Publications by authors named "W A Cavanaugh"

8 Publications

Plasmacytoma of the Cervical Spine: A Case Study.

J Chiropr Med 2017 Jun 2;16(2):170-174. Epub 2017 Mar 2.

Private Practice, Garden City, NY.

Objective: The purpose of this case study is to describe the presentation of a patient with plasmacytoma.

Clinical Features: A 49-year-old man presented with progressive neck pain, stiffness, and dysphagia to a chiropractic office. A radiograph indicated a plasmacytoma at C3 vertebral body. The lesion was expansile and caused a mass effect anteriorly on the esophagus and posteriorly on the spinal cord. Neurologic compromise was noted with fasciculations and hypesthesia in the right forearm. The patient was referred to a neurosurgeon.

Intervention And Outcome: Surgical resection of the tumor was performed with a vertebral body spacer and surrounding titanium cage. Bony fusion was initiated by inserting bone grafts from the iliac crests into the titanium cage. Additional laboratory analysis and advanced imaging confirmed that the plasmacytoma had progressed to multiple myeloma and radiation and chemotherapy were also necessary.

Conclusion: A chiropractor recognized a large, expansile plasmacytoma in the C3 vertebral body and referred the patient for surgical care. This case suggests that all practitioners of manual medicine should provide a careful analysis of the patient's clinical presentation and, if clinically warranted, radiographic examination to determine neck or back pain is due to an underlying malignant condition.
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http://dx.doi.org/10.1016/j.jcm.2015.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440636PMC
June 2017

Pancortins interact with amyloid precursor protein and modulate cortical cell migration.

Development 2012 Nov 19;139(21):3986-96. Epub 2012 Sep 19.

Center for Neurologic Diseases, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.

Neuronal precursor cell migration in the developing mammalian brain is a complex process requiring the coordinated interaction of numerous proteins. We have recently shown that amyloid precursor protein (APP) plays a role in migration into the cortical plate through its interaction with two cytosolic signaling proteins, disabled 1 (DAB1) and disrupted in schizophrenia 1 (DISC1). In order to identify extracellular factors that may signal through APP to regulate migration, we performed an unbiased mass spectrometry-based screen for factors that bind to the extracellular domain of APP in the rodent brain. Through this screen, we identified an interaction between APP and pancortins, proteins expressed throughout the developing and mature cerebral cortex. Via co-immunoprecipitation, we show that APP interacts with all four of the mammalian pancortin isoforms (AMY, AMZ, BMY, BMZ). We demonstrate that the BMZ and BMY isoforms of pancortin can specifically reduce β-secretase- but not α-secretase-mediated cleavage of endogenous APP in cell culture, suggesting a biochemical consequence of the association between pancortins and APP. Using in utero electroporation to overexpress and knock down specific pancortin isoforms, we reveal a novel role for pancortins in migration into the cortical plate. Interestingly, we observe opposing roles for alternate pancortin isoforms, with AMY overexpression and BMZ knock down both preventing proper migration of neuronal precursor cells. Finally, we show that BMZ can partially rescue a loss of APP expression and that APP can rescue effects of AMY overexpression, suggesting that pancortins act in conjunction with APP to regulate entry into the cortical plate. Taken together, these results suggest a biochemical and functional interaction between APP and pancortins, and reveal a previously unidentified role for pancortins in mammalian cortical development.
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http://dx.doi.org/10.1242/dev.082909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472593PMC
November 2012

Dynamic analysis of amyloid β-protein in behaving mice reveals opposing changes in ISF versus parenchymal Aβ during age-related plaque formation.

J Neurosci 2011 Nov;31(44):15861-9

Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

Growing evidence supports the hypothesis that soluble, diffusible forms of the amyloid β-peptide (Aβ) are pathogenically important in Alzheimer's disease (AD) and thus have both diagnostic and therapeutic salience. To learn more about the dynamics of soluble Aβ economy in vivo, we used microdialysis to sample the brain interstitial fluid (ISF), which contains the most soluble Aβ species in brain at steady state, in >40 wake, behaving APP transgenic mice before and during the process of Aβ plaque formation (age 3-28 months). Diffusible forms of Aβ, especially Aβ(42), declined significantly in ISF as mice underwent progressive parenchymal deposition of Aβ. Moreover, radiolabeled Aβ administered at physiological concentrations into ISF revealed a striking difference in the fate of soluble Aβ in plaque-rich (vs plaque-free) mice: it clears more rapidly from the ISF and becomes more associated with the TBS-extractable pool, suggesting that cerebral amyloid deposits can rapidly sequester soluble Aβ from the ISF. Likewise, acute γ-secretase inhibition in plaque-free mice showed a marked decline of Aβ(38), Aβ(40), and Aβ(42), whereas in plaque-rich mice, Aβ(42) declined significantly less. These results suggest that most of the Aβ(42) that populates the ISF in plaque-rich mice is derived not from new Aβ biosynthesis but rather from the large reservoir of less soluble Aβ(42) in brain parenchyma. Together, these and other findings herein illuminate the in vivo dynamics of soluble Aβ during the development of AD-type neuropathology and after γ-secretase inhibition and help explain the apparent paradox that CSF Aβ(42) levels fall as humans develop AD.
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http://dx.doi.org/10.1523/JNEUROSCI.3272-11.2011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227224PMC
November 2011

In utero electroporation followed by primary neuronal culture for studying gene function in subset of cortical neurons.

J Vis Exp 2010 Oct 8(44). Epub 2010 Oct 8.

Center for Neurologic Diseases, Harvard Medical School.

In vitro study of primary neuronal cultures allows for quantitative analyses of neurite outgrowth. In order to study how genetic alterations affect neuronal process outgrowth, shRNA or cDNA constructs can be introduced into primary neurons via chemical transfection or viral transduction. However, with primary cortical cells, a heterogeneous pool of cell types (glutamatergic neurons from different layers, inhibitory neurons, glial cells) are transfected using these methods. The use of in utero electroporation to introduce DNA constructs in the embryonic rodent cortex allows for certain subsets of cells to be targeted: while electroporation of early embryonic cortex targets deep layers of the cortex, electroporation at late embryonic timepoints targets more superficial layers. Further, differential placement of electrodes across the heads of individual embryos results in the targeting of dorsal-medial versus ventral-lateral regions of the cortex. Following electroporation, transfected cells can be dissected out, dissociated, and plated in vitro for quantitative analysis of neurite outgrowth. Here, we provide a step-by-step method to quantitatively measure neuronal process outgrowth in subsets of cortical cells. The basic protocol for in utero electroporation has been described in detail in two other JoVE articles from the Kriegstein lab. We will provide an overview of our protocol for in utero electroporation, focusing on the most important details, followed by a description of our protocol that applies in utero electroporation to the study of gene function in neuronal process outgrowth.
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http://dx.doi.org/10.3791/2103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185628PMC
October 2010