IVIG blocks complement deposition mediated by anti-GM1 antibodies in multifocal motor neuropathy

The pathogenesis of multifocal motor neuropathy (MMN) has yet to be established. MMN patients often carry anti-GM1 IgM antibodies, suggesting an autoimmune process involving complement. Intravenous immunoglobulin (IVIG) is the first line treatment, but its action mechanism is unknown.

[Ultrasound and arthritis]

Musculoskeletal ultrasonography (US) is an established and validated imaging technique in rheumatology. Ultrasonography is able to directly visualize soft tissue pathologies such as synovial tissue changes. Pathological findings in superficial cartilage, bone lesions and synovial tissue changes in the context of rheumatoid arthritis, spondyloarthritis or crystal arthropathies may only be seen by sonography or detected earlier by ultrasonography compared to conventional imaging techniques. The activity of an inflammatory arthropathy can be visualized using Doppler and power Doppler US. US is helpful in the detection of early inflammatory changes, particularly in patients with undifferentiated arthritis and/or unremarkable conventional radiography. In addition to diagnosis in early arthritis and monitoring of therapy in rheumatoid arthritis, sonography is able to detect pivotal pathologies in spondyloarthritis and crystal deposition diseases such as gout, pseudogout and apatite deposition disease. Ultrasound-guided diagnostic and therapeutic interventions are characterized by their excellent accuracy and improvement of clinical effectiveness compared to unguided procedures. In conclusion, ultrasonography plays a pivotal role in the assessment and monitoring of therapy in rheumatic diseases.

Evidence for selection on coloration in a Panamanian poison frog: a coalescent-based approach

Aim The strawberry poison frog, Oophaga pumilio, has undergone a remarkable radiation of colour morphs in the Bocas del Toro archipelago in Panama. This species shows extreme variation in colour and pattern between populations that have been geographically isolated for < 10,000 years. While previous research has suggested the involvement of divergent selection, to date no quantitative test has examined this hypothesis. Location Bocas del Toro archipelago, Panama. Methods We use a combination of population genetics, phylogeography and phenotypic analyses to test for divergent selection in coloration in O. pumilio. Tissue samples of 88 individuals from 15 distinct populations were collected. Using these data, we developed a gene tree using the mitochondrial DNA (mtDNA) d-loop region. Using parameters derived from our mtDNA phylogeny, we predicted the coalescence of a hypothetical nuclear gene underlying coloration. We collected spectral reflectance and body size measurements on 94 individuals from four of the populations and performed a quantitative analysis of phenotypic divergence. Results The mtDNA d-loop tree revealed considerable polyphyly across populations. Coalescent reconstructions of gene trees within population trees revealed incomplete genotypic sorting among populations. The quantitative analysis of phenotypic divergence revealed complete lineage sorting by colour, but not by body size: populations showed non-overlapping variation in spectral reflectance measures of body coloration, while variation in body size did not separate populations. Simulations of the coalescent using parameter values derived from our empirical analyses demonstrated that the level of sorting among populations seen in colour cannot reasonably be attributed to drift. Main conclusions These results imply that divergence in colour, but not body size, is occurring at a faster rate than expected under neutral processes. Our study provides the first quantitative support for the claim that strong diversifying selection underlies colour variation in the strawberry poison frog.

Meta-analysis of mould and dampness exposure on asthma and allergy in eight European birth cohorts: an ENRIECO initiative

