Steven London - Academia.edu (original) (raw)

Papers by Steven London

Journal of Dental Education, 2019

The aim of this study was to assess the development of personalized dentistry in the curricula of... more The aim of this study was to assess the development of personalized dentistry in the curricula of North American dental schools from 2014 to 2017. In 2014, a web-based survey on personalized medicine/dentistry (PM/PD) was distributed to academic deans of all U.S. (n=65) and Canadian (n=10) dental schools with graduating classes. The results (n=42; 56% response rate) showed that few schools had plans for implementation of PM/PD at the time, even though the majority of respondents reported feeling that PM/PD should be taught in the curriculum and will impact clinical practice in the future. A three-year followup survey in 2017, sent to the same 75 schools, was designed to reassess the teaching/practice of PM/PD in dental schools in both didactic and clinical curricula. In the results of the 2017 survey (n=30; 40% response rate), the majority of respondents reported feeling that PM/PD should be taught in dental curricula. However, while most respondents indicated their schools did not teach PM/PD as a portion of their didactic curricula, they reported that specific pertinent PM/PD topics were taught as part of other courses in their curricula. The 2017 survey also evaluated the use of seven genetics-based and eight non-genetics-based PM/PD diagnostics in the schools' clinical curricula. Overall, non-genetics-based diagnostics were used more often than genetics-based diagnostics, and the use of genetics-based diagnostics was more prevalent in postgraduate than predoctoral clinics. Personalized dentistry will inevitably be part of the dental professional's future and should be reflected in basic science research, clinical settings, and dental school curricula in both predoctoral and postgraduate programs.

American Journal of Physiology-Lung Cellular and Molecular Physiology, 2001

Resident cells of the respiratory and gastrointestinal tracts, including epithelial and fibroblas... more Resident cells of the respiratory and gastrointestinal tracts, including epithelial and fibroblast cells, are the initial sites of entry for many viral pathogens. We investigated the role that these cells play in the inflammatory process in response to infection with reovirus 1/L. In A549 human bronchial or HT-29 human colonic epithelial cells, interferon (IFN)-β, regulated on activation T cell expressed and secreted (RANTES), IFN-γ-inducible protein (IP)-10, and interleukin-8 were upregulated regardless of whether cells were infected with replication-competent or replication-deficient reovirus 1/L. However, in CCD-34Lu human lung fibroblast cells, IFN-β, IP-10, and RANTES were expressed only after infection with replication-competent reovirus 1/L. Expression of interleukin-8 in CCD-34Lu fibroblast cells was viral replication independent. This differential expression of IFN-β, RANTES, and IP-10 was shown to be due to the lack of induction of IFN regulatory factor-1 and -2 in CCD-34L...

Handbook of Mucosal Immunology, 1994

PLoS ONE, 2013

Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome characterized by diffuse alveol... more Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage usually secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or noninfectious insult often leading to the development of intra-alveolar and interstitial fibrosis. Curcumin, the principal curcumoid of the popular Indian spice turmeric, has been demonstrated as an anti-oxidant and anti-inflammatory agent in a broad spectrum of diseases. Using our well-established model of reovirus 1/L-induced acute viral pneumonia, which displays many of the characteristics of the human ALI/ARDS, we evaluated the anti-inflammatory and anti-fibrotic effects of curcumin. Female CBA/J mice were treated with curcumin (50 mg/kg) 5 days prior to intranasal inoculation with 10 7 PFU reovirus 1/L and daily, thereafter. Mice were evaluated for key features associated with ALI/ARDS. Administration of curcumin significantly modulated inflammation and fibrosis, as revealed by histological and biochemical analysis. The expression of IL-6, IL-10, IFNc, and MCP-1, key chemokines/cytokines implicated in the development of ALI/ARDS, from both the inflammatory infiltrate and whole lung tissue were modulated by curcumin potentially through a reduction in the phosphorylated form of NFkB p65. While the expression of TGFß1 was not modulated by curcumin, TGFß Receptor II, which is required for TGFß signaling, was significantly reduced. In addition, curcumin also significantly inhibited the expression of a-smooth muscle actin and Tenascin-C, key markers of myofibroblast activation. This data strongly supports a role for curcumin in modulating the pathogenesis of viral-induced ALI/ARDS in a pre-clinical model potentially manifested through the alteration of inflammation and myofibroblast differentiation.

