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F Schmitz

Publications and source records attributed to F Schmitz.

At least 19 recordsLinked to original sources
PubMed2003

The interleukin-6 promoter polymorphism is associated with elevated leukocyte, lymphocyte, and monocyte counts and reduced physical fitness in young healthy smokers.

Smoking and interleukin-6 are important factors in driving inflammation. This study assessed the relationship between smoking, interleukin-6 genotype, physical fitness, and peripheral blood count in healthy young men. For this interleukin-6 promoter polymorphism -174 genotype-phenotype association study 1,929 healthy German male aviators recruited at the central German Air Force Institute of Aviation Medicine were stratified by smoking habits. Cardiovascular fitness was expressed as maximal physical working capacity (PWCmax) in watts per kilogram body weight as assessed by maximal exercise testing by cycle ergometry up to physical exhaustion. Smokers had higher leukocyte and lymphocyte counts than nonsmokers and lower PWCmax. In the overall study population the C allele of the interleukin-6 polymorphism was weakly associated with elevated leukocytes and lymphocytes; in nonsmokers the interleukin-6 polymorphism was not associated with altered phenotypes, but in smokers the interleukin-6 C allele was associated with higher leukocytes, lymphocytes, and monocytes and with lower PWCmax. Smoking is thus associated with elevated leukocytes and lymphocytes and with reduced physical fitness. Gene carriers with the interleukin-6 C allele may suffer particularly from cigarette smoking.

Adult↗
PubMed2003

Relation between the angiotensinogen (AGT) M235T gene polymorphism and blood pressure in a large, homogeneous study population.

The aim of this study was to assess the association of the angiotensinogen M235T polymorphism with arterial blood pressure (BP) at rest and under physical stress in a homogeneous large-scale study population. In all, 1903 men who passed routine medical examination for military flying duty were recruited. BP and heart rate were measured at rest, during, and after bicycle ergometry. Genotyping for the AGT M235T polymorphism was carried out by PCR and RFLP technique. The AGT T235 allele was associated with a significantly higher diastolic BP (n=1903; MM 81+/-8, MT 83+/-7, TT 83+/-8; P=0.003). Pulse pressure (PP) at rest differed significantly between AGT genotypes (n=1903; MM 51+/-10 mmHg, MT 49+/-10 mmHg, TT 49+/-10 mmHg; P=0.001). During physical activity, BP values showed no significant difference between genotypes. In healthy young men, the AGT T235 allele is significantly associated with elevated diastolic BP but also reduced PP at rest. During physical activity, the AGT polymorphism had no impact on blood pressure, indicating the existence of other counteracting mechanisms, which might balance the influence of this gene.

Adult↗
PubMed2003

Cardiovascular risk factors in patients with aortic stenosis predict prevalence of coronary artery disease but not of aortic stenosis: an angiographic pair matched case-control study.

BACKGROUND: Traditional cardiovascular risk factors have been associated with aortic stenosis and coronary artery disease. As these two conditions often co-exist, the association of cardiovascular risk factors with aortic stenosis may reflect confounding. OBJECTIVE: To compare the cardiovascular risk profile in patients with severe aortic stenosis undergoing elective coronary angiography with that of patients without aortic stenosis or calcification undergoing coronary angiography for suspected coronary artery disease. METHODS: 523 patients referred for elective diagnostic left heart catheterisation because of severe aortic stenosis formed the case population; 3925 patients without valve disease referred for elective diagnostic left heart catheterisation formed the base control population. Of the latter, 523 were pair matched to the case population for sex, age, and prevalence of relevant coronary artery disease, forming a pair matched control population. Cardiovascular risk factors (male sex, hypertension, hypercholesterolaemia, smoking, diabetes mellitus, family history of coronary artery disease) were assessed in all the patients. RESULTS: None of the cardiovascular risk factors was more prevalent in patients with aortic stenosis than in the base control population or in the pair matched control population. However, male sex, hypercholesterolaemia, smoking, diabetes mellitus, and a family history of coronary artery disease were significantly associated with the presence of additional coronary artery disease in patients with aortic stenosis. CONCLUSIONS: Cardiovascular risk factors are commonly present in patients with aortic stenosis. However, when compared with controls matched for age, sex, and angiographically defined coronary artery disease, no risk factor was significantly associated with the prevalence of aortic stenosis. Thus other factors are likely to be more important in the pathogenesis of aortic stenosis.

