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51.
Boot EP Koning GA Storm G Wagenaar-Hilbers JP van Eden W Everse LA Wauben MH 《Arthritis research & therapy》2005,7(3):R604-R615
T cells have an important role during the development of autoimmune diseases. In adjuvant arthritis, a model for rheumatoid
arthritis, we found that the percentage of CD4+ T cells expressing the activation marker CD134 (OX40 antigen) was elevated before disease onset. Moreover, these CD134+ T cells showed a specific proliferative response to the disease-associated epitope of mycobacterial heat shock protein 60,
indicating that this subset contains auto-aggressive T cells. We studied the usefulness of CD134 as a molecular target for
immune intervention in arthritis by using liposomes coated with a CD134-directed monoclonal antibody as a drug targeting system.
Injection of anti-CD134 liposomes subcutaneously in the hind paws of pre-arthritic rats resulted in targeting of the majority
of CD4+CD134+ T cells in the popliteal lymph nodes. Furthermore, we showed that anti-CD134 liposomes bound to activated T cells were not
internalized. However, drug delivery by these liposomes could be established by loading anti-CD134 liposomes with the dipalmitate-derivatized
cytostatic agent 5'-fluorodeoxyuridine. These liposomes specifically inhibited the proliferation of activated CD134+ T cells in vitro, and treatment with anti-CD134 liposomes containing 5'-fluorodeoxyuridine resulted in the amelioration of adjuvant arthritis.
Thus, CD134 can be used as a marker for auto-aggressive CD4+ T cells early in arthritis, and specific liposomal targeting of drugs to these cells via CD134 can be employed to downregulate
disease development. 相似文献
52.
Mechanics of interstitial-lymphatic fluid transport: theoretical foundation and experimental validation 总被引:5,自引:0,他引:5
Swartz MA Kaipainen A Netti PA Brekken C Boucher Y Grodzinsky AJ Jain RK 《Journal of biomechanics》1999,32(12):311-1307
Interstitial fluid movement is intrinsically linked to lymphatic drainage. However, their relationship is poorly understood, and associated pathologies are mostly untreatable. In this work we test the hypothesis that bulk tissue fluid movement can be evaluated in situ and described by a linear biphasic theory which integrates the regulatory function of the lymphatics with the mechanical stresses of the tissue. To accomplish this, we develop a novel experimental and theoretical model using the skin of the mouse tail. We then use the model to demonstrate how interstitial–lymphatic fluid movement depends on a balance between the elasticity, hydraulic conductivity, and lymphatic conductance as well as to demonstrate how chronic swelling (edema) alters the equipoise between tissue fluid balance parameters. Specifically, tissue fluid equilibrium is perturbed with a continuous interstitial infusion of saline into the tip of the tail. The resulting gradients in tissue stress are measured in terms of interstitial fluid pressure using a servo-null system. These measurements are then fit to the theory to provide in vivo estimates of the tissue hydraulic conductivity, elastic modulus, and overall resistance to lymphatic drainage. Additional experiments are performed on edematous tails to show that although chronic swelling causes an increase in the hydraulic conductivity, its greatly increased distensibility (due to matrix remodeling) dampens the driving forces for fluid movement and leads to fluid stagnation. This model is useful for examining potential treatments for edema and lymphatic disorders as well as substances which may alter tissue fluid balance and/or lymphatic drainage. 相似文献
53.
Pandinus imperator scorpion venom blocks voltage-gated potassium channels in GH3 cells 总被引:1,自引:1,他引:0
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We examined the effects of Pandinus imperator scorpion venom on voltage-gated potassium channels in cultured clonal rat anterior pituitary cells (GH3 cells) using the gigohm-seal voltage-clamp method in the whole-cell configuration. We found that Pandinus venom blocks the voltage-gated potassium channels of GH3 cells in a voltage-dependent and dose-dependent manner. Crude venom in concentrations of 50-500 micrograms/ml produced 50-70% block of potassium currents measured at -20 mV, compared with 25-60% block measured at +50 mV. The venom both decreased the peak potassium current and shifted the voltage dependence of potassium current activation to more positive potentials. Pandinus venom affected potassium channel kinetics by slowing channel opening, speeding deactivation slightly, and increasing inactivation rates. Potassium currents in cells exposed to Pandinus venom did not recover control amplitudes or kinetics even after 20-40 min of washing with venom-free solution. The concentration dependence of crude venom block indicates that the toxins it contains are effective in the nanomolar range of concentrations. The effects of Pandinus venom were mimicked by zinc at concentrations less than or equal to 0.2 mM. Block of potassium current by zinc was voltage dependent and resembled Pandinus venom block, except that block by zinc was rapidly reversible. Since zinc is found in crude Pandinus venom, it could be important in the interaction of the venom with the potassium channel. We conclude that Pandinus venom contains toxins that bind tightly to voltage-dependent potassium channels in GH3 cells. Because of its high affinity for voltage-gated potassium channels and its irreversibility, Pandinus venom may be useful in the isolation, mapping, and characterization of voltage-gated potassium channels. 相似文献
54.
Howe GT; Bucciaglia PA; Hackett WP; Furnier GR; Cordonnier-Pratt MM; Gardner G 《Molecular biology and evolution》1998,15(2):160-175
The phytochrome photoreceptors play important roles in the photoperiodic
control of vegetative bud set, growth cessation, dormancy induction, and
cold-hardiness in trees. Interestingly, ecotypic differences in
photoperiodic responses are observed in many temperate- zone tree species.