The Journal of Spinal Cord Medicine, 2011

Objective: To characterize adults with spinal cord injury (SCI) who seek oral health information ... more Objective: To characterize adults with spinal cord injury (SCI) who seek oral health information online, and investigate whether seeking oral health information online is associated with oral health knowledge and behaviors. Methods: An online oral health survey was posted on the South Carolina Spinal Cord Injury Association website. Respondents were 192 adult residents of the US ages 19-83 years who identified themselves as having SCI occurring at least 1 year before the survey date. Results: About 12% (n = 23) of the respondents searched oral health information online in the past 12 months. Significant associations between the proportion of respondents who searched for oral health information online and socio-demographic and the proportion of respondents who engaged in various oral health behaviors were not detected. However, multivariable logistic regression indicated that respondents who searched oral health information online in the past 12 months have 3.4 times the odds of possessing adequate oral health knowledge compared to respondents who did not search oral health information online (adjusted odds ratio = 3.41, 95% confidence interval = 1.35, 8.62, P = 0.01). Conclusions: Given the significant association between seeking oral health information online and adequate oral health knowledge, this study suggests that online oral health information may be a potential avenue for dental health professionals to supplement oral health education in adults with SCI.

Toxicology, 1999

The immune system is believed to be a sensitive indicator for adverse polychlorinated biphenyl (P... more The immune system is believed to be a sensitive indicator for adverse polychlorinated biphenyl (PCB)-induced health effects. Four commercial PCB mixtures (Aroclors) or six individual PCB congeners were evaluated for their effect on splenocyte viability and lipopolysaccharide (LPS)-induced splenocyte proliferation in vitro in two strains of mice, C57B1/6 (high affinity aromatic hydrocarbon receptor (AhR) complex) and DBA/J (low affinity AhR complex). All four Aroclors, the selected individual noncoplanar congeners, or two tertiary mixtures containing one congener from each class significantly decreased the in vitro LPS-induced proliferation of murine splenocytes in either strain of mice without inducing a significant decrease in viability. In contrast, selected individual coplanar or mono-orthocoplanar congeners did not inhibit splenocyte proliferation or viability at any concentration. These results suggest that mixtures of PCBs and/or congener class (specifically, noncoplanar congeners) may be more highly immunotoxic than individual planar and mono-ortho-coplanar congeners alone. Thus, this in vitro assay has revealed a more complex pattern of immunotoxicity of Aroclors versus individual congeners than has previously been reported or anticipated based on both in vivo derived immunotoxic data and standard comparisons to 2,3,7,8-tetrachlorodibenzop-dioxin (TCDD). These results have important practical significance since mixtures of PCB congeners were used industrially and now contaminate the environment.

The FASEB Journal, 2014

Salivary glands, a major component of the mucosal immune system, confer antigen-specific immunity... more Salivary glands, a major component of the mucosal immune system, confer antigen-specific immunity to mucosally acquired pathogens. We investigated whether a physiological route of inoculation and a subunit vaccine approach elicited MCMV-specific and protective immunity. Mice were inoculated by retrograde perfusion of the submandibular salivary glands via Wharton's duct with tcMCMV or MCMV proteins focused to the salivary gland via replication-deficient adenovirus expressing individual MCMV genes (gB, gH, IE1; controls: saline and replication deficient adenovirus without MCMV inserts). Mice were evaluated for MCMV-specific antibodies, T-cell responses, germinal center formation, and protection against a lethal MCMV challenge. Retrograde perfusion with tcMCMV or adenovirus expressed MCMV proteins induced a 2to 6-fold increase in systemic and mucosal MCMVspecific antibodies, a 3-to 6-fold increase in GC marker expression, and protection against a lethal systemic challenge, as evidenced by up to 80% increased survival, decreased splenic pathology, and decreased viral titers from 10 6 pfu to undetectable levels. Thus, a focused salivary gland immunization via a physiological route with a protein antigen induced systemic and mucosal protective immune responses. Therefore, salivary gland immunization can serve as an alternative mucosal route for administering vaccines, which is directly applicable for use in humans.

