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)

We describe a high-resolution radiation hybrid map of the proximal long arm of human chromosome 11 containing the bcl-1 and multiple endocrine neoplasia type 1 (MEN-1) disease gene loci. We used X-ray irradiation and cell fusion to generate a panel of 102 hamster-human somatic cell hybrids containing fragments of human chromosome 11. Sixteen human loci in the 11q12-13 region were mapped by statistical analysis of the cosegregation of markers in these radiation hybrids. The most likely order for these loci is C1NH-OSBP-(CD5/CD20)-PGA-FTH1-COX8-PYGM -SEA-KRN1-(MTC/P11EH/HSTF1/INT2)-GST3- PPP1A. Our localization of the human protooncogene SEA between PYGM and INT2, two markers that flank MEN-1, suggests SEA as a potential candidate for the MEN-1 locus. We map two mitogenic fibroblast growth factor genes, HSTF1 and INT2, close to bcl-1, a mapping that is consistent with previously published data. Our map places the human leukocyte antigen genes CD5 and CD20 far from the bcl-1 locus, indicating that CD5 and CD20 expression is unlikely to be altered by bcl-1 rearrangements. PPP1A, which has been postulated as a MEN-1 candidate tumor suppressor gene, and GST3, a gene transcriptionally active in many human cancers, both map distal to the bcl-1 translocation cluster and the region containing MEN-1, and therefore are unlikely to be directly involved in bcl-1 or MEN-1.
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PMID:A radiation hybrid map of the proximal long arm of human chromosome 11 containing the multiple endocrine neoplasia type 1 (MEN-1) and bcl-1 disease loci. 168 84

Amplification of several markers which map to chromosome 11q13 was detected by Southern blotting in transitional cell tumours of the urinary bladder. The oncogenes INT2 and HST and the BCL1 locus were co-amplified in 20/97 (20.6%) tumours and the locus-specific minisatellite probe pMS51 (D11S97) detected amplification in 17/97 (17.5%) tumours. The high frequency of heterozygosity (greater than 70%) detected by this latter probe on HaeIII-digested DNAs provided a sensitive means to measure low levels of gene amplification (2-fold) by comparing signals obtained from each allele. A number of probes which map to 11q were used in an attempt to map the region of amplification more precisely. PGA, PGR, STMY, D11Z1 and D11S149 were not amplified in any tumours studied. SEA was amplified in 1/59 tumours and D11S146 in 12/89 tumours. A comparison of the patterns of co-amplification of individual markers in this series of tumours revealed that of the 23 tumours with amplification at this site, 11 had co-amplification of D11S97, D11S146, BCL1, INT2 and HST, 3 had co-amplification of D11S97, BCL1, INT2 and HST, 6 had co-amplification of BCL1, INT2 and HST, 1 had co-amplification of D11S97 and D11S146 and 2 had amplification of D11S97 alone. Based on available linkage data for these markers, this suggests that a putative target gene within this amplicon lies centromeric to BCL1. Amplification at 11q13 showed no correlation with tumour grade or with HER2 amplification.
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PMID:Amplification at chromosome 11q13 in transitional cell tumours of the bladder. 205 57

Forty loci (16 polymorphic and 24 non-polymorphic) together with 23 cosmids isolated from a chromosome 11-specific library were used to construct a detailed genetic map of 11p13-11q13. The map was constructed by using a panel of 13 somatic cell hybrids that sub-divided this region into 19 intervals, a meiotic mapping panel of 33 multiple endocrine neoplasia type 1 (MEN1) families (134 affected and 269 unaffected members) and a mitotic mapping panel that was used to identify loss of heterozygosity in 38 MEN1-associated tumours. The results defined the most likely order of the 16 loci as being: 11pter-D11S871-(D11S288, D11S149)-11cen-CNTF-PGA-ROM1-D11S480-PYGM- SEA-D11S913-D11S970-D11S97- D11S146-INT2-D11S971-D11S533-11qter. The meiotic mapping studies indicated that the most likely location of the MEN1 gene was in the interval flanked by PYGM and D11S97, and the results of mitotic mapping suggested a possible location of the MEN1 gene telomeric to SEA. Mapping studies of the gene encoding mu-calpain (CAPN1) located CAPN1 to 11q13 and in the vicinity of the MEN1 locus. However, mutational analysis studies did not detect any germ-line CAPN1 DNA sequence abnormalities in 47 unrelated MEN1 patients and the results therefore exclude CAPN1 as the MEN1 gene. The detailed genetic map that has been constructed of the 11p13-11q13 region should facilitate the construction of a physical map and the identification of candidate genes for disease loci mapped to this region.
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PMID:Genetic mapping studies of 40 loci and 23 cosmids in chromosome 11p13-11q13, and exclusion of mu-calpain as the multiple endocrine neoplasia type 1 gene. 864 89

