Dynamically stabilized magnetic skyrmions.

Magnetic skyrmions are topologically non-trivial spin textures that manifest themselves as quasiparticles in ferromagnetic thin films or noncentrosymmetric bulk materials. So far attention has focused on skyrmions stabilized either by the Dzyaloshinskii-Moriya interaction (DMI) or by dipolar interaction, where in the latter case the excitations are known as bubble skyrmions. Here we demonstrate the existence of a dynamically stabilized skyrmion, which exists even when dipolar interactions and DMI are absent. We establish how such dynamic skyrmions can be nucleated, sustained and manipulated in an effectively lossless medium under a nanocontact. As quasiparticles, they can be transported between two nanocontacts in a nanowire, even in complete absence of DMI. Conversely, in the presence of DMI, we observe that the dynamical skyrmion experiences strong breathing. All of this points towards a wide range of skyrmion manipulation, which can be studied in a much wider class of materials than considered so far.

Skyrmion-Based Dynamic Magnonic Crystal.

A linear array of periodically spaced and individually controllable skyrmions is introduced as a magnonic crystal. It is numerically demonstrated that skyrmion nucleation and annihilation can be accurately controlled by a nanosecond spin polarized current pulse through a nanocontact. Arranged in a periodic array, such nanocontacts allow the creation of a skyrmion lattice that causes a periodic modulation of the waveguide's magnetization, which can be dynamically controlled by changing either the strength of an applied external magnetic field or the density of the injected spin current through the nanocontacts. The skyrmion diameter is highly dependent on both the applied field and the injected current. This implies tunability of the lowest band gap as the skyrmion diameter directly affects the strength of the pinning potential. The calculated magnonic spectra thus exhibit tunable allowed frequency bands and forbidden frequency bandgaps analogous to that of conventional magnonic crystals where, in contrast, the periodicity is structurally induced and static. In the dynamic magnetic crystal studied here, it is possible to dynamically turn on and off the artificial periodic structure, which allows switching between full rejection and full transmission of spin waves in the waveguide. These findings should stimulate further research activities on multiple functionalities offered by magnonic crystals based on periodic skyrmion lattices.

Artificial kagome spin ice: dimensional reduction, avalanche control and emergent magnetic monopoles.

Artificial spin-ice systems consisting of nanolithographic arrays of isolated nanomagnets are model systems for the study of frustration-induced phenomena. We have recently demonstrated that monopoles and Dirac strings can be directly observed via synchrotron-based photoemission electron microscopy, where the magnetic state of individual nanoislands can be imaged in real space. These experimental results of Dirac string formation are in excellent agreement with Monte Carlo simulations of the hysteresis of an array of dipoles situated on a kagome lattice with randomized switching fields. This formation of one-dimensional avalanches in a two-dimensional system is in sharp contrast to disordered thin films, where avalanches associated with magnetization reversal are two-dimensional. The self-organized restriction of avalanches to one dimension provides an example of dimensional reduction due to frustration. We give simple explanations for the origin of this dimensional reduction and discuss the disorder dependence of these avalanches. We conclude with the explicit demonstration of how these avalanches can be controlled via locally modified anisotropies. Such a controlled start and stop of avalanches will have potential applications in data storage and information processing.

Magnetic domain formation in itinerant metamagnets.

We examine the effects of long-range dipolar forces on metamagnetic transitions and generalize the theory of Condon domains to the case of an itinerant electron system undergoing a first-order metamagnetic transition. We demonstrate that, within a finite range of the applied field, dipolar interactions induce a spatial modulation of the magnetization in the form of stripes or bubbles. Our findings are consistent with recent observations in the bilayer ruthenate Sr(3)Ru(2)O(7).

Very low seroprevalence of Lyme borreliosis in young Greek males.

We studied the prevalence of anti-Borrelia burgdorferi antibodies in a sample of 1100 Greek male Navy recruits. Thirty-six (3.27%) subjects were found IgG positive by an enzyme immunoassay. Only three of the positive subjects (0.27%) were reactive by an IgG Western Blot. The seroprevalence of Lyme disease is very low in the Greek young male adult population.

The quantitative measurement of autoantibodies to thyroglobulin and thyroid peroxidase by automated microparticle based immunoassays in Hashimoto's disease, Graves' disease and a follow-up study on postpartum thyroid disease.