Social Work in Public Health, 2011

Objective-The aim of this study is to explore behavioral factors associated with toothache among ... more Objective-The aim of this study is to explore behavioral factors associated with toothache among African American adolescents living in rural South Carolina. Methods-Using a self-administered questionnaire, data were collected on toothache experience in the past 12 months, oral hygiene behavior, dental care utilization, and cariogenic snack and non-diet soft drink consumption in a convenience sample of 156 African American adolescents aged 10-18 years old living in rural South Carolina. Univariable and multivariable logistic regression analyses were used to assess the associations between reported toothache experience and socio-demographic variables, oral health behavior, and snack consumption. Results-Thirty-four percent of adolescents reported having toothache in the past 12 months. In univariable modeling, age, dental visit in the last two years, quantity and frequency of cariogenic snack consumption, and quantity of non-diet soft drink consumption were each significantly associated with experiencing toothache in the past 12 months (all p-values < 0.05). Multivariable logistic regression analysis indicated that younger age, frequent consumption of cariogenic snacks, and number of cans of non-diet soft drink consumed during the weekend significantly increased the odds of experiencing toothache in the past 12 months (all p-values ≤ 0.01).

The Journal of Immunology, 2005

Intraduodenal priming of mice with reovirus serotype 1/strain Lang (reovirus 1/L) stimulates gut ... more Intraduodenal priming of mice with reovirus serotype 1/strain Lang (reovirus 1/L) stimulates gut lymphocytes and generates precursor and effector CTLs. Our earlier studies demonstrated that germinal center and T cell Ag (GCT) is a marker which identifies reovirus 1/L-specific precursor CTL and effector CTL in Peyer's patches (PP) of reovirus 1/L-inoculated mice. In this study, we characterized the expression of the activation markers, GCT and CD11c, on reovirus 1/L-stimulated gut lymphocytes and the effector mechanisms involved in reovirus 1/L-specific cytotoxicity. We found that intraduodenal reovirus 1/L inoculation of mice induced the expression of both GCT and CD11c on PP lymphocytes (PPL), intraepithelial lymphocytes (IEL), and lamina propria lymphocytes (LPL), and these activated cells expressed Fas ligand (FasL). The majority of the GCT ؉ CD11c ؉ IEL and LPL expressed a phenotype, TCR␣␤ ؉ Thy-1 ؉ CD8 ؉ similar to that expressed on reovirus 1/L-stimulated PPL. However, splenic lymphocytes expressed GCT but not CD11c after stimulation with reovirus 1/L. Perforin, Fas-FasL, and TRAIL pathways were found to be involved in PPL, IEL, and LPL cytotoxic activity against reovirus 1/L-infected targets. In PPL, perforin and Fas-FasL pathways were more effective than TRAIL. In IEL, all three cytotoxic mechanisms were equally as effective. However, LPL prefer Fas-FasL and TRAIL over perforin. Further, we demonstrated the preferential migration of GCT ؉ PPL to the intraepithelial compartment and the lamina propria. These results suggest that GCT and CD11c can be used as activation markers for gut lymphocytes and CD11c can also be used to differentiate between activated gut and systemic lymphocytes.

