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1.
J Infect Dis ; 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38394609

RESUMO

BACKGROUND: Chlamydia trachomatis (CT) testing and treatment strategies have not decreased infection rates, justifying need for a CT vaccine. A murine study showed that a vaccine consisting of MOMP and 4 polymorphic membrane proteins (Pmps E, F, G, H) elicited protective immunity; studies on human cellular immune responses to Pmps are sparse. METHODS: Interferon gamma (IFN-γ) responses to these 5 CT proteins were measured by ELISPOT in PBMCs from women returning for treatment of a positive CT screening test. Responses were compared in those with spontaneous CT clearance vs. persisting infection at baseline and no reinfection vs. reinfection at a 3-month follow-up visit. RESULTS: IFN-γ response to one or more proteins was detected in 39% at baseline and 51.5% at follow-up; PmpE and MOMP most often elicited positive responses. IFN-γ responses to MOMP were detected less often at follow-up vs. baseline in women with reinfection, but were maintained in those without reinfection. Women with spontaneous clearance had a higher magnitude of IFN-γ response to PmpE and MOMP. CONCLUSIONS: IFN-γ responses to these 5 CT vaccine candidate proteins were heterogenous and primarily directed against MOMP and PmpE. Spontaneous clearance of infection and absence of reinfection may be clinical correlates of protection.

2.
J Infect Dis ; 228(8): 1119-1126, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37163744

RESUMO

BACKGROUND: Natural clearance of Chlamydia trachomatis in women occurs in the interval between screening and treatment. In vitro, interferon-γ (IFN-γ)-mediated tryptophan depletion results in C. trachomatis clearance, but whether this mechanism occurs in vivo remains unclear. We previously found that women who naturally cleared C. trachomatis had lower cervicovaginal levels of tryptophan and IFN-γ compared to women with persisting infection, suggesting IFN-γ-independent pathways may promote C. trachomatis clearance. METHODS: Cervicovaginal lavages from 34 women who did (n = 17) or did not (n = 17) naturally clear C. trachomatis were subjected to untargeted high-performance liquid chromatography mass-spectrometry to identify metabolites and metabolic pathways associated with natural clearance. RESULTS: In total, 375 positively charged metabolites and 149 negatively charged metabolites were annotated. Compared to women with persisting infection, C. trachomatis natural clearance was associated with increased levels of oligosaccharides trehalose, sucrose, melezitose, and maltotriose, and lower levels of indoline and various amino acids. Metabolites were associated with valine, leucine, and isoleucine biosynthesis pathways. CONCLUSIONS: The cervicovaginal metabolome in women who did or did not naturally clear C. trachomatis is distinct. In women who cleared C. trachomatis, depletion of various amino acids, especially valine, leucine, and isoleucine, suggests that amino acids other than tryptophan impact C. trachomatis survival in vivo.


Assuntos
Infecções por Chlamydia , Chlamydia trachomatis , Feminino , Humanos , Triptofano/metabolismo , Leucina , Isoleucina/metabolismo , Infecções por Chlamydia/metabolismo , Aminoácidos/metabolismo , Interferon gama/metabolismo , Valina/metabolismo
3.
Sex Transm Dis ; 50(11): e30-e33, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37732834

RESUMO

ABSTRACT: The contribution of chlamydia to secondary infertility in women is poorly understood. Among 404 female participants enrolled in a previous study in Cameroon, 142 had secondary infertility (cases) and 262 were pregnant with no history of infertility (controls) , Chlamydia trachomatis seropositivity was 92%. Seropositivity did not significantly differ by case/control status.


Assuntos
Infecções por Chlamydia , Infertilidade Feminina , Gravidez , Feminino , Humanos , Chlamydia trachomatis , Infecções por Chlamydia/complicações , Infecções por Chlamydia/epidemiologia , Camarões/epidemiologia , Formação de Anticorpos , Anticorpos Antibacterianos
4.
Int J Mol Sci ; 24(21)2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37958786

RESUMO

Associations of HLA class II alleles with genital chlamydial infection outcomes have been reported, especially HLA DQB1*06. However, the potential role of DQB1*06 in influencing reinfection risk has still not been established. The purpose of this study was to determine whether the association of DQB1*06 with chlamydia reinfection was impacted by any other nearby HLA class II variants that were also associated with reinfection. We used next-generation sequencing to map HLA class II variants spanning the HLA-DQ and -DR loci. DQB1*06 as well as DQB1*04 were confirmed as significant predictors of chlamydia reinfection, when controlling for age and percent African ancestry. SKAT analysis revealed one region each in DRB1, DRB5, DQA2, and three intergenic regions that had variants associated with reinfection. Further analyses of these variants revealed that rs112651494 within DRB5 and an intergenic SNP rs617058 in DRB1:DQA1 were significantly associated with reinfection, but this did not impact the significance of the association of DQB1*06 or DQB1*04 with reinfection.


