Frequency of hereditary nonpolyposis colorectal cancer

PURPOSE: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant cancer syndrome characterized by early onset of colorectal carcinomas (CRC). Recently, two HNPCC genes have been mapped and cloned, one in the short arm of chromosome 2 and another in the short arm of chromosome 3. There has been a major controversy about the frequency of HNPCC. The few estimates available have been based on series selected by age or series representing local area. The purpose of the present study was to design a nonselected, prospective, multicenter study, taking into account the family background and other risk factors of CRC. METHODS: The proportion of HNPCC of all (N=406) CRC cases was evaluated in a prospective multicenter study. Family history and other risk factors were investigated over a 12-month period for all new CRC patients in ten hospitals. These cases constituted 23 percent of all CRCs diagnosed in Finland during the study period. RESULTS: Three (0.7 percent) cases of verified and seven (1.7 percent) cases of suspected HNPCC were identified, following the evaluation of all families with features indicative of susceptibility to cancer. The proportion of identifiable risk factors of CRC was 5.8–7.5 percent (HNPCC, 0.7-2.4 percent; previous CRC, 3.4 percent; ulcerative colitis, 1.0 percent; familial adenomatous polyposis coli, 0.7 percent). CONCLUSION. This prospective multicenter study revealed that the frequency of hereditary colorectal cancer is lower than in some previous studies, when diagnosis is based on extensive pedigree analysis. This result with recent findings of common ancestral founding mutation in Finnish HNPCC families indicates that there may be geographic differences in the occurrence of HNPCC. However, this does not change the fact that identification of HNPCC—perhaps one of the most common inherited diseases identified in humans—has become a question of vital importance now when diagnosis of the syndrome and largescale screening of gene carriers using specific tests are on the horizon.Supported by grants from the Finnish Cancer Society, the Finnish Foundation for Gastroenterological Research, the Sigrid Juselius Foundation, and the Academy of Finland, Helsinki, Finland.     

In vitro electroretinogram for the study of the functionality of differentiated retinal pigment epithelium cells

The purpose of this study is to develop and test a method to reveal if the retinal pigment epithelium (RPE) cells differentiated from human embryonic stem cells (hESC) support the functions of photoreceptors. hESC-derived RPE (hESC–RPE) cells offer a potent cell source for cell replacement therapy that may be used to prevent certain eye diseases. Methods to assure the functionality of the RPE cells are well warranted. Electroretinograms (ERG) measure the electrophysiological response of the retina to light stimuli. A setup was developed that enables the measurement of ERG in vitro from mice retinas cultured together with hESC–RPE cells. The co-culture of RPE and retinas seems to be a viable tool to assess the functionality of RPE in vitro. However, owing to limited sample size results were somewhat mixed, and thus it was not possible to prove that hESC–RPE cells enhance the ERG response of a mouse retina in vitro. The long-term culturing of the retinas needs to be refined to acquire more conclusive evidence of the supporting role of the RPE and to explore the full potential of the co-culture and ERG methods in assessing RPE functionality.     

Evaluation of a New Automated Homogeneous PCR Assay,GenomEra C. difficile,for Rapid Detection of Toxigenic Clostridium difficile in Fecal Specimens

We evaluated a new automated homogeneous PCR assay to detect toxigenic Clostridium difficile, the GenomEra C. difficile assay (Abacus Diagnostica, Finland), with 310 diarrheal stool specimens and with a collection of 33 known clostridial and nonclostridial isolates. Results were compared with toxigenic culture results, with discrepancies being resolved by the GeneXpert C. difficile PCR assay (Cepheid). Among the 80 toxigenic culture-positive or GeneXpert C. difficile assay-positive fecal specimens, 79 were also positive with the GenomEra C. difficile assay. Additionally, one specimen was positive with the GenomEra assay but negative with the confirmatory methods. Thus, the sensitivity and specificity were 98.8% and 99.6%, respectively. With the culture collection, no false-positive or -negative results were observed. The analytical sensitivity of the GenomEra C. difficile assay was approximately 5 CFU per PCR test. The short hands-on (<5 min for 1 to 4 samples) and total turnaround (<1 h) times, together with the high positive and negative predictive values (98.8% and 99.6%, respectively), make the GenomEra C. difficile assay an excellent option for toxigenic C. difficile detection in fecal specimens.     

