Browsing by Subject "Muscles"
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Item Open Access A blinded study using laser induced endogenous fluorescence spectroscopy to differentiate ex vivo spine tumor, healthy muscle, and healthy bone.(Scientific reports, 2024-01) Sperber, Jacob; Zachem, Tanner J; Prakash, Ravi; Owolo, Edwin; Yamamoto, Kent; Nguyen, Annee D; Hockenberry, Harrison; Ross, Weston A; Herndon, James E; Codd, Patrick J; Goodwin, C RoryTen patients undergoing surgical resection for spinal tumors were selected. Samples of tumor, muscle, and bone were resected, de-identified by the treating surgeon, and then scanned with the TumorID technology ex vivo. This study investigates whether TumorID technology is able to differentiate three different human clinical fresh tissue specimens: spine tumor, normal muscle, and normal bone. The TumorID technology utilizes a 405 nm excitation laser to target endogenous fluorophores, thereby allowing for the detection of tissue based on emission spectra. Metabolic profiles of tumor and healthy tissue vary, namely NADH (bound and free emission peak, respectively: 487 nm, 501 nm) and FAD (emission peak: 544) are endogenous fluorophores with distinct concentrations in tumor and healthy tissue. Emission spectra analyzed consisted of 74 scans of spine tumor, 150 scans of healthy normal bone, and 111 scans of healthy normal muscle. An excitation wavelength of 405 nm was used to obtain emission spectra from tissue as previously described. Emission spectra consisted of approximately 1400 wavelength intensity pairs between 450 and 750 nm. Kruskal-Wallis tests were conducted comparing AUC distributions for each treatment group, α = 0.05. Spectral signatures varied amongst the three different tissue types. All pairwise comparisons among tissues for Free NADH were statistically significant (Tumor vs. Muscle: p = 0.0006, Tumor vs. Bone: p < 0.0001, Bone vs. Muscle: p = 0.0357). The overall comparison of tissues for FAD (506.5-581.5 nm) was also statistically significant (p < 0.0001), with two pairwise comparisons being statistically significant (Tumor vs. Muscle: p < 0.0001, Tumor vs. Bone: p = 0.0045, Bone vs. Muscle: p = 0.249). These statistically significant differences were maintained when stratifying tumor into metastatic carcinoma (N = 57) and meningioma (N = 17). TumorID differentiates tumor tissue from normal bone and normal muscle providing further clinical evidence of its efficacy as a tissue identification tool. Future studies should evaluate TumorID's ability to serve as an adjunctive tool for intraoperative assessment of surgical margins and surgical decision-making.Item Open Access Characterization of a canine model of glycogen storage disease type IIIa.(Dis Model Mech, 2012-11) Yi, Haiqing; Thurberg, Beth L; Curtis, Sarah; Austin, Stephanie; Fyfe, John; Koeberl, Dwight D; Kishnani, Priya S; Sun, BaodongGlycogen storage disease type IIIa (GSD IIIa) is an autosomal recessive disease caused by deficiency of glycogen debranching enzyme (GDE) in liver and muscle. The disorder is clinically heterogeneous and progressive, and there is no effective treatment. Previously, a naturally occurring dog model for this condition was identified in curly-coated retrievers (CCR). The affected dogs carry a frame-shift mutation in the GDE gene and have no detectable GDE activity in liver and muscle. We characterized in detail the disease expression and progression in eight dogs from age 2 to 16 months. Monthly blood biochemistry revealed elevated and gradually increasing serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) activities; serum creatine phosphokinase (CPK) activity exceeded normal range after 12 months. Analysis of tissue biopsy specimens at 4, 12 and 16 months revealed abnormally high glycogen contents in liver and muscle of all dogs. Fasting liver glycogen content increased from 4 months to 12 months, but dropped at 16 months possibly caused by extended fibrosis; muscle glycogen content continually increased with age. Light microscopy revealed significant glycogen accumulation in hepatocytes at all ages. Liver histology showed progressive, age-related fibrosis. In muscle, scattered cytoplasmic glycogen deposits were present in most cells at 4 months, but large, lake-like accumulation developed by 12 and 16 months. Disruption of the contractile apparatus and fraying of myofibrils was observed in muscle at 12 and 16 months by electron microscopy. In conclusion, the CCR dogs are an accurate model of GSD IIIa that will improve our understanding of the disease progression and allow opportunities to investigate treatment interventions.Item Open Access Electron tomography of cryofixed, isometrically contracting insect flight muscle reveals novel actin-myosin interactions.