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Biomedical subjects

Paul A Moore

Publications and source records attributed to Paul A Moore.

35 records · Page 2Linked to original sources
PubMed2003

An IFN-beta-albumin fusion protein that displays improved pharmacokinetic and pharmacodynamic properties in nonhuman primates.

The long half-life and stability of human serum albumin (HSA) make it an attractive candidate for fusion to short-lived therapeutic proteins. Albuferon (Human Genome Sciences [HGS], Inc., Rockville, MD) beta is a novel recombinant protein derived from a gene fusion of interferon-beta (IFN-beta ) and HSA. In vitro, Albuferon beta displays antiviral and antiproliferative activities and triggers the IFN-stimulated response element (ISRE) signal transduction pathway. Array analysis of 5694 independent genes in Daudi-treated cells revealed that Albuferon beta and IFN-beta induce the expression of an identical set of 30 genes, including 9 previously not identified. In rhesus monkeys administered a dose of 50 microg/kg intravenously (i.v.) or subcutaneously (s.c.) or 300 microg/kg s.c., Albuferon beta demonstrated favorable pharmacokinetic properties. Subcutaneous bioavailability was 87%, plasma clearance at 4.7-5.7 ml/h/kg was approximately 140-fold lower than that of IFN-beta, and the terminal half-life was 36-40 h compared with 8 h for IFN-beta. Importantly, Albuferon beta induced sustained increases in serum neopterin levels and 2',5' mRNA expression. At a molar dose equivalent to one-half the dose of IFN-beta, Albuferon beta elicited comparable neopterin responses and significantly higher 2',5'-OAS mRNA levels in rhesus monkeys. The enhanced in vivo pharmacologic properties of IFN-beta when fused to serum albumin suggest a clinical opportunity for improved IFN-beta therapy.

Animals↗
PubMed2003

Xerostomia: etiology, recognition and treatment.

BACKGROUND: Clinicians may encounter symptoms of xerostomia, commonly called "dry mouth," among patients who take medications, have certain connective tissue or immunological disorders or have been treated with radiation therapy. When xerostomia is the result of a reduction in salivary flow, significant oral complications can occur. TYPES OF STUDIES REVIEWED: The authors conducted an Index Medicus--generated review of clinical and scientific reports of xerostomia in the dental and medical literature during the past 20 years. The literature pertaining to xerostomia represented the disciplines of oral medicine, pathology, pharmacology, epidemiology, gerodontology, dental oncology, immunology and rheumatology. Additional topics included the physiology of salivary function and the management of xerostomia and its complications. RESULTS: Xerostomia often develops when the amount of saliva that bathes the oral mucous membranes is reduced. However, symptoms may occur without a measurable reduction in salivary gland output. The most frequently reported cause of xerostomia is the use of xerostomic medications. A number of commonly prescribed drugs with a variety of pharmacological activities have been found to produce xerostomia as a side effect. Additionally, xerostomia often is associated with Sjögren's syndrome, a condition that involves dry mouth and dry eyes and that may be accompanied by rheumatoid arthritis or a related connective tissue disease. Xerostomia also is a frequent complication of radiation therapy. CONCLUSIONS AND CLINICAL IMPLICATIONS: Xerostomia is an uncomfortable condition and a common oral complaint for which patients may seek relief from dental practitioners. Complications of xerostomia include dental caries, candidiasis or difficulty with the use of dentures. The clinician needs to identify the possible cause(s) and provide the patient with appropriate treatment. Remedies for xerostomia usually are palliative but may offer some protection from the condition's more significant complications.

Candidiasis, Oral↗
PubMed2003

Field observations of intraspecific agonistic behavior of two crayfish species, Orconectes rusticus and Orconectes virilis, in different habitats.

Agonistic behavior is a fundamental aspect of ecological theories on resource acquisition and sexual selection. Crustaceans are exemplary models for agonistic behavior within the laboratory, but agonistic behavior in natural habitats is often neglected. Laboratory studies do not achieve the same ecological realism as field studies. In an attempt to connect laboratory results to field data and investigate how habitat structure affects agonistic interactions, the nocturnal behavior of two crayfish species was observed by scuba diving and snorkeling in two northern Michigan lakes. Intraspecific agonistic interactions were analyzed in three habitats: two food resources-macrophytes and detritus-and one sheltered habitat. The overall observations reinforce the concept that resources influence agonistic bouts. Fights in the presence of shelters were longer and more intense, suggesting that shelters have a higher perceived value than food resources. Fights in the presence of detritus patches had higher average intensities and ended with more tailflips away from an opponent, suggesting that detritus was a more valuable food resource than macrophytes. In addition, observations of aggressive behavior within a natural setting can add validity to laboratory studies. When fights in nature are compared with laboratory fights, those in nature are shorter, less intense, and less likely to end with a tailflip, but do show the fundamental fight dynamics associated with laboratory studies. Extrinsic and intrinsic factors affect intraspecific aggression in many ways, and both should always be recognized as having the potential to alter agonistic behavior.

