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Biomedical subjects

B Combes

Publications and source records attributed to B Combes.

96 records · Page 6Linked to original sources
PubMedDate not supplied

The immunologic diagnosis of chronic active "autoimmune" hepatitis: distinction from systemic lupus erythematosus.

We have evaluated the immunologic characteristics often associated with systemic lupus erythematosus in a series of patients with a variety of different liver diseases. Antibody to double-stranded DNA as measured by the Farr assay was detected frequently in patients with various forms of liver disease. No patient with liver disease, including those with a presumed immunologic etiology, was found to have antibody to double-stranded DNA using more specific assays. Other immunologic phenomena such as the presence of immunofluorescent staining at the dermal-epidermal junction in the lupus band test, circulating immune complexes and the presence of antinuclear antibody were present in a number of patients with different forms of liver disease. The absence of antibody to double-stranded DNA in patients with liver disease suggests that there may be a true immunologic distinction between systemic lupus erythematosus and chronic active ("lupoid") hepatitis.

Adult↗
PubMedDate not supplied

The effect of glutathione depletion on 14CO2 evolution from [14C]methyl-labeled aminopyrine in intact rats.

The effect of hepatic glutathione depletion on 14CO2 evolution from [14C]methyl-labeled aminopyrine was assessed in fed male Sprague-Dawley rats. Within 30 min of i.p. administration of either diethylmaleate or phorone, hepatic glutathione fell approximately 75 to 80% and remained depressed for the ensuing 120 min. [14C]Aminopyrine was i.p. administered 30 min after the glutathione-lowering agents (zero time) and exhaled 14CO2 was collected at 15-min intervals for the next 120 min. Parameters of 14CO2 exhalation including peak exhalation rate, cumulative exhalation from 0 to 120 min and the elimination rate constant were all impaired in glutathione-depleted rats. Metabolism of the [14C]methyl groups involves N-demethylation with formation of formaldehyde, oxidation to formate and conversion to 14CO2. Glutathione depletion did not affect CO2 evolution from i.p. administered formate or bicarbonate. The glutathione-dependent step presumably involves either or both generation of formaldehyde or its subsequent oxidation to formate.

Aminopyrine↗
PubMedDate not supplied

CCl4-induced toxicity in isolated hepatocytes: the importance of direct solvent injury.

CCl4 is proposed to induce cellular injury through its metabolites that are generated by a cytochrome P-450 dependent step. These free radical products can interact with membrane structures, thereby generating lipid peroxides. The latter process has been implicated as a major mechanism of CCl4 hepatoxicity, although this relationship has been difficult to demonstrate when using isolated hepatocyte preparations. This report demonstrates that there are at least two mechanisms by which CCl4 induces injury in isolated hepatocytes. One occurs within minutes of exposure to CCl4 and is characterized by modest malondialdehyde formation and no decline in cellular-reduced glutathione. SKF 525A, metyrapone and promethazine did not protect against this early damage. A second phase of damage, evident particularly after 3 hr, is characterized by a marked increase in malondialdehyde formation, a fall in cellular glutathione and substantial further cellular damage. These changes could be moderated by the cytochrome P-450 inhibitors and promethazine, and antioxidant. Further examination of the initial phase of damage reveals an immediate dose-related inhibition of O2 consumption. This could not be prevented by SKF 525A or metyrapone and was associated with loss of ability to stimulate mitochondrial respiration with dinitrophenol. Rapid recovery to initial O2 consumption rates occurred with time as CCl4 evaporated from the incubation system. This was associated with a partial return of dinitrophenol stimulation of mitochondrial O2 consumption despite significant glutamate dehydrogenase release. A portion of this recovery could be inhibited by SKF 525A, suggesting that some O2 consumption was due to CCl4 metabolism and ensuing lipid peroxidation. These data suggest that early CCl4 toxicity is a direct consequence of its solvent properties and is partially reversible; subsequent damage may be mediated by lipid peroxidation. This solvent injury has not been previously recognized and may have relevance not only to a reversible toxicity as demonstrated with isolated hepatocytes but also in vivo as well.

Animals↗
PubMedDate not supplied

Low serum alkaline phosphatase activity in Wilson's disease.

Low values for serum alkaline phosphatase activity were observed early in the course of two patients with Wilson's disease presenting with the combination of severe liver disease and Coombs' negative acute hemolytic anemia. A review of other cases of Wilson's disease revealed that 11 of 12 patients presenting with hemolytic anemia had values for serum alkaline phosphatase less than their respective sex- and age-adjusted mean values; in eight, serum alkaline phosphatase activity was less than the lower value for the normal range of the test. Low values for serum alkaline phosphatase were much less common in Wilson's disease patients with more chronic forms of presentation. Copper added in high concentration to serum in vitro did not have an important effect on serum alkaline phosphatase activity. The mechanism responsible for the decrease in serum alkaline phosphatase activity in patients is uncertain.

Adolescent↗
PubMedDate not supplied

Changes in bile flow and composition induced by radiographic contrast materials.

The hepatic excretion of radiographic contrast materials has a major impact on the composition and volume of bile. One obvious effect is the presence of the contrast agent in bile at a concentration that is determined by the rate of hepatic excretion, the rate of basal bile flow, and the rate of bile flow induced by the biliary excretion of the contrast agent. The magnitude of the choleretic response associated with the biliary transfer of contrast materials varies over a wide range. Iopanoic acid does not increase bile flow, whole RCK-136, an experimental contrast material that is similar to iopanoic acid chemically (both are triiodophenyl alkanoates), is a potent choleretic, generating 44 microliter of bile for each mumol excreted into bile. In distinction, the contrast materials in another chemical class, the dimers of triiodobenzoic acid, increase bile flow, but over a narrow range (20-25 microliter/mumol). The changes in bile flow and composition accompanying the administration of iodoxamate, one of the compounds of the dimer type, were compared to the choleresis induced by taurocholate. The additional bile flow was canalicular in origin in both instances, but the electrolyte composition of the bile was different. Bicarbonate concentration in the iodoxamate-induced increment of bile was nearly twice the concentration of bicarbonate in bile stimulated by taurocholate (52.3 and 25.3 mEq/1, respectively). This suggests a canalicular mechanism for iodoxamate-stimulated bicarbonate entry into the bile. The characteristics of bile induced by iodoxamate were also compared to bile associated with a variety of other choleretic agents, including diethyl maleate, DBcAMP, SC2644, and secretin. Only SC2644 stimulated canalicular bile flow with a high bicarbonate concentration similar to iodoxamate.

Animals↗