Increased T-cell reactivity and elevated levels of CD8+ memory T-cells in Alzheimer's disease-patients and T-cell hyporeactivity in an Alzheimer's disease-mouse model: implications for immunotherapy.

Neuroinflammation is observed in neurodegenerative diseases like Alzheimer's disease (AD). However, a little is known about the mechanisms of neural-immune interactions. The involvement of peripheral T-cell function in AD is still far from clear, though it plays an important role in immunotherapy. The aim of this study was to determine peripheral T-cell reactivity in AD patients and in an AD mouse model. Mitogenic activation via ligation of the T-cell receptor (TCR) with PHA-L was measured in T lymphocytes from AD patients and Thy1(APP 751SL) x HMG(PS1 M146L)-transgenic mice (APP x PS1). In order to uncover failures in TCR signaling, the TCR was also bypassed by PMA and ionomycin treatment. All patients were sporadic late onset cases and the transgenic mice expressed no mutant APP in lymphocytes, so that direct interactions of mutant APP on T-cell function can be excluded. CD4+ and CD8+ T-cell showed increased reactivity (tyrosine phosphorylation, CD69 expression, and proliferation) in AD, while APP x PS1 transgenic mice displayed hyporeactive CD8+ T-cells after TCR ligation. Increased levels of CD8+ T memory cells and down regulation of CD8 receptor were found in AD and the animal model. Anergic TCR uncoupling was associated with loss of MAPK signaling (p38, ERK1 and ERK2) in APP x PS1. Our data implicate the generation of reactive memory T-cell in AD and of anergic memory T-cells in transgenic mice and should be taken into concern when designing immunotherapy.

Preoperative magnetic resonance imaging-guided localization of 131 breast lesions with modified embolization coils.

OBJECTIVES: The objectives of this study were to assess practicability, outcome, and possible advantages of magnetic resonance imaging (MRI)-guided localizations with modified embolization coils for exclusively MRI-detected suspicious breast lesions. MATERIALS AND METHODS: We performed 131 MRI-guided preoperative localizations in 105 patients with exclusively MRI-detected breast lesions. Contrast-enhanced, T1-weighted, 3-dimensional gradient echo sequences were used for imaging. Breast fixation and needle guidance were achieved by a perforated plate. Lesion localization was performed with a modified embolization coil. The distance between coil and lesion was measured. Results of specimen radiography and histopathology were analyzed. RESULTS: Thirty-four of 131 lesions (26%) were malignant. Lesion localization and excision was successful in all patients. The mean distance between the coil and the lesion was 0.5 mm (+/-1.7 mm standard deviation). CONCLUSIONS: Exact MRI-guided preoperative localization of exclusively MRI-detected breast lesions by using a modified embolization coil is feasible with excellent precision. Advantages over wire localization procedures are the possibility of specimen x-ray and the independence from time and place of operation.

MR imaging-detected breast lesions: histopathologic correlation of lesion characteristics and signal intensity data.

OBJECTIVE: The aim of our study was to differentiate benign from malignant breast lesions that had been detected exclusively on MR imaging by analyzing qualitative and quantitative lesion characteristics. MATERIALS AND METHODS: We performed 51 MR imaging-guided breast interventions (41 preoperative lesion localizations and 10 large-core needle biopsies) in 45 patients with exclusively MR imaging-detected lesions. All patients had previously undergone diagnostic dynamic contrast-enhanced MR imaging of the breast with a double breast coil at 1.0 T (n = 36) or 1.5 T (n = 15). The diagnostic MR images were evaluated on a workstation. Lesion morphology (size, shape, margin type, enhancement pattern), signal intensity parameters (time to peak enhancement, maximum slope of enhancement curve, washout, relative water content), and scores analogous to the Breast Imaging Reporting and Data System (BI-RADS) categories were correlated with histology. RESULTS: Histology revealed malignancy in 37.3% (19/51) of the lesions. The positive predictive value for malignancy of exclusively MR imaging-detectable lesions increased as the analogous BI-RADS category increased. Late inhomogeneous contrast enhancement was the only morphologic criterion that was statistically significantly correlated with malignancy. Malignant and benign lesions did not differ significantly in any of the quantitatively evaluated signal intensity parameters. Carcinomas showed a tendency toward faster and stronger enhancement and stronger washout. CONCLUSION: The classification of exclusively MR imaging-detectable breast lesions according to a combination of morphologic and perfusion parameters including the late enhancement pattern helps identify the lesions for which interventional MR imaging is required. Quantitative signal intensity data alone do not suffice.