Biomedical subjects

Kimerly Powell

Publications and source records attributed to Kimerly Powell.

11 recordsLinked to original sources

PubMed2006

Osteogenic progenitors in bone marrow aspirates from smokers and nonsmokers.

UNLABELLED: Bone marrow aspirates contain connective tissue progenitor cells which can proliferate to form cell colonies that express connective tissue phenotypes. The number of osteogenic connective tissue progenitor cells can be estimated by counting colonies that express alkaline phosphatase, an early marker of osteoblastic differentiation. Because tobacco use is associated with decreased bone mass and fracture nonunion, we tested the hypothesis that current or previous tobacco use is an independent determinant of marrow cellularity or prevalence of osteogenic connective tissue progenitor cells among marrow-derived cells. Marrow aspirates were obtained from the anterior iliac crest of 62 patients who were grouped as never smoked, past smokers, or current smokers. The number of nucleated cells per aspirate was determined. Cells were cultured for 6 days in osteogenic media. The prevalence of osteogenic connective tissue progenitor cells was determined by counting colony forming units. The area of each colony was assessed using quantitative image analysis. Cellularity of bone marrow was found to decrease with age. We observed no relationship between smoking status and marrow cellularity, colony prevalence, or colony area. This suggests that tobacco use is not associated with a change in prevalence of osteogenic connective tissue progenitor cells in bone marrow, or their intrinsic biologic capacity to undergo early osteoblastic differentiation. LEVEL OF EVIDENCE: Diagnostic Study, Level I (testing of previously developed diagnostic criteria on consecutive patients--with universally applied reference "gold" standard). See the Guidelines for Authors for a complete description of levels of evidence.

Adult↗

PubMed2006

Regulation of procollagen amino-propeptide processing during mouse embryogenesis by specialization of homologous ADAMTS proteases: insights on collagen biosynthesis and dermatosparaxis.

Mutations in ADAMTS2, a procollagen amino-propeptidase, cause severe skin fragility, designated as dermatosparaxis in animals, and a subtype of the Ehlers-Danlos syndrome (dermatosparactic type or VIIC) in humans. Not all collagen-rich tissues are affected to the same degree, which suggests compensation by the ADAMTS2 homologs ADAMTS3 and ADAMTS14. In situ hybridization of Adamts2, Adamts3 and Adamts14, and of the genes encoding the major fibrillar collagens, Col1a1, Col2a1 and Col3a1, during mouse embryogenesis, demonstrated distinct tissue-specific, overlapping expression patterns of the protease and substrate genes. Adamts3, but not Adamts2 or Adamts14, was co-expressed with Col2a1 in cartilage throughout development, and with Col1a1 in bone and musculotendinous tissues. ADAMTS3 induced procollagen I processing in dermatosparactic fibroblasts, suggesting a role in procollagen I processing during musculoskeletal development. Adamts2, but not Adamts3 or Adamts14, was co-expressed with Col3a1 in many tissues including the lungs and aorta, and Adamts2(-/-) mice showed widespread defects in procollagen III processing. Adamts2(-/-) mice had abnormal lungs, characterized by a decreased parenchymal density. However, the aorta and collagen fibrils in the aortic wall appeared normal. Although Adamts14 lacked developmental tissue-specific expression, it was co-expressed with Adamts2 in mature dermis, which possibly explains the presence of some processed skin procollagen in dermatosparaxis. The data show how evolutionarily related proteases with similar substrate preferences may have distinct biological roles owing to tissue-specific gene expression, and provide insights into collagen biosynthesis and the pathobiology of dermatosparaxis.

ADAM Proteins↗

PubMed2005

Three-dimensional texture analysis of cancellous bone cores evaluated at clinical CT resolutions.

The objective of this study was to determine if three-dimensional (3D) Haralick co-occurrence texture measures calculated from low-resolution CT images of trabecular bone correlate with 3D structural indices measured from high-resolution CT images. Thirty-three cubical regions of trabecular bone from human calcanei were analyzed using images obtained from a micro-computed tomography (micro-CT) scanner. 3D measures of bone architecture were calculated. The original images were then subsampled by factors of 5, 10, 15, and 20, and 3D texture features were calculated for each set of subsampled images. Linear regression models showed that co-occurrence texture features were significantly correlated with structural indices. Over 90% of the variation in three different structural indices was explained in two-variable regression models using texture features as predictors when the voxel side length was reduced by a factor of 10. Texture features calculated from clinical images may increase our ability to obtain trabecular bone architectural information when high-resolution images are unobtainable.

