Reduced CD8+ T cells infiltration can be associated to a malignant transformation in potentially malignant oral epithelial lesions

Clinical Oral Investigations - The aim of this study was to evaluate the immunohistochemical expressions of PD1, CD4+, and CD8+ in premalignant lesions (OPML) that were transformed into oral...     

Genetic variation may explain why females are less susceptible to dental erosion

Not all individuals at risk for dental erosion (DE) display erosive lesions. The prevalence of DE is higher among male subjects. The occurrence of DE may depend on more than just acidic challenge, with genetics possibly playing a role. The aim of this study was to investigate the association of enamel‐formation genes with DE. One premolar and a saliva sample were collected from 90 individuals. Prepared teeth were immersed in 0.01 M HCl (pH 2.2), and enamel loss (μm) was measured using white light interferometry. DNA was extracted from saliva, and 15 single‐nucleotide polymorphisms were analysed. Allele and genotype frequencies were related to the enamel loss of the specimens. Single‐marker and haplotype analyses were performed using sex as a covariate. Mean enamel loss was higher for male donors than for female donors (P = 0.047). Significant associations were found between enamel loss and amelogenin, X‐linked (AMELX), tuftelin 1 (TUFT1), and tuftelin‐interacting protein 11 (TFIP11). Analyses showed significant associations between variation in enamel‐formation genes and a lower susceptibility to DE in female subjects. The results indicate that susceptibility to DE is influenced by genetic variation, and may, in part, explain why some individuals are more susceptible than others to DE, including differences between female subjects and male subjects.     

Nickel titanium T-loop wire dimensions for en masse retraction

Objective:To compare the force system produced by nickel-titanium T-loop springs made with wires of different dimensions.Material and Methods:Thirty compound T-loop springs were divided into three groups according to the dimensions of the nickel-titanium wire used for its design: 0.016” × 0.022”, 0.017” × 0.025”, and 0.018” × 0.025”. The loops were tested on the Orthodontic Force Tester machine at an interbracket distance of 23 mm and activated 9 mm. The force in the y-axis and the moment in the x-axis were registered while the calculated moment to force ratio was recorded at each .5 mm of deactivation. The data were analyzed by three analyses of variance of repeated measures to detect differences and interactions between deactivation and wire size on force, moment, and moment-force ratios (M/F).Results:All groups had significantly different forces (P < .001). The 0.016” × 0.022” wire produced 1.78N of force while the 0.017” × 0.025” and the 0.018” × 0.025” produced 2.81 N and 3.25 N, respectively. The 0.016” × 0.022” wire produced lower moments (11.6 Nmm) than the 0.017” × 0.025” and 0.018” × 0.025” wires, which produced similar moments (13.9 Nmm and 14.4Nmm, respectively). The M/F produced was different for all groups; 0.016” × 0.022” T-loops produced 6.7 mm while the 0.017” × 0.025” and 0.018” × 0.025” T-loops produced 5.0 mm and 4.5 mm, respectively. An interaction was detected for all variables between deactivation and groups.Conclusion:The larger wires tested produced higher forces with slight increase on the moments, but the M/F produced by the 0.016” × 0.022” wire was the highest found.     

DNA and Heparin Alter the Internalization Process of Anti-DNA Monoclonal Antibodies According to Patterns Typical of Both the Charged Molecule and the Antibody

