SEARCH · PubMed Health

Results for “ABC”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources

PubMed1990

Experimental chemonucleolysis with chondroitinase ABC.

Chemonucleolysis has recently become an established treatment for intervertebral disc protrusion. However, the exact mechanism of chemonucleolysis is still unknown. If mechanisms of chemonucleolysis include diminution of intradiscal pressure followed by subsequent regeneration of the nucleus pulposus, then a more selective enzyme for glycosaminoglycan, chondroitinase ABC, might be used for chemonucleolysis instead of chymopapain. Thus experimental chemonucleolysis with chondroitinase ABC compared with chymopapain was investigated. In rabbits, chondroitinase ABC is as effective for chemonucleolysis as chymopapain, but the chemonucleolysis process with chondroitinase ABC was milder than with chymopapain. At an early chemonucleolysis phase, chondroitinase ABC action was chiefly limited to digestion of the matrix, and a large number of cells in the nucleus pulposus remained. During long-term observations of chemonucleolysis with chondroitinase ABC, nuclear structure was restored to a nearly normal state. Although limited, this study indicates that chondroitinase ABC might be more suitable than chymopapain for chemonucleolysis.

Animals↗

PubMed1995

Effects of chondroitinase ABC on degenerative intervertebral discs.

The effects of chondroitinase ABC on surgically induced degenerative rabbit intervertebral discs were determined during a 12-week period by magnetic resonance imaging, radiography, and histologic examination. Rabbit intervertebral discs were surgically extruded, inducing disc degeneration 12 weeks before injection of chondroitinase ABC. Magnetic resonance imaging showed a hypointense area in the center of the surgically induced disc degeneration. After injection of chondroitinase ABC, the hypointense area became more intense, but reversed somewhat by the end of the 12-week period. Additional evidence of the effects of chondroitinase ABC on a surgically induced degenerative disc model was shown by radiographic evidence of shrinkage of the disc after injection. Histologic examination revealed a fibrous degenerative disc induced by surgical extrusion. However, the staining properties of the matrix of the nucleus pulposus was similar to that of normal discs before chondroitinase ABC injection, but diminished after the injection, with slight recovery at 12 weeks. The results suggest that chondroitinase ABC induces chemonucleolysis in the degenerated disc. Also, chondroitinase ABC does not destroy the degenerative disc matrix ability to regenerate after 12 weeks.

Animals↗

PubMed1993

Comparison of tissue reaction with chondroitinase ABC and chymopapain in rabbits as the basis of clinical application in chemonucleolysis.

Although chemonucleolysis with chymopapain is an approved treatment for lumbar intervertebral disk herniation, recent serious complications have raised doubt concerning its safety. It is therefore necessary to search for a safer and more selective agent than chymopapain for chemonucleolysis. Experimental chemonucleolysis with chondroitinase ABC was thus tested and compared with chymopapain. Acute tissue reactions to chondroitinase ABC were investigated and compared with chymopapain. The epidural space, yellow ligament, sciatic nerve, knee joint, and Achilles tendon were examined. Chymopapain damaged nervous and ligamentous tissues as well as cartilaginous tissue. Chondroitinase ABC did not damage nervous and ligamentous tissue. Chondroitinase ABC affected only cartilaginous tissue, and its action was chiefly limited to digestion of the matrix. Chondroitinase ABC has high enzymatic specificity for matrix in vivo. In addition, chondroitinase ABC is less toxic to noncartilaginous tissues than chymopapain. Chondroitinase ABC might be a more suitable and safer enzyme than chymopapain for chemonucleolysis.

Achilles Tendon↗

PubMedDate not supplied

Osteogenic protein-1 is most effective in stimulating nucleus pulposus and annulus fibrosus cells to repair their matrix after chondroitinase ABC-induced in vitro chemonucleolysis.

