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Article ; Online: Characterization of Microscopic Multicellular Foci in Grossly Normal Renal Parenchyma of Von Hippel-Lindau Kidney.

Al-Gharaibeh, Nayef S / Shively, Sharon B / Vortmeyer, Alexander O

2022 Volume 58, Issue 12

Abstract: Background and ... ...

Abstract	Background and Objectives
Language	English
Publishing date	2022-11-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2188113-3
ISSN	1648-9144 ; 1010-660X
ISSN (online)	1648-9144
ISSN	1010-660X
DOI	10.3390/medicina58121725
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Article: Editorial: Traumatic Brain Injury and Autoimmune Disease.

Shively, Sharon Baughman / Wannamaker, Braxton B / Willis, Adam M / Brugge, John F / Ness, James

Frontiers in neurology

2021 Volume 12, Page(s) 702431

Language	English
Publishing date	2021-06-18
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2021.702431
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Article ; Online: Pathophysiology of Traumatic Brain Injury, Chronic Traumatic Encephalopathy, and Neuropsychiatric Clinical Expression.

Shively, Sharon Baughman / Priemer, David S / Stein, Murray B / Perl, Daniel P

The Psychiatric clinics of North America

2021 Volume 44, Issue 3, Page(s) 443–458

Abstract: This article focuses on neuropsychiatric clinical expression and neuropathology associated with chronic traumatic encephalopathy (CTE), which is thought to develop years after traumatic brain injury. The incidence, prevalence, additional risk factors, ... ...

Abstract	This article focuses on neuropsychiatric clinical expression and neuropathology associated with chronic traumatic encephalopathy (CTE), which is thought to develop years after traumatic brain injury. The incidence, prevalence, additional risk factors, and pathophysiology remain largely unknown. CTE is considered a tauopathy because the endogenous brain protein tau, in its hyperphosphorylated state (p-tau), defines the predominant neuropathological findings and may underlie aspects of cell toxicity, synapse and circuit dysfunction, and clinical signs and symptoms. We discuss pathophysiological mechanisms possibly affecting p-tau accumulation. Finally, we interweave how clinical features and neuroanatomical sites associated with CTE potentially intersect with posttraumatic stress disorder.
MeSH term(s)	Brain ; Brain Injuries, Traumatic/complications ; Chronic Traumatic Encephalopathy ; Humans ; Stress Disorders, Post-Traumatic ; tau Proteins/metabolism
Chemical Substances	tau Proteins
Language	English
Publishing date	2021-07-07
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	431518-2
ISSN	1558-3147 ; 0193-953X
ISSN (online)	1558-3147
ISSN	0193-953X
DOI	10.1016/j.psc.2021.04.003
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Article ; Online: Kidney in VHL disease: Early clear cell proliferation occurs in the distal tubular system.

Al-Gharaibeh, Nayef S / Temm, Constance J / Shively, Sharon B / Vortmeyer, Alexander O

Oncology reports

2022 Volume 48, Issue 6

Abstract: Renal clear cell carcinoma commonly occurs in patients with von Hippel‑Lindau disease (VHL). Kidneys of VHL disease patients (VHL kidneys) contain an abundance of independent clear cell proliferation events that have been hypothesized to represent ... ...

