Different HLA-DRB1 allele distributions in distinct clinical subgroups of sarcoidosis patients

<p>Abstract</p> <p>Background</p> <p>A strong genetic influence by the MHC class II region has been reported in sarcoidosis, however in many studies with different results. This may possibly be caused by actual differences between distinct ethnic groups, too small sample sizes, or because of lack of accurate clinical subgrouping.</p> <p>Subjects and methods</p> <p>In this study we HLA typed a large patient population (n = 754) recruited from one single centre. Patients were sub-grouped into those with Löfgren's syndrome (LS) (n = 302) and those without (non-Löfgren's) (n = 452), and the majority of them were clinically classified into those with recovery within two years (resolving) and those with signs of disease for more than two years (non-resolving). PCR was used for determination of HLA-DRB1 alleles. Swedish healthy blood donors (n = 1366) served as controls.</p> <p>Results</p> <p>There was a dramatic difference in the distribution of HLA alleles in LS compared to non-LS patients (p = 4 × 10^-36). Most notably, DRB1*01, DRB1*03 and DRB1*14, clearly differed in LS and non-LS patients. In relation to disease course, DRB1*07, DRB1*14 and DRB1*15 generally associated with, while DRB1*01 and DRB1*03 protected against, a non-resolving disease. Interestingly, the clinical influence of DRB1*03 (good prognosis) dominated over that of DRB1*15 (bad prognosis).</p> <p>Conclusions</p> <p>We found several significant differences between LS and non-LS patients and we therefore suggest that genetic association studies in sarcoidosis should include a careful clinical characterisation and sub-grouping of patients, in order to reveal true genetic associations. This may be particularly accurate to do in the heterogeneous non-LS group of patients.</p

Monodromy of Cyclic Coverings of the Projective Line

We show that the image of the pure braid group under the monodromy action on the homology of a cyclic covering of degree d of the projective line is an arithmetic group provided the number of branch points is sufficiently large compared to the degree.Comment: 47 pages (to appear in Inventiones Mathematicae

Direct replacement of oral sodium benzoate with glycerol phenylbutyrate in children with urea cycle disorders

Long-term management of urea cycle disorders (UCDs) often involves unlicensed oral sodium benzoate (NaBz) which has a high volume and unpleasant taste. A more palatable treatment is licenced and available (glycerol phenylbutyrate [GPB], Ravicti) but guidance on how to transition patients from NaBz is lacking. A retrospective analysis of clinical and biochemical data was performed for eight children who transitioned from treatment with a single ammonia scavenger, NaBz, to GPB at a single metabolic centre; UCDs included arginosuccinic aciduria (ASA) (n = 5), citrullinaemia type 1 (n = 2) and carbamoyl phosphate synthetase I deficiency (CPS1) (n = 1). Patients transitioned either by gradual transition over 1–2 weeks (n = 3) or direct replacement of NaBz with GPB (n = 5). Median initial dose of GPB was 8.5 mL/m2/day based on published product information; doses were revisited subsequently in clinic and titrated individually (range 4.5–11 mL/m2/day). Pre-transition and post-transition mean ammonia levels were 37 μmol/L (SD 28 μmol/L) and 29 μmol/L (SD 22 μmol/L), respectively (p = 0.09), and mean glutamine levels were 664 μmol/L (SD 225 μmol/L) and 598 μmol/L (SD 185 μmol/L), respectively (p = 0.24). There were no reductions in levels of branched chain amino acids. No related adverse drug reactions were reported. Patients preferred GPB because of its lower volume and greater palatability. Direct replacement of NaBz with GPB maintained metabolic control and was simple for the health service and patients to manage. A more cautious approach with additional monitoring would be warranted in brittle patients and patients whose ammonia levels are difficult to control

Expansion in perfect groups

Let Ga be a subgroup of GL_d(Q) generated by a finite symmetric set S. For an integer q, denote by Ga_q the subgroup of Ga consisting of the elements that project to the unit element mod q. We prove that the Cayley graphs of Ga/Ga_q with respect to the generating set S form a family of expanders when q ranges over square-free integers with large prime divisors if and only if the connected component of the Zariski-closure of Ga is perfect.Comment: 62 pages, no figures, revision based on referee's comments: new ideas are explained in more details in the introduction, typos corrected, results and proofs unchange

Contractions of Low-Dimensional Lie Algebras

Theoretical background of continuous contractions of finite-dimensional Lie algebras is rigorously formulated and developed. In particular, known necessary criteria of contractions are collected and new criteria are proposed. A number of requisite invariant and semi-invariant quantities are calculated for wide classes of Lie algebras including all low-dimensional Lie algebras. An algorithm that allows one to handle one-parametric contractions is presented and applied to low-dimensional Lie algebras. As a result, all one-parametric continuous contractions for the both complex and real Lie algebras of dimensions not greater than four are constructed with intensive usage of necessary criteria of contractions and with studying correspondence between real and complex cases. Levels and co-levels of low-dimensional Lie algebras are discussed in detail. Properties of multi-parametric and repeated contractions are also investigated.Comment: 47 pages, 4 figures, revised versio

Two-dimensional model of dynamical fermion mass generation in strongly coupled gauge theories

We generalize the $N_F=2$ Schwinger model on the lattice by adding a charged scalar field. In this so-called $\chi U\phi_2$ model the scalar field shields the fermion charge, and a neutral fermion, acquiring mass dynamically, is present in the spectrum. We study numerically the mass of this fermion at various large fixed values of the gauge coupling by varying the effective four-fermion coupling, and find an indication that its scaling behavior is the same as that of the fermion mass in the chiral Gross-Neveu model. This suggests that the $\chi U\phi_2$ model is in the same universality class as the Gross-Neveu model, and thus renormalizable and asymptotic free at arbitrary strong gauge coupling.Comment: 18 pages, LaTeX2e, requires packages rotating.sty and curves.sty from CTA

Universal Prefactor of Activated Conductivity in the Quantum Hall Effect

The prefactor of the activated dissipative conductivity in a plateau range of the quantum Hall effect is studied in the case of a long-range random potential. It is shown that due to long time it takes for an electron to drift along the perimeter of a large percolation cluster, phonons are able to maintain quasi-equilibrium inside the cluster. The saddle points separating such clusters may then be viewed as ballistic point contacts between electron reservoirs with different electrochemical potentials. The prefactor is universal and equal to 2$e^2/h$ at an integer filling factor $\nu$ and to 2$e^2/q^{2}h$ at $\nu=p/q$.Comment: 4 pages + 2 figures by reques

The complex TIE between macrophages and angiogenesis

Macrophages are primarily known as phagocytic immune cells, but they also play a role in diverse processes, such as morphogenesis, homeostasis and regeneration. In this review, we discuss the influence of macrophages on angiogenesis, the process of new blood vessel formation from the pre-existing vasculature. Macrophages play crucial roles at each step of the angiogenic cascade, starting from new blood vessel sprouting to the remodelling of the vascular plexus and vessel maturation. Macrophages form promising targets for both pro- and anti-angiogenic treatments. However, to target macrophages, we will first need to understand the mechanisms that control the functional plasticity of macrophages during each of the steps of the angiogenic cascade. Here, we review recent insights in this topic. Special attention will be given to the TIE2-expressing macrophage (TEM), which is a subtype of highly angiogenic macrophages that is able to influence angiogenesis via the angiopoietin-TIE pathway