Insights into HLA-G genetics provided by worldwide haplotype diversity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

HLA-E coding and 3' untranslated region variability determined by next-generation sequencing in two West-African population samples

HLA-E is a non-classical Human Leucocyte Antigen class I gene with immunomodulatory properties. Whereas HLA-E expression usually occurs at low levels, it is widely distributed amongst human tissues, has the ability to bind self and non-self antigens and to interact with NK cells and T lymphocytes, being important for immunosurveillance and also for fighting against infections. HLA-E is usually the most conserved locus among all class I genes. However, most of the previous studies evaluating HLA-E variability sequenced only a few exons or genotyped known polymorphisms. Here we report a strategy to evaluate HLA-E variability by next-generation sequencing (NGS) that might be used to other HLA loci and present the HLA-E haplotype diversity considering the segment encoding the entire HLA-E mRNA (including 5'UTR, introns and the 3'UTR) in two African population samples, Susu from Guinea-Conakry and Lobi from Burkina Faso. Our results indicate that (a) the HLA-E gene is indeed conserved, encoding mainly two different protein molecules; (b) Africans do present several unknown HLA-E alleles presenting synonymous mutations; (c) the HLA-E 3'UTR is quite polymorphic and (d) haplotypes in the HLA-E 3'UTR are in close association with HLA-E coding alleles. NGS has proved to be an important tool on data generation for future studies evaluating variability in non-classical MHC genes.

Structural insights into substrate binding of brown spider venom class II phospholipases D

Phospholipases D (PLDs), the major dermonecrotic factors from brown spider venoms, trigger a range of biological reactions both in vitro and in vivo. Despite their clinical relevance in loxoscelism, structural data is restricted to the apo-form of these enzymes, which has been instrumental in understanding the functional differences between the class I and II spider PLDs. The crystal structures of the native class II PLD from Loxosceles intermedia complexed with myo-inositol 1-phosphate and the inactive mutant H12A complexed with fatty acids indicate the existence of a strong ligand-dependent conformation change of the highly conserved aromatic residues, Tyr 223 and Trp225 indicating their roles in substrate binding. These results provided insights into the structural determinants for substrate recognition and binding by class II PLDs.

Aplicação da análise de jarabak, no estudo da relação entre a altura total facial anterior e posterior, em pacientes portadores de má-oclusão de classe I e classe II divisão 1 de angle, por meio de radiografias cefalométricas

ln order to predict the facial growth using Jarahak's analysis, cephalometric radiographies of 120 subjects during the mixed dentition and between 6 and 10 years of age were studied. From the total, 60 subjects (30 males and 30 females) were classified as Angle's Class I and 60 subjects (30 males and 30 females) were classified as Angle's Class II, Division 1. AIl subjects did not receive any orthodontic treatment. The proportion between anterior and posterior facial heigth (SGo-NMe) was studied, which is determined by the formula PFH x 100/ AFH = %, neither being straight (> 62% < 65), clockwise ( > 58% < 62%) and anti-clockwise ( > 65% - 80%). Mean average, standard deviation and facial height proportion (SGo - NMe) were determined for males and females according to Angle's classification of malocc!usion. Sexual dimorphism was examined with regard to different types of Angle's malocclusion and the direction of the facial growth, and the correlation of four cephalometrics measurements were analvsed

Low expression of human histocompatibility soluble leukocyte antigen-G (HLA-G5) in invasive cervical cancer with and without metastasis, associated with Papilloma Virus (HPV)

Human leukocyte antigen-G (HLA-G) is a non-classical major histocompatibility complex class Ib molecule that acts as a specific immunosuppressor. Some studies have demonstrated that human papillomavirus (HPV) seems to be involved in lower or absent HLA-G expression, particularly in cervical cancer. In this study, we performed a cross-sectional study, systematically comparing the qualitative expression of the HLA-G5 isoform in invasive cervical carcinoma (ICC), stratifying patients according to the presence [ICC with metastasis (ICCW)] and absence [ICC without metastasis (ICCWT)] of metastasis, correlating these findings with interference of HPV and demographic and clinical variables. Seventy-nine patients with a diagnosis of ICC were stratified into two groups: ICCWT (n=52 patients) and ICCW (n=27). Two biopsies were collected from each patient (one from the tumor lesion and one from a lymph node). Immunohistochemistry analyses were performed for the HLA-G5 isoform, for HPV detection, and virus typing. HLA-G5 isoform molecules were detected in 25 cases (31.6%), 17 (32.7%) without metastasis and 8 (29.6%) with metastasis. HPV was detected in the cervical lesions of 74 patients (93.7%), but low expression of the HLA-G5 isoform was observed in all HPV-related cases. These findings are important; however, additional studies are necessary to identify the influence of HPV with HLA-G5 isoform expression on invasive cervical malignancies.

