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Biomedical subjects

L A Miller

Publications and source records attributed to L A Miller.

At least 19 recordsLinked to original sources
PubMed2001

Allergic asthma induced in rhesus monkeys by house dust mite (Dermatophagoides farinae).

To establish whether allergic asthma could be induced experimentally in a nonhuman primate using a common human allergen, three female rhesus monkeys (Macaca mulatta) were sensitized with house dust mite (Dermatophagoides farinae) allergen (HDMA) by subcutaneous injection, followed by four intranasal sensitizations, and exposure to allergen aerosol 3 hours per day, 3 days per week for up to 13 weeks. Before aerosol challenge, all three monkeys skin-tested positive for HDMA. During aerosol challenge with HDMA, sensitized monkeys exhibited cough and rapid shallow breathing and increased airway resistance, which was reversed by albuterol aerosol treatment. Compared to nonsensitized monkeys, there was a fourfold reduction in the dose of histamine aerosol necessary to produce a 150% increase in airway resistance in sensitized monkeys. After aerosol challenge, serum levels of histamine were elevated in sensitized monkeys. Sensitized monkeys exhibited increased levels of HDMA-specific IgE in serum, numbers of eosinophils and exfoliated cells within lavage, and elevated CD25 expression on circulating CD4(+) lymphocytes. Intrapulmonary bronchi of sensitized monkeys had focal mucus cell hyperplasia, interstitial infiltrates of eosinophils, and thickening of the basement membrane zone. We conclude that a model of allergic asthma can be induced in rhesus monkeys using a protocol consisting of subcutaneous injection, intranasal instillation, and aerosol challenge with HDMA.

Animals↗
PubMed2001

Expression of the beta6 integrin subunit is associated with sites of neutrophil influx in lung epithelium.

Inhalation of ozone by Rhesus monkeys results in epithelial injury and granulocyte influx in both conducting airways and respiratory bronchioles. We have reported that ozone-induced neutrophil recruitment and subsequent epithelial repair can be inhibited in vivo with a CD18 antibody. The antibody-mediated effect is abrogated by local instillation of C5a (a CD18-independent neutrophil chemoattractant), thereby demonstrating a role for neutrophils in lung epithelial repair processes. As an extension of this study, we examined the effect of ozone and neutrophil influx on epithelial expression of the beta6 integrin, an adhesion molecule associated with proliferation and repair. Expression of beta6 integrin was determined by immunohistochemistry for ozone-exposed monkeys treated with either control immunoglobulins or a CD18 antibody. The tracheal epithelium of ozone-exposed monkeys treated with control immunglobulins expressed the beta6 integrin. In contrast, the tracheal epithelium of ozone-exposed monkeys treated with CD18 antibody exhibited very low to undetectable expression of beta6 integrin. In association with C5a instillation and neutrophil influx, beta6 integrin was also observed in respiratory bronchiolar epithelium from both control and ozone-exposed animals. These findings cumulatively suggest that lung epithelial cell expression of beta6 integrin is associated with sites of neutrophil recruitment.

Administration, Inhalation↗
PubMed2001

Detection of prey in a cluttered environment by the northern bat Eptesicus nilssonii.

We studied the acoustic behaviour of bats (Eptesicus nilssonii) hunting for large (wing span 5 cm) non-hearing hepialid moths (Hepialus humuli). Groups of silvery-white male H. humuli perform a short (30 min) hovering display flight over grassland at dusk. They typically hover at, or below, the tops of grass panicles and are therefore situated in a highly acoustically cluttered habitat. Occasionally, they move to a new position by making short (1-5 s) flights at higher levels. E. nilssonii is not a clutter specialist, and yet we found that they attacked H. humuli within the 'clutter overlap zone'. The bats did not change their signal design in any marked manner for this specific task. Measurements of echoes from a moth 10 cm above or below the grass tops showed that information for detecting the moths was available to the bats. Nevertheless, the bats did not attack moths in stationary hovering display flight, only when they moved above the grass panicles. The duration of the up/down flights (movements) were almost always longer than an entire capture sequence by the bats. Apparently, the bats rely on the movement of the moth in space, monitored over successive echoes, to discriminate moth echoes from overlapping clutter echoes.

