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Time Course Of Substance P Expression In Dorsal Root Ganglia Following Complete Spinal Nerve Transection, Wendy Weissner, Barbara J. Winterson, Alan Stuart-Tilley, Marshall Devor, Geoffrey M. Bove

Biomedical Sciences Faculty Publications

Recent evidence suggests that substance P (SP) is upregulated in primary sensory neurons following axotomy, and that this change occurs in larger neurons that do not usually produce SP. If so, this upregulation may allow normally neighboring, uninjured, and non-nociceptive dorsal root ganglion (DRG) neurons to become effective in activating pain pathways. Using immunohistochemistry, we performed a unilateral L5 spinal nerve transection upon male Wistar rats, and measured SP expression in ipsilateral L4 and L5 DRGs and contralateral L5 DRGs, at 1 to 14 days postoperatively (dpo), and in control and sham operated rats. In normal and sham operated DRGs, …

Endoscopic Sphincterotomy With Or Without Cholecystectomy For Choledocholithiasis In High Risk Surgical Patients: A Decision Analysis, Ali Siddiqui, Pradnya Mitroo, Thomas E. Kowalski, David Loren

Department of Medicine Faculty Papers

Background

Laparoscopic cholecystectomy (LC) is recommended for patients with choledocholithiasis after ERCP with sphincterotomy (ES) and stone extraction.

Aim: We designed a decision model to address whether ES alone versus ES followed by LC (ES + LC) is the optimal treatment in high-risk patients with choledocholithiasis.

Methods:

Our cohort were patients with obstructive jaundice who have undergone an ES with biliary clearance. Recurrent biliary complications over a 2-year period stratified by gallbladder status (in/out) and age-stratified surgical complication rates were obtained from the literature. Failure of therapy was defined as either recurrent symptoms or death attributed to biliary complications.

Results …

Visualization Of Intracellular Transport Of Vesicular Stomatitis Virus Nucleocapsids In Living Cells, Subash C. Das, Debasis Nayak, You Zhou, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

The phosphoprotein (P) of vesicular stomatitis virus (VSV) is a subunit of the viral RNA polymerase. In previous studies, we demonstrated that insertion of 19 amino acids in the hinge region of the protein had no significant effect on P protein function. In the present study, we inserted full-length enhanced green fluorescent protein (eGFP) in frame into the hinge region of P and show that the fusion protein (PeGFP) is functional in viral genome transcription and replication, albeit with reduced activity. A recombinant vesicular stomatitis virus encoding PeGFP in place of the P protein (VSV-PeGFP), which possessed reduced growth kinetics …

Cross-Subtype T-Cell Immune Responses Induced By A Human Immunodeficiency Virus Type 1 Group M Consensus Env Immunogen†0--, Eric A. Weaver, Zhongjing Lu, Zenaido T. Camacho, Fatiha Moukdar, Hua-Xin Liao, Ben-Jiang Ma, Mark Muldoon, James Theiler, Gary J. Nabel, Norman L. Letvin, Bette T. Korber, Beatrice H. Hahn, Barton F. Haynes, Feng Gao

Nebraska Center for Virology: Faculty Publications

The genetic diversity among globally circulating human immunodeficiency virus type 1 (HIV-1) strains is a serious challenge for HIV-1 vaccine design. We have generated a synthetic groupMconsensus env gene (CON6) for induction of cross-subtype immune responses and report here a comparative study of T-cell responses to this and natural strain env immunogens in a murine model. Three different strains of mice were immunized with CON6 as well as subtype A, B, or C env immunogens, using a DNA prime-recombinant vaccinia virus boost strategy. T-cell epitopes were mapped by gamma interferon enzyme-linked immunospot analysis using five overlapping Env peptide sets from …

Protection Against Ischemia And Reperfusion Injury, Peter R. Oeltgen, Paul D. Bishop, Mark S. Kindy, Juan A. Sanchez

Pathology and Laboratory Medicine Faculty Patents

A compound and method for using the compound to reduce injury associated with ischemia and reperfusion of mammalian organs such as the heart. The compound, either Deltorphin A and/or Dermorphin H, may be administered as part of a preconditioning strategy which reduces the extent of injury and improves organ function following cessation and restoration of blood flow. The compound may be used in preparation for planned ischemia or in a prophylactic manner in anticipation of further ischemic events.

