Search PubMed⌕ Search

Biomedical subjects

R L Erickson

Publications and source records attributed to R L Erickson.

At least 19 recordsLinked to original sources
PubMed2001

p300 coactivates the adipogenic transcription factor CCAAT/enhancer-binding protein alpha.

Despite the knowledge that CCAAT/enhancer-binding protein alpha (C/EBPalpha) plays an important role in preadipocyte differentiation, our understanding of how C/EBPalpha interacts with nuclear proteins to regulate transcription is limited. Based on the hypothesis that evolutionarily conserved regions are functionally important and likely to interact with coactivators, we compared the amino acid sequence of C/EBPalpha from different species (frog to human) and identified four highly conserved regions (CR1-CR4) within the transactivation domain. A series of amino-terminal truncations and internal deletion constructs were made creating forms of C/EBPalpha which lack single or multiple conserved regions. To determine which regions of the C/EBPalpha transactivation domain are important in its ability to induce spontaneous differentiation of 3T3-L1 preadipocytes, we infected preadipocytes with expression vectors encoding the C/EBPalpha conserved region mutants and observed their ability to induce differentiation. We found that CR2 fused to the DNA binding domain is able to induce spontaneous differentiation independent of the other conserved regions. However, CR2 was not necessary for the adipogenic action of C/EBPalpha because a combination of CR1 and CR3 can also induce adipogenesis. Because the transcriptional coactivator p300 participates in the signaling of many transcription factors to the basal transcriptional apparatus, we examined whether functional interaction exists between C/EBPalpha and p300. Cotransfection of p300 with p42C/EBPalpha results in a synergistic increase in leptin promoter activity, indicating that p300 acts as a transcriptional coactivator of C/EBPalpha. Analyses using C/EBPalpha conserved region mutants suggest that multiple regions (CR2 and CR3) of the C/EBPalpha transactivation domain functionally interact with p300.

3T3 Cells↗
PubMed2001

A fluoride-releasing composite for dental applications.

OBJECTIVES: The aim of this work was to attempt formulation of a dental composite, for investigational purposes, which will release fluoride at a rate comparable to glass ionomer materials, while retaining physical properties adequate for potential use in a number of dental applications. METHODS: An organic fluoride material, tetrabutylammonium tetrafluoroborate (TBATFB), was incorporated into a hydrophilic monomer system made of 2,2-bis[4-(2-hydroxy-3-methacroyloxypropoxy)phenyl]-propane (BisGMA) and 2-hydroxyethyl methacrylate (HEMA). This fluoride-containing monomer system was filled with silane treated quartz to 81 wt%. The resultant material was tested for fluoride release, physical strength properties and bond strength to enamel, each in comparison to control materials. RESULTS: Cumulative fluoride release from the experimental composite was approximately linear over time and comparable to glass ionomer materials. The long term rate of release exceeded several of the glass ionomer materials tested. Diametral tensile strength was comparable to resin-modified glass ionomer (RMGI) materials. Bond strength to etched enamel was statistically equivalent to a commercially available hybrid composite control. SIGNIFICANCE: The experimental resin-based composite material could potentially be used as an alternative to glass ionomer materials in non-stress bearing restorative applications and for orthodontic bracket bonding, where high fluoride release is desirable.

Acid Etching, Dental↗
PubMed2001

Effect of enamel pretreatments on bond strength of compomer.

OBJECTIVES: The objective of this study was to evaluate the effect of various enamel surface treatments on the bond strength of a compomer to enamel. METHODS: Ground bovine enamel specimens were divided into four groups. A compomer (F2000, 3M) was bonded to the specimens using different enamel surface treatments. Two groups examined the effect of application of the F2000 self-etching primer/adhesive (3M) with respect to static or dynamic priming. A third examined use of the primer/adhesive after phosphoric acid etching, and the fourth (control) group provided bond strength of the compomer to phosphoric acid etched enamel with a resin bonding system (Single Bond, 3M). Shear bond strengths for the specimens were measured after 24h storage in water at 37 degrees C. Effects of the various surface treatments on enamel were examined by SEM. RESULTS: Significant differences in bond strength of compomer to enamel were found that were related to the various surface pretreatments. Dynamic priming resulted in higher enamel bond strengths than static priming, and the best bond strengths were obtained when the enamel was etched with phosphoric acid. SEM analysis showed that depth of etch and resin penetration was also directly related to the bond strengths measured. SIGNIFICANCE: Bond strength of compomer to enamel is significantly affected by the method of pretreatment of the enamel.

