The growing importance of continuing medical education in nuclear medicine: The role of the European School of Nuclear Medicine

In summary, the ESNM provides educational activities not only for young colleagues but also for established nuclear medicine physicians. There is also close contact with physicists, radiopharmacists and technologists. In the future, more interactive education and increasing activities on the web are planned. On behalf of all members of the School, I (P.L.) would like to thank Andrea Bauer and her team at the executive secretariat in Vienna for their professional help in organising the meetings and hosting the ESNM

Concentration and Subclass Distribution of Anti-ADAMTS13 IgG Autoantibodies in Different Stages of Acquired Idiopathic Thrombotic Thrombocytopenic Purpura

Background: The acquired form of idiopathic thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease, in which the underlying deficiency of the ADAMTS13 protease is caused by autoantibodies, predominantly of the IgG isotype. Certain HLADR-DQ haplotypes were associated with the risk of developing TTP. Objectives: To investigate the development of the ADAMTS13-specific antibody response during the course of the disease, we analyzed the concentration, subclass distribution, and inhibitory potential of anti-ADAMTS13 IgG autoantibodies in samples of TIP patients drawn during the first acute phase, in remission, and during relapse. Additionally, we compared the anti-ADAMTS13 IgG levels between patients carrying and not carrying risk and protective HLA-DR-DQ haplotypes. Patients and Methods: We determined the anti-ADAMTS13 IgG concentration and subclass distribution in 101 antibody-positive samples of 81 acquired TIP patients by ELISA methods. The presence and semi-quantitative amount of anti-ADAMTS13 inhibitors were determined in 97 of 100 deficient samples, and the specific inhibitory potential of anti-ADAMTS13 autoantibodies was determined in 49 selected samples, by mixing ADAMTS13-activity assays. HLA-DR-DQ typing and haplotype prediction were performed in 70 of the above patients. Results: We found that IgG1 and IgG4 were the predominant subclasses, present in almost all samples. While IgG1 was the dominant subclass in almost half of the samples taken during the first acute episode, IgG4 was dominant in all samples taken during or following a relapse. The inhibitory potential of the samples correlated with levels of the IgG4 subclass. Anti-ADAMTS13 antibodies of IgG4-dominant samples had higher specific inhibitory potentials than IgG1-dominant samples, independently of disease stage. Interestingly, we found that patients carrying the protective DR7-DQ2 and DR13-DQ6 haplotypes had higher anti-ADAMTS13 IgG levels. Conclusion: Our results indicate that IgG4 becomes the dominant subtype at some point of the disease course, apparently before the first relapse, parallel to the increase in inhibitory potential of the anti-ADAMTS13 autoantibodies. Furthermore, we found an association between the genetic background and the antibody response in TTP

The energy response of a Victoreen condenser ionization chamber

NRC publication: Ye

Study of neutrons from a Po---F([alpha],n) source

NRC publication: Ye

A novel method for monitoring Mycobacterium bovis BCG trafficking with recombinant BCG expressing green fluorescent protein.

To better understand intracellular and extracellular trafficking of Mycobacterium bovis bacillus Calmette-Guérin (BCG) when used as an intravesical agent in the treatment of transitional cell carcinoma (TCC) of the bladder, recombinant BCG (rBCG) expressing the jellyfish green fluorescent protein (GFP) was created. When the MB49.1 murine TCC cell line was incubated with GFP-expressing rBCG, internalization of the pathogen could be directly visualized by UV microscopy and quantitated by flow cytometry. The in vitro internalization of the GFP rBCG by the bladder tumor cells was temperature dependent, occurring most readily at 37 degrees C and being severely inhibited at 4 degrees C. Optimum internalization was achieved in vitro at a 10:1 BCG-to-tumor cell ratio over 24 h during which approximately 16% of the tumor cells became infected. Cytochalasin B, a phagocytosis inhibitor, abrogated the ingestion by almost 100% at a concentration of 200 micrograms/ml, indicating that contractile microfilaments likely played an important role in this process. By using mitomycin, a DNA cross-linking reagent, to inhibit proliferation of MB49.1 cells, clearance of about 40% of the green rBCG was achieved by 3 days postinfection. No significant difference between the GFP rBCG and wild-type BCG was observed in the ability to induce the expression of cell membrane proteins of major histocompatibility classes I and II, ICAM-I and -II, B7-1 and -2, of Fas from MB49.1 cells or cytokine production from mouse spleen cells. These results indicate that GFP rBCG may serve as a useful substitute for wild-type BCG in future studies of in vivo trafficking experimental and clinical immunotherapy