Expression of nonclassical molecule human leukocyte antigen-G in oral lesions

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Características clínicas associadas à evolução desfavorável na miocardiopatia periparto

OBJETIVOS: Avaliar as características clínicas de mulheres com diagnóstico prévio de miocardiopatia periparto e verificar as características associadas à evolução desfavorável. MÉTODOS: Variáveis clínicas, obstétricas e ecocardiográficas foram estudadas em 12 pacientes com miocardiopatia periparto, avaliadas no momento do diagnóstico e em consulta atual, quando foram divididas em dois grupos: GF (n= 6, sem alterações cardíacas) e GD (n= 6, com cardiomegalia e disfunção ventricular persistentes). As comparações foram feitas com o teste t de Student e exato de Fisher (p<0,05). RESULTADOS: No diagnóstico, a idade média das pacientes (8 brancas e 4 negras/pardas) foi de 24±7,4 anos; todas em classe funcional IV (NYHA) e 8 relataram hipertensão gestacional ou pré-eclâmpsia. A mediana do tempo de seguimento foi de 25 meses. Dez pacientes evoluíram para classe funcional I/II. A comparação entre os grupos mostrou GD com menor fração de ejeção do ventrículo esquerdo (0,30±0,05 vs. 0,58±0,09; p<0,001) e maior diâmetro sistólico do VE (58±5mm vs. 46±3mm; p<0,001), no momento do diagnóstico. A evolução desfavorável foi mais frequente entre as pardas (p=0,01). Na avaliação atual o GD apresentou menor espessura relativa da parede (0,13±0,02 vs. 0,17±0,02; p< 0,05) e maior massa do VE (283±90g vs. 186±41g; p<0,05). CONCLUSÃO: Pacientes com miocardiopatia periparto prévia apresentam evolução desfavorável associada à raça negra e alterações cardíacas iniciais mais acentuadas e a evolução favorável está associada à redução da massa miocárdica e aumento da espessura relativa da parede ventricular.

Autopsy: quality assurance in the ICU

Objective: To examine the correlation between the clinical diagnosis and autopsy findings in adult patients who died in an intensive care unit (ICU). To determine the rate of agreement of the basic and terminal causes of death and the types of errors in order to improve quality control of future care,Design, Retrospective study.Setting: Adult ICU in a university hospital.Patients: 30 adult patients who died in the ICU. with the exclusion of medicolegal cases.Methods and main results: Anatomo-clinical meetings were held to analyze the pre- and postmortem correlations in 30 consecutive autopsies at the ICU of the University Hospital, School of Medicine of Botucatu/ UNESP, from January 1994 to January 1997. The rate of correct clinical diagnoses of the basic cause was 66.7 %; in 23.3 % of cases, if the correct diagnosis was made, management would have been different, as would have been the evolution of the patient's course (Class I error): in 10 % of the cases the error would not have led to a change in management (Class II error). The rate of correct clinical diagnoses of terminal cause was 80 %.Conclusions: the rate of recognition of the basic cause was 66.7 %, which is consistent with the literature, but the Class I error rate was higher than that reported in the literature.

Use of the connective tissue graft for the coverage of composite resin-restored root surfaces in maxillary central incisors

The purpose of this article is to report the use of the subepithelial connective tissue graft technique combined with the coronally positioned flap on a composite resin-restored root surface to treat Miller Class I gingival recessions associated with deep cervical abrasions in maxillary central incisors. Clinical measurements, including gingival recession height, probing depth, and bleeding on probing (BoP), were recorded during the preoperative clinical examination and at 2, 6, 12, and 24 months postoperatively. During the follow-up periods, no periodontal pockets or BoP were observed. The periodontal tissue of the teeth presented normal color, texture, and contouring. In addition, it was observed that creeping attachment had occurred on the restoration. This case report shows that this form of treatment can be highly effective and predictable in resolving gingival recession associated with a deep cervical abrasion. (Quintessence Int 2012;43:597-602)

