Digital Commons Network^™

The Case For Patient Navigation In Lung Cancer Screening In Vulnerable Populations: A Systematic Review., Christine S Shusted, Julie A Barta, Michael Lake, Rickie Brawer, Brooke Ruane, Teresa E Giamboy, Baskaran Sundaram, Nathaniel R Evans, Ronald E Myers, Gregory C Kane

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

Patient navigation has been proposed to combat cancer disparities in vulnerable populations. Vulnerable populations often have poorer cancer outcomes and lower levels of screening, adherence, and treatment. Navigation has been studied in various cancers, but few studies have assessed navigation in lung cancer. Additionally, there is a lack of consistency in metrics to assess the quality of navigation programs. The authors conducted a systematic review of published cancer screening studies to identify quality metrics used in navigation programs, as well as to recommend standardized metrics to define excellence in lung cancer navigation. The authors included 26 studies evaluating navigation metrics …

Comparative Spending Of Medicaid Dollars On Child Participants Of Kentucky’S Sobriety Treatment And Recovery Teams Program Versus A Matched Comparison Group., Matthew Thomas Walton

Electronic Theses and Dissertations

Child protective services agencies have long observed the complicating role that parental substance use and addiction plays in cases of child maltreatment. Families who struggle with these problems present unique challenges for child welfare professionals. These families are typically more difficult to engage, more likely to have children removed from the home, and have poorer outcomes when compared to other families. These poorer outcomes often include health problems. Addiction has well-known effects on health, and the specific manifestations of these problems for parents have been documented for years in child protection casework. However, what has been less investigated are the …

Evaluating The Therapeutic Efficacy Of Grb2 Inhibition In Ovarian Malignancies, Olivia Lara

Dissertations and Theses (Open Access)

Purpose: Adaptor proteins such as growth factor receptor-bound protein-2 (Grb2) play important roles in cancer cell signaling. In the present study, we examined the biological effects of liposomal antisense oligodeoxynucleotide that blocks Grb2 expression (L-Grb2) in ovarian cancer models.

Experimental Design: Murine orthotopic models of ovarian cancer (OVCAR5 and SKOV3ip1) were used to study the biological effects of L-Grb2 on tumor growth. In vitro experiments (cell viability assay, Western blot analysis, siRNA transfection, and reverse phase protein array) were carried out to elucidate the mechanism and potential predictors of tumor response to L-Grb2.

Results: Treatment with L-Grb2 decreased tumor growth …

Modeling Proton Relative Biological Effectiveness Using Monte Carlo Simulations Of Microdosimetry, Mark A. Newpower

Dissertations and Theses (Open Access)

Proton therapy is a radiotherapy modality that can offer a better physical dose distribution when compared to photon radiotherapy by taking advantage of the Bragg peak, a narrow region of rapid energy loss. Proton therapy is also known to offer an enhanced relative biological effectiveness (RBE) compared to photons. In the current clinical standard, RBE is fixed at 1.1 at all points along the proton beam, meaning protons are assumed to require 10% less dose than photons to achieve target coverage and organ at risk (OAR) sparing. However, there is mounting clinical evidence, and a significant number of in vitro …

Oxidative Phosphorylation: A Critical Feature And Novel Therapeutic Target In Melanoma Brain Metastases, Grant Fischer

Dissertations and Theses (Open Access)

We recently showed via RNA-sequencing (RNA-seq) analysis of clinical samples that melanoma brain metastases (MBMs) have higher expression of oxidative phosphorylation (OXPHOS) genes (including PPARGC1A or PGC1α) than patient-matched extracranial metastases (ECMs). Thus, the central hypothesis of this dissertation is that OXPHOS plays a critical role in the pathogenesis of MBMs.

