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Biomedical subjects

L Lumeng

Publications and source records attributed to L Lumeng.

At least 127 records · Page 7Linked to original sources
PubMed1992

Identification of hepatitis C viruses with a nonconserved sequence of the 5' untranslated region.

The nucleotide sequence of the 5' untranslated region of hepatitis C virus (HCV) has been shown to be conserved. In contrast, we have detected more sequence variation in this region in several HCV isolates than hitherto expected. The nucleotide sequences of the 5' untranslated regions of these isolates differ significantly from that of the prototype but are very similar to each other. We believe that these isolates belong to the same type of HCV. Among 240 HCV RNA polymerase chain reaction-positive specimens that we examined, 7 belong to this type. The results suggest that the HCV variants that we detected represent a different type of HCV and that they are responsible for approximately 3% of HCV infections in patients that we have examined.

Base Sequence↗
PubMed1991

High-intensity focused ultrasound in the treatment of experimental liver cancer.

High-intensity focused ultrasound (HIFU) was used to treat Morris rat hepatoma 3924A implanted in the liver. Treatment was administered with a lens-focused 4-MHz transducer that created a focused beam of 550 W/cm2 at peak intensity. One hundred twelve rats with liver tumors were divided into two groups of 56 each. Group 1 received HIFU therapy while group 2 (the control group) did not. All rats were killed immediately or 1, 3, 7, 14, 21, or 28 days after treatment. Eight rats in each group were killed at each interval for pathologic and biochemical studies. Significant inhibition of the tumor growth was seen in the HIFU-treated group, with tumor growth inhibition rates of 65.4% to 93.1% from the third to the 28th day after treatment. Ultrasound-treated tumors showed direct thermal cytotoxic necrosis and fibrosis. An additional 56 ACl rats with liver tumors were divided into four groups of 14 each. Group 1 received doxorubicin hydrochloride intraperitoneally and HIFU therapy; group 2, HIFU therapy; group 3, doxorubicin hydrochloride; and group 4 (the control group), neither HIFU nor doxorubicin hydrochloride. Significantly improved survival rates were noted in HIFU-treated animals (groups 1 and 2) compared with those of groups 3 and 4. These data suggest that HIFU may be a useful method for local treatment of hepatic tumors.

Animals↗
PubMed1991

Importance of delta opioid receptors in maintaining high alcohol drinking.

We have previously reported that naloxone, a nonspecific opioid receptor antagonist, suppresses alcohol but not water consumption by male rats that have been genetically selected for high voluntary alcohol drinking. However, the identity of the specific opioid receptor subtype that may mediate alcohol drinking is not known. This paper reports that a selective delta opioid receptor antagonist is as effective as naloxone in suppressing alcohol consumption and that an enkephalinase inhibitor, which potentiates the action of endogenous enkephalins, increases alcohol intake. These results suggest that alcohol-induced activation of the endogenous enkephalinergic system, and occupation of delta opioid receptors, are involved in the maintenance of continued alcohol drinking.

Alcohol Drinking↗
PubMed1991

Chronic alcohol consumption in alcohol-preferring P rats attenuates subsequent conditioned taste aversion produced by ethanol injections.

Rats of the P line were tested for the development of tolerance to the aversive effects of ethanol during 33 days of continuous availability of food, water and a 10% (v/v) ethanol solution. Beginning on the day following the removal of ethanol, five daily conditioned taste aversion (CTA) trials were administered to the ethanol-drinking P rats and an ethanol-naive control group. The CTA trials consisted of a 20-min access to a Polycose solution, followed by IP injection of saline, 0.5, 1.0, or 1.5 g ethanol/kg. The ethanol-drinking rats developed a preference for the Polycose solution when it was paired with 0.5 g ethanol injections, but the control rats did not. Both control and ethanol groups had similar CTAs at the 1.5 g dose. However, at the 1.0 g dose, the ethanol group had an attenuated CTA compared with the water control group. The results suggest that P rats develop tolerance to aversive effects of ethanol during chronic drinking. This tolerance could contribute to the high ethanol intake in these selectively-bred rats.

Alcohol Drinking↗
PubMed1991

Electrophysiological response to ethanol in P and NP rats.

