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Biomedical subjects

Christopher Turner

Publications and source records attributed to Christopher Turner.

15 recordsLinked to original sources
PubMed2006

Music perception with cochlear implants and residual hearing.

AIM: The aims of this study were to examine the music perception abilities of Cochlear Nucleus Hybrid (acoustic plus electric stimulation) cochlear implant (CI) recipients and to compare their performance with that of normal-hearing (NH) adults and CI recipients using conventional long-electrode (LE) devices (Advanced Bionics: 90K, Clarion, CIIHF; Cochlear Corporation: CI24M, CI22, Contour; Ineraid). Hybrid CI recipients were compared with NH adults and LE CI recipients on recognition of (a) real-world melodies and (b) musical instruments. PATIENTS AND METHODS: We tested 4 Hybrid CI recipients, 17 NH adults, and 39 LE CI recipients on open-set recognition of real-world songs presented with and without lyrics. We also tested 14 Hybrid CI recipients, 21 NH adults, and 174 LE CI recipients on closed-set recognition of 8 musical instruments playing a 7-note phrase. RESULTS: On recognition of real-world songs, both the Hybrid recipients and NH listeners were significantly more accurate (p < 0.0001) than the LE CI recipients in the no lyrics condition, which required reliance on musical cues only. The LE group was significantly less accurate than either the Hybrid or NH group (p < 0.0001) on instrument recognition for low and high frequency ranges. CONCLUSIONS: These results, while preliminary in nature, suggest that preservation of low-frequency acoustic hearing is important for perception of real-world musical stimuli.

Acoustic Stimulation↗
PubMed2006

Acoustic plus electric speech processing: preliminary results of a multicenter clinical trial of the Iowa/Nucleus Hybrid implant.

AIM: This communication details the latest preliminary results from an ongoing multicenter single-subject design clinical trial of the Iowa/Nucleus Hybrid 10-mm cochlear implant. Selection criteria, surgical strategies used for hearing preservation, and the benefits of preserved residual low-frequency hearing, improved word understanding in noise, and music appreciation are described. PATIENTS AND METHODS: The device has been implanted in 48 individuals with residual low-frequency hearing. RESULTS: Hearing preservation has been accomplished in 46/48 subjects. Acoustic speech perception has also been preserved. Combined acoustic plus electric speech processing has enabled most of this group of volunteers to gain improved word understanding as compared to their preoperative hearing with bilateral hearing aids. A subset of subjects with 12 months or more experience demonstrates CNC word understanding continues to improve more than 24 months after implantation. Improved word understanding in noise is also a benefit of acoustic plus electric speech processing. CONCLUSIONS: The improvement of speech in noise and melody recognition is linked to the ability to distinguish fine pitch differences as the result of preserved residual low-frequency acoustic hearing. Both of these measures are very important in real life to the hearing impaired. Preservation of residual low-frequency hearing should be considered when expanding candidate selection criteria for standard cochlear implants.

Acoustic Stimulation↗
PubMed2006

Using a cross-coil to reduce RF heating by an order of magnitude in triple-resonance multinuclear MAS at high fields.

Four different coil designs for use with MAS in triple-resonance multi-nuclear experiments at high fields are compared, using a combination of finite element analysis (FEA) software and NMR experiments, with respect to RF field strength per unit power and relative sample heating, as governed by mean E/B(1) within the sample region. A commercial FEA package, Microwave Studio 5.1 by Computer Simulation Technology (CST) is shown to obtain remarkably accurate agreement with the experiments in Q(L), L, B, E, and mode frequencies in all cases. A simplified treatment of RF heating in NMR MAS samples is derived and shown to agree with the NMR experimental results within about 10% for two representative stator designs. The coil types studied include: (1) a variable-pitch solenoid outside a ceramic coilform, (2) a conventional solenoid very closely spaced to the MAS rotor, (3) a scroll coil, and (4) a segmented saddle cross coil (XC) for (1)H with an additional solenoid over it for the two lower-frequency channels. The XC/solenoid is shown to offer substantial advantages in reduced decoupler heating, improved S/N, and improved compatibility with multinuclear tuning and high-power decoupling. This seems largely because the division of labor between two orthogonal coils allows them each, and their associated circuitry, to be separately optimized for their respective regimes.

Equipment Design↗
PubMed2005

Gene expression in Huntington's disease skeletal muscle: a potential biomarker.