Agonistic Behavior↗
PubMed2003

DcR3/TR6 effectively prevents islet primary nonfunction after transplantation.

Islet primary nonfunction (PNF) is defined as the loss of islet function after transplantation for reasons other than graft rejection. It is a major obstacle to successful and efficient islet transplantation. DcR3/TR6 is a soluble death decoy receptor belonging to the tumor necrosis factor (TNF) receptor family, and it can block apoptosis mediated by several TNF receptor family members such as Fas and LT beta R. In this study, we used TR6 to protect islets from PNF after transplantation. Untreated isogeneic or allogeneic islet transplantation had PNF incidence of 25 and 26.5%, respectively. Administration of TR6 totally prevented PNF in allogeneic islet transplantation. In vitro experiments showed an increased apoptosis among islets that were treated with FasL and gamma-interferon (IFN-gamma) in combination. TR6 significantly reduced such apoptosis. Functional study showed that insulin release was compromised after FasL and IFN-gamma treatment, and the compromise could be prevented with TR6-Fc. This indicates that TR6 indeed protected beta-cells from damage caused by FasL and IFN-gamma. Further in vivo experiments showed that syngeneic islet transplantation between lpr/lpr and gld/gld mice was significantly more efficacious than that conducted between wild-type mice. These results suggest that Fas-mediated apoptosis plays an important role in PNF, and use of TR6 may be a novel strategy to prevent PNF in clinical islet transplantation.

Animals↗
PubMed2002

Regulatory effect of IFN-kappa, a novel type I IFN, on cytokine production by cells of the innate immune system.

IFN-kappa is a recently identified type I IFN that exhibits both structural and functional homology with the other type I IFN subclasses. In this study, we have investigated the effect of IFN-kappa on cells of the innate immune system by comparing cytokine release following treatment of human cells with either IFN-kappa or two recombinant IFN subtypes, IFN-beta and IFN-alpha2a. Although IFN-alpha2a failed to stimulate monocyte cytokine secretion, IFN-kappa, like IFN-beta, induced the release of several cytokines from both monocytes and dendritic cells, without the requirement of a costimulatory signal. IFN-kappa was particularly effective in inhibiting inducible IL-12 release from monocytes. Unlike IFN-beta, IFN-kappa did not induce release of IFN-gamma by PBL. Expression of the IFN-kappa mRNA was observed in resting dendritic cells and monocytes, and it was up-regulated by IFN-gamma stimulation in monocytes, while IFN-beta mRNA was minimally detectable under the same conditions. Monocyte and dendritic cell expression of IFN-kappa was also confirmed in vivo in chronic lesions of psoriasis vulgaris and atopic dermatitis. Finally, biosensor-based binding kinetic analysis revealed that IFN-kappa, like IFN-beta, binds strongly to heparin (K(d): 2.1 nM), suggesting that the cytokine can be retained close to the local site of production. The pattern of cytokines induced by IFN-kappa in monocytes, coupled with the unique induction of IFN-kappa mRNA by IFN-gamma, indicates a potential role for IFN-kappa in the regulation of immune cell functions.

Adjuvants, Immunologic↗
PubMed2002

Stimulation of IRF-7 gene expression by tumor necrosis factor alpha: requirement for NFkappa B transcription factor and gene accessibility.

Interferon regulatory factor 7 (IRF-7) plays an important role in innate immunity, where, together with IRF-3, it controls the expression of interferon A/B genes as well as chemokine RANTES (regulated on activation normal T cell expressed and secreted). Previously, we characterized human IRF-7 promoter and showed that an interferon-stimulated response element site in the first intron binds interferon-stimulated gene factor 3 (ISGF3) and confers the response to interferon. Here we report the stimulation of IRF-7 expression by 12-O-tetradecanoylphorbol-13-acetate (TPA) and tumor necrosis factor alpha (TNFalpha) in human peripheral blood monocytes. Using promoter analysis in combination with electrophoretic mobility shift assays, we have demonstrated that an NFkappaB site located next to the TATA box, binds p50 and p65 heterodimer and is required for the induction of the IRF-7 gene by TPA and TNFalpha. In addition, we report stimulation of IRF-7 gene expression by topoisomerase II (TOPII) inhibitors. We show by chromatin immunoprecipitation assay that treatment with the TOPII inhibitor etoposide induces association of acetylated histone 3 with the promoter of IRF-7 gene, indicating that TOPII-mediated changes in chromatin structure could be responsible for the induction. This suggests that the IRF-7 gene is localized in the condensed area of the chromosome where it is inaccessible to transcription factors that would promote its constitutive expression.

