Search PubMed⌕ Search

Biomedical subjects

A J Dannenberg

Publications and source records attributed to A J Dannenberg.

83 records · Page 5Linked to original sources
PubMed1993

Changes in microsomal phospholipases and arachidonic acid in experimental alcoholic liver injury: relationship to cytochrome P-450 2E1 induction and conjugated diene formation.

We evaluated the role of changes in microsomal phospholipases (A and C) and arachidonic acid in the intragastric rat feeding model. The experimental animals (male Wistar rats), divided into 4-5 rats/group, were fed the following diets: corn oil and ethanol and corn oil plus dextrose. One set of groups was killed after 2 weeks of feeding, and the second set was killed after 1 month. For each animal, microsomal analysis of cytochrome P-450 2E1 (CYP 2E1) and fatty acids was done. Fourteen animals had analyses of phospholipase C (PLC) and phospholipase A (PLA), and 10 animals had measurements of conjugated dienes. A significant correlation was obtained between the level of CYP 2E1 and the decrease in arachidonic acid (AA) from baseline levels (r = 0.69, p < 0.01). The decrease in AA also correlated with the increase in conjugated dienes (r = 0.70, p < 0.05). PLA and PLC activities were both significantly increased in the corn oil and ethanol groups. The activity of PLC correlated with the decline in AA (r = 0.69, p < 0.01). The correlations noted between the decrease in microsomal AA and CYP 2E1 induction and conjugated diene formation suggest that these processes may be interlinked especially in regard to generation of lipid peroxides that may play a role in alcoholic liver injury.

Animals↗
PubMed1992

Effect of dietary lipids on levels of UDP-glucuronosyltransferase in liver.

Others have shown recently that dietary fish oil protects against acetaminophen-induced liver injury in vivo. Fish oil was protective because it increased the clearance of acetaminophen via glucuronidation. This work left unresolved the basis for increased rates of glucuronidation in animals fed fish oil. We therefore have determined how the amount and type of lipid in the diet affect the activity of liver microsomal UDP-glucuronosyltransferase activity. Male Wistar rats were fed a fat-free diet or isocaloric diets containing 5% corn oil, olive oil or fish oil for 4 weeks. The activity of UDP-glucuronosyltransferase was highest in rats fed fish oil and lowest in rats fed the fat-free diet. Treatment with corn oil and olive oil resulted in intermediate levels of activity. Diet-induced differences in amounts of UDP-glucuronosyltransferase were shown by immunoblotting and kinetic measurements. Treatment with fish oil resulted in a 3-fold increase in the amount of UDP-glucuronosyltransferase versus the fat-free diet. Corn oil and olive oil diets caused 2-fold increases in the amount of UDP-glucuronosyltransferase versus the fat-free diet. Fatty acid analysis of microsomal lipids showed that the fat-free diet was associated with decreased levels of arachidonic acid versus the corn oil or olive oil diets. The fish oil diet resulted in increased levels of omega-3 fatty acids versus the other diets.

Animals↗
PubMed1992

Developmental changes in the amount and functional state of UDP-glucuronosyltransferase.

The effect of postnatal development on the activity of liver microsomal UDP-glucuronosyltransferase was determined in male Wistar rats between 25 and 200 days of age using p-nitrophenol as aglycone. Enzyme activity (measured at 1.0 mM UDP-glucuronic acid, 0.05 mM p-nitrophenol) decreased 55% between 25 and 88 days of age and was constant thereafter. Treatment of microsomes with palmitoyl-lysophosphatidylcholine, which allows for an estimation of the amount of enzyme, showed approximately a four-fold decrease in enzyme concentration during the same period. This decrease was confirmed by Western blotting of microsomes with anti-UDP-glucuronosyltransferase antiserum. The fact that a nearly four-fold decline in enzyme concentration led to only a 55% decrease in activity indicates that there was an increase in activity per molecule of UDP-glucuronosyltransferase as the concentration of enzyme decreased. Treatment of microsomes with high pressure or detergent caused a greater extent of enzyme activation in microsomes prepared from 25 than 200 day old rats, suggesting that a fraction of the enzyme in older rats was activated in untreated microsomes. Fatty acid analysis of liver microsomal lipids during postnatal development revealed changes in docosahexaenoic acid (22:6) which correlated with levels of UDP-glucuronosyltransferase activity.

