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Biomedical subjects

P A Moore

Publications and source records attributed to P A Moore.

At least 19 recordsLinked to original sources

Prevention of Escherichia coli respiratory infection in broiler chickens with bacteriophage (SPR02).

Bacteriophages are viruses that can infect and kill bacteria. Three studies were conducted to determine the efficacy of bacteriophage to prevent an Escherichia coli respiratory infection in broiler chickens. In the first study 3-d-old-birds were challenged with an air sac inoculation of 10(3) cfu of E. coli per mL mixed with either 10(3) or 10(6) pfu of bacteriophage, or 10(4) cfu E. coli mixed with 10(4) or 10(8) pfu of bacteriophage. In the second study, drinking water of birds to 1 wk of age was treated with 10(3) or 10(4) pfu of bacteriophage per mL and birds were air sac challenged with 10(3) cfu of E. coli, or water was treated with 10(4) or 10(6) pfu of bacteriophage per milliliter and birds were challenged with 10(4) cfu of E. coli. In the third study, birds were air sac challenged at 1 wk of age with 10(4) cfu of E. coli and given 10(5) or 10(6) pfu of bacteriophage per mL of water from 1 d of age to 2 wk of age. In Studies 1 and 2, there were two replicate pens per treatment with 10 birds per pen, and in Study 3, there were four replicate pens per treatment with 10 birds per pen. The studies were all concluded when the birds were 3 wk of age. In Study 1, BW was decreased at 1 and 2 wk of age in the birds that were challenged with 10(3) or 10(4) cfu of E. coli and was decreased at 2 wk of age in the birds challenged with 10(4) cfu of E. coli mixed with 10(4) pfu of the bacteriophage. Mortality was decreased from 80% in the birds challenged with 10(3) cfu of E. coli to 25 and 5% when mixed with 10(3) or 10(6) pfu of the bacteriophage, respectively. Mortality was decreased from 85% in birds challenged with 10(4) cfu of E. coli to 35% when mixed with 10(4) pfu of the bacteriophage, and no mortality occurred when mixed with 10(8) pfu of bacteriophage. There was essentially no protection observed in Studies 2 and 3 when the birds were challenged with 10(3) or 10(4) cfu of E. coli with bacteriophage present in their drinking water at any level. These data suggest that bacteriophage can protect birds from a respiratory challenge with E. coli, but that adding the bacteriophage to the drinking water offered no protection to the birds. The complete protection of the birds observed in Study 1 suggests that bacteriophage may possibly be developed as an alternative to antibiotic use in poultry.

Animals↗

Lobster sniffing: antennule design and hydrodynamic filtering of information in an odor plume.

The first step in processing olfactory information, before neural filtering, is the physical capture of odor molecules from the surrounding fluid. Many animals capture odors from turbulent water currents or wind using antennae that bear chemosensory hairs. We used planar laser-induced fluorescence to reveal how lobster olfactory antennules hydrodynamically alter the spatiotemporal patterns of concentration in turbulent odor plumes. As antennules flick, water penetrates their chemosensory hair array during the fast downstroke, carrying fine-scale patterns of concentration into the receptor area. This spatial pattern, blurred by flow along the antennule during the downstroke, is retained during the slower return stroke and is not shed until the next flick.

Animals↗

Interferon-kappa, a novel type I interferon expressed in human keratinocytes.

High throughput cDNA sequencing has led to the identification of interferon-kappa, a novel subclass of type I interferon that displays approximately 30% homology to other family members. Interferon-kappa consists of 207 amino acids, including a 27-amino acid signal peptide and a series of cysteines conserved in type I interferons. The gene encoding interferon-kappa is located on the short arm of chromosome 9 adjacent to the type I interferon gene cluster and is selectively expressed in epidermal keratinocytes. Expression of interferon-kappa is significantly enhanced in keratinocytes upon viral infection, upon exposure to double-stranded RNA, or upon treatment with either interferon-gamma or interferon-beta. Administration of interferon-kappa recombinant protein imparts cellular protection against viral infection in a species-specific manner. Interferon-kappa activates the interferon-stimulated response element signaling pathway and a panel of genes similar to those regulated by other type I interferons including anti-viral mediators and transcriptional regulators. An antibody that neutralizes the type I interferon receptor completely blocks interferon-kappa signaling, demonstrating that interferon-kappa utilizes the same receptor as other type I interferons. Interferon-kappa therefore defines a novel subclass of type I interferon that is expressed in keratinocytes and expands the repertoire of known proteins mediating host defense.