Connective Tissue Growth Factor and Its Correlation to Other Growth Factors in Experimental Granulation Tissue

Connective tissue growth factor (CTGF) is upregulated in a variety of fibrotic disorders, probably secondary to the activation and production of transforming growth factor-beta (TGF- &#103 ). We have studied the expression of CTGF in a rat wound-healing model using Northern blot, in situ hybridization, and immunohistochemistry. The expression of CTGF mRNA in Northern blot and immunohistochemistry were correlated to the expression of TGF- &#103 1 and platelet-derived growth factor (PDGF). Northern hybridization showed the maximum expression of CTGF mRNA on day 14, whereas TGF- &#103 1 expression was maximal on days 7 and 14 and the time-related changes were smaller than for CTGF. PDGF A and PDGF B mRNA expressions were at maximum on day 14 and on day 21, respectively. In situ hybridization showed that fibroblast-like cells expressed CTGF most intensively, expression declining rapidly after day 14. CTGF mRNA and protein were found in blood vessel cells during the first week. In immunohistochemistry, all growth factors were expressed by fibroblast-like cells, macrophage-like cells, and blood vessels but CTGF-positive cells were fewer and were more restricted on days 5 and 7. These results demonstrate that CTGF expression together with TGF- &#103 and PDGF are upregulated in wound healing, and CTGF expression in blood vessels suggests that CTGF is involved in angiogenesis.     

N170 response to facial expressions is modulated by the affective congruency between the emotional expression and preceding affective picture

Does contextual affective information influence the processing of facial expressions already at the relatively early stages of face processing? We measured event-related brain potentials to happy and sad facial expressions primed by preceding pictures with affectively positive and negative scenes. The face-sensitive N170 response amplitudes showed a clear affective priming effect: N170 amplitudes to happy faces were larger when presented after positive vs. negative primes, whereas the N170 amplitudes to sad faces were larger when presented after negative vs. positive primes. Priming effects were also observed on later brain responses. The results support an early integration in processing of contextual and facial affective information. The results also provide neurophysiological support for theories suggesting that behavioral affective priming effects are based, at least in part, on facilitation of encoding of incoming affective information.     

Effects of chitosan and bioactive glass modifications of knitted and rolled polylactide‐based 96/4 L/D scaffolds on chondrogenic differentiation of adipose stem cells

The performance of biodegradable knitted and rolled 3‐dimensional (3D) polylactide‐based 96/4 scaffolds modified with bioactive glass (BaG) 13‐93, chitosan and both was compared with regard to the viability, proliferation and chondrogenic differentiation of rabbit adipose stem cells (ASCs). Scaffold porosities were determined by micro‐computed tomography (μCT). Water absorption and degradation of scaffolds were studied during 28‐day hydrolysis in Tris‐buffer. Viability, number and differentiation of ASCs in PLA96/4 scaffolds were examined in vitro. The dimensions of the scaffolds were maintained during hydrolysis and mass loss was detected only in the BaG13‐93 containing scaffolds. ASCs adhered and proliferated on each scaffold type. Cell aggregation and expression of chondral matrix components improved in all scaffold types in chondrogenic medium. Signs of hypertrophy were detected in the modified scaffolds but not in the plain PLA96/4 scaffold. Chondrogenic differentiation was most enhanced in the presence of chitosan. These findings indicate that the plain P scaffold provided a good 3D‐matrix for ASC proliferation whereas the addition of chitosan to the PLA96/4 scaffold induced chondrogenic differentiation independent of the medium. Accordingly, a PLA96/4 scaffold modified by chitosan could provide a functional and bioactive basis for tissue‐engineered chondral implants. Copyright © 2012 John Wiley & Sons, Ltd.     

