T cell epitope spreading to myelin oligodendrocyte glycoprotein in HLA-DR4 transgenic mice during experimental autoimmune encephalomyelitis

Epitope spreading has been implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and human multiple sclerosis (MS). T cell epitope spreading has been demonstrated in rodents for myelin basic protein (MBP) and proteolipid protein (PLP) determinants, but not for myelin oligodendrocyte glycoprotein (MOG), another important myelin antigen. Moreover, the role of human autoimmunity-associated MHC molecules in epitope spreading, including HLA-DR2 and DR4, has not been formally examined. To address these questions, we investigated epitope spreading to MOG determinants in HLA-DR4 (DRB1*0401) transgenic mice during EAE. The data show that upon induction of EAE in HLA-DR4 transgenic mice with the immunodominant HLA-DR4-restricted MOG peptide 97-108 (MOG(97-108); TCFFRDHSYQEE), the T cell response diversifies over time to MOG(181-200) (core: MOG(183-191); FVIVPVLGP) and MBP. The spreading epitope MOG(181-200) binds with high affinity to HLA-DRB1*0401 and is presented by human HLA-DRB1*0401+antigen presenting cells. Moreover, this epitope is encephalitogenic in HLA-DRB1*0401 transgenic mice. This study demonstrates intra- and intermolecular epitope spreading to MOG and MBP in "humanized" HLA-DR4 transgenic mice.     

Mouse spinal cord compression injury is ameliorated by intrathecal cationic manganese(III) porphyrin catalytic antioxidant therapy

This study evaluated the effects of the cationic manganese(III) tetrakis(N,N'-diethylimidazolium-2-yl)porphyrin catalytic antioxidant Mn(III)TDE-2-ImP5+ (AEOL 10150) on outcome from spinal cord compression (SCC) in the mouse. C57BL/6J mice were subjected to 60 min thoracic SCC after discontinuation of halothane anesthesia. In Experiment 1, mice were given intravenous Mn(III)TDE-2-ImP5+ (0.5 mg/kg bolus followed by 1 mg kg(-1) h(-1) for 24 h), methylprednisolone (30 mg/kg bolus followed by 5.4 mg kg(-1) h(-1) for 24 h), or vehicle (n = 25 per group). In Experiment 2, mice were given intrathecal Mn(III)TDE-2-ImP5+ (2.5 or 5.0 microg/kg) or vehicle (n = 18 per group). In both experiments, treatment began 5 min post-SCC onset. Rotarod performance was measured on post-SCC days 3, 7, 14, and 21. On post-SCC day 21, the spinal cord was histologically examined and a total damage score was calculated. Neither intravenous Mn(III)TDE-2-ImP5+ nor methylprednisolone altered rotarod performance (accelerated rate P = 0.11, fixed rate P = 0.11) or mean +/- S.D. total damage score (Mn(III)TDE-2-ImP5+ = 21 +/- 9, methylprednisolone = 24 +/- 8, vehicle = 22 +/- 10; P = 0.47; shams = 0). Intrathecal Mn(III)TDE-2-ImP5+ (both 2.5 and 5.0 microg) given at SCC-onset improved rotarod performance (P = 0.05) and total damage score (2.5 microg = 19 +/- 10, P = 0.04; 5.0 microg =19 +/- 8, P = 0.03) versus vehicle (26 +/- 10). These studies demonstrate sustained benefit from manganese(III) porphyrin catalytic antioxidant therapy after SCC. However, efficacy was dependent upon route of administration suggesting that bioavailability is critical in defining efficacy.     

Detection of hyphal fusion in filamentous fungi using differently fluorescence-labeled histones

Cell fusion occurs regularly during the vegetative and sexual phases of the life cycle in filamentous fungi. Here, we present a simple and efficient method that can detect even rare hyphal fusion events. Using the homothallic ascomycete Sordaria macrospora as an experimental system, we developed a histone-assisted merged fluorescence (HAMF) assay for the investigation of hyphal fusion between vegetative mycelia. For this purpose, two reporter vectors were constructed encoding the histone proteins HH2B or HH2A fused at their C terminus either with the cyan or yellow fluorescent protein, respectively. The chimeric proteins generate fluorescently labeled nuclei and thus enable the distinction between different strains in a mycelial mixture. For example, hyphae with nuclei that show both cyan as well as yellow fluorescence indicate the formation of a heterokaryon as a result of hyphal fusion. To test the applicability of our HAMF assay, we used two S. macrospora developmental mutants that are supposed to have reduced hyphal fusion rates. The simple and efficient HAMF assay described here could detect even rare fusion events and should be applicable to a broad range of diverse fungal species including those lacking male or female reproductive structures or asexual spores. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Christine Rech and Ines Engh contributed equally to this work.     

Psychological problems in children of war veterans with posttraumatic stress disorder in Bosnia and Herzegovina: cross-sectional study

Aim

To assess psychological problems in children as reported by their veteran fathers with war-related posttraumatic stress disorder (PTSD).

Method

The study group consisted of 154 veterans with war-related PTSD who were treated at the Mostar University Hospital. The control group consisted of 77 veterans without war-related PTSD who were selected from veteran associations by the snowball method. General Demographic Questionnaire, the first and fourth module of the Harvard Trauma Questionnaire–Bosnia and Herzegovina version, and the Questionnaire on Developmental, Emotional, and Behavioral Problems in Children, created specifically for the needs of this study, were used to collect data on veterans’ perception of psychological problems in their children.

