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Biomedical subjects

B M Davis

Publications and source records attributed to B M Davis.

At least 73 records · Page 4Linked to original sources
PubMed1994

Overexpression of nerve growth factor in transgenic mice induces novel sympathetic projections to primary sensory neurons.

Peripheral nerve crush induces novel projections from noradrenergic sympathetic neurons to sensory ganglia, and it has been suggested that these projections provide an anatomical substrate for chronic pain syndromes that occur after nerve injury. The present study demonstrates that novel sympathetic projections to sensory neurons are also induced in transgenic mice that overexpress nerve growth factor (NGF) in the skin. Specifically, a large proportion of trigeminal neurons in NGF transgenic mice were innervated by tyrosine hydroxylase (TH)-positive pericellular arborizations that were seen only rarely in controls. Electron microscopic analysis of NGF transgenic mice revealed that trigeminal neurons were surrounded by numerous axonal varicosities containing synaptic specializations. Removal of the superior cervical ganglion abolished TH-immunoreactive arborizations in the ipsilateral trigeminal ganglion confirming that these fibers were sympathetic axons. A two-site enzyme-linked immunosorbent assay revealed that transgenic ganglia contained a tenfold increase in NGF peptide compared to controls. However, reverse transcriptase polymerase chain reaction analysis showed no apparent expression of transgene mRNA in sensory ganglia, suggesting that the additional NGF was derived from increased NGF expression in the skin. These results indicate that NGF can induce novel sympathetic projections to sensory neurons in vivo and suggests a model in which increased NGF expression plays a role in the development of sympathetic hyperalgesia after nerve injury.

Animals↗
PubMed1994

Distribution of preproenkephalin mRNA in the chicken and pigeon telencephalon.

Bioassay and immunological studies have detected the presence of opioid peptides in the nervous system of representatives of all classes of vertebrates. The present study evaluates the expression and localization of preproenkephalin (PPE) mRNA to determine the sites of synthesis of the enkephalin peptides in the adult chicken and pigeon telencephalon using in situ hybridization histochemistry. We used a 500-base-pair chicken RNA probe corresponding to chicken PPE cDNA. In both the chicken and the pigeon telencephalon, the highest concentration of PPE mRNA-containing cells was observed in the lobus parolfactorius, paleostriatum augmentatum, nucleus accumbens, and septum. Distinct populations of labeled cells were also detected in the hyperstriatum accessorium, hippocampus, area parahippocampalis, nucleus of the diagonal band, cortex dorsolateralis, and cortex piriformis. Differences in PPE mRNA expression between chicken and pigeon were observed in several telencephalic regions. For instance, the bulbus olfactorius was heavily labeled in the pigeon, but was not labeled in the chicken, and numerous PPE mRNA-containing cells were present in the area parahippocampalis of pigeons but not of chickens. In contrast, in the hyperstriatum dorsale and hyperstriatum ventrale, numerous PPE mRNA-expressing cells were detected in the chicken but not in the pigeon. Overall, PPE mRNA-expressing cells were more numerous than enkephalin-immunoreactive cells described in previous studies. In addition, our results suggest that the general pattern of enkephalin expression in the avian telencephalon is similar to that found in other vertebrates. Finally, the results of the present study illustrate some differences in the pattern of PPE mRNA distribution between closely related species, indicating the existence of species-specific neurochemical pathways, which may influence and perhaps mediate different behaviors characteristics of these species.

Animals↗
PubMed1994

Ontogeny and effect of activity on proenkephalin mRNA expression during development of the chick spinal cord.

Numerous studies have shown in the adult nervous system that mRNA expression can be regulated by neuronal activity. To examine the effect of activity during embryogenesis, the ontogeny of proenkephalin mRNA expression and expression following activity blockade was investigated during development of chick spinal cord. A cDNA fragment (ca. 0.5 kb) coding for chick proenkephalin was cloned and sequenced. With this cDNA, a cRNA probe was made to examine proenkephalin mRNA expression in the spinal cord during embryogenesis. Proenkephalin mRNA was expressed in spinal cord in clusters of cells located in the developing dorsal horn and intermediate lamina at the earliest stages examined (stage 22; E4). Proenkephalin-positive cells in the intermediate lamina were located immediately adjacent to the ventricular zone. At stage 28 (E6) an additional cluster of proenkephalin mRNA-positive cells was seen at the lateral border of the developing intermediate lamina. At stage 33 (E7.5-5-8) the pattern of hybridization positive cells was similar to earlier stages, but individual cells could be identified. At stage 39 (E13) densely labeled cells were seen throughout the dorsal horn and intermediate laminae including the column of Terni. To determine whether neural activity affects proenkephalin mRNA expression, d-tubocurarine (an inhibitor of neural activity) was injected into developing embryos. Following administration of d-tubocurarine a dramatic decrease was seen in proenkephalin mRNA hybridization in the dorsal horn and intermediate lamina of the spinal cord. This study demonstrates in vivo that changes in the level of neural activity can alter gene expression during embryogenesis and suggests that activity is required for expression of nervous system-specific genes.

