Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial cell growth factor (ECGF) stimulates vascularization, however its relatively short half-life requires this angiogenic factor to be frequently administrated by non-specific and uncontrolled methods. This work describes the use of biocompatible chitosan, a polysaccharide having structural similarity to glycosaminoglycans, -albumin microspheres, as well as its fiber form, as a potential delivery system for the controlled and localized release of ECGF. Chitosan-albumin microspheres (400-600 microns) and fibers, formed in 0.5 M sodium hydroxide-methanol solution were incubated with ECGF. In vitro release was performed in PBS at 37 degrees C, under constant stirring. In vivo experiments were realized by implanting ECGF loaded matrices subcutaneously into rat groin fascia. After an initial ECGF burst of 1.32-1.62 mg (22-27%) within the first 2 hours, a daily release of 120-420 micrograms (2-7%) during the first, and 60-240 micrograms (1-4%) during the second week was observed from M(r) 70.000, 750.000, and 2,000.000 chitosan containing microspheres of 6 mg/ml loading. ECGF release rate of < 30 micrograms (0.5%)/day was maintained during the third week of experiments. By the increase in ECGF loading (12 mg/ml polymer), while the amount of release increased, percent release decreased. Chitosan-albumin fibers gave a ECGF release rate nearly similar to microspheres, and in vivo studies demonstrated a high degree of neovascularization for both types of implants, starting from 7 day-post implantation. Control animals that received ECGF injection did not show any significant neovascularization, after same period of time.
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PMID:Controlled release of endothelial cell growth factor from chitosan-albumin microspheres for localized angiogenesis: in vitro and in vivo studies. 877 42

The engraftment of human peripheral blood mononuclear cells (Hu-PBMC) from adult donors in scid mice has been published by MOSIER et al. in 1988. The possibility to obtain a secondary human immune response in human-scid mice has also been reported but attempts to induce a primary human immune response still remain difficult to achieve. In this work, an antigen (Canine albumin) or a hapten (DNP) was coupled with tetanus toxoid, an antigenic protein against which our human donors already had memory T cells through vaccination. In this way, hu-scid mice immunized with coupled DNP-tetanus toxoid (TT-DNP) or coupled Canine albumin-Tetanus toxoid (Calb-TT) mounted a specific human immune response anti-DNP or anti-Canine albumin (Calb) respectively. A secondary human immune response anti-tetanus toxoid was also detected in the sera of hu-scid mice immunized with product containing TT but not in the sera of those injected with PBS alone. The scid mice grafted with Hu-PBMC from a TT naive donor and challenged with Calb-TT or Calb alone failed to produce specific anti-Calb antibodies. These observations demonstrate that memory T cells can give a substantial help to naive B cells which interact with them for obvious B cell activation and differentiation into plasma cells. This model of immunization might be useful for other antigens of choice, allowing the production of human monoclonal antibodies, in combination with a suitable system of immortalization. Attempts to immunize human cells in scid mice against DNP coupled to LO-BM2 (a rat monoclonal antibody anti-human IgM) failed to induce a specific human response either anti-rat immunoglobulins (Igs), or anti-DNP and led to a decrease of human Ig production in hu-scid. We also immunized hu-scid mice against ovalbumin alone but, only in some cases, a low specific human immune response was observed, so this system seems to be unreliable.
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PMID:A promising model of primary human immunization in human-scid mouse. 887 9

The hyperpermeability of tumor vessels to macromolecules, compared with normal vessels, is presumably due to vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) released by neoplastic and/or host cells. In addition, VEGF/VPF is a potent angiogenic factor. Removal of this growth factor may reduce the permeability and inhibit tumor angiogenesis. To test these hypotheses, we transplanted a human glioblastoma (U87), a human colon adenocarcinoma (LS174T), and a human melanoma (P-MEL) into two locations in immunodeficient mice: the cranial window and the dorsal skinfold chamber. The mice bearing vascularized tumors were treated with a bolus (0.2 ml) of either a neutralizing antibody (A4.6.1) (492 micrograms/ml) against VEGF/VPF or PBS (control). We found that tumor vascular permeability to albumin in antibody-treated groups was lower than in the matched controls and that the effect of the antibody was time-dependent and influenced by the mode of injection. Tumor vascular permeability did not respond to i.p. injection of the antibody until 4 days posttreatment. However, the permeability was reduced within 6 h after i.v. injection of the same amount of antibody. In addition to the reduction in vascular permeability, the tumor vessels became smaller in diameter and less tortuous after antibody injections and eventually disappeared from the surface after four consecutive treatments in U87 tumors. These results demonstrate that tumor vascular permeability can be reduced by neutralization of endogenous VEGF/ VPF and suggest that angiogenesis and the maintenance of integrity of tumor vessels require the presence of VEGF/VPF in the tissue microenvironment. The latter finding reveals a new mechanism of tumor vessel regression-i.e., blocking the interactions between VEFG/VPF and endothelial cells or inhibiting VEGF/VPF synthesis in solid tumors causes dramatic reduction in vessel diameter, which may block the passage of blood elements and thus lead to vascular regression.
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PMID:Time-dependent vascular regression and permeability changes in established human tumor xenografts induced by an anti-vascular endothelial growth factor/vascular permeability factor antibody. 896 29

