Medicine and Health Sciences Commons^™

Chloride Equilibrium Potential In Salamander Cones., Wallace B. Thoreson, Eric J. Bryson

Journal Articles: Ophthalmology

BACKGROUND: GABAergic inhibition and effects of intracellular chloride ions on calcium channel activity have been proposed to regulate neurotransmission from photoreceptors. To assess the impact of these and other chloride-dependent mechanisms on release from cones, the chloride equilibrium potential (ECl) was determined in red-sensitive, large single cones from the tiger salamander retinal slice.

RESULTS: Whole cell recordings were done using gramicidin perforated patch techniques to maintain endogenous Cl- levels. Membrane potentials were corrected for liquid junction potentials. Cone resting potentials were found to average -46 mV. To measure ECl, we applied long depolarizing steps to activate the calcium-activated chloride current …

Multiple Roles Of Mucins In Pancreatic Cancer, A Lethal And Challenging Malignancy., N. Moniaux, M. Andrianifahanana, R. E. Brand, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Mucins are members of an expanding family of large multifunctional glycoproteins. Pancreatic mucins have important biological functions, including the protection, lubrication, and moisturisation of the surfaces of epithelial tissues lining ductal structures within the pancreas. Several lines of evidence support the notion that deregulated mucin production is a hallmark of inflammatory and neoplastic disorders of the pancreas. Herein, we discuss the factors that contribute to the lethality of pancreatic cancer as well as the key role played by mucins, particularly MUC1 and MUC4, in the development and progression of the disease. Aspects pertaining to the aberrant expression and glycosylation of …

Distinct Gene Expression Profiles In Different B-Cell Compartments In Human Peripheral Lymphoid Organs., Yulei Shen, Javeed Iqbal, Li Xiao, Ryan C. Lynch, Andreas Rosenwald, Louis M. Staudt, Simon Sherman, Karen Dybkaer, Guimei Zhou, James D. Eudy, Jan Delabie, Timothy W. Mckeithan, Wing C. Chan

Journal Articles: Eppley Institute

BACKGROUND: There are three major B-cell compartments in peripheral lymphoid organs: the germinal center (GC), the mantle zone (MNZ) and the marginal zone (MGZ). Unique sets of B-cells reside in these compartments, and they have specific functional roles in humoral immune response. MNZ B cells are naive cells in a quiescent state and may participate in GC reactions upon proper stimulation. The adult splenic MGZ contains mostly memory B cells and is also known to provide a rapid response to particulate antigens. The GC B-cells proliferate rapidly and undergo selection and affinity maturation. The B-cell maturational process is accompanied by …

Immunopathogenesis Of Brain Abscess., Tammy Kielian

Journal Articles: Pathology and Microbiology

Brain abscess represents a significant medical problem despite recent advances made in detection and therapy. Due to the emergence of multi-drug resistant strains and the ubiquitous nature of bacteria, the occurrence of brain abscess is likely to persist. Our laboratory has developed a mouse experimental brain abscess model allowing for the identification of key mediators in the CNS anti-bacterial immune response through the use of cytokine and chemokine knockout mice. Studies of primary microglia and astrocytes from neonatal mice have revealed that S. aureus, one of the main etiologic agents of brain abscess in humans, is a potent stimulus for …

Transcriptional Activation Of The Human Prostatic Acid Phosphatase Gene By Nf-Kappab Via A Novel Hexanucleotide-Binding Site., Stanislav Zelivianski, Richard Glowacki, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

Human prostatic acid phosphatase (PAcP) is a prostate epithelium-specific differentiation antigen. Cellular PAcP functions as a neutral protein tyrosine phosphatase and is involved in regulating androgen-promoted prostate cancer cell proliferation. Despite the fact that the promoter of the PAcP gene has been cloned, the transcriptional factors that regulate PAcP expression remain unidentified. This article describes our analyses of the promoter of the PAcP gene. Deletion analyses of the promoter sequence up to -4893 (-4893/+87) revealed that a 577 bp fragment (-1356/-779) represents the unique positive cis-active element in human prostate cancer cells but not in HeLa cervix carcinoma cells. Interestingly, …

Molecular Dynamics Simulations Of The O-Glycosylated 21-Residue Muc1 Peptides, A. Rubinstein, L. Kinarsky, S. Sherman

Journal Articles: Eppley Institute

The conformational propensities of the 21-residue peptide and its Oglycosylated analogs were studied by molecular dynamics (MD) simulations. This polypeptide motif comprises the tandem repeat of the human mucin (MUC1) protein core that is differently glycosylated in normal and cancer cells. To evaluate the structural effects of O-glycosylation on the polypeptide backbone, conformations of the nonglycosylated peptide and its glycosylated analogs were monitored during the 1 ns MD simulations. Radius gyration for whole peptide and its fragments, as well as root-mean-square-deviation between coordinate sets of the backbone atoms of starting structures and generated structures, were calculated. It was shown that …