Animals↗
PubMed2000

Immunocontraception of white-tailed deer using native and recombinant zona pellucida vaccines.

We conducted a 2-year feasibility study with native porcine zona pellucida (PZP) vaccine and three recombinant rabbit zona pellucida vaccines (RC55, RC75a and a combination of RC55, RC75a and RC75b) as an initial phase of developing a recombinant immunocontraceptive vaccine to control reproduction in overpopulated herds of white-tailed deer (Odocoileus virginianus). Forty captive white-tailed does were divided into five groups (one sham and four treated), of eight each and injected with a 500microg prime dose of vaccine. Each prime dose was followed by a 300microg booster dose at 3-7 weeks post prime. The frequency and number of months of observed breeding were higher in PZP immunized does than in sham controls. Although the antibody titers of the three recombinant groups were 1000 or less, as compared with the PZP group with titers often over 128,000, the fawning rates of the two recombinants were significantly lower than that of the control group. The combined antigen group did not have a significantly lower fawning rate.

Animals↗
PubMed2000

Region-specific decline in the expression of metabotropic glutamate receptor 7 mRNA in rat brain during aging.

Age-dependent changes in the expression of group III metabotropic glutamate receptors (mGluR4 and mGluR7) were studied by quantitative in situ hybridization using male Fisher 344 rats 3, 12 and 25 months of age. Results indicate an early decrease in mGluR7 mRNA level in several cortical areas including the frontal, parietal and temporal cortices. In the hippocampus, mGluR7 mRNA levels decreased in the CA1 region and the lower blade of the dentate gyrus. Moreover, significant decrease was found in the laterodorsal thalamic nucleus at 12 months of age. Other regions such as the caudate putamen and nucleus accumbens showed no age-related changes in mGluR7 mRNA levels. Analysis of emulsion autoradiograms revealed a 36% decrease of mGluR7 mRNA in Purkinje neurons in the 12-month-old group and a 48% decline in the 25-month-old group as compared to the 3-month-old group. A substantial decrease in mGluR4 mRNA level was found in the granule cell layer of the cerebellum during aging. The difference between the young and aged groups exceeded 35%. These region-specific decreases may have important implication in some of the age-related changes in cognitive, motor and/or sensory functions.

Aging↗
PubMed2000

Comparison of cation-adjusted Mueller-Hinton broth with Iso-Sensitest broth for the NCCLS broth microdilution method.

Comparison of MIC results obtained in different parts of the world is currently difficult because of variations in methods. In this study, cation-adjusted Mueller-Hinton broth, the NCCLS-recommended medium, was compared with Iso-Sensitest broth, which is widely used in Europe. Microbroth dilution testing, using the NCCLS procedure, was performed on 124 Gram-positive (staphylococci and enterococci) and Gram-negative (Enterobacteriaceae and Pseudomonas aeruginosa) isolates from the CDC reference set, with the only variable being the medium used. Twelve antimicrobial agents were tested: amoxycillin-clavulanic acid, ampicillin, ciprofloxacin, erythromycin, gentamicin, imipenem, levofloxacin, oxacillin, gemifloxacin, trimethoprim- sulphamethoxazole, tetracycline and vancomycin. Vancomycin, erythromycin and oxacillin were only evaluated for the Gram-positive organisms. Trimethoprim-sulphamethoxazole was only evaluated for a subset of Gram-negative organisms because of off-scale results. The 124 isolates were tested in one American and one UK laboratory with two batches of cation-adjusted Mueller-Hinton broth and two of Iso-Sensitest broth. A statistical evaluation of the data used a 24 fully specified factorial analysis to determine if there were significant differences in results owing to Gram reaction, site of testing and type and/or batch of broth. In addition, the cumulative results for each antimicrobial agent in each broth were plotted against the range of MIC dilutions tested. MICs of ciprofloxacin, levofloxacin, gemifloxacin, gentamicin and tetracycline were slightly higher (half a doubling dilution) with Iso-Sensitest broth than with Mueller-Hinton broth. MIC results for the other antimicrobial agents were equivalent. Essential and category agreement rates were comparable for all agents (88.4-100% and 88.2-99.0%, respectively).

