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Biomedical subjects

R Moon

Publications and source records attributed to R Moon.

At least 19 recordsLinked to original sources
PubMed2000

Expression, crystallization and preliminary X-ray studies of the PDZ domain of Dishevelled protein.

Dishevelled (Dsh) protein is an important component of the Wnt signal-transduction pathway. It has three relatively conserved domains: DIX, PDZ and DEP. The PDZ domain of the Xenopus laevis homolog of Dsh, which consists of residues 254-348, was overexpressed as a soluble protein in Escherichia coli, purified and crystallized. The crystals were obtained by the vapor-diffusion method, using 1.4 M sodium formate as a precipitant. The crystals diffracted to 2.3 A resolution. The space group was determined to be P6(1)22 or P6(5)22, with unit-cell dimensions a = b = 95.9, c = 93.9 A.

Adaptor Proteins, Signal Transducing↗
PubMed1999

IgG reactivities against recombinant Rhoptry-Associated Protein-1 (rRAP-1) are associated with mixed Plasmodium infections and protection against disease in Tanzanian children.

A cross-sectional sero-epidemiological study was performed in Magoda, Tanzania, an area where malaria is holoendemic. Blood samples were collected from children (1-4 years) and tested for IgG antibody reactivity against 2 recombinant protein fragments of Plasmodium falciparum Rhoptry-Associated Protein-1 (rRAP-1). The data were related to the prevalence of malarial disease and single P. falciparum or mixed Plasmodium infections. Fever (> or = 37.5 degrees C) in combination with parasite densities > 5000/microliter were used to distinguish between children with asymptomatic malaria infections and those with acute clinical disease. Furthermore, C-reactive protein (CRP) was applied as a surrogate marker of malaria morbidity. The prevalence of Plasmodium infections was 96.0%. Eleven children were defined as clinical malaria cases, all with single P. falciparum infections. The density of P. falciparum was significantly lower in children with mixed Plasmodium infections compared to those with single P. falciparum infections. Children with asymptomatic P. falciparum infections had higher IgG reactivities to rRAP-1, compared to IgG reactivities of children with malarial disease. Children with mixed Plasmodium infections generally showed elevated IgG reactivity to rRAP-1, when compared to children with single P. falciparum infections. The possible relationship between mixed species infections, clinical outcome of the disease and antibody responses to RAP-1 is discussed.

Age Factors↗
PubMed1999

Stress response decreases the interleukin-1beta-induced production of complement component C3 in human intestinal epithelial cells.

Interleukin-1beta (IL-1beta) increases the production of complement component C3 in enterocytes. Heat shock regulates the response to cytokines and other inflammatory mediators in various cell types. We tested the hypothesis that the heat-shock response regulates IL-1beta-induced C3 production in the enterocyte. Cultured Caco-2 cells, a human intestinal epithelial cell line, were treated with sodium arsenite (10-500 microM) for 1 h or subjected to hyperthermia (43 degrees C) for 1-4 h, and allowed to recover for 1 h. The cells were then treated with IL-1beta (0.5 ng/ml) for up to 24 h, whereafter C3 levels were measured by ELISA and C3 mRNA by Northern blot analysis. Heat-shock protein of 72 kDa (hsp72) was determined by Western blot analysis. Treatment of the cells with sodium arsenite or subjecting them to hyperthermia induced the expression of hsp72. The IL-1beta-induced expression of C3 mRNA and C3 production were down-regulated by hyperthermia and sodium arsenite in a dose-dependent fashion. The results suggest that the stress response induced by hyperthermia or sodium arsenite decreases IL-1beta-induced C3 production in human enterocytes.

Arsenites↗
PubMed1998

Nuclear factor-kappaB is activated in intestinal mucosa during endotoxemia.

