59 research outputs found
Efficacy of pegylated interferon plus ribavirin in combination with corticosteroid for two cases of combined hepatitis C and autoimmune hepatitis
The treatment strategy for cases of combined autoimmune hepatitis (AIH) and chronic hepatitis C (CHC) has not yet been established. A 47-year-old woman and a 53-year-old-woman were hospitalized for treatment of CHC. Ultrasonography and histological findings revealed that their liver was not cirrhotic but did have chronic damage. The histological findings of both patients were suggestive of AIH. The patients were systematically treated with pegylated interferon-alpha 2b plus ribavirin which was preceded by and combined with corticosteroid (CS), and showed sustained virological responses and normal liver function. Although these two patients with combined AIH and CHC were successfully treated with this regimen, careful attention to exacerbation of hepatic inflammation is needed because hepatitis C viral load was increased due to immunosuppression during CS treatment
An Active Site Aromatic Triad in Escherichia coli DNA Pol IV Coordinates Cell Survival and Mutagenesis in Different DNA Damaging Agents
DinB (DNA Pol IV) is a translesion (TLS) DNA polymerase, which inserts a
nucleotide opposite an otherwise replication-stalling
N2-dG lesion in vitro, and
confers resistance to nitrofurazone (NFZ), a compound that forms these lesions
in vivo. DinB is also known to be part of the cellular
response to alkylation DNA damage. Yet it is not known if DinB active site
residues, in addition to aminoacids involved in DNA synthesis, are critical in
alkylation lesion bypass. It is also unclear which active site aminoacids, if
any, might modulate DinB's bypass fidelity of distinct lesions. Here we
report that along with the classical catalytic residues, an active site
“aromatic triad”, namely residues F12, F13, and Y79, is critical for
cell survival in the presence of the alkylating agent methyl methanesulfonate
(MMS). Strains expressing dinB alleles with single point
mutations in the aromatic triad survive poorly in MMS. Remarkably, these strains
show fewer MMS- than NFZ-induced mutants, suggesting that the aromatic triad, in
addition to its role in TLS, modulates DinB's accuracy in bypassing
distinct lesions. The high bypass fidelity of prevalent alkylation lesions is
evident even when the DinB active site performs error-prone NFZ-induced lesion
bypass. The analyses carried out with the active site aromatic triad suggest
that the DinB active site residues are poised to proficiently bypass distinctive
DNA lesions, yet they are also malleable so that the accuracy of the bypass is
lesion-dependent
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