Anti-Bacterial Agents↗
PubMed2000

Immunocontraception of white-tailed deer with GnRH vaccine.

PROBLEM: Reduction of excess numbers of white-tailed deer (Odocoileus virginianus) is an example of a potential use for immunocontraception as a means of wildlife population management. METHOD OF STUDY: A 4 year multifaceted study was conducted to determine the long term effects of gonadotropin releasing hormone (GnRH) contraceptive vaccine on the fertility and behavior of female and male white-tailed deer. Deer were monitored for breeding behavior, hormone levels, pregnancy, fawning and GnRH specific antibody levels. RESULTS: Treatment lead to reduced fawning rates, altered estrus behavior, reduced concentrations of progesterone, contraception and failure to maintain pregnancy following conception. GnRH immunized does bred to untreated bucks had an 88% reduction in fawning caused by either immunocontraception or immunocontragestion. The vaccine effect is reversible, directly related to the antibody titer. Infertility lasted up to two years without boosting. GnRH immunized bucks demonstrated no interest in sexual activity when paired with control females. Depending on the immunization schedule, antlers either dropped early or remained in velvet. CONCLUSIONS: The results of this study demonstrate that GnRH vaccine is effective in inducing a reversible infertility in white-tailed deer, the infertility lasting up to two years without boosting.

Animals↗
PubMed2000

Sperm whale clicks: directionality and source level revisited.

In sperm whales (Physeter catodon L. 1758) the nose is vastly hypertrophied, accounting for about one-third of the length or weight of an adult male. Norris and Harvey [in Animal Orientation and Navigation, NASA SP-262 (1972), pp. 397-417] ascribed a sound-generating function to this organ complex. A sound generator weighing upward of 10 tons and with a cross-section of 1 m is expected to generate high-intensity, directional sounds. This prediction from the Norris and Harvey theory is not supported by published data for sperm whale clicks (source levels of 180 dB re 1 microPa and little, if any, directionality). Either the theory is not borne out or the data is not representative for the capabilities of the sound-generating mechanism. To increase the amount of relevant data, a five-hydrophone array, suspended from three platforms separated by 1 km and linked by radio, was deployed at the slope of the continental shelf off Andenes, Norway, in the summers of 1997 and 1998. With this system, source levels up to 223 dB re 1 microPa peRMS were recorded. Also, source level differences of 35 dB for the same click at different directions were seen, which are interpreted as evidence for high directionality. This implicates sonar as a possible function of the clicks. Thus, previously published properties of sperm whale clicks underestimate the capabilities of the sound generator and therefore cannot falsify the Norris and Harvey theory.

Animal Communication↗
PubMed2000

A comparative In vitro surveillance study of gemifloxacin activities against 2,632 recent Streptococcus pneumoniae isolates from across Europe, North America, and South America. The Gemifloxacin Surveillance Study Research Group.

