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)

Experiments were carried out on Buffalo rats with implantable Morris hepatoma 5123 growing in the skeletal muscles of the limbs. Mutein VI (a protein which differs from the native TNF-alpha molecule in its N-terminal amino acid composition) was administered at a dose of 10 micrograms per rat once a day in a cycle of 8 days. Control animals were given saline (PBS). Ultrastructural changes within the pulmonary tissue were evaluated with an electron transmission microscope (TEM), with special attention paid to endothelial cells and alveolar epithelial cells. Quantitative analysis of neoplastic metastases to the lungs was carried out. The animals given mutein VI compared to those injected with PBS demonstrated a decrease in the number of metastases. TEM pictures showed accumulations of eosinophilic granulocytes and monocytes in the lumen of the blood vessels. Enhanced activity of endothelial cells was observed. In pulmonary alveoli conglomerates of fibrin, and fragments of damaged cells were found, with erythrocytes, granulocytes and macrophages in their vicinity. The epithelium of pulmonary alveoli showed signs of considerable damage, including necrosis. The mutein VI-hrec TNF-alpha was found to block the neoplastic process, illustrated by a reduction in the volume of lung parenchyma occupied by neoplastic metastases. Also, the ultrastructural changes observed in the pulmonary tissue indicate the possibility of peripheral action of mutein VI after its administration to rats carrying the Morris hepatoma.
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PMID:Studies on pulmonary tissue after administration of mutein VI-HREC TNF-alpha into implantable experimental Morris hepatoma. 906 67

The diblock polymer poly(l-leucine-block-l-glutamate), bLE, was synthesized by acid hydrolysis of the ester poly(l-leucine-block-l-methyl glutamate). During the hydrolysis reaction the leucine block precipitates from the reaction mixture, forming nanosized particulate structures. These particles can be purified and further suspended in water or in 0.15 M phosphate saline buffer (PBS) to give stable, colloidal dispersions. TEM analysis shows the predominant particle form to be that of platelets with a diameter of 200 nm. Smaller cylindrical or spherical particles form a relatively minor fraction of the sample. After fractionation, analysis shows the platelets to be compositionally rich in leucine, while the spheres are glutamate-rich. (1)H NMR, CD, and X-ray diffraction indicate that the core of the platelets is composed of crystalline, helical leucine segments. The poly(l-glutamate) polyelectrolyte brush extending out from the two faces of the disk stabilizes individual particles from flocculation. At pH 7.4, the nanoparticles (platelets and cylinders) spontaneously adsorb proteins, such as insulin, directly from solution. Partial desorption of the protein in its native configuration can be induced by simple dilution. The reversibility of the insulin-nanoparticle complex is the basis for a potential new delivery system. Copyright 1999 Academic Press.
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PMID:Macromolecular Colloids of Diblock Poly(amino acids) That Bind Insulin. 1046 44

Chitosan nanoparticles (CS NP) with various formations were produced based on ionic gelation process of tripolyphosphate (TPP) and chitosan. They were examined with diameter 20-200 nm and spherical shape using TEM. FTIR confirmed tripolyphosphoric groups of TPP linked with ammonium groups of chitosan in the nanoparticles. Factors affecting delivery properties of bovine serum albumin (BSA) as model protein have been tested, they included molecular weight (Mw) and deacetylation degree (DD) of chitosan, the concentration of chitosan and initial BSA, and the presence of polyethylene glycol (PEG) in encapsulation medium. Increasing Mws of chitosan from 10 to 210 kDa, BSA encapsulation efficiency was enhanced about two times, BSA total release in PBS (phosphate buffer saline) pH 7.4 in 8 days was reduced from 73.9 to 17.6%. Increasing DD from 75.5 to 92% promoted slightly the encapsulation efficiency and decelerated the release rate. The encapsulation efficiency was highly decreased by increase of initial BSA and chitosan concentration; higher loading capacity of BSA speeded the BSA release from the nanoparticles. Adding PEG hindered the BSA encapsulation and accelerated the release rate.
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PMID:Effect of molecular structure of chitosan on protein delivery properties of chitosan nanoparticles. 1248 Feb 87

