Frederik B. J. M. Thunnissen

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The previous World Health Organisation (WHO) histological classifications of lung tumours (1967 and 1981) have been diYcult to apply consistently and reproducibly. This has been particularly problematical for small biopsies. It has resulted in considerable diYculties in interpreting studies of the frequency of the various histological types in diVerent(More)
Pulmonary arterial hypertension (PAH), a fatal disease of unknown etiology characterized by impaired regulation of pulmonary hemodynamics and vascular growth, is associated with low levels of pulmonary nitric oxide (NO). Based upon its critical role in mediating vasodilation and cell growth, decrease of NO has been implicated in the pathogenesis of PAH. We(More)
Detection of lung cancer at early stages could potentially increase survival rates. One promising approach is the application of suitable lung cancer-specific biomarkers to specimens obtained by non-invasive methods. Thus far, clinically useful biomarkers that have high sensitivity have proven elusive. Certain genes, which are involved in cellular pathways(More)
Airway hyperresponsiveness and remodeling are defining features of asthma. We hypothesized that impaired superoxide dismutase (SOD) antioxidant defense is a primary event in the pathophysiology of hyperresponsiveness and remodeling that induces apoptosis and shedding of airway epithelial cells. Mechanisms leading to apoptosis were studied in vivo and in(More)
Small cell carcinoma with the histological appearance of pulmonary small cell carcinoma is a rare tumour in the urinary bladder. In previous case reports the neuroendocrine nature of small cell bladder carcinoma has been accepted, but on review the evidence for true neuroendocrine differentiation appears unsatisfactory. In this study the histological,(More)
Cytoglobin (CYGB) is a recently discovered vertebrate globin distantly related to myoglobin with unknown function. CYGB is assigned to chromosomal region 17q25, which is frequently lost in multiple malignancies. Previous studies failed to detect evidence for mutations in the CYGB gene. Recent studies provided preliminary evidence for increased methylation(More)
BACKGROUND Retinoic acid plays an important role in lung development and differentiation, acting primarily via nuclear receptors encoded by the retinoic acid receptor-beta (RARbeta) gene. Because receptor isoforms RARbeta2 and RARbeta4 are repressed in human lung cancers, we investigated whether methylation of their promoter, P2, might lead to silencing of(More)
PURPOSE An increase in the activity of the mitogen-activated protein kinases (MAPKs) has been correlated with a more malignant phenotype in several tumor models in vitro and in vivo. A key regulatory mechanism of the MAPKs [extracellular signal-regulated kinase (ERK); c-jun NH(2)-terminal kinase (JNK); and p38] is the dual specificity phosphatase CL100,(More)
Experimental pathologic studies suggest that Clara cells are one of the types of airway stem cells but the proliferation of Clara cells in human lungs has not yet been examined. The purpose of this study was to assess in conducting airways of normal human lungs: (1) the number of Clara cells; and (2) the contribution of Clara cells to the proliferation(More)
PURPOSE Inflammation is a constant finding in the ileal reservoir of patients with an ileal pouch-anal anastomosis and is associated with decreased fecal concentrations of the short chain fatty acid butyrate, increased fecal pH, changes in fecal flora, and increased concentrations of secondary bile acids. In healthy subjects, inulin, a dietary fiber, is(More)