Biomedical subjects

J A Helms

Publications and source records attributed to J A Helms.

29 records · Page 2Linked to original sources

PubMed1998

LMP-1, a LIM-domain protein, mediates BMP-6 effects on bone formation.

Glucocorticoids can promote osteoblast differentiation from fetal calvarial cells and bone marrow stromal cells. We recently reported that glucocorticoid specifically induced bone morphogenetic protein-6 (BMP-6), a glycoprotein signaling molecule that is a multifunctional regulator of vertebrate development. In the present study, we used fetal rat secondary calvarial cultures to determine genes induced during early osteoblast differentiation as initiated by glucocorticoid treatment. Glucocorticoid, and subsequently BMP-6, was found to induce a novel rat intracellular protein, LIM mineralization protein-1 (LMP-1), that in turn resulted in synthesis of one or more soluble factors that could induce de novo bone formation. Blocking expression of LMP-1 using antisense oligonucleotide prevented osteoblast differentiation in vitro. Overexpression of LMP-1 using a mammalian expression vector was sufficient to initiate de novo bone nodule formation in vitro and in sc implants in vivo. These data demonstrate that LMP-1 is an essential positive regulator of the osteoblast differentiation program as well as an important intermediate step in the BMP-6 signaling pathway.

Adaptor Proteins, Signal Transducing↗

PubMed1997

Neuronal pentraxin receptor, a novel putative integral membrane pentraxin that interacts with neuronal pentraxin 1 and 2 and taipoxin-associated calcium-binding protein 49.

We have identified the first putative integral membrane pentraxin and named it neuronal pentraxin receptor (NPR). NPR is enriched by affinity chromatography on columns of a snake venom toxin, taipoxin, and columns of the taipoxin-binding proteins neuronal pentraxin 1 (NP1), neuronal pentraxin 2 (NP2), and taipoxin-associated calcium-binding protein 49 (TCBP49). The predominant form of NPR contains an putative NH2-terminal transmembrane domain and all forms of NPR are glycosylated. NPR has 49 and 48% amino acid identity to NP1 and NP2, respectively, and NPR message is expressed in neuronal regions that express NP1 and NP2. We suggest that NPR, NP1, NP2, and TCBP49 are involved in a pathway responsible for the transport of taipoxin into synapses and that this may represent a novel neuronal uptake pathway involved in the clearance of synaptic debris.

Amino Acid Sequence↗

PubMed1997

Sonic hedgehog participates in craniofacial morphogenesis and is down-regulated by teratogenic doses of retinoic acid.

The face is one of the most intricately patterned structures in human and yet little is known of the mechanisms by which the tissues are instructed to grow, fuse, and differentiate. We undertook a study to determine if the craniofacial primordia used the same molecular cues that mediate growth and patterning in other embryonic tissues such as the neural tube and the limb. Here we provide evidence for the presence of organizer-like tissues in the craniofacial primordia. These candidate organizers express the polarizing signal sonic hedghog (shh) and its putative receptor, patched, as well as fibroblast growth factor 8 and bone morphogeneic protein 2. Shh-expressing epithelial grafts functioned as organizing tissues in a limb bud assay system, where they evoked duplications of the digit pattern. High doses of retinoic acid, which are known to truncate the growth of the frontonasal and maxillary processes and thus produce bilateral clefting of the lip and palate, inhibited the expression of shh and patched but not fgf8, in the craniofacial primordia, and abolished polarizing activity of these tissues. From these studies we conclude that the embryonic face contains signaling centers in the epithelium that participate in craniofacial growth and patterning. In addition, we discuss a novel mechanism whereby retinoids can exert a teratogenic effect on craniofacial morphogenesis independent of its effects on Hox gene expression or neural crest cell migration.

Animals↗

PubMed1997

Seasonal variation of gas exchange and pigmentation in branches of three grafted clones of mature ponderosa pine exposed to ozone and acid rain.

Gas exchange and pigmentation responses of mature ponderosa pine (Pinus ponderosa Laws.) branches to ozone and acid rain exposure were investigated using three grafted clones growing in a managed seed orchard. Exposure of one-year-old foliage to twice ambient ozone (2 x AMB) resulted in significant decreases in net photosynthesis (Pn), stomatal conductance (gsw) and pigmentation relative to charcoal-filtered (CF) and ambient (AMB) ozone treatments. Ozone effects on gas exchange and pigmentation were most pronounced during late-season and differed significantly among clones. Environmental parameters (e.g. light, vapor pressure deficit, and temperature) accounted for more variation in Pn than did cumulative ozone exposure. Minimal differences in gsw and Pn among ozone treatments occurred during seasonal periods of high temperature and evaporative demand. Negative effects of 2 x AMB ozone on gsw and pigmentation were greatest for the clones having highest and lowest phenotypic vigor under ambient conditions; the clone of moderate phenotypic vigor under ambient conditions was least sensitive to ozone. Application of simulated acid rain of pH 3.0, pH 5.1 or no rain (NR) had little impact on gas exchange or pigmentation.