Huntington's disease (HD) is an incurable and fatal neurodegenerative disorder. Improvements in the objective measurement of HD will lead to more efficient clinical trials and earlier therapeutic intervention. We hypothesized that abnormalities seen in the R6/2 mouse, a greatly accelerated HD model, might highlight subtle phenotypes in other mouse models and human HD. In this paper, we identify common gene expression changes in skeletal muscle from R6/2 mice, Hdh(CAG(150)) homozygous knock-in mice and HD patients. This HD-triggered gene expression phenotype is consistent with the beginnings of a transition from fast-twitch to slow-twitch muscle fiber types. Metabolic adaptations similar to those induced by diabetes or fasting are also present but neither metabolic disorder can explain the full phenotype of HD muscle. The HD-induced gene expression changes reflect disease progression. This raises the possibility that muscle gene expression may be used as an objective biomarker to complement clinical HD-rating systems. Furthermore, an understanding of the molecular basis of muscle dysfunction in HD should provide insight into mechanisms involved in neuronal abnormalities and neurodegeneration.

Animals↗
PubMed2005

Analysis of normal and mutant iduronate-2-sulphatase conformation.

Mammalian sulphatases (EC 3.1.6) are a family of enzymes that have a high degree of similarity in amino acid sequence, structure and catalytic mechanism. IDS (iduronate-2-sulphatase; EC 3.1.6.13) is a lysosomal exo-sulphatase that belongs to this protein family and is involved in the degradation of the glycosaminoglycans heparan sulphate and dermatan sulphate. An IDS deficiency causes the lysosomal storage disorder MPS II (mucopolysaccharidosis type II). To examine the structural alterations in heat-denatured and mutant IDS, a panel of four monoclonal antibodies was raised to the denatured protein and used as probes of protein conformation. The linear sequence epitope reactivity of a polyclonal antibody raised against the native protein and the monoclonal antibodies were defined and mapped to distinct regions on the IDS protein. The antigenicity of native IDS was higher in regions without glycosylation, but reactivity was not restricted to protein surface epitopes. One monoclonal epitope was relatively surface accessible and in close proximity to an N-linked glycosylation site, while three others required additional thermal energy to expose the epitopes. The monoclonal antibodies demonstrated the capacity to differentiate progressive structural changes in IDS and could be used to characterize the severity of MPS type II in patients based on variable denatured microstates.

Age of Onset↗
PubMed2005

Antioxidant treatment of patients with Friedreich ataxia: four-year follow-up.

BACKGROUND: Decreased mitochondrial respiratory chain function and increased oxidative stress have been implicated in the pathogenesis of Friedreich ataxia (FRDA), raising the possibility that energy enhancement and antioxidant therapies may be an effective treatment. OBJECTIVE: To evaluate the long-term efficacy of a combined antioxidant and mitochondrial enhancement therapy on the bioenergetics and clinical course of FRDA. DESIGN: Open-labeled pilot trial over 47 months.Patients Seventy-seven patients with clinical and genetically defined FRDA. Intervention A combined coenzyme Q(10) (400 mg/d) and vitamin E (2100 IU/d) therapy of 10 patients with FRDA over 47 months. MAIN OUTCOME MEASURES: Clinical assessment using echocardiography and the International Cooperative Ataxia Rating Scale and cardiac and skeletal muscle bioenergetics as assessed using phosphorus P 31 magnetic resonance spectroscopy. RESULTS: There was a significant improvement in cardiac and skeletal muscle bioenergetics that was maintained throughout the 47 months of therapy. Echocardiographic data revealed significantly increased fractional shortening at the 35- and 47-month time points. Comparison with cross-sectional data from 77 patients with FRDA indicated the changes in total International Cooperative Ataxia Rating Scale and kinetic scores over the trial period were better than predicted for 7 patients, but the posture and gait and hand dexterity scores progressed as predicted. CONCLUSION: This therapy resulted in sustained improvement in mitochondrial energy synthesis that was associated with a slowing of the progression of certain clinical features and a significant improvement in cardiac function.

Adolescent↗
PubMed2005

Preservation of hearing in cochlear implant surgery: advantages of combined electrical and acoustical speech processing.

