PubMed Health⌕ Search

Biomedical subjects

B M Davis

Publications and source records attributed to B M Davis.

At least 19 recordsLinked to original sources
PubMed2006

Transient receptor potential vanilloid 1-immunopositive neurons in the mouse are more prevalent within colon afferents compared to skin and muscle afferents.

Previous studies in our laboratories found that isolectin B(4)(IB(4))-positive polymodal nociceptors in the mouse do not express transient receptor potential vanilloid 1 (TRPV1), nor does deletion of TRPV1 compromise the ability of these afferents to detect thermal stimuli. Considering that IB(4)-positive afferents account for over 70% of cutaneous nociceptors and that 30-50% of all mouse primary afferents express TRPV1, it is highly likely that many TRPV1-positive fibers project to non-cutaneous structures. To investigate this issue, Alexa Fluor-conjugated wheat germ agglutinin (WGA) or IB(4) was injected into the nerves innervating quadriceps muscle (femoral) or hindlimb skin (saphenous) of male C57Bl/6 mice. Similarly, Alexa Fluor-conjugated cholera toxin-beta was injected subserosally into the distal colon. Spinal ganglia at the appropriate level (L2-3 for saphenous and femoral nerves; L6 for colon) were processed for TRPV1, calcitonin gene-related peptide (CGRP), neurofilament heavy chain (NHF) and IB(4) visualization and examined on a confocal microscope. Colon afferents contained the highest percentage of both TRPV1- and CGRP-positive neurons, followed by femoral (WGA) and saphenous afferents (WGA and IB(4)). In contrast, NHF staining was more prevalent among femoral afferents, followed by saphenous (WGA) and colon afferents. IB(4) binding was observed in very few colon or saphenous (WGA) afferents, with no femoral afferents binding or transporting IB(4). Considering that the largest percentages of TRPV1-positive neurons observed in this study were within visceral and muscle afferent populations (neurons that typically are not subject to noxious temperatures), these results suggest that TRPV1 may not function primarily as a temperature sensor but rather as a detector of protons, vanilloid compounds or through interactions with other membrane proteins.

Animals↗
PubMed2005

Numerical simulations of radon as an in situ partitioning tracer for quantifying NAPL contamination using push-pull tests.

Presented here is a reanalysis of results previously presented by [Davis, B.M., Istok, J.D., Semprini, L., 2002. Push-pull partitioning tracer tests using radon-222 to quantify non-aqueous phase liquid contamination. J. Contam. Hydrol. 58, 129-146] of push-pull tests using radon as a naturally occurring partitioning tracer for evaluating NAPL contamination. In a push-pull test where radon-free water and bromide are injected, the presence of NAPL is manifested in greater dispersion of the radon breakthrough curve (BTC) relative to the bromide BTC during the extraction phase as a result of radon partitioning into the NAPL. Laboratory push-pull tests in a dense or DNAPL-contaminated physical aquifer model (PAM) indicated that the previously used modeling approach resulted in an overestimation of the DNAPL (trichloroethene) saturation (S(n)). The numerical simulations presented here investigated the influence of (1) initial radon concentrations, which vary as a function of S(n), and (2) heterogeneity in S(n) distribution within the radius of influence of the push-pull test. The simulations showed that these factors influence radon BTCs and resulting estimates of S(n). A revised method of interpreting radon BTCs is presented here, which takes into account initial radon concentrations and uses non-normalized radon BTCs. This revised method produces greater radon BTC sensitivity at small values of S(n) and was used to re-analyze the results from the PAM push-pull tests reported by Davis et al. The re-analysis resulted in a more accurate estimate of S(n) (1.8%) compared with the previously estimated value (7.4%). The revised method was then applied to results from a push-pull test conducted in a light or LNAPL-contaminated aquifer at a field site, resulting in a more accurate estimate of S(n) (4.1%) compared with a previously estimated value (13.6%). The revised method improves upon the efficacy of the radon push-pull test to estimate NAPL saturations. A limitation of the revised method is that 'background' radon concentrations from a non-contaminated well in the NAPL-contaminated aquifer are needed to accurately estimate NAPL saturation. The method has potential as a means of monitoring the progress of NAPL remediation.