Aged↗

PubMed2005

Use of ultra-high-resolution data for temporal bone dissection simulation.

OBJECTIVES: For the past 5 years, our group has been developing a virtual temporal bone dissection environment for training otologic surgeons. Throughout the course of our development, a recurring challenge is the acquisition of high-resolution, multimodal, and multi-scale data sets that are used for the visual as well as haptic (sense of touch) display. This study presents several new techniques in temporal bone imaging and their use as data for surgical simulation. METHODS: At our institution (OSU), we are fortunate to have a high-field (8 Tesla) magnetic resonance imaging (MRI) research magnet that provides an order of magnitude higher resolution compared to clinical 1.5T MRI scanners. Magnetic resonance imaging has traditionally been superb at delineating soft tissue structure, and certainly, the 8T unit does indeed do this at a resolution of 100-200 microm(3). To delineate the bony structure of the mastoid and middle ear, computed tomography (CT) has traditionally been used because of the high signal-to-noise ratio delineating bone signal from air and soft tissue. We have partnered with researchers at other institutions (CCF) to make use of a "microCT" that provides a resolution of 214 x 214 x 390 micrometers of bony structure. RESULTS: This report provides a description of the 2 methodologies and presentation of the striking image data capable of being generated. See images presented. CONCLUSIONS: Using these 2 new and innovative imaging modalities, we provide an order of magnitude greater resolution to the visual and haptic display in our temporal bone dissection simulation environment.

Cadaver↗

PubMed2005

Changes in rotator cuff muscle volume, fat content, and passive mechanics after chronic detachment in a canine model.

BACKGROUND: Long-standing tears of the rotator cuff can lead to substantial and perhaps irreversible changes in the affected rotator cuff muscles. We developed a chronic rotator cuff tear in a canine model to investigate and quantify the time-related changes in passive mechanics, volume, and fat of the infraspinatus muscle. We hypothesized that infraspinatus muscle stiffness would increase, volume would decrease, and fat content would increase at twelve weeks following tendon detachment. METHODS: The right infraspinatus tendon of eight adult mongrel dogs were surgically detached from the proximal part of the humerus. The uninvolved left shoulder served as a control. Muscle volume changes were quantified with use of magnetic resonance imaging. At twelve weeks, the passive mechanical properties of the chronically detached and control muscles were determined intraoperatively with use of a custom-designed device. Intramuscular fat was evaluated histologically at the time that the animals were killed. RESULTS: After twelve weeks of detachment, the stiffness was significantly increased in the detached infraspinatus muscles relative to that in the controls (p < 0.0001). Magnetic resonance image analysis demonstrated that the detached muscle volumes decreased by an average of 32% in the first six weeks and remained constant thereafter. Intramuscular fat increased significantly in the detached muscles and to a greater extent in the lateral regions (p < 0.05). CONCLUSIONS: The chronically detached muscle is not merely a smaller version of the original muscle but, rather, a different muscle. The detached muscle becomes stiffer, and the passive loads required to repair it can become excessive. A significant reduction in muscle volume occurs within days to weeks following tendon detachment (p < 0.0001). The nonuniformity of changes in muscle fat suggests that fat content should be used cautiously as an indicator of muscle quality.

Adipose Tissue↗

PubMed2004

Extracellular bone acidic glycoprotein-75 defines condensed mesenchyme regions to be mineralized and localizes with bone sialoprotein during intramembranous bone formation.

