Medical Specialties Commons^™

Na/K-Atpase Mimetic Pnaktide Peptide Inhibits The Growth Of Human Cancer Cells, Zhichuan Li, Zhongbing Zhang, Joe X. Xie, Xin Li, Jiang Tian, Ting Cai, Hongaun Cui, Hanfei Ding, Joseph I. Shapiro Md, Zijian Xie

Biochemistry and Microbiology

Cells contain a large pool of non-pumping Na/K-ATPase that participates in signal transduction. Here, we show that the expression of α1 Na/K-ATPase is significantly reduced in human prostate carcinoma as well as in several human cancer cell lines. This down-regulation impairs the ability of Na/K-ATPase to regulate Src-related signaling processes. Supplement of pNaKtide, a peptide derived from α1 Na/K-ATPase, reduces activities of Src and Src effectors. Consequently, these treatments stimulate apoptosis and inhibit growth in cultures of human cancer cells. Moreover, administration of pNaKtide inhibits angiogenesis and growth of tumor xenograft. Thus, the new findings demonstrate the in vivo effectiveness …

Standing In The Gap: The Primary Care Physician And Alzheimer’S Disease, Shirley M. Neitch

Internal Medicine

There is a huge volume of information recently published about Alzheimer’s disease, but most of it is not targeted to the average busy primary care physician, even though these PCPs are providing the bulk of care to patients with dementia. This paper is a succinct clinical review of the current state of diagnosis and treatment of Alzheimer’s disease, including citations of resources for physicians and caregivers.

Driving Assessment Results In Patients With A Diagnosis Of Dementia, Shirley M. Neitch, Guillermo Madero, Shawn Maynard

Internal Medicine

Primary care physicians are frequently involved in cases in which they must decide if a patient with dementia should stop driving. The decision is complex, and there are no firm clinical guidelines available. We examined the results of a number of patients who have undergone assessment in our Driving Assessment Clinic, to determine if any of our findings correlated with the diagnosis of dementia. If any associations exist, recommendations may be possible to assist PCPs in making the decision to have patients stop driving, even if full formal testing cannot be done.

The Implications Of Chronic Pain Models For Rehabilitation Of Distal Radius Fracture, Saurabh Mehta, Joy Macdermid, Mary Tremblay

Physical Therapy Faculty Research

Distal radius fracture (DRF) is the most common fracture and usually occurs as a result of a fall. Most patients recover following DRF with minimal residual pain or disability; however, a small subset of patients continue to experience pain and disability even one year after the injury. Currently, there are no practice guidelines for early identification and treatment of patients who are potentially at greater risk of developing these adverse outcomes. As a result, hand therapy management of patients following DRF does not incorporate screening of these at-risk patients. The objective of this paper is to apply constructs from learned …

Dietary Interventions Against Mammary Glands And Prostate Cancers, Juliana Adedayo Akinsete

Theses, Dissertations and Capstones

Dietary components modulate normal cellular functions and, in cancer cells, alter processes that lead to cancer and/or its progression. The change in the patterns of human food production and consumption over time has contributed to increasing risk for diseases including cancer. Omega-3 and omega-6 fatty acids are classes of essential polyunsaturated fatty acids in the human diet and are required for normal growth and development. Omega-3 and omega-6 fats are thought to be required in the ratio of 1:1 to 1:4 on which humans are thought to have evolved. However, the Western diet has greatly shifted from this ratio. The …

Pitx2 Is Overexpressed In Follicular Cell-Derived Thyroid Cancer And Promotes Thyroid Cancer Proliferation By Regulating Cell Cycle, Yue Huang

Theses, Dissertations and Capstones

Thyroid cancer is the most prevailing malignancy of the endocrine system. Its incidence is rapidly rising at the second fastest rate of all malignancies in the United States, making it a significant health problem. Although the majority of thyroid cancer is slowly-growing and well-differentiated, available treatment options are very limited, and most of them require complete removal of the thyroid gland and surrounding tissues. Patients who have undergone thyroid removal have to take life-long hormone replacement therapy, which is very inconvenient and costly. Therefore, there is an urgent need to develop new treatments for this disease. As a prerequisite for …

