Biomedical subjects
K Krabill
Publications and source records attributed to K Krabill.
Subcellular localization and antiviral activity of carminic acid/poly r(A-U) combinations.
Carminic acid (CAR) enhances the antiviral activity of poly r(A-U) twelve-fold without increasing interferon induction, inactivating the vesicular stomatitis virus or inducing host cell cytotoxicity. Phase contrast photomicrographs of human foreskin fibroblasts (HSF) incubated with CAR alone, poly r(A-U) alone or with a CAR/poly r(A-U) combination illustrate that the CAR/poly r(A-U) combinations display altered subcellular distribution with the CAR being localized in the nucleoli and chromatin. Phase contrast and fluorescence photomicrographs of adriamycin (ADR)-treated and ADR/poly r(A-U)-treated HSF cells corroborate these findings. These results suggest that modulation of one or more nucleolar processes may be responsible for the enhanced antiviral activity.
Enhanced antiviral activity and altered subcellular distribution of magnesium/poly r(A-U) combinations.
When Mg2+ or ethidium bromide (EB) were combined with poly r(A-U) at a ligand/ribonucleotide ratio of 1/4, the antiviral activity of the Mg2+ and EB increased 136-fold and 154-fold. Eriochrome Blue SE was employed to visualize the subcellular distribution of Mg2+ following co-incubation of Human Foreskin Fibroblasts (HSF) with Mg2+ alone or with the Mg2+/poly r(A-U) combination. Phase contrast micrographs of these Mg(2+)-treated HSF cells as well as phase contrast and fluorescence micrographs of EB-treated or EB/poly r(A-U)-treated HSF cells illustrated that the Mg2+ (or EB)/poly r(A-U) combinations display altered subcellular distribution with the Mg2+ and EB being localized in the nucleoli and chromatin of the HSF cells. These results suggest that modulation of nuclear processes may be responsible for the enhanced antiviral activity.
Diagnostic and therapeutic advances in pediatric cardiology (2).
The practice of pediatric cardiology has undergone remarkable changes over the past decade. Cardiac structural abnormalities may frequently be diagnosed with echocardiography alone, and treatment for many of these structural problems may be corrected during cardiac catheterization. Arrhythmia diagnosis and management have made similar progress, such that diagnosis of arrhythmia mechanisms and catheter ablative therapy may be performed during a single procedure, sparing the young patient a lifetime of antiarrhythmic drug therapy. Cardiac transplantation is now included among the treatment options for some patients with severe congenital or acquired cardiac abnormalities unresponsive to standard therapy. In this paper, we provide a brief description of current applications of recent advances in the practice of pediatric cardiology.
Enhancement of the antiviral activity of poly r(A-U) by ametantrone and mitoxantrone.
The role of ametantrone (HAQ) and mitoxantrone (DHAQ) in modulating the antiviral and interferon-inducing activities of poly r(A-U) was examined using the human foreskin fibroblast-vesicular stomatitis virus (HSF-VSV) bioassay system in which the concentration of poly r(A-U) was fixed at 0.05 mM or 0.2 mM while the HAQ or DHAQ concentration was varied to produce variable HAQ (or DHAQ)/ribonucleotide ratios ranging from 1:16 to 2:1. HAQ, DHAQ and poly r(A-U) tested individually were not efficacious antiviral agents. When poly r(A-U) was combined with the ametantrone or mitoxantrone the antiviral activity was potentiated 10-fold at HAQ (or DHAQ)/ribonucleotide ratios in the region of 1/4 to 1/6. The interferon-inducing activity of the HAQ (or DHAQ)/poly r(A-U) combinations were equal to the sum of the interferon-inducing activity of the poly r(A-U) and the HAQ (or DHAQ). These results indicate that the HAQ and DHAQ potentiate the antiviral activity of the poly r(A-U) without the superinduction of interferon. The direct viral inactivation study demonstrated that HAQ, DHAQ, poly r(A-U) and the HAQ (or DHAQ)/poly r(A-U) combinations did not inactivate the VSV at concentrations near the viral 50% inhibitory dose.
In vitro antiviral activity of poly (A-U) and ellipticines.