BACKGROUND CONTEXT: Chondroitinase ABC (C-ABC) is used in chemonucleolysis to degrade, with great specificity, the chondroitin sulfate and dermatan sulfate chains of proteoglycans (PGs). A recent study showed that osteogenic protein-1 (OP-1) is very effective in stimulating the production and formation of the extracellular matrix by rabbit intervertebral disc cells. PURPOSE: To test the hypothesis that the repair of the extracellular matrix of the intervertebral disc after chemonucleolysis by C-ABC can be stimulated by exposure to a low dose of a growth factor, OP-1. STUDY DESIGN: An alginate bead cell culture system was used to monitor the effects of OP-1 on the repair of damaged matrices after in vitro chemonucleolysis with C-ABC. METHODS: Rabbit nucleus pulposus (NP) or annulus fibrosus (AF) cells cultured for 2 weeks in alginate gel were briefly exposed to low concentrations of C-ABC and then cultured in the presence or absence of OP-1. The control group was cultured without enzyme treatment for the same period in the absence of OP-1. At each time point, the contents of DNA and proteoglycan accumulation and proteoglycan synthesis were measured. RESULTS: NP or AF cells cultured in alginate beads, which were digested with C-ABC and then treated with OP-1, recover PG content more rapidly than those cultured in the absence of OP-1. The major contributor to the superior matrix repair in the cells treated with OP-1 was an up-regulation of proteoglycan synthesis. CONCLUSIONS: OP-1 was effective in stimulating matrix repair by NP and AF cells after their matrices were nearly totally depleted of sulfated glycosaminoglycans. The use of OP-1 after chemonucleolysis might help the disc to regain biomechanical strength, weakened by enzyme digestion, by stimulating matrix metabolism.

Alginates↗

PubMed2003

Crystal structure of Proteus vulgaris chondroitin sulfate ABC lyase I at 1.9A resolution.

Chondroitin Sulfate ABC lyase I from Proteus vulgaris is an endolytic, broad-specificity glycosaminoglycan lyase, which degrades chondroitin, chondroitin-4-sulfate, dermatan sulfate, chondroitin-6-sulfate, and hyaluronan by beta-elimination of 1,4-hexosaminidic bond to unsaturated disaccharides and tetrasaccharides. Its structure revealed three domains. The N-terminal domain has a fold similar to that of carbohydrate-binding domains of xylanases and some lectins, the middle and C-terminal domains are similar to the structures of the two-domain chondroitin lyase AC and bacterial hyaluronidases. Although the middle domain shows a very low level of sequence identity with the catalytic domains of chondroitinase AC and hyaluronidase, the residues implicated in catalysis of the latter enzymes are present in chondroitinase ABC I. The substrate-binding site in chondroitinase ABC I is in a wide-open cleft, consistent with the endolytic action pattern of this enzyme. The tryptophan residues crucial for substrate binding in chondroitinase AC and hyaluronidases are lacking in chondroitinase ABC I. The structure of chondroitinase ABC I provides a framework for probing specific functions of active-site residues for understanding the remarkably broad specificity of this enzyme and perhaps engineering a desired specificity. The electron density map showed clearly that the deposited DNA sequence for residues 495-530 of chondroitin ABC lyase I, the segment containing two putative active-site residues, contains a frame-shift error resulting in an incorrectly translated amino acid sequence.

Amino Acid Sequence↗

PubMed2001

Effects of chondroitinase ABC on intradiscal pressure in sheep: an in vivo study.

STUDY DESIGN: In vivo intradiscal measurements of pressure in lumbar discs treated with chondroitinase ABC were performed. OBJECTIVE: To determine the decrease in lumbar intradiscal pressure after chemonucleolysis by chondroitinase ABC in sheep. SUMMARY OF BACKGROUND DATA: No previous study has assessed in vivo intradiscal pressure after chemonucleolysis. This study investigated the effect of chondroitinase ABC on intradiscal pressure in terms of a dose and time relation. It also included roentgenographic observations and evaluation of the correlation between disc space narrowing and decrease in intradiscal pressure. METHODS: Chondroitinase ABC was injected in the lumbar intervertebral discs of sheep at doses of 1, 5, and 50 U. Phosphate buffered saline also was injected as a negative control measure. One week before injection, then 1 and 4 weeks afterward, intradiscal pressure was measured using a catheter microtip pressure transducer. Simultaneously, standard lateral roentgenographs were taken, and the disc height index was calculated. RESULTS: The intradiscal pressure clearly was decreased 1 week after chondroitinase ABC injection. A further decrease was observed up to 4 weeks. This pressure decrease was dose dependent. The disc height indexes also decreased with time, but the state of the change was different from that of the changes in intradiscal pressure. No clear quantitative correlation was found between intradiscal pressure and disc height index. CONCLUSIONS: Chondroitinase ABC can induce the reduction of intradiscal pressure in the lumbar spine.

