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Biomedical subjects

M Köller

Publications and source records attributed to M Köller.

At least 91 records · Page 5Linked to original sources
PubMed1987

Metabolism of leukotriene B4 by polymorphonuclear granulocytes of severely burned patients.

Leukotriene B4 release from polymorphonuclear granulocytes of severely burned patients was reduced as compared to healthy donor cells. This decrease is due to an enhanced conversion of LTB4 into the 20-hydroxy- and 20-carboxy-metabolites and further to a decreased LTB4-synthesis. In addition, studies on the exogenous LTB4-conversion revealed an unidentified compound which was derived from LTB4. Our data suggest a modulation of the enzymatic activities involved in omega-oxidation of LTB4 (isoenzymes of cytochrome P-450).

Adult↗
PubMed1987

Altered arachidonic acid metabolism in granulocytes of polytraumatized patients.

The generation and metabolism of leukotrienes (LTs) from polymorphonuclear granulocytes of four polytraumatic patients on stimulation with the Ca-Ionophore A 23187 were studied by high performance liquid chromatography. In contrast to healthy donors the concentration of LTB4 within the supernatant of the stimulated granulocytes from these patients is reduced. The ratio of LTB4 versus the combined amounts of the biologically inactive 6-trans and 12-epi-6-trans-isomers is significantly decreased. In one patient who suffered from an Adult Respiratory Distress Syndrome (ARDS) a pronounced enhancement of LTC4 synthesis was observed.

Calcimycin↗
PubMed1987

Characterization of leukotriene B4-omega-hydroxylase activity within human polymorphonuclear granulocytes.

Human polymorphonuclear granulocytes (PMN) metabolize exogenous [3H]leukotriene B4 (LTB4) into 20-hydroxy- and 20-carboxy-[3H]LTB4. The conversion was enhanced at acidic pH values (pH 6.0-7.0). Sonication of purified PMN and subcellular fractionation by differential centrifugation showed that major LTB4-hydroxylase activity was associated with the microsomal fraction (105,000 g pellet). In contrast to intact cells, LTB4-hydroxylase activity within the microsomal fraction revealed optimal activity at neutral pH and was inhibited by a wide range of divalent cations. There was a strict requirement for the presence of suitable electron donors such as NADPH. Heterocyclic nitrogenous bases, such as imidazole and pyridine, inhibited the LTB4 conversion induced by intact PMN as well as by their microsomes. These observations combined with the spectrophotometric analysis (carbon monoxide dithionite-reduced difference spectrum) supported the assumption that LTB4-hydroxylase resembled a cytochrome P-450 enzyme. The LTB4-hydroxylase within human PMN was not identical with the cytochrome P-450 of rat liver; hepatic microsomes only showed minute conversion of LTB4.

Animals↗
PubMed1987

Release and functional characterization of the leukotriene D4-metabolizing enzyme (dipeptidase) from human polymorphonuclear leucocytes.

Polymorphonuclear leucocytes released LTD4-dipeptidase activity in a time-, calcium-, and cell number-dependent fashion. The LTD4-dipeptidase released from polymorphonuclear leucocytes (PMN) by incubation with calcium (0.91 mM) was detectable up to a cell concentration of 1 X 10(6)/ml and increased with higher concentrations. Maximal LTD4-dipeptidase activity within the extracellular environment was detected after 15 min of incubation (2 X 10(7)/ml) in the presence of 2-4.5 mM calcium or after 30 min, when stimulation was carried out with 0.91 mM calcium. The activity of the released LTD4-dipeptidase was modulated by various metal ions and other compounds. The addition of Mn2+, Co2+, and Zn2+ (final concentration 1 mM) enhanced the LTD4-dipeptidase activity, while Cu2+ led to a complete inhibition. In the absence of exogenous calcium EDTA inhibited LTD4-dipeptidase. Calcium up to a concentration of 5 and 10 mM decreased the dipeptidase activity. The LTD4-dipeptidase is not affected by bestatin, leupeptin, or N-ethyl-maleinimide (NEM). The Km of LTD4-dipeptidase for LTD4 was 0.95 +/- 0.2 microM and Vmax was 737.5 +/- 112.5 pmol/min X mg protein (n = 3 +/- SEM). The highest LTD4-dipeptidase activity was obtained at physiological pH values. LTD4-dipeptidase activity can also be released from other cell types, but the enzyme activity from human PMN exceeded that of other cells (e.g. human lymphocytes/monocytes and basophils (LMB) and human lung cell suspension).

