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Biomedical subjects

J Riese

Publications and source records attributed to J Riese.

At least 19 recordsLinked to original sources
PubMed2006

[Off-label use in oncology: an inexhaustible topic?!].

In 2002, with its "Off-label verdict", the German Federal Social Court (Bundessozialgericht; BSG) issued a fundamental decision to the effect that in certain circumstances an off-label prescription might be payable by health insurance firms, these circumstances being: severe illness with no prospect of a cure being brought about by any therapy approved for this illness and an evidence-based chance that an off-label treatment could yield a cure. Subsequently, the former German Federal Ministry of Health and Social Security (BMGS) appointed its "expert group on off-label use of treatments". This panel's task was to formulate professional comments and expert recommendations to the Federal Joint Committee (G-BA) on scientific evidence relating to selected medications used for off-label treatment. The group was found not to be sufficiently efficient and was laid down in August 2005. Meanwhile, it has been replaced by other work groups. However, the constant increase in the amount of medical evidence available means that off-label use is a continuing process that cannot easily be regulated by expert committees. It would be preferable for reimbursement for off-label prescriptions to be linked to the qualifications of the attendant physician. One suggestion might be that only specifically authorised physicians with special additional skills be permitted to apply and be reimbursed for off-label prescriptions.

Antineoplastic Agents↗
PubMed2004

Expression of interleukin-6 and monocyte chemoattractant protein-1 by peritoneal sub-mesothelial cells during abdominal operations.

Cytokines and chemokines including interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) are secreted in response to major abdominal operations. The aim of this study was to identify the peritoneal cells that produce IL-6 and MCP-1. Samples of peritoneal tissue were taken from patients at the beginning and end of major abdominal operations. The samples were incubated in culture medium on microtitre plates for 5 h. The concentrations of IL-6 and MCP-1 were measured in culture supernatants by enzyme-linked immunosorbent assay (ELISA). In paraffin sections, cells that expressed IL-6 or MCP-1 were identified by combined in situ hybridization and immunohistochemistry. Antibodies against CD68, CD34, actin, and calretinin were included in these experiments. The median production of IL-6 increased significantly from 6256 pg/ml at the start of the operation to 20,000 pg/ml at the end. Production of MCP-1 rose from 7700 pg/ml to 11,820 pg/ml. IL-6 mRNA was mainly confined to endothelial cells. MCP-1 was expressed by a broader range of cells, consisting of actin-positive smooth muscle cells and endothelial cells, fibroblast-like cells, as well as occasional macrophages and mesothelial cells. Peritoneal endothelial cells contribute to the transient increase in concentrations of IL-6 in the circulation after surgical trauma. Recruitment of monocytes to the site of the trauma seems to be mainly effected by actin-positive smooth muscle cells and endothelial cells.

Adult↗
PubMed2003

Mannan-binding lectin (MBL) serum levels and post-operative infections.

Mannan-binding lectin (MBL) is a central component of the innate immune system. Here we investigated the role of MBL in surgical patients during the peri-operative phase. Basal and post-operative (days 1-3 post-surgery) serum samples were obtained prospectively from 156 patients undergoing major elective gastrointestinal surgery for malignant disease. In contrast to procalcitonin (a typical acute-phase protein), there was no significant difference in serum MBL between pre- and post-operative samples (P=0.62). Nevertheless, patients who developed post-operative infections showed significantly lower pre- and post-operative MBL levels than those who did not (P=0.013 and P=0.005, respectively). There was no significant difference in pre-operative procalcitonin between the two groups (P=0.56). We conclude (i) that serum MBL levels did not respond immediately to surgical trauma, and (ii) that lower MBL levels were associated with an increased occurrence of post-operative infections. Studies on larger patient groups are necessary, however, to assess the value of MBL measurements in identifying patients at risk of post-operative complications.

Adult↗
PubMed2000

The diminished postoperative capacity of blood leukocytes to produce IL-6 is associated with high concentrations of IL-6 in the circulation.

Surgical trauma is followed both by a transient increase of interleukin 6 (IL-6) concentrations in the serum and impaired function of circulating leukocytes. Perioperatively, we investigated the relationship of IL-6 concentrations in the serum with lipopolysaccharide (LPS)-stimulated cytokine production in the whole blood of patients undergoing elective major abdominal operations. In 50 patients, we found a transient increase of IL-6 concentrations in the serum. Six hours after skin incision, in vitro stimulated production of IL-6 and TNFalpha was diminished by 72% (P<0.05). A significant increase in cytokine production was observed three days postoperatively, however this was 63% below the preoperative values. Patients with high concentrations of circulating IL-6 showed a significantly lower stimulated IL-6 production than patients with low serum concentrations of IL-6. We conclude, that two opposing effects are associated with surgery: an activation leading to IL-6-release into the circulation, and a prolonged hyporesponsiveness of circulating leukocytes. These reactions are positively related.

