Expression of IL-5 in thymocytes/T cells leads to the development of a massive eosinophilia, extramedullary eosinophilopoiesis, and unique histopathologies.

Transgenic mice were generated using regulatory elements from the CD3delta gene to drive T cell expression of IL-5. Expression of this cytokine resulted in white blood cell counts that expand virtually unabated (approximately 400,000 cells/mm3). This expansion is characterized by a profound eosinophilia (>60%) and commensurate increases in the absolute numbers of all other white blood cell types. In particular, circulating B220+ B lymphocyte populations increased >30-fold over wild-type (+/+) levels. Cell differentials and expression studies using a marker for eosinophil precursor cells (major basic protein gene expression) suggest that the peripheral eosinophilia is induced primarily through the establishment of extramedullary sites of eosinophilopoiesis. These mice display a massive peritoneal cavity cell exudate (1-2 x 10(8) cells) dominated by eosinophils (approximately 50%) and the infiltration of eosinophils in nearly all organ systems. Sudden unexplained death occurs in 70% of all transgenic animals by 12 mo of age. Surviving transgenic animals display severe inflammatory pathologies that include ulcerating skin lesions as well as lower bowel inflammation. These pathologies parallel clinical observations of patients with a profound eosinophilia and imply that IL-5 effector functions during some inflammatory responses may be contingent upon peripheral lymphohemopoietic expression.

[Knowledge of good clinical practice among Danish physicians. A questionnaire study among hospital-employed physicians in the Copenhagen area]. / Danske laegers kendskab til Good Clinical Practice. En spørgeskemaundersøgelse blandt hospitalsansatte loeger i hovedstadsområdet.

To investigate knowledge of current requirements concerning clinical research among researching physicians, and to compare this knowledge among physicians in different research areas, a survey based on twenty-two questions was sent to 1000 hospital physicians in the Copenhagen area. Forty six percent and three hundred and four of these were used for further analysis. Eighty-two percent of the physicians replied that they had knowledge of GCP, nevertheless only 24% were able to recognize the meaning of the terms "monitor", "investigator" and "SOP". When asked about six different fictitious situations concerning making reports to an Ethical Review Board, only 33% replied correctly to all reporting situations. A frequent distinction was seen between physicians who respectively had or had not co-operated with the pharmaceutical industry for trials of medicinal products during the past three years.