An immunohistochemical study of the vasculature and stem cells and carbonic anhydrase IV in the ducts of irradiated and normal human submandibular salivary glands.

Therapeutic irradiation for cancers of the head and neck causes serious and irreversible damage to the salivary glands; the resulting adverse effects on salivary quality and quantity produce detrimental effects on teeth and oral mucosa. The salivary effects have been related mostly to loss of serous acini; damage to the ducts is relatively minor. Other radiation effects include fibrosis, adiposis and vascular damage.

Identifying stem cells in the main excretory ducts of rat major salivary glands: adventures with commercial antibodies.

We investigated the entire length of the main excretory ducts (MED) of the major sublingual, parotid and submandibular salivary glands of mature laboratory rats for mucous (goblet) and luminal ciliated cells, biomarkers of cell proliferation, apoptosis, and five biomarkers of stem cells. Spleen and testis were used as positive controls. We used formalin fixed, paraffin embedded tissues.

Follow-up study of veterans with white and red oral mucosal lesions at Veterans Affairs Dental Clinics.

Objectives: This analysis examined the clinical and histopathological characteristics of white and red oral mucosal lesions and patient lifestyle behaviors to understand how the lesions changed over 19-23 years, including among patients who developed oral and pharyngeal cancer.

Materials And Methods: Seventy-five individuals with red and/or white oral mucosal lesions with clinical diagnoses of smokeless tobacco lesions, leukoplakia, erythroplakia, lichen planus, ulcer, and virus-associated lesions were identified in six Veterans Affairs Medical Center Dental Clinics (VAMC) from 1996 to 2001. Biopsy results and patients' sociodemographic, medical, and tobacco/alcohol use characteristics were obtained.

Donepezil inhibits neuromuscular junctional acetylcholinesterase and enhances synaptic transmission and function in isolated skeletal muscle.

Background And Purpose: Donepezil, a piperidine inhibitor of acetylcholinesterase (AChE) prescribed for treatment of Alzheimer's disease, has adverse neuromuscular effects in humans, including requirement for higher concentrations of non-depolarising neuromuscular blockers during surgery. Here, we examined the effects of donepezil on synaptic transmission at neuromuscular junctions (NMJs) in isolated nerve-muscle preparations from mice.

Experimental Approach: We measured effects of therapeutic concentrations of donepezil (10 nM to 1 μM) on AChE enzymic activity, muscle force responses to repetitive stimulation, and spontaneous and evoked endplate potentials (EPPs) recorded intracellularly from flexor digitorum brevis muscles from CD01 or C57BlWld mice.

"Calcium bombs" as harbingers of synaptic pathology and their mitigation by magnesium at murine neuromuscular junctions.

Excitotoxicity is thought to be an important factor in the onset and progression of amyotrophic lateral sclerosis (ALS). Evidence from human and animal studies also indicates that early signs of ALS include degeneration of motor nerve terminals at neuromuscular junctions (NMJs), before degeneration of motor neuron cell bodies. Here we used a model of excitotoxicity at NMJs in isolated mouse muscle, utilizing the organophosphorus (OP) compound omethoate, which inhibits acetylcholinesterase activity.

Immunohistochemical localization of carbonic anhydrase IV in the human parotid gland.

Carbonic anhydrases (CAs) catalyze the hydration and dehydration of carbon dioxide. They are important for regulating ions, fluid and acid-base balance in many tissues. The location of CAs by cell type is important for understanding their roles in these functions.

Immunohistochemical profile of the anti-apoptosis, apoptosis and proliferation markers Bcl-2, caspase-3, p53, and Ki-67 in botryoid odontogenic cysts compared to lateral periodontal cysts and gingival cysts of the adult.

We investigated the differences in growth and rates of recurrence of the botryoid odontogenic cyst (BOC) and the less aggressive lateral periodontal cyst (LPC) and gingival cyst of the adult (GCA). We compared the immunohistochemical expression of selected biomarkers of apoptosis and proliferation and of regulators of their activity. Sections from archival paraffin blocks of 15 BOCs, six GCAs, six LPCs, and three odontogenic keratocysts (OKCs) were processed for immunohistochemical localization of Bcl-2, caspase-3, p53 and Ki-67.

Positive Association Between Neutrophil-Lymphocyte Ratio and Presence of Panoramically Imaged Carotid Atheromas Among Men.

Purpose: Heightened levels of systemic inflammation documented by increased neutrophil-to-lymphocyte ratios (NLRs) characterize a robust atherosclerosis processes evidenced by carotid and coronary artery plaques at ultrasound and angiography with associated strokes and myocardial infarctions (MIs). Therefore, this study investigated whether calcified carotid artery plaques (CCAPs) on panoramic images (PIs), known to herald future stroke and MI, are associated with increased NLRs.

