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D E Wright

Publications and source records attributed to D E Wright.

At least 37 records · Page 2Linked to original sources
PubMed1998

Estimating the spontaneous loss of Down syndrome fetuses between the times of chorionic villus sampling, amniocentesis and livebirth.

Recent publications concerning the prevalence of Down syndrome at times of chorionic villus sampling (CVS), amniocentesis and livebirth were reviewed with particular interest in estimates of spontaneous loss of Down syndrome fetuses during pregnancy. Data from several studies were combined to provide information on 258,206 pregnancies. A logistic regression was applied to provide new estimates and confidence intervals (CIs) for spontaneous loss rates between the time of CVS and livebirth (estimate = 39 per cent; 90 per cent CI 32 to 45 per cent), and the time of amniocentesis and livebirth (estimate = 12 per cent; 90 per cent CI 5 to 18 per cent).

Abortion, Spontaneous↗
PubMed1997

Cyclophosphamide/granulocyte colony-stimulating factor induces hematopoietic stem cells to proliferate prior to mobilization.

We isolated hematopoietic stem cells (HSC) from mice treated with cyclophosphamide (CY) and granulocyte colony-stimulating factor (G-CSF). All mobilized multipotent progenitor activity was contained in two populations: Thy-1(lo) Sca-1+ Lin- Mac-1- CD4- c-kit+ long-term reconstituting progenitors and Thy-1(lo) Sca-1+ Lin- Mac-1(lo) CD4- transiently reconstituting progenitors. CY/G-CSF treatment drove both long-term and transient multipotent progenitors into cycle, leading to a more than 12-fold expansion in the number of long-term self-renewing HSC prior to mobilization. After CY and 2 days of G-CSF treatment the number of bone marrow HSC began to decline and the number of blood and splenic HSC increased. HSC continued to proliferate in the bone marrow and spleen through 8 days of G-CSF treatment, but HSC released into the blood tended to be in G0/G1 phase. Mobilized multipotent progenitors isolated from the spleen were less efficient than normal bone marrow multipotent progenitors in engrafting irradiated mice but did not differ in colony forming unit-spleen (CFU-S) activity or single cell in vitro assays of primitive progenitor activity. The data suggest that mobilized HSC isolated from the spleen are less efficient at homing to and engrafting the bone marrow of irradiated recipient mice.

Animals↗
PubMed1997

Cloning and expression of a novel murine semaphorin with structural similarity to insect semaphorin I.

We describe a novel semaphorin family member, Sema VIa, with 25-36% sequence identity at the amino acid level in the semaphorin domain to previously published mouse homologues. This novel family member shares considerable homology with the best characterized murine semaphorin, Sema III (also known as SemD), at the 5' end but is divergent from Sema III near the 3' end because it contains a putative transmembrane domain. Remarkably, of the known semaphorins, Sema VIa bears the greatest structural similarity to insect Sema I, although it contains a much larger intracellular domain. We propose, therefore, that Sema VIa is the prototype of a new class (class VI) of semaphorins. In order to gain insights into potential functions of Sema VIa, we have compared mRNA expression of Sema VIa to that of Sema III during development. In the nervous system, Sema VIa is expressed in strikingly localized and transient patterns that are markedly different from those of Sema III. Interestingly, Sema VIa and Sema III frequently exhibit complementary or adjacent loci of expression. We suggest that Sema VIa may be important to nervous system development via a mechanism that involves cell-cell communication.

Amino Acid Sequence↗
PubMed1997

Introduction of a neurotrophin-3 transgene into muscle selectively rescues proprioceptive neurons in mice lacking endogenous neurotrophin-3.

