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Biomedical subjects

R L Bowen

Publications and source records attributed to R L Bowen.

At least 19 recordsLinked to original sources

A review of the ethnic differences in breast cancer.

Women of African descent have a lower incidence of breast cancer than their white counterparts; however, the overall age-adjusted breast cancer mortality rates are higher. They also present at a younger age, and have more advanced disease that exhibits poor prognostic features including significantly larger tumors of higher grade, higher rates of estrogen receptor and progesterone receptor negativity and a higher rate of p53 mutations and HRAS1 proto-oncogene expression, all of which confer a poor prognosis. While there are many possible contributory factors to the discrepancies in outcome in women of African descent, there is no satisfactory explanation as to why women of African origin tend to present at a younger age with hormone receptor-negative tumors and more adverse prognostic features.

Black or African American↗

Evidence for the role of gonadotropin hormones in the development of Alzheimer disease.

Differences in the prevalence and age of onset of Alzheimer disease (AD) in men and women, and observations that hormone replacement therapy (HRT) may prevent the development of AD, caused many to hypothesize that estrogen deficiency contributes to AD. However, recent trials using estrogen failed to show any benefit in preventing or alleviating the disease. To address this and other inconsistencies in the estrogen hypothesis, we suspect that another hormone of the hypothalamic-pituitary-gonadal axis, luteinizing hormone (LH), as a major factor in AD pathogenesis. Individuals with AD have elevated levels of LH when compared with controls, and both LH and its receptor are present in increased quantities in brain regions susceptible to degeneration in AD. LH is also known to be mitogenic, and could therefore initiate the cell cycle abnormalities known to be present in AD-affected neurons. In cell culture, LH increases amyloidogenic processing of amyloid-beta protein precursor, and in animal models of AD, pharmacologic suppression of LH and FSH reduces plaque formation. Given the evidence supporting a pathogenic role for LH in AD, a trial of leuprolide acetate, which suppresses LH release, has been initiated in patients.

Aging↗

Novel therapeutic strategies for Alzheimer's disease based on the forgotten reproductive hormones.

The relationship between hormones and Alzheimer's disease (AD) has been intensely researched. While the majority of this work has focused on the sex steroids, estrogens, and more recently androgens, a serendipitous patient encounter led one of us (R.L.B.) to question whether other hormones of the hypothalamic-pituitary-gonadal axis might play a role in the pathogenesis of AD. The age-related decline in reproductive function results in a dramatic decrease in serum estrogen and testosterone concentrations and an equally dramatic compensatory increase in serum gonadotropin concentrations. Indeed, there is growing evidence that the gonadotropin luteinizing hormone, which regulates serum estrogen and testosterone concentrations, is an important causative factor in the development of AD. This review provides information supporting the 'gonadotropin hypothesis'. We put forth a novel mechanism of how changes in serum luteinizing hormone concentrations could contribute to the pathogenesis of AD and discusses potential therapeutic anti-gonadotropin compounds.

Aging↗

Human adenovirus-36 is associated with increased body weight and paradoxical reduction of serum lipids.

BACKGROUND: Human adenovirus-36 (Ad-36) increases adiposity and paradoxically lowers serum cholesterol and triglycerides in chickens, mice, and non-human primates. The role of Ad-36 in human obesity is unknown. OBJECTIVES: To determine the prevalence of Ad-36 antibodies in obese and nonobese humans. To evaluate the association of Ad-36 antibodies with body mass index (BMI) and serum lipids. DESIGN: Cohort study. Volunteers from obesity treatment programs, communities, and a research study. SUBJECTS: Obese and nonobese volunteers at the University of Wisconsin, Madison, WI, and the Bowen Center, Naples, Florida. Obese and thin volunteer research subjects and 89 twin pairs at Columbia University, New York. INTERVENTIONS: Study 1: 502 subjects; serum neutralization assay for antibodies to Ad-2, Ad-31, Ad-36, and Ad-37; serum cholesterol and triglycerides assays. Study 2: BMI and %body fat in 28 twin pairs discordant for Ad-36 antibodies. MAIN OUTCOME MEASURES: Presence of antibodies to adenoviruses, BMI, serum cholesterol and triglycerides levels. RESULTS: Significant (P < 0.001) association of obesity and positive Ad-36 antibody status, independent of age, sex, and collection site. Ad-36 antibodies in 30% of obese, 11% of nonobese. Lower serum cholesterol and triglycerides (P < 0.003) in Ad-36 antibody-positive vs -negative subjects. Twin pairs: antibody-positive twins had higher BMIs (24.5+/-5.2 vs 23.1+/-4.5 kg/m2, P < 0.03) and %body fat (29.6+/-9.5% vs 27.5+/-9.9%, P < 0.04). No association of Ad-2, Ad-31, or Ad-37 antibodies with BMI or serum lipids. CONCLUSIONS: Ad-36 is associated with increased body weight and lower serum lipids in humans. Prospective studies are indicated to determine if Ad-36 plays a role in the etiology of human obesity.

