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C B Moore

Publications and source records attributed to C B Moore.

At least 37 records · Page 2Linked to original sources

Lack of correlation of in vitro amphotericin B susceptibility testing with outcome in a murine model of Aspergillus infection.

Amphotericin B has been the standard therapy for invasive aspergillosis since its introduction in 1957. It is only moderately effective. Many susceptibility tests have been used but little variation has been noted between strains. We have studied three strains of Aspergillus fumigatusand one of Aspergillus terreusin a neutropenic mouse model of invasive aspergillosis and attempted to correlate the variable efficacy in vivowith MICs generated by over 30 different susceptibility test formats. One strain of A. fumigatus(AF65) and the strain of A. terreus(AT49) were 'resistant' and the remaining two strains of A. fumigatus(AF210 and AF294) were 'susceptible' in vivo. Only AT49 had elevated MICs of amphotericin (MIC 2 mg/L) by 41 of 54 in vitrotesting systems. With each test format, including Etest, there was no distinction between MICs obtained for AF65, AF210 and AF294 (MICs 0.125-64 mg/L depending on the test). Thus despite extensive efforts we have been unable to correlate susceptible test results with in vivooutcome in A. fumigatusbut we have with A. terreus, with some test formats. This suggests that, at present, amphotericin B susceptibility testing of A. fumigatus is of limited clinical value and further work needs to be done to find testing systems that can identify the 'resistance' documented in vivo.

Amphotericin B↗

Integration of repellents, attractants, and insecticides in a "push-pull" strategy for managing German cockroach (Dictyoptera: Blattellidae) populations.

"Push-pull" is a behavior manipulation strategy in which behavior-modifying stimuli are integrated with a pest control agent. We evaluated the efficacy of an insecticide bait in combination with attractants ("pull"), repellents ("push"), or both ("push-pull") using a hydramethylnon-based bait, feces-contaminated surfaces as an attractant, and methyl neodecanamide-treated surfaces to repel cockroaches. Both adult males and first-instar German cockroaches, Blattella germanica (L.), chose shelters nearest the attractant-treated surfaces and farthest from the repellent-treated surfaces. Food consumption was highest from food nearest the preferred shelters, and mortality was highest when the insecticide bait was near the preferred shelter. These patterns were more apparent in first instars than in adults. Our results from large arena studies in the laboratory show that the push-pull strategy can be used to displace pests from resources or commodities that are to be protected, and simultaneously lure the pest to an attractant source coupled with a pest control agent. Concentrating cockroaches into a limited area should facilitate the precision-targeting of the pest population and promises to reduce insecticide use.

Animals↗

In vivo activity of amphotericin B lipid complex in immunocompromised mice against fluconazole-resistant or fluconazole-susceptible Candida tropicalis.

We compared four doses of amphotericin B lipid complex (ABLC) with three doses of fluconazole in temporarily neutropenic mice in a murine model of disseminated candidiasis due to four different isolates of Candida tropicalis. The mice were infected with a 90% lethal dose of four strains of C. tropicalis for which the fluconazole MICs ranged from 1 to >125 mg/liter 3 days after receiving 200 mg of cyclophosphamide/kg of body weight. Treatment was started 18 h after infection and lasted for 7 days. ABLC (1, 2, 5, and 10 mg/kg) was administered once a day intravenously, fluconazole was administered by oral gavage once daily (25 and 50 mg/kg/day) or twice daily (125 mg/kg). MICs determined in five different ways with 24- and 48-h endpoints were also compared. The overall survival rates were controls, 14%; fluconazole, 64%; and ABLC, 82%. Treatment with ABLC at 2 to 10 mg/kg increased survival compared to controls (P = <0.0001) and was also superior to fluconazole at 25 and 50 mg/kg (P = 0.006). In the fluconazole-resistant C. tropicalis model (MIC, 128 microg/ml), ABLC at 2 to 10 mg/kg was superior to fluconazole at 250 mg/kg and ABLC at 10 mg/kg was superior to all fluconazole doses (P = <0.05). Fluconazole at 250 mg/kg daily was superior to both 25 and 50 mg/kg at reducing mortality with most isolates. ABLC was superior to fluconazole (P = <0.01), and fluconazole at 250 mg/kg was superior to fluconazole at both 25 and 50 mg/kg (P = 0.02) in all models at reducing C. tropicalis counts in the kidneys. Neither drug consistently sterilized the brain or kidneys. A 48-h endpoint reading with the NCCLS susceptibility testing microtiter variation overestimates resistance to fluconazole. ABLC is an effective treatment for fluconazole-resistant C. tropicalis at all doses tested.