RNA-seq analysis identified increased expression of OXPHOS genes in intracranial (ICr) vs. subcutaneous (SQ) xenografts of 4 different human melanoma cell lines. Increased OXPHOS in the ICr xenografts was confirmed by direct metabolite analysis and [U-¹³C]-glucose tracing analysis. Together, these studies indicate that the brain TME …

Tracking Treatment Response And Resistance To Parp Inhibition (Talazoparib) In Hereditary Pancreatic Cancer., Jennifer Goldstein

Dissertations and Theses (Open Access)

polyADP ribose polymerase (PARP) inhibitors are a class of drugs that block the PARP enzymes, involved in the repair of singe-stranded DNA breaks through the base excision repair pathway. PARP inhibition leads to replication-associated double stranded DNA breaks, which are repaired by homologous recombination (HR). In tumors with HR defects (i.e. BRCA mutants), there is a shift to error-prone DNA repair and subsequent genomic instability and cell death.

In 2014, Olaparib became the first FDA-approved PARP inhibitor for the treatment of BRCA-mutant ovarian cancer. In the phase III POLO (Pancreas cancer OLaparib Ongoing) trial presented at the American Society …

Fasting Reduces Intestinal Radiotoxicity Enabling Dose-Escalated Radiotherapy For Pancreatic Cancer, Marimar De La Cruz Bonilla

Dissertations and Theses (Open Access)

Surgical resection is the only potentially curative treatment for pancreatic cancer, but only 15-20% of patients have resectable tumors. In unresectable cases, stereotactic body radiotherapy (SBRT) may be used to give tumor-directed radiotherapy (RT). Unfortunately, this can cause severe gastrointestinal (GI) toxicity due to proximity of the pancreatic head to the duodenum. Protecting the intestine from the toxic side-effects of radiation may enable dose-escalation that could achieve more effective local control of disease. We and others have previously shown that a fast of 24 hours protects mice from lethal doses of the DNA-damaging agent etoposide. In this study, we demonstrate …

Association Of Office And Ambulatory Blood Pressure With Mortality And Cardiovascular Outcomes, Wen-Yi Yang, Jesus D. Melgarejo, Lutgarde Thijs, Zhen-Yu Zhang, José Boggia, Fang-Fei Wei, Tine W. Hansen, Kei Asayama, Gladys E. Maestre, Takayoshi Ohkubo

School of Medicine Publications

Importance Blood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes.

Objective To evaluate the association of BP indexes with death and a composite CV event.

Design, Setting, and Participants Longitudinal population-based cohort study of 11 135 adults from Europe, Asia, and South America with baseline observations collected from May 1988 to May 2010 (last follow-ups, August 2006-October 2016).

Exposures Blood pressure measured by an observer or an automated office machine; measured for 24 hours, during the day or …

Early Life Child Micronutrient Status, Maternal Reasoning, And A Nurturing Household Environment Have Persistent Influences On Child Cognitive Development At Age 5 Years: Results From Mal-Ed, Benjamin J J. Mccormick, Stephanie A. Richard, Laura E. Caulfield, Laura L. Pendergast, Jessica C. Seidman, Beena Koshy, Reeba Roshan, Rita Shrestha, Erling Svensen, Muneera Rasheed

Department of Paediatrics and Child Health

Background: Child cognitive development is influenced by early-life insults and protective factors. To what extent these factors have a long-term legacy on child development and hence fulfillment of cognitive potential is unknown.
Objective: The aim of this study was to examine the relation between early-life factors (birth to 2 y) and cognitive development at 5 y.
Methods: Observational follow-up visits were made of children at 5 y, previously enrolled in the community-based MAL-ED longitudinal cohort. The burden of enteropathogens, prevalence of illness, complementary diet intake, micronutrient status, and household and maternal factors from birth to 2 y were extensively measured …

Intralesional Corticosteroids For Long-Term Control Of Primary Cutaneous Marginal Zone Lymphoma Without Systemic Involvement, Pragya Tiwari, John Hall, Anand Rajpara, Carol Stanford, Daniel Aires

