Identification of differentially expressed genes in brains of newborn Borna disease virus-infected rats in the absence of inflammation

Summary.  Infection of newborn rats with Borna disease virus (BDV) leads to viral persistence in the central nervous system without overt signs of inflammation. Nevertheless, these rats display distinct behavioral and neurodevelopmental abnormalities. The molecular basis of the latter is still unknown. Using a cDNA array representing 1200 genes, we sought to identify cellular genes which are differentially expressed following perinatal BDV-infection. RNA samples prepared from different brain regions were analysed at various time points before or after BDV-induced defects become evident. In infected brains, we found upregulated expression of genes encoding brain fatty acid binding protein (B-FABP), β2-microglobulin (β2m) and, as described previously, the chemokine IP-10. Kinetic studies revealed sustained increased expression of B-FABP in infected frontal cortices beginning about three weeks p.i. Moreover, a slight transient increase of B-FABP expression in infected hippocampi was observed 3–5 weeks p.i. In situ hybridization studies combined with immunohistochemistry suggested that expression of β2m was predominantly upregulated in glial cells and possibly also in some neurons. Employing cultured infected hippocampus slices and infected genetically modified mice, we provide evidence, that the observed upregulation of β2m expression is not triggered by IFN-γ, but rather by IFN-α/β. Present address: Institute for Medical Virology, University of Zürich, Gloriastr. 30, CH-8028 Zürich, Switzerland. Received April 29, 2002; accepted August 19, 2002     

Comparison of device‐supported sensorimotor training and splint intervention for myofascial temporomandibular disorder pain patients

This study was to compare the short‐term therapeutic efficacy of device‐supported sensorimotor training with that of standard splint therapy for patients with myofascial temporomandibular disorder (TMD) pain over a treatment period of 3 months. We tested the hypothesis that both types of intervention are equally effective for pain reduction. In addition, the electromyographic (EMG) activity of the temporal and masseter muscles was recorded under conditions of force‐controlled submaximum and maximum biting in intercuspation. Of consecutive patients seeking treatment for non‐odontogenic oro‐facial pain, 45 patients with myofascial TMD pain (graded chronic pain status, GCPS, I and II) were randomly assigned to 2 treatment groups (sensorimotor training and conventional splint treatment). Patients were evaluated 4 times (initial examination, 2, 6 and 12 weeks later) by use of the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Electromyographic activity was recorded at the initial session and after 3 months. Ease‐of‐use of the treatment options was also evaluated. Significant (P < .0001) pain reduction (sensorimotor training 53%, splint therapy 40%) was achieved for both groups, with no significant differences (P > .05) between the groups. Force‐controlled sub‐maximum normalized electromyographic activity was significantly different between T0 and T3 for group A (sensorimotor training, P < .05) but was not significantly different for group B (splint, P > .05). For normalized maximum‐biting EMG activity in intercuspation, however, a significant increase in EMG activity was observed for group A for the masseter and temporal muscles (P < .001) and for group B for the masseter muscle only (P < .001). Moreover, sensorimotor training was significantly (P < .05) less easy to use than the splint. The results of this study confirm the pain‐reducing effect of sensorimotor training for patients with myofascial TMD pain (GCPS I and II). This innovative active treatment might be a promising option for TMD pain patients.     

Tumor progression and serum anti-HuD antibody concentration in patients with paraneoplastic neurological syndromes

The aim of this study was to investigate whether there are clues for a correlation between tumor progression and serum anti-Hu antibody concentration in patients with anti-Hu-associated paraneoplastic neurological syndromes (PNS). 19 patients with anti-Hu-associated PNS were assigned to three groups according to the course of tumor progression. Group 1 corresponds to patients with rapid tumor progression [n = 5; mean survival in months/standard deviation (SD); 24/10]; in group 2 patients with a favorable tumor prognosis were included (n = 7; mean/SD 79/25, 6 patients still alive); group 3 consisted of patients in whom tumor progression could not be assessed (n = 7; mean/SD 23/20). The anti-Hu antibody concentrations in sera were measured in a recombinant HuD-ELISA. In sera from patients of group 1 the anti-Hu antibody concentration was modest (mean OD 0.56, SD 0.08) whereas a significantly higher anti-Hu antibody concentration was detected in sera from patients with a favorable tumor prognosis (group 2, mean OD 1.86, SD 0.34). These results hint at a negative correlation between tumor progression and the anti-Hu antibody concentration in sera from patients with PNS. These findings confirm and extend previous reports of more indolent tumor growth in patients with an anti-Hu immune response.     

