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Biomedical subjects

S Han

Publications and source records attributed to S Han.

27 records · Page 2Linked to original sources

Novobiocin blocks the Drosophila heat shock response.

In the studies reported here we show that the antibiotic novobiocin, an in vitro inhibitor of topoisomerase II, blocks the Drosophila heat shock response. If novobiocin is added prior to induction, there is no detectable expression of the Drosophila heat shock genes. Moreover, analysis of the chromatin organization of the 87A7 heat shock locus indicates that the antibiotic prevents the structural alterations which normally accompany heat induction. When novobiocin is added after induction, transcription appears to be rapidly turned off, and the chromatin organization of the 87A7 locus is "fixed" in an "active" configuration. Novobiocin also prevents the re-establishment of the pre-induced 87A7 chromatin organization which occurs during recovery from heat shock. We have also presented data suggesting that this antibiotic blocks transcription at 25 degrees C. These findings raise the possibility that topoisomerase II may be required in eukaryotes for both gene activation and deactivation.

Autoradiography

Transcriptionally active chromatin is sensitive to Neurospora crassa and S1 nucleases.

We have examined the distribution of Neurospora crassa and S1 nuclease cleavage products in the chromatin of the 87A7 heat shock locus of Drosophila melanogaster. Both of these nucleases generate single and double-strand breaks in chromatin at specific sites in the 87A7 locus. Before heat induction, we find that the 5' ends of the two 87A7 hsp 70 genes contain N. crassa and S1 nuclease hypersensitive sites, while there are only a few cleavage products from elsewhere in the locus. With N. crassa nuclease, we observe one major 5' fragment, and this is derived from cleavage in a DNA segment mapping about 90 to 115 base-pairs from the beginning of the transcription unit. With S1 nuclease, we find two 5' cleavage products. The first maps about 120 to 130 base-pairs from the beginning of the gene. Interestingly, this site is also sensitive to S1 nuclease in supercoiled but not linear naked DNA. The other fragment maps very close to the transcription start site (approximately 0 to -15 base-pairs). After heat induction, there is a transition in the chromatin architecture of 87A7. First, there is a marked reduction in the yield of the prominent 5' N. crassa and S1 nuclease fragments. Second, the entire hsp 70 gene, as well as the spacer DNA just downstream from the 3' end of the gene, becomes highly sensitive to both of these nucleases.

Animals

Ribosomal RNA genes of Drosophila melanogaster have a novel chromatin structure.

We have examined the chromatin organization of the Drosophila melanogaster ribosomal RNA genes using both micrococcal nuclease and DNase I. Several findings are of interest. First, the transcribed DNA segments of the rRNA repeat unit appear to be packaged into an unstable or "multiphasic" nucleosome structure. Second, the 5' end of the transcription unit is preferentially exposed to nuclease attack. Third, the non-transcribed spacer immediately upstream from the transcription start site has a novel chromatin organization with micrococcal nuclease and DNase I cleavage sites spaced at intervals of about 240 base-pairs. This unusual fragment distribution appears to reflect the underlying sequence organization of the spacer DNA segment, which consists of a series of tandemly repeated 239 base-pair sequence blocks. We have also examined the chromatin structure of the rRNA repeat unit after extraction of nuclei with different concentrations of salt. Our results suggest that the higher order structures may be of importance in determining the novel chromatin organization of the rRNA repeat unit.

Animals

HLA studies in acquired immune deficiency syndrome patients with Kaposi's sarcoma.

To investigate the possible contribution of genetic susceptibility to Kaposi's sarcoma associated with acquired immune deficiency syndrome (AIDS-KS), 21 patients were typed for HLA-A, B, C, and DR antigens. Significantly increased frequencies of HLA-Aw23, and HLA-Bw49 antigens were observed in the Caucasian AIDS-KS group. In this same group, the frequencies of HLA-DR5 and HLA-Bw44 antigens were increased at the P less than 0.1 level. Increased frequencies of HLA-A29 and HLA-Cw4 antigens and a decreased frequency of HLA-B8 antigen were also noted, but with P greater than 0.1, in the Caucasian AIDS-KS group.

Acquired Immunodeficiency Syndrome

Gastric diverticula following subtotal gastrectomy.

Four cases of gastric diverticula following subtotal gastrectomy are described. This type of diverticula associated with partial gastrectomy are probably true, acquired, pulsion diverticula. In two of our patients the diverticula were associated with significant prolapse of gastric mucosa causing obstruction at the anastomosis.

Adult