Marshall Journal of Medicine

Primary cutaneous marginal zone lymphoma (PCMZL) is a B cell lymphoma with a very low metastatic rate. Radiographic monitoring for internal involvement may be indicated initially. Favored treatments include radiation and excision. Radiation has high risk of local recurrence. Excision carries risk of infection and scarring. We report successful long-term treatment of recurrent PCMZL via intralesional steroid injections into new lesions as they arose. This was preferred by the patient over her prior radiation and surgical treatments. Intralesional steroids have the advantages of being simple and well tolerated, without exposure to ionizing radiation, or to the infection and scarring associated …

Group A Streptococcus Brain Abscess In A Patient On Adalimumab Therapy, Ryan Carroll, Ahmad Abu-Hashyeh, James Gainer, Kara Willenburg, Charles Meadows

Marshall Journal of Medicine

Brain abscesses represent a group of dangerous infections typically caused by a number of classic organisms. Group A Streptococcus is a rare cause of brain abscesses and those patients that do have this particular condition will typically have a distal source of infection. We present a case of patient with a biopsy confirmed Group A Streptococcal without a distal source of infection. His only identifiable risk factor was his adalimumab therapy for ankylosing spondylitis. While adalimumab has not been linked to Streptococcal infection in the past, it has been associated with multiple atypical infections and some of the consequences of …

Plasticity In The Human Gut Microbiome Defies Evolutionary Constraints, Andres Gomez, Ashok Kumar Sharma, Elizabeth K. Mallott, Klara J. Petrzelkova, Carolyn A. Jost Robinson, Carl J. Yeoman, Franck Carbonero, Barbora Pafco, Jessica M. Rothman, Alexander Ulanov, Klara Vickova, Katherine R. Amato, Stephanie L. Schnorr, Nathaniel J. Dominy, David Modry, Angelique Todd, Manolito Torralba, Karen E. Nelson, Michael B. Burns, Ran Blekhman, Melissa Remis, Rebecca M. Stumpf, Brenda A. Wilson, H. Rex Gaskins, Paul A. Garber, Bryan A. White, Steven R. Leigh

Anthropology Faculty Research

The gut microbiome of primates, including humans, is reported to closely follow host evolutionary history, with gut microbiome composition being specific to the genetic background of its primate host. However, the comparative models used to date have mainly included a limited set of closely related primates. To further understand the forces that shape the primate gut microbiome, with reference to human populations, we expanded the comparative analysis of variation among gut microbiome compositions and their primate hosts, including 9 different primate species and 4 human groups characterized by a diverse set of subsistence patterns (n = 448 samples). The results …

Beyond Sequencing: Re-Visiting Annotations For Pjl As A Test Case, Waqasuddin Khan, Aisha Ghani, Muhammad Bilal Azmi, Safina Abdul Razzak

Department of Paediatrics and Child Health

Objectives: Current developments in sequencing techniques have enabled rapid and high-throughput generation of sequence data. however, there is a growing gap between the generation of raw sequencing data and the extraction of meaningful biological information. variant annotation is a crucial step in the analysis of genome sequencing data. incorrect or incomplete annotations can cause researchers to dilute interesting variants in a pool of false positives. we require consistent, accurate and reliable annotation of variants for making diagnostic and treatment decisions. current annotation depends on the set of transcripts, and software used can be managed, with sufficient care, in the research …

Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang, Jack Jhamandas

Pharmacy Faculty Articles and Research

Recent evidence supports involvement of amylin and the amylin receptor in the pathogenesis of Alzheimer’s disease (AD). We have previously shown that amylin receptor antagonist, AC253, improves spatial memory in AD mouse models. Herein, we generated and screened a peptide library and identified two short sequence amylin peptides (12–14 aa) that are proteolytically stable, brain penetrant when administered intraperitoneally, neuroprotective against Aβ toxicity and restore diminished levels of hippocampal long term potentiation in AD mice. Systemic administration of the peptides for five weeks in aged 5XFAD mice improved spatial memory, reduced amyloid plaque burden, and neuroinflammation. The common residue SQELHRLQTY …