Assuntos
Chlamydia , Antígenos HLA-DQ , Humanos , Antígenos HLA-DQ/genética , Cadeias HLA-DRB1 , Reinfecção , Cadeias alfa de HLA-DQ/genética , Haplótipos , Alelos , Frequência do Gene
5.
Sex Transm Dis ; 49(9): e97-e99, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35728006

RESUMO

ABSTRACT: Among 73 women presenting to a sexually transmitted infection (STI) clinic in Birmingham, Alabama for reported sexual contact to a chlamydia-infected partner, Chlamydia trachomatis was detected in genital specimens in 24 (32.8%), less often in women reporting prior chlamydial infection ( P = 0.001). Most women (93.2%) were C. trachomatis seropositive.


Assuntos
Infecções por Chlamydia , Chlamydia trachomatis , Alabama/epidemiologia , Infecções por Chlamydia/epidemiologia , Feminino , Humanos , Comportamento Sexual
6.
Sex Transm Dis ; 49(3): e53-e55, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34561371

RESUMO

ABSTRACT: We adapted a simple hydroxylamine-based indole assay to detect indole from stored vaginal swab specimens from women with and without bacterial vaginosis (BV). Women with BV had significantly higher vaginal indole levels compared with women without BV (6451.5 vs 5632.4 µM; P = 0.01), suggesting that indole-producing bacteria are a component of BV.


Assuntos
Vaginose Bacteriana , Bactérias , Feminino , Humanos , Indóis , Vagina/microbiologia , Vaginose Bacteriana/diagnóstico
7.
Sex Transm Dis ; 48(11): 813-818, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-33993163

RESUMO

BACKGROUND: African Americans have the highest rates of Chlamydia trachomatis (CT) infection in the United States and also high reinfection rates. The primary objective of this study was to develop a Bayesian model to predict the probability of CT reinfection in African American women using immunogenetic data. METHODS: We analyzed data from a cohort of CT-infected African American women enrolled at the time they returned to a clinic in Birmingham, AL, for the treatment of a positive routine CT test result. We modeled the probability of CT reinfection within 6 months after treatment using logistic regression in a Bayesian framework. Predictors of interest were presence or absence of an HLA-DQB1*06 allele and CT-specific CD4+ IFN-γ response, both of which we had previously reported were independently associated with CT reinfection risk. RESULTS: Among 99 participants evaluated, the probability of reinfection for those with a CT-specific CD4+ IFN-γ response and no HLA-DQB1*06 alleles was 14.1% (95% credible interval [CI], 3.0%-45.0%), whereas the probability of reinfection for those without a CT-specific CD4+ IFN-γ response and at least one HLA-DQB1*06 allele was 61.5% (95% CI, 23.1%-89.7%). CONCLUSIONS: Our model demonstrated that presence or absence of an HLA-DQB1*06 allele and CT-specific CD4+ IFN-γ response can have an impact on the predictive probability of CT reinfection in African American women.


Assuntos
Negro ou Afro-Americano , Infecções por Chlamydia , Reinfecção/genética , Negro ou Afro-Americano/genética , Alabama , Teorema de Bayes , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/genética , Chlamydia trachomatis , Feminino , Cadeias beta de HLA-DQ/genética , Humanos , Interferon gama
8.
Sex Transm Dis ; 48(2): e27-e29, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33346592

RESUMO

ABSTRACT: We used the Food and Drug Administration-cleared Aptima Mycoplasma genitalium assay to evaluate for M. genitalium infection among young women without urogenital symptoms presenting to a community-based emergency department in Birmingham, Alabama, between August 2016 to August 2019 for evaluation of nongynecological concerns. M. genitalium was detected in 23 (14.8%) of 155 women.


