CMC is more than a measure of corticospinal tract integrity in acute stroke patients.

In healthy subjects, motor cortex activity and electromyographic (EMG) signals from contracting contralateral muscle show coherence in the beta (15-30 Hz) range. Corticomuscular coherence (CMC) is considered a sign of functional coupling between muscle and brain. Based on prior studies, CMC is altered in stroke, but functional significance of this finding has remained unclear. Here, we examined CMC in acute stroke patients and correlated the results with clinical outcome measures and corticospinal tract (CST) integrity estimated with diffusion tensor imaging (DTI). During isometric contraction of the extensor carpi radialis muscle, EMG and magnetoencephalographic oscillatory signals were recorded from 29 patients with paresis of the upper extremity due to ischemic stroke and 22 control subjects. CMC amplitudes and peak frequencies at 13-30 Hz were compared between the two groups. In the patients, the peak frequency in both the affected and the unaffected hemisphere was significantly (p < 0.01) lower and the strength of CMC was significantly (p < 0.05) weaker in the affected hemisphere compared to the control subjects. The strength of CMC in the patients correlated with the level of tactile sensitivity and clinical test results of hand function. In contrast, no correlation between measures of CST integrity and CMC was found. The results confirm the earlier findings that CMC is altered in acute stroke and demonstrate that CMC is bidirectional and not solely a measure of integrity of the efferent corticospinal tract.

Three-year follow-up study of allergen-induced in vitro cytokine and signalling lymphocytic activation molecule mRNA responses in peripheral blood mononuclear cells of allergic rhinitis patients undergoing specific immunotherapy.

BACKGROUND: Allergen-specific immunotherapy (SIT) is known to affect the allergen-specific T helper cell (Th2/Th1) balance and to induce T regulatory (Treg) cells. These observations have usually been made during the first treatment year and often without symptom monitoring. This study was performed to investigate allergen-induced Th2 (IL-4, IL-5)-, Th1 [IFN-gamma, IL-18, signalling lymphocytic activation molecule (SLAM)]- and Treg (IL-10)-type immune responses in peripheral blood mononuclear cells (PBMC) and their association with symptom improvement in allergic rhinitis patients after 3 years of SIT. METHODS: Twenty patients were treated with SIT and 8 patients were studied as untreated controls. PBMC were collected before and after 1 and 3 years of SIT and stimulated with specific allergen. Cytokine and SLAM mRNA expression was determined by TaqMan(R) RT-PCR. Symptoms were recorded yearly using visual analogue scale (VAS) scoring. RESULTS: IL-18, SLAM and IL-10 mRNA expression increased after 3 years of SIT, with a peak at 1 year, whereas IL-5 mRNA expression transiently decreased and IFN-gamma mRNA expression transiently increased after 1 year of SIT. The increases in IL-18 and SLAM expression were not associated with symptom improvement, whereas decreases in both IL-4 expression and the IL-4/IFN-gamma ratio after 1 year of SIT were found in patients with a good therapeutic outcome (>40 percentage unit reduction in VAS). CONCLUSIONS: SIT has long-term effects on allergen-specific immune responses. The induced Treg- and Th1-type responses persist over 3 years of SIT, whereas Th2-type responses are transiently decreased only during early therapy.

Vacancies in wurtzite GaN and AlN.

Vacancies in wurtzite GaN and AlN are studied using a computational method which is based on the density functional theory (DFT) and takes into account the errors arising from use of finite-sized supercells and the DFT band gap underestimation. Negatively charged N vacancies in GaN and AlN are found to be stable, with formation energies similar to and higher than those of Ga and Al vacancies in n-type material under Ga- and Al-rich growth conditions, respectively. The localization and energies of the defect levels close to the computational conduction band edge are considered in detail.

Nitrogen interstitial defects in GaAs.

