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K Burger

Publications and source records attributed to K Burger.

At least 37 records · Page 2Linked to original sources
PubMed1998

Porcine myelomonocytic markers: summary of the Second International Swine CD Workshop.

Forty five mAbs submitted to the Second International Swine CD workshop were analyzed by six different laboratories for their possible reactivity with porcine myelomonocytic cells using flow cytometry and immunohistochemistry. As a result of these analyses, a new swine workshop cluster, SWC9, composed of two mAbs that recognize an antigen selectively expressed on mature macrophages, was defined. In addition, several mAbs were identified, allowing the differentiation of granulocytes from monocytes/macrophages, or monocytes from macrophages. Further work is required to identify the antigen recognized by these mAbs. Nevertheless, they should already prove useful for the identification of different stages in the macrophage maturation/differentiation, and will certainly aid analyses on the complexity of the mononuclear phagocyte system in the pig. Finally, the cross-reactivity of three anti-human CD14 mAbs with porcine myelomonocytic cells was established in this workshop.

Animals↗
PubMed1998

Workshop studies with monoclonal antibodies identifying a novel porcine differentiation antigen, SWC9.

Two monoclonal antibodies (mAb) within cluster M4 of the myeloid section of the Second International Swine CD Workshop, C4 (No. 144) and PM18-7 (No. 192), showed reactivity with thymocytes and among cells of myelomonocytic origin with mature macrophages but not with monocytes and granulocytes. Both mAb recognize a protein showing two bands of 205 kDa and 130 kDa under both reducing and non-reducing conditions. Although epitope mapping with these mAb could not be performed, this cluster received the SWC9 designation.

Animals↗
PubMed1998

Enkephalin analogs containing 4,4-difluoro-2-aminobutyric acid: synthesis and fluorine effect on the biological activity.

Analogs of Met-enkephalin and [D-Pen2, D-Pen5]enkephalin (DPDPE) containing the partially fluorinated amino acid 4,4-difluoro-2-aminobutyric acid (DFAB) in the 2- or 3-position of the peptide sequence were synthesized and their opioid activities and receptor selectivities were determined in vitro. The linear fluorinated [D-DFAB2, Met5-NH2]enkephalin showed mu and delta agonist potencies comparable to those of natural [Leu5]enkephalin. The partially fluorinated DPDPE analogs behaved differently as compared with their non-fluorinated correlates. While L-amino acid substitution in position 3 of DPDPE usually resulted in higher delta agonist potency than D-amino acid substitution. [D-DFAB3]DPDPE turned out to be a more potent delta agonist than [L-DFAB3]DPDPE. Furthermore, [D-DFAB3]DPDPE showed over 100-fold higher delta agonist potency than [D-Abu3]DPDPE (Abu = 2-aminobutyric acid), indicating that the fluorine substituents interact favorably with a delta opioid receptor subsite.

Aminobutyrates↗
PubMed1998

Acute effects of recombinant human interleukin-6 on endocrine and central nervous sleep functions in healthy men.

Interleukin-6 (IL-6) is a proinflammatory cytokine that has been shown to mediate, in addition to immune reactions, various endocrine and central nervous components of the acute phase response. In this context, the present study aimed to specify the contributions of IL-6 to the regulation of pituitary-adrenal secretory activity and GH and TSH secretion, as well as to the regulation of central nervous sleep and mood in healthy men. Effects of a low dose of IL-6 (0.5 microgram/kg body weight) were assessed, inducing plasma IL-6 concentrations closely comparable with those typically observed after infectious challenge. Each of the 16 male subjects participated in two 14-h sessions (between 1800 and 0800 h), receiving either placebo or human recombinant IL-6 sc at 1900 h. Blood was collected repeatedly to determine plasma hormone levels, serum concentrations of cytokines, and C-reactive protein. Moreover, mood was assessed, and sleep recordings were obtained between 2300 and 0700 h. The cytokine induced a prolonged increased in plasma concentrations of ACTH and cortisol (P < 0.001), but led to a decrease in TSH concentrations (P < 0.01). In response to IL-6, subjects reported fatigue and felt more inactive and less capable of concentrating than after placebo. Sleep architecture was altered significantly by the cytokine. Slow-wave sleep was decreased during the first half and increased during the second half of sleep. Rapid eye movement sleep during the entire nocturnal sleep time was significantly decreased. After IL-6, body temperature rose slightly. C-reactive protein concentrations were dramatically increased 12.5 h after substance administration (P < 0.001). IL-6 did not affect serum concentrations of IL-2, IL-8, interferon-alpha, and interferon-gamma. The results underscore the importance of IL-6 in the cascade of cytokines for the neuroendocrine response during the acute phase reaction. In addition, IL-6 appears to be involved in changes of sleep and behavior accompanying infection and inflammatory disorders.