Molecular Diagnosis Of Burkitt's Lymphoma., Sandeep S. Dave, Kai Fu, George W. Wright, Lloyd T. Lam, Philip Kluin, Evert-Jan Boerma, Timothy Greiner, Dennis D. Weisenburger, Andreas Rosenwald, German Ott, Hans-Konrad Müller-Hermelink, Randy D. Gascoyne, Jan Delabie, Lisa M. Rimsza, Rita M. Braziel, Thomas M. Grogan, Elias Campo, Elaine S. Jaffe, Bhavana J. Dave, Warren Sanger, M Bast, Julie M. Vose, James O. Armitage, Joseph M. Connors, Erlend B. Smeland, Stein Kvaloy, Harald Holte, Richard I. Fisher, Thomas P. Miller, Emilio Montserrat, Wyndham H. Wilson, Manisha Bahl, Hong Zhao, Liming Yang, John Powell, Richard Simon, Wing C. Chan, Louis M. Staudt

Journal Articles: Pathology and Microbiology

BACKGROUND: The distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma is crucial because these two types of lymphoma require different treatments. We examined whether gene-expression profiling could reliably distinguish Burkitt's lymphoma from diffuse large-B-cell lymphoma.

METHODS: Tumor-biopsy specimens from 303 patients with aggressive lymphomas were profiled for gene expression and were also classified according to morphology, immunohistochemistry, and detection of the t(8;14) c-myc translocation.

RESULTS: A classifier based on gene expression correctly identified all 25 pathologically verified cases of classic Burkitt's lymphoma. Burkitt's lymphoma was readily distinguished from diffuse large-B-cell lymphoma by the high level of expression of c-myc target …

Substratum As A Driver Of Variation In Periphyton Chlorophyll And Productivity In Lakes, Yvonne Vadeboncoeur

Biological Sciences Faculty Publications

Quantifying periphyton (attached algal) contributions to autotrophic production in lakes is confounded by properties of substratum that affect community biomass (as chlorophyll content) and productivity. We compared chlorophyll content and productivity of natural algal communities (phytoplankton, epipelon, epilithon, epixylon, and epiphyton) experiencing high (>10%) incident radiation in lakes in the US, Greenland, and Quebec, Canada. Chlorophyll content and productivity differed significantly among regions, but they also differed consistently among communities independent of region. Chlorophyll content of periphyton on hard substrata (rocks and wood) was positively related to water-column total P (TP), whereas chlorophyll content of algae on sediment (epipelon) …

The Role Of Cd4 T Cells In The Pathogenesis Of Murine Aids, Wen Li, William R. Green

Dartmouth Scholarship

LP-BM5, a retroviral isolate, induces a disease featuring retrovirus-induced immunodeficiency, designated murine AIDS (MAIDS). Many of the features of the LP-BM5-induced syndrome are shared with human immunodeficiency virus-induced disease. For example, CD4 T cells are critical to the development of MAIDS. In vivo depletion of CD4 T cells before LP-BM5 infection rendered genetically susceptible B6 mice MAIDS resistant. Similarly, MAIDS did not develop in B6.nude mice. However, if reconstituted with CD4 T cells, B6.nude mice develop full-blown MAIDS. Our laboratory has shown that the interaction of B and CD4 T cells that is central to MAIDS pathogenesis requires ligation of …

Representation Of Head-Centric Flow In The Human Motion Complex., Jeroen Goossens, Sean P Dukelow, Ravi S Menon, Tutis Vilis, Albert V Van Den Berg

Brain and Mind Institute Researchers' Publications

Recent neuroimaging studies have identified putative homologs of macaque middle temporal area (area MT) and medial superior temporal area (area MST) in humans. Little is known about the integration of visual and nonvisual signals in human motion areas compared with monkeys. Through extra-retinal signals, the brain can factor out the components of visual flow on the retina that are induced by eye-in-head and head-in-space rotations and achieve a representation of flow relative to the head (head-centric flow) or body (body-centric flow). Here, we used functional magnetic resonance imaging to test whether extra-retinal eye-movement signals modulate responses to visual flow in …

