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At least 973 records · Page 54Linked to original sources

PubMed2002

Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma.

OBJECT: Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study is to evaluate the efficacy and role of gamma knife radiosurgery (GKS) in the management of residual or recurrent nonfunctioning pituitary adenomas. METHODS: A review was conducted of the data obtained in 42 patients who underwent adjuvant GKS at the University of Pittsburgh between 1987 and 2001. Prior treatments included transsphenoidal resection, craniotomy and resection, or conventional radiotherapy. Endocrinological, ophthalmological, and radiological responses were evaluated. The duration of follow-up review varied from 6 to 102 months (mean 31.2 months). Fifteen patients were observed for more than 40 months. The mean radiation dose to the tumor margin was 16 Gy. Conformal radiosurgery planning was used to restrict the dose to the optic nerve and chiasm. Tumor control after GKS was achieved in 100% of patients with microadenomas and 97% of patients with macroadenomas. Gamma knife radiosurgery was equally effective in controlling adenomas with cavernous sinus invasion and suprasellar extension. No patient developed a new endocrinological deficiency following GKS. One patient's tumor enlarged with an associated decline in visual function. Another patient experienced a deterioration of visual fields despite a decrease in tumor size. CONCLUSIONS: Gamma knife radiosurgery can achieve tumor control in virtually all residual or recurrent nonfunctioning pituitary adenomas. Dose sparing facilitates tumor management even when the adenoma is close to the optic apparatus or invades the cavernous sinus.

Adenoma↗

PubMed1994

Polymer delivery of chemotherapy for squamous cell carcinoma of the head and neck.

BACKGROUND: The role of chemotherapy for the treatment of squamous cell carcinoma of the head and neck is limited by the systemic toxicity of chemotherapeutic agents. An attractive alternative is the controlled and sustained release of anticancer agents from a resorbable polymer delivery system that is implanted next to the tumor. The advantages are a high locoregional drug concentration with low systemic levels and a delivery system that is not limited by poor blood supply caused by previous radiation therapy or surgery. METHODS/SUBJECTS: The polymer used in this study was a biodegradable polyanhydride made up of fatty acid dimer and sebacic acid, Poly (FAD-SA), loaded with cisplatin. The tumor animal model was the nude mouse carrying human floor of mouth squamous cell carcinoma xenografts. Polymer-cisplatin pharmacokinetics and the effect of polymer delivery of cisplatin (5% and 7% drug/polymer at a weight/weight load) on tumor growth rates were evaluated. MAIN RESULT: Thirty-five days after implantation of the polymer, the mean treated tumor size was 65.5% of controls in the 5% group and 31.8% in the 7% group. Seventy days after implantation, the mean treated tumor size was 41.4% of controls in the 5% group and 38.1% in the 7% group, indicating a statistically significant delay of tumor growth compared with controls or with intraperitoneally injected cisplatin. CONCLUSION: This study demonstrates that continuous release of cisplatin directly at the tumor site, using an implantable polymer, is effective against human head and neck squamous cell carcinoma xenografts in nude mice.

Animals↗

PubMed2000

Enhanced protein renaturation by temperature-responsive polymers.

The application of temperature-sensitive polymer (PNIPAAm) for the renaturation of beta-lactamase from inclusion bodies was investigated. It was observed that PNIPAAm was more effective than PEG in enhancing protein renaturation. At a concentration of 0.1%, PNIPAAm improved the yield of beta-lactamase activity by 41% from 46. 5 to 65.4 IU/mL, compared to 26% with PEG from 46.5 to 58.7 IU/mL. Kinetic study indicated that PNIPAAm did not significantly affect the initial rate of protein renaturation but did increase final activity yield. In the presence of PEG and PNIPAAm, the activity yields increased with temperature, indicating that hydrophobic interactions between denatured protein and polymer molecules contributed to the enhanced protein renaturation with polymers. The sequential addition approach, aiming at enhancing protein renaturation by reducing local protein concentration during renaturation, was also shown effective in enhancing protein renaturation, especially in the presence of polymers. With the sequential addition approach, the activity yield was increased by 60. 5% from 46.5 to 74.6 IU/mL with PNIPAAm. Similar behavior was also observed with PEG. PNIPAAm exhibited similar behavior as PEG on the renaturation of beta-lactamase in terms of temperature effect and concentration effect, indicating that the mechanism for enhanced protein renaturation for the two polymers might be similar. PNIPAAm exhibits a lower critical solution temperature (LCST) of 32 degrees C and can be effectively separated from aqueous solution and recycled. A protein renaturation process employing PNIPAAm, which offers the advantages of enhanced renaturation efficiency, minimum loss of protein aggregates, and ease of polymers recycling, was proposed.