Fetal Fibronectin Testing For Reducing The Risk Of Preterm Birth., Vincenzo Berghella, Gabriele Saccone

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Fetal fibronectin (FFN) is an extracellular matrix glycoprotein localized at the maternal-fetal interface of the amniotic membranes, between chorion and decidua, where it is concentrated in this area between decidua and trophoblast. In normal conditions, FFN is found at very low levels in cervicovaginal secretions. Levels greater than or equal to 50 ng/mL at or after 22 weeks have been associated with an increased risk of spontaneous preterm birth. In fact, FFN is one of the best predictors of preterm birth in all populations studied so far, and can help in selecting which women are at significant risk for …

Comparison Of The Use Of Wireless Capsule Endoscopy With Magnetic Resonance Enterography In Children With Inflammatory Bowel Disease., Nadia Mazen Hijaz, Thomas M. Attard, Jennifer Colombo, Neil J. Mardis, Craig A. Friesen

Manuscripts, Articles, Book Chapters and Other Papers

Background: Magnetic resonance enterography (MRE) and wireless capsule endoscopy (WCE) are equally accepted modalities for noninvasive screening of small bowel involvement (SBI) in children with Crohn's disease (CD) and indeterminate colitis (IC) albeit there is a paucity of data comparing the two and thereby guiding the clinician in selecting the ideal diagnostic approach. Therefore, the goal of this study is to provide additional evidence for capsule endoscopy role in the evaluation of established Crohn's disease exacerbation compared to MRE in relation to Pediatric Crohn's Disease Activity Index (PCDAI), and histological indices.

Aim: To prospectively compare the findings of MRE and …

Functionalization Of Cd36 Cardiovascular Disease And Expression Associated Variants By Interdisciplinary High Throughput Analysis., Namrata Madan, Andrew R. Ghazi, Xianguo Kong, Edward S. Chen, Chad A. Shaw, Leonard C. Edelstein

Department of Medicine Faculty Papers

CD36 is a platelet membrane glycoprotein whose engagement with oxidized low-density lipoprotein (oxLDL) results in platelet activation. The CD36 gene has been associated with platelet count, platelet volume, as well as lipid levels and CVD risk by genome-wide association studies. Platelet CD36 expression levels have been shown to be associated with both the platelet oxLDL response and an elevated risk of thrombo-embolism. Several genomic variants have been identified as associated with platelet CD36 levels, however none have been conclusively demonstrated to be causative. We screened 81 expression quantitative trait loci (eQTL) single nucleotide polymorphisms (SNPs) associated with platelet CD36 expression …

Bilateral And Unilateral Resistance Training And Athletic Performance, Brendyn B. Appleby

Theses: Doctorates and Masters

Specificity is a key programming principle for optimal transfer of physiological adaptation of training to improved athletic performance. In resistance training, it has long been identified that the closer the mechanical specificity between the training exercise and outcome performance, the greater the transfer of improved capacity. Bilateral resistance exercises are predominately prescribed for the development of maximum strength and are well demonstrated to enhance athletic performance. However, unilateral exercises appear to demonstrate greater specificity to movements such as running and change of direction as these movements are predominantly single leg actions. Nonetheless, the unstable nature and comparatively lower magnitude of …

Prognostic Significance Of Tumor-Associated Macrophage Content In Head And Neck Squamous Cell Carcinoma: A Meta-Analysis., Ayan Tyagi Kumar, Alexander Knops, Brian Swendseid, Md, Ubaldo E. Martinez-Outshoorn, Larry Harshyne, Nancy Philp, Ulrich Rodeck, Adam Luginbuhl, David Cognetti, Jennifer Johnson, Joseph Curry