Computer Simulation↗
PubMed2005

Basic and clinical aspects of visceral sensation: transmission in the CNS.

Pain and discomfort are the leading cause for consultative visits to gastroenterologists. Acute pain should be considered a symptom of an underlying disease, thereby serving a physiologically important function. However, many patients experience chronic pain in the absence of potentially harmful stimuli or disorders, turning pain into the primary problem rather than a symptom. Vagal and spinal afferents both contribute to the sensory component of the gut-brain axis. Current evidence suggests that they convey different elements of the complex sensory experience. Spinal afferents play a key role in the discriminatory dimension, while vagal input primarily affects the strong emotional and autonomic reactions to noxious visceral stimuli. Drugs, surgical and non-pharmacological treatments can target these pathways and provide therapeutic options for patients with chronic visceral pain syndromes.

Afferent Pathways↗
PubMed2002

Push-pull partitioning tracer tests using radon-222 to quantify non-aqueous phase liquid contamination.

Naturally occurring radon in groundwater can be used as an in situ partitioning tracer for locating and quantifying non-aqueous phase liquid (NAPL) contamination in the subsurface. When combined with the single-well, push-pull test, this methodology has the potential to provide a low-cost alternative to inter-well partitioning tracer tests. During a push-pull test, a known volume of test solution (radon-free water containing a conservative tracer) is first injected ("pushed") into a well; flow is then reversed and the test solution/groundwater mixture is extracted ("pulled") from the same well. In the presence of NAPL radon transport is retarded relative to the conservative tracer. Assuming linear equilibrium partitioning, retardation factors for radon can be used to estimate NAPL saturations. The utility of this methodology was evaluated in laboratory and field settings. Laboratory push-pull tests were conducted in both non-contaminated and trichloroethene NAPL (TCE)-contaminated sediment. The methodology was then applied in wells located in non-contaminated and light non-aqueous phase liquid (LNAPL)-contaminated portions of an aquifer at a former petroleum refinery. The method of temporal moments and an approximate analytical solution to the governing transport equations were used to interpret breakthrough curves and estimate radon retardation factors; estimated retardation factors were then used to calculate TCE saturations. Numerical simulations were used to further investigate the behavior of the breakthrough curves. The laboratory and field push-pull tests demonstrated that radon retardation does occur in the presence of TCE and LNAPL and that radon retardation can be used to calculate TCE saturations. Laboratory injection-phase test results in TCE-contaminated sediment yielded radon retardation factors ranging from 1.1 to 1.5, resulting in calculated TCE saturations ranging from 0.2 to 0.9%. Laboratory extraction-phase test results in the same sediment yielded a radon retardation factor of 5.0, with a calculated TCE saturation of 6.5%. Numerical simulation breakthrough curves provided reasonably good matches to the approximate analytical solution breakthrough curves. However, non-equilibrium radon partitioning and heterogeneous TCE distributions may affect the retardation factors and TCE saturation estimates.

Environmental Monitoring↗
PubMed2001

Epithelial overexpression of BDNF or NT4 disrupts targeting of taste neurons that innervate the anterior tongue.

Brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4) are essential for the survival of geniculate ganglion neurons, which provide the sensory afferents for taste buds of the anterior tongue and palate. To determine how these target-derived growth factors regulate gustatory development, the taste system was examined in transgenic mice that overexpress BDNF (BDNF-OE) or NT4 (NT4-OE) in basal epithelial cells of the tongue. Overexpression of BDNF or NT4 caused a 93 and 140% increase, respectively, in the number of geniculate ganglion neurons. Surprisingly, both transgenic lines had severe reduction in fungiform papillae and taste bud number, primarily in the dorsal midregion and ventral tip of the tongue. No alterations were observed in taste buds of circumvallate or incisal papillae. Fungiform papillae were initially present on tongues of newborn BDNF-OE animals, but many were small, poorly innervated, and lost postnatally. To explain the loss of nerve innervation to fungiform papillae, the facial nerve of developing animals was labeled with the lipophilic tracer DiI. In contrast to control mice, in which taste neurons innervated only fungiform papillae, taste neurons in BDNF-OE and NT4-OE mice innervated few fungiform papillae. Instead, some fibers approached but did not penetrate the epithelium and aberrant innervation to filiform papillae was observed. In addition, some papillae that formed in transgenic mice had two taste buds (instead of one) and were frequently arranged in clusters of two or three papillae. These results indicate that target-derived BDNF and NT4 are not only survival factors for geniculate ganglion neurons, but also have important roles in regulating the development and spatial patterning of fungiform papilla and targeting of taste neurons to these sensory structures.