The internalization into CHO-K1 fibroblasts of three polyreactive monoclonal IgG2a anti-DNA autoantibodies (mAbs), F14.6, J20.8 and F4.1, isolated from the same unimmunized (NZBxNZW) F1 mouse, and synthetic peptides derived from F4.1 was studied using a technique which quantifies nuclear accumulation. The localization of the mAbs was intranuclear. We compared the influence of two negatively-charged molecules, DNA or heparin. At low concentrations, DNA had dual effects-inhibitory or stimulatory-depending on the mAb. Heparin was inhibitory or had no effect. The possibility that proteoglycans are 'receptors' recognized by anti-DNA mAbs which bind through heparin-sensitive reactions, was explored. Only F4.1 internalization was partly inhibited in glycosaminoglycan-deficient cells. We propose that the complex alterations of internalization patterns of these polyreactive mAbs by the two negatively charged molecules can be explained by (a) the potential of polyreactive mAbs to bind to various charge (or conformation-) dependent 'receptors', (b) the potential of a subclass of mAbs complexed with DNA to utilize additional 'receptor(s)'. Glycosaminoglycans were required for internalization of F4.1-derived peptides, which remained extranuclear, suggesting that nuclear internalization of mAb F4.1 is a multistep process that requires certain sequences present on the intact mAb.     

Evidence for an association of TP53 codon 72 polymorphism with breast cancer risk

BACKGROUND: A common Arg/Pro polymorphism at codon 72 of the TP53 gene has been investigated as a risk factor for cancer in different populations. So far, the results have been controversial. Our purpose was to investigate the association of this polymorphism with breast carcinoma in women from Southern Brazil, a high-risk area for breast cancer. METHODS: Blood samples collected from 118 women with primary breast carcinoma and from 202 female blood donors were analyzed through polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. RESULTS: The relative frequency of each allele was 0.75 for Arg and 0.25 for Pro in patients with cancer, and 0.62 for Arg and 0.38 for Pro in normal controls (P < 0.001). The Arg/Arg genotype was significantly associated with an increased risk for breast cancer (OR 2.9; 95% CI 1.43-3.6; P < 0.002). No correlation between the genotype distribution and specific prognostic predictors for the disease outcome was observed. DISCUSSION: TP53 codon 72 polymorphism might be implicated in breast carcinogenesis, with the Arg/Arg genotype being associated with an increased susceptibility for this malignancy.     

Absence of IFNγ expression induces neuronal degeneration in the spinal cord of adult mice

Background  

Interferon gamma (IFNγ) is a pro-inflammatory cytokine, which may be up-regulated after trauma to the peripheral or central nervous system. Such changes include reactive gliosis and synaptic plasticity that are considered important responses to the proper regenerative response after injury. Also, IFNγ is involved in the upregulation of the major histocompatibility complex class I (MHC class I), which has recently been shown to play an important role in the synaptic plasticity process following axotomy. There is also evidence that IFNγ may interfere in the differentiation and survival of neuronal cells. However, little is known about the effects of IFNγ absence on spinal cord neurons after injury.     

Activation of the ubiquitin proteolytic pathway in human septic heart and diaphragm

ObjectiveMechanisms of sepsis-induced myocardial and diaphragmatic alteration are multiple and remain largely unknown, particularly in humans. In the present study, we compared the inducible nitric oxide synthase (NOS-2) expression, the peroxynitrite production and the expression and activation of the ubiquitin proteolytic pathway in the wall of the 4 cardiac chambers, in the diaphragm, and in the rectus abdominis.PatientsSeven patients who died from septic shock associated with a myocardial depression and 5 nonseptic (control) patients.Measurements and resultsWe evaluated protein expression by Western blot. Nitrotyrosin and ubiquitin residues were localized by immunofluorescence. NOS-2, nitrated proteins, free ubiquitin, and ubiquitinated proteins are overexpressed in the wall of the four cardiac cavities, in the diaphragm and in the rectus abdominis of septic patients at a similar level. Ubiquitinated proteins with a molecular mass of 50, 35, 30, and 25 kD were consistently detected in heart, diaphragm, and rectus abdominis of septic shock patients but lacking in nonseptic patients. In situ immunolabelling of ubiquitin showed a colocalisation with nitrotyrosine residues at the sarcomeric level of cardiac myocytes in septic patients.ConclusionsThis study showed the first evidence for the activation of the proteolytic ubiquitin–proteasome pathway in human heart and diaphragm in septic shock.