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1.
Clin Immunol ; 192: 58-67, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29679709

RESUMO

Primary Sjögren's syndrome (pSS) is an autoimmune disease in which the underlying cause has yet to be elucidated. The main objective of this study was to determine the T cell receptor (TCR) repertoires of individual infiltrating T helper (Th)-1 and 17 cells of pSS patients using single-cell analysis. Single-cell analysis of ex-vivo infiltrating T cells demonstrated that pSS patients had higher frequencies of activated Th17 cells. Single-cell TCR sequencing revealed that TCRß variable (TRBV)3-1/joint (J)1-2 (CLFLSMSACVW) and TRBV20-1/J1-1 (SVGSTAIPP*T) were expressed by activated Th1 and Th17 cells in both cohorts. Uniquely, TCRα variable (TRAV)8-2/J5 (VVSDTVLETAGE) was expressed by Th1 cells present only in patients and complementarity-determining region (CDR)3α-specific motif (LSTD*E) present in both Th1/Th17 cells. The study demonstrates that both activated Th1 and Th17 cells of pSS patients showed restricted clonal diversities of which two CDR3 motifs were present in controls and patients, with another two motifs unique to pSS.


Assuntos
Análise de Célula Única/métodos , Síndrome de Sjogren/imunologia , Células Th1/imunologia , Células Th17/imunologia , Adulto , Idoso , Motivos de Aminoácidos/genética , Motivos de Aminoácidos/imunologia , Sequência de Aminoácidos , Estudos de Coortes , Feminino , Humanos , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Síndrome de Sjogren/genética , Síndrome de Sjogren/metabolismo , Células Th1/metabolismo , Células Th17/metabolismo
2.
Eur J Immunol ; 41(7): 2029-39, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21469088

RESUMO

MicroRNAs (miRNAs), small non-coding RNA molecules that post-transcriptionally regulate gene expression, are known to play key roles in regulating immune responses and autoimmunity. We investigated miR-146a expression in Sjögren's syndrome (SjS) patients as well as in the SjS-prone C57BL/6.NOD-Aec1Aec2 mouse model, to elucidate its involvement in SjS pathogenesis. Expression of miR-146a was examined in the PBMCs of 25 SjS patients and ten healthy donors, as well as in PBMCs, salivary and lacrimal glands of SjS-prone mice and WT C57BL/6J mice. Functional assays using THP-1 human monocytes were conducted to determine the biological roles of miR-146a in innate immunity. Expression of miR-146a was significantly increased in SjS patients compared with healthy controls, and was upregulated in the salivary glands and PBMCs of the SjS-prone mouse at both 8 wk (prior to disease onset) and 20 wk (full-blown disease) of age. More importantly, functional analysis revealed roles for miR-146a in increasing phagocytic activity and suppressing inflammatory cytokine production while migration, nitric oxide production and expression of antigen-presenting/costimulatory molecules are not affected in human monocytic THP-1 cells. Taken together, our data suggest that abnormal expression/regulation of microRNAs in innate immunity may contribute to, or be indicative of, the initiation and progression of SjS.


Assuntos
Imunidade Inata , MicroRNAs/metabolismo , Síndrome de Sjogren/genética , Síndrome de Sjogren/imunologia , Adulto , Idoso , Animais , Apresentação de Antígeno , Quimiotaxia de Leucócito , Citocinas/biossíntese , Feminino , Expressão Gênica , Regulação da Expressão Gênica , Inativação Gênica , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , MicroRNAs/genética , Pessoa de Meia-Idade , Monócitos/imunologia , Óxido Nítrico/biossíntese , Fagocitose , Reação em Cadeia da Polimerase , Glândulas Salivares/citologia , Glândulas Salivares/metabolismo , Transdução de Sinais/genética , Síndrome de Sjogren/metabolismo , Adulto Jovem
3.
Genes Chromosomes Cancer ; 49(6): 549-59, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20232482

RESUMO

Recent reports have demonstrated that Dicer, an RNase III endonuclease required for microRNA (miRNA) maturation, is aberrantly expressed in different types of cancer. Furthermore, Dicer has been reported to be regulated by the let-7 family of miRNA genes. We hypothesize that Dicer is aberrantly expressed in oral cancer cells due to altered expressions of let-7 and that Dicer contributes to the development and progression of the disease. Western blot examination of Dicer protein levels in four head and neck squamous cell carcinoma (HNSCC) cell lines, including two oral cancer cell lines, demonstrated that Dicer had between 4- and 24-fold higher expression levels when compared to normal human primary gingival epithelial cells. Furthermore, five of six oral cancer tissues analyzed by indirect immunofluorescence had increased Dicer protein expression, compared to normal gingival epithelial tissue. The Dicer mRNA levels were not found to correlate well with protein expression in the HNSCC cell lines, suggesting that Dicer protein expression was post-transcriptionally regulated. Analysis of let-7a and let-7b levels in HNSCC cell lines by real-time PCR demonstrated that let-7b, but not let-7a, was significantly reduced in the HNSCC cell lines compared to control cells. Lastly, transfection of oral cancer cells with chemically synthesized let-7b and small interfering RNAs targeting Dicer significantly inhibited cell proliferation up to 83% and >100%, respectively, as early as 3 days post-transfection. Together, these data demonstrate that elevated expression levels of Dicer in oral cancer cells correlate with downregulation of let-7b and increased cell proliferation.