Adenovirus Infections, Human↗

Elevated gonadotropin levels in patients with Alzheimer disease.

OBJECTIVE: To determine whether gonadotropin levels are elevated in patients with Alzheimer disease (AD). PATIENTS AND METHODS: We measured luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels from stored plasma samples from 284 patients seen at a tertiary care center. We also reviewed their medical charts to record age and estrogen use in the women. The primary aim of our study was to determine whether gonadotropin levels were elevated in 134 patients with AD compared with levels from 45 patients with frontotemporal dementia (FTD) and 105 cognitively normal controls. RESULTS: Although overlap between LH and FSH levels was considerable, LH (P=.046) and FSH (P=.007) were significantly elevated in estrogen-free women with AD (LH: median, 26.3 IU/L; interquartile range, 14.9-34.6 IU/ L; FSH: median, 62.0 IU/L; interquartile range, 45.9-78.5 IU/L) compared with normal controls (LH: median, 20.1 IU/L; interquartile range, 13.7-25.3 IU/L; FSH: median, 47.7 IU/L; interquartile range, 34.1-57.5 IU/L). Levels of LH were also significantly higher (P=.03) in estrogen-free women with AD compared with women with FTD (LH: median, 20.7 IU/L; interquartile range, 19.0-28.5 IU/L; FSH: median, 53.3 IU/L; interquartile range, 27.6-77.9 IU/ L). When we controlled for age, no differences in LH and FSH were observed in men with AD compared with normal controls. CONCLUSIONS: Gonadotropin levels are elevated in some patients with AD, ie, women not taking estrogen. Elevated gonadotropin levels may have a role in the production of amyloid-beta protein, which is related to formation of senile plaques. Therefore, elevated gonadotropin levels may be involved in the pathogenesis of AD.

Aged↗

An association of elevated serum gonadotropin concentrations and Alzheimer disease?

Alzheimer disease affects almost 4 million Americans and costs $65 billion annually. The disease is more common in women than in men, and studies suggest that oestrogen may have a protective effect. Oestrogen replacement lowers circulating concentrations of gonadotropins. When gonadotropins are added to rat granulosa cells in culture, the number of low density lipoprotein (LDL) receptors and the rate of uptake of low density lipoprotein increases. Many proteins found in Alzheimer disease plaques are ligands for low density lipoprotein receptors (LDLR) on central nervous system (CNS) neurones. This study evaluated whether gonadotropins may be associated with Alzheimer disease. Circulating concentrations of follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels in 40 male residents of long-term care facilities with the primary diagnosis of dementia were compared to 29 age-matched controls. Serum concentrations of FSH and LH were significantly higher in dementia patients. We speculate they may play an aetiologic role in the deposition of abnormal proteins, particularly those associated with low density lipoprotein receptors, in CNS neurones.

Alzheimer Disease↗

MALDI-TOF MS analysis of a library of polymerizable cyclodextrin derivatives.

Polymerizable cyclodextrin derivatives (PCDs) have been proposed as candidates for use in dental therapeutics (Bowen, 1996; Bowen and Reed, 1997). Here, PCD "libraries" were synthesized by quasi-random reactions of 6 moles of methacrylic anhydride plus 6 moles of cyclic glutaric anhydride per mole of beta-cyclodextrin (BCD) in solution. BCD has 21 reactive sites on each of its molecules. These proportions were based on probability calculations, which predicted that the products should have a minimum of 2 polymerizable substituents and acidic ligand groups on practically every one of the diverse product molecules. Matrix-assisted laser desorption/ionization (MALDI) time of flight (TOF) mass spectrometry (MS) gave valuable information regarding the masses of molecular ions representing the molecules that made up the PCD libraries. For the MALDI-TOF MS analyses, small samples were analyzed by the successive application of 3 solutions to the sample holder: the matrix in acetone, the products in water, and sodium trifluoroacetate in water. The resulting spectra had > 40 envelopes of mass peaks above background. The ionic-abundance peak heights had quasi-Gaussian configurations, with central peaks having masses in the neighborhood of 2000 g/mol (Daltons). Regardless of structural permutations within each peak, the range of these peaks was between about 1500 g/mol and 2900 g/mol. This range of masses was in accord with, but perhaps somewhat more narrow than, that predicted by the statistical method, which was based on equal reactivity of all hydroxyl groups. Analysis by MALDI-TOF MS gave valuable data regarding the masses, structures, and characteristics of the products formed and provided unanticipated information to facilitate improvements in future PCD syntheses.