Abdomen↗
PubMed2000

Production of IL-6 and MCP-1 by the human peritoneum in vivo during major abdominal surgery.

Both inflammatory and anti-inflammatory mediators are released into the circulation during major abdominal surgery. In addition, some of these mediators have been detected postoperatively in peritoneal fluids. Thus, it appears that the peritoneum may be a potential source of circulating immunomodulators following major abdominal surgery. With this in mind, we quantified the intraoperative production of interleukin (IL)-6 and monocyte chemoattractant protein-1 (MCP-1) by human peritoneum. A small chamber was sewed to the parietal peritoneum of 19 patients at the beginning of the operation. This chamber was perfused with buffered salt solution, and the perfusate was collected hourly and assayed for IL-6 and MCP-1 concentrations by enzyme-linked immunosorbent assay. Expression of the corresponding mRNAs was determined by reverse-transcription polymerase chain reaction from additional peritoneal biopsies taken at the beginning and at the end of operation. Peritoneal production of IL-6 and MCP-1 started within the first hour of operation and continued with increasing amounts of up to 435 (43-1925) pg/cm2/h [median (range)] of IL-6 and 435 (59-1930) pg/cm2/h of MCP-1. There was induction of peritoneal IL-6 and MCP-1 mRNA expression. A suppressed MCP-1 production was seen only in one patient who suffered from severe septic complications in the postoperative course. Using a new technique that allows for the quantification of local cytokine production in vivo, we demonstrated that the peritoneum rapidly reacts to abdominal surgery with increased production of IL-6 and MCP-1. Early detection of impaired production may help to identify patients at risk of postoperative septic complications.

Abdomen↗
PubMed1999

Association of low preoperative serum albumin concentrations and the acute phase response.

OBJECTIVE: To investigate the incidence of a preoperative acute phase response and its association with low albumin concentrations. DESIGN: Prospective open study. SETTING: Teaching hospital, Germany. SUBJECTS: 225 patients who were to undergo major abdominal operations, and who had no acute infections. INTERVENTIONS: Measurements of serum concentrations of albumin, C-reactive protein (CRP), alpha-1 antitrypsin, and interleukin-6 (IL-6). RESULTS: Abnormal concentrations of acute phase proteins (indicating an acute phase response) were detected in 43 of 225 patients (19%). The mean (SD) albumin concentration in these patients (35[5]g/L) was lower than that of patients who did not mount an acute phase response preoperatively (40[5]g/L). High concentrations of CRP (> or =60mg/L) were associated with low albumin concentrations (33[5]g/L); high alpha-1 antitrypsin concentrations (> or =4.0g/L) were associated with low albumin concentrations (34[6]g/L); and high IL-6 concentrations (> or =4pg/ml) were associated with low albumin concentrations (37[6]g/L) compared with a mean(SD) albumin concentration of 40(5)g/L in patients who had no evidence of an acute phase response. CONCLUSION: A metabolic response to disease referred to as an acute phase response may explain low preoperative albumin concentrations. This association interferes with the association of low preoperative albumin concentrations and malnutrition. It is a new aspect of preoperative risk evaluation and may indicate a potential for prevention.

Acute-Phase Proteins↗
PubMed1999

Tumour necrosis factor-alpha and interleukin-10 production in septic patients and the regulatory effect of plasma.

OBJECTIVE: To investigate the capacity of patients' whole blood to produce proinflammatory and antiinflammatory cytokines in severe sepsis and to relate abnormalities to the effect of the patients' plasma on cytokine production in healthy donor blood. DESIGN: Open, prospective clinical study. SETTING: Teaching hospital, Germany. PATIENTS: Ten patients in the surgical intensive care unit with shock and a systemic inflammatory response syndrome (SIRS), a mean APACHE II score of 27, and dysfunction of at least two organ systems at the time of investigation, resulting in 70% mortality. MAIN OUTCOME MEASURES: Tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) concentrations. RESULTS: TNF-alpha and IL-10 production of the whole blood in response to lipopolysaccharide (LPS) was reduced from 2000 pg/ml to 90 pg/ml and from 9163 pg/ml to 622 pg/ml, respectively (p < 0.01). When the plasma of these septic patients was added to the whole blood cells of healthy donors TNF-alpha production decreased by 38% to 1238 pg/ml (p < 0.01) and IL-10 production by 36% to 5857 pg/ml (p = 0.03). CONCLUSION: The effect of plasma from septic patients on the cytokine production in healthy donor blood cells paralleled the decreased production of proinflammatory TNF-alpha and antiinflammatory IL-10 in the whole blood of septic patients. Efforts to modulate cytokine production in septic patients therefore need to take account of the signals from the plasma as well as the functional capacity of the cells.

