Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inactivation of the p53 tumor suppressor gene usually involves somatic mutation or binding of viral oncoproteins to the p53 protein. However, several types of malignant and premalignant tissues harbor a genetically wild-type, but transcriptionally inactive, form of p53, often localized in the cytoplasm. Electrophilic prostaglandins (PGs) are known to sequester and inactivate p53 in the cytoplasm, an effect that is likely to occur when cyclooxygenase (COX)-2 levels become elevated during colon carcinogenesis. We determined the localization and expression of p53 in the presence of PGA(1) and celecoxib, a selective COX-2 inhibitor in human colon cell lines HCT-116 (wild-type p53) and HT-29 (mutant p53). In the absence of treatment, p53 protein accumulated preferentially in the nucleus in both cell lines. We observed that the total cellular levels of p53 protein increased with exposure time and concentration of PGA(1). By contrast, p21 protein levels remained unchanged as a function of time and concentration of PGA(1). In the presence of 20 micro M PGA(1), p53 accumulated preferentially in the cytosol. The nuclear:cytosol ratios of p53 were 31 and 2.1 in the controls and in the presence of PGA(1) in HCT-116 cells but were 22 and 4, respectively, in HT-29 cells. Treatment with 50 micro M celecoxib for 24 h did not significantly change p53 expression and localization. However, in the presence of 100 micro M celecoxib, p53 levels increased in the nucleus. The nuclear:cytosol ratios were then 31 (control) and 60 (100 micro M celecoxib) in HCT-116 cells and 22 (control) and 36 (100 micro M celecoxib) in HT-29 cells. These results indicate that electrophilic PGs cause wild-type p53 accumulation in the cytosol where it is inactive. Inhibition of COX-2 by celecoxib appears to alleviate this effect on p53 by reducing electrophilic PG synthesis. Thus, COX-2 inhibition of electrophilic PG formation appears to protect p53 tumor suppressor function.
Cancer Res 2003 Sep 01
PMID:Inhibition of COX-2 in colon cancer cell lines by celecoxib increases the nuclear localization of active p53. 1508 16

This paper explores the influence of initial molecular weight and porosity on the release of the drug, theophylline, from polyglycolide (PGA). PGA was made by a variety of processes to vary the molecular weight and was blended with NaCl with different crystal sizes and in different proportions to vary the pore size and volume. Overall, results showed that decreasing the molecular weight and increasing the pore size and volume increased the rate of drug release. The exact variation of these trends agreed well with the previously established four-stage degradation mechanism for PGA, but was more complex than a simple linear behaviour. Because both the molecular weight and the porosity of PGA have a substantial influence on the polymer degradation, and can be varied in a controlled manner, these parameters can play an important role in developing PGA as a controlled drug delivery material with tailored drug release.
Int J Pharm 2004 Sep 10
PMID:The effects of molecular weight and porosity on the degradation and drug release from polyglycolide. 1533 79

Many bacteria, including Escherichia coli, have a unique gene that encodes glutamate racemase. This enzyme catalyses the formation of d-glutamate, which is necessary for cell wall peptidoglycan synthesis. However, Bacillus subtilis has two glutamate racemase genes, named racE and yrpC. Since racE appears to be indispensable for growth in rich medium, the role of yrpC in d-amino acid synthesis is vague. Experiments with racE- and yrpC-knockout mutants confirmed that racE is essential for growth in rich medium but showed that this gene was dispensable for growth in minimal medium, where yrpC executes the anaplerotic role of racE. LacZ fusion assays demonstrated that racE was expressed in both types of media but yrpC was expressed only in minimal medium, which accounted for the absence of yrpC function in rich medium. Neither racE nor yrpC was required for B. subtilis cells to synthesize poly-gamma-dl-glutamate (gamma-PGA), a capsule polypeptide of d- and l-glutamate linked through a gamma-carboxylamide bond. Wild-type cells degraded the capsule during the late stationary phase without accumulating the degradation products, d-glutamate and l-glutamate, in the medium. In contrast, racE or yrpC mutant cells accumulated significant amounts of d- but not l-glutamate. Exogenous d-glutamate utilization was somewhat defective in the mutants and the double mutation of race and yrpc severely impaired d-amino acid utilization. Thus, both racemase genes appear necessary to complete the catabolism of exogenous d-glutamate generated from gamma-PGA.
Microbiology (Reading) 2004 Sep
PMID:Roles and regulation of the glutamate racemase isogenes, racE and yrpC, in Bacillus subtilis. 1534 50