Acetone↗

New surface-active comonomer for adhesive bonding.

Previous studies have indicated that chemical and physical characteristics of aromatic amines can be influenced by the nature of their substituents. The experimental question examined in the present study relates to the effects of replacing specific hydrogen atoms with methyl groups in a surface-active comonomer utilized in adhesive bonding protocols. N-2-propionic acid-N-3-(2-hydroxy-1-methacryloxy)propyl-3,5-dimethylaniline sodium salt (N35A) was synthesized by an addition reaction of glycidyl methacrylate with the sodium salt of N-reaction of glycidyl methacrylate with the sodium salt of N-(3,5-dimethylphenyl)alanine, which was formed by alkaline hydrolysis of ethyl-N-(3,5-dimethylphenyl)alanate that was prepared by condensation of ethyl-2-bromopropionate with 3,5-dimethylaniline. 1H and 13C NMR spectra and analysis by mass spectroscopy were consistent with N35A after it had been recrystallized from acetone. Color stability and adhesion-promoting capability of N35A were compared with those of N-2-acetic acid-N-3-(2-hydroxy-1-methacryloxy)propyl-4-methylanaline sodium salt (Na-NTG-GMA), the latter being widely used in commercial bonding formulations. Both N35A and Na-NTG-GMA polymerized within a few minutes at 23 degrees C when dissolved in aliquots from a stock solution containing benzene 85 wt%, ethanol 14 wt%, and benzoyl peroxide 1.0 wt%; but with each at 0.018 molal concentration, the N35A suspension was more color-stable than that of the Na-NTG-GMA. In the protocol used, shear bond strengths of a hybrid composite to human dentin with N35A were 30.2 MPa, SD = 7.5 MPa, and with Na-NTG-GMA, 29.7 MPa, SD = 11.8 MPa(n = 7 each; t test, p = 0.93).

Adhesiveness↗

Physical and chemical properties of resin-reinforced calcium phosphate cements.

OBJECTIVES: The purpose of this study was to improve the handling and physical properties of a self-setting, water-based calcium phosphate cement by combining it with polymerizable resins and to study the setting reactions involved. METHODS: Dual-cured composite cements were prepared from a calcium phosphate cement powder and dental monomers that contain carboxylated hydrophilic resins or resin/water mixtures. The setting reaction of the calcium phosphate cement in the presence of the resins was evaluated by pH measurements, infrared spectroscopy, diametral tensile strength, x-ray diffraction analysis, and scanning electron microscopy. RESULTS: Carboxylated resins were chosen because they can form ionic bonds to the mineral filler, which was confirmed by appearance of an infrared absorbance peak at 1552 cm-1 within 24 h after mixing due to the formation of a carboxylate salt. Hydroxyapatite did not develop in composites prepared from resin and calcium phosphate cement. However, composites from calcium phosphate cement, resin and water showed approximately 40% hydroxyapatite. The resulting composite cements have moderately high DTS of 14-15 MPa and high pH. SIGNIFICANCE: Hydrophilic acidic resins allows mixing with water and/or allow rapid diffusion of water into the resinous cement so that the dissolution and reprecipitation processes required for the conversion of the calcium phosphate components to hydroxyapatite can occur. The characteristics of the resulting composite cements suggest that the materials may be useful in pulp capping and/or cavity lining.

Calcium Phosphates↗

An esthetic glass-ceramic for use in composite restoration inserts.