Acid Etching, Dental↗
PubMed2000

Inhibition of adipogenesis by Wnt signaling.

Wnts are secreted signaling proteins that regulate developmental processes. Here we show that Wnt signaling, likely mediated by Wnt-10b, is a molecular switch that governs adipogenesis. Wnt signaling maintains preadipocytes in an undifferentiated state through inhibition of the adipogenic transcription factors CCAAT/enhancer binding protein alpha (C/EBPalpha) and peroxisome proliferator- activated receptor gamma (PPARgamma). When Wnt signaling in preadipocytes is prevented by overexpression of Axin or dominant-negative TCF4, these cells differentiate into adipocytes. Disruption of Wnt signaling also causes transdifferentiation of myoblasts into adipocytes in vitro, highlighting the importance of this pathway not only in adipocyte differentiation but also in mesodermal cell fate determination.

3T3 Cells↗
PubMed2000

Induction of the peroxisomal glycerolipid-synthesizing enzymes during differentiation of 3T3-L1 adipocytes. Role in triacylglycerol synthesis.

The glycerophosphate backbone for triglyceride synthesis is commonly believed to be created through the conversion of dihydroxyacetone phosphate (DHAP) by glycerophosphate dehydrogenase (GPD) to sn-glycerol 3-phosphate (GP), which is then converted by glycerophosphate acyltransferase (GPAT) to 1-acyl-GP. Consistent with this, GPD and GPAT are highly induced during differentiation of mouse 3T3-L1 preadipocytes. While the acyl dihydroxyacetone phosphate (acyl-DHAP) pathway for glycerolipid synthesis is commonly believed to be involved only in glycerol ether lipid synthesis, we report here that during conversion of 3T3-L1 preadipocytes to adipocytes, the specific activity of peroxisomal DHAP acyltransferase (DHAPAT) is increased by 9-fold in 6 days, while acyl-DHAP:NADPH reductase is induced by 5-fold. A parallel increase in the catalase (the peroxisomal marker enzyme) activity is also seen. In contrast, the specific activity of alkyl-DHAP synthase, the enzyme catalyzing the synthesis of the ether bond, is decreased by 60% during the same period. Unlike microsomal GPAT, the induced DHAPAT is found to have high activity at pH 5.5 and is resistant to inhibition by sulfhydryl agents, heat, and proteolysis. On subcellular fractionation, DHAPAT is found to be associated with microperoxisomes whereas GPAT activity is mainly present in microsomes. Northern blot analyses reveal that induction of DHAPAT can be largely explained through increases in DHAPAT mRNA. A comparison of microsomal and peroxisomal glycerolipid synthetic pathways, using D-[3-(3)H, U-(14)C]glucose as the precursor of the lipid glycerol backbone shows that about 40-50% of triglyceride is synthesized via the acyl-DHAP pathway. These results indicate that the acyl-DHAP pathway is important not only for the synthesis of ether lipids, but also for the synthesis of triacylglycerol and other non-ether glycerolipids.

3T3 Cells↗
PubMed1999

Glycogen synthase kinase 3 is an insulin-regulated C/EBPalpha kinase.

