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A Lochner

Publications and source records attributed to A Lochner.

At least 73 records · Page 4Linked to original sources
PubMed1990

Glycosphingolipid expression on murine L1-fibrosarcoma cells: analysis of clonal in vivo and in vitro selected sublines with different lung colonisation potential.

The patterns of acidic and neutral glycosphingolipids (GSLs) were examined in a syngeneic tumour system in Balb/c mice consisting of closely related cell lines with different colonisation potentials directed to the murine lungs (in vivo selected highly metastatic sublines of L1-fibrosarcoma cells and their WGA-resistant mutants with low metastatic potential). GSLs were analysed by high-performance thin-layer chromatography and structurally identified by fast atom bombardment mass spectrometry combined with compositional analyses and exo-glycosidase digestion. The results suggest that highly metastatic sublines L1-LM and L1-LM12 derived by in vivo selection from mouse fibrosarcoma cells (cell line L1) exhibit a drastic increase of polar ganglioside expression and a restriction to globo-series GSLs. Contrasting with this the low metastatic mutant cells (L1-LM13WGA) express a reduced portion of acidic GSLs and exhibit a shift to less polar ganglioside components. Total cellular and plasma membrane-integrated GSLs were demonstrated to exhibit largely identical patterns. Concomitant with a significant decrease in LacCer expression a substantial reduction of GM2 and a complete lack of GM3 expression can be assigned to the highly metastatic sublines of L1-cells. On the other hand, the more polar gangliosides GM1a and, to an even greater extent, GD1a (exceeding 70% of total gangliosides) accumulate on L1-LM and their clonal sublines. The shift to acidic GSLs of higher polarity is less pronounced on the low metastatic WGA-resistant mutant cells (L1-LM13WGA) showing a preponderance of GM1a. The portion of GD1a within the fractions of acidic GSLs does not correspond to the cellular activities of CMP-NeuAc/GM1 (alpha 2-3) sialyltransferase measured for high and low metastatic cell variants. Total sialic acid content of the various cell lines differs, but is not associated with the metastatic potential. Gangliosides on L1-cells exhibit a significant substitution of N-glycolyl for N-acetylneuraminic acid (13%) compared to their metastatic sublines and to mutant cells (less than 1%). A conversion of surface exposed GD1a to GM1a on membranes of metastatic cells by in situ treatment with Vibrio cholerae sialidase is associated with a significant reduction of tumour cell colonisation directed to the murine lungs.

Animals↗
PubMed1990

[Behavior of postoperative viscosity of bile fluid from T-drainage. A contribution to cholelithogenesis].

The results obtained by the examination of the post-operative bile viscosity behaviour sampled by T-drainages of 29 patients (investigations of the relative viscosity with the help of a modified horizontal capillary viscometer from the day of operation until the 9th postoperative day) confirm the importance of the biorheological classification of bile fluid as a Maxwell fluid (investigations of the absolute dynamic viscosity of 33 bile specimens with a Contraves-Low-Shear-Viscometer and representation of flow curves for rheological characterization). The Maxwell flow behaviour is characterized--among other things--by an exponential increase in the case of prestasis. This fact is important in all "low-flow-states" of different pathophysiological genesis and offers a concept with respect to a pathogenetically orientated cholelithiasis prophylaxis.

Adult↗
PubMed1989

Phosphatidylcholine biosynthesis in myocardial ischaemia.

In this study the effect of myocardial ischaemia was evaluated on two aspects of phospholipid metabolism: (i) the de novo synthesis of myocardial phospholipids, as indicated by the incorporation of (methyl-3H) choline and (ii) the incorporation of radiolabelled long chain fatty acids into tissue phospholipids. Two models of ischaemia were used namely normothermic ischaemic arrest and hypoxic, low-flow perfusion of the isolated rat heart. The results showed that within 10 min, hypoxic low-flow perfusion significantly inhibited the incorporation rate of (methyl-3H) choline into tissue phospholipids. Since the tissue choline content remained unaltered under these conditions, the results suggested that the de novo synthesis of phosphatidylcholine is very susceptible to ischaemic damage. Inhibition of (methyl-3H) choline incorporation into tissue phospholipids appeared to be due to both a reduction in choline uptake and specific inhibition of the CDP pathway. Perfusion with glucose (10 mM) as substrate completely abolished the ischaemia-induced reduction in (methyl-3H) choline incorporation, indicating that glycolytically produced ATP played an important role in phosphatidylcholine biosynthesis. In contrast to these results, myocardial ischaemia stimulated the incorporation of long-chain saturated and unsaturated fatty acids into tissue phospholipids. In summary, the results obtained showed that myocardial ischaemia profoundly affected phospholipid metabolism which, in turn, might contribute to membrane damage.