Amino Acid Sequence↗
PubMed1994

Band 3 antagonists, p-azidobenzylphlorizin and DIDS, mediate erythrocyte shape and flexibility changes as characterized by digital image morphometry and microfiltration.

Two nonpenetrating membrane probes, p-azidobenzylphlorizin (p-AzBPhz) and 4,4'-diisothiocyano-2,2'-stilbene disulfonate (DIDS), have been shown in earlier studies to induce dose-dependent changes in red blood cell (RBC) shape and volume at the same low concentrations that inhibit anion transport. In the present work, these ligand-induced morphology and rheology changes were studied using video digital image morphometry (VDIM) and microfiltration techniques. The results of these experiments corroborate our earlier investigation. RBCs were filmed using a Nomarski optics microscope with video camera attachment and cell size and shape changes were computer analyzed using VDIM. Low microM p-AzBPhz or DIDS levels caused collapse of the cell's biconcave structure and cell flattening occurred within 1-2 sec after drug exposure. Higher doses of either agent converted cells to a new steady-state in which a concurrent limited increase in erythrocyte volume and blunt membrane protrusions were produced. These changes were reversed in less than 2 sec by washing the drug from the membrane. Both ligands increased the deformability of RBCs in a dose-dependent manner as determined by filtration through Nuclepore polycarbonate filters (3 microns pore diameter). The improvement in deformability of drug-treated sickle cells was much more dramatic than for normal cells at low p-AzBPhz concentrations. These results support our earlier conclusions that the ligands, through a common interaction with band 3, induce volume-associated cytoskeletal alterations which lead to changes in morphology and flexibility.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Overexpression of nerve growth factor in epidermis of transgenic mice causes hypertrophy of the peripheral nervous system.

Survival of developing neurons is dependent on access to a limited supply of target-derived neurotrophic factors. NGF is the most extensively characterized of these molecules and during development is synthesized by neuronal and nonneuronal target tissues such as the skin. To investigate how target-derived NGF affects neuron survival and development of the PNS, we used an epidermal-specific gene promoter to produce transgenic mice that overexpress the mouse NGF cDNA in skin. Analysis of transgenic skin mRNA synthesis by Northern and in situ hybridizations showed increased levels of transgene-derived mRNA in the epidermis and associated hair follicles. The increase in NGF mRNA correlated with a hypertrophy of peripheral sensory and sympathetic nerves. Immunological analysis of skin using an anti-150 kDa neurofilament antibody showed numerous large nerve bundles and fibers coursing throughout the dermis. Increased numbers of nerve processes in the transgenic skin had immunoreactivity for calcitonin gene-related peptide and tyrosine hydroxylase, indicating that both the sensory and sympathetic systems were hypertrophied. The trigeminal and superior cervical ganglia were greatly enlarged. Cell counts of trigeminal ganglia of control and transgenic mice showed a 26-117% increase in the number of neurons in the transgenics, indicating a reduction or total prevention of the program of naturally occurring cell death. These results demonstrate that NGF production by the epidermal target tissue controls neuronal survival, and in so doing, establishes the level of innervation.

Animals↗
PubMed1993

Characterization of cell lines established from human gastric-esophageal adenocarcinomas. Biologic phenotype and invasion potential.