The role of N2-methyl-9-hydroxy-ellipticine (NMHE) and N2,N6-dimethyl-9-hydroxy-ellipticine (DMHE) in modulating the antiviral activity of poly (A-U) was examined using a human foreskin fibroblast-vesicular stomatitis virus (HSF-VSV) bioassay in which the concentration of poly (A-U) was fixed at 0.05 mM or 0.2 mM while the NMHE or DMHE concentration was varied to produce variable NMHE (or DMHE)/ribonucleotide ratios ranging from 1:16 to 2:1. Poly (A-U), NMHE and DMHE tested individually were not efficacious antiviral agents. When the poly (A-U) was combined with the NMHE or DMHE, the antiviral activity of the poly (A-U) was potentiated 16- to 20-fold a NMHE (or DMHE)/ribonucleotide ratios in the region of 1/4. Poly (A-U), NMHE and DMHE induce beta-IFN. The interferon-inducing activity of the NMHE (or DMHE)/poly (A-U) combination was equal to the sum of the interferon-inducing activity of the poly (A-U) alone and the NMHE (or DMHE) alone. The direct viral inactivation study demonstrated that NMHE, DMHE, poly (A-U) and the NMHE (or DMHE)/poly (A-U) combinations did not inactivate VSV at concentrations near the 50% viral inhibitory dose. Photomicrographs of HSF cells incubated with NMHE alone or with a NMHE/poly (A-U) combination suggest that poly (A-U) affects the subcellular distribution of the NMHE by steering the NMHE to the nucleolus. These observations suggest that modulation of a nuclear process may be responsible for the enhanced antiviral activity.
Potentiation of the antiviral activity of poly r(A-U) by xanthene dyes.
Ten xanthene dyes (XAN) are evaluated for their ability to potentiate the antiviral activity of poly r(A-U) using a human foreskin fibroblast-vesicular stomatitis virus bioassay in which the XAN is combined with 0.2 mM poly r(A-U) to produce a XAN/ribonucleotide ratio of 1/4. Four of the ten XANs tested in this study, rhodamine 123, rhodamine B, rhodamine 6G and sulforhodamine B, enhance the antiviral activity of poly r(A-U) 8- to 15-fold. The interferon-inducing activity of the four active XAN/poly r(A-U) combinations is equal to the sum of the activities of their constituents. These four XANs appear to potentiate the antiviral activity of the poly r(A-U) without superinduction of interferon. The direct viral inactivation study demonstrates that the XANs, poly r(A-U) and the XAN/poly r(A-U) combinations do not inactivate the VSV at concentrations near the 50% effective dose.
Polyribonucleotide-anthraquinone interactions: in vitro antiviral activity studies.
Twelve anthraquinones (AQ) were evaluated for their ability to potentiate the antiviral activity of poly r(A-U) using a human foreskin fibroblast-vesicular stomatitis virus bioassay in which the AQ was combined with 0.2 mM poly r(A-U) to produce an AQ/ribonucleotide ratio of 1/4. Poly r(A-U) and the AQ alone were not effective antiviral agents. Five of the twelve AQs tested, mitoxantrone, adriamycin, ametantrone, carminic acid and daunomycin, enhanced the antiviral activity of poly r(A-U) 9- to 13-fold. The interferon-inducing activity of the five active AQ/poly r(A-U) combinations was equal to the sum of the interferon-inducing activities of their constituents. These five AQs appear to potentiate the antiviral activity of poly r(A-U) without superinduction of interferon.
Potentiation of the antiviral activity of poly r(A-U) by riboflavin, FAD and FMN.
The role of riboflavin (RFN), FAD or FMN in modulating the antiviral activity of poly r(A-U) was examined by the human foreskin fibroblast-vesicular stomatitis virus bioassay in which the concentrations of poly r(A-U) was fixed at 0.1 mM or 0.2 mM while the riboflavin, FAD or FMN concentration was varied to produce variable RFN (or FAD or FMN)/ribonucleotide ratios ranging from 1/16 to 2/1. Riboflavin, FAD and FMN tested individually did not exhibit any antiviral activity, while poly r(A-U) alone exhibited antiviral activity. When poly r(A-U) was combined with riboflavin, FAD or FMN, the antiviral activity was potentiated seven- to twelve-fold at RFN (or FAD or FMN)/ribonucleotide ratios in the region of 1/4.
Enhancement of the antiviral and interferon-inducing activities of poly r(A-U) by carminic acid.
Experiments have been designed to systematically examine the effects of carminic acid (CAR) on the antiviral/interferon-inducing activity of poly r(A-U), using the human foreskin fibroblast-vesicular stomatitis virus bioassay system. Modulation of the antiviral/interferon-inducing activity of poly r(A-U) by carminic acid was examined at fixed poly r(A-U) concentrations of 0.05 mM or 0.2 mM while varying the carminic acid concentrations to produce variable CAR/ribonucleotide ratios ranging from 1:16 to 2:1. Carminic acid and poly r(A-U) were tested individually at the concentrations employed in the CAR/poly r(A-U) combinations. Neither the carminic acid alone nor poly r(A-U) alone were effective antiviral agents/interferon inducers. The antiviral/interferon-inducing activity of poly r(A-U) was potentiated twelve-fold at CAR/ribonucleotide ratios in the region of 1/6 to 1/4. These results suggest a synergism between the poly r(A-U) and the carminic acid at the concentrations employed in this study.