Alveolitis correlates with clinical pulmonary involvement in primary Sj?gren's syndrome

Bronchoalveolar lavage (BAL) was performed in 23 patients with primary Sj?gren's syndrome (1Ss) and ten healthy controls to evaluate alveolitis and correlate it with pulmonary and systemic manifestations. Patients with 1Ss had higher BAL total cell count (9.2 +/- 6.7 millions/ml vs 6.1 +/- 2.9 millions/ml) and higher percentage of lymphocytes 23.3 +/- 15.6 percent vs 6.5 +/- 2.9 percent, p less than 0.001) than controls. Twelve patients (group A) constituted the "high alveolitis" group (lymphocytes greater than 15.2 percent) and ten (group B) constituted the "low alveolitis" group (lymphocytes less than 15.2 percent). Group A had more frequent cough (6/12 vs 2/10, p = 0.07), dyspnea (4/12 vs 1/10), and roentgenologic evidence of interstitial lung disease (5/12 vs 0/10, p less than 0.05). They also had lower total lung capacity (85.6 +/- 14.2 percent pred vs 105.8 +/- 23.3 percent pred, p less than 0.05) and Dco (87.7 +/- 20.6 percent pred vs 103.6 +/- 21.0 percent pred). All patients with +3 or +4 grading or lymphocytic infiltrates in lip biopsy specimen belonged in group A (5/12). Finally, T-helper/T-suppressor ratio was lower in group A than in group B. The intensity of alveolitis was not correlated with clinical or serologic manifestations of systemic disease.     

Prazosin,an α1-adrenoceptor antagonist,prevents memory deterioration in the APP23 transgenic mouse model of Alzheimer's disease

Noradrenergic deficits have been described in the hippocampus and the frontal cortex of Alzheimer's disease brains, which are secondary to locus coeruleus degeneration. Locus coeruleus is the brain stem nucleus responsible for synthesis of noradrenaline and from where all noradrenergic neurons project. In addition, it has been suggested that noradrenaline might play a role in modulating inflammatory responses in Alzheimer's disease. In this study we aimed to investigate the effect of various agonists and antagonists for adrenergic receptors on amyloid precursor protein processing. Among them, we found that prazosin, an α₁-adrenoceptor antagonist, was able to reduce the generation of amyloid β in N2a cells. Treatment of transgenic APP23 mice with prazosin prevented memory deficits over time. Although prazosin did not influence amyloid plaque load, it induced astrocytic proliferation and increased the release of apolipoprotein E and anti-inflammatory cytokines. These findings suggest that chronic treatment with prazosin leads to an anti-inflammatory response with potential beneficial effects on cognitive performance.     

Expression of mDab1 promotes the stability and processing of amyloid precursor protein and this effect is counteracted by X11alpha

The cytoplasmic tail of amyloid precursor protein (APP) possesses the NPTY motif to which several phosphotyrosine-binding domain-containing proteins bind, including X11alpha and mDab1. X11alpha has been shown to slow cellular APP processing and reduce secretion of Abeta peptides. However, the effect of mDab1 on APP processing has not been determined. Here, we show that mDab1 increases the levels of cellular mature APP and promotes its processing by the secretases in both transiently transfected HEK 293 cells and in neuroglioma U251 cells. These effects derive specifically from the interaction of APP with mDab1 since they are not observed in APP deletion mutants lacking the interaction module NPTY. We further demonstrate that mDab1 enhances cell surface expression of APP, possibly by interfering with its endocytosis. Interestingly, X11alpha and mDab1 exert opposing effects on APP processing. However, when both proteins are co-expressed the effect of X11alpha overrides that of mDab1. Taken together, these results suggest that the relative stoichiometry and binding affinity of the adaptor proteins determines the final outcome on APP metabolism.     

Image-Guided Radiofrequency Ablation (RFA) of Unresectable Hepatic Tumors Using a Triple-Spiral-Shaped Electrode Needle: Initial Experience in 34 Patients

We evaluated the safety and efficacy of image-guided radiofrequency ablation (RFA) using a triple-spiral-shaped electrode needle for unresectable primary or metastatic hepatic tumors. Thirty-four patients with 46 index tumors were treated. Ablation zone, morbidity, and complications were assessed. The lesions were completely ablated with an ablative margin of about 1 cm. Five patients (14.7%) with a lesion larger than 4.5 cm had local tumor progression after 1 month and were retreated. Hemothorax, as a major complication, occurred in 1 of 34 patients (3.0%) or 1 of 46 lesions ablated (2.2%). RFA using this new electrode needle can be effective in the treatment of large unresectable hepatic tumors.