Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a survey done in East Germany between 1981 and 1988, we found that 93 of 120 male scleroderma patients had long-term exposure to silica dust. We describe our findings in 12 patients with scleroderma and silicosis. The exposure time to silica dust was between 3 and 34 years; the interval between the beginning of exposure and the onset of scleroderma averaged 27.3 years (range 9 to 40 years). Antinuclear antibodies in titers between 80 and 10,240 with nucleolar and/or speckled patterns were found in 10 patients, antibodies against double-stranded DNA in three, Scl-70 (topoisomerase I) in three, and anticentromere antibodies in five. The following markers of collagen metabolism were increased in serum: beta-galactosidase in 12 patients, laminin peptide-P1 in 10 patients, N-terminal procollagen type III peptide in 10, and urinary sialic acid excretion in 7. We propose that crystalline particles of silica less than 5 microns may be phagocytosed by macrophages and release lymphokines and monokines, which activate fibroblasts and enhance their collagen and glycosaminoglycan synthesis. In addition, silica may act as an adjuvant to increase immune reactivity.
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PMID:Silica-induced scleroderma. 215 53

We studied the influence of DNA topological changes on Escherichia coli recA gene expression. This was monitored by measuring beta-galactosidase activity in cells containing a recA-lacZ fusion. To modulate DNA supercoiling we used mutations in the genes encoding for topoisomerase I and DNA gyrase. After either UV irradiation or treatment with the gyrase inhibitor ciprofloxacin, induction of the recA gene was reduced in topA10 mutants, this reduction being alleviated when gyrA or gyrB mutations causing DNA relaxation were present. A reduced induction of recA was also observed after incubation of cells carrying the recA441 mutation at 42 degrees C in the presence of adenine. Using bacteria deficient in the LexA repressor, we have demonstrated that the topA10 mutation reduces the constitutive expression of the recA gene. We suggest that the increase in negative supercoiling resulting from topoisomerase I deficiency interferes with transcription from the recA promoter. The reduction in the expression of the recA gene in topA10 bacteria could determine their increased UV sensitivity as well as their partial defectiveness in SOS mutability.
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PMID:Expression of the recA gene is reduced in Escherichia coli topoisomerase I mutants. 215 80

Topoisomerase I inhibitors have been shown to have clinical activity against human colorectal cancer. Previous studies showed that the cytotoxicity of camptothecin, a topoisomerase I inhibitor, occurs mainly in the S -phase of the cell cycle and is protectable by aphidicolin, an inhibitor of replicative DNA polymerase in some camptothecin-sensitive colorectal cells. Transcription factor E2F-1 regulates the G1/S transition, and recent studies have shown that E2F-1 potentiated the cytotoxicity of some cell-cycle-related drugs. Therefore, the present study was designed to investigate the effect of adenovirus-mediated E2F-1 gene transfer on chemosensitivity of colorectal cancer to camptothecin, in vitro and in vivo. Two human colorectal cancer cells, SW620 (mutant p53) and RKO (wild-type p53), were treated with camptothecin, alone or in combination with adenoviral vectors expressing beta-galactosidase (Ad-LacZ), or E2F-1 (Ad-E2F-1). E2F-1 overexpression was confirmed by Western blot analysis. Ad-E2F-1 gene transfer at low doses (less than the LD(20) dose) markedly increased the sensitivity of human colorectal cancer cells to camptothecin in vitro, which is because of induction of apoptosis. Aphidicolin did not have any protective effect on the Ad-E2F-1/camptothecin-mediated cytotoxicity. The level of topoisomerase I expression was not affected by combination treatment as well, suggesting that DNA replication and topoisomerase I activity may not account for the molecular mechanism of cell killing in response to Ad-E2F-1/camptothecin treatment. Fas and Fas ligand expression were not altered by treatment with camptothecin and/or Ad-E2F-1. Moreover, combination of camptothecin and Ad-E2F-1 has an additive antitumor effect in an in vivo nude mouse xenograft model. When combined with camptothecin, E2F-1 adenovirus therapy resulted in a 95.7% decrease in tumor size compared to control groups (P<.05). These results suggest a chemosensitization strategy that may have clinical utility in human colorectal cancer.
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PMID:E2F-1 overexpression sensitizes colorectal cancer cells to camptothecin. 1263 37