Expression of MAGE-A cancer/testis antigens in esophageal squamous cell carcinomas.

BACKGROUND: Although the diagnosis and therapy of esophageal cancer have improved over the past decade, the prognosis remains dismal. Since MAGE-A cancer/testis antigens (CTA) are potential targets for immunotherapy, this study was aimed at evaluating their expression in these patients and its prognostic value. MATERIALS AND METHODS: Using 57B monoclonal antibody, MAGE-A CTA expression was analyzed in paraffin-embedded tumor specimens of 98 patients with esophageal squamous cell carcinoma or adenocarcinomas who had undergone surgical resection. For all patients, a postoperative follow-up of at least 4 years was available. The expression was quantified using a scoring system considering intensity and homogeneity of the immunostaining. The prognostic relevance of MAGE-A expression was analyzed in univariate analyses as well as Cox proportional hazard regression analysis. RESULTS: 57B positivity could be detected in 38 tumors (38.8%). Positive staining was observed in five out of 32 adenocarcinomas (15.2%) and in 33 out of 66 (50%) squamous cell carcinomas. MAGE-A expression did not correlate with the TNM classification, grading or age of the patients. Both univariate (p=0.88) and multivariate analyses (p = 0.82) revealed that MAGE-A expression lacked prognostic significance in esophageal carcinomas. CONCLUSION: MAGE-A was expressed in half of the squamous cell carcinomas of the esophagus, but rarely in adenocarcinomas. Although its immunodetection was insufficient for prognostic evaluation, the high expression rate suggests MAGE-A as a potential target for immunotherapy in the first group with the ability for pretherapeutic testing.

[Evaluation of a tumor of the rib]. / Abklärung einer kostalen Raumforderung.

A 39-year old man was referred for evaluation of a left sided tumor in the region of the third and fourth rib. Computed tomography revealed a slightly enhancing costal tumor with mainly intrathoracic expansion. Calcifications inside the tumor were present. Assuming a chondrogenic tumor of unknown dignity, en bloc tumor resection and reconstruction of the chest wall was performed. By means of the histopathological examination the diagnosis of a chondrosarcoma grade I was made.

The effect of a polyhexamethylene biguanide mouthrinse compared with a triclosan rinse and a chlorhexidine rinse on bacterial counts and 4-day plaque re-growth.

OBJECTIVES: For various clinical applications, polyhexamethylene biguanide hydrochloride (PHMB) has been used for many years as an antiseptic in medicine. Recently, a 0.04% and a 0.12% PHMB mouthwash were shown to inhibit plaque re-growth and to reduce oral bacterial counts. In this study, a 0.2% PHMB mouthrinse (A) was compared with a positive control 0.12% aqueous chlorhexidine solution (B), a commercially available 0.3% triclosan/2.0% polyvinyl methyl ether maleic acid copolymer mouthrinse (Colgate Total Plax) (C), and a negative control placebo rinse (10% ethanol, flavour) (D). MATERIALS AND METHODS: The controlled clinical study was a double blind, randomized, four replicate cross - over design. Plaque re-growth was assessed with the Turesky et al. (1970) modification of the Quigley & Hein (1962) plaque index. The antibacterial effect was assessed by taking bacterial counts on the tooth surface (smears from the buccal surface of 16/26) and mucosa (smears from the buccal mucosa in opposite of area 16/26) after the professional prophylaxis and after the first rinse with the preparations on day 1 and prior to the clinical examination on day 5. Sixteen volunteers participated and, on day 1 of each study period were rendered plaque-free, ceased toothcleaning, and rinsed twice daily with the allocated mouthrinse. On day 5, plaque was scored and smears were collected according to the protocol. A 10-day wash-out period was carried out between each rinse evaluation. Data were analysed using ancova with Bonferroni HSD adjustment for multiple comparisons (colony forming units per sample) with a significance level alpha=0.05. RESULTS: The 0.2% PHMB mouthrinse (A) was significantly better at inhibiting plaque than the placebo (D), but significant less effective than the 0.12% aqueous chlorhexidine solution (B). There is no significant difference between A and the 0.3% triclosan/2.0% copolymer mouthrinse (C). Bacterial count reductions (tooth surface and mucosa) with PHMB (A) were significantly greater compared with the placebo (D) and triclosan (C), but significantly lower compared with chlorhexidine (B) (tooth surface) and equally effective compared with chlorhexidine (B) (mucosa). CONCLUSION: Consistent with previous studies, a PHMB mouthrinse was shown to inhibit plaque re-growth and to reduce oral bacterial counts, indicating that PHMB could be an alternative to established mouthrinses in preventive applications.

Novel mutations in the cathepsin C gene in patients with pre-pubertal aggressive periodontitis and Papillon-Lefèvre syndrome.

Aggressive periodontitis (AP) in pre-pubertal children is often associated with genetic disorders like Papillon-Lefèvre syndrome (PLS). PLS is caused by mutations in the cathepsin C (CTSC) gene. We report a novel CTSC mutation (c.566-572del) in an otherwise healthy AP child and two novel compound heterozygous mutations (c.947T>G, c.1268G>C) in a PLS patient. We conclude that at least a subset of pre-pubertal AP is due to CTSC mutations and therefore may be an allelic variant of PLS.

Expression of N-acetyltransferases in periodontal granulation tissue.