To clarify the role of muscle-derived neurotrophin-3 (NT-3) in the development of sensory neurons, we generated transgenic mice selectively overexpressing NT-3 in skeletal muscles under the control of a myogenin promoter (myo-NT-3 mice). The myo-NT-3 transgene was then bred into an NT-3 null mutant (-/-) line to generate myo-NT-3, NT-3(-/-) mice in which NT-3 was expressed in muscles, but not elsewhere. Transient overexpression of NT-3 in developing muscles increased the number of proprioceptive neurons as well as the density of both their central and peripheral projections, resulting in more Ia afferents in spinal cord and more spindles (end organs of Ia afferents) in muscles. NT-3 expression restricted to muscles was sufficient to secure the development of proprioceptive neurons and their central and peripheral projections in myo-NT-3, NT-3(-/-) mice. The loss of nonproprioceptive neurons observed in NT-3(-/-) mice was not reversed by the transgene, suggesting that these neurons are regulated by NT-3 from sources other than muscle. We conclude that target-derived rather than intraganglionic NT-3 is preeminent in supporting the development of proprioceptive neurons. The level of NT-3 in developing muscles may be the principal factor determining the number of proprioceptive neurons in dorsal root ganglions and spindles in skeletal muscles of adults.

Afferent Pathways↗
PubMed1997

IB4-binding DRG neurons switch from NGF to GDNF dependence in early postnatal life.

We have tested the role of glial cell line-derived neurotrophic factor (GDNF) in regulating a group of putatively nociceptive dorsal root ganglion (DRG) neurons that do not express calcitonin gene-related peptide (CGRP) and that downregulate the nerve growth factor (NGF) receptor tyrosine kinase, TrkA, after birth. We show that mRNA and protein for the GDNF receptor tyrosine kinase, Ret, are expressed in the DRG in patterns that differ markedly from those of any of the neurotrophin receptors. Most strikingly, a population of small neurons initiates expression of Ret between embryonic day 15.5 and postnatal day 7.5 and maintains Ret expression into adulthood. These Ret-expressing small neurons are selectively labeled by the lectin IB4 and project to lamina IIi of the dorsal horn. Ret-expressing neurons also express the glycosyl-phosphatidyl inositol-linked (GPI-linked) GDNF binding component GDNFR-alpha and retrogradely transport 125I-GDNF, indicating the presence of a biologically active GDNF receptor complex. In vitro, GDNF supports the survival of small neurons that express Ret and bind IB4 while failing to support the survival of neurons expressing TrkA and CGRP. Together, our findings suggest that IB4-binding neurons switch from dependence on NGF in embryonic life to dependence on GDNF in postnatal life and are likely regulated by GDNF in maturity.

Aging↗
PubMed1997

Hematopoietic stem cells: challenges to expectations.

The past year provided a number of challenges to our expectations regarding hematopoietic stem cell (HSC) biology. Evidence has emerged that HSCs arise intraembryonically before they can be detected in the yolk sac. A number of genes that may regulate the formation, self-renewal, or differentiation of HSC have been identified. New markers for purifying HSCs have also been described. Although different groups have attributed different properties to HSCs, it now appears that the differences may be explained by variations in assay conditions rather than by differences in the HSCs themselves. Finally, insights have emerged into the complexity of the regulation of HSC proliferation and adhesion properties.

Animals↗
PubMed1997

From stem cells to lymphocytes: biology and transplantation.

We review the development of the hematopoietic system, focusing on the transition from hematopoietic stem cells (HSCs) to T cells. This includes the isolation of HSCs, and recent progress in understanding their ontogeny, homing properties, and differentiation. HSC transplantation is reviewed, including the kinetics of reconstitution, engraftment across histocompatibility barriers, the facilitation of allogeneic engraftment, and the mechanisms of graft rejection. We describe progress in understanding T-cell development in the bone marrow and thymus as well as the establishment of lymph nodes. Finally, the role of bcl-2 in regulating homeostasis in the hematopoietic system is discussed.

Animals↗
PubMed1997

Identification of a lineage of multipotent hematopoietic progenitors.

