Serum DU-PAN-2 in the differential diagnosis of pancreatic cancer: influence of jaundice and liver dysfunction

The usefulness of serum DU-PAN-2 in diagnosing pancreatic cancer and in distinguishing between this cancer and other benign and malignant diseases, and to assess the role of liver dysfunction in altering the serum levels of this marker were investigated. DU-PAN-2 was measured in the sera of 31 patients with pancreatic cancer, 32 with chronic pancreatitis, 20 with benign and 21 with malignant extra-pancreatic diseases. DU-PAN-2 was found to be above 300 U ml-1 in 21/31 patients with pancreatic cancer (sensitivity 68%). Only 3/32 patients with chronic pancreatitis had abnormal values. A substantial number of patients with both benign and malignant extra-pancreatic diseases had an elevated serum DU-PAN-2 (9/20 and 15/21, respectively). Correlations were found between DU-PAN-2 and (1) total bilirubin, (2) alanine-amino-transferase and (3) alkaline phosphatase. Of the patients with high DU-PAN-2 values, jaundice was found in: 2/3 with chronic pancreatitis, 9/10 with benign and 12/14 with malignant extra-pancreatic diseases. In conclusion, the serum DU-PAN-2 test for pancreatic malignancy is not completely satisfactory, because it is not sensitive enough. While the test for chronic pancreatitis has an acceptable specificity, the assay cannot distinguish between pancreatic cancer and other extra-pancreatic diseases, mainly of the liver and biliary tract. Liver dysfunction as well as jaundice seem to considerable affect the levels of this marker, as reported elsewhere for CA 19-9.     

The unusual association of three autoimmune diseases in a patient with Noonan syndrome.

We report on a 26-year-old female affected by Noonan syndrome (NS), a congenital disorder characterized by various phenotypic features and congenital anomalies) associated with a variety of autoimmune diseases, including systemic lupus erythematosus, celiac disease, and Hashimoto thyroiditis. Autoimmunity is seldom described in NS and the association between this congenital disease and three autoimmune disorders has not been previously reported. Should the occurrence of autoimmune disorders in NS be confirmed, a relevant clinical and laboratory evaluation of NS patients should be performed in order to clarify whether the immune system involvement represents only an occasional event or is a feature of the disease.     

High affinity neurotrophin receptors in the human pre-term newborn, infant, and adult cerebellum

The immunohistochemical occurrence of the high affinity neurotrophin (NT) receptors trkA, trkB, and trkC is shown in the pre-term newborn, infant, and adult human post-mortem cerebellum. Immunoreactive neuronal perikarya and processes were observed in all specimens examined, where they appeared unevenly distributed in the cerebellar cortical layers and deep nuclei, and showed regional differences among cerebellar lobules and folia. The trk receptor-antibodies, tested by Western blot on human cerebellum homogenates, revealed multiple immunoreactive bands for trkA and single bands for trkB and trkC. The results obtained show the tissue localization of the trk receptor-like immunoreactivity in the human cerebellum from prenatal to adult age. The analysis for codistribution of the receptors with the relevant ligand and among the receptors in discrete cortical and deep nuclei tissue fields shows a wide variety of conditions, from a good similarity in terms of type and density of labeled structures, to a lack of correspondence, and suggests the possibility of colocalization of trk receptors with the relevant neurotrophin and among them in the cerebellar cortex. These results sustain the concept that the neurotrophin trophic system participates in the development, differentiation, and maintenance of the human cerebellar connectivity and support the possibility of a multifactorial trophic support for the neurotrophins through target-derived and local mechanisms.     

Association between the occurrence of antibodies to simian vacuolating virus 40 and bladder cancer in male smokers

An association between the occurrence of antibodies to simian vacuolating virus 40 and bladder cancer in male smokers was found in a case-control study conducted in 200 male patients with bladder cancer and 400 control men. The risk of bladder cancer increases with the years of cigarette smoking.     

Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an Italian series of patients affected by Paget's disease of bone (PDB).

PDB is genetically heterogeneous. Mutations of the sequestosome1 gene have been reported in sporadic and familial forms of Paget's in patients of French Canadian and British descent. Mutational analyses in different ethnic groups are needed to accurately investigate hereditary diseases. We describe two novel mutations of sequestosome1 in 62 Italian sporadic patients, confirming the role of the encoded protein in this disorder. INTRODUCTION: Paget's disease of bone (PDB) is a relatively common disease of bone metabolism reported to affect up to 3% of whites over 55 years of age. The disorder is genetically heterogeneous, and at present, there is scientific evidence that at least eight different human chromosomal loci are correlated with its pathogenesis. Mutations of the sequestosome1 (SQSTM1) gene were identified as responsible for most of the sporadic and familial forms of Paget in patients of French Canadian and British descent. Such mutations were located at exon 7 and 8 levels, encoding for the ubiquitin protein-binding domain (UBA) and representing a mutational hot spot area. MATERIALS AND METHODS: To verify the involvement of this gene in Italian subjects affected by PDB, we performed mutational analysis in 62 sporadic PDB cases. RESULTS: We described three different mutations at exon 8 level: P392L, already described in the French Canadian population and families predominantly of British descendent, and two novel mutations consisting of the amino acid substitutions M404V and G425R. No significant differences in the clinical history of PDB have been observed in patients with SQSTM1 mutations in respect to those without. CONCLUSIONS: Even though our findings suggest a minor involvement of the SQSTM1 gene in the pathogenesis of sporadic Italian Paget's cases, the identification of different significant mutations within the SQSTM1 gene in unrelated, but clinically similar individuals, offers extremely convincing evidence for a causal relationship between this gene and PDB. Longitudinal studies are needed to assess the penetrance of genotype/phenotype correlations. Our findings confirm the evidence of a clustered mutation area at this level in this disorder.