Recent advances in the immunogenetics of idiopathic inflammatory myopathy

This review summarizes the previous and current literature on the immunogenetics of idiopathic inflammatory myopathy (IIM) and updates the research progress that has been made over the past decade. A substantial part of the genetic risk for developing adult- and juvenile-onset IIM lies within the major histocompatibility complex (MHC), and a tight relationship exists between individual human leukocyte antigen alleles and specific serological subtypes, which in turn dictate clinical disease phenotypes. Multiple genetic regions outside of the MHC are increasingly being identified in conferring IIM disease susceptibility. We are still challenged with the task of studying a serologically and clinically heterogeneous disorder that is rarer by orders of magnitude than the likes of rheumatoid arthritis. An ongoing and internationally coordinated IIM genome-wide association study may provide further insights into IIM immunogenetics.     

Extreme variations in the ratios of non-synonymous to synonymous nucleotide substitution rates in signal peptide evolution.

Nucleotide sequences encoding signal peptides from the precursors of alpha-amylase/trypsin inhibitors from cereals are homologous to those corresponding to the precursors of thaumatin II and of plastocyanins. Non-synonymous (KA) and synonymous (KS) rates of nucleotide substitutions have been calculated for all possible binary combinations. Extreme variation in KA/KS ratios has been observed; from the 0.167 average found within the plastocyanin family to an average of 1.90 calculated for the inhibitors/thaumatin II transition. A similar calculation has been carried out for the signal peptide sequences of thionins, which are unrelated to those of the alpha-amylase/trypsin inhibitor family, and an average KA/KS of 0.12 has been obtained. This variation can be largely explained in terms of an empirical index of stability related to amino acid composition and seems to be independent of functional constraints.     

Intraclonal variation in RNA viruses: generation, maintenance and consequences

This paper explores the evolutionary implications of the enormous variability that characterizes populations of RNA viruses and retroviruses. It begins by examining the magnitude of genetic variation in both natural and experimental populations. In natural populations, differences arise even within individual infected patients, with the per-site nucleotide diversity at this level ranging from < 1% to 6%. In laboratory populations, two viruses sampled from the same clone differed by ∼0.7% in their fitness. Three different mechanisms that may be important in maintaining viral genetic variability were tested: (1) Fisher's fundamental theorem, to compare the observed rate of fitness change with the extent of fitness-related variation within the same experimental populations; (2) magnitude of genomic mutation rate, to assess whether it correlated with fitness-related variation, as predicted by the mutation-selection balance hypothesis; (3) frequency-dependent selection, which affords rare genotypes an advantage. The paper concludes with a discussion of two evolutionary consequences of variability: the fixation of deleterious mutations by drift in small populations and the role of clonal interference in large ones.  © 2003 The Linnean Society of London. Biological Journal of the Linnean Society , 2003, 79 , 17–26.     

Mountain birch under multiple stressors – heavy metal‐resistant populations co‐resistant to biotic stress but maladapted to abiotic stress

Stress adaptations often include a trade‐off of weakened performance in nonlocal conditions, resulting in divergent selection, and potentially, genetic differentiation and evolutionary adaptation. Results of a two‐phase (greenhouse and field) common garden experiment demonstrated adaptation of mountain birch (Betula pubescens subsp. czerepanovii) populations from industrially polluted areas of the Kola Peninsula, north‐western Russia, to heavy metals (HM), whereas no adaptations to wind or drought stress were detected in populations from wind‐exposed sites. HM‐adapted seedlings were maladapted to drought but less palatable (co‐resistant) to insect herbivores, even under background HM concentrations. The absence of adaptations to harsh microclimate and the generally high adaptive potential of mountain birch, a critical forest forming tree in subarctic Europe, need to be accounted for in models predicting consequences of human‐driven environmental changes, including the projected climate change.     

Direct cord implantation in brachial plexus avulsions: revised technique using a single stage combined anterior (first) posterior (second) approach and end-to-side side-to-side grafting neurorrhaphy

Background

The superiority of a single stage combined anterior (first) posterior (second) approach and end-to-side side-to-side grafting neurorrhaphy in direct cord implantation was investigated as to providing adequate exposure to both the cervical cord and the brachial plexus, as to causing less tissue damage and as to being more extensible than current surgical approaches.

Methods

The front and back of the neck, the front and back of the chest up to the midline and the whole affected upper limb were sterilized while the patient was in the lateral position; the patient was next turned into the supine position, the plexus explored anteriorly and the grafts were placed; the patient was then turned again into the lateral position, and a posterior cervical laminectomy was done. The grafts were retrieved posteriorly and side grafted to the anterior cord. Using this approach, 5 patients suffering from complete traumatic brachial plexus palsy, 4 adults and 1 obstetric case were operated upon and followed up for 2 years. 2 were C5,6 ruptures and C7,8T1 avulsions. 3 were C5,6,7,8T1 avulsions. C5,6 ruptures were grafted and all avulsions were cord implanted.

Results

Surgery in complete avulsions led to Grade 4 improvement in shoulder abduction/flexion and elbow flexion. Cocontractions occurred between the lateral deltoid and biceps on active shoulder abduction. No cocontractions occurred after surgery in C5,6 ruptures and C7,8T1 avulsions, muscle power improvement extended into the forearm and hand; pain disappeared.

Limitations include

spontaneous recovery despite MRI appearance of avulsions, fallacies in determining intraoperative avulsions (wrong diagnosis, wrong level); small sample size; no controls rule out superiority of this technique versus other direct cord reimplantation techniques or other neurotization procedures; intra- and interobserver variability in testing muscle power and cocontractions.

Conclusion

Through providing proper exposure to the brachial plexus and to the cervical cord, the single stage combined anterior (first) and posterior (second) approach might stimulate brachial plexus surgeons to go more for direct cord implantation. In this study, it allowed for placing side grafts along an extensive donor recipient area by end-to-side, side-to-side grafting neurorrhaphy and thus improved results.

Level of evidence

Level IV, prospective case series.