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Mice Deficient In Involucrin, Envoplakin, And Periplakin Have A Defective Epidermal Barrier., Lisa M Sevilla, Rachida Nachat, Karen R Groot, John F Klement, Jouni Uitto, Philippe Djian, Arto Määttä, Fiona M Watt

Department of Dermatology and Cutaneous Biology Faculty Papers

The cornified envelope is assembled from transglutaminase cross-linked proteins and lipids in the outermost epidermal layers and is essential for skin barrier function. Involucrin, envoplakin, and periplakin form the protein scaffold on which the envelope assembles. To examine their combined function, we generated mice deficient in all three genes. The triple knockouts have delayed embryonic barrier formation and postnatal hyperkeratosis (abnormal accumulation of cornified cells) resulting from impaired desquamation. Cornified envelopes form but are ultrastructurally abnormal, with reduced lipid content and decreased mechanical integrity. Expression of proteases is reduced and the protease inhibitor, serpina1b, is highly upregulated, resulting in defective …

Short-Wavelength Light Sensitivity Of Circadian, Pupillary, And Visual Awareness In Humans Lacking An Outer Retina, Farhan H. Zaidi, Joseph T. Hull, Stuart N. Peirson, Katharina Wulff, Daniel Aeschbach, Joshua J. Gooley, George C. Brainard, Kevin Gregory-Evans, Joseph F. Rizzo Iii, Charles A. Czeisler, Russell G. Foster, Merrick J. Moseley, Steven W. Lockley

Department of Neurology Faculty Papers

As the ear has dual functions for audition and balance, the eye has a dual role in detecting light for a wide range of behavioral and physiological functions separate from sight. These responses are driven primarily by stimulation of photosensitive retinal ganglion cells (pRGCs) that are most sensitive to short-wavelength ( approximately 480 nm) blue light and remain functional in the absence of rods and cones. We examined the spectral sensitivity of non-image-forming responses in two profoundly blind subjects lacking functional rods and cones (one male, 56 yr old; one female, 87 yr old). In the male subject, we found …

Oral Immunization Of Rhesus Macaques With Adenoviral Hiv Vaccines Using Enteric-Coated Capsules, George T. Mercier, Pramod N. Nehete, Marco F. Passeri, Bharti N. Nehete, Eric A. Weaver, Nancy Smyth Templeton, Kimberly Schluns, Stephanie S. Buchl, K. Buchl, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Targeted delivery of vaccine candidates to the gastrointestinal (GI) tract holds potential for mucosal immunization, particularly against mucosal pathogens like the human immunodeficiency virus (HIV). Among the different strategies for achieving targeted release in the GI tract, namely the small intestine, pH sensitive enteric coating polymers have been shown to protect solid oral dosage forms from the harsh digestive environment of the stomach and dissolve relatively rapidly in the small intestine by taking advantage of the luminal pH gradient. We developed an enteric polymethacrylate formulation for coating hydroxy-propyl-methyl-cellulose (HPMC) capsules containing lyophilized Adenoviral type 5 (Ad5) vectors expressing HIV-1 gag …

Interventional Options For Malignant Upper Gi Obstruction, 2nd Ed, James R. Ouellette, Lisa Patterson, Paula M. Termuhlen

Department of Surgery Faculty Publications

Background

Patients with unresectable cancers of the upper gastrointestinal tract often suffer severe symptoms due to pain, nausea and vomiting, weight loss, cachexia, and poor food tolerance. This can be related to gastric and duodenal cancers causing intrinsic obstruction of the intestinal lumen or pancreatic and biliary cancers causing extrinsic biliary compression. Management options vary depending on the site of obstruction, the patient’s functional status, the patient-defined goals of care, and estimated prognosis. Fast Fact #45 discussed medical management options. This Fact Fact reviews interventional approaches for upper GI obstructions, especially when further radiation, chemotherapy, medical management, or curative surgical …

Renal Cell Carcinoma Metastatic To The Duodenum: Treatment By Classic Pancreaticoduodenectomy And Review Of The Literature, Robert Adamo, Patrick J. Greaney Jr., Agnieszka Witkiewicz, Eugene P. Kennedy, Charles J. Yeo

Department of Surgery Faculty Papers

Renal cell cancer (RCC) most commonly metastasizes to the lungs, bones, liver, renal fossa, and brain, although metastases can occur elsewhere. RCC metastatic to the duodenum is especially rare, with only a small number of cases reported in the literature. Herein, we describe a case of an 86-year-old woman with a history of RCC treated by radical nephrectomy 13 years previously. The patient presented with duodenal obstruction and anemia from a solitary duodenal mass invading into the pancreas and was treated via classic pancreaticoduodenectomy. Preoperative imaging and intra-operative assessment showed no evidence of other disease. Pathology confirmed metastatic RCC without …