We have studied nitrogen interstitial defects in GaAs with first-principles calculations. On the basis of calculated formation energies we have determined the most common nitrogen defects and the transition levels for various charge states. The lowest energy interstitial-type defects are found to be N-N and N-As split interstitials for most of the experimentally relevant conditions. We have also compared two different methods of obtaining the potential correction needed in an accurate calculation of the formation energies and transition levels.

Food and water intake, growth, and adiposity of Sprague-Dawley rats with diet board for 24 months.

Ad libitum (AL) feeding of rats leads to obesity and increased result variability, as well as premature morbidity and mortality. It may also alter metabolism and responses to foreign compounds. Moderate dietary restriction (DR) reduces these untoward effects without compromising the sensitivity of rodent bioassays. The diet board (DB) is a novel method for achieving moderate DR in group housing. Food pellets are firmly attached into grooves in an aspen board, and rats have to gnaw the wood in order to eat. Food is available continuously, but due to the effort involved rats eat less. This study simulated a chronic safety test to assess the long-term effects of DB feeding. A total of 146 male and female outbred Sprague-Dawley rats, nine weeks old at onset, were housed in groups of three and fed either AL or with DBs for two years. Food and water consumption were measured at six time points. The rats were weighed every one to two weeks. Body and tibial lengths and epididymal fat weight were measured at necropsy. Modified body mass index was calculated at five time points after one year of age. DB feeding reduced body weight and fat tissue moderately, more so in males. DB males ate less than AL males, but no differences were seen in the total food consumption in the females. There was no consistent difference in the within-group variations of the measured parameters. DB is a workable DR method, albeit some modification could enhance and standardize its DR effects, especially in female rats.

Allergen-induced in vitro expression of IL-18, SLAM and GATA-3 mRNA in PBMC during sublingual immunotherapy.

BACKGROUND: Signalling lymphocytic activation molecule (SLAM) and interleukin (IL)-18 induce interferon (IFN)-gamma production from Th1 cells. The allergen-induced SLAM and IL-18 mRNA expressions are increased during subcutaneous immunotherapy (SCIT), but nothing is known about their role during sublingual immunotherapy (SLIT). Transcription factor GATA-3 is associated with Th2 cells but its role in SCIT and SLIT is yet unexplored. This study was undertaken to analyse the allergen induced in vitro mRNA expression of IL-18, SLAM and GATA-3 in peripheral blood mononuclear cells (PBMC) of children with allergic rhinitis (AR) during SLIT. METHODS: Ten patients with AR undergoing pollen SLIT with a weekly dose of 200,000 SQ-U, 10 with 24,000 SQ-U of mixture of Betula verrucosa, Corylus avellana and Alnus glutinosa and 10 with placebo were included. Peripheral blood mononuclear cell were stimulated with birch extract prior to, after 1 and 2 years of the treatment. The mRNA expression was assessed using kinetic real-time RT-PCR (TaqMan); Applied Biosystems, Foster City, CA, USA). RESULTS: The expression of IL-18 mRNA was increased in the high-dose group in comparison to the placebo group after 1 year of therapy (P = 0.028) and had an inverse correlation with the late phase skin reaction after the second study year (r = -0.41, P = 0.041). SLAM mRNA expression increased in the high-dose group from baseline to 1 year (P = 0.028) and correlated with IL-10 (r = 0.96, P < 0.0001) and transforming growth factor-beta (r = 0.80, P = 0.0037) mRNA expression. No significant changes were seen in GATA-3 mRNA expression. CONCLUSIONS: During SLIT, IL-18 and SLAM are upregulated, suggesting that the Th2 type inflammatory response is downregulated during SLIT by increased Th1 type response.

Increased expression of allergen-induced in vitro interleukin-10 and interleukin-18 mRNA in peripheral blood mononuclear cells of allergic rhinitis patients after specific immunotherapy.