APACHE↗
PubMed1999

Secretion of IL-6, monocyte chemoattractant protein-1, macrophage inflammatory protein-1alpha, and TNFalpha by cultured intact human peritoneum.

The peritoneum is an important site of host defence. The mesothelial cells, lining the peritoneum, and the fibroblasts found in the layers below are potent sources of a variety of mediators. Furthermore, granulocytes, mast cells, and macrophages, either resident or attracted by inflammatory processes, are interspersed within the tissue. We investigated the production of mediators by samples of fresh human peritoneum. The method described here has the advantage that the cellular composition of the human peritoneum remains intact. Samples of peritoneum were excised at the beginning of elective abdominal operations in infection-free patients. The tissue was placed across the wells of a microtitre plate, fixed in place by the plate cover and incubated with culture medium with or without lipopolysaccharide (LPS) for up to 5 h. The accumulation of IL-6, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha) and TNFalpha in culture supernatants was measured by ELISA. Production of MCP-1 and IL-6 occurred spontaneously during incubation and was enhanced by as much as 4-fold in the presence of different concentrations of LPS (0. 5-500 ng/ml) in a dose-dependent manner. MIP-1alpha and TNFalpha were detected in culture supernatants of LPS-stimulated samples with concentrations about 8 times as high as those of samples cultured with no such stimulus. The addition of IL-1beta resulted in an increase in the release of IL-6 and MCP-1, similar to that observed with LPS stimulation, but failed to increase the production of TNFalpha. MIP-1alpha production was only marginally enhanced by IL-1beta. In conclusion, our experimental system is suitable for the investigation of chemokine and cytokine production by the human peritoneum, with the aim of assessing aspects of local immunocompetence.

Cell Survival↗
PubMed1999

[Production of chemokines by the human peritoneum].

AIM OF THE STUDY: Peritonitis is characterised by a continued infiltration of the peritoneal cavity with leukocytes, attracted by chemotactic mediators. The aim of this study was to demonstrate the capacity of the human peritoneum to secrete chemokines and to show a therapeutic option by impairing the proinflammatory function of the peritoneum. METHODS: Peritoneum was obtained from 12 consenting patients undergoing abdominal surgery for noninflammatory diseases. After opening the peritoneal cavity a piece of the parietal peritoneum was excised and subsequently incubated with lipopolysaccharide (LPS, 50 ng/ml) +/- interleukin-10 (IL-10, 100 U/ml) for five hours in vitro. The culture supernatants were assayed for concentrations of interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and monocyte inflammatory protein-1 alpha (MIP-1 alpha) by using the ELISA. RESULTS: The cultured peritoneum secreted MCP-1 (mean (SEM): 3416 (659) pg/ml) and IL-8 (2946 (894) pg/ml). The presence of LPS resulted in a fourfold enhancement of this secretion (MCP-1: 13563 (1613), IL-8: 9854 (1305) pg/ml) and led to the production of MIP-1 alpha (1476 (240) pg/ml). The LPS-stimulated production of all of these chemokines was significantly diminished by the presence of IL-10. CONCLUSION: The reaction of the peritoneum to LPS indicates its proinflammatory function in the context of peritonitis caused by gram-negative bacteria. This inflammatory reaction might be diminished by application of IL-10.

Chemokine CCL2↗
PubMed1998

Transcriptional repression due to high levels of Wingless signalling.

Extracellular signals can act at different threshold levels to elicit distinct transcriptional and cellular responses. Here, we examine the transcriptional regulation of the Wingless target gene Ultrabithorax (Ubx) in the embryonic midgut of Drosophila. Our previous work showed that Ubx transcription is stimulated in this tissue by Dpp and by low levels of Wingless signalling. We now find that high levels of Wingless signalling can repress Ubx transcription. The response sequence within the Ubx midgut enhancer required for this repression coincides with a motif required for transcriptional stimulation of Dpp, namely a tandem of binding sites for the Dpp-transducing protein, Mad. Indeed, Wingless-mediated repression depends on low levels of Dpp, although apparently not on Mad itself. In contrast, high levels of Dpp signalling antagonize Wingless-mediated repression. This suggests that transcriptional activation of Ubx is subject to competition between Dpp-activated Mad and another Smad whose function as a transcriptional repressor depends on high Wg signalling. Finally, we show that Wingless can repress its own expression via an autorepressive feedback loop that results in a change of the Wingless signalling profile during development.