Animals↗
PubMed2001

Applied molecular evolution of O6-benzylguanine-resistant DNA alkyltransferases in human hematopoietic cells.

Applied molecular evolution is a rapidly developing technology that can be used to create and identify novel enzymes that nature has not selected. An important application of this technology is the creation of highly drug-resistant enzymes for cancer gene therapy. Seventeen O(6)-alkylguanine-DNA alkyltransferase (AGT) mutants highly resistant to O(6)-benzylguanine (BG) were identified previously by screening 8 million variants, using genetic complementation in Escherichia coli. To examine the potential of these mutants for use in humans, the sublibrary of AGT clones was introduced to human hematopoietic cells and stringently selected for resistance to killing by the combination of BG and 1,3-bis(2-chloroethyl)-1-nitrosourea. This competitive analysis between the mutants in human cells revealed three AGT mutants that conferred remarkable resistance to the combination of BG and 1,3-bis(2-chloroethyl)-1-nitrosourea. Of these, one was recovered significantly more frequently than the others. Upon further analysis, this mutant displayed a level of BG resistance in human hematopoietic cells greater than that of any previously reported mutant.

Amino Acid Sequence↗
PubMed2001

Effect of peripheral nerve lesion and lumbar sympathectomy on peptide regulation in dorsal root ganglia in the NGF-overexpressing mouse.

Galanin is a peptide normally expressed at low levels both in sensory and in sympathetic neurons. It is strongly upregulated after peripheral nerve lesions, and it has been proposed that nerve growth factor (NGF) plays a role in this regulation. In the present study the effect of both sciatic nerve transection and lumbar sympathectomy on galanin in lumbar dorsal root ganglia (DRGs) was examined in mice overexpressing NGF (NGFOE) in the skin under the keratin promoter. The superior cervical ganglia (SCG) were also studied. In the DRG pericellular baskets containing tyrosine hydroxylase- (TH) and galanin-like immunoreactivity (LI) were found, mostly in the same fibers. Galanin-positive baskets were also found in the trigeminal ganglia. However, only single neuropeptide Y (NPY)-positive baskets were observed within the DRGs. No marked difference in number of galanin-positive neurons was seen between wild-type and NGFOE mice. After sciatic nerve transection galanin was upregulated in DRG neurons to about the same extent in NGFOE mice as in wild-type mice. Galanin-, but not TH-LIs decreased in the pericellular baskets. After lumbar sympathectomy both galanin- and TH-immunoreactive baskets disappeared, suggesting a sympathetic origin. In the SCG the very low galanin mRNA levels were strongly increased after lesion of the carotid nerves, both in wild-type and in NGFOE mice. However, whereas NPY mRNA levels decreased in the SCG after axotomy in the wild-type mice, there was a distinct increase in the NGFOE mice. Our results show that high NGF levels in skin induce formation of pericellular baskets in DRGs expressing galanin- and TH-LI and that galanin in these baskets is strongly influenced by peripheral axotomy. However, overexpression of NGF did not markedly influence galanin expression in DRG neurons, neither normally nor after nerve lesions. Finally, expression of NPY in sympathetic ganglia is differently regulated in NGFOE compared to wild-type mice.

Animals↗
PubMed2001

Overexpression of GDNF induces and maintains hyperinnervation of muscle fibers and multiple end-plate formation.