Assuntos
Carcinoma de Células Escamosas/genética , RNA Helicases DEAD-box/genética , MicroRNAs/genética , Neoplasias Bucais/genética , Ribonuclease III/genética , Análise de Variância , Animais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Processos de Crescimento Celular/genética , Linhagem Celular Tumoral , RNA Helicases DEAD-box/biossíntese , RNA Helicases DEAD-box/metabolismo , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Histocitoquímica , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , MicroRNAs/metabolismo , Microscopia de Fluorescência , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Transplante de Neoplasias , Ribonuclease III/biossíntese , Ribonuclease III/metabolismo , Transfecção
4.
J Am Dent Assoc ; 139(3): 291-9; quiz 358-9, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18310733

RESUMO

BACKGROUND: The importance of oral health to systemic health and quality of life (QOL) is gaining attention. Although several studies have examined generic (general) QOL in Sjögren syndrome (SS), little information exists on the effect of oral health on QOL and relationships among self-reported oral health, systemic health and objective clinical measures of health. The authors conducted this study to characterize these relationships in a sample of patients with SS. METHODS: Thirty-nine patients with a diagnosis of SS ascertained by means of the 2002 American-European Consensus criteria completed both the Oral Health Impact Profile (OHIP-14) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) QOL questionnaires. OHIP-14 measures pain; functional limitation; and psychological, emotional and social disability associated with the mouth. SF-36 measures physical and emotional health and the ability to perform usual activities. Additional measures included the number of self-reported autoimmune symptoms and an index of disease damage. Statistical analysis was performed by using hierarchical regression analysis. RESULTS: Both generic and oral health-related QOL were poor in these patients. Specifically, the findings indicated that salivary flow rate was correlated significantly with both Disease Damage Index and OHIP-14 ratings, the number of autoimmune symptoms was correlated significantly with both oral and generic QOL, and oral health accounted for a significant percentage of variance in SF-36 domains of general health and social function. CONCLUSIONS: Oral health appears to have an independent influence on general QOL in patients with SS. These findings underscore the importance of proactive dental management of the oral manifestations of SS. CLINICAL IMPLICATIONS: Dentists and physicians must work collaboratively to maintain oral health and quality of life for patients with Sjögren syndrome. The dentist should address patients' concerns of xerostomia and hyposalivation in an aggressive manner.


Assuntos
Qualidade de Vida , Saliva/metabolismo , Síndrome de Sjogren/fisiopatologia , Síndrome de Sjogren/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Indicadores Básicos de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Taxa Secretória , Perfil de Impacto da Doença , Inquéritos e Questionários , Xerostomia/fisiopatologia , Xerostomia/psicologia
5.
Gen Dent ; 56(6): 559-62, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18810917

RESUMO

A case of florid cemento-osseous dysplasia (COD) mimicking periapical pathology is presented. The fact that the patient's lesion failed to resolve three years after root canal therapy, in addition to the presence of a mixed radiolucency with discreet radiopacities, mandated a biopsy which (along with radiographic co-relation) confirmed the diagnosis of cemento-osseous dysplasia. This case report illustrates the point that periapical radiolucencies may represent benign fibro-osseous lesions that may be overlooked or result in unnecessary endodontic treatment.


Assuntos
Cementoma/patologia , Displasia da Dentina/patologia , Doenças Maxilares/patologia , Neoplasias Maxilares/patologia , Doenças Periapicais/patologia , Adulto , Cementoma/diagnóstico por imagem , Displasia da Dentina/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Doenças Maxilomandibulares/diagnóstico por imagem , Doenças Maxilomandibulares/patologia , Doenças Maxilares/diagnóstico por imagem , Neoplasias Maxilares/diagnóstico por imagem , Doenças Periapicais/diagnóstico por imagem , Ligamento Periodontal/diagnóstico por imagem , Ligamento Periodontal/patologia , Radiografia , Tratamento do Canal Radicular/métodos
6.
J Am Dent Assoc ; 138(12): 1574-81; quiz 1614-5, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18056101

