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Biomedical subjects

E F Wheeler

Publications and source records attributed to E F Wheeler.

At least 19 recordsLinked to original sources
PubMed2000

Effects of deprivation of neonatal nerve growth factor on the expression of neurotrophin receptors and brain-derived neurotrophic factor by dental pulp afferents of the adult rat.

The dental pulp is richly innervated by peptidergic nociceptive neurones that are of special interest because of their central role in dental pain and because they have some features that are not typical of other somatic nociceptors. Here, (35)S-riboprobes were used to determine whether pulpal afferents of adult (2-month-old) rats express the nerve growth-factor (NGF) receptors, p75(NTR) and trkA, which are characteristic of peptidergic nociceptors, and additionally, whether these cells express receptors (trkB and trkC) for other members of the neurotrophin family. In order to begin characterizing the postnatal role of NGF in regulating these neurones, the susceptibility of pulpal afferents to antiserum-mediated early postnatal NGF depletion spanning the period of pulpal innervation development was also examined. In control animals, about 200 trigeminal ganglion cells were labelled after application of the retrograde tracer Fluoro-gold to the first maxillary molar. Among the labelled cells, 79% had positive hybridization signals for p75(NTR), 72% for trkA, 34% for trkB, 1% for trkC, and 77% for BDNF. Neonatal NGF depletion reduced the number of retrogradely labelled pulpal afferents by 33%, with numbers of smaller neurones being most strikingly subnormal. This reduction could be attributed to a partial depletion of the neurone population that expressed p75(NTR) and trkA. Consistent with reports that NGF-responsive neurones also express BDNF, NGF deprivation resulted in a reduction in the number of pulpal afferents that expressed BDNF to an extent similar to that seen for trkA. In contrast, anti-NGF exposure had little effect on the number of pulpal afferents that expressed trkB. These findings indicate that most pulpal afferents in the adult express the NGF receptors p75(NTR) and trkA, and thus have a continuing potential susceptibility to NGF-mediated regulation of functions such as neuropeptide and BDNF synthesis. However, only a subpopulation of this group of neurones requires NGF in order to develop connections to the pulp during the neonatal period. Few, if any, pulpal afferents express the high-affinity neurotrophin-3 (NT3) receptor trkC, although many have large cell bodies typical of NT3-responsive sensory neurones. A small subpopulation of pulpal afferents seems to express no neurotrophin receptors, yet it is unlikely that these cells belong to the class of small sensory cells known to bind isolectin IB4.

Age Factors↗
PubMed2000

Time course of the increase in trk A expression in trigeminal neurons after tooth injury.

Injury to tooth pulp often results in extensive sprouting of sensory nerve fibers at the site of wound repair due to local increases in nerve growth factor (NGF) concentration. NGF interacts with high-affinity binding sites, termed trk A receptors, located on the cell membranes of responsive neurons. If NGF induces wound repair and/or nociceptive responses in tooth pulp, then changes in expression of NGF receptors (trk A receptors) in response to dentin injury would be expected. To characterize the role of trk A receptors in mediating NGF-induced signals to sensory neurons, trigeminal ganglia from adult male rats were examined for changes in expression of trk A as a function of time after injury to maxillary molar dentin. In situ hybridization was performed with 35S-labeled riboprobes encoding the sense or antisense trk A sequences, and grain densities quantified over maxillary neurons. As early as 12 h after tooth injury, grain density counts increased by 71% above control level, indicating an increase in trk A receptor mRNA expression. Grain densities obtained from ganglia harvested at all time points through 168 h after injury remained elevated. At 336 h (14 days) after injury, trk A receptor expression had decreased such that grain density counts were not different from preinjury levels. Thus our results suggest that NGF may be mediating repair and pain responses by the sustained upregulation of its cell surface receptor, trk A, in neurons of the trigeminal ganglia.

Analysis of Variance↗
PubMed2000

Characteristics of veal calves upon arrival, at 28 and 84 days, and at end of the production cycle.

