Anatomy Commons^™

Skin Disease And Non-Syndromic Hearing Loss-Linked Cx30 Mutations Exhibit Several Distinct Cellular Pathologies, Amy Berger, John Kelly, Patrick Lajoie, Qing Shao, Dale Laird

Anatomy and Cell Biology Publications

Connexin 30 (Cx30), a member of the large gap junction protein family, plays a role in the homeostasis of the epidermis and inner ear through gap junctional intercellular communication (GJIC). Here, we investigated the underlying mechanisms of four autosomal dominant Cx30 gene mutations linked to hearing loss and/or various skin diseases. First, the T5M mutant linked to non-syndromic hearing loss formed functional gap junction channels and hemichannels, similar to wild type Cx30. The loss-of-function V37E mutant associated with Clouston syndrome or keratitis-ichthyosis-deafness syndrome was retained in the endoplasmic reticulum and significantly induced apoptosis. The G59R mutant linked to Vohwinkel and …

Recent Advances In The Molecular Characterization Of Circulating Tumor Cells, Lori E. Lowes, Alison L. Allan

Anatomy and Cell Biology Publications

Although circulating tumor cells (CTCs) were first observed over a century ago, lack of sensitive methodology precluded detailed study of these cells until recently. However, technological advances have now facilitated the identification, enumeration, and characterization of CTCs using a variety of methods. The majority of evidence supporting the use of CTCs in clinical decision-making has been related to enumeration using the CellSearch((R)) system and correlation with prognosis. Growing evidence also suggests that CTC monitoring can provide an early indication of patient treatment response based on comparison of CTC levels before and after therapy. However, perhaps the greatest potential that CTCs …

Classifying Lower Extremity Muscle Fatigue During Walking Using Machine Learning And Inertial Sensors, Jian Zhang, Thurmon Lockhart, Rahul Soangra

Physical Therapy Faculty Articles and Research

Fatigue in lower extremity musculature is associated with decline in postural stability, motor performance and alters normal walking patterns in human subjects. Automated recognition of lower extremity muscle fatigue condition may be advantageous in early detection of fall and injury risks. Supervised machine learning methods such as Support Vector Machines (SVM) have been previously used for classifying healthy and pathological gait patterns and also for separating old and young gait patterns. In this study we explore the classification potential of SVM in recognition of gait patterns utilizing an inertial measurement unit associated with lower extremity muscular fatigue. Both kinematic and …

Dysphagia And Disrupted Cranial Nerve Development In A Mouse Model Of Digeorge/22q11 Deletion Syndrome, Beverly A. Karpinski, Thomas M. Maynard, Matthew S. Fralish, Samar Nuwayhid, Irene Zohn, Sally Ann Moody, Anthony-Samuel Lamantia

Anatomy and Regenerative Biology Faculty Publications

We assessed feeding-related developmental anomalies in the LgDel mouse model of Chromosome 22q11 Deletion Syndrome (22q11DS), a common developmental disorder that frequently includes perinatal dysphagia - debilitating feeding, swallowing and nutrition difficulties from birth onward - within its phenotypic spectrum. LgDel pups gain significantly less weight during the first postnatal weeks, and have several signs of respiratory infections due to food aspiration. Most 22q11 genes are expressed in anlagen of craniofacial and brainstem regions critical for feeding and swallowing, and diminished expression in LgDel embryos apparently compromises development of these regions. Palate and jaw anomalies indicate divergent oro-facial morphogenesis. Altered …

Implementation Of Do Not Attempt Resuscitate Orders In A Japanese Nursing Home, Nobuhiro Asai, Yoshihiro Ohkuni, Lonny Ashworth, Norihiro Kaneko

Respiratory Therapy Faculty Publications and Presentations

Objective: To investigate whether do not attempt resuscitation (DNAR) orders can be implemented in a standard nursing home in Japan, where routine DNAR orders are not yet common in many facilities including hospitals.

Method: Ninety-eight residents in a 100-bed nursing home were evaluated. All of the eligible residents and/or their family members were asked whether they wanted to receive resuscitation, including mechanical ventilation.

Result: The residents were 54 to 101 years of age (mean 83.3), with 27 males and 71 females. After administering the questionnaire, 92 (94%) patients did not want resuscitation and mechanical ventilation.