Our previous studies have indicated that the IgG-binding M-family proteins (IgGBP) of group A streptococci may be involved in eliciting experimental acute poststreptococcal glomerulonephritis (APSGN) in the rabbit. These surface proteins were also found to trigger production of anti-IgG, which might conceivably act to enhance renal deposition of immune complexes (IC). In the present study, a clinical isolate of serotype M22 (strain AL168), an isogenic double mutant deficient for both the IgGBPs Mrp and Emm, as well as mutants deficient in only one of the proteins were tested for capacity to induce glomerulonephritis. Streptococci to be used for injecting rabbits were heat-killed. Surface-bound IgG was removed by 1 M KSCN and cells were then repeatedly washed in PBS before use. Rabbits were injected intravenously with 109 cells three times a week for 8 weeks and, following one month of rest, for another 6 weeks. Deposits of IgG and C3 as well as induced chemokines TNF-alpha, IL-1beta and IL-6 were traced in cryostat sections using specific antibodies and appropriate peroxidase-labelled anti-antibodies. In four rabbits immunized with the double mutant strain, no deposits were found, and as examined by TEM, only subtle and transient renal changes were observed. In contrast, the original strain AL168 induced pronounced inflammatory and degenerative glomerular changes in all four rabbits injected, and deposits of TNF-alpha, IL-1beta and IL-6 were found in mesangial and endothelial cells. Similar deposits and glomerular changes were seen in all eight rabbits injected with the mrp-emm+ mutant and in four out of seven animals receiving the mrp+emm- mutant. There was a highly significant correlation between high levels of circulating anti-IgG and development of APSGN. These results confirm an important role of streptococcal IgGBP in triggering experimental APSGN as earlier proposed by our group.
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PMID:Role of group A streptococcal IgG-binding proteins in triggering experimental glomerulonephritis in the rabbit. 1461 48

The layer-by-layer (LbL) self-assembly of poly-l-lysine (PLL) and deoxyribonucleic acid (DNA) was used to construct the enzymatic biodegradable multilayered films. The LbL build up of DNA multilayers was monitored by UV-vis spectrometry, and atomic force microscopy (AFM). AFM, UV-vis spectrometry and fluorescence spectrometry measurements indicated that 90% of DNA within the films was released almost linearly under 5 U mL(-1)alpha-chymotrypsin in PBS at 37 degrees C in 35 h. TEM and zeta potential experiments revealed that the released DNA molecules were condensed into the slight positive complexes with size from 20 to several hundred nanometers. The well-structured, easy processed enzymatic biodegradable multilayered film may have great potential for gene applications in tissue engineering, medical implants, etc.
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PMID:Construction and enzymatic degradation of multilayered poly-l-lysine/DNA films. 1610 14

Thermally responsive amphiphilic poly(N-isopropylacrylamide) (PNIPAm)-grafted-polyphosphazene (PNIPAm-g-PPP) was synthesized by stepwise cosubstitution of chlorine atoms on polymer backbones with amino-terminated NIPAm oligomers and ethyl glycinate (GlyEt). Polymer structure was confirmed by FT-IR, (1)H NMR, elemental analysis, and GPC. The thermosensitivity of PNIPAm-g-PPP aqueous solution was investigated by turbidity method. The lower critical solution temperature (LCST) of PNIPAm-g-PPP was observed to be approximately 30 degrees C in water, while it was 24 degrees C in 0.1M PBS (pH 7.4). Micellization behavior of PNIPAm-g-PPP in aqueous solution was characterized by fluorescence probe technique, TEM, and DLS. The critical micelle concentration (CMC), thus, determined was 0.0187 g/L. Both TEM and DLS measurement suggested that the diameter of micelles was approximately 190 nm at 20 degrees C. Diflunisal (DIF)-loaded micelles were prepared by dialysis method. In vitro release test at various temperatures was also performed to study the effect of temperature on the drug release profiles. It was demonstrated that DIF release from PNIPAm-g-PPP micelles was slower at the temperature of 37 degrees C than that at 4 degrees C.
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PMID:Thermally responsive polymeric micelles self-assembled by amphiphilic polyphosphazene with poly(N-isopropylacrylamide) and ethyl glycinate as side groups: polymer synthesis, characterization, and in vitro drug release study. 1634 95

The objective of this study was to assess the in vitro release kinetics and the in vivo angiogenic effect of human vascular endothelial growth factor (VEGF)-activated poly(DL-lactide-co-glycolide) (PLGA) sponge. The highly porous sponges (each 3 x 4 x 4 mm(3)) were activated by soaking in a VEGF solution (2.5 or 5.0 microg) and then freeze-drying. In vitro release in PBS was investigated by a competitive enzyme immunoassay for up to 3 weeks. The burst-type initial release within the first 3 days followed a more controlled one lasting for >2 weeks. The angiogenic potential of the VEGF sponge was evaluated by subcutaneous implantation into the epigastric groin fascia of Wistar rats. Histomorphometry and SEM confirmed the formation of new capillaries infiltrating the sponge pores starting from the first week and the drastic anostomosis at weeks 2 and 3. However, the rats implanted with control sponges or receiving VEGF injection exhibited much lower or no angiogenic response, respectively. TEM revealed the neo-vessels had a single endothelial layer surrounded by the matrix inoculated with the rat circulation. The results indicate that VEGF-activated PLGA sponge can be considered as a tool to establish neovascularized subcutaneous transplantation sites for tissue-engineering applications.
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PMID:Localized angiogenesis induced by human vascular endothelial growth factor-activated PLGA sponge. 1667 7

