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P A Moore

Publications and source records attributed to P A Moore.

At least 19 recordsLinked to original sources
PubMed1999

Activation of NF-kappaB by RANK requires tumor necrosis factor receptor-associated factor (TRAF) 6 and NF-kappaB-inducing kinase. Identification of a novel TRAF6 interaction motif.

Various members of the tumor necrosis factor (TNF) receptor superfamily activate nuclear factor kappaB (NF-kappaB) and the c-Jun N-terminal kinase (JNK) pathways through their interaction with TNF receptor-associated factors (TRAFs) and NF-kappaB-inducing kinase (NIK). We have previously shown that the cytoplasmic domain of receptor activator of NF-kappaB (RANK) interacts with TRAF2, TRAF5, and TRAF6 and that its overexpression activates NF-kappaB and JNK pathways. Through a detailed mutational analysis of the cytoplasmic domain of RANK, we demonstrate that TRAF2 and TRAF5 bind to consensus TRAF binding motifs located in the C terminus at positions 565-568 and 606-611, respectively. In contrast, TRAF6 interacts with a novel motif located between residues 340 and 358 of RANK. Furthermore, transfection experiments with RANK and its deletion mutants in human embryonic 293 cells revealed that the TRAF6-binding region (340-358), but not the TRAF2 or TRAF5-binding region, is necessary and sufficient for RANK-induced NF-kappaB activation. Moreover, a kinase mutant of NIK (NIK-KM) inhibited RANK-induced NF-kappaB activation. However, RANK-mediated JNK activation required a distal portion (427-603) of RANK containing the TRAF2-binding domain. Thus, our results indicate that RANK interacts with various TRAFs through distinct motifs and activates NF-kappaB via a novel TRAF6 interaction motif, which then activates NIK, thus leading to NF-kappaB activation, whereas RANK most likely activates JNK through a TRAF2-interacting region in RANK.

Amino Acid Sequence↗
PubMed1999

Reducing phosphorus runoff and improving poultry production with alum.

This is a review paper on the effects of aluminum sulfate (alum) on ammonia volatilization and P runoff from poultry litter. Initially, laboratory studies were conducted that showed P solubility could be reduced in poultry litter with Al, Ca, and Fe amendments, indicating that these amendments may reduce P runoff. These results were confirmed in small plot studies in which alum applications to litter were shown to decrease P concentrations in runoff by as much as 87%, while improving tall fescue yields. Leaf tissue analyses indicated that the yield improvements were due to increased N availability, which we hypothesized was due to reduced NH3 volatilization. This result was confirmed in laboratory studies that showed that alum was one of the most effective (and cost-effective) compounds for reducing NH3 volatilization. Field trials conducted at commercial broiler farms in conjunction with the Environmental Protection Agency showed that alum additions to poultry litter lowered litter pH, particularly during the first 3 to 4 wk of each growout, which resulted in less NH3 volatilization and lower atmospheric NH3. Ammonia volatilization rates were reduced by 97% for the first 4 wk of the growout. Broilers grown on alum-treated litter were heavier than the controls (1.73 vs 1.66 kg) and had lower mortality (3.9 vs 4.2%) and better feed efficiency (1.98 vs 2.04). Electricity and propane use were lower for alum-treated houses. As a result of these economic benefits to the integrator and grower, the benefit:cost ratio of alum addition was 1.96. Phosphorus concentrations in runoff from small watersheds were 75% lower from alum-treated litter than normal litter over a 3-yr period. Long-term small plot studies on alum use have shown that alum-treated litter results in lower soil test P levels than normal litter and does not increase Al availability in soils or uptake by plants.

Agriculture↗
PubMed1999

Adverse drug interactions in dental practice. Professional and educational implications.