Cancer Cachexia And Cardiac Atrophy In The Apcmin/+ Mice Model Of Colon Cancer, Nandini Durga Prasanna Kumar Manne

Theses, Dissertations and Capstones

Cancer cachexia is a muscle wasting condition that occurs in response to a malignant growth in the body. Cachexia is associated with heart failure and is estimated to be the immediate cause of death in about a third of all cancer patients. The purpose of this study was to investigate cardiac atrophy in the APCmin/+ mouse model of colorectal cancer. Compared to age matched C57BL/6 (BL6) mice, APCmin/+ body mass and heart mass were lower at 12 (11.1 Ѡ4.5% and 7.6 Ѡ2.8%, respectively) and 20-weeks (26.1 Ѡ2.5% and 6.0 Ѡ3.8%, respectively) of age (P < 0.05). Immunoblot analysis revealed that these changes in mass were accompanied by increased activation of protein kinase B (Akt Thr 473: 74.4 Ѡ10.9% and 216.0 Ѡ19.6% ; Akt Ser 308: 161.6 Ѡ31.7% and 367.4 Ѡ41.6% at 12- and 20-weeks, respectively, (P < 0.05)), mammalian target of rapamycin (mTOR Ser2448: 23.2 Ѡ13.2% and 44.0 Ѡ16.4% at 12- and 20-weeks, respectively, (P < 0.05)), 5' adenosine monophosphate-activated protein kinase (AMPK: 19.6 Ѡ5.2% and 22.5 Ѡ5.5% at 12- and 20-weeks, respectively, (P < 0.05)) and elevated levels of the autophagy regulator beclin1 (4.7 Ѡ3.3% and 9.5 Ѡ3.0% at 12- and 20-weeks, respectively, (P < 0.05)). No evidence of increased cardiac apoptosis, protein ubiquitination or activation of cardiac caspases or calpains was noted. Taken together, these data suggest that the cardiac atrophy that occurs in the 12- and 20-week old APCmin/+ mouse is relatively modest compared to that seen with other tumor models [1] and is associated with evidence of increased cardiac autophagy.

Predictors Of Postoperative Respiratory Failure In Patients Receiving Anesthesia, Marty Henley

Theses, Dissertations and Capstones

Introduction: Postoperative Respiratory failure has been identified as a prevention quality indicator by The Agency for Health Research and Quality (AHRQ). Postoperative Respiratory Failure is associated with increased length of stay, increased costs and increased morbidity and mortality. Unfortunately, current research is limited regarding scoring methods which are predictive for postoperative respiratory failure. This retrospective case control study was conducted to determine if the various tools of evaluation of risk currently available and to determine if any are predictive of the risk of developing postoperative respiratory failure.

Methodology: The design of this research was a retrospective case control study conducted …

Identification Of Genes Involved In Hematopoietic Stem Cell Differentiation And Leukemia Differentiation And Leukemia, Jasjeet Bhullar

Theses, Dissertations and Capstones

Hematopoiesis is maintained by a proper balance between self renewal and multipotent differentiation of the hematopoietic stem cells (HSC). Acute myelogenous leukemia (AML) is characterized by the blockage in the differentiation of HSC, while self renewal and proliferation is preserved. It is important to understand the mechanisms involved in the inhibition of hematopoietic differentiation and maintenance of the HSC state in order to develop better therapies for AML. In these studies I have explored the role of Hsp90, omega-3 fatty acids and YB-1 in hematopoietic differentiation. EML, a hematopoietic precursor cell line, was used as a model for the hematopoietic …

Residency Corner, Tamara Gravano

Physical Therapy Faculty Research

The new Residency Corner will feature articles written by residents that describe topics such as in-depth case analysis, problem solving, and practice as nonphysician primary care providers. Here residents will get to discuss their findings and thought-processes with an audience of their peers--those clinicians and academics interested in the advancement of geriatric health care. Also, for those who may be interested to see what geriatric residency education is really all about, these clinical snapshots can help remove the veil and provide a glimpse into the level of practice our residents are experiencing. Yet, this is only one half of the …

Systematic Review Of Home Physiotherapy After Hip Fracture Surgery, Saurabh Mehta, Jean-Sébastien Roy

Physical Therapy Faculty Research

OBJECTIVE: To compare the benefits of home physiotherapy, institution-based physiotherapy and no physiotherapy following hip fracture surgery.