Bacterial Proteins↗

PubMed2000

Investigating the effects of polymer chemistry on activity of biocatalytic plastic materials.

The affects of polymer chemistry on the organic solvent activity of alpha-chymotrypsin-containing biocatalytic plastic materials are investigated in this study. To incorporate alpha-chymotrypsin into the polymer, the enzyme is first acryloylated, then solubilized into organic solvents via hydrophobic ion paring with surfactant molecules. Once in the organic solvent, a vinyl monomer and crosslinker are added and copolymerized with the enzyme. Due to the intimate contact between the enzyme and the resulting polymer network, the polymer chemistry plays an important role in the activity of these biocatalytic materials. The chemical composition of the monomer/polymer has the greatest effect on catalytic activity. The activity spans a range of 100-fold and appears to correlate with the hydrophilicity of the monomer, with the lowest activity exhibited for poly(methyl methacrylate) and the highest for poly(2-hydroxyethyl methacrylate). The effect of the chemical structure of the monomer/polymer appears to be an intrinsic kinetic effect, whereas other polymer chemistry conditions investigated, including crosslinker concentration and length and ratio of solvent:monomer during synthesis, appear to effect the rate of substrate diffusion, thereby affecting observed enzyme activity. Changes in the conditions of polymer synthesis can cause as much as a 20-fold change in activity for a given polymeric material. This is most likely due to an increase in the porosity of the materials, and thus a relaxation of diffusional limitations.

Biotechnology↗

PubMed1996

A highly porous 3-dimensional polyphosphazene polymer matrix for skeletal tissue regeneration.

Current methods for the replacement of skeletal tissue in general involve the use of autografts or allografts. There are considerable drawbacks in the use of either of these tissues. In an effort to provide an alternative to traditional graft materials, a degradable 3-dimensional (3-D) osteoblast cell-polymer matrix was designed as a construct for skeletal tissue regeneration. A degradable amino acid containing polymer, poly[(methylphenoxy)(ethyl glycinato) phosphazene], was synthesized and a 3-D matrix system was prepared using a salt leaching technique. This 3-D polyphosphazene polymer matrix system, 3-D-PHOS, was then seeded with osteoblast cells for the creation of a cell-polymer matrix material. The 3-D-PHOS matrix possessed an average pore diameter of 165 microns. Environmental scanning electron microscopy revealed a reconnecting porous network throughout the polymer with an even distribution of pores over the surface of the matrix. Osteoblast cells were found attached and grew on the 3-D-PHOS at a steady rate throughout the 21-day period studied in vitro, in contrast to osteoblast growth kinetics on similar, but 2-D polyphosphazene matrices, that showed a decline in cell growth after 7 days. Characterization of 3-D-PHOS osteoblastpolymer matrices by light microscopy revealed cells growing within the pores as well as on surface of the polymer as early as day 1. This novel porous 3-D-PHOS matrix may be suitable for use as a bioerodible scaffold for regeneration of skeletal tissue.

Animals↗

PubMed1999

Persistent adhesion of epithelial tissue is sensitive to polymer topography.

