Original antigenic sin to influenza in rats

The presumed influenza anamnesis of the human population born before 1956—the year when A(H1NI) influenza viruses came out of circulation—is modelled on sixty male white rats. The model is an essay to clarify why these people demonstrated higher resistance to influenza A(H1N1) during its recurrence in late 1977, compared with young individuals, who obviously contacted this subtype for the first time. The dynamics of anti-influenza antibody formation (assessed by the indirect haemagglutination test, IHT) against different A subtypes used for reimmunizations reflected the status of immunological memory (IM) of the animals. Both humoral and secretory immune systems of the rats showed long lasting IM to influenza A(H1N1) antigens. However, the characteristics of the original antigenic sin (OAS) were manifested only by the humoral immune system. The antibodies against the original A(H1N1) viruses in the group, that received consecutive immunizations with A(H2N2) and A(H3N2) viruses, remained constantly higher than the same antibodies in the group intact to other subtypes, except to A(H1N1). This is an indication, that the OAS might serve as a natural mechanism for the maintenance of a sufficiently high concentration of antibodies, that could provide a secure protection at the time of return of the corresponding influenza viruses. In this respect, two types of manifestations of IM are discussed.     

Expression of c-ABL,c-KIT,and platelet-derived growth factor receptor-beta in ovarian serous carcinoma and normal ovarian surface epithelium

BACKGROUND: Tyrosine kinases, such as c-KIT, c-ABL, and platelet-derived growth factor-beta (PDGFR-beta), are important regulators of cell growth. Highly potent and selective inhibitors of tyrosine kinases are being investigated as alternatives to standard chemotherapy. One such inhibitor, imatinib mesylate, is being used to treat gastrointestinal stromal tumors and chronic myelogenous leukemia. Ovarian carcinomas frequently develop resistance to conventional chemotherapeutic agents. Immunohistochemical expression of c-ABL, PDGFR-beta, and c-KIT was evaluated in ovarian carcinomas to determine whether treatment with imatinib mesylate might be feasible. METHODS: The expression of c-ABL, c-KIT, and PDGFR-beta in tumors was evaluated by immunohistochemical analysis of 52 ovarian serous carcinomas, including 21 low-grade (well differentiated) and 31 high-grade (poorly differentiated) tumors. Fourteen normal ovaries were also evaluated. RESULTS: In normal ovarian surface epithelium, c-ABL was expressed universally. PDGFR-beta was expressed in the majority (93%) of samples of normal ovarian epithelium, whereas the c-KIT protein was undetectable in normal ovarian surface epithelium. Overall, c-ABL was expressed in 71% of serous carcinomas. c-ABL was expressed more frequently in the low-grade serous carcinomas (81%) compared with the high-grade serous carcinomas (65%). PDGFR-beta expression was observed in 81% of serous carcinomas overall and was observed more frequently in higher-grade tumors. c-KIT immunohistochemical staining was absent in low-grade tumors but was present in 26% of high-grade serous carcinomas. CONCLUSIONS: The majority of ovarian serous carcinomas express one or more of the kinases targeted by the tyrosine kinase inhibitor, imatinib mesylate, suggesting the potential usefulness of this drug in the treatment of ovarian carcinoma.