This study examined the role of glial cell line-derived neurotrophic factor (GDNF) in synaptic plasticity at the developing neuromuscular junction. Transgenic mice overexpressing GDNF in skeletal muscle under the myosin light chain-1 promoter were isolated. Northern blot and ELISA at 6 weeks of age indicated that GDNF mRNA and protein levels were elevated threefold in the lateral gastrocnemius muscle (LGM) of the GDNF-transgenic animals. Histochemical examination of LGM tissue sections at 6 weeks of age revealed a 70% increase in the number of cholinesterase-positive end plates without changes in end-plate area. Multiple end plates on a single muscle fiber were also observed, in addition to multiple axonal processes terminating on individual end plates. No change in the number of spinal motoneurons, overall LGM size, or muscle type composition was observed. Finally, overexpression of GDNF in muscle caused hypertrophy of neuronal somata in dorsal root ganglia without affecting their number. These findings demonstrate that overexpression of a single neurotrophic factor in skeletal muscle induces multiple end-plate formation and maintains hyperinnervation well beyond the normal developmental period. We suggest that GDNF, a muscle-derived motoneuron neurotrophic factor, serves an important role in the regulation of synaptic plasticity in the developing and adult neuromuscular junction.

Animals↗
PubMed2001

Skin-derived nerve growth factor blocks programmed cell death in the trigeminal ganglia but does not enhance neuron proliferation.

Development of the cutaneous sensory nervous system is dependent on the production of neurotrophic factors, such as nerve growth factor (NGF), by the skin. Limited synthesis of NGF in developing skin is thought to underlie programmed cell death and cause a 50% neuronal loss. This loss does not occur in transgenic mice that overexpress NGF in the skin, which have double the number of neurons (J. Neurosci. 14 (1994) 1422). To determine whether increased NGF blocks neuronal death and/or increases neuronal precursor replication, we analyzed the trigeminal ganglia at embryonic days E12.5, E14.5 and E16.5 using transferase-mediated dUTP nick-end labeling (TUNEL) and bromodeoxyuridine labeling. Results show that excess target-derived NGF causes a major decrease in the percent of TUNEL-labeled neurons without affecting the percent of replicating neurons. Analysis of RNA and protein expression suggests this block in cell death is mediated via the anti-apoptotic protein bcl-2.

Animals↗
PubMed2001

Bacteriophage-bacteriophage interactions in the evolution of pathogenic bacteria.

Many bacteriophages carry virulence genes encoding proteins that play a major role in bacterial pathogenesis. Recently, investigators have identified bacteriophage-bacteriophage interactions in the bacterial host cell that also contribute significantly to the virulence of bacterial pathogens. The relationships between the bacteriophages pertain to one bacteriophage providing a helper function for another, unrelated bacteriophage in the host cell. Accordingly, these interactions can involve the mobilization of bacteriophage DNA by another bacteriophage, for example in Escherichia coli, Vibrio coli and Staphylococcus aureus; the host receptor for one bacteriophage being encoded by another, as found in V. cholerae; and the presence of one bacteriophage potentiating the virulence properties of another bacteriophage, as found in V. cholerae and Salmonella enterica.

Bacteria↗
PubMed2001

Excess target-derived neurotrophin-3 alters the segmental innervation of the skin.

It is thought that dermatomes are established during development as a result of competition between afferents of neighbouring segments. Mice that overexpress neurotrophins in the skin provide an interesting model to test this hypothesis, as they possess increased numbers of sensory neurons, and display hyperinnervation of the skin. When dermatomal boundaries were mapped in adult mice, it was found that those in nerve growth factor and brain-derived neurotrophic factor overexpressers were indistinguishable from wild-type animals but that overlap between adjacent segments was greatly reduced in neurotrophin-3 (NT-3) overexpressers. However, dermatomes in heterozygous NT-3 knockout mice displayed no more overlap than wild-types. In order to quantify differences across strains, innervation territories of thoracic dorsal cutaneous nerves were mapped and measured in adult mice. Overlap between adjacent dorsal cutaneous nerves was normal in nerve growth factor overexpressing mice, but much reduced in NT-3 overexpressers. However, this restriction was not reflected in the central projection of the dorsal cutaneous nerve, creating a mismatch between peripheral and central projections. Dorsal cutaneous nerve territories were also mapped in neonatal mice aged postnatal day 7-8. In neonates, nerve territories of NT-3 overexpressers overlapped less than wild-types, but in neonates of both strains the amount of overlap was much greater than in the adult. These results indicate that substantial separation of dermatomes occurs postnatally, and that excess NT-3 enhances this process, resulting in more restricted dermatomes. It may exert its effects either by enhancing competition, or by direct effects on the stability and formation of sensory endings in the skin.

