Neurochemical Characterization of PSA-NCAM+ Cells in the Human Brain and Phenotypic Quantification in Alzheimer's Disease Entorhinal Cortex.

Polysialylated neural cell adhesion molecule (PSA-NCAM) is widely expressed in the adult human brain and facilitates structural remodeling of cells through steric inhibition of intercellular NCAM adhesion. We previously showed that PSA-NCAM immunoreactivity is decreased in the entorhinal cortex in Alzheimer's disease (AD). Based on available evidence, we hypothesized that a loss of PSA-NCAM+ interneurons may underlie this reduction. PSA-NCAM expression by interneurons has previously been described in the human medial prefrontal cortex. Here we used postmortem human brain tissue to provide further evidence of PSA-NCAM+ interneurons throughout the human hippocampal formation and additional cortical regions. Furthermore, PSA-NCAM+ cell populations were assessed in the entorhinal cortex of normal and AD cases using fluorescent double labeling and manual cell counting. We found a significant decrease in the number of PSA-NCAM+ cells per mm2 in layer II and V of the entorhinal cortex, supporting our previous description of reduced PSA-NCAM immunoreactivity. Additionally, we found a significant decrease in the proportion of PSA-NCAM+ cells that co-labeled with NeuN and parvalbumin, but no change in the proportion that co-labeled with calbindin or calretinin. These results demonstrate that PSA-NCAM is expressed by a variety of interneuron populations throughout the brain. Furthermore, that loss of PSA-NCAM expression by NeuN+ cells predominantly contributes to the reduced PSA-NCAM immunoreactivity in the AD entorhinal cortex.

The effects of long-term noninvasive ventilation in hypercapnic COPD patients: a randomized controlled pilot study.

INTRODUCTION: Noninvasive ventilation (NIV) is a well-established treatment for acute-on- chronic respiratory failure in hypercapnic COPD patients. Less is known about the effects of a long-term treatment with NIV in hypercapnic COPD patients and about the factors that may predict response in terms of improved oxygenation and lowered CO(2) retention. METHODS: In this study, we randomized 15 patients to a routine pharmacological treatment (n = 5, age 66 [standard deviation ± 6] years, FEV(1) 30.5 [±5.1] %pred, PaO(2) 65 [±6] mmHg, PaCO(2) 52.4 [±6.0] mmHg) or to a routine treatment and NIV (using the Synchrony BiPAP device [Respironics, Inc, Murrsville, PA]) (n = 10, age 65 [±7] years, FEV(1) 29.5 [±9.0] %pred, PaO(2) 59 [±13] mmHg, PaCO(2) 55.4 [±7.7] mmHg) for 6 months. We looked at arterial blood gasses, lung function parameters and performed a low-dose computed tomography of the thorax, which was later used for segmentation (providing lobe and airway volumes, iVlobe and iVaw) and post-processing with computer methods (providing airway resistance, iRaw) giving overall a functional image of the separate airways and lobes. RESULTS: In both groups there was a nonsignificant change in FEV(1) (NIV group 29.5 [9.0] to 38.5 [14.6] %pred, control group 30.5 [5.1] to 36.8 [8.7] mmHg). PaCO(2) dropped significantly only in the NIV group (NIV: 55.4 [7.7] → 44.5 [4.70], P = 0.0076; control: 52.4 [6.0] → 47.6 [8.2], NS). Patients actively treated with NIV developed a more inhomogeneous redistribution of mass flow than control patients. Subsequent analysis indicated that in NIV-treated patients that improve their blood gases, mass flow was also redistributed towards areas with higher vessel density and less emphysema, indicating that flow was redistributed towards areas with better perfusion. There was a highly significant correlation between the % increase in mass flow towards lobes with a blood vessel density of >9% and the increase in PaO(2). Improved ventilation-perfusion match and recruitment of previously occluded small airways can explain the improvement in blood gases. CONCLUSION: We can conclude that in hypercapnic COPD patients treated with long-term NIV over 6 months, a mass flow redistribution occurs, providing a better ventilation-perfusion match and hence better blood gases and lung function. Control patients improve homogeneously in iVaw and iRaw, without improvement in gas exchange since there is no improved ventilation/perfusion ratio or increased alveolar ventilation. These differences in response can be detected through functional imaging, which gives a more detailed report on regional lung volumes and resistances than classical lung function tests do. Possibly only patients with localized small airway disease are good candidates for long-term NIV treatment. To confirm this and to see if better arterial blood gases also lead to better health related quality of life and longer survival, we have to study a larger population.