Desulfovibrio Desulfuricans G20 Tetraheme Cytochrome Structure At 1.5 A˚ And Cytochrome Interaction With Metal Complexes, Mrunalini Pattarkine, J J. Tanner, C A. Bottoms, Y H. Lee, Judy D. Wall

Faculty Works

The structure of the type I tetraheme cytochrome c3 from Desulfovibrio desulfuricans G20 was determined to 1.5 A˚ by X-ray crystallography. In addition to the oxidized form, the structure of the molybdate-bound form of the protein was determined from oxidized crystals soaked in sodium molybdate. Only small structural shifts were obtained with metal binding, consistent with the remarkable structural stability of this protein. In vitro experiments with pure cytochrome showed that molybdate could oxidize the reduced cytochrome, although not as rapidly as U(VI) present as uranyl acetate. Alterations in the overall conformation and thermostability of the metal-oxidized protein were investigated …

Abdominal Pain With Rigidity Secondary To The Anti-Emetic Drug Metoclopramide, Nadeem Ullah Khan, Junaid A. Razzak

Department of Emergency Medicine

We report a case of abdominal pain with rigidity, mimicking an acute abdomen, caused by metoclopramide, a common anti-emetic drug. Extrapyramidal symptoms are commonly reported side-effects of this medication. They generally include involuntary movements of limbs, torticollis, oculogyric crisis, rhythmic protrusion of tongue, trismus, or dystonic reactions resembling tetanus, etc. Abdominal rigidity due to this medication, resembling an acute abdomen, has not been reported previously. This case report illustrates the importance of considering medication side-effects when evaluating a patient with abdominal pain and rigidity.

The Burden Of Anxiety And Depression Among Patients With Chronic Rheumatologic Disorders At A Tertiary Care Hospital Clinic In Karachi, Pakistan, Abdul Waheed, Kamran Hameed, Abdul Moiz Khan, Junaid Ali Syed, Ahmed Iqbal Mirza

Medical College Documents

Objectives: To study the burden of anxiety and depression as a comorbid among patients of chronic rheumatological disorders and to investigate possible determinants of depression and anxiety.Methods: It was a cross-sectional study conducted at the rheumatology clinic of The Aga Khan University Hospital (AKUH) Karachi, Pakistan. With convenient sampling, 111 patients who fulfilled inclusion/exclusion criteria were screened for anxiety and depression with help of Aga Khan University Anxiety and Depression Scale (AKUADS). The data was entered and analyzed by Statistical Package for Social Sciences (Version 10.0).Results: The population consisted mainly of middle aged (mean age 41) females (80.2%). The most …

Secondary N-Nitrosocarbamate Anions: Structure And Alkylation Reactions. A Dft Study, Vladimir Benin

Chemistry Faculty Publications

The current article reports theoretical studies (DFT: B3LYP/6-31+G(d)) on the structure and alkylation reactions of the anions of some secondary N-nitrosocarbamates, a class of ambident nucleophiles whose chemistry has been little explored. Several anions (1–4), with an increasing size of the carbamate alkyl (aryl) group were investigated, in an attempt to establish the influence of the size of that group on the thermal stability and regioselectivity of alkylation of the title anions. The conclusion is that thermal stability and the mode of reaction are affected significantly only in the presence of very large and branched carbamate groups. The thermal …

Gαq And Its AktIons, David M. Harris, Andrea D. Eckhart, Walter J. Koch

Department of Medicine Faculty Papers

No abstract available.