International Immunology, 2007

Intestinal intra-epithelial lymphocytes (IELs) form a highly specialized lymphoid compartment. IE... more Intestinal intra-epithelial lymphocytes (IELs) form a highly specialized lymphoid compartment. IELs consist primarily of T cells that are dispersed as single cells within the epithelial cell layer that surrounds the intestinal lumen. These lymphocytes along with lamina propria lymphocytes are considered to play an important role in the regulation of immune responses. IELs are heterogeneous with regard to phenotype, and they contain sub-populations with diverse functions. In our most recent study, we found that intra-duodenal inoculation of mice with reovirus serotype 1/strain Lang (reovirus 1/L) induced expression of both germinal center and T cell antigen and CD11c on IELs suggesting these cells to be the recently stimulated cells in gut mucosal tissue. We also demonstrated that IELs from these mice when cultured in vitro in the presence of reovirus 1/L-pulsed antigen-presenting cells generated reovirus 1/L-specific MHC-restricted CTL whose function was mediated utilizing perforin, Fas-FasL and TRAIL mechanisms. This present study provides a comprehensive analysis of the diverse subsets of IELs, which function with other mucosal cells to provide a strong, protective immunity in a highly regulated fashion inside the microenvironment of the intestinal epithelium. We demonstrated that the IEL population contains both thymus-dependent (TD) and thymus-independent (TI) lymphocytes in mice and that a complex phenotype is present when sub-populations are analyzed for TCR, Thy-1, CD4, CD8 and B220 expression in a comprehensive manner. In reovirus 1/L-inoculated mice, we found a decrease in the TI population and an increase in the TD population characterized by significant alterations in various sub-populations. This increase was largely due to an increase in CD4 1 , CD8 1 and CD4/CD8 double-positive sub-populations of TD IELs. Intracellular cytokine analysis demonstrated induction of IFN-g and an increase in effector/ cytotoxic CD8 and CD4 cells after reovirus 1/L infection. These results suggest that TD IELs may play an important role in the clearance of reovirus 1/L infection from gut.

Experimental Cell Research, 2007

Osteoclast differentiation is tightly regulated by receptor activator of NF-kappaB ligand (RANKL)... more Osteoclast differentiation is tightly regulated by receptor activator of NF-kappaB ligand (RANKL) signaling. Matrix metalloproteinase-9 (MMP-9), a type IV collagenase is highly expressed in osteoclast cells and plays an important role in degradation of extracellular matrix; however, the molecular mechanisms that regulate MMP-9 gene expression are unknown. In this study, we demonstrate that RANKL signaling induces MMP-9 gene expression in osteoclast precursor cells. We further show that RANKL regulates MMP-9 gene expression through TRAF6 but not TRAF2. Interestingly, blockade of p38 MAPK activity by pharmacological inhibitor, SB203580 increases MMP-9 activity whereas ERK1/2 inhibitor, PD98059 decreases RANKL induced MMP-9 activity in RAW264.7 cells. These data suggest that RANKL differentially regulates MMP-9 expression through p38 and ERK signaling pathways during osteoclast differentiation. Transient expression of MMP-9 gene (+1 to -1174 bp relative to ATG start codon) promoter-luciferase reporter plasmids in RAW264.7 cells and RANKL stimulation showed significant increase (20-fold) of MMP-9 gene promoter activity; however, there is no significant change with respect to +1 bp to -446 bp promoter region and empty vector transfected cells. These results indicated that MMP-9 promoter sequence from -446 bp to -1174 bp relative to start codon is responsive to RANKL stimulation. Sequence analysis of the mouse MMP-9 gene promoter region further identified the presence of binding motif (-1123 bp to -1153 bp) for the nuclear factor of activated T cells 1 (NFATc1) transcription factor. Inhibition of NFATc1 using siRNA and VIVIT peptide inhibitor significantly decreased RANKL stimulation of MMP-9 activity. We further confirm by oligonucleotide pull-down assay that RANKL stimuli enhanced NFATc1 binding to MMP-9 gene promoter element. In addition, over-expression of constitutively active NFAT in RAW264.7 cells markedly increased (5-fold) MMP-9 gene promoter activity in the absence of RANKL. Taken together, our results suggest that RANKL signals through TRAF6 and that NFATc1 is a downstream effector of RANKL signaling to modulate MMP-9 gene expression during osteoclast differentiation.

