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Biomedical subjects

W L Davis

Publications and source records attributed to W L Davis.

At least 19 recordsLinked to original sources
PubMed2005

Imidacloprid/moxidectin topical solution for the prevention of heartworm disease and the treatment and control of flea and intestinal nematodes of cats.

Sixteen controlled laboratory studies, involving 420 kittens and cats, were conducted to evaluate the efficacy and safety of topically applied formulations of imidacloprid and moxidectin for the prevention of feline heartworm disease, treatment of flea infestations and treatment and control of intestinal nematodes. Unit-dose applicators and the dosing schedule used in these studies were designed to provide a minimum of 10mg imidacloprid and 1mg moxidectin/kg. Treatments were applied topically by parting the hair at the base of the skull and applying the solution on the skin. Imidacloprid treatment alone did not display activity against Dirofilaria immitis or intestinal nematodes and moxidectin treatment alone provided little or no activity against adult Ctenocephalides felis infestations. The formulation containing 10% imidacloprid and 1% moxidectin was 100% efficacious against the development of adult D. immitis infections when cats were treated 30 days after inoculation with third-stage larvae. A single treatment with this formulation also provided 88.4-100% control of adult C. felis for 35 days. Imidacloprid/moxidectin was 100% efficacious against adult Toxocara cati and 91.0-98.3% efficacious against immature adults and fourth-stage T. cati larvae. The formulation provided 98.8-100% efficacy against adult Ancylostoma and immature adults and third-stage A. tubaeforme larvae. Monthly topical application with 10% imidacloprid/1% moxidectin is convenient, efficacious and safe for the prevention of feline heartworm disease, treatment of flea infestation and for the treatment and control of intestinal nematode infections of cats.

Administration, Topical↗
PubMed2005

Field evaluation of the efficacy and safety of emodepside/praziquantel spot-on solution against naturally acquired nematode and cestode infections in domestic cats.

Two controlled, blinded and randomized multi-site clinical field studies evaluated the efficacy and safety of emodepside/praziquantel spot-on in the treatment of gastrointestinal nematode and cestode infections in cats. In a study conducted in Europe, faecal egg count reductions of >98% for all nematode eggs and eggs of Toxocara cati, respectively, were observed in cats treated with emodepside/praziquantel spot-on (Profender, Bayer AG, Leverkusen, Germany). For a positive-control product containing selamectin (Stronghold) reductions of >95% were observed. A 100% reduction of faecal eggs and proglottids was observed in cats treated with emodepside/praziquantel spot-on that were infected with cestodes. In a study conducted in North America, cats were treated with either emodepside/praziquantel spot-on plus a placebo tablet or a combination of two control products containing, respectively, selamectin (Revolution) and epsiprantel (Cestex). Faecal egg count reduction for eggs of T. cati was >99% for both treatments. For faecal eggs and proglottids of Dipylidium caninum reductions of >99 and >97% were recorded for cats treated with emodepside/praziquantel spot-on and the control group, respectively. No adverse reactions were observed in the European study, and only mild ones of short duration in a few cats from both treatment groups of the North American study. The two studies demonstrated that emodepside/praziquantel spot-on is highly efficacious and safe under field conditions.

Administration, Topical↗
PubMed2005

Safety of imidacloprid plus moxidectin topical solution applied to cats heavily infected with adult heartworms (Dirofilaria immitis).