Aged↗
PubMed2002

The neural basis of intermittent motor control in humans.

The basic question of whether the human brain controls continuous movements intermittently is still under debate. Here we show that 6- to 9-Hz pulsatile velocity changes of slow finger movements are directly correlated to oscillatory activity in the motor cortex, which is sustained by cerebellar drive through thalamus and premotor cortex. Our findings suggest that coupling of 6- to 9-Hz oscillatory activity in the cerebello-thalamo-cortical loop represents the neural mechanism for the intermittent control of continuous movements.

Adult↗
PubMed2002

The effects of acetylsalicylic acid on proliferation, apoptosis, and invasion of cyclooxygenase-2 negative colon cancer cells.

BACKGROUND: Acetylsalicylic acid (ASA, aspirin), the most common nonsteroidal anti-inflammatory drug (NSAID), has been shown to have a protective effect against the incidence and mortality of colorectal cancer. However, the mechanism of its anticancer function remains unclear. The aim of this study was to determine the effects of acetylsalicylic acid on proliferation, apoptosis, and invasion in human cyclooxygenase-2 (COX-2) negative colorectal cancer cell lines. MATERIALS AND METHODS: After treatment with various concentrations of ASA, cell proliferation was measured in the human colon cancer cell line SW480. Apoptotic cells were identified by transmission electron microscopy, acridine orange staining, and flow cytometry. The invasive potential of SW480 cells was detected using an in vitro invasion assay. The production of carcinoembryonic antigen was measured by microparticle enzyme immunoassay. Expression of Bcl2, Bax, CD44v6, and nm23 were evaluated by immunocytochemistry. RESULTS: ASA significantly inhibited the proliferation of SW480 cells and stimulated apoptosis. Production of carcinoembryonic antigen and the invasive potential of SW480 cells were also inhibited by ASA. After treatment with ASA, down-regulation of Bcl2 and CD44v6 expression and up-regulation of nm23 expression were observed in SW480 cells. No obvious effect of ASA was found on Bax expression. CONCLUSION: Our findings reveal that ASA inhibits the proliferation and promotes apoptosis in the human colon cancer cell line SW480. Down-regulation of Bcl2 expression might represent a potential mechanism by which ASA induces apoptosis in this COX-2 negative colon cancer cell line. Our results also suggest that ASA decreases the invasive potential of these colon cancer cells. Decreased CEA content and CD44v6 expression and elevated nm23 expression may contribute to the effect of ASA on invasive potential of SW480 colon cancer cells.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

[The nuclear medicine department and the TEP/Biomedical Cyclotron unit].

During the last 25 years, the clinical and experimental activity in nuclear medicine at Erasme hospital has been influenced by the implementation of positron emission tomography (PET) in 1990 as a method of brain functional investigation. The activity of the PET/biomedical cyclotron unit has been dedicated to various subjects in neurology, neurosciences, psychiatry, oncology and cardiology. This has been made possible by developments in radiochemistry. The radiochemistry laboratory has designed and produced original tracers such as 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)-methyl]guanine (FHPG), a tracer of viral thymidine kinase activity in gene therapy protocols. We have brought new applications of PET, such as its integration into stereotactic neurosurgical and radioneurosurgical techniques in order to improve their diagnostic and therapeutic performance in neurooncology. We have also conducted multiple studies on brain physiology and pathophysiology, in particular with the use of functional and metabolic brain mapping methods and the use of tracers of neurotransmission systems. The Department of nuclear medicine has also performed studies on bone metabolism and investigated in vivo imaging methods of infectious and immune processes.

Belgium↗
PubMed2001

Cellular expression of CCK-A and CCK-B/gastrin receptors in human gastric mucosa.