Aging↗
PubMed2001

A single-institutional, multidisciplinary approach to primary sarcomas involving the chest wall requiring full-thickness resections.

OBJECTIVE: Primary sarcomas involving the chest wall requiring full-thickness excision are rare. We reviewed our experience with these lesions in a tertiary referral cancer center by using multidisciplinary approaches. METHODS: A 10-year retrospective study identified 51 patients referred with primary sarcomas of the chest wall: 40 for initial treatment and 11 after previous unsuccessful surgical excisions elsewhere (secondary referral). Presenting symptoms were pain alone in 23 (45%) of 51 patients, pain with an associated mass in 8 (16%) patients, and an asymptomatic mass alone in 13 (25%) patients. Median symptom duration was 241 days in the primary group and 225 days in the recurrent group. Tumor locations were the sternum (n = 11), the rib alone (n = 36), and the posterior rib with extension into vertebral bodies (n = 4). Histologic types included the following: chondrosarcomas (n = 15), malignant fibrous histiocytomas (n = 9), osteosarcomas (n = 4), Ewing sarcomas (n = 3), desmoid tumors (n = 7), and other types (n = 13). The median tumor volume of those referred initially was 311 cm(3) compared with 84 cm(3) in patients with recurrent lesions. RESULTS: Twenty-six (51%) of 51 patients received treatment before resection, including chemotherapy alone (n = 22), radiation alone (n = 3), and combined chemotherapy and radiation therapy (n = 1). The complete sternum was removed in 6 of 11 patients, and the average number of ribs requiring resection was 3.8. Four patients had vertebral body resections. Prosthetic meshes alone were required in 16 of 51 patients, and meshes with methylmethacrylate were required in 18 of 51 patients. Muscle flap reconstructions by plastic surgery were required in 24 patients. Negative margins were obtained in 47 of 51 patients. There were no perioperative deaths with morbidities occurring in 12 (24%) of 51 patients (wound [n = 3], prolonged air leak [n = 1], prolonged ventilator requirement [n = 1], arrhythmias [n = 3], doxorubicin (Adriamycin)-induced cardiomyopathy [n = 1], and other [n = 3]). Postoperative treatment was administered to 13 patients (chemotherapy alone, n = 9; chemotherapy with radiation therapy, n = 4). The cumulative 5-year survival of all patients was 64% (initial referral, 61.3%; secondary referral, 72.7%). The average follow-up is 44.7 months. CONCLUSIONS: A combined aggressive multidisciplinary approach to primary sarcomas of the chest wall resulted in no treatment-related deaths and a cumulative 5-year survival of 64% in patients referred to our tertiary care cancer center.

Adolescent↗
PubMed2000

Levels of nerve growth factor and neurotrophin-3 are affected differentially by the presence of p75 in sympathetic neurons in vivo.

The development and survival of sympathetic neurons is critically dependent on the related neurotrophic factors nerve growth factor (NGF) and neurotrophin-3 (NT3), the actions of which must be executed appropriately despite spatial and temporal overlaps in their activities. The tyrosine receptor kinases, trkA and trkC, are the cognate receptors for NGF and NT3, respectively. The p75 neurotrophin receptor has been implicated in neurotrophin binding and signaling for both NGF and NT3. In this study, the authors used mice that overexpressed NGF (NGF-OE) or NT3 (NT3-OE) in skin and mice that lacked p75 (p75(-/-)) to understand the dynamics of sympathetic neuron response to each neurotrophin and to address the role of p75. NGF and NT3 were measured in sympathetic ganglia and skin (a major target of sympathetic neurons) by using the enzyme-linked immunosorbent assay (ELISA) technique. A three- to four-fold increase in skin NT3 was seen in both NT3-OE and p75(-/-) mice. Moreover, both mouse lines exhibited a three-fold increase in ganglionic NT3. However, the increase in ganglionic NT3 was accompanied by a decrease in ganglionic NGF in p75(-/-) mice but not in NT3-OE mice. This indicated that p75 plays an important role in determining the level of NGF within sympathetic neurons. In NGF-OE mice, the overexpression of NGF was correlated with increased ganglionic NGF and increased ganglionic expression of p75 mRNA. In addition, in NGF-OE mice, ganglionic trkC expression was decreased, as was the amount of NT3 present within sympathetic ganglia. These results indicate that the level of p75 is integral in determining the level of sympathetic NGF and that NGF competes with NT3 by increasing the expression of p75 and decreasing the expression of trkC.