All multipotent hematopoietic progenitors in C57BL-Thy-1.1 bone marrow are divided among three subpopulations of Thy-1.1(lo) Sca-1+ Lin(-/lo) c-kit+ cells: long-term reconstituting Mac-1- CD4- c-kit+ cells and transiently reconstituting Mac-1(lo) CD4- or Mac-1(lo) CD4(lo) cells. This study shows that the same populations, with similar functional activities, exist in mice whose hematopoietic systems were reconstituted by hematopoietic stem cells after lethal irradiation. We demonstrate that these populations form a lineage of multipotent progenitors from long-term self-renewing stem cells to the most mature multipotent progenitor population. In reconstituted mice, Mac-1- CD4- c-kit+ cells gave rise to Mac-1(lo) CD4- cells, which gave rise to Mac-1(lo) CD4(lo) cells. Mac-1- CD4- c-kit+ cells had long-term self-renewal potential, with each cell being capable of giving rise to more than 10(4) functionally similar Mac-1- CD4- c-kit+ cells. At least half of Mac-1(lo) CD4- cells had transient self-renewal potential, detected in the spleen 7 days after reconstitution. Mac-1(lo) CD4(lo) cells did not have detectable self-renewal potential. The identification of a lineage of multipotent progenitors provides an important tool for identifying genes that regulate self-renewal and lineage commitment.

Animals↗
PubMed1996

Nerve growth factor regulates the expression of brain-derived neurotrophic factor mRNA in the peripheral nervous system.

Neurotrophins are profound regulators of neuronal survival in the developing peripheral nervous system and are synthesized by peripheral neurons themselves both during development and in maturity. Neuronal neurotrophin expression may be importantly related to survival of mature neurons, both in normal and pathological states. We show here that brain-derived neurotrophic factor (BDNF) gene expression in dorsal root ganglia is strongly stimulated in vivo by another neurotrophin, nerve growth factor (NGF). Furthermore, colocalization studies show that many BDNF-expressing sensory neurons also express trk A, the high-affinity NGF receptor. These results demonstrate a novel regulatory mechanism for neurotrophin gene expression and suggest a paracrine function for neurotrophins in mature animals.

Animals↗
PubMed1996

Focal expression of glial cell line-derived neurotrophic factor in developing mouse limb bud.

Glial cell line-derived neurotrophic factor (GDNF) is known to support the survival of motoneurons in vitro and in vivo, as well as subpopulations of sensory neurons in vitro. To clarify the mechanisms by which GDNF supports these neurons, we examined the patterns of GDNF mRNA expression in relation to motor and sensory axons during early stages of mouse development. Between embryonic days (E) 10 and 12, a time when motor and sensory axons are entering the periphery, GDNF mRNA is expressed at high levels in a restricted region in proximal limb buds where axons converge and enter the limb. At later ages (E14-16), GDNF mRNA was detected in non-neuronal cells along peripheral nerve, in dermis, and in some muscles. To characterize cells that express GDNF in the proximal limb, GDNF expression in the forelimb was compared to expression patterns of two markers of muscle, Pax 3 and myogenin, as well as with the pan neurotrophin receptor (p75) which is expressed by Schwann cell precursors. We show that expression of GDNF in the proximal limb bud at E11-12 does not correlate with markers of muscle or Schwann cell precursors, which supports the idea that GDNF is expressed by mesenchymal cells in this region. Our results suggest that GDNF expression in proximal limb buds may function as a transient survival factor, particularly for motor neurons, before they reach their final targets. GDNF expression in muscle and dermis at later stages suggests that GDNF may have additional functions as motor and sensory neurons mature.

Animals↗
PubMed1996

A new approach to exploring biases in educational assessment.

This paper presents and illustrates an approach to the study of marking biases based on multi-sample confirmatory factor analysis. This is applied to the marks awarded by two independent markers to the final year dissertations of 197 female and 58 male psychology undergraduates. One of the two markers had supervised the work on which the dissertation was based on a one-to-one basis. The results suggest that about 30 per cent of the variance in the supervisor's mark is attributable to influences which are specific to the supervisor, orthogonal to the merit of the project as assessed by the two markers jointly, and general across each of the four marks awarded by the supervisor. The most plausible interpretation of these influences is that they represent a contamination of the supervisor's mark by personal knowledge of the student. These biases in the supervisor's marking were found to have more influence for male than for female students and to elevate the marks of males relative to those of females to a small but significant extent. It would be unwise to overgeneralize from these findings, but they demonstrate the potential value of this method of studying marking biases.