Animals↗

PubMed1989

Improved sensitivity of detection by avidin-biotin complex (ABC) immunocytochemistry in Epstein-Barr virus serology.

Serum antibodies against Epstein-Barr virus (EBV)-determined antigens have traditionally been titrated by the indirect immunofluorescence (IIF) technique. The avidin-biotin complex (ABC) immunocytochemical technique was used to determine the serum levels of IgA against EBV viral capsid antigen (IgA/VCA) and IgA against EBV early antigen (IgA/EA) in sera of 106 nasopharyngeal carcinoma (NPC) patients prior to treatment and 100 normal individuals. The sensitivity of the ABC technique is enhanced by an amplification of the antigen-antibody reaction, which involves the binding of the enzyme-linked ABC to the second biotinylated antibody. There was a good correlation (r = 0.9988) between ABC and IIF-determined IgA/VCA-positive titres, with the ABC technique being more sensitive than IIF in the detection of IgA/VCA in NPC sera: 94% (99/106) and 76% (80/106), respectively. The frequency of IgA/EA reactivity in NPC sera was also markedly increased by immunodetection with the ABC technique as compared with IIF technique: 63% (69/106) and 28% (30/106) respectively. Both the immunocytochemical techniques were equally specific in discriminating between elevated serum titres of IgA/VCA and IgA/EA in NPC sera from normal human sera.

Antibodies, Viral↗

PubMed2000

Characterization of the ABC transporter genes MgAtr1 and MgAtr2 from the wheat pathogen Mycosphaerella graminicola.

ATP-binding cassette (ABC) transporters are membrane-bound transporters involved in various physiological processes. In this paper we describe the cloning of the ABC transporter encoding genes MgAtr1 and MgAtr2 from the wheat pathogen Mycosphaerella graminicola (anamorph Septoria tritici). Both deduced proteins MgAtr1 and MgAtr2 are highly homologous to other fungal ABC transporters. RT-PCR revealed that the MgAtr2 mRNA population consists of partially and fully spliced transcripts. Putative substrates of ABC transporters, modulators of ABC transporter activity, and inducers of ABC transporter gene transcription were analyzed for their potential to induce expression of MgAtr1 and MgAtr2 in m. graminicola. The genes are differently upregulated by compounds such as the plant secondary metabolites eugenol and reserpine. Similar results are obtained for several antibiotics and the azole fungicides cyproconazole and imazalil. Moreover, a different expression pattern between yeast-like cells and mycelium of this dimorphic fungus was observed. These results indicate that MgAtr1 and MgAtr2 play a role in protection of m. graminicola against natural toxic compounds and xenobiotics. A putative role in protection against plant defense compounds during pathogenesis is suggested.

ATP-Binding Cassette Transporters↗

PubMed1996

Primary structure of a novel ABC transporter with a chromosomal localization on the band encoding the multidrug resistance-associated protein.

Complementary DNA clones encoding a novel protein, ABC-C, with the typical structural features of the ABC transporter family were identified in a human medullary thyroid carcinoma cell line. The transporter consists of 1704 amino acid residues with two homologous repeats, each harboring six putative transmembrane helices and an ATP-binding cassette motif. The mRNA is expressed highest in normal lung, but also in varying amounts in other tissues and in C-cell carcinoma. The ABC-C gene is mapped on chromosome 16p13.3, in close physical proximity to another ABC transporter, the multidrug resistance-associated protein. This related protein is assumed to confer resistance to chemotherapeutic drugs in small cell lung carcinoma. The genomic clustering of both transporters, typical also for other members of the ABC family, supports the notion that ABC-C may be involved in development of resistance to xenobiotics.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

Mediation of annexin 1 secretion by a probenecid-sensitive ABC-transporter in rat inflamed mucosa.