The aim of this study was to investigate the association between various autoimmune thyroid diseases and the presence of anti-TPO and anti-Tg antibodies using two novel automated microparticle based immunoassays developed for the AxSYM analyzer. Serum samples from 65 individuals with Hashimoto's Disease, 38 with Graves' Disease and 80 UK blood donors were assayed. In addition, samples were taken from 50 women known to be positive for TPO antibodies, for up to 24 weeks following delivery. Precision for both assays ranges from 5.7-9.1% CV, while analytical sensitivity was determined to be 1.0 IU/ml for Anti-Tg and 0.3 IU/ml for Anti-TPO. The Anti-TPO test showed positive results in 86% of Hashimoto's Disease and 87% of Graves' Disease. The figures obtained for Anti-Tg were 58% and 73% respectively. Specificity was 94% with Anti-TPO and 99% with Anti-Tg. The postpartum women were divided into 2 groups, group A remained symptomless while group B developed thyroid dysfunction. Within the 2 groups, medians calculated at each time point were compared between and within groups using the Mann-Whitney Rank Sum Test or the Kruskal-Wallis One Way ANOVA on Ranks. Anti-TPO baseline levels (week 6) were statistically different between both groups (median 36 vs. 167 IU/ml, p = 0.002). In group A, the median values increased from 36 to 87 IU/ml within the observation period, although the difference was not statistically significant. In group B, antibody titres showed a statistically significant increase from 168 IU/ml (week 6) up to 676 IU/ml after 20 weeks (p < 0.001). Anti-Tg baseline levels were not statistically different between the two groups. In group A, the median values did not change significantly over time (range: 47-86 IU/ml) whereas antibody titres in group B showed a statistically significant increase from 79 IU/ml (week 6) to 276 IU/ml after 24 weeks (p = 0.002). Results obtained indicate that these assays provide useful tools for the quantitative determination of autoantibodies in both primary diagnosis as shown with the Hashimoto's disease and Graves' disease samples and patient follow-up as demonstrated with the postpartum samples. The automation and high precision of the assays make them perfectly suited to routine diagnostic use.

Prediction of successful outcome in a randomised controlled trial of the long-term efficacy of interferon alpha treatment for chronic hepatitis C.

To evaluate the efficacy of a 12-month course of recombinant interferon alpha (IFN-alpha2b), and to assess predictive factors of successful response to IFN therapy in chronic active hepatitis C (HCV CAH), 242 patients with histologically proven HCV CAH were assigned randomly to two groups, one treated with IFN-alpha2b (3 MU three times weekly, intramuscularly), the other untreated. To determine the efficacy of IFN-alpha2b 12 months after therapy, a second liver biopsy was carried out on 100 treated patients and 27 untreated patients. The biochemical, virological, and serological response of patients followed up for at least 50 months after treatment was also evaluated to confirm the efficacy of IFN-alpha2b. The genotypes of infecting HCV, anti-HCV core IgM, and HCV-RNA concentrations were also analysed and the predictors of response determined by univariate and multivariate analyses. Response was defined in terms of the normalisation of aminotransferase activities and the disappearance of HCV-RNA. The overall long-term response was 39.4%. Anti-HCV core IgM levels were significantly lower in long-term responders. Patients with increased levels of IgM anti HCV core (>3.8 sample/cut-off), infected with genotype 1b were nonresponders. Liver histology improved significantly in patients with long-term response. Multivariate analysis identified three independent predictors of the likelihood of long-term response to IFN therapy: age younger than 40 years, basal anti-HCV core IgM levels < or = 3.8, and genotypes other than 1b. These data indicate that the treatment with IFN-alpha2b used in this randomised controlled trial is effective in HCV CAH. Anti-HCV core IgM was the strongest predictor of long-term response in the present study.

Absence of LKM-1 antibody reactivity in autoimmune and hepatitis-C-related chronic liver disease in Sweden. Swedish Internal Medicine Liver club.

BACKGROUND: Type-2 autoimmune hepatitis is a subgroup of chronic hepatitis characterized by the presence of liver/kidney microsomal autoantibodies type 1 (LKM-1). A frequent association with chronic hepatitis C suggests that hepatitis virus might trigger autoimmune reactivity. LKM-1-positive chronic hepatitis is not uncommon in southern Europe but is rarely seen in the USA and the UK. The prevalence in Scandinavia is hitherto unknown. METHODS: We used an automated prototype LKM-1 immunometry-based assay (IMx) to detect LKM-1 antibodies in sera from 350 Swedish patients with chronic liver diseases (100 with primary biliary cirrhosis, 80 with primary sclerosing cholangitis, 100 with hepatitis C, and 70 patients with various forms of chronic hepatitis, including 36 autoimmune cases), and from 17 children with autoimmune hepatitis. Sera reactive in the IMx assay were subjected to immunofluorescence testing. RESULTS: No clearly LKM-reactive sera were detected. Serum samples from 29 patients were borderline reactive in the IMx assay but tested negative in the confirmatory immunofluorescence test. Positive tests in the former assay were likely caused by reactivity against microsomal antigens other than LKM-1/cytochrome P450IID6. CONCLUSIONS: LKM-1-positive type-2 autoimmune hepatitis is very rare in Sweden. Furthermore, chronic hepatitis C did not trigger this type of autoimmune reactivity in our patients, probably owing to genetic insusceptibility.