Assuntos
Infecções por Mycoplasma , Mycoplasma genitalium , Alabama/epidemiologia , Serviço Hospitalar de Emergência , Feminino , Humanos , Infecções por Mycoplasma/diagnóstico , Infecções por Mycoplasma/epidemiologia , Prevalência
9.
Sex Transm Dis ; 48(8): 529-535, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34110759

RESUMO

BACKGROUND: Chlamydia trachomatis (CT) infection remains highly prevalent, and young women are disproportionately affected. Most CT-infected women are asymptomatic, and their infection often goes unrecognized and untreated. We hypothesized that testing for active CT infection with molecular diagnostics and obtaining a reported history of CT infection underestimate the prevalence of current and past CT infection, and incorporating serum CT antibody testing in addition to these other prevalence measures would generate more accurate estimates of the prevalence of CT infection in asymptomatic young women. METHODS: We enrolled 362 asymptomatic women aged 16 to 29 years at 4 different clinical settings in Birmingham, AL, between August 2016 and January 2020 and determined the prevalence of CT infection based on having 1 or more of the following prevalence measures: an active urogenital CT infection based on molecular testing, reported prior CT infection, and/or being CT seropositive. Multivariable regression analysis was used to determine predictors of the prevalence of CT infection after adjustment for participant characteristics. RESULTS: The prevalence of CT infection was 67.7% (95% confidence interval, 62.6%-72.5%). Addition of CT antibody testing to the other individual prevalence measures more than doubled the CT infection prevalence. Non-Hispanic Black race, reported prior gonorrhea, and reported prior trichomoniasis predicted a higher prevalence of CT infection. CONCLUSIONS: More than half of women were unaware of ever having CT infection, suggesting many were at risk for CT-associated reproductive complications. These data reinforce the need to adhere to chlamydia screening guidelines and to increase screening coverage in those at risk.


Assuntos
Infecções por Chlamydia , Gonorreia , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis , Feminino , Humanos , Programas de Rastreamento , Prevalência , Fatores de Risco
10.
Epilepsia ; 61(11): 2534-2544, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32944945

RESUMO

OBJECTIVE: In patients with medically refractory focal epilepsy, stereotactic-electroencephalography (SEEG) can aid in localizing epileptogenic regions for surgical treatment. SEEG, however, requires long hospitalizations to record seizures, and ictal interpretation can be incomplete or inaccurate. Our recent work showed that non-directed resting-state analyses may identify brain regions as epileptogenic or uninvolved. Our present objective is to map epileptogenic networks in greater detail and more accurately identify seizure-onset regions using directed resting-state SEEG connectivity. METHODS: In 25 patients with focal epilepsy who underwent SEEG, 2 minutes of resting-state, artifact-free, SEEG data were selected and functional connectivity was estimated. Using standard clinical interpretation, brain regions were classified into four categories: ictogenic, early propagation, irritative, or uninvolved. Three non-directed connectivity measures (mutual information [MI] strength, and imaginary coherence between and within regions) and four directed measures (partial directed coherence [PDC] and directed transfer function [DTF], inward and outward strength) were calculated. Logistic regression was used to generate a predictive model of ictogenicity. RESULTS: Ictogenic regions had the highest and uninvolved regions had the lowest MI strength. Although both PDC and DTF inward strengths were highest in ictogenic regions, outward strengths did not differ among categories. A model incorporating directed and nondirected connectivity measures demonstrated an area under the receiver-operating characteristic (ROC) curve (AUC) of 0.88 in predicting ictogenicity of individual regions. The AUC of this model was 0.93 when restricted to patients with favorable postsurgical seizure outcomes. SIGNIFICANCE: Directed connectivity measures may help identify epileptogenic networks without requiring ictal recordings. Greater inward but not outward connectivity in ictogenic regions at rest may represent broad inhibitory input to prevent seizure generation.


Assuntos
Encéfalo/fisiopatologia , Eletroencefalografia/métodos , Epilepsias Parciais/fisiopatologia , Rede Nervosa/fisiopatologia , Descanso , Técnicas Estereotáxicas , Adulto , Encéfalo/diagnóstico por imagem , Epilepsias Parciais/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Adulto Jovem
11.
Int J Hyperthermia ; 37(2): 84-93, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32672117

