Biomedical subjects
A H Jacobs
Publications and source records attributed to A H Jacobs.
Management of atopic dermatitis in childhood.
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Tinea facei due to Microsporum canis in an eight-day-old infant.
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Local management of atopic dermatitis in infants and children.
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GROUP A HEMOLYTIC STREPTOCOCCUS ANTIBODIES. I. GRIFFITH TYPE AGGLUTININ AND ANTISTREPTOLYSIN TITERS IN NORMAL MEN AND IN ACUTE INFECTIONS.
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GROUP A HEMOLYTIC STREPTOCOCCUS ANTIBODIES. II. GRIFFITH TYPE AGGLUTININ AND ANTISTREPTOLYSIN TITERS IN CARRIERS AND NON-CARRIERS.
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HSV-1 infected cell proteins influence tetracycline-regulated transgene expression.
BACKGROUND: This study investigates elements of herpes simplex virus type 1 (HSV-1) which influence transgene expression in tetracycline-regulated expression systems. METHODS: Different HSV-1 mutants were used to infect Vero cells that had been transfected with plasmids containing the luciferase gene under the control of tet-off or tet-on tetracycline-regulation systems. RESULTS: The baseline level of luciferase expression was elevated after infection with HSV-1 mutants lacking one or more immediate early genes encoding transactivating factors: ICP27, ICP4 and ICP0. With the tet-off system, not only was baseline expression elevated, but there was a complete loss of induction upon removal of tet when this regulatory system was brought into the cell by infection with helper virus-free amplicon vectors. Elevation of luciferase expression was also observed upon infection with the same HSV-1 mutants following transfection with a plasmid containing only a CMV minimal promoter driving luciferase (pUHC13-3). Only one HSV mutant (14Hdelta3), which bears a disruption in the transactivation domain of VP16 and is deleted for both ICP4 genes, did not increase baseline luciferase expression after transfection of pUHC13-3. The disregulating effects were dependent on virus dose and were not influenced by treatment with interferon (IFN)-alpha, which suppresses viral gene expression. Additional assays involving cotransfection of pUHC13-3 with a plasmid encoding of the HSV-1 transactivating factor ICP4 revealed that ICP4 was the most potent inducer of gene expression from the tetO/CMV minimal promoter. CONCLUSION: These results indicate that proteins encoded in the HSV-1 genome, especially the transactivating immediate early gene products (ICP4, ICP27 and ICP0) and the VP16 tegument protein can activate the tetO/ minimal CMV promoter and thereby interfere with the integrity of tetracycline-regulated transgene expression.