Abstract	Renal clear cell carcinoma commonly occurs in patients with von Hippel‑Lindau disease (VHL). Kidneys of VHL disease patients (VHL kidneys) contain an abundance of independent clear cell proliferation events that have been hypothesized to represent precursor structures of clear cell carcinoma. In the present study, it was tried to identify the site of origin of clear cell proliferation, and the immunophenotype of clear cells. Using 3D histological tracking, the topographic origin of microscopic clear cell proliferation was investigated by identification of informative structures of interest and immunohistochemical staining for cluster of differentiation 10 (CD10) and cytokeratin 7 (CK7) in consecutive serial sections. In addition, the CD10/CK7 immunophenotype of proliferating clear cells was evaluated. Clear cell proliferation uniformly occurred in the distal tubular system. Some clear cell proliferation, however, revealed proximal tubule immunophenotype. It was concluded that early proliferation of VHL‑deficient clear cells occurs in the distal tubular system. Despite the association with the distal tubular system, the immunohistochemical profile of early clear cell proliferation may be inconsistent with its distal tubular origin.
MeSH term(s)	Humans ; Kidney Neoplasms/genetics ; Carcinoma, Renal Cell/genetics ; Kidney/pathology ; von Hippel-Lindau Disease/complications ; von Hippel-Lindau Disease/genetics ; von Hippel-Lindau Disease/pathology ; Cell Proliferation ; Keratin-7 ; Von Hippel-Lindau Tumor Suppressor Protein/genetics
Chemical Substances	Keratin-7 ; VHL protein, human (EC 6.3.2.-) ; Von Hippel-Lindau Tumor Suppressor Protein (EC 2.3.2.27)
Language	English
Publishing date	2022-11-02
Publishing country	Greece
Document type	Journal Article
ZDB-ID	1222484-4
ISSN	1791-2431 ; 1021-335X
ISSN (online)	1791-2431
ISSN	1021-335X
DOI	10.3892/or.2022.8437
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Article ; Online: Viewing the Invisible Wound: Novel Lesions Identified in Postmortem Brains of U.S. Service Members With Military Blast Exposure.

Shively, Sharon B / Perl, Daniel P

Military medicine

2017 Volume 182, Issue 1, Page(s) 1461–1463

MeSH term(s)	Autopsy/methods ; Blast Injuries/complications ; Blast Injuries/mortality ; Brain/abnormalities ; Brain/anatomy & histology ; Humans ; Military Personnel/statistics & numerical data ; United States
Language	English
Publishing date	2017-01-03
Publishing country	England
Document type	Journal Article
ZDB-ID	391061-1
ISSN	1930-613X ; 0026-4075
ISSN (online)	1930-613X
ISSN	0026-4075
DOI	10.7205/MILMED-D-16-00239
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Article ; Online: Astroglial scarring after blast exposure: unproven causality - Authors' reply.

Shively, Sharon B / Perl, Daniel P

The Lancet. Neurology

2016 Volume 16, Issue 1, Page(s) 27

MeSH term(s)	Astrocytes ; Cicatrix ; Humans
Language	English
Publishing date	2016-12-12
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	2079704-7
ISSN	1474-4465 ; 1474-4422
ISSN (online)	1474-4465
ISSN	1474-4422
DOI	10.1016/S1474-4422(16)30336-2
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Article ; Online: Chronic Traumatic Encephalopathy: Known Causes, Unknown Effects.

Iacono, Diego / Shively, Sharon B / Edlow, Brian L / Perl, Daniel P

Physical medicine and rehabilitation clinics of North America

2017 Volume 28, Issue 2, Page(s) 301–321

Abstract: Chronic traumatic encephalopathy (CTE) is a neuropathologic diagnosis typically made in human brains with a history of repetitive traumatic brain injury (rTBI). It remains unknown whether CTE occurs exclusively after rTBI, or whether a single TBI (sTBI) ... ...

Abstract	Chronic traumatic encephalopathy (CTE) is a neuropathologic diagnosis typically made in human brains with a history of repetitive traumatic brain injury (rTBI). It remains unknown whether CTE occurs exclusively after rTBI, or whether a single TBI (sTBI) can cause CTE. Similarly, it is unclear whether impact (eg, motor vehicle accidents) and non-impact (eg, blasts) types of energy transfer trigger divergent or common pathologies. While it is established that a history of rTBI increases the risk of multiple neurodegenerative diseases (eg, dementia, parkinsonism, and CTE), the possible pathophysiologic and molecular mechanisms underlying these risks have yet to be elucidated.
MeSH term(s)	Brain/physiopathology ; Brain Injury, Chronic ; Chronic Traumatic Encephalopathy/complications ; Chronic Traumatic Encephalopathy/etiology ; Dementia ; Humans
Language	English
Publishing date	2017-03-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1196791-2
ISSN	1558-1381 ; 1047-9651
ISSN (online)	1558-1381
ISSN	1047-9651
DOI	10.1016/j.pmr.2016.12.007
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Article ; Online: Traumatic brain injury, shell shock, and posttraumatic stress disorder in the military--past, present, and future.

Shively, Sharon B / Perl, Daniel P

The Journal of head trauma rehabilitation

2012 Volume 27, Issue 3, Page(s) 234–239

Abstract: With preferential use of high explosives in modern warfare, traumatic brain injury (TBI) has become a common injury for troops. Most TBIs are classified as "mild," although military personnel with these injuries can have persistent symptoms such as ... ...