HLA genetic diversity in Hungarians and Hungarian Gypsies: complementary differentiation patterns and demographic signals revealed by HLA-A, -B and -DRB1 in Central Europe

Systematic analyses of human leukocyte antigen (HLA) profiles in different populations may increase the efficiency of bone marrow donor selection and help reconstructing human peopling history. We typed HLA-A, -B, and -DRB1 allele groups in two bone marrow donor cohorts of 2402 Hungarians and 186 Hungarian Gypsies and compared them with several Central-European, Spanish Gypsy, and Indian populations. Our results indicate that different European Gypsy populations share a common origin but diverged genetically as a consequence of founder effect and rapid genetic drift, whereas other European populations are related genetically in relation to geography. This study also suggests that while HLA-A accurately depicts the effects of genetic drift, HLA-B, and -DRB1 conserve more signatures of ancient population relationships, as a result of balancing selection

ATG16L1 and IL23 receptor (IL23R) genes are associated with disease susceptibility in Hungarian CD patients

Background. North American and European genome-wide association scans have identified ATG16L1 and IL23R as novel inflammatory bowel disease (11313) susceptibility genes and Subsequent reports continued these findings in large independent populations. The aims of this study were to investigate the association and examine genotype-phenotype relationships in a Hungarian 1131) cohort. Methods. 415 unrelated IBD patients (CD: 266, age: 35.2 +/- 12.1 years, duration: 8.7 +/- 7.5 years and UC: 149, age: 44.4 +/- 15.4 years, duration: 10.7 +/- 8.9 years) and 149 healthy subjects were investigated. IL23R Arg381GIn (R381Q, rs 11209026) and ATG16L1 Thr300Ala (T300A, rs2241880) polymorphisms were tested using LightCycler allele discrimination method. Detailed clinical phenotypes were determined by reviewing the medical charts. Results. The association between IL23R rs 11209026, ATG16L1 rs2241880 and CD was confirmed (ORIL23R381Q: 0.38, 95% CI: 0.16-0.87; ORATG161-1300AA: 1.86, 95% CI: 1.04-3.40). No difference was found between patients with UC and either controls or CD. In CID, IL23R 381Gln heterozygosity was associated with inflammatory disease (70% vs. 34%, p = 0.037), while disease restricted to the colon was more prevalent in patients with the ATG16L1 300Ala/Ala homozygosity (33.3% vs. 21.1%, p = 0.036). In addition, carriage of the variant alleles did not predict response to steroids, infliximab or need for surgery. Conclusions. We confirmed that ATG16L1 and IL23R are susceptibility loci for CD in Hungarian CID patients. Further studies are needed to confirm the reported phenotype-genotype associations found in this Study

Sex-specific survival difference in association with HLA-DRB1 *04 following allogeneic haematopoietic stem cell transplantation for lymphoid malignancies

The role of HLA system in allogeneic haematopoietic stem cell transplantation (allo-HSCT) outcome is unarguable. In this study we investigated association of HLA-A,-B and-DRB1 alleles with overall survival (OS) in 186 patients undergoing allo-HSCT for lymphoid malignancies. Analyses confirmed significantly better OS for HLA-DRB1 *04 carriers compared with non-carriers (p=0.01). Survival benefit was confined to male patients (in multivariate analyses p=0.034, hazard ratio 0.35, 95% confidence interval 0.13-0.92), whereas in females no difference was noted (p=0.82). Furthermore, donor gender also affected outcome and transplantation from female HLA-DRB1 *04 carrier donors resulted in superior survival compared with female non-carrier donors (p=0.01). Combined analyses including recipient/donor gender and HLA-DRB1 *04 showed that survival of male patients varied significantly according to donor gender and HLA-DRB1 *04 carriership (p=0.04) with best survival among HLA-DRB1 *04 carriers transplanted from female donors. Of relevance to our results, HLA-DRB1 *04 has been documented as risk allele group for lymphoid malignancies, and studies described a male-specific risk. We believe that our findings provide further supporting evidence for sex-specific alterations secondary to HLA-DRB1 *04 or related genes. Further studies are warranted to evaluate whether in contrast to general favour of male donors HLA-DRB1 *04 carrier patients with lymphoid malignancies could benefit from transplantation from female donors