BACKGROUND: Rapid progress in dental pharmacotherapeutics requires that clinicians constantly update their knowledge of new drugs, drug interactions and useful therapeutic trends. This article is the first in a five-part series based on a 1998 International Association for Dental Research symposium entitled "Adverse Drug Interactions in Dentistry: Separating the Myths From the Facts." The goal of the series is to identify specific adverse drug interactions that are relevant to the therapeutic agents commonly used in general dental practice: analgesics, antibiotics, sedatives, local anesthetics and vasoconstrictors. METHODS: A group of dentist/clinical pharmacologists, with documented expertise in specific areas of dental therapeutics, reviewed the current literature regarding adverse drug interactions in dentistry. This expert panel evaluated the quality of information used to document these drug interactions and assess the severity of these drug reactions with respect to the drugs' use in dental practice. RESULTS: On the basis of the quality and severity of each reported interaction, the authors summarized the clinical importance of these drug interactions using a Significance Rating for Dental Drug Interactions. The participants presented their recommendations at the above-mentioned IADR symposium. CONCLUSIONS: Although thousands of drug interactions are described in the literature, the authors found many to be poorly documented or of minor importance to dental practitioners. For interactions that they determined to be relevant, the participants provided recommendations and precautions for preventing these potential complications. This article discusses the professional impact of drug interactions on dental practice; the classification and documentation of drug interactions; the determination of causality between drug interactions and adverse effects; risk factors; and unique characteristics of dental therapeutics. Subsequent articles will present specific summary recommendations for drug interactions associated with the use of antibiotics, analgesics, sedatives, and local anesthetics and vasoconstrictors. CLINICAL IMPLICATIONS: Although thousands of drug interactions have been reported in the literature, only a few are significantly associated with dental therapeutic agents. Avoiding these drug interactions will prevent potentially severe reactions in dental practice.

Adverse Drug Reaction Reporting Systems↗
PubMed1999

Adverse drug interactions in dental practice: interactions associated with local anesthetics, sedatives and anxiolytics. Part IV of a series.

BACKGROUND: This article is the fourth in a five-part series based on a 1998 International Association for Dental Research symposium entitled "Adverse Drug Interactions in Dentistry: Separating the Myths From the Facts." The symposium evaluated the significance of various drug interactions associated with dental therapeutics. METHODS: Local anesthesia and preoperative oral sedative/anxiolytic therapy often are indicated for routine oral surgery and restorative dentistry. The author conducted a literature review of the drug interactions associated with the use of local anesthetics and sedatives. The quality of the information used to document these interactions and the severity of the possible adverse outcome were assessed using a significance rating scale for dental drug interactions. RESULTS: Many of the frequently described drug interactions were found to be poorly documented in the dental and medical literature. Others were determined not to be relevant to current dental practice. The use of local anesthetics, sedatives or anxiolytic agents in combination with other central nervous system depressant agents or in combination with drugs that inhibit their metabolism was associated with a few serious adverse drug interactions or complications. CONCLUSIONS: The adverse drug interactions associated with the use of local anesthetics and oral sedative/anxiolytic agents in general practice vary in significance. An understanding of possible adverse drug interactions in dentistry may help practitioners avoid and prevent these complications.

Aged↗
PubMed1999

Type 1 diabetes mellitus and oral health: assessment of periodontal disease.