Amphotericin B↗

In vitro activity of the new triazole BMS-207147 against Aspergillus species in comparison with itraconazole and amphotericin B.

The in vitro activity of BMS-207147 against 80 clinical isolates of Aspergillus was compared with that of itraconazole and amphotericin B, using a validated microtiter method. Geometric mean MICs (in microg/ml) were as follows: 1.71 for BMS-207147, 0.67 for itraconazole, and 0.63 for amphotericin B. The range of concentrations of each drug was 0.125 to >16 microg/ml. Aspergillus fumigatus was significantly more susceptible to BMS-207147 (P < 0. 05) than A. terreus and A. flavus. No BMS-207147-resistant A. fumigatus isolates were identified, though eight itraconazole-resistant (MIC, >8 microg/ml) isolates were. BMS-207147 is active against Aspergillus spp. at slightly high concentrations compared with itraconazole and amphotericin B.

Amphotericin B↗

Zinc-dependent structural stability of human Sonic hedgehog.

The role of the zinc site in the N-terminal fragment of human Sonic hedgehog (ShhN) was explored by comparing the biophysical and functional properties of wild-type ShhN with those of mutants in which the zinc-coordinating residues H140, D147, and H182, or E176 which interacts with the metal ion via a bridging water molecule, were mutated to alanine. The wild-type and E176A mutant proteins retained 1 mol of zinc/mol of protein after extensive dialysis, whereas the H140A and D147A mutants retained only 0.03 and 0.05 mol of zinc/mol of protein, respectively. Assay of the wild-type and mutant proteins in two activity assays indicated that the wild-type and E176A mutant proteins had similar activity, whereas the H140A and D147A mutants were significantly less active. These assays also indicated that the H140A and D147A mutants were susceptible to proteolysis. CD, fluorescence, and (1)H NMR spectra of the H140A, D147A, and E176A mutants measured at 20 or 25 degrees C were very similar to those observed for wild-type ShhN. However, CD measurements at 37 degrees C showed evidence of some structural differences in the H140A and D147A mutants. Guanidine hydrochloride (GuHCl) denaturation studies revealed that the loss of zinc from the H140A and D147A mutants destabilized the folded proteins by approximately 3.5 kcal/mol, comparable to the effect of removing zinc from wild-type ShhN by treatment with EDTA. Thermal melting curves of wild-type ShhN gave a single unfolding transition with a midpoint T(m) of approximately 59 degrees C, whereas both the H140A and D147A mutants displayed two distinct transitions with T(m) values of 37-38 and 52-54 degrees C, similar to that observed for EDTA-treated wild-type ShhN. Addition of zinc to the H140A and D147A mutants resulted in a partial restoration of stability against thermal and GuHCl denaturation. The ability of these mutants to bind zinc was confirmed using a fluorescence-based binding assay that indicated that they bound zinc with K(d) values of approximately 1.6 and approximately 15 nM, respectively, as compared to a value of </=100 pM for wild-type ShhN. The properties of the E176A mutant were indistinguishable from those of wild-type ShhN in all biophysical and functional assays, indicating that this residue does not contribute significantly to stabilization of the zinc-binding site and that ShhN does not require hydrolase activity for in vitro biological function.

Alkaline Phosphatase↗

Activity of pradimicin BMS-181184 against Aspergillus spp.

The pradimicins are a new class of antifungal agents with activity against the majority of human fungal pathogens. In this study, the in vitro activity of pradimicin BMS-181184 was investigated against a range of the most common species of Aspergillus. The results were compared with itraconazole and amphotericin B. BMS-181184 was found to be active against most Aspergillus spp., but at higher concentrations than itraconazole and amphotericin B.

Amphotericin B↗

Periodontal attachment loss in HIV-infected patients is associated with the major histocompatibility complex 8.1 haplotype (HLA-A1,B8,DR3).