From 1997 to 1999, 94 study centers in 15 European, 3 North American, and 2 South American countries contributed 2,632 isolates of Streptococcus pneumoniae to an international antimicrobial susceptibility testing study. Only 62.0% of isolates were susceptible to penicillin, while 22.3% were penicillin intermediate and 15.6% were penicillin resistant. Resistance to trimethoprim-sulfamethoxazole (24.4%), azithromycin (26.0%), and clarithromycin (27.1%) was also highly prevalent. For the penicillin-resistant isolates (n = 411), the MICs at which 90% of isolates are inhibited (MIC(90)s) for gemifloxacin, levofloxacin, ofloxacin, clarithromycin, and azithromycin were 0.03, 1, 2, >16, and >64 microgram/ml, respectively. Similarly, for isolates resistant to both azithromycin and clarithromycin (n = 649), gemifloxacin, levofloxacin, ofloxacin, and penicillin MIC(90)s were 0.03, 1, 2, and 4 microgram/ml, respectively. Overall rates of resistance to trovafloxacin (0.3%), levofloxacin (0.3%), grepafloxacin (0.6%), and ofloxacin (0.7%) were low. For ofloxacin-intermediate and -resistant isolates (n = 142), gemifloxacin had the lowest MIC(90) (0.12 microgram/ml) compared to the MIC(90)s of trovafloxacin (0.5 microgram/ml), grepafloxacin (1 microgram/ml), and levofloxacin (2 microgram/ml). For all S. pneumoniae isolates tested, gemifloxacin MICs were </=0.5 microgram/ml, suggesting that gemifloxacin has the potential to be used as a treatment for pneumococcal infections, including those arising from isolates resistant to beta-lactams and macrolides.

Adolescent↗
PubMed2000

Trafficking of neutrophils across airway epithelium is dependent upon both thioredoxin- and pertussis toxin-sensitive signaling mechanisms.

Leukocyte recruitment from the circulation into the airways is a multi-step process, involving both chemotactic and adhesive mechanisms. Using an in vitro model of leukocyte transepithelial trafficking, we show that movement of human peripheral blood neutrophils (PMN) across airway epithelium in the optimal basolateral-to-apical surface direction is partially blocked by pertussis toxin, an inhibitor of G(alphai)-protein-linked receptors. A neutralizing monoclonal antibody against interleukin-8 (IL-8; constitutively expressed by airway epithelium) did not inhibit PMN transepithelial migration, suggesting that alternative pertussis toxin-sensitive signaling mechanisms are involved in this process. However, a neutralizing antibody against thioredoxin, a redox enzyme with pertussis toxin-insensitive chemoattractant activity, did reduce PMN migration across airway epithelium. We conclude that trafficking of PMN across airway epithelium is mediated by both thioredoxin- and pertussis toxin-sensitive signaling mechanisms that are independent of IL-8.

Cell Movement↗
PubMed1999

Long-term effects of PZP immunization on reproduction in white-tailed deer.

A 6-year study was conducted to determine the long-term effects of porcine zona pellucida (PZP) vaccine on the immune and hormonal responses, and reproduction of the white-tailed deer. The first 2 years of active immunization resulted in an 89% reduction in fawning. Vaccination with PZP produced reversible infertility lasting 1-4 years. Infertility was directly related to immune titers to PZP. Doe fertility was restored when the antibody titer dropped to minimal levels, but following re-immunization, infertility was reestablished. Reduction in fawning throughout the 6-year study was 76%. It was also observed that immune responses among deer were variable, especially in the first year of treatment. Variability was also observed among deer for the duration of infertility following the initial vaccination.

Animals↗
PubMed1999

The engagement of beta1 integrins on promonocytic cells promotes phosphorylation of Syk and formation of a protein complex containing Lyn and beta1 integrin.

The protein-tyrosine kinase Syk participates in signal transduction pathways downstream from multiple immune recognition receptors. Recent evidence indicates that Syk is also functionally coupled to cell surface integrins, which mediate interactions between the actin cytoskeleton and extracellular matrix proteins. The interactions of undifferentiated, promonocytic HL60 or U937 cells with fibronectin or anti-beta1 integrin antibodies leads to an apparent activation and tyrosine phosphorylation of Syk that is independent of tight cellular adhesion and spreading. In response to fibronectin or anti-beta1 integrin antibodies, beta1 integrins become associated with a complex of proteins that include the Lyn protein tyrosine kinase and endogenous kinase substrates of 29 and 75-80 kDa. Lyn becomes transiently activated following integrin engagement and co-localizes with the actin cytoskeleton. These studies suggest a major role for Lyn in coupling beta1 integrins to the activation of Syk.