Basophils↗
PubMed1987

The role of leukotriene-inducing and -metabolizing enzymes in inflammation.

Leukotrienes are potent mediators of allergy and inflammation. Polymorphonuclear granulocytes which participate in acute and chronic disease processes can be activated by immunological and nonimmunological stimuli to generate leukotrienes. It appears that on activation of the cells 5-lipoxygenase is released into the supernatant and thus may exert a potent role with regard to interdependent cellular interactions. The release of leukotriene-metabolizing enzymes (e.g., gamma-glutamyl-transpeptidase, dipeptidase) is stimulus-dependent. Polymorphonuclear granulocytes alter their release profile once the cells have been prestimulated. Thus, a precise knowledge on the leukotriene-inducing and -metabolizing enzymes is of utmost importance for future immunopharmacological interventions. It appears that the enzyme activity reflects the state of cellular activation.

Arachidonate 5-Lipoxygenase↗
PubMed1986

[Significance of leukotrienes in chronic respiratory tract diseases in childhood].

The role of lipoxygenase products was studied in children suffering from chronic diseases of the lung. Leukotrienes C4, D4, E4 and B4 were measured by high performance liquid chromatography (HPLC) and a specific radioimmunoassay (RIA) for C4. Elevated levels (up to 40 ng/ml), especially for leukotriene E4, were found in plasma of asthmatic and bronchitic patients (leukotriene C4 concentrations varied between 0.05 and 40 ng/ml, mean 4.9 +/- 7.8 ng/ml). In healthy donors the concentrations were below the detection limits of HPLC, leukotriene C4 ranging between 5 +/- 4 ng/ml (RIA data). The conversion of leukotriene C4 to D4 and E4 was observed by incubating the samples with synthetic leukotriene C4. The half-life of leukotriene C4 in plasma varied greatly, ranging from less than 12 min to 72 min (mean 39 +/- 16 min). Bronchial lavages yielded leukotriene C4 concentrations of 0.2 to 7 ng. Leukotriene E4 was detected in 10 of 41 cases. Conversion of leukotriene C4 did not occur in 50% of all cases, but was regularly observed in putrid lavages. These data suggest that leukotrienes play an important role in allergic and infectious lung diseases.

Adolescent↗
PubMed1986

Studies on the degradation of imipenem within serum and a renal kidney fraction.

The degradation of imipenem in vitro was analyzed using reversed-phase HPLC. The incubation of imipenem with a microsomal kidney fraction revealed the generation of two metabolites (UV-maxima at 275 or 308 nm, respectively). The metabolism of imipenem by the renal enzyme was completely inhibited by cilastatin (2 micrograms/ml). The lowest detectable inhibitory concentration of cilastatin was at 6.5 X 10(-10) M. The recovery of imipenem from serum was 52.6% after incubation for 2 h at 37 degrees C. The stability of the antibiotic within serum was improved by 13.9% in the presence of EDTA (10 mM) indicating a possible involvement of serum dipeptidases in the systemic breakdown of the imipenem molecule.

Animals↗
PubMed1986

[Present role of urethrocystography in the diagnosis of female stress incontinence].

Urethrocystography was performed in 72 women with stress urinary incontinence (SUI). The radiological findings were compared with the clinical diagnosis. 8 Patients with a normal radiological study had SUI grade I by clinical criteria. Explanations of this discrepancy are discussed. In 4 cases the interpretation interfered with a large cystocele. In 60 patients (83.5%) the radiological study confirmed the clinical diagnosis and supported the gynaecologist in the indication for operation on SUI. However this indication cannot be based on the radiological study by itself; it must in fact take into account all the other aspects of the disease.

Adult↗
PubMed1985

Cilastatin (MK 0791) is a potent and specific inhibitor of the renal leukotriene D4-dipeptidase.

The metabolism of leukotriene D4 to leukotriene E4 by a dipeptidase of kidney tissue is strongly inhibited by cilastatin (MK 0791) a known renal dehydropeptidase-I inhibitor. The comparison with similar enzyme activities from other tissues (liver, lung, serum, polymorphonuclear granulocytes) revealed a high specificity of cilastatin for the kidney enzyme which was found to be associated with the microsomal fraction. The lowest detectable inhibitory concentration of cilastatin within renal tissue was 8 X 10(-8)M.

