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F Schmitz

Publications and source records attributed to F Schmitz.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed2000

Interlaboratory trial to determine the analytical state-of-the-art of bromate determination in drinking water.

The new European Directive for water intended for human consumption has established a regulatory level for bromate at 10 microg L(-1). This Maximum Admissible Concentration requires analytical methods with detection limits of a least 2.5 microg L(-1). A project funded by the Standards, Measurements and Testing Programme of the European Commission has enabled the improvement and/or development of methods for the determination of bromate at such concentration levels. This collaborative work was concluded by the organisation of an interlaboratory trial involving 26 European laboratories, which enabled the testing of both a draft ISO Standard method and alternative methods. This paper presents the results of this interlaboratory trial, along with results of a bromate stability study. The progress made with respect to the analytical state-of-the-art for bromate will greatly benefit the quality of measurements carried out in water quality monitoring.

Bromates↗
PubMed2000

Expression of keratinocyte growth factor and its receptor in colorectal cancer.

BACKGROUND AND AIMS: The mesenchymal derived keratinocyte growth factor stimulates growth, differentiation and migration of intestinal epithelial cells. In the human gastrointestinal tract an overexpression of this growth factor has been reported in inflammatory bowel disease and pancreatic cancer. In the present study we investigated expression patterns of keratinocyte growth factor and receptor in normal and neoplastic colonic mucosa and in metastases. Furthermore, biological effects on normal intestinal and colorectal cancer cell lines were determined. MATERIALS AND METHODS: Expression patterns were analysed at the mRNA level by reverse transcription-polymerase chain reaction (RT-PCR) and at the protein level by Western blotting. Localization of ligand and receptor in normal intestinal mucosa and cancer tissue was investigated by immunohistochemistry. Mitogenic effects of keratinocyte growth factor were assayed by [3H]thymidine incorporation in normal (Intestine-407, IEC-6, IEC-18) and colorectal cancer cell lines (Colo320, LoVo, SW403, SW707). RESULTS: mRNA expression of keratinocyte growth factor and receptor was detected in the majority of normal and cancer samples without significant alterations. At the protein level keratinocyte growth factor expression did not differ between normal and malignant specimens, whereas protein expression of the receptor was increased up to twofold in well- to moderately differentiated colorectal cancers. DNA synthesis was significantly stimulated by keratinocyte growth factor in all three normal intestinal cell lines, whereas this growth factor did not significantly alter the [3H]thymidine incorporation in the colorectal cancer cell lines. CONCLUSION: Keratinocyte growth factor and its receptor were detected in the majority of samples from normal and neoplastic colonic mucosa, with an overexpression of the receptor seen in the more differentiated tumour samples. Keratinocyte growth factor is a strong mitogen for normal intestinal cells, whereas it is less effective in neoplastic cells.

Blotting, Western↗
PubMed2000

C-met protooncogene expression and its regulation by cytokines in the regenerating pancreas and in pancreatic cancer cells.

BACKGROUND: Activation of the receptor c-met stimulates motility, mitosis, morphogenesis, processes involved in organ regeneration, or progression of malignancies. In the present study we investigated the expression of c-met protein in the regenerating pancreas and characterized the influence of cytokines on c-met expression. METHODS: Acute pancreatitis was induced in rats by cerulein injection. Rat acini and rat and human pancreatic cancer cells were stimulated with interleukin-1alpha (IL-1alpha), IL-6, tumor necrosis factor-alpha (TNF-alpha) or transforming growth factor-beta1 (TGF-beta1). C-met expression was analyzed by means of Western blotting and localization in pancreatic tissue by immunohistochemistry. RESULTS: C-met protein expression was significantly upregulated in the regenerating pancreas and localized in areas of regenerating tissue. Stimulation with cytokines resulted in a two- to threefold increase of c-met expression in vitro. CONCLUSION: Enhanced c-met expression after acute pancreatitis suggests that HGF/met has an important role in pancreatic regeneration, which is probably mediated by cytokines. This regulatory mechanism is also of importance in pancreatic cancer.

Acute Disease↗
PubMed2000

Single word reading in developmental stutterers and fluent speakers.