Poly(epsilon-caprolactone) (PCL) microspheres containing c. 3% bovine serum albumin (BSA) were prepared by melt encapsulation and solvent evaporation techniques. PCL, because of its low Tm, enabled the melt encapsulation of BSA at 75 degrees C thereby avoiding potentially toxic organic solvents such as dichloromethane (DCM). Unlike the solvent evaporation method, melt encapsulation led to 100% incorporation efficiency which is a key factor in the microencapsulation of water-soluble drugs. Examination of the stability of the encapsulated protein by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that protein integrity was unaffected by both methods of encapsulation. In vitro release of the protein into phosphate buffer examined at 37 degrees C from microspheres prepared by both techniques showed that the release rate from melt-encapsulated microspheres was somewhat slower compared to the release from solvent-evaporated spheres. Both released around 20% of the incorporated protein in 2 weeks amounting to approximately 6.5 micrograms mg-1 of microspheres. Although the diffusivity of macromolecules in PCL is rather low, it is shown that PCL microspheres are capable of delivering sufficient quantity of proteins by diffusion for prolonged periods to function as a carrier for many vaccines. Unlike poly(lactic acid) (PLA) and poly(glycolic acid) (PGA) polymers which generate extreme acid environments during their degradation, the delayed degradation characteristics of PCL do not generate an acid environment during protein release and, therefore, may be advantageous for sustained delivery of proteins and polypeptides.
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PMID:Protein release from poly(epsilon-caprolactone) microspheres prepared by melt encapsulation and solvent evaporation techniques: a comparative study. 915 Nov 93

Bioabsorbable polymer implants may provide a viable alternative to metal implants for internal fracture fixation. One of the potential difficulties with absorbable implants is the possible toxicity of the polymeric degradation products especially if they accumulate and become concentrated. Accordingly, material evaluation must involve dose-response toxicity data as well as mechanical properties and degradation rates. In this study the toxicity and rates of degradation for six polymers were determined, along with the toxicity of their degradation product components. The polymers studied were poly(glycolic acid) (PGA), two samples of poly(L-lactic acid) (PLA) having different molecular weights, poly(ortho ester) (POE), poly(epsilon-caprolactone) (PCL), and poly(hydroxy butyrate valerate) (5% valerate) (PHBV). Polymeric specimens were incubated at 37 degrees C in 0.05 M Tris buffer (pH 7.4 at 37 degrees C) and sterile deionized water. The solutions were not changed during the incubation intervals, providing a worst-case model of the effects of accumulation of degradation products. The pH and acute toxicity of the incubation solutions and the mass loss and logarithmic viscosity number of the polymer samples were measured at 10 days, 4, 8, 12, and 16 weeks. Toxicity was measured using a bioluminescent bacteria, acute toxicity assay system. The acute toxicity of pure PGA, PLA, POE, and PCL degradation product components was also determined. Degradation products for PHBV were not tested. PGA incubation solutions were toxic at 10 days and at all following intervals. The lower molecular weight PLA incubation solutions were not toxic in buffer but were toxic by 4 weeks in water.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Six bioabsorbable polymers: in vitro acute toxicity of accumulated degradation products. 1014 75