BACKGROUND: The periodontal disease status of 320 dentate adults, diagnosed 23.7 years previously with Type 1 insulin dependent diabetes mellitus, was evaluated. These patients had been monitored at 2-year intervals as part of a large University of Pittsburgh longitudinal study assessing the medical complications associated with insulin dependent diabetes. METHODS: During one of their regularly scheduled medical examinations, a group of 320 adult dentate subjects (mean age of 32.1 years) received a periodontal examination as part of a comprehensive oral health assessment. The oral health assessment collected data regarding demographics, oral health behaviors, tooth loss, coronal and root caries, salivary functions, and soft tissue pathologies. For the periodontal assessments, 3 facial sites (mesial, midcervical, distal) of the teeth in the right maxillary/left mandibular or left maxillary/right mandibular quadrants were evaluated for calculus, bleeding on probing (BOP) and loss of gingival attachment (LOA). RESULTS: Attachment loss was significantly greater for older patients whereas BOP and calculus levels were relatively constant across age categories. Univariate analyses of factors possibly related to extensive periodontal disease (LOA > or =4 mm for at least 10% of sites examined) indicated an association with older age; lower income and education; past and current cigarette smoking; infrequent visits to the dentist; tooth brushing less than once per day; older age of onset; longer duration of diabetes; and the diabetic complication of neuropathy. A multivariate regression model of all possibly significant factors found current cigarette use (odds ratio [OR] = 9.73), insulin dependent diabetes onset after 8.4 years of age (OR = 3.36), and age greater than 32 years (OR = 3.00) explained the majority of the extensive periodontal disease in this group of diabetic patients. CONCLUSIONS: Management and prevention of extensive periodontal disease for Type 1 diabetic patients should include strong recommendations to discontinue cigarette smoking.

Adult↗
PubMed1998

Characterization of the interferon regulatory factor-7 and its potential role in the transcription activation of interferon A genes.

The family of interferon regulatory factors (IRFs) plays an important role in modulating cellular responses to viral infection and cytokines, including IFNs. The transcription factors that are involved in the transcriptional activation of the IFNB gene have been extensively studied. However, the molecular mechanism by which virus activates the expression of the IFNA gene remains to be defined. Recently, we have identified a new IRF-7 isoform, denoted as IRF-7H, which encodes a protein of 514 amino acids and is most closely related to the IRF-3. The expression of IRF-7 is restricted to the lymphoid cell types and is inducible by virus, lipopolysaccharide, and IFNA. The functional characterization of IRF-7H reveals a presence of transactivation domain located carboxyl-terminal to its DNA binding domain. Overexpression of IRF-7H results in an activation of IFNA promoter in transient transfection assay and a strong enhancement of virus-mediated activation of this promoter. Whereas in uninfected cells, overexpressed IRF-7H is present mainly in the cytoplasm, viral infection facilitates the transfer of IRF-7H to the nucleus; overexpression of IRF-3 interferes with the virus-induced translocation of IRF-7H. Thus, IRF-7 exhibits functional similarity to IRF-3; however, the preferential expression of IRF-7 in lymphoid cells (the cell type that expresses IFNA) suggests that IRF-7 may play a critical role in regulating the IFNA gene expression.

Alternative Splicing↗
PubMed1998

Characterization of the intracellular domain of receptor activator of NF-kappaB (RANK). Interaction with tumor necrosis factor receptor-associated factors and activation of NF-kappab and c-Jun N-terminal kinase.

Various members of the tumor necrosis factor (TNF) receptor superfamily interact directly with signaling molecules of the TNF receptor-associated factor (TRAF) family to activate nuclear factor kappaB (NF-kappaB) and the c-Jun N-terminal kinase (JNK) pathway. The receptor activator of NF-kappaB (RANK), a recently described TNF receptor family member, and its ligand, RANKL, promote survival of dendritic cells and differentiation of osteoclasts. RANK contains 383 amino acids in its intracellular domain (residues 234-616), which contain three putative TRAF-binding domains (termed I, II, and III). In this study, we set out to identify the region of RANK needed for interaction with TRAF molecules and for stimulation of NF-kappaB and JNK activity. We constructed epitope-tagged RANK (F-RANK616) and three C-terminal truncations, F-RANK330, F-RANK427, and F-RANK530, lacking 85, 188, and 285 amino acids, respectively. From this deletion analysis, we determined that TRAF2, TRAF5, and TRAF6 interact with RANK at its C-terminal 85-amino acid tail; the binding affinity appeared to be in the order of TRAF2 > TRAF5 > TRAF6. Furthermore, overexpression of RANK stimulated JNK and NF-kappaB activation. When the C-terminal tail, which is necessary for TRAF binding, was deleted, the truncated RANK receptor was still capable of stimulating JNK activity but not NF-kappaB, suggesting that interaction with TRAFs is necessary for NF-kappaB activation but not necessary for activation of the JNK pathway.

