Abstract:
:Exposed to a diverse array of potentially noxious agents, the respiratory tract is protected by a highly developed innate defense system. Physiologically regulated epithelial ion and water transport coordinated with mucin secretion, beating cilia, and cough results in continuous flow of fluid and mucus over airway surfaces toward the larynx. This cleansing action is the initial and perhaps most quantitatively important innate defense mechanism. Repeated lung infections and eventual respiratory insufficiency characteristic of human cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) illustrate the consequences of impaired mucus clearance. Altered mucus clearance likely contributes to the initiation, progression, and chronicity of other airway diseases characterized by inflammation and mucous secretory cell hyper/metaplasia that afflict millions worldwide, including chronic obstructive pulmonary disease (COPD). This review concisely discusses the pathophysiology of human diseases characterized by genetic defects that impair mucus clearance. It then explores animal models in which components of the mucus clearance system have been disrupted. These models firmly establish the importance of mucus clearance for respiratory health, and will help elucidate disease mechanisms and therapeutic strategies in CF, PCD and COPD.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Livraghi A,Randell SHdoi
10.1080/01926230601060025subject
Has Abstractpub_date
2007-01-01 00:00:00pages
116-29issue
1eissn
0192-6233issn
1533-1601pii
770781273journal_volume
35pub_type
杂志文章,评审abstract::Aging is a multifactorial process associated with functional deficits, and the brain is more prone to developing chronic degenerative diseases such as Parkinson's disease. Several groups have tried to correlate the age-related ultrastructural alterations to the neurodegeneration process using in vivo pharmacological m...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623318767065
更新日期:2018-04-01 00:00:00
abstract::Overexpression of c-myc and transforming growth factor-alpha (TGF-alpha) has been frequently observed in human hepatocellular carcinoma (HCC),suggesting a pivotal role played by these protooncogenes in liver oncogenesis. In order to investigate the molecular events underlying human hepatic malignant transformation, we...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230590522095
更新日期:2005-01-01 00:00:00
abstract::Macrophages appearing in lesions are polarized toward M1 (for inflammation) and M2 (for anti-inflammation/fibrosis) types. We analyzed immunophenotypes of macrophages appearing in myocardial lesion in rats injected once with isoproterenol (10 mg/kg body weight). Inflammation following myocardial necrosis on day 1 was ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623320982526
更新日期:2021-01-05 00:00:00
abstract::The preclinical safety of RPR 106541, a novel 17-thiosteroid, was evaluated in young adult and mature dogs by inhalation exposure for 26 weeks and 52 weeks, respectively. A dry powder formulation of RPR 106541 in lactose was administered to young adult dogs (approximately 6 months of age at initiation) at doses of 0 (...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262330002800202
更新日期:2000-03-01 00:00:00
abstract::Histopathology is a widely used approach to evaluate effects of endocrine-active chemicals in the thyroid. However, effects at an ultrastructural level have hardly been examined in fish thyroids. In the present study, zebrafish was exposed to sublethal concentrations of propylthiouracil (PTU; 0-50 mg/L) and perchlorat...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623317721748
更新日期:2017-07-01 00:00:00
abstract::The evaluation of neurotoxic damage involves a unique set of challenges. Vulnerable structures, such as neocortex, hippocampus, spinal cord, and peripheral nerve are complex and sharply differentiated; deficits can result from insults to one or more element(s) in the system (e.g., myelin, axon, soma, synapse, or glia)...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623310390231
更新日期:2011-01-01 00:00:00
abstract::Analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) are well recognized as a major class of therapeutic agent that causes renal papillary necrosis (RPN). Over the last decade a broad spectrum of other therapeutic agents and many chemicals have also been reported that have the potential to cause this lesion in...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262339802600110
更新日期:1998-01-01 00:00:00
abstract::Laser scanning cytometry (LSC) is a powerful tool for qualitative and quantitative analysis of tissue sections in preclinical drug development. LSC combines the strengths of flow cytometry with tissue architecture retention. This technology has been used predominantly with immunofluorescent techniques on cell culture ...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623307312704
