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E Hildebrandt

Publications and source records attributed to E Hildebrandt.

22 records · Page 2Linked to original sources

Identification and characterization of an endo/exonuclease in Pneumocystis carinii that is inhibited by dicationic diarylfurans with efficacy against Pneumocystis pneumonia.

Dicationic diarylfurans and dicationic carbazoles are under development as therapeutic agents against opportunistic infections. While their ability to bind to the minor groove of DNA has been established, the complete mechanism of action has not. We demonstrate here that an effective diarylfuran, 2,5-bis[4-(N-isopropylguanyl)phenyl]furan, inhibits an endo/exonuclease activity present in Pneumocystis carinii, Cryptococcus neoformans, Candida albicans, and Saccharomyces cerevisiae. This activity was purified from the particulate fraction of P. carinii. The enzyme requires Mg++ or Mn++, and shows preferences for single-over double stranded DNA and for AT-rich over GC-rich domains. A panel of 12 dicationic diarylfurans and eight dicationic carbazoles, previously synthesized, were evaluated for inhibition of the purified nuclease and for efficacy against Pneumocystis pneumonia in rats. Among the diarylfurans, potency of nuclease inhibition, in vivo antimicrobial activity, and DNA binding strength were all strongly correlated (p < 0.001). These findings suggest that one target for antimicrobial action of the diarylfurans may be a nucleolytic or other event requiring unpairing of DNA strands. Dicationic carbazoles which were strong nuclease inhibitors all displayed anti-Pneumocystis activity in vivo, but there were also noninhibitory carbazoles with in vivo efficacy.

Animals↗

Focus groups and vulnerable populations. Insight into client strengths and needs in complex community health care environments.

Focus groups are a useful qualitative research technique to assist in interpreting quantitative community assessment data. Data obtained from focus groups can provide sociological and psychological insights into the perceptions of population subgroups and suggest answers to the "why" questions raised by descriptive data about such issues as teen pregnancy, poverty, immunization levels, or lifestyle-related morbidity and mortality. Application of these insights can lead to the better use of community strengths and the creation of community-specific responses to barriers to health care. Focus groups work well for involving hard-to-reach members of a community in program development, planning, and evaluation. They may be more effective than face-to-face interviews and questionnaires because people often have not thought about how they feel and tend not to form opinions in isolation (1). The information sought through the use of focus groups is not randomly distributed in the population. Thus, groups are not randomly selected, and data are not gathered with the intent to generalize to all populations.

Adult↗