Aging↗
PubMed1992

Effects of high pressure on the catalytic and regulatory properties of UDP-glucuronosyltransferase in intact microsomes.

The effects of high pressure on the kinetic properties of microsomal UDP-glucuronosyltransferase (assayed with 1-naphthol as aglycon) were studied in the range of 0.001-2.2 kbar to clarify further the basis for regulating this enzyme in untreated microsomes. Activity changed in a discontinuous manner as a function of pressure. Activation occurred at pressure as low as 0.1 kbar, reaching one of two maxima at 0.2 kbar. As pressure was increased above 0.2 kbar, activity decreased, reaching a minimum at about 1.4 kbar followed by a second activation. The pathway for activation at pressure greater than 1.4 kbar was complex. The immediate effect of 2.2 kbar was nearly complete inhibition of activity. The inhibited state relaxed, however, over about 10 min (at 10 degrees C), to a state that was activated as compared with enzyme at 0.001 kbar or enzyme at pressures between 1.4 and 2.2 kbar, which was the highest pressure we could test. Examination of the detailed kinetic properties of UDP-glucuronosyltransferase indicated that the effects of pressure were due to selective stabilization of unique functional states of the enzyme at 0.2 and 2.2 kbar. Activation at 0.2 kbar was reversible when pressure was released. This was true as well as for activation at pressure greater than 1.4 kbar, but after prolonged treatment at 2.2 kbar, UDP-glucuronosyltransferase became activated irreversibly on release of pressure. The process by which prolonged treatment at 2.2 kbar led to permanent activation of UDP-glucuronosyltransferase after release of pressure was not reflected, however, by time-dependent changes in the functional state of UDP-glucuronosyltransferase at this pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Dietary lipid regulates the amount and functional state of UDP-glucuronosyltransferase in rat liver.

The effect of a fat-free diet on the amount and functional state of UDP-glucuronosyltransferase was studied in rat liver microsomes. Measurements of enzyme activity showed that activity was approximately 30% lower in untreated microsomes in response to the fat-free diet as compared with the control diet. Immunoblotting with anti-UDP-glucuronosyltransferase showed approximately 200% less enzyme in rats fed the fat-free diet. A kinetic method for measuring total UDP-glucuronosyltransferase confirmed the result of the immunoblot. Thus, the total amount of enzyme declined to a greater extent than enzyme activity. Responses of the enzyme to activation by palmitoyl-lysophosphatidylcholine or UDP-N-acetyl-glucosamine suggested that rats fed the fat-free diet had a greater activity per molecule of UDP-glucuronosyltransferase than did rats fed the control diet. This result explained the relatively small decline in enzyme activity as compared with enzyme concentration in microsomes prepared from animals fed the fat-free diet. Fatty acid analysis of microsomal lipids demonstrated that the fat-free diet was associated with lower levels of arachidonic and linoleic acids and greater amounts of palmitoleic, oleic and cis-vaccenic acids.

Animals↗
PubMed1992

Gastrointestinal manifestations of epidermolysis bullosa. A study of 101 patients.

One hundred one patients with EB were evaluated by a combination of prospective and retrospective review, and analyzed regarding the nature, incidence, and prevalence of their gastrointestinal (GI) manifestations. Involvement of the GI tract is a well-known extracutaneous manifestation of dystrophic EB, but it also occurred in more than one-half and one-third, respectively, of those with junctional and simplex EB. Most of the serious consequences, such as esophageal strictures and microstomia, occurred in recessive dystrophic EB but were also seen, although infrequently, in the junctional and simplex forms. The majority of patients with dysphagia had an esophageal stricture, and the cervical esophagus was the most common location. The onset of dysphagia generally occurred in the first decade of life, in patients much younger than previously recognized. Diagnostic endoscopy did not reveal lesions which could not have been detected radiographically. Lower GI complaints were common, especially constipation and perianal blistering, and affected all types of EB. These complaints contributed substantially to management problems but they did not correlate with colonic pathology and appeared to reflect anal or perianal disease.