BACKGROUND: Gastric carcinoma is one of the most common malignancies worldwide, with an overall survival of about 10%. Improvement in therapy awaits better understanding of the biologic behavior of this tumor. Establishment of cell lines permits detailed analysis of the biology of gastric cancer. The authors report on the establishment and characterization of five cell lines arising from primary proximal gastric and distal esophageal adenocarcinomas. METHODS: Cultures of epithelial cells from adenocarcinomas of the proximal stomach or adenocarcinoma of the lower esophagus were established. Gastric cancer cell lines were analyzed for doubling times, anchorage-independent growth, tumorigenic and metastatic potential in nu/nu mice, expression of keratin proteins by indirect immunofluorescence, invasive potential in a Boyden Chamber, and growth factor production by reverse transcription of mRNA in cDNA and subsequent amplification by the polymerase chain reaction. RESULTS: Five cell lines were derived from primary gastric adenocarcinomas of the proximal stomach and from Barrett esophagus. All five cell lines were tumorigenic but not metastatic in vivo. None were capable of anchorage independent growth in vitro. Two lines were highly invasive in the Boyden chamber assay, whereas two lines were minimally or noninvasive. All five cell lines expressed RNA transcripts specific for the growth factors TGF beta 1, TGF beta 2, TGF beta 3, TGF alpha, and platelet-derived growth factor A, whereas subsets of cell lines expressed transcripts for aFGF, bFGF, FGF-5, Hst, and platelet-derived growth factor B. CONCLUSIONS: Five cell lines derived from primary gastric-esophageal adenocarcinomas were established in tissue culture. These cell lines show differences in morphologic features, growth potential, and invasiveness. These newly established gastric cancer cell lines should prove useful for a wide range of studies attempting to decipher the biology of proximal gastric adenocarcinoma.

Adenocarcinoma↗
PubMed1993

Altered expression of nerve growth factor in the skin of transgenic mice leads to changes in response to mechanical stimuli.

It has recently become clear that the neurotrophic factor, nerve growth factor, interacts specifically with nociceptive sensory neurons during development and maturity. Indeed, it may serve as a critical link between inflammation and the hyperalgesia that ensues in adult animals. Nerve growth factor is normally expressed in limiting amounts in target tissues of sensory and postganglionic sympathetic neurons. In the present study we have altered the basal level of nerve growth factor expression in the skin by producing transgenic mice that express a fusion gene construct containing either a sense or antisense nerve growth factor complementary DNA linked to the K14 keratin promoter. The K14-nerve growth factor transgene (sense or antisense) is abundantly expressed in skin from approximately embryonic day 15 and is then constitutively expressed throughout the life of the animal. In light of the fact that systemic administration of nerve growth factor to neonatal or adult rats leads to hyperalgesia, we have asked whether mice expressing the sense K14-nerve growth factor transgene exhibit similar sensory abnormalities and whether mice expressing the antisense nerve growth factor complementary DNA were hypoalgesic. Here we show that mice over-expressing nerve growth factor in skin display a profound hyperalgesia to noxious mechanical stimulation. Additionally, K14-nerve growth factor antisense mice displayed a profound hypoalgesia to the same stimuli.

Animals↗
PubMed1992

Axonal sprouting and frank regeneration in the lizard tail spinal cord: correlation between changes in synaptic circuitry and axonal growth.

In our previous studies, we found that the number of supraspinal neurons projecting to the level of tail spinal cord increases by 74% during tail regeneration and that the number of local spinal neurons with descending projections increases 233%. However, only a small fraction of the supraspinal axons (less than 4%) and half of the local spinal axons actually enter the regenerated spinal cord. We suggested that this may be the result of "synaptic capture" in which regrowing axons make synapses on denervated targets rostral to the transection, aborting further regeneration. To examine this hypothesis, morphometric analysis of electron microscope (EM) photomontages was used to test for changes in synaptic distribution on ventral horn neurons rostral to regenerating tail spinal cord. In addition, 3H-thymidine and retrograde markers were used to determine whether the regenerate axons arose from cut axons, neurogenesis, or sprouting from uninjured neurons. 3H-thymidine injections during regeneration, combined with retrograde HRP pathway tracing, did not reveal the production of new neurons in the tail spinal cord. To test whether cut axons regenerate, fluorescein isothiocyanate conjugated latex beads were applied to the exposed end of the tail spinal cord. After tail regeneration, HRP was applied to the new spinal cord in the regenerated tail. Examination of local spinal neurons (the primary source of axons that enter the regenerated tail spinal cord) revealed that 28% of the neurons contained both labels. This indicated that cut axons successfully regrew into the new tail spinal cord. The regenerated axons that fail to enter the new tail spinal cord can be found in the normal spinal cord immediately rostral to the regenerated tail. To determine whether these axons were making synaptic contacts, lamina IX ventral horn neurons were examined. EM photomontages of the spinal cord rostral to the regenerate tail revealed the following properties: (1) neurons rostral to regenerated tails are larger in area compare to non-regenerates (mean increase = 112%); (2) axosomatic contacts cover a greater percentage of the neuronal soma following regeneration compared to normal (mean increase = 23%); and (3) this increased innervation is the result of an increase in the number of synaptic boutons rather than larger boutons. The number of synaptic contacts in regenerated lizards returned to normal following lumbar transection, indicating that supraspinal and/or long descending propriospinal afferents were the major source of the increased synaptic contacts.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Nocturnal growth hormone secretion in schizophrenic patients and healthy subjects.