Journal Article↗

PubMed1997

Expression of indian hedgehog, bone morphogenetic protein 6 and gli during skeletal morphogenesis.

A complex signaling pathway involving members of the Hedgehog, Bone morphogenetic protein (Bmp) and Gli families regulates early patterning events in fetal skeletogenesis (Hui and Joyner, 1993. A mouse model of Greig cephalopolysyndactyly syndrome: the extra-toes mutation contains an intragenic deletion of the Gli3 gene. Nat. Genet. 3, 241-246; Bitgood and McMahon, 1995. Hedgehog and Bmp genes are coexpressed at many diverse sites of cell-cell interaction in the mouse embryo. Dev. Biol. 172, 126-138; Lanske et al., 1996. PTH/PTHrP receptor in early development and Indian hedgehog-regulated bone growth. Science 273, 663-666; Vortkamp et al., 1996. Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein. Science 273, 613-622). Hedgehog genes encode secreted proteins that mediate patterning and growth through the induction of secondary signals (reviewed in Hammerschmidt et al., 1997. The world according to hedgehog. Trends Genet. 13, 14-21). Two potential targets of Ihh are bmp6 and gli (Johnson et al., 1995. Patched overexpression alters wing disc size and pattern: transcriptional and post-transcriptional effects on hedgehog targets. Development 121, 4161-4170; Dominguez et al., 1996. Sending and receiving the hedgehog signal: control by the Drosophila Gli protein Cubitus interruptus. Science 272, 1621-1625; Marigo et al., 1996. Sonic hedgehog differentially regulates expression of GLI and GLI3 during limb development. Dev. Biol. 180, 273-283). We investigated the molecular similarities and differences between fetal and postnatal skeletal development by analyzing the coincident and complimentary expression domains of indian hedgehog (ihh), bmp6 and gli in adjacent sections throughout the process of skeletogenesis. In almost all of the skeletal tissues examined, the expression domains of ihh and bmp6 were adjacent to one another and this region was surrounded by gli-expressing cells. These observations are in keeping with the proposed function of gli as a negative regulator of Ihh signaling and the induction of Bmps by Hedgehog proteins (Roberts et al., 1995. Sonic hedgehog is an endodermal signal inducing Bmp-4 and Hox genes during induction and regionalization of the chick hindgut. Development 121, 3163-3174; Kawakami et al., 1996. BMP signaling during bone pattern determination in the developing limb. Development 122, 3557-3566). By puberty, ihh, bmp6 and gli transcripts were no longer detected in the growth plate, despite the fact that physeal chondrocytes continued to hypertrophy and differentiate. Although bmp6 was expressed, ihh transcripts were not found in primordia of intramembranous bones, nor in cells lining the future articular surfaces. Collectively our findings suggest that ihh participates in, but is not required for chondrocyte hypertrophy.

Animals↗

PubMed1996

Effects of simulated acid rain and ozone on foliar chemistry of field-grown Pinus ponderosa seedlings and mature trees.

We investigated the additive and interactive effects of simulated acid rain and elevated ozone on C and N contents, and the C:N ratio of one-year-old and current-year foliage of field-grown mature trees and their half-sib seedlings of a stress tolerant genotype of ponderosa pine. Acid rain levels (pH 5.1 and 3.0) were applied weekly to foliage only (no soil acidification or N addition), from January to April, 1992. Plants were exposed to two ozone levels (ambient and twice-ambient) during the day from September 1991 to November 1992. The sequential application of acid rain and elevated ozone mimicked the natural conditions. Twice-ambient ozone significantly decreased foliar N content (by 12-14%) and increased the C:N ratio of both one-year-old and current-year foliage of seedlings. Although similar ozone effects were also observed on one-year-old foliage of mature trees, the only statistically significant effect was an increased C:N ratio when twice-ambient ozone combined with pH 3.0 rain (acid rain by ozone interaction). Enhancing the effect of twice-ambient ozone in increasing the C:N ratio of one-year-old foliage of mature trees in June was the only significant effect of acid rain.

Journal Article↗

PubMed1996

Retinoic acid signaling is required during early chick limb development.

In the chick limb bud, the zone of polarizing activity controls limb patterning along the anteroposterior and proximodistal axes. Since retinoic acid can induce ectopic polarizing activity, we examined whether this molecule plays a role in the establishment of the endogenous zone of polarizing activity. Grafts of wing bud mesenchyme treated with physiologic doses of retinoic acid had weak polarizing activity but inclusion of a retinoic acid-exposed apical ectodermal ridge or of prospective wing bud ectoderm evoked strong polarizing activity. Likewise, polarizing activity of prospective wing mesenchyme was markedly enhanced by co-grafting either a retinoic acid-exposed apical ectodermal ridge or ectoderm from the wing region. This equivalence of ectoderm-mesenchyme interactions required for the establishment of polarizing activity in retinoic acid-treated wing buds and in prospective wing tissue, suggests a role of retinoic acid in the establishment of the zone of polarizing activity. We found that prospective wing bud tissue is a high-point of retinoic acid synthesis. Furthermore, retinoid receptor-specific antagonists blocked limb morphogenesis and down-regulated a polarizing signal, sonic hedgehog. Limb agenesis was reversed when antagonist-exposed wing buds were treated with retinoic acid. Our results demonstrate a role of retinoic acid in the establishment of the endogenous zone of polarizing activity.