CCAAT/enhancer binding protein alpha (C/EBPalpha) is a transcription factor involved in creating and maintaining the adipocyte phenotype. We have shown previously that insulin stimulates dephosphorylation of C/EBPalpha in 3T3-L1 adipocytes. Studies to identify the insulin-sensitive sites of phosphorylation reveal that a C/EBPalpha peptide (amino acids H215 to K250) is phosphorylated on T222, T226, and S230 in vivo. The context of these phosphoamino acids implicates glycogen synthase kinase 3 (GSK3), whose activity is known to be repressed in response to insulin, as a potential kinase for phosphorylation of T222 and T226. Accordingly, GSK3 phosphorylates the predicted region of C/EBPalpha on threonine in vitro, and GSK3 uses C/EBPalpha as a substrate in vivo. In addition, the effect of pharmacological agents on GSK3 activity correlates with regulation of C/EBPalpha phosphorylation. Treatment of 3T3-L1 adipocytes with the phosphatidylinositol 3-kinase inhibitor wortmannin results in phosphorylation of C/EBPalpha, whereas treatment with the GSK3 inhibitor lithium results in dephosphorylation of C/EBPalpha. Collectively, these data indicate that insulin stimulates dephosphorylation of C/EBPalpha on T222 and T226 through inactivation of GSK3. Since dephosphorylation of C/EBPalpha in response to lithium is blocked by okadaic acid, strong candidates for the T222 and T226 phosphatase are protein phosphatases 1 and 2a. Treatment of adipocytes with insulin alters the protease accessibility of widespread sites within the N terminus of C/EBPalpha, consistent with phosphorylation causing profound conformational changes. Finally, phosphorylation of C/EBPalpha and other substrates by GSK3 may be required for adipogenesis, since treatment of differentiating preadipocytes with lithium inhibits their conversion to adipocytes.

3T3 Cells↗
PubMed1999

Clinical performance and caries inhibition of resin-modified glass ionomer cement and amalgam restorations.

BACKGROUND: The authors clinically examined two restorative materials to evaluate their effectiveness in Class II restorations in primary molars and their ability to inhibit recurrent caries. METHODS: Forty subjects, each in need of two Class II restorations in primary molars, took part in this study. Each patient received one Class II restoration of resin-modified glass ionomer cement and one of amalgam. The authors evaluated the restorations at six-month, one-year, two-year and three-year recall appointments. On exfoliation, teeth with experimental restorations were retrieved and microscopically examined for inhibition of demineralization at restoration margins. RESULTS: The results of the clinical evaluation demonstrated no significant differences between the resin-modified glass ionomer cement restorations and the amalgam restorations (P < .05). Polarized light microscopic examination of the returned teeth that were restored as a part of this study indicated that the resin-modified glass ionomer cement had significantly less enamel demineralization at restoration margins than did amalgam (P < .0001). CONCLUSIONS: The resin-modified glass ionomer cement functioned clinically as well as amalgam for Class II restorations in primary molars. However, the resin-modified glass ionomer exhibited significantly less enamel demineralization at restoration margins than did amalgam. CLINICAL IMPLICATIONS: Resin-modified glass ionomer cement restorative material functions well for Class II restorations in primary molars and exhibits less recurrent caries at restoration margins than does amalgam.

Cariostatic Agents↗
PubMed1999

Protective effects of resin impregnation on demineralization of enamel.

PURPOSE: To determine if resin penetrated into the enamel etch pattern, in the absence of a polymerized outer surface film, could reduce the degree of demineralization of enamel subjected to a simulated caries challenge, and to evaluate whether the addition of fluoride to the resin would enhance reductions in demineralization. MATERIALS AND METHODS: Enamel surfaces of extracted human incisors were acid-etched. One-half of the etched area was treated with an unfilled bonding resin, while the other one-half was left untreated as a control. In another group, this same procedure was followed except the unfilled bonding resin contained fluoride. The applied resin was aggressively air thinned to ensure oxygen inhibition throughout the external surface film thickness. The thinned film was visible light-cured and the area was wiped with an ethanol swab to remove the inhibited layer. The specimens were exposed to a buffer solution of pH = 4.7 for 4 days, and were sectioned and examined by polarized light microscopy and microradiography. RESULTS: In each of the two test groups, the demineralization of the resin-treated side was significantly lower than the control side (P < 0.015). Under the conditions of this study, the experimental fluoride resin did not produce statistically significant reductions in demineralization compared with the non-fluoride resin.

Acid Etching, Dental↗
PubMed1998

Regulation of CCAAT/enhancer binding protein alpha (C/EBP alpha) gene expression by thiazolidinediones in 3T3-L1 adipocytes.