Amino Acid Sequence↗
PubMed1998

Cloning of Drosophila GCN5: conserved features among metazoan GCN5 family members.

PCAF and hGCN5 are distinct human genes that encode proteins related to the yeast histone acetyltransferase and transcriptional adapter GCN5. The PCAF protein shares extensive similarity with the 439 amino acids of yGCN5, but it has an approximately 350 amino acid N-terminal extension that interacts with the transcriptional co-activator p300/CBP. Adenoviral protein E1a can disrupt PCAF-CBP interactions and prevent PCAF-dependent cellular differentiation. In this report, we describe the cloning and initial characterization of a Drosophila homolog of yGCN5. In addition to the homology to yGCN5, the Drosophila protein shares sequencesimilarity with the N-terminal portion of human PCAF that is involved in binding to CBP. In the course of characterizing dGCN5, we have discovered that hGCN5 also contains an N-terminal extension with significant similarity to PCAF. Interestingly, in the case of the h GCN5 gene, alternative splicing may regulate the production of full-length hGCN5. The presence of the N-terminal domain in a Drosophila GCN5 homolog and both human homologs suggests that it was part of the ancestral form of metazoan GCN5.

Acetyl-CoA C-Acyltransferase↗
PubMed1998

Regulation of type I interferon gene expression by interferon regulatory factor-3.

The genes of the family of interferon (IFN) regulatory factors (IRF) encode DNA binding transcriptional factors that are involved in modulation of transcription of IFN and interferon-induced genes (ISG). The presence of IRF binding sites in the promoter region of IFNA and IFNB genes indicates that IRF factors recognizing these sites play an important role in the virus-mediated induction of these genes. We have described a novel human gene of this family, IRF-3, that is constitutively expressed in a variety of cell types. IRF-3 binds to the interferon-sensitive response element (ISRE) present in the ISG15 gene promoter and activates its transcriptional activity. In the present study, we examined whether IRF-3 can modulate transcriptional activity of IFNA and IFNB promoter regions. Our results demonstrate that IRF-3 can bind to the IRF-like binding sites present in the virus-inducible region of the IFNA4 promoter and to the PRDIII region of the IFNB promoter but cannot alone stimulate their transcriptional activity in the human cell line, 293. However, the fusion protein generated from the IRF-3 binding domain and the RelA(p65) activation domain effectively activates both IFNA4 and IFNB promoters. Cotransfection of IRF-3 and RelA(p65) expression plasmids activates the IFNB gene promoter but not the promoter of IFNA4 gene that does not contain the NF-kB binding site. Surprisingly, activation of the IFNA4 gene promoter by virus and IRF-1 in these cells was inhibited by IRF-3. These data indicate that in 293 cells IRF-3 does not stimulate expression of IFN genes but can cooperate with RelA(p65) to stimulate the IFNB promoter.

Amino Acid Sequence↗
PubMed1998

Tramadol hydrochloride: analgesic efficacy compared with codeine, aspirin with codeine, and placebo after dental extraction.

