RESUMO
Rifamycin derivatives, such as rifampicin, have potent antibiotic activity and have long been used in the clinic as mainstay components for the treatment of tuberculosis, leprosy, and AIDS-associated mycobacterial infections. However, the extensive usage of these antibiotics has resulted in the rapid development of bacterial resistance. The resistance mechanisms mainly include mutations of the rifamycin target RNA polymerase of bacteria and enzymatic modifications of rifamycin antibiotics. One modification is the recently characterized rifamycin degradation catalyzed by Rox enzymes, which belong to the widely occurring flavin monooxygenases. Intriguingly, our recent sequence analysis revealed the rifamycin producers also encode Rox homologs that are not yet characterized. In this work, we expanded the study of the Rox-catalyzed rifamycin degradation. We first showed that the Rox proteins from rifamycin producers have the enzymatic rifamycin SV-degrading activity. Then we used the structurally diverse rifamycin compounds rifampicin and 16-demethylrifamycin W to probe the substrate scope and found that they each have a slightly different substrate scope. Finally, we demonstrated that Rox proteins can also catalyze the transformation of 16-demethylsalinisporamycin to 16-demethylsaliniketal A. Since 16-demethylsalinisporamycin and 16-demethylsaliniketal A are the counterpart analogs of salinisporamycin and saliniketal A, our biochemical findings not only uncover a previously uncharacterized self-resistance mechanism in the rifamycin producers, but also bridge the gap between the biosynthesis of the potential antitumor compound saliniketal A.
RESUMO
OBJECTIVE: Study on the diagnostic accuracy of fine needle aspiration biopsy of cervical lymph nodes and to discuss the reasons of making a misdiagnosis. METHODS: Five hundred and eighty cases of cervical lymph node fine needle aspiration biopsy were reviewed retrospectively. Among them, histologic findings were available in 161 cases. The cytologic and histologic diagnoses were compared. RESULTS: There were altogether 226 cases of reactive lymphoid hyperplasia, 202 cases of specific inflammation, 45 cases of malignant lymphoma and 107 cases of metastatic carcinoma. The concordance rate between the cytologic and corresponding histologic diagnoses was 94.4%. The primary foci of most cases with metastatic carcinoma could be delineated by reviewing the clinical and pathologic finding. Inadequate cellularity was the main reason of making misdiagnosis and useful diagnostic clues might be obtained by careful study of the clinical findings. CONCLUSIONS: Fine needle aspiration biopsy of cervical lymph node carries a high diagnostic accuracy. It provides important clues in guiding subsequent clinical management. However, for detailed subtyping of certain disease entities such as malignant lymphoma, surgical biopsy for histologic and immunohistochemical studies are required.