Materials And Methods: Using a cross-sectional study design, electronic medical records and PIs of non-Hispanic white men at least 55 years old who were treated by the dental service (January 1, 2017 to December 31, 2017) were retrieved.

Microcalcifications in stone-obstructed human submandibular gland are associated with apoptosis and cell proliferation.

Objective: Human submandibular gland (SMG) stones are associated with inflammation, fibrosis and microcalcifications in the surrounding tissues. However, there is little information about the accompanying cell injury-repair process, apoptosis, and cell proliferation. The purpose of this study was to investigate such an association and its clinical significance.

Effects of glucose and sucrose variants of the caries-promoting Diet 2000 on the feeding patterns and parotid glands of prematurely weaned rats.

Objective: The hypothesis of this study was that feeding glucose instead of sucrose in the cariogenic Diet 2000 to rats weaned at age 18 days would result in greater light/dark differences in feeding activity and secretion and storage of parotid salivary enzymes.

Design Of Study: Diet 2000 and a stock commercial diet (controls) were prepared in pelleted and powdered forms, as the increased mastication required by pellets has been shown to support circadian rhythms in rats. Food jars were weighed at lights on and just prior to lights off daily.

Performance of self-reported measures for periodontitis in rheumatoid arthritis and osteoarthritis.

Background: This study evaluates the performance of self-report against the reference standard of clinically defined periodontitis in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) after accounting for factors associated with periodontitis.

Methods: Six self-report periodontitis questions were evaluated in patients with RA and OA. Questions were validated against a reference standard of severe and moderate-to-severe periodontitis based on full-mouth examination.

Periodontitis and Porphyromonas gingivalis in patients with rheumatoid arthritis.

Objective: To examine the degree to which shared risk factors explain the relationship of periodontitis (PD) to rheumatoid arthritis (RA) and to determine the associations of PD and Porphyromonas gingivalis with pathologic and clinical features of RA.

Methods: Patients with RA (n = 287) and patients with osteoarthritis as disease controls (n = 330) underwent a standardized periodontal examination. The HLA-DRB1 status of all participants was imputed using single-nucleotide polymorphisms from the extended major histocompatibility complex.

CYP2E1, oxidative stress, post-translational modifications and lipid metabolism.

Chronic alcohol-mediated down-regulation of hepatic ST6Gal1 gene leads to defective glycosylation of lipid-carrying apolipoproteins such as apo E and apo J, resulting in defective VLDL assembly and intracellular lipid and lipoprotein transport, which in turn is responsible for alcoholic hepatosteatosis and ALD. The mechanism of ethanol action involves thedepletion of a unique RNA binding protein that specifically interacts with its 3'-UTR region of ST6Gal1 mRNA resulting in its destabilization and consequent appearance of asialoconjugates as alcohol biomarkers. With respect to ETOH effects on Cardio-Vascular Diseases, we conclude that CYP2E1 and ETOH mediated oxidative stress significantly down regulates not only the hepatic PON1 gene expression, but also serum PON1 and HCTLase activities accompanied by depletion of hepatic GSH, the endogenous antioxidant.

Microchimerism in salivary glands after blood- and marrow-derived stem cell transplantation.

Blood- and marrow-derived stem cells (BMDSCs) provide disease-ameliorating effects for cardiovascular and autoimmune diseases. Microchimerism from donor BMDSCs has been reported in several recipient tissues. We hypothesized that this finding suggests a potential use of BMDSCs in the treatment of salivary dysfunctions.

Association of periodontitis with rheumatoid arthritis: a pilot study.

Background: Similarities exist in the epidemiology and immunopathogenesis of periodontitis and rheumatoid arthritis (RA), but the associations between their respective disease activities and severities are less well documented. We evaluated the prevalence and severity of periodontitis in United States (U.S.

Isolation of intact nuclei of high purity from mouse liver.

Current methods of nuclear isolation from liver disrupt the plasmalemmae via homogenization and separation of the nuclei by high centrifugal force (HCF) through gradients of sucrose or other substances for up to 80 min. The use of HCF for such a long time increases the potential for nuclear damage and degradation by endogenous proteases. We compared four combinations of alterations to classical nuclear isolation methods as follows.

Down-regulation of liver Galbeta1, 4GlcNAc alpha2, 6-sialyltransferase gene by ethanol significantly correlates with alcoholic steatosis in humans.