The persistent adhesion of corneal epithelial tissue to the surface of a porous polymer is of interest in the development of a corneal onlay. Using an in vitro model system, this study examined the effect of polymer surface topography on the assembly of basement membrane and hemidesmosomes. Corneal epithelial tissue was grown on polycarbonate surfaces with a range of pore sizes (0.1-3.0 micron, pore diameter) and an equivalent nonporous surface. The ultrastructure of the tissue-polymer interface was evaluated using electron microscopy. On the porous surfaces, the tissue responded to a balance between the size of the discontinuity (pores) and the amount of polymer surface between the pores. Continuous basement membrane and a regular pattern of hemidesmosomal plaque occurred only on the 0.1 micron surface, where both the pores and the total surface area covered by pores were relatively small. The assembly of adhesive structures on surfaces with pore diameters between 0.4-2.0 microns was restricted to regions of polymer between pores. No adhesive structures assembled on the nonporous or on the 3.0-micron surface. These results demonstrate that, in addition to porosity, surface topography is a significant factor in the formation of structures involved in the persistent adhesion of stratified epithelial tissue on a polymer.

Animals↗

PubMed1999

MRI of acute myocardial ischemia: comparing a new contrast agent, Gd-DTPA-24-cascade-polymer, with Gd-DTPA.

A new macromolecular contrast agent, gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA)-24-cascade-polymer, was compared with Gd-DTPA for time-dependent delineation of acute myocardial ischemia. Acute myocardial ischemia was produced in 12 rats by occluding the anterior branch of the left coronary artery for 20-40 minutes. Dynamic spin-echo magnetic resonance imaging (MRI) was performed for 30 minutes after injection of Gd-DTPA (n = 6) or the cascade polymer (n = 6) using equimolar doses (0.1 mmol of Gd/kg). The contrast agent-induced changes in signal intensity (deltaSI) in normal and ischemic myocardium were observed. In normal myocardium, both contrast agents caused a sharp increase in deltaSI, followed by a decline to baseline values over the 30-minute period. Enhancement in the ischemic myocardium was attenuated. Gd-DTPA showed greater deltaSI in ischemic myocardium than the cascade polymer, which gave rise to virtually no enhancement. Significant differences (P<0.05) in signal enhancement between normal and ischemic myocardium persisted for only 6 minutes using Gd-DTPA but for 18 minutes with the cascade polymer. Use of Gd-DTPA-24-cascade-polymer extends the temporal window of dynamic contrast-enhanced MRI for the differentiation of ischemic and normal myocardium. Identification of the ischemic zone is easier with the cascade polymer, which demonstrates virtually no signal enhancement in this territory.

Animals↗

PubMed2000

Abundance of polymers degrading microorganisms in a sea-based solid waste disposal site.

In order to assess the degradability of plastics in solid waste disposal landfill sites, microbial populations capable of degrading five kinds of plastic-constituting polymers, poly epsilon-caprolactone (PCL), polylactic acid (PLA), polyethylene glycol (PEG), poly-beta-hydroxybutyrate (PHB) and cellulose acetate (CA), in a sea-based solid waste disposal site were investigated. Enumeration of aerobic and anaerobic polymers-degrading microorganisms (PDMs) was performed against to total 8 leachate samples, which were seasonally collected from the facultative pretreatment pond and the aerated lagoon. Both aerobic and anaerobic PDMs for natural polymers, PHB and CA, were found in all of the samples, while those for chemically-synthesized polymers, PCL, PLA and PEG, could not be always detected. In most cases, the ratios of the PHB- and CA-degraders to the heterotrophic bacterial population were more than 0.1%. On the other hand, the ratios of PCL-, PLA- and PEG-degraders were often much lower. These data indicate that the plastics degradation potential is commonly present in the studied disposal site, and that the degradation potential for plastics composed of chemically-synthesized polymers is inferior to that of natural polymers. Population sizes of the PDMs correlated to those of heterotrophic bacteria, and the counts of aerobic heterotrophic bacteria and PDMs in the aerated lagoon tended to be higher than those of anaerobic ones, indicating that the aeration of the leachate resulted in the activation of growth of whole aerobic microbial community including the PDMs.