更新日期:2008-01-01 00:00:00
abstract::The spleen is the largest secondary lymphoid organ, is considered the draining site for compounds that are administered intravenously, and is therefore considered an important organ to evaluate for treatment-related lesions. Due to the presence of B and T lymphocytes, the immunotoxic effects of xenobiotics or their me...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230600865523
更新日期:2006-01-01 00:00:00
abstract::Expression of antigens in cells and tissues can be readily studied immunohistochemically with the use of antibodies. A panel of antibodies to cell-specific markers can be used to diagnose lesions, including tumors, in the hematopoietic and lymphoid systems. This review discusses the use of readily available antibodies...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623311430695
更新日期:2012-01-01 00:00:00
abstract::Exposure to synthetic fibers with employment in textile mills can be associated with an elevated risk of interstitial lung disease (ILD). A mechanism of injury has not been determined. ILD can follow exposures to inorganic fibers (e.g., asbestos) which are associated with a mobilization of iron and catalysis of an oxi...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230600932448
更新日期:2006-01-01 00:00:00
abstract::The two-year rodent bioassay is one of several tests that are widely used by governmental regulatory agencies as well as pharmaceutical and chemical companies to determine the carcinogenic potential of chemicals or environmental agents where human exposure is anticipated. That this assay has remained relatively unchan...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230390201273
更新日期:2003-07-01 00:00:00
abstract::Age-related changes in gross and microscopic structure of the nasal cavity may alter local tissue susceptibility as well as the dose of inhaled toxicant delivered to susceptible sites. This article describes a novel method for the use of magnetic resonance imaging, 3-dimensional airway modeling, and morphometric techn...
journal_title:Toxicologic pathology
pub_type: 杂志文章,多中心研究
doi:10.1080/01926230601072343
更新日期:2007-01-01 00:00:00
abstract::Hyaline droplet formation in the proximal tubular cells of the kidney commonly occurs under different pathological conditions in experimental animals. In rats, intracytoplasmic hyaline droplet formation is predominantly associated with accumulation of the male rat-specific alpha(2u)-globulin, whereas under other (path...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230390213775
更新日期:2003-07-01 00:00:00
abstract::Helicobacter hepaticus infection induces sustained inflammation and carcinoma of the liver in A/JCr mice, and serves as a model of human cancers associated with viral hepatitis and H. pylorichronic gastritis. Here we describe the pathogenesis of premalignant disease in A/JCr mice infected with H. hepaticus. We inocula...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230490524247
更新日期:2004-11-01 00:00:00
abstract::Alternate transgenic mouse models are accepted as replacements for the standard carcinogenicity mouse bioassay by regulatory agencies with a companion 2-year rat bioassay. The slower rate of industry acceptance of these shorter transgenic mouse cancer bioassays has been due to lack of historical data and diagnostic cr...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623311436181
更新日期:2012-06-01 00:00:00
abstract::Nephrotoxic renal injury, and especially drug nephrotoxicity is now a common cause of acute renal failure. The most common patterns of renal injury produced by nephrotoxins, tubular damage, and interstitial nephritis, are discussed here. Toxic agents which are primarily tubular toxins include certain antibiotics, cisp...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338601400106
更新日期:1986-01-01 00:00:00
abstract::Although arsenic exposure causes liver disease and/or hepatoma, little is known about molecular mechanisms of arsenic-induced liver toxicity or carcinogenesis. We investigated the effects of arsenic on expression of cancer-related genes in a rat liver following subchronic exposure to sodium arsenate (1, 10, 100 ppm in...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230490261348
更新日期:2004-01-01 00:00:00
abstract::Osteogenic Protein-1 (OP-1) is a bone morphogen involved in tissue repair and development. We have shown that OP-1 is downregulated during acute ischemic renal injury. Here we report the use of the rat remnant kidney model (RRKM) to evaluate changes in kidney OP-1 expression during chronic injury, and determine if tre...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230490440925