Adrenal Glands↗
PubMed1997

Cholesterol as modulator of receptor function.

The modulatory effect of cholesterol on the function of two structurally related peptide receptors, the oxytocin receptor and the brain cholecystokinin receptor in plasma membranes as well as in intact cells, was analyzed. Different approaches for cholesterol modification were applied: (i) depletion and reloading of cholesterol mediated by methyl-beta-cyclodextrin and cholesterol-methyl-beta-cyclodextrin, respectively, in a reversible manner; (ii) mild treatment of the plasma membranes with cholesterol oxidase under control of the membrane fluidity as measured by fluorescence anisotropy of diphenylhexatriene; and (iii) filipin pretreatment of membranes. The results allowed us to distinguish two mechanisms of cholesterol affecting the ligand-binding function of receptors: changes of the membrane fluidity as demonstrated for the cholecystokinin receptor, or a putatively specific cholesterol-receptor interaction as shown for the oxytocin receptor. This was confirmed in a structure-activity analysis with a variety of sterol analogues substituting for cholesterol in the membranes. While the agonist binding of the cholecystokinin receptor was supported by each of the tested steroids and was well correlated with the corresponding fluorescence anisotropy values, a stringent and unique requirement of the oxytocin receptor's affinity state for structural features of the sterol molecule was found. The molecular requirements differ both from those postulated for sterol-phospholipid interactions and from those known to be necessary for the functional activity of other proteins. The different behavior of both peptide receptors concerning the cholesterol dependence of their ligand binding was also present in vivo at the level of signal transduction. The results suggest that cholesterol can modulate receptor function by two distinct mechanisms, by changes of the membrane fluidity, and/or by a highly specific molecular interaction.

Animals↗
PubMed1997

Peripheral blood stem cell (PBSC) mobilization with chemotherapy followed by sequential IL-3 and G-CSF administration in extensively pretreated patients.

Extensive pretreatment has been identified as a significant risk factor for failure of sufficient PBSC mobilization. From published data and our own experience we defined pretreatment variables which render patients at risk for not collecting at least 2.5 x 10(6) CD34-positive cells per kg bodyweight (BW). These variables were previous unsuccessful PBSC mobilization trial, previous large field radiotherapy, four or more cycles of myelosuppressive chemotherapy regimens, and combinations of extended field radiotherapy plus chemotherapy. Based on these inclusion criteria we treated 19 patients with disease-specific conventional-dose chemotherapy followed by sequential subcutaneous administration of IL-3 (5 microg/kg BW) for 5 consecutive days and G-CSF (10 microg/kg) until PBSC collection or neutrophil recovery. Patients were 10 males and nine females with a median age of 43 years. Diagnoses were non-Hodgkin's lymphoma n = 5, Hodgkin's disease n = 2, multiple myeloma n = 2, CML n = 4, AML n = 4 and testicular cancer n = 2. Twelve patients had prior unsuccessful trial of PBSC mobilization with chemotherapy followed by G-CSF. Except for mobilization chemotherapy-related neutropenic fever, no major toxicities (WHO grade > or = 2) were observed. Growth factors were well tolerated. Collection of at least 2.5 x 10(6) CD34-positive cells per kg BW was possible in 11 out of 19 patients (58%). In five out of 12 patients with a previous unsuccessful trial of PBSC mobilization, the study regimen mobilized sufficient CD34-positive cells. Nine patients went on to high-dose chemotherapy followed by autologous PBSC transplantation. Prompt hematologic recovery was seen in all of them. In conclusion, the sequential administration of IL-3 followed by G-CSF after conventional-dose chemotherapy allows successful PBSC collection in the majority of extensively pretreated patients.

