HLA-DO increases bacterial superantigen binding to human MHC molecules by inhibiting dissociation of class II-associated invariant chain peptides

HLA-DO (H2-O in mice) is an intracellular non-classical MHC class II molecule (MHCII). It forms a stable complex with HLA-DM (H2-M in mice) and shapes the MHC class II-associated peptide repertoire. Here, we tested the impact of HLA-DO and H2-O on the binding of superantigens (SAgs), which has been shown previously to be sensitive to the structural nature of the class II-bound peptides. We found that the binding of staphylococcal enterotoxin (SE) A and B, as well as toxic shock syndrome toxin 1 (TSST-1), was similar on the HLA-DO⁺ human B cell lines 721.45 and its HLA-DO⁻ counterpart. However, overexpressing HLA-DO in MHC class II⁺ HeLa cells (HeLa-CIITA-DO) improved binding of SEA and TSST-1. Accordingly, knocking down HLA-DO expression using specific siRNAs decreased SEA and TSST-1 binding. We tested directly the impact of the class II-associated invariant chain peptide (CLIP), which dissociation from MHC class II molecules is inhibited by overexpressed HLA-DO. Loading of synthetic CLIP on HLA-DR⁺ cells increased SEA and TSST-1 binding. Accordingly, knocking down HLA-DM had a similar effect. In mice, H2-O deficiency had no impact on SAgs binding to isolated splenocytes. Altogether, our results demonstrate that the sensitivity of SAgs to the MHCII–associated peptide has physiological basis and that the effect of HLA-DO on SEA and TSST-1 is mediated through the inhibition of CLIP release.     

Magnetic and spectroscopic properties of Ni–Zn–Al ferrite spinel: from the nanoscale to microscale

This article presents the annealing effect on the structural, elastic, thermodynamic, optical, magnetic, and electric properties of Ni_0.6Zn_0.4Fe_1.5Al_0.5O₄ (NZFAO) nanoparticles (NPs). The samples were successfully synthesized by the sol–gel method followed by annealing of the as-synthesized at 600, 800, 900, 1050, and 1200 °C. This approach yielded the formation of a highly crystalline structure with crystallite size ranging from 17 nm to 40 nm. X-ray diffraction (XRD), scanning electron microscopy (SEM) techniques, as well as energy disperse spectroscopy (EDS), Fourier transform infrared (FTIR) and Raman spectroscopy, were used in order to determine the structural and morphological properties of the prepared samples. Rietveld XRD refinement reveals that Ni–Zn–Al ferrite nanoparticles crystallize in inverse cubic (Fd$\bar{3}$m) spinel structure. Using FTIR spectra, the elastic and thermodynamic properties were estimated. It was observed that the particle size had a pronounced effect on elastic and thermodynamic properties. Magnetic measurements were performed up to 700 K. The prepared ferrite samples present the highest Curie temperature, which decreases with increasing particle size and which is consistent with finite-size scaling. The thickness of the surface shell of about 1 nm was estimated from size-dependent magnetization measurements using the core–shell model. Besides, spin resonance, magnetostriction, temperature coefficient of resistance (TCR), and electrical resistivity properties have been scientifically studied and appear to be different according to their size. The optical properties of synthesized NZFAO nanoparticles were investigated, and the differences caused by the particle sizes are discussed on the basis of the phonon confinement effect. This effect was also inspected by the Raman analysis. Tuning of the physical properties suggests that the Ni–Zn–Al ferrite samples may be promising for multifunctional diverse applications.

This article presents the annealing effect on the structural, elastic, thermodynamic, optical, magnetic, and electric properties of Ni_0.6Zn_0.4Fe_1.5Al_0.5O₄ (NZFAO) nanoparticles (NPs).     

Effective treatment of diabetic diarrhoea with somatostatin analogue, octreotide.