Holstein bull calves arriving at five special-fed veal farms (eight production groups) were scored for various physical condition traits and blood-sampled within 2 h after arrival and at 28 d, 84 d, and 1 wk prior to slaughter at 116 to 143 d. Of 1179 total calves in the production groups, 758 calves were scored and evaluated. Blood cell analyses (red and white blood cell counts, hemoglobin, and packed cell volume) were conducted at all four sampling times; total serum protein concentration was obtained at 0 and 28 d. The study was initiated in autumn and ended the following autumn. Mean initial and final body weights were 46.3+/-0.17 and 209.7+/-0.77 kg; mean mortality was 2.5%. Average daily gain of the eight groups ranged from 1.23 to 1.70 kg/d. Subjective scores of 5 = excellent to 1 = very poor condition were used to evaluate 16 different physical condition characteristics. With the exception of leg joint, hoof, and foot scores, most of the physical condition scores exhibited improvement during the first 28 d. Foot and leg impairments did not appear to hinder the ambulatory ability of the calves during the production period. Physical condition scores at d 0 and 28 were generally not related to numbers or types of medical treatments (enteric, respiratory, other, or total) or to average daily gain during the production period. Means for most erythrocytic and leukocytic traits upon arrival (d 0) were within normal ranges, although 27.4% of the calves were clinically or marginally anemic. Final mean hemoglobin and packed cell volume were 8.53 g/dl and 26.1%. Forty-three percent of the calves at d 0 were colostral deficient, assuming that total serum protein concentrations of <5.5 g/dl indicate colostral deficiency. No blood trait was consistently correlated with body weight gain when gain during the production period was divided into quartiles and the blood traits were averaged by gain quartile. Calves in the lowest serum total protein quartile (mean 4.58 g/dl) had more respiratory and total medical treatments than quartiles with higher total protein means. Dairy bull calves arriving at veal production units after transporting from the dairy farm to the auction market (or other collection facility) have several physical impairments. However, most of these physical impairments are improved early in the veal feeding period and are not generally related to subsequent growth rate or medical treatment.

Aging↗
PubMed1999

Neurotrophic factor regulation of developing avian oculomotor neurons: differential effects of BDNF and GDNF.

Neurotrophic factors support the development of motoneurons by several possible mechanisms. Neurotrophins may act as target-derived factors or as afferent factors derived from the central nervous system (CNS) or sensory ganglia. We tested whether brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), neurotrophin 4 (NT-4), and glial cell line-derived neurotrophic factor (GDNF) may be target-derived factors for neurons in the oculomotor (MIII) or trochlear (MIV) nucleus in chick embryos. Radio-iodinated BDNF, NT-3, NT-4, and GDNF accumulated in oculomotor neurons via retrograde axonal transport when the trophic factors were applied to the target. Systemic GDNF rescued oculomotor neurons from developmental cell death, while BDNF and NT-3 had no effect. BDNF enhanced neurite outgrowth from explants of MIII and MIV nuclei (identified by retrograde labeling in ovo with the fluorescent tracer DiI), while GDNF, NT-3, and NT-4 had no effect. The oculomotor neurons were immunoreactive for BDNF and the BDNF receptors p75(NTR) and trkB. To determine whether BDNF may be derived from its target or may act as an autocrine or paracrine factor, in situ hybridization and deprivation studies were performed. BDNF mRNA expression was detected in eye muscles, but not in CNS sources of afferent innervation to MIII, or the oculomotor complex itself. Injection of trkB fusion proteins in the eye muscle reduced BDNF immunoreactivity in the innervating motoneurons. These data indicate that BDNF trophic support for the oculomotor neurons was derived from their target.

Animals↗
PubMed1998

Neurotrophin receptor expression is induced in a subpopulation of trigeminal neurons that label by retrograde transport of NGF or fluoro-gold following tooth injury.