Bruxism Is Unlikely to Cause Damage to the Periodontium: Findings From a Systematic Literature Assessment

Background: This paper systematically reviews the MEDLINE and SCOPUS literature to answer the following question: Is there any evidence that bruxism may cause periodontal damage per se? Methods: Clinical studies on humans, assessing the potential relationship between bruxism and periodontal lesions (i.e., decreased attachment level, bone loss, tooth mobility/migration, altered periodontal perception) were eligible. Methodologic shortcomings were identified by the adoption of the Critical Appraisal Skills Program quality assessment, mainly concerning the internal validity of findings according to an unspecific bruxism diagnosis. Results: The six included articles covered a high variability of topics, without multiple papers on the same argument. Findings showed that the only effect of bruxism on periodontal structures was an increase in periodontal sensation, whereas a relationship with periodontal lesions was absent. Based on the analysis of Hill criteria, the validity of causation conclusions was limited, mainly owing to the absence of a longitudinal evaluation of the temporal relationship and dose‐response effects between bruxism and periodontal lesions. Conclusions: Despite the scarce quantity and quality of the literature that prevents sound conclusions on the causal link between bruxism and the periodontal problems assessed in this review, it seems reasonable to suggest that bruxism cannot cause periodontal damage per se. It is also important to emphasize, however, that because of methodologic problems, particularly regarding sleep bruxism assessment, more high‐quality studies (e.g., randomized controlled trials) are needed to further clarify this issue.     

Role of Childhood Food Patterns on Adult Cardiovascular Disease Risk

Accumulating evidence indicates that childhood nutrition plays a role in the adulthood cardiovascular health. A lifelong tracking of dietary habits, following a long-term exposure to unhealthy dietary patterns or independent effects, is a potential effect-mediating mechanism. Dietary patterns have been studied by data-driven and hypothesis-based approaches. Typically, either data-driven healthy or prudent childhood dietary patterns have been characterized and found to be associated with lower adulthood cardiovascular disease (CVD) risk in the published cohort studies. With regard to the individual food groups or food quality indices, intakes particularly of vegetables and fruits (or fiber indicating plant food intake) and polyunsaturated fatty acids have shown protective effects. The evidence which could confirm the long-term healthiness of a hypothesis-based Mediterranean diet is limited, requiring further investigation. Overall, the recent literature strengthens the view that a healthy childhood diet is associated with lowered adulthood CVD risk.     

High frequency of BRAF V600E mutations in ameloblastoma

Ameloblastoma is a benign but locally infiltrative odontogenic neoplasm. Although ameloblastomas rarely metastasise, recurrences together with radical surgery often result in facial deformity and significant morbidity. Development of non‐invasive therapies has been precluded by a lack of understanding of the molecular background of ameloblastoma pathogenesis. When addressing the role of ERBB receptors as potential new targets for ameloblastoma, we discovered significant EGFR over‐expression in clinical samples using real‐time RT–PCR, but observed variable sensitivity of novel primary ameloblastoma cells to EGFR‐targeted drugs in vitro. In the quest for mutations downstream of EGFR that could explain this apparent discrepancy, Sanger sequencing revealed an oncogenic BRAF V600E mutation in the cell line resistant to EGFR inhibition. Further analysis of the clinical samples by Sanger sequencing and BRAF V600E‐specific immunohistochemistry demonstrated a high frequency of BRAF V600E mutations (15 of 24 samples, 63%). These data provide novel insight into the poorly understood molecular pathogenesis of ameloblastoma and offer a rationale to test drugs targeting EGFR or mutant BRAF as novel therapies for ameloblastoma. Published by John Wiley & Sons, Ltd. www.pathsoc.org.uk