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Biomedical subjects

W Haupt

Publications and source records attributed to W Haupt.

At least 19 recordsLinked to original sources
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↗
PubMed2001

The centromere1 (CEN1) region of Arabidopsis thaliana: architecture and functional impact of chromatin.

We have analysed the centromere 1 (CEN1) of Arabidopsis thaliana by integration of genetic, sequence and fluorescence in situ hybridisation (FISH) data. CEN1 is considered to include the centromeric core and the flanking left and right pericentromeric regions, which are distinct parts by structural and/or functional properties. CEN1 pericentromeres are composed of different dispersed repetitive elements, sometimes interrupted by functional genes. In contrast the CEN1 core is more uniformly structured harbouring only two different repeats. The presented analysis reveals aspects concerning distribution and effects of the uniformly shaped heterochromatin, which covers all CEN1 regions. A lethal mutation tightly linked to CEN1 enabled us to measure recombination frequencies within the heterochromatin in detail. In the left pericentromere, the change from eu- to heterochromatin is accompanied by a gradual change in sequence composition but by an extreme change in recombination frequency (from normal to 53-fold decrease) which takes place within a small region spanning 15 kb. Generally, heterochromatin is known to suppress recombination. However, the same analysis reveals that left and right pericentromere, though similar in sequence composition, differ markedly in suppression (53-fold versus 10-fold). The centromeric core exhibits at least 200-fold if not complete suppression. We discuss whether differences in (fine) composition reflect quantitative and qualitative differences in binding sites for heterochromatin proteins and in turn render different functional properties. Based on the presented data we estimate the sizes of Arabidopsis centromeres. These are typical for regional centromeres of higher eukaryotes and range from 4.4 Mb (CEN1) to 3.55 Mb (CEN4).

Arabidopsis↗
PubMed2000

Post-transcriptional inhibition of glutamine synthetase induction in rat liver epithelial cells exerted by conditioned medium from rat hepatocytes.

Recently, a soluble factor produced by primary periportal hepatocytes and different from glutamine was found to completely block induction of glutamine synthetase (GS) by dexamethasone (DEX) in the liver cell line RL-ET-1G. Using Northern and Western blotting we investigated whether this block is regulated on the transcriptional or the post-transcriptional level. Three different species of GS mRNA were detected that all increased (though in different proportions), when the cells were exposed to DEX for 24 h. Further maintenance for another 24 h in normal DEX-containing culture medium, conditioned medium from primary periportal hepatocytes or medium containing glutamine did not result in significant differences in GS mRNA levels. In contrast, GS protein and specific GS-activity remained high only under normal culture conditions, whereas both returned to basal levels in conditioned and glutamine-supplemented culture medium. Throughout, GS protein content and specific GS-activity strongly correlated (r = 0.98) excluding that GS-activity is regulated by chemical modification. These data suggest that the decrease in enzyme activity caused by cultivation in CM is controlled on the post-transcriptional level.

Animals↗
PubMed2000

Immunological surrogate parameters in a prognostic model for multi-organ failure and death.

OBJECTIVE: To assess the ability of clinical or biochemical parameters to predict outcome (survival or non-survival; severe or moderate/no complication) using multiple regression analyses. DESIGN: Prospective, descriptive cohort study with no interventions SETTING: 12 surgical intensive care units of university hospitals and large community hospitals; four medical school research laboratories in eight European countries PATIENTS: 128 surgical patients with major intra-abdominal surgery admitted for at least two days to an intensive care unit MAIN OUTCOME MEASURES: Prediction of complications or survival based on analysis of clinical (Multiple Organ Dysfunction Score, Multi-Organ-Failure Score, Acute Physiology and Chronic Health Evaluation II scores) and immunological (plasma levels of endotoxin, endotoxin neutralizing capacity, IL-6, IL-8, cell associated IL-8, Fc-receptor polymorphism, soluble CD-14) parameters, with comparison of predicted and actual outcomes. RESULTS: APACHE II, MODS score, MOF score, platelets, IL-6, IL-8, ENC, cell ass. IL-8 were significantly different between survivors and non-survivors and patients with/without severe complications by univariate analysis. By multivariate analysis only MOF, MODS score, IL-6, platelets, comorbidity predicted complications with a sensitivity of 82% and a specificity of 87%. Multivariate analysis demonstrated that only APACHE II score, plasma IL-8 and complications predicted death (sensitivity 84%; specificity 90%). CONCLUSION: Immunological surrogate parameters may predict complications and death of surgical ICU patients. The use of several parameters may add to increase sensitivity and specificity in a prognostic model.