The quantitative humoral immune response to the hepatitis C virus is correlated with disease activity and response to interferon-alpha.

BACKGROUND/AIM: Virus-host interactions may have pathogenetic significance in chronic hepatitis. Thus the humoral immune response was evaluated during the clinical course of HCV-infected patients. METHODS: Eighteen selected chronic HCV patients received three doses of 3 or 6 MU interferon-alpha 2a weekly for 6 to 12 months and were followed up for 6 to 60 months. Anti-HCV antibody levels were serially measured either in end-point diluted sera with the Matrix-Assay or with quantitative anti-HC34-IgG and -IgM ELISA. Circulating immune complexes were assessed by flow cytometry and the results were correlated with histology, quantitative HCV-RNA levels and genotypes. RESULTS: Nine complete responders (CR; genotypes 1a n = 4; 1b n = 1; 2a n = 1; 3a n = 3) showing sustained virus elimination and ALT normalisation had low HCV-RNA pretreatment levels (mean 14 x 10(3) copies/ml) compared to six nonresponders and three partial responders (NR/PR; genotypes 1a n = 2; 1b n = 7) who had significantly higher HCV-RNA pretreatment levels (mean 254 x 10(3) copies/ml; p < 0.01). In untreated NR/PR the HC34 core-antigen was most immunogenic, in CR the NS3-derived HC29-antigen. Pre-treatment levels of anti-HC 34-IgG and -IgM antibody levels in NR/PR were higher than in CR (IgM/IgG p = 0.05, n.s.) and these differences became significant during or after therapy (3 months therapy: IgM p < 0.02/IgG p < 0.07; end of therapy: IgM 0.006/IgG p < 0.04; 6 months post-therapy: IgM p < 0.002/IgG p < 0.004). The PR patients showed recurrent anti-HC34 antibody levels that preceded disease reactivation and detectable HCV-RNA in serum. Immune complex formation increased in some patients during treatment but did not correlate with disease activity, quantitative viraemia, antibody levels or therapy outcome. CONCLUSION: Anti-HC34 antibodies, i.e. of the IgM-subtype, correlated quantitatively with viraemia and disease activity. Monitoring the antibody levels may predict the long-term therapy outcome during interferon-alpha treatment.

Quantitative assessment of hepatitis C virus RNA and IgM antibodies to hepatitis C core in chronic hepatitis C.

BACKGROUND/AIMS: IgM antibodies to hepatitis C virus have been found in a variable proportion of patients with chronic hepatitis C. We have evaluated whether IgM anti-core antibodies correlate with viraemia or hepatic injury in chronic hepatitis C. METHODS: Serum from 106 patients with chronic hepatitis C with varying stages of disease were tested for IgM anti-core hepatitis C virus by immunoassay. All patients were seropositive for IgG antibody to hepatitis C virus by second-generation ELISA; 25 had histologic cirrhosis and 57 chronic hepatitis. IgM anti-core was detected in 84/106 (79.2%) patients. HCV-RNA was tested by branched (bDNA) signal amplification assay or by polymerase chain reaction in 92 patients. RESULTS: All IgM-anti-HCV positive patients had detectable HCV-RNA. Seventy of 87 (80.5%) HCV-RNA-positive patients were IgM anti-core positive. Levels of IgM anti-HCV were significantly higher in patients with HCV-RNA detected by bDNA than in those who were bDNA negative, but there was no correlation between HCV-RNA concentrations and IgM anti-HCV levels. Of the 84 patients with positive results for IgM anti-core hepatitis C virus, 59 (70.2%) had abnormal alanine aminotransferase levels. The levels of IgM anti-core hepatitis C virus were likewise significantly higher in those with abnormal alanine aminotransferase levels. There was no difference in the percentage of patients with a positive IgM anti-HCV, or in levels of IgM anti-core hepatitis C virus in those with chronic hepatitis versus cirrhosis. CONCLUSIONS: These data suggest that the majority of patients with chronic hepatitis C virus infection are IgM anti-core hepatitis C virus positive, and the detection seems to be associated with viral replication and biochemical evidence of hepatic necrosis. IgM anti-core hepatitis testing may prove useful as an adjunct in the clinical assessment of patients with chronic hepatitis C.

Anti-GOR and anti-thyroid autoantibodies in patients with chronic hepatitis C.