The objective of the preliminary work reported here was to prepare an improved formulation of intrinsically colored microcrystalline glass-ceramic. Applications could include "megafillers" for direct composite restorations, precision castings, and CAD-CAM prostheses. The experimental glass-ceramic reported here contained SiO2 56.9, AI2O3 19, LiO2 7, ZnO 6, MgO 5, TiO22, ZrO22, P2O52, and CeO20.1 mole%. The batch materials were melted and stirred at 1,610 degrees C for 2 h, quenched in water and also formed into a block of a clear, slightly yellow glass. To identify the crystalline phases that developed during transformation of the glass to the ceramic, x-ray diffraction was used on ten aliquots taken during 15 h of stepwise heating from 750 to 1050 degrees C. With heating, the yellow color deepened to a very translucent "dark yellow" dental shade, then lightened with gradually increasing opacity during formation of secondary crystalline phases. X-ray opacity was approximately equivalent to that of dental enamel. The refractive index of the glass, nD1.554, increased during nucleation and growth of the crystalline phases to a maximum of 1.586. Intrinsic coloration of these glass-ceramic materials can be controlled by varying the heat treatment and/or composition to match typical dental shades.

Ceramics↗

Adhesion of composites to dentin and enamel.

Extrapolations based on the history of the development of composites and an adhesion system for bonding dental resins and composites to hard tooth tissues can rightfully be the basis for strong optimism regarding future improvements in esthetic and conservative treatment modalities. Improved understanding of mechanisms of action and the clinical application steps common to current adhesion systems will certainly lead to improved oral healthcare.

Acid Etching, Dental↗

Dental composites/glass ionomers: the materials.

Most commercial dental composites contain liquid dimethacrylate monomers (including BIS-GMA or variations of it) and silica-containing compositions as inorganic reinforcing filler particles coated with methacrylate-functional silane coupling agents to bond the resin to the filler. They also contain initiators, accelerators, photo-initiators, photosensitizers, polymerization inhibitors, and UV absorbers. Durability is a major problem with posterior composites. The typical life-span of posterior composites is from three to 10 years, with large fillings usually fewer than five years. Polymerization shrinkage and inadequate adhesion to cavity walls are remaining problems. Some pulp irritation can occur if deep restorations are not placed over a protective film. Some have advocated the use of glass-ionomer cement as a lining under resin composite restorations in dentin. The concept of glass-ionomer cements (GICs) was introduced to the dental profession in the early 1970's. Current GICs may contain poly(acrylic acid) or a copolymer. Higher-molecular-weight copolymers may also be used to improve the physical properties of some GICs. Stronger and less-brittle hybrid materials have been produced by the addition of water-soluble compatible polymers to form light-curing GIC formulations. The ion-leachable aluminosilicate glass powder, in an aqueous solution of a polymer or copolymer of acrylic acid, is attacked by the hydrated protons of the acid, causing the release of aluminum and calcium ions. Salt bridges are formed, and a gel matrix surrounds the unreacted glass particles. The matrix is adhesive to mineralized tissues. Provisions must be made for maintenance of the water balance of restorations for the first 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Bisphenol A-Glycidyl Methacrylate↗

Development of an adhesive bonding system.

Building on findings concerning adhesion to enamel, R L Bowen and his colleagues at the Paffenbarger Research Center, National Institute of Standards and Technology began addressing and solving problems associated with (1) silicate cements and unfilled resins, (2) bonding in an aqueous environment, and (3) the development of an adhesion system for both dentin and enamel that could withstand various stresses. This article reviews the development of an adhesion system for bonding dental composites to dentin and enamel.

Benzoates↗

The effect of catalyst structure on the synthesis of a dental restorative monomer.

The addition product of 2-hydroxyethyl methacrylate (HEMA) and pyromellitic dianhydride (PMDA), known as PMDM, is a mixture of two structural isomers. The para PMDM isomer--currently used in mediating adhesive bonding of restorative materials to hard tooth tissues--is a crystalline solid. The meta isomer is a liquid. In the synthesis of PMDM, the para isomer, which can be purified by crystallization, is usually present to the extent of only 50% of the product mixture. The effect of the amine catalyst structure was studied relative to its role in increasing the yield of the para isomer, either by a reduction in the amount of the meta isomer or by an increase in the extent of overall reaction. The chemical structure of the amine catalyst had an important role in the synthesis of PMDM and influenced the ratio of the isomers. Among aliphatic amines, especially noteworthy as catalysts that gave excellent yields of the para isomer in high purity were N,N-di-isopropyl-ethylamine and hexamethylenetetramine.

Adhesives↗