Gastrin stimulates gastric acid secretion in various species, but the role of the structurally related CCK for the peripheral regulation of acid secretion in humans remains controversial. Moreover, species differences in CCK receptor function and expression have been reported. We therefore sought to identify the cellular targets of CCK and gastrin within the human gastric mucosa in situ. Gastric biopsies were collected from 15 patients without gastric disease. Expression of CCK receptor subtypes was detected in individual cells of the gastric mucosa by reverse transcription (RT)-PCR in situ, immunohistochemistry and confocal laser scanning microscopy, using antisera against the CCK-A or CCK-B/gastrin receptor subtype. Both CCK-A and CCK-B receptors were detected in antral and oxyntic mucosa at the mRNA and protein level. In fundic mucosa, CCK-A receptor mRNA and protein mapped to D cells (37.4+/-7.7). Besides, individual chief cells, mucous neck cells and parietal cells (12.3+/-4.7%) expressed CCK-A receptors. CCK-B/gastrin receptor mRNA and protein were detected in parietal cells (57.4+/-11.1%) and in neuroendocrine cells (33.2+/-4.4%) expressing chromogranin A. Furthermore, epithelial cells within the neck of the gastric gland were found to express the CCK-B/gastrin receptor. We conclude that (i) identification of CCK-A receptors on somatostatin producing D cells in humans provide the anatomical basis for a receptor-mediated mode of action of CCK on somatostatin release and (ii) detection of either CCK receptor subtype in the putative stem cell compartment implies a role of CCK in the maintenance of tissue homeostasis in human gastric mucosa.

Adult↗
PubMed2001

Immunological heterogeneity of synaptic and extrasynaptic forms of non-erythroid alpha-spectrin in the rat retina.

alpha-, beta- Spectrin is ubiquitously distributed in neuronal compartments, i.e. at the plasma membrane of neuronal cell bodies, axonal and dendritic processes, pre- and postsynaptic nerve terminals and around synaptic vesicles, "Brain Res. Bull. 50 (1999) 345". Ultrastructural analyses in the rat retina using the monoclonal antibody AA6, "Hear. Res. 43 (1990) 199", against non-erythroid alpha-spectrin, alphaSPII (spectrin nomenclature according to "Blood 81 (1993) 3173"), revealed that the antibody intensively labeled the cytoplasmic face of the plasma membrane in virtually all neuronal processes. However, no significant immunolabel was observed at the presynaptic plasma membrane, around synaptic vesicles, at presynaptic densities and synaptic ribbons. Therefore, synaptic non-erythroid alpha-spectrin differs immunologically from extrasynaptic non-erythroid alpha-spectrin. This heterogeneity might contribute to the generation of distinct retinal microdomains.

Animals↗
PubMed2001

Identification of CCK-B/gastrin receptor splice variants in human peripheral blood mononuclear cells.

There is increasing evidence for a direct interaction of the enteric nervous and immune system. Receptors for neuropeptides such as VIP, somatostatin, and substance P have been characterised in human immuno-haematopoietic cells but little is known about the functional significance and expression of receptors for cholecystokinin (CCK) on cells of the immune system. There are only few studies that describe the expression of CCK receptors on human leukaemia-derived cell lines but the receptor structure and function in normal leukocytes have not been clearly established. We therefore sought to determine CCK receptor expression, structure, and function in nontransformed human peripheral blood mononuclear cells.Full-length cDNA clones encoding the human CCK-A and CCK-B/gastrin receptor are expressed in peripheral blood mononuclear cells from healthy volunteers without haematopoietic malignancy. In addition to wild-type CCK-B/gastrin receptor cDNAs, we isolated a splice variant with an in frame insertion of 69 amino acids within its putative third intracellular receptor loop. Dideoxy sequence analysis revealed that the cDNA of this splice variant comprises exons 1-4 but retains intron 4 (207 bp) in the absence of mutations within the splice donor sites. Transient expression of this splice variant in COS-7 cells reveals wild-type affinity for CCK-8, Gastrin-17, and antagonist L-365,260. Affinity for glycine-extended gastrin-17 was not increased when compared to the wild-type CCK-B/gastrin receptor. In vitro, gastrin decreased 3H-thymidine labelling in phytohaemagglutinin-pretreated mononuclear cells at a half-maximally effective concentration of 1.5 nM. We also isolated a cDNA encoding another splice variant of the CCK-B/gastrin receptor with a 158 bp deletion of the entire exon 4 sequence. We conclude that wild-type transcripts of both CCK receptor subtypes and splice variants of the CCK-B/gastrin receptor are expressed in nontransformed human mononuclear cells and that gastrin exhibits antiproliferative effects.