Event-related potentials (ERPs) have been successfully used in human subjects to evaluate alcoholics as well as those at risk for the future development of alcoholism. In the present study, two lines of rats, those with a preference for ethanol consumption (P) and those not preferring (NP) to drink ethanol were studied using ERP-producing stimuli. Rats were implanted with electrodes in the frontal cortex and dorsal hippocampus (DHPC). A passive auditory "oddball" paradigm was used to record ERP responses following saline and two doses (0.5, 1.0 g/kg) of ethanol. P and NP rats differed under the saline condition in that P rats had smaller N1-like ERP components and larger P2 waves in both cortex and hippocampus. P and NP rats were also found to differ in response to ethanol administration. NP rats evidenced dose-dependent reductions in ERP component amplitudes such as the N1 recorded from cortical sites. P rats did not have such reductions in N1 amplitudes and in fact, displayed increased N1 amplitudes in hippocampal sites. These studies provide further electrophysiological evidence that rats with a genetically influenced preference for ethanol consumption differ from nonpreferring rats at baseline and have a less intense depressant or more stimulating response to ethanol challenge.

Alcohol Drinking↗
PubMed1991

Polymorphism of the rat liver mitochondrial aldehyde dehydrogenase cDNA.

In humans, a deficiency in mitochondrial aldehyde dehydrogenase (Class 2 ALDH) activity due to a single base-pair exchange in its structural gene serves as a deterrent to excessive alcohol consumption. Differences in Class 2 ALDH isozyme patterns on isoelectric focusing gels have been observed in the selectively bred, alcohol-preferring (P) and alcohol-nonpreferring (NP) lines of rats. To determine whether the differences are the result of sequence variation in the structural gene, we sequenced the cDNAs for Class 2 ALDH from P and NP rats. A synonymous exchange was seen in the codon for amino acid 473 in both lines, when compared with published sequences. Additionally, when the cDNA from P rats was used as reference, a substitution (G for A) was identified in the cDNA of NP rats which changes amino acid 67 from Gln (CAG codon; ALDH2Q allele) to Arg (CGG codon; ALDH2R allele). The Arg for Gln substitution makes the enzyme more basic and could account for the different electrophoretic mobilities. To determine whether the polymorphism was associated with drinking behavior, we genotyped the ALDH2 locus by amplifying rat genomic DNA encompassing the nucleotide exchange followed by probing with allele-specific oligonucleotides. There are highly significant differences in the frequencies of the two alleles in the P and NP rat lines. The frequency of the ALDH2R allele is 63% in the NP line and only 18% in the P line, whereas the frequency of the ALDH2Q allele is 82% in the P line and 37% in the NP line.

Alcoholism↗
PubMed1991

Effect of chronic ethanol feeding on high density lipoprotein subfractions in rats.

We have reported previously that chronic alcohol consumption in the rat produced elevated total serum high density lipoprotein (HDL) fraction, but HDL particles of the alcohol-fed rat were deficient in apolipoprotein (apo) E. In that report, serum HDL particles were prepared by successive ultracentrifugation method and there were concerns that the apo E deficiency in HDL particles was artificially produced by centrifugal forces. In the present report, apo Al affinity column chromatography was used instead of successive ultracentrifugation and it likewise yielded HDL particles from alcohol-fed rats that exhibited lower apo E: apo Al ratio than HDL from control rats (0.185 +/- 0.016 vs. 0.303 +/- 0.017, respectively). When the total serum lipoprotein fraction (d less than 1.21) was analyzed by high performance liquid chromatography (HPLC), both HDL and VLDL peaks were higher in alcohol-fed rats than controls. The size of apo E deficient HDL particles from alcohol-fed rats determined by HPLC did not differ from that of normal HDL particles. When HDL (1.063 less than d less than 1.21) was subfractionated into HDL2 (1.063 less than d less than 1.125) and HDL3 (1.125 less than d less than 1.21), only HDL2 of alcohol-fed rats showed lowered apo E: apo Al ratio when compared with same HDL subfraction of control animals. Therefore, the molecular structure of only HDL2 (but not HDL3) was affected by alcohol-feeding. Another HDL subpopulation which is enriched with apo E, i.e. HDL1 (1.054 less than d less than 1.063), was also prepared.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMed1991

The effects of ethanol initiation procedures on ethanol reinforced behavior in the alcohol-preferring rat.