RESUMO

Surgical treatment of deep or difficult to access lesions represents a unique and significant challenge for pediatric neurosurgeons. The introduction of stereotactic magnetic resonance-guided laser interstitial thermal therapy (LITT) over the last decade has had a dramatic impact on the landscape of pediatric neurosurgery. LITT provides a safe and effective option for children with epilepsy from hypothalamic hamartoma that represents a ground-breaking new therapy for a condition which was historically very difficult to treat with previous neurosurgical techniques. LITT has also been used as an alternative surgical technique for mesial temporal sclerosis, focal cortical dysplasia, MR-negative epilepsy, cavernoma-related epilepsy, insular epilepsy, and corpus callosotomy among other epilepsy etiologies. In some cases, LITT has been associated with improved cognitive outcomes compared to standard techniques, as in mesial temporal lobe epilepsy. Initial experiences with LITT for neuro-oncologic processes are also promising. LITT is often attractive to patients and providers as a minimally invasive approach, but the differences in safety and clinical outcome between LITT and traditional approaches are still being studied. In this review, we examine the emerging indications and clinical evidence for LITT in pediatric neurosurgery.


Assuntos
Hipertermia Induzida , Doenças Hipotalâmicas , Terapia a Laser , Procedimentos Neurocirúrgicos/tendências , Criança , Humanos , Doenças Hipotalâmicas/cirurgia , Lasers , Imageamento por Ressonância Magnética , Resultado do Tratamento
12.
J Neurol Neurosurg Psychiatry ; 90(10): 1109-1116, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31123139

RESUMO

OBJECTIVE: The effects of temporal lobe epilepsy (TLE) on subcortical arousal structures remain incompletely understood. Here, we evaluate thalamic arousal network functional connectivity in TLE and examine changes after epilepsy surgery. METHODS: We examined 26 adult patients with TLE and 26 matched control participants and used resting-state functional MRI (fMRI) to measure functional connectivity between the thalamus (entire thalamus and 19 bilateral thalamic nuclei) and both neocortex and brainstem ascending reticular activating system (ARAS) nuclei. Postoperative imaging was completed for 19 patients >1 year after surgery and compared with preoperative baseline. RESULTS: Before surgery, patients with TLE demonstrated abnormal thalamo-occipital functional connectivity, losing the normal negative fMRI correlation between the intralaminar central lateral (CL) nucleus and medial occipital lobe seen in controls (p < 0.001, paired t-test). Patients also had abnormal connectivity between ARAS and CL, lower ipsilateral intrathalamic connectivity, and smaller ipsilateral thalamic volume compared with controls (p < 0.05 for each, paired t-tests). Abnormal brainstem-thalamic connectivity was associated with impaired visuospatial attention (ρ = -0.50, p = 0.02, Spearman's rho) while lower intrathalamic connectivity and volume were related to higher frequency of consciousness-sparing seizures (p < 0.02, Spearman's rho). After epilepsy surgery, patients with improved seizures showed partial recovery of thalamo-occipital and brainstem-thalamic connectivity, with values more closely resembling controls (p < 0.01 for each, analysis of variance). CONCLUSIONS: Overall, patients with TLE demonstrate impaired connectivity in thalamic arousal networks that may be involved in visuospatial attention, but these disturbances may partially recover after successful epilepsy surgery. Thalamic arousal network dysfunction may contribute to morbidity in TLE.


Assuntos
Nível de Alerta/fisiologia , Tronco Encefálico/diagnóstico por imagem , Epilepsia do Lobo Temporal/diagnóstico por imagem , Neocórtex/diagnóstico por imagem , Núcleos Talâmicos/diagnóstico por imagem , Adulto , Tronco Encefálico/fisiopatologia , Estudos de Casos e Controles , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/cirurgia , Feminino , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neocórtex/fisiopatologia , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Procedimentos Neurocirúrgicos , Núcleos Talâmicos/fisiopatologia , Tálamo/diagnóstico por imagem , Tálamo/fisiopatologia
13.
J Clin Microbiol ; 56(9)2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29899001

RESUMO

Chlamydia trachomatis serological assays with improved sensitivity over commercially available assays are needed to evaluate the burden of C. trachomatis infection and the effectiveness of prevention efforts. We evaluated the performance of a C. trachomatis outer membrane complex protein B (OmcB) enzyme-linked immunosorbent assay (ELISA) in the detection of anti-C. trachomatis antibody responses in C. trachomatis-infected women. OmcB ELISA was less sensitive than our C. trachomatis elementary body (EB) ELISA, but it was highly specific. The magnitude of the antibody response was higher in African-Americans and those with prior C. trachomatis infection. Unlike EB ELISA, the IgG1 response to C. trachomatis OmcB was short-lived and was not maintained by repeat C. trachomatis infection.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Infecções por Chlamydia/diagnóstico , Chlamydia trachomatis/isolamento & purificação , Ensaio de Imunoadsorção Enzimática , Testes Sorológicos , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Formação de Anticorpos , Infecções por Chlamydia/sangue , Chlamydia trachomatis/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Testes Sorológicos/normas , Adulto Jovem
14.
J Infect Dis ; 215(11): 1653-1656, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28444306