Blotting, Northern↗
PubMed2002

Adverse drug reactions to local anesthesia.

A dentist's ability to safely administer regional anesthesia is essential for dental practice. Local anesthetic solutions used in the United States for dental anesthesia are formulated with several components. The contents of a standard local anesthetic cartridge may include an amide or ester local anesthetic drug, an adrenergic vasoconstrictor, and an antioxidant. In susceptible patients, any of these components may induce systemic, dose-dependent adverse reactions. Although extremely rare, allergic reactions may also occur. Signs and symptoms of the various adverse reactions associated with local anesthetics are quite distinctive, permitting rapid diagnosis and treatment. Serious reactions are extremely infrequent and, when treated properly, unlikely to result in significant morbidity or mortality.

Anesthesia, Dental↗
PubMed2002

Local anesthesia: advances in agents and techniques.

The improvements in agents and techniques for local anesthesia are possibly the most important advances in dental science to have occurred in the past 100 years. The agents currently available in dentistry have most of the characteristics of an ideal local anesthetic. Today's anesthetics can be administered with minimal irritation and little concern for stimulating allergic reactions. A variety of agents are available that provide rapid onset of surgical anesthesia with adequate duration. This article provides a brief review of the local anesthetic agents, formulations, and techniques used in dentistry with special emphasis on newly introduced agents and procedures.

Anesthesia, Dental↗
PubMed2002

Sedation for pediatric dental patients.

There are few areas of dental therapeutics as controversial as the pharmacologic management of fearful and uncooperative pediatric dental patients. A pediatric dentist is faced with one of the most difficult tasks in our profession: maximizing comfort and cooperation while minimizing risks and costs of dental care for the unmanageable child. Pharmacosedation provides the means for children to avoid psychologically traumatic experiences that might inhibit regular oral health care when they become adults. By controlling disruptive behaviors, the pediatric dentist is able to provide quality dental care in an environment that is pleasant for the child, the parent, and the practitioner.

Adjuvants, Anesthesia↗
PubMed2002

TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator.

DR3 is a death domain-containing receptor that is upregulated during T cell activation and whose overexpression induces apoptosis and NF-kappaB activation in cell lines. Here we show that an endothelial cell-derived TNF-like factor, TL1A, is a ligand for DR3 and decoy receptor TR6/DcR3 and that its expression is inducible by TNF and IL-1alpha. TL1A induces NF-kappaB activation and apoptosis in DR3-expressing cell lines, while TR6-Fc protein antagonizes these signaling events. Interestingly, in T cells, TL1A acts as a costimulator that increases IL-2 responsiveness and secretion of proinflammatory cytokines both in vitro and in vivo. Our data suggest that interaction of TL1A with DR3 promotes T cell expansion during an immune response, whereas TR6 has an opposing effect.

Amino Acid Sequence↗
PubMed2002

B lymphocyte stimulator (BLyS): a therapeutic trichotomy for the treatment of B lymphocyte diseases.

B Lymphocyte Stimulator (BLyS protein) is a member of the tumor necrosis factor (TNF) family of ligands and functions as an essential in vivo regulator of B lymphocyte homeostasis. As such, changes in systemic BlyS protein expression caused by disruption of the gene encoding BLyS or administration of neutralizing soluble receptors have resulted in profound losses in mature B cell numbers and impaired humoral immunity. A similar phenotype has been observed in A/WySnJ mice that express a truncated BLyS receptor and are thus defective in BLyS signal transduction. In contrast, overexpression of BLyS protein in BLyS-transgenic mice results in B cell hyperplasia, hypergammaglobulinemia, and development of autoimmune-like disease. The ability of BLyS to regulate both the size and repertoire of the peripheral B cell compartment raises the possibility that BLyS and antagonists thereof may form the basis of a therapeutic trichotomy. As an agonist, BLyS protein may enhance humoral immunity in congenital or acquired immunodeficiencies such as those resulting from viral infection or cancer therapy. BLyS-specific antagonists (antibodies or soluble receptors) that inhibit the biological activity of BLyS may be effective therapies for those autoimmune diseases characterized by polyclonal hypergammaglobulinemia and elevated autoantibody titers. Finally, the specificity of BLyS for B-lineage cells raises the possibility that BLyS may be used as a targeting vehicle for delivery of a cytotoxic or cytolytic signal to neoplastic B-lineage cells expressing one or more of the three known BLyS receptors. This review discusses the therapeutic potential of BLyS in the context of BLyS structure, function and receptor specificity.