OBJECTIVES/HYPOTHESIS: This study documents the importance of preserving residual low-frequency acoustic hearing as those with more residual hearing are selected for cochlear implantation. Surgical strategies used for hearing preservation with a short hybrid cochlear implant are outlined. The benefits of preserved residual low-frequency hearing, improved word understanding in noise, and music appreciation are described. STUDY DESIGN: Multicenter, prospective, single-subject design. METHODS: Records were reviewed of 21 individuals participating in an Food and Drug Administration (FDA) feasibility clinical trial who have received an Iowa/Nucleus 10 mm electrode. A second group of subjects receiving implants at the University of Iowa that have used the 10 mm device between 2 years and 6 months were also reviewed. Outcome measures included standardized tests of monosyllabic word understanding, spondees in noise, and common melody recognition. RESULTS: Low-frequency hearing was maintained in all individuals immediately postoperative. One subject lost hearing at 2.5 months postoperative after a viral infection. The group has averaged a loss of -9 dB low-frequency acoustic hearing between 125 and 1,000 Hz. Monosyllabic word understanding scores at 6 months for a group being followed for an FDA clinical trial using the implant plus hearing aids was 69% correct. For the long-term group receiving implants at Iowa, monosyllabic word understanding in those who have used the device between 6 months and 2 years is 79%. Other important findings include improved recognition of speech in noise (9 dB improvement) as compared with standard cochlear implant recipients who were matched for speech recognition in quiet and near normal recognition of common melodies. CONCLUSION: The surgical strategies outlined have been successful in preservation of low-frequency hearing in 96% of individuals. Combined electrical and acoustical speech processing has enabled this group of volunteers to gain improved word understanding as compared with their preoperative hearing with bilateral hearing aids and a group of individuals receiving a standard cochlear implant with similar experience with their device. The improvement of speech in noise and melody recognition is attributed to the ability to distinguish fine pitch differences as the result of preserved residual low-frequency acoustic hearing. Preservation of low-frequency acoustic hearing is important for improving speech in noise and music appreciation for the hearing impaired, both of which are important in real-life situations.

Audiometry, Pure-Tone↗
PubMed2004

Cardiomyocyte apoptosis triggered by RAFTK/pyk2 via Src kinase is antagonized by paxillin.

Altered cellular adhesion and apoptotic signaling in cardiac remodeling requires coordinated regulation of multiple constituent proteins that comprise cytoskeletal focal adhesions. One such protein activated by cardiac remodeling is related adhesion focal tyrosine kinase (RAFTK, also known as pyk2). Adenoviral-mediated expression of RAFTK in neonatal rat cardiomyocytes involves concurrent increases in phosphorylation of Src, c-Jun N-terminal kinase, and p38 leading to characteristic apoptotic changes including cleavage of poly(ADP-ribose) polymerase, caspase-3 activation, and increased DNA laddering. DNA laddering was decreased by mutation of the Tyr(402) Src-binding site in RAFTK, suggesting a central role for Src activity in apoptotic cell death that was confirmed by adenoviral-mediated Src expression. Multiple apoptotic signaling cascades are recruited by RAFTK as demonstrated by prevention of apoptosis using caspase-3 inhibitor IV (caspase-3 specific inhibitor), PP2 (Src-specific kinase inhibitor), or Csk (cellular negative regulator for Src), as well as dominant negative constructs for p38beta or MKP-1. These RAFTK-mediated phenotypic characteristics are prevented by concurrent expression of wild-type or a phosphorylation-deficient paxillin mutated at Tyr(31) and Tyr(118). Wild-type or mutant paxillin protein accumulation in the cytoplasm has no overt effect upon cell structure, but paxillin accumulation prevents losses of myofibril organization as well as focal adhesion kinase, vinculin, and paxillin protein levels mediated by RAFTK. Apoptotic signaling cascade inhibition by paxillin indicates interruption of signaling proximal to but downstream of RAFTK activity. Chronic RAFTK activation in cardiac remodeling may represent a maladaptive reactive response that can be modulated by paxillin, opening up novel possibilities for inhibition of cardiomyocyte apoptosis and structural degeneration in heart failure.

Adenoviridae↗
PubMed2004

A clinical, genetic and biochemical study of SPG7 mutations in hereditary spastic paraplegia.

Mutations in the SPG7 gene, encoding the mitochondrial protein paraplegin, were the first to be identified in autosomal recessive hereditary spastic paraplegia (ARHSP). Four different SPG7 mutations have been described so far in association with both pure and complicated HSP phenotypes. Muscle biopsies from the most severely affected patients have shown histological evidence of an oxidative phosphorylation defect. We identified six ARHSP kindreds, in whom linkage to SPG7 could not be excluded, and 29 sporadic spastic paraplegia patients. The 17 exons and flanking regions of the SPG7 gene were screened for mutations using a combination of single-stranded conformation polymorphism (SSCP) analysis and sequencing. Three patients were found to carry compound heterozygous SPG7 mutations, comprising five novel and one previously described mutation. Muscle biopsies from two SPG7 mutation patients did not show any histological evidence of an oxidative phosphorylation defect. However, biochemical analysis revealed a reduction in citrate synthase-corrected complex I and complex II/III activities in muscle and complex I activity in mitochondrial-enriched fractions from cultured myoblasts, suggesting that either a primary or a secondary defect of respiratory chain function may play an important role in the pathogenesis of the disease.

ATPases Associated with Diverse Cellular Activitie↗
PubMed2004

Combining acoustic and electrical speech processing: Iowa/Nucleus hybrid implant.