Prevalence of removable partial dentures users treated at the Aracatuba Dental School - UNESP

Objectives: The aim of this study was to evaluate the frequency of removable partial dentures (RPD) at the Aracatuba Dental School.Methods: The study was conducted by analysing 412 clinical history of patients attended at the RPD clinics in the period from 2000 to 2007.Results: 412 charts were analysed: 148 (35.9%) men and 264 (64.1%) women. The mean age was 53.8 years (men) and 52.4 years (women). A total of 556 dentures were made; of these, 233 (41.90%) were maxillary and 323 (58.09%) were mandibular dentures. The most frequent Kennedy classification found was Class III (maxilla) and Class I (mandible). In the maxilla, 55% (126) of the major connectors were of the anterior-posterior palatal bar, while in the mandible, 64% (202) were the lingual bar. As regards the claps, 401 were circumferential and 318 were bar claps.Conclusion: The mean age of the patients was 52.9 years with higher prevalence of female patients; the most frequent Kennedy's classification was Class I in mandible and Class III in maxilla; the most common major connector was anterior-posterior palatal bar for maxilla and lingual bar for mandible; the circumferential clasps were the most common retainer used in both jaws.

Prevalence of Malocclusion and Related Oral Habits in 5-to 6-year-old Children

Purpose: To verify the prevalence of malocclusion and the influence of harmful oral habits on deciduous dentition in 5- and 6-year-old children enrolled in Brazilian public elementary schools during 2010.Materials and Methods: Exams were conducted in 1385 children from 56 Brazilian elementary schools using the method recommended by the World Health Organization (WHO) for epidemiological surveys on oral health. Information about the type of arch, social and economic data and harmful oral habits of the children were collected through a structured questionnaire.Results: In relation to canine occlusion, a high prevalence of Class I (74.5%), followed by Class II (19.4%), was found. Among all participants, 22% showed high overjet, 7.8% showed edge-to-edge occlusion and 2.3% showed anterior crossbite. In relation to overbite, 13.2% had short overbite, 14.3% open bite and 16.8% high overbite. The presence of posterior crossbite occurred in 14.6% of children. Maxillae predominantly exhibited the type I arch (67.9%) and mandibles predominantly exhibited type II (51.7%). In relation to harmful oral habits, 43.4% used a pacifier, 84.8% used a bottle and finger sucking was reported by 17.2%.Conclusion: There was a high prevalence of malocclusion associated with oral habits harmful to deciduous dentition.

Características cefalométricas do padrão face longa

Este estudo determinou as características cefalométricas dos indivíduos portadores de Padrão Face Longa em comparação com indivíduos Padrão I. Um total de 73 telerradiografias em norma lateral, sendo 34 Padrão Face Longa e 39 Padrão I, foram selecionadas com base na morfologia facial, não considerando as relações oclusais e sagitais. Foram avaliados: padrão de crescimento facial, alturas faciais anteriores e posterior, relação maxilo-mandibular, além das relações dentárias com suas bases apicais. de uma forma geral, os indivíduos Padrão Face Longa apresentaram grandes desvios em relação aos indivíduos Padrão I, sendo a doença decorrente de um desequilíbrio entre os componentes verticais. Pôde-se observar que os valores das grandezas AFAT, AFAI, AFATperp, AFAIperp, 1-PP, 6-PP, 1-PM, SNB, ANB, ângulo goníaco, ângulo plano mandibular, além das proporções AFAI/AFAT e AFAIperp/AFATperp, estavam significantemente alterados para os indivíduos Padrão Face Longa. Com base nos resultados obtidos neste estudo, verificou-se que esses indivíduos caracterizavam-se pelo padrão de crescimento vertical e por um aumento da altura facial anterior inferior - conseqüentemente, da altura facial anterior total - estando a deformidade localizada abaixo do plano palatino. Foram observados ainda um retrognatismo maxilar e mandibular, além da presença de extrusão dentária anterior (superior e inferior) e póstero-superior, com os incisivos superiores bem posicionados em suas bases e os inferiores lingualizados.