Adult↗
PubMed1996

ATP-dependent redistribution of phosphatidylethanolamine in the plasma membrane of an epithelial and a hepatocytic cell line.

The redistribution of spin-labeled phospholipid analogues of sphingomyelin (SM) and phosphatidylethanolamine (PE) from the outer to the inner leaflet of the plasma membrane of an epithelial (CaCo-2) and a hepatocytic cell line (HepG2) was investigated. The amount of analogues in the outer leaflet was determined by their back-exchange to bovine serum albumin (BSA). For both cell lines a fast ATP-dependent inward movement of spinlabeled PE (SL-PE) was found while SL-SM redistributed only slowly by a passive mechanism. After depletion of intracellular ATP transverse diffusion of SL-PE was similar to that of SL-SM. The data are compatible with the presence of an aminophospholipid translocase in both cell lines.

Adenosine Triphosphate↗
PubMed1996

Endocrine effects of recombinant interleukin 6 in man.

In a phase II study, 5 male patients with a good performance status, who had metastatic renal cell carcinoma, received interleukin 6 (IL-6) to evaluate a possible antitumor effect of the cytokine. This offered the opportunity to investigate endocrine effects of IL-6 in man. The patients were studied the day before (day-1), and on days +1 and +21 of the IL-6 therapy (150 micrograms administered subcutaneously every day at 09.00 h). Blood was sampled at 09.00, 11.00, 13.00, 16.00, and 20.00 h. Compared with day -1, on days +1 and +21 serum levels of IL-6 were substantially elevated between 11.00 and 20.00 h. IL-6 significantly decreased serum thyrotropin (TSH) levels on day +1 (p < 0.05). The decrease was even more pronounced on day +21 when TSH concentrations were persistently below the respective values of day +1, suggesting, in addition to the acute action of IL-6, an effect developing with repeated IL-6 administrations. Total serum T3 and T4 levels were significantly lower on day +21 than on days -1 and +1. In contrast, free T3 and free T4 values did not differ among days -1, +1 and +21. Acutely, IL-6 had no effect on serum luteinizing hormone (LH) concentrations. However, on day +21, averaged serum LH levels (between 11.00 and 20.00 h) were significantly higher (8.4 +/- 1.1 IU/l) than on days -1 (6.5 +/- 0.2 IU/l) and +1 (6.4 +/- 0.4 IU/l). Average serum testosterone levels were slightly but not significantly enhanced on day +21. IL-6 did not influence follicle-stimulating hormone, growth hormone, or prolactin levels, neither acutely nor after 3 weeks of daily administration. The data indicate a modulating effect of IL-6 on secretory activity of different endocrine axes in man.

Carcinoma, Renal Cell↗
PubMed1996

Transbilayer movement of fluorescent and spin-labeled phospholipids in the plasma membrane of human fibroblasts: a quantitative approach.