Annexin 1 is secreted by mammalian cells but lacks a leader signal sequence necessary to lead it to the classical secretory pathway via the endoplasmic reticulum. The mechanisms involved in the secretion of leaderless proteins remain uncertain. It has been suggested to involve membrane translocation via an ABC-transporter (ATP binding cassette). Using cultured inflamed mucosa from rectocolitis induced in rats, we studied if annexin 1 secretion followed the two main characteristics of ABC-transporter substrates: dependency on ATP hydrolysis and competitive inhibition by several other ABC-transporter substrates. Annexin 1 secretion is inhibited in a dose-dependent manner by two ATPase inhibitors. The inhibition reached 63.2+/-3.2%, 66.1+/-3.73% and 88.6+/-1.4% in the presence of 2mM vanadate, 0.5 and 1mM pervanadate, respectively. The efflux of calcein, a known ABC-transporter substrate, is similarly inhibited by 69.4+/-2.8% in the presence of 1mM pervanadate. Probenecid, an inhibitor of several ABC-transporters of the subfamilly ABCC or MRP (multidrug resistant associated protein), also inhibited annexin 1 secretion in a dose-dependent manner. As compared to control, 10mM probenecid reduced annexin 1 secretion by 72+/-20% and 20mM by 95.0+/-9%. By contrast, annexin 1 secretion is not blocked by other inhibitors of MRP1 (indomethacin, MK571), MRP2 (ochratoxin A1 or MK571), MRP5 (trequinsin or sulfinpyrazone) or by verapamil, cyclosporin A or glyburide. Taken together, our results show that annexin 1 secretion appears to share the efflux properties of ABC-transporter substrates.

ATP-Binding Cassette Transporters↗

PubMed2005

Multidrug resistance in parasites: ABC transporters, P-glycoproteins and molecular modelling.

Parasitic diseases, caused by protozoa, helminths and arthropods, rank among the most important problems in human and veterinary medicine, and in agriculture, leading to debilitating sicknesses and loss of life. In the absence of vaccines and with the general failure of vector eradication programs, drugs are the main line of defence, but the newest drugs are being tracked by the emergence of resistance in parasites, sharing ominous parallels with multidrug resistance in bacterial pathogens. Any of a number of mechanisms will elicit a drug resistance phenotype in parasites, including: active efflux, reduced uptake, target modification, drug modification, drug sequestration, by-pass shunting, or substrate competition. The role of ABC transporters in parasitic multidrug resistance mechanisms is being subjected to more scrutiny, due in part to the established roles of certain ABC transporters in human diseases, and also to an increasing portfolio of ABC transporters from parasite genome sequencing projects. For example, over 100 ABC transporters have been identified in the Escherichia coli genome, but to date only about 65 in all parasitic genomes. Long established laboratory investigations are now being assisted by molecular biology, bioinformatics, and computational modelling, and it is in these areas that the role of ABC transporters in parasitic multidrug resistance mechanisms may be defined and put in perspective with that of other proteins. We discuss ABC transporters in parasites, and conclude with an example of molecular modelling that identifies a new interaction between the structural domains of a parasite P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Nonrigid registration method to assess reproducibility of breath-holding with ABC in lung cancer.

PURPOSE: To study the interfraction reproducibility of breath-holding using active breath control (ABC), and to develop computerized tools to evaluate three-dimensional (3D) intrathoracic motion in each patient. METHODS AND MATERIALS: Since June 2002, 11 patients with non-small-cell lung cancer enrolled in a Phase II trial have undergone four CT scans: one during free-breathing (reference) and three using ABC. Patients left the room between breath-hold scans. The patient's breath was held at the same predefined phase of the breathing cycle (about 70% of the vital capacity) using the ABC device, then patients received 3D-conformal radiotherapy. Automated computerized tools for breath-hold CT scans were developed to analyze lung and tumor interfraction residual motions with 3D nonrigid registration. RESULTS: All patients but one were safely treated with ABC for 7 weeks. For 6 patients, the lung volume differences were <5%. The mean 3D displacement inside the lungs was between 2.3 mm (SD 1.4) and 4 mm (SD 3.3), and the gross tumor volume residual motion was 0.9 mm (SD 0.4) to 5.9 mm (SD 0.7). The residual motion was slightly greater in the inferior part of the lung than the superior. For 2 patients, we detected volume changes >300 cm(3) and displacements >10 mm, probably owing to atelectasia and emphysema. One patient was excluded, and two others had incomplete data sets. CONCLUSION: Breath-holding with ABC was effective in 6 patients, and discrepancies were clinically accountable in 2. The proposed 3D nonrigid registration method allows for personalized evaluation of breath-holding reproducibility with ABC. It will be used to adapt the patient-specific internal margins.