Alternative Splicing↗
PubMed2001

The synaptic vesicle priming protein Munc13-1 is absent from tonically active ribbon synapses of the rat retina.

Ribbon synapses, for example of the retina, are specialized synapses that differ from conventional, phasically active synapses in several aspects. Ribbon synapses can tonically and yet very rapidly release neurotransmitter via synaptic vesicle exocytosis. This requires an optimization of the synaptic machinery and is at least partly due to the presence of synaptic ribbons that bind large numbers of synaptic vesicles and which are believed to participate in priming synaptic vesicles for exocytosis. In this paper we analyzed whether ribbon synapses of the retina employ similar priming factors, i.e. Munc13-1, as do conventional, non-ribbon containing phasically active synapses. We found that though present in conventional synapses of the retina Munc13-1 was completely absent from ribbon-containing synapses of the retina, both in the outer as well as in the inner plexiform layer. This indicates that ribbon synapses of the retina employ other, possibly more potent priming factors than phasically active conventional synapses.

Animals↗
PubMed2001

Involvement of the motor cortex in pseudochoreoathetosis.

The pathophysiological background of involuntary movements in pseudochoreoathetosis is unclear. We therefore recorded in four patients with pseudochoreoathetosis and in six age-matched controls cortical activity with a whole-head magnetoencephalography (MEG) system and surface EMGs from hand muscles. Subjects performed the following tasks: 1) rest, and 2) constant finger stretch during forearm elevation; controls additionally simulated pseudochoreoathetotic finger movements. During rest, the patients showed involuntary finger movements associated with excessive MEG-EMG coherence at frequencies between 6 and 20 Hz, whereas coherence in controls simulating pseudochoreoathetotic movements did not exceed noise level (P < 0.02). During finger stretch, MEG-EMG coherence in patients was similar to that of controls. Cortical sources of MEG-EMG coherence in patients were localized in the contralateral motor cortex. We conclude that pseudochoreoathetosis is associated with pathologically increased corticomuscular coherence and thus differs, neurophysiologically, from voluntarily simulated pseudochoreoathetotic movements. The enhanced MEG-EMG coherence in pseudochoreoathetosis probably reflects a pathologically strong motor cortical drive of spinal motorneurons after deafferentation.

Adult↗
PubMed2001

[Retinoscopy. A multi-media teaching program on CD].

INTRODUCTION: Retinoscopy is a classical method to determine the refraction of the eye by observing the dynamics of reflexes and varying the experimental parameters until a specific reflex (neutralisation point) is observed. Until now photographs and geometrical drawings of the different ray tracings have been commonly used to visualise the pathways. We intend to use new media such as video and CD to offer the students a better understanding of retinoscopy. METHODS: With the aid of appropriate experimental devices, retinoscopal reflexes of artificial and human eyes are recorded on video. The video sequences are converted in computer files and together with computer animations of the geometrical ray tracings, text files and audio sequences, they are stored in a suitable CBT-programme. RESULTS: The systematically prepared computer compatible contents offer a modern individually controllable method to perform the instruction programme by multimedia. The CBT-program and the specific files are stored on CDs or can be distributed on the internet. A collection of retinoscopy records of patients, some with extraordinary reflex phenomena is also available. DISCUSSION: Video and animation procedures are more suitable for matching the dynamic phenomena on retinoscopy than photographs or drawings as they offer a more direct basis for understanding of the sometimes difficult processes of retinoscopy. The collection of recorded reflexes also offers the direct visualised experience of particular patient findings such as the appearance in context of implanted spherical and aspherical intraocular lenses or the irregularities of the optic system of eyes with keratokonus.