Plasma growth hormone concentrations were measured at hourly intervals between 10 p.m. and 8 a.m. the next morning in 15 drug-free chronic schizophrenic male inpatients and 14 healthy males. Growth hormone secretion was significantly lower in the patients as compared with the controls. Growth hormone release peaked around 1 a.m. in the controls, but a growth hormone peak was absent in the patient group. Increased dopamine activity, increased serotonin activity, or both could explain the absence of a nocturnal growth hormone surge in the schizophrenic patients.

Adult↗
PubMed1992

Agitation and postdexamethasone cortisol levels in Alzheimer's disease.

The clinical correlates of hypothalamic-pituitary-adrenal (HPA) functioning were examined in 29 patients with probable Alzheimer's disease. The 8:00 a.m. postdexamethasone cortisol levels of these patients were highly correlated with higher agitation scores but not with the degree of depressed mood or memory impairment. The possible neural basis for the association between hypercortisolism and behavioral disturbance in Alzheimer's disease warrants further exploration and replication.

Alzheimer Disease↗
PubMed1991

Induction of growth factor RNA expression in human malignant melanoma: markers of transformation.

Alteration in the expression of growth factors is widely accepted as being one of several critical defects in the generation of the malignant cell. In the present study, 19 human metastatic melanoma cell lines were compared to 14 normal human foreskin melanocyte cell lines for the production of RNA transcripts specific for 11 different growth factors. Using the extremely sensitive technique of polymerase chain reaction to amplify growth factor-specific complementary DNAs, we analyzed the following: transforming growth factor (TGF) types alpha, beta 1, beta 2, and beta 3, acidic (a) fibroblast growth factor (FGF), basic (b) FGF, FGF-5, keratinocyte growth factor (KGF), HST, and platelet-derived growth factor (PDGF) types A and B. There were clear distinctions among the patterns of growth factor RNA expression by normal melanocytes and malignant melanoma cells. The prototypic melanocyte pattern of expression included TGF beta 1, TGF beta 3, and KGF. A subset of melanocyte cell lines also expressed PDGFA transcripts. In contrast, melanoma cells characteristically expressed RNA transcripts of TGF beta 1, TGF beta 2, TGF beta 3, TGF alpha, bFGF, KGF, and PDGFA. Subsets of melanoma cell lines also expressed aFGF, FGF-5, and PDGFB. The results presented indicated that TGF beta 2, TGF alpha, and bFGF may be particularly important in melanomagenesis and that these, as well as FGF-5, aFGF, and PDGFB, can be used as markers of transformation in this tumor type.

Base Sequence↗
PubMed1990

Time course of salamander spinal cord regeneration and recovery of swimming: HRP retrograde pathway tracing and kinematic analysis.

The time course of regeneration of supraspinal and descending brachial intraspinal axons was studied using HRP retrograde tracing and kinematic analysis. Five groups of salamanders (10 salamanders/group) received complete thoracic transection 1.0 cm rostral to the hind limbs abolishing swimming. Groups 1-4 recovered for 2, 4, 6, and 8 weeks, respectively, before being filmed to record the animal's ability to swim. After filming, a second transection was made 1.0 cm caudal to the first (at the level of the lumbar enlargement) and HRP was used to label descending axons which had grown past the first lesion. The fifth group was filmed every 2 weeks for 12 weeks before the second transection was made for HRP application. The films were used to perform frame by frame computer analysis of the amplitude and timing of cyclic lateral flexion waves which make up swimming behavior. The earliest return of coordinated swimming behavior was seen 4 weeks after transection (1 of 20 animals). At 6 weeks post-transection, 5 of 10 animals exhibited coordinated swimming. However, the behavior in these animals was subnormal. In the group surviving 8 weeks post-transection, 5 of 10 animals recovered coordinated swimming behavior. In the group that was filmed every 2 weeks, 5 of the 10 salamanders which did recover, exhibited coordinated swimming behavior by the eighth week post-transection. Kinematic analysis of salamanders that exhibited a return of coordinated swimming revealed quantitative differences compared to normal salamanders. While continuous head to tail undulatory waves were present, the propagation time and period were faster than those in normal salamanders. Retransection of the spinal cord abolished coordinated swimming. The numbers and distribution of HRP-labeled supraspinal neurons varied greatly among the animals that displayed recovery of locomotor abilities. In the salamanders examined 6 weeks post-transection the majority of labeled cells were found in medullary nuclei. In recovered salamanders examined 8 and 12 weeks post-transection, HRP-labeled neurons were found in the red nucleus, in the interstitial nucleus of the fasciculus longitudinalis medialis, and in the mesencephalic as well as the medullary reticular neurons. Recovery of coordinated swimming was only observed in salamanders in which descending supraspinal and intraspinal axons were present at the level of the lumbar enlargement (as demonstrated by HRP retrograde labeling). These results indicate that recovery of locomotion is dependent on the reestablishment of descending input and is not a result of changes in spinal reflexes or propagation of electrical activity through the body wall.