The changing morphology of quenched polyglycolide (PGA) is investigated during hydrolytic degradation in phosphate buffered saline at pH 7.4. Analysis techniques include small and wide-angle X-ray scattering (SAXS and WAXS), mass measurements, DSC, pH measurement and UV-spectrophotometry. It is postulated that the degradation process can be separated into four distinct stages. In stage I, water diffuses quickly into the sample. During stage II, the polymer crystallizes by insertion crystallization, whilst the molecular weight gradually falls. This stage is characterized by a dramatic fall in the long period together with an increase in the crystallinity, minimal mass loss and minimal water uptake. At the onset of stage III, at around 10 days, a critical molecular weight is reached. Degradation products are now small enough to diffuse from the surface of the sample which begins to swell, water diffuses into the space created, and the crystals are freed from constraint. A co-operation between degradation products diffusing out of the sample and the water diffusing in causes "reaction-erosion" fronts to develop inside the sample. Ahead of these fronts, the trapped acidic degradation products remain to catalyze the hydrolysis. Stage III is characterized by swelling and an increase in the long period, together with mass loss and further water uptake. It is postulated that these reaction-erosion fronts move through the sample and meet in the centre at the beginning of stage IV, at which point the degradation again becomes homogeneous throughout the sample.
J Mater Sci Mater Med 2001 Sep
PMID:Polyglycolide: degradation and drug release. Part I: changes in morphology during degradation. 1534 29

Evaluations of efficacy of the new biologic therapies for psoriasis have used both physician-assessed endpoints and patient-reported outcome measures. The Psoriasis Area and Severity Index (PASI) is commonly used in clinical trials but is too labor intensive for clinical practice, which uses more subjective measures (physician global assessment [PGA] of change and Overall Lesion Severity [OLS] scale). Because psoriasis affects quality of life (QOL), patient-reported assessments of their satisfaction with treatment also are important. The purpose of this study was to evaluate some of the measurement tools used in clinical trials to make them more applicable to the practicing dermatologist. We used results of a placebo-controlled clinical study of efalizumab for the treatment of patients with moderate to severe plaque psoriasis. After treatment, ratings of improvement in psoriasis as measured by the PASI and PGA were closely aligned. It was noted the latter tool could provide a more practical and user-friendly evaluation in clinical practice. After 12 weekly subcutaneous injections of efalizumab, patients who achieved > or = 50% but < 75% improvement in PASI had treatment responses rated as primarily good or excellent using the PGA; additionally, the patients treated with efalizumab had statistically significant improvements (P<.001) in all patient-reported QOL assessments compared with placebo-treated patients, as did patients who achieved a > or = 75% improvement in PASI (PASI 75).
Cutis 2004 Sep
PMID:Clinical benefits in patients with psoriasis after efalizumab therapy: clinical trials versus practice. 1549 62

Considering Alcaligenes faecalis pencillin G acylase(AfPGA), which possesses the attractive characteristics for beta-lactam antibiotics conversions, the gene of PGA was cloned into an expressing vector pKKFPGA. The recombinant plasmid contained multicopy replicon(COLE 1), trc promoter, AfPGA gene, rrnB transcript terminator and ampicillin marker transformed Escherichia coli DH5alpha. As both the recombinant plasmid and the host DH5alpha had no laclq gene, the trc promoter was always active and the AfPGA could be constitutively expressed without IPTG induction in the host DH5alpha. In the shaking flask, the recombinant cell was inoculated into the fermentation medium (tryptone 10g/L, yeast extract 5g/L, MgSO4 x 7 H2O 1g, KH2 PO4 2g/L, K2HPO4 x 3H2O 5g/L, Na2HPO4 x 12H2O 7g/L, (NH4)2SO4 1.2g/L, NH4Cl 0.2 g/L, NaCl 0.1g/L, dextrin 30g/L) and cultured at 28 degrees C for 20h. The production of AfPGA reached 2,590u/L(NIPAB method), with a cell-density-specific activity of more than 300(u/L)/A600, this yield increased 432 fold higher than the native expression of Alcaligenes faecalis . Without ammonium sulphate fractionation and dialysis, the supernatant of crude extract was directly loaded on DEAE-Sepharose CL 6B column equilibrated by phosphate buffer (50mmol/L, pH7.8), and the enzyme fraction was not absorbed on the column but impurities were absorbed. Subsequently the effluent was added ammonium sulphate to 1mol/L and loaded on Butyl-Sepharose CL 4B column equilibrated by 50mmol/L phosphate buffer pH7.8-1mol/L ammonium sulphate. The enzyme was eluted as concentration of ammonium sulphate in phosphate buffer decreased to 0, PGA was eluted. After these two column chromatography, the enzyme was enriched 20 times with a 91% activity recovery. The purified enzyme had a specific activity of 68.6u/mg protein. However, the overproduction of PGA was often limited by translocation and/or periplasmic processing steps, subsequently resulted in intracellular accumulation of various types of PGA precursors and then formed inclusion bodies in the cytoplasm and/or periplasm. In this study, 5% PGA precursors formed as inclusion bodies in the cytoplasm while no inclusion bodies formed in the periplasm. It suggested most PGA precursors were transported to the periplasm and matured to active PGA and also explained why PGA gene was highly expressed in the host DH5alpha. On the other hand, inclusion bodies in the cytoplasm indicated that the maturation of PGA in the host DHSalpha was limited by the translocation step.
Sheng Wu Gong Cheng Xue Bao 2004 Sep
PMID:[Constitutive expression and purification of Alcaligenes faecalis penicillin G acylase in Escherichia coli]. 1597