Conclusion: In a nursing home, …

Adaptation Of Semiautomated Circulating Tumor Cell (Ctc) Assays For Clinical And Preclinical Research Applications, Lori E. Lowes, Benjamin D. Hedley, Michael Keeney, Alison L. Allan

Anatomy and Cell Biology Publications

The majority of cancer-related deaths occur subsequent to the development of metastatic disease. This highly lethal disease stage is associated with the presence of circulating tumor cells (CTCs). These rare cells have been demonstrated to be of clinical significance in metastatic breast, prostate, and colorectal cancers. The current gold standard in clinical CTC detection and enumeration is the FDA-cleared CellSearch system (CSS). This manuscript outlines the standard protocol utilized by this platform as well as two additional adapted protocols that describe the detailed process of user-defined marker optimization for protein characterization of patient CTCs and a comparable protocol for CTC …

Activation Of Mglur2/3 Receptors In The Ventral Prefrontal Cortex Reverses Sensorimotor Gating Deficits Induced By A Systemic Nmda Receptor Antagonist, Bridget Valsamis, Michael Chang, Marei Typlt, Susanne Schmid

Anatomy and Cell Biology Publications

Prepulse inhibition (PPI) of acoustic startle is an operational measure of sensorimotor gating, which is disrupted in schizophrenia. NMDA receptor (NMDAR) antagonist induced PPI disruption has become an important pharmacological model for schizophrenia; however, knowledge of the underlying mechanism remains incomplete. This study examines the role of NMDAR in the caudal pontine reticular nucleus (PnC) and the medial prefrontal cortex (mPFC) in NMDARs antagonist induced PPI deficits, as well as the NMDA receptor subtypes involved. We administered the NMDA antagonist MK-801 locally into the caudal pontine reticular formation (PnC), where the PPI mediating pathway converges with the primary startle pathway, …

A Nicotinic Acetylcholine Receptor Agonist Prevents Loss Of Retinal Ganglion Cells In A Glaucoma Model, Kazuhiro Iwamoto, Patrick Birkholz, Austin Schipper, David Mata, David M. Linn, Cindy L. Linn

Peer Reviewed Articles

Purpose.: The purpose of this study was to analyze the neuroprotective effect of an α7 nAChR agonist, PNU-282987, using an in vivo model of glaucoma in Long Evans rats.

Methods.: One eye in each animal was surgically manipulated to induce glaucoma in control untreated animals and in animals that were treated with intravitreal injections of PNU-282987. To induce glaucoma-like conditions, 0.05 mL of 2 M NaCl was injected into the episcleral veins of right eyes in each rat to create scar tissue and increase intraocular pressure. The left eye in each rat acted as an internal control. One month following …

Variation In Feeding Practices Following The Norwood Procedure., Linda M. Lambert, Nancy A. Pike, Barbara Medoff-Cooper, Victor Zak, Victoria L. Pemberton, Lisa Young-Borkowski, Martha L. Clabby, Kathryn N. Nelson, Richard G. Ohye, Bethany Trainor, Karen Uzark, Nancy Rudd, Louise Bannister, Rosalind Korsin, David S. Cooper, Christian Pizarro, Sinai C. Zyblewski, Bronwyn H. Bartle, Richard V. Williams, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To assess variation in feeding practice at hospital discharge after the Norwood procedure, factors associated with tube feeding, and associations among site, feeding mode, and growth before stage II.

STUDY DESIGN: From May 2005 to July 2008, 555 subjects from 15 centers were enrolled in the Pediatric Heart Network Single Ventricle Reconstruction Trial; 432 survivors with feeding data at hospital discharge after the Norwood procedure were analyzed.

RESULTS: Demographic and clinical variables were compared among 4 feeding modes: oral only (n = 140), oral/tube (n = 195), nasogastric tube (N-tube) only (n = 40), and gastrostomy tube (G-tube) only …

Roles Of Dopamine Receptor On Chemosensory And Mechanosensory Primary Cilia In Renal Epithelial Cells, Viralkumar S. Upadhyay, Brian S. Muntean, Samred H. Kathem, Jangyoun J. Hwang, Wissam A. Aboualaiwi, Surya M. Nauli

Pharmacy Faculty Articles and Research

Dopamine plays a number of important physiological roles. However, activation of dopamine receptor type-5 (DR5) and its effect in renal epithelial cells have not been studied. Here, we show for the first time that DR5 is localized to primary cilia of LLCPK kidney cells. Renal epithelial cilia are mechanosensory organelles that sense and respond to tubular fluid-flow in the kidney. To determine the roles of DR5 and sensory cilia, we used dopamine to non-selectively and fenoldopam to selectively activate ciliary DR5. Compared to mock treatment, dopamine treated cells significantly increases the length of cilia. Fenoldopam further increases the length of …

Two Distinct Dynamic Modes Subtend The Detection Of Unexpected Sounds, Jean-Rémi King, Alexandre Gramfort, Aaron Schurger, Lionel Naccache, Stanislas Dehaene

