Enrichment and characterization of dendritic cells from human bronchoalveolar lavages

In the present study about 0.3% to 1.6% of human bronchoalveolar lavage (BAL) cells were identified as typical dendritic cells (DC), having an irregular outline, lobulated nucleus, and clear distinguishable acid phosphatase activity or EBM11 (anti-CD68) reactivity in a spot near the nucleus. After DC enrichment, using transient adherence to plastic, FcR-panning, and a density metrizamide gradient, a population containing 7-8% typical DC was obtained. This DC-enriched low density fraction, containing the highest percentages of DC, very strongly induced T cell proliferation in an allogeneic mixed leucocyte reaction (MLR), which was significantly higher than that induced by other partly (un)fractionated BAL cells. These data indicate that DC seem to be the major accessory cells in the BAL fluid, and therefore may be important in the regulation of T cell immune responses in the lung

Methylglyoxal down-regulates the expression of cell cycle associated genes and activates the p53 pathway in human umbilical vein endothelial cells

Abstract Although methylglyoxal (MGO) has emerged as key mediator of diabetic microvascular complications, the influence of MGO on the vascular transcriptome has not thoroughly been assessed. Since diabetes is associated with low grade inflammation causing sustained nuclear factor-kappa B (NF-κB) activation, the current study addressed 1) to what extent MGO changes the transcriptome of human umbilical vein endothelial cells (HUVECs) exposed to an inflammatory milieu, 2) what are the dominant pathways by which these changes occur and 3) to what extent is this affected by carnosine, a putative scavenger of MGO. Microarray analysis revealed that exposure of HUVECs to high MGO concentrations significantly changes gene expression, characterized by prominent down-regulation of cell cycle associated genes and up-regulation of heme oxygenase-1 (HO-1). KEGG-based pathway analysis identified six significantly enriched pathways of which the p53 pathway was the most affected. No significant enrichment of inflammatory pathways was found, yet, MGO did inhibit VCAM-1 expression in Western blot analysis. Carnosine significantly counteracted MGO-mediated changes in a subset of differentially expressed genes. Collectively, our results suggest that MGO initiates distinct transcriptional changes in cell cycle/apoptosis genes, which may explain MGO toxicity at high concentrations. MGO did not augment TNF-α induced inflammation

De waarde van ambulante 24-uursslokdarmmanometrie bij de diagnostiek van retrosternale pijn van niet-cardiale origine

The clinical relevance of a system of ambulatory 24-hour oesophageal pressure and pH recording with automated data analysis was investigated in 33 unselected patients with non-cardiac chest pain. After conventional manometry with edrophonium (Tensilon) provocation, 24-hour oesophageal pH and pressure monitoring was performed. In 17 patients conventional manometry, edrophonium provocation and 24-hour pH recording revealed an oesophageal origin of the symptoms: 6 patients had oesophageal motility disorders, 3 were positive responders to edrophonium and 8 had chest pain associated with gastro-oesophageal reflux. In none of the patients who had a pain attack during prolonged oesophageal pressure recording, was a new motility disorder detecte

Acute noncardiac chest pain in a coronary care unit. Evaluation by 24-hour pressure and pH recording of the esophagus

Twenty-four-hour recording of esophageal pressure and pH was performed successfully in 41 patients admitted to the coronary care unit of a general hospital who had an episode of acute, prolonged retrosternal chest pain and who were initially suspected of suffering from coronary artery disease (severe angina pectoris, myocardial infarction), but in whom the pain was subsequently shown not to be of cardiac origin. The recordings were analyzed with fully automated techniques. A pain episode was considered to be related to abnormal esophageal motility when contraction amplitudes or durations in the pain episode exceeded the patient's upper limit of normal (97.5th percentile) or when the proportion of abnormal propagated contractions (simultaneous, nontransmitted) in the pain episode was significantly increased (chi 2 test). Thirty patients (73%) had one or more pain episodes (in total 63 pain episodes) during the 24-hour recording. Forty-three percent of the pain episodes was related to abnormal motility and 30% to reflux, and 27% was not related to esophageal function disturbance. Using the criterium that the symptom index had to be greater than or equal to 75%, it was found that the pain was related to reflux in 13 patients (43%) and to motor abnormalities in 10 patients (33%). It is concluded that in the majority of patients acutely admitted with noncardiac chest pain, esophageal motor abnormalities and reflux can be shown to be the likely cause of the symptom

Physiological gastroesophageal reflux and esophageal motor activity studied with a new system for 24-hour recording and automated analysis

Gastroesophageal reflux and esophageal motility were studied for 24 hr in 32 ambulatory healthy volunteers (20-73 years old), using a newly developed system, consisting of a microprocessor-based data recorder and algorithms for fully automated data analysis. Physiological reflux was more extensive than expected on the basis of widely used normal values. The percentage of time with pH less than 4 and the duration of the reflux episodes increased with age. Of the more than 2000 esophageal contractions occurring per day, peristaltic contractions constituted 50.9 +/- 2.0%. Their amplitude was significantly lower between meals than during meals and during the night. The duration of the peristaltic contractions increased with age. Simultaneous contractions constituted 10.4 +/- 1.2% of the esophageal contractions. Their incidence increased with age. We conclude that continuous ambulatory 24-hr recording with automated analysis of esophageal motility and pH profile is feasible, that the upper limits of normal in ambulatory esophageal pH recording are higher than previously accepted, and that age, meals, and body position must be taken into account in the interpretation of both 24-hr esophageal pH and pressure dat

Microcomputer-based system for 24-hour recording of oesophageal motility and pH profile with automated analysis

A system developed for long-term simultaneous recording of oesophageal motility and pH in the ambulant patient is described. The system consists of a microprocessor based data-acquisition and preprocessing device, a personal computer for postprocessing, report generation and data storage, a miniature two-sensor pressure catheter and a pH electrode. Identification and classification of oesophageal contractions are performed in separate steps, using online preprocessing software for identification and offline postprocessing software for categorisation, classification and report generation. Contractions are categorised as peristaltic, simultaneous or nontransmitte and classified according to their amplitude, duration and propagation velocity. The method described reduces the amount of data from 870 kbyte to approximately 40 kbyte per 24 hours in a multiparameter recording device, and offers the opportunity for offline postprocessing with different sets of criteria. The system has been found to be accurate and reliable in 24-hour studies in both healthy volunteers and patients with non-cardiac chest pai