All phospholipids in the plasma membrane of eukaryotic cells are subject to a slow passive transbilayer movement. In addition, aminophospholipids are recognized by the so-called aminophospholipid translocase, and are rapidly moved from the exoplasmic to the cytoplasmic leaflet of the plasma membrane at the expense of ATP hydrolysis. Though these principal pathways of transbilayer movement of phospholipids probably apply to all eukaryotic plasma membranes, studies of the actual kinetics of phospholipid redistribution have been largely confined to non-nucleated cells (erythrocytes). Experiments on nucleated cells are complicated by endocytosis and metabolism of the lipid probes inserted into the plasma membrane. Taking these complicating factors into account, we performed a detailed kinetic study of the transbilayer movement of short-chain fluorescent (N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl); NBD) and, for the first time, spin-labeled analogues of phosphatidylcholine (PC), -ethanolamine (PE), -serine (PS), and sphingomyelin (SM) in the plasma membrane of cultured human gingival fibroblasts. At 20 degrees C, the passive transbilayer diffusion of NBD analogues was very slow, and the choline-containing NBD analogues were internalized predominantly by endocytosis. Spin-labeled analogues of PC and SM showed higher passive transbilayer diffusion rates, and probably entered the cell by both passive transbilayer movement and endocytosis. In contrast, the rapid uptake of NBD- and spin-labeled aminophospholipid analogues could be mainly ascribed to the action of the aminophospholipid translocase, since it was inhibited by ATP depletion and N-ethylmaleimide pretreatment. The initial velocity of NBD-aminophospholipid translocation was eight to ten times slower than that of the corresponding spin-labeled lipid, and the half-times of redistribution of NBD-PS and spin-labeled PS were 7.2 and 3.6 minutes, respectively. Our data indicate that in human fibroblasts the initial velocity of aminophospholipid translocation is at least one order of magnitude higher than that in human erythrocytes, which should be sufficient to maintain the phospholipid asymmetry in the plasma membrane.

Adenosine Triphosphate↗
PubMed1996

Effects of furosemide on hemorheologic alterations induced by incremental treadmill exercise in thoroughbreds.

OBJECTIVE: To determine whether furosemide treatment altered the blood flow properties and serum and RBC electrolyte concentrations of Thoroughbreds during submaximal treadmill exercise. DESIGN: Thoroughbreds were subjected to submaximal treadmill exercise with and without treatment with furosemide (1 mg/kg of body weight, IV). ANIMALS: 5 healthy Throughbreds that had raced within the past year and had no history of exercise-induced pulmonary hemorrhage. PROCEDURE: Venous blood samples were obtained before exercise, at treadmill speeds of 9 and 13 m/s, and 10 minutes after exercise, and hemorheologic and electrolyte test results were determined. RESULTS: Hemorheologic changes 60 minutes after furosemide administration included increased PCV, plasma total protein concentration, whole blood viscosity, mean RBC volume, and RBC potassium concentration, and decreased serum potassium concentration, serum chloride concentration, and RBC chloride concentration. Furosemide treatment attenuated the exercise-associated changes in RBC size, serum sodium concentration, serum potassium concentration, RBC potassium and chloride concentrations, and RBC density; exacerbated exercise-associated increases in whole blood viscosity; and had no effect on RBC filterability. CONCLUSIONS: The hemorheologic effects of furosemide probably occurred secondary to total body and transmembrane fluid and electrolyte fluxes and would not improve blood flow properties. CLINICAL RELEVANCE: The beneficial effects of furosemide treatment in reducing the severity of bleeding in horses with exercise-induced pulmonary hemorrhage cannot be explained by improved blood flow properties.

Animals↗
PubMed1996

Effects of pentoxifylline on hemorheologic alterations induced by incremental treadmill exercise in thoroughbreds.

OBJECTIVES: To determine whether pentoxifylline treatment altered hematologic, rheologic, electrolyte, or blood gas test results of Thoroughbreds during submaximal treadmill exercise. ANIMALS: 5 healthy Thoroughbreds that had raced within the past year and had no history of exercise-induced pulmonary hemorrhage. PROCEDURE: Mixed venous blood samples were obtained before exercise, at treadmill speeds of 9 and 13 m/s, and 20 minutes after exercise; hematologic, rheologic, electrolyte, and blood gas test results were determined. RESULTS: Pentoxifylline treatment resulted in a 45% reduction in RBC filtration pressures for horses at rest. The improved RBC filterability persisted during treadmill exercise. Horses treated with pentoxifylline had a greater decrease in Po2 values and a lesser increase in plasma lactate concentration during treadmill exercise. CONCLUSION: Administration of pentoxifylline improved RBC deformability of horses at rest and during treadmill exercise. CLINICAL RELEVANCE: Improved RBC deformability resulting from pentoxifylline treatment may reduce exercise-associated shear stress in pulmonary capillaries, thereby attenuating exercise-induced pulmonary hemorrhage.