RESUMO

BACKGROUND: Although the oral manifestations of Crohn disease are well-established, there is little specific documentation of the gingival involvement. CASE DESCRIPTION: The authors describe four patients with significant gingival involvement and identify clinical signs and symptoms of the disease involving the gingivae, along with other oral manifestations. Patients had persistent gingival lesions manifesting as pustular ulcerations, erythema, swelling and cobblestoning. The authors also discuss the differential diagnosis, treatment options and prognostic factors. CLINICAL IMPLICATIONS: Patients with gingival and/or other oral lesions with or without other constitutional symptoms should be evaluated for Crohn disease. Dentists can play a critical role in the early diagnosis, and they can help prevent complications and improve the prognosis.


Assuntos
Doença de Crohn/complicações , Doenças da Gengiva/etiologia , Adulto , Doença de Crohn/diagnóstico , Diagnóstico Diferencial , Feminino , Doenças da Gengiva/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Úlceras Orais/diagnóstico , Úlceras Orais/etiologia , Estomatite/diagnóstico , Estomatite/etiologia
7.
Sci Rep ; 7(1): 12512, 2017 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-28970488

RESUMO

The development of Sjögren's syndrome (SjS) is a dynamic and temporal process with a female predilection. Following the initial influx of immune cells, T cell clusters develop, accelerating the pathology in the salivary glands. Proinflammatory cytokines, IFN-γ and IL-17A, produced by T cells contribute synergistically to the disease. In this study, we examined the sexual dimorphism in cellular infiltrates of the salivary glands by using functional single-cell microengraving analysis. Using high-throughput sequencing, we investigated the clonal diversity of the T cell receptors (TCRs) of infiltrating IFN-γ and IL-17A-producing T cells in male and female SjS-susceptible (SjSs) C57BL/6.NOD-Aec1Aec2 mice. There were elevated frequencies of IFN-γ and IL-17A-producing effector T cell populations in female SjSS mice compared to male SjSS mice. MEME analysis shows high frequency and unique, sexually dimorphic motifs in the TCR hypervariable regions in the SjSS mice. Male mice selected for TRAV8/TRAJ52 (CATDLNTGANTGKLTFG) TCR genes in Th1 cells and TRBV16/(TRBD1/2)TRBJ1-7 (CGGKRRLESIFR) in Th1 and Th17 cells. Female SjSS mice selected for TRAV8/TRAJ52 (CATDLNTGANTGKLTFG), TRAV13D-2/TRAJ23 (CVYLEHHFE), and TRBV23/(TRBD2)TRBJ2-2 (CRKLHSCATCALNFL) in Th1 cells. These findings suggest that there is an elevated prevalence of pathogenic effector T cells in the glands with a sexually dimorphic selection bias of TCR repertoires.


Assuntos
Interferon gama/genética , Interleucina-17/genética , Glândulas Salivares/imunologia , Síndrome de Sjogren/genética , Animais , Seleção Clonal Mediada por Antígeno/genética , Seleção Clonal Mediada por Antígeno/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Interferon gama/imunologia , Interleucina-17/imunologia , Masculino , Camundongos , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Glândulas Salivares/metabolismo , Glândulas Salivares/patologia , Caracteres Sexuais , Análise de Célula Única , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/patologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Células Th1/imunologia , Células Th17/imunologia
8.
J Dent Educ ; 70(5): 525-30, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16687637

RESUMO

The purpose of this study was to identify performance differences in subgroups of dental students during dental school and on state dental licensure examinations. One of the specific aims was to determine if gender is predictive of performance in dental school and on state licensure examinations. The study consisted of a retrospective analysis of 416 graduates (136 females and 280 males) from the University of Florida College of Dentistry (UFCD) between 1996 and 2003. Four categories of variables were assessed: academic measures, clinical productivity measures, performance on a senior mock board examination, and performance on the state licensure examination. The academic measures consisted of the Dental Admission Test (DAT) academic average, DAT Perceptual Ability Test (PAT), and dental school entering and graduating grade point average (GPA). Based on univariate analyses, males had significantly higher DAT academic averages and PAT scores than females. More importantly, males had significantly higher state board clinical scores. Using stepwise regression and the maximum R2 procedure, factors most predictive for the performance on the state licensure clinical exam were the PAT, numbers of amalgams completed, and the UFCD senior mock board clinical score. Each factor was highly significant (p<0.001). After controlling for these three factors, the difference in genders was no longer statistically significant. With increasing enrollment of females in dental schools, it is important to periodically assess student performance to determine whether instructional modifications are needed to accommodate gender differences. Due to consistency of our findings with similar recent reports, it might be reasonable to think the gender gap is narrowing. Additional studies from other regions would provide support for this concept.