The functional properties of 125I-labeled antibodies and antigens adsorbed on polystyrene and silicone were compared to their counterparts immobilized by non-adsorptive methods. Less than 20% of polyclonal (pAb) and 1-2% of monoclonal (mAb) capture antibody equivalents remained functional after adsorption as a monolayer. Survivability circa doubled or was totally rescued, when the same antibodies were immobilized via a streptavidin bridge or by using a first stage polyclonal antiglobulin capture antibody, respectively. Similarly, the antigenicity of bovine IgGs for pAb and mAb anti-IgGs was highest when the IgGs were immobilized via a streptavidin bridge or when secondarily adsorbed to an albumin monolayer. IgGs in these configurations were significantly more antigenic than when directly adsorbed on polystyrene or a silicone elastomer. Similar activity was seen after adsorption on polystyrene or silicone. Interestingly, these IgGs were equally antigenic when denatured and subsequently adsorbed in 6M guanidine-HCl versus adsorption in PBS without prior denaturation. Although many of the above finding on antibodies and antigens could be explained by the greater accessibility of antigenic epitopes or antibody binding sites when molecules are immobilized by some type of underlying molecular layer, we also show that certain mAb and pAbs preferentially recognized allotopes on IgG2a when IgG2a was adsorbed. Furthermore, such antigenicity was highest when IgG2a was adsorbed at low, sub-monolayer concentrations. Finally, we show that differences in antigenicity need not be related to the method of immobilization, but can also result from differences in the microenvironment of the epitope. This was demonstrated using a filamentous phage clone specific for fluorescein (FLU). This clone recognizes the fluorescein hapten differently depending on the carrier protein used and the method of conjugation. Data presented in this report indicate that antibodies and antigens adsorbed on hydrophobic polymers undergo changes in their functional properties. Data suggest that both changes in conformation and the accessibility of antigen epitopes or antibody binding sites, most likely occur. Especially in the case of the latter, the functional concentration may be 1-2 orders of magnitude lower than the antibody protein concentration. These observations have implications for immunodiagnostics and emphasize the need to determine the specificity of an antibody in the assay in which it is employed and to make no assumptions about the behavior of solid-phase antigens and antibodies from their behavior in solution. Our studies are also relevant to the use of silicone medical prostheses. The antigenicity of IgGs adsorbed on silicone as a multilayer (secondary layer) is much higher than when directly adsorbed. Since such surfaces would be exposed to very high protein concentrations in vivo, multilayers not a monolayer, would be expected. Thus it would seem from these studies that host protein adsorbed on silicone would be expressed to the immune system at the surface of multilayers. This being the case, it seems unlikely that the adsorption of host protein in vivo would generate new epitopes against which the host's immune system could respond and subsequently initiate an autoimmune syndrome.
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PMID:Adsorption-induced antigenic changes and their significance in ELISA and immunological disorders. 903 11

