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Biomedical subjects

E A Lewis

Publications and source records attributed to E A Lewis.

At least 19 recordsLinked to original sources
PubMed2006

Binding of netropsin to several DNA constructs: evidence for at least two different 1:1 complexes formed from an -AATT-containing ds-DNA construct and a single minor groove binding ligand.

Isothermal titration calorimetry, ITC, has been used to determine the thermodynamics (DeltaG, DeltaH, and -TDeltaS) for binding netropsin to a number of DNA constructs. The DNA constructs included: six different 20-22mer hairpin forming sequences and an 8-mer DNA forming a duplex dimer. All DNA constructs had a single -AT-rich netropsin binding with one of the following sequences, (A(2)T(2))(2), (ATAT)(2), or (AAAA/TTTT). Binding energetics are less dependent on site sequence than on changes in the neighboring single stranded DNA (hairpin loop size and tail length). All of the 1:1 complexes exhibit an enthalpy change that is dependent on the fractional saturation of the binding site. Later binding ligands interact with a significantly more favorable enthalpy change (partial differential DeltaH(1-2) from 2 to 6 kcal/mol) and a significantly less favorable entropy change (partial differential (-TDeltaS(1-2))) from -4 to -9 kcal/mol). The ITC data could only be fit within expected experimental error by use of a thermodynamic model that includes two independent binding processes with a combined stoichiometry of 1 mol of ligand per 1 mol of oligonucleotide. Based on the biophysical evidence reported here, including theoretical calculations for the energetics of "trapping" or structuring of a single water molecule and molecular docking computations, it is proposed that there are two modes by which flexible ligands can bind in the minor groove of duplex DNA. The higher affinity binding mode is for netropsin to lay along the floor of the minor groove in a bent conformation and exclude all water from the groove. The slightly weaker binding mode is for the netropsin molecule to have a slightly more linear conformation and for the required curvature to be the result of a water molecule that bridges between the floor of the minor groove and two of the amidino nitrogens located at one end of the bound netropsin molecule.

Base Sequence↗
PubMed2001

Van't Hoff and calorimetric enthalpies from isothermal titration calorimetry: are there significant discrepancies?

The enthalpy of a reaction is most often determined through one of two means; it can be determined directly using calorimetry or indirectly by measuring the temperature dependence of the equilibrium constant (i.e., the van't Hoff method). Recently, discrepancies have been noted between the enthalpy measured by calorimetry, and the enthalpy determined by the van't Hoff method,. This has been suggested to indicate that the binding reaction is more complex than the simple one-to-one binding model used to describe the data. To better understand possible discrepancies between and, we have undertaken both experimental studies using isothermal titration calorimetry to measure the binding energetics of Ba(2+) binding 18-crown-6 ether and 2'-CMP binding RNase A, along with a simulation of a system involving a molecule in conformational equilibrium coupled with binding. We find that when experimental setup and analysis are correctly performed, no statistically significant discrepancies between and exist even for the linked system.

Barium↗
PubMed1995

Corporate compliance programs: risk management for the future.

The Department of Justice has estimated that the government loses $100 billion annually in health care fraud. Consequently, the government's health care fraud enforcement activities with respect to all health care providers and suppliers continue to grow. Last year alone, the government collected more than $8 billion in settlements, fines, and penalties involving health care fraud. Recent settlements with the government have begun to include corporate compliance programs that require continued government oversight of the health care organization as an essential part of the settlement. The first section of this article describes the legal significance of health care companies' having corporate compliance programs. The second section provides a sample list of topics that should be included in any corporate compliance program. Finally, we describe various issues related to the creation and implementation of corporate compliance programs.

Fraud↗
PubMed1990

The determination of nicotine and cotinine by ion pair reversed-phase chromatography.

An ion chromatographic method is described for the determination of nicotine and cotinine in aqueous solutions. This method is based on a type of reversed-phase chromatography involving ion pair formation of protonated nicotine, cotinine, pyridine, and pyridine derivatives. Detection is accomplished by measuring the UV absorption at 262 nm. Detection limits for nicotine and cotinine are 8 ng/mL and 2 ng/mL, respectively. Analyses of environmental samples and spiked environmental samples by both this ion chromatographic method and a previously reported gas chromatographic method have been used to demonstrate the accuracy and precision of this technique. The results of the analyses of both sets of samples by the two methods are in excellent agreement with a linear correlation coefficient of 0.97.