RESUMO

Chlamydia trachomatis elementary body enzyme-linked immunosorbent assay (ELISA) was used to investigate serum anti-CT immunoglobulin G1 (IgG1; long-lived response) and immunoglobulin G3 (IgG3; short-lived response indicating more recent infection) from treatment (enrollment) and 6-month follow-up visits in 77 women previously classified as having spontaneous resolution of chlamydia. Of these women, 71.4% were IgG1+IgG3+, consistent with more recent chlamydia resolution. 15.6% were IgG3- at both visits, suggesting absence of recent chlamydia. Using elementary body ELISA, we demonstrated approximately 1 in 6 women classified as having spontaneous resolution of chlamydia might have been exposed to C. trachomatis but not infected. Further, we classified their possible infection stage.


Assuntos
Anticorpos Antibacterianos/sangue , Infecções por Chlamydia/imunologia , Chlamydia trachomatis/imunologia , Imunoglobulina G/sangue , Adolescente , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Adulto Jovem
15.
J Bacteriol ; 196(11): 1992-2003, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24659769

RESUMO

Streptococcus pneumoniae produces a protective capsular polysaccharide whose production must be modulated for bacterial survival within various host niches. Capsule production is affected in part by a phosphoregulatory system comprised of CpsB, CpsC, and CpsD. Here, we found that growth of serotype 2 strain D39 under conditions of increased oxygen availability resulted in decreased capsule levels concurrent with an ∼5-fold increase in Cps2B-mediated phosphatase activity. The change in Cps2B phosphatase activity did not result from alterations in the levels of either the cps2B transcript or the Cps2B protein. Recombinant Cps2B expressed in Escherichia coli similarly exhibited increased phosphatase activity under conditions of high-oxygen growth. S. pneumoniae D39 derivatives with defined deletion or point mutations in cps2B demonstrated reduced phosphatase activity with corresponding increases in levels of Cps2D tyrosine phosphorylation. There was, however, no correlation between these phenotypes and the level of capsule production. During growth under reduced-oxygen conditions, the Cps2B protein was essential for parental levels of capsule, but phosphatase activity alone could be eliminated without an effect on capsule. Under increased-oxygen conditions, deletion of cps2B did not affect capsule levels. These results indicate that neither Cps2B phosphatase activity nor Cps2D phosphorylation levels per se are determinants of capsule levels, whereas the Cps2B protein is important for capsule production during growth under conditions of reduced but not enhanced oxygen availability. Roles for factors outside the capsule locus, possible interactions between capsule regulatory proteins, and links to other cellular processes are also suggested by the results described in this study.


Assuntos
Cápsulas Bacterianas/metabolismo , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica/fisiologia , Regulação Enzimológica da Expressão Gênica/fisiologia , Oxigênio/metabolismo , Proteínas Tirosina Fosfatases/metabolismo , Streptococcus pneumoniae/enzimologia , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Dados de Sequência Molecular , Mutação , Fosforilação , Isoformas de Proteínas , Proteínas Tirosina Fosfatases/genética
16.
Front Cell Infect Microbiol ; 14: 1342621, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38371301