Prognosis Of Hospitalized New-Onset Systolic Heart Failure In Indo-Asians--A Lethal Problem, Fahim H. Jafary, Mahesh Kumar, Irfan E. Chandna

Section of Cardiology

Background: Systolic heart failure (SHF), particularly when requiring hospital admission carries a poor prognosis. There is a paucity of data in Indo-Asians on outcomes of SHF, among whom the burden of cardiovascular disease is consistently rising. The purpose of this study was to determine the frequency and predictors of mortality and morbidity amongst patients admitted with new-onset SHF at a tertiary care hospital in Pakistan.

Methods and Results: Hospital charts of 196 patients with a diagnosis of new or recent onset (!3 months) SHF (ejection fraction [EF] !40%) were reviewed. Patients who died during the admission, those with life-limiting concomitant …

Longitudinal Tracking Of Cytokines After Acute Exposure To Tuberculosis: Association Of Distinct Cytokine Patterns With Protection And Disease Development, Rabia Hussain, Najeeha Talat, Firdaus Shahid, Ghaffar Dawood

Department of Pathology and Laboratory Medicine

Household contacts (HCs) of patients with tuberculosis (TB) are at higher risk of infection as well as the development of active disease. Longitudinal tracking of antigen-specific cytokines after acute exposure may significantly advance our understanding of the dynamic changes in cytokine patterns associated with disease establishment. To achieve this objective, we carried out a prospective cohort study with healthy HCs after exposure to TB. The patterns of cytokines (gamma interferon [IFN-gamma] and interleukin 10 [IL-10]) in response to mycobacterial antigens (culture filtrate [CF] proteins) and nonspecific mitogens (phytohemagglutinin [PHA] and lipopolysaccharide [LPS]) were assessed at 0, 6, 12, and 24 …

Breast Cancer In Pakistan - Awareness And Early Detection, Saba Sohail, Shams Nadeem Alam

Department of Radiology

No abstract provided.

Perforated Appendicitis: Accuracy Of Ct Diagnosis And Correlation Of Ct Findings With The Length Of Hospital Stay, Asma Hina Siddiqui, Shaista Afzal

Department of Radiology

Objective: To determine the sensitivity and specificity of CT findings in the differentiation of perforated from nonperforated appendicitis and correlate CT diagnosis with the length of hospital stay.STUDY Design: An analytical study.PLACE AND DURATION OF STUDY: This study was conducted at Radiology Department of Aga Khan University Hospital, Karachi, from January 2004 to June 2005.PATIENTS AND Methods: The study included 70 patients who presented with right lower quadrant abdominal pain and underwent pre-operative CT scan followed by appendectomy. Patients were divided into two groups of having perforated and nonperforated appendicitis on the basis of CT scan findings. The surgical and …

Laryngeal Mask Airway Insertion Anaesthesia And Insertion Techniques, Abdul Monem, Fauzia A. Khan

Department of Anaesthesia

Laryngeal Mask Airway has gained wide acceptance for routine airway management, difficult airway and in emergency situations. The classical method of insertion was recommended by Dr Brain. Over the years various induction and insertion techniques have been described with variable results. Combination of induction agents with narcotics, with or without small dose muscle relaxants has been found to be very effective. There is less also lesser incidence of mucosal trauma with partially inflated cuff. Insertion with cuff facing laterally or backwards and rotating it forwards into position has also been described. A review of various options and their advantages and …

Glucose-6-Phosphate Dehydrogenase (G6pd) Screening In Pakistani Neonates: To Be Or Not To Be, Bushra Moiz

Department of Pathology and Laboratory Medicine

No abstract provided.

Special Article: Physical Activity, Physical Fitness, And Cardiovascular Risk Factors In Childhood, Samuel S. Gidding

Department of Pediatrics Faculty Papers

In adults, physical activity and exercise training are associated with reduced cardiovascular morbidity and mortality, a reduced likelihood of developing adverse cardiovascular risk factors, and improved insulin sensitivity. In childhood, participation in appropriate physical activity may prevent the development of cardiovascular risk factors in the future and complement treatment of existing cardiovascular risk factors, including hypertension, dyslipidemia, and overweight. Exercise in children can also significantly improve insulin sensitivity independent of weight loss. These e fects are mediated in overweight children by increases in lean body mass relative to fat mass and associated improvements in inflammatory mediators, endothelial function, and the …

How To Prevent Perioperative Myocardial Injury: The Conundrum Continues, Jian-Zhong Sun, David Maguire

Department of Anesthesiology Faculty Papers

BACKGROUND: Perioperative myocardial injury (PMI) remains a major cause of perioperative morbidity and mortality but clinical strategies to prevent PMI are still uncertain.