Analysis of Variance↗
PubMed1995

Inflammatory cytokine expression in swine experimentally infected with Actinobacillus pleuropneumoniae.

An Actinobacillus pleuropneumoniae infection model in swine was established to study the expression of inflammatory cytokines during acute respiratory disease. Lavage fluid, lavage cells consisting primarily of alveolar macrophages, and lung tissue were analyzed for the presence of various cytokines at 2, 4, 8, and 24 h following endotracheal inoculation of A. pleuropneumoniae. Interleukin-1 beta (IL-1) and IL-8 mRNA levels were elevated within 2 h in lavage cells of animals inoculated with A. pleuropneumonia but not in cells from controls treated with saline-bovine serum albumin, based on Northern (RNA blot) analysis. Tumor necrosis factor (TNF) mRNA was present at low levels in all animals, and the level was not increased at any time point. In situ hybridization was more sensitive than Northern blotting and revealed elevations of all three cytokines in lavage cells within 2 to 4 h of A. pleuropneumoniae inoculation. IL-6 was detected in lavage cells by in situ hybridization but not by Northern blotting. In lung tissue obtained 18 to 24 h after A. pleuropneumoniae instillation, all cytokine mRNAs, including that of IL-6, were detected by Northern blot analysis. The levels of bioactive IL-1 and IL-6 in lavage fluids increased approximately 1,000-fold following A. pleuropneumoniae inoculation, but TNF bioactivity was not detected. Morphological localization of cytokine mRNAs by in situ hybridization indicated markedly increased levels of TNF, IL-1, and IL-8 mRNAs at the periphery of focal lung lesions. These findings indicate that inflammatory cytokines, particularly IL-1 and IL-8, are associated with the development of pleuropneumonia and may contribute to disease severity.

Actinobacillus Infections↗
PubMed1993

[Structural and equilibrium studies of the proton and copper(II) complexes of N-D-gluconylglycine].

N-D-Gluconylglycine, a pseudopeptide derivative glucono-delta-lactone and glycine, was prepared and the equilibrium constants of its protonation and copper(II) coordination and the structures of the copper complexes formed were studied in aqueous solution by potentiometry, spectrophotometry, CD, EPR and 13C-NMR relaxation. The parent complexes formed in acidic medium have low stabilities, characteristic of carboxylate coordination. In the pH range 5-9, the amide group and the 2-OH group of the ligand undergo deprotonation. In parallel with these processes, one ligand is replaced from the copper(II) coordination sphere. For the species MLH-2' we propose (30, 1N) coordination in the equatorial plane around the copper(II). EPR measurements indicate that dimeric species are also formed. At pH > 9, further base-consuming processes start as an indication of the deprotonation of other alcoholic hydroxy groups of the sugar moiety or the formation of mixed hydroxy complexes.

Circular Dichroism↗
PubMed1992

Lymphoma imaging with a new technetium-99m labelled antibody, LL2.

The lesion detection capability of a new technetium-99m labelled B-cell lymphoma monoclonal antibody (MoAb) imaging agent, LL2, was evaluated in 8 patients with non-Hodgkin's lymphoma and 1 patient with chronic lymphocytic leukaemia. The MoAb kit consists of a 1-vial, 1-mg Fab' form of LL2 ready for instant labelling with technetium. The patients were injected with approximately 925 MBq (25 mCi) of 99mTc-LL2 Fab' (1 mg), and planar and single photon emission tomography (SPET) studies were performed at 3-4 h post injection and at 24 h. There was no evidence of thyroid or stomach activity up to 24 h. Uniform splenic uptake was seen in all patients. Two non-lymphoma patients were also administered with the same agent and demonstrated a similar splenic distribution; therefore, splenic targeting was not scored as tumour-specific. A total of 29 from 48 tumour sites were detected by scintigraphy, including tumours of various grades and histological types. Excluding 1 patient who had a large tumour burden of over 500 g, 29 of 33 lesions were detected. One patient was free of disease at the time of the study and had a negative scan. Another patient showed excellent targeting of gallium-negative sites in the liver and bone. The bone involvement was not known prior to the antibody study and was subsequently confirmed by a bone scan. Additional sites of MoAb localization could not be followed in this group, since most patients went on to radioimmunotherapy immediately following the 99mTc-LL2 study.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1991

Sex hormone concentrations in men with angiographically assessed coronary artery disease--relationship to obesity and body fat distribution.

