ABSTRACT
Transglutaminases are a family of enzymes which show the common capacity to catalyse the cross-linking of protein substrates. Some members of this family of enzymes are also capable to catalyse other chemical reactions for the cell life. The distribution and the role of these enzymes have been studied in numerous cell types and tissues, but only recently their expression and functions started to be investigated in the Nervous System. One of the main biochemical properties of the Transglutaminase enzymes is to form large protein aggregates that are insoluble in all known protein detergents. Recently, the Transglutaminase activity has been hypothesised to be involved in the pathogenetic mechanisms responsible for the formation of cellular inclusions present in the Corea Major and in other polyglutamine diseases. In this review we describe the biochemical mechanisms by which the Transglutaminases could play a critical role in the physiopathology of the polyglutamine diseases.
Subject(s)
Nervous System Diseases/enzymology , Peptides/metabolism , Transglutaminases/metabolism , Animals , Humans , Inclusion Bodies/chemistry , Inclusion Bodies/metabolism , Nervous System/enzymologyABSTRACT
BACKGROUND AND STUDY AIMS: It is difficult to measure the prevalence of hereditary non-polyposis colorectal cancer (HNPCC) in geographical areas that do not have tumor registers, as is the case in the present study, and it was therefore decided to assess the prevalence in Italy using different methods. PATIENTS AND METHODS: The pedigree was established for 485 of 501 colorectal cancer patients diagnosed with colorectal carcinomas. Patients were included consecutively in 13 gastroenterology centers; they had not taken part in prevention examinations. Information was collected regarding the neoplastic pathology observed in the families, confirmed in 90% of cases among 3515 first-degree relatives and in 79.5% of cases among 7068 second-degree relatives. RESULTS: In the 3515 first-degree relatives (1002 parents, 1560 siblings and 953 children), 61 colorectal carcinomas, 29 carcinomas in the digestive tract outside the colon, and 99 carcinomas in other locations were reported. Only five of the 485 patients (1%) satisfied the Amsterdam criteria (three cancers, two of which were in first-degree relatives in different generations and one in a relative younger than 50). When broadening the criteria that we are proposing (satisfying only two of the three Amsterdam criteria), the prevalence would increase to 3% (15 cases). CONCLUSIONS: Modifying the criteria makes it easier to identify new mutations or confirm the existence of those already known, as well as allowing preventative treatment in relatives who are apparently healthy.
Subject(s)
Colonoscopy , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/epidemiology , Adenocarcinoma, Mucinous/diagnosis , Adenocarcinoma, Mucinous/epidemiology , Adenocarcinoma, Mucinous/genetics , Adult , Aged , Cause of Death , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Diagnosis, Differential , Female , Humans , Italy/epidemiology , Male , Middle Aged , Pedigree , Prevalence , Prospective Studies , Registries , Surveys and Questionnaires , Survival RateABSTRACT
Serum levels of alpha 1-antitrypsin were measured in 118 patients. Among these, 90 subjects presented with hepatic pathology of which 42 were of cryptogenetic origin. Not one of the subjects studied showed a decrease in alpha 1-antitrypsin nor did the results of liver biopsies prove positive for PAS cytoplasmic corpuscles. It is suggested that alpha 1-antitrypsin deficit does not play an important role in cryptogenetic cirrhosis.