METHODS AND RESULTS: We comprehensively searched PubMed for major research articles concerning clinical strategies to prevent PMI. The key findings are as follows: (1) the American College of Cardiology/American Heart Association guideline update for perioperative cardiovascular evaluation for noncardiac surgery is very useful to stratify cardiac risk preoperatively; (2) cardiac troponin has emerged as a biomarker to diagnose postoperative PMI and to predict clinical outcomes; (3) coronary revascularization before noncardiac surgery probably would provide cardiac protection in …

Aoa Symposium. Orthopaedists Partnering With Other Physicians To Provide Musculoskeletal Care., Alan Hilibrand, Kurt P Spindler, Scott D Boden

Rothman Institute Faculty Papers

No abstract provided.

Modulation Of Tgf-Beta Signaling By Proinflammatory Cytokines In Articular Chondrocytes., Jorge A. Roman-Blas, David G. Stokes, Sergio A. Jimenez

Department of Medicine Faculty Papers

OBJECTIVE: The normal structure and function of articular cartilage are the result of a precisely balanced interaction between anabolic and catabolic processes. The transforming growth factor-beta (TGF-beta) family of growth factors generally exerts an anabolic or repair response; in contrast, proinflammatory cytokines such as interleukin 1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) exert a strong catabolic effect. Recent evidence has shown that IL-1beta, and TNF-alpha, and the TGF-beta signaling pathways share an antagonistic relationship. The aim of this study was to determine whether the modulation of the response of articular chondrocytes to TGF-beta by IL-1beta or TNF-alpha signaling pathways …

Cheilitis Glandularis Progressing To Squamous Cell Carcinoma In An Hiv-Infected Patient: Case Report, F. M. A. Butt, M. L. Chindia, F. S. Rana, A. Ashani

Pathology, East Africa

Cheilitis glandularis (CG), is a rare inflammatory minor salivary gland disease affecting the lower lip.The hallmarks of which include progressive enlargement and eversion of the lower labial mucosa resulting in the obliteration of the mucosal vermillion interface. A case is presented of a 47-year-old HIV-infected woman who initially manifested clinical features of CG with a typical histopathology picture of a non-specific sialadenitis while a second biopsy performed six months later revealed well differentiated squamous cell carcinoma (SCC). She is symptom free one year following excision and radiotherapy treatment.

Targeted Therapies In The Management Of Metastatic Bladder Cancer., Matteo Fassan, Edouard J. Trabulsi, Leonard G Gomella, Raffaele Baffa

Department of Urology Faculty Papers

The management of metastatic urothelial carcinoma (UC) of the bladder is a common and complex clinical challenge. Despite the fact that UC is one of the most frequent tumors in the population, long term survival for metastatic disease remains low, and chemotherapy is curative for only a small minority of patients. UC is genetically heterogeneous, and it is surrounded by a complex tissue microenvironment. The problems of clinical practice in the field of metastatic bladder cancer have begun to stimulate translational research. Advances in the understanding of the molecular biology of urothelial cancer continue to contribute to the identification of …

Comparison Of Eight Prosthetic Aortic Valves In A Cadaver Model., Benjamin A. Youdelman, Hitoshi Hirose, Harsh Jain, J Yasha Kresh, John W.C. Entwistle, Andrew S. Wechsler

Department of Surgery Faculty Papers

OBJECTIVES: Proper valve selection is critical to ensure appropriate valve replacement for patients, because implantation of a small valve might place the patient at risk for persistent gradients. Labeled valve size is not the same as millimeter measure of prosthetic valve diameters or the annulus into which it will fit. Studies that use the labeled valve size in lieu of actual measured diameter in millimeters to compare different valves might be misleading. Using human cadaver hearts, we sized the aortic annulus with 8 commonly used prosthetic aortic valve sizers and compared the valves using geometric orifice area. This novel method …

Outcome Of Triple Procedure In Older Children With Developmental Dysplasia Of Hip (Ddh), Masood Umer, Haq Nawaz, Pashtoon Murtaza Kasi, Mahmood Ahmed