Mixed Germ Cell Sex Cord-Stromal Tumors Of The Testis And Ovary. Morphological, Immunohistochemical, And Molecular Genetic Study Of Seven Cases, Michal Michal, Tomas Vanacek, Radek Sima, Petr Mukensnabl, Ondrej Hes, Dmitry V. Kazakov, Jozef Matoska, Anna Zuntova, Vladimir Dvorak, Alexander Talerman

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

We present the morphological, immunohistochemical, and molecular genetic features of three cases of testicular and four cases of ovarian mixed germ cell sex cord-stromal tumors (MGSCT). The germ cells in the testicular MGSCTs morphologically differed from those in classical seminomas by lacking the typical "square off" quality of the nuclei. In contrast to the nuclei in classical seminomas, their size in testicular MGSCTs was smaller and nucleoli were inconspicuous and the cytoplasm was Periodic Acid-Schiff(PAS) negative. Quite on the contrary, the variability in the size of the nuclei of the germ cells in the testicular MGSCTs was more similar to …

Heme Deficiency In Alzheimer's Disease: A Possible Connection To Porphyria, Barney E. Dwyer, Meghan L. Stone, Xiongwei Zhu, George Perry, Mark A. Smith

Dartmouth Scholarship

Mechanisms that cause Alzheimer's disease (AD), an invariably fatal neurodegenerative disease, are unknown. Important recent data indicate that neuronal heme deficiency may contribute to AD pathogenesis. If true, factors that contribute to the intracellular heme deficiency could potentially alter the course of AD. The porphyrias are metabolic disorders characterized by enzyme deficiencies in the heme biosynthetic pathway. We hypothesize that AD may differ significantly in individuals possessing the genetic trait for an acute hepatic porphyria. We elaborate on this hypothesis and briefly review the characteristics of the acute hepatic porphyrias that may be relevant to AD. We note the proximity …

Pro-Opiomelanocortin Co-Localizes With Corticotropin-Releasing Factor In Axon Terminals Of The Noradrenergic Nucleus Locus Coeruleus, Beverly A.S. Reyes, Julia D. Glaser, Ronaldo Magtoto, Elisabeth K. Van Bockstaele

Department of Neurosurgery Faculty Papers

We previously demonstrated that the opioid peptide, enkephalin, and corticotropin-releasing factor (CRF) are occasionally co-localized in individual axon terminals but more frequently converge on common dendrites in the locus coeruleus (LC). To further examine potential opioid co-transmitters in CRF afferents, we investigated the distribution of proopiomelanocortin (POMC), the precursor that yields the potent bioactive peptide, ß-endorphin, with respect to CRF immunoreactivity using immunofluorescence and immunoelectron microscopic analyses of the LC. Coronal sections were collected through the dorsal pontine tegmentum of rat brain and processed for immunocytochemical detection of POMC and CRF or tyrosine hydroxylase (TH). POMC-immunoreactive processes exhibited a distinct …

Metaplastic Carcinoma Of The Breast, An Intriguing Rarity., Naila Kayani, Fozia Rauf, Yasmin Bhurgri

Department of Pathology and Laboratory Medicine

Abstract Metaplastic carcinoma breast is categorized as a rare heterogenous neoplasm generally characterized by a mixtureof adenocarcinoma with dominant areas of spindle cell, squamous and/or other mesenchymal differentiation. Todetermine the epidemio-demographic and histopathologic characteristics of this rare entity a retrospective studywas conducted to review all cases at the Aga Khan University Hospital (AKUH) Karachi, received during 1st January2000 to 31st August 2005. Twenty-four patients were identified with a mean age at diagnosis of 46.4 (±SD 3.8) years,and an age range of 28-68 years. The mean tumor size was 7.9 cm, range 2.0–17.0 cms (±SD 4.77). The specimenswere mostly obtained by …

Phylloides Tumors In Adolescent Girls And Young Women In Pakistan., Naila Kayani, Amna Khurshid, Yasmin Bhurgri

Department of Pathology and Laboratory Medicine

Abstract The objective of this study was to determine the frequency of phylloides tumor (PT) in adolescent girls and youngwomen (less than and equal to 25 years of age) and to define the clinico-pathological features of PT in this unusualclinical setting. This descriptive study was carried out at the Aga Khan University Hospital (AKUH) pathologydepartment. All consecutive cases of PT diagnosed during the last sixteen years in the section of histopathology from1st January 1990 to 31st June 2005 were included. Selection of cases was restricted to patients up to 25 years of age.A total of 42 cases of PT in …