Bacteria↗

PubMed2000

Polymer solutions as a pseudostationary phase for capillary electrochromatographic separation of DNA diastereomers.

The solutions of linear polymers traditionally used for DNA separation have been employed for the capillary electrophoresis (CE) of diastereomers of chemically modified DNA. The selectivity of diastereomeric separation of the phosphorothioate (PS) and 2'-O-methylated (2-OMe) PS oligonucleotides depends on the nature of the polymer additive in the CE background electrolyte. The selectivity of separation for different polymers increases in the line: linear polyacrylamide < polyethylene glycol < polyvinyl pyrrolidone. The separation of oligomer diastereomers was shown to be primarily based on the hydrophobic interaction with the polymer network that acts as a pseudostationary phase. While lowering the temperature resulted in improved separation, the addition of organic modifiers such as formamide, methanol or acetonitrile counteracts the solute adsorption on the polymer network, and decreases the selectivity of DNA diastereoseparation. The effect of molecular mass and concentration of the polymer on the separation selectivity was investigated.

Animals↗

PubMed2001

Electrophoretic migration behavior of DNA fragments in polymer solution.

A newly developed polymer coil shrinking theory is described and compared with the existing entangled solution theory to explain electrophoretic migration behaviour of DNA in hydroxypropylmethylcellulose (HPMC) polymer solution in buffer containing 100 mM tris(hydroxymethyl)aminomethane 100 mM boric acid, 2 mM ethylenediaminetetraacetic acid at pH 8.3. The polymer coil shrinking theory gave a better model to explain the results obtained. The polymer coil shrinking concentration, Cs, was found to be 0.305% and the uniform entangled concentration, C+, 0.806%. The existence of three regions (the dilute, semidilute, and concentrated solution) at different polymer concentrations enables a better understanding of the system to guide the selection of the best conditions to separate DNA fragments. For separating large fragments (700/ 800 bp), dilute solutions (HPMC < 0.3%) should be used to achieve a short migration time (10 min). For small fragments (200/300 bp), concentrated solutions are preferred to obtain constant resolution and uniform separation. The best resolution is 0.6% HPMC due to a combined interaction of the polymer coils and the entangled structure. The possibility of DNA separation in semidilute solution is often neglected and the present results indicate that this region has a promising potential for analytical separation of DNA fragments.

Buffers↗

PubMed2006

Helix formation in synthetic polymers by hydrogen bonding with native saccharides in protic media.

Water-soluble poly(m-ethynylpyridine)s were designed to realize saccharide recognition in protic media. UV/Vis, 1H NMR, and fluorescence measurements revealed that the polymer forms a helical higher order structure by solvophobic interactions between the ethynylpyridine units in the protic medium. The resulting pore in the helix behaves like a binding pocket in proteins, by taking advantage of inwardly directed hydrogen-bonding functional groups of the polymers. Molecular recognition of native saccharides by the polymers was investigated by circular dichroism (CD). The chirality of the saccharide was transferred to the helical sense of the polymers, accompanied by the appearance of induced CDs (ICDs) in the absorptive region of the polymers. In MeOH/water (10/1), mannose and allose showed intense ICDs, and the apparent association constant between the polymer and D-mannose was 14 M(-1).

Carbohydrate Conformation↗

PubMed1989

Influence of a soluble anionic polymer on the electrophoresis of proteins.

The influence of a soluble anionic polymer on electrophoresis of proteins was studied in relation to the nonspecific ionic effect of an affinophore on application to affinophoresis. Zone electrophoresis of proteins was carried out in agarose gel in the presence of succinyl-poly-L-lysine (degree of polymerization, 120) by using three electrophoresis buffers differing in ionic strength (0.06, 0.12 and 0.18) and pH (7.0 and 7.9). Proteins migrated as distinct single bands even in the presence of the polymer. The mobility of cationic proteins towards the cathode was first decreased and then increased towards the anode as the polymer concentration increased, while that of anionic proteins was not affected. The dependence of the apparent mobility changes of the proteins on the concentration of the polymer was treated quantitatively in the same way as affinity electrophoresis. The extent of the ionic interaction between a cationic protein and the polymer could be estimated as an apparent dissociation constant. It greatly depended on the ionic strength of the electrophoresis buffer. Except for the extremely cationic proteins such as lysozyme, the ionic interaction with up to 0.1 mM of the polymer could be practically suppressed by the use of 0.1 M sodium phosphate buffer (pH 7.0).