Pulmonary rehabilitation and non-invasive ventilation in COPD.

A multidisciplinary pulmonary rehabilitation program has become an important part of the treatment of chronic obstructive pulmonary disease. It can improve both exercise tolerance and health related quality of life in these patients. Exercise training has to be included for the program to be successful. The intensity of the training is of great importance: there is more physiological benefit in high-intensity training, compared to moderate-intensity training. High-intensity training results in reduced levels of blood lactate and pulmonary ventilation at a given heavy work rate. High-intensity training is limited in COPD patients because of exercise-induced dyspnoea. Flow limitation, as a consequence of increased ventilatory demands of exercise, causes a breathing pattern with greater demands on their inspiratory muscles: this results in a pattern of low tidal volume and high-frequency breathing. Increased inspiratory muscle work causes dyspnoea and limitation in exercise intensity. Artificial ventilatory assistance could improve exercise tolerance and hence help severe COPD patients to achieve a higher level of training. It could help to unload and assist the overburdened ventilatory muscles and give a possibility for higher levels of exercise intensity. In this review article we will discuss the effectiveness and feasibility of training with ventilatory aids.

High content image cytometry in the context of subnuclear organization.

The organization of proteins in space and time is essential to their function. To accurately quantify subcellular protein characteristics in a population of cells with regard for the stochasticity of events in a natural context, there is a fast-growing need for image-based cytometry. Simultaneously, the massive amount of data that is generated by image-cytometric analyses, calls for tools that enable pattern recognition and automated classification. In this article, we present a general approach for multivariate phenotypic profiling of individual cell nuclei and quantification of subnuclear spots using automated fluorescence mosaic microscopy, optimized image processing tools, and supervised classification. We demonstrate the efficiency of our analysis by determination of differential DNA damage repair patterns in response to genotoxic stress and radiation, and we show the potential of data mining in pinpointing specific phenotypes after transient transfection. The presented approach allowed for systematic analysis of subnuclear features in large image data sets and accurate classification of phenotypes at the level of the single cell. Consequently, this type of nuclear fingerprinting shows potential for high-throughput applications, such as functional protein assays or drug compound screening.

Primary tracheobronchial amyloidosis: a series of 3 cases.

Primary tracheobronchial amyloidosis is a form of localized pulmonary amyloidosis, characterised by the deposition of AL-amyloid in trachea and bronchi. It is a rare and slowly progressive disease, usually requiring repeated endoscopic treatment. In this case series we describe symptoms, diagnostic and therapeutic procedures, radiological findings and pulmonary function testing in 3 cases of different presentation and severity. Two patients were treated by endoscopic debulking and stent placement during rigid bronchoscopy, both with excellent clinical and functional results. In one of these patients regular endoscopic and clinical control exams were performed in the 5 years following the initial treatment, showing stable disease, requiring no further therapeutic intervention until today.

Murine M cells express annexin V specifically.

The specialized epithelium covering the lymphoid follicles of Peyer's patches in the gut mediates transcytosis of antigens to the underlying immune cells, mainly through the membranous, or M, cells. At present, the molecular processes involved in the mucosal immune response, and in antigen transport across the follicle-associated epithelium (FAE) and M cells, are poorly understood. To characterize FAE and M cells, we compared the gene expression profiles of small intestine FAE and villus epithelium (VE) in BALB/c mice by microarray analysis; 91 genes were found to be up-regulated and four down-regulated at least two-fold (p<0.01) in the FAE. The differential expression of a subset of these genes was shown to be confirmed by quantitative RT-PCR. Using immunohistochemistry on BALB/c Peyer's patches, cathepsin H and clusterin expression was increased in the FAE compared to the VE. Moreover, we demonstrated M cell-specific expression of annexin V, which has recently been reported to be important in endocytic transport and membrane scaffolding, suggesting that annexin V has a function in M cell-mediated transcytosis.