Assuntos
Competência Clínica/estatística & dados numéricos , Educação em Odontologia/estatística & dados numéricos , Avaliação Educacional/estatística & dados numéricos , Licenciamento em Odontologia/estatística & dados numéricos , Estudantes de Odontologia/estatística & dados numéricos , Feminino , Florida , Humanos , Masculino , Estudos Retrospectivos , Fatores Sexuais
9.
Genom Data ; 7: 178-84, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26981401

RESUMO

TH17 cells and their associated signature cytokines, IL-17 and IL-22, are highly elevated in primary Sjögren's syndrome (pSjS). The levels of IL-22 present in sera showed significant correlations with many disease parameters, specifically hyposalivation, anti-SSB, anti-SSA/SSB, hypergammaglobulinemia and rheumatoid factor. The present study aims to examine the biological function of IL-22 on human salivary glands. To accomplish the goal, microarray analysis using the HumanHT-12 v4 Expression BeadChip was utilized to determine the biological function of IL-22. Differential expression analyses were conducted using the LIMMA package from the Bioconductor project. MTT assay, flow cytometry and Western blotting were used to identify the function of IL-22 on human salivary gland cells. Results indicate an extensive effect of IL-22 on many major molecular functions including activation of antimicrobial genes and downregulation of immune-associated pathways. Functional studies performed in-vitro using human salivary gland cells treated with IL-22 indicated a direct effect of IL-22 on cell cycling, specifically reducing cellular proliferation at the G2-M phase by activation of STAT3. These results suggest the important role of IL-22 in the salivary gland function. The present study suggests that IL-22 might be involved in regulating inflammation and controlling the cell proliferation in SjS.

10.
Arthritis Res Ther ; 18(1): 95, 2016 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-27142093

RESUMO

BACKGROUND: Sjögren's syndrome (SjS) monocytes have a pro-inflammatory phenotype, which may influence SjS pathogenesis. MicroRNAs (miRNAs) are small endogenously expressed molecules that can inhibit protein expression of their targeted genes and have important functions in regulating cell signaling responses. We profiled miRNAs in SjS monocytes to identify a SjS-specific miRNA profile and determine the potential roles of miRNAs in SjS pathogenesis. METHODS: Total RNA was extracted from healthy control (HC, n = 10), SjS (n = 18), systemic lupus erythematosus (SLE, n = 10), and rheumatoid arthritis (RA, n = 10) peripheral blood CD14(+) monocytes for miRNA microarray analysis. To validate select miRNAs from the microarray analysis, the original cohort and a new cohort of monocyte RNA samples from HC (n = 9), SjS (n = 12), SLE (n = 8), and RA (n = 9) patients were evaluated by quantitative reverse transcription (RT)-PCR. Functional predictions of differentially expressed miRNAs were determined through miRNA target prediction database analyses. Statistical analyses performed included one-way analysis of variance with Bonferroni post tests, linear regression, and receiver operating characteristic curve analyses. RESULTS: MiRNAs were predominantly upregulated in SjS monocytes in comparison with controls. Quantitative RT-PCR confirmations supported co-regulation of miR-34b-3p, miR-4701-5p, miR-609, miR-300, miR-3162-3p, and miR-877-3p in SjS monocytes (13/30, 43.3 %) in comparison with SLE (1/17, 5.8 %) and RA (1/18, 5.6 %). MiRNA-target pathway predictions identified SjS-associated miRNAs appear to preferentially target the canonical TGFß signaling pathway as opposed to pro-inflammatory interleukin-12 and Toll-like receptor/NFkB pathways. CONCLUSIONS: Our results underscore a novel underlying molecular mechanism where SjS-associated miRNAs may collectively suppress TGFß signaling as opposed to pro-inflammatory interleukin-12 and Toll-like receptor/NFκB pathways in SjS pathogenesis.


Assuntos
MicroRNAs/imunologia , Monócitos/imunologia , Síndrome de Sjogren/imunologia , Transcriptoma , Fator de Crescimento Transformador beta/imunologia , Perfilação da Expressão Gênica , Humanos , Receptores de Lipopolissacarídeos/imunologia , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Fator de Crescimento Transformador beta/metabolismo
11.
J Immunol Methods ; 437: 28-36, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27460476

