Search PubMed⌕ Search

Biomedical subjects

N Amos

Publications and source records attributed to N Amos.

At least 37 records · Page 2Linked to original sources

Serum soluble interleukin 2 receptor levels and radiological progression in early rheumatoid arthritis.

OBJECTIVE: To investigate the association between serum soluble interleukin 2 receptor (sIL-2R) levels and radiological changes in patients with early rheumatoid arthritis (RA). METHODS: sIL-2R levels from 155 patients with active RA were measured by immunoassay over a 2 year period and the associations with radiological change and other measures of disease activity were analyzed. RESULTS: The area under the curve for sIL-2R is weakly associated with the change in the modified Larsen score over a 2 year period; this is weaker than the association of radiological change with serum C-reactive protein. CONCLUSION: We found no significant association of sIL-2R levels with erosive change in early RA.

Arthritis, Rheumatoid↗

Measurement of the W-->taunu production cross section in pp collisions at square root s=1.8 TeV.

We report on a measurement of sigma(pp-->W+X)B(W-->taunu) in pp collisions at sqrt[s]=1.8 TeV at the Fermilab Tevatron. The measurement is based on an integrated luminosity (lum) of 18 pb-1 of data collected with the D0 detector during 1994-1995. We find that sigma(pp-->W+X)B(W-->taunu)=2.22+/-0.09 (stat)+/-0. 10 (syst)+/-0.10 (lum) nb. Lepton universality predicts that the ratio of the tau and electron electroweak charged current couplings to the W boson, gWtau/gWe, be unity. We find gWtau/gWe=0.980+/-0.031, in agreement with lepton universality.

Journal Article↗

Probing Balitsky-Fadin-Kuraev-Lipatov dynamics in the dijet cross section at large rapidity intervals in pp collisions at sqrt[s]=1800 and 630 GeV.

Inclusive dijet production at large pseudorapidity intervals (Deltaeta) between the two jets has been suggested as a regime for observing Balitsky-Fadin-Kuraev-Lipatov (BFKL) dynamics. We have measured the dijet cross section for large Deltaeta in pp collisions at sqrt[s]=1800 and 630 GeV using the D0 detector. The partonic cross section increases strongly with the size of Deltaeta. The observed growth is even stronger than expected on the basis of BFKL resummation in the leading logarithmic approximation. The growth of the partonic cross section can be accommodated with an effective BFKL intercept of alphaBFKL(20 GeV)=1.65+/-0.07.

Journal Article↗

The suppression of rat collagen-induced arthritis and inhibition of macrophage derived mediator release by liposomal methotrexate formulations.

OBJECTIVE AND DESIGN: This study was designed to determine whether liposomes are suitable vehicles for the delivery of methotrexate (MTX-gamma-DMPE) for arthritis therapy. MATERIAL OR SUBJECTS: Liposomal formulations containing either egg lecithin (EPC), cholesterol (CHOL) and phosphatidic acid (PA) (MTX-EPC) or distearoylphosphatidylcholine (DSPC), CHOL and distearoylphosphatidylethanolamine conjugated to polyethyleneglycol (PEG) (MTX-PEG) were employed. Rat peritoneal macrophages (rPM phi) were used to test the mechanism of action of these liposomes in vitro, whilst, the rat collagen-induced arthritis (CIA) model was used to evaluate the in vivo efficacy of MTX-EPC and MTX-PEG. TREATMENT: In vitro, rPM phi were incubated with liposomal MTX concentrations ranging from 0 to 15 microg/well. In vivo, rats were given 4 daily intravenous injections of liposomal MTX (2.5 mg/Kg). METHODS: IL-1beta and prostaglandin-E2 (PGE2) release from rPM phi were quantified by immunoradiometric assay. Arthritis progression, in vivo, was measured by serial clinical score and hind paw diameter measurements. RESULTS: MTX-EPC and MTX-PEG respectively (15 microg of MTX and 0.15 mg of lipid) were powerful inhibitors of both IL-1beta (77 +/- 2.3%; 79 +/- 4.0%) and PGE2 (75.5 +/- 4.9%; 68.5 +/- 2.3%) release (mean +/- SEM % inhibition) from lipopolysaccaride stimulated rPM phi. In vivo, only MTX-EPC exerted an anti-inflammatory effect, clinical score (p < 0.001) and paw diameter (p < 0.001) measurements being significantly lower than in control rats, after 2 days treatment. CONCLUSIONS: MTX-EPC and MTX-PEG are potent inhibitors of pro-inflammatory mediators in vitro, but liposomes with long circulation times do not appear to have therapeutic potential for treating arthritis in vivo.

Animals↗

Interleukin-1beta (IL-1beta) inhibition: a possible mechanism for the anti-inflammatory potency of liposomally conjugated methotrexate formulations in arthritis.