Tramadol hydrochloride is a novel, centrally acting analgesic with two complementary mechanisms of action: opioid and aminergic. Relative to codeine, tramadol has similar analgesic properties but may have fewer constipating, euphoric, and respiratory depressant effects. A two-center randomized double-blind controlled clinical trial was performed to assess the analgesic efficacy and reported side effects of tramadol 100 mg, tramadol 50 mg, codeine 60 mg, aspirin (ASA) 650 mg with codeine 60 mg, and placebo. Using a third molar extraction pain model, 200 healthy subjects were enrolled in a 6-hour evaluation after a single dose of drug. Of the 200 patients enrolled, seven provided incomplete efficacy data or discontinued prematurely and one was lost to follow-up. Using standard measures of analgesia, including total pain relief score (TOTPAR), maximum pain relief score (MaxPAR), sum of pain intensity difference scores (SPID), peak pain intensity difference (Peak PID), remedication, and global evaluations, all active treatments were found to be numerically superior to placebo. ASA/codeine was found to be statistically superior to placebo for all measures of efficacy. Tramadol 100 mg was statistically superior to placebo for TOTPAR, SPID, and time of remedication, whereas tramadol 50 mg was statistically superior to placebo onlyfor remedication time. Codeine was not found to be statistically superior to placebo for any efficacy measure. A greater TOTPAR response compared with all other active measures was seen for ASA/codeine during the first 3 hours of study. The 6-hour TOTPAR scores for the tramadol groups and ASA/ codeine group were not significantly different. Gastrointestinal side effects (nausea, dysphagia, vomiting) were reported more frequently with tramadol 100 mg, ASA/ codeine, and codeine 60 mg than with placebo.

Adolescent↗
PubMed1998

Effect of dietary phytase and high available phosphorus corn on broiler chicken performance.

Two trials were conducted to determine the effects on broiler chicken performance and health of reducing dietary phosphorus levels by treating feed with the enzyme phytase, formulating diets using high available phosphorus (HAP) corn, or when diets were formulated with HAP corn and treated with phytase. Cobb x Cobb male broiler chickens were placed in an experimental design consisting of four dietary treatments with six replicate pens of 50 broilers per pen. The dietary treatments consisted of untreated control feed, phytase-supplemented feed (500 U/kg), diets prepared with HAP corn, and diets prepared with HAP corn and supplemented with phytase. The chickens were maintained on these dietary treatments from 1 to 49 d of age with feed and water made available for ad libitum consumption. When the two trials were combined, there was a significant (P < or = 0.05) increase in body weight in the broilers fed the phytase treated diets at 49 d of age. The serum activity of alkaline phosphatase was significantly decreased in the diets supplemented with phytase, and serum cholesterol was significantly decreased in the diets prepared with HAP corn. These data indicate that total phosphorus can be reduced by at least 11% in diets prepared with HAP corn, or in diets supplemented with phytase, without affecting the performance or health of broiler chickens. When diets are prepared with HAP corn and supplemented with phytase, the dietary addition of total phosphorus can be reduced by at least 25% without affecting broiler chicken performance or health.

6-Phytase↗
PubMed1998

Type 1 diabetes mellitus and oral health: assessment of tooth loss and edentulism.

OBJECTIVE: The oral health of an adult population previously diagnosed with juvenile onset insulin dependent-diabetes was comprehensively assessed. The goal of this exploratory cross-sectional evaluation was to described the characteristics related to partial tooth loss edentulism in subjects with Type 1 diabetes mellitus. METHODS: An adult population of 406 Type 1 diabetes mellitus subjects, who had been monitored for 6-8 years as part of a University of Pittsburgh longitudinal study of medical complications associated with diabetes, received an oral health examination for missing teeth, edentulism, coronal and root caries, periodontal status, and oral health behaviors. RESULTS: Of the 406 subjects evaluated, 204 had no missing teeth, 186 had partial tooth loss (1-27 missing teeth), and 16 were edentulous. Patients who had partial tooth loss or who were edentulous were generally older; had lower incomes and levels of education; and had higher rates of nephropathy, neuropathy, retinopathy, and peripheral vascular disease. A logistic regression model found partial tooth loss to be significantly associated with extensive periodontal disease in remaining teeth (OR = 7.35), a duration of diabetes longer than 24 years (OR = 5.32), not using dental floss (OR = 2.37), diabetic neuropathy (OR = 2.29), household income less than $20,000 (OR = 2.21), multiple coronal caries and fillings (OR = 1.98), and bleeding on probing (OR = 1.82). CONCLUSIONS: Although the majority of these adult Type 1 diabetes patients had serious medical complications associated with their diabetes, the possible impact of diabetes mellitus on oral health should be included in their overall management.