Chromatography, Gas↗
PubMed1989

Kinetics of drug decomposition by heat conduction calorimetry.

The application of heat conduction calorimetry to the determination of decomposition mechanisms and rates for drugs is shown to be a rapid and generally useful method. The application of the method to determine the nature of the decomposition reaction, sources of systematic errors in the method, the equations relating the calorimetric signal to the kinetics of the reaction, and some examples of results are presented and discussed.

Calorimetry↗
PubMed1988

Clinical and laboratory evaluation of visible light-cured denture base resins and their application to orthodontics.

A series of investigations is being conducted to examine the applicability of visible light-cured resins to orthodontics. The experimental vehicle is the Hawley retainer, which is made from autopolymerized (AP), heat-cured (HC), thermoplastic Biocryl 2 (BC), and Traid visible light-cured (VLC) resins. In all physical property testing, it was found that VLC resins met or exceeded required values as established by ADA Specification No. 12 for denture base polymers. In vitro bacterial adherence studies showed that more organisms adhered to heat-cured specimens than to the other specimens. In vivo studies using split-palate Hawley retainers demonstrated slightly less bacterial adherence to BC than to the other resins. Scanning electron microscopy (SEM) observations have shown the BC surface to be the smoothest, although surface chemistry also seems important. None of the materials being tested appears to cause any significant change in the subjacent subgingival bacterial flora. There was no adverse tissue reaction under any of the materials when observed clinically. Manipulation characteristics and time of fabrication appear to be dependent on the depth of the palate and the skill of the operator.

Acrylic Resins↗
PubMed1988

Subependymal giant-cell astrocytoma in children. An unusual discrepancy between histological and clinical features.

The authors describe five cases of subependymal giant-cell astrocytoma in children in which many clinical, histological, immunohistochemical, and ultrastructural features typical of this tumor were present. However, prominent focal necrosis and mitoses, features usually associated with high-grade tumors, were seen in all cases. Despite the presence of necrosis and mitoses, clinical follow-up studies have revealed a lack of aggressive tumor behavior after surgery alone. The discrepancy between the histological and clinical features in these cases is emphasized so that excessive treatment of a basically low-grade tumor may be avoided. Mast cells were seen in all five cases, often in large numbers.

Cerebral Ventricle Neoplasms↗
PubMed1986

A new visible light-cured resin system applied to removable prosthodontics.

Preliminary studies of VLC resins have produced promising results; however, additional research is necessary to completely define qualities of this material. Biologic testing of VLC (Triad) resins indicated that they are nontoxic and biocompatible. They have a wide range of uses in all subdisciplines of prosthodontics. Advantages such as accuracy of fit, superior strength, complete polymerization without residual compounds, ease of fabrication and manipulation, patient acceptance, ability to bond with other denture base resins, and low bacterial adherence make this material an important addition to the choices available to dentists. As with many new materials, there are initial problems or hurdles that must be overcome before there is widespread use. Initial formulations of material had insufficient flexural strength and tended to fracture when flexed over uncut sites on a stone cast. This problem has been reduced by Dentsply International, Inc. with the introduction of the new improved formulation. The original VLC bonding agent did not provide sufficient bond strength with acrylic resin denture base materials, but this also has been improved with development of a new VLC bonding agent. The problem of microporosity and small voids produced when adapting VLC resin sheets against a stone cast may be overcome with pressure or vacuum adaptation techniques. A promising application of VLC resin material is in direct intraoral procedures such as relining of dentures. Physical and chemical properties are superior to autopolymerizing methacrylates. Preliminary studies have shown successful patient acceptance to this clinical procedure. It is of particular advantage to the patient not to be without dentures for the period of at least 1 day necessary for a laboratory-processed relining. Immediate light-curing is time-saving and convenient compared to indirect (heat-cured) relining. Until recently, most direct intraoral applications of autopolymerizing acrylic resin reliner material were considered temporary or expedient to a permanent procedure. The patient and dentist may now have another treatment choice. The release of residual methyl methacrylate, among other shortcomings of AP materials, is not a concern when using the VLC reliner material. Some patients may notice a nonobjectionable taste to the uncured material; however, they can be reassured that the taste will be only temporary until the material is completely polymerized in the curing unit. The flow of the material can be regulated by selection of appropriate viscosity, warming and cooling measures, and partial intraoral polymerization with hand-held curing lights.(ABSTRACT TRUNCATED AT 400 WORDS)

Acrylic Resins↗
PubMed1985

Post-haemorrhagic hydrocephalus in the preterm infant.