OBJECTIVES: In this paper we test the concept of combining electrical stimulation for high-frequency sound with acoustic hearing for low-frequency information in the same ear. In addition, we test whether residual hearing can be preserved when an electrode is placed up to 10 mm into the inner ear, and whether the site of electrical stimulation influences speech perception. MATERIAL AND METHODS: Nine post-lingual adults with severe high-frequency hearing impairment were recruited to participate in the study. A single-subject clinical trial design was employed. A unique six-channel cochlear implant was designed for this clinical trial. The intracochlear electrodes were either 6 or 10 mm in length based on a Nucleus CI-24 multichannel implant. Monosyllabic word understanding and consonant identification in a recorded sound-only condition were used to assess changes in speech perception. Follow-up was > 12 months. RESULTS: Acoustic hearing was preserved in all nine subjects. Preoperative monosyllabic word and sentence scores were unchanged in all subjects following implantation. A 30-40% improvement in consonant recognition occurred with the 10-mm electrode. The 10-mm electrode subjects were able to understand 83-90% of the monosyllabic words using the implant plus binaural hearing aids. Scores were more than doubled when compared to preoperative scores achieved with hearing aids only. CONCLUSIONS: The human ear has the capability to integrate both acoustic and high-frequency electrically processed speech information. Placement of a short 10-mm electrode does not appear to damage residual low-frequency inner ear hair cell function, interfere with the micro-mechanics of normal cochlear vibration or decrease residual speech perception. The improvement in speech recognition was due primarily to the increased perception of higher-frequency consonantal speech cues. Such a device can provide a substantial benefit in terms of speech understanding to those with severe high-frequency hearing loss, while still maintaining the benefits of the residual lower-frequency acoustic hearing. The position of the electrode and the site of frequency information within the cochlea are shown to be important factors in the success of such a device.

Acoustic Stimulation↗
PubMed2002

The transfection of Jurkat T-leukemic cells by use of pH sensitive immunoliposomes.

A gene transfer vector has been developed utilising anionic liposomes as a carrier of plasmid DNA (pEGlacZ, 7.6 kb) to transfect CD3+ T lymphocytes (Jurkat cells). The plasmid DNA that contained the Escherichia coli beta-galactosidase reporter gene was condensed using poly-l-lysine of molecular mass 20,700 (PLK99) to form a polyplex which was interacted with several anionic liposome formulations to form lipopolyplexes. The liposome formulations where based on dioleoylphosphatidylethanolamine (DOPE) in combination with cholesterol and dioleoylphosphatidylcholine (DOPC) and oleic acid, or dimyristoylphosphatidylethanolamine (DMPE). For targeting to the Jurkat cells distearoylphosphatidylethanolamine (DSPE) linked to poly (ethylene glycol) molecular mass 2,000 and coupled to anti-CD3 antibody was incorporated. The polyplexes and lipopolyplexes were characterised in terms of size, zeta potential, agarose gel electrophoresis and electron microscopy and the permeability of the lipopolyplexes to liposome-encapsulated glucose was determined. The polyplexes consisted of a mixed population of rod-like structures (53-160 nm long and 23-31 nm diameter) and spheres (18-30 nm diameter). The lipopolyplexes retained a permeability barrier although were more permeable to glucose than their component liposomes. The poly-l-lysine condensing agent was still susceptible to pronase digestion suggesting that the polyplex was associated with the outer surface of the liposome. The lipopolyplexes with lipid composition DOPE/cholesterol/OA/DSPE-PEG2000 anti-CD3+ PLK99-plasmid DNA had significant gene transfer activity, as monitored by beta-galactosidase expression, that depended on the charge ratio of the component polyplex and the lipid/DNA weight ratio. The anti-CD3 antibody, the liposomal lipid and pH sensitivity were essential for transfection activity.

Antibodies↗
PubMedDate not supplied

The transfection of Jurkat T-leukemic cells by use of pH-sensitive immunoliposomes.

An effective pH-sensitive gene transfer vector has been developed utilising anionic liposomes with various formulations as a carrier of plasmid DNA (pEGlacZ, 7.6 kb) to transfect CD3 T+ lymphocytes (Jurkat cells). The plasmid DNA was condensed using poly-l-lysines with a range of molecular masses to form polyplexes that were interacted with several anionic liposome formulations to form lipopolyplexes. For targeting to the Jurkat cells, distearoylphosphatidylethanolamine (DSPE) linked to poly (ethylene glycol) molecular mass 2000 and coupled to anti-CD3 antibody was incorporated in the liposomes. The polyplexes and lipopolyplexes were characterised in terms of size, zeta potential, gel electrophoresis and electron microscopy. The gene transfer activity of the lipopolyplexes, assessed from beta-galactosidase expression, depended on the charge ratio (NH(3)+/PO(4)-) of the component polyplex and the lipid/DNA weight ratio of the lipopolyplex.

CD3 Complex↗