Anions↗

PubMed1994

A transient entanglement coupling mechanism for DNA separation by capillary electrophoresis in ultradilute polymer solutions.

Using capillary electrophoresis, large DNA molecules (2.0-23.1 kbp) may be rapidly separated in ultradilute polymer solutions (< 0.002% w/w) under a high-voltage, steady field (265 V/cm). At this polymer concentration, the separation mechanism appears to be significantly different from that postulated to occur in crosslinked gels. Based on experimental results obtained with DNA restriction fragments and with negatively charged latex microspheres, we conclude that the Ogston and reptation models typically used to describe gel electrophoresis are not appropriate for DNA separations in such dilute polymer solutions. Electrophoresis experiments employing solutions of both small and large hydroxyethyl cellulose polymers highlight the importance of polymer length and concentration for the optimum resolution of DNA fragments varying in size from 72 bp to 23.1 kbp. A transient entanglement coupling mechanism for DNA separation in dilute polymer solutions is developed, which suggests that there is no a priori upper size limit to DNA that can be separated by capillary electrophoresis in a constant field.

Cellulose↗

PubMed1998

The effect of blob size and network dynamics on the size-based separation of polystyrenesulfonates by capillary electrophoresis in the presence of entangled polymer solutions.

This work focuses on the separation of standard polystyrenesulfonates (PSS), with molecular masses (Mr) between 16 and 990 x 10(3) in capillaries filled with semidilute (entangled) linear hydrophilic polymers. Contrary to cross-linked chemical gels, which produce permanent networks, solutions of linear polymers lead to dynamic networks. The analytical performances and migration mechanisms are discussed on the basis of experiments performed in solutions of linear polyethyleneoxides and derivatized celluloses of various molecular masses. The influence of the mesh size and of the lifetime of the obstacles of the separating network has been investigated in detail. The mesh size is assimilated to the blob size of the separating polymer and is a decreasing function of its concentration. The lifetime of the obstacles of the network, identified with the reptation time of the polymer chain, characterizes its dynamics. This characteristic time increases with both the molecular weight of the separating polymer and its concentration. Its impact was first examined at fixed blob size. Then, the influence of the blob size was studied while keeping the reptation time of the network constant. By doing so, the existence of interactions between the solute and the separating polymer or between the solute and capillary wall can be more safely assessed. It appears that the reptation time of the mesh has a large influence on the electrophoretic mobility of the PSSs under a threshold value, which is of the order of magnitude of the time taken by the PSS to migrate on the blob size. Also shown are separations using networks made up with mixtures of polyethyleneoxides of the same nature and same mass concentration, but of very different molecular masses. This latter approach allows one to adapt the viscosity of the solution and the dynamics of the network, keeping the blob size constant.

Electrophoresis, Capillary↗

PubMed1998

A theory for the electrophoretic separation of DNA in polymer solutions.

We present a mathematical model of DNA capillary electrophoresis in polymer solutions based on nonentangling collisions between DNA and polymer molecules. Using videomicroscopy images of DNA migrating through polymer solutions, we propose a modified transient entanglement coupling mechanism for DNA separations that includes nonentangling DNA/polymer collisions. We show that a mathematical model based on individual nonentangling DNA/polymer collisions is able to predict the mobilities of DNA in solutions of low molecular mass polymer. We compare the model predictions to mobility data for separations of DNA in a range of concentrations for solutions of both hydroxypropylcellulose (Mw 100,000) and hydroxyethylcellulose (Mw 139,000). The model relies on one fitted parameter, the time constant for the interaction between the DNA and polymer molecules, which is based on the physical properties of DNA and polymers.