Experimental and Molecular Pathology, 2007

While the salivary gland has been recognized as an important effector site of the common mucosal ... more While the salivary gland has been recognized as an important effector site of the common mucosal immune system, a useful model for studying anti-viral salivary gland immune responses in vivo and for exploring the role of the salivary gland within the common mucosal system has been lacking. Murine cytomegalovirus (MCMV) is a beta-herpesvirus that displays a strong tropism for the salivary gland and produces significant morbidity in susceptible mice when introduced by intraperitoneal (i.p.) inoculation. This study tested the hypothesis that MCMV morbidity and pathology could be reduced by injecting the virus directly the submandibular salivary gland (intraglandular (i.g.)), using either in vivo derived MCMV or the less virulent, tissue culturederived MCMV (tcMCMV). Peak salivary gland viral titers were completely unaffected by infection route (i.p vs. i.g.) after inoculation with either MCMV or tcMCMV. However, i.g. tcMCMV inoculation reduced viremia in all systemic tissues tested compared to i.p. inoculation. Further, systemic organ pathology observed in the liver and spleen after i.p. inoculation with either MCMV or tcMCMV was completely eliminated by i.g. inoculation with tcMCMV. Cellular infiltrates in the salivary glands, after i.p. or i.g. inoculation were composed of both B and T cells, indicating the potential for a local immune response to occur in the salivary gland. These results demonstrate that a focused MCMV infection of the salivary gland without systemic organ pathology is possible using i.g. delivery of tcMCMV.

Diabetes Research and Clinical Practice, 2009

The purpose of this study was to determine levels of oral health knowledge and factors associated... more The purpose of this study was to determine levels of oral health knowledge and factors associated with adequate oral health knowledge in adults with diabetes. A convenience sample of 253 adult US residents with diabetes completed an oral health survey to assess their knowledge. Results showed that only 47% of the participants answered five or more (out of a maximum of seven) oral health knowledge items related to diabetes correctly. Participants who received oral health information related to diabetes have 2.9 times the odds of possessing adequate oral health knowledge (i.e., answered five or more items correctly) compared to participants who did not received that information controlling for education and race (OR = 2.86, 95% CI 1.26-6.24, P = 0.008). Given that oral health information provided by health professionals (dental and/or medical) contributes to improve oral health knowledge among adults with diabetes, health professionals should take the opportunity to educate patients with diabetes about the oral manifestations (e.g., dry mouth) and complications (e.g., periodontitis and oral candidiasis) of diabetes and to promote proper oral health behaviors.

Diabetes Research and Clinical Practice, 2010

Oral health information was included in 89.5% of diabetes education programs in states with high ... more Oral health information was included in 89.5% of diabetes education programs in states with high diabetes prevalence compared to 85.9% in low prevalence states (P=0.22). However, management of dry mouth, demonstrations and return demonstrations of oral hygiene techniques were covered by 27.0%, 10.1% and <1% programs, respectively.

Clinical Immunology, 1999

Viruses which infect mucosal surfaces commonly infect these particular anatomical sites based on ... more Viruses which infect mucosal surfaces commonly infect these particular anatomical sites based on both the virion structure and the interaction of the virus with a particular microenvironment. We infected a human lung epithelial cell line, a human gut epithelial cell line, and a human lung fibroblast cell line with reovirus 1/L to explore how this natural isolate of both the lung and the gut may interact with mucosal surfaces. While reovirus infection of the gut and lung epithelial cell lines was lytic, a chronic infection was established in the human lung fibroblast cell line. All three cell lines also produced interleukin-8 (IL-8) after infection with reovirus 1/L, and IL-8 production was not dependent upon viral replication. A prolonged production of IL-8 was observed in the chronically infected lung fibroblast cell line, suggesting that this mucosal population may be involved in the generation of inflammatory responses after the resolution of the initial lytic infection of the epithelium. These studies provide an in vitro model system for analyzing the interaction of reovirus 1/L with resident mucosal cell populations.