BACKGROUND: The transcription factor nuclear factor-kappaB (NF-kappaB) regulates a large number of genes involved in the inflammatory response to critical illness. The intestinal mucosa plays an active role in the inflammatory and metabolic response to sepsis and endotoxemia, but it is not known if NF-kappaB is activated in the mucosa during these conditions. OBJECTIVE: To test the hypothesis that endotoxemia in mice activates NF-kappaB in intestinal mucosa. METHODS: Mice were injected subcutaneously with lipopolysaccharide, 12.5 mg/kg, or a corresponding volume of saline. At various intervals following injection, jejunal mucosa was harvested and nuclear and cytoplasmic fractions were prepared. The nuclear fractions were analyzed by electrophoretic mobility shift assay for NF-kappaB activation and by Western blot analysis for the NF-kappaB subunits p50 and p65. Cytoplasmic fractions were analyzed by Western blotting for the NF-kappaB inhibitory proteins IkappaB-alpha and IkappaB-beta. RESULTS: Electrophoretic mobility shift assay showed that NF-kappaB was activated in jejunal mucosa 1 hour after injection of lipopolysaccharide and persisted for at least 4 hours. The NF-kappaB subunits p50 and p65 were present in nuclear fractions of mucosa from endotoxemic mice at the corresponding time points. Cytoplasmic levels of the inhibitory proteins IkappaB-alpha and IkappaB-beta decreased during endotoxemia, and the proteins were nearly absent 60 minutes after injection of lipopolysaccharide. CONCLUSIONS: The results suggest that IkappaB is degraded and NF-kappaB is activated in intestinal mucosa during endotoxemia. The findings support the concept that the intestinal mucosa is an important component of the inflammatory response to sepsis and endotoxemia.

Animals↗
PubMed1997

Complement C3 production in human intestinal epithelial cells is regulated by interleukin 1beta and tumor necrosis factor alpha.

BACKGROUND: Sepsis and endotoxemia are associated with increased mucosal production of complement component C3; the enterocyte may be a source of C3 in these conditions. OBJECTIVE: To test the hypothesis that interleukin 1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) regulate the production of C3 in the enterocyte at the transcriptional level and that this regulation is potentiated by interferon gamma (IFN-gamma). METHODS: Cultured Caco-2 cells, a human intestinal epithelial cell line, were treated with various concentrations of human recombinant IL-1beta (0.005-1.25 ng/mL) or TNF-alpha (1-1000 U/mL) with or without the addition of IFN-gamma (250 U/mL). C3 levels in the culture medium were measured by enzyme-linked immunosorbent assay and cellular messenger RNA levels by Northern blot analysis. RESULTS: Treatment of the Caco-2 cells with IL-1beta or TNF-alpha resulted in a time- and dose-dependent increase in C3 production. The use of IFN-gamma alone did not affect C3 production but potentiated the effect of IL-1beta and TNF-alpha in a synergistic manner. C3 messenger RNA levels were increased following stimulation with either cytokine. CONCLUSIONS: C3 production in the enterocyte is regulated by IL-1beta and TNF-alpha at the transcriptional level, and this response is potentiated by IFN-gamma. The results suggest that C3 production in the intestinal mucosa may be regulated locally by cytokines in a paracrine or autocrine manner.

Caco-2 Cells↗
PubMed1996

Influence of owner personality type on expression and treatment outcome of dominance aggression in dogs.

OBJECTIVE: To determine the success rate of positive training methods and behavioral modification techniques in dogs with dominance aggression and to compare personality profiles between owners of dominant-aggressive and nondominant dogs. DESIGN: Prospective clinical study. ANIMALS: 10 dominant-aggressive dogs and 10 non-dominant, nonaggressive control dogs. PROCEDURE: Dominance aggression was quantified, using an aggression score, in the 10 dominant dogs before and after a nonconfrontational behavior modification program. The personality profile of the owners of dominant and control dogs, assessed by means of a Keirsey temperament sorter, was compared, as was the influence of owner personality on the outcome of behavioral modification in the dominant dogs. RESULTS: 9 of 10 dominant dogs responded to the nonconfrontational treatment program by a decrease in aggressive response to similar eliciting stimuli. Significant differences were not found between the personality of the owners of dominant versus control dogs, and owner personality did not significantly affect the outcome of behavior modification treatment. CLINICAL IMPLICATIONS: Nonconfrontational behavior modification programs are effective in reducing owner-directed dominance aggression in dogs. Owner personality does not necessarily predispose certain individuals to assaults by dominant dogs or profoundly affect their ability to engage in a successful behavioral modification program.