Animals↗
PubMed2002

Bilateral and unilateral antennal lesions alter orientation abilities of the crayfish, Orconectes rusticus.

Numerous animals use chemical cues within their environments to execute various behaviors. One of these behaviors is orientation to an odor source. Crayfish, in particular, can orient to food sources under a number of different conditions. It has not been determined, however, what kind of search strategy these animals employ to successfully locate a food source. To determine the role of antennae and antennules in this behavior and to investigate different modes of orientation behavior, the orientation patterns of crayfish with complete and partial antennal lesions were examined. Detailed analysis of orientation paths confirmed that crayfish could not locate odor sources with either bilateral or unilateral lesions. This suggests that crayfish are using the spatial information obtained from these appendages to successfully orient. Animals using information from the bilaterally paired appendages in the control group exhibited increased walking speed, increased speed to source and decreased heading angles towards the source compared to these measurements taken from lesioned groups. There was no significant difference in any parameters between animals with unilateral or bilateral lesions. This strongly suggests that these animals are reliant on the spatial comparison of differences between bilaterally paired olfactory appendages for successful orientation.

Animals↗
PubMed1979

The submaximal effort tourniquet test: its use in evaluating experimental and chronic pain.

The submaximal effort tourniquet test has been widely used to evaluate experimental and chronic pain; however, there has been great variation in the manner in which the test has been applied. The present study systemitically evaluates how different levels of exercise duration and effort affect subjects' report of pain. The data indicate the following: (1) the manner in which the exercise is performed has an important effect on subjects' rating of pain, and (2) under all conditions studied, the pain ratings do not increase as a linear function of time. Both findings warrant precautions when using the submaximal effort tourniquet test to study experimental and chronic pain.

Chronic Disease↗
PubMedDate not supplied

Dental therapeutic practice patterns in the U.S. I. Anesthesia and sedation.

For this first of a two-part article, anesthetic treatment modalities and specific drugs administered for third molar extractions were assessed to determine current office-based therapeutic practices. Questionnaires were mailed to a random national sample of 850 practicing oral surgeons. Survey design and pilot testing was conducted to assure clarity of questions and usefulness of responses. To maximize the response rate, two follow-up letters were sent to non-responders after the initial mailing. Completed questionnaires were returned by 563 practitioners (66.2% response rate). Practicing oral and maxillofacial surgeons were estimated to have performed an average of 52.7 third molar extraction surgery cases per month, using either general anesthesia (46.3%), intravenous conscious sedation (33.4%), nitrous oxide sedation (5.8%), oral sedation (1.7%), or local anesthesia alone (12.9%). For intravenous conscious sedation, a three-drug technique using midazolam, fentanyl, and propofol was reported most commonly. The most frequently selected local anesthetic formulations were 2% lidocaine, 1:100,000 epinephrine for surgical anesthesia and 0.5% bupivacaine, 1:200,000 epinephrine for postoperative pain management.

Anesthesia, Dental↗
PubMedDate not supplied

Dental therapeutic practice patterns in the U.S. II. Analgesics, corticosteroids, and antibiotics.

This article examines the prescribing practices for peripherally acting and centrally acting analgesics, corticosteroids, and antibiotics following third molar extraction. A nationwide survey involving the prescribing patterns of a random national sample of 850 practicing oral surgeons was performed in 2004. Ibuprofen was the peripherally acting analgesic respondents used most frequently in the previous month, selected by 73.5% of the respondents. The ibuprofen dose prescribed most frequently was 800 mg, followed by doses of 600 mg and 400 mg. The centrally acting analgesic prescribed most frequently was the combination formulation of hydrocodone with acetaminophen, selected by 64.0% of the respondents. Recommendations for oral analgesics to manage postoperative pain relied on the peripherally acting analgesic ibuprofen or the centrally acting analgesic combination formulation hydrocodone with acetaminophen. Routine instructions to use centrally acting analgesics "as needed for pain" suggest that centrally acting analgesics are offered to manage pain that postoperative peripherally acting analgesics and intraoperative long-acting local anesthetics do not control adequately. The frequency with which oral and maxillofacial surgeons administered antibiotics and corticosteroids varied widely based on perceived patient need and dentist expectations.

Acetaminophen↗