Bone acidic glycoprotein-75 is expressed very early during in vivo models of intramembranous bone formation, highly enriched in condensing osteogenic mesenchyme after marrow ablation and the osteoprogenitor layer of tibial periosteum. Bone sialoprotein accumulates within bone acidic glycoprotein-75-enriched matrix areas at a later stage in both models. Decalcification of initial sites of mineralization consistently revealed focal immunostaining for bone acidic glycoprotein-75 underneath these sites suggesting that mineralization occurs within bone acidic glycoprotein-75-enriched matrix areas. Ultrastructural immunolocalization of bone acidic glycoprotein-75 does not support a direct association with banded collagen fibrils, but rather suggests it is a component of a separate, amorphous scaffold occupying interfibrillar spaces. Double immunogold labeling demonstrated that a sizeable proportion of bone sialoprotein particles were located within a 50-nm radius of bone acidic glycoprotein-75. These results define bone acidic glycoprotein-75 as the earliest bone-restricted, extracellular marker of osteogenic mesenchyme. Based on this early bone-restricted expression pattern and a previously documented propensity of bone acidic glycoprotein-75 to form supramolecular complexes through self-association, bone acidic glycoprotein-75 may serve a key structural role in setting boundary limits of condensing osteogenic mesenchyme.

Animals↗

PubMed2004

Bone acidic glycoprotein-75 delineates the extracellular sites of future bone sialoprotein accumulation and apatite nucleation in osteoblastic cultures.

Addition of an organophosphate source to UMR osteoblastic cultures activates a mineralization program in which BSP localizes to extracellular matrix sites where hydroxyapatite crystals are subsequently nucleated. This study identifies for the first time novel extracellular spherical structures, termed biomineralization foci (BMF), containing bone acidic glycoprotein-75 (BAG-75), bone sialoprotein (BSP), and alkaline phosphatase that are the exclusive sites of initial nucleation of hydroxyapatite crystals in the UMR model. Importantly, in the absence of added phosphate, UMR cultures after reaching confluency contain two size populations of morphologically identifiable BMF precursors enriched in BAG-75 (15-25 and 150-250 microm in diameter). The shape and size of the smaller population are similar to structures assembled in vitro through self-association of purified BAG-75 protein. After organophosphate addition, BSP accumulates within these BAG-75-containing BMF precursors, with hydroxyapatite crystal nucleation occurring subsequently. In summary, BAG-75 is the earliest detectable biomarker that accurately predicts the extracellular sites of de novo biomineralization in UMR cultures. We hypothesize that BAG-75 may perform a key structural role in the assembly of BMF precursors and the recruitment of other proteins such as alkaline phosphatase and BSP. Furthermore, we propose a hypothetical mechanism in which BAG-75 and BSP function actively in nucleation of apatite within BMF.

Alkaline Phosphatase↗

PubMed2003

Donor spontaneous intracerebral hemorrhage is associated with systemic activation of matrix metalloproteinase-2 and matrix metalloproteinase-9 and subsequent development of coronary vasculopathy in the heart transplant recipient.

BACKGROUND: Matrix metalloproteinase (MMP)-2 and MMP-9 have been shown to play a role in the progression of hemorrhagic stroke. We hypothesized that donor intracerebral hemorrhage (ICH) is associated with activation of the metalloproteinases before transplantation that play a key role in the subsequent development of transplant vasculopathy. METHODS AND RESULTS: We evaluated mRNA expressions of MMP-2 and MMP-9 in donor spleen lymphocytes (before transplantation) and in heart biopsies at 1 week after transplantation in 20 recipients from ICH donors and 20 recipients from trauma donors. Patients underwent serial coronary intravascular ultrasound, and interstitial myocardial fibrosis was quantified at 1 year. The baseline characteristics were similar except for increased donor age in the ICH group. Heart biopsies from the ICH group showed significant increased expression of MMP-2 (17-fold, P<0.0001) and MMP-9 (20-fold, P<0.0001) compared with the trauma group. Furthermore, the ICH group showed 1.8-fold (P=0.016) increased mRNA expression of MMP-2 and 1.7-fold (P=0.015) increased mRNA expression of MMP-9 in the donor spleen lymphocytes, suggesting the presence of systemic activation of metalloproteinases before transplantation. At 1 year, the ICH group showed increased myocardial fibrosis and accelerated coronary vasculopathy. Using multivariate regression analysis, MMP-9 was found to be associated with increased risk for vasculopathy independent of donor age (OR, 2.41; P=0.01; 95% CI, 1.24 to 4.69). CONCLUSIONS: This is the first report to describe systemic activation of MMP-2 and MMP-9 in donors with intracerebral hemorrhage and subsequent development of allograft vasculopathy.

