IL‐17 is a T cell cytokine with a complex and important role in the immune system. It has been detected in rheumatoid arthritis (RA) synovial membrane and found to stimulate the production of the ...proinflammatory cytokines IL‐6, IL‐8, tumour necrosis factor‐alpha (TNF‐α) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) in vitro. To date, there are few data available on the agents that stimulate IL‐17 production. We therefore investigated the in vitro IL‐17 response to a variety of mitogens and antigens, and compared the IL‐17 response to interferon‐gamma (IFN‐γ), IL‐4, IL‐10 and TNF‐α. In this study we used a type‐0 antigen, tetanus toxoid (TT), a type‐1 antigen, PPD from Mycobacterium tuberculosis, a potential type‐2 rye grass (RG) antigen (Lol I) and an autoantigen SS.B (La), to stimulate PBMC from healthy controls. Cytokine mRNA was measured using semiquantitative reverse transcriptase‐polymerase chain reaction and cytokine protein measured using specific ELISA techniques, while the frequency of IL‐17‐producing T cells was determined by flow cytometry. The mitogens concanavalin A, phytohaemagglutinin and phorbol myristate acetate/ionomycin induced a significant increase in IL‐17, with the highest levels being produced by anti‐CD3/anti‐CD28 stimulation. The antigens TT and PPD significantly increased IL‐17 mRNA expression over time, but failed to have such an effect at the protein level. IL‐17 protein was also detectable in both antigen‐specific (TT, SS.B) and non‐specific T cell clones, but at levels lower than IFN‐γ. IL‐17 production did not correlate with either the type‐1 cytokine IFN‐γ or TNF‐α or the type‐2 cytokine IL‐4 or IL‐10 at either the mRNA or protein level.
The NA62 experiment at CERN reports a search for the lepton number violating decays K+→π−e+e+ and K+→π−μ+μ+ using a data sample collected in 2017. No signals are observed, and upper limits on the ...branching fractions of these decays of 2.2×10−10 and 4.2×10−11 are obtained, respectively, at 90% confidence level. These upper limits improve on previously reported measurements by factors of 3 and 2, respectively.
A
bstract
A search for the
K
+
→
π
+
X
decay, where
X
is a long-lived feebly interacting particle, is performed through an interpretation of the
K
+
→
π
+
ν
ν
¯
analysis of data collected in 2017 by ...the NA62 experiment at CERN. Two ranges of
X
masses, 0–110 MeV
/c
2
and 154–260 MeV
/c
2
, and lifetimes above 100 ps are considered. The limits set on the branching ratio, BR(
K
+
→
π
+
X
), are competitive with previously reported searches in the first mass range, and improve on current limits in the second mass range by more than an order of magnitude.
PedvaxHIB is a pediatric vaccine that protects children from severe disease caused by the gram-negative bacterium
Haemophilus influenzae type b (Hib). The vaccine is made by chemically conjugating ...Hib capsular polysaccharide to the outer membrane protein complex of
Neisseria meningitidis. The protein-conjugated vaccine has proven to be extremely effective in preventing invasive Hib disease in infants and young children. This paper presents the nuclear magnetic resonance (NMR) methodology for the quantitative characterization of derivatized polysaccharide and its validation closely following ICH guidelines. The assay has been shown to be precise and accurate (relative standard deviation RSD ⩽1%), specific (no observable matrix interference), rugged (RSD <3% for day-to-day and operator-to-operator variations), and robust (to changes in temperature and polysaccharide concentration). Therefore, the quantitative NMR assay can be used as a reliable product release or process monitoring method and can replace several labor-intensive chromatographic and colorimetric methods.
Purified capsular polysaccharide preparations from
Streptococcus pneumoniae that are used for vaccine production typically contain residual levels of C-polysaccharide (C-Ps). Residual C-Ps is ...typically found in one of two forms, either chemically linked to the capsular polysaccharide (bound) or present by itself (free). Two analytical methods have been developed and applied to determine the relative percentages of the two C-Ps forms present in various capsular polysaccharide preparations. Both methods differentiate the two forms of C-Ps according to the difference of their hydrodynamic sizes. One method is based on labeling C-Ps with a fluorescent tag and separating the two forms of C-Ps by high-performance size exclusion chromatography with on-line refractive index and fluorescence detection, and the other method is based on measuring self-diffusion rates of the two forms of C-Ps by nuclear magnetic resonance (NMR) and quantifying each form with deconvolution. Both methods were evaluated for relative accuracy, precision, and ease of application, and they were found to provide comparable results for a large number of pneumococcal polysaccharide preparations. These analyses, combined with other quantitative NMR measurement of total C-Ps in the polysaccharide powder, provide a more refined means of evaluating the amount of each form of C-Ps in polysaccharide preparations targeted for vaccine production.
A measurement of the K+→ π+μ+μ− decay Cortina Gil, E.; Kleimenova, A.; Minucci, E. ...
The journal of high energy physics,
11/2022, Letnik:
2022, Številka:
11
Journal Article
Recenzirano
Odprti dostop
A
bstract
A sample of 2
.