RESUMO

Anti-muscarinic type 3 receptor autoantibodies (anti-M3R) are reported as potential inhibitors of saliva secretion in Sjögren's syndrome (SjS). However, despite extensive efforts to establish an anti-M3R detection method, there is no clinical test available for these autoantibodies. The purpose of this study was to propose inclusion of anti-M3R testing for SjS diagnosis through investigation of their prevalence using a modified In-Cell Western (ICW) assay. A stable cell line expressing human M3R tagged with GFP (M3R-GFP) was established to screen unadsorbed and adsorbed plasma from primary SjS (n=24), rheumatoid arthritis (RA, n=18), systemic lupus erythematosus (SLE, n=18), and healthy controls (HC, n=23). Anti-M3R abundance was determined by screening for the intensity of human IgG interacting with M3R-GFP cells by ICW assay, as detected by an anti-human IgG IRDye800-conjugated secondary antibody and normalized to GFP. Method comparisons and receiver-operating-characteristic (ROC)-curve analyses were performed to evaluate the diagnostic value of our current approaches. Furthermore, clinical parameters of SjS were also analyzed in association with anti-M3R. Anti-M3R was significantly elevated in SjS plasma in comparison with HC, SLE, or RA (P<0.01). SjS anti-M3R intensities were greater than two-standard deviations above the HC mean for both unadsorbed (16/24, 66.67%) and adsorbed (18/24, 75%) plasma samples. Furthermore, anti-M3R was associated with anti-SjS-related-antigen A/Ro positivity (P=0.0353). Linear associations for anti-M3R intensity indicated positive associations with focus score (R(2)=0.7186, P<0.01) and negative associations with saliva flow rate (R(2)=0.3052, P<0.05). Our study strongly supports our rationale to propose inclusion of anti-M3R for further testing as a non-invasive serological marker for SjS diagnosis.


Assuntos
Autoantígenos/imunologia , RNA Citoplasmático Pequeno/imunologia , Receptor Muscarínico M3/imunologia , Ribonucleoproteínas/imunologia , Testes Sorológicos/métodos , Síndrome de Sjogren/diagnóstico , Adulto , Idoso , Artrite Reumatoide/diagnóstico , Autoanticorpos/sangue , Feminino , Proteínas de Fluorescência Verde/genética , Células HEK293 , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Receptor Muscarínico M3/genética , Proteínas Recombinantes de Fusão/genética
12.
Arch Gen Psychiatry ; 59(2): 173-9, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11825139

RESUMO

BACKGROUND: Abnormalities in the prefrontal cortex have been implicated in the pathogenesis of major depressive disorder (MDD). To our knowledge, no prior study has examined prefrontal cortical anatomy in pediatric patients with MDD near the onset of illness before receiving treatment. METHODS: Volumetric magnetic resonance imaging studies were conducted in 22 psychotropic-naive patients with MDD, aged 9 to 17 years (10 males and 12 females), and 22 case-matched healthy comparison control subjects. Twelve of the 22 patients with MDD had at least 1 first-degree relative with MDD (familial MDD), whereas 10 had no clear family history of MDD (nonfamilial MDD). RESULTS: Patients with nonfamilial MDD had significantly larger left-sided but not right-sided prefrontal cortical volumes than patients with familial MDD (17% larger) and controls (11% larger). Left-sided and right-sided prefrontal cortical volumes did not differ significantly between patients with familial MDD and controls. CONCLUSIONS: These results provide new evidence of prefrontal cortical alterations in pediatric MDD that may differ in familial and nonfamilial subtypes of MDD. Our findings must be considered preliminary, however, in view of the small sample size.


Assuntos
Transtorno Depressivo Maior/diagnóstico , Imageamento por Ressonância Magnética , Córtex Pré-Frontal/patologia , Adolescente , Cefalometria , Criança , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/psicologia , Dominância Cerebral/fisiologia , Feminino , Predisposição Genética para Doença/genética , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Valores de Referência , Fatores de Risco
13.
J Periodontol ; 76(7): 1171-4, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16018761

RESUMO

BACKGROUND: Clinical and epidemiological data strongly support a link between smoking and periodontal disease. The mechanism by which smoking contributes to the destruction of periodontal tissue is not clear and cannot be attributed solely to the vasoconstrictive effects of nicotine. Our hypothesis is that nornicotine, a metabolite of nicotine, upregulates the expression of the receptor for the advanced glycation end products (RAGE) in the gingiva of smokers and triggers the proinflammatory effects of AGE by stimulating the secretion of cytokines and reactive oxygen species which directly cause destruction of the periodontal apparatus. METHODS: Human gingival cells grown in tissue culture were exposed to 1 microM nornicotine for 72 hours. Following the nornicotine pretreatment, some of the cells were also treated with AGE that was generated with nornicotine for 48 hours and another group was continued on nornicotine only for 48 hours. Control cells that were not exposed to either nornicotine or AGE were also cultured. The cells were harvested and RNA was extracted for reverse transcription-polymerase chain reaction (RT-PCR) and RAGE mRNA was amplified. RESULTS: The nornicotine-treated cells increased their expression of RAGE by approximately 4-fold (P <0.05, Student t test). These data suggest that nornicotine, a byproduct of cigarette smoke, can induce RAGE expression in gingival tissues. Therefore, our data support the hypothesis that RAGE potentially plays a significant role in the progression of periodontal disease exacerbated by smoking. CONCLUSION: Nornicotine, AGE, and upregulation of RAGE may be involved in the pathogenesis of periodontal disease associated with smoking.