Adult↗

PubMed2003

Spine fusion using cell matrix composites enriched in bone marrow-derived cells.

Bone marrow-derived cells including osteoblastic progenitors can be concentrated rapidly from bone marrow aspirates using the surface of selected implantable matrices for selective cell attachment. Concentration of cells in this way to produce an enriched cellular composite graft improves graft efficacy. The current study was designed to test the hypothesis that the biologic milieu of a bone marrow clot will significantly improve the efficacy of such a graft. An established posterior spinal fusion model and cancellous bone matrix was used to compare an enriched cellular composite bone graft alone, bone matrix plus bone marrow clot, and an enriched bone matrix composite graft plus bone marrow clot. Union score, quantitative computed tomography, and mechanical testing were used to define outcome. The union score for the enriched bone matrix plus bone marrow clot composite was superior to the enriched bone matrix alone and the bone matrix plus bone marrow clot. The enriched bone matrix plus bone marrow clot composite also was superior to the enriched bone matrix alone in fusion volume and in fusion area. These data confirm that the addition of a bone marrow clot to an enriched cell-matrix composite graft results in significant improvement in graft performance. Enriched composite grafts prepared using this strategy provide a rapid, simple, safe, and inexpensive method for intraoperative concentration and delivery of bone marrow-derived cells and connective tissue progenitors that may improve the outcome of bone grafting.

Animals↗

PubMed2002

Myocardial ischemic injury after heart transplantation is associated with upregulation of vitronectin receptor (alpha(v)beta3), activation of the matrix metalloproteinase induction system, and subsequent development of coronary vasculopathy.

BACKGROUND: Myocardial ischemic injury after heart transplantation is associated with subsequent development of graft vasculopathy. Both vitronectin receptor (integrin alpha(v)beta3) and tissue factor play key roles in vascular endothelial cell injury. Matrix metalloproteinases (MMPs) are activated in ischemic injury models. METHODS AND RESULTS: Thirteen patients developed myocardial ischemic injury within 2 weeks of cardiac transplantation (ischemia group). These were compared with 10 transplantation patients who had no evidence of ischemia (control group). Endomyocardial biopsies were evaluated within 2 weeks of transplantation for alpha(v)beta3, tissue factor, and extracellular MMP inducer (EMMPRIN). At 1 year, MMPs were evaluated, and interstitial myocardial fibrosis was quantified. All patients underwent intravascular ultrasound at 1 month and 1 year after transplantation. Compared with control, the ischemia group demonstrated evidence of significant increased expression of alpha(v)beta3 (3.2-fold, P<0.001), tissue factor (2.5-fold, P<0.001), and EMMPRIN (1.9-fold, P=0.01). At 1 year, the ischemia group had a significant increase in myocardial fibrosis (24+/-1.8% versus 14+/-1.1%, P<0.001) and zymographic activity of MMP-2 (1.4-fold, P<0.001), MMP-3 (1.2-fold, P<0.001), and MMP-9 (1.3-fold, P=0.01). Coronary vasculopathy progression was also more advanced in the ischemia group (change in coronary maximal intimal thickness over 1 year 0.54+/-0.1 versus 0.26+/-0.06 mm; P=0.031). CONCLUSIONS: Myocardial ischemic injury after cardiac transplantation is associated with upregulation of alpha(v)beta3, tissue factor, and activation of the MMP induction system, which may contribute to the subsequent development of allograft remodeling and vasculopathy.

Adult↗

PubMed2002

Temporal bone dissection simulation--an update.

We report on our continued development of a virtual simulation for temporal bone dissection that provides stereoscopic display, haptic feedback, and aural simulation into a straightforward, comprehensive learning environment. The multimodal interface provides a seamless simulation for non-deterministic drilling and cutting of bone in the surgical context, as well as an intuitive interface for the intelligent tutor for learning regional anatomy. We present novel methodologies for integrating multimodal and multiresolution data sets, including extension to functional and structural segmentation. We will present our initial efforts to validate this environment. Through continued iterations, it is our hope that the system will provide a valuable tool for training future otologic surgeons as well as an environment for the quantitative evaluation of surgical skill.

Aged↗