RESUMO

Murine research has revealed a significant role for antibody responses in protection against Chlamydia reinfection. To explore potential humoral immune markers of protection elicited by Chlamydia trachomatis (CT) antigens in humans in the context of presumed clinical correlates of protection, we used both an IgG1-based ELISA and a conventional total IgG ELISA to evaluate antibody responses. We evaluated responses to five CT outer membrane proteins (PmpE, PmpF, PmpG, PmpH, and MOMP), along with other promising CT antigens (Pgp3 and HSP60), negative control antigens (RecO and AtpE), and CT elementary bodies (EBs) in sera from a well-characterized cohort of 60 women with different CT infection outcomes, including two outcomes that are likely clinical correlates of protective immunity: spontaneous resolution of infection and absence of reinfection after treatment. Furthermore, we used a flow cytometry-based assay to measure antibody-mediated phagocytosis by neutrophils in these sera. Results demonstrated that IgG1 ELISA displayed higher sensitivity than conventional total IgG ELISA in assessing antibody responses to CT EBs and antigens. Pgp3 IgG1 ELISA exhibited the highest sensitivity compared to IgG1 ELISA incorporating CT EBs or other antigens, confirming Pgp3 IgG1 ELISA as an ideal assay for CT antibody detection. Most (95%) sera from women with CT infection outcomes exhibited antibody-mediated phagocytosis of CT EBs, which was significantly correlated with IgG1 antibody responses to MOMP, Pgp3, HSP60, and PmpF. However, neither IgG1 responses to CT antigens and EBs nor antibody-mediated phagocytosis were associated with clinical correlates of protection. These findings suggest that neither CT IgG1 antibody detection nor antibody-mediated phagocytosis will be useful as immune correlates of protection against CT infection in humans.


Assuntos
Infecções por Chlamydia , Vacinas , Humanos , Feminino , Animais , Camundongos , Chlamydia trachomatis , Formação de Anticorpos , Reinfecção , Antígenos de Bactérias , Infecções por Chlamydia/prevenção & controle , Infecções por Chlamydia/diagnóstico , Anticorpos Antibacterianos , Imunoglobulina G , Fagocitose
17.
J Bacteriol ; 195(24): 5469-78, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24097952

RESUMO

The capsular polysaccharide (CPS) is essential for Streptococcus pneumoniae virulence. Its synthesis requires multiple enzymes, and defects that block completion of the pathway can be lethal in the absence of secondary suppressor mutations. In this study, we examined the functions of three capsular glycosyltransferases (Cps2F, Cps2G, and Cps2I) involved in serotype 2 CPS synthesis, whose deletions select for secondary mutations. We demonstrate that Cps2F is a rhamnosyltransferase that catalyzes addition of the third and fourth sugars in the capsule repeat unit, while Cps2G adds the fifth sugar (glucose). Addition of the terminal residue (glucuronic acid) could not be detected; however, activities of the other glycosyltransferases together with bioinformatic analyses suggest that this step is mediated by Cps2I. Most of the secondary suppressor mutations resulting from loss of these enzymes occur in cps2E, the gene encoding the initiating glycosyltransferase. Examination of the 69 S. pneumoniae serotypes containing Cps2E homologues yielded a consensus amino acid sequence for this protein and demonstrated that there is a highly significant association between the residues that are 100% conserved and those altered by suppressor mutations. Cps2E contains an extracytoplasmic loop whose function is unknown. Among our collection of mutants, six contained missense mutations affecting amino acids in the extracytoplasmic loop. These residues are highly conserved among S. pneumoniae Cps2E homologues, and mutations therein severely reduced CPS synthesis and Cps2E activity. The critical functions of these amino acids suggest a role for the Cps2E extracytoplasmic loop in initiation, and possibly regulation, of capsule synthesis.


Assuntos
Cápsulas Bacterianas/metabolismo , Glicosiltransferases/metabolismo , Streptococcus pneumoniae/enzimologia , Streptococcus pneumoniae/metabolismo , Supressão Genética , Deleção de Genes , Glicosiltransferases/genética , Mutação de Sentido Incorreto , Streptococcus pneumoniae/genética
18.
Ann Diagn Pathol ; 17(6): 518-21, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24090509

RESUMO

Tumors arising from epithelium of the odontogenic apparatus or from its derivatives or remnants exhibit considerable histologic variation and are classified into several benign and malignant entities. A high proliferative activity of the odontogenic epithelium in ameloblastoma (AM) and keratocystic odontogenic tumor (KCOT) has been demonstrated in some studies individually. However, very few previous studies have simultaneously evaluated cell proliferation and apoptotic indexes in AM and KCOT, comparing both lesions. The aim of this study was to assess and compare cell proliferation and apoptotic rates between these two tumors. Specimens of 15 solid AM and 15 KCOT were evaluated. The proliferation index (PI) was assessed by immunohistochemical detection of Ki-67 and the apoptotic index (AI) by methyl green-pyronin stain. KCOT presented a higher PI than AM (P < .05). No statistically significant difference was found in the AI between AM and KCOT. PI and AI were higher in the peripheral cells of AM and respectively in the suprabasal and superficial layers of KCOT. In conclusion, KCOT showed a higher cell proliferation than AM and the AI was similar between these tumors. These findings reinforce the classification of KCOT as an odontogenic tumor and should contribute to its aggressive clinical behavior.