(PLoS One, 2010-09-09) Wu, Shenping; Liu, Jun; Reedy, Mary C; Tregear, Richard T; Winkler, Hanspeter; Franzini-Armstrong, Clara; Sasaki, Hiroyuki; Lucaveche, Carmen; Goldman, Yale E; Reedy, Michael K; Taylor, Kenneth ABACKGROUND: Isometric muscle contraction, where force is generated without muscle shortening, is a molecular traffic jam in which the number of actin-attached motors is maximized and all states of motor action are trapped with consequently high heterogeneity. This heterogeneity is a major limitation to deciphering myosin conformational changes in situ. METHODOLOGY: We used multivariate data analysis to group repeat segments in electron tomograms of isometrically contracting insect flight muscle, mechanically monitored, rapidly frozen, freeze substituted, and thin sectioned. Improved resolution reveals the helical arrangement of F-actin subunits in the thin filament enabling an atomic model to be built into the thin filament density independent of the myosin. Actin-myosin attachments can now be assigned as weak or strong by their motor domain orientation relative to actin. Myosin attachments were quantified everywhere along the thin filament including troponin. Strong binding myosin attachments are found on only four F-actin subunits, the "target zone", situated exactly midway between successive troponin complexes. They show an axial lever arm range of 77°/12.9 nm. The lever arm azimuthal range of strong binding attachments has a highly skewed, 127° range compared with X-ray crystallographic structures. Two types of weak actin attachments are described. One type, found exclusively in the target zone, appears to represent pre-working-stroke intermediates. The other, which contacts tropomyosin rather than actin, is positioned M-ward of the target zone, i.e. the position toward which thin filaments slide during shortening. CONCLUSION: We present a model for the weak to strong transition in the myosin ATPase cycle that incorporates azimuthal movements of the motor domain on actin. Stress/strain in the S2 domain may explain azimuthal lever arm changes in the strong binding attachments. The results support previous conclusions that the weak attachments preceding force generation are very different from strong binding attachments.Item Open Access Imaging of musculoskeletal bacterial infections by [124I]FIAU-PET/CT.(PLoS One, 2007-10-10) Diaz, Luis A; Foss, Catherine A; Thornton, Katherine; Nimmagadda, Sridhar; Endres, Christopher J; Uzuner, Ovsev; Seyler, Thorsten M; Ulrich, Slif D; Conway, Janet; Bettegowda, Chetan; Agrawal, Nishant; Cheong, Ian; Zhang, Xiaosong; Ladenson, Paul W; Vogelstein, Barry N; Mont, Michael A; Zhou, Shibin; Kinzler, Kenneth W; Vogelstein, Bert; Pomper, Martin GBACKGROUND: Traditional imaging techniques for the localization and monitoring of bacterial infections, although reasonably sensitive, suffer from a lack of specificity. This is particularly true for musculoskeletal infections. Bacteria possess a thymidine kinase (TK) whose substrate specificity is distinct from that of the major human TK. The substrate specificity difference has been exploited to develop a new imaging technique that can detect the presence of viable bacteria. METHODOLOGY/PRINCIPAL FINDINGS: Eight subjects with suspected musculoskeletal infections and one healthy control were studied by a combination of [(124)I]FIAU-positron emission tomography and CT ([(124)I]FIAU-PET/CT). All patients with proven musculoskeletal infections demonstrated positive [(124)I]FIAU-PET/CT signals in the sites of concern at two hours after radiopharmaceutical administration. No adverse reactions with FIAU were observed. CONCLUSIONS/SIGNIFICANCE: [(124)I]FIAU-PET/CT is a promising new method for imaging bacterial infections.Item Open Access Overview of FEED, the feeding experiments end-user database.