanol (EtOH) and n-propanol (nPA). Both exhibited an affinity for the aqueous phase within the entire two-phase region. As much as 88% by volume (88% vol.) EtOH and 80% vol. nPA were necessary to achieve full miscibility of the PCB in the aqueous phase. DNAPL-water interfacial tension (IFT) was reduced from 38.9 dyn/cm to 4.7 dyn/cm and 2.4 dyn/cm with 80% vol. EtOH and 76% vol. nPA. The addition of alcohol brought about 41% and 54% reductions in DNAPL viscosity at maximal concentrations of EtOH and nPA. Density of the PCB-DNAPL was relatively unaffected by the presence of alcohol. A series of seven experiments were conducted where successive slugs of nPA and xanthan gum polymer solutions were injected into a fractured shale sample. A 30% vol. nPA solution injected under a hydraulic gradient of 0.36 allowed enhanced PCB removal primarily through reduction of IFT and resulted in 72% DNAPL recovery. Several pore volumes of alcohol solution were necessary to displace all the potentially mobile non-wetting phase since the high-viscosity DNAPL was mobilized at a lower flow rate than the overall fluid velocity, illustrating non-piston displacement. The injection of a 95% vol. nPA alcohol solution, theoretically at a sufficient concentration to produce fully miscible displacement of the residual DNAPL at equilibrium, resulted in non-equilibrium partitioning of the PCB into the flushing solution, likely due to the high fluid velocities in the fracture. The injection of 200 pore volumes of 95% vol. nPA solution resulted in 94% DNAPL recovery. Alcohol floods operated below the miscibility envelope appear to be a valuable source zone remedial alternative where the objective is to reduce DNAPL mobility to zero, but it should be noted that DNAPL mobility is increased during the application of the technology and steps may need to be taken to prevent unwanted vertical mobilization.

Alcohols↗
PubMed2003

High-performance thin-film transistors using semiconductor nanowires and nanoribbons.

Thin-film transistors (TFTs) are the fundamental building blocks for the rapidly growing field of macroelectronics. The use of plastic substrates is also increasing in importance owing to their light weight, flexibility, shock resistance and low cost. Current polycrystalline-Si TFT technology is difficult to implement on plastics because of the high process temperatures required. Amorphous-Si and organic semiconductor TFTs, which can be processed at lower temperatures, but are limited by poor carrier mobility. As a result, applications that require even modest computation, control or communication functions on plastics cannot be addressed by existing TFT technology. Alternative semiconductor materials that could form TFTs with performance comparable to or better than polycrystalline or single-crystal Si, and which can be processed at low temperatures over large-area plastic substrates, should not only improve the existing technologies, but also enable new applications in flexible, wearable and disposable electronics. Here we report the fabrication of TFTs using oriented Si nanowire thin films or CdS nanoribbons as semiconducting channels. We show that high-performance TFTs can be produced on various substrates, including plastics, using a low-temperature assembly process. Our approach is general to a broad range of materials including high-mobility materials (such as InAs or InP).

Journal Article↗
PubMed1998

The impact of L1 retrotransposons on the human genome.

The 'master' human mobile element, the L1 retrotransposon, has come of age as a biological entity. Knowledge of how it retrotransposes in vivo, how its proteins act to retrotranspose other poly A elements and the extent of its role in shaping the human genome should emerge rapidly over the next few years. We review the impact of retrotransposons and how new insight is likely to lead to important practical applications for these intriguing mobile elements.

Genome, Human↗
PubMed2006

Prioritization of pesticide environmental transformation products in drinking water supplies.

Receiving waters within catchments may be exposed to many different transformation products following the application of pesticides. As environmental waters are abstracted for drinking water treatment these compounds may pose a risk to human health. This paper describes a prioritization approach for identifying the most important transformation products in drinking water sources. The approach can be applied to different geographical areas that have suitable pesticide usage data. The risk based approach incorporates data on pesticide usage and toxicity as well as transformation product formation, mobility, and persistence. The application of the approach is illustrated for two geographical areas that have good quality pesticide usage data: Great Britain and California. The transformation products with the highest risk index and a complete experimentally derived data set for Great Britain were 3,5,6-trichloro-2-pyridinol, thifensulfuron acid, and kresoxim-methyl acid and for California were carbendazim, aldicarb sulfoxide, and RP30228.

California↗
PubMed2004

The presence of long-lived spin states in organic solids with rapid molecular motions.

For organic solids with sufficiently mobile molecular segments, the application of a long and weak pulse (gammaB1/2pi approximately Hz) can yield inverted sharp peaks with linewidths of approximately 100 Hz in the 1H NMR spectra, and the use of multi-frequency weak pulses can excite multiple inverted sharp peaks. For these compounds, the normal 1H free induction decay (FID) of a static sample contains a slowly decaying part, which can be detected by acquisition delay up to about 2 ms. The presence of highly mobile molecular segments can also be identified by using a "dipolar filter."

Electron Spin Resonance Spectroscopy↗