Robert S. Redman

Bio: Robert S. Redman is an academic researcher from United States Department of Veterans Affairs. The author has contributed to research in topics: Salivary gland & Submandibular gland. The author has an hindex of 30, co-authored 89 publications receiving 2870 citations. Previous affiliations of Robert S. Redman include Georgetown University & University of Colorado Boulder.

Periodontitis and Porphyromonas gingivalis in patients with rheumatoid arthritis.

Abstract: Periodontitis (PD) has emerged as a risk factor in a number of health conditions including rheumatoid arthritis (RA) (1). Sharing both morphologic and histopathologic similarities with RA (2), PD is an inflammatory disease initiated by bacterial infection resulting in soft and hard tissue destruction and ultimately leading to tooth loss. In addition to shared inflammatory pathways, PD and RA share risk factors for susceptibility and progression, most notably cigarette smoking and, possibly, shared epitope-containing HLA-DRB1 alleles, the latter associated with localized aggressive periodontitis (3–10). Although a causal link between these conditions has not been established, several reports have demonstrated an increased PD prevalence in RA patients compared to controls (11–18). Growing evidence suggests that pathogens associated with PD could play a role in RA propagation. Chief among the organisms of interest is Porphyromonas gingivalis (P. gingivalis) (19). P. gingivalis is the only known pathogen expressing peptidylarginine deiminase (PPAD). Similar to its human counterpart, P. gingivalis-expressed PAD catalyzes the citrullination of arginine-containing peptides. This is noteworthy because citrullinated antigens are thought to drive adaptive immune responses that are nearly exclusive to RA. The potential role of P. gingivalis in RA pathogenesis has been borne out in epidemiologic investigations. Concentrations of circulating antibody to P. gingivalis have been demonstrated to be associated with the expression of anti-citrullinated peptide antibody (ACPA) (20–22). More recently, our group has shown that antibody to P. gingivalis is associated with the presence of RA-related autoantibody (a combination of rheumatoid factor [RF] and/or ACPA) among individuals at increased risk for disease but who have not yet developed RA symptoms (23), underscoring the potential role of this pathogen in RA development. As part of the present study, we conducted a large case-control investigation to examine the relationship of PD with established RA. We sought to examine the degree to which this relationship is impacted by shared genetic and/or environmental factors. We also sought to elucidate the degree to which the relationship of PD with RA may be related to infection and/or colonization with P. gingivalis. By using a rigorously selected control population, we attempted to mitigate issues of bias or unmeasured confounding that may have impacted other efforts often using healthy volunteers as comparators (16–18). Finally, using a multiplex approach, we examined the associations of PD and P. gingivalis with autoreactivity to several citrullinated autoantigens that have been implicated in RA disease pathogenesis.

Association of Periodontitis With Rheumatoid Arthritis: A Pilot Study

Abstract: 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.) veterans with RA and their relationship to RA disease activity and severity.Methods: Patients with RA from an outpatient rheumatology clinic were eligible, and patients with osteoarthritis (OA) served as controls. Dentists, masked to the rheumatologic diagnoses, performed periodontal probing and examined dental panoramic radiographs to assess the presence and severity of periodontitis. Associations of periodontitis with RA were examined using multivariate regression, whereas the association of periodontitis with disease-severity measures in RA was examined using the χ2 test.Results: Sixty-nine patients with RA (57 males and 12 females) and 35 patients with OA (30 males and five females) were studied. ...

Myoepithelium of salivary glands.

Abstract: In salivary glands and other exocrine organs, there are starfish-shaped cells that lie between the basal lamina and the acinar and ductal cells. These have structural features of both epithelium and smooth muscle cells, and so are called myoepithelial cells. Their functions include contraction when the gland is stimulated to secrete, compressing or reinforcing the underlying parenchymal cells, thus aiding in the expulsion of saliva and preventing damage to the other cells. They also may aid in the propagation of secretory and other stimuli. Their common developmental origin with the basal cells of the larger ducts is displayed in the mature glands by shared structural and immunohistochemical features, but most such basal cells do not have the distinguishing features of myoepithelial cells, such as myofibrils. Although myoepithelial cells can be identified by light microscopy through enzyme histochemistry and special stains and immunohistochemistry for their myofibrils, these techniques can be misleading in salivary gland neoplasms. Thus, the most reliable means of identifying neoplastic myoepithelial cells is with a combination of histochemistry and electron microscopy. The extent to which these cells are derived from undifferentiated stem cells in both normal and neoplastic growth is controversial. The presentation here of transmission electron microscopy (TEM) of well-differentiated myoepithelial cells in mitotic division indicates that stem cells are not necessarily the only source of myoepithelial cells in the later stages of salivary gland development or in neoplasia.