Nmr-Based Structural Studies Of The Glycosylated Muc1 Tandem Repeat Peptide, G. Suryanarayanan, P. A. Keifer, G. Wang, L. Kinarsky, M. A. Hollingsworth, S. Sherman

Journal Articles: Eppley Institute

MUC1 is a glycoprotein that plays an important role in cancer pathogenesis. In order to study the effect of glycosylation on the conformational propensities of the tandem repeat domain of MUC1, we have determined the structure of the MUC1 tandem repeat peptide AHGVTSAPDTRPAPGSTAPP, O-glycosylated with the trisaccharide (α-Glc-1,4-β-Glc-1,4-α-GalNAc-) at Thr5. This glycopeptide was synthesized to model a heavily Oglycosylated threonine residue in the tandem repeat domain. The NMR experiments used in this study included TOCSY, NOESY, ROESY, DQF-COSY, HSQC and 1D NMR. The peak volumes determined using the program SPARKY were converted into distance constraints using the program CALIBA. The …

Muc4 Mucin Expression In Human Pancreatic Tumours Is Affected By Organ Environment: The Possible Role Of Tgfbeta2., A. Choudhury, N. Moniaux, A. B. Ulrich, B. M. Schmied, J. Standop, Parviz M. Pour, S. J. Gendler, Michael A. Hollingsworth, J-P Aubert, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

MUC4 is highly expressed in human pancreatic tumours and pancreatic tumour cell lines, but is minimally or not expressed in normal pancreas or chronic pancreatitis. Here, we investigated the aberrant regulation of MUC4 expression in vivo using clonal human pancreatic tumour cells (CD18/HPAF) grown either orthotopically in the pancreas (OT) or ectopically in subcutaneous tissue (SC) in the nude mice. Histological examination of the OT and SC tumours showed moderately differentiated and anaplastic morphology, respectively. The OT tumour cells showed metastases to distant lymph nodes and faster tumour growth (P

Albumin Enhanced Morphometric Image Analysis In Cll., Matthew A. Lunning, Vincent E. Zenger, Ricardo Dreyfuss, Maryalice Stetler-Stevenson, Margaret E. Rick, Therese A. White, Wyndham H. Wilson, Gerald E. Marti

Journal Articles: Oncology and Hematology

BACKGROUND: The heterogeneity of lymphocytes from patients with chronic lymphocytic leukemia (CLL) and blood film artifacts make morphologic subclassification of this disease difficult.

METHODS: We reviewed paired blood films prepared from ethylene-diamine-tetraacetic acid (ETDA) samples with and without bovine serum albumin (BSA) from 82 CLL patients. Group 1 adhered to NCCLS specifications for the preparations of EDTA blood films. Group 2 consisted of blood films containing EDTA and a 1:12 dilution of 22% BSA. Eight patients were selected for digital photomicroscopy and statistical analysis. Approximately 100 lymphocytes from each slide were digitally captured.

RESULTS: The mean cell area +/- standard …

Creation Of Non-Human Primate Neurogenetic Disease Models By Gene Targeting And Nuclear Transfer, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

Genetically modified rhesus macaques are necessary because mouse models are not suitable for a number of important neurogenetic disorders; for example, Kallmann's syndrome, Lesch-Nyhan's disease and Ataxia-Telangiectasia. Mouse models may not be suitable because there may be no mouse ortholog of the human gene of interest, as is the case for Kallmann's syndrome, or because mutant mice do not exhibit the same phenotype observed in humans, as is the the case for Lesch-Nyhan's disease and Ataxia-Telangiectasia. Non-human primate models of neurogenetic diseases are expected to more closely resemble human diseases than existing mouse models. Genetically modified rhesus macaques can be …

Surveillance For Waterborne-Disease Outbreaks Associated With Drinking Water--United States, 2001-2002, Brian G. Blackburn, Gunther F. Craun, Jonathan S. Yoder, Vincent Hill, Rebecca L. Calderon, Nora Chen, Sherline H. Lee, Deborah A. Levy, Michael J. Beach

Journal Articles: Epidemiology

PROBLEM/CONDITION: Since 1971, CDC, the U.S. Environmental Protection Agency, and the Council of State and Territorial Epidemiologists have maintained a collaborative surveillance system for collecting and periodically reporting data related to occurrences and causes of waterborne-disease outbreaks (WBDOs). This surveillance system is the primary source of data concerning the scope and effects of waterborne disease outbreaks on persons in the United States.

REPORTING PERIOD COVERED: This summary includes data on WBDOs associated with drinking water that occurred during January 2001-December 2002 and on three previously unreported outbreaks that occurred during 2000.