Carcinoma, Non-Small-Cell Lung↗

PubMed2000

Plant ABC transporters.

The ATP binding cassette (ABC) superfamily is a large, ubiquitous and diverse group of proteins, most of which mediate transport across biological membranes. ABC transporters have been shown to function not only as ATP-dependent pumps, but also as ion channels and channel regulators. Whilst members of this gene family have been extensively characterised in mammalian and microbial systems, the study of plant ABC transporters is a relatively new field of investigation. Sequences of over 20 plant ABC proteins have been published and include homologues of P-glycoprotein, MRP, PDR5 and organellar transporters. At present, functions have been assigned to a small proportion of these genes and only the MRP subclass has been extensively characterised. This review aims to summarise literature relevant to the study of plant ABC transporters, to review methods of cloning, to discuss the utility of yeast and mammalian systems as models and to speculate on possible roles of uncharacterised ABC transporters in plants.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview.

Active drug efflux transporters of the ATP binding cassette (ABC)-containing family of proteins have a major impact on the pharmacological behavior of most of the drugs in use today. Pharmacological properties affected by ABC transporters include the oral bioavailability, hepatobiliary, direct intestinal, and urinary excretion of drugs and drug-metabolites and -conjugates. Moreover, the penetration of drugs into a range of important pharmacological sanctuaries, such as brain, testis, and fetus, and the penetration into specific cell- and tissue compartments can be extensively limited by ABC transporters. These interactions with ABC transporters determine to a large extent the clinical usefulness, side effects and toxicity risks of drugs. Many other xenotoxins, (pre-)carcinogens and endogenous compounds are also influenced by the ABC transporters, with corresponding consequences for the well-being of the individual. We aim to provide an overview of properties of the mammalian ABC transporters known to mediate significant transport of clinically relevant drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Active breathing control (ABC) for Hodgkin's disease: reduction in normal tissue irradiation with deep inspiration and implications for treatment.

PURPOSE: Active breathing control (ABC) temporarily immobilizes breathing. This may allow a reduction in treatment margins. This planning study assesses normal tissue irradiation and reproducibility using ABC for Hodgkin's disease. METHODS AND MATERIALS: Five patients underwent CT scans using ABC obtained at the end of normal inspiration (NI), normal expiration (NE), and deep inspiration (DI). DI scans were repeated within the same session and 1-2 weeks later. To simulate mantle radiotherapy, a CTV1 was contoured encompassing the supraclavicular region, mediastinum, hila, and part of the heart. CTV2 was the same as CTV1 but included the whole heart. CTV3 encompassed the spleen and para-aortic lymph nodes. The planning target volume (PTV) was defined as CTV + 9 mm. PTVs were determined at NI, NE, and DI. A composite PTV (comp-PTV) based on the range of NI and NE PTVs was determined to represent the margin necessary for free breathing. Lung dose-mass histograms (DMH) for PTV1 and PTV2 and cardiac dose-volume histograms (DVH) for PTV3 were compared at the three different respiratory phases. RESULTS: ABC was well-tolerated by all patients. DI breath-holds ranged from 34 to 45 s. DMHs determined for PTV1 revealed a median reduction in lung mass irradiated at DI of 12% (range, 9-24%; n = 5) compared with simulated free-breathing. PTV2 comparisons also showed a median reduction of 12% lung mass irradiated (range, 8-28%; n = 5). PTV3 analyses revealed the mean volume of heart irradiated decreased from 26% to 5% with deep inspiration (n = 5). Lung volume comparisons between intrasession and intersession DI studies revealed mean variations of 4%. CONCLUSION: ABC is well tolerated and reproducible. Radiotherapy delivered at deep inspiration with ABC may decrease normal tissue irradiation in Hodgkin's disease patients.

