PubMed · 15432290
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G MILLER, I M BECKER, H K TAYLOR. 1950. Auricular calcification.. https://doi.org/10.1016/0002-8703(50)90173-6
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BACKGROUND AND AIMS: Tropical calcific pancreatitis (TCP) is a type of chronic pancreatitis unique to countries in the tropics. Mutations in pancreatic secretory trypsin inhibitor (SPINK1) rather than cationic trypsinogen (PRSS1) explain the disease in only 50% of TCP patients. As cathepsin B (CTSB) is known to activate cationic trypsinogen, we attempted to understand the role of CTSB mutations in TCP. Evidence of epistatic interaction was investigated with the previously associated N34S SPINK1 allele, a variant considered to be a modifier rather than a true susceptibility allele. SUBJECTS AND METHODS: We sequenced the coding region of CTSB gene in 51 TCP patients and 25 controls and further genotyped 89 patients and 130 controls from the same cohort for Leu26Val, C595T, T663C, and Ser53Gly polymorphisms. The positive findings observed in the earlier cohort were re-examined in an ethnically matched replication cohort comprising 166 patients and 175 controls. Appropriate statistical analyses were performed and Bonferroni correction for multiple testing was applied. RESULTS: We found a statistically significant association of the Val26 allele at Leu26Val polymorphism with an odds ratio (OR) of 2.15 (95% confidence interval (CI) 1.60-2.90 (p = 0.009)), after Bonferroni correction (corrected p value = 0.025). This significant association of Leu26Val with TCP was replicated in another cohort (OR 2.10 (95% CI 1.56-2.84); p = 0.013). Val26 allele also showed significantly higher frequency in N34S positive and N34S negative patients than in controls (p = 0.019 and 0.013, respectively). We also found significant differences in the mutant allele frequencies at Ser53Gly and C595T single nucleotide polymorphisms between N34S positive patients and controls (p = 0.008 and 0.001, respectively). Although haplotype analysis did not complement the results of allelic association, it did uncover a unique haplotype protective for TCP (p = 0.0035). CONCLUSION: Our study suggests for the first time that CTSB polymorphisms are associated with TCP. As PRSS1 mutations are absent in TCP and the N34S SPINK1 mutation is proposed to play a modifier role, these variants may be critical as a trigger for cationic trypsinogen activation.
Cardiovascular disease is the leading cause of morbidity and mortality in the western world and atherosclerosis is the major common underlying disease. The pathogenesis of atherosclerosis involves local vascular injury, inflammation and oxidative stress as well as vascular calcification. Vascular calcification has long been regarded as a degenerative process leading to mineral deposition in the vascular wall characteristic for late stages of atherosclerosis. However, recent studies identified vascular calcification in early stages of atherosclerosis and its occurrence has been linked to clinical events in patients with cardiovascular disease. Its degree correlates with local vascular inflammation and with the overall impact and the progression of atherosclerosis. Over the last decade, diverse and highly regulated molecular signaling cascades controlling vascular calcification have been described. Local and circulating molecules such as osteopontin, osteoprogerin, leptin and matrix Gla protein were identified as critical regulators of vascular calcification. We here review the current knowledge on molecular pathways of vascular calcification and their relevance for the progression of cardiovascular disease.
Chest pain is one of the most frequent complaints for patients seen in the emergency department. The current article describes the clinical stratification of patients who present to the emergency department with chest pain and discusses imaging options and analysis for these patients. It reviews conventional imaging approaches to assessing chest pain including chest radiography and stress testing. The main discussion focuses on the potential utility use of cross-sectional imaging, particularly multidetector CT, in the evaluation of chest pain in the emergency department.