Animals↗

PubMed1995

Effects of chlorhexidine on human taste perception.

Chlorhexidine gluconate at a dose used to control bacteria in the mouth has a reversible effect on taste perception. Taste-intensity ratings and taste-quality identification for concentration series of sucrose, sodium chloride, citric acid and quinine hydrochloride were obtained from 15 healthy humans. The participants rinsed with 0.12% chlorhexidine for 3 min twice a day. Each individual was tested 3 times: before the 4-day rinse period, 30 min after the final rinse, and 4 days after the rinse period. Chlorhexidine rinses reduced the perceptual intensity of sodium chloride and quinine hydrochloride, not sucrose or citric acid. No effects on taste perception were detected 4 days after the rinse period. The identification of sodium chloride as salty was seriously impaired by chlorhexidine but the identification of quinine hydrochloride as bitter was not affected. Specific sites of action of chlorhexidine on the taste epithelium are not known but its effects on salty taste may be related to its strong positive charge and its effect on bitter taste may be related to its amphiphilicity. Chlorhexidine has promise as a probe of taste transduction, as well as for the management of salty/bitter dysgeusias in humans.

Adult↗

PubMed1995

Neuronal pentraxin, a secreted protein with homology to acute phase proteins of the immune system.

We have identified, by affinity chromatography, a binding protein for the snake venom toxin taipoxin. The sequence of this 47 kDa protein is unique, is characteristic of a secreted protein, and has homology to the acute phase proteins serum amyloid P protein and C-reactive protein of the pentraxin family. We have named this protein neuronal pentraxin (NP), as Northern analysis and in situ hybridization demonstrate high message levels in neurons of cerebellum, hippocampus, and cerebral cortex. Because NP may be released synaptically and has homology to immune proteins potentially involved in uptake of lipidic, toxic, or other antigenic material, we suggest that NP may be involved in a general uptake of synaptic macromolecules.

Amino Acid Sequence↗

PubMed1994

Cloning and analysis of a new developmentally regulated member of the basic helix-loop-helix family.

We have isolated a basic helix-loop-helix (bHLH) family member from an embryonic chick-brain cDNA library. This 3.86-Kb cDNA, GbHLH1.4, exhibits extensive sequence similarity in the bHLH domain with Drosophila daughterless and the vertebrate cDNAs E12 and HTF4. Outside of the bHLH region the similarity is significantly reduced. GbHLH1.4 recognizes a 4.0-Kb mRNA and in situ hybridization analysis shows that GbHLH1.4 mRNA is widely expressed at early stages of development but becomes progressively restricted as embryogenesis proceeds. At later stages of embryonic development, mRNA transcripts are localized to several structures including the ventricular layers of the spinal cord and brain, the facial primordia, dorsal root ganglia and heart muscle and cardiac valves. Strikingly, GbHLH1.4 expression in chick embryos exhibits significant overlap with that reported for the murine negative HLH regulator, Id.

Amino Acid Sequence↗

PubMed1987

Effect of timing on long-term clinical success of alveolar cleft bone grafts.

Despite the almost universal agreement on the desirability of bone grafting in the cleft alveolar process, there are little long-term data to support preference for grafting at one time versus another. Investigation was undertaken to compare the clinical success of grafts placed at three distinct developmental stages: the "primary" group consisting of 20 rib grafts placed at less than 1 year of age; the "secondary" group consisting of 19 iliac crest grafts placed when the permanent canine was one fourth to one half formed; and the "delayed" group consisting of 18 iliac crest grafts placed after eruption of the permanent canines. Patients were a minimum of 15 years of age at time of final evaluation. Records were made a minimum of 5 years postsurgery. Biometric data and periapical x-ray films were evaluated. There was a trend for the delayed group to have a decreased incidence of successful bony bridging of the graft site compared with the other treatment groups. The primary group exhibited significantly (P less than 0.001) greater ridge height and increased bone attachment than the secondary and delayed groups. There were significantly fewer teeth lost adjacent to the cleft for the primary group compared with the secondary and delayed groups. Before orthodontic treatment, there were no significant differences among groups in incidence of anterior crossbite; posterior crossbites were seen more frequently in the secondary and delayed graft groups than in the primary group (P less than 0.001). At final evaluation, there were significantly fewer anterior and posterior crossbites in the primary group than in the secondary and delayed groups (P less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