Abstract	With preferential use of high explosives in modern warfare, traumatic brain injury (TBI) has become a common injury for troops. Most TBIs are classified as "mild," although military personnel with these injuries can have persistent symptoms such as headache, memory impairment, and behavioral changes. During World War I, soldiers in the trenches, undergoing unrelenting artillery bombardment, suffered from similar symptoms, designated at the time as "shell shock." Dr Frederick Mott proposed studying the brains of deceased soldiers to elucidate the neuropathology of this clinical entity. Subsequent to a British government enquiry after World War I, the term "shell shock" was banned and further investigation into a possible organic cause for these symptoms was discontinued. Nevertheless, similar clinical entities, such as combat or battle fatigue and posttraumatic stress disorder, continue to be encountered by combatants in subsequent military conflicts. To this day, there exists a paucity of neuropathology studies investigating the effects of high explosives on the human brain. By analogy, studies have recently revealed that athletes with repeated head trauma can develop a neurodegenerative disease, chronic traumatic encephalopathy, who present with similar clinical features. Given current circumstance, we propose completing the work envisioned by Dr Mott almost 100 years ago.
MeSH term(s)	Blast Injuries/diagnosis ; Blast Injuries/epidemiology ; Blast Injuries/therapy ; Brain Injuries/diagnosis ; Brain Injuries/epidemiology ; Brain Injuries/therapy ; Chronic Disease ; Combat Disorders/diagnosis ; Combat Disorders/epidemiology ; Combat Disorders/therapy ; Disease Progression ; Female ; Humans ; Incidence ; Injury Severity Score ; Iraq War, 2003-2011 ; Male ; Military Personnel/psychology ; Military Personnel/statistics & numerical data ; Quality of Life ; Risk Assessment ; Sickness Impact Profile ; Stress Disorders, Post-Traumatic/diagnosis ; Stress Disorders, Post-Traumatic/epidemiology ; Stress Disorders, Post-Traumatic/therapy ; United States/epidemiology ; Warfare ; World War I
Language	English
Publishing date	2012-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	639221-0
ISSN	1550-509X ; 0885-9701
ISSN (online)	1550-509X
ISSN	0885-9701
DOI	10.1097/HTR.0b013e318250e9dd
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Article ; Online: Localized cortical chronic traumatic encephalopathy pathology after single, severe axonal injury in human brain.

Shively, Sharon B / Edgerton, Sarah L / Iacono, Diego / Purohit, Dushyant P / Qu, Bao-Xi / Haroutunian, Vahram / Davis, Kenneth L / Diaz-Arrastia, Ramon / Perl, Daniel P

Acta neuropathologica

2016 Volume 133, Issue 3, Page(s) 353–366

Abstract: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild impact traumatic brain injury from contact sports. Recently, a consensus panel defined the pathognomonic lesion for CTE as accumulations of abnormally ... ...