Armadillo Domain Proteins↗
PubMed1998

Reduced TNFalpha and IL-6 production in patients who mount a preoperative acute phase response.

BACKGROUND/AIMS: In some patients postoperative infective complications are related to a reduced resistance to the operative trauma and the perioperative microbiological challenge. To investigate preoperative alterations in the immune responses in patients who had mounted an acute-phase response before the operation, we measured the capacity of tumor necrosis factor alpha and interleukin-6 production in whole blood. PATIENTS/METHODS: Serum concentrations of C-reactive protein, alpha1-antitrypsin, albumin, and prealbumin were measured in 89 patients submitted for major abdominal surgery on their admission to hospital. RESULTS: In 23 patients (26%) we found concentrations of at least one, and in 16 patients (18%) of two or more of these variables beyond the reference range. Patients who mounted an acute-phase response released 37% less TNFalpha (1339 vs. 848 pg/ml) and 31% less IL-6 (24293 vs. 16900 pg/ml) when whole blood was stimulated with lipopolysaccharide 0.5 microg/ml. CONCLUSION: Patients who mount an acute-phase response before operation may thus have a downregulated immune response at the level of proinflammatory cytokines. This is likely to alter their resistance to invasive micro-organisms in the perioperative period.

Acute-Phase Reaction↗
PubMed1998

Monocyte function before and after surgical trauma.

The monocyte/macrophage plays a key role in the network of immune reactions. Dependent on activation, it is able to produce various cytokines which act on other cells of the immune system in the sense of upregulation or downregulation. In addition, it presents antigens by the HLA-DR molecule as an initial trigger of an antigen-specific T-cell response. Monocyte function is affected by surgical disease and further affected by surgical trauma. We found the monocyte to be activated in a subgroup of patients before the operation, related to an increased rate of postoperative septic complications. After the operation, plasma concentrations of IL-6 and IL-10 were increased indicating the activation of an immune response. After surgery HLA-DR expression decreased as well as LPS-stimulated TNFalpha and IL-6 production, the latter indicating a hyporesponsiveness of peripheral blood cells (presumably monocytes) to further stimulation. On the other hand, continuously high plasma concentrations of activation markers like neopterin and IL-6 in the postoperative course were associated with complications and poor outcome. In postoperative septic shock monocytes may be almost areactive towards natural stimuli like bacteria and endotoxin, since IL-6 and TNFalpha production decreased to very low amounts. Adequate pre- and postoperative monocyte function is related to an uneventful postoperative course after major surgical operations. Surgical trauma affects monocyte function rendering it less reactive, which is a potential risk factor for postoperative septic complications.

Humans↗
PubMed1997

A CREB-binding site as a target for decapentaplegic signalling during Drosophila endoderm induction.

Decapentaplegic (Dpp) is an extracellular signal of the transforming growth factor-beta family with multiple functions during Drosophila development. For example, it plays a key role in the embryo during endoderm induction. During this process, Dpp stimulates transcription of the homeotic genes Ultrabithorax in the visceral mesoderm and labial in the subjacent endoderm. Here, we show that a cAMP response element (CRE) from an Ultrabithorax enhancer mediates Dpp-responsive transcription in the embryonic midgut, and that endoderm expression from a labial enhancer depends on multiple CREs. Furthermore, the Drosophila CRE-binding protein dCREB-B binds to the Ultrabithorax CRE, and ubiquitous expression of a dominant-negative form of dCREB-B suppresses CRE-mediated reporter gene expression and reduces labial expression in the endoderm. Therefore, a CREB protein may act as a nuclear target, or as a partner of a nuclear target, for Dpp signalling in the embryonic midgut.