Actins↗
PubMed1999

Inhibition of transforming growth factor beta production by nitric oxide-treated chondrocytes: implications for matrix synthesis.

OBJECTIVE: Nitric oxide (NO) is generated copiously by articular chondrocytes activated by interleukin-1beta (IL-1beta). If NO production is blocked, much of the IL-1beta inhibition of proteoglycan synthesis is prevented. We tested the hypothesis that this inhibitory effect of NO on proteoglycan synthesis is secondary to changes in chondrocyte transforming growth factor beta (TGFbeta). METHODS: Monolayer, primary cultures of lapine articular chondrocytes and cartilage slices were studied. NO production was determined as nitrite accumulation in the medium. TGFbeta bioactivity in chondrocyte- and cartilage-conditioned medium (CM) was measured with the mink lung epithelial cell bioassay. Proteoglycan synthesis was measured as the incorporation of 35S-sodium sulfate into macromolecules separated from unincorporated label by gel filtration on PD-10 columns. RESULTS: IL-1beta increased active TGFbeta in chondrocyte CM by 12 hours; by 24 hours, significant increases in both active and latent TGFbeta were detectable. NG-monomethyl-L-arginine (L-NMA) potentiated the increase in total TGFbeta without affecting the early TGFbeta activation. IL-1beta stimulated a NO-independent, transient increase in TGFbeta3 at 24 hours; however, TGFbeta1 was not changed. When NO synthesis was inhibited with L-NMA, IL-1beta increased CM concentrations of TGFbeta1 from 24-72 hours of culture. L-arginine (10 mM) reversed the inhibitory effect of L-NMA on NO production and blocked the increases in TGFbeta1. Anti-TGFbeta1 antibody prevented the restoration of proteoglycan synthesis by chondrocytes exposed to IL-1beta + L-NMA, confirming that NO inhibition of TGFbeta1 in IL-1beta-treated chondrocytes effected, in part, the decreased proteoglycan synthesis. Furthermore, the increase in TGFbeta and proteoglycan synthesis seen with L-NMA was reversed by the NO donor S-nitroso-N-acetylpenicillamide. Similar results were seen with cartilage slices in organ culture. The autocrine increase in CM TGFbeta1 levels following prior exposure to TGFbeta1 was also blocked by NO. CONCLUSION: NO can modulate proteoglycan synthesis indirectly by decreasing the production of TGFbeta1 by chondrocytes exposed to IL-1beta. It prevents autocrine-stimulated increases in TGFbeta1, thus potentially diminishing the anabolic effects of this cytokine in chondrocytes.

Animals↗
PubMed1999

A comparison of 18-MV and 6-MV treatment plans using 3D dose calculation with and without heterogeneity correction.

Homogeneity of the dose distribution in irradiation of the intact breast for stage I and II cancers is an important factor, particularly for larger breasts. In the present work, we have studied dose homogeneity for 6- and 18-MV treatment plans in 10 patients, typically with larger breasts. For each patient, 6 3-dimensional (3D) dose distributions were calculated using patient computed tomography data and the ADAC Pinnacle3 treatment planning system. First, a dose distribution was calculated, assuming the patient was water, with the 6-MV beam parameters used to treat the patient. Second, the calculation was repeated using the actual patient anatomy. Comparison of these 2 distributions showed how patient heterogeneity affected dose. Third, individual beam weights were optimized, and the dose calculation was repeated. Each of these 3 dose calculations was repeated at 18 MV. Results showed that: (1) at 6 MV, the ratio of mean dose in the target volume calculated with heterogeneity considerations to that without was 1.014 +/- 0.006, and the ratio of the standard deviation of dose in the target volume was 0.919 +/- 0.042; (2) at 18 MV, the ratio of mean dose to the target volume calculated with heterogeneity considerations to that without was 1.001 +/- 0.005, and the ratio of the standard deviation of dose in the target volume was 1.15 +/- 0.09; and (3) the dose homogeneity, measured by the standard deviation of the dose distribution in the target volume, was 25% less for the 18-MV treatment plan for patients with breast volumes greater than 1600 cm3. We conclude that: (1) 3D, heterogeneity-corrected dose calculation is necessary to fairly evaluate any advantage of 18 MV over 6 MV; (2) excluding the dose buildup region, 18 MV produces a significantly more homogeneous dose distribution for breast volumes greater than 1600 cm3; and (3) when prescribing dose using heterogeneity-corrected dose distributions, dose prescriptions should be increased by 1.5% at 6 MV, but no increase is needed for 18 MV.