Periodontal attachment loss is mediated by overproduction of tumour necrosis factor (TNF) and interleukin (IL)-1, and appears to have a genetic component. The 8.1 major histocompatibility complex (MHC) ancestral haplotype (HLA-A1,B8,TNFA-308(2),DR3) is associated with elevated TNF production and predisposes carriers to several autoimmune/immunopathological disorders, including rapid progression of HIV disease, but not early onset periodontal disease in healthy individuals. Rather a high proportion of subjects with severe periodontal disease carry allele 2 at IL-1A-889 and IL-1B+3953. We predicted that genetic associations may be different or clearer in HIV patients, as they often show elevated production of TNF and IL-1 and periodontal attachment loss. Hence periodontal parameters and IL-1 polymorphisms were assessed in HIV-positive subjects expressing HLA-B8 with or without other markers of the 8.1 haplotype. Of 16 HLA-B8 subjects, 13 demonstrated elevated probing pocket depth and clinical attachment loss. The difference was statistically significant and did not correlate with smoking, age, CD4 T-cell counts, HIV viral load or levels of dental plaque. As TNFA-308 (allele 2) was present in four non-B8 subjects who had minimal attachment loss, it may not mediate the effect of the 8.1 haplotype. Moreover, polymorphisms at IL-1A-889 and IL-1B+3953 did not significantly affect periodontal parameters. Thus a central MHC gene characteristic of the 8.1 haplotype was the clearest determinant of periodontal attachment loss in HIV-infected individuals.

Adult↗

Comparison of in vitro activity of liposomal nystatin against Aspergillus species with those of nystatin, amphotericin B (AB) deoxycholate, AB colloidal dispersion, liposomal AB, AB lipid complex, and itraconazole.

We compared the in vitro activity of liposomal nystatin (Nyotran) with those of other antifungal agents against 60 Aspergillus isolates. Twelve isolates were itraconazole resistant. For all isolates, geometric mean (GM) MICs (micrograms per milliliter) were 2.30 for liposomal nystatin, 0.58 for itraconazole, 0.86 for amphotericin B (AB) deoxycholate, 9.51 for nystatin, 2.07 for liposomal AB, 2.57 for AB lipid complex, and 0.86 for AB colloidal dispersion. Aspergillus terreus (GM, 8.72 micrograms/ml; range, 8 to 16 micrograms/ml) was significantly less susceptible to all of the polyene drugs than all other species (P = 0.0001).

Amphotericin B↗

In-vitro activity of voriconazole against Aspergillus spp. and comparison with itraconazole and amphotericin B.

The in-vitro activity of the triazole antifungal agent voriconazole was compared with itraconazole and amphotericin B against 60 aspergillus isolates. Susceptibility tests were performed using two methods: a macrodilution and a microdulution method. For macrodilution methodology, geometric mean (GM) MIC values and ranges were 0.4 and 0.125-4 mg/L for voriconazole, 0.24 and 0.06-->16 mg/L for itraconazole, and 1.04 and 0.5-4 mg/L for amphotericin B. For the microdilution method, GM MICs and ranges were 0.66 and 0.125-2 mg/L for voriconazole, 0.27 and 0.06-->16 mg/L for itraconazole, and 1.62 and 0.25-32 mg/L for amphotericin B. In conclusion, voriconazole is active against Aspergillus spp. in vitro, and at similar concentrations to itraconazole.

Amphotericin B↗

In vitro activity of the echinocandin antifungal agent LY303,366 in comparison with itraconazole and amphotericin B against Aspergillus spp.

LY303,366 (LY) is a novel derivative of the echinocandin class of antifungal agents. The in vitro activities of LY, itraconazole (ITZ), and amphotericin B (AMB) were assessed against 60 Aspergillus isolates, including 35 isolates of A. fumigatus, eight isolates of A. terreus, eight isolates of A. flavus, eight isolates of A. niger and one isolate of A. nidulans. Four A. fumigatus isolates were resistant to ITZ. Susceptibility testing for all drugs was performed with a broth microdilution procedure. LY was tested in two media: antibiotic medium 3 (AM3) and Casitone with 2% glucose (CAS) with an inoculum of 2 x 10(3) spores/ml. ITZ and AMB were tested in RPMI 1640 with 2% glucose with an inoculum of 1 x 10(6) spores/ml. All tests were incubated at 37 degrees C for 48 h. A novel end point was used to determine a minimal effective concentration (MEC) for LY, i. e., almost complete inhibition of growth save a few tiny spherical colonies attached to the microplate. MICs were measured for ITZ and AMB with a no-growth end point. Ranges and geometric mean (GM) MECs were from 0.0018 to >0.5 and 0.0039 mg/liter and from 0.0018 to >0.5 and 0.008 mg/liter for LY in AM3 and LY in CAS, respectively. Differences between species were apparent, with A. flavus being significantly less susceptible to LY than any other species tested with both media (P </= 0.05). Ranges and GM MICs were from 0.125 to >16 and 0.7 mg/liter for ITZ and from 0.25 to 16 and 1.78 mg/liter for AMB. Minimal fungicidal concentrations (MFCs) were also determined for all drugs. GM MFCs were 0.018, 0.09, 19.76, and 12.64 mg/liter for LY in AM3, LY in CAS, ITZ, and AMB, respectively. LY in AM3 and LY in CAS were fungicidal for 86.7 and 68% of isolates, respectively (98% killing). In comparison, ITZ and AMB were fungicidal for 35 and 70% of isolates, respectively (99.99% killing). A reproducibility study was performed on 20% of the isolates. For 12 isolates retested, the MEC or MIC was the same or was within 1 dilution of the original value for 11, 11, 10, and 9 isolates for LY in AM3, LY in CAS, ITZ, and AMB, respectively. In conclusion, LY seems to be a promising antifungal agent with excellent in vitro activity against Aspergillus spp.

