Association of tumor necrosis factor receptor type 2 +587 gene polymorphism with severe chronic periodontitis

BACKGROUND: Genetic polymorphisms for cytokines and their receptors have been proposed as potential markers for periodontal disease. Tumor necrosis factor receptor 2 (TNFR2) is one of the cell surface receptors for TNF-alpha. Recent studies have suggested that TNFR2 gene polymorphism is involved in autoimmune and other diseases. OBJECTIVES: The aim of the present study is to evaluate whether TNFR2(+587T/G) gene polymorphism is associated with chronic periodontitis (CP). METHODS: One hundred and ninety-six unrelated subjects (age 40-65 years) with different levels of CP were identified according to established criteria, including measurements of probing pocket depth (PPD), clinical attachment level (CAL), and alveolar bone loss (BL). All subjects were of Japanese descent and non-smokers. Single nucleotide polymorphism at position +587(T/G) in the TNFR2 gene was detected by a polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method. RESULTS: The frequency and the positivity of the +587G allele were significantly higher in severe CP patients than in controls (p=0.0097; odds ratio=2.61, p=0.0075; odds ratio=3.06). In addition, mean values of PPD, CAL, and BL were significantly higher in the +587G allele positive than in the negative subjects (p=0.035, 0.022, and 0.018, respectively). CONCLUSIONS: These findings suggest that the TNFR2(+587G) polymorphic allele could be associated with severe CP in Japanese.     

Twins and twinning, dentists and dentistry

Comparisons of physical features within identical (monozygous) and non-identical (dizygous) twin pairs have provided valuable insights into the relative contributions of genetic and environmental influences to observed variability. The special nature of the twinning process itself also provides an opportunity to learn more about early human development, including how body symmetry is determined. The mechanisms of twinning, mortality and morbidity in twins, determination of body symmetry including the phenomenon of mirror-imaging, postnatal growth and development of twins, and zygosity determination are discussed. Twin studies with direct relevance to clinical dentistry are reviewed and illustrated by examples from an ongoing investigation of dentofacial morphology in South Australian twins.     

Mandibulofacial dysostosis. Case report

A case of mandibulofacial dysostosis (Treacher Collins syndrome) is presented. Clinical features and skull radiographs revealed typical anomalies associated with the syndrome. Cleft of the soft palate and unerupted multiple supernumerary teeth were present in this case. No haematological, biochemical or immunological abnormalities could be detected in the patient. Pedigree analysis showed an autosomal dominant mode of transmission of the disease. Chromosomal studies did not reveal any structural or numerical discrepancies.     

腭心面综合征研究进展

腭心面综合征（velo-cardio-facial syndrome,VCFS）是人类常见的染色体缺失综合征之一,缺失基因大多定位于22q染色体长臂的22q11.21～q11.23区。其复杂临床表现集中体现在颅面、心脏、免疫、腺体等方面的发育性畸形,作者就其临床表现、发病机制、候选基因及其相关作用通路的最近研究进展做一综述。     

Drug-impaired driving and traffic collisions: Study on a cross section of the Italian population

The present study focuses on the association between road accidents and the presence of drugs of abuse markers in the biological fluids of the drivers. Biological fluids collected from 1236 drivers involved in road accidents (54 fatal and 1182 non-fatal crashes) in the Rome area were analyzed for alcohol and psychotropic drugs, as required by judicial authorities. The substance most frequently detected was alcohol (in 19% of non-fatal and 32% of fatal crashes), followed by cannabinoids (12% of non-fatal crashes) and cocaine (9% of non-fatal and 20% of fatal crashes). The results obtained for cocaine and cannabinoids in blood and urine were compared. We observed the absence or low concentrations of the active drug in blood (cocaine was often below 5 ng/ml and THC below 1 ng/ml), whereas urinary concentrations of metabolites were generally high (benzoylecgonine 250–above 5000 ng/ml, THCCOOH 15–270 ng/ml). The risk of being involved in a road accident if cocaine or cannabis markers were present in the urine specimens was evaluated compared to a control population. The odds ratios calculated, being 8.13 for cannabis and 5.32 for cocaine, suggest a strong association between the presence of these drugs in the urine of drivers and traffic accidents, regardless of their presence in blood samples. The present data suggest that the chance of being involved in a road accident is higher than in the control population even if the subject is no longer “under the influence” of cannabis or cocaine at the time of the accident.     