Adult↗
PubMed1996

Organization of GnRH and FMRF-amide systems in two primitive bony fishes (order polypteriformes).

To investigate the evolution of the neural organization of gonadotropin-releasing hormone (GnRH), we have examined GnRH-immunoreactivity in two brachiopterygian fishes (Polypterus palmas and Calamoichthys calabaricus). Distal regions of the terminal nerve (TN) within the medial olfactory nerve contained clusters of GnRH-immunoreactive (ir) perikarya (< 10 microns). More proximal, isolated GnRH-ir neurons were present among TN fascicles as they penetrated the ventral forebrain, and a few ir neurons were observed accompanying GnRH-ir fibers in the rostromedial telencephalon. GnRH-ir neurons were not observed in the preoptic area or ventral hypothalamus. In contrast, a small group of GnRH-ir neurons was localized in the periventricular nucleus of the posterior tuberculum. GnRH-ir fibers were present in widespread areas of the brain, including the olfactory bulb, telencephalon, optic nerve, hypothalamus, thalamus, habenula, optic tectum, tegmentum, pituitary and spinal cord. To further characterize projections of TN neurons, we utilized antiserum to FMRF-amide, a small peptide produced by TN cells in other vertebrates. Perikarya that were FMRF-amide-ir within the TN were similar in distribution to GnRH-TN neurons, and the distribution of FMRF-amide-ir fibers overlapped those of GnRH-ir fibers, thus providing a useful marker for identifying TN projections. An additional population of FMRF-amide-ir neurons was present in the periventricular hypothalamus. Our results suggest that in the polypteriformes, GnRH and FMRF-amide neurons of the TN are similar to those observed in other vertebrates; however, the paucity of GnRH cells in the basal forebrain may be unique to primitive actinopterygians and elasmobranchs, and may result from the lack of migration of GnRH neurons into the forebrain, a phenomenon that likely occurs in all other vertebrate classes. Finally, the identification of GnRH-ir neurons in the posterior tuberculum is consistent with similar, and perhaps homologous, GnRH neurons present in nearly all other vertebrate classes.

Animals↗
PubMed1995

The guidance molecule semaphorin III is expressed in regions of spinal cord and periphery avoided by growing sensory axons.

The protein collapsin was purified from chick brain on the basis of its ability to inhibit sensory neuron growth cones, implicating this molecule in sensory axon guidance (Luo et al. [1993] Cell 75:217-227). To examine the relationship between collapsin and sensory axon growth, we examined the pattern of mRNA expression of collapsin's mammalian paralogue, Semaphorin III (Sema III), and compared it to dorsal root ganglion (DRG) axon pathways in the developing rat embryo. Centrally, DRG axons enter the spinal cord by embryonic (E) 11 and branch into the gray matter by E15 in brachial and thoracic regions. Laminar specific targets are reached by E17. Between E13 and E17, Sema III mRNA is expressed at high levels in the entire ventral half of the spinal cord except the floor plate. This pattern suggests that Sema III may inhibit non-proprioceptive sensory axons from penetrating the ventral spinal cord. Peripherally, sensory axons have entered the anterior sclerotome by E11 at all rostrocaudal levels. At this age, Sema III mRNA is already expressed in the dermamyotome and ventral aspect of the posterior sclerotome, areas which axons pass between but do not penetrate en route to their peripheral targets. From E12 to E15, the axons lengthen and branch into smaller fascicles which extend toward peripheral targets. During this time, Sema III mRNA is expressed by many mesodermal structures surrounding the axon fascicles, with highest levels observed in the dermamyotome, perinotochordal mesenchyme, pelvic girdle, and limb. As development proceeds, Sema III mRNA expression is quickly downregulated before disappearing by birth. Taken together, our results demonstrate that the gene for Sema III is expressed in central and peripheral regions which are avoided by growing DRG axons. These findings are consistent with the idea that Sema III inhibits growth and branching of axons into inappropriate areas during development.

