Biomedical subjects

J S Jacobsen

Publications and source records attributed to J S Jacobsen.

23 records · Page 2Linked to original sources

PubMed1986

Chloroperbenzoic acid induced DNA damage and peracid activation of alfatoxin B1.

The activated form of aflatoxin B1 (AFB1) in vitro and in vitro is believed to be the 2,3-oxide, which cannot be isolated, presumably due to its reactivity. In addition to in vitro activation by crude metabolic enzymes, two chemical procedures are available, one involving oxidation with the mild organic oxidant chloroperbenzoic acid and another involving the synthesis of AFB1-2,3-dichloride, an electronic analog of AFB1-2,3-oxide. Here we show that chloroperbenzoic acid by itself can modify DNA, primarily at non-basepaired adenine and guanine residues, as revealed by 'replication block' analysis.

Aflatoxin B1↗

PubMed1985

Sequence context effects in DNA replication blocks induced by aflatoxin B1.

The genotoxic effects of the potent mutagenic carcinogen aflatoxin B1 (AFB1) are believed to be mediated by its reaction with the N-7 atom of guanine residues in DNA. We have analyzed the effect of AFB1-induced chemical modification on the template function of single-stranded DNA in vitro. The experimental strategy involves the elongation of a primer on a modified template by Escherichia coli DNA polymerase I (large fragment) and analysis of the products by high-resolution gel electrophoresis. Our data show that (i) AFB1 induces specific replication blocks one nucleotide 3' to the sites of occurrence of guanine residues on template DNA; (ii) AFB1-induced replication blocks occur predominantly at sequences capable of participation in intrastrand base pairing; (iii) within the intrastrand base-paired regions there are strong sequence context effects, in accordance with the previously described [Muench, K. F., Misra, R. P. & Humayun, M. Z. (1983) Proc. Natl. Acad. Sci. USA 80, 6-10] specificity "rules" that apply to the reaction of AFB1 with guanine residues in double-stranded DNA; (iv) there is evidence that the (7-guanyl)-AFB1 adducts as well as secondary derivatives such as the formamidopyrimidine-AFB1 act as replication blocks. In summary, these data suggest that previously observed inhibition of DNA replication and transcription by AFB1 is directly attributable to (7-guanyl)-AFB1 adducts or their secondary reaction products.

Aflatoxin B1↗

PubMed1982

Comparison of cell-surface human melanoma-associated antigens identified by rabbit and murine antibodies.

Melanoma-associated antigens (MAAs) recognized by murine monoclonal and rabbit polyclonal antibodies were compared. Two rabbit antimelanoma sera raised in our laboratory recognized five human cell-surface MAAs with approximate MWs of 75, 95, 120, 150, and 240 kd. These antigens were easily detected by SDS-PAGE of specific immunoprecipitates on a melanoma cell (HM31) which failed to reveal antigens reactive with the panel of murine monoclonal antibodies studied. By contrast, these five antigens could not be detected on another melanoma cell (SK-MEL-28), which was reactive with several of the murine monoclonals. These results suggest that the MAAs recognized by rabbit and murine antibodies are different and imply that the antigens which are immunogeneic in man may not necessarily be immunogeneic in mice.

Animals↗

PubMedDate not supplied

A novel species-specific RNA related to alternatively spliced amyloid precursor protein mRNAs.

Using an S1 nuclease protection assay, we have identified a novel "variant" Amyloid Precursor Protein (APP) RNA in human brain which is 3-6-fold more abundant than APP-770, but less abundant than APP-751 or APP-695. This variant, referred to as amyloid precursor-related protein 365 (APRP-365), is not detected in mouse and rat brain RNAs. A 1.6 kilo-basepair cDNA clone corresponding to this variant APP RNA predicts the existence of a 365 amino acid protein that is similar to the amino-terminal end of APP-770 but lacks the beta-amyloid peptide and any hydrophobic transmembrane spanning domains. In a modified polymerase chain reaction (PCR), we used amplification of reverse transcribed mRNA to confirm and extend our S1 observations. Together, the features of APRP-365 suggest that the human variant is a soluble protein containing a Kunitz protease inhibitor domain.

Amino Acid Sequence↗

PubMedDate not supplied

Quantitative measurement of alternatively spliced amyloid precursor protein mRNA expression in Alzheimer's disease and normal brain by S1 nuclease protection analysis.

We have used an S1 nuclease protection strategy to measure alternatively spliced amyloid precursor protein (APP) mRNAs associated with Alzheimer's disease (AD) to determine whether the expression of either one or more of the transcripts correlate with observed amyloid plaque pathology. Comparison of AD with normal cortex reveals that increasing plaque density parallels an increase in the fraction of APP-695 and a corresponding decrease in APP-770 and 751 mRNA fractions. A specific increase of APP-695, the protease inhibitor-lacking APP RNA form, in those brain regions most involved with amyloid plaque formation, suggests that an imbalance in the protease inhibitor is potentially significant in the disease. These data are consistent with cellular/tissue region-specific regulation of alternative splicing accounting for AD-related changes in the expression of APP mRNA forms.

Adult↗