APACHE↗
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

Prostaglandin EP receptor subtypes have distinctive effects on jejunal afferent sensitivity in the rat.

BACKGROUND & AIMS: Tissue levels of prostaglandin (PG) E(2) are increased in inflammatory bowel disease. The aim of this study was to characterize the potential for PGE(2) to modulate the sensitivity of intestinal afferents. METHODS: Electrophysiologic recordings were obtained from mesenteric afferent supplying the proximal jejunum of anesthetized rats. RESULTS: PGE(2) evoked a dose-dependent increase in afferent nerve discharge that was biphasic at higher doses. An early response phase, peak discharge frequency of 165.4 +/- 14.3 imp. s(-1), and duration of 20.2 +/- 1.2 seconds were followed by a plateau of elevated afferent nerve discharge lasting several minutes. The increase in afferent nerve discharge was accompanied by an increase in intestinal pressure of 4.4 +/- 0.5 cm H(2)O. Nifedipine (1 mg. kg(-1)) attenuated the pressure response and the plateau phase of afferent discharge, whereas the early component remained unchanged. In contrast, the early phase, but not the plateau phase, was reduced by luminal anesthetic. Experiments with EP receptor-selective agonists and the EP(1)-receptor antagonist AH-6809 (500 microg. kg(-1)) implicate EP1 receptors in the early response, and EP(2) receptors appeared to play a major role in the plateau phase. CONCLUSIONS: PGE(2) has complex actions on intestinal afferent discharge acting by direct and indirect mechanisms and mediated by different receptor subtypes.

Animals↗
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↗
PubMed2000

[Volumetry of pleural effusion in multi-morbidity, postoperative patients of a surgical intensive care unit. Comparison of ultrasound diagnosis and thoracic bedside image].

Aim of this study was to evaluate the importance of chest ultrasound and chest x-ray for the indication of thoracic drainage of pleural effusions in patients of an operative intensive care unit. Between December 1996 and June 1997 21 patients were included in a prospective trial in the operative intensive care unit. 26 thoracic drainages were used to drain pleural effusions. In all patients chest radiography in supine position and chest ultrasound were performed to assess the need of pleural drainage. Pleural fluid measured radiologically was categorized into 3 groups: pleural fluid less than 500 ml, 500 to 1,000 ml or more than 1,000 ml. The amount of the pleural effusion was sonographically determined by a standardized formula. After complete drainage of the pleural space the real volume of the fluid was measured and compared with the estimated value. The real amount of the fluid was correctly determined by chest radiographs in 16 cases (62%) and by chest ultrasound in 18 patients (69%). Pleural effusions less than 600 ml sonographically correlated much better with the real amount of the fluid than pleural effusions above 600 ml. In 8 cases (31%) ultrasound provided an additional information for correct indication of drainage. Considering both x-ray of the chest in supine position and chest ultrasound the correct indication to drain the pleural effusion was achieved in 25 cases (96%). In this prospective trial we compared chest ultrasound and chest radiography and demonstrated that ultrasound is more suitable to determine the amount of pleural effusions than radiography. In case of clinical and radiological suspicion on pleural effusion demanding for drainage a chest ultrasound should be performed to avoid underestimation of pleural fluid.