Animals↗
PubMed2000

CTXphi contains a hybrid genome derived from tandemly integrated elements.

CTXphi is a filamentous, temperate bacteriophage whose genome includes ctxAB, the genes that encode cholera toxin. In toxigenic isolates of Vibrio cholerae, tandem arrays of prophage DNA, usually interspersed with the related genetic element RS1, are integrated site-specifically within the chromosome. We have discovered that these arrays routinely yield hybrid virions, composed of DNA from two adjacent prophages or from a prophage and a downstream RS1. Coding sequences are always derived from the 5' prophage whereas most of an intergenic sequence, intergenic region 1, is always derived from the 3' element. The presence of tandem elements is required for production of virions: V. cholerae strains that contain a solitary prophage rarely yield CTX virions, and the few virions detected result from imprecise excision of prophage DNA. Thus, generation of the replicative form of CTXphi, pCTX, a step that precedes production of virions, does not depend on reversal of the process for site-specific integration of CTXphi DNA into the V. cholerae chromosome. Production of pCTX also does not depend on RecA-mediated homologous recombination between adjacent prophages. We hypothesize that the CTXphi-specific proteins required for replication of pCTX can also function on a chromosomal substrate, and that, unlike the processes used by other integrating phages, production of pCTX and CTXphi does not require excision of the prophage from the chromosome. Use of this replication strategy maximizes vertical transmission of prophage DNA while still enabling dissemination of CTXphi to new hosts.

Bacteriophages↗
PubMed2000

Limiting numbers of G156A O(6)-methylguanine-DNA methyltransferase-transduced marrow progenitors repopulate nonmyeloablated mice after drug selection.

The limited efficacy of hematopoietic gene therapy can be improved by in vivo selection for transduced long-term repopulating cells (LTRC). We selected for G156A MGMT (triangle upMGMT) transduced LTRC present in 5 x 10(4) to 100 x 10(4) marrow cells infused into nonmyeloablated mice by the administration of O(6)-benzylguanine (BG) and BCNU every 3 to 4 weeks. To facilitate engraftment, mice were given a nonablative dose of BG and BCNU before infusion. Without selection, triangle upMGMT was not detected in any hematopoietic colony-forming units (CFU) 24 to 30 weeks after infusion. After BG and BCNU, triangle upMGMT(+) CFU were frequently detected, and their proportions increased with each treatment cycle. After 2 to 3 cycles of BG and BCNU, many mice were stably reconstituted with 75% to 100% triangle upMGMT(+) CFU for at least 6 months, representing up to 940-fold enrichment. Thus, BG and BCNU stem cell toxicity allows triangle upMGMT-transduced LTRC to repopulate the bone marrow. This degree of selection pressure in nonmyeloablated mice is far greater than that observed in previous drug-resistance gene transfer studies. These data support our approved clinical trial to select for drug-resistant, transduced hematopoietic cells, potentially decreasing cumulative drug-induced myelosuppression in patients with cancer. These data also suggest that triangle upMGMT may be a potent, dominant, selectable marker for use in dual gene therapy.

Animals↗
PubMed2000

Convergence of the secretory pathways for cholera toxin and the filamentous phage, CTXphi.

Virulence of Vibrio cholerae depends on secretion of cholera toxin (CT), which is encoded within the genome of a filamentous phage, CTXphi. Release of CT is mediated by the extracellular protein secretion (eps) type II secretion system. Here, the outer membrane component of this system, EpsD, was shown to be required for secretion of the phage as well. Thus, EpsD plays a role both in pathogenicity and in horizontal transfer of a key virulence gene. Genomic analysis suggests that additional filamentous phages also exploit chromosome-encoded outer membrane channels.

Bacterial Outer Membrane Proteins↗