The mechanisms involved in the bioavailability of chlorambucil or 4-[p-(bis[2-hydroxyethyl]amino)phenyl]-butyric acid are poorly understood. The effects of different matrices on the disintegration of chlorambucil were investigated by HPLC, 1H NMR, 31P NMR, and mass spectrometry. Cellular incorporation and protein binding of the drug in vitro was assessed with [3H]-chlorambucil. Decomposition of chlorambucil and its major metabolite, phenylacetic acid mustard, to mono- and dihydroxy derivatives, was significantly faster in water than in PBS, (phosphate-buffered saline, pH 7.4). The hydrolysis of chlorambucil was as fast in plasma ultrafiltrate as in PBS; plasma proteins, preferentially albumin, prevented this disintegration. In phosphate-buffered media, two additional stabile hydrolysis products were found which were characterised as the mono- and bis-phosphates of 4-[p-(bis[2-hydroxyethyl]amino)phenyl]butyric acid, results of the reaction of nucleophilic buffer species with the aziridinium ion intermediates. Chlorambucil bound covalently to plasma proteins and was incorporated into red cells. These interactions are likely to have a significant role in vivo, reducing the bioavailability of the drug. High H+ concentration associated with high chloride concentration in human gastric juice had a stabilizing effect on chlorambucil. Incorporation of [3H]-chlorambucil into red cells was inhibited in a concentration-dependent fashion by whole human plasma as well as by albumin. We conclude that the chemico-biological interactions demonstrated in the present investigation provide explanations for the remarkable pharmacokinetic differences observed intra- and inter-individually in the clinical use of chlorambucil. The present information is important, when clinical or in vitro evaluation of efficacy and bioavailability of chlorambucil is considered.
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PMID:Kinetics of chlorambucil in vitro: effects of fluid matrix, human gastric juice, plasma proteins and red cells. 913 9

Hemodilution with plasma expanders is a widely applied practice during extracorporeal circulation and hemodialysis. Despite the immediate beneficial effects of hemodilution, such as reduction of blood viscosity and red blood cell (RBC) aggregation, elevation of blood flow in the microcirculation, etc., the dilution of plasma may cause some unfavorable effects on RBCs, amplifying the mechanical damage caused by circulatory assist devices. The authors investigated the effect of partial and total replacement of plasma on susceptibility of human and bovine RBCs to mechanical stress in vitro. Hemolysis was measured after the exposure of RBCs suspended in different media to similar mechanical stress. Experiments were performed at room temperature with control of osmolality and viscosity of the suspension media. The lowest hemolysis was obtained for RBCs suspended in serum, plasma, and albumin solutions. Hemolysis in PBS and Dextran suspensions was more than three times higher than that in plasma (p < 0.001). The protective effect depended upon protein concentration. Human RBCs were found to be significantly more sensitive to mechanical stress than bovine RBCs in all investigated suspension media (p < 0.005). Human RBCs from men suspended in plasma were found to be significantly (p < 0.05) more fragile than RBCs from women. The presence of even small amounts of plasma (such as 25%) in the suspension media significantly (p < 0.001) decreased hemolysis. However, a 30% replacement of plasma with PBS or Dextran solutions caused a statistically significant (p < 0.001) increase in mechanical hemolysis. This suggests that a decrease in the concentration of plasma proteins due to hemodilution may elevate blood damage during extracorporeal circulation and hemodialysis.
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PMID:Plasma protective effect on red blood cells exposed to mechanical stress. 936 Jan 9

During tobacco burning smoker to run up substances to contain smoke as far as pulmonary tissue that is damage. In cigarette 600 degrees C are in ignition extreme, but in the other side, in contact with edge of the mouth smoker, the temperature is lower. Smoke could be delivery tobacco products until respiratory tract when temperature gradients occur in cigarette burn. For demonstration of the immunoreactive substances in tobacco smoke condense (TSC) we used a model with two cigarette arrangements: several concentrations of bovine seric albumin (BSA) applied to experimental group of cigarettes and phosphate-saline solution (PBS), 0.15 M pH 7.5 without protein to control cigarettes. Both series, experimental and control, remained at 20 degrees C during 48 h, soon afterward TSC was obtained. Higher protein concentration was observe in the experimental TSC of cigarettes expose to more elevated quantities of BSA, this was identify with polyclonal antibodies toward BSA employing counter-immunoelectrophoresis, immunoelectrophoresis, radial immunodiffusion and hemagglutination inhibition test. In summary: TSC of treat cigarettes had a little quantity of protein (BSA), but immunochemical properties of BSA in TSC were preserve because polyclonal antibodies against BSA bind to this protein. In habitual smoker some compounds present in cigarette smoke could be induce an immune response due to immunogen in tobacco substances.
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PMID:[Effect of tobacco combustion on the immunochemical properties of albumin]. 943 71