Assuntos
Fibroblastos/efeitos dos fármacos , Gengiva/efeitos dos fármacos , Produtos Finais de Glicação Avançada/biossíntese , Nicotina/análogos & derivados , Receptores Imunológicos/biossíntese , Linhagem Celular , Fibroblastos/metabolismo , Gengiva/citologia , Gengiva/metabolismo , Produtos Finais de Glicação Avançada/fisiologia , Humanos , Mediadores da Inflamação/metabolismo , Nicotina/farmacologia , Doenças Periodontais/etiologia , RNA Mensageiro/biossíntese , Receptor para Produtos Finais de Glicação Avançada , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Fumar/efeitos adversos , Regulação para Cima
14.
J Dent Educ ; 69(8): 864-9, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16081568

RESUMO

This study assessed relationships between academic performance in dental school and "first attempt" performance on a state dental licensure examination for 1996-2003 graduates from the University of Florida College of Dentistry (UFCD). The 524 graduates were ranked into quartiles based on graduating GPA. Using analysis of variance (ANOVA), the students' mean exam score (or exam section score) for each respective quartile (n=131) was compared with mean score for graduates in the combined four quartiles (n=524). ANOVA assessments, by quartile, were performed for the following six measures: 1) overall composite score on the dental licensure exam, 2) clinical periodontics section, 3) clinical amalgam section, 4) combination of clinical periodontics and clinical amalgam, 5) laboratory (manikin exam) with a written prosthodontic exam, and 6) manikin exam without the prosthodontic exam. For the overall exam and all exam sections, a significant (p<0.001) relationship was found between higher mean exam scores and academic ranking in quartile 1. A significant relationship was found between performance (lower mean scores) and ranking in quartile 4 for all exam sections, with the exception of the clinical periodontal section. The results of this study indicate a correlation between performance in dental school and performance on the Florida dental licensure exam for 1996-2003 UFCD graduates.


Assuntos
Educação em Odontologia , Avaliação Educacional , Licenciamento em Odontologia , Análise de Variância , Florida , Humanos , Manequins , Conselhos de Especialidade Profissional
15.
Mol Immunol ; 68(2 Pt C): 606-16, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26505653

RESUMO

Sjögren's syndrome (SjS) is an autoimmune condition that primarily affects salivary and lacrimal glands, causing loss of secretion. We have previously shown that microRNA-146a (miR-146a) is over-expressed in the salivary glands and peripheral blood mononuclear cells (PBMC) of SjS-prone mice (C57BL/6.NOD-Aec1Aec2, B6DC) and in PBMC of SjS patients. The purpose of this research was to identify a target molecule of miR-146a and identify subpopulations of cells affected by altered miR-146a in the salivary glands of SjS-prone mice. In silico analyses identified costimulatory molecule CD80 as a potential target of miR-146a. Luciferase assay of the human CD80 3'untranslated region demonstrated miR-146a directly inhibited CD80 protein expression as indicated by reduced luciferase reporter expression and an examination of B6DC salivary glands revealed a reduction in CD80 protein. More interestingly, the specific reduction in CD80 protein was detected from the salivary gland epithelial cell population and in interstitial dendritic cells in the glands as well. The reduction in CD80 protein levels in salivary gland epithelial cells were negatively associated with elevated miR-146a expression. Therefore, this study provides the first indication that salivary gland epithelial cells may be critically involved in SjS progression by altering CD86:CD80 protein ratio in response to miR-146a upregulation.


Assuntos
Antígeno B7-1/biossíntese , Antígeno B7-2/biossíntese , Regulação da Expressão Gênica/imunologia , MicroRNAs/genética , Síndrome de Sjogren/genética , Animais , Antígeno B7-1/genética , Antígeno B7-1/imunologia , Antígeno B7-2/imunologia , Western Blotting , Modelos Animais de Doenças , Citometria de Fluxo , Imunofluorescência , Regulação da Expressão Gênica/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/imunologia , Reação em Cadeia da Polimerase , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Síndrome de Sjogren/imunologia , Transfecção , Regulação para Cima
16.
J Dent Educ ; 68(4): 426-32, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15112919