Department of Surgery

Objective: To evaluate the radiographic and functional results of the triple procedure (open reduction, femoral shortening and Salter's Osteotomy) in the treatment of Developmental Dysplasia of the Hip (DDH) disease in older children. Methods: This case-series comprising 23 patients (29 hips) underwent the triple procedure of open reduction, femoral shortening and Salter osteotomy, at Aga Khan University Hospital between June 1995 and June 2005. Patients were classified pre-operatively according to the Tonnis class. Postoperative functional evaluation was performed using Modified MacKay's scoring system and radiographic assessment using Severin's scoring method. Results: The mean age of patients at presentation was 6.84 …

Bullet-Induced Synovitis As A Cause Of Secondary Osteoarthritis Of The Hip Joint: A Case Report And Review Of Literature, A Rehman, Masood Umer, Yasir J Sepah, Muhammad A Wajid

Department of Surgery

Abstract

BACKGROUND:

With increasing prevalence of gunshot injuries we are seeing more patients with retained bullet fragments lodged in their bodies. Embedded lead bullets are usually considered inert after their kinetic energy has dissipated hence these are not removed routinely. However, exposure of any foreign body to synovial fluid may lead to rapid degradation and hence result in systemic absorption, causing local and systemic symptoms. We present the case of a thirty year old man who came to our out patient department with a history of progressive, severe hip pain ten years after a gun shot injury to his right …

Illusory Predictors: Generalizability Of Findings In Cocaine Treatment Retention Research, Angela L Stotts, Marc E Mooney, Shelly L Sayre, Meredith Novy, Joy M Schmitz, John Grabowski

Journal Articles

Treatment retention is of paramount importance in cocaine treatment research as treatment completion rates are often 50% or less. Failure to retain cocaine patients in treatment has both significant research and clinical implications. In this paper we qualitatively and quantitatively demonstrate the inconsistency found across analyses of retention predictors in order to highlight the problem. First, a qualitative review of the published literature was undertaken to identify the frequency of predictors studied and their relations to treatment retention. Second, an empirical demonstration of predictor stability was conducted by testing a common set of variables across three similar 12-week cocaine clinical …

Neurogranin Controls The Spatiotemporal Pattern Of Postsynaptic Ca2+/Cam Signaling, Yoshihisa Kubota, John A Putkey, M Neal Waxham

Journal Articles

Neurogranin (Ng) is a postsynaptic IQ-motif containing protein that accelerates Ca(2+) dissociation from calmodulin (CaM), a key regulator of long-term potentiation and long-term depression in CA1 pyramidal neurons. The exact physiological role of Ng, however, remains controversial. Two genetic knockout studies of Ng showed opposite outcomes in terms of the induction of synaptic plasticity. To understand its function, we test the hypothesis that Ng could regulate the spatial range of action of Ca(2+)/CaM based on its ability to accelerate the dissociation of Ca(2+) from CaM. Using a mathematical model constructed on the known biochemistry of Ng, we calculate the cycle …

Nonsexual Transmission Of Anogenital Warts In Children: A Retrospective Analysis, Valerie Jones, Shawn J. Smith, Hatim A. Omar

Pediatrics Faculty Publications

The purpose was to evaluate the prevalence of sexual abuse in patients who were referred to a pediatric gynecologist for evaluation based on the clinical findings of anogenital warts. A retrospective analysis was performed on 131 patients between the ages 6 month and 9 years referred to a pediatric gynecologist after the finding of anogenital warts by a clinical provider, parent or caregiver. A complete physical examination under colposcopy by a the same, trained pediatric gynecologist was completed, and a complete medical and family history including maternal and sibling history for evidence of Human Papillomavirus (HPV) and anogenital warts. The …

Membranous Dysmenorrhea: A Case Series, Hatim A. Omar, Shawn J. Smith

Pediatrics Faculty Publications

The purpose was to illustrate the variability of hormonal contraception of patients that presented with membranous dysmenorrheal. A case analysis chart review was completed on six patients referred to a Pediatric Gynecologist in an academic setting. In each case the patient underwent a thorough pelvic and bimanual exam. Following the initial presentation, each patient continued to be followed on a regular visits. Cases: Two were using the transdermal contraceptive patch and oral contraceptive, but following the expulsion of decidual cast, they were both placed on depot medroxyprogesterone acetate (DMPA) without further complications. Three of the six cases were on DMPA …

Adaptive Radiotherapy Planning On Decreasing Gross Tumor Volumes As Seen On Megavoltage Computed Tomography Images., Curtis Woodford, Slav Yartsev, R. Dar, Glenn Bauman, Jacob Van Dyk

Oncology Publications

PURPOSE: To evaluate gross tumor volume (GTV) changes for patients with non-small-cell lung cancer by using daily megavoltage (MV) computed tomography (CT) studies acquired before each treatment fraction on helical tomotherapy and to relate the potential benefit of adaptive image-guided radiotherapy to changes in GTV.