Pepsin: hydrochloric acid digestion and histological examination of the myocardium of 51 hearts from five to nine month-old lambs from the southern half of the North Island, showed that 47 (92%) were infected with microscopic sarcocysts that are presumed to be dog-derived. Of 157 sarcocysts detected histologically, 32 corresponded morphologically with Sarcocystis ovicanis and 120 with Sarcocystis tenella (Syn. S. arieticanis). The remainder could not be identified as to type.
N Z Vet J 1987 Sep
PMID:Prevalence of dog-derived Sarcocystis spp. in some New Zealand lambs. 1603 10

The work aims to provide a histological investigation of Fisiograft, a PLA/PGA copolymer, used as filler for bone defects in humans. The study was performed on biopsies of sinus lifts where Bio-Oss and Fisiograft gel were applied as graft material. Bone regeneration was satisfactory in all sinus lifts, even when Fisiograft was applied alone. Due to remarkable osteoclast activity, Bio-Oss granules were cleared from the majority of biopsy cores. At histology, Fisiograft gel appeared as globes enveloped by fibroblasts, displaying an epithelial-like cell appearance. Due to its solubility in solvents, undegraded Fisiograft (recorded for 7 months or more) did not stain whereas degraded Fisiograft stained positive. The loose connective tissue, that surrounded Fisiograft and bone contained isolated mastocytes. Bone grew inside the loose connective and often reached the surface of Fisiograft by intervening cells. The results seem to indicate that Fisiograft may be considered both a polymer useful for fastening bone substitutes inside a defect and in addition a material capable of prompting bone regeneration, with or without the use of a bone substitute. In addition to space-former and space-maintainer functions, Fisiograft shows potential bone stimulation function, which may be labelled as osteopromotive capability.
J Mater Sci Mater Med 2005 Sep
PMID:Histological study on sinus lift grafting by Fisiograft and Bio-Oss. 1616 6

Natural polymeric materials are gaining interest for application as adsorbents in wastewater treatment due to their biodegradable and non-toxic nature. In this study, a biopolymer, poly-gamma-glutamic acid (gamma-PGA) derived from bacterial sources (Bacillus species) was evaluated for its efficiency in removing basic dyes from aqueous solution. Sorption studies under batch mode were conducted using C.I. Basic blue 9 (BB9) and C.I. Basic green 4 (BG4) as test dyes. Equilibrium process conformed well with the Redlich-Peterson isotherm equation and the monolayer sorption capacity obtained from the Langmuir model was 352.76 and 293.32mg/g for BB9 and BG4 dyes, respectively. The kinetic studies of dye sorption on gamma-PGA gave high coefficients of determination (>0.98) for a pseudo second-order equation. An ion-exchange model, which assumes adsorption as a chemical phenomenon, was also found to fit the kinetic data precisely. The dye sorption largely depended on the initial pH of the solution with maximum uptake occurring at pH above 5. About 98% of the dye adsorbed on gamma-PGA could be recovered at pH 1, which facilitates the reuse of spent gamma-PGA.
J Hazard Mater 2006 Sep 01
PMID:Removal of cationic dyes from aqueous solution using an anionic poly-gamma-glutamic acid-based adsorbent. 1654 Feb 39

Insulin-mimetic vanadyl-poly(gamma-glutamic acid) complex, VO-gamma-PGA, is proposed as a novel drug delivery system for treating type 1 diabetic animals. The structure of VO-gamma-PGA in solution as well as in solid state was analyzed by electronic absorption, infra-red, and electron spin resonance spectra, and proposed that the equatorial coordination mode of VO(2+) is in either carboxylate(O)-VO-(OH(2))(3) or 2 carboxylate(O(2))-VO-(OH(2))(2). In vitro insulin-mimetic activity, metallokinetic feature in the blood of healthy rats, and in vivo normoglycemic effect of the complex prepared in solution were evaluated in streptozotocin(STZ)-induced type 1 diabetic mice, and these effects were compared with those of a solution containing only VOSO(4) as a positive control. The in vitro insulin-mimetic activity of VO-gamma-PGA was examined by determining both inhibition of free fatty acid (FFA) release and glucose uptake in isolated rat adipocytes, in which the concentration of VO-gamma-PGA for 50% inhibition of FFA release was significantly lower than that of VOSO(4). Metallokinetic study suggested that the bioavailability of VO-gamma-PGA complex was much higher than that of VOSO(4). The complex showed a significant hypoglycemic activity within at least 4h after a single oral administration, the effect being sustained for at least 24h. Furthermore, VO-gamma-PGA normalized the hyperglycemia in STZ-mice within 3 days when it was given orally at doses of 5-10mgVkg(-1) body mass for 16 days. The improvement in diabetes was also supported by the results on oral glucose tolerance test, HbA(1c) levels, and blood pressure.
J Inorg Biochem 2006 Sep
PMID:A novel drug delivery system for type 1 diabetes: insulin-mimetic vanadyl-poly(gamma-glutamic acid) complex. 1682 5


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