Animals↗
PubMed1995

Neurotrophin receptor mRNA expression defines distinct populations of neurons in rat dorsal root ganglia.

The biological actions of neurotrophins are mediated by specific neurotrophin receptor tyrosine kinases (Trks). A low-affinity nerve growth factor (NGF) receptor, p75, appears to modulate sensitivity to neurotrophins in some neuronal populations. It has been recently demonstrated that genes encoding members of the Trk family are expressed in distinct patterns in the dorsal root ganglia (DRG; Mu et al. [1993] (J. Neurosci. 13:4029- 4041). However, the extent to which different neurotrophin receptor genes are coexpressed by individual DRG neurons is unknown. The question of coexpression is important since the expression of more than one member of the trk family by DRG neurons would suggest the potential for regulation by multiple neurotrophins. To address this question, a combination of isotopic and colorimetric in situ hybridization was performed on rat thoracic DRG using riboprobes specific for trkA, trkB, trkC, and p75. We show here that neurons that express trkA are largely distinct from those that express trkC, although there is a small subpopulation that expresses both of these genes. We also show that there is a distinct population of DRG neurons that expresses trkB and does not coexpress either trkA or trkC. P75 is expressed in almost all neurons that express trkA or trkB, but is coexpressed in only 50% of trkC-expressing neurons. Importantly, p75 is not expressed in DRG neurons independent of trk expression. Finally, a subpopulation of DRG neurons does not express any of the neurotrophin receptor mRNAs. Our results demonstrate that there are distinct populations of DRG neurons that express each member of the neurotrophin receptor tyrosine kinase family. Our findings of extensive colocalization of p75 with trkA and trkB lend support to the idea that p75 is important in mediating the actions of NGF and brain-derived neurotrophic factor on DRG neurons. Interestingly, however, p75 expression is clearly unimportant for a subpopulation of neurons that require neurotrophin-3. The fact that p75 is not expressed in the absence of trkA, trkB, or trkC suggests that the function of p75 is closely related to functions of the known neurotrophin-receptor tyrosine kinases. Finally, our results suggest that a significant percentage of DRG neurons may be regulated by non-neurotrophin neuronal growth factors.

Animals↗
PubMed1995

Comparative localization of serotonin1A, 1C, and 2 receptor subtype mRNAs in rat brain.

Serotonin (5-HT) mediates its effects on neurons in the central nervous system through a number of different receptor types. To gain better insight as to the localization of 5-HT responsive cells, the distribution of cells expressing mRNAs encoding the three 5-HT receptor subtypes 1A, 1C, and 2 was examined in rat brain with in situ hybridization using cRNA probes. 5-HT1A receptor mRNA labeling was most pronounced in the olfactory bulb, anterior hippocampal rudiment, septum, hippocampus (dentate gyrus and layers CA1-3), entorhinal cortex, interpeduncular nucleus, and medullary raphe nuclei. 5-HT1C receptor mRNA labeling was the most abundant and widespread of the three 5-HT receptor subtypes examined. Hybridization signal was densest in the choroid plexus, anterior olfactory nucleus, olfactory tubercle, piriform cortex, septum, subiculum, entorhinal cortex, claustrum, accumbens nucleus, striatum, lateral amygdala, paratenial and paracentral thalamic nuclei, subthalamic nucleus, substantia nigra, and reticular cell groups. 5-HT2 receptor mRNA was localized to the olfactory bulb, anterior hippocampal rudiment, frontal cortex, piriform cortex, entorhinal cortex, claustrum, pontine nuclei, and cranial nerve motor nuclei including the oculomotor, trigeminal motor, facial, dorsal motor nucleus of the vagus, and hypoglossal nuclei. The distributions of mRNAs for the three different 5-HT receptor subtypes overlap with regions that bind various 5-HT receptor-selective ligands and are present in nearly all areas known to receive serotonergic innervation. The results of this study demonstrate that neurons which express these 5-HT receptor subtypes are very widespread in the central nervous system, yet possess unique distributions within the rat brain. Moreover, previously unreported regions of 5-HT receptor subtype expression were observed, particularly with the 5-HT2 receptor riboprobe in the brainstem. Finally, several brain areas contain multiple 5-HT receptor subtype mRNAs, which leads to the possibility that individual cells may express more than one 5-HT receptor subtype.