Heart↗

PubMed2001

Crystal structures of the MJ1267 ATP binding cassette reveal an induced-fit effect at the ATPase active site of an ABC transporter.

BACKGROUND: ATP binding cassette (ABC) transporters are ubiquitously distributed transmembrane solute pumps that play a causative role in numerous diseases. Previous structures have defined the fold of the ABC and established the flexibility of its alpha-helical subdomain. But the nature of the mechanical changes that occur at each step of the chemical ATPase cycle have not been defined. RESULTS: Crystal structures were determined of the MJ1267 ABC from Methanococcus jannaschii in Mg-ADP-bound and nucleotide-free forms. Comparison of these structures reveals an induced-fit effect at the active site likely to be a consequence of nucleotide binding. In the Mg-ADP-bound structure, the loop following the Walker B moves toward the Walker A (P-loop) coupled to backbone conformational changes in the intervening "H-loop", which contains an invariant histidine. These changes affect the region believed to mediate intercassette interaction in the ABC transporter complex. Comparison of the Mg-ADP-bound structure of MJ1267 to the ATP-bound structure of HisP suggests that an outward rotation of the alpha-helical subdomain is coupled to the loss of a molecular contact between the gamma-phosphate of ATP and an invariant glutamine in a segment connecting this subdomain to the core of the cassette. CONCLUSIONS: The induced-fit effect and rotation of the alpha-helical subdomain may play a role in controlling the nucleotide-dependent change in cassette-cassette interaction affinity believed to represent the power-stroke of ABC transporters. Outward rotation of the alpha-helical subdomain also likely facilitates Mg-ADP release after hydrolysis. The MJ1267 structures therefore define features of the nucleotide-dependent conformational changes that drive transmembrane transport in ABC transporters.

ATP-Binding Cassette Transporters↗

PubMed2002

ATP binding to the motor domain from an ABC transporter drives formation of a nucleotide sandwich dimer.

It has been proposed that the reaction cycle of ATP binding cassette (ABC) transporters is driven by dimerization of their ABC motor domains upon binding ATP at their mutual interface. However, no such ATP sandwich complex has been observed for an ABC from an ABC transporter. In this paper, we report the crystal structure of a stable dimer formed by the E171Q mutant of the MJ0796 ABC, which is hydrolytically inactive due to mutation of the catalytic base. The structure shows a symmetrical dimer in which two ATP molecules are each sandwiched between the Walker A motif in one subunit and the LSGGQ signature motif in the other subunit. These results establish the stereochemical basis of the power stroke of ABC transporter pumps.

ATP-Binding Cassette Transporters↗

PubMed2001

Solute-binding protein-dependent ABC transporters are responsible for solute efflux in addition to solute uptake.

The ATP-binding cassette (ABC) transporter superfamily is one of the most widespread of all gene families and currently has in excess of 1100 members in organisms ranging from the Archaea to manQ1. The movement of the diverse solutes of ABC transporters has been accepted as being strictly unidirectional, with recent models indicating that they are irreversible. However, contrary to this paradigm, we show that three solute-binding protein-dependent (SBP) ABC transporters of amino acids, i.e. the general amino acid permease (Aap) and the branched-chain amino acid permease (Bra) of Rhizobium leguminosarum and the histidine permease (His) of Salmonella typhimurium, are bidirectional, being responsible for efflux in addition to the uptake of solutes. The net solute movement measured for an ABC transporter depends on the rates of uptake and efflux, which are independent; a plateau is reached when both are saturated. SBP ABC transporters promote active uptake because, although the Vmax values for uptake and efflux are not significantly different, there is a 103-104 higher affinity for uptake of solute compared with efflux. Therefore, the SBP ABC transporters are able to support a substantial concentration gradient and provide a net uptake of solutes into bacterial cells.

ATP-Binding Cassette Transporters↗