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Introduction: This study was conducted to clarify whether injuries that are likely to be revealed by initial clinical and conventional radiological examination at the trauma bay (e.g., right-side rib fractures) meaningfully contribute to the prior probability of accompanying hepatic lesions in multiple injured patients., Material and Methods: Fifty-five subjects (sampled from a cohort of 218 patients) with liver injury fulfilling the definition of polytrauma were compared with 55 polytrauma patients without liver injury. Controls were individually matched for age, gender, and Injury Severity Scores. Whole-body, helical, contrast-enhanced computed tomography was applied to all participants. We modeled independent predictors of liver involvement by conditional logistic and random-effects regression analysis., Results: In the present sample, the prevalence of hepatic injury was 25.2%. Neither the injury mechanism (car crash, pedestrian accident, fall from height) nor certain accompanying injuries (right-side serial rib fractures, lumbar spine fractures) predicted the presence of hepatic injury. Liver injury was particularly unlikely in bikers [odds ratio (OR) 0.78, 95% confidence interval (CI) 0.59-1.03] and patients with left-side rib fractures (OR 0.80, 95% CI 0.66-0.98)., Discussion: There are no index injuries that will reliably indicate the presence of liver involvement in multiple trauma cases. Also, the absence of these injuries cannot rule out liver damage.

The estimated prevalence of liver injury in patients with blunt multiple trauma ranges from 1% to 8%. The objective of this study was to investigate the profile of accompanying liver injury in a cohort of polytraumatized patients who had regularly undergone contrast-enhanced, whole-body helical computed tomography (CT). We enrolled consecutive patients admitted between September 1997 and January 2001 to a level I trauma center. Clinical baseline data were compiled as part of a nationwide trauma registry. Morphologic features were evaluated descriptively, whereas prognostic variables were assessed by logistic regression analysis. We identified 218 patients [149 men, mean age 35 +/- 18 years, mean injury severity score (ISS) 35 +/- 10], 55 of whom had sustained blunt liver trauma [25.2%, 95% confidence interval (CI) 19.6-31.5%]. The prevalence of Moore III to V lesions was 10.1%. There were 99 parenchymal contusions, 15 capsular tears, and 2 liver fractures. Surgery was required in 15 patients and was best predicted by the classification of the American Association for the Surgery of Trauma [odds ratio (OR) 3.91, 95% CI 1.59-9.61]. The mortality rate was 0.0035/person/day. Patients requiring surgical repair had fourfold increased relative odds of case fatality (OR 4.50, 95% CI 1.01-19.96). Sevenfold increased relative odds were observed if liver laceration was considered the leading injury (OR 7.17, 95% CI 1.17-43.97). The prevalence of liver lacerations among multiple-trauma patients is likely to be underestimated and must be determined by the independent application of reference standards, such as helical CT. High-grade hepatic injuries and the need for surgical repair are associated with poorer survival prognosis.

The complete cDNA encoding the beta-subunit of the human liver signal transducing proteins Gs/Gi (beta G) has been cloned from a lambda gtll library using an oligonucleotide as a screening agent. The cDNA has 3088 nucleotides and an 11 nucleotide poly(A) tail, of which 280 nucleotides constitute the 5'-untranslated region, 1023 form the open reading frame (ORF) and its stop codon, and 1785 are the 3'-untranslated region with two AATAAA cleavage and polyadenylation signals separated by 1467 nucleotides. The ORF codes for a 340 amino acid polypeptide that is identical to that encoded by bovine retinal rod cell cDNA of the beta-subunit of transducin. Yet, it does so by using 87 different codons. Curiously, the 280 nucleotide 5' leader sequence obtained starts with an ATG that is part of another ORF encoding a putative peptide X of 75 amino acids (nucleotide 280 to 55). This work proves for the first time that the beta-subunits of all signal-transducing G-proteins, including transducin, are the same.