Activating Transcription Factor 1↗
PubMed1997

LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic.

wingless and decapentaplegic signal during endoderm induction in Drosophila to regulate expression of the homeotic gene Ultrabithorax. Here, we define a minimal wingless response sequence in the midgut enhancer of Ultrabithorax. We show that this sequence is recognized by the murine transcription factor LEF-1 (lymphocyte enhancer binding factor 1) in a ternary complex with armadillo protein, the cytoplasmic target of the wingless signaling pathway. In stable transformants, transcriptional stimulation of the Ultrabithorax enhancer by LEF-1 depends on armadillo. Furthermore, overexpression of LEF-1 bypasses the need for wingless signaling and causes phenotypes in the midgut, notum, and wing that mimic wingless hyperstimulation. Finally, efficient transcriptional stimulation by LEF-1 in the midgut depends also on the decapentaplegic response sequence and is limited spatially by decapentaplegic signaling. Thus, LEF-1 coordinates inputs from multiple positional signals, consistent with its architectural role in regulating the assembly of multiprotein enhancer complexes.

Animals↗
PubMed1997

Standardized characterization of gene expression in human colorectal epithelium by two-dimensional electrophoresis.

New diagnostic and prognostic markers are needed in colorectal cancer. They can be found by differential analysis at DNA, RNA or protein level. The accuracy of phenotypic comparisons of tumor and normal tissues depends on the purity of the samples. We present an effective method to identify and isolate proteins that are differentially expressed under altered conditions, and a two-dimensional reference protein map of the normal human colonic epithelium. Normal colonic mucosa, primary tumors and liver metastases were prepared in the operating room. After washing in an ice-cold medium containing protease inhibitors, crypts were isolated by mechanical preparation without using metalloproteinases. Epithelial cells were then selected using Ber-EP4 Dynabeads. The samples were denaturated before processing for immobilized pH gradient two-dimensional polyacrylamide gel electrophoresis according to SWISS-2DPAGE standards. The samples contained more than 95% epithelial cells as confirmed by fluorescence-activated cell sorting using pan-anticytokeratin antibodies. Cell surfaces were not damaged, as assessed by scanning electronic microscope. A protein reference map of the normal colonic epithelium was defined. Using gel matching, N-terminal sequencing and/or immunoblotting techniques, 60 polypeptides - including proteins specifically expressed in colorectal epithelium - have now been identified. This reproducible method of sample preparation permits the comparison of protein patterns found in various pathological states with the present reference map (http://www.expasy.ch). Some of these patterns might provide diagnostic or prognostic markers, or even molecular targets for therapy in the future.

Colorectal Neoplasms↗
PubMed1997

D-Fos, a target gene of Decapentaplegic signalling with a critical role during Drosophila endoderm induction.

The Drosophila endoderm is patterned by the signals Decapentaplegic and Wingless secreted from the visceral mesoderm. This induction culminates in a precise pattern of spatially restricted expression of labial, a selector gene with a role in cell type specification in the larval midgut. Here, we show that Decapentaplegic signalling induces elevated expression of the Drosophila AP-1 transcription factor D-Fos in a slightly broader endodermal region than labial. This induction occurs in parallel to, and independently of, that of labial. Furthermore, we present evidence that D-Fos is required for labial induction in the embryo as well as for maintenance of labial expression through larval stages; and that D-Fos is critical for cellular differentiation in the larval gut. We propose that Decapentaplegic, by inducing D-Fos, broadly defines an endodermal region which thus becomes predisposed to express labial, and that D-Fos cooperates with signal-activated response factors to confer the precise pattern of labial expression in this region.

Animals↗
PubMed1995

Nucleo-cytoplasmic translocation and secretion of fibroblast growth factor-2 during avian gastrulation.

The expression and distribution of the fibroblast growth factor-2 (FGF-2 or bFGF) proteins during early avian embryogenesis has been analysed in detail. Three FGF-2 protein isoforms of 18.5, 20.0 and 21.5 kDa are expressed during gastrulation of chicken embryos. Using whole mount immunohistochemistry, these proteins were found to be predominantly nuclear in prestreak blastodiscs during mesoderm induction. Distribution of positive cells in the epiblast was mosaic, whereas all cells of the forming hypoblast expressed the FGF-2 proteins. During primitive streak formation, the proteins started to translocate to the cytoplasm in epiblast cells but remained nuclear in the hypoblast. The FGF-2 proteins became predominantly cytoplasmic in all cells during the subsequent developmental stages. Their highest levels were detected in endodermal cells underlying Hensen's node and the newly formed notochord, the dorsal apex of all epiblast cells and, most interestingly, in the extra-cellular basal lamina separating the epiblast from newly formed mesoderm. Heparin and suramin treatment of these advanced embryos (stage 4) revealed a dose-dependent inhibition on the regression of Hensen's node and formation of mesodermal derivatives such as somites. The results are discussed with respect to current models on FGF-mediated functions during vertebrate mesoderm induction and regionalization.

Animals↗