Poly(lactide co-glycolide) (PLG) microparticles with a mean size of less than 2 microns, prepared by the water-in oil-in water method, exhibited a maximum surface protein (ovalbumin) content in excess of 50% of the total loading. The surface-core distribution was found to be sensitive to stabiliser concentration and the type of albumin used in the formulation. The degradation of OVA was monitored following incubation of microparticles for 14 days in PBS and for 2 h in simulated gastric and intestinal fluids, respectively. OVA removed from the surface of particles, following incubation in PBS, was found to be intact as measured by SDS-PAGE. After 7 days in PBS at 37 degrees C, protein extracted from the microparticles was found to be partly hydrolysed with the prevalence of an antigen fragment at 36.1 kDa. The relative amount of intact OVA in 50:50 PLG microparticles decreased more rapidly than in the slower degrading 75:25 PLG microparticles. Importantly, the degradation of extracted OVA over 14 days was similar for microparticles incubated either with regular changes of release medium or in a dialysis tube. Almost all the OVA encapsulated in PLG microparticles remained intact after incubation in simulated gastric and intestinal media for 2 h. In contrast, the surface protein was rapidly degraded by trypsin and pepsin and was not detected by SDS-PAGE.
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PMID:The distribution of protein associated with poly(DL-lactide co-glycolide) microparticles and its degradation in simulated body fluids. 968 90

The efficacy of mafosfamide purging depends on factors like incubation time, drug and erythrocyte concentration. To determine the influence of protein-bound SH groups in the incubation medium, the cytotoxicity of mafosfamide on G-CSF mobilized CD34+/- cells was evaluated by short-term culture assays and drug concentration measurements. 100 micromol/ml mafosfamide was incubated for 30 min in five buffers (PBS, PBS with 1%, 5% and 10% BSA and plasma). The mean calculated areas under the concentration-time curves (AUC) were 2489 +/- 198, 1561 +/- 286, 976 +/- 201, 585 +/- 62 and 605 +/- 196 micromol/l/min. The mean reductions of CFU-GM growth were 79.4%, 73.0%, 62.5%, 30.3%, 6.2% respectively. Similar results were obtained for BFU-E. Regression analysis showed a good correlation between cytotoxicity and AUCs (CFU-GM: r = 0.8195; BFU-E: r = 0.8207). This effect is well explained by the different concentrations of SH moieties in the incubation medium resulting in a higher drug binding capacity. The profound difference between AUCs and CFU-GMs in plasma and 10% BSA cannot be explained by the quantity of SH-groups. It is probably due to an additional enzymatic drug degeneration by the 3'-5'exonuclease subsite of plasma DNA polymerase. In conclusion, the concentration of albumin-associated SH groups strongly influences the cytotoxicity of mafosfamide. It has to be considered as a new and important aspect in ex vivo bone marrow purging.
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PMID:The cytotoxicity of mafosfamide on G-CSF mobilized hematopoietic progenitors is reduced by SH groups of albumin--implications for further purging strategies. 1019 1

Red blood cell (RBC) aggregation is of prime importance in vivo and in vitro for low flow rates. It may be estimated by rheometrical measurements at low shear rates, but these are perturbed by slip and migrational effects which have already been highlighted in the past. These effects lead to a torque decay with time so that the true value of the stress at low shear rates may be greatly underestimated. Elevated aggregation being associated with different diseases, pathological blood samples show more pronounced perturbing effects and a strong time dependency in low shear rate rheometry. To test the dependence of slip and migrational effects on RBC aggregation, and particularly to determine the way in which they depend upon fibrinogen concentration ([Fb]), a home-made measuring system with roughened internal and external walls (170 microns roughness) was used to study low shear rate rheometry for RBC suspensions in PBS buffer containing albumin (at 50 g/l) and fibrinogen at various concentrations. The influences of hematocrit, shear rate, and fibrinogen concentration were investigated. Particular attention was paid to data acquisition at low shear rates (10(-3) s-1 to 3 x 10(-2) s-1). The combined influence of hematocrit and fibrinogen was investigated by adjusting hematocrit to 44 or 57% and fibrinogen concentration ([Fb]) to 3.0-4.5-6.5 g/l. Microscopic observations of the blood samples at rest were performed. They showed that different structures were formed according to fibrinogen concentration. The rheometrical measurements indicated that torque decay with shearing duration was strongly dependent on fibrinogen concentration and on shear rate at fixed hematocrit. Migrational and slip effects were more pronounced as shear rate decreased, fibrinogen concentration was raised, and hematocrit was lowered. The results have been explained on the basis of the expected microstructure of flowing blood in relation to the microscopic observations at rest.
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PMID:Blood low shear rate rheometry: influence of fibrinogen level and hematocrit on slip and migrational effects. 1047 59


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