This prospective study documents the incidence, clinical features and risk factors for post-haemorrhagic hydrocephalus (PHH) as well as the short-term outcome after serial CSF taps. Serial real-time ultrasound scans were performed on 220 infants: on all admissions less than or equal to 1250 g and on an additional 130 infants with birthweights greater than 1250 g with risk factors for intraventricular haemorrhage (IVH). Based on percentile charts of postnatal increase in ventricular size and head circumference growth rate, PHH was defined as ventricular dilatation greater than 95th centile associated with either a head circumference growth greater than 95th centile or with clinical features of raised intracranial pressure (ICP). Forty-eight (22%) infants were found to have IVH of whom 14 had intracerebral extension of IVH. Sixteen (40%) of 40 infants who survived the acute episode of IVH developed PHH. PHH occurred more commonly in those who survived severe birth asphyxia and/or intracerebral extension of IVH. Fifteen infants who developed clinical features of raised ICP were treated with serial CSF taps. This procedure was effective in a staged treatment for PHH in relieving clinical symptoms and deferring ventriculo-peritoneal (VP) shunting. Morbidity associated with serial CSF taps and VP shunting is minimal. A high red cell count and protein concentration in the CSF at diagnosis of PHH identified all five infants who subsequently required VP shunting.

Cerebral Hemorrhage↗
PubMed1983

A dental-facial attractiveness scale. Part I. Reliability and validity.

Since the decision to seek orthodontic treatment is frequently the result of concerns about appearance, assessment of need for treatment should include an impartial evaluation of dental-facial appearance. While some of the standardized techniques for assessing malocclusion have included a consideration of esthetic impairment, they tend to confound this with functional impairment. The purpose of this study was to develop a valid and reliable index that provides relatively objective judgments of dental-facial attractiveness. The subjects in this study were eighth- and ninth-grade children seeking orthodontic treatment and their siblings, and eighth- and ninth-grade children not seeking treatment and their siblings. Photographs of the children were rated for dental-facial attractiveness by lay and dental judges. Children were also assessed for severity of malocclusion by means of the Treatment Priority index. Children seeking treatment were perceived as significantly less attractive than children not seeking treatment. Dental judges rated children seeking treatment as more attractive than did nondental judges. Intraclass reliability coefficients were moderate to high.

Adolescent↗
PubMed1983

Histone H1: ultracentrifugation studies of the effects of ionic strength and denaturants on the solution conformation.

The conformation of histone H1 has been examined under native and denaturing conditions in the absence of DNA or chromatin. Sedimentation coefficients were determined for Histone H1 in 0.1 M KCl and in 6 M guanidine hydrochloride solutions at pH 7.4. The influence of ionic strength on the conformation of histone H1 has been determined by measurement of the sedimentation coefficient in tetramethylammonium chloride solutions of up to 2.5 M and extrapolated to infinite ionic strength. Results from these experiments suggest that the native conformation of histone H1 is very asymmetric in shape. The molecule is best described as a prolate ellipsoid with axes of 312 A (2a) and 16 A (2b) in low ionic strength media and also as a prolate ellipsoid with axes of 202 A (2a) and 20 A (2b) at high ionic strength or when associated with polyanions, e.g., DNA. Denaturation of histone H1 by guanidine hydrochloride was found to be completely reversible. In 6 M guanidine hydrochloride, the H1 molecule collapses to a sphere but the original extended conformation of the protein is readily restored on dialysis. This suggests rigid conformational requirements for the H1 molecule as incorporated into chromatin. The shape and dimensions for the H1 molecule at high ionic strength are not sufficiently conclusive to locate H1 in the chromatin structure. It is proposed, however, that viable models for chromatin architecture must be consistent with the histone H1 solution dimensions obtained here.