Rats from the alcohol preferring (P) line developed at Indiana University were initiated to self-administer ethanol orally without food or water restriction using either a sucrose-fading or a secondary-conditioning procedure. Following initiation, they were tested under a variety of operant conditions to examine the ability of ethanol to reinforce lever pressing behavior. Regardless of initiation procedure, the animals maintained lever pressing behavior with ethanol reinforcement, even at ethanol concentrations as high as 40% (v/v). Slightly higher daily session intakes (g/kg) were found at the higher ethanol concentrations following the secondary-conditioning initiation procedure compared with the sucrose-fading technique. When both ethanol and water were concurrently available, the rats showed a high preference for ethanol reinforcement. When varying concentrations of sucrose were substituted for water, the amount of ethanol ingested decreased as the concentration of the alternative sucrose increased. However, if the response requirement for the sucrose was substantially greater than that for ethanol, the rats shifted their responding to the lever associated with ethanol presentation. The results are discussed in relation to prior work using similar procedures with Long-Evans non-selected rats and with the alcohol non-preferring (NP) rat line.

Alcohol Drinking↗
PubMed1991

Formation of a 37 kilodalton liver protein-acetaldehyde adduct in vivo and in liver cell culture during chronic alcohol exposure.

With the use of antibodies that can recognize acetaldehyde adducts and the application of various immunological techniques, several protein-AAs have now been shown to form in vivo during chronic alcohol ingestion. These protein-AAs include the 37-kDa liver protein-AA, the CytP450IIE1-AA, hemoglobin-AA, two serum protein-AAs with molecular weights of 50 kDa and 103 kDa, and collagen type I protein-AA in liver. If acetaldehyde is the agent responsible for alcoholic liver injury, acetaldehyde toxicity in chronic alcohol ingestion must be linked to the ability of acetaldehyde to form adducts with proteins and perhaps other macromolecules. This is at least one mechanism of acetaldehyde-mediated liver injury. For proteins that serve critical functions, acetaldehyde adduct formation may alter their functions and thereby produce organ damage. Acetaldehyde adduct formation can also elicit humoral or cytotoxic immune responses and these responses may also lead to organ injury.

Animals↗
PubMed1991

Serotonin and dopamine systems regulating alcohol intake.

Neurochemical and neuropharmacological studies were undertaken to assess the involvement of CNS serotonin (5-HT) and dopamine (DA) pathways in regulating the alcohol intake of rats selectively bred for their high alcohol seeking behavior (P and HAD lines). Neurochemical data indicate that high alcohol seeking behavior (when compared with data from rats with low alcohol seeking characteristics) is associated with (a) lower contents of 5-HT in certain limbic regions, e.g., n. accumbens (Acb), frontal cortex, (b) a lower content of DA in the Acb, and (c) higher densities of 5-HT1A receptors in certain limbic regions, e.g., cerebral cortex. Neurochemical data also suggest that ethanol can activate the DA and 5-HT systems projecting to the Acb. Neuropharmacological studies demonstrated that local microinfusion of a 5-HT agonist into the Acb of the P line of rats enhanced ethanol drinking. Intracranial self-administration studies established that P rats will self-administer ethanol directly into the ventral tegmental area (VTA). Overall the data suggest the involvement of certain VTA DA and dorsal raphe nucleus 5-HT pathways in regulating high alcohol drinking behavior.

Alcohol Drinking↗
PubMed1991

Formation of the 37KD liver protein-acetaldehyde adduct in vivo and in vitro.

A liver protein with molecular weight of 37,000 can form adducts with acetaldehyde in vivo when rats are fed alcohol chronically. This 37KD protein is not directly involved in the hepatic metabolism of ethanol but it requires alcohol dehydrogenase activity to form adducts with acetaldehyde. The 37KD protein-AA is located in cytosol of the liver. However, under certain circumstances e.g. when fed an alcohol-containing liquid diet supplemented with cyanamide (an aldehyde dehydrogenase inhibitor that raises blood acetaldehyde concentrations), this 37KD protein-acetaldehyde adduct (protein-AA) becomes incorporated into liver plasma membranes. The same 37KD protein-AA can also form in vitro with cultured rat hepatocytes treated with ethanol. The formation of the 37KD protein-AA in the cultured liver cells increased with time and was dependent on concentrations of ethanol in the culture medium. Thus, protein-AAs can form in vivo and in liver cell culture upon chronic alcohol exposure, and a 37KD protein in liver is highly susceptible to chemical modification by acetaldehyde.