Hepatic steatosis and steatohepatitis are frequent results of long-term ethanol exposure. We have previously demonstrated that long-term ethanol down-regulates Galbetal, 4GlcNAc alpha2, 6-sialyltransferase (ST6Gal1), leading to defective glycosylation of a number of proteins including apolipoprotein (apo) E and apo J and the appearance of asialoconjugates in the blood of continuously alcohol-fed animals as well as in human alcoholics. In the current study, we have explored the possibility of whether ethanol-induced down-regulation of ST6Gal1 could contribute toward alcoholic steatosis in human alcoholics presumably because of impaired lipid and lipoprotein transport caused by this down-regulation.

Proinflammatory cytokines tumor necrosis factor-alpha and interferon-gamma alter tight junction structure and function in the rat parotid gland Par-C10 cell line.

Sjögren's syndrome (SS) is an autoimmune disorder characterized by inflammation and dysfunction of salivary glands, resulting in impaired secretory function. The production of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) is elevated in exocrine glands of patients with SS, although little is known about the effects of these cytokines on salivary epithelial cell functions necessary for saliva secretion, including tight junction (TJ) integrity and the establishment of transepithelial ion gradients. The present study demonstrates that chronic exposure of polarized rat parotid gland (Par-C10) epithelial cell monolayers to TNF-alpha and IFN-gamma decreases transepithelial resistance (TER) and anion secretion, as measured by changes in short-circuit current (I(sc)) induced by carbachol, a muscarinic cholinergic receptor agonist, or UTP, a P2Y(2) nucleotide receptor agonist.

Effects of exogenous thyroid hormone on the postnatal morphogenesis of the rat parotid gland.

Administration of thyroid hormone has been shown to accelerate the early postnatal development of the rat parotid gland, but these studies have dwelt almost entirely on biochemical changes. The objective of this study was to describe the effects of exogenous thyroid hormone on morphologic aspects of the developing parotid gland, in particular the transient appearance of scattered mucous cells in this otherwise serous gland. Pups were given a daily subcutaneous injection of thyroxine (T(4)) of 0.

Self-awareness of premalignant oral lesions among veterans attending six U.S. Veterans Affairs Medical Centers.

Early identification is key to reducing the morbidity and mortality of oropharyngeal cancer. This study identified factors associated with self-awareness among patients newly diagnosed with a premalignant oral lesion. Data describing sociodemographics, medical/dental histories, tobacco/alcohol use and oral health were obtained by questionnaire and clinical examination of 73 veterans at six U.

Further evidence for AQP8 expression in the myoepithelium of rat submandibular and parotid glands.

Previously (Wellner et al., Pflugers Arch 441:49-56, 2000) we suggested that the localization of the aquaporins (AQPs) AQP5 and AQP8 in the apical and basolateral membranes of rat submandibular gland (SMG) acinar cells, respectively, provides for transcellular water flow during saliva formation. While the localization of AQP5 in this gland has been verified in several laboratories, there have been differing reports regarding AQP8 localization.

Transforming growth factor-beta suppresses nonmetastatic colon cancer through Smad4 and adaptor protein ELF at an early stage of tumorigenesis.

Although transforming growth factor-beta (TGF-beta) is both a suppressor and promoter of tumorigenesis, its contribution to early tumor suppression and staging remains largely unknown. In search of the mechanism of early tumor suppression, we identified the adaptor protein ELF, a beta-spectrin from stem/progenitor cells committed to foregut lineage. ELF activates and modulates Smad4 activation of TGF-beta to confer cell polarity, to maintain cell architecture, and to inhibit epithelial-to-mesenchymal transition.

Apical localization of a functional TRPC3/TRPC6-Ca2+-signaling complex in polarized epithelial cells. Role in apical Ca2+ influx.

Receptor-coupled [Ca2+]i increase is initiated in the apical region of epithelial cells and has been associated with apically localized Ca2+-signaling proteins. However, localization of Ca2+ channels that are regulated by such Ca2+-signaling events has not yet been established. This study examines the localization of TRPC channels in polarized epithelial cells and demonstrates a role for TRPC3 in apical Ca2+ uptake.

Orofacial and gastrointestinal hyperplasia and neoplasia in smad4+/- and elf+/-/smad4+/- mutant mice.

Background: Smad4 is vital to the roles of Smads 2 and 3 in transforming growth factor-beta (TGF)-beta signal transduction, and inactivated Smad4 is common to human gastrointestinal cancers. The embryonic liver fodrin (ELF) is a beta-spectrin that facilitates the nuclear translocation of activated Smad4.

Methods: Smad4+/- mice, known to develop gastrointestinal cancer, were crossbred with elf+/- mice.