Animals↗
PubMed1985

Functional characteristics of leukotriene C4- and D4-metabolizing enzymes (gamma-glutamyl transpeptidase, dipeptidase) within human plasma.

Several properties of the leukotriene C4- and leukotriene D4-metabolizing enzymes within human plasma were studied after fractionation of the plasma proteins using ammonium sulfate precipitation. Leukotriene D4-metabolizing enzymes were widely distributed among the fractions obtained. They showed different pH optima (pH 6.5, pH 7.0 and pH greater than or equal to 8.5) and revealed a different degree of thermal stability. The results indicate the presence of more than one enzyme in plasma which interacts with leukotriene D4. EDTA and L-cysteine inhibited the metabolism of leukotriene D4. Two leukotriene C4-metabolizing activities (gamma-glutamyl transpeptidases) differing in their molecular weights were detected after gel filtration. Their molecular weights were estimated to be Mr greater than or equal to 150 000 and Mr between 55 000 and 100 000.

Chromatography, Gel↗
PubMed1985

The metabolism of leukotrienes in blood plasma studied by high-performance liquid chromatography.

The metabolism of leukotrienes (B4, C4, D4, and E4) within human plasma was studied and a simple sample preparation is presented. It was demonstrated that leukotriene E4 and leukotriene B4 were stable during incubation at 37 degrees C using the in vitro system. In contrast, leukotriene C4 was metabolized by gamma-glutamyl transpeptidase activities into leukotriene D4 which was further metabolized by dipeptidase activities of plasma into leukotriene E4. The transition state inhibitor of gamma-glutamyl transpeptidase L-serine-borate decreased the metabolism of leukotriene C4 in plasma. Dilution of plasma demonstrated that the dipeptidase was more active compared to the gamma-glutamyl transpeptidase. The metabolizing activities of plasma were functionally characterized by fractionating the plasma proteins.

Blood Proteins↗
PubMed1979

Endogenous brain angiotensin II disrupts passive avoidance behavior in rats.

The presence of angiotensinogen, the precursor of angiotensin II (ANG II), in brain tissue and in cerebrospinal fluid (CSF) allows stimulation of endogenous brain ANG II by renin. Passive avoidance tests were performed in female Wistar rats. The animals received an electrical shock after entering a black box on the first experimental day. Avoidance was tested every 24 h for 5 consecutive days. Renin in doses of 0.01 and 0.1 units was injected once into the lateral brain ventricles 2 min before the first test. CSF ANG II increased from 40 to 4547 and 5152 fmol per ml (means), respectively. A dose-dependent disruption of avoidance learning was observed, the frequency to enter the black box increasing from 11% (control) to 29% and 46%, and the latency decreasing from 165 (control) to 143 and 116 sec, respectively. These effects were statistically significant (P less than 0.001) for more than 24 h and returned to control levels after 48 to 120 h. Administration of the converting-enzyme inhibitor SQ 14225 i.v.t. prior to renin injections abolished the renin effects. Injections of renin given 22 h after learning were without effect.

Angiotensin II↗
PubMedDate not supplied

Immunosuppressive agents enhance the cytokine-induced priming of inflammatory cells.

The influence of the immunosuppressive substances cyclosporin A (CsA), FK506 and rapamycin on inflammatory mediators from cytokine-primed human leukocytes was studied. The cells were primed with granulocyte/macrophage-colony-stimulating factor, granulocyte-stimulating factor (G-CSF) and interleukin-3 (IL-3), and subsequently stimulated with the chemotactic peptide fMLP. The immunosuppressive agents CsA and FK506 enhanced the release of leukotriene B4 (LTB4) from human neutrophil granulocytes dependent on the priming with G-CSF and IL-3. IL-3-primed neutrophils released up to threefold higher amounts of LTB4 after subsequent stimulation with FK506 and fMLP. In contrast, the immunosuppressant rapamycin inhibited the formation of LTB4 after subsequent stimulation with fMLP. In addition to the well-documented inhibitory effects on lymphocyte function, our results indicate an enhancing effect of the immunosuppressive agents on the cellular inflammatory response of human peripheral blood neutrophils.

Cytokines↗