Adult↗
PubMed1999

Rabies--risk of exposure and current trends in prevention of human cases.

According to official WHO data more than 2.5 billion people are at risk in over 100 countries reporting the disease. Rabies mortality ranks ten in all infectious diseases worldwide. There are still about 50,000 to 60,000 human deaths annually although effective vaccines for post-exposure treatment are available. Most affected are the tropical countries in Africa, Asia, South America, and Oceania. The mortality figures range from about 0.001 per 100,000 for the US to 18 per 100,000 in Ethiopia. The vast majority (95-98%) of the 60,000 annual human death cases worldwide occur in canine (dog rabies) endemic regions with large stray dog population. Control of the disease is hampered by cultural, social and economic realities. In the rabies infested developing countries modern cell culture vaccines are hardly affordable. Dangerous neural tissue derived vaccines are still used. Three dose-saving treatment schedules have been developed: The reduced dose intramuscular 2-1-1 regimen, the two-site intradermal and the 8-site intradermal regimen. There is a critical shortage of human and purified equine rabies immunoglobulins, which are essential biologicals in the treatment of severe exposures.

Animals↗
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

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

Conditioned medium from cultured rat hepatocytes completely blocks induction of glutamine synthetase by dexamethasone in several rat liver epithelial cell lines.

A variant RL-ET-1G of a rat liver epithelial cell line (RL-ET-1) characterized by a very high inducibility for glutamine synthetase (GS) in response to dexamethasone was established by cultivation in glutamine-free, glutamate-supplemented culture medium. Using this cell line, conditioned medium produced by periportal hepatocytes in primary culture was found to suppress this induction, acting with a lag-phase of about 8 h irrespective whether the GS activity was basal or preinduced. Analysis of the response of several epithelial cell lines to the conditioned medium showed a reciprocal relationship between the dexamethasone-dependent induction and the residual activity after exposure to the conditioned medium, indicating that a hypothetical factor in the conditioned medium was interfering with the induction process but not with the basal GS level of these cells. Careful analysis revealed that the effect of the conditioned medium was neither due to deficiency of a component used up by the hepatocytes, nor due to glutamine or ammonia, both of which affected GS activity at concentrations above 0.5 mmol/L. The hypothetical factor was found to be quite small (molecular mass range 100-500 Da), heat and acid stable, as well as highly water soluble. Most interestingly, the conditioned medium did not suppress GS induction in astroglial cells and in the two hepatoma cell lines C2 and FAO, but strongly diminished the spontaneous induction of GS in cocultured pig hepatocytes, suggesting that the hypothetical factor acts primarily on normal nontransformed liver-derived cell populations.

Animals↗
PubMed1998

Histamine sensitivity of mesenteric afferent nerves in the rat jejunum.

The concept of functional interaction between mast cells and intestinal afferents is gaining support. We have therefore characterized the action of histamine on jejunal afferent discharge in the anesthetized rat. Whole nerve mesenteric afferent discharge was recorded in conjunction with intestinal pressure in response to a range of histamine agonists and antagonists. Histamine at 2, 4, and 8 micromol/kg (iv) evoked a dose-dependent biphasic increase in afferent discharge together with a biphasic rise in intestinal pressure. However, these two events were mediated independently, since nifedipine (1 mg/kg) substantially reduced the intestinal pressure increase but not the afferent discharge. These responses were completely inhibited by pyrilamine (5 mg/kg) but unaffected by ranitidine (5 mg/kg) or thioperamide (2 mg/kg). Neither the selective H2 receptor agonist dimaprit nor the selective H3 receptor agonist R-alpha-methylhistamine caused any modulation of afferent discharge. We conclude that histamine stimulates an H1 receptor-mediated increase in mesenteric afferent discharge that is independent of intestinal motor events. This suggests that histamine potentially acts as a mediator in mast cell-to-afferent nerve communication in the small intestine.

Afferent Pathways↗
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↗