RESUMO

Many dental schools consider the successful completion of a state or regional dental licensure examination as one of the significant benchmarks for assessing effectiveness of the curriculum. At the University of Florida College of Dentistry (UFCD), performance on the state dental licensure examination is monitored and compared with senior year mock board performance and clinical productivity to identify factors that may contribute to state board "pass" rates. A retrospective analysis was conducted of "first-time" performance on the Florida Dental Licensure Exam for graduates from classes 1996 to 2003. Using ANOVA, licensure exam performance data was analyzed and compared with performance on the senior mock board exam and clinical productivity, determined by numbers of procedures completed in each discipline. Significant relationships were noted between four of thirteen aspects of mock board performance and clinical productivity data and performance on the Florida Dental Licensure Exam. First, a significant relationship (p<0.05) was found between passing the senior mock board fixed prosthodontic preparation and successful completion of that procedure on the state licensure exam. Second, a significant relationship (p<0.05) was noted between the clinical (patient-based) Class II amalgam on the senior mock board and passing that procedure on the state licensure exam. Third, a significant relationship was noted (p<0.05) between the number of Class IV clinical composite procedures completed during dental school and passing the licensure exam Class IV manikin composite procedure. Fourth, there was a significant relationship (p<0.01) between the number of clinical Class II amalgam procedures completed during the junior and senior years and passing the state licensure exam clinical amalgam procedure. No significance was found between the remaining five mock board procedures (Class II composites, Class IV composites, pin amalgams, endodontic, and periodontal scaling/root planing) and performance on the like procedures on the licensure exam. Likewise, no significance was found between the remaining four productivity measures (numbers of Class II composites, endodontic teeth treated, crowns and abutments completed, and quadrants of periodontal scaling/root planing) and performance of these procedures on the state licensure exam.


Assuntos
Certificação/estatística & dados numéricos , Competência Clínica/estatística & dados numéricos , Educação em Odontologia/estatística & dados numéricos , Avaliação Educacional/métodos , Licenciamento em Odontologia/estatística & dados numéricos , Florida , Humanos , Valor Preditivo dos Testes , Avaliação de Programas e Projetos de Saúde , Conselhos de Especialidade Profissional , Estudantes de Odontologia/estatística & dados numéricos , Ensino/métodos
17.
J Dent Educ ; 68(8): 829-33, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15286105

RESUMO

In an attempt to improve performance of University of Florida College of Dentistry (UFCD) graduates on the endodontic section of the Florida Dental Licensure Examination, a retrospective analysis was conducted for classes graduating between 1996 and 2003 to assess potential relationships between passing and failing performance and three factors with potential impact on "first attempt" pass rates. The three factors were clinical endodontic experience, performance on the senior mock board examination, and dialogue with representatives of the licensure examination, which resulted in modification of the endodontic section of the licensure exam. Using ANOVA, we found no differences in performance on the endodontic section of the senior mock board exam between graduates who passed the endodontic section of the dental licensure exam and those who failed this section. Furthermore, no differences were found in the mean number of clinical endodontic experiences (number of teeth treated) between graduates who passed the endodontic section of the licensure exam and those who failed. However, in 2003 following dialogue between representatives of the Florida Board of Dentistry and endodontic faculty from the two dental schools in Florida, a significant difference in senior mock board endodontic scores (p>0.05) and a significant difference in performance on the endodontic section of the licensure exam scores (p>0.005) was observed for the 2003 graduates when compared to the 2002 graduates. The mean mock board scores and the mean state board endodontic section scores were higher for the 2003 graduates. In addition, the UFCD failure rate on the endodontic section of the state board exam dropped from 34 percent in 2002 to 6 percent in 2003. The primary factors believed responsible for these improvements were a direct result of dialogue between dental school faculty and state board representatives. They include a greater appreciation by the UFCD faculty for the performance criteria used by the Board of Dentistry to evaluate procedures and a change by the board in the tooth selection criteria for the endodontic experience. The options in tooth-type used in the board exams increased from a two-rooted maxillary premolar to any anterior or premolar tooth. In conclusion, this report supports the positive benefits from ongoing discussions between dental school faculty and representatives of the state licensure board.


