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Full-Text Articles in Medicine and Health Sciences

Idiopathic Nodular Glomerulosclerosis In A Chronic Marijuana User; A Case Report And Review Of The Literature, Mehri Mollaee, Tibor Fülöp, Sohil Abdul Salim, Seyed Mehrdad Hamrahian Dec 2017

Idiopathic Nodular Glomerulosclerosis In A Chronic Marijuana User; A Case Report And Review Of The Literature, Mehri Mollaee, Tibor Fülöp, Sohil Abdul Salim, Seyed Mehrdad Hamrahian

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Nodular glomerulosclerosis is a characteristic histological finding of diabetic nephropathy (DN) with thickened glomerular basement membrane (GBM) and hyalinized arterioles. Idiopathic nodular glomerulosclerosis (ING), a rare distinct clinicopathologic entity, is the term used to denote classic DN confirmed by light microscopy, immuno-fluorescence, and electron microscopy in the absence of diabetes mellitus (DM). ING has been linked to heavy tobacco smoking, chronic hypertension, obesity and insulin resistance. Its association with marijuana use is unknown. Case Presentation: We report a case of biopsy-proved ING in the absence of pre-existing history of DM and heavy smoking. This report addresses the possible accentuation …


How Should Clinicians Weigh The Benefits And Harms Of Discussing Politicized Topics That Influence Their Individual Patients' Health?, Diana Alame, Robert D. Truog Dec 2017

How Should Clinicians Weigh The Benefits And Harms Of Discussing Politicized Topics That Influence Their Individual Patients' Health?, Diana Alame, Robert D. Truog

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Health implications of politically charged phenomena are particularly difficult for physicians to discuss with their patients and communities. Addressing climate change and its associated health effects involves trade-offs between health and economic prosperity, necessitating that physicians weigh the potential benefits and risks of discussing climate change health effects. We argue that the potential benefits of physician communication and advocacy ultimately outweigh the potential risks. Therefore, physicians should be supported in their efforts to educate their patients and communities about climate change health effects. Furthermore, democratic deliberation could prove helpful in addressing disagreements among physicians within a practice about such politicized …


Life After Being A Pathology Department Chair Ii: Lessons Learned., David N. Bailey, Mary F. Lipscomb, Fred Gorstein, David Wilkinson, Fred Sanfilippo Oct 2017

Life After Being A Pathology Department Chair Ii: Lessons Learned., David N. Bailey, Mary F. Lipscomb, Fred Gorstein, David Wilkinson, Fred Sanfilippo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The 2016 Association of Pathology Chairs annual meeting featured a discussion group of Association of Pathology Chairs senior fellows (former chairs of academic departments of pathology who have remained active in Association of Pathology Chairs) that focused on how they decided to transition from the chair, how they prepared for such transition, and what they did after the transition. At the 2017 annual meeting, the senior fellows (encompassing 481 years of chair service) discussed lessons they learned from service as chair. These lessons included preparation for the chairship, what they would have done differently as chair, critical factors for success …


Developmental Lead And/Or Prenatal Stress Exposures Followed By Different Types Of Behavioral Experience Result In The Divergence Of Brain Epigenetic Profiles In A Sex, Brain Region, And Time-Dependent Manner: Implications For Neurotoxicology., Deborah A. Cory-Slechta, Marissa Sobolewski, Garima Varma, Jay S. Schneider Oct 2017

Developmental Lead And/Or Prenatal Stress Exposures Followed By Different Types Of Behavioral Experience Result In The Divergence Of Brain Epigenetic Profiles In A Sex, Brain Region, And Time-Dependent Manner: Implications For Neurotoxicology., Deborah A. Cory-Slechta, Marissa Sobolewski, Garima Varma, Jay S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Over a lifetime, early developmental exposures to neurocognitive risk factors, such as lead (Pb) exposures and prenatal stress (PS), will be followed by multiple varied behavioral experiences. Pb, PS and behavioral experience can each influence brain epigenetic profiles. Our recent studies show a greater level of complexity, however, as all three factors interact within each sex to generate differential adult variation in global post-translational histone modifications (PTHMs), which may result in fundamentally different consequences for life-long learning and behavioral function. We have reported that PTHM profiles differ by sex, brain region and time point of measurement following developmental exposures to …