Acetaldehyde↗
PubMed1991

Microinjection of sulpiride into the nucleus accumbens increases ethanol drinking in alcohol-preferring (P) rats.

The effects of dopamine antagonists microinjected into the nucleus accumbens (Acb) on alcohol-drinking behavior were studied in the selectively bred alcohol-preferring (P) line of rats. P female rats (N = 8) were given access to food and water ad lib, while availability of a 10% (v/v) ethanol solution was limited to 1 hr/day. After implantation of guide cannulas bilaterally into the Acb and recovery from surgery, the rats were microinjected with either the D1 antagonist SCH 23390 (0.1 to 2.0 micrograms/side), the D2 antagonist sulpiride (0.1 to 2.0 micrograms/side) or vehicle, and ethanol intake was monitored. The D1 antagonist SCH 23390 had little effect on alcohol intake although the 0.5 ug/side dose produced a small increase which was not statistically significant. The D2 antagonist sulpiride increased, in a dose dependent manner, the intake of ethanol to as high as 215% of control values (F(4,28) = 39.9; p < 0.001). Additional experiments indicated that the 2.0 micrograms/side dose of sulpiride did not alter the consumption of a 14% glucose nor a 0.25% saccharin solution. These data suggest that D2 receptors in the Acb are important in the regulation of alcohol drinking by the P line of rats.

Alcohol Drinking↗
PubMed1990

Formation of the 37-kD protein-acetaldehyde adduct in primary cultured rat hepatocytes exposed to alcohol.

We have previously reported that a 37-kD liver protein formed an adduct with acetaldehyde in vivo when rats were fed alcohol chronically. To understand the mechanism of the formation of this protein-acetaldehyde adduct, rat hepatocytes in primary culture were treated with ethanol in vitro for several days. When cultured in hormone-enriched and trace metal-enriched Waymouth's medium, alcohol dehydrogenase activities in hepatocytes decreased only about 30% during 6 days of culture. At the end of the specified time, protein extracts of hepatocytes were immunotransblotted with rabbit immunoglobulin G that recognized acetaldehyde adduct as an epitope. The 37-kD protein-acetaldehyde adduct band could be detected within 3 days in cells that had been treated with alcohol at a steady-state concentration as low as 5 mmol/L. Although the maximal intensity was obtained at approximately 10 to 40 mmol/L ethanol, addition of cyanamide (an inhibitor of aldehyde dehydrogenase) further increased the intensity of this protein-acetaldehyde adduct band by more than twofold. A good correlation existed between acetaldehyde concentration in the medium and the intensity of the 37-kD protein-acetaldehyde adduct band. Formation of the 37-kD liver protein-acetaldehyde adduct is thus dependent on acetaldehyde, and the 37-kD protein is apparently unusually susceptible to chemical modification by acetaldehyde.

Acetaldehyde↗
PubMed1990

Ruptured mycotic pseudoaneurysm of the gastroduodenal artery presenting with hemoperitoneum and subcapsular liver hematoma.

We report a case of a patient with mycotic pseudoaneurysm of the gastroduodenal artery who presented with hemoperitoneum and subcapsular hematoma of the liver. The diagnosis was established with contrasted abdominal CT scanning. Visceral angiography was not needed. Prompt recognition and surgical intervention led to a favorable outcome. Pseudoaneurysm of visceral vessels is an uncommon disease process, and to our knowledge, this is the first reported case that has presented with free blood in the peritoneal cavity and beneath the liver capsule. This case may also represent a rare complication of therapeutic ERCP procedures. Mycotic aneurysm or pseudoaneurysm of visceral vessels may develop from bacteremia and its dissection or rupture should be suspected in patients presenting with sepsis and abdominal pain.

Aged↗