Thiazolidinediones are a class of antidiabetic drugs that induce preadipocyte differentiation by binding and activating peroxisome proliferator-activated receptor gamma 2. Although thiazolidinediones are commonly thought of as insulin-sensitizing agents, these drugs have opposing and antagonistic effects to that of insulin on CCAAT/enhancer binding protein alpha (C/EBP alpha) gene expression in fully differentiated 3T3-L1 adipocytes. Thiazolidinediones induce expression of C/EBP alpha mRNA and protein, while insulin stimulates a rapid decline in C/EBP alpha mRNA and protein. When added in combination, thiazolidinediones block the suppression of C/EBP alpha mRNA by insulin; however, thiazolidinediones do not block the insulin-induced decline in GLUT4 mRNA, indicating that repression of C/EBP alpha mRNA is not required for insulin to suppress expression of a C/EBP alpha-responsive gene such as GLUT4. Instead, insulin may regulate GLUT4 mRNA by inactivating C/EBP alpha through dephosphorylation as well as by inducing the expression of the dominant-negative form of C/EBP beta (liver inhibitory protein), since both of these processes occur in the presence of thiazolidinediones.

3T3 Cells↗
PubMed1997

Signaling pathways through which insulin regulates CCAAT/enhancer binding protein alpha (C/EBPalpha) phosphorylation and gene expression in 3T3-L1 adipocytes. Correlation with GLUT4 gene expression.

Treatment of 3T3-L1 adipocytes with insulin (IC50 approximately 200 pM insulin) or insulin-like growth factor-1 (IC50 approximately 200 pM IGF-1) stimulates dephosphorylation of CCAAT/enhancer binding protein alpha (C/EBPalpha), a transcription factor involved in preadipocyte differentiation. As assessed by immunoblot analysis of one- and two-dimensional PAGE, insulin appears to dephosphorylate one site within p30C/EBPalpha and an additional site within p42C/EBPalpha. Consistent with insulin causing dephosphorylation of C/EBPalpha through activation of phosphatidylinositol 3-kinase, addition of phosphatidylinositol 3-kinase inhibitors (e.g. wortmannin) blocks insulin-stimulated dephosphorylation of C/EBPalpha. In the absence of insulin, wortmannin or LY294002 enhance C/EBPalpha phosphorylation. Similarly, blocking the activity of FKBP-rapamycin-associated protein with rapamycin increases phosphorylation of C/EBPalpha in the absence of insulin. Dephosphorylation of C/EBPalpha by insulin is partially blocked by rapamycin, consistent with a model in which activation of FKBP-rapamycin-associated protein by phosphatidylinositol 3-kinase results in dephosphorylation of C/EBPalpha. The dephosphorylation of C/EBPalpha by insulin, in conjunction with the insulin-dependent decline in C/EBPalpha mRNA and protein, has been hypothesized to play a role in repression of GLUT4 transcription by insulin. Consistent with this hypothesis, the decline of GLUT4 mRNA following exposure of adipocytes to insulin correlates with dephosphorylation of C/EBPalpha. However, the repression of C/EBPalpha mRNA and protein levels by insulin is blocked with an inhibitor of the mitogen-activated protein kinase pathway without blocking the repression of GLUT4 mRNA, thus dissociating the regulation of C/EBPalpha and GLUT4 mRNAs by insulin. A decline in C/EBPalpha mRNA and protein may not be required to suppress GLUT4 transcription because insulin also induces expression of the dominant-negative form of C/EBPbeta (liver inhibitory protein), which blocks transactivation by C/EBP transcription factors.

3T3 Cells↗
PubMed1996

Serotonergic and noradrenergic effects on respiratory neural discharge in the medullary slice preparation of neonatal rats.