Strain Specific Effects Of Low Level Lead Exposure On Associative Learning And Memory In Rats., Megha Verma, J. S. Schneider Sep 2017

Strain Specific Effects Of Low Level Lead Exposure On Associative Learning And Memory In Rats., Megha Verma, J. S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Exposure to lead (Pb) remains a significant public health concern. Lead exposure in early life impairs the normal development of numerous cognitive and neurobehavioral processes. Previous work has shown that the effects of developmental Pb exposure on gene expression patterns in the brain are modulated by various factors including the developmental timing of the exposure, level of exposure, sex, and genetic background. Using gene microarray profiling, we previously reported a significant strain-specific effect of Pb exposure on the hippocampal transcriptome, with the greatest number of differentially expressed transcripts in Long Evans (LE) rats and the fewest in Sprague Dawley (SD) …


Posttranscriptional Upregulation Of Idh1 By Hur Establishes A Powerful Survival Phenotype In Pancreatic Cancer Cells., Mahsa Zarei, Shruti Lal, Seth J. Parker, Avinoam Nevler, Ali Vaziri-Gohar, Katerina Dukleska, Nicole C. Mambelli-Lisboa, Cynthia Moffat, Fernando F Blanco, Saswati N. Chand, Masaya Jimbo, Joseph A. Cozzitorto, Wei Jiang, Charles J. Yeo, Eric R. Londin, Erin L. Seifert, Christian M. Metallo, Jonathan R. Brody, Jordan M. Winter Aug 2017

Posttranscriptional Upregulation Of Idh1 By Hur Establishes A Powerful Survival Phenotype In Pancreatic Cancer Cells., Mahsa Zarei, Shruti Lal, Seth J. Parker, Avinoam Nevler, Ali Vaziri-Gohar, Katerina Dukleska, Nicole C. Mambelli-Lisboa, Cynthia Moffat, Fernando F Blanco, Saswati N. Chand, Masaya Jimbo, Joseph A. Cozzitorto, Wei Jiang, Charles J. Yeo, Eric R. Londin, Erin L. Seifert, Christian M. Metallo, Jonathan R. Brody, Jordan M. Winter

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Cancer aggressiveness may result from the selective pressure of a harsh nutrient-deprived microenvironment. Here we illustrate how such conditions promote chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Glucose or glutamine withdrawal resulted in a 5- to 10-fold protective effect with chemotherapy treatment. PDAC xenografts were less sensitive to gemcitabine in hypoglycemic mice compared with hyperglycemic mice. Consistent with this observation, patients receiving adjuvant gemcitabine (n = 107) with elevated serum glucose levels (HgbA1C > 6.5%) exhibited improved survival. We identified enhanced antioxidant defense as a driver of chemoresistance in this setting. ROS levels were doubled in vitro by either nutrient withdrawal …


Novel Influences Of Il-10 On Cns Inflammation Revealed By Integrated Analyses Of Cytokine Networks And Microglial Morphology., Warren D. Anderson, Andrew D. Greenhalgh, Aditya Takwale, Samuel David, Rajanikanth Vadigepalli Aug 2017

Novel Influences Of Il-10 On Cns Inflammation Revealed By Integrated Analyses Of Cytokine Networks And Microglial Morphology., Warren D. Anderson, Andrew D. Greenhalgh, Aditya Takwale, Samuel David, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Coordinated interactions between cytokine signaling and morphological dynamics of microglial cells regulate neuroinflammation in CNS injury and disease. We found that pro-inflammatory cytokine gene expression in vivo showed a pronounced recovery following systemic LPS. We performed a novel multivariate analysis of microglial morphology and identified changes in specific morphological properties of microglia that matched the expression dynamics of pro-inflammatory cytokine TNFα. The adaptive recovery kinetics of TNFα expression and microglial soma size showed comparable profiles and dependence on anti-inflammatory cytokine IL-10 expression. The recovery of cytokine variations and microglial morphology responses to inflammation were negatively regulated by IL-10. Our novel …


Intracellular Ca 2+ Sensing: Role In Calcium Homeostasis And Signaling, Rafaela Bagur, György Hajnóczky Jun 2017