The relationship between circulating sex hormone levels and the occurrence of coronary artery disease (CAD) was studied in a group of 274 men undergoing coronary angiography. Hormone levels in men with CAD (n = 200) were compared to those in men found to be free of coronary lesions (n = 74). No significant differences were found for serum concentrations of estradiol, total testosterone, sex-hormone-binding globulin, free androgen index, dehydroepiandrosterone sulfate, or cortisol between the two groups. Serum androgens were negatively correlated to age in both groups, whereas estradiol was weakly associated with total cholesterol in the group of men without CAD. No consistent associations were detected between sex hormone levels and the degree of obesity or the distribution of body fat, the latter being assessed by the ratio of waist-to-hip circumferences. The results of this study do not support a significant role of sex steroid hormones in coronary artery disease in men.

Adult↗
PubMed1990

Body fat distribution in men with angiographically confirmed coronary artery disease.

Body fat distribution and its relationship to coronary artery disease and established cardiovascular risk factors have been studied in a cohort of 286 men aged between 30 and 74 years undergoing coronary angiography. 207 (72.4%) patients showed stenosis (greater than 30%) or occlusion of one or more coronary arteries. whereas the remaining 79 (27.6%) men were free of coronary lesions and served as a control group. 112 men with angiographically defined coronary artery disease had an additional history of myocardial infarction. Body fat distribution was assessed by determining the waist-to-hip circumference ratio. A stepwise logistic regression analysis revealed that in addition to LDL-cholesterol (P = 0.0001) and age (P = 0.0005) an abdominal type of body fat distribution (P = 0.0129) is also a significant risk indicator for the occurrence of coronary artery disease (CAD) independent of body weight and other factors such as total cholesterol, HDL-cholesterol, triglycerides, insulin, systolic and diastolic blood pressure. The results of this study suggest that an abdominal type of fat distribution is associated with an increased risk of coronary artery disease.

Adipose Tissue↗
PubMed1990

Antiischemic and hemodynamic effects of intravenous isradipine, a new calcium antagonist, in coronary heart disease: a comparative double-blind cross-over study with nifedipine.

In a double-blind cross-over study, 10 patients with stable angina pectoris owing to coronary heart disease were investigated in supine position during rest and bicycle exercise for the effect of 0.4 mg of intravenous (i.v.) isradipine in comparison to 2 mg i.v. nifedipine on cardiac hemodynamics and myocardial ischemia. At rest, both drugs significantly decreased total peripheral resistance (TPR) and mean arterial blood pressure (MAP), whereas heart rate (HR) increased. The pressures and resistance of the pulmonary circulation remained uninfluenced at rest. During symptom limited-exercise, both medications reduced TPR despite an unchanged MAP. Mean pulmonary artery pressure decreased significantly after both medications, whereas right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVR) decreased significantly only after nifedipine. The improvement of mean ischemic ST-segment depression averaged 44 +/- 6% (mean +/- SEM, p less than or equal to 0.01) after nifedipine and 45 +/- 7% (p less than or equal to 0.01) after isradipine. The time until angina appeared increased after isradipine by 89 +/- 28% (p less than or equal to 0.05) and after nifedipine by 105 +/- 42% (p less than or equal to 0.01). Significant differences between the two medications appeared only for cardiac output (CO) at rest (p less than or equal to 0.05), during which state the increase after isradipine was higher than after nifedipine, and for exercise HR (p less than or equal to 0.01), during which state only nifedipine induced a significant increase in frequency. We conclude that at the chosen dosages the hemodynamic and antiischemic effects of isradipine are similar to the effects that occur after nifedipine.

Calcium Channel Blockers↗