Longitudinale Untersuchungen der kardialen Morphologie von knockin-Mäusen mit humanen Myosinmutationen / Longitudinal analyses of cardiac morphology in knockin mice carrying human myosin mutations

Primary spinal cord injury (SCI) results from direct mechanical damage to the spinal cord. The resulting pathochemical and pathophysiological events, including oxidative stress and inflammation, lead to secondary injury. The ability to decrease secondary injury may lead to improved recovery. Increasing glutathione production after SCI leads to decreased secondary injury. Glutamine is an important precursor to glutathione following trauma. Skeletal muscle phenotype is strongly influenced by neuromuscular activity. SCI causes myosin heavy chain (MyHC) profiles to shift towards faster isoforms in slow muscles and slower isoforms in fast muscles. The hypothesis was that glutamine, as a precursor of glutathione, administration to SCI rats would lead to better functional recovery and a more preserved MyHC phenotype in locomotory muscles. <p> Rats were assigned to one of four groups; healthy, laminectomy only, untreated SCI, and SCI treated with an intraperitoneal injection of 1mmol/kg glutamine every 12 hours for one week after injury. SCIs were performed at T6 with a modified aneurism clip. Functional recovery was measured weekly using the Basso-Beattie-Bresnahan scale and the angle board method. Six weeks later, all rats were killed, and their extensor digitorum longus and soleus muscles excised and weighed. MyHC composition of the muscles was determined using SDS-PAGE.<p>The hypothesis that glutamine treatment following SCI would lead to better functional recovery and a more preserved MyHC profile was validated. Glutamine treated rats received significantly higher BBB scores (p<0.01) and angle board scores (p<0.001) than untreated SCI rats. Glutamine treatment also reduces muscle atrophy in the soleus muscle, but not the extensor digitorum longus (EDL). In untreated rats the soleus muscle accounted for significantly (p<0.001) less of the percentage of total body weight than the soleus muscle from glutamine treated rats. Finally, SCI rats with preserved functional abilities displayed a significantly better preserved MyHC profile compared to untreated SCI rats. In the soleus healthy rats contain 94% type 1 myosin, treated rats maintained 68% which was significantly (p<0.001) greater than 28% maintained by untreated rats. In the EDL healthy rats contain 55% type 2b myosin, treated rats maintained 32% which was greater than 26% type 2b myosin maintained by untreated rats.

Primary spinal cord injury (SCI) results from direct mechanical damage to the spinal cord. The resulting pathochemical and pathophysiological events, including oxidative stress and inflammation, lead to secondary injury. The ability to decrease secondary injury may lead to improved recovery. Increasing glutathione production after SCI leads to decreased secondary injury. Glutamine is an important precursor to glutathione following trauma. Skeletal muscle phenotype is strongly influenced by neuromuscular activity. SCI causes myosin heavy chain (MyHC) profiles to shift towards faster isoforms in slow muscles and slower isoforms in fast muscles. The hypothesis was that glutamine, as a precursor of glutathione, administration to SCI rats would lead to better functional recovery and a more preserved MyHC phenotype in locomotory muscles. <p> Rats were assigned to one of four groups; healthy, laminectomy only, untreated SCI, and SCI treated with an intraperitoneal injection of 1mmol/kg glutamine every 12 hours for one week after injury. SCIs were performed at T6 with a modified aneurism clip. Functional recovery was measured weekly using the Basso-Beattie-Bresnahan scale and the angle board method. Six weeks later, all rats were killed, and their extensor digitorum longus and soleus muscles excised and weighed. MyHC composition of the muscles was determined using SDS-PAGE.<p>The hypothesis that glutamine treatment following SCI would lead to better functional recovery and a more preserved MyHC profile was validated. Glutamine treated rats received significantly higher BBB scores (p<0.01) and angle board scores (p<0.001) than untreated SCI rats. Glutamine treatment also reduces muscle atrophy in the soleus muscle, but not the extensor digitorum longus (EDL). In untreated rats the soleus muscle accounted for significantly (p<0.001) less of the percentage of total body weight than the soleus muscle from glutamine treated rats. Finally, SCI rats with preserved functional abilities displayed a significantly better preserved MyHC profile compared to untreated SCI rats. In the soleus healthy rats contain 94% type 1 myosin, treated rats maintained 68% which was significantly (p<0.001) greater than 28% maintained by untreated rats. In the EDL healthy rats contain 55% type 2b myosin, treated rats maintained 32% which was greater than 26% type 2b myosin maintained by untreated rats.

Thesis (M.S.)--West Virginia University, 2008. / Title from document title page. Document formatted into pages; contains ix, 115 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 103-105).

Thesis (Ph. D.)--University of California, San Diego, and San Diego State University, 2004. / Vita. Includes bibliographical references.

Thesis (Ph. D.)--Florida State University, 2003. / Advisor: Dr. Tim Logan, Florida State University, College of Arts and Sciences, Program in Molecular Biophysics. Title and description from dissertation home page (viewed Oct. 3, 2003). Includes bibliographical references.

No description available.

published_or_final_version / Biochemistry / Master / Master of Philosophy

No description available.

Variable-temperature Fourier transform infrared (VT-FTIR) and circular dichroism (far-UV CD) spectroscopy were employed to investigate the sequence of structural changes responsible for the thermally induced formation of myosin gels with various rheological properties, as measured by dynamic oscillatory rheology, as well as the effects of prior high-pressure processing (HPP) on thermally induced gel formation. The viscoelastic properties of the protein gels were monitored as a function of temperature and were also measured at three fixed temperatures (44, 48, and 68°C). Examination was done of changes in the secondary structure-sensitive amide l'band in the FTIR spectra of the protein in D2O buffer (0.6M KCl, pH 6.4) as a function of temperature, as well as far-UV CD spectra. Myosin solutions were exposed to increasing hydrostatic pressure (100--400 MPa for 10 min at 16°C). The extent of unfolding of the tail was shown to be proportional to the pressure treatment, suggesting that the slight increase of gel strength may partly originate from the facilitated tail-tail interaction. (Abstract shortened by UMI.)