A topically applied formulation containing 10% imidacloprid+1% moxidectin (Advocate/Advantage multi) has been developed for monthly application to cats for the prevention of feline heartworm (HW) disease caused by Dirofilaria immitis; and for the treatment and control of flea infestations, ear mite infestations, and intestinal nematode infections. A study model was designed to evaluate the safety of this product in cats harboring adult D. immitis infections. Eighty adult cats (40 males/40 females) were each inoculated with 60 third-stage D. immitis larvae on test day (TD) 1. On TD 243-245 echocardiographic imaging was performed on each cat to confirm and estimate the number of adult D. immitis residing in the cardiovascular system. A total of 35 cats were subsequently eligible for safety evaluation based on inclusion criteria. Four treatment groups were established and randomly selected for treatment: imidacloprid+moxidectin solution at the label dose (n=9) (group 1), imidacloprid+moxidectin solution at 5x the Iabel dose (n=9) (group 2), 6% selamectin topical solution (Revolution) at the label dose (positive control, n=8) (group 3), and topical treatment with placebo (negative control, n=9) (group 4). All cats were treated on TD 250. Treatments for groups 1, 3, and 4 were repeated on TDs 278 and 306. Group 2 cats were euthanized and examined for adult D. immitis on TD 288. All other cats were euthanized and examined for adult D. immitis on TD 334. No adverse events attributable to treatment with the test articles were observed during the study. The geometric mean numbers of adult D. immitis recovered at necropsy from treatment groups 1-4 were 2.9, 3.2., 4.0, and 2.7, respectively. There were no statistically significant differences in the comparison of adult D. immitis recovered at necropsy (ANOVA overall group effect P-value of 0.5356). The results of this study demonstrate that imidacloprid+moxidectin topical solution can be used safely in cats heavily infected with adult D. immitis.

Animals↗
PubMed2001

Functional characterization of phosphorylation of 69-kDa human choline acetyltransferase at serine 440 by protein kinase C.

Choline acetyltransferase, the enzyme that synthesizes the transmitter acetylcholine in cholinergic neurons, is a substrate for protein kinase C. In the present study, we used mass spectrometry to identify serine 440 in recombinant human 69-kDa choline acetyltransferase as a protein kinase C phosphorylation site, and site-directed mutagenesis to determine that phosphorylation of this residue is involved in regulation of the enzyme's catalytic activity and binding to subcellular membranes. Incubation of HEK293 cells stably expressing wild-type 69-kDa choline acetyltransferase with the protein kinase C activator phorbol 12-myristate 13-acetate showed time- and dose-related increases in specific activity of the enzyme; in control and phorbol ester-treated cells, the enzyme was distributed predominantly in cytoplasm (about 88%) with the remainder (about 12%) bound to cellular membranes. Mutation of serine 440 to alanine resulted in localization of the enzyme entirely in cytoplasm, and this was unchanged by phorbol ester treatment. Furthermore, activation of mutant enzyme in phorbol ester-treated HEK293 cells was about 50% that observed for wild-type enzyme. Incubation of immunoaffinity purified wild-type and mutant choline acetyltransferase with protein kinase C under phosphorylating conditions led to incorporation of [(32)P]phosphate, with radiolabeling of mutant enzyme being about one-half that of wild-type, indicating that another residue is phosphorylated by protein kinase C. Acetylcholine synthesis in HEK293 cells expressing wild-type choline acetyltransferase, but not mutant enzyme, was increased by about 17% by phorbol ester treatment.

Acetylcholine↗
PubMed2001

Filling-in at the natural blind spot contributes to binocular rivalry.

The human natural blind spot is usually filled in based on the contextual information. When two sufficiently different images are presented to the two eyes, observers typically perceive an alternation between the two images (binocular rivalry). Both the filling-in process and binocular rivalry have been the subject of considerable research. This study investigates whether filled information in one eye's natural blind spot can contribute to binocular rivalry. A radial grating (D=12 degrees ) was presented to one eye, centered on the natural blind spot. Observers perceived a complete figure in monocular view; the blind spot area was filled-in based on the surrounding information. Simultaneously, a circular grating smaller than the blind spot (D=4 degrees ), was presented to the fellow eye in the region corresponding to the other eye's blind spot. The amount of rivalry as indexed by how often the smaller circular grating remained visible was measured. The results suggest that the filled information in the area of the blind spot does contribute to the rivalry process.

Humans↗
PubMed2000

Expression, purification and characterization of recombinant human choline acetyltransferase: phosphorylation of the enzyme regulates catalytic activity.