Assuntos
Educação em Odontologia , Avaliação Educacional , Endodontia/educação , Licenciamento em Odontologia , Análise de Variância , Dente Pré-Molar , Dente Canino , Docentes de Odontologia , Florida , Humanos , Incisivo , Estudos Retrospectivos , Tratamento do Canal Radicular/normas , Conselhos de Especialidade Profissional , Estudantes de Odontologia
18.
Cancer Biol Ther ; 10(7): 694-9, 2010 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-21068540

RESUMO

AIMS: Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy of the oral cavity resulting in severe morbidity and mortality. To date only few proteins have been suggested as potential biomarkers or targets for this type of cancer. Cancerous inhibitor of PP2A (CIP2A) is a protein expressed in epithelial tissues that stabilizes the oncogene c-Myc and causes cell transformation. This study was designed to investigate the expression of CIP2A in OSCC cell lines and tissues representing human normal, dysplasia and OSCC. METHODS: Using quantitative real time PCR, mRNA quantification for CIP2A was performed in a primary gingival cell line and OSCCs CAL 27 and SCC-25. Paraffin embedded human specimen classified as normal, dysplastic or OSCC were immunohistochemically stained for CIP2A expression. EGFR and CIP2A were also stained by immunofluorescence for co-localization. Samples of human normal oral tissue and OSCC were studied by PCR for mRNA expression of CIP2A. RESULTS: CIP2A was significantly increased in the human carcinoma cell lines compared to the primary gingival cell line. CIP2A was overexpressed in the human oral dysplasia and OSCC tissues compared to normal oral tissues. CIP2A was also preferentially localized in the dysplastic and OSCC epithelial areas compared to EGFR that was expressed mainly in areas of relatively normal epithelium and in dysplastic tissues above the basal layers. CONCLUSIONS: CIP2A may play a significant role in oral malignant transformation and therefore, it may be a potential target for chemotherapy of OSCC.


Assuntos
Autoantígenos/metabolismo , Carcinoma de Células Escamosas/metabolismo , Proteínas de Membrana/metabolismo , Doenças da Boca/metabolismo , Neoplasias Bucais/metabolismo , Autoantígenos/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Células Cultivadas , Receptores ErbB/genética , Receptores ErbB/metabolismo , Imunofluorescência , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana/genética , Doenças da Boca/genética , Doenças da Boca/patologia , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
Front Biosci (Landmark Ed) ; 14(10): 3733-9, 2009 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-19273306

RESUMO

Nuclear Autoantigen of 14 kDa (NA14) was originally identified using the serum of a Sjögren's syndrome (SS) patient as probe in screening a human testis cDNA expression library. To date there is no report in the systematic analysis of the prevalence of autoantibodies to NA14. In this study, anti-NA14 was determined in several rheumatic diseases from independent cohorts in the US and Japan. The prevalence of anti-NA14 were 18/132 (13.6%) in primary SS, 0/50 (0%) secondary SS, 2/100 (2%) SLE, 1/43 (2.3%) scleroderma, 0/54 (0%) rheumatoid arthritis, 1/29 (3.4%) polymyositis/dermatomyositis, and 0/58 (0%) normal healthy controls. The frequencies of anti-NA14 positive sera in primary SS are statistically greater than normal healthy controls (p=0.006), secondary SS (p=0.044), and other rheumatic diseases. Furthermore, among 11 anti-NA14 positive primary SS sera, 4/11 (36.3%) sera were negative for both anti-SS-A/Ro and SS-B/La antibodies. Thus anti-NA14 autoantibodies may be useful for the discrimination of primary versus secondary SS and serve as a diagnostic marker for primary SS especially in seronegative (anti-SS-A/Ro and anti-SS-B/La antibodies negative) patients with SS.


Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Biomarcadores/sangue , Proteínas Nucleares/imunologia , Síndrome de Sjogren/imunologia , Especificidade de Anticorpos , Autoanticorpos/sangue , Western Blotting , Ensaio de Imunoadsorção Enzimática , Humanos
20.
Quintessence Int ; 39(4): 343-8, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19081905

RESUMO

Hepatitis C virus (HCV) infection is a liver disease characterized by the development of necrosis, inflammatory changes, and progressive liver fibrosis, leading to complications including cirrhosis, end-stage liver disease, and hepatocellular carcinoma. The clinical features resemble those of other forms of acute viral hepatitis, namely, malaise, nausea, abdominal discomfort, pale stools, dark urine, and jaundice. The most frequently reported extrahepatic manifestations of HCV are lichen planus, sialadenitis, and cutaneous lesions. Sjogren's syndrome-like symptoms and lichenoid reactions have been previously reported in association with hepatitis C. This article describes a case of sicca-like syndrome and oral lichenoid reaction associated with interferon-alpha therapy for HCV infection. In this unique case, significant oral symptoms arose right after initiation of interferon-alpha treatment and resolved completely within days upon completion of treatment with interferon-alpha. Physicians and oral health care specialists should be aware of the association among HCV infection, interferon-alpha therapy, and development of possible oral signs and symptoms including lichenoid lesions and xerostomia.


Assuntos
Antivirais/efeitos adversos , Hepatite C/tratamento farmacológico , Interferon-alfa/efeitos adversos , Líquen Plano Bucal/induzido quimicamente , Xerostomia/induzido quimicamente , Doença Aguda , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Ribavirina/uso terapêutico
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