Tissue responses to injury are regulated by neurotrophins and neurotrophin receptor levels and can involve both retrograde and paracrine/autocrine trophic signaling. To determine how neurotrophins may contribute to the injury response, the timing and the extent of the up-regulation of neurotrophins and their receptors was examined in a model system which is particularly well suited for the analysis of trophic signaling pathways in response to injury. Injury to the occlusal surfaces of rat molar cusps induces a localized increase in nerve growth factor (NGF) expression in the dental pulp within 4-6 h. Radiolabeled NGF was transported in a receptor-mediated fashion from the teeth to a subset of neurons in the trigeminal ganglion within 15 h, indicating that these neurons possess NGF receptors (trk A and/or p75NTR). To test for NGF responses in the tooth sensory afferent neurons, levels of expression of neurotrophins and their receptors were examined by in situ hybridization in the trigeminal ganglion at 0, 4, 12, 20, 28 and 52 h post-injury. Within the maxillary division of the trigeminal ganglion, trk A expression was elevated at 4 h post-injury, with a maximum increase (2-fold) after 52 h. p75NTR was increased by 28 h post-injury and was increased 1.35-fold by 52 h. BDNF mRNA was increased 12 h after injury (1.8-fold), and 2.5-3-fold at 52 h post-injury. The trk B expression was increased only late after injury (28 and 52 h). To determine the receptor/neurotrophin phenotype of trigeminal neurons with projections to the molar teeth, these neurons were double-labeled with the retrograde tracer fluoro-gold and probes for either BDNF or trk B. The results show that tooth-innervating trigeminal neurons express BDNF, but not trk B. The timing of mRNA expression after injury and the phenotype of identified trigeminal neurons suggests a complex signaling cascade in which NGF at the injury site regulates NGF receptor expression at the levels of the cell body as well as increases in BDNF expression. Upregulated BDNF may act in a paracrine fashion on neighboring trigeminal cells expressing trk B. This signaling cascade may be a common feature of the response to mild peripheral inflammatory injuries within nociceptive pathways.

Animals↗
PubMed1998

p75NTR and Trk receptors are expressed in reciprocal patterns in a wide variety of non-neural tissues during rat embryonic development, indicating independent receptor functions.

The p75 kDa neurotrophin receptor (p75NTR) has been detected in a number of non-neural tissues, especially during development. Reports of Trk receptor transcripts in non-neural tissues raise the possibility that the sites of p75NTR expression during development may correlate with Trk receptor expression. Coexpression of p75NTR with the Trk receptors in developing non-neural tissues would support the hypothesis that there is a cooperative function between the two receptor subclasses. To address these questions, p75NTR was localized relative to the three known Trk receptors in adjacent sections of rat embryos at stages of development when the highest levels of p75NTR have been observed in the muscle, maxillary pad, kidney, and lung. Using in situ hybridization and immunhistochemical analyses, we show here that the Trk receptors are expressed extensively in non-neural tissues during cell differentiation and tissue morphogenesis but in patterns that are generally reciprocal to that of p75NTR. The results indicate p75NTR most likely functions independently of the Trk receptors in most developing non-neural tissues. However, the p75NTR consistently appears in non-neural cells adjacent to those expressing Trk receptors. The reciprocal patterns of expression indicate that the separate activities of the two receptors most likely complement each other in regulating cell-cell interactions important for the innervation of developing non-neural tissues.

Animals↗
PubMed1996

Consideration in selecting crops for the human-rated life support system: a Linear Programming model.

A Linear Programming model has been constructed which aids in selecting appropriate crops for CELSS (Controlled Environment Life Support System) food production. A team of Controlled Environment Agriculture (CEA) faculty, staff, graduate students and invited experts representing more than a dozen disciplines, provided a wide range of expertise in developing the model and the crop production program. The model incorporates nutritional content and controlled-environment based production yields of carefully chosen crops into a framework where a crop mix can be constructed to suit the astronauts' needs. The crew's nutritional requirements can be adequately satisfied with only a few crops (assuming vitamin mineral supplements are provided) but this will not be satisfactory from a culinary standpoint. This model is flexible enough that taste and variety driven food choices can be built into the model.

Crops, Agricultural↗
PubMed1994

Expression of BDNF and NT-3 mRNA in hair cells of the organ of Corti: quantitative analysis in developing rats.

Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are synthesized by inner and outer hair cells of the developing organ of Corti. This raises the possibility that the reorganization of cochlear innervation patterns that occurs postnatally may be influenced by changing levels of neurotrophin expression. To determine if differential expression of BDNF or NT-3 in the inner and outer hair cells correlates with the reorganization of afferent and efferent innervation, we used in situ hybridization techniques to quantify relative levels of transcript biosynthesis in hair cells of developing rats. BDNF transcripts decreased in inner and outer hair cells from E17 to insignificant levels at P4. NT-3 expression was high at E17 in inner and outer hair cells, decreased in outer hair cells by E21, in inner hair cells by P1, remained low during the first postnatal week and was increased in the adult. The decreases in expression of both neurotrophins at birth precede the retraction of afferent nerve terminals from outer hair cells. BDNF and NT-3 transcription decreases substantially in outer hair cells between E21 and P4 when efferent innervation begins, indicating target biosynthesis of these neurotrophins is not likely to be instrumental in efferent target selection.

Animals↗
PubMed1992

Altered expression of NGF and P75 NGF-receptor by fibroblasts of injured teeth precedes sensory nerve sprouting.

Profuse sprouting of sensory nerve fibers occurs in tooth pulp by 1-4 days following dentin injury. A possible role for nerve growth factor (NGF) in that neural response is suggested here by the demonstration that NGF mRNA and protein are increased 6 hr after injury to adult rat molars. The enhanced expression of NGF mRNA was localized to fibroblasts underlying the injury. A concomitant depletion of mRNA encoding the 75 Kd NGF receptor (NGFR) was observed in those fibroblasts. The increase in NGF mRNA was transitory and mRNA levels fell below normal levels by 2 days after injury. Both NGF and NGFR mRNA remained low thereafter in injured pulp. The inverse shifts in fibroblastic mRNA encoding NGF and NGFR were not affected by prior denervation of the tissue, or by pretreatment with dexamethasone. The regulatory mechanisms therefore must involve endogenous, non-neuronal, non-inflammatory factors that are released in response to injury.

Aging↗
PubMed1992

Spatiotemporal patterns of expression of NGF and the low-affinity NGF receptor in rat embryos suggest functional roles in tissue morphogenesis and myogenesis.

We show here that NGF and its low-affinity receptor (p75NGFR) are expressed during rat embryogenesis at sites that are known to have important roles in tissue morphogenesis and myogenesis. The developing skin of the maxilla, the mandible, and the limb showed very similar patterns of NGF and p75NGFR expression. However, NGF and p75NGFR expression in the developing limb initiated at the limb bud stage and was concentrated at proximal and distal developmental sites that have been reported to be involved in limb morphogenesis. Expression at the proximal/distal ends of the limb persisted throughout limb development, with some of the highest levels of expression occurring at the limb axillary sites, which were not highly innervated. We have also found p75NGFR expression at sites of mesenchymal/epithelial interactions in several developing organs that do not appear to have an adjacent source of NGF and may therefore be sites that bind and respond to the other members of the NGF family (brain-derived neurotrophic factor and neurotrophin-3). These organs include the lung, testes, and kidney, where expression of p75NGFR occurred during the morphogenesis of specific epithelial structures and was coexpressed with the cell adhesion molecule NCAM. In addition, we found that NGF and p75NGFR were expressed during myogenesis. p75NGFR was observed in myoblast cells expressing MyoD1, a myoblast differentiation marker, and NGF transcripts in cells just adjacent to the developing myoblasts. When the myoblasts differentiate into myotubes, p75NGFR and MyoD1 cease to be expressed and the adjacent cells concomitantly cease to be make NGF. However, NGF and p75NGFR were not present in the early muscle precursor cells of the myotome of the somites but were observed in the dermatome and sclerotome, respectively. These results suggest that NGF and p75NGFR have functional roles in developmental processes that affect morphogenesis and cell differentiation.

Animals↗
PubMed1992

Reactions of sensory nerves to dental restorative procedures.