Choline acetyltransferase synthesizes acetylcholine in cholinergic neurons and, in humans, may be produced in 82- and 69-kDa forms. In this study, recombinant choline acetyltransferase from baculovirus and bacterial expression systems was used to identify protein isoforms by two-dimensional SDS/PAGE and as substrate for protein kinases. Whereas hexa-histidine-tagged 82- and 69-kDa enzymes did not resolve as individual isoforms on two-dimensional gels, separation of wild-type choline acetyltransferase expressed in insect cells revealed at least nine isoforms for the 69-kDa enzyme and at least six isoforms for the 82-kDa enzyme. Non-phosphorylated wild-type choline acetyltransferase expressed in Escherichia coli yielded six (69 kDa) and four isoforms (82 kDa) respectively. Immunofluorescent labelling of insect cells expressing enzyme showed differential subcellular localization with the 69-kDa enzyme localized adjacent to plasma membrane and the 82-kDa enzyme being cytoplasmic at 24 h. By 64 h, the 69-kDa form was in cytoplasm and the 82-kDa form was only present in nucleus. Studies in vitro showed that recombinant 69-kDa enzyme was a substrate for protein kinase C (PKC), casein kinase II (CK2) and alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaM kinase), but not for cAMP-dependent protein kinase (PKA); phosphorylation by PKC and CK2 enhanced enzyme activity. The 82-kDa enzyme was a substrate for PKC and CK2 but not for PKA or alpha-CaM kinase, with only PKC yielding increased enzyme activity. Dephosphorylation of both forms of enzyme by alkaline phosphatase decreased enzymic activity. These studies are of functional significance as they report for the first time that phosphorylation enhances choline acetyltransferase catalytic activity.

Animals↗
PubMed2000

The role of pH and osmolarity in evoking the acetic acid-induced wiping response in a model of nociception in frogs.

Acetic acid applied to the hindlimb of a frog evokes a vigorous wiping of the exposed skin. The aim of this study was to determine if acetic acid evokes this wiping response by decreasing subepidermal pH. Because acetic acid is hyperosmolar, a second aim was to determine if the osmolarity of acetic acid contributed to evoking the wiping response. In behavioral experiments, different acids or acetic acid/sodium acetate buffers at different pHs were used to evoke the wiping response. In separate experiments, subepidermal pH was measured in vitro while these same solutions were applied to samples of skin from frogs. The wiping response evoked by acetic acid was associated with a decrease in subepidermal pH to a level that has been shown to activate nociceptors. Interestingly, formic, oxalic, sulfuric, and hydrochloric acid evoked the wiping response without decreasing subepidermal pH. The osmolarity of acetic acid contributed to evoking the wiping response because buffers at subthreshold pHs evoked the wiping response. Also, the osmolarity required to evoke the wiping response depended upon the pH of the buffer. Thus, acetic acid and the buffers at pH 2.97 and 4.67 could evoke the wiping response by decreasing subepidermal pH. In contrast, formic, oxalic, sulfuric, and hydrochloric acid, as well as the buffers at pH 5.17 and 5.67, evoked the wiping response through another mechanism, perhaps by increasing subepidermal osmolarity. These studies demonstrate that both pH and osmolarity may contribute to nociception produced by algesic chemicals and may be important in inflammatory pain.

Acetic Acid↗
PubMed2000

The ultraviolet environment of Mars: biological implications past, present, and future.