(Integr Comp Biol, 2011-08) Wall, Christine E; Vinyard, Christopher J; Williams, Susan H; Gapeyev, Vladimir; Liu, Xianhua; Lapp, Hilmar; German, Rebecca ZThe Feeding Experiments End-user Database (FEED) is a research tool developed by the Mammalian Feeding Working Group at the National Evolutionary Synthesis Center that permits synthetic, evolutionary analyses of the physiology of mammalian feeding. The tasks of the Working Group are to compile physiologic data sets into a uniform digital format stored at a central source, develop a standardized terminology for describing and organizing the data, and carry out a set of novel analyses using FEED. FEED contains raw physiologic data linked to extensive metadata. It serves as an archive for a large number of existing data sets and a repository for future data sets. The metadata are stored as text and images that describe experimental protocols, research subjects, and anatomical information. The metadata incorporate controlled vocabularies to allow consistent use of the terms used to describe and organize the physiologic data. The planned analyses address long-standing questions concerning the phylogenetic distribution of phenotypes involving muscle anatomy and feeding physiology among mammals, the presence and nature of motor pattern conservation in the mammalian feeding muscles, and the extent to which suckling constrains the evolution of feeding behavior in adult mammals. We expect FEED to be a growing digital archive that will facilitate new research into understanding the evolution of feeding anatomy.Item Open Access Pairing of competitive and topologically distinct regulatory modules enhances patterned gene expression.(Mol Syst Biol, 2008) Yanai, Itai; Baugh, L Ryan; Smith, Jessica J; Roehrig, Casey; Shen-Orr, Shai S; Claggett, Julia M; Hill, Andrew A; Slonim, Donna K; Hunter, Craig PBiological networks are inherently modular, yet little is known about how modules are assembled to enable coordinated and complex functions. We used RNAi and time series, whole-genome microarray analyses to systematically perturb and characterize components of a Caenorhabditis elegans lineage-specific transcriptional regulatory network. These data are supported by selected reporter gene analyses and comprehensive yeast one-hybrid and promoter sequence analyses. Based on these results, we define and characterize two modules composed of muscle- and epidermal-specifying transcription factors that function together within a single cell lineage to robustly specify multiple cell types. The expression of these two modules, although positively regulated by a common factor, is reliably segregated among daughter cells. Our analyses indicate that these modules repress each other, and we propose that this cross-inhibition coupled with their relative time of induction function to enhance the initial asymmetry in their expression patterns, thus leading to the observed invariant gene expression patterns and cell lineage. The coupling of asynchronous and topologically distinct modules may be a general principle of module assembly that functions to potentiate genetic switches.Item Open Access Pilot Study of [18F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET)/Magnetic Resonance Imaging (MRI) for Staging of Muscle-invasive Bladder Cancer (MIBC).(Clinical genitourinary cancer, 2020-10) Eulitt, Patrick J; Altun, Ersan; Sheikh, Arif; Wong, Terence Z; Woods, Michael E; Rose, Tracy L; Wallen, Eric M; Pruthi, Raj S; Smith, Angela B; Nielsen, Matthew E; Whang, Young E; Kim, William Y; Godley, Paul A; Basch, Ethan M; David, Grace U; Ramirez, Juanita; Deal, Allison M; Rathmell, W Kimryn; Chen, Ronald C; Bjurlin, Marc A; Lin, Weili; Lee, Joseph K; Milowsky, Matthew IIntroduction
Computed tomography (CT) has limited diagnostic accuracy for staging of muscle-invasive bladder cancer (MIBC). [18F] Fluorodeoxyglucose positron emission tomography (FDG-PET)/magnetic resonance imaging (MRI) is a novel imaging modality incorporating functional imaging with improved soft tissue characterization. This pilot study evaluated the use of preoperative FDG-PET/MRI for staging of MIBC.Patients and methods
Twenty-one patients with MIBC with planned radical cystectomy were enrolled. Two teams of radiologists reviewed FDG-PET/MRI scans to determine: (1) presence of primary bladder tumor; and (2) lymph node involvement and distant metastases. FDG-PET/MRI was compared with cystectomy pathology and computed tomography (CT).Results
Eighteen patients were included in the final analysis, most (72.2%) of whom received neoadjuvant chemotherapy. Final pathology revealed 10 (56%) patients with muscle invasion and only 3 (17%) patients with lymph node involvement. Clustered analysis of FDG-PET/MRI radiology team reads revealed a sensitivity of 0.80 and a specificity of 0.56 for detection of the primary tumor with a sensitivity of 0 and a specificity of 1.00 for detection of lymph node involvement when compared with cystectomy pathology. CT imaging demonstrated similar rates in evaluation of the primary tumor (sensitivity, 0.91; specificity, 0.43) and lymph node involvement (sensitivity, 0; specificity, 0.93) when compared with pathology.Conclusions
