Saliva Stimulants and the Oral Health of Geriatric Patients

Root-surface caries (RSC) has been recognized as a specific and important dental disease. Significant advances have been made in the pathology and microbiology of RSC, and the need to standardize the guidelines for recording RSC data has been recognized. Researchers have emphasized the increasing impact RSC will have on the geriatric population, especially since the methods to treat and prevent this disease are limited. The purpose of this study was to investigate the possibility of limiting RSC in a Veterans Administration (VA) patient population, using polyol-containing saliva stimulants that were voluntarily consumed by residents of a VA Medical Center (VAMC) over a period of from six to 30 months. Another aim was to study the effect of this program on the gingival health of periodontal patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68278/2/10.1177_08959374950090020901.pd

Polyol-combinant saliva stimulants and oral health in Veterans Affairs patients—An exploratory study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72530/1/j.1754-4505.1996.tb00843.x.pd

To the Graduate Council:

I am submitting herewith a dissertation written by Stephen Edward Bales entitled “Aristotle’s Contribution to Scholarly Communication. ” I have examined the final electronic copy of this dissertation for form and content and recommend that it b

Formation of the Open Complex by Bacterial RNA Polymerase—A Quantitative Model

Over the last two decades, a large amount of data on initiation of transcription by bacterial RNA polymerase (RNAP) has been obtained. However, a question of how the open complex is formed still remains open, and several qualitative hypotheses for opening of DNA by RNAP have been proposed. To provide a theoretical framework needed to analyze the assembled experimental data, we here develop the first quantitative model of the open complex formation by bacterial RNAP. We first show that a simple hypothesis (which might follow from recent bioinformatic and experimental results), by which promoter DNA is melted in one step through thermal fluctuations, is inconsistent with experimental data. We next consider a more complex two-step view of the open complex formation. According to this hypothesis, the transcription bubble is formed in the −10 region, and consequently extends to the transcription start site. We derive how the open complex formation rate depends on DNA duplex melting energy and on interaction energies of RNAP with promoter DNA in the closed and open complex. This relationship provides an explicit connection between transcription initiation rate and physical properties of the promoter sequence and promoter-RNAP interactions. We compare our model with both biochemical measurements and genomics data and report a very good agreement with the experiments, with no free parameters used in model testing. This agreement therefore strongly supports both the quantitative model that we propose and the qualitative hypothesis on which the model is based. From a practical point, our results allow efficient estimation of promoter kinetic parameters, as well as engineering of promoter sequences with the desired kinetic properties

Binding of the Unorthodox Transcription Activator, Crl, to the Components of the Transcription Machinery*

The small regulatory protein Crl binds to σS, the RNA polymerase stationary phase σ factor. Crl facilitates the formation of the σS-associated holoenzyme (EσS) and thereby activates σS-dependent genes. Using a real time surface plasmon resonance biosensor, we characterized in greater detail the specificity and mode of action of Crl. Crl specifically forms a 1:1 complex with σS, which results in an increase of the association rate of σS to core RNA polymerase without any effect on the dissociation rate of EσS. Crl is also able to associate with preformed EσS with a higher affinity than with σS alone. Furthermore, even at saturating σS concentrations, Crl significantly increases EσS association with the katN promoter and the productive isomerization of the EσS-katN complex, supporting a direct role of Crl in transcription initiation. Finally, we show that Crl does not bind to σ70 itself but is able at high concentrations to form a weak and transient 1:1 complex with both core RNA polymerase and the σ70-associated holoenzyme, leaving open the possibility that Crl might also exert a side regulatory role in the transcriptional activity of additional non-σS holoenzymes

Immunomodulatory Gene Therapy Prevents Antibody Formation and Lethal Hypersensitivity Reactions in Murine Pompe Disease

Infantile Pompe disease progresses to a lethal cardiomyopathy in absence of effective treatment. Enzyme-replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) has been effective in most patients with Pompe disease, but efficacy was reduced by high-titer antibody responses. Immunomodulatory gene therapy with a low dose adeno-associated virus (AAV) vector (2 × 1010 particles) containing a liver-specific regulatory cassette significantly lowered immunoglobin G (IgG), IgG1, and IgE antibodies to GAA in Pompe disease mice, when compared with mock-treated mice (P < 0.05). AAV-LSPhGAApA had the same effect on GAA-antibody production whether it was given prior to, following, or simultaneously with the initial GAA injection. Mice given AAV-LSPhGAApA had significantly less decrease in body temperature (P < 0.001) and lower anaphylactic scores (P < 0.01) following the GAA challenge. Mouse mast cell protease-1 (MMCP-1) followed the pattern associated with hypersensitivity reactions (P < 0.05). Regulatory T cells (Treg) were demonstrated to play a role in the tolerance induced by gene therapy as depletion of Treg led to an increase in GAA-specific IgG (P < 0.001). Treg depleted mice were challenged with GAA and had significantly stronger allergic reactions than mice given gene therapy without subsequent Treg depletion (temperature: P < 0.01; symptoms: P < 0.05). Ubiquitous GAA expression failed to prevent antibody formation. Thus, immunomodulatory gene therapy could provide adjunctive therapy in lysosomal storage disorders treated by enzyme replacement