A radiative transfer model is used to quantitatively investigate aspects of the martian ultraviolet radiation environment, past and present. Biological action spectra for DNA inactivation and chloroplast (photosystem) inhibition are used to estimate biologically effective irradiances for the martian surface under cloudless skies. Over time Mars has probably experienced an increasingly inhospitable photobiological environment, with present instantaneous DNA weighted irradiances 3.5-fold higher than they may have been on early Mars. This is in contrast to the surface of Earth, which experienced an ozone amelioration of the photobiological environment during the Proterozoic and now has DNA weighted irradiances almost three orders of magnitude lower than early Earth. Although the present-day martian UV flux is similar to that of early Earth and thus may not be a critical limitation to life in the evolutionary context, it is a constraint to an unadapted biota and will rapidly kill spacecraft-borne microbes not covered by a martian dust layer. Microbial strategies for protection against UV radiation are considered in the light of martian photobiological calculations, past and present. Data are also presented for the effects of hypothetical planetary atmospheric manipulations on the martian UV radiation environment with estimates of the biological consequences of such manipulations.

Atmosphere↗
PubMed1999

Remote sensing for organics on Mars.

The detection of organics on Mars remains an important scientific objective. Advances in instrumentation and laboratory techniques provide new insight into the lower level detection limit of complex organics in closely packed media. Preliminary results demonstrate that algae present in a palagonite medium do exhibit a spectral reflectance feature in the visible range for dry mass weight ratios of algae to palagonite greater than 6%--which corresponds to 30 mg algae in a 470 mg (just optically thick (< 3 mm) layer) palagonite matrix. This signature most probably represents chlorophyll a, a light harvesting pigment with an emission peak at 678 nm.

Chlorophyll↗
PubMed1999

Effect of ankle and knee position on tension in the Achilles tendon.

The purpose of this study was to evaluate the relative contributions of ankle and knee position to tension in the Achilles tendon and to determine whether there exists a position of plantarflexion at which the passive tensioning effect of knee extension is eliminated. Seven matched pairs of fresh-frozen cadaver lower extremities were tested. A buckle transducer was used to measure forces in the tendon throughout the full range of knee motion, with the hindfoot fixed. Positioning the hindfoot in 20 degrees to 25 degrees of plantarflexion effectively eliminates tension in the Achilles tendon, regardless of knee position. This information is directly applicable both to the nonoperative treatment of ruptures of the Achilles tendon employing a short leg cast and to surgical repairs, in which tension must be controlled precisely.

Achilles Tendon↗
PubMed1996

Origins of life: a comparison of theories and application to Mars.

The field of study that deals with the origins of life does not have a consensus for a theory of life's origin. An analysis of the range of theories offered shows that they share some common features that may be reliable predictors when considering the possible origins of life on another planet. The fundamental datum dealing with the origins of life is that life appeared early in the history of the Earth, probably before 3.5 Ga and possibly before 3.8 Ga. What might be called the standard theory (the Oparin-Haldane theory) posits the production of organic molecules on the early Earth followed by chemical reactions that produced increased organic complexity leading eventually to organic life capable of reproduction, mutation, and selection using organic material as nutrients. A distinct class of other theories (panspermia theories) suggests that life was carried to Earth from elsewhere--these theories receive some support from recent work on planetary impact processes. Other alternatives to the standard model suggest that life arose as an inorganic (clay) form and/or that the initial energy source was not organic material but chemical energy or sunlight. We find that the entire range of current theories suggests that liquid water is the quintessential environmental criterion for both the origin and sustenance of life. It is therefore of interest that during the time that life appeared on Earth we have evidence for liquid water present on the surface of Mars.

Earth, Planet↗
PubMed1995

The circum-Chryse region as a possible example of a hydrologic cycle on Mars: geologic observations and theoretical evaluation.