The effects of forskolin on rat liver plasma membrane adenylyl cyclase were studied. The diterpene stimulated the Vmax of the enzyme system with apparent Km values of 3-5 microM. Stimulations were marked both in the absence (20-fold over control) as well as in the presence of various stimulators such as GTP, GuoPP[NH]P, NaF alone or in combination with glucagon. Except with GTP, where stimulations of activities by forskolin and the nucleotide were synergistic (more than additive), stimulations of combinations of GuoPP[NH]P, NaF or glucagon with forskolin were additive. Forskolin did not alter significantly the apparent Km values of the enzyme for MgATP or MnATP or the apparent Ka values (concentrations giving stimulations that are 50% of maximum) for Mg or Mn ions, GTP, GuoPP[NH]P or NaF. Forskolin caused a decrease in the concentration of glucagon required for half-maximal stimulation from 5 microM to 1.5 microM. Except for this effect on the Ka for the glucagon, the only kinetic parameter altered was the Vmax under all conditions tested. Although proteolysis stimulated liver membrane adenylyl cyclase under control conditions, it did not enhance forskolin-stimulated activities. More extensive proteolysis, which resulted in decreased activities in the absence of forskolin, also resulted in reduced forskolin-stimulated activities. 'Uncoupling' of the guanine-nucleotide-binding regulatory component, that mediates guanine nucleotide stimulation by addition of 30 mM MnCl2, did not result in 'uncoupling' of forskolin stimulation. The data indicate that the diterpene forskolin stimulates adenylyl cyclase activity by a novel mechanism that differs from that by which NaF or guanylyl nucleotides affect this membrane-bound system and that the diterpene should be a useful tool with which to explore as yet unrecognized modes of regulation of cyclic AMP production.

Treatment of rat liver plasma membranes with various commercial preparations of crude collagenase from Clostridium histolyticum at concentrations as low as 1 mug/ml, resulted in activation of the adenylate cyclase system. Maximal activation occurred at 50 to 100 mug/ml of collagenase, and promoted a 2- to 3-fold increase in the basal activity as well as in the activities stimulated by catecholamines, glucagon, fluoride, or GTP. This was due to an increase in the maximal velocity of the cyclizing reaction without any increase in the affinity of the enzyme for its substrate. Treatment of plasma membranes with crude collagenase did not induce gross structural modifications as judged by electron microscopic examination. 5'-Nucleotidase activity was slightly inhibited and ATPase activity remained unaffected. The stimulatory substance was nondialyzable, thermolabile, and inhibited by both EDTA and -SH reagents, thus appearing to be a protein. The following observations suggest the effects observed were due to other protease(s) present in crude collagenase: (a) only crude collagenase was active on liver adenylate cyclase: treatment with purified collagenase from C. histolyticum or from Achromobacter iophagus gave no stimulation; (b) the stimulatory activity was irreversible since washing of the membranes after treatment was without effect; (c) crude collagenase contained no lecithinase or sphingomyelinase activity under our conditions of adenylate cyclase assay; (d) after chromatography on Sephadex G-100, the activator appeared as a peak in the 30,000-dalton region and was clearly separated from the collagenase and clostripain peaks, but coincident with elastolytic and caseinolytic activities; (e) the effect of crude collagenase could be prevented by addition of elastin in vitro and was mimicked by purified elastase from hog pancreas. It remains to be seen whether the effects observed result from an increase in the catalytic constant of adenylate cyclase, or an unmasking of new catalytic sites.

We have previously shown that liver plasma membrane (Ca2+-Mg2+)-ATPase activity is inhibited by glucagon. To investigate the possible involvement of a GTP-binding (G) protein in this regulation, we have examined the effects of pertussis toxin and cholera toxin on inhibition of (Ca2+-Mg2+)-ATPase by glucagon. Treatment of liver plasma membranes with pertussis toxin did not affect the sensitivity of (Ca2+-Mg2+)-ATPase to the hormone. In contrast, treatment of plasma membranes or prior injection of animals with cholera toxin prevented inhibition of the (Ca2+-Mg2+)-ATPase by glucagon. Even though adenylate cyclase activity was increased by cholera toxin treatment, addition of cyclic AMP did not mimic the effect of cholera toxin in blocking glucagon-mediated inhibition of (Ca2+-Mg2+)-ATPase activity. These data suggest that a cholera toxin-sensitive protein, perhaps Gs or a Gs-like protein, is involved in the regulation of liver (Ca2+-Mg2+)-ATPase activity. The results emphasize the possible role of Gs-like proteins in regulation of enzymes other than adenylate cyclase and suggest that the study of (Ca2+-Mg2+)-ATPase may provide a useful enzymatic system to examine such regulation.