Amino Acid Sequence↗

Cloning and sequencing of human Eppin: a novel family of protease inhibitors expressed in the epididymis and testis.

In this report we describe the discovery of Eppin (Epididymal protease inhibitor), a gene on human chromosome 20 expressing three mRNAs encoding two isoforms of a cystine-rich protein containing both Kunitz-type and WAP-type four disuffide core protease inhibitor consensus sequences. Analysis of Eppin's genomic sequence from chromosome 20q12-13.2 predicts the existence of all three splice variants of Eppin and that all the exons conform to the AG/GT splicing rule. The presence of single bands on a Southern blot of human genomic DNA suggests that Eppin is a single copy gene. TATA box transcription initiation sites are present for both of the different Eppin 5' UTRs and examination of the promoter region 1800 bp upstream of the start codon revealed a number of putative transcription enhancer binding sites typical of genes expressed in the epididymis or testis. Northern blot and tissue specific PCR data indicate Eppin-1 is expressed only in the testis and epididymis; Eppin-2 is expressed only in the epididymis and Eppin-3 only in the testis. Antiserum prepared against recombinant EPPIN recognizes several strong bands on Western blots of human epididymal extracts from the caput and corpus regions. Immunohistochemistry indicates a strong pattern of expression by the ciliated cells of the efferent ducts and strong staining of ejaculated spermatozoa. Eppin represents the first member of a family of protease inhibitors characterized by dual inhibitor consensus sequences, both WAP-type and Kunitz-type consensus sequences. A second family member is predicted to exist on chromosome 20 approximately 4 kb downstream from Eppin's exon I, which has two WAP-type sequences and one Kumtz-type consensus sequence.

Alternative Splicing↗

Virus-specific activation of a novel interferon regulatory factor, IRF-5, results in the induction of distinct interferon alpha genes.

Interferon regulatory factor (IRF) genes encode DNA-binding proteins that are involved in the innate immune response to infection. Two of these proteins, IRF-3 and IRF-7, serve as direct transducers of virus-mediated signaling and play critical roles in the induction of type I interferon genes. We have now shown that another factor, IRF-5, participates in the induction of interferon A (IFNA) and IFNB genes and can replace the requirement for IRF-7 in the induction of IFNA genes. We demonstrate that, despite the functional similarity, IRF-5 possesses unique characteristics and does not have a redundant role. Thus, 1) activation of IRF-5 by phosphorylation is virus-specific, and its in vivo association with the IFNA promoter can be detected only in cells infected with NDV, not Sendai virus, while both viruses activate IRF-3 and IRF-7, and 2) NDV infection of IRF-5-overexpressing cells preferentially induced the IFNA8 subtype, while IFNA1 was primarily induced in IRF-7 expressing cells. These data indicate that multiple signaling pathways induced by infection may be differentially recognized by members of the IRF family and modulate transcription of individual IFNA genes in a virus and cell type-specific manner.

B-Lymphocytes↗

Synthesis and release of B-lymphocyte stimulator from myeloid cells.

B-lymphocyte stimulator (BLyS) is a recently identified novel member of the tumor necrosis factor ligand superfamily shown to exist in a membrane-bound and soluble form. BLyS was found to be specifically expressed on cells of myeloid lineage and to selectively stimulate B-lymphocyte proliferation and immunoglobulin production. The expression of a cytokine involved in potentiation of humoral immune responses, such as BLyS, is expected to be strictly controlled. The goal of the present study was to examine regulation of BLyS levels in monocytic cells in response to cytokines and during their differentiation to macrophages and dendritic cells. The presence of BLyS on the cell surface and in the culture medium of both normal blood monocytes and on tumor cells of myelomonocytic origin was demonstrated. BLyS gene expression and levels of membrane-associated and soluble BLyS were found to be regulated by cytokines, in particular interferon (IFN)-gamma and to a lesser extent interleukin-10 (IL-10). The expression of BLyS on monocyte membranes was retained following differentiation into macrophages, but detection on the surface of monocyte-derived dendritic cells required stimulation with IFN-gamma. Both IFN-gamma and IL-10 enhanced the release of soluble BLyS that was active in B-cell proliferation assays. Cells transfected with BLyS complementary DNA mutated in a predicted cleavage site failed to release BLyS into the culture medium, thereby suggesting that soluble BLyS was derived from the membrane form. These results provide further support for an important role for BLyS expressed in myeloid cells in B-cell expansion and antibody responses.