Aggression↗
PubMed1996

Organic Electroluminescent Devices

Electroluminescence from organic materials has the potential to enable low-cost, full-color flat-panel displays, as well as other emissive products. Some materials have now demonstrated adequate efficiencies (1 to 15 lumens/watt) and lifetimes (>5000 hours) for practical use; however, the factors that govern lifetime remain poorly understood. This article provides a brief review of device principles and applications requirements and focuses on the understanding of reliability issues.

Journal Article↗
PubMed1996

Combined third-generation implantable cardioverter defibrillator with permanent unipolar pacemakers: preliminary observations.

UNLABELLED: As implantable cardioverter defibrillators (ICDs) are strictly contraindicated in the presence of unipolar pacemakers, currently available options in patients having such chronic pacing systems include: abandoning the implanted pacemaker and selecting an ICD with ventricular demand (VVI) pacing; or replacing the chronic (dual chamber) unipolar pacing system with a dedicated bipolar version prior to ICD implantation. In three patients with previously implanted unipolar pacemakers, we challenged the premise that all ICD systems are incompatible by combining with a third-generation transvenous ICD system (Medtronic 7217B PCD) incorporating true bipolar sensing, a self-limiting auto-adjusting sensitivity, and a tolerant VF detection algorithm. The potential for pacemaker-ICD interaction was minimized by separating the tip of the ICDs transvenous right ventricular pace/sense-defibrillation coil lead from that of the chronic pacemaker lead by > or = 2-3 cm, and by performing "worst case" intraoperative testing. Although ICD double-counting of the dual chamber pacemaker's atrial and ventricular pacing spikes could be provoked at extreme high output settings, it did not occur at clinically appropriate settings. More importantly, continuous high output asynchronous pacing during ventricular fibrillation (VF) did not interfere with ICD detection. During a mean follow-up period of 18 months, one patient has had VF appropriately terminated by the ICD. In the remaining two patients, proper VF detection and ICD function was reassessed at 3 months and/or at 1 year during noninvasive testing. CONCLUSION: These preliminary findings demonstrate that this transvenous ICD system's VF sensing and detection features combined with careful implant technique, rigorous "worst case" testing for possible pacemaker-ICD interaction with regular follow-up, may permit implantation of this ICD system in patients with chronic unipolar pacing systems. Further studies are needed to validate the long-term clinical safety of this promising revised approach to a currently contraindicated device combination.

Aged↗
PubMed1995

Flavonoids as DNA topoisomerase antagonists and poisons: structure-activity relationships.

Selected flavonoids were tested for their ability to inhibit the catalytic activity of DNA topoisomerase (topo) I and II. Myricetin, quercetin, fisetin, and morin were found to inhibit both enzymes, while phloretin, kaempferol, and 4',6,7-trihydroxyisoflavone inhibited topo II without inhibiting topo I. Flavonoids demonstrating potent topo I and II inhibition required hydroxyl group substitution at the C-3, C-7, C-3', and C-4' positions and also required a keto group at C-4. Additional B-ring hydroxylation enhanced flavonoid topo I inhibitory action. A C-2, C-3 double bond was also required, but when the A ring is opened, the requirement for the double bond was eliminated. Genistein has been previously reported to stabilize the covalent topo II-DNA cleavage complex and thus function as a topo II poison. All flavonoids were tested for their ability to stabilize the cleavage complex between topo I or topo II and DNA. None of the agents stabilized the topo I-DNA cleavage complex, but prunetin, quercetin, kaempferol, and apigenin stabilized the topo II DNA-complex. Competition experiments have shown that genistein-induced topo II-mediated DNA cleavage can be inhibited by myricetin, suggesting that both types of inhibitors (antagonists and poisons) interact with the same functional domain of their target enzyme. These results are of use for the selection of flavonoids that can inhibit specific topoisomerases at specific stages of the topoisomerization reaction.

DNA Damage↗
PubMed1995

The dietary anticancer agent ellagic acid is a potent inhibitor of DNA topoisomerases in vitro.