BACKGROUND: During specific pollen immunotherapy (SIT) there is a local mucosal shift from Th2- to Th1- type cytokine predominance, with IL-12 having a major role in this shift. IL-10-induced tolerance is supposed to be a key phenomenon in venom immunotherapy (VIT). However, the role of Th1-promoting cytokines, on the one hand, and the role of regulatory cytokines, on the other hand, have not been studied in parallel during SIT. OBJECTIVE: This study was undertaken to analyse the allergen-induced in vitro mRNA expression of Th1-type effector cytokine IL-18 and regulatory cytokines IL-10 and TGF-beta during SIT in peripheral blood mononuclear cells (PBMC) of allergic rhinitis (AR) patients. METHODS: Thirty patients with AR undergoing pollen SIT and 10 patients with AR who were not treated with SIT were included in the study. The symptoms and medications were registered post-seasonally before the beginning of SIT and after 1 year of therapy. PBMC samples were collected and stimulated with pollen allergen extract prior to the treatment, at the maintenance phase in 12 patients and after 1 year of the treatment. The cytokine mRNA expression was assessed using kinetic real-time RT-PCR (TaqMan). RESULTS: There was a clear increase in the treated AR patients, in comparison with untreated AR patients, in the expression of both IL-10 (mean change from baseline (SEM): 3.1 (0.8) vs. -0.3 (0.3), P<0.002, Mann-Whitney U-test) and IL-18 (2.7 (0.9) vs. -0.2 (0.6), P<0.03) mRNA after 1 year. The clearest increase in IL-10 mRNA expression was seen in patients who did not benefit at all (6.0 (2.3), P<0.001 vs. untreated) and the least increase in patients that had the greatest reduction of symptoms (0.8 (0.6), n.s. vs. untreated) at 1 year. The clearest increase in IL-18 mRNA expression was seen in patients with moderate outcome (3.4 (1.6), P<0.04 vs. untreated). In intermediate samples, taken when the maintenance dose was reached, the peak expression of allergen-induced IL-10 mRNA was associated with the most favourable outcome of SIT (P=0.01, Fisher exact test). A similar trend was seen in IL-18 mRNA expression. CONCLUSIONS: The results suggest that an early and transient increase in allergen-specific IL-10 and IL-18 mRNA expression in PBMC is essential for the therapeutic outcome after 1 year of SIT.

In vitro kinetics of allergen- and microbe-induced IL-4 and IFN-gamma mRNA expression in PBMC of pollen-allergic patients.

BACKGROUND: According to a hypothesis allergens induce Th2 responses in allergic patients, and microbes induce Th1 responses. We studied the kinetics of in vitro allergen-, tuberculin (PPD)- and tetanus toxin (TT)-induced IFN-gamma and IL-4 mRNA expression in peripheral blood mononuclear cell (PBMC) cultures of pollen-allergic patients and healthy controls. METHODS: PBMC of 10 birch or timothy pollen-allergic patients and of 13 healthy controls were stimulated in vitro with allergen (birch or timothy), PPD or TT. Pellets and supernatants were collected at 24, 48, 72 and 96 h after stimulation. IFN-gamma and IL-4 production was measured by enzyme linked immunosorbent assay and mRNA expression using RT-PCR and time-resolved fluorometry. RESULTS: Allergen induced IFN-gamma production and mRNA expression in PBMC more in allergic patients than in healthy controls. Also allergen induced IL-4 mRNA expression more in allergic patients than in healthy controls. PPD induced IFN-gamma mRNA expression both in allergic patients and healthy controls, whereas IFN-gamma production was induced only in healthy controls and IL-4 was not induced at all. TT induced IFN-gamma mRNA expression in both groups, IFN-gamma production in allergic patients, and IL-4 mRNA expression in both allergic patients and healthy controls. CONCLUSIONS: In vitro stimulation with allergen induced both IFN-gamma and IL-4 mRNA expression of PBMC in allergic patients. These observations challenge the clearcut division of microbe-specific Th1 and allergen-specific Th2 responses in peripheral blood.