DESCRIPTION OF SYSTEM: Public health departments in the states, …

Sars Surveillance During Emergency Public Health Response, United States, March-July 2003, Stephanie J. Schrag, John T. Brooks, Chris Van Beneden, Umesh D. Parashar, Patricia M. Griffin, Larry J. Anderson, William J. Bellini, Robert F. Benson, Dean D. Erdman, Alexander Klimov, Thomas G. Ksiazek, Teresa C. T. Peret, Deborah F. Talkington, W. Lanier Thacker, Maria L. Tondella, Jacquelyn S. Sampson, Allen W. Hightower, Dale F. Nordenberg, Brian D. Plikaytis, Ali S. Khan, Nancy E. Rosenstein, Tracee A. Treadwell, Cynthia G. Whitney, Anthony E. Fiore, Tonji M. Durant, Joseph F. Perz, Annemarie Wasley, Daniel Feikin, Joy L. Herndon, William A. Bower, Barbara W. Klibourn, Deborah A. Levy, Victor G. Coronado, Joanna Buffington, Clare A. Dykewicz, Rima F. Khabbaz, Mary E. Chamberland

Journal Articles: Epidemiology

In response to the emergence of severe acute respiratory syndrome (SARS), the United States established national surveillance using a sensitive case definition incorporating clinical, epidemiologic, and laboratory criteria. Of 1,460 unexplained respiratory illnesses reported by state and local health departments to the Centers for Disease Control and Prevention from March 17 to July 30, 2003, a total of 398 (27%) met clinical and epidemiologic SARS case criteria. Of these, 72 (18%) were probable cases with radiographic evidence of pneumonia. Eight (2%) were laboratory-confirmed SARS-coronavirus (SARS-CoV) infections, 206 (52%) were SARS-CoV negative, and 184 (46%) had undetermined SARS-CoV status because of …

Did A Severe Flood In The Midwest Cause An Increase In The Incidence Of Gastrointestinal Symptoms?, Timothy J. Wade, Sukhminder K. Sandhu, Deborah A. Levy, Sherline Lee, Mark W. Lechevallier, Louis Katz, John M. Colford

Journal Articles: Epidemiology

Severe flooding occurred in the midwestern United States in 2001. Since November 2000, coincidentally, data on gastrointestinal symptoms had been collected for a drinking water intervention study in a community along the Mississippi River that was affected by the flood. After the flood had subsided, the authors asked these subjects (n = 1,110) about their contact with floodwater. The objectives of this investigation were to determine whether rates of gastrointestinal illness were elevated during the flood and whether contact with floodwater was associated with increased risk of gastrointestinal illness. An increase in the incidence of gastrointestinal symptoms during the flood …

Epidemiologic And Environmental Investigation Of A Recreational Water Outbreak Caused By Two Genotypes Of Cryptosporidium Parvum In Ohio In 2000, Els Mathieu, Deborah A. Levy, Fran Veverka, Mary-Kay Parrish, John Sarisky, Nancy Shapiro, Stephanie Johnston, Thomas Handzel, Allen Hightower, Lihua Xiao, Yeuk-Mui Lee, Steve York, Michael Arrowood, Robin Lee, Jeffrey L. Jones

Journal Articles: Epidemiology

In August 2000, the Ohio Department of Health requested assistance to investigate a cryptosporidiosis outbreak with more than 700 clinical case-patients. An epidemiologic and environmental investigation was conducted. Stool specimens, pool water, and sand filter samples were analyzed. A community-based case-control study showed that the main risk factor was swimming in pool A (odds ratio [OR] = 42, 95% confidence interval [CI] = 12.3-144.9). This was supported by results of polymerase chain reaction (PCR) analysis, which showed the presence of both the human and bovine genotypes of Cryptosporidium parvum in case-patients and samples from the filter of pool A. A …

Surveillance For Waterborne-Disease Outbreaks Associated With Recreational Water--United States, 2001-2002, Jonathan S. Yoder, Brian G. Blackburn, Gunther F. Craun, Vincent Hill, Deborah A. Levy, Nora Chen, Sherline H. Lee, Rebecca L. Calderon, Michael J. Beach

Journal Articles: Epidemiology

PROBLEM/CONDITION: Since 1971, CDC, the U.S. Environmental Protection Agency, and the Council of State and Territorial Epidemiologists have maintained a collaborative surveillance system for collecting and periodically reporting data related to occurrences and causes of waterborne-disease outbreaks (WBDOs) related to drinking water; tabulation of recreational water-associated outbreaks was added to the surveillance system in 1978. This surveillance system is the primary source of data concerning the scope and effects of waterborne disease outbreaks on persons in the United States.

REPORTING PERIOD COVERED: This summary includes data on WBDOs associated with recreational water that occurred during January 2001-December 2002 and on …