Demonstration of anti-HuD specific oligoclonal bands in the cerebrospinal fluid from patients with paraneoplastic neurological syndromes. Qualitative evidence of anti-HuD specific IgG-synthesis in the central nervous system

The presence of HuD-specific oligoclonal IgG bands in the CSF was investigated in five patients with paraneoplastic neurological syndromes. All patients revealed intrathecal synthesis of HuD specific antibodies in the CSF, as estimated from elevated antibody indices (>1.5) in an IgG-ELISA using recombinant HuD-protein as antigen. Isoelectrofocussing combined with affinity blotting showed reactivity of IgG bands with recombinant HuD antigen in all CSF samples. These data support the idea that HuD specific antibodies in the CSF are produced mainly by B-cell clones in the central nervous system. These findings support the hypothesis of autoimmunity in the pathogenesis of anti-Hu associated paraneoplastic neurological syndromes.     

Aerodynamic model of ventilation efficacy in patients after laser arytenoidectomy

The treatment of bilateral vocal cord paralysis presents a challenge to otolaryngologists. All surgical procedures are designed to widen the lumen of the glottis without impairing vocal function and laryngeal closure during swallowing and respiration. The aim of the study was to evaluate the effectiveness of the laser arytenoidectomy by our own method. Based on the analysis of the results of 36 patients operated on due to bilateral vocal cord paralysis the aerodynamic model of ventilation efficacy changes was introduced and then verified. On the basis of the study an increase of the cross-sectional area of the glottis after laser arytenoidectomy can be combined with air flow improvement in upper airways. Thanks to this relation the postoperative ventilation efficiency may be predicted on the basis of its preoperative value and geometrical parameters of the glottis.     

Risk factors for airway obstruction in school children with respiratory symptoms assessed in a five year prospective study

The aim of this prospective study was to assess age-related changes of the respiratory status and to evaluate risk factors for persistent airflow obstruction in symptomatic school children. One hundred fifty children aged 7-12 years (mean age 9.5 yr.) were followed-up. In 1994 parents--administered questionnaire, skin prick tests and three dynamic spirometries in 4-6 week intervals were performed. Airways flow limitation was defined as FEV1%, MEF50 or MEF25 below minimal value. In 1999 questionnaires and spirometry were repeated by the same methods. The response rate was 74.7%. Children's respiratory status generally improved. Frequency of respiratory symptoms and obstructive disturbances (37.5% in 1994 versus 22.3% in 1999) decreased. Significant risk factors for airways flow limitation in 1999 were nocturnal dry cough, doctor diagnosed asthma, female gender and parental smoking. Advanced or persisting airway obstruction during several month in 1994 was valuable to predict lung function impairment in 1999. No relation between skin tests results and persistent airway obstruction was observed.     

Specific antibody index in cerebrospinal fluid from patients with central and peripheral paraneoplastic neurological syndromes

We evaluated the concentration of antineuronal antibodies in paired cerebrospinal fluid (CSF) and serum samples from 19 patients with central and peripheral paraneoplastic neurological syndromes (PNS), using an enzyme linked immunosorbent assay (ELISA) employing recombinant antineuronal antigens (HuD, Yo, Ri, CV2/CRMP5, amphiphysin, PNMA2/Ma2). The specific antibody index (AI) [Qspec/QIgG] was calculated to estimate specific intrathecal antibody synthesis. An AI>1.3 was considered as evidence of intrathecal specific antibody synthesis. 14 (88%) of 16 patients with exclusive or predominant paraneoplastic involvement of the central nervous system (CNS) showed an AI>1.3, indicating a specific intrathecal antibody synthesis, while all three patients with isolated involvement of the peripheral nervous system showed an AI<0.8. All together, in 17 of 19 patients (89%) we found a significant association (p<0.05) between central or peripheral neurological manifestations on the one hand and presence or absence of specific intrathecal synthesis respectively on the other hand. These data support the hypothesis that autoimmunity is involved in the pathogenesis of PNS.