A 22 year old insulin dependent diabetic with high volume, secretory chronic diarrhoea refractory to standard andiarrhoeal drugs was treated with the somatostatin analogue octreotide, 50 micrograms twice daily by subcutaneous injection. She improved markedly with a decrease in mean stool weight from 1170 g/24 h range 440-2900 g) to 440 g/24 h (range 180-800 g) (p < 0.05). Stool frequency also decreased from six (range two to 12) to one (range one to three) bowel movements per day (p < 0.01). Mouth to caecum transit time increased from 45 minutes to > 210 minutes, although total gut transit time was unchanged and remained rapid at nine hours. Thus octreotide can reduce stool volume and frequency in high volume diabetic diarrhoea when conventional antidiarrhoeal agents have failed. Its therapeutic benefit appeared to be predominantly related to a marked increase in mouth to caecum transit time.     

Erythropoietin production in a primary culture of human renal carcinoma cells maintained in nude mice

The present studies report erythropoietin (Ep) production in primary cultures of a human renal carcinoma from a patient with erythrocytosis that has been serially transplanted to BALB/c nude mice. The levels of erythropoietin in the culture media were estimated using the exhypoxic polycythemic mouse assay (EHPCMA), fetal mouse liver erythroid colony- forming technique (FMLC), and a radioimmunoassay (RIA). The spent culture media of the exponentially growing cells contained less than 10 mU/ml of Ep measured by RIA. However, after the cells became confluent, Ep levels (RIA) in the spent media showed a marked increase to approximately 300 mU/ml. Ep levels estimated using the FMLC and EHPCMA were approximately 2/3 and 1/10, respectively, of those measured by RIA. Rabbit antiserum to highly purified human urinary Ep (70,400 U/mg protein) was utilized for immunocytochemical (peroxidase-antiperoxidase method) localization of Ep in the cultured cells. Very few of the cells in exponential growth exhibited Ep-like immunoreactivity, whereas intense Ep-like immunoreactivity was observed in the cytoplasm of the cells maintained in culture for a prolonged period after reaching confluency. The most intense staining was observed in some of the cells forming domes. The domes developed after the cells reached confluency, and their numbers increased with increasing time in confluent culture, in parallel with the increase in Ep levels in the spent media. This primary cell culture system of a renal cell carcinoma maintained in nude mice, which produces immunologically and biologically active Ep, may provide a useful model for studies of the mechanism of Ep production.     

Corrélation entre les dosages des dérivés methoxylés urinaires et l’index d’apnée-hypopnée dans une population d’hypertendus : étude pilote

Aims

Sleep disorders like obstructive sleep apnea in adults are associated with increased sympathetic activity, which induced high blood pressure and could be associated with resistant hypertension. Some studies have demonstrated that high urinary catecholamine levels in obstructive sleep apnea patients may be decreased with continuous positive airway pressure therapy. However, very few studies have demonstrated a correlation between apnea-hypopnea index and urinary catecholamine levels in hypertension patients.

Methods

In this pilot study, 20 hypertensive patients referred for hypertension work-up including night-time polygraphy and 24 h urinary catecholamine dosage were included.

Results

Mean age was 51 ± 11 years (30–76), 68% were males. Diagnosis of obstructive sleep apnea was confirmed in 13 patients at the end of the work-up. Mean apnea-hypopnea index was 14 ± 9 (2–32). The only urinary catecholamine parameter significantly increased in patients with obstructive sleep apnea was 24 h urinary normetanephrine (1931 ± 1285 vs 869 ± 293 nmol/24 h; P < 0.05). However, this difference was not significant when this parameter was adjusted to 24 h urinary creatinine. We observed a significant positive correlation between AHI and 24 h urinary normetanephine (r = 0.486; P = 0.035).

Conclusion

This pilot study confirms an isolated elevation of 24 h urinary normetanephrine in hypertensive patients with obstructive sleep apnea and shows a significant correlation between sleep disorders expressed by apnea-hypopnea index and urinary catecholamines excretion.