Ten fluent speakers and nine developmental stutterers read isolated nouns aloud in a delayed reading paradigm. Cortical activation sequences were mapped with a whole-head magnetoencephalography system. The stutterers were mostly fluent in this task. Although the overt performance was essentially identical in the two groups, the cortical activation patterns showed clear differences, both in the evoked responses, time-locked to word presentation and mouth movement onset, and in task-related suppression of 20-Hz oscillations. Within the first 400 ms after seeing the word, processing in fluent speakers advanced from the left inferior frontal cortex (articulatory programming) to the left lateral central sulcus and dorsal premotor cortex (motor preparation). This sequence was reversed in the stutterers, who showed an early left motor cortex activation followed by a delayed left inferior frontal signal. Stutterers thus appeared to initiate motor programmes before preparation of the articulatory code. During speech production, the right motor/premotor cortex generated consistent evoked activation in fluent speakers but was silent in stutterers. On the other hand, suppression of motor cortical 20-Hz rhythm, reflecting task-related neuronal processing, occurred bilaterally in both groups. Moreover, the suppression was right-hemisphere dominant in stutterers, as opposed to left-hemisphere dominant in fluent speakers. Accordingly, the right frontal cortex of stutterers was highly active during speech production but did not generate synchronous time-locked responses. The speech-related 20-Hz suppression concentrated in the mouth area in fluent speakers, but was evident in both the hand and mouth areas in stutterers. These findings may reflect imprecise functional connectivity within the right frontal cortex and incomplete segregation between the adjacent hand and mouth motor representations in stutterers during speech production. A network including the left inferior frontal cortex and the right motor/premotor cortex, likely to be relevant in merging linguistic and affective prosody with articulation during fluent speech, thus appears to be partly dysfunctional in developmental stutterers.

Adult↗
PubMed2000

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Journal Article↗
PubMed2000

Differential organization of touch and pain in human primary somatosensory cortex.

Processing of tactile stimuli within somatosensory cortices has been shown to be complex and hierarchically organized. However, the precise organization of nociceptive processing within these cortices has remained largely unknown. We used whole-head magnetoencephalography to directly compare cortical responses to stimulation of tactile and nociceptive afferents of the dorsum of the hand in humans. Within the primary somatosensory cortex (SI), nociceptive stimuli activated a single source whereas tactile stimuli activated two sequentially peaking sources. Along the postcentral gyrus, the nociceptive SI source was located 10 mm more medially than the early tactile SI response arising from cytoarchitectonical area 3b and corresponded spatially to the later tactile SI response. Considering a mediolateral location difference between the hand representations of cytoarchitectonical areas 3b and 1, the present results suggest generation of the single nociceptive response in area 1, whereas tactile stimuli activate sequentially peaking sources in areas 3b and 1. Thus nociceptive processing apparently does not share the complex and hierarchical organization of tactile processing subserving elaborated sensory capacities. This difference in the organization of both modalities may reflect that pain perception rather requires reactions to and avoidance of harmful stimuli than sophisticated sensory capacities.

Adult↗
PubMed2000

Functional expression of HGF and its receptor in human colorectal cancer.

BACKGROUND: Hepatocyte growth factor (HGF) stimulates proliferation, migration and morphogenesis of epithelial cells by specific binding to its receptor c-met. Overexpression of HGF or c-met has been reported for human gastric or pancreatic cancer. In colorectal cancer overexpression of c-met but not HGF has been shown. However, elevated HGF serum levels have been detected in colorectal cancer patients. Therefore, the present study was performed to investigate expression patterns of both c-met and HGF in colorectal cancers and metastasis in comparison to normal mucosa. Furthermore, the mitogenic actions of HGF on colorectal cancer cells were studied in vitro. METHODS: Expression of c-met and HGF were analyzed by RT-PCR and Western blotting and localized in the tissues utilizing immunohistochemistry. Mitogenic effects of HGF were determined in four human colon cancer cell lines by (3)H-thymidine incorporation studies. RESULTS: C-met and HGF mRNA were detectable in 60% of the normal specimen, but in the majority of cancer samples, and in just 33% of the liver metastasis. In cancer samples a coexpression of c-met and HGF was detected in 77% of the specimens. The extent of protein expression of receptor and ligand correlated with the mRNA expression. Moreover, c-met protein expression was increased 2- to 3-fold in colorectal cancers. C-met was detected in cells of epithelial origin, whereas HGF was expressed by mesenchymal cells. In vitro, HGF significantly stimulated cell growth in all four cell lines. CONCLUSION: Overexpression of c-met protein in colorectal cancers is combined with an expression of HGF in the majority of cases suggesting a paracrine manner of growth enhancement, while only a weak expression of c-met or HGF was detected in metastatic tissues.

Adenocarcinoma↗