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Background: Head and neck squamous cell carcinoma (HNSCC) exists within a microenvironment rich in immune cells. Macrophages are particularly abundant in and around tumor tissue, and have been implicated in the growth, malignancy, and persistence of HNSCC (1). However, current literature reports variable degrees of association between the density of tumor-associated macrophages (TAMs) and clinicopathologic markers of disease (2, 3). These inconsistent findings may be a result of differences in approach to TAM detection. Authors have measured total TAMs in tumor tissue, while others have stained tumor samples for individual subtypes of TAMs, which include pro-inflammatory (M1-like) and immunosuppressive (M2-like). …

Study Of Environmental Enteropathy And Malnutrition (Seem) In Pakistan: Protocols For Biopsy Based Biomarker Discovery And Validation, Najeeha Talat Iqbal, Sana Saeed, Kamran Sadiq, Marium N. Khan, Junaid Iqbal, Jennie Z. Ma, Fayaz Umrani, Sheraz Ahmed, Elizabeth A. Maier, Lee A. Denson, Shahida Qureshi, Syed Asad Ali

Department of Paediatrics and Child Health

Background:
Environmental Enteropathy (EE), characterized by alterations in intestinal structure, function, and immune activation, is believed to be an important contributor to childhood undernutrition and its associated morbidities, including stunting. Half of all global deaths in children < 5 years are attributable to under-nutrition, making the study of EE an area of critical priority.
Methods:
Community based intervention study, divided into two sub-studies, 1) Longitudinal analyses and 2) Biopsy studies for identification of EE features via omics analyses. Birth cohorts in Matiari, Pakistan established: moderately or severely malnourished (weight for height Z score (WHZ) < − 2) children, and well-nourished (WHZ > 0) children. Blood, urine, and fecal samples, for evaluation of potential biomarkers, will be collected at various time points from all participants (longitudinal …

Physician Practices For Withdrawal Of Medications In Inactive Systemic Juvenile Arthritis, Childhood Arthritis And Rheumatology Research Alliance (Carra) Survey., Susan Shenoi, Kabita Nanda, Grant S. Schulert, John F. Bohnsack, Ashley M. Cooper, Bridget Edghill, Miriah C. Gillispie-Taylor, Baruch Goldberg, Olha Halyabar, Thomas G. Mason, Tova Ronis, Rayfel Schneider, Richard K. Vehe, Karen Onel, Childhood Arthritis And Rheumatology Research Alliance Systemic Juvenile Idiopathic Arthritis Workgroup

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: We describe a Childhood Arthritis and Rheumatology Research Alliance (CARRA) survey of North American pediatric rheumatologists that assesses physician attitudes on withdrawal of medications in systemic juvenile idiopathic arthritis (SJIA).

METHODS: A REDCap anonymous electronic survey was distributed to 100 random CARRA JIA workgroup physician-voting members. The survey had three broad sections including: A) demographic information; B) physicians' opinions on clinical inactive disease (CID) in SJIA and C) existing practices for withdrawing medications in SJIA.

RESULTS: The survey had an 86% response rate. 88 and 93% of participants agreed with the current criteria for CID and clinical remission on …

The Bone Extracellular Matrix As An Ideal Milieu For Cancer Cell Metastases., Alexus D. Kolb, Karen M. Bussard

Department of Cancer Biology Faculty Papers

Bone is a preferential site for cancer metastases, including multiple myeloma, prostate, and breast cancers.The composition of bone, especially the extracellular matrix (ECM), make it an attractive site for cancer cell colonization and survival. The bone ECM is composed of living cells embedded within a matrix composed of both organic and inorganic components. Among the organic components, type I collagen provides the tensile strength of bone. Inorganic components, including hydroxyapatite crystals, are an integral component of bone and provide bone with its rigidity. Under normal circumstances, two of the main cell types in bone, the osteoblasts and osteoclasts, help to …