Intracellular Ca 2+ Sensing: Role In Calcium Homeostasis And Signaling, Rafaela Bagur, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Ca2+ is a ubiquitous intracellular messenger that controls diverse cellular functions but can become toxic and cause cell death. Selective control of specific targets depends on spatiotemporal patterning of the calcium signal and decoding it by multiple, tunable, and often strategically positioned Ca2+-sensing elements. Ca2+ is detected by specialized motifs on proteins that have been biochemically characterized decades ago. However, the field of Ca2+ sensing has been reenergized by recent progress in fluorescent technology, genetics, and cryo-EM. These approaches exposed local Ca2+-sensing mechanisms inside organelles and at the organellar interfaces, revealed how Ca …


Intratumoral Heterogeneity Analysis Reveals Hidden Associations Between Protein Expression Losses And Patient Survival In Clear Cell Renal Cell Carcinoma., Wei Jiang, Essel Dulaimi, Karthik Devarajan, Theodore Parsons, Qiong Wang, Raymond O'Neill, Charalambos C. Solomides, Stephen C. Peiper, Joseph R. Testa, Robert Uzzo, Haifeng Yang Jun 2017

Intratumoral Heterogeneity Analysis Reveals Hidden Associations Between Protein Expression Losses And Patient Survival In Clear Cell Renal Cell Carcinoma., Wei Jiang, Essel Dulaimi, Karthik Devarajan, Theodore Parsons, Qiong Wang, Raymond O'Neill, Charalambos C. Solomides, Stephen C. Peiper, Joseph R. Testa, Robert Uzzo, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Intratumoral heterogeneity (ITH) is a prominent feature of kidney cancer. It is not known whether it has utility in finding associations between protein expression and clinical parameters. We used ITH that is detected by immunohistochemistry (IHC) to aid the association analysis between the loss of SWI/SNF components and clinical parameters.160 ccRCC tumors (40 per tumor stage) were used to generate tissue microarray (TMA). Four foci from different regions of each tumor were selected. IHC was performed against PBRM1, ARID1A, SETD2, SMARCA4, and SMARCA2. Statistical analyses were performed to correlate biomarker losses with patho-clinical parameters. Categorical variables were compared between groups …


Microscopic Examination Of Findings Encountered During Cadaver Dissection: Malignant, Benign Or Anatomic Variation?, Maria Cicioni, Vandi Ly, Guiyun Zhang, Bruce Fenderson Mar 2017

Microscopic Examination Of Findings Encountered During Cadaver Dissection: Malignant, Benign Or Anatomic Variation?, Maria Cicioni, Vandi Ly, Guiyun Zhang, Bruce Fenderson

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Pathologic findings encountered during cadaver dissection provide an opportunity for integrating the preclinical basic sciences and encouraging critical thinking. The objective of this study was to determine whether it is possible to make a pathologic diagnosis of an unknown mass from an embalmed cadaver. Diagnoses would have to be based solely on gross and microscopic appearance of tissue, without clinical histories of the cadaveric donors. The tissue samples we removed from each mass were surprisingly well preserved and showed minimal autolysis. Indeed, some of the histological detail was as clear as may be found in any textbook. We were able …


Proteoglycan Neofunctions: Regulation Of Inflammation And Autophagy In Cancer Biology., Liliana Schaefer, Claudia Tredup, Maria A. Gubbiotti, Renato V. Iozzo Jan 2017

Proteoglycan Neofunctions: Regulation Of Inflammation And Autophagy In Cancer Biology., Liliana Schaefer, Claudia Tredup, Maria A. Gubbiotti, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Inflammation and autophagy have emerged as prominent issues in the context of proteoglycan signaling. In particular, two small, leucine-rich proteoglycans, biglycan and decorin, play pivotal roles in the regulation of these vital cellular pathways and, as such, are intrinsically involved in cancer initiation and progression. In this minireview, we will address novel functions of biglycan and decorin in inflammation and autophagy, and analyze new emerging signaling events triggered by these proteoglycans, which directly or indirectly modulate these processes. We will critically discuss the dual role of proteoglycan-driven inflammation and autophagy in tumor biology, and delineate the potential mechanisms through which …