Antibodies↗

Chemical orientation of brown bullheads, Ameiurus nebulosus, under different flow conditions.

The spatiotemporal information in chemical signals provides critical information for organisms during chemical orientation. Information in chemical signals is influenced by the hydrodynamic conditions of the environment. Hydrodynamically distinct environments will contain different types of information, which will influence how organisms orient. This study was designed to examine how the orientation behavior of the brown bullhead (Ameiurus nebulosus) is influenced by flow regime. The experiment was conducted in a flume under two different flow conditions. Treatments consisted of control (no odor) and plain gelatin (odor). Percent success, swimming speed, turning angle, heading angle, heading angle upstream, and net-to-gross ratio were analyzed. Brown bullheads were 100% successful in finding the odor source under no flow and 57% successful in flow. Bullheads swam differently in the no-flow condition when compared to the flow condition. Since, these fish did not orient the same under different flow conditions, it appears that hydrodynamics plays a role in shaping their behavior.

Animals↗

Type 1 diabetes mellitus and oral health: assessment of coronal and root caries.

OBJECTIVES: The oral health of a large cohort of adult insulin-dependent diabetic patients (Type 1), diagnosed 24 years previously with juvenile onset, was comprehensively assessed. This paper describes the prevalence of coronal and root caries in this adult Type 1 diabetic population and evaluates demographic, dietary, behavioral, physiologic, salivary and medical variables associated with decayed and filled surfaces in the crown (DFS) or root (RDFS). METHODS: Type 1 diabetes mellitus subjects participating in this oral health evaluation had been monitored for 6-8 years as participants in the University of Pittsburgh, Department of Epidemiology, longitudinal study of medical complications associated with diabetes. Four hundred and six diabetic subjects received a comprehensive oral health examination during one of their regularly scheduled medical visits. Oral assessments included coronal and root caries, missing teeth, edentulism, periodontal status, soft tissue pathologies, salivary function and health behaviors. Sixteen diabetic subjects and one control subject were edentulous. Coronal and root caries data from the remaining 390 dentate diabetic subjects were compared with 202 dentate nondiabetic control subjects. RESULTS: The adult Type 1 diabetic subjects were not found to have significantly higher DFS rates as compared with our control subjects or published age-adjusted NHANES III findings. Both control and diabetic subjects had low decayed to filled tooth surface ratios. A linear regression model evaluated possible associations with coronal decayed and filled tooth surfaces (DFS) within the diabetic population. Significant factors included older age, women, fewer missing teeth, more frequent use of dental floss, more frequent visits to the dentist during the last 12 months, and diabetic nephropathy. The prevalence of RDFS was higher in the diabetic subjects as compared to recruited control subjects. Neither dietary behaviors nor glycemic control were found to contribute to coronal or root caries. CONCLUSIONS: Factors associated with presence of coronal and root caries and fillings are discussed. Possible causes and implications for the association between DFS and diabetic nephropathy are provided.

Adult↗

Examination techniques and interpretation of ophthalmic findings.

Before the patient can be properly treated for an ophthalmic condition, the examiner must correctly assess any abnormal ophthalmic findings. This is best accomplished by taking a complete history and by performing a thorough ophthalmic examination. When performing an ophthalmic examination, the examiner must evaluate all areas of the adnexa, globe, and orbit and must be comfortable with ophthalmic examination techniques and interpretation of examination findings. To aid the examiner in this process, ophthalmic examination technique and normal and abnormal ophthalmic findings are discussed.

Animals↗

Type 1 diabetes mellitus, xerostomia, and salivary flow rates.