1. Liposomes with conventional and long-circulation times were employed as carriers for the methotrexate derivative MTX-gamma-DMPE (MTX-EPC and MTX-PEG respectively), their mechanism of action was investigated in vitro and in vivo and their therapeutic efficacy assessed using the rat collagen-induced arthritis (CIA) model. 2. At non-toxic dose, both MTX-EPC and MTX-PEG inhibited the lipopolysaccharide (LPS) induced release of IL-1beta from activated rat peritoneal macrophages (rPMPhi) in a dose and time dependent manner. Free methotrexate (MTX) was not active in this respect. After a single intravenous injection (i.v.), and at equivalent doses, both free MTX (500 microg) and MTX-EPC inhibited the LPS induced rise in plasma IL-1beta levels observed in MTX-PEG and saline treated rats. 3. When used to treat established CIA, MTX-EPC resulted in significantly lower clinical score (CS) (1.0+/-0.42 (P<0.001)) and hind paw diameter (HPD) (6.5+/-0.34 mm (P<0.001)) measurements than controls (3.0+/-0.26; 7.33+/-0.41 mm), after only two i.v. doses, and remained significantly lower for the entire experimental period. By day 24 both CS (2+/-0.61 (P<0.001)) and HPD (6.97+/-0.25 mm (P<0.002)) measurements had also become significantly lower in MTX-PEG treated rats than in saline treated controls (3.62+/-0.17, 7. 92+/-0.38 mm) and remained lower until day 30. Joint inflammation in MTX treated rats was completely ameliorated by day 20 but the health and well being of the animals was compromised and the experiment terminated at this time-point. 4. Our results clearly demonstrate that both MTX-EPC and MTX-PEG liposomes have potential for development into therapeutic modalities for the treatment of inflammatory joint disease in man.

Animals↗

Pro-inflammatory effects of the aminobisphosphonate ibandronate in vitro and in vivo.

OBJECTIVES: To investigate the effects of the aminobisphosphonate, ibandronate, on the course of joint inflammation in rat antigen-induced arthritis (AIA) and the release of pro-inflammatory cytokines in partially purified human peripheral blood mononuclear cells (PBMC). METHODS: Rats with AIA received a single intra-articular injection of ibandronate (1 mg) 7 days post-arthritis induction and knee swelling was measured for 7 days thereafter. The effects of ibandronate (300 microg/ml) on PBMC cytokine production and activation marker expression were determined using polymerase chain reaction (PCR)/ELISA and FACS analysis, respectively. RESULTS: Joint swelling, associated with AIA, was sustained in ibandronate-treated rats compared with saline-treated control rats. Ibandronate stimulated the production of interferon gamma (IFN-gamma) in adherent PBMC, and increased the surface expression of FcgammaRI and HLA DP, DQ, DR on the adherent monocyte population. Activation by lipopolysaccharide (LPS) of PBMC previously incubated with ibandronate led to enhanced levels of tumour necrosis factor alpha (TNF-alpha) secretion, and this could be partially inhibited by neutralizing antibodies to IFN-gamma. CONCLUSIONS: The enhanced production of TNF-alpha by ibandronate-treated PBMC in vitro involves stimulation of adherent monocytes by IFN-gamma prior to LPS-induced activation. Similar cellular interactions may be involved in the pro-inflammatory effects of ibandronate in vivo.

Animals↗

Effects of pre-existing hearing loss on proposed ANSI S12.13 outcomes for characterizing hearing conservation program effectiveness: follow-up investigation.

Draft ANSI S12.13 1991 Standard Evaluating the Effectiveness of Hearing Conservation Programs presents statistical protocols purportedly sensitive to temporary threshold shift (TTS) in occupational hearing conservation program (HCP) audiometric databases. Because it is well established that less TTS is found in humans with hearing loss than in those with essentially normal hearing, one might predict baseline hearing level to be a confounding variable in interpreting ANSI S12.13 outcomes, with better-hearing industrial populations tending to demonstrate greater year-to-year audiometric variability than poorer-hearing groups. However, in a large industrial sample from the public domain audiometric database, poorer-hearing groups systematically demonstrated greater audiometric threshold variability than better-hearing groups, and ANSI S12.13 outcome magnitudes were highly positively correlated to baseline hearing levels. These findings generally do not support notions that ANSI S12.13 outcomes clearly provide indirect measures of TTS. HCP managers should exercise extreme caution in interpreting ANSI S12.13 outcomes to rate overall program performance. In particular, HCP managers should not rely upon these outcomes for decisions regarding hearing protection policies without careful consideration of pre-existing hearing loss in the populations involved.

Adult↗

Influence of the HLA-DRB1 locus on susceptibility and severity in rheumatoid arthritis.

We examined HLA-DR genotype risk in 288 patients with rheumatoid arthritis who were carefully categorized for disease severity. Five hundred ethnically-matched bone-marrow donors were controls. A hierarchy of positive allelic associations was noted with DRB1*0401 (p < 10(-38), *0404,8 (p < 10(-43), *0405 (p < 10(-8), *10 (p < 10(-3) and *0101,2 (p < 10(-2), while DRB1*0403 was negatively associated (p = 0.02). The DRB1 genotype relative risks (and 95% CIs) for RA were: *0404,5,8/*0404,5,8 = 36.2 (15-87), *0401/*0404,5,8 = 31.3 (18-55), *401/*0401 = 18.8 (11-35), *0101,2/*0404,5,8 = 6.0 (2-14), *0101,2/*0401 = 6.4 (3-12), *0101,2/*0101,2 = 1.3 (0.3-6), *10/*0404,5,8 = 27.8 (5-148), *10/*0401 = 20.8 (5-89), *10/*0101,2 = 22.3 (5-96), *0404,5,8/DRX = 5.0 (3-8), *0401/DRX = 4.7 (3-7), *0101,2/DRX = 2.3 (1.4-4), *10/DRX = 3.4 (0.8-14). No significant correlation of DRB1 genotypes was found with severity of RA as judged by nodules or articular erosions.

Arthritis, Rheumatoid↗