White Matter Hyperintensity Regression: Comparison Of Brain Atrophy And Cognitive Profiles With Progression And Stable Groups, Omar M. Al-Janabi, Christopher E. Bauer, Larry B. Goldstein, Richard R. Murphy, Ahmed A. Bahrani, Charles D. Smith, Donna M. Wilcock, Brian T. Gold, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

Subcortical white matter hyperintensities (WMHs) in the aging population frequently represent vascular injury that may lead to cognitive impairment. WMH progression is well described, but the factors underlying WMH regression remain poorly understood. A sample of 351 participants from the Alzheimer’s Disease Neuroimaging Initiative 2 (ADNI2) was explored who had WMH volumetric quantification, structural brain measures, and cognitive measures (memory and executive function) at baseline and after approximately 2 years. Selected participants were categorized into three groups based on WMH change over time, including those that demonstrated regression (n = 96; 25.5%), stability (n = 72; 19.1%), and …

Mdivi-1, A Mitochondrial Fission Inhibitor, Modulates T Helper Cells And Suppresses The Development Of Experimental Autoimmune Encephalomyelitis., Yan-Hua Li, Fang Xu, Rodolfo Thome, Min-Fang Guo, Man-Luan Sun, Guo-Bin Song, Rui-Lan Li, Zhi Chai, Bogoljub Ciric, A. M. Rostami, Mark T. Curtis, Cun-Gen Ma, Guang-Xian Zhang

Department of Neurology Faculty Papers

BACKGROUND: Unrestrained activation of Th1 and Th17 cells is associated with the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). While inactivation of dynamin-related protein 1 (Drp1), a GTPase that regulates mitochondrial fission, can reduce EAE severity by protecting myelin from demyelination, its effect on immune responses in EAE has not yet been studied.

METHODS: We investigated the effect of Mdivi-1, a small molecule inhibitor of Drp1, on EAE. Clinical scores, inflammation, demyelination and Drp1 activation in the central nervous system (CNS), and T cell responses in both CNS and periphery were determined.

RESULTS: Mdivi-1 effectively …

Cc Chemokine Ccl1 Receptor Ccr8 Mediates Conversion Of Mesenchymal Stem Cells To Embryoid Bodies Expressing Foxp3+Ccr8+ Regulatory T Cells, Nasreen Haque, Tuteja Akaash, Niloufar Haque

Publications and Research

Embryoid bodies (EBs) are three dimensional aggregates of pluripotent stem cells primarily used to investigate morphogenesis and cell toxicity, are also attractive tools in regenerative medicine. While embryonic stem cells (ESCs) and induced pluripotent cells (IPSCs) have been shown to form EBs in mouse, primate and humans, EB formation have not been previously demonstrated in mesenchymal stem cells (MSCs). Here we show that rat MSCs form EBs; which express regulatory T cell (Treg) marker Foxp3 and CC chemokine CCL1 receptor CCR8. We show a novel method for formation of EBs from MSCs under stress and demonstrate that the induction of …

Bitter Taste Receptors For Asthma Therapeutics., Ajay P. Nayak, Sushrut D. Shah, James V. Michael, Deepak A. Deshpande

Center for Translational Medicine Faculty Papers

Clinical management of asthma and chronic obstructive pulmonary disease (COPD) has primarily relied on the use of beta 2 adrenergic receptor agonists (bronchodilators) and corticosteroids, and more recently, monoclonal antibody therapies (biologics) targeting specific cytokines and their functions. Although these approaches provide relief from exacerbations, questions remain on their long-term efficacy and safety. Furthermore, current therapeutics do not address progressive airway remodeling (AR), a key pathological feature of severe obstructive lung disease. Strikingly, agonists of the bitter taste receptors (TAS2Rs) deliver robust bronchodilation, curtail allergen-induced inflammatory responses in the airways and regulate airway smooth muscle (ASM) cell proliferation and mitigate …