Breast↗
PubMed1999

Differences between the activity of penicillin, amoxycillin, and co-amoxyclav against 5,252 Streptococcus pneumoniae isolates tested in the Alexander Project 1992-1996.

A number of published studies have shown that the MICs of amoxycillin and/or co-amoxyclav are lower than those of ampicillin and/or penicillin for Streptococcus pneumoniae. Other published studies have concluded that the activities of amoxycillin and co-amoxyclav are comparable with that of penicillin for S. pneumoniae. A collection of 5252 S. pneumoniae isolates obtained during a 5 year period (1992-1996) was analysed to determine differences between the MICs of penicillin, amoxycillin and co-amoxyclav. Among the isolates analysed, 3788 (72%) were penicillin-susceptible, 615 (12%) were penicillin-intermediate and 849 (16%) were penicillin-resistant. Differences between the agents were assessed by examination of MIC distribution functions and simultaneous 95% CIs. In addition, penicillin-intermediate and -resistant isolates were analysed to determine the number and percentage of isolates which had an amoxycillin and co-amoxyclav MIC less than, equal to, or greater than the penicillin MIC. Results showed that the amoxycillin and co-amoxyclav MIC90s were one two-fold dilution lower than those of penicillin for all isolates collected between 1992-1993 and 1994-1996. Simultaneous 95% CIs showed that the mean differences between MICs of amoxycillin and penicillin, and between MICs of co-amoxyclav and penicillin, were less than zero. The majority of the penicillin-intermediate and penicillin-resistant isolates had an amoxycillin and co-amoxyclav MIC less than the penicillin MIC. In conclusion, amoxycillin and co-amoxyclav MICs were shown to be lower than the penicillin MICs for the S. pneumoniae isolates analysed in this study.

Amoxicillin↗
PubMed1999

Oral vaccination of white-tailed deer using a recombinant Bacillus Calmette-Guérin vaccine expressing the Borrelia burgdorferi outer surface protein A: prospects for immunocontraception.

PROBLEM: Reduction of excess numbers of white-tailed deer (Odocoileus virginianus) is a prime example of a potential use for immunocontraception as a means of wildlife population management. Oral vaccination appears to be the most pragmatic way to deliver immunocontraceptive vaccines to free-roaming populations of deer, but there was little, if any, prior evidence that oral vaccination is a viable concept in deer. METHOD OF STUDY: We used live Bacillus Calmette-Guérin (BCG) in a recombinant form (rBCG), which expressed Borrelia burgdorferi outer surface protein A, to test whether deer vaccinated orally with a specific antigen expressed in a live vector produce detectable antibody titers. RESULTS: The data indicate that oral vaccination of deer with an expressed antigen is feasible, as demonstrated by peak antibody titers to the expressed antigen. Also, peak titers measured by enzyme-linked immunosorbent assay were highest in orally vaccinated deer: 1600 in deer vaccinated by injection and 6400 in those vaccinated orally. CONCLUSIONS: The results of this study demonstrate that it is feasible to vaccinate deer orally with a live vector.

Administration, Oral↗