This pilot single-institution experience of FDG-PET/MRI for preoperative staging of MIBC performed similar to CT for the detection of the primary tumor; however, the determination of lymph node status was limited by few patients with true pathologic lymph node involvement. Further studies are needed to evaluate the potential role for FDG-PET/MRI in the staging of MIBC.Item Open Access Profound muscle weakness and hypokalemia due to clay ingestion.(Southern medical journal, 1988-02) Severance, HW; Holt, T; Patrone, NA; Chapman, LWe have presented the case of a 43-year-old woman with severe myositis due to clay ingestion and hypokalemia. EMG studies revealed a pattern consistent with myositis, and muscle biopsy showed a nonspecific diffuse myositis. The clay was shown to act as a potassium binder. With potassium replacement and discontinuance of clay ingestion, the symptoms and signs abated and laboratory values returned to normal.Item Open Access Prophylactic Muscle Flaps Decrease Wound Complication Rates in Patients with Oncologic Spine Disease.(Plastic and reconstructive surgery, 2024-01) Dalton, Tara; Darner, Grant; McCray, Edwin; Price, Meghan; Baëta, Cesar; Erickson, Melissa; Karikari, Isaac O; Abd-El-Barr, Muhammad M; Goodwin, C Rory; Brown, David ABackground
Patients with oncologic spine disease face a high systemic illness burden and often require surgical intervention to alleviate pain and maintain spine stability. Wound healing complications are the most common reason for reoperation in this population and are known to impact quality of life and initiation of adjuvant therapy. Prophylactic muscle flap (MF) closure is known to reduce wound healing complications in high-risk patients; however, the efficacy in oncologic spine patients is not well established.Methods
A collaboration at our institution presented an opportunity to study the outcomes of prophylactic MF closure. The authors performed a retrospective cohort study of patients who underwent MF closure versus a cohort who underwent non-MF closure in the preceding time. Demographic and baseline health data were collected, as were postoperative wound complication data.Results
A total of 166 patients were enrolled, including 83 patients in the MF cohort and 83 control patients. Patients in the MF group were more likely to smoke ( P = 0.005) and had a higher incidence of prior spine irradiation ( P = 0.002). Postoperatively, five patients (6%) in the MF group developed wound complications, compared with 14 patients (17%) in the control group ( P = 0.028). The most common overall complication was wound dehiscence requiring conservative therapy, which occurred in six control patients (7%) and one MF patient (1%) ( P = 0.053).Conclusions
Prophylactic MF closure during oncologic spine surgery significantly reduces the wound complication rate. Future studies should examine the precise patient population that stands to benefit most from this intervention.Clinical question/level of evidence
Therapeutic, III.Item Open Access Synthetic lethal analysis of Caenorhabditis elegans posterior embryonic patterning genes identifies conserved genetic interactions.(Genome Biol, 2005) Baugh, L Ryan; Wen, Joanne C; Hill, Andrew A; Slonim, Donna K; Brown, Eugene L; Hunter, Craig PPhenotypic robustness is evidenced when single-gene mutations do not result in an obvious phenotype. It has been suggested that such phenotypic stability results from 'buffering' activities of homologous genes as well as non-homologous genes acting in parallel pathways. One approach to characterizing mechanisms of phenotypic robustness is to identify genetic interactions, specifically, double mutants where buffering is compromised. To identify interactions among genes implicated in posterior patterning of the Caenorhabditis elegans embryo, we measured synthetic lethality following RNA interference of 22 genes in 15 mutant strains. A pair of homologous T-box transcription factors (tbx-8 and tbx-9) is found to interact in both C. elegans and C. briggsae, indicating that their compensatory function is conserved. Furthermore, a muscle module is defined by transitive interactions between the MyoD homolog hlh-1, another basic helix-loop-helix transcription factor, hnd-1, and the MADS-box transcription factor unc-120. Genetic interactions within a homologous set of genes involved in vertebrate myogenesis indicate broad conservation of the muscle module and suggest that other genetic modules identified in C. elegans will be conserved.