DESIGN: Systematic review and meta-analysis of randomized controlled trials.

METHODS: Two reviewers independently extracted data from 5 included studies. Standardized mean differences were pooled for health-related quality of life and performance-based outcomes. Review Manager Version 5 was used for data analysis.

RESULTS: Analysis of the 5 included studies indicated that home physiotherapy was better than no physiotherapy and similar to outpatient physiotherapy in improving patient-reported health-related quality of life. Performance-based outcomes were marginally better following outpatient physiotherapy compared with home physiotherapy 3 and …

Physician’S Ability To Manually Detect Isolated Elevation In Leg Intracompartmental Pressure., Franklin D. Shuler Md, Matthew J. Dietz

Orthopaedics

Background: Serial physical examination is recommended for patients for whom there is a high index of suspicion for compartment syndrome. This examination is more difficult when performed on an obtunded patient and relies on the sensitivity of manual palpation to detect compartment firmness—a direct manifestation of increased intracompartmental pressure. This study was performed to establish the sensitivity of manual palpation for detecting critical pressure elevations in the leg compartments most frequently involved in clinical compartment syndrome.

Methods: Reproducible, sustained elevation of intracompartmental pressure was established in fresh cadaver leg specimens. Pressures tested included 20 and 40 mm Hg (negative controls) …

Cast-Saw Burns: Evaluation Of Skin, Cast, And Blade Temperatures Generated During Cast Removal, Franklin D. Shuler Md, Frank N. Grisafi

Orthopaedics

Background: The use of an oscillating saw for cast removal creates a potential for iatrogenic injury and patient discomfort. Burns and abrasions can occur from the heat created by frictional forces and direct blade contact. With use of a cadaver model system, skin temperature measurements were recorded during cast removal with an oscillating saw.

Methods: Casts of uniform thickness were applied to cadavers equilibrated to body temperature. The casts were removed by a single individual while simultaneously measuring temperatures at the skin-padding interface, cast-padding interface, and the blade. Variables tested include two removal techniques, two casting materials (fiberglass and plaster), …

The Development Of Attribute Dominance In The Knowledge Base, Marc A. Lindberg Ph.D.

Psychology Faculty Research

Two cuing, free-recall studies were conducted to test Bach and Underwood's (1970) hypothesis that acoustic encoding is dominant among second graders and semantic encoding is dominant among sixth graders. When retrieval cues were presented with to-be-remembered items at both input and output (Experiment 1), and when cues were presented only at output (Experiment 2), semantic cues were more efficient in elevating recall than were acoustic cues for both second and sixth graders. When these and other results generally found using recognition, sorting, incidental learning, and free-recall experimental designs are compared, it seems plausible that item presentation and memory-testing formats interact …

Inhibition Of Proliferation And Induction Of Apoptosis In Multiple Myeloma Cell Lines By Cd137 Ligand Signaling, Charles A. Gullo Phd, Liang Kai Koh, Wan Lu Pang, Kian Tong Ho, Shi Hao Tan, Herbert Schwarz

Biochemistry and Microbiology

Background

Multiple myeloma (MM) is a malignancy of terminally-differentiated plasma cells, and the second most prevalent blood cancer. At present there is no cure for MM, and the average prognosis is only three to five years. Current treatments such as chemotherapy are able to prolong a patient's life but rarely prevent relapse of the disease. Even hematopoietic stem cell transplants and novel drug combinations are often not curative, underscoring the need for a continued search for novel therapeutics. CD137 and its ligand are members of the Tumor Necrosis Factor (TNF) receptor and TNF superfamilies, respectively. Since CD137 ligand cross-linking enhances …