The transection and superposition relationships among channels, chaos, surface materials units, and other features in the circum-Chryse region of Mars were used to evaluate relative age relationships and evolution of flood events. Channels and chaos in contact (with one another) were treated as single discrete flood-carved systems. Some outflow channel systems form networks and are inferred to have been created by multiple flood events. Within some outflow channel networks, several separate individual channel systems can be traced to a specific chaos which acted as flood-source area to that specific flood channel. Individual flood-carved systems were related to widespread materials units or other surface features that served as stratigraphic horizons. Chryse outflow channels are inferred to have formed over most of the perceivable history of Mars. Outflow channels are inferred to become younger with increasing proximity to the Chryse basin. In addition, outflow channels closer to the basin show a greater diversity in age. The relationship of subsequent outflow channel sources to the sources of earlier floods is inferred to disfavor episodic flooding due to the progressive tapping of a juvenile near-surface water supply. Instead, we propose the circum-Chryse region as a candidate site of past hydrological recycling. The discharge rates necessary to carve the circum-Chryse outflow channels would have inevitably formed temporary standing bodies of H2O on the Martian surface where the flood-waters stagnated and pooled (the Chryse basin is topographically enclosed). These observations and inferences have led us to formulate and evaluate two hypotheses: (1) large amounts of the sublimated H2O off the Chryse basin flood lakes precipitated (snowed) onto the flood-source highlands and this H2O was incorporated into the near surface, recharging the H2O sources, making possible subsequent deluges; and (2) ponded flood-water in Chryse basin drained back down an anti basinward dipping subsurface layer accessed long the southern edge of the lake, recharging the flood-source aquifers. H2O not redeposited in the flood-source region was largely lost to the hydrologic cycle. This loss progressively lowered the vitality of the cycle, probably by now killing it. Our numerical evaluations indicate that of the two hypotheses we formulated, the groundwater seep cycle seems by far the more viable. Optimally, approximately 3/4 of the original mass of an ice-covered cylindrical lake (albedo 0.5, 1 km deep, 100-km radius, draining along its rim for one quarter of its circumference into substrata with a permeability of 3000 darcies) can be modeled to have moved underground (on timescales of the order of 10(3) years) before the competing mechanisms of sublimation and freeze down choked off further water removal. Once underground, this water can travel distances equal to the separation between Chryse basin and flood-source sites in geologically short (approximately 10(6) year-scale) times. Conversely, we calculate that optimally only approximately 40% of the H2O carried from Chryse can condense at the highlands, and most of the precipitate would either collect at the base of the highlands/lowlands scarp or sublimate at rates greater than it would accumulate over the flood-source sites. Further observations from forthcoming missions may permit the determination of which mechanisms may have operated to recycle the Chryse flood-waters.

Disasters↗
PubMed1995

The voxel sensitivity function in Fourier transform imaging: applications to magnetic resonance angiography.

In this paper the problem of small structure visualization in magnetic resonance imaging (MRI) is considered. The relationship between the structure and the image intensities is defined in terms of the voxel sensitivity function (VSF). Using the VSF, the spatial dependence of the voxel signal for small spheres and cylinders is computed. Although the spatial fluctuation is smaller in the MRI VSF than that which would be obtained from a uniformly sensitive cubical voxel, the deviation still results in significant signal loss near the edges and corners of the voxels. Finally, the VSF formalism is used to demonstrate the improvement in signal uniformity that can be obtained by using zero-filled (band-limited or sinc) interpolation.

Algorithms↗
PubMed1995

BSH distributions in the canine head and a human patient using 11B MRI.

A 3D projection reconstruction (3DPR) method was used to obtain in vivo 11B images in a large canine brain tumor model and in a human infused with borocaptate sodium (BSH). Studies were performed in dogs with and without gliosarcomas implanted and grown to a size of 2-3 cm. The 3DPR method demonstrates a signal-to-noise ratio (SNR) that allows qualitative kinetic studies of the boron compound in normal and tumor tissue of the head. The measurements indicate initial uptake of the BSH compound in tumor to be less than that in muscle with no uptake in normal brain tissue. Moreover, uptake of BSH in tissue was found to lag the boron concentration in blood with delays that depend on tissue type. In addition, the first human boron images were obtained on a patient who underwent surgical resection and volumetric debulking of a large (7 cm) glioblastoma multiforme. BSH was readily taken up in residual tumor tissue, while diffusion into the resection volume was slower.

Animals↗
PubMed1995

CT and MRI of the normal and diseased perivertebral space.