Adolescent↗
PubMed1998

Reliability of self-reported heart murmur history: possible impact on antibiotic use in dentistry.

Administration of prophylactic antibiotics to a dental patient with a history of heart murmur, rheumatic fever or mitral valve prolapse should be based on a reliable diagnosis of heart valve disease. The authors conducted a study of 68 diabetic patients who reported having these conditions and found that at least 65 percent of these patients actually had no evidence of a pathological heart murmur during two previous physical examinations. They concluded that a self-reported history of heart valve disease should not be the sole criterion for antibiotic premedication.

Adolescent↗
PubMed1998

Selecting drugs for the pregnant dental patient.

When treating pregnant patients, dental practitioners should avoid prescribing some drugs routinely used for local anesthesia, sedation, analgesia or infection. Dental practitioners need to determine that the potential benefits of the drug required for the mother's dental care outweigh the risks to her fetus. This article briefly reviews the relative risks of therapeutic agents commonly used in dental care to help practitioners select the safest drugs for use by pregnant patients.

Analgesics↗
PubMed1997

The human transcriptional adaptor genes TADA2L and GCN5L2 colocalize to chromosome 17q12-q21 and display a similar tissue expression pattern.

The chromosomal locations and the tissue expression patterns of the human transcriptional adaptors TADA2L and GCN5L2 have been determined. Northern blot analysis across a range of human tissues revealed that both the TADA2L and the GCN5L2 mRNAs are expressed to varying degrees in all tissue types. Furthermore, in most tissue types, the genes are expressed at relatively similar levels, suggesting coordinated regulation of TADA2L and GCN5L2 transcription. Chromosomal mapping by fluorescence in situ hybridization indicated that these genes reside near each other on chromosome 17; TADA2L mapped within bands 17q12-q21, while GCN5L2 mapped distally within band 17q21.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Mechanical isolation and in vitro growth of preantral and small antral human follicles.

OBJECTIVE: To develop a procedure for isolating small human follicles and to determine their growth requirements. DESIGN: Preantral and early antral follicles were isolated manually, allocated randomly to experimental groups, and cultured for a few weeks. SETTING: Patients giving informed consent in hospitals. PATIENT(S): Women undergoing laparotomy or oophorectomy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Follicular size, E2, histology. RESULT(S): Human FSH (at a dose of 1.5 U/mL) induced antral growth of follicles, and the addition of human LH (2.5 ng/mL) to human FSH stimulated growth and antral development. Histologic studies showed that most of the early antral follicles did not contain an oocyte and already had begun to undergo atresia before culturing. Levels of E2 increased in the incubation medium as the follicles increased in size, but those levels were significantly greater when the follicles contained oocytes. CONCLUSION(S): It is possible to grow small human follicles after they have been isolated manually. To develop successfully, they require a low concentration of human LH in addition to human FSH. The rate of atresia between the preantral and early antral stages in vivo is very high; therefore, it is worthwhile to develop techniques for isolating and culturing the follicles before the antral stages.

Adult↗
PubMed1997

Multidrug intravenous sedation: determinants of the sedative dose of midazolam.

OBJECTIVES: The efficacy of multidrug intravenous sedation regimens in oral surgery is based on the ability to titrate opioids, benzodiazepines, and barbiturates to a desired level of relaxation. Dosage requirements to reach the initial sedation end points of slurred speech and ptosis of eyelids vary widely from one patient to another. STUDY DESIGN: An assessment of physical, cardiovascular, behavioral, and pharmacologic factors that might predict midazolam dosage requirements for the initial sedation titration was carried out with data collected from a large controlled clinical trial of fentanyl, midazolam, and methohexital sedation for third molar surgery. RESULTS: Dosage requirements for the initial titration of midazolam were found to be significantly higher when fentanyl was not included in the sedation regimen and when presedation heart rate and presedation systolic blood pressure were elevated.

Adolescent↗