The effect of polymer chemistry on adhesion, proliferation, and morphology of human articular cartilage (HAC) chondrocytes was evaluated on synthetic degradable polymer films and tissue culture polystyrene (TCPS) as a control. Two-dimensional surfaces of poly(glycolide) (PGA), poly(L-lactide) (L-PLA), poly(D,L-lactide) (D,L-PLA), 85:15 poly(D,L-lactide-co-glycolide) (D,L-PLGA), poly(epsilon-caprolactone) (PCL), 90:10 (D,L-lactide-co-caprolactone) (D,L-PLCL), 9:91 D,L-PLCL, 40:60 L-PLCL, 67:33 poly(glycolide-co-trimethylene carbonate) (PGTMC), and poly(dioxanone) (PDO) were made by spin-casting into uniform thin films. Adhesion kinetics were studied using TCPS and PCL films and revealed that the rate of chondrocyte adhesion began to level off after 6 h. Degree of HAC chondrocyte adhesion was studied on all the substrates after 8 h, and ranged from 47 to 145% of the attachment found on TCPS. The greatest number of chondrocytes attached to PGA and 67:33 PGTMC polymer films, and attachment to PCL and L-PLA films was statistically lower than that found on PGA (p < 0.05). There was no correlation between amount of chondrocyte attachment to the substrates and the substrates' water contact angle. Chondrocytes proliferated equally well on all the substrates resulting in equivalent cell numbers on all the substrates at both day 4 and day 7 of the culture. However, these total cell numbers were reached as a result of a 88- and 42-fold expansion on PDO and PLA, respectively, which was significantly higher than the 11-fold expansion found on TCPS (p < 0.05). The greater fold expansion of the cells on PDO and L-PLA films may be attributed to the availability of space for cells to grow, since their numbers at the start of culture were fewer following the 8 h attachment period. This suggests that regardless of initial seeding density on these degradable polymer substrates (i.e., if some minimum number of cells are able to attach), they will eventually populate the surfaces of all these polymers given sufficient space and time.
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PMID:Human articular chondrocyte adhesion and proliferation on synthetic biodegradable polymer films. 1061 31

Several different bioabsorbable scaffolds designed and manufactured for guided bone regeneration and generation have been developed. In order to enhance the bioactivity and potential osteoconductivity of the scaffolds, different bioabsorbable polymers, composites of polymer and bioactive glass, and textured surface structures of the manufactured devices and composites were investigated in in vitro studies and experimental animal models. Solid, self-reinforced polyglycolide (SR-PGA) rods and self-reinforced poly L-lactide (SR-PLLA) rods were successfully used as scaffolds for bone formation in muscle by free tibial periosteal grafts in animal experiments. In an experimental maxillary cleft model, a bioabsorbable composite membrane of epsilon-caprolactone and L-lactic acid 50/50 copolymer (PCL/LLA) film and mesh and poly 96L,4D-lactide (PLA96) mesh were found to be suitable materials for guiding bone regeneration in the cleft defect area. The idea of solid layer and porous layer combined together was also transferred to stiff composite of poly 70L,30DL-lactide (PLA70) plate and PLA96 mesh which structure is introduced. The osteoconductivity of several different biodegradable composites of polymers and bioactive glass (BG) was shown by apatite formation in vitro. Three composites studied were self-reinforced composite of PLA70 and bioactive glass (SR-(PLA70 + BG)), SR-PLA70 plate coated with BG spheres, and Polyactive with BG.
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PMID:Bioabsorbable scaffolds for guided bone regeneration and generation. 1107 99

Tissue generation by autogenous cell transplantation is one of the most promising treatment concepts being developed as it eliminates problems of donor site scarcity, immune rejection and pathogen transfer. Cultured cells are seeded onto a three-dimensional biocompatible scaffold that will slowly degrade and resorb as the soft and hard structures grow and assimilate in vitro and/or in vivo. The 3-D scaffold provides the necessary template for cells to proliferate and maintain their differentiated state. Ultimately, it defines the overall shape of the tissue-engineered transplant. The aim of this review is to describe and discuss the scaffold materials of natural and synthetic origin that are of specific interest to tissue engineers. This review is based on previous publications and our own experience in the use of biomaterials of natural and synthetic origin for tissue engineering applications. Biodegradable polymers which have been used for tissue engineering applications are mainly based on clinically established medical devices and implants. In the group of macromolecules of natural origin collagen, alginate, agarose, hyaluronic acid derivatives, chitosan, and fibrin glue have been used as scaffolds. Man-made polymers such as polyglycolide (PGA), polylactides (PLLA, PDLA), poly(caprolactone) (PCL), and poly(dioxanone) (PDS) have been studied as matrix material to guide the differentiation and proliferation of cells into the targeted functional premature and/or mature tissue. Appropriate selection of scaffold material with respect to the targeted tissue is essential. Today, biomaterials of choice remain to be those approved by the US Food and Drug Administration. In spite of that, novel biomaterials should be developed specifically designed for tissue engineering applications.
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PMID:An introduction to biodegradable materials for tissue engineering applications. 1137 17