The perivertebral space is in the midline, in the deep tissues of the neck, and can be identified from the skull base above to the mediastinum below. It is a discrete space completely enclosed by the deep layer of deep cervical fascia. The fascial attachments of the perivertebral space divide it into two areas, the anterior prevertebral and posterior paraspinal portions. We made a retrospective analysis of the radiologic and clinical records of 52 patients with lesions in the perivertebral space, to identify the imaging features that mark a lesion as originating in the perivertebral space and define the spectrum of pathology which occurs in the space. Mass lesions present in the prevertebral or paraspinal portions. In the former they usually involve the vertebral body, displacing the prevertebral muscles anteriorly. Epidural extension from lesions in the perivertebral space proper is common. Masses in the paraspinal perivertebral space usually displace the paraspinal muscles away from the spine. We found 9 inflammatory lesions, 29 malignant and 6 benign tumors, and 8 miscellaneous lesions.

Adolescent↗
PubMed1994

A model for the evolution of CO2 on Mars.

We have constructed a model that predicts the evolution of CO2 on Mars from the end of the heavy bombardment period to the present. The model draws on published estimates of the main processes believed to affect the fate of CO2 during this period: chemical weathering, regolith uptake, polar cap formation, and atmospheric escape. Except for escape, the rate at which these processes act is controlled by surface temperatures which we calculate using a modified version of the Gierasch and Toon energy balance model (1973, J. Atmos. Sci. 30, 1502-1508). The modifications account for the change in solar luminosity with time, the greenhouse effect, and a polar and solar equatorial energy budget. Using published estimates for the main parameters, we find no evolutionary scenario in which CO2 is capable of producing a warm (global mean temperatures>250 K) and wet (surface pressures>30 mbar) early climate, and then evolves to present conditions with approximately 7 mbar in the atmosphere, <300 mbar in the regolith, and <5 mbar in the caps. Such scenarios would only exist if the early sun were brighter than standard solar models suggest, if greenhouse gases other than CO2 were present in the early atmosphere, or if the polar albedo were significantly lower than 0.75. However, these scenarios generally require the storage of large amounts of CO2 (>1 bar) in the carbonate reservoir. If the warm and wet early Mars constraint is relaxed, then we find best overall agreement with present day reservoirs for initial CO2 inventories of 0.5-1.0 bar. We also find that the polar caps can a profound effect on how the system evolves. If the initial amount of CO2 is less than some critical value, then there is not enough heating of the poles to prevent permanent caps from forming. Once formed, these caps control how the system evolves, because they set the surface pressure and, hence, the thermal environment. If the initial amount of CO2 is greater than this critical value, then caps do not form initially, but can form later on, when weathering and escape lower the surface pressure to a point at which polar heating is no longer sufficient to prevent cap formation and the collapse of the climate system. Our modeling suggests this critical initial amount of CO2 is between 1 and 2 bar, but its true value will depend on all factors affecting the polar heat budget.

Atmosphere↗
PubMed1994

Immunolocalization of ubiquitin in degenerating insect flight muscle.

Ubiquitin was localized by immunofluorescence microscopy during post-mating histolysis of fibrillar flight muscle in female fire ants, Solenopsis spp. Normal muscles, as well as histolysing muscles from artificially inseminated and haemolymph-injected females contained ubiquitin in association with nuclei, Z-lines, myofilaments and mitochondria. However, the density of the ubiquitin immunoreaction was markedly increased in the nuclei, Z-lines and mitochondria of degenerating tissues 6, 12 and 24 h posttreatment. At these times the heaviest immunoreactivity for ubiquitin was seen in association with the nuclei, Z-lines and mitochondria. Immuno-controls, incubated in the absence of the primary antibody, showed no similar immunostaining. When insemination was preceded by the injection of actinomycin D, muscle degradation was significantly depressed after a 24-h period. Also, ubiquitin immunofluorescence was markedly reduced in tissues pre-treated with actinomycin D. These observations suggest that insemination increases the ubiquitination of specific myofibrillar proteins destined for degradation.

Animals↗