Results

In comparison with veterans without PTSD, veterans with PTSD reported significantly more developmental (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.51-3.73), behavioral (OR, 3.92; 95% CI, 1.53-10.03), and emotional problems (OR, 17.74; 95% CI, 2.40-131.10) in their children.

Conclusion

Veterans with war-related PTSD more often reported developmental problems in their children. Father’s PTSD may have long-term and long-lasting consequences on the child’s personality.Posttraumatic stress disorder (PTSD) in one family member can negatively influence other family members and affect entire family dynamics (1-3). For many reasons, children in such families are especially vulnerable (4).Many studies have established that, in comparison with children of combat veterans without PTSD, the children of combat veterans with PTSD have more frequent and more serious developmental, behavioral, and emotional problems (2,5-10). Some of them also have specific psychiatric problems (11).Interviews with spouses and partners of combat veterans revealed that children of veterans with PTSD have more behavioral problems (5) and more frequent problems with authority, depression, anger, hyperactivity, and personal relationships (6-10) than children of veterans without PTSD. They are also more aggressive, use opiate drugs more often (6), and have learning difficulties and problems with diadic relations and emotional regulation (8). However, Harkness (8,12) did not find a significant association between the intensity of PTSD symptoms in veteran fathers and behavior of their children. On the other hand, it seems that the children of Vietnam War veterans did have behavioral problems, with veterans’ PTSD being a possible indirect factor in this association (13). It is assumed that direct war experience may disrupt the later capability of veterans to function as parents, leading to difficulties in the development and behavior of their children (12,13).With respect to the degree of individual and social traumatization caused by war trauma and post-war social situation in Bosnia and Herzegovina (BH), we assumed that war-related PTSD in veterans would have noticeable effect on the development of their children and that children of veterans with PTSD would have more psychological problems than children of veterans without PTSD.The aim of our study was to determine developmental, behavioral, and emotional problems of children in BH as reported by their veteran fathers with combat-related PTSD.     

Elevated serum thiobarbituric acid reactive substances in clinically symptomatic schizophrenic males

Impaired antioxidant defenses are suggested to participate in the pathophysiology of schizophrenia. Altered superoxide dismutase (SOD) and increased lipid peroxidation, measured by the thiobarbituric acid reactive substances (TBARS), are increased in schizophrenia. The aim of this study was to determine the effects of clinical course and subtype on oxidative stress parameters. In this study, 68 male patients, classified according to DSM-IV schizophrenia subtypes and clinical course (partial remission, marked symptoms, and deteriorated), were studied, and TBARS and SOD measured. Mean serum SOD and mean serum TBARS concentrations were similarly not significantly different among different subtypes (paranoid, disorganized and undifferentiated). However, marked symptoms status was associated with higher TBARS levels compared to the deteriorated group. This suggests a possible relationship between symptom acuity and oxidative stress in males.     

The diagnosis and management of allergic reactions in patients sensitized to non-specific lipid transfer proteins

Sensitization to one or more non-specific lipid transfer proteins (nsLTPs), initially thought to exist mainly in southern Europe, is becoming accepted as a cause of allergic reactions to plant foods across Europe and beyond. The peach nsLTP allergen Pru p 3 is a dominant sensitizing allergen and peaches a common food trigger, although multiple foods can be involved. A frequent feature of reactions is the requirement for a cofactor (exercise, alcohol, non-steroidal anti-inflammatory drugs, Cannabis sativa) to be present for a food to elicit a reaction. The variability in the food and cofactor triggers makes it essential to include an allergy-focused diet and clinical history in the diagnostic workup. Testing on suspected food triggers should also establish whether sensitization to nsLTP is present, using purified or recombinant nsLTP allergens such as Pru p 3. The avoidance of known trigger foods and advice on cofactors is currently the main management for this condition. Studies on immunotherapy are promising, but it is unknown whether such treatments will be useful in populations where Pru p 3 is not the primary sensitizing allergen. Future research should focus on the mechanisms of cofactors, improving diagnostic accuracy and establishing the efficacy of immunotherapy.     

Successful Two-Stage Exchange Arthroplasty for Periprosthetic Infection Following Total Knee Arthroplasty: The Impact of Timing on Eradication of Infection

Background: Periprosthetic joint infection (PJI) represents a serious complication following total knee arthroplasty. In the setting of chronic infections, the two-staged approach has traditionally been the preferred treatment method. The aim of this study was to determine the optimal period of rest between the first and second stage. Furthermore, we analyzed potentially outcome-relevant parameters, such as general and local conditions and the presence of difficult-to-treat or unidentified microorganisms, with regard to their impact on successful treatment of PJI.Patients and Methods: We performed a retrospective analysis of prospectively collected data for all patients treated for PJI at our institution. Seventy-seven patients who had undergone two-stage revision arthroplasty for PJI of the knee were included into the study. Antibiotic-loaded cement spacers were used for all patients.Results: After a median follow-up time of 24.5 months, infection had reoccurred in 14 (18.7%) patients. A prolonged spacer-retention period of more than 83 days was related to a significantly higher proportion of reinfections. Furthermore, significant compromising local conditions of the prosthetic tissue and surrounding skin, as well as repeated spacer-exchanges between first- and second-stage surgery, negatively influenced the outcome. Neither the patients'' age nor gender exerted a significant influence on the outcome regarding reinfection rates for patients'' age or gender.Conclusions: We observed the best outcome regarding infection control in patients who had undergone second-stage surgery within 12 weeks after first-stage surgery. Nearly 90% of these patients stayed free from infection until the final follow-up. An increased number of performed spacer-exchanges and a bad local extremity grade also had a negative impact on the outcome.