OBJECTIVE: The Oral Health Science Institute at the University of Pittsburgh has completed a cross-sectional epidemiologic study of 406 subjects with type 1 diabetes and 268 control subjects without diabetes that assessed the associations between oral health and diabetes. This report describes the prevalence of dry-mouth symptoms (xerostomia), the prevalence of hyposalivation in this population, and the possible interrelationships between salivary dysfunction and diabetic complications. STUDY DESIGN: The subjects with diabetes were participants in the Pittsburgh Epidemiology of Diabetes Complications study who were enrolled in an oral health substudy. Control subjects were spouses or best friends of participants or persons recruited from the community through advertisements in local newspapers. Assessments of salivary function included self-reported xerostomia measures and quantification of resting and stimulated whole saliva flow rates. RESULTS: Subjects with diabetes reported symptoms of dry mouth more frequently than did control subjects. Salivary flow rates were also impaired in the subjects with diabetes. Regression models of potential predictor variables were created for the 3 self-reported xerostomia measures and 4 salivary flow rate variables. Of the medical diabetic complications studied (ie, retinopathy, peripheral and autonomic neuropathy, nephropathy, and peripheral vascular disease), only neuropathy was found to be associated with xerostomia and decreased salivary flow measures. A report of dry-mouth symptoms was associated with current use of cigarettes, dysgeusia (report of a bad taste), and more frequent snacking behavior. Xerogenic medications and elevated fasting blood glucose concentrations were significantly associated with decreased salivary flow. Resting salivary flow rates less than 0.01 mL/min were associated with a slightly higher prevalence of dental caries. Subjects who reported higher levels of alcohol consumption were less likely to have lower rates of stimulated salivary flow. CONCLUSIONS: Subjects with type 1 diabetes who had developed neuropathy more often reported symptoms of dry mouth as well as symptoms of decreased salivary flow rates. Because of the importance of saliva in the maintenance and the preservation of oral health, management of oral diseases in diabetic patients should include a comprehensive evaluation of salivary function.

Adult↗

CRB1 mutations may result in retinitis pigmentosa without para-arteriolar RPE preservation.

PURPOSE: To report a new phenotype in retinitis pigmentosa (RP) patients with CRB1 mutations at the RP12 locus. PATIENTS: Thirty-seven patients from two Pakistani families with severe retinitis pigmentosa. METHODS: Samples were screened with single-strand conformation polymorphism analysis followed by DNA sequencing of the coding sequence of the CRB1 gene. RESULTS: Two novel CRB1 mutations were discovered. No patients had evidence of preservation of the para-arteriolar retinal pigment epithelium (PPRPE) that has been previously reported in all cases of RP associated with CRB1 mutations. CONCLUSIONS: Patients with severe autosomal recessive (or simplex) RP who lack the finding of PPRPE should not be excluded from molecular analysis of CRB1 purely because they lack the clinical feature of PPRPE. This report illustrates that RP at the RP12 locus is not clinically uniform. The absence of PPRPE cannot be used to exclude CRB1 as a potential molecular explanation for RP.

Adolescent↗

Modulation of T-cell responses to alloantigens by TR6/DcR3.

TR6 (DcR3) is a new member of the TNF receptor (TNFR) family that lacks a transmembrane domain in its sequence, indicating that it is a secreted molecule. TR6 can bind to FasL and prevent FasL-induced apoptosis; it can also associate with LIGHT, another TNF family member. The role of TR6 in immune responses was investigated in this study. According to flow cytometry, recombinant human TR6-Fc binds to human LIGHT expressed on 293 cells or on activated human T cells and competes with the LIGHT receptor TR2 for the binding to LIGHT on these cells. Human TR6 could cross-react with mouse LIGHT in immunoprecipitation. TR6-Fc also downregulates cytotoxic T lymphocyte activity in vitro and graft-versus-host responses in mice. Moreover, TR6-Fc modulates lymphokine production by alloantigen-stimulated mouse T cells. TR6-Fc ameliorated rejection response to mouse heart allograft. These results indicate that TR6 can dampen T-cell responses to alloantigens. Such regulatory effects of TR6 probably occur via interference with interaction between pairs of related TNF and TNFR family members, LIGHT/TR2 being one of the possible candidate pairs.

Animals↗

Celecoxib and rofecoxib. The role of COX-2 inhibitors in dental practice.