Computer-Assisted Instruction↗
PubMed2001

CCK-B/gastrin receptors in human colorectal cancer.

BACKGROUND: Mature amidated gastrin (G17 amide) mediates its effects in the gastrointestinal tract by activating G protein-coupled CCK-B/gastrin receptors. Although trophic actions of gastrin on the gastric mucosa have been well-established, the effect of G17 amide, progastrin and intermediates to colon neoplasia in humans is controversial. While epidemiological evidence from patients with elevated serum gastrin levels related to pernicious anaemia does not support an increased risk for colon cancer, a recent study suggests that prolonged hypergastrinaemia is associated with an increased risk for colon cancer. The extent to which trophic actions of gastrin in colorectal cancer are mediated by functional gastrin receptors remains to be defined. The aim of the present study was to determine CCK-B/gastrin receptor expression, structure, and function in 79 patients with colon cancer. MATERIALS AND METHODS: CCK-B/gastrin receptor cDNAs were isolated from 79 human colorectal cancer specimens and 15 control tissues, subcloned into the eukaryotic expression vector pCR3.1 and subjected to DNA sequence analysis. Wild-type and mutant cDNAs were transiently expressed in COS-7 cells to determine ligand affinities by 125I-labelled CCK-8S competition binding. Activation of the MAP kinase signalling cascade by G17 amide was determined in transfected Colo 320 cells expressing the wild-type or mutant CCK-B/gastrin receptors. Clonal expansion of single cells was quantified in transfected Colo 320 cells. RESULTS: Gastrin mRNA is expressed in 44% of colorectal cancers and in 13% of control tissues. CCK-B/gastrin receptor mRNA is expressed in 38% of colorectal cancers and 13% of normal colonic tissue. Co-expression of gastrin and CCK-B/gastrin receptor message is significantly increased in colorectal cancer specimens (32% vs. 0%). There is no correlation between CCK-B/gastrin receptor expression and disease stage or histological grading. DNA sequence analysis revealed one spontaneous CCK-B/gastrin receptor mutation within the third intracellular loop with an exchange of valine-287 for phenylalanine. Pharmacological characterisation of the 287V --> F CCK-B/gastrin receptor reveals wild-type affinities for G17 amide, glycine-extended gastrin, CCK-8S and L-365,260. Mutation 287V --> F is associated with a loss of gastrin-induced MAPK p44/p42 signalling in Colo 320 cells while clonal expansion from single cells is increased by 53.1 +/- 15.9% when compared to Colo 320 cells expressing wild-type CCK-B/gastrin receptors. CONCLUSIONS: Structural alterations of CCK-B/gastrin receptors may account for increased growth-promoting effects of amidated gastrins in colorectal cancer.

Aged↗
PubMed2001

Expression of hepatocyte growth factor, keratinocyte growth factor and their receptors in experimental chronic pancreatitis.

BACKGROUND: Hepatocyte (HGF) and Keratinocyte growth factors (KGF) are key factors of tissue organization and regeneration. These peptide growth factors and their receptors c-met and keratinocyte growth factor receptor (KGFR) are overexpressed in pancreatic cancer. AIM: Expression and localization of ligands and receptors were investigated during the development of experimental chronic pancreatitis. METHODS: Chronic pancreatitis was induced in rats by intravenous injection of dibutyltin dichloride. One to 60 days after treatment, the expression of growth factors and receptors was analysed by competitive polymerase chain reaction, Western blot analysis and immunohistochemistry. RESULTS: HGF mRNA expression increased (10-fold) until days 7-14 followed by a decrease to control level. Expression of c-met mRNA constantly increased (15-fold). KGF and KGFR mRNA expression were increased after 14-28 days (5-fold) and then returned to control levels. mRNA expression patterns correlated with changes in the protein expression, whereas protein levels of KGF remained unchanged. Ligands were localized in mesenchymal cells and their receptors on epithelial cells. CONCLUSIONS: The significant increase of HGF and c-met expression suggests an essential role of this growth factor in the morphological changes during the development of chronic pancreatitis. Changes in the expression of KGF and KGFR are less pronounced.