Características cefalométricas do Padrão Face Longa: considerando o dimorfismo sexual

OBJETIVO: o presente estudo avaliou a hipótese de variação das características cefalométricas de acordo com o gênero para portadores de Padrão Face Longa. METODOLOGIA: foi analisado um total de 73 telerradiografias em norma lateral, sendo 34 Padrão Face Longa e 39 Padrão I (grupo controle), selecionadas com base na morfologia facial, sem considerar as relações oclusais. Foram avaliados: padrão de crescimento facial, alturas faciais anteriores e posterior, relação maxilomandibular, além das relações dentárias com suas bases apicais. RESULTADOS: o grupo controle (Padrão I) apresentou dimorfismo (p<0,001) no comprimento efetivo da maxila e da mandíbula, além das alturas faciais avaliadas. Foram significantes também (p<0,05) as proporções entre as alturas faciais e as distâncias entre os incisivos e molares em relação aos planos palatino e mandibular. Para os portadores de Padrão Face Longa, as mesmas variáveis cefalométricas não mostraram diferenças significantes entre os gêneros (p>0,05), exceto os comprimentos efetivos da maxila e da mandíbula, além da altura facial anterior inferior e posterior (p<0,05). CONCLUSÕES: concluiu-se que enquanto ocorreu dimorfismo nos indivíduos Padrão I, para as estruturas influenciadas pela diferença no tamanho esquelético entre os gêneros, isso não aconteceu nos portadores de Padrão Face Longa. Essa maior similaridade entre os gêneros provavelmente ocorreu porque a deformidade, mais grave no gênero feminino, foi suficiente para anular o menor tamanho esquelético esperado para estes indivíduos.

O efeito da retração dos dentes anteriores sobre o ponto A em pacientes submetidos ao tratamento ortodôntico corretivo

OBJETIVO: avaliar o efeito da retração anterior sobre o ponto A sagital e verticalmente, bem como a correlação e a previsibilidade do comportamento dessas estruturas. METODOLOGIA: sessenta telerradiografias em norma lateral foram usadas, tomadas no início e no final do tratamento ortodôntico corretivo, a partir de 30 pacientes (22 feminino e 8 masculino) com idade entre 10 e 17 anos antes do tratamento, com má oclusão de Classe II, divisão 1 ou Classe I, que foram submetidos às extrações dos quatro primeiros pré-molares ou somente dois primeiros pré-molares superiores. Além das variáveis .1NA,1-NA, 1.PP e 1-A, mensurações lineares horizontais e verticais foram feitas em relação a uma linha de referência construída a partir da linha SN menos 7º e uma linha perpendicular a ela. Todos os dados foram mensurados duas vezes, e as médias foram submetidas ao teste t emparelhado, de correlação linear e de regressão. RESULTADOS: em média, o ponto A retraiu 0,71mm e movimentou para baixo 2,38mm, seguindo 1,03mm e 4,13mm de retração, respectivamente, do ápice radicular e da borda incisal, e 2,35mm de extrusão dentária. A retração do ponto A apresentou correlação positiva em relação ao ápice radicular (r = 0,75; alfa < 0,0001) e em relação à retração da borda incisal (r = 0,70; alfa < 0,0001), mostrando um comportamento ântero-posterior previsível. CONCLUSÕES: concluiu-se que o ponto A retraiu-se e movimentou-se para baixo seguindo o dente, e a retração do ponto A em relação aos incisivos foi previsível.

Clinical assessment of postoperative sensitivity in posterior composite restorations

This incidence of postoperative sensitivity was evaluated in resin-based posterior restorations. Two hundred and ninety-two direct restorations were evaluated in premolars and molars. A total of 143 Class I and 149 Class 11 restorations (MO/OD and MOD) were placed in patients ranging in age from 30 to 50 years. After the cavity preparations were completed, a rubber dam was placed, and the preparations were restored using a total-etch system (Prime & Bond NT) and a resin-based restorative material (TPH Spectrum). The patients were contacted after 24 hours and 7, 30 and 90 days postoperatively and questioned regarding the presence of sensitivity and the stimuli that triggered that sensitivity. The Chi-square and Fisher's Exact Test were used for statistical analysis. Evaluation at 24 hours after restorative treatment revealed statistically significant differences among the types of cavity preparations restored and the occurrence of postoperative sensitivity (p=0.0003), with a higher frequency of sensitivity in Class H MOD restorations (26%), followed by Class II MO/DO (15%) and Class I restorations (5%). At 7, 30 and 90 days after restorative treatment, there was a decrease in the occurrence of sensitivity for all groups. The percentage of sensitivity among the groups was not significantly different. This study shows that the occurrence of sensitivity is correlated with the complexity of the restoration.