Voltage-Dependent Gating Rearrangements In The Intracellular T1-T1 Interface Of A K+ Channel., Guangyu Wang, Manuel Covarrubias

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The intracellular tetramerization domain (T1) of most eukaryotic voltage-gated potassium channels (Kv channels) exists as a "hanging gondola" below the transmembrane regions that directly control activation gating via the electromechanical coupling between the S4 voltage sensor and the main S6 gate. However, much less is known about the putative contribution of the T1 domain to Kv channel gating. This possibility is mechanistically intriguing because the T1-S1 linker connects the T1 domain to the voltage-sensing domain. Previously, we demonstrated that thiol-specific reagents inhibit Kv4.1 channels by reacting in a state-dependent manner with native Zn(2+) site thiolate groups in the T1-T1 interface; …

The Ribosome-Recycling Step: Consensus Or Controversy?, Go Hirokawa, Natalia Demeshkina, Nobuhiro Iwakura, Hideko Kaji, Akira Kaji

Department of Biochemistry and Molecular Biology Faculty Papers

Ribosome recycling, the last step in translation, is now accepted as an essential process for prokaryotes. In 2005, three laboratories showed that ribosome-recycling factor (RRF) and elongation factor G (EF-G) cause dissociation of ribosomes into subunits, solving the long-standing problem of how this essential step of translation occurs. However, there remains ongoing controversy regarding the other actions of RRF and EF-G during ribosome recycling. We propose that the available data are consistent with the notion that RRF and EF-G not only split ribosomes into subunits but also participate directly in the release of deacylated tRNA and mRNA for the next …

Follicular Dendritic Cell Sarcoma Of Lymph Node - A Rare Entity, Safoorah Khalid, Nausheen Yaqoob, Shahid Pervez

Department of Pathology and Laboratory Medicine

Follicular dendritic cells (FDC) are non-lymphoid, non-phagocytic accessory cells in the immune system that are essential for antigen presentation and germinal center reaction regulation1. These cells are CD21+, CD35+, CD1a- and S100 protein + and they show desmosomes ultrastructurally.

The most commonly involved sites by FDC tumors are lymph nodes but may arise at a variety of extranodal sites including oral cavity, tonsil, gastrointestinal tract and liver. Most studies represent single case reports or case series.

Our patient presented with tumor in the lymph nodes. Histology revealed tumor cells with abundant eosinophilic cytoplasm, hyperchromatic and pleomorphic nuclei, and prominent nucleoli. …

Cell-Signalling Dynamics In Time And Space, Boris N. Kholodenko Phd, Dsci

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The specificity of cellular responses to receptor stimulation is encoded by the spatial and temporal dynamics of downstream signalling networks. Computational models provide insights into the intricate relationships between stimuli and responses and reveal mechanisms that enable networks to amplify signals, reduce noise and generate discontinuous bistable dynamics or oscillations. These temporal dynamics are coupled to precipitous spatial gradients of signalling activities, which guide pivotal intracellular processes, but also necessitate mechanisms to facilitate signal propagation across a cell.

H2-M3-Restricted Cd8+ T Cells Are Not Required For Mhc Class Ib-Restricted Immunity Against Listeria Monocytogenes, Sarah E. F. D'Orazio, Christine A. Shaw, Michael N. Starnbach

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Studies using major histocompatibility complex (MHC)-Ia–deficient mice have shown that MHC-Ib–restricted CD8⁺ T cells can clear infections caused by intracellular pathogens such as Listeria monocytogenes. M3-restricted CD8⁺ T cells, which recognize short hydrophobic N-formylated peptides, appear to comprise a substantial portion of the MHC-Ib–restricted T cell response in the mouse model of L. monocytogenes infection. In this study, we isolated formyltransferase (fmt) mutant strains of L. monocytogenes that lacked the ability to add formyl groups to nascent polypeptides. These fmt mutant Listeria strains did not produce antigens that could be recognized by M3-restricted T …