BACKGROUND: In recent years, dental practitioners have relied on ibuprofen and other nonsteroidal anti-inflammatory drugs, or NSAIDs--such as naproxen, diflunisal and ketoprofen--to manage acute and chronic orofacial pain. Two NSAIDs that recently came on the market, celecoxib and rofecoxib, have been developed to limit the adverse effects seen after chronic use of NSAIDs. LITERATURE REVIEWED: The authors have summarized all available publications describing the human pharmacokinetics, clinical pharmacology and known adverse effects of these new specific cyclooxygenase-2, or COX-2, inhibitors. CONCLUSIONS: Although peripherally acting analgesics are remarkably effective, chronic administration of nonselective COX inhibitors has been associated with gastrointestinal ulceration and prolonged bleeding. The authors present the distinctive mechanism of action for these new COX-2 inhibitors, compare their relative anti-inflammatory and analgesic properties and describe their safety profile. They also summarize indications, contraindications and dosing recommendations. CLINICAL IMPLICATIONS: Celecoxib and rofecoxib are valuable dental therapeutic agents for the management of inflammatory joint disorders and associated chronic orofacial pain. Additionally, rofecoxib, with its more rapid onset, may be useful in treating selected cases of acute postsurgical pain.

Analgesics↗

Comparing efficacy and safety of four intravenous sedation regimens in dental outpatients.

BACKGROUND: Management of patients' fear and anxiety during dental treatment is a primary concern of dental practitioners. Pharmacological strategies used in outpatient dental settings must be both safe and effective. Regimens of intravenously administered sedative drugs were evaluated in a collaborative, multicenter study of outpatients undergoing removal of impacted third molars. METHODS: A total of 997 patients randomly received one of five treatments: placebo; midazolam administered to a clinical endpoint of conscious sedation (mean dose, 8.6 milligrams); midazolam plus additional midazolam as needed during the procedure (mean total dose, 12.2 mg); fentanyl (1.4 micrograms/kilogram) plus midazolam to achieve the same endpoint of conscious sedation (mean dose, 5.7 mg); or fentanyl (1.4 (micrograms/kg), midazolam (mean dose, 5.8 mg) and methohexital as needed during the procedure (mean dose, 61.0 mg). RESULTS: Each drug regimen reduced anxiety during surgery in comparison with placebo, with the combination of midazolam, fentanyl and methohexital resulting in significantly less anxiety in comparison with the other treatment groups. Pain reports by patients during surgery also were reduced significantly by the combination of fentanyl, midazolam and methohexital. Patients' global evaluations of the efficacy of sedation ranked midazolam with supplemental midazolam and the combination of fentanyl, midazolam and methohexital as significantly more efficacious than the other two drug regiments. The authors noted transient respiratory depression in patients in the two opioid-treated groups, but no other physiological changes were detected. CONCLUSIONS: These data provide evidence that the drugs and doses evaluated resulted in therapeutic benefit to dental outpatients, with minimal incidence of potentially serious adverse effects. CLINICAL IMPLICATIONS: The results of this large-scale study provide assurance to both the public and the dental profession of the safety of parenteral sedation with these drugs and combinations of these drugs when titrated slowly in the recommended doses by appropriately trained dentists.

Ambulatory Surgical Procedures↗

In vivo inhibition of Fas ligand-mediated killing by TR6, a Fas ligand decoy receptor.

TR6, a member of the tumor necrosis factor (TNF) receptor superfamily, has recently been shown to bind to Fas ligand (FasL) and inhibit FasL-mediated cell killing in vitro. In the current study, we demonstrate that TR6 can block the lethal activity of FasL in multiple in vitro systems, and extend this finding to an in vivo model of hepatitis. The binding of human TR6 to human FasL was verified with BIAcore chip technology. Human primary hepatocytes, HT-29 cells and Jurkat cells were assayed for viability to demonstrate TR6 inhibition of FasL-mediated cytotoxicity in vitro. Human TR6 was also shown to cross-react with membrane-bound mouse FasL, since the in vitro cytotoxic activity of L929 cells transfected with murine FasL was inhibited in the presence of human TR6. In vivo, FasL-induced acute, lethal, fulminant hepatic apoptosis resulting in death within 2 h of intravenous injection into Fas+ mice, but not Fas- MRL/lpr mice. Pretreatment of mice with TR6 blocked FasL-induced mortality, presumably by attenuating FasL-induced hepatic apoptosis. Thus, in both in vitro and in vivo systems, TR6 acts as a functional FasL decoy receptor and may be clinically useful in the treatment of hepatitis and other diseases associated with FasL-mediated tissue injury.

