No abstract

We here summarize the analysis of 126 DNA samples from patients with hematopoietic neoplasias and solid tumors and from various tumor cell lines that were screened in the tumorigenicity assay. Thirty-eight samples were able to induce tumors after transfection in NIH/3T3 cells and injection into nude mice. Southern-blot analysis with a panel of onco-gene probes revealed human ras genes in the vast majority of cases (25 N-ras, 2 K-ras, 1 H-ras) but also activated FGF4, dbl, ret and mas genes respectively. DNA samples from the 6 remaining transfectants were cloned into EMBL-3 phages and screened with a human specific repetitive Alu probe. Direct hybridization of a transfectant cDNA library allowed cloning of the ufo oncogene. Application of the exon-trapping technique to alu-positive phage DNA from the other transfec-tants enabled us to isolate tre, cot, B-raf, p85/HUMORF8 and a novel oncogene. Int.

Individual groups of nephrologists - in their responsibility for their patients - initiated a most controversial discussion whether or not caffeine - coformulated to analgesics - might initiate or sustain analgesic overdosing. The original sources (data) of such suspicion have got lost during the debate of the last two decades. Therefore, it seemed to be appropriate to investigate the original data background and the reasons why nephrologists started to suspect caffeine as a stimulant of analgesic overdosing by employing a systematic and exhaustive review of primary nephrological publications. Their selection followed a precise selection plan, including all epidemiological studies on analgesic-associated nephropathy, the original papers of all groups having been involved in those studies, further originals from the mainly involved countries (academically, politically), and any literature thereof cited as a proof. The following results emerged from the investigation: (i) The epidemiological studies warranted no conclusion about a role of caffeine in prompting excessive analgesic use. (ii) The identified groups of nephrologists provided not substantial data to advocate the said suspicion, except for the observation of a preferential choice of phenacetin-containing combinations, especially powder preparations. (iii) Only two cited original data sources revealed drug-seeking behaviour with phenacetin-containing preparations which subsided, after phenacetin was banned from the respective markets. Conclusively, it appears that there is no substantial data to support a pivotal role of caffeine in initiating or sustaining analgesic overdosing. However, there is strong data that phenacetin, by its psychotropic properties, may have caused drug-seeking behaviour and thus led to analgesic overdosing. This conclusion is convincingly supported by thorough pharmacokinetic investigations. Note: All caffeine-related statements within the reviewed literature have been collected in tables (referred to as Table SX) which are provided in full text for check on the following website: http://www.blackwellpublishing.com/products/journals/suppmat/FCP/FCP174/FCP174sm.htm