PADI4 polymorphisms and the functional haplotype are associated with increased rheumatoid arthritis susceptibility: A replication study in a Southern Mexican population

Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The peptidyl arginine deiminase type IV (PADI4) gene has been associated with RA susceptibility in several populations. We addressed the relationship between three exonic PADI4 gene single nucleotide polymorphisms (SNPs) PADI4_89 (rs11203366), PADI4_90 (rs11203367) and PADI4_92 (rs874881) and related haplotypes with RA in a population from Southern México. This study included 200 RA patients and 200 control subjects. The SNPs were evaluated using the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) technique, and antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). In this population, the minor alleles of PADI4_891G, PADI4_901T and PADI4_921G gene polymorphisms were associated with RA susceptibility (OR = 1.34, p = 0.04; OR = 1.35, p = 0.03; OR = 1.34, p = 0.04; respectively). The GTG haplotype was also significantly associated with RA (OR = 2.27 95%CI = 1.18–4.41; p = 0.008), but did not show association with levels of anti-CCP antibodies and clinical parameters. In conclusion, our replication study in a Southern Mexican population suggests that PADI4 individual polymorphisms and the related susceptibility haplotype (GTG) are also genetic risk markers for RA.     

Determinants of survival following hepatocellular carcinoma in Egyptian patients with untreated chronic HCV infection in the pre-DAA era

Background and Study Aims

In this study we assessed rates and determinants of survival in people with untreated chronic HCV infection and hepatocellular carcinoma (HCC) in an Egyptian liver clinic setting.

Effects of aging on the dimensional stability of custom-made mouthguards.

OBJECTIVE: The purpose of this investigation was to assess the effects of aging on the dimensional stability of vacuum-formed, pressure-formed, and pressure-laminated custom-made mouthguards. METHOD AND MATERIALS: A master model representing the dental arch was fabricated in acrylic resin. Two ethylene vinyl acetate thermoplastic materials were tested: Essix (regular) and Proform (prelaminated). The model was benchmarked in five places along the curvature of the arch. The model was used to fabricate 10 specimens for each of the following groups: 1 = vacuum-formed (3-mm) Essix; 2 = vacuum-formed (4-mm) Proform; 3 = pressure-formed (3-mm) Essix; 4 = pressure-formed (4-mm) Proform; 5 = pressure-laminated (3-mm + 2-mm) Essix; 6 = pressure-laminated (3-mm + 3-mm) Essix. Die stone was poured into the newly made specimens and measured. Aging of the specimens was simulated by reproducing cleaning cycles (48 hours' soaking in water at 60 degrees F and brushing 100 times with a soft denture brush in soapy water at 140 degrees F for 20 minutes). Die stone was poured into the aged specimens and measured. Initial and postaging measurements were compared. RESULTS: All specimens showed dimensional changes post-aging, mainly decreases. Pressure-laminated specimens showed the best dimensional stability. CONCLUSION: Aging induced various dimensional changes in mouthguards, depending on the materials and processing techniques used. Most of the dimensional change for all mouthguards occurred at the central incisor region, the most important area for the protection of the anterior teeth and the premaxilla. Pressure-laminated mouthguard specimens showed the smallest range of changes at the central incisor region, suggesting potentially improved fit, comfort, and protection.     

Pneumocystis carinii pneumonia in AIDS patients. Aspects of clinical evolution in 37 cases

This study concerns 37 cases of Pneumocystis carinii pneumonia in AIDS patients. The time elapsed between human immunodeficiency virus (HIV) seropositivity and the onset of pneumocystosis has been established. Three clinical types are individualized. In cases with normal X-ray films of the chest, measurement of carbon dioxide transfer capacity, always reduced, has led to a bronchoalveolar lavage which provided an early diagnosis. In spite of good response to treatment, the prognosis of pneumocystosis is poor owing to the frequency of associated diseases.     

Variability of anti-αGal antibodies in human serum and their relation to serum cytotoxicity against pig cells

Abstract: One of the major obstacles in pig-to-human xenografting is hyperacute rejection (HAR) of pig cells caused by preformed anti-pig antibodies and complement. In 1991 we suggested that anti-αGal antibodies play a major role in the HAR of pig cells. Anti-αGal antibodies recognize terminal α-galactose-containing epitopes on glycoproteins and glycolipids. They are present in humans, apes, and Old World monkeys, but not in lower mammals such as pigs. However, pigs, unlike humans, express terminal α-galactose epitopes on vascular endothelium which represent targets for human anti-αGal antibodies. Despite increasing recognition that anti-αGal antibodies are an important factor, many questions related to their precise role in HAR remain to be answered.
In this study, we analyzed 75 human AB sera in terms of (i) cytotoxic activity against cultured pig (PK-15) cells, (ii) anti-αGal titers, (iii) immunoglobulin-binding to pig cells, and (iv) immunoglobulin concentrations. The results demonstrated considerable variability in cytotoxicity, anti-αGal titers, and immunoglobulin binding to pig cells, whereas the serum immunoglobulin concentrations were less variable. Positive correlations were found between cytotoxicity and binding of IgG and IgM to the surface of pig cells. The surface-bound IgG and IgM also correlated with the serum anti-αGal IgG and IgM titers. Anti-αGal IgA, however, did not show any relation with cytotoxicity or cell binding. Concentrations of serum total immunoglobulins correlated with neither I cytotoxic activity nor cell binding.     

New destruxins from the marine-derived fungus Beauveria felina

Chemical investigation of the cytotoxic and anti-tuberculosis active butanone extract obtained from the growth media of the marine-derived fungus Beauveria felina led to the isolation of two new destruxins, [beta-Me-Pro] destruxin E chlorohydrin (1) and pseudodestruxin C (3), along with five known cyclic depsipeptides. The structures of the new destruxin derivatives were established by analysis of spectroscopic data, while the absolute configuration of the common amino acid residues was established by Marfey's analysis. The absolute configuration of the 2(R),4(S)-5-chloro-2,4-dihydroxypentanoic acid residue in 1 could be established by application of a J-based configuration method followed by derivatization with R-MPA-Cl and NMR analysis.