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Biomedical subjects

R L Erickson

Publications and source records attributed to R L Erickson.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

Root surface treatment with glass ionomers and resin composites.

Recommendations for restorative treatments of root surfaces are made difficult by a lack of information on the etiology of root conditions and on the clinical performance of available materials used to treat these conditions. Resin composite and glass ionomer materials are popular restorative materials because they are esthetic and can bond to tooth structure. However, the role each can play in restoration of root surface lesions is not well documented. This article presents a rationale for using these materials for a number of restorative situations.

Chlorhexidine

Shear bond strength of composite to enamel and dentin using Scotchbond Multi-Purpose.

A laboratory study was conducted to determine the shear bond strength to enamel and dentin using the Scotchbond Multi-Purpose dental adhesive system. High shear bond strengths of P50 composite to both human enamel (26.8 +/- 5.2 MPa) and bovine enamel (24.8 +/- 4.1 MPa) were found when the system was used according to manufacturer's directions. The mean bond strength for human dentin (25.5 +/- 7.5 MPa) was also similar to that found for bovine dentin (23.4 +/- 4.9 MPa). Variations in the recommended application technique were examined on bovine dentin. Extreme air drying of the primer slightly reduced the mean shear bond strength (19.7 +/- 6.4 MPa), while a significant reduction was observed when the adhesive resin was aggressively air-thinned (10.1 +/- 6.6 Mpa).

Acid Etching, Dental

An in vitro study of mechanical heart valve sound loudness.

The purpose of the study was to measure the valve sound loudness of eight 25 mm aortic mechanical heart valve prostheses under controlled laboratory conditions in an isolated acoustic environment. A specially designed single-chamber pulse duplicator was constructed within an anechoic box that isolated the sounds of the valve from external noise. The valves were closed with a stimulated aortic pressure waveform of three different amplitudes. Valve sound loudness was measured with ISO-532/B (Zwicker method), which is based on a model of loudness perception that is better than dB(A), the traditional A-weighted sound pressure level. The average loudness for each valve was St. Jude Medical, 0.97 sones; CarboMedics, 0.98 sones; Sorin Biomedica Bicarbon, 1.08 sones; Edwards Tekna, 1.92 sones; Edwards Duromedics, 2.36 sones; Monostrut, 2.48 sones; Sorin Biomedica Carbocast, 3.17 sones; and Medtronic Hall, 3.57 sones. There was a positive trend between valve sound loudness and aortic drive pressure for most valves in the study.

Aortic Valve

Preventing disease and non-battle injury in deployed units.

Most military physicians know that disease and non-battle injuries (DNBIs) have historically caused more death during war than battle injury. Most DNBIs are preventable, but many unit surgeons and physician assistants, especially at battalion/squadron and brigade/wing level, may not have had the benefit of preventive medicine training or experience. The authors present a logical and thorough framework that all unit surgeons can use to organize their preventive efforts.

Humans

Decreases in invasive Haemophilus influenzae diseases in US Army children, 1984 through 1991.

OBJECTIVE: To document trends in the incidence of invasive Haemophilus influenzae diseases in young children of US Army active duty soldiers following the publication of H influenzae type b immunization recommendations for young children between 1985 and 1990. DESIGN: A population-based surveillance of hospital discharge diagnoses for H influenzae invasive diseases. SETTING: Military and civilian medical treatment facilities around the world. PATIENTS: There was a mean population of nearly 200,000 US Army health care beneficiaries younger than 5 years of age each year of the study. OUTCOME MEASURES: Annual total and age-specific incidences of the six most common H influenzae invasive diseases in this population (meningitis, epiglottitis, septicemia, pneumonia, cellulitis, and septic arthritis). RESULTS: The annual number of cases of H influenzae invasive diseases decreased from a high of 188 in 1986 to 43 in 1991. The incidence in the age group at highest risk for H influenzae disease, those 6 to 11 months of age, decreased from 355 per 100,000 children in 1986 to 116 per 100,000 in 1991 (P < .0001, chi 2 for trend). The incidence for H influenzae meningitis declined from 59 per 100,000 children in 1986 to 6 per 100,000 in 1991 (P < .0001, chi 2 for trend). CONCLUSIONS: The decrease in H influenzae invasive diseases closely follows the dates of H influenzae type b vaccine licensure for use in progressively younger age groups. Some age groups, however, experienced a decline in disease rates even before becoming eligible for vaccination.

Bacterial Capsules

The susceptibility of young adult Americans to vaccine-preventable infections. A national serosurvey of US Army recruits.

OBJECTIVE: Due to recent resurgences of measles, mumps, and rubella among young US adults, we sought to generate antibody prevalence data for national and military immunization policy evaluations. DESIGN: We used a questionnaire and serological survey of Army recruits to assess antibody status to measles, mumps, rubella, and varicella by enzyme-linked immunosorbent assay and to poliovirus types 1, 2, and 3 by microneutralization assay. SETTING: Basic training reception centers at Fort Benning, Ga., and Fort Jackson, SC. PATIENTS: The study included 1547 US Army recruits who were inducted during September and October 1989. OUTCOME MEASURES: Seronegativity by various demographic factors. RESULTS: Seronegativity rates, directly adjusted to the 15- to 24-year-old US population in 1980, were 20.7% for measles, 15.6% for mumps, 17.5% for rubella, and 6.9% for varicella. For measles, mumps, and rubella, susceptibility was less in females, blacks, and college-educated recruits, and varicella susceptibility was greater in females and blacks. Recruitment who were born after 1969 lacked measles, mumps, and rubella antibodies more often than older recruits. The adjusted seronegativity rates for poliovirus types 1, 2, and 3 were 2.3%, 0.6%, and 14.6%, respectively; trends by age, sex, and race-ethnicity were generally unremarkable. CONCLUSIONS: Among young adult Americans, susceptibility to measles, mumps, and rubella is unevenly distributed and may be substantial. Our findings support national objectives to further improve immunization coverage in school-age and adult populations and provide further impetus for legislation requiring college entrants to present evidence of having received at least two doses of measles vaccine, with one on or after entry into elementary school.

Adult

Radiopacity of restorations and detection of secondary caries.

The aim of this study was to compare the accuracy of radiographic diagnosis of secondary carious lesions adjacent to filling materials with different radiopacities. Class II preparations were made in extracted teeth. One group of teeth (n = 49) had caries in the gingival wall, simulating secondary caries. The control teeth (n = 29) had no caries. Three posterior composite materials (P-30 and two experimental composites) with different radiopacities and amalgam were successively inserted into each cavity. After being radiographed, the "restorations" were removed and a new material inserted. The radiographs were interpreted by 11 dentists, and secondary caries was diagnosed according to a five-point confidence rating. The results obtained with the receiver operating characteristics (ROC) method showed that a semi-radiopaque restoration seemed favorable and that the best radiopacity slightly exceeded that of enamel.

Composite Resins