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IFN gamma inhibits the rise in transferrin receptor mRNA level which is normally observed when stationary WISH cells are stimulated to proliferate. This effect is not attributable to a change in the transcription rate of the transferrin receptor gene or in the cytoplasmic stability of the mRNA. The IFN gamma-induced reduction of the transferrin receptor mRNA content is already present at the nuclear level to an extent comparable to that observed in whole cells. Thus, IFN gamma does not impair the passage of this mRNA from the nuclear to the cytoplasmic compartment but probably interferes with a nuclear post-transcriptional event during the processing of the immature transferrin receptor mRNA. Two different levels of regulation of transferrin receptor mRNA have been previously reported. Iron modulates the cytoplasmic stability of this mRNA through the binding of a specific cytoplasmic factor, whereas cell growth variation influences the transcription of this gene. Our results suggest the existence of another mechanism of regulation for transferrin receptor gene expression not so far considered. Furthermore, the distinction between the mechanism of regulation exerted by IFN gamma and that exerted by cell proliferation on transferrin receptor gene expression suggests that, in WISH cells, the IFN-induced transferrin receptor decay is not a consequence of cell growth arrest but rather one of the causes of the antiproliferative effect of IFN through iron deprivation.

Diagnosis of endemic nephropathy (EN) is based on the combination of several clinical and laboratory criteria. Despite extensive research no specific diagnostic biomarker for EN has yet been identified. The aim of the study was to evaluate the diagnostic significance of the variables previously proposed as diagnostic criteria, but also new ones. After an extended questionnaire, the clinical and laboratory examination population in EN villages was classified according to the modified WHO criteria. The urinary active form of TGF-β was measured with a bioassay using a cell line which expresses luciferase activity. In the study we used ROC analysis to examine the predictive value of the tested variables. In the study there was no difference in haemoglobin level between the study subgroups. Leucine aminopeptidase (LAP) in urine and active urinary TGF-β levels were increased in the EN diseased group when compared to other subgroups, but they did not fulfil the statistical criteria needed for differentiating a diseased form from other study subgroups. Both kidney length and parenchima thickness, alfa1microglobulinuria, and kidney function assessed by MDRD formula were the variables that differentiated the study subgroups well. Based on our results the cut off value of alfa1microglobulin for screening should be 23.5 mg/g creatinine instead of 15 mg/g creatinine in the present criteria, and for making a diagnosis of EN 31, 5 mg/g creatinine. Persons with a positive family history for EN had a 5.8 times greater risk of developing EN when compared to a negative one. Taken together, the abovementioned variables should be implemented in new uniform diagnostic criteria for EN.