Administration and detection of gene therapy in horses: A systematic review

Gene therapy uses genetic modification of cells to produce a therapeutic effect. Defective or missing genes can be repaired or replaced, or gene expression can be modified using a variety of technologies. Repair of defective genes can be achieved using specialized gene editing tools. Gene addition promotes gene expression by introducing synthetic copies of genes of interest (transgenes) into cells where they are transcribed and translated into therapeutic proteins. Protein production can also be modified using therapies that regulate gene expression. Gene therapy is currently prohibited in both human and equine athletes because of the potential to induce production of performance-enhancing proteins in the athlete's body, also referred to as “gene doping.” Detection of gene doping is challenging and necessitates development of creative, novel analytical methods for doping control. Methods for detection of gene doping must be specific to and will vary depending on the type of gene therapy. The purpose of this paper is to present the results of a systematic review of gene editing, gene therapy, and detection of gene doping in horses. Based on the published literature, gene therapy has been administered to horses in a large number of experimental studies and a smaller number of clinical cases. Detection of gene therapy is possible using a combination of PCR and sequencing technologies. This summary can provide a basis for discussion of appropriate and inappropriate uses for gene therapy in horses by the veterinary community and guide expansion of methods to detect inappropriate uses by the regulatory community.     

Pig-to-baboon lung xenotransplantation: Extended survival with targeted genetic modifications and pharmacologic treatments

Galactosyl transferase knock-out pig lungs fail rapidly in baboons. Based on previously identified lung xenograft injury mechanisms, additional expression of human complement and coagulation pathway regulatory proteins, anti-inflammatory enzymes and self-recognition receptors, and knock-down of the β4Gal xenoantigen were tested in various combinations. Transient life-supporting GalTKO.hCD46 lung function was consistently observed in association with either hEPCR (n = 15), hTBM (n = 4), or hEPCR.hTFPI (n = 11), but the loss of vascular barrier function in the xenograft and systemic inflammation in the recipient typically occurred within 24 h. Co-expression of hEPCR and hTBM (n = 11) and additionally blocking multiple pro-inflammatory innate and adaptive immune mechanisms was more consistently associated with survival >1 day, with one recipient surviving for 31 days. Combining targeted genetic modifications to the lung xenograft with selective innate and adaptive immune suppression enables prolonged initial life-supporting lung function and extends lung xenograft recipient survival, and illustrates residual barriers and candidate treatment strategies that may enable the clinical application of other organ xenografts.     

Molecular diagnosis of kidney transplant failure based on urine

In light of the organ shortage, there is a great responsibility to assess postmortal organs for which procurement has been consented and to increase the life span of transplanted organs. The former responsibility has moved many centers to accept extended criteria organs. The latter responsibility requires an exact diagnosis and, if possible, omission of the harmful influence on the transplant. We report the course of a kidney transplant that showed a steady decline of function over a decade, displaying numerous cysts of different sizes. Clinical workup excluded the most frequent causes of chronic transplant failure. The filed allocation documents mentioned the donor’s disease of oral‐facial‐digital syndrome, a rare ciliopathy, which can also affect the kidney. Molecular diagnosis was performed by culturing donor tubular cells from the recipient´s urine more than 10 years after transplantation. Next‐generation panel sequencing with DNA from tubular urinary cells revealed a novel truncating mutation in OFD1, which sufficiently explains the features of the kidney transplants, also found in the second kidney allograft. Despite this severe donor disease, lifesaving transplantation with good long‐term outcome was enabled for 5 recipients.     

Marker chromosome genomic structure and temporal origin implicate a chromoanasynthesis event in a family with pleiotropic psychiatric phenotypes

Small supernumerary marker chromosomes (sSMC) are chromosomal fragments difficult to characterize genomically. Here, we detail a proband with schizoaffective disorder and a mother with bipolar disorder with psychotic features who present with a marker chromosome that segregates with disease. We explored the architecture of this marker and investigated its temporal origin. Array comparative genomic hybridization (aCGH) analysis revealed three duplications and three triplications that spanned the short arm of chromosome 9, suggestive of a chromoanasynthesis‐like event. Segregation of marker genotypes, phased using sSMC mosaicism in the mother, provided evidence that it was generated during a germline‐level event in the proband's maternal grandmother. Whole‐genome sequencing (WGS) was performed to resolve the structure and junctions of the chromosomal fragments, revealing further complexities. While structural variations have been previously associated with neuropsychiatric disorders and marker chromosomes, here we detail the precise architecture, human life‐cycle genesis, and propose a DNA replicative/repair mechanism underlying formation.