The reactions of sensory nerves to restorative procedures can be classified as immediate, early and late. For each of these, the neural response depends upon the severity of pulpal injury and the stages of inflammation and healing. Immediate responses in the first few minutes include destruction of nerve fibers in the injured dentin and pulp, hypersensitivity of surviving fibers, release of neuropeptides into the pulp and neurogenic inflammation. Early responses occur during the first few days after cavity preparation, with nerve fibers sprouting in the surviving pulp and gaining increased axonal transport and neuropeptide contents. Sensory fibers containing calcitonin gene related peptide (CGRP) greatly outnumber those with substance P (SP); but both types grow toward the surviving odontoblasts and associated pulp tissue surrounding the lesion. Later during subsequent weeks the nerve fibers accompany granulation tissue as it replaces acute inflammation; and nerve sprouting subsides when inflammation is reduced and when reparative dentin covers the injury site. An important response to tooth injury that may regulate nerve sprouting reactions is the increased production of nerve growth factor (NGF) by pulpal fibroblasts near the lesion. The timing of the nerve sprouting reactions suggests that they may contribute to tooth hypersensitivity after restorative procedures.

Animals↗
PubMed1991

Molecular cloning and characterization of B-cadherin, a novel chick cadherin.

Calcium-dependent cell-cell adhesion is mediated in large part by a set of homologous integral membrane glycoproteins termed cadherins. In this report, antibodies to conserved domains in previously described cadherins have been used to isolate cDNAs encoding a novel chick cadherin. The deduced primary structure of this novel molecule, assigned the name B-cadherin, contains 726 amino acid residues which include five extracellular domains characteristic of this class of adhesion molecules, a single putative transmembrane spanning region, and a cytoplasmic tail. In each domain, B-cadherin shares extensive homologies with other cadherins, but is more closely related to E-cadherin, P-cadherin, and L-CAM than to N-cadherin. It is expressed in a wide variety of chick tissues at embryonic day 13. In particular, immunohistochemical staining and in situ hybridization localize B-cadherin protein and mRNA to the epithelial lining of the choroid plexus and to cells in specific layers of the optic tectum in chick brain. Levels of the protein and RNA transcript change dramatically as development proceeds in chick brain. These results suggest that B-cadherin has important functions in neurogenesis, in at least some epithelia, and in embryogenesis.

Amino Acid Sequence↗
PubMed1991

Infant feeding and growth in rural Ghana: is the use of the traditional fermented porridge a case for early supplementation?

Thirty infants were studied longitudinally for 6 months. Breast milk and intakes of supplements were measured at the first and third months post-partum. Mode of feeding, morbidity, and weights were recorded monthly. Variations in growth were found to be related to levels of breast milk intakes, and timely and effective supplementation with the traditional weaning porridge prepared from fermented maize dough. No diarrhoeal incidence was recorded before 3 months. It is suggested that coupled with true demand breast feeding, the traditional weaning porridge could adequately support growth if introduced on time, even when breast milk intakes are less than optimal.

Body Weight↗
PubMed1991

Expression of nerve growth factor (NGF) receptors in the developing inner ear of chick and rat.

The expression of nerve growth factor receptors (NGFRs) was studied in the developing inner ear with in situ hybridization in chick embryos and with immunocytochemistry in rat embryos to determine sites of possible functions of NGF or NGF-like molecules in inner ear development. NGFR expression in the chick otocyst and acoustic ganglion is compared with epithelial differentiation and the onset of afferent innervation as determined with fluorescent carbocyanine tracers. In the inner ear of the chick embryo, NGFR mRNA expression shows an alternating pattern in mesenchymal and epithelial tissues. NGFR mRNA is heavily expressed in the mesenchyme surrounding the otocyst (E2-3), ceases at E3-5, and reappears in a thin layer of mesenchymal cells surrounding the membraneous epithelia (E5-13). In the otocyst epithelium, NGFR mRNA expression develops in one anterior and one posterior focus at E3-4.5. NGFR mRNA is expressed in the primordia of the ampullary cristae (E5-7) and possibly the anlage of the utricle; label transiently concentrates in the planum semilunatum of the cristae ampullares and in superior portions of the semicircular canals at E9, but is not seen in differentiating hair cells. In the acoustic ganglion, NGFR mRNA expression begins at E4; at the same time, the first peripheral acoustic nerve processes penetrate the otic epithelium (E4-4.5). The acoustic ganglia remain weakly NGFR mRNA-labeled in the posthatch animal. In the rat embryo, NGFR immunoreactivity is present in the auditory placode at E9, in the periotic mesenchyme at E9-10, and in the medial half of the otocyst at E10-11. At E12, epithelial NGFR expression becomes restricted anteriorly and posteriorly in a pattern similar to that of the chick otocyst and ceases at E13. NGFR immunoreactivity appears transiently in pillar cells of the cochlea in the third week of gestation. NGFR and NGFR mRNA is expressed after E11 in the acoustic ganglia. While NGFR transcripts are expressed in the cochlear ganglion cell bodies, NGFR protein becomes restricted to neuronal processes by the third week of gestation. The vestibular, but not the cochlear (spiral) ganglia remain NGFR-labeled in the adult rat. Onset of NGFR mRNA expression in the acoustic ganglion during the period of afferent fiber ingrowth into the otocyst epithelium is consistent with the hypothesis that NGF-like molecules may have a neurotrophic function for acoustic ganglion cells. Transient expression of NGFRs in secretory cells of the vestibular endorgan and pillar cells in the organ of Corti implicate a role for neurotrophins in the differentiation of these epithelial cell types.