Assuntos
Ameloblastoma/metabolismo , Neoplasias Maxilomandibulares/metabolismo , Antígeno Ki-67/metabolismo , Cistos Odontogênicos/patologia , Tumores Odontogênicos/metabolismo , Adulto , Ameloblastoma/classificação , Ameloblastoma/patologia , Apoptose , Ciclo Celular , Proliferação de Células , Epitélio/metabolismo , Epitélio/patologia , Feminino , Humanos , Neoplasias Maxilomandibulares/classificação , Neoplasias Maxilomandibulares/patologia , Pessoa de Meia-Idade , Cistos Odontogênicos/classificação , Cistos Odontogênicos/metabolismo , Tumores Odontogênicos/classificação , Tumores Odontogênicos/patologia
19.
J Cancer Res Ther ; 18(Supplement): S205-S209, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36510965

RESUMO

Background: The benign neoplasms are normally slow growing, indolent with no invasive potential. However, there exist a few locally aggressive benign odontogenic tumors that have a tendency to invade and deform the surrounding structures. The exact reason for the aggressiveness of these benign neoplasms remained an enigma. Their biology and clinical expression can often be destructive and ominous. An appropriate treatment protocol needs to be followed to combat the high recurrence rate and aggressiveness of these entities. Aggressive and noniaggressive epithelial odontogenic tumors were analyzed immunohistochemically with Ki-67 and glypican 3 (GPC3). Materials and Methods: Fifty-nine cases of tumors were divided into aggressive odontogenic tumors (20 solid ameloblastomas, four unicystic ameloblastoma, and 28 keratocystic odontogenic tumors) and nonaggressive odontogenic tumors (five adenomatoid odontogenic tumors and two calcifying cystic odontogenic itumors). Results: Statistical analysis using Pearson correlation showed Ki-67 to be a better marker for differentiating aggressive from nonaggressive odontogenic tumor as compared to GPC3 (P < 0.001, highly significant), whereas among aggressive tumors, GPC3 turned out to be more useful as compared to Ki-67 (P < 0.001, highly significant). Conclusion: The present study provides an insight into the different biological behavior of odontogenic tumors, which can thus be helpful in determining the therapy strategies for more aggressive odontogenic tumors.


Assuntos
Ameloblastoma , Cistos Odontogênicos , Tumores Odontogênicos , Humanos , Ameloblastoma/patologia , Glipicanas , Imuno-Histoquímica , Antígeno Ki-67 , Cistos Odontogênicos/patologia , Tumores Odontogênicos/patologia
20.
Int J STD AIDS ; 32(13): 1196-1203, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34229513

RESUMO

Mycoplasma genitalium (MG) infection, a sexually transmitted infection (STI), causes cervicitis and may cause reproductive sequelae and adverse pregnancy outcomes. Some MG-infected women report dysuria, a symptom frequently attributed to urinary tract infection (UTI). Given potential MG-associated morbidity and the likelihood that UTI treatment would be ineffective in eradicating MG, an improved understanding of MG infection frequency and clinical significance in young women reporting dysuria is needed. We conducted MG testing on stored urogenital specimens collected in a pilot study on frequency of STIs in young women presenting to an emergency department for dysuria evaluation and performed a literature review on MG infection frequency in women reporting dysuria. Among 25 women presenting for dysuria evaluation in our pilot study, 6 (24.0%) had MG detected and one-third had co-infection with chlamydia and one-third with trichomoniasis; half with MG detected did not receive an antibiotic with known efficacy against MG, while the other half received azithromycin. In five studies identified in the literature review, dysuria was reported by 7%-19% of women and MG detected in 5%-22%. MG infection is common in young women with dysuria and empiric UTI treatment may not be effective against MG. Studies evaluating the clinical significance of MG infection in women reporting dysuria are needed.


Assuntos
Infecções por Mycoplasma , Mycoplasma genitalium , Cervicite Uterina , Disuria/epidemiologia , Feminino , Humanos , Infecções por Mycoplasma/diagnóstico , Infecções por Mycoplasma/tratamento farmacológico , Infecções por Mycoplasma/epidemiologia , Projetos Piloto , Prevalência
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