Psychology Faculty Articles and Research

The brain response to auditory novelty comprises two main EEG components: an early mismatch negativity and a late P300. Whereas the former has been proposed to reflect a prediction error, the latter is often associated with working memory updating. Interestingly, these two proposals predict fundamentally different dynamics: prediction errors are thought to propagate serially through several distinct brain areas, while working memory supposes that activity is sustained over time within a stable set of brain areas. Here we test this temporal dissociation by showing how the generalization of brain activity patterns across time can characterize the dynamics of the underlying …

Superoxide Signaling In Perivascular Adipose Tissue Promotes Age-Related Artery Stiffness, Bradley S. Fleenor, Jason S. Eng, Amy L. Sindler, Bryant T. Pham, Jackson D. Kloor, Douglas R. Seals

Graduate Center for Nutritional Sciences Faculty Publications

We tested the hypothesis that superoxide signaling within aortic perivascular adipose tissue (PVAT) contributes to large elastic artery stiffening in old mice. Young (4-6 months), old (26-28 months), and old treated with 4-Hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL), a superoxide scavenger (1 mm in drinking water for 3 weeks), male C57BL6/N mice were studied. Compared with young, old had greater large artery stiffness assessed by aortic pulse wave velocity (aPWV, 436 ± 9 vs. 344 ± 5 cm s(-1)) and intrinsic mechanical testing (3821 ± 427 vs. 1925 ± 271 kPa) (both P < 0.05). TEMPOL treatment in old reversed both measures of arterial stiffness. Aortic PVAT superoxide production was greater in old (P < 0.05 vs. Y), which was normalized with TEMPOL. Compared with young, old controls had greater pro-inflammatory proteins in PVAT-conditioned media (P < 0.05). Young recipient mice transplanted with PVAT from old compared with young donors for 8 weeks had greater aPWV (409 ± 7 vs. 342 ± 8 cm s(-1)) and intrinsic mechanical properties (3197 ± 647 vs. 1889 ± 520 kPa) (both P < 0.05), which was abolished with TEMPOL supplementation in old donors. Tissue-cultured aortic segments from old in the presence of PVAT had greater mechanical stiffening compared with old cultured in the absence of PVAT and old with PVAT and TEMPOL (both, P < 0.05). In addition, PVAT-derived superoxide was associated with arterial wall hypertrophy and greater adventitial collagen I expression with aging that was attenuated by TEMPOL. Aging or TEMPOL treatment did not affect blood pressure. Our findings provide evidence for greater age-related superoxide production and pro-inflammatory proteins in PVAT, and directly link superoxide signaling in PVAT to large elastic artery stiffness.

Morphine Enhances Hiv-1sf162-Mediated Neuron Death And Delays Recovery Of Injured Neurites, Ruturaj R. Masvekar, Nazira El-Hage, Kurt F. Hauser, Pamela E. Knapp

Anatomy and Neurobiology Publications

HIV-1 enters the CNS soon after initial systemic infection; within the CNS parenchyma infected and/or activated perivascular macrophages, microglia and astrocytes release viral and cellular toxins that drive secondary toxicity in neurons and other cell types. Our previous work has largely modeled HIV-neuropathology using the individual viral proteins Tat or gp120, with murine striatal neurons as targets. To model disease processes more closely, the current study uses supernatant from HIV-1-infected cells. Supernatant from HIV-1SF162-infected differentiated-U937 cells (HIV+sup) was collected and p24 level was measured by ELISA to assess the infection. Injection drug abuse is a significant risk factor for HIV-infection, …

Neuropathological Responses To Chronic Nmda In Rats Are Worsened By Dietary N-3 Pufa Deprivation But Are Not Ameliorated By Fish Oil Supplementation, Vasken L. Keleshian, Matthew Kellom, Hyung-Wook Kim, Ameer Y. Taha, Yewon Cheon, Miki Igarashi, Stanley I. Rapoport, Jagadeesh S. Rao

Anatomy and Neurobiology Publications

Background

Dietary long-chain n-3 polyunsaturated fatty acid (PUFA) supplementation may be beneficial for chronic brain illnesses, but the issue is not agreed on. We examined effects of dietary n-3 PUFA deprivation or supplementation, compared with an n-3 PUFA adequate diet (containing alpha-linolenic acid [18:3 n-3] but not docosahexaenoic acid [DHA, 22:6n-3]), on brain markers of lipid metabolism and excitotoxicity, in rats treated chronically with NMDA or saline.

Methods

Male rats after weaning were maintained on one of three diets for 15 weeks. After 12 weeks, each diet group was injected i.p. daily with saline (1 ml/kg) or a subconvulsive dose …

The Importance Of Managing Psychosocial Health: A Case Study, Mary Insana Fisher, Harold L. Merriman

Physical Therapy Faculty Publications

Managing the physical aspects of lymphedema requires an individual to be committed to daily treatment of this chronic condition. Performing manual lymph drainage, using compression bandaging or compression garments, exercising, and caring for the skin all take time and a high level of dedication. This commitment to self-care can be emotionally and psychologically exhausting.