METHODS AND MATERIALS: Seventeen patients were prescribed 30 fractions of radiotherapy on helical tomotherapy for non-small-cell lung cancer at London Regional Cancer Program from Dec 2005 to March 2007. The GTV was contoured on the daily MVCT studies of each patient. Adapted plans were created using merged MVCT-kilovoltage CT image sets to investigate the advantages …

Wingless Activity In The Precursor Cells Specifies Neuronal Migratory Behavior In The Drosophila Nerve Cord, Krishna Moorthi Bhat

Journal Articles

Neurons and their precursor cells are formed in different regions within the developing CNS, but they migrate and occupy very specific sites in the mature CNS. The ultimate position of neurons is crucial for establishing proper synaptic connectivity in the brain. In Drosophila, despite its extensive use as a model system to study neurogenesis, we know almost nothing about neuronal migration or its regulation. In this paper, I show that one of the most studied neuronal pairs in the Drosophila nerve cord, RP2/sib, has a complicated migratory route. Based on my studies on Wingless (Wg) signaling, I report that the …

Ua12/2/1 College Heights Herald, Vol. 83, No. 20, Wku Student Affairs

WKU Archives Records

WKU campus newspaper reporting campus, athletic and Bowling Green, Kentucky news.

Anti-Tumor Effect Of Doxycycline On Glioblastoma Cells, Andrea Wang-Gillam, Eric Siegel, Debra A. Mayes, Laura F. Hutchins, Yi-Hong Zhou

Neuroscience, Cell Biology & Physiology Faculty Publications

AIM: Glioblastoma multiforme (GBM) is the most common primary brain tumor in humans, and it is highly invasive. Doxycycline, first identified as an antimicrobial agent, is a nonspecific inhibitor of matrix metalloproteinases (MMPs). Our objective was to investigate the anti-MMP effect of doxycycline at therapeutically acceptable levels on glioma cells in vitro.

METHODS: The MTT assay was used to determine the anti-proliferative effects of doxycycline. MMP2 activity and expression were determined by gelatinase zymography and real-time quantitative RT-PCR, respectively. Cell invasion was assessed by Matrigel invasion assay.

RESULTS: Doxycycline exerted mild anti-proliferative effects on all three glioma cell lines …

Understanding Barriers For Adherence To Follow-Up Care For Abnormal Pap Tests, Katherine S. Eggleston, Ann L. Coker, Irene Prabhu Das, Suzanne T. Cordray, Kathryn J. Luchok

CRVAW Faculty Journal Articles

Objective: Approximately 4000 women annually will die from preventable and treatable cervical cancer. Failure to adhere to follow-up recommendations after an abnormal Pap test can lead to development of cervical cancer. This paper summarizes the body of literature on adherence to follow-up after an abnormal Pap test in order to facilitate development of interventions

to decrease morbidity and mortality due to cervical cancer.

Methods: We conducted a comprehensive search of published literature addressing risk factors for adherence or interventions to improve adherence following an abnormal Pap test as the outcome. We included peer-reviewed original research conducted in the …

Robot-Assisted Prostate Brachytherapy, Yan Yu, Tarun Podder, Y D. Zhang, W S. Ng, V Misic, J Sherman, L Fu, D Fuller, D J. Rubens, J D. Strang, R A. Brasacchio, E M. Messing

Department of Radiation Oncology Faculty Papers

Abstract: In contemporary brachytherapy procedures, needle placement at the desired target is challenging due to a variety of reasons. A robot-assisted brachytherapy system can potentially improve needle placement and seed delivery, resulting in enhanced therapeutic delivery. In this paper we present a 16 DOF (degrees-of-freedom) robotic system (9DOF positioning module and 7DOF surgery module) developed and fabricated for prostate brachytherapy. Strategies to reduce needle deflection and target movement were incorporated after extensive experimental validation. Provisions for needle motion and force feedback were included into the system for improving robot control and seed delivery. Preliminary experimental results reveal that the prototype …