Rhythmically active medullary slice preparations isolated from neonatal rats (postnatal days 0-3, P0-P3) were used to study the modulation of respiraory rhythmogenesis and hypoglossal (XII) nerve discharge by serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline (NA). 5-HT, NA and their respective receptor agonists and antagonists were applied either to the bathing medium or focally via pressure injection into regions encompassing the pre-Botzinger complex or XII motoneurons. The effects of endogenously released 5-HT were also studied by chemical stimulation of neurons within the raphe obscurus. The frequency of respiratory burst discharge was increased when 5-HT was applied: (1) to the bathing medium (37+/-16%; 30 "mu"M; P < 0.05); (2) via pressure injection into the region of the pre-Botzinger complex (22 +/- 14%; < 25 pmol; P < 0. 05); or (3) endogenously released in response to activation of neurons within the raphe obscurus via pressure injection of (R,S)- "alpha"-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (AMPA, 34 +/- 15%; P < 0.05) or 5-HT (33 +/- 5%; P < 0. 05). All of these effects were antagonized by bath application of methysergide (30-40 "mu"M). NA caused a reduction of respiratory burst frequency when applied to the bathing medium (40 +/- 15%; 100 "mu"M; P < 0.05) or when pressure injected into the region of the pre-Botzinger complex (22 +/- 11%; < 25 pmol; P < 0.05). These effects were blocked by the bath application of the "alpha"2-receptor antagonist idazoxan (2 "mu"M). 5-HT and NA both caused an augmentation of tonic discharge of XII nerves when applied either to the bathing medium or via pressure injection into the XII motoneuron pool. The 5-HT-induced XII nerve tonic discharge was mimicked by the 5-HT2 receptor agonist R(-)2-(2, 5-dimethoxy-4-iodophenyl) (DOI.HCl, 5 "mu"M) and blocked by the 5-HT2 receptor antagonist ketanserine tartrate (30-40 "mu"M). The NA-induced XII nerve tonic discharge was mimicked by the "alpha"1-receptor agonist phenylephrine HCl (500 nM) and blocked by the "alpha"1-receptor antagonist prozasin HCl (1 "mu"M).

Action Potentials↗
PubMed1995

Model investigations of caries inhibition by fluoride-releasing dental materials.

Fluoride-releasing dental materials are generally believed to reduce or prevent secondary caries. The evidence for this is largely anecdotal and centers on clinical experience with silicate cements and, more recently, with glass-ionomer cements. Unfortunately, corroborating evidence from controlled clinical trials is inadequate to establish precisely how effective these materials are or under what conditions they might be effective. Even less is known about the clinical effectiveness of newer materials that, often, release less fluoride. In vitro model systems have been used to study the effects of dental materials on de/remineralization of surrounding tooth structure. Fluoride-releasing materials have been shown in these models to reduce demineralization of both enamel and dentin compared with a material that does not release fluoride. This is useful from a mechanistic standpoint, but without clinical "standards" to guide model results, it is not possible to define an acceptable level of fluoride release or the length of time such release is required. A limited number of in situ model studies has been conducted, and some fluoride dose-response information has been obtained. These models are closer to the real situation and perhaps provide the best means to define required levels of fluoride release from materials in the absence of adequate clinical information.

Cariostatic Agents↗
PubMed1994

Acoustic correlates of breathy vocal quality.

The purpose of this study was to evaluate the effectiveness of several acoustic measures in predicting breathiness ratings. Recordings were made of eight normal men and seven normal women producing normally phonated, moderately breathy, and very breathy sustained vowels. Twenty listeners rated the degree of breathiness using a direct magnitude estimation procedure. Acoustic measures were made of: (a) signal periodicity, (b) first harmonic amplitude, and (c) spectral tilt. Periodicity measures provided the most accurate predictions of perceived breathiness, accounting for approximately 80% of the variance in breathiness ratings. The relative amplitude of the first harmonic correlated moderately with breathiness ratings, and two measures of spectral tilt correlated weakly with perceived breathiness.

Adult↗
PubMed1994

Evidence for a recent decrease in measles susceptibility among young American adults.

As part of an ongoing evaluation of US Army immunization policies, two serologic surveys were conducted at an army basic training center. Antibody status to measles, mumps, and rubella were determined by an ELISA in 969 soldiers in 1989 and 992 soldiers in 1990. Measles seronegativity rates, directly adjusted to the 15- to 24-year-old US population in 1980, decreased from 21.3% in 1989 to 12.5% in 1990 (P < .001). Decreases also were observed in mumps (16.2% to 14.7%) and rubella seronegativity rates (18.4% to 14.3%) from 1989 to 1990 but were not statistically significant. In subgroup analyses, significant decreases in measles seronegativity were observed in younger, white, male, and female cohorts. There is evidence that susceptibility among young adults had declined, although it remains unclear if this is due to increased immunization or exposure to natural disease.

Adolescent↗