Capsaicin Displays Anti-Proliferative Activity Against Human Small Cell Lung Cancer In Cell Culture And Nude Mice Models Via The E2f Pathway, Kathleen C. Brown, Theodore R. Witte, W. Elaine Hardman, Haitao Luo, Yi C. Chen, A. Betts Carpenter, Jamie K. Lau, Piyali Dasgupta

Biochemistry and Microbiology

Background: Small cell lung cancer (SCLC) is characterized by rapid progression and low survival rates. Therefore, novel therapeutic agents are urgently needed for this disease. Capsaicin, the active ingredient of chilli peppers, displays antiproliferative activity in prostate and epidermoid cancer in vitro. However, the anti-proliferative activity of capsaicin has not been studied in human SCLCs. The present manuscript fills this void of knowledge and explores the anti-proliferative effect of capsaicin in SCLC in vitro and in vivo.

Methodology/Principal Findings: BrdU assays and PCNA ELISAs showed that capsaicin displays robust anti-proliferative activity in four human SCLC cell lines. Furthermore, capsaicin potently …

Rbc And Wbc Fatty Acid Composition Following Consumption Of An Omega 3 Supplement: Lessons For Future Clinical Trials, Theodore R. Witte, Alexander J. Salazar, Oscar F. Ballester, W. Elaine Hardman

Biochemistry and Microbiology

Background: Results from increasing numbers of in vitro and in vivo studies have demonstrated that omega 3 fatty acids incorporated in cell culture media or in the diet of the animals can suppress the growth of cancers. When human clinical trials are initiated to determine the ability of omega 3 fatty acids to alter growth or response to chemotherapeutic interventions of cancers, it will be essential to determine the omega 3 intake of individuals in the trial to determine compliance with consumption of the supplement and to correlate with endpoints of efficacy. We wondered if the fatty acid composition of …

Treatment Strategies In Acute Myelogenous Leukemia : Investigating Hsp90 And P53 As Targets, Jennifer M. Napper

Theses, Dissertations and Capstones

Acute myelogenous leukemia (AML) is the deadliest of the lymphatic and bone marrow cancers. Patients diagnosed with AML have a five year survival rate of 23.4%. AML is characterized by an accumulation of undifferentiated and functionless myeloid precursors in the bone marrow and blood. Heat shock protein 90 (Hsp90) inhibitors, such as 17-AAG, an analog of geldanamycin (GM), are currently undergoing phase I, and II and III clinical trials for various cancers with mixed results. I found distinct responses to 17-AAG treatment among the AML cell lines tested. I also discovered two mutant TP53 alleles in Kasumi-3 cells, an AML …

Genetic And Environmental Factors Suggest That Dietary Fatty Acid Content, Lipid Metabolism, And Bone Properties Are Key Regulators Of Myeloid Progenitor Cell Frequency, Melinda E. Varney

Theses, Dissertations and Capstones

Acute myelogenous leukemia (AML) and its precursors are the result of the dysregulation of hematopoiesis. Hematopoiesis proceeds in a stepwise manner, beginning with hematopoietic stem cells, continuing to develop into various stages of progenitor cells, and finally becoming fully functional blood cells. As this process goes awry, immature, functionless cells of the myeloid lineage proliferate out of control. Discerning how myeloid progenitor frequency is regulated allows for a better understanding of how the process may lose control. Hematopoiesis has been shown to depend on genetic and environmental factors. In this work, I have added to this knowledge base by providing …

The Expression And Function Of Hypoxia Inducible Factor-1Α In Human Melanoma, Sandeep S. Joshi

Theses, Dissertations and Capstones

Hypoxia inducible factor-1α (HIF-1α) protein, a key regulator of oxygen homeostasis, is stabilized under hypoxia and degraded under normal oxygen tension. Here, the human melanoma cells were found to express an elevated amount of HIF-1α mRNA and protein relative to normal human melanocytes under normoxic conditions. The amount of HIF-1α expressed is roughly correlated with the stage of melanoma from which the cell line was established. In addition, a splice variant mRNA of HIF-1α785 is expressed at higher levels than full-length HIF-1α mRNA in the more aggressive melanoma cells. This splice variant lacks part of the oxygen regulation domain. Ectopic …