Animal Carcinogenicity Studies: 1. Poor Human Predictivity, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Experimentation Collection

The regulation of human exposure to potentially carcinogenic chemicals constitutes society’s most important use of animal carcinogenicity data. Environmental contaminants of greatest concern within the USA are listed in the Environmental Protection Agency’s (EPA’s) Integrated Risk Information System (IRIS) chemicals database. However, of the 160 IRIS chemicals lacking even limited human exposure data but possessing animal data that had received a human carcinogenicity assessment by 1 January 2004, we found that in most cases (58.1%; 93/160), the EPA considered animal carcinogenicity data inadequate to support a classification of probable human carcinogen or non-carcinogen. For the 128 chemicals with human or …

Animal Carcinogenicity Studies: 2. Obstacles To Extrapolation Of Data To Humans, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Experimentation Collection

Due to limited human exposure data, risk classification and the consequent regulation of exposure to potential carcinogens has conventionally relied mainly upon animal tests. However, several investigations have revealed animal carcinogenicity data to be lacking in human predictivity. To investigate the reasons for this, we surveyed 160 chemicals possessing animal but not human exposure data within the US Environmental Protection Agency chemicals database, but which had received human carcinogenicity assessments by 1 January 2004. We discovered the use of a wide variety of species, with rodents predominating, and of a wide variety of routes of administration, and that there were …

Animal Carcinogenicity Studies: 3. Alternatives To The Bioassay, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Experimentation Collection

Conventional animal carcinogenicity tests take around three years to design, conduct and interpret. Consequently, only a tiny fraction of the thousands of industrial chemicals currently in use have been tested for carcinogenicity. Despite the costs of hundreds of millions of dollars and millions of skilled personnel hours, as well as millions of animal lives, several investigations have revealed that animal carcinogenicity data lack human specificity (i.e. the ability to identify human non-carcinogens), which severely limits the human predictivity of the bioassay. This is due to the scientific inadequacies of many carcinogenicity bioassays, and numerous serious biological obstacles, which render profoundly …

Neuromechanics Of Coordination During Swallowing In Aplysia Californica, Hui Ye, Douglas W. Morton, Hillel J. Chiel

Faculty Scholarship

Bernstein (1967) hypothesized that preparation of the periphery was crucial for correct responses to motor output. To test this hypothesis in a behaving animal, we examined the roles of two identified motor neurons, B7 and B8, which contribute to feeding behavior in the marine mollusk Aplysia californica. Neuron B7 innervates a hinge muscle and has no overt behavioral effect during smaller-amplitude (type A) swallows, because the hinge muscle is too short to exert force. Neuron B8 activates a muscle (I4) that acts solely to grasp material during type A swallows. During larger-amplitude (type B) swallows, the behavioral actions of both …

Antisense Inhibition Of Cyclin D1 Expression Is Equivalent To Flavopiridol For Radiosensitization Of Zebrafish Embryos, Mary Frances Mcaleer, Kevin T. Duffy, William R. Davidson, Gabor Kari, Adam P. Dicker, Ulrich Rodeck, Eric Wickstrom

Department of Biochemistry and Molecular Biology Faculty Papers

Purpose: Flavopiridol, a small molecule pan-cyclin inhibitor, has been shown to enhance the radiation response of tumor cells both in vitro and in vivo. The clinical utility of flavopiridol, however, is limited by toxicity, previously attributed to pleiotropic inhibitory effects on several targets affecting multiple signal transduction pathways. Here we utilized zebrafish embryos to investigate radiosensitizing effects of flavopiridol in normal tissues.

Methods and Materials: Zebrafish embryos at the 1-4 cell stage were treated with 500 nM flavopiridol or injected with 0.5 pmol antisense hydroxylprolyl-phosphono nucleic acid oligomers to reduce cyclin D1 expression, then subjected to ionizing radiation (IR) or …

Keeping Their Options Open: Acute Versus Persistent Infections, S. Furukawa, S. L. Kuchma, G. A. O'Toole

Dartmouth Scholarship

No abstract provided.