Animals↗
PubMed1989

Development of central projections of lumbosacral sensory neurons in the chick.

The development of central projections of sensory neurons in lumbosacral dorsal root ganglia (DRGs) was examined by using horseradish peroxidase labeling techniques in chick embryos from stage 23 (E4) to stage 39 (E13). Our results show that primary afferents reach the spinal cord by stage 23. Afferent axons extend in the primordium of the dorsal funiculus for several segments rostral and caudal to their segment of entry for over 24 hours before invading the gray matter at stage 28 (E6). Sensory fibers grow into the vicinity of motoneuron dendrites by stage 32 (E7.5), about the time that reflexes and apparent monosynaptic EPSPs can first be elicited. Dense projections into the dorsal laminae of the spinal cord, presumably representing cutaneous afferents, appear somewhat later, at about stage 39 (E13), when the segmental projection pattern begins to resemble the mature pattern.

Animals↗
PubMed1989

Bulbospinal and intraspinal connections in normal and regenerated salamander spinal cord.

The salamander is the only limbed adult vertebrate which can regenerate portions of cervical, thoracic, or lumbar spinal cord. While the salamander has been a popular model for regeneration of the spinal cord, it is still not known what portions of the nervous system participate in the regeneration process. In the experiments reported here we examine the bulbospinal and intraspinal projections to the lumbar spinal cord in normal and regenerated salamanders (Notophthalmus viridescens). HRP application to the lumbar enlargement of normal salamanders labeled cells in the ventral thalamus, the rostral tegmentum in the proposed homolog of the red nucleus, the reticular neurons of the rhombencephalon, and the midline regions of the rhombencephalon which are possibly equivalent to raphe nuclei of other vertebrates. In the brachial spinal cord HRP-labeled cells were located in dorsal, intermediate, and ventral regions of the spinal gray matter and tended to be located at the periphery of the gray matter. To examine the spinal circuitry of regenerated salamanders, animals received complete spinal transections at the junction of the thoracic and lumbar spinal cord, abolishing all spontaneous coordinated hindlimb and tail movements. Animals exhibited walking and swimming within 60 days at which time a pledget of HRP was inserted into a gap in the spinal cord made by a transection 10.0 mm (six animals) or 5.0 mm (one animal) caudal to the first lesion. On average, the number of HRP labeled brain stem neurons in regenerated animals was 40% of that found in normal animals. The number of labeled cells in the brachial spinal cord was within the range of normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Amputation, Surgical↗
PubMed1989

Perturbation of experimental ultraviolet light-induced erythema by passive transfer of serum from subacute cutaneous lupus erythematosus patients.

Several lines of investigation have implicated anti-Ro/SS-A antibody in the pathogenesis of photosensitive forms of cutaneous lupus erythematosus such as neonatal lupus erythematosus and subacute cutaneous lupus erythematosus. To further explore this possibility, we have developed a quantitative, experimental system for examining the effect of passively transferring anti-Ro/SS-A antibody-containing and antibody-deficient subacute cutaneous lupus erythematosus patient sera on one aspect of cutaneous photoreactivity, UV-induced erythema. Laser-Doppler velocimetry was used to quantitate the microvascular flow rates in normal control, disease control (rheumatoid arthritis, discoid lupus erythematosus), and subacute cutaneous lupus erythematosus serum-injected guinea pig skin test sites before and after combined ultraviolet B and A radiation from a solar simulator. Results, expressed as change in milli-electron voltage (perturbed milli-electron volts after irradiation minus baseline milli-electron volts before irradiation), revealed that subacute cutaneous lupus erythematosus serum injections consistently resulted in greater UV-induced microvascular flow rates than those elicited by normal or disease control serum injections. Anti-Ro/SS-A containing subacute cutaneous lupus erythematosus sera produced the greatest flow rates observed in this study. Earlier studies have suggested that the pathogenesis of lupus photosensitivity is very likely multifactorial. Our current data suggest that anti-Ro/SS-A autoantibody or other closely related humoral elements should also be considered among the factors which might contribute to this clinical phenomenon.

Acute Disease↗