Background:  Several cross-sectional studies during the past 10 years have observed an increased risk of allergic outcomes for children living in damp or mouldy environments. Objective:  The objective of this study was to investigate whether reported mould or dampness exposure in early life is associated with the development of allergic disorders in children from eight European birth cohorts. Methods:  We analysed data from 31 742 children from eight ongoing European birth cohorts. Exposure to mould and allergic health outcomes were assessed by parental questionnaires at different time points. Meta-analyses with fixed- and random-effect models were applied. The number of the studies included in each analysis varied based on the outcome data available for each cohort. Results:  Exposure to visible mould and/or dampness during first 2 years of life was associated with an increased risk of developing asthma: there was a significant association with early asthma symptoms in meta-analyses of four cohorts [0–2 years: adjusted odds ratios (aOR), 1.39 (95%CI, 1.05–1.84)] and with asthma later in childhood in six cohorts [6–8 years: aOR, 1.09(95%CI, 0.90–1.32) and 3–10 years: aOR, 1.10 (95%CI, 0.90–1.34)]. A statistically significant association was observed in six cohorts with symptoms of allergic rhinitis at school age [6–8 years: aOR, 1.12 (1.02–1.23)] and at any time point between 3 and 10 years [aOR, 1.18 (1.09–1.28)]. Conclusion:  These findings suggest that a mouldy home environment in early life is associated with an increased risk of asthma particularly in young children and allergic rhinitis symptoms in school-age children.

Purification, cDNA structure and biological significance of a single insulin-like growth factor-binding domain protein (SIBD-1) identified in the hemocytes of the spider Cupiennius salei

Cupiennius salei single insulin-like growth factor-binding domain protein (SIBD-1), which exhibits an IGFBP N-terminal domain-like profile, was identified in the hemocytes of the spider C. salei. SIBD-1 was purified by RP-HPLC and the sequence determined by a combination of Edman degradation and 5'-3'- RACE PCR. The peptide (8676.08 Da) is composed of 78 amino acids, contains six intrachain disulphide bridges and carries a modified Thr residue at position 2. SIBD-1 mRNA expression was detected by quantitative real-time PCR mainly in hemocytes, but also in the subesophageal nerve mass and muscle. After infection, the SIBD-1 content in the hemocytes decreases and, simultaneously, the temporal SIBD-1 expression seems to be down-regulated. Two further peptides, SIBD-2 and IGFBP-rP1, also exhibiting IGFBP N-terminal domain variants with unknown functions, were identified on cDNA level in spider hemocytes and venom glands. We conclude that SIBD-1 may play an important role in the immune system of spiders.

The 2002 European registry of cardiac catheter interventions

OBJECTIVE: The tradition of yearly reports on cardiac catheter interventions in Europe has been initiated in 1992. This 11th report presents aggregated data on cardiac catheter procedures in 30 European countries in the year 2002. DESIGN AND SETTING: A detailed questionnaire addressing summary data of all cardiac interventions was mailed to presidents or delegates of the national societies of cardiology in Europe. The questionnaire was distributed to all institutions with cardiac catheterisation programs. All questionnaires were compiled in a national summary data sheet, then entered into a central database and subsequently analysed. MAIN OUTCOME MEASURES: Coronary angiography, PTCA, and stenting in absolute numbers and per million inhabitants in the participating countries and the whole of Europe. RESULTS: Overall, 1,901,932 coronary angiograms were reported. The population-adjusted rate of coronary angiograms amounted to an absolute mean of 3358 per 10(6) inhabitants, an increase of 7% compared with 2001. A total of 686,869 PTCA procedures were reported. The mean European number of PTCAs per 10(6) inhabitants increased by 10% from 1103 in 2001 to 1213 in 2002. Procedures with stenting increased by 17% from 508,999 to 593,906. The stenting rate was 86% compared with 82% in 2001. CONCLUSIONS: In pace with epidemiological demand and the need to catch-up from underuse in certain countries, a continuous and considerable growth of coronary interventions can be observed. It will take years to find out whether the announced change of paradigm in the treatment of multivessel disease in the wake of drug-eluting stents will come true.

