SEARCH · PubMed Health

Results for “Characterization”

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 829 records · Page 46Linked to original sources

PubMed2006

Molecular cloning and initial characterization of three novel human sulfatases.

Sulfatases constitute a group of enzymes capable of hydrolyzing the sulphate ester bond of a variety of biological compounds. To date, thirteen members of this family have been cloned and characterized as part of the human genome. In this work, the identification, molecular cloning and initial characterization of three new members of this human gene family is reported. Two map in chromosome 5 (5q15 and 5q32), whereas the third one maps in chromosome 4 (4q26). Two of them are closely related and are coded in only two exons, what is a unique genomic feature among the known sulfatases. The three new members were cloned from different DNA sources, and the predicted protein sizes range from 536 aa to 596 aa. Interestingly, initial characterization of two of them showed that their expression pattern was mainly restricted to embryonic tissues and some cancer cell lines.

Amino Acid Sequence↗

PubMed2006

Characterization of the murine Inpp4b gene and identification of a novel isoform.

Inositol polyphosphate phosphatases and phosphoinositides second messengers have been associated with major cellular functions as growth, differentiation, apoptosis, protein trafficking and motility. To characterize the role of inositol phosphatases in cell physiology, we have isolated the mouse Inositol polyphosphate 4-phosphatase type II (Inpp4b) cDNA. The murine Inpp4b locus was mapped on chromosome 8 in a synthenic region of the human 4q27-31 interval between Il-15 and Usp38. The mouse Inpp4b proteins, alpha and beta isoforms, encoded by this locus contained 927 and 941 amino acids respectively with a consensus phosphatase catalytic site and a conserved C2 domain that are highly similar with the human and rat homologues. Interestingly, we characterized a novel shorter isoform of Inpp4balpha resulting from an alternative translation initiation site and exon 5 skipping. Inpp4b C2 domain interacted with preferential affinity to phosphatidic acid and phosphatidylinositol 3,4,5-triphosphate (PI(3,4,5)P(3)) lipids. While analysis of Inpp4b transcript and protein expression demonstrated a broad tissue distribution for the alpha isoform, as for the paralogue Inpp4aalpha and beta isoforms, it also displayed a limited hematopoietic lineage distribution whereas the Inpp4bbeta isoform had a highly restricted pattern. Importantly, the Inpp4bbeta localized to the Golgi apparatus whereas Inpp4balpha was mainly cytosolic, suggesting a different cellular function for this isoform. Together our characterization of the murine Inpp4b gene expression pattern, cellular sublocalization and interacting lipids support highly specific function for individual Inpp4 phosphatase proteins.

Amino Acid Sequence↗

PubMed2006

First hsp70 from two hydrothermal vent shrimps, Mirocaris fortunata and Rimicaris exoculata: characterization and sequence analysis.

The vent shrimps, Mirocaris fortunata and Rimicaris exoculata, live in a highly fluctuating thermal environment and undergo frequent temperature bursts. As a first step in the investigation of the response to heat stress, this work aimed to characterize stress proteins in these two species. Complementary deoxyribonucleic acid (cDNA) clones encoding a 70-kDa heat shock protein (HSP) were isolated and characterized from M. fortunata and R. exoculata. The cDNA clones were of 2055 and 1941 base pairs in length, and contained a 2018-bp complete open reading frame (ORF) and a 1785-bp partial coding sequence, respectively. The amino acid sequences corresponding to these ORF are 645 residues in length for M. fortunata and 595 for R. exoculata, and were clearly characterized as members of the HSP70 family. The C-terminal extremity would identify R. exoculata sequence as a cytoplasm HSP70. The relationships between the crustacean HSP70 sequences were examined by two phylogenetic methods, i.e. Maximum Likelihood and Bayesian methods. The resulting trees suggested that M. fortunata sequence may correspond to constitutively expressed HSP70, named HSC70, whereas R. exoculata sequence may correspond to an inducible form of HSP70. The HSP70 sequences from the hydrothermal shrimps proved to be very similar to the other homologous shrimp sequences, except for the presence of an insertion of unknown function in the ATPase domain of R. exoculata sequence.

Amino Acid Sequence↗

PubMed2026

Characterization of the genotypic and phenotypic spectrum of TCF7L2-related neurodevelopmental disorder (TRND).

PURPOSE: TCF7L2 (OMIM 602228; HGNC:11641) is a transcription factor and a critical effector of the Wnt/ β-Catenin pathway. In 2021, 11 pediatric patients with monoallelic predicted loss-of-function (pLOF) TCF7L2 variants and syndromic features were observed. Characterization of patients with pLOF TCF7L2 variants and neurodevelopmental features-herein referred to as TCF7L2-related neurodevelopmental disorder-is urgently needed. METHODS: We leveraged multiple methods (eg, GeneMatcher, DECIPHER, literature review, and public/private repositories) to identify an international cohort of 76 patients with pLOF TCF7L2 variants and neurodevelopmental features and phenotypically characterized them. We also retrospectively searched for an independent cohort of adults with pLOF TCF7L2 variants (n = 11) from more than 60,000 PennMedicine BioBank patients. RESULTS: Among 76 patients with pLOF TCF7L2 variants, speech delay (95.3%), craniofacial dysmorphisms (73.3%), ophthalmologic conditions (65.5%), autism (62.1%), and orthopedic abnormalities (52.6%) were the most commonly observed. Phenotypic differences did not cluster by variant type or genomic locus. Among PennMedicine BioBank patients, an association of nominal significance with type 2 diabetes with renal manifestations (odds ratio = 5.8; P = .03) was detected, warranting further investigation. CONCLUSION: This study represents the most comprehensive characterization of TCF7L2-related neurodevelopmental disorder to date, a novel neurodevelopmental disorder, defining its genotypic and phenotypic spectra. We opened a Simons Searchlight natural history study that is now available for patient enrollment to enhance the understanding of this condition.

Neurodevelopmental syndrome↗

PubMed2006

Towards a molecular characterization of pharmaceutical excipients: mass spectrometric studies of ethoxylated surfactants.

The in-depth characterization of excipients is a prerequisite for their safe application in pharmaceutical products. In case of surfactants, this task can be a challenge, since many industrial products are mixtures of variable composition. In this work, mass spectrometric methods are applied to characterize some ethoxylated surfactants that are widely used by the pharmaceutical industry. Among them are ethoxylated fatty alcohols with ether structure (e.g., Brij, ethoxylated fatty acids with ester structure (e.g., Myrj, ethoxylated sorbitane fatty acid esters (e.g., Tween, ethoxylated glycerides (e.g., Tagat, and Triton X-100. MALDI-TOF mass spectrometry is best suitable to obtain molecular mass distributions of polymeric products, namely those with higher molecular mass. Electrospray and nanoelectrospray molecular mass shows a greater tendency for multiple charges. However, it is best suitable for small MM products, and multiple charges have been de-convoluted successfully using the MaxEnt 3 algorithm. Tandem mass spectrometry helps to identify the chemical composition, e.g. for identification of acyl chains. The work is intended to serve as a reference for mass spectrometric characterization of surfactants in the course of R&D, validation or change control.

Algorithms↗

PubMed2026

Leveraging Interradiomic Feature Relationships for Enhanced Prediction of Distant Metastasis and Characterization of Heterogeneity in Head and Neck Cancer.

PURPOSE: Distant metastasis remains a major cause of treatment failure in head and neck (HN) cancer, highlighting the need for more accurate early risk stratification. This study developed and validated a deep radiomics framework to characterize tumor heterogeneity from pretreatment computed tomography (CT) images and improve prediction of distant metastasis-free survival (DMFS). METHODS AND MATERIALS: This multicenter study included 3421 patients with HN cancer from 4 cohorts across 12 institutions. Radiomics features were extracted from primary tumors and transformed into OmicsMaps, a structured representation that spatially organizes interfeature relationships to facilitate learning of complex prognostic patterns. A convolutional neural network was trained to derive prognostic signatures, which were integrated with key clinical variables to construct an OmicsMap-clinical fusion model for patient risk stratification. Model performance was assessed using the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) in the CT Images from Large Head and Neck Cohort (RADCURE), HEAD-NECK-RADIOMICS-HN1 (HN1), and Head-Neck-Positron Emission Tomography-Computed Tomography (HN-PET-CT) cohorts. Radiogenomic analyses using RNA-seq data were conducted in the Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma (TCGA-HNSC) cohort to investigate biological characteristics associated with the imaging-defined risk groups. RESULTS: The OmicsMap achieved C-index values of 0.742, 0.768, and 0.671 in the RADCURE, HN1, and HN-PET-CT cohorts, outperforming the conventional radiomics approach by 5.40%-6.37%. Incorporating clinical variables further improved generalizability, yielding a C-index of 0.864 (HN1) and 0.730 (HN-PET-CT), with time-dependent AUC of 0.727-0.895. The fusion model consistently stratified patients into distinct high- and low-risk groups for both DMFS and overall survival across cohorts (P <.01). Radiogenomic analyses revealed enrichment of immune-related pathways in the low-risk group, whereas the high-risk group exhibited a more aggressive phenotype enriched for proliferation, hypoxia, and epithelial-mesenchymal transition pathways, along with a fibrosis-prone tumor microenvironment characterized by extracellular matrix remodeling. CONCLUSIONS: Modeling interradiomic feature relationships using the OmicsMap representation substantially improves CT-based prediction of DMFS and characterization of tumor heterogeneity in HN cancer, supporting precision risk stratification in clinical oncology.

Journal Article↗

PubMed2006

Optical coherence tomography for the characterization of basal cell carcinoma in vivo: a pilot study.

BACKGROUND: Optical coherence tomography combines principles of ultrasonography and optical interferometry to provide real-time cross-sectional images of subsurface microstructure of tissue in vivo. OBJECTIVE: The purpose of this pilot study was to define and characterize basal cell carcinoma by using optical coherence tomography. METHODS: Twenty-three patients with 49 lesions clinically suggestive of superficial basal cell carcinoma were recruited. Optical coherence tomography was used to characterize the features of the pearly papules in real time and in vivo. Shave biopsy and light microscopic images were compared with images from optical coherence tomography. RESULTS: Basal cell carcinoma was identified in 27 patients; all 27 had optical coherence tomographic images for comparison. Seven images were uninterpretable, probably because of technical problems. Of the remainder, 20 sites matched the histologic features seen on light microscopy, with excellent correlation between optical coherence tomographic images and histopathologic features of superficial, nodular, micronodular and infiltrative basal cell carcinomas. LIMITATIONS: This study was limited by the small number of patients examined. Also, as this study was not designed as an intent-to-diagnose study, the actual predictive value of optical coherence tomography technology remains unproven. CONCLUSIONS: Optical coherence tomography technology has potential for the diagnosis and histopathologic characterization of basal cell cancer. Additional studies to determine any practical role for optical coherence tomography are indicated.

Aged↗

PubMed2006

Bipolar II and anxious reactive "comorbidity": toward better phenotypic characterization suitable for genotyping.

OBJECTIVE: In DSM-IV, bipolar II (BP-II) disorder is defined by depression and hypomania. There is little appreciation of affective instability, often associated with anxiety-particularly panic disorder and agoraphobia (PDA)-comorbidity. This association has genetic-familial implications, which we believe must be incorporated in refining the BP-II phenotype suitable for genotyping purposes. METHOD: We examined in a semi-structured format 107 consecutive patients who met DSM-IV criteria for major depressive episode with atypical features and separated them into two subgroups according to the co-occurring criteria for PDA. They were further evaluated on the basis of the Atypical Depression Diagnostic Scale (ADDS), the Hopkins Symptoms Check-list (HSCL 90), and the Hamilton Rating Scale for Depression (HRSD), coupled with its modified form for reverse vegetative features, as well as Axis I and II comorbidity and temperamental dispositions, particularly cyclothymic instability. RESULTS: Fifty (46.7%) of our patients met the DSM-IV criteria for PDA. In terms of significant results, PDA+ was more frequently female, had higher number of hypomanic episodes, and stressors; they were also more often BP-II, and cyclothymic. Ratings of reactivity, somatization, OCD and phobic anxiety too were significantly higher among the PDA+. In related analyses, most AD (75.7%) met criteria for BP-II; the BP-II subgroup was characterized by PDA, as well as borderline personality features and cyclothymic and hyperthymic temperaments. LIMITATIONS: Correlational clinical study in which clinicians could not be kept entirely blind to the variables under investigation. CONCLUSIONS: In line with the description by the French psychiatrist Pierre Kahn a century earlier, cyclothymic reactivity and neurotic features (i.e., atypicality and panic attacks) appear relevant to the definition of what today we consider BP-II disorder. These data, which are in line with current familial-genetic models of this disorder, suggest that the DSM-IV characterization of BP-II must be enriched by greater emphasis on temperamentally based mood and anxious reactivity. Such phenotypic characterization is likely to assist in better genotyping. Previous work by us further suggests the relevance of bulimic and addictive tendencies, as well as "borderline personality" diagnosis in the proband and/or the family. We submit that these conditions, rather than being "comorbid," constitute, along with BP-II, a spectrum of overlapping underlying genetic diatheses.

Adolescent↗

PubMed2006

Characterization of cardiolipin as the sodiated ions by positive-ion electrospray ionization with multiple stage quadrupole ion-trap mass spectrometry.

The application of multiple-stage ion-trap (IT) mass spectrometric methods for the structural characterization of cardiolipin (CL), a 1,3-bisphosphatidyl-sn-glycerol that consists of four fatty acyl chains and three glycerol backbones (designated as A, B, and central glycerol, respectively), as the sodiated adduct ions in the positive-ion mode was evaluated. Following collisionally activated dissociation (CAD), the [M - 2H + 3Na]+ ions of CL yield two prominent fragment ion pairs that consist of the phosphatidyl moieties attached to the 1'- and 3'-position of the central glycerol, respectively, resulting from the differential losses of the diacylglycerol moieties containing A and B glycerol, respectively. The results are consistent with those previously described for the [M - H]- and [M - 2H + Na]- ions in the negative-ion mode, thus permitting assignment of the two phosphatidyl moieties attached to the 1'- or 3'-position of the central glycerol. The identities of the fatty acyl substituents and their positions on the glycerol backbones (glycerol A and B) are deduced from further degradation of the above ion pairs that give the fragment ions reflecting the fatty acid substituents at the sn-1 (or sn-1') and sn-2 (or sn-2') positions. The ions that arise from losses of the fatty acid substituents at sn-1 and sn-1', respectively, are prominent, but the analogous ions from losses of the fatty acid substituents at sn-2 and sn-2', respectively, are of low abundance in the MS2 product-ion spectra. This feature further confirms the assignment of the positions of the fatty acid substituents. The similar IT multiple-stage mass spectrometric approaches including MS2 and MS3 for structural characterization of CL using its [M + Na]+ and the [M - H + 2Na]+ ions are also readily applicable. However, their uses for structural characterization are less desirable because formation of the [M + Na]+ and the [M - H + 2Na]+ ions for CL is not predictable.

Cardiolipins↗

PubMed2004

Development of advanced image analysis techniques for the in situ characterization of multiphase dispersions occurring in bioreactors.

Fermentation bioprocesses typically involve two liquid phases (i.e. water and organic compounds) and one gas phase (air), together with suspended solids (i.e. biomass), which are the components to be dispersed. Characterization of multiphase dispersions is required as it determines mass transfer efficiency and bioreactor homogeneity. It is also needed for the appropriate design of contacting equipment, helping in establishing optimum operational conditions. This work describes the development of image analysis based techniques with advantages (in terms of data acquisition and processing), for the characterization of oil drops and bubble diameters in complex simulated fermentation broths. The system consists of fully digital acquisition of in situ images obtained from the inside of a mixing tank using a CCD camera synchronized with a stroboscopic light source, which are processed with a versatile commercial software. To improve the automation of particle recognition and counting, the Hough transform (HT) was used, so bubbles and oil drops were automatically detected and the processing time was reduced by 55% without losing accuracy with respect to a fully manual analysis. The system has been used for the detailed characterization of a number of operational conditions, including oil content, biomass morphology, presence of surfactants (such as proteins) and viscosity of the aqueous phase.

Bacteria↗

PubMed2005

A method for the characterization of emulsions, thermogranulometry: application to water-in-crude oil emulsion.

Emulsions are used in a wide range of applications and industries. Their size distribution is an important parameter because it influences most of the emulsion properties of emulsions. Several techniques of characterization are used to determine the granulometric distribution of emulsions, but they are generally limited to dilute samples and are based on complex algorithms. We describe a method that allows characterization of the droplet size distribution of emulsions using thermal analysis (thermogranulometry). This method permits the use of very concentrated samples without any dilution or perturbation of the system. We first define our method by a thermodynamic and kinetic approach. We studied a real system, i.e., crude oil emulsions, which form very concentrated, viscous, and opaque emulsions with water. We present a correlation between the size of droplets and their freezing temperature, corresponding to our system. Then we compare the size distributions obtained by our method with those derived by direct microscopy observations. The results obtained show that thermogranulometry may be an interesting method of characterization of emulsions, even for concentrated systems.

Journal Article↗

PubMed2005

Quantitative characterization of food products by two-dimensional D-T2 and T1-T2 distribution functions in a static gradient.

We present new NMR techniques to characterize food products that are based on the measurement of two-dimensional diffusion-T2 relaxation and T1-T2 relaxation distribution functions. These measurements can be performed in magnets of modest strength and low homogeneity and do not require pulsed gradients. As an illustration, we present measurements on a range of dairy products that include milks, yogurt, cream, and cheeses. The two-dimensional distribution functions generally exhibit two distinct components that correspond to the aqueous phase and the liquid fat content. The aqueous phase exhibits a relatively sharp peak, characterized by a large T1/T2 ratio of around 4. The diffusion coefficient and relaxation times are reduced from the values for bulk water by an amount that is sample specific. The fat signal has a similar signature in all samples. It is characterized by a wide T2 distribution and a diffusion coefficient of 10(-11) m2/s for a diffusion time of 40 ms, determined by bounded diffusion in the fat globules of 3 microm diameter.

Dairy Products↗

PubMed2006

Characterization and removal of DNAPL from sand and clay layered media.

Important characterization and remediation techniques (e.g. partitioning tracer tests (PTT), cosolvent and surfactant flushing) have been developed over the years to deal with dense nonaqueous phase liquid (DNAPL) sources in the saturated zone. Unfortunately, subsurface media layering and heterogeneity pose a major challenge to the efficiency of these and other techniques that rely on flushing fluids through porous media. Using laboratory column experiments with both single media and layered-media columns and computer modeling of tracer breakthrough results, we examined the difficulty that layering poses to subsurface remediation and characterization techniques. Quantifying tetrachloroethylene (PCE) saturation in layered media was determined using PTT and effluent mass determinations. Conservative tracer breakthrough curves were used to determine permeability and the flow through layers before and after PCE contamination. The removal efficiency of alcohol flushing in the layered systems was also determined. Results showed that even a relatively simple layering with less than an order magnitude difference in permeability leads to difficulty in characterization and remediation using flushing technologies. These results suggest that much greater volumes of flushing solutions will be needed in heterogeneous environments to ensure adequate flushing of lower permeable lenses and layers.

Alcohols↗

PubMed2006

Source-zone characterization of a chlorinated-solvent contaminated Superfund site in Tucson, AZ.

An extensive site-characterization project was conducted at a large chlorinated-solvent contaminated Superfund site in Tucson, AZ. The project consisted of several components, including traditional site-characterization activities, tracer tests, laboratory experiments conducted with core material collected from the site, and mathematical modeling. The primary focus of the work presented herein is the analysis of induced-gradient contaminant elution tests conducted in a source zone at the site, investigation of the potential occurrence of immiscible liquid in the saturated zone, characterization of the relationship between mass flux reduction and mass removal, and evaluation of the impact of source-zone management on site remediation. The results of the present study, along with those of prior work, indicate that immiscible liquid is likely present in the saturated zone at the site source zones. Extensive tailing and rebound was observed for the contaminant-elution tests, indicating nonideal transport and mass-transfer behavior. The elution data were analyzed with a source-zone-scale mathematical model, and the results indicated that nonideal immiscible-liquid dissolution was the primary cause of the observed behavior. The time-continuous relationship between mass flux reduction and mass removal associated with the plume-scale pump-and-treat operation exhibited an initial large drop in mass flux with minimal mass removed, followed by a period of minimal mass flux reduction and a second period of large reduction. This behavior reflects the impact of both source-zone and aqueous-plume mass removal dynamics. Ultimately, a greater than 90% reduction in mass flux was achieved for a mass removal of approximately 50%. The influence of source-zone management on site remediation was evaluated by conducting two predictive simulations, one for which the source zones were controlled and one for which they were not. A plume-scale model was used to simulate the composite contaminant concentrations associated with groundwater extracted with the pump-and-treat system, which were compared to measured data. The information generated from this study was used to enhance the site conceptual model, help optimize operation of the pump-and-treat system, and evaluate the utility of source-zone remediation.

Arizona↗

PubMed2004

Characterization and in vitro degradation of poly(2,3-(1,4-diethyl tartrate)-co-2,3-isopropyliden tartrate).

In the present study, a less known polyester based on tartaric acid was characterized with respect to its degradation mechanism. Poly(2,3-(1,4-diethyl tartrate)-co-2,3-isopropyliden tartrate) (PTA) differs from commonly used biodegradable polyesters, such as poly(lactides-co-glycolides) (PLGA) by the presence of additional cleavable bonds in the polymer side chains. This modification results in different polymer properties and influences polymer degradation. The hydrolytic degradation of PTA was studied in parallel to PLGA using disc-shape matrices, which were obtained by compression-molding. The discs were incubated in pH 7.4 phosphate buffer solution at 37 degrees C. The degraded samples were characterized for percentage mass loss, water absorption, decay of molecular weight and change in glass transition temperature. The results demonstrate that the degradation of PTA proceeds via bulk erosion similar to PLGA. However, the degradation of PTA implants is characterized by a rapid mass loss within a short period of time appearing after a definite lag phase without remarkable mass loss. This makes the polymer promising for pulsatile drug release systems.

Alkenes↗

PubMed2005

Quantification and characterization of myosin peptide-specific CD4+ T cells in autoimmune myocarditis.

Characterization of autoantigen-specific CD4+ T cells at the single cell level is crucial for understanding the immunopathological mechanisms underlying autoimmune diseases. Cardiac myosin heavy chain (myhca) is the major autoantigen associated with autoimmune myocarditis both in humans and in experimental autoimmune myocarditis (EAM) in mice. In the current study, we evaluated two methods for the enumeration and phenotypic characterization of myhca-specific CD4+ T cells during the course of EAM. Both enzyme-linked immunospot (ELISPOT) and cytokine flow cytometry (CFC) assays were suitable for the detection and characterization of myhca-specific Th cells during acute myocardial inflammation and the late healing phase of the disease. Cytokine production of myhca-specific Th cells was restricted to interferon-gamma (IFNgamma). Only trace amounts of the Th2 cytokines IL-4 and IL-5 could be detected. Concomitant surface marker analysis in the CFC assay revealed the prototypical effector phenotype of myhca-specific Th1 cells during the acute phase of the disease. Taken together, the combination of both methods appears to be most appropriate for a comprehensive ex vivo single cell analysis of Th cells in heart-specific autoimmune disorders.

Animals↗

PubMed2004

Characterization and quantification of triple helix formation in chromosomal DNA.

DNA-binding molecules that recognize specific sequences offer a high potential for the understanding of chromatin structure and associated biological processes in addition to their therapeutic potential, e.g. as positioning agents for validated anticancer drugs. A prerequisite for the development of DNA-binding molecules is the availability of appropriate methods to assess their binding properties quantitatively at the desired target sequence in the human genome. We have further developed a capture assay to assess triplex-forming oligonucleotide (TFO) binding efficiency quantitatively. This assay is based on bifunctional, psoralen and biotin-conjugated, TFOs and real-time PCR analysis. We have applied this novel quantification method to address two issues that are relevant for DNA-binding molecules. First, we have compared directly the extent of TFO-binding in three experimental settings with increasing similarity to the situation in vivo, i.e. naked genomic DNA, isolated cell nuclei, or whole cells. This comparison allows us to characterize factors that influence genomic triplex formation, e.g. chromosomal DNA organization or intracellular milieu. In isolated nuclei, the binding was threefold lower compared to naked DNA, consistent with a decreased target accessibility int he nucleosomal environment. Binding was detected in whole cells, indicating that the TFO enters the nucleus and binds to its target in intact cells in vivo, but the efficiency was decreased (tenfold) compared to nuclei. Secondly, we applied the method to characterize the binding properties of two different TFOs targeting the same sequence. We found that an antiparallel-binding GT-containing TFO bound more efficiently, but with less target sequence selectivity compared to a parallel-binding CU-containing TFO. Collectively, a sensitive method to characterize genomic triplex formation was described. This may be useful for the determination of factors driving TFO binding efficiency and, thus, may improve the usefulness of triplex-mediated gene targeting for studies of chromatin structure as well as for therapeutic antigene strategies.

Base Sequence↗

PubMed2004

Ex vivo characterization of articular cartilage and bone lesions in a rabbit ACL transection model of osteoarthritis using MRI and micro-CT.

OBJECTIVE: To characterize the rabbit anterior cruciate ligament transection (ACLT) model of osteoarthritis (OA) at various stages of disease using high-resolution 3-D medical imaging systems, which, in turn, will facilitate future longitudinal studies evaluating disease progression and response to therapy in live animals. METHODS: Degenerative changes in femorotibial cartilage, volumetric bone mineral density (vBMD), bone volume fraction (BV/TV), and osteophyte volume were characterized ex vivo using 4-T magnetic resonance imaging (MRI) and micro-computed tomography (micro-CT) at 4, 8, and 12 weeks post-ACLT. These changes were subsequently correlated to macroscopic joint evaluation. RESULTS: Macroscopic assessment demonstrated progressive cartilage degeneration post-surgery, which was significantly correlated to MRI evaluation (r=0.82, P<0.0001). Linear regression analysis indicated that vBMD and BV/TV are linearly related such that as vBMD increases, BV/TV increases (P<0.0001). Micro-CT revealed bone loss at 4 and 8 weeks post-ACLT, but recovery to control values at 12 weeks post-ACLT. Volumetric BMD was not strongly correlated with macroscopic assessment of articular cartilage degeneration (r=-0.35, P<0.0001). Quantitative measurement of osteophyte volume demonstrated a statistically significant difference (with respect to control groups) at both 8 and 12 weeks post-ACLT, but not at 4 weeks post-ACLT. CONCLUSIONS: The rabbit ACLT model of OA demonstrates progressive cartilage degeneration and intermediate bone changes at 4, 8, and 12 weeks post-surgery. Cartilage and bone lesions were characterized ex vivo using 4-T MRI and micro-CT, and MRI assessment of cartilage degeneration was correlated to macroscopic grading.

Animals↗