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Biomedical subjects

B Bacon

Publications and source records attributed to B Bacon.

7 recordsLinked to original sources

Hepatic lipid peroxidation in hereditary hemochromatosis and alcoholic liver injury.

Studies in experimental animals have indicated that enhanced lipid peroxidation may play a role in the hepatic injury produced by iron overload or by excessive alcohol consumption. The aim of this study was to compare the formation of lipid peroxidation-derived aldehydes in the liver of patients with hereditary hemochromatosis (HH) and alcohol abuse. Liver biopsy specimens from 10 nondrinking patients with HH were evaluated. These patients were classified as having HH based on hepatic iron index or human leukocyte antigen identity with a known proband. All patients were homozygous for the Cys282Tyr mutation. In addition, 8 patients with alcoholic liver disease were examined, 2 of whom also had hemochromatosis. For comparison, 17 patients with liver diseases unrelated to iron overload or alcohol abuse were studied. Liver biopsy specimens were immunostained for protein adducts with malondialdehyde and 4-hydroxynonenal. Both malondialdehyde- and 4-hydroxynonenal-protein adducts were found from liver specimens of patients with HH and alcohol abuse in more abundant amounts than from patients in a control group. In alcoholics the adducts were primarily in zone 3, whereas in hemochromatosis staining had an acinar zone 1 predominance, which followed the localization of iron. The most abundant amounts of protein adducts were noted in patients with alcohol abuse plus iron overload. The data support the concept that both chronic alcohol use and iron overload induce hepatic lipid peroxidation. Through formation of reactive aldehydic products, excessive alcohol consumption and iron overload may have additive hepatotoxic effects.

Adult↗

Selenite supplementation decreases expression of MAZ in HT29 human colon adenocarcinoma cells.

Low dietary intake of the essential trace element selenium can increase the risk of colon cancer. Utilizing RNA arbitrarily primed polymerase chain reaction (RAP-PCR), we sought to identify genes differentially expressed in HT29 human colon adenocarcinoma cells cultured with or without supplemental sodium selenite. One cDNA fragment, present at lower levels in samples from cells supplemented with selenite, had 97% nucleotide sequence identity with a sequence from the 3'-untranslated region of myc-associated zinc-finger protein (MAZ) cDNA. Northern blot analysis showed that steady-state levels of mRNA detected using this fragment as a probe were three times greater in unsupplemented (Se-) than in supplemented (Se+) samples. When a duplicate Northern blot was probed with a 300-bp fragment from the open reading frame of an MAZ cDNA clone, signal intensity was 2.2 times greater in Se- than in Se+ lanes. The MAZ protein has been shown to be a transcription regulator of the c-myc protooncogene. Signal intensity on a Northern blot probed with a segment of c-myc Exon 1 cDNA was 94% greater in Se- than in Se+ lanes. These findings are consistent with the established role for MAZ in regulating c-myc gene expression. They also suggest a molecular mechanism by which selenium intake may affect risk of colon cancer.

Base Sequence↗

Hepatitis C testing: interpretation, implications, and counseling.

New molecular biology techniques recently identified hepatitis C virus (HCV) as the major cause of non-A, non-B hepatitis. Serologic assays for HCV specific antibodies are a significant advance, but they require cautious interpretation due to problems with the tests' sensitivity and specificity. Patients with suspected HCV infection should be thoroughly evaluated to verify the presence of infection, to exclude other forms of chronic liver disease, and to determine the extent of liver damage prior to considering treatment.

Hepatitis C↗

Three-dimensional structural analysis of the group B polysaccharide of Neisseria meningitidis 6275 by two-dimensional NMR: the polysaccharide is suggested to exist in helical conformations in solution.

The solution conformations of the group B polysaccharide of Neisseria meningitidis were analyzed by DQF-COSY and pure absorption 2D NOE NMR with three mixing times. The pyranose ring of the sialic acid residue was found to be in the 2C5 conformation. The DQF-COSY analysis indicated that the orientations of H6 and H7 and of H7 and H8 are both gauche. In order to overcome the difficulties in analyzing the NOE data due to the two sets of proton overlaps, molecular modeling of alpha-2,8-linked sialic acid oligomers was carried out to investigate possible conformers, and theoretical NOE calculations were performed by using CORMA (complete relaxation matrix analysis). Our analysis suggests that the polysaccharide adopts helical structures for which the phi (defined by O6-C2-O8-C8) and psi (C2-O8-C8-C7) angles are in the following ranges: phi -60 to 0 degrees, psi 115-175 degrees or phi 90-120 degrees, psi 55-175 degrees. The weak affinity of anti-B antibodies for smaller alpha-2,8-linked oligosaccharides may be due to the fact that such oligomers are more flexible and may not form an ordered structure as the poly(sialic acid) does.

Antigens, Bacterial↗

Deoxyuridine suppression studies in bone marrow in primary refractory sideroblastic anemia.

Because unexplained megaloblastic erythroid maturation occurs in patients with primary refractory sideroblastic anemia (PRSA), deoxyuridine (dU) suppression tests using 125I-UdR were performed on bone marrow from five patients with PRSA. All patients had megaloblastic alterations in the marrow erythroid precursors (with normal serum folate and B12 levels) and numerous ringed sideroblasts, and most had marrow iron overload. Results of the dU suppression tests were normal in all five, both with and without incubation with pharmacologic amounts of folate, B12, and pyridoxal phosphate with or without 1-serine. Despite occasional hematologic improvement subsequent to folate, pyridoxine, or pyridoxal phosphate (PLP) administration in some patients with PRSA, normal dU suppression implies that in our group the availability of B12 and folate (and possibly PLP) was not limiting in the utilization of folate for DNA-thymine synthesis. The marrow erythroid maturation defect remains unexplained.

Adult↗