Abstract	Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild impact traumatic brain injury from contact sports. Recently, a consensus panel defined the pathognomonic lesion for CTE as accumulations of abnormally hyperphosphorylated tau (p-tau) in neurons (neurofibrillary tangles), astrocytes and cell processes distributed around small blood vessels at sulcal depths in irregular patterns within the cortex. The pathophysiological mechanism for this lesion is unknown. Moreover, a subset of CTE cases harbors cortical β-amyloid plaques. In this study, we analyzed postmortem brain tissues from five institutionalized patients with schizophrenia and history of surgical leucotomy with subsequent survival of at least another 40 years. Because leucotomy involves severing axons bilaterally in prefrontal cortex, this surgical procedure represents a human model of single traumatic brain injury with severe axonal damage and no external impact. We examined cortical tissues at the leucotomy site and at both prefrontal cortex rostral and frontal cortex caudal to the leucotomy site. For comparison, we analyzed brain tissues at equivalent neuroanatomical sites from non-leucotomized patients with schizophrenia, matched in age and gender. All five leucotomy cases revealed severe white matter damage with dense astrogliosis at the axotomy site and also neurofibrillary tangles and p-tau immunoreactive neurites in the overlying gray matter. Four cases displayed p-tau immunoreactivity in neurons, astrocytes and cell processes encompassing blood vessels at cortical sulcal depths in irregular patterns, similar to CTE. The three cases with apolipoprotein E ε4 haplotype showed scattered β-amyloid plaques in the overlying gray matter, but not the two cases with apolipoprotein E ε3/3 genotype. Brain tissue samples from prefrontal cortex rostral and frontal cortex caudal to the leucotomy site, and all cortical samples from the non-leucotomized patients, showed minimal p-tau and β-amyloid pathology. These findings suggest that chronic axonal damage contributes to the unique pathology of CTE over time.
MeSH term(s)	Aged ; Aged, 80 and over ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Apolipoproteins E/genetics ; Cerebral Cortex/pathology ; Chronic Traumatic Encephalopathy/pathology ; Female ; Glial Fibrillary Acidic Protein/metabolism ; Humans ; Male ; Neurofibrillary Tangles/pathology ; Neurons/metabolism ; Neurons/pathology ; Plaque, Amyloid/pathology ; Psychosurgery ; Schizophrenia/complications ; Schizophrenia/pathology ; tau Proteins/metabolism
Chemical Substances	Antigens, CD ; Antigens, Differentiation, Myelomonocytic ; Apolipoproteins E ; CD68 antigen, human ; Glial Fibrillary Acidic Protein ; tau Proteins
Language	English
Publishing date	2016-11-24
Publishing country	Germany
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	1079-0
ISSN	1432-0533 ; 0001-6322
ISSN (online)	1432-0533
ISSN	0001-6322
DOI	10.1007/s00401-016-1649-7
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Article ; Online: Tumor derived vasculogenesis in von Hippel-Lindau disease-associated tumors.

Zhuang, Zhengping / Frerich, Jason M / Huntoon, Kristin / Yang, Chunzhang / Merrill, Marsha J / Abdullaev, Ziedulla / Pack, Svetlana D / Shively, Sharon B / Stamp, Gordon / Lonser, Russell R

Scientific reports

2014 Volume 4, Page(s) 4102

Abstract: von Hippel-Lindau disease (VHL) patients develop highly vascular tumors, including central nervous system hemangioblastomas. It has been hypothesized that the vascular nature of these tumors is the product of reactive angiogenesis. However, recent data ... ...

Abstract	von Hippel-Lindau disease (VHL) patients develop highly vascular tumors, including central nervous system hemangioblastomas. It has been hypothesized that the vascular nature of these tumors is the product of reactive angiogenesis. However, recent data indicate that VHL-associated hemangioblastoma neoplastic cells originate from embryologically-arrested hemangioblasts capable of blood and endothelial cell differentiation. To determine the origin of tumor vasculature in VHL-associated hemangioblastomas, we analyzed the vascular elements in tumors from VHL patients. We demonstrate that isolated vascular structures and blood vessels within VHL-associated hemangioblastomas are a result of tumor-derived vasculogenesis. Further, similar to hemangioblastomas, we demonstrate that other VHL-associated lesions possess vascular tissue of tumor origin and that tumor-derived endothelial cells emerge within implanted VHL deficient UMRC6 RCC murine xenografts. These findings further establish the embryologic, developmentally arrested, hemangioblast as the tumor cell of origin for VHL-associated hemangioblastomas and indicate that it is also the progenitor cell for other VHL-associated tumors.
MeSH term(s)	Animals ; Cell Line, Tumor ; Cerebellar Neoplasms/blood supply ; Cerebellar Neoplasms/etiology ; Cerebellar Neoplasms/pathology ; Endothelial Cells/metabolism ; Endothelial Cells/pathology ; Factor VIII/metabolism ; Hemangioblastoma/blood supply ; Hemangioblastoma/etiology ; Hemangioblastoma/pathology ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Loss of Heterozygosity ; Male ; Mice ; Mice, Inbred NOD ; Neovascularization, Pathologic ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; Transplantation, Heterologous ; von Hippel-Lindau Disease/complications ; von Hippel-Lindau Disease/diagnosis ; von Hippel-Lindau Disease/pathology
Chemical Substances	Platelet Endothelial Cell Adhesion Molecule-1 ; Factor VIII (9001-27-8)
Language	English
Publishing date	2014-02-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep04102
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