Pulmonary Embolism Presenting With Sudden Respiratory Failure In Two Previously Stable Neonates, Joseph Werthammer, Audra Pritt, Laura Reechi, Linda Brown, Mahmood Heydarian

Pediatrics

Pulmonary artery embolism (PE) is a rare and life-threatening complication in the neonate. We describe two previously stable infants who incurred respiratory failure from PE. The first case is a late preterm infant with gastroschisis with autopsy confirmation of PE presumably as a result of a central venous line (CVL) with thromboembolism. The second case is an extreme low birth weight infant with sudden onset of respiratory failure, abnormal chest x-ray, disseminated intravascular coagulation (DIC), and echocardiographic confirmation of a thrombus at the junction of the superior vena cava and right atrium (SVC/RA) at the site of a previous CVL. …

Prieurianin Causes Weight Loss In Diet-Induced Obese Mice And Inhibits Adipogenesis In Cultured Preadipocytes, Ahmed Kablan, Rudel A. Saunders, Maria Szkudlarek-Mikho, Andrew J.B. Chin, Raul M. Bosio, Kazuyuki Fujii, Joseph I. Shapiro M.D., Khew-Voon Chin

Biochemistry and Microbiology

The global increase in the incidence of obesity has emerged as one of the most serious public health risks in recent years. Despite the enormity of the obesity pandemic, there are currently only two FDA-approved therapies for its treatment and these drugs exhibit modest effi cacy and have limiting side effects. Prieurianin is a plant limonoid product that deters feeding in insect larvae. We investigated in this study the effects of prieurianin on weight loss and adipogenesis. Our results showed that prieurianin causes weight loss by reducing energy intake in obese mice on highcalorie diet. We also found that prieurianin …

Epocrates….Is It Useful At The Neonatal Bedside?, Bobby L. Miller Md

Biochemistry and Microbiology

Most physicians, including residents and medical students have heard of, and many use, a mobile drug database called Epocrates. The purpose of this review is to evaluate Epocrates as a bedside tool from the perspective of a neonatologist on a busy teaching service.

Expression And Function Of Hypoxia Inducible Factor-1 Alpha In Human Melanoma Under Non-Hypoxic Conditions, Caroline N. Mills, Sandeep S. Joshi, Richard M. Niles

Biochemistry and Microbiology

Background

Hypoxia inducible factor-1 alpha (HIF-1α) protein is rapidly degraded under normoxic conditions. When oxygen tensions fall HIF-1α protein stabilizes and transactivates genes involved in adaptation to hypoxic conditions. We have examined the normoxic expression of HIF-1α RNA and protein in normal human melanocytes and a series of human melanoma cell lines isolated from radial growth phase (RGP), vertical growth phase (VGP) and metastatic (MET) melanomas.

Results

HIF-1α mRNA and protein was increased in RGP vs melanocytes, VGP vs RGP and MET vs VGP melanoma cell lines. We also detected expression of a HIF-1α mRNA splice variant that lacks part …

Colocalization Of Increased Transforming Growth Factor-Β-Induced Protein (Tgfbip) And Clusterin In Fuchs Endothelial Corneal Dystrophy, Ula V. Jurkunas, Maya Bitar, Ian Rawe

Ophthalmology

PURPOSE: To investigate the differential expression of TGFBIp in normal human and Fuchs endothelial corneal dystrophy (FECD) endothelial cell-Descemet’s membrane (HCEC-DM) complex, and to asses the structural role of TGFBIp and clusterin (CLU) in guttae formation.

