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Biomedical subjects

R Moser

Publications and source records attributed to R Moser.

At least 91 records · Page 5Linked to original sources
PubMed1989

Interleukin 1 and tumor necrosis factor stimulate human vascular endothelial cells to promote transendothelial neutrophil passage.

In an attempt to understand the regulatory mechanisms governing passage of neutrophils from the vascular bed to the interstitial tissue, we analyzed the effect of the pleiotropic monokines interleukin 1 (IL-1) and tumor necrosis factor (TNF) on transendothelial neutrophil traffic. Short-time preincubation of human umbilical vein endothelial cell (HUVE) monolayers with IL-1 and TNF led to an impressive time- and dose-dependent increase of endothelial cell-associated neutrophils when working in a full plasma system on petri dishes. Electron microscopic analysis revealed junctional penetration of monolayers by neutrophils. More quantitatively, when using a monolayer-on-filter-system, priming led to a severalfold increase in complete layer passage occurring in the absence of an external chemotactic gradient. Direct comparison with an upside-down modification of the system together with data demonstrating the vectorial behavior of such migration revealed that IL-1-stimulated transendothelial neutrophil traffic is polarized. The described enhancement of neutrophil transendothelial passage was found to be a unique feature of IL-1/TNF-activated HUVE since HUVE-dependent transmigration potentiation was not observed as a consequence of mere neutrophil attachment to endothelial cells (e.g., induced by Fc-mediated adherence of PMN to HUVE). IL-1 acts selectively on endothelial cells as demonstrated by total inhibition of its effect by actinomycin D. Moreover, IL-1 does not induce HUVE monolayers to secrete a chemotaxin, and the neutrophil passage guiding principle is removable from the HUVE surface by short trypsin exposure. Congruent results were obtained with human adult arterial as well as saphenous vein endothelial cells. As shown by blockade of neutrophil migration with pertussis toxin, IL-1- and TNF-inducible transendothelial migration can be dissected into an initial anchoring step, which is succeeded by active neutrophil migration, possibly along a putative endothelial membrane-bound gradient.

Cell Adhesion↗
PubMed1988

Fluorometric continuous kinetic assay of alpha-chymotrypsin using new protease substrates possessing long-wave excitation and emission maxima.

A direct and continuous kinetic method for the fluorometric determination of alpha-chymotrypsin and trypsin is described, and 2-aminoacridone (2-AA) is introduced as a promising new fluorophore in analytical biochemistry. N-Succinyl- and N-glutaryl-phenylalanine as well as N-benzoylarginine were coupled to 2-AA via a peptide bond and the resulting fluorogenic substrates are shown to be cleaved by the two enzymes. Since the substrate and product of hydrolysis have quite different spectral properties, the increase in the long-wave fluorescence of 2-AA (measured at 570 nm under 450-nm excitation) is a parameter for the enzyme activity. Chymotrypsin (0.5 microgram/ml) and trypsin (0.1 microgram/ml) were detectable in a 3-min assay. The major advantages of the new substrates over existing ones are the analytical wavelengths which are distinctly outside the background fluorescence of most biological matter and the somewhat faster reaction rates which can reduce the time of analysis.

Aminoacridines↗
PubMed1987

Central nervous system (CNS) penetration of homoharringtonine (HHT).

Generally tritiated homoharringtonine ([3H]HHT, 150 microCi, 430 micrograms) was administered intravenously to seven patients at varying times before surgical resection of malignant brain tumor. Plasma, urine, cerebrospinal fluid (CSF), and tumor specimens were obtained during surgery, and the concentrations of HHT, its major metabolite, and [3H]HHT equivalent were determined chromatographically and radiochemically. For [3H]HHT equivalent, the concentration in tumor ranged from 0.6 to 4.3 ng/g and the ratio of tumor to plasma concentration from 0.5 to 1.8. In one patient who had CSF available for drug determination, the CSF to plasma ratio of total [3H]HHT was 0.3 at 45 minutes after drug administration and less than 0.2 ng/ml was unchanged HHT. For unchanged HHT, drug concentration in tumor ranged from undetectable (4 patients) to 1.8 ng/g. A major metabolite of HHT was detectable in the tumor specimens of all the patients. These results indicate that homoharringtonine can penetrate into brain tumors; in 3 patients with brain tumors, the ratios of HHT concentration in the tumor to that in the concurrent plasma were greater than one.

Alkaloids↗
PubMed1987

In vitro lining of fibronectin coated PTFE grafts with cryopreserved saphenous vein endothelial cells.

In an attempt to produce instant endothelial cell (EC) monolayers on graft surfaces, cryopreserved cultivated human saphenous vein endothelial cells (HSVEC) were cultivated on reinforced PTFE prostheses. The graft surface was precoated with 40 micrograms/ml human fibronectin (HFN) prior to seeding with 200 x 10(3) EC/cm2. The seeding procedure was performed in a specially designed rotation device. After a cultivation period of 9 days, the seeded endothelial cells on the PTFE prostheses were exposed to shear stresses in a perfusion circuit, containing a bubble oxygenator, a roller pump and a tygon perfusion loop. The applied shear forces were 3 and 6 dyn/cm2, respectively. In control grafts, spontaneous cell detachment occurred from day 11 onwