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At least 361 records · Page 20Linked to original sources

PubMed2004

Clinical and functional comparison of uni- and bicondylar sledge prostheses.

The aim of the present study was the evaluation of differences in clinical results, proprioceptive performance and gait in patients with unicondylar and bicondylar sledge prostheses of the knee. In a retrospective study, 17 patients with unicondylar sledge prostheses were compared with 15 patients with bicondylar sledge prostheses. Clinical examination was rated using HSS, Knee Society, and patellar scores and a visual analogue scale for pain. Proprioceptive performance was examined using sway measurements during single leg stance on a force platform. In addition, the patients underwent 3-D gait analysis including measurements of ground reaction forces and surface electromyographic (EMG) investigation of the lower extremity. Comparing both patient groups in clinical scores, gait, EMG and proprioception, no significant differences were found. Implantation of bicondylar sledge prostheses retaining both cruciate ligaments achieves functional results as good as unicompartmental arthroplasty. The presented results might encourage future research on new models of total joint replacement with preservation of both cruciate ligaments.

Aged↗

PubMed2006

Point-of-care biosensor systems for cancer diagnostics/prognostics.

With the growing number of fatalities resulting from the 100 or so cancer-related diseases, new enabling tools are required to provide extensive molecular profiles of patients to guide the clinician in making viable diagnosis and prognosis. Unfortunately with cancer-related diseases, there is not one molecular marker that can provide sufficient information to assist the clinician in making effective prognoses or even diagnoses. Indeed, large panels of markers must typically be evaluated that cut across several different classes (mutations in certain gene fragments--DNA; over/under-expression of gene activity as monitored by messenger RNAs; the amount of proteins present in serum or circulating tumor cells). The classical biosensor format (dipstick approach for monitoring the presence of a single element) is viewed as a valuable tool in many bioassays, but possesses numerous limitations in cancer due primarily to the single element nature of these sensing platforms. As such, if biosensors are to become valuable tools in the arsenal of the clinician to manage cancer patients, new formats are required. This review seeks to provide an overview of the current thinking on molecular profiling for diagnosis and prognosis of cancers and also, provide insight into the current state-of-the-art in the biosensor field and new strategies that must be considered to bring this important technology into the cancer field.

Biomarkers, Tumor↗

PubMed2005

Nanodroplet profiling of enzymatic activities in a microarray.

We describe a generic method for the large-scale functional characterization of enzymes in a microarray. Poly-l-lysine and amine reactive slides were coated with fluorogenic substrates sensitive to proteases and phosphatases. Patterning enzymes on the slides by robotic printing produced spatially addressable, segregated droplets that were simultaneously exposed to the on-chip sensors. Multiple enzymes were profiled using this system that provided fluorescence readouts across temporal and stoichiometric dimensions concurrently on a single microarray substrate. This integrated microarray platform is applicable not only for the functional annotation of proteins, but also for the rapid agonist and antagonist discovery and in performing on-chip kinetics.

Microarray Analysis↗

PubMed2004

Changes in ground reaction force during jump landing in subjects with functional instability of the ankle joint.

OBJECTIVE: To identify changes in ground reaction force during jump landing in subjects with functional instability of the ankle joint. DESIGN: Comparison of ground reaction force during jump landing between subjects with functional instability and healthy controls. BACKGROUND: We have recently demonstrated significantly altered patterns of ankle and knee movement immediately pre- and post-impact in subjects with functional instability compared to healthy controls. We now examine the changes in timing and magnitude of forces sustained by the unstable ankle during jump landing. METHODS: Fourteen subjects with unstable ankles and 10 age, sex and activity matched controls performed five single leg jumps onto a force platform whilst ground reaction forces were sampled. Timing and magnitudes of forces during the first 150 ms following impact were analysed and compared between groups. RESULTS: Lateral and anterior force peaks occurred significantly earlier in subjects with functional instability. Significant differences were seen between groups' time-averaged vertical, frontal and sagittal components of ground reaction force. These ranged from 5% (frontal force) to 100% (vertical force) of body mass. These changes occur immediately post-impact and too early for reflex correction/modification. CONCLUSIONS: The disordered force patterns observed in subjects with functional instability are likely to result in repeated injury due to significant increase in stress on ankle joint structures during jump landing. We suggest that they are most likely to result from deficits in feed-forward motor control. RELEVANCE: These results identify the potentially injurious nature of the changes in the forces applied to the unstable ankle joint during jump landing. The timing of these changes suggests that they are caused by a motor control deficit. Treatment approaches aimed at retraining feed-forward control of ankle joint movement could succeed in restoring more normal patterns of force absorption and reduce the occurrence of repeated micro-trauma to ankle structures.

Adaptation, Physiological↗

PubMed2026

CRISPR activation reveals SOX5/6/9 as key transcriptional regulators directing iPSC-derived cells toward a notochordal lineage.

Intervertebral disc (IVD) degeneration, a leading cause of chronic lower back pain, is associated with loss of vacuolated notochordal cells (NCs) and fibrotic remodeling of the nucleus pulposus. Emerging therapies increasingly focus on NCs, which are rare but therapeutically relevant cells for regenerating degenerated IVDs. In this study, we used CRISPR-based transactivation (CRISPRa) to direct the differentiation of human induced pluripotent stem cells (iPSCs) into the NC lineage. We tested CRISPRa-mediated activation of NOTO, TBXT, FOXA2, SOX5, SOX6, and SOX9, coupled with single-cell sequencing of Aggrecan-2A-mScarlet reporter iPSCs. This approach identified the SOX5/6/9 combination (SOX-trio) as critical for promoting NC lineage commitment. The SOX-trio yielded the largest cell population expressing a range of genes previously associated with NC identity, including SHH, FOXA1, FOXA2, FOXJ1, FN1, ALCAM, KRT8, and KRT18. Our study demonstrates the integration of CRISPRa with single-cell technologies as a powerful platform for investigating and enriching iPSC-derived NCs, supporting future regenerative strategies across various fields.

Humans↗

PubMed2026

Protocol for haplotype-resolved structural variant detection via long-read sequencing using cuteHap.

Long-read sequencing technologies have revolutionized human genome exploration at an unparalleled resolution, particularly facilitating the analysis of structural variation (SV) at haplotype resolution. Here, we present a protocol for using cuteHap, a robust framework for haplotype-aware SV detection through phased alignment reads generated by diverse long-read sequencing platforms. We describe procedures for single-nucleotide variant (SNV) calling, read phasing, SV calling, and genotyping. We also establish a benchmarking pipeline to evaluate the detected SV callsets. For complete details on the use and execution of this protocol, please refer to Cao et al.1.

Bioinformatics↗

PubMed1998

Ankle orthoses effect on single-limb standing balance in athletes with functional ankle instability.

OBJECTIVE: To test whether a rigid or a flexible ankle orthosis affects postural sway in single-limb stance as quantified by stabilometry. DESIGN: Crossover trial. SETTING: University laboratory. PARTICIPANTS: Twenty-two athletes with functional ankle instability (consecutive sample of patients with recurrent ankle sprains but without mechanical instability) and 22 healthy athletes (control group of volunteers matched to age, height, weight, physical activity). INTERVENTIONS: Stabilometry in single-limb stance on a force platform. Participants were tested on each leg with and without a rigid or a flexible ankle orthosis. The order of test conditions was randomized. MAIN OUTCOME MEASURES: Sway velocities, sway pattern, and sway area as calculated from center of pressure movements. The two groups were compared by Mann-Whitney test, and the different orthoses within each group were compared by Wilcoxon test, paired samples (type I error 5%, Bonferroni adjustment). RESULTS: In athletes with functional ankle instability, both a rigid and a flexible ankle orthosis significantly reduced mediolateral sway velocity. A flexible ankle orthosis also changed sway pattern significantly, by reducing the percentage of linear movements of less than 5 degrees per .01 sec. CONCLUSIONS: In athletes with functional ankle instability, ankle orthoses reduce mediolateral sway velocity, possibly because of improved mediolateral proprioception.

Adult↗

PubMed1999

Effects of chronic anterior cruciate ligament deficiency on muscle activation patterns during an abrupt deceleration task.

OBJECTIVE: This study examined the influence of chronic anterior cruciate ligament deficiency on muscle activation patterns displayed during abrupt deceleration, relative to timing of tibiofemoral shear forces (Fs) generated during the task. DESIGN: Experimental data were collected for both limbs of 11 chronic functional anterior cruciate ligament deficient subjects and 11 matched controls. METHODS: Electromyographic, high speed film and ground reaction force data were sampled as subjects landed in single-limb stance on a force platform after receiving a chest level pass and decelerating abruptly. Temporal characteristics of each muscle burst relative to initial foot-ground contact were derived and Fs were calculated from net joint reaction forces and the patellar tendon force occasioned by the net moments and inertial forces predicted about the knee. RESULTS: Compared to controls, anterior cruciate ligament deficient subjects displayed a delay in hamstring activation so that peak hamstring activity was more synchronous with initial contact and with the high Fs which occurred after initial contact. CONCLUSIONS: It was concluded the delayed hamstring activation was an adaptation developed to enable peak muscle activity to better coincide with the high anterior Fs, thereby stabilizing the injured limb against a giving-way episode via increased joint compression and posterior tibial drawer.

Adult↗

PubMed2001

Is lower limb muscle synchrony during landing affected by gender? Implications for variations in ACL injury rates.

This study examined whether lower limb muscle synchrony during abrupt landings was affected by gender, thereby predisposing females to a higher incidence of non-contact anterior cruciate ligament (ACL) injuries than males. Seven males and 11 females landed in single-limb stance on a force platform after receiving a chest-height netball pass and decelerating abruptly. Ground reaction force and electromyographic data for rectus femoris, vastus lateralis, vastus medialis, semimembranosus (SM), biceps femoris, and gastrocnemius were sampled (1000 Hz) during landing. Subjects' sagittal plane motion was also filmed (200 Hz). Knee joint reaction forces and sagittal planar net moments of force were estimated using Newtonian equations of motion and inverse dynamics. Tibiofemoral shear forces (F(s)) were obtained and muscle bursts temporally analysed with respect to initial foot-ground contact (IC) and peak F(s) times. Males displayed significantly delayed SM onset relative to IC (113+/-46 ms) compared to females (173+/-54 ms; p=0.03), and significantly delayed SM peak activity relative to peak F(s) (54+/-27 ms) compared to females (77+/-15 ms; p=0.03). Delayed SM activity during landing was suggested to allow peak muscle activity to better coincide with high anterior F(s), thereby acting as an ACL synergist via increased joint compression and posterior tibial drawer. It was concluded that females displayed muscle synchrony less protective of the ACL than males, possibly increasing their susceptibility to non-contact ACL injuries.

Adult↗

PubMed2003

A smart microfluidic affinity chromatography matrix composed of poly(N-isopropylacrylamide)-coated beads.

The efficient upstream processing of complex biological or environmental samples for subsequent biochemical analysis remains a challenge in many analytical systems. New microfluidic platforms that provide multidiagnostic capabilities on single chips face a similar challenge in getting specific analytes purified or contaminants removed in different fluid streams. Here, stimuli-responsive polymers have been used to construct "smart" beads that can be reversibly immobilized on microfluidic channel walls to capture and release targets. The 100-nm latex beads were surface-modified with the temperature-sensitive polymer poly(N-isopropylacrylamide) (PNIPAAm). At room temperature, a suspension of these beads flows through a microfluidic channel constructed of poly(ethylene terephthalate). However, when the temperature in the channel is raised above the lower critical solution temperature (LCST) of PNIPAAm, the beads aggregate and adhere to the walls of the channel. The adhered beads are stable for long durations on the channel walls (demonstrated up to 70 min) in the presence of flow. The beads were further modified with the affinity moiety biotin, which tightly binds streptavidin. The dual-modified beads were adhered to the channel walls and functioned as a chromatographic affinity separation matrix, capable of binding streptavidin that was flowed through the microfluidic channel. Upon the reverse thermal stimulation to below the PNIPAAm LCST, the beads and captured streptavidin were observed to quickly dissolve and elute from the channel walls. This temperature-responsive affinity chromatography matrix can thus be flowed into a column and aggregated via temperature change, followed by the controlled release of affinity-captured targets back into the microfluidic flow stream.

Acrylamides↗

PubMed2003

Surface-enhanced Raman scattering substrate based on a self-assembled monolayer for use in gene diagnostics.

The development of surface-enhanced Raman scattering (SERS)-active substrates for cancer gene detection is described. The detection method uses Raman active dye-labeled DNA gene probes, self-assembled monolayers, and nanostructured metallic substrates as SERS-active platforms. The mercaptohexane-labeled single-stranded DNA (SH-(CH(2))(6)-ssDNA)/6-mercapto-1-hexanol system formed on a silver surface is characterized by atomic force microscopy. The surface-enhanced Raman gene (SERGen) probes developed in this study can be used to detect DNA targets via hybridization to complementary DNA probes. The probes do not require the use of radioactive labels and have a great potential to provide both sensitivity and selectivity. The effectiveness of this approach and its application in cancer gene diagnostics (BRCA1 breast cancer gene) are investigated.

BRCA1 Protein↗

PubMed2005

Single molecule spectroscopic investigation on conformational heterogeneity of directly linked zinc(II) porphyrin arrays.

We have comparatively investigated the photophysical properties of a series of meso-meso directly linked orthogonal porphyrin arrays (Zn, n = 1, 2, 3, 4, 6, 8, 9, 12, 16, 32, 48, 64, and 96) by ensemble average and single molecule fluorescence spectroscopy. In single molecule fluorescence study, we have recorded the fluorescence intensity trajectories of Zn arrays as the number of porphyrin molecules in the array increases. Up to Z8 in porphyrin arrays, each single array exhibits multiple stepwise photobleaching behaviors in fluorescence intensity trajectories, indicating that each porphyrin unit in the array acts as an individual fluorescent unit due to a maintenance of linear rigid structure of the array. On the other hand, porphyrin arrays longer than Z8 such as Z16, Z32, Z48, and Z64 show complicated photobleaching behaviors in fluorescence intensity trajectories. The origin of complex photobleaching behaviors is believed to be increasing nonradiative decay channels contributed by the enhanced structural nonlinearity in longer arrays. The fluorescence measurements of Zn arrays on single molecule level show a mismatch in the maximum fluorescence intensity level as compared to the solution measurements, which is attributable to the difference in local environment surrounding the porphyrin array. In this work, we have demonstrated the presence of conformational heterogeneity in longer porphyrin arrays by analyzing average survival times and fluorescence spectra of single arrays as the number of porphyrin molecules in the array increases. We believe that the fluorescence properties of porphyrin arrays on single molecule level will provide a platform for further applications as molecular photonic wires.

Journal Article↗

PubMed2006

Carbon nanotube amplification strategies for highly sensitive immunodetection of cancer biomarkers.

We describe herein the combination of electrochemical immunosensors using single-wall carbon nanotube (SWNT) forest platforms with multi-label secondary antibody-nanotube bioconjugates for highly sensitive detection of a cancer biomarker in serum and tissue lysates. Greatly amplified sensitivity was attained by using bioconjugates featuring horseradish peroxidase (HRP) labels and secondary antibodies (Ab(2)) linked to carbon nanotubes (CNT) at high HRP/Ab(2) ratio. This approach provided a detection limit of 4 pg mL(-)(1) (100 amol mL(-)(1)), for prostate specific antigen (PSA) in 10 microL of undiluted calf serum, a mass detection limit of 40 fg. Accurate detection of PSA in human serum samples was demonstrated by comparison to standard ELISA assays. PSA was quantitatively measured in prostate tissue samples for which PSA could not be differentiated by the gold standard immunohistochemical staining method. These easily fabricated SWNT immunosensors show excellent promise for clinical screening of cancer biomarkers and point-of-care diagnostics.

Biomarkers, Tumor↗

PubMed2003

Noncovalent functionalization of carbon nanotubes for highly specific electronic biosensors.

Novel nanomaterials for bioassay applications represent a rapidly progressing field of nanotechnology and nanobiotechnology. Here, we present an exploration of single-walled carbon nanotubes as a platform for investigating surface-protein and protein-protein binding and developing highly specific electronic biomolecule detectors. Nonspecific binding on nanotubes, a phenomenon found with a wide range of proteins, is overcome by immobilization of polyethylene oxide chains. A general approach is then advanced to enable the selective recognition and binding of target proteins by conjugation of their specific receptors to polyethylene oxide-functionalized nanotubes. This scheme, combined with the sensitivity of nanotube electronic devices, enables highly specific electronic sensors for detecting clinically important biomolecules such as antibodies associated with human autoimmune diseases.

Biosensing Techniques↗

PubMedDate not supplied

GM-CSF gene-modifed cancer cell immunotherapies: of mice and men.

GVAX cancer immunotherapies are composed of whole tumor cells genetically modified to secrete the immune stimulatory cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF), and then irradiated to prevent further cell division. Both autologous (patient specific) and allogeneic (non-patient specific) GVAX platforms have been evaluated either as single agents or in combination with other immunomodulatory strategies. Many early-phase clinical trials have now been completed. Results have consistently demonstrated a favorable safety profile manifested primarily by injection site reactions and flu-like symptoms. Consistent evidence of immune activation and clinical activity, including radiologic tumor regressions, has been seen across multiple cancer indications in both early- and late-stage disease. Phase 3 trials evaluating an allogeneic GVAX immunotherapy product in prostate cancer are under way.

Animals↗

PubMed2002

MArray: analysing single, replicated or reversed microarray experiments.

UNLABELLED: MArray is a Matlab toolbox with a graphical user interface that allows the user to analyse single or paired microarray datasets by direct input of the raw data output file from image analysis packages, such as QuantArray or GenePiX. The application provides simple procedures to manually evaluate the quality of each measurement, multiple approaches to both ratio normalization (simple normalization, intensity dependent normalization) and evaluation of the reproducibility of paired experiments (using the techniques 'simple statistical method' and 'quality control ellipse' and 'significance analysis of microarrays'). Specifically, interactive spot evaluation functions are available in MArray and an online gene information database (NCBI UniGene) is linked. The application may provide a valuable aid in selecting and optimizing experimental procedures, as well as serving as an analytical tool for two-state biological comparisons, such as a study of single-dose activation. It is entirely platform independent, and only requires Matlab installed. AVAILABILITY: http://matrise.uio.no/marray/marray.html

Computer Graphics↗

PubMed2003

Proprioception with bicondylar sledge prostheses retaining cruciate ligaments.

The current study was designed to evaluate the proprioceptive performance of the knee after implantation of bicondylar sledge prostheses in comparison with contralateral knees and knees of healthy control subjects. After implantation of a sledge prosthesis in the medial and lateral condyles of a knee retaining all ligaments, 15 patients were evaluated clinically and by proprioceptive testing. Clinical examination was done using common scoring systems. Proprioceptive performance was examined using sway measurements during single-leg stance on a force platform. Eleven healthy subjects of the same age served as a control group. Clinical results of both groups differed significantly in all applied scores, except for the subcategories gait, muscle force, and pain. Sway measurements did not differ between right and left legs of subjects in the control group. The patients' surgically treated legs had slightly higher values than the control group, but a statistical significance was not found. Statistical analysis revealed no significant correlation between clinical scores and sway measurement results. Total knee arthroplasty that retains all intraarticular ligaments achieves proprioceptive results comparable with healthy subjects of the same age.

Aged↗

PubMed2004

Gamma-COP appendage domain - structure and function.

COPI-coated vesicles mediate retrograde transport from the Golgi back to the ER and intra-Golgi transport. The cytosolic precursor of the COPI coat, the heptameric coatomer complex, can be thought of as composed of two subcomplexes. The first consists of the beta-, gamma-, delta- and zeta-COP subunits which are distantly homologous to AP clathrin adaptor subunits. The second consists of the alpha-, beta'- and epsilon-COP subunits. Here, we present the structure of the appendage domain of gamma-COP and show that it has a similar overall fold as the alpha-appendage of AP2. Again, like the alpha-appendage the gamma-COP appendage possesses a single protein/protein interaction site on its platform subdomain. We show that in yeast this site binds to the ARFGAP Glo3p, and in mammalian gamma-COP this site binds to a Glo3p orthologue, ARFGAP2. On the basis of mutations in the yeast homologue of gamma-COP, Sec21p, a second binding site is proposed to exist on the gamma-COP appendage that interacts with the alpha,beta',epsilon COPI subcomplex.

ADP-Ribosylation Factors↗