Animals↗
PubMed2001

Differential coding of pain intensity in the human primary and secondary somatosensory cortex.

The primary (SI) and secondary (SII) somatosensory cortices have been shown to participate in human pain processing. However, in humans it is unclear how SI and SII contribute to the encoding of nociceptive stimulus intensity. Using magnetoencephalography (MEG) we recorded responses in SI and SII in eight healthy humans to four different intensities of selectively nociceptive laser stimuli delivered to the dorsum of the right hand. Subjects' pain ratings correlated highly with the applied stimulus intensity. Activation of contralateral SI and bilateral SII showed a significant positive correlation with stimulus intensity. However, the type of dependence on stimulus intensity was different for SI and SII. The relation between SI activity and stimulus intensity resembled an exponential function and matched closely the subjects' pain ratings. In contrast, SII activity showed an S-shaped function with a sharp increase in amplitude only at a stimulus intensity well above pain threshold. The activation pattern of SI suggests participation of SI in the discriminative perception of pain intensity. In contrast, the all-or-none-like activation pattern of SII points against a significant contribution of SII to the sensory-discriminative aspects of pain perception. Instead, SII may subserve recognition of the noxious nature and attention toward painful stimuli.

Adult↗
PubMed2001

Mechanisms of lectin (phytohemagglutinin)-induced growth in small intestinal epithelial cells.

BACKGROUND/AIMS: The lectin phytohemagglutinin is a mitogen for intestinal epithelial cells in vivo. The mechanisms of action are unknown and were therefore analyzed in vitro. METHODS: Human (Intestine-407) and rat (IEC-6; IEC-18) intestinal epithelial cell lines were stimulated with phytohemagglutinin. Proliferation was assayed by (3)H-thymidine incorporation, activation of mitogen-activated protein kinase (MAPK) by Western blotting, and induction of c-fos mRNA expression by semiquantitative polymerase chain reaction. Control experiments were performed with phenyl-N-acetyl-alpha-D-galactosaminide or the tyrosine kinase inhibitor tyrphostin A25. RESULTS: Phytohemagglutinin (0.1 microg/ml) significantly stimulated proliferation in all three cell lines after 48-72 h. MAPK activation was detected after 15-30 min, and an induction of c-fos mRNA expression after 15- 30 min of stimulation. Mitogenic effects were blocked by preincubation with phenyl-N-acetyl-alpha-D-galactosaminide or tyrphostin A25. CONCLUSION: Phytohemagglutinin stimulated proliferation, MAPK activation and induction of c-fos mRNA expression. The lectin may contribute to intestinal mucosal growth and regeneration thereby preventing gut atrophy.

Animals↗
PubMed2000

RIBEYE, a component of synaptic ribbons: a protein's journey through evolution provides insight into synaptic ribbon function.

Photoreceptor cells utilize ribbon synapses to transmit sensory signals at high resolution. Ribbon synapses release neurotransmitters tonically, with a high release rate made possible by continuous docking of synaptic vesicles on presynaptic ribbons. We have partially purified synaptic ribbons from retina and identified a major protein component called RIBEYE. RIBEYE is composed of a unique A domain specific for ribbons, and a B domain identical with CtBP2, a transcriptional repressor that in turn is related to 2-hydroxyacid dehydrogenases. The A domain mediates assembly of RIBEYE into large structures, whereas the B domain binds NAD(+) with high affinity, similar to 2-hydroxyacid dehydrogenases. Our results define a unique component of synaptic ribbons and suggest that RIBEYE evolved in vertebrates under utilization of a preexisting protein to build a unique scaffold for a specialized synapse.

Alcohol Oxidoreductases↗