Animals↗
PubMed1990

Structure and developmental expression of the chicken NGF receptor.

The nucleotide and deduced amino acid sequence of a cDNA clone of the chicken NGF receptor (NGFR) is reported and is compared with sequences of mammalian NGF receptors. A model is presented in which monodentate or bidentate binding of NGF dimers to repeated cysteine-rich sequence elements of the receptor yields low- or high-affinity NGF binding, respectively. In situ hybridization is used to characterize expression of NGFR in developing chick from 40 hr to 10 days of embryogenesis. NGFR mRNA expression is detected in premigratory neural crest cells, in epibranchial placode cells, and in all sensory, sympathetic and parasympathetic derivatives of these structures. In the embryonic CNS, NGFR mRNA is detected in the mantle zone but not the periventricular germinal zone throughout most of the neural tube. By Embryonic Day 8, NGFR mRNA is detected in a substantial fraction of cells in every brain region, with highest levels present in developing motor neurons. NGFR mRNA also is transiently expressed in many mesenchymal cell populations including cells in branchial arch, sclerotome, muscle anlagen, and feather follicles. The functional significance of wide-spread embryonic expression of the NGF receptor is discussed.

Amino Acid Sequence↗
PubMed1988

Is the message getting through? Nutritional knowledge of pregnant women in Edinburgh and London.

This paper reports the results of a survey in which pregnant women in London and Edinburgh were asked about their knowledge and understanding of the recent recommendations of expert committees (James, 1983; DHSS, 1984). In general, Londoners had a better understanding, although in both regions manual groups were less knowledgeable, with the Edinburgh manual group the least well informed.

Adolescent↗
PubMed1987

The v-fms oncogene induces factor-independent growth and transformation of the interleukin-3-dependent myeloid cell line FDC-P1.

The normal cellular counterpart of the v-fms oncogene product is a receptor for the mononuclear phagocyte colony-stimulating factor, CSF-1. An interleukin-3 (IL-3)-dependent mouse myeloid cell line, FDC-P1, was infected with a murine retrovirus vector containing v-fms linked to a gene encoding resistance to neomycin (neo). Infected cells selected for resistance to the aminoglycoside G418 contained few proviral DNA copies per haploid genome, expressed low levels of the v-fms-coded glycoprotein, remained IL-3 dependent for growth, and were nontumorigenic in nude mice. In contrast, infected cells selected for their ability to grow in the absence of IL-3 contained an increased number of proviral insertions, expressed high levels of the v-fms-coded glycoprotein, and were tumorigenic in nude mice. The IL-3-independent cells expressed IL-3 receptors of comparable number and affinity to those detected in uninfected FDC-P1 cells and did not produce a growth factor able to support replication of the parental cells. Thus, the synthesis of high levels of the v-fms gene product in FDC-P1 cells abrogated their requirement for IL-3 and rendered the cells tumorigenic by a nonautocrine mechanism. The data suggest that v-fms encodes a promiscuous tyrosine kinase able to transform cells of the myeloid lineage that do not normally express CSF-1 receptors.

Animals↗