With this tissue engineering (TE) technique, the peripheral pulmonary artery was successfully reconstructed, using the patient's own venous cells in a 4-year-old girl, 2 years after Fontan procedure. A 4-year-old girl was given a diagnosis of single right ventricle, double-outlet right ventricle and pulmonary atresia. She underwent left modified Blalock-Taussig shunt at a month old, pulmonary artery angioplasty at a year and 3 months old, and bidirectional cavopulmonary shunt at 2 years and a month old. She underwent again pulmonary artery angioplasty and Fontan operation at 3 years and 3 months. An angiographical examination 7 months after the operation revealed total occlusion of the right intermediate pulmonary artery. TE technique using autologous cells was indicated. The application of this procedure was approved by the ethical committee in Tokyo Women's Medical University. The patient's parents were thoroughly informed and signed a consent form. Approximately 2 cm of the peripheral vein was explanted under sterile conditions. The tissue was minced, placed in tissue culture dishes and cultured at 37 degrees C, 100% humidity and a 5% CO2 atmosphere for almost a month. The number of cells substantially increased to reach 12 millions for almost a month. The culture medium was changed every 3 days. The polymer tube that served as a scaffold for cells was composed of the copolymer of PCL-PLA (50:50) with reinforcement by woven PGA. The polymer conduit, 10 mm in diameter, 20 mm in length and 1 mm in thickness, was designated to biodegradate within 8 weeks. The number of seeded cells was approximately a million/cm2. The graft transplantation was performed 10 days after seeding cells. The occlusive right intermediate pulmonary artery was reconstructed with the TE vessel graft under extracorporeal circulation with a pump-oxygenator. The patient followed a satisfactory postoperative course. The postoperative angiography demonstrated that the graft was not constricted and dilated but that it preserved good patency. Long-term follow-up are necessary. We plan to continue to use the TE technique using autologous cells in the low pressure system like venous or pulmonary circulation. Because our results even in early experimental phase were valuable and promising, we believe that the TE approach may play an important role in the near future as an another alternative, together with transplantation and artificial organ, especially in the field of cardiovascular surgery that mostly needs replants.
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PMID:[First successful clinical application of tissue engineered blood vessel]. 1199 17

Heme oxygenase-1 (HO-1) is induced as a beneficial and adaptive response in cells and tissues exposed to oxidative stress. Herein we examined how various eicosanoids affect the induction of HO-1, and the possible mechanism underlying 15-deoxy-Delta(12,14)- prostaglandin J(2) (15d-PGJ(2))-induced HO-1 expression. PGH(2), PGD(2) and its metabolites of the PGJ(2) series, and PGA(1) markedly induced the protein expression of HO-1. Arachidonic acid (AA), docosahexaenoic acid (DHA), PGE(2), PGF(2 alpha), and thromboxane B(2) (TXB(2)) were shown to have no effect on the induction of HO-1. 15d-PGJ(2) was the most potent activator achieving significance at 5 microM. Although 15d-PGJ(2) significantly activated the MAPKs of JNK and ERK, the activation of JNK and ERK did not contribute to the induction of HO-1 as determined using transfection of dominant-negative plasmids and MAPKs inhibitors. Additional experiment indicated that 15d-PGJ(2) induced HO-1 expression through peroxisome proliferator-activated receptor (PPAR)-independent pathway. 15d-PGJ(2) significantly decreased the intracellular level of reduced glutathione; and the thiol antioxidant, N-acetyl-L-cysteine (NAC), and the thiol-reducing agent, dithiothreitol (DTT), inhibited the induction of HO-1 by 15d-PGJ(2). Finally, NAC and DTT exhibited significant inhibition of HO-1 mRNA and HO-1 promoter reporter activity induced by 15d-PGJ(2). These results suggest that thiol antioxidant and reducing agents attenuate the expression of HO-1 induced by 15d-PGJ(2), and that the cellular thiol-disulfide redox status may be linked to HO-1 activation.
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PMID:Thiol antioxidant and thiol-reducing agents attenuate 15-deoxy-delta 12,14-prostaglandin J2-induced heme oxygenase-1 expression. 1499 22


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