Adenosine Triphosphate↗
PubMed1989

Radiation-induced changes in the ultrastructure and mechanical function of the rat heart.

A time sequence study was performed to study the early effects of radiation on the ultrastructure of the rat heart. Wistar rats were exposed to 20 Gy electron irradiation to a field including the heart and a third of the lung. The hearts were excised at varying time intervals (1 h-180 days), and the ultrastructure of perfusion-fixed subepicardium and subendocardium studied. Changes were observed in both myocytes and interstitium at all time intervals. The most pronounced change observed in the myocyte was that of intercalated disc damage which reached a peak at 30 days post-irradiation. Mitochondrial damage, characterized by swelling and fenestration in areas of myofibrillar contracture, was focal and relatively scarce. Swelling of the capillary endothelial cells and collapse of the capillaries were marked up to 60 days. Of significance was the observation that the damage to both myocytes and interstitium receded after 60 days and the hearts exhibited an almost normal ultrastructure from 100 to 180 days post-irradiation. Mechanical function of these hearts followed a similar pattern: maximal depression was observed 60 days after irradiation. Thereafter the work performance of these hearts improved significantly, almost reaching control levels after 180 days.

Animals↗
PubMed1988

Sarcolemmal phospholipid fatty acid composition and permeability.

In this study, the mechanism of ischaemia-induced increased sarcolemmal permeability, as manifested by release of intracellular enzymes, was investigated. The role of changes in the sarcolemmal phospholipid bilayer in this process was evaluated by experimental modulation of the phospholipid fatty acid composition. The isolated perfused rat heart subjected to low-flow hypoxia, was used as a model of global ischaemia. Glucose as well as saturated (palmitate) and unsaturated (linoleate) long-chain fatty acids were used as substrates. Hearts perfused with palmitate or linoleate (1.5 mM, fatty acid/albumin ratio, 3.4) showed a significantly higher rate of lactate dehydrogenase release in both control and ischaemic conditions than hearts perfused with glucose (10 mM). Lactate dehydrogenase release in the fatty acid-perfused hearts was associated with a significant increase in the percentage unsaturation of the sarcolemmal phospholipid fatty acids. Glucose-perfused hearts, on the other hand, showed only minor changes in the sarcolemmal phospholipid fatty acid composition. Attempts to correlate enzyme release directly with an increase in the percentage unsaturation of phospholipid fatty acids failed, since enzyme release was also stimulated in control fatty-acid-perfused hearts which (when compared with glucose) contained a higher percentage saturated phospholipid fatty acids. The results suggest that myocardial ischaemia, apart from changes in the sarcolemmal phospholipid fatty acid composition, also induces several other changes in sarcolemmal composition (e.g., cholesterol loss) which may affect is permeability for macromolecules.

Animals↗
PubMed1988

Enzymatic and structural modifications of mitochondrial NADH-ubiquinone reductase with autolysis as experimental model.

Complex I (nicotinamide adenine dinucleotide-ubiquinone reductase) is a complex enzyme system located in the inner mitochondrial membrane. It has the ability to catalyze several different enzymatic reactions in electron transport, and is known to be one of the respiratory chain components most sensitive to ischaemia. Mitochondria and two complexes I (complex IA and complex IB) were isolated from normal and ischaemic myocardial tissue. Enzymatic activities, polypeptide composition, as well as other components such as non-haem iron, acid-labile sulphur and ubiquinone, were determined. The results indicated that complex IB reflected the enzymatic changes in the mitochondria during myocardial ischaemia, but complex IA did not. The lesion that resulted from ischaemia was localised as altered enzymatic activities due to a different polypeptide composition, as well as loss of ubiquinone and non-haem iron from complex IB.