The Society For Immunotherapy Of Cancer Consensus Statement On Immunotherapy For The Treatment Of Squamous Cell Carcinoma Of The Head And Neck (Hnscc)., Ezra E W Cohen, Richard Bryan Bell, Carlo Bifulco, Barbara Burtness, Maura L Gillison, Kevin J Harrington, Quynh-Thu Le, Nancy Y Lee, Rom Leidner, Rebecca L Lewis, Lisa Licitra, Hisham Mehanna, Loren K Mell, Adam Raben, Andrew G Sikora, Ravindra Uppaluri, Fernanda Whitworth, Dan P Zandberg, Robert L Ferris

Articles, Abstracts, and Reports

Head and neck cancers, including those of the lip and oral cavity, nasal cavity, paranasal sinuses, oropharynx, larynx and nasopharynx represent nearly 700,000 new cases and 380,000 deaths worldwide per annum, and account for over 10,000 annual deaths in the United States alone. Improvement in outcomes are needed for patients with recurrent and or metastatic squamous cell carcinoma of the head and neck (HNSCC). In 2016, the US Food and Drug Administration (FDA) granted the first immunotherapeutic approvals - the anti-PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab - for the treatment of patients with recurrent squamous cell carcinoma of the …

Patient Registries In Idiopathic Pulmonary Fibrosis., Daniel A. Culver, Jürgen Behr, John A. Belperio, Tamera J. Corte, Joao A. De Andrade, Kevin R. Flaherty, Mridu Gulati, Tristan J. Huie, Lisa H. Lancaster, Jesse Roman, Christopher J. Ryerson, Hyun J. Kim

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

Over the past decade, several large registries of patients with idiopathic pulmonary fibrosis (IPF) have been established. These registries are collecting a wealth of longitudinal data on thousands of patients with this rare disease. The data collected in these registries will be complementary to data collected in clinical trials because the patient populations studied in registries have a broader spectrum of disease severity and comorbidities and can be followed for a longer period of time. Maintaining the quality and completeness of registry databases presents administrative and resourcing challenges, but it is important to ensuring the robustness of the analyses. Data …

Spg7 Targets The M-Aaa Protease Complex To Process Mcu For Uniporter Assembly, Ca2 Influx, And Regulation Of Mitochondrial Permeability Transition Pore Opening, Stephen Hurst, Ariele Baggett, György Csordás, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

The mitochondrial matrix ATPase associated with diverse cellular activities (m-AAA) protease spastic paraplegia 7 (SPG7) has been recently implicated as either a negative or positive regulatory component of the mitochondrial permeability transition pore (mPTP) by two research groups. To address this controversy, we investigated possible mechanisms that explain the discrepancies between these two studies. We found that loss of the SPG7 gene increased resistance to Ca²-induced mPTP opening. However, this occurs independently of cyclophilin D (cyclosporine A insensitive) rather it is through decreased mitochondrial Ca² concentrations and subsequent adaptations mediated by impaired formation of functional mitochondrial Ca …

Tumor-Released Autophagosomes Induces Cd4, Yong-Qiang Chen, Peng-Cheng Li, Ning Pan, Rong Gao, Zhi-Fa Wen, Tian-Yu Zhang, Fang Huang, Fang-Yuan Wu, Xi-Long Ou, Jin-Ping Zhang, Xue-Jun Zhu, Hong-Ming Hu, Kang Chen, Yun-Lang Cai, Li-Xin Wang

Articles, Abstracts, and Reports

BACKGROUND: CD4

METHODS: TRAPs isolated from tumor cell lines and pleural effusions or ascites of cancer patients were incubated with CD4

RESULTS: Heat shock protein 90α (HSP90α) on the surface of TRAPs from malignant effusions of cancer patients and tumor cell lines stimulated CD4

CONCLUSIONS: HSP90α on the surface of TRAPs programs the immunosuppressive functions of CD4