Animals↗

Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS.

An expression cloning approach was employed to identify the receptor for B-lymphocyte stimulator (BLyS) and identified the tumor necrosis factor receptor superfamily member TACI as a BLyS-binding protein. Expression of TACI in HEK293T cells confers on the cells the ability to bind BLyS with subnanomolar affinity. Furthermore, a TACI-Fc fusion protein recognizes both the cleaved, soluble form of BLyS as well as the membrane BLyS present on the cell surface of a recombinant cell line. TACI mRNA is found predominantly in B-cells and correlates with BLyS binding in a panel of B-cell lines. We also demonstrate that TACI interacts with nanomolar affinity with the BLyS-related tumor necrosis factor homologue APRIL for which no clear in vivo role has been described. BLyS and APRIL are capable of signaling through TACI to mediate NF-kappaB responses in HEK293 cells. We conclude that TACI is a receptor for BLyS and APRIL and discuss the implications for B-cell biology.

B-Cell Activation Factor Receptor↗

Tumor rejection and immune memory elicited by locally released LEC chemokine are associated with an impressive recruitment of APCs, lymphocytes, and granulocytes.

The human beta chemokine known as LEC (also called NCC-4, HCC-4, or LMC) displays chemotactic activity for monocytes and dendritic cells. The possibility that its local presence increases tumor immunogenicity is addressed in this paper. TSA parental cells (TSA-pc) are poorly immunogenic adenocarcinoma cells that grow progressively, kill both nu/nu and syngeneic BALB/c mice, and give rise to lung metastases. TSA cells engineered to release LEC (TSA-LEC) are still able to grow in nu/nu mice, but are promptly rejected and display a marginal metastatic phenotype in BALB/c mice. Rejection is associated with a marked T lymphocyte and granulocyte infiltration, along with extensive macrophage and dendritic cell recruitment. NK cells and CD4+ T lymphocytes are uninfluential in TSA-LEC cell rejection, whereas both CD8+ lymphocytes and polymorphonuclear leukocytes play a major role. An antitumor immune memory is established very quickly after rejection, since 6 days later 75% of BALB/c mice were already resistant to a TSA-pc challenge. Spleen cells from rejecting mice display specific cytotoxic activity against TSA-pc and secrete IFN-gamma and IL-2 when restimulated by TSA-pc. The ability of LEC to markedly improve recognition of poorly immunogenic cells by promoting APC-T cell cross-talk suggests that it could be an effective component of antitumor vaccines.

Adenocarcinoma↗

A testis-specific transcription factor IIA (TFIIAtau) stimulates TATA-binding protein-DNA binding and transcription activation.

The general transcription factor IIA (TFIIA) stimulates RNA polymerase II-specific transcription by stabilizing the association of the TATA-binding protein (TBP) with promoter DNA, inhibiting repressors of TBP, and facilitating activator-dependent conformational changes in the preinitiation complex. TFIIA is encoded by two genes (alphabeta and gamma) that are highly conserved between human and yeast. Here, we report the molecular cloning of a novel human gene that shares significant sequence similarity to the evolutionarily conserved amino- and carboxyl-terminal domains of TFIIAalphabeta. The TFIIA-related protein (TFIIAtau) was cloned from a testis-specific cDNA library, and its mRNA is expressed predominantly in testis tissue as determined by expressed sequence tag data base analysis and Northern blotting analysis. The TFIIA complex reconstituted with the testis-specific subunit, TFIIA (tau+gamma), formed the TFIIA-TBP-TATA DNA (T-A) and TFIIA-TFIIB-TBP-TATA DNA (TAB) complexes indistinguishably from TFIIA (alphabeta+gamma). TFIIA (tau+gamma) supported basal and activated transcription for most activators in reactions reconstituted with TFIIA-depleted nuclear extracts. However, TFIIA (tau+gamma) was reduced relative to TFIIA (alphabeta+gamma) for stimulating transcription with at least one activator, suggesting that these two forms of TFIIA have activator specificity. These results suggest that TFIIAtau may be important for testis-specific transcription regulation.

Amino Acid Sequence↗