Animals↗
PubMed1988

Oxygen requirements of the isolated rat heart during hypothermic cardioplegia. Effect of oxygenation on metabolic and functional recovery after five hours of arrest.

Previous studies from this laboratory demonstrated that the use of an oxygenated cardioplegic solution in the hypothermic arrested rat heart resulted in improved preservation of high-energy phosphate stores (adenosine triphosphate and creatine phosphate), mechanical recovery during reperfusion, and preservation of myocardial ultrastructure. In the current study the effect of cardioplegic solutions oxygenated with 30%, 60%, and 95% oxygen was evaluated in the isolated rat heart with reference to the maintenance of adenosine triphosphate, creatine phosphate, oxygen consumption, functional recovery, and mitochondrial oxidative phosphorylation in vitro. Results indicate that the hearts receiving cardioplegic solutions supplemented with 95% oxygen and 5% carbon dioxide maintained adenosine triphosphate and creatine phosphate at control values for at least 5 hours. The oxygen consumption during elective cardiac arrest, mechanical performance during reperfusion, and in vitro mitochondrial oxygen uptake and phosphorylation rate were highest in the hearts receiving cardioplegic solutions supplemented with 95% oxygen when compared to solutions with 30% and 60% oxygen. Addition of glucose and insulin to the cardioplegic solution (95% oxygen) increased the adenosine triphosphate levels but failed to improve function after reperfusion. Although myocardial adenosine triphosphate and creatine phosphate were well preserved by the oxygenated cardioplegic solution, there was a discrepancy between the adenosine triphosphate levels at the end of the arrest period, which represents the potential for mechanical function, and the actual function of the hearts after 5 hours.

Adenosine Triphosphate↗
PubMed1987

Mitochondrial Ca2+ fluxes and levels during ischaemia and reperfusion: possible mechanisms.

It has been shown that myocardial ischaemia depresses the uptake and enhances the release of Ca2+ by mitochondria. Reperfusion of the ischaemic areas may result in a further deterioration of the above processes. Despite these marked changes in Ca2+ fluxes, reperfusion has been shown always to be associated with a marked increase in mitochondrial Ca2+ content. To explain the latter observation, it has been proposed that reperfusion promotes respiration-supported mitochondrial Ca2+ uptake in preference to ADP phosphorylation. To evaluate this hypothesis, the effect of exogenous ADP on mitochondrial respiration-linked Ca2+ uptake was investigated in control, ischaemic and ischaemic-reperfused hearts. The results show that ADP significantly depresses mitochondrial Ca2+ uptake in all three preparations, indicating that Ca2+ is not taken up preferentially to ADP phosphorylation in reperfused tissue. It is suggested that reperfusion-induced increased mitochondrial Ca2+ levels are probably not due to increased respiration-linked Ca2+ uptake, but rather to augmented conversion of ionized Ca2+ to calcium phosphate which does not participate in ionic fluxes.

Adenosine Diphosphate↗
PubMed1987

Ultrastructural observations on the effects of different substrates on ischaemic contracture in global subtotal ischaemia in the rat heart.

Ultrastructural morphology was examined in myocardia perfused with different substrates, following the hypothesis that ultrastructural changes or differences would indicate the mechanism of early ischaemic contracture. Substrates used were glucose, acetate and no substrate (substrate-free). Isolated rat hearts were subjected to global low flow ischaemia followed by perfusion fixation at either no contracture, early contracture (5%) or full contracture (100%). Total tissue adenosine triphosphate (ATP) levels were analysed from myocardia of each group. Glucose perfused myocardia did not develop contracture for at least 30 minutes and maintained ultrastructural and ATP normality. Substrate-free and acetate perfused myocardia developed contracture after 10-12 minutes of ischaemia at which time myofibrillar morphology was altered within small sparse foci of developing mild oedema with contracture and hyperextension of myofibrils. ATP levels were normal. At full ischaemic contracture, both substrate-free and acetate perfused myocardia showed severe mitochondrial damage, oedema, myofibrillar contracture and hyperextension with accompanying distortion and swelling of the sarcoplasmic reticulum.