Clinical Immunology, 2002

Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by diffuse alveol... more Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage (DAD) secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or noninfectious insult. We have previously described a unique animal model in which CBA/J mice infected with reovirus 1/L develop ARDS. This model recapitulates the histopathological changes observed in human ARDS, which consist of the overlapping phases of exudation, including the formation of hyaline membranes, regeneration, and healing via repair with fibrosis. In this report, we show that the development of DAD in the acute phase of the disease and intraalveolar fibrosis in the late phase of the disease was not modulated by treatment with methylprednisolone (MPS). In the presence or absence of MPS, the majority of cells infiltrating the lungs after reovirus 1/L infection were polymorphonuclear leukocytes and macrophages. A number of key proinflammatory and anti-inflammatory cytokines/ chemokines that are observed in the BAL fluid of ARDS patients were also found in the lungs of mice after reovirus 1/L infection and were not modulated by MPS. These include interferon-␥, interleukin-10, and monocyte chemoattractant protein. The histopathology, cytokine/chemokine expression, and response to corticosterids in reovirus 1/L-induced ARDS are similar to what is observed in human patients, making this a clinically relevant model.

Cellular Immunology, 1999

While the in vitro properties of CD4(+) and CD8(+) cytokine-producing lymphocytes have been well ... more While the in vitro properties of CD4(+) and CD8(+) cytokine-producing lymphocytes have been well studied, the in vivo cytokine production patterns and relative roles of CD4(+) and CD8(+) T lymphocytes during a primary in vivo immune response remain unclear. In this study, mice were inoculated intranasally with reovirus 1/L, and respiratory T lymphocyte populations were analyzed using multicolor flow cytometric analysis for the production of cytokine within and between classical type 1/type 2 patterns. Cytokine production observed in vivo following infection did not correlate with classical T cell cytokine expression patterns; instead, multiple types of lymphocyte populations that produced one of several possible cytokine combinations were present. Cytokine production by CD4(+) lymphocytes appears in the early and middle stages of the immune response, while CD8(+) lymphocytes produce more cytokine in the later stages. Early cytokine responses occurred predominantly in the whole lung and lung-associated lymph node populations. The complex patterns of cytokine expression seen in this study likely influence local cell-mediated immunity as well as the complex interaction of T cell subsets and the interaction of T cells with B cells which are necessary for the generation of cell-mediated and humoral immune responses required for effective broad-spectrum immunity.

The American Journal of Pathology, 2003

Microbial Pathogenesis, 1989

Reovirus, a virus that contains neither an envelope nor glycosylated polypeptides, has been found... more Reovirus, a virus that contains neither an envelope nor glycosylated polypeptides, has been found to induce virus-specific, major histocompatibility complex (MHC) class I antigen restricted, cytotoxic T lymphocyte (CTL) responses. The cytotoxic T cells require in vitro stimulation in the presence of virus to phenotypically express cytotoxic activity. Utilizing reovirus types 1 and 3, the CTLs derived from mice infected with one serotype can lyse target cells infected with a second serotype of reovirus. In addition, lymphocytes primed in vivo with one serotype develop into fully functional CTLs during in vitro stimulation with the other serotype of reovirus. Therefore, these results suggest that reovirus induced CTLs are virus, but not serotype specific. Common determinants shared by reovirus polypeptides from reovirus types 1 and 3 are most likely the stimuli for the majority of CTLs responses to reovirus.