When coupled with other emotional stressors in a patient’s life, successful treatment of lymphedema is challenging. We present a case demonstrating how the physical and psychological aspects of care interplay, and, when well-managed, can positively affect the outcome.

Breast Cancer Edge Task Force Outcomes - Clinical Measures Of Strength And Muscular Endurance: A Systematic Review, Mary Insana Fisher, Claire Davies, Christine Beuthin, Genevieve Colon, Brittany Zoll, Lucinda Pfalzer

Physical Therapy Faculty Publications

Background: Muscular strength deficits are a common morbidity following treatment for breast cancer. Accurate assessment of strength and muscular endurance following breast cancer treatments is essential in identifying deficits and planning rehabilitation strategies.

Purpose: The purpose of this systematic review was to identify strength and muscular endurance outcome measures for use with women treated for breast cancer that possess strong psychometric properties and are clinically useful.

Methods: Multiple electronic databases were searched between February and June 2013. Included studies of tools used to assess strength and muscular endurance met the following criteria: reported psychometric properties, clinically feasible methods, adults (preferably …

Test Items In The Complete And Short Forms Of The Bot-2 That Contribute Substantially To Motor Performance Assessments In Typically Developing Children 6-10 Years Of Age, Kadi Carmosino, Ashley Grzeszczak, Kaylie Mcmurray, Ali Olivo, Bo Slutz, Brittany Zoll, Betsy Donahoe-Fillmore, C. Jayne Brahler

Physical Therapy Faculty Publications

Objectives: Determine the magnitude of association between individual subtest items of the Bruininks-Oseretsky Test of Motor Proficiency, second edition (BOT-2), and the respective total subtest scores and to review items on the BOT-2 Short Form.

Background: The Bruininks-Oseretsky Test of Motor Proficiency, second edition (BOT-2), is a test used to measure gross motor proficiency in both typically developing children and children with developmental disabilities between the ages of four and twenty-one. The BOT-2 Short Form consists of fourteen test items proportionally selected from the subtests of the Complete Form. It can be used as a screening tool and takes less …

Interleukin-1 Receptor Antagonist Modulates Inflammation And Scarring After Ligament Injury, Connie S. Chamberlain, Ellen M. Leiferman, Kayt E. Frisch, Sarah E. Duenwald-Kuehl, Stacey L. Brickson, William L. Murphy, Georffrey S. Baer, Ray Vanderby

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

Ligaments have limited regenerative potential and as a consequence, repair is protracted and results in a mechanically inferior tissue more scar-like than native ligament. We previously reported that a single injection of interleukin-1 receptor antagonist (IL-1Ra) delivered at the time of injury, decreased the number of M2 macrophage-associated inflammatory cytokines. Based on these results, we hypothesized that IL-1Ra administered after injury and closer to peak inflammation (as would occur clinically), would more effectively decrease inflammation and thereby improve healing. Since IL-1Ra has a short half-life, we also investigated the effect of multiple injections. The objective of this study was to …

The Influence Of Partial And Full Thickness Tears On Infraspinatus Tendon Strain Patterns, Kayt E. Frisch, David Marcu, Geoffrey S. Baer, Darryl G. Thelen, Ray Vanderby

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

Tears on the bursal and articular sides of the rotator cuff tendons are known to behave differently and strain is thought to play a role in this difference. This study investigates the effect of tear location on the changes in three strain measurements (grip-to-grip, insertion, and mid-substance tissue) in a sheep infraspinatus tendon model during axial loading. We introduced a 14mm wide defect near the insertion from either the articular or bursal side of the tendon to three depths (3 mm, 7mm & full) progressively. For each condition, tendons were sinusoidally stretched (4% at 0.5 Hz) while insertion and midsubstance …

Influence Of Tendon Tears On Ultrasound Echo Intensity In Response To Loading, Kayt E. Frisch, David Marcu, Geoffrey S. Baer, Darryl G. Thelen, Ray Vanderby

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

Acoustoelastic (AE) ultrasound image analysis is a promising non-invasive approach that uses load-dependent echo intensity changes to characterize stiffness of tendinous tissue. The purpose of this study was to investigate whether AE can detect localized changes in tendon stiffness due to partial and full-thickness tendon tears. Ovine infraspinatus tendons with different levels of damage (Intact, 33%, 66% and full thickness cuts initiated on the articular and bursal sides) were cyclically loaded in a mechanical testing system while cine ultrasound images were recorded. The load-induced changes in echo intensity on the bursal and articular side of the tendon were determined. Consistent …