Animals↗
PubMed1986

Gas chromatographic-mass spectrometric analysis of volatile constituents in saliva.

Present methods for the development of metabolic profiles are limited to the use of headspace techniques and solvent extraction methods. A new method for the development of saliva profiles which provides information complementary to existing analyses has been developed. The results of the developed methodology provide a reliable, reproducible method for metabolic profiling. Gas chromatographic-mass spectrometric analysis of the volatile constituents provided positive identification of 39 compounds. Application of the developed protocol toward the investigation of saliva as a vehicle for the non-invasive detection of certain pathological states, specifically diabetes mellitus and liver disorders, may be possible.

Cholesterol↗
PubMed1986

Mitochondrial Ca2+ fluxes: role of free fatty acids, acyl-CoA and acylcarnitine.

It has been suggested that accumulation of lipid metabolites, such as fatty acids, fatty acyl-CoA and acylcarnitine, in the ischaemic myocardium, may be responsible for disturbances in mitochondrial Ca2+ fluxes. In view of the presence of an intracellular fatty acid binding protein, the question arose whether these intermediates affect mitochondrial Ca2+ uptake and release similarly in vivo. In this study the effects of linoleic acid, palmitic acid, palmitoyl-CoA and palmitoylcarnitine were studied on mitochondrial Ca2+ fluxes in the absence and presence of albumin, an avid binder of fatty acid derivatives. Albumin reversed the effects of the above compounds on mitochondrial Ca2+ uptake and release, suggesting that the presence of an intracellular fatty acid binding protein may protect the ischaemic myocardial cell against the deleterious effects of accumulated fatty acid derivatives.

Acyl Coenzyme A↗
PubMed1986

Isolation of a physiologically active and a physiologically inactive mitochondrial NADH-ubiquinone reductase (complex I) from donkey hearts.

The method described for the isolation of mitochondrial complex I (NADH-ubiquinone reductase) from bovine hearts could not be applied to donkey hearts as unacceptably large losses in enzyme activity occurred. This method was modified for the isolation of complex I using donkey hearts and two complexes were obtained: complex IA which was physiologically inactive and complex IB which was physiologically active as it catalyzed the reaction from NADH to ubiquinone. Both complexes had relatively low enzyme activity with artificial electron acceptors, except with potassium ferricyanide, and had more or less the same amount of acid-labile sulfur and nonheme iron although the polypeptide composition differed to a great extent.

2,6-Dichloroindophenol↗
PubMed1986

Changes in NADH-ubiquinone reductase (complex I) with autolysis in the rat heart as experimental model.

Complex I (NADH-ubiquinone reductase) is a complex system located in the inner mitochondrial membrane and has the ability to catalyse several different enzymatic reactions concerned in electron transport. It is known to be one of the first components of the respiratory chain to be damaged by ischemia. Our results, using autolysis in the rat heart as experimental model, indicate that the NADH dehydrogenase system was impaired relatively early during ischemia while transhydrogenation and NADPH dehydrogenation appeared to be relatively resistant.

2,6-Dichloroindophenol↗
PubMed1986

Effect of oxygenated crystalloid cardioplegia on the functional and metabolic recovery of the isolated perfused rat heart.

The use of an oxygenated crystalloid cardioplegic solution to improve myocardial preservation during elective cardiac arrest was evaluated with the isolated perfused rat heart used as a model. Experiments were conducted at 4 degrees C and 20 degrees C. The oxygen tension of the nonoxygenated and oxygenated cardioplegic solutions averaged 117 and 440 mm Hg, respectively. At 4 degrees C, the adenosine triphosphate content of hearts subjected to 120 minutes of oxygenated cardioplegia was significantly higher than that of the nonoxygenated cardioplegia group. However, functional recovery during reperfusion was similar for both groups. At 20 degrees C, the myocardial adenosine triphosphate concentration decreased at a significantly faster rate during ischemia in the group receiving nonoxygenated cardioplegia compared with the oxygenated cardioplegia group. Hearts subjected to 180 minutes of ischemia with oxygenated cardioplegia had a normal ultrastructural appearance whereas hearts subjected to 120 minutes of nonoxygenated cardioplegia showed severe ischemic damage. Myocardial functional recovery in the group receiving oxygenated cardioplegia exceeded that of the group receiving nonoxygenated cardioplegia. The use of myocardial adenosine triphosphate concentration at the end of the ischemic period to predict subsequent cardiac output, peak systolic pressure, and total myocardial work showed significant positive correlations.

