A novel mutation in the E-cadherin gene in the first family with hereditary diffuse gastric cancer reported in Spain.

AIMS: Mutations of the E-cadherin gene (CDH1) result in dominantly inherited hereditary diffuse gastric cancer (HDGC). We report a study in the first family diagnosed with HDGC in Spain, examining the presence of mutations in the CDH1 gene. METHODS: The presence of mutations was studied by direct sequencing of all CDH1 exons. Immunohistochemical analysis with specific antibodies was used to detect the expression of E-cadherin in normal and tumour tissue. RESULTS: A novel 1610delC mutation in exon 11 has been found in a Spanish family diagnosed with HDGC. This mutation generates a premature stop codon at position 1667 giving rise to a truncated protein that lacks the transmembrane and beta-catenin-binding domains. The presence of a 1610delC germline mutation was confirmed in three family members diagnosed with diffuse gastric cancer, and also in six asymptomatic members. Of note, the diffuse gastric cancer coexisted with a gastric lymphoma in the proband. Furthermore, immunohistochemical analyses of tumour tissue showed the complete absence of E-cadherin in the proband, revealing a second genetic hit at the CDH1 locus. CONCLUSIONS: We have identified a HDGC family in Spain that carries a novel germline truncating mutation in the CDH1 gene.

Antibody levels and immunity to infectious bovine rhinotracheitis virus (IBR) infections in Wisconsin dairy cattle.

Individual cows and calves in 7 Holstein-Friesian herds with a history of respiratory disease in Green County, Wisconsin, USA, were swabbed intranasally and bled monthly, some for periods over 1 year. Virus isolation and serological procedures were completed on the samples in an attempt to recognize the problems and peculiarities that IBR virus continues to cause in dairy cows, in spite of, and possibly because of vaccines available for immunization against this agent. While IBR virus was isolated from animals on 6/7 farms over the period of study the history of vaccination with Nasalgen IP prevented the differentiation of vaccine (avirulent) virus from field (virulent) virus. IBR virus was isolated from apparently healthy animals as well as animals having signs of respiratory disease. IBR virus was assumed to be the cause of recurrent respiratory disease and ocular disease on at least two of the farms studied as established by virus isolation, serology, and the presence of characteristic signs of respiratory disease. While IBR virus was present on the other five farms its precise role in the diseases observed was not determined. IBR virus, whether vaccine virus or field virus, appeared to be persistent in 6/7 of the herds studied. Keratoconjunctivitis and corneal ulceration were the only signs of disease in animals in one herd where the etiologic agent was presumed to be field strain IBR virus. Antibody to IBR virus did not protect animals from respiratory or ocular disease in which IBR virus was thought to be a causative agent. Adult animals that had antibody to IBR virus at the time of vaccination with Nasalgen IP generally did not respond after vaccination with an increase in IBR virus antibody. Those adults that did not have antibody prior to vaccination, generally responded to vaccination with a rise in antibody. Vaccination of calves with Nasalgen IP generally did not cause an increase in antibody. IBR virus antibody was higher in vaccinated herds with recurrent respiratory disease.