Guanidines↗
PubMed1982

Reliability and validity of clinical assessments of malocclusion.

The purpose of this research was to determine the reliability and validity of selected clinical judgments of malocclusion, including general evaluations of occlusal status and more specific aspects of dentofacial malrelations. Study casts of twenty-one adolescents planning orthodontic treatment and twenty-nine not planning treatment were examined and rated. The examiners were five dentists in an orthodontic specialty-training program. They completed ratings on six dimensions: (1) need for treatment, (2) degree of malocclusion, (3) potential for tissue loss, (4) negative effect on occlusal stability, (5) negative effect on dental-facial attractiveness, and (6) negative effect on masticatory function. Six weeks later the same five rates scored the fifty casts, using the standardized Treatment Priority Index (TPI). Three weeks later, or 9 weeks after the initial ratings, the casts were again rated on the two general dimensions: need for treatment and degree of malocclusion. Correlations among all the measures were examined. Inter-rater reliability was highest for the ratings of impact on dental-facial attractiveness (r = 0.88). The two general assessments also yielded relatively high rater reliabilities, and the second rating yielded stability coefficients of 0.84 for both of these ratings. Correlations with total TPI scores were 0.70 for the dental-facial attractiveness measure and 0.65 and 0.64, respectively, for assessments of need for treatment and degree of malocclusion. The data indicate that clinical evaluations of the severity of malocclusions are comparable to objective measures in terms of inter-rater reliability. Clinical evaluations are also relatively stable over time. Correlations with the TPI scores also provide evidence of the concurrent validity of clinical judgments.

Adolescent↗
PubMed1981

Variables discriminating individuals who seek orthodontic treatment.

Overall, these results support the view that dental-facial esthetics and self-perceptions of occlusal appearance, as well as attitudes toward malocclusion and orthodontic treatment, are important factors in the individual's decision to obtain orthodontic treatment. The data indicate that psychosocial variables not directly related to occlusal problems and treatment, do not add significantly to the description of differences between those who seek treatment and those who do not. While these analyses did not include a number of variables--such as socioeconomic factors or attitudes of significant others--which may also be important in predicting individual response to malocclusion, they do suggest strongly that psychosocial factors directly related to need for treatment are probably most productively assessed in terms of self-perceptions of occlusal appearance and attitudes regarding dental malrelations and their treatment.

Adolescent↗
PubMed1981

Natural history of chronic duodenitis: incidence in Nigerians.

Chronic peptic duodenitis accounted for four percent of endoscopic diagnoses of upper gastrointestinal disorders in lbadan, Nigeria. This clinicopathologic entity was a frequent cause of x-ray negative dyspepsia and was a cause of significant bleeding in two of the 26 patients included in this study. None progressed to frank duodenal ulceration during the follow-up period. It is emphasized that accurate assessment of dyspepsia must include endoscopic and histologic examinations.

Adult↗
PubMed1980

Binding of the Triton X series of nonionic surfactants to bovine serum albumin.

The binding of a series of Triton X nonionic surfactants (NIS) tobivine serum albumin (BSA) has been studied by equilibrium dialysis and titration calorimetry. At pH 7.0, Triton X molecules bind to two classes of sites, the first 2 molecules binding with positive cooperativity to high-affinity sites following by the binding of approximately 15 additional molecules to lower affinity, thermodynamically identical, and independent sites. The strength of the binding decreases as the number of oxyethylene units is increased in the surfactants Triton X-114, X-100, X-102, and X-165. Calorimetric measurements show the enthalpy change for the NIS-BSA interaction to be small and endothermic. Increasing the hydrophilic oxyethylene chain length results in a more endothermic enthalpy change and a smaller association constant. Electron spin resonance studies of Triton X binding to BSA, covalently spin-labeled with N-(2,2,6,6-tetramethyl-piperidinyl-1-oxy)maleimide, indicated that the protein conformation in the vicinity of the labeled sulfhydryl was insensitive to NIS binding from dilute monomeric solutions. Calorimetric experiments near the critical micelle concentration indicate, however, that the protein probably undergoes a conformational change associated with the population of the lower affinity NIS binding sites.

Animals↗