Amphotericin B↗

Amphotericin B resistance testing of Candida spp.: a comparison of methods.

Several methods of susceptibility testing were compared for their ability to detect amphotericin B resistance among yeast isolates, including isolates known to be amphotericin-B-resistant in an animal model. A microtitre MIC method using antibiotic medium no. 3 and Etest strips were able to discriminate susceptible and resistant isolates. A disc susceptibility test was also able to identify resistant isolates and this method may be suitable for routine use as a screening test. A survey of resistance in 644 clinical isolates showed that the incidence of elevated MICs (> or = 0.25 mg/L) was only 1.2%.

Amphotericin B↗

Speaker normalization in the perception of Mandarin Chinese tones.

This study investigated speaker normalization in perception of Mandarin tone 2 (midrising) and tone 3 (low-falling-rising) by examining listeners' use of F0 range as a cue to speaker identity. Two speakers were selected such that tone 2 of the low-pitched speaker and tone 3 of the high-pitched speaker occurred at equivalent F0 heights. Production and perception experiments determined that turning point (or inflection point of the tone), and delta F0 (the difference in FO between onset and turning point) distinguished the two tones. Three tone continua varying in either turning point, delta FO, or both acoustic dimensions, were then appended to a natural precursor phrase from each of the two speakers. Results showed identification shifts such that identical stimuli were identified as low tones for the high precursor condition, but as high tones for the low precursor condition. Stimuli varying in turning point showed no significant shift, suggesting that listeners normalize only when the precursor varies in the same dimension as the stimuli. The magnitude of the shift was greater for stimuli varying only in delta FO, as compared to stimuli varying in both turning point and delta FO, indicating that normalization effects are reduced for stimuli more closely matching natural speech.

Adult↗

In vitro activity of SCH-56592 and comparison with activities of amphotericin B and itraconazole against Aspergillus spp.

In this study, we investigated the in vitro activity of SCH-56592 (SCH), a new triazole antifungal agent. We compared the activity of SCH with those of itraconazole (ITZ) and amphotericin B (AB) against 60 clinical isolates of Aspergillus spp. by using a microtiter format. Incubation was done at 37 degrees C for 48 h, and MIC endpoints (no growth) were read visually. The medium used for all of the drugs was RPMI 1640 buffered with morpholinepropanesulfonic acid (MOPS) and supplemented with 2% glucose. MICs and minimum fungicidal concentrations (MFCs; killing of > or = 99.99%) were measured for all isolates. The geometric mean (GM) MICs and ranges (in micrograms per milliliter) were as follows: SCH, 0.09 and < or = 0.01 to 1; ITZ, 0.25 and 0.06 to 32; AB, 1.46 and 0.25 to 32. Aspergillus terreus (n = 7) was markedly more susceptible to SCH (GM, 0.05 microg/ml) and ITZ (GM, 0.07 microg/ml) than to AB (GM, 8.8 microg/ml). For all isolates, the GM MFCs and ranges (in micrograms per milliliter) were as follows: SCH, 3.64 and 0.125 to 16; ITZ, 15.09 and 0.125 to 32; AB, 10.3 and 1 to 32. In the drug concentration range tested, 71, 32, and 64% of the isolates against which SCH, ITZ, and AB, respectively, were tested were killed. A reproducibility study was performed with 20% of the isolates; for 11 of the 12 isolates retested, the MIC was the same or within 1 well of the original MIC of each drug. Therefore, in vitro mould testing of SCH is feasible and reproducible. SCH was found to be very active against all species of Aspergillus and at lower concentrations than either ITZ or AB.

Amphotericin B↗