Evaluation of the biological activity of a growth hormone (GH) mutant (R77C) and its impact on GH responsiveness and stature

CONTEXT AND OBJECTIVE: A single missense mutation in the GH-1 gene converting codon 77 from arginine (R) to cysteine (C) yields a mutant GH-R77C peptide, which was described as natural GH antagonist. DESIGN, SETTING, AND PATIENTS: Heterozygosity for GH-R77C/wt-GH was identified in a Syrian family. The index patient, a boy, was referred for assessment of his short stature (-2.5 SD score) and partial GH insensitivity was diagnosed. His mother and grandfather were also carrying the same mutation and showed partial GH insensitivity with modest short stature. INTERVENTIONS AND RESULTS: Functional characterization of the GH-R77C was performed through studies of GH receptor binding and activation of Janus kinase 2/Stat5 pathway. No differences in the binding affinity and bioactivity between wt-GH and GH-R77C were found. Similarly, cell viability and proliferation after expression of both GH peptides in AtT-20 cells were identical. Quantitative confocal microscopy analysis revealed no significant difference in the extent of subcellular colocalization between wt-GH and GH-R77C with endoplasmic reticulum, Golgi, or secretory vesicles. Furthermore studies demonstrated a reduced capability of GH-R77C to induce GHR/GHBP gene transcription rate when compared with wt-GH. CONCLUSION: Reduced GH receptor/GH-binding protein expression might be a possible cause for the partial GH insensitivity with delay in growth and pubertal development found in our patients. In addition, this group of patients deserves further attention because they could represent a distinct clinical entity underlining that an altered GH peptide may also have a direct impact on GHR/GHBP gene expression causing partial GH insensitivity.

Upregulation of endothelin converting enzyme-1 in host liver during chronic cardiac allograft rejection

Endothelin regulates cytokine expression in vitro and in vivo. This study investigated the effects of chronic allograft rejection on hepatic endothelin-converting enzyme-1 (ECE-1) gene expression and endothelin-1 (ET-1) plasma clearance. Using the Lewis-F344 minor histocompatibility mismatch model of heterotopic cardiac transplantation, hepatic ECE-1 gene expression was measured by real-time polymerase chain reaction and host plasma clearance of ET-1 was measured 8 weeks after transplantation in the absence of immunosuppression. In animals undergoing allograft rejection, hepatic ECE-1 gene expression increased 2-fold (P < 0.05), whereas no effect of rejection on ET-1 clearance from plasma was observed. In summary, upregulation of ECE-1 gene expression occurs in the liver of the host during chronic allograft rejection. Because the liver represents both a key organ for cytokine production and for endothelin metabolism, increased hepatic ECE-1-mediated ET-1 synthesis may contribute to host responses and cytokine production during allograft rejection.

Feasibility of T2* mapping for the evaluation of hip joint cartilage at 1.5T using a three-dimensional (3D), gradient-echo (GRE) sequence: a prospective study

This study defines the feasibility of utilizing three-dimensional (3D) gradient-echo (GRE) MRI at 1.5T for T(2)* mapping to assess hip joint cartilage degenerative changes using standard morphological MR grading while comparing it to delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). MRI was obtained from 10 asymptomatic young adult volunteers and 33 patients with symptomatic femoroacetabular impingement (FAI). The protocol included T(2)* mapping without gadolinium-enhancement utilizing a 3D-GRE sequence with six echoes, and after gadolinium injection, routine hip sequences, and a dual-flip-angle 3D-GRE sequence for dGEMRIC T(1) mapping. Cartilage was classified as normal, with mild changes, or with severe degenerative changes based on morphological MRI. T(1) and T(2)* findings were subsequently correlated. There were significant differences between volunteers and patients in normally-rated cartilage only for T(1) values. Both T(1) and T(2)* values decreased significantly with the various grades of cartilage damage. There was a statistically significant correlation between standard MRI and T(2)* (T(1)) (P < 0.05). High intraclass correlation was noted for both T(1) and T(2)*. Correlation factor was 0.860 to 0.954 (T(2)*-T(1) intraobserver) and 0.826 to 0.867 (T(2)*-T(1) interobserver). It is feasible to gather further information about cartilage status within the hip joint using GRE T(2)* mapping at 1.5T.