Adenosine Triphosphate↗
PubMed1985

Mitochondrial phospholipid composition and microviscosity in myocardial ischaemia.

Normothermic ischaemic arrest of the isolated perfused rat heart causes profound changes in mitochondrial ultrastructure. Since the mitochondrial membranes contain a high percentage of phospholipids, an evaluation of the effect of different periods of ischaemia on mitochondrial phospholipid content and fatty acid composition was made. The results showed that ischaemia had no effect on the content of the different phospholipid classes and no correlation was observed between ultrastructural changes and mitochondrial phospholipid content. However, the phospholipid fatty acid composition of several phospholipids showed marked changes. For example, with lysophosphatidylcholine a progressive increase in the percentage saturated fatty acids was observed with increasing periods of ischaemia, while a reduction occurred in lysophosphatidylethanolamine. To determine whether the ischaemia-induced changes in mitochondrial phospholipid fatty acid composition had an effect on the physical properties of the membrane, the microviscosity of mitochondrial preparations was studied, using the lipophilic probe, 1,6-diphenyl-1,3,5-hexatrine. Mitochondria isolated from ischaemic hearts showed a progressive increase in fluorescence polarization with longer periods of ischaemia, indicating an overall increase in microviscosity. This phenomenon may be responsible for the increased mitochondrial fragility which is characteristic of ischaemic damage.

Animals↗
PubMed1984

Myocardial tissue free fatty acids.

Myocardial ischaemia, whether produced by coronary artery ligation or by hypoxic low-flow perfusion of the isolated rat heart, has been shown to be associated with a significant depression in mitochondrial function, as well as an increase in tissue free fatty acid (FFA) levels. Although the effects of FFA on mitochondrial oxidative phosphorylation function in vitro are well established, it has not yet been shown that increased tissue FFA levels are causing the depression in mitochondrial function in ischaemia. Using the isolated perfused rat heart, several experiments were performed to gain more information regarding (i) the validity of the Dole FFA extraction technique; (ii) controlling factors; (iii) the relationship between tissue FFA and mitochondrial function and (iv) sources of tissue FFA in ischaemia. Significant elevation of tissue FFA was achieved by perfusion with (i) substrate-free Ringer and (ii) phosphatidylcholine. Elevation of tissue FFA obtained by perfusing with long-chain fatty acids was due to extracellular accumulation. Reduction of tissue FFA levels was observed by perfusing with (i) albumin, (ii) glucose, insulin and propranolol. Our results also suggest that lysosomal involvement could cause the increase in tissue FFA levels in myocardial ischaemia.

Animals↗
PubMed1983

Lymphocyte subsets in the peripheral blood of patients with multiple myeloma and benign monoclonal gammopathy.

A panel of monoclonal antibodies that identify various antigens present on T and B cells was used to characterize circulating blood lymphocyte subsets in multiple myeloma [(MM)--13 patients] and benign monoclonal gammopathy [(BMG)--5 patients]. In MM and BMG an increase in B cell proportions (BA 1 positive cells) was observed, whereas T cells (Lyt 3 positive cells) were reduced compared to normal controls. However, with respect to the T cell subset distribution, a marked diversity between MM and BMG was noted. This may help to differentiate BMG from MM. In MM a relative decrease in inducer/helper T cells (OKT 4 positive cells) and increase in suppressor/cytotoxic T cells (OKT 8 positive cells) as well as in NK/K T cells (Leu 7 positive cells) was observed. On the other hand, in BMG the relative T cell subset distribution was comparable to those seen in normal subjects.

Adult↗