Anti-thyroid autoantibodies have been described in anti-hepatitis C virus (HCV)-positive patients. It has been suggested that the anti-GOR response is closely related to HCV infection and may reflect an HCV-associated autoimmune phenomenon. This study was designed to evaluate the humoral anti-GOR response in anti-HCV-positive patients with anti-thyroid autoantibodies (group 1, 22 patients) and to compare it with the response in anti-HCV-positive patients without anti-thyroid autoantibodies (group 2, 44 patients) and in anti-HCV-negative patients with autoimmune thyroiditis (group 3, 28 patients). The prevalences of anti-GOR in groups 1, 2, and 3 were, respectively, 72.7, 61.3, and 3.5%. Anti-GOR levels were higher in group 1 than in group 2 or group 3 (P = 0.0001). Moreover, comparison of the Anti-GOR levels of groups 1 and 2 also revealed a statistically significant difference (P = 0.008). Detection of more elevated anti-GOR levels in group 1 patients suggests that anti-thyroid autoantibodies in anti-HCV-positive patients may be related to HCV.

In vitro secretion of anti-GOR protein and anti-hepatitis C virus antibodies in patients with chronic hepatitis C.

BACKGROUND/AIMS: Anti-GOR antibodies may reflect hepatitis C virus (HCV)--related autoimmunity or cross-reactivity with HCV core antigen. This study aimed to evaluate the clinical significance of anti-GOR antibodies. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from 35 patients with HCV and 48 controls and cultured for 8 days. The in vitro antibody secretion by PBMC was determined using specific enzyme-linked immunosorbent assays and recombinant immunoblot assay. RESULTS: In 22 of 35 patients with HCV (62.9%), PBMCs secreted anti-c22-3 or anti-c33c antibodies. However, in 3 of 48 controls (6.2%), PBMCs secreted anti-c33c antibodies alone. A significant in vitro anti-GOR response was found in 13 of 35 patients (37.1%) with HCV in relation to 4 of 48 controls (8.3%). In 12 of these patients (92.3%), anti-GOR were found in vitro and in serum. Two patients with HCV produced in vitro anti-GOR but not anti-c22-3 antibodies. Regarding disease activity, in vitro anti-GOR-positive patients with HCV had significantly higher alanine aminotransferase levels (108.8 +/- 17.8 U/L vs. 64.5 +/- 7.6 U/L; P < 0.01) and more frequent signs of chronic active hepatitis (10 of 13 [76.9%] vs. 10 of 22 [45.5%]) than patients with HCV without in vitro anti-GOR response. CONCLUSIONS: The humoral anti-GOR response in vitro is closely related to HCV infection and disease activity. Anti-GOR and anti-HCV core antibodies are regulated independently. It is likely that anti-GOR may reflect an HCV-associated autoimmune phenomenon.

GOR-antibodies in patients with chronic liver disease and hepatocellular carcinoma.

HCV infection frequently leads to liver cirrhosis and the development of hepatocellular carcinoma, while the mechanisms of carcinogenesis are still unclear. Autoantibodies like antinuclear antibodies have been described to increase and change their specificity in patients with hepatocellular carcinoma. Autoantibodies against GOR, an antigen not encoded by the viral but by the host's genome and overexpressed in tumor cells, are frequently associated with hepatitis C infection, but their significance during the development of hepatocellular carcinoma has not been determined yet. We analysed the frequency of GOR-antibodies in 38 patients with hepatocellular carcinoma on the grounds of liver cirrhosis of different origin, 38 patients with extrahepatic tumors, 24 patients with hepatitis C infection and 30 healthy controls. GOR-antibodies were found to be specifically associated with hepatitis C and were only found in patients with hepatocellular carcinoma if the liver cirrhosis was due to HCV-infection. Patients with extrahepatic tumors with or without liver metastasis had no detectable GOR antibodies, if no HCV infection was present. The determination of antibodies to the autoantigen GOR therefore has no clinical significance in patients with hepatic or extrahepatic tumors not related to HCV infection.

Anti-GOR in hepatitis D: specific association with hepatitis C virus superinfection.

A group of 113 patients with chronic hepatitis D was investigated for the presence of anti-GOR and liver kidney microsomal antibodies. Eight patients were anti-GOR positive and also positive for hepatitis C virus-infection. In sera from 16 patients liver-kidney microsomal antibodies were detectable by immunofluorescence. They were classified as LKM-3 due to their fluorescence pattern. Two of the LKM-3-positive sera were also anti-hepatitis C virus and anti-human immunodeficiency virus positive. None of these patients were positive for anti-GOR. Fourteen sera from LKM-3-positive patients reacted in Western blot with a microsomal protein at 55 kDa that differs from the 50-kDa LKM-1 (cytochrome P450IID6) antigen. Our studies demonstrate that hepatitis D virus itself does not induce an autoimmune reaction against the GOR antigen and that autoimmunity to the LKM-3 antigen induced by hepatitis D virus infection does not correlated with anti-GOR. These studies support the specificity of the anti-GOR response for hepatitis C virus infection.