Animals↗
PubMed1995

Expression of two new protein isoforms of the neurofibromatosis type 1 gene product, neurofibromin, in muscle tissues.

The neurofibromatosis type 1 (NF1) gene encodes a tumor suppressor protein, termed neurofibromin, which is expressed predominantly in neurons, Schwann cells, oligodendrocytes, and leukocytes. There are at least three isoforms of neurofibromin produced by the alternative use of exons 23a and 48a. Previously we described the identification of an NF1 mRNA isoform containing an additional 54 nucleotides from exon 48a (type 3 NF1) in human skeletal, cardiac and smooth muscle tissues by reverse-transcribed (RT)-PCR. To extend our initial observations, we have produced high titer chicken IgY antibodies which specifically recognize this muscle-specific neurofibromin isoform. An NF1 cDNA was generated containing human exon 48a sequences and expressed as a fusion protein in bacteria. The muscle-specific neurofibromin antibodies detected this exon 48a fusion protein by Western immunoblotting. Immunoprecipitation using these type 3 neurofibromin antibodies also specifically detected a 250 kDa protein in human and rat muscle tissues. Type 3 neurofibromin was found in rat heart and muscle, but not in liver brain, kidney or spleen with levels of expression declining after postnatal day 7. Expression of total NF1 RNA during rat embryonic development was detected at high levels in E15 heart, tongue, and limb bud. In addition, using type 2 neurofibromin-specific antibodies, the existence of a fourth isoform of neurofibromin (type 4 neurofibromin) containing both exon 23a and 48a sequences was demonstrated in rat heart muscle tissues. The identification of two muscle-specific isoforms of neurofibromin expands our definition of this important tumor suppressor protein and suggests additional roles for neurofibromin in muscle development and differentiation.

Amino Acid Sequence↗
PubMed1995

Increased expression of 5HT2 receptor mRNA in rat striatum following 6-OHDA lesions of the adult nigrostriatal pathway.

Neonatal destruction of the dopaminergic nigrostriatal system with the specific neurotoxin 6-hydroxydopamine (6-OHDA) leads to increases in several components of the adult serotonergic raphe-striatal system. Although results following similar lesions of adult ventral midbrain dopaminergic neurons are less consistent, increases in striatal serotonin (5-hydroxytryptamine; 5HT) fiber density, content, and metabolites have been reported. The effect of such lesions upon gene expression for striatal 5HT receptors, however, has not been determined. The purpose of the present study was to investigate possible changes in expression of several 5HT receptor mRNAs in rat striatum following destruction of the adult nigrostriatal pathway. In situ hybridization for 5HT1A, 5HT1C, and 5HT2 receptor subtype mRNAs was performed in rat striatum following unilateral injection of 6-OHDA into the medial forebrain bundle or directly into the ventral midbrain. Compared to the uninjected control side, a significant increase in the hybridization density for 5HT2 receptor mRNA was observed in the caudate-putamen ipsilateral to the 6-OHDA lesion (P < 0.05). In contrast, no significant changes in the hybridization densities for 5HT1A or 5HT1C receptor mRNAs were detected. The observed increase in striatal 5HT2 receptor mRNA levels after the dopamine-depleting lesion provides evidence for plasticity of the serotonergic raphe-striatal system in the adult rat at the level of striatal gene expression. Furthermore, the present data indicate that dopaminergic mechanisms differentially regulate the expression of 5HT receptor mRNAs in adult rat striatum.

Animals↗