Ellagic acid and 12 related agents have been tested for their ability to inhibit the activities of human DNA topoisomerase (topo) I and II. Using specific in vitro assays, we found ellagic acid and flavellagic acid to be potent inhibitors of the catalytic activities of the two topoisomerases. The minimum concentration required to inhibit > or = 50% of catalytic activity (IC50) of ellagic acid was determined at 0.6 and 0.7 micrograms/ml for topo I and topo II, respectively. Flavellagic acid's IC50 was determined at 3.0 and 3.6 micrograms/ml for topo I and topo II, respectively. Unlike topoisomerase poisons, these two plant phenols did not trap the enzyme-DNA reaction intermediate, known as the cleavable complex. In contrast, ellagic acid prevented other topo I and topo II poisons from stabilizing the cleavable complex, suggesting that the mode of its action is that of an antagonist. Structure-activity studies identified the 3,3'-hydroxyl groups and the lactone groups as the most essential elements for the topoisomerase inhibitory actions of plant phenols. On the basis of these findings and other properties of ellagic acid, a mechanistic model for the documented anticarcinogenic effects of the agent is proposed.

Anticarcinogenic Agents↗
PubMed1995

Settings as an important dimension in health education/promotion policy, programs, and research.

Settings--community, worksite, schools, and healthcare sites--constitute an important dimension of health education/health promotion policy and programs and for research about program needs, feasibility, efficacy, and effectiveness. These settings vary in the extent of coverage of and relationships with their respective constituencies, valued outcomes, and quantity and quality of evidence about the effectiveness of setting-specific and cross-setting programs. Main sources of evidence for program efficacy and effectiveness are summarized, leading to the conclusion that strides have been made toward building a strong evidentiary base for health education/health promotion in these settings. Gaps in research exist, especially for diffusion of effective programs, new technologies, the influence of policy, relations between settings, and approaches to marginal and special subgroups. Recommendations are offered for cross-setting and within-setting research related to intervention.

Community Health Services↗
PubMed1993

Tumour necrosis factor and interleukin-6 production induced by components associated with merozoite proteins of Plasmodium falciparum.

P. falciparum merozoite antigens, merozoite surface protein-1 (MSP-1) and rhoptry associated protein-1 (RAP-1), were shown to be liberated into the supernatant of in vitro parasite cultures and to be included in the endotoxin-like exoantigen complex, previously designated Ag7. Material affinity purified from culture supernatants, using immobilized monoclonal antibodies specific for RAP-1 or MSP-1, stimulated normal human mononuclear cells to produce TNF and IL-6 in vitro. However, stimulation of TNF was absent, and that of IL-6 was reduced, when the antigens were purified from detergent extracts of infected erythrocytes. These results indicate that the RAP-1 and MSP-1 proteins themselves do not stimulate the production of TNF. Instead, other components associating with these exoantigens may be responsible for the TNF production. Mouse antisera blocking TNF production stimulated by P. yoelii exoantigens also blocked TNF production stimulated by material affinity purified from P. falciparum culture supernatants using RAP-1 specific monoclonal antibody, indicating the conserved structure of the TNF inducing component.

Animals↗
PubMed1985

Enalapril maleate and atenolol combined with hydrochlorothiazide in moderate to severe essential hypertension.

This open randomised parallel trial compared the antihypertensive efficacy of enalapril and atenolol given alone once a day or with hydrochlorothiazide in 20 patients with moderate to severe hypertension. Active treatment was over a 26 week period, consisting of an initial titration phase followed by a fixed dose phase. Both treatment regimes effectively lowered systolic and diastolic blood pressures. All patients on enalapril reached normotension (supine diastolic blood pressure less than or equal to 90 mmHg) compared with 78% on atenolol. Pulse rate was not appreciably changed by enalapril, but was significantly reduced by atenolol. No serious adverse reactions or significant changes in laboratory values were noted in either group. The commonest adverse reaction with enalapril was dizziness which occurred in two cases and resolved on dosage reduction. Enalapril with hydrochlorothiazide given once daily may provide a useful combination in the treatment of moderate to severe hypertension.

Adult↗