Immediate inflammatory responses to adenovirus-mediated gene transfer in rat salivary glands

Abstract: Although replication-deficient adenoviruses can efficiently transfer genes to the salivary glands, the current vectors precipitate an immediate, transient decrease in salivary function. To study the cause of this salivary hypofunction, 10(6)-10(10) plaque-forming units (pfu) of the vector AdCMV beta gal were delivered by retrograde ductal infusion to the submandibular glands (SMGs) of rats. Microscopic analysis of infected glands showed a dose-related, rapidly developing inflammatory response, which at the highest amount of virus was characterized by a predominantly neutrophil-containing infiltrate, focal necrosis, and edema. Moreover, the glands of nude rats developed similar morphologic changes to those of immunocompetent rats. After 3 days, the volume of stimulated saliva secreted from SMGs receiving AdCMV beta gal (6.75 x 10(9) pfu) was approximately 20% that of controls. UV-inactivated virus caused a similar decrease in saliva output. We evaluated to what extent the anti-inflammatory glucocorticoid, dexamethasone, could suppress inflammation and preserve salivary function. Three days after infusion with a high dose of AdCMV beta gal (6.75 x 10(9) pfu), the glands from dexamethasone-treated animals showed markedly less inflammation and no necrosis. Furthermore, there was no significant difference in the average amount of saliva secreted from the infected glands (105 +/- 17 microliters) compared to the control glands (123 +/- 18 microliters). In addition, dexamethasone extended the expression of beta-galactosidase in the SMGs. These results suggest that the adenovirus-mediated acute inflammation in rat SMG is responsible for diminished gland function and transgene expression. Furthermore, we demonstrate a useful role for glucocorticoids in controlling acute inflammation during experimental gene transfer with current adenovirus vectors.

Intestinal mucosal barrier function in health and disease.

Abstract: Mucosal surfaces are lined by epithelial cells. These cells establish a barrier between sometimes hostile external environments and the internal milieu. However, mucosae are also responsible for nutrient absorption and waste secretion, which require a selectively permeable barrier. These functions place the mucosal epithelium at the centre of interactions between the mucosal immune system and luminal contents, including dietary antigens and microbial products. Recent advances have uncovered mechanisms by which the intestinal mucosal barrier is regulated in response to physiological and immunological stimuli. Here I discuss these discoveries along with evidence that this regulation shapes mucosal immune responses in the gut and, when dysfunctional, may contribute to disease.

Periodontitis: from microbial immune subversion to systemic inflammation

Abstract: Periodontitis is a dysbiotic inflammatory disease with an adverse impact on systemic health. Recent studies have provided insights into the emergence and persistence of dysbiotic oral microbial communities that can mediate inflammatory pathology at local as well as distant sites. This Review discusses the mechanisms of microbial immune subversion that tip the balance from homeostasis to disease in oral or extra-oral sites.

TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function.

Abstract: Progressive kidney failure is a genetically and clinically heterogeneous group of disorders. Podocyte foot processes and the interposed glomerular slit diaphragm are essential components of the permeability barrier in the kidney. Mutations in genes encoding structural proteins of the podocyte lead to the development of proteinuria, resulting in progressive kidney failure and focal segmental glomerulosclerosis. Here, we show that the canonical transient receptor potential 6 (TRPC6) ion channel is expressed in podocytes and is a component of the glomerular slit diaphragm. We identified five families with autosomal dominant focal segmental glomerulosclerosis in which disease segregated with mutations in the gene TRPC6 on chromosome 11q. Two of the TRPC6 mutants had increased current amplitudes. These data show that TRPC6 channel activity at the slit diaphragm is essential for proper regulation of podocyte structure and function.