更新日期:2004-07-01 00:00:00
abstract::Cyclodextrins are oligosaccharides which are used in the pharmaceutical industry and research as vehicles for application of apolar substances such as steroids. The aim of this study was to examine the long-term effects of parenteral administration of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) on bone. Sham-operated (SH...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623312441405
更新日期:2012-07-01 00:00:00
abstract::Documentation of Chinese materia medica (CMM) dates back to around 1,100 BC when only dozens of drugs were first described. By the end of the 16th century, the number of drugs documented had reached close to 1,900. And by the end of the last century, published records of CMM have reached 12,800 drugs. The recorded tra...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230600773958
更新日期:2006-01-01 00:00:00
abstract::To investigate pathogenesis of post-bile duct (BD) injury fibrosis, interlobular BD epithelial injury was induced in male F344 rats by a single IP injection of α-naphthylisothiocyanate (75 mg/kg body weight) and rats were observed for 12 days. On days 1 to 2, cholangiocytes were injured and desquamated. On days 3 to 5...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623311413790
更新日期:2011-08-01 00:00:00
abstract::Clinical, pathologic, and analytical records from 200 cattle were reviewed to determine if long-term exposures to elevated fluorides resulted in previously unrecognized or unreported pathologic changes, especially skeletal neoplasia. Animals were part of comprehensive field and laboratory investigations of bovine fluo...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339202000216
更新日期:1992-01-01 00:00:00
abstract::d-galactosamine (d-GalN) is a well-known hepatotoxic agent that causes liver injury. Conversely, hepatic macrophages play a crucial role in maintaining liver tissue integrity. Macrophage functions were investigated in hepatic lesions induced by a single intraperitoneal injection of d-GalN (800 mg/kg body weight [BW]) ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623318801574
更新日期:2018-10-01 00:00:00
abstract::The first part of this paper focuses on the secondary immunodeficiencies caused by immunosuppressive drugs and environmental chemicals. The mechanism of action and the therapeutic effects of azathioprine, glucocorticosteroids, cyclophosphamide, cyclosporin A, and anticancer drugs will be discussed. The immunotoxic act...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262338701500310
更新日期:1987-01-01 00:00:00
abstract::The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak that started in Wuhan, China, in 2019 resulted in a pandemic not seen for a century, and there is an urgent need to develop safe and efficacious vaccines. The scientific community has made tremendous efforts to understand the disease, and unpara...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623320959090
更新日期:2020-10-01 00:00:00
abstract::Statistical issues related to the design, analysis and interpretation of carcinogenicity studies are considered. A proposed modification of the "standard" National Cancer Institute (NCI) design of carcinogenicity studies in rodents is discussed. The primary objective was to obtain a design that maintained the power of...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338301100113
更新日期:1983-01-01 00:00:00
abstract::The mechanisms underlying the development of gastrointestinal (GI) damage by the NSAIDs differ considerably from drug to drug. Aside from environmental or intersubject influence (e.g., concurrent disease, physical or sociopsychologic stress, dietary and genetic status), the intrinsic pharmacokinetic and physicochemica...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262338801600218
更新日期:1988-01-01 00:00:00
abstract::A compendium of carcinogenesis bioassay results organized by target organ is presented for 738 chemicals that are carcinogenic in chronic-exposure, long-term bioassays in at least 1 species. This compendium is based primarily on experiments in rats or mice; results in hamsters, monkeys, and dogs are also reported. The...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/019262301753385979
更新日期:2001-11-01 00:00:00
abstract::Previous work in our laboratory revealed that the pubertal period of reproductive development in the male rat was particularly vulnerable to gossypol exposure, with a higher frequency of round structures in the lumen of the cauda epididymidis in the treated rats. Herein, we utilized hemicastration and electron microsc...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230600932455
更新日期:2006-01-01 00:00:00