8 × 10
4
K
+
→
π
+
μ
+
μ
−
candidates with negligible background was collected by the NA62 experiment at the CERN SPS in 2017–2018. The model-independent branching fraction ...is measured to be (9
.
15 ± 0
.
08) × 10
−
8
, a factor three more precise than previous measurements. The decay form factor is presented as a function of the squared dimuon mass. A measurement of the form factor parameters and their uncertainties is performed using a description based on Chiral Perturbation Theory at
O
(
p
6
).
Mitochondrial autoantibodies are characteristic of the disease primary biliary cirrhosis (PBC), but the immunoreactive mitochondrial antigens have not been defined. We used a rat liver cDNA library ...in lambda gt 11-Amp3 to clone a 1370-base pair insert that coded for a polypeptide reactive with PBC sera. This insert was subcloned for expression into pBTA224, a plasmid vector in the same reading frame as lambda-Amp3. A positive clone, designated pRMIT, that expressed a fused polypeptide of 160 kd, was recognized by 25 of 25 sera from patients with PBC and none of 96 sera from normal persons or patients with systemic lupus erythematosus, rheumatoid arthritis, or chronic active hepatitis. This fused polypeptide was shown to correspond with the 70 kd mitochondrial autoantigen by several experiments. First, lysates of pRMIT in J101 absorbed out the 70 kd reactivity of PBC sera when probed against fractionated placental mitochondria. Second, affinity-purified antisera reactive with the fused polypeptide also reacted with the 70 kd mitochondrial antigen. Third, such affinity-purified antisera produced the characteristic anti-mitochondrial pattern of immunofluorescence on tissue sections. Finally, immunization of BALB/c mice with the fused polypeptide elicited antibodies to mitochondria. These murine antibodies reacted with the 70 kd mitochondrial protein and also produced typical mitochondrial immunofluorescence on tissue sections. The nucleotide and amino acid sequence of the recombinant protein, which encodes for approximately a 48 kd protein, showed no significant homologies with known proteins, and there were no homologies with mitochondrial genomic DNA. The availability of a recombinant form of the 70 kd mitochondrial autoantigen will allow several definitive questions to be addressed in PBC, including identification of B cell epitopes, T cell recognition, and a model of PBC in mice.
To report the efficacy and tolerability of mycophenolate mofetil (MMF) and azathioprine (AZA) in the management of systemic sclerosis-associated interstitial lung disease (SSc-ILD).
Patients in the ...Australian Scleroderma Cohort Study treated with at least 3 months of MMF or AZA for SSc-ILD confirmed on high resolution computed tomography (HRCT) chest were identified and their pulmonary function tests (PFTs) retrieved. Individuals with available results for T-1 (12 months prior to treatment commencement), T0 (date of treatment commencement) and at least one subsequent time point were included in the drug efficacy analysis. The Wilcoxon signed-rank test was used to compare absolute FVC at T1, T0, 12 months (T1), 24 months (T2) and 36 months (T3). Analysis of drug tolerability included all identified patients treated with MMF or AZA.
18/22 patients treated with MMF and 29/49 treated with AZA had adequate PFTs for inclusion in the drug efficacy analysis. Median absolute FVC at T1 for MMF treatment was 2.50L, declining to 2.12L at T0 (p=0.02). Following MMF therapy, FVC results were stable at T1 (2.13L, p=0.86), T2 (2.17L, p=0.65) and T3 (2.25L, p=0.78). In the AZA group, a statistically significant decline did not occur prior to treatment, however FVC results remained stable at T1, T2 and T3.Adverse events leading to early discontinuation (<12 months treatment) were less common in the MMF group (4/22 vs. 13/49). Gastrointestinal complications were the main cause of discontinuation in both groups.
In patients with SSc-ILD with declining pulmonary function, MMF therapy was associated with stability for up to 36 months. Early adverse events leading to discontinuation occurred less frequently in patients treated with MMF than in AZA treated patients.
Inhaled nitric oxide (NO) is a selective pulmonary vasodilator that reduces pulmonary vascular resistance (PVR) in patients with primary pulmonary hypertension. Their responses to inhaled NO predict ...their responses to other vasodilators, such as prostacyclin, and provide an estimate of the "fixed" component of their increased PVR. Some patients with limited cutaneous systemic sclerosis develop isolated pulmonary hypertension with a similar clinical course. Therefore, we have measured the acute hemodynamic response to inhaled NO in such patients.
Seven patients were studied during inhalation of increasing concentrations of NO (0 to 80 ppm). Complete hemodynamic data were collected on five patients. They demonstrated a selective, dose-dependent, and rapidly reversible fall in PVR (34%) and mean pulmonary artery pressure (17%). There was a nonsignificant increase in cardiac index but no change in mean arterial pressure or systemic vascular resistance. The mean right atrial pressure fell (27%), but there was no change in pulmonary artery occlusion pressure. Of the seven patients, five responded to inhaled NO ( < or = 40 ppm) with a decrease in total pulmonary resistance of at least 20%.
Inhaled NO is an effective and selective pulmonary vasodilator in a significant number of patients with pulmonary hypertension associated with limited cutaneous systemic sclerosis. It may be useful in determining the potentially reversible contribution to the increased PVR and should be considered for patients with acute pulmonary vascular crisis.
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