DNA↗

PubMed2005

Quantitative isolation of alphalAT mutant Z protein polymers from human and mouse livers and the effect of heat.

Alpha-1-antitrypsin (alpha1AT) deficiency in its most common form is caused by homozygosity for the alpha1AT mutant Z gene. This gene encodes a mutant Z secretory protein, primarily synthesized in the liver, that assumes an abnormal conformation and accumulates within hepatocytes causing liver cell injury. Studies have shown that mutant alpha1ATZ protein molecules form unique protein polymers. These Z protein polymers have been hypothesized to play a critical role in the pathophysiology of liver injury in this disease, although a lack of quantitative methods to isolate the polymers from whole liver has hampered further analysis. In this study, we demonstrate a quantitative alpha1ATZ polymer isolation technique from whole liver and show that the hepatocellular periodic acid-Schiff-positive globular inclusions that are the histopathological hallmark of this disease are composed almost entirely of the polymerized alpha1ATZ protein. Furthermore, we examine the previously proposed but untested hypothesis that induction of alpha1ATZ polymerization by the heat of physiological fever is part of the mechanism of hepatic alpha1ATZ protein accumulation. The results, however, show that fever-range temperature elevations have no detectable effect on steady-state levels of intrahepatic Z protein polymer in a model in vivo system. In conclusion, methods to separate insoluble protein aggregates from liver can be used for quantitative isolation of alpha1ATZ protein polymers, and the effect of heat from physiological fever may be different in vivo compared with in vitro systems.

Animals↗

PubMed2002

In situ gelling and mucoadhesive polymer vehicles for controlled intranasal delivery of plasmid DNA.

Nasal administration of plasmid DNA is emerging as a new route of delivery for therapeutic genes and DNA vaccines. To improve the intranasal absorption of plasmid DNA, we designed delivery systems composed of in situ gelling and mucoadhesive polymers. Poloxamers (Pol) were used to provide in situ gelling property. Polycarbophil (PC) or polyethylene oxide (PEO) was used as mucoadhesive polymers. The gelation temperatures of the formulations slightly decreased by the mucoadhesive polymers, but not by plasmid DNA. The in vitro release of plasmid DNA from the gels followed Fickian diffusion. The absorption of plasmid DNA varied with the contents and type of mucoadhesive polymers. Of vehicles, Pol/PC 0.2% showed the highest absorption with an area under the curve value 11-fold higher than saline, the conventional vehicle. The nasal retention of plasmid DNA was highly prolonged by mucoadhesive polymers. At 3 h postdose, the nasal tissue levels of plasmid DNA given in Pol/PC and Pol/PEO 0.8% were 10- and 40-fold higher relative to saline. The histopathology of nasal tissues was not altered after repeated dosing over 2 weeks. The mRNA expression of plasmid DNA delivered by Pol or Pol/PEO 0.4% was observed in the nasal tissues. These results indicate that the nasal absorption of plasmid DNA can be effectively and safely enhanced by using in situ gelling and mucoadhesive polymer-based vehicles.

Adhesives↗

PubMed1988

Endothelialization of polymer surfaces.

The role that substrate surface properties play in influencing the extent of endothelialization of polymer surfaces has been investigated. For a wide range of polymer surfaces, the degree of endothelialization for both porcine and bovine endothelial cells is directly related to polymer surface tension: increased endothelialization occurring with increasing substrate surface tension. As a result of adsorption of the proteins in the culture media, the surface properties of the polymers are altered considerably. The protein-coated polymers were characterized by means of liquid-liquid contact angle measurements under non-denaturing conditions. A striking correlation is observed between the degree of endothelialization and the measured dextran contact angle. The degree of endothelial cell spreading is not related to polymer surface tension. Cell morphology and extracellular matrix production, however, are influenced by substrate surface properties.

Adsorption↗