We investigated the molecular mechanism underlying the progressive loss of Na(+)-dependent bile salt uptake in primary cultured rat hepatocytes. A specific cDNA probe was used to quantitate the levels of mRNA encoding the Na(+)-taurocholate-cotransporting polypeptide at various culture times. Hepatocytes were cultured on collagen in the presence of insulin (10(-7) mol/L), dexamethasone (10(-7) mol/L) and 10% fetal calf serum for up to 72 hr. During this time period the dissociation constant of Na(+)-dependent taurocholate uptake remained stable (19 to 39 mumol/L), whereas the maximum velocity values decreased from 100% at 3 hr to 55%, 22% and 4% at 24, 48 and 72 hr, respectively. Concomitantly the levels of the Na(+)-taurocholate-cotransporting polypeptide mRNA also decreased from 100% at 3 hr to 41%, 24% and 4% at the later time points. In contrast, Northern hybridization with complementary DNA probes for three common housekeeping gene products revealed a 1.8- to 3.4-fold increase in the levels of mRNA encoding the alpha-subunit of the Na+K(+)-ATPase, beta-actin and glycerol-3-phosphate dehydrogenase. These data indicate that the loss of Na(+)-dependent bile salt uptake in primary cultures of rat hepatocytes is caused by decreased levels of its specific mRNA. Hence the studies further confirm that without specific measures (primary) cultured rat hepatocytes reverse their liver-specific phenotype to a more fetal pattern of gene expression.

Mitochondria of patients with alcoholic liver disease are morphologically abnormal, and mitochondria isolated from animals exposed to ethanol exhibit functional deficiencies in vitro. Because the functional consequences of the morphological alterations and the relevance of in vitro observations to mitochondrial function in alcoholic subjects are not clear, we assessed mitochondrial function noninvasively with a breath test. Mitochondrial function was assessed by measuring the exhalation of 14CO2 after administration of 1 microCi 2-keto[1-14C]isocaproic acid, the decarboxylation of which occurs in mitochondria. The results of the 2-keto[1-14C]isocaproic acid breath test in 17 alcoholic subjects were compared with the results in healthy controls and patients with nonalcoholic liver disease. The peak exhalation of 14CO2 and the fraction of the administered dose decarboxylated in 60 min were significantly lower in alcoholic patients than in healthy controls or patients with nonalcoholic liver disease. In alcoholic patients 2-keto[1-14C]isocaproic acid decarboxylation was impaired in the presence of normal conventional and quantitative liver function as assessed by aminopyrine breath test and galactose elimination capacity, indicating that 2-keto[1-14C]isocaproic acid decarboxylation does not simply reflect decreased functional liver mass. We conclude that mitochondrial function as reflected by 2-keto[1-14C]isocaproic acid decarboxylation is impaired in chronic alcoholic patients. The functional impairment is specific for excessive ethanol consumption and not a reflection of decreased global liver function or the presence of cirrhosis. 2-Keto[1-14C]isocaproic acid decarboxylation could thus be useful as a marker of excessive ethanol consumption.

myositis with Kaposi's sarcoma in a patient without human immunodeficiency virus-1 infection. Can J Gastroenterol 1991;5(1):l-4. The first case of dermatomyosit is complicating cutaneous and visceral Kaposi's sarcoma is presented in a 75-year-old man without human immunodeficiency virus infection. Dermacomyositis preceded a definitive diagnosis of Kaposi's sarcoma by six months, although in retrospect unrecognized lesions may have presented simultaneously. He was treated with prednisone and azathioprine, thus raising the possibility of the role of immunosuppression in promoting progress ion of the sarcoma. le is suggested that although the association between dermatomyosicis and Kaposi's sarcoma occurs rarely, dennatomyositis should be considered a paraneoplastic syndrome of Kaposi's sarcoma. Further, the finding of cutaneous les ions of Kaposi's sa rcoma co uld pred ict gastrointestinal involvement when dermatomyositis and Kaposi's sarcoma occur in the same patient Key Words: Dennatomyositis , Kaposi's sarcoma Dermatomyosite associee a un sarcome de Kaposi chez un patient non infecte par le virus d'immunodeficience humaine 1 RESUME: O n presence un cas de dcrmatomyosite compliquant un sa rcome de Kaposi (SK) cuta ne et visceral chez un homme de 75 ans qui n 'etait pas in fecte par le VIH. La dermatomyosite a precede le diagnostic fennel du SK de six mois, bien qu'en re trospective des lesions meconnues aie nt p u se manifest er simultanement. Le patient a ere traitc par la prednisone et l'azathioprine, ce qui evoque la possibilite du role de l'immunosuppression comme agent favorisant !'evolution du sarcome. On suggere que, bien que !'association dermatomyosite et sarcome de Kaposi soit ra re, la dennatomyosice soit consideree comme syndrome paraneoplasique d'un sa rcome de Kaposi. Plus encore, la decouverte des lesions cutanees du SK pourrait evoquer une atteinte gastrointestinale quand la dermatomyosite et le sarcome de Kaposi se declarent c hez un meme patient.