Adolescent↗
PubMed1991

Eosinophilic ascites due to hyperinfection with Strongyloides stercoralis.

We report the case of a patient with cryptogenic cirrhosis, new onset ascites, and hyperinfection with Strongyloides stercoralis who had significant eosinophilia of the peritoneal fluid. The eosinophilia resolved with treatment of the S. stercoralis infection, and did not recur during two subsequent episodes of ascites and spontaneous bacterial peritonitis. Eosinophilic ascites is rare in parasitic infection, but it has been described in a variety of disorders which are discussed.

Animals↗
PubMed1990

Organization of microsomal UDP-glucuronosyltransferase. Activation by treatment at high pressure.

Treatment of microsomes at pressures as high as 2.25 kbar led to an apparent irreversible activation of UDP-glucuronylsyltransferase when pressure was released. The response of the enzyme to pressure, as reflected by activity measured after release of pressure, appeared to be discontinuous in that no activation was seen for any preparation at pressures less than 1.2 kbar. In addition, activation was temperature dependent. Maximum activation at 2.25 kbar occurred at about 12 degrees C; the extent of activation in 10 min was less for either higher or lower temperatures. Activation was also time dependent. Maximum activation at 2.25 kbar and 9 degrees C required 90 min of pressure treatment. Activation appeared to occur more slowly at lower pressure. Pressure-induced activation was associated with a loss of sensitivity of the enzyme to allosteric activation by UDP-N-Ac-Glc and a conversion of the kinetic pattern from non-Michaelis-Menten to Michaelis-Menten. Pressure did not activate enzyme that had previously been activated maximally by adding detergent to microsomes. Pressure also did not activate pure UDP-glucuronosyltransferase reconstituted into unilamellar vesicles of dioleoylphosphatidylcholine. Pressure treatment did not release UDP-glucuronosyltransferase from microsomes into water. Pressure had a continuous effect on the polarization and excimer/monomer formation of fluorescent probes incorporated into microsomes, and the properties returned essentially to their values at 1 atm when pressure was released. Measurements of activity at 2.2 kbar showed that pressure-induced activation of UDP-glucuronosyltransferase in microsomes occurred via two intermediates that were inactive and that the activated state of the enzyme was generated during/after release of pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Non-steroidal anti-inflammatory drugs and the risk of oral cancer: a nested case-control study.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) seem to prevent several types of cancer, but could increase the risk of cardiovascular complications. We investigated whether use of NSAIDs was associated with a change in the incidence of oral cancer or overall or cardiovascular mortality. METHODS: We undertook a nested case-control study to analyse data from a population-based database (Cohort of Norway; CONOR), which consisted of prospectively obtained health data from all regions of Norway. People with oral cancer were identified from the 9241 individuals in CONOR who were at increased risk of oral cancer because of heavy smoking (15 pack-years), and matched controls were selected from the remaining heavy smokers (who did not have cancer). FINDINGS: We identified and analysed 454 (5%) people with oral cancer (279 men, 175 women, mean [SD] age at diagnosis 63.3 [13.2] years) and 454 matched controls (n=908); 263 (29%) had used NSAIDs, 83 (9%) had used paracetamol (for a minimum of 6 months), and 562 (62%) had used neither drug. NSAID use (but not paracetamol use) was associated with a reduced risk of oral cancer (including in active smokers; hazard ratio 0.47, 95% CI 0.37-0.60, p<0.0001). Smoking cessation also lowered the risk of oral cancer (0.41, 0.32-0.52, p<0.0001). Additionally, long-term use of NSAIDs (but not paracetamol) was associated with an increased risk of cardiovascular-disease-related death (2.06, 1.34-3.18, p=0.001). NSAID use did not significantly reduce overall mortality (p=0.17). INTERPRETATION: Long-term use of NSAIDs is associated with a reduced incidence of oral cancer (including in active smokers), but also with an increased risk of death due to cardiovascular disease. These findings highlight the need for a careful risk-benefit analysis when the long-term use of NSAIDs is considered.

Acetaminophen↗