A new member of the MER2 repeat family is detected in the promoter region of the human X11 gene

AIMS: To evaluate the clinical utility of two new tests for serum trypsinogen 2 and trypsin 2-alpha 1 antitrypsin complex (trypsin 2-AAT) in diagnosing and assessing the severity of acute pancreatitis (AP) induced by endoscopic retrograde cholangiopancreatography (ERCP). PATIENTS: Three hundred and eight consecutive patients undergoing ERCP at Helsinki University Central Hospital in 1994 and 1995. METHODS: Patients were followed prospectively for pancreatitis and clinical outcome. They were tested for serum trypsinogen 2, trypsin 2-AAT, and amylase in samples obtained before and one, six, and 24 hours after ERCP. RESULTS: Pancreatitis developed in 31 patients (10%). Their median serum trypsinogen 2 increased 26-fold to 1401 micrograms/l at six hours after the procedure and trypsin 2-AAT showed an 11-fold increase to 88 micrograms/l at 24 hours. The increase in both markers was stronger in severe than in mild pancreatitis, and in patients without pancreatitis there was no significant increase. Baseline trypsinogen 2 and trypsin 2-AAT concentrations were elevated in 29% and 32% of patients, respectively. The diagnostic accuracy of a threefold elevation over the baseline value was therefore analysed. The sensitivity and specificity of these parameters in the diagnosis of post-ERCP pancreatitis was 93% and 91%, respectively, for serum trypsinogen 2 at six hours after the examination, and 93% and 90%, for trypsin 2-AAT at 24 hours. CONCLUSIONS: Serum trypsinogen 2 and trypsin 2-AAT reflect pancreatic injury after ERCP. High concentrations are associated with severe pancreatic damage. The delayed increase in trypsin 2-AAT compared with trypsinogen 2 appears to reflect the pathophysiology of AP. A greater than threefold increase in trypsinogen 2 six hours after ERCP is an accurate indicator of pancreatitis.     

Subchronic toxicity studies with the leukotriene D4 antagonist RG 12525

Preclinical safety studies with the leukotriene D4 antagonist RG 12525 were conducted by the oral route in mice, rats, and monkeys. Oral administration of RG 12525 was repeated daily in studies up to 6 months in duration. RG 12525 was shown to have limited high-dose toxicity after repeated oral administration. The effects of RG 12525 were strongly dependent upon the species considered. High doses of RG 12525 caused significant increases in liver weight in mice, rats, and monkeys that were associated with diffuse hepatocellular hypertrophy in mice and rats but not in monkeys. No related clinical chemistry changes were observed in any of the species and hepatic activities of peroxisomal enzymes or cytochrome P450 were increased only slightly. Proliferation of brown adipose tissue (BAT) was observed in rats and mice but not in monkeys. The BAT reaction was more pronounced in the interscapular area but it was also observed in other subcutaneous locations as well as in mediastinal and bone marrow fat. In all locations, the RG 12525-induced BAT had some morphological similarities with cold-adapted BAT. Repeated administration of RG 12525 at high doses to female rats resulted in a lack of progression to the luteal phase of the estrous cycle that was reversible after discontinuation of treatment. Finally, RG 12525 was nephrotoxic in mice with males being more sensitive than females.     

The isolation and characteristics of the green monkey lentivirus

We characterized the simian immunodeficiency virus isolated from Cercopithecus aethiops (subspecies C. a. pygerythrus) originating from Kenya. SIV was isolated and continuously produced with the MOLT4 clone 8 cell line and was designated as SIV-SU1. SIV-SU1 isolate replicated with high efficiency in MOLT4 clone 8, MT-2 with moderate efficiency in CEM x 174 and with poor efficiency in HUT-78, U937, C8166. The infection of MT-2, C8166 and HUT-78 resulted in extensive cell killing. Western blotting of purified preparations of SIV-SU1 revealed viral proteins of 130, 68, 55, 41, 24, 17 kDa. Cross-reactivity of SIV-SU1 proteins with HIV-1, HIV-2, SIVmac, SIVsm, SIVmnd was studied by radioimmunoprecipitation assay. The most extensive cross-reactivity was observed with SIVmac. Total cellular DNA from chronically infected cells was hybridized to SIVagm266 DNA probes. Detection of cross-hybridizing DNA sequences required very low stringency, and the restriction endonuclease fragmentation pattern of SIV-SU1 differed from other SIVs.     

Glucocorticoids protect against suppression of T cell responses in a murine model of acute ethanol exposure and thermal injury by regulating IL-6

Previous reports by this laboratory demonstrated that acute alcohol exposure combined with a 15% body surface area dorsal scald injury results in significant reductions in delayed-type hypersensitivity (DTH) and splenocyte proliferative responses compared to either insult alone. Previous studies by this lab have also shown that these defects are mediated, in part, by increased production of interleukin-6 (IL-6). Because both alcohol exposure and thermal injury are known to modulate glucocorticoid (CORT) levels, and CORT regulates IL-6 gene expression, the relationship between circulating CORT and IL-6 production in burn + ethanol mice was examined. At 24 and 48 h post-burn, a positive correlation existed between circulating CORT levels and measurements of cellular immune function. Administration of exogenous CORT to burn + ethanol-treated mice resulted in significant restoration (to 60% of control) of DTH and splenocyte proliferative responses. This restoration was concomitant with a down-regulation of circulating and macrophage-derived IL-6. The specificity of CORT in modulating these responses was tested by assessing cellular immune function and IL-6 levels after glucocorticoid receptor blockade with RU486. Taken together, these data strongly suggest that under normal circumstances CORT protects burned mice from severe immune dysfunction, a protection that is not afforded to burn + ethanol-treated mice. Furthermore, the immune dysfunction observed in burn + ethanol mice may be due to a lack of glucocorticoid attenuation of IL-6.