Thermally sensitive micelles self-assembled from poly(N-isopropylacrylamide-co- N,N-dimethylacrylamide)-b-poly(d,l-lactide-co-glycolide)[P(NIPAAm-co-DMAAm)-b-PLGA] are fabricated and used as a carrier for the controlled delivery of paclitaxel. Paclitaxel is efficiently loaded into the micelles by a membrane dialysis method. The lower critical solution temperature (LCST) of the micelles is 39.0 degrees C in PBS. Encapsulation efficiency and loading level of paclitaxel are affected by the initial loading level of paclitaxel, fabrication temperature and polymer composition. The blank and paclitaxel-loaded micelles are characterized by particle size analysis (DLS), morphology (TEM and AFM) and paclitaxel distribution (NMR, DSC and WAXRD). The micelles are spherical in shape, having an average size less than 130 nm. Paclitaxel is molecularly distributed within the core of micelles. Sustained release of paclitaxel is achieved, which is much faster at a temperature above the LCST than at the normal body temperature (37 degrees C). Cytotoxicity of free paclitaxel and paclitaxel-loaded micelles against a human breast carcinoma cell line (MDA-MB-435S) is studied at different temperatures. The cytotoxicity of the paclitaxol-loaded micelles is greater as compared to free paclitaxel. Enhanced cytotoxicity is achieved by the paclitaxol-loaded micelles when the environmental temperature increases slightly above the LCST. Paclitaxel-loaded P(NIPAAm-co-DMAAm)-b-PLGA micelles may provide a good formulation for cancer therapy.
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PMID:Thermally sensitive micelles self-assembled from poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)-b-poly(D,L-lactide-co-glycolide) for controlled delivery of paclitaxel. 1688 Sep 79

Dynamic light scattering, steady-state fluorescence, NMR diffusometry and cryo-TEM have been used to gain more insight into the aggregation behaviour of LPS from Escherichia coli O55:B5. Knowledge of this behaviour of the amphiphilic LPS molecule is in many cases of importance for the design of experiments and interpretation of results when using LPS in solution. The aim of this work was to study the aggregation and determine the aggregate size of E. coli O55:B5. The mean hydrodynamic radius of the LPS aggregates was determined by NMR diffusometry and dynamic light scattering to 14 and 26 nm, respectively. The cryo-TEM technique revealed predominantly spherical aggregates of 9-19 nm. We wish to report 10 microg/ml as the aggregation start for LPS E. coli O55:B5 in PBS buffer, pH 7.2. We suggest that the aggregation is a continuous process that starts at 10 microg/ml and proceeds up to 300 microg/ml.
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PMID:Aggregation behavior and size of lipopolysaccharide from Escherichia coli O55:B5. 1693 60

Eight-arm poly(ethylene glycol)-poly(L-lactide), PEG-(PLLA)(8), and poly(ethylene glycol)-poly(D-lactide), PEG-(PDLA)(8), star block copolymers were synthesized by ring-opening polymerization of either L-lactide or D-lactide at room temperature in the presence of a single-site ethylzinc complex and 8-arm PEG (M(n) = 21.8 x 10(3) or 43.5 x 10(3)) as a catalyst and initiator, respectively. High lactide conversions (>95%) and well-defined copolymers with PLLA or PDLA blocks of the desired molecular weights were obtained. Star block copolymers were water-soluble when the number of lactyl units per poly(lactide) (PLA) block did not exceed 14 and 17 for PEG21800-(PLA)(8) and PEG43500-(PLA)(8), respectively. PEG-(PLA)(8) stereocomplexed hydrogels were prepared by mixing aqueous solutions with equimolar amounts of PEG-(PLLA)(8) and PEG-(PDLA)(8) in a polymer concentration range of 5-25 w/v % for PEG21800-(PLA)(8) star block copolymers and of 6-8 w/v % for PEG43500-(PLA)(8) star block copolymers. The gelation is driven by stereocomplexation of the PLLA and PDLA blocks, as confirmed by wide-angle X-ray scattering experiments. The stereocomplexed hydrogels were stable in a range from 10 to 70 degrees C, depending on their aqueous concentration and the PLA block length. Stereocomplexed hydrogels at 10 w/v % polymer concentration showed larger hydrophilic and hydrophobic domains as compared to 10 w/v % single enantiomer solutions, as determined by cryo-TEM. Correspondingly, dynamic light scattering showed that 1 w/v % solutions containing both PEG-(PLLA)(8) and PEG-(PDLA)(8) have larger "micelles" as compared to 1 w/v % single enantiomer solutions. With increasing polymer concentration and PLLA and PDLA block length, the storage modulus of the stereocomplexed hydrogels increases and the gelation time decreases. Stereocomplexed hydrogels with high storage moduli (up to 14 kPa) could be obtained at 37 degrees C in PBS. These stereocomplexed hydrogels are promising for use in biomedical applications, including drug delivery and tissue engineering, because they are biodegradable and the in-situ formation allows for easy immobilization of drugs and cells.
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PMID:In-situ formation of biodegradable hydrogels by stereocomplexation of PEG-(PLLA)8 and PEG-(PDLA)8 star block copolymers. 1702 54


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