METHODS: HCEC-DM complex was dissected from stroma in normal and FECD samples. Proteins were separated by 2-D gel electrophoresis and subjected to proteomic analysis. N-terminal processing of TGFBIp was detected by Western blot analysis with two separate antibodies against the N- and C-terminal regions of TGFBIp. Expression of TGFBI mRNA was compared by using real-time PCR. Subcellular localization of TGFBIp and CLU in corneal …

Characterization Of Babies Discharged From Cabell Huntington Hospital During The Calendar Year 2005 With The Diagnoses Of Neonatal Abstinence Syndrome, F. Ross Baxter Md, Robert Nerhood Md, David Chaffin Md

Family and Community Health

Recent concern regarding the impact of maternal drug abuse on neonatal well-being was the impetus for this retrospective cohort study of newborns diagnosed with neonatal abstinence syndrome that were discharged from Cabell Huntington Hospital during the calendar year 2005. Medical records of the neonates and their mothers were analyzed for a variety of health related outcomes and healthcare cost. Forty-eight neonates were diagnosed with Neonatal Abstinence Syndrome in 2005, forty of which required NICU assistance. The average maternal age at delivery was 26; gravity was 3.1 and most were single, separated or divorced. The majority had poor or inconsistent prenatal …

The P53-Induced Siva-1 Plays A Significant Role In Cisplatin-Mediated Apoptosis, John L. Barkinge, Radhika Gudi, Hawkins Sarah, Fei Chu, Alip Borthakur, Bellur S. Prabhakar

Clinical & Translational Sciences

Background: The pro-apoptotic protein Siva-1 functions in both extrinsic and intrinsic cell death signaling; however, the exact contribution of the endogenous Siva-1 to DNA damage-induced apoptosis is unclear. Using cisplatin, a chemotherapeutic drug, to induce DNA damage and cell death, we determined the role of Siva-1.

Methods: Cisplatin treated HCT116 colorectal carcinoma cells (p53+/+ and -/-) were used in the study. With the help of recombinant lentivirus that can express siSiva (siRNA that specifi cally targets Siva-1), we also generated Siva-1 knockdown HCT116 cells. Apoptosis was determined by tetramethyl rhodamine methyl ester (TMRM) staining and propidium iodide (PI) staining.

Results: …

Helicobacter Pylori Infection Rate Decreases In Symptomatic Children: A Retrospective Analysis Of 13 Years (1993-2005) From A Gastroenterology Clinic In West Virginia, Yoram Elitsur, Yulia Dementieva, Mary Rewalt, Zanda Lawrence

Pediatrics

Background: The rate of Helicobacter pylori is decreasing in the developed countries, but few long-term studies are available from the United States. We retrospectively assessed the annual H. pylori infection rate in symptomatic children seen in our clinic over a 13-year study period.

Study: A retrospective analysis of all children who had histologic diagnosis of H. pylori infection between January 1993 and December 2005 in our pediatric gastroenterology clinic was performed. The annual infection rate and the overall infection rate were calculated.

Results: A total of 1743 upper endoscopy reports were reviewed, of which 212 (12.1%) were diagnosed with H. …

Loss Of Ski Expression In Testicular Cancer Leads To An Enhanced Invasive Phenotype Through Both Bmp-Dependent And Bmp-Independent Pathways, Amy N. Nash

Theses, Dissertations and Capstones

The proto-oncogene SKI is a transcription factor and a co-repressor of the TGFβ superfamily, including TGF

β and BMP. However, additional data suggests that SKI may function as a tumor suppressor in some cell types. The TGFβ superfamily has been implicated in cancer progression and germ cell migration. Testicular cancer afflicts men during their peak reproductive years and is the most common cancer among men of this age group. Cisplatin-based chemotherapy is the standard treatment for testicular cancer. This treatment can lead to undesirable side effects, including infertility. We have shown that SKI expression is decreased in testicular germ cell …

Testing Educational Strategies For Shaken Baby Syndrome, Todd W. Gress, Mary Bailey, Donna Bolden, Lisa Pfitzer

Internal Medicine

Shaken Baby Syndrome (SBS) occurs from the violent shaking of an infant, which may lead to brain damage or death. The goal of this study was to assess educational methods used to teach new mothers about SBS.