Smoking is a major risk of periodontal diseases. At the site of first contact, the gingiva is exposed to aromatic amines and polycyclic hydrocarbons. These are metabolized by the N-acetyltransferases (NAT), leading to local detoxification and/or activation reactions contributing to the risk of periodontal destruction in smokers. The purpose of this study was to detect the expression of N-acetyltransferase isoenzymes NAT1 and NAT2 in periodontal granulation tissue. In 24 specimens obtained from periodontitis patients or control subjects, mRNA encoding for NAT1 and NAT2 was detected by RT-PCR, and proteins were identified by immunohistochemistry. In periodontal granulation tissues, immunoreactivity for NAT1 and NAT2 was detected in infiltrating leukocytes and fibroblasts. In normal gingiva, both enzymes were found in epithelial cells, whereas NAT1 was also detected in endothelial cells. The results suggest that these enzymes may play a role in the defense against xenobiotics and the accelerated progression of periodontal disease in smokers.

Gender and smoking-related risk reduction of periodontal disease with variant myeloperoxidase alleles.

Myeloperoxidase (MPO) is an oxidative enzyme expressed in polymorphonuclear leukocytes. It is involved in the defence against periodontal bacteria, and is also able to mediate inflammatory tissue destruction in periodontal disease. A G/A polymorphism in the promoter region of the MPO gene at position -463 has been assumed to exert profound effects on the expression of the enzyme. It is the aim of this study to evaluate whether this polymorphism may influence the risk of periodontal diseases. A total of 3148 subjects were randomly selected from the general population in the SHIP study (Study of Health in Pomerania). Periodontal status, health-related and socio-economic items were assessed. All subjects aged 40-60 years (n = 1103) were included in this study, and 1083 genotyped for the MPO -463 G/A polymorphism by PCR and RFLP methods. The genotype frequencies determined were homozygous wild type G/G 65.9% (95% CI 63.5-68.6), heterozygous A/G 31.4% (28.8-34.4), and homozygous variant A/A 2.7% (2.0-3.8). Only female subjects have a significantly reduced risk of severe periodontal disease when bearing the variant genotypes A/G or A/A. In female subjects the reduction in periodontal risk was significant for non-smokers (OR = 0.48; 95% CI 0.23-0.96); the smoke-related increase in risk was also reduced (OR = 0.50; 95% CI 0.22-1.10). When adjusted for age, smoking, and education the odds ratios were calculated as 0.52 (P = 0.01) and 0.97 (P = 0.90) for female and male subjects, respectively. The results of this study confirm the assumption that the MPO -463A allele variants are protective in the pathogenesis of periodontal diseases. This holds true only with women but not with men. The results are discussed with respect to the known influences of sexual hormones on MPO activity.

CT findings in eosinophilic enterocolitis with predominantly serosal and muscular bowel wall infiltration.

A 44-year-old female presented with tenderness of her abdomen, vomiting, intestinal obstruction, hypoalbuminemia and blood eosinophilia. Gastroscopy was normal and colonoscopic biopsies showed only non-specific inflammation of the colonic mucosa and submucosa. CT revealed large amounts of ascites and bilateral pleural effusions but eosinophil counts in the ascites were normal. At CT the jejunum was dilated and showed marked prominence of the valvulae whereas the ileum and the colon presented with a diffuse and hypoattenuating bowel wall thickening. The bowel wall thickening was most pronounced in the colon which especially showed also an impressive thickening and hyperenhancement mainly of its outer bowel wall layers. Parasitic infection could be excluded as well as a specific allergic response. In context with the known blood eosinophilia the diagnosis of an eosinophilic enterocolitis was suspected already by CT but finally only surgical full thickness biopsies could confirm the rare diagnosis of an eosinophilic enterocolitis with predominantly serosal and muscular bowel wall infiltration.

Smoking and polymorphisms of the interleukin-1 gene cluster (IL-1alpha, IL-1beta, and IL-1RN) in patients with periodontal disease.

BACKGROUND: Polymorphisms within the interleukin-1 cluster are known to be associated with adult periodontal disease. However, interactions of genetic with other risk factors, especially smoking, remain questionable. The aim of this cross-sectional study was to evaluate the genetic influence on periodontal variables in relation to environmental factors. METHODS: One-hundred fifty-four (154) Caucasian subjects were clinically and radiographically assessed for their periodontal status, their smoking history recorded, and their allelic pattern of IL-1alpha, IL-1beta, and IL-1RN polymorphisms determined by genotyping. RESULTS: In assessing periodontitis with mean probing depth, mean attachment loss, or mean bone loss, no differences were found in allele frequencies or combined allotypes between subjects with mild or moderate versus those with severe signs of periodontitis. However, the extent of attachment loss defined as percentage of sites >4 mm was significantly associated with the composite genotype of IL-1alpha/1beta in smokers (odds ratio [OR] = 4.00; 95% confidence interval [CI] 1.03 to 16.70; P= 0.02). No differences were found in genotype negative subjects irrespective of their smoking status. They had nearly identical attachment loss as genotype positive non-smokers. Similar non-significant results were found with respect to extent of bone loss. An increased risk of more extended attachment loss was observed also in individuals carrying mutations of the combined genotype IL-1alpha/IL-1RN, again showing enhanced risk only in genotype-positive and smoking subjects. CONCLUSIONS: The results provide evidence that the composite genotypes studied show interaction with smoking, the main exposition-related risk factor of periodontal disease. Non-smoking subjects are not at increased risk, even if they are genotype-positive.