Richard G. Wehby

Bio: Richard G. Wehby is an academic researcher from University of Connecticut Health Center. The author has contributed to research in topics: Neural crest & Stimulus (physiology). The author has an hindex of 3, co-authored 3 publications receiving 131 citations.

Number of adrenergic and islet-1 immunoreactive cells is increased in avian trunk neural crest cultures in the presence of human recombinant osteogenic protein-1.

Abstract: OP-1, also known as BMP-7, is a member of the TGF-β superfamily of proteins and was originally identified on the basis of its ability to induce new bone formation in vivo. OP-1 mRNA is found in the developing kidney and adrenal gland as well as in some brain regions (Ozkaynak et al. [1991] Biochem. Biophys. Res. Commun. 179:116–123). We have tested the effect of recombinant human OP-1 on quail trunk neural crest cultures. The number of catechol-amine-positive cells which developed after 7 days in vitro in the presence of OP-1 was increased in a dose-dependent manner, with a greater than 100-fold maximal stimulation observed. The increase in the number of catecholamine-positive cells in the presence of OP-1 was paralleled by an increase in the number of tyrosine hydroxylase (TH)-positive cells. In contrast, total and melanocyte cell number were unaffected by the presence of OP-1. The number of Islet-1-immunoreactive cells was also increased by OP-1, but to only about half the value seen for TH. Double label experiments revealed these Islet-1-positive cells were a subset of the TH-positive cells. Inhibitors of DNA synthesis prevented the OP-1-mediated increase in adrenergic cell number, indicating that OP-1 does not act on a postmitotic cell population. However, labeling studies with bromodeoxyuridine indicated that OP-1 did not increase the proportion of the cell population engaged in DNA synthesis. Thus, the OP-1-mediated increase in adrenergic cell number most likely occurs as a result of the enhanced survival of a subpopulation of adrenergic precursors or an increase in their probability of adrenergic differentiation, but not by increasing the mitotic rate of adrenergic precursors or adrenergic cells themselves. In contrast to OP-1, TGF-β1 decreased adrenergic cell number. When OP-1 and TGF-β1 were added simultaneously, TGF-β1 antagonized the OP-1-mediated increase in adrenergic cell number in a dose-dependent manner. �1995 Wiley-Liss, Inc.

NOS- and Non-NOS NADPH Diaphorases in the Insular Cortex of the Syrian Golden Hamster

Abstract: SUMMARY We had previously shown NADPH diaphorase activity in fixed tissue slices of the insular cortex of the Syrian golden hamster (Mesocricetus auratus). The objective of this work was to determine the chemical identity of agents responsible for the observed NADPH diaphorase activities. Three different enzymatic NADPH diaphorase activities were distinguished in the insular cortex. (a) The activity seen in endothelial cells was not characterized histochemically, but it co-localized with eNOS-like immunoreactivity. (b) The neuronal Type I activity showed little sensitivity to 10 � 5 M dicoumarol, could use either � - or � -NADPH with almost equal facility, and co-localized with nNOS-like immunoreactivity. This activity was primarily attributable to nNOS. (c) The neuronal Type II activity was greatly attenuated by 10 � 5 M dicoumarol, had a strong preference for � -NADPH (rather than � -NADPH), and did not co-localize with any NOS-like immunoreactivity. These characteristics also apply to the NADPH diaphorase activity observed in the diffuse blue band in Layers II and III of agranular and dysgranular insular cortex and in the meshwork of cortical fibers. This staining was due primarily to a dicoumarol-sensitive dehydrogenase(s), either an isozyme of DT diaphorase (EC 1.6.99.2), or NADPH dehydrogenase (quinone) (EC 1.6.99.6), or to a novel dicoumarol-sensitive NADPH dehydrogenase. (J Histochem Cytochem 47:197–207, 1999)

Histochemistry, Theoretical and Applied.

Abstract: municable disease control to the newer responsibilities of the hazards of ionizing radiation and medical defense against atomic attack. The individual topics are adequately developed with emphasis, in the majority, on brevity of presentation rather than complete and exhaustive detail. References are listed after each chapter for the reader desiring more definitive information. \"Epidemiologic Methods and Inferences\" by Dr. Dienfeld and \"Official and Voluntary Health Agencies\" by Dr. Hilleboe are two chapters which offer especially well-organized, succinct, and effective discussions of their respective subjects. The editors state in their preface that they are presenting \". . a new way to look at preventive medicine for the medical students, general practitioners, specialists, and professional workers in official and voluntary health agencies.\" In the opinion of the reviewer, the authors have achieved their purpose by editing a book which is more an introductory text than a reference tome.

Overlapping expression domains of bone morphogenetic protein family members potentially account for limited tissue defects in BMP7 deficient embryos

Abstract: BMP7 is expressed at diverse sites in the developing mouse embryo, including visceral endoderm, notochord, heart, eye, kidney, and bone. A null mutation in BMP7 results in defects largely confined to the developing kidney and eye. To examine whether other bone morphogenetic protein (BMP) family members potentially substitute for BMP7 in mutant embryos, thereby restricting the observed defects, we analyzed the expression patterns of BMP2 through BMP7 in wild-type and mutant tissues. In the central nervous system and heart, which develop normally in the absence of BMP7 signaling, expression domains of other BMP family members completely overlap with that of BMP7. The variable expressivity of the eye defect correlates with partially overlapping BMP4 and BMP7 expression domains during early eye induction. The loss of BMP7 signaling in the kidney results in apoptosis in the metanephric mesenchyme, a cell population that exclusively expresses BMP7. Thus, tissue defects observed in BMP7 deficient embryos are restricted to cell populations exclusively expressing BMP7. These data suggest that BMP family members can functionally substitute for BMP7 at sites where they colocalize in vivo.

Culture in Reduced Levels of Oxygen Promotes Clonogenic Sympathoadrenal Differentiation by Isolated Neural Crest Stem Cells

Abstract: Isolated neural crest stem cells (NCSCs) differentiate to autonomic neurons in response to bone morphogenetic protein 2 (BMP2) in clonal cultures, but these neurons do not express sympathoadrenal (SA) lineage markers. Whether this reflects a developmental restriction in NCSCs or simply inappropriate culture conditions was not clear. We tested the growth and differentiation potential of NCSCs at ∼5% O_2, which more closely approximates physiological oxygen levels. Eighty-three percent of p75^+P_0 ^− cells isolated from embryonic day 14.5 sciatic nerve behaved as stem cells under these conditions, suggesting that this is a nearly pure population. Furthermore, addition of BMP2 plus forskolin in decreased oxygen cultures elicited differentiation of thousands of cells expressing tyrosine hydroxylase, dopamine-β-hydroxylase, and the SA lineage marker SA-1 in nearly all colonies. Such cells also synthesized and released dopamine and norepinephrine. These data demonstrate that isolated mammalian NCSCs uniformly possess SA lineage capacity and further suggest that oxygen levels can influence cell fate. Parallel results indicating that reduced oxygen levels can also promote the survival, proliferation, and catecholaminergic differentiation of CNS stem cells (Studer et al., 2000) suggests that neural stem cells may exhibit a conserved response to reduced oxygen levels.