Northern and southern ecotypes of black cottonwood (Populus trichocarpa
Torr. & Gray), for example, exhibit marked differences in the timing of
short-day-induced bud set and growth cessation, and these responses are
controlled by phytochrome. Therefore, as a first step toward determining
the molecular genetic basis of photoperiodic ecotypes in trees, we
characterized the phytochrome gene (PHY) family in black cottonwood. We
recovered fragments of one PHYA and two PHYB using PCR-based cloning and by
screening a genomic library. Results from Southern analyses confirmed that
black cottonwood has one PHYA locus and two PHYB loci, which we arbitrarily
designated PHYB1 and PHYB2. Phylogenetic analyses which included PHY from
black cottonwood, Arabidopsis thaliana and tomato (Solanum lycopersicum)
suggest that the PHYB/D duplications in these species occurred
independently. When Southern blots were probed with PHYC, PHYE, and PHYE
heterologous probes, the strongest bands that we detected were those of
black cottonwood PHYA and/or PHYB. These results suggest that black
cottonwood lacks members of the PHYC/F and PHYE subfamilies. Although black
cottonwood could contain additional PHY that are distantly related to known
angiosperm PHY, our results imply that the PHY family of black cottonwood
is less complex than that of other well-characterized dicot species such as
Arabidopsis and tomato. Based on Southern analyses of five black cottonwood
genotypes representing three photoperiodic ecotypes, substantial
polymorphism was detected for at least one of the PHYB loci but not for the
PHYA locus. The novel character of the PHY family in black cottonwood, as
well as the differences in polymorphism we observed between the PHYA and
PHYB subfamilies, indicates that a number of fundamental macro- and
microevolutionary questions remain to be answered about the PHY family in
dicots.
相似文献
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57.
Salerno A Zeppetelli S Di Maio E Iannace S Netti PA 《Biotechnology and bioengineering》2011,108(4):963-976
In this study, we investigated the processing/structure/property relationship of multi-scaled porous biodegradable scaffolds prepared by combining the gas foaming and NaCl reverse templating techniques. Poly(ε-caprolactone) (PCL), hydroxyapatite (HA) nano-particles and NaCl micro-particles were melt-mixed by selecting different compositions and subsequently gas foamed by a pressure-quench method. The NaCl micro-particles were finally removed from the foamed systems in order to allow for the achievement of the multi-scaled scaffold pore structure. The control of the micro-structural properties of the scaffolds was obtained by the optimal combination of the NaCl templating concentration and the composition of the CO2-N2 mixture as the blowing agent. In particular, these parameters were accurately selected to allow for the fabrication of PCL and PCL-HA composite scaffolds with multi-scaled open pore structures. Finally, the biocompatibility of the scaffolds has been assessed by cultivating pre-osteoblast MG63 cells in vitro, thus demonstrating their potential applications for bone regeneration. 相似文献
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59.
Dermis is a heterogeneous tissue in which extracellular matrix components change in relative amount and spatial assembly across the tissue thickness. The effect of the microstructural and compositional heterogeneities on the overall mechanical response of dermis is, however, largely ignored. In this work, we aimed at gaining a better insight into the effect of extracellular matrix microstructure and composition on the mechanical behaviour of different dermal strata by combining mechanical analysis and selective enzymatic digestion of extracellular matrix components. The dynamical–mechanical tests we performed on bovine dermal splits show that the upper dermal stratum, which is richer in papillary dermis, is characterized by higher mechanical properties than the lower one, which is almost composed of reticular dermis. Moreover, the depletion of interfibrillar proteins, proteoglycans and glycosamminoglycans decreases the dynamic moduli of dermis, especially at small frequencies. Of the two dermal layers tested, the upper dermal layer is more sensitive to the enzymatic treatment than the lower layer. Interestingly, the disruption of the elastic network greatly influenced the viscoelastic properties of upper dermis, inducing a dramatic decrease of both storage (G′) and loss (G″) moduli, suggesting that the spatial assembly of the elastin and collagen networks as well as their mutual interactions dominate the dynamical mechanical response of the tissue. 相似文献
60.
Guidobono F Pagani F Sibilia V Netti C Lattuada N Rapetti D Mrak E Villa I Cavani F Bertoni L Palumbo C Ferretti M Marotti G Rubinacci A 《Peptides》2006,27(6):1426-1433
This study was designed to evaluate whether or not continuous intracerebroventricular infusion of leptin (1.5 microg/rat/24 h, for 28 days) produced different regional response on the skeleton of growing rats. Leptin reduce the accretion of total femoral bone mineral content (BMC) and density (BMD). This effect was related to a reduction of metaphyseal femur as no changes were detected in the diaphysis. Despite the reduced accretion in the volumetric of both femur and tibia compared to controls, leptin had no significant effects on the lumbar vertebrae. Urine deoxypyrydinoline and serum osteocalcin remained more elevated in the leptin-treated group as compared to controls. The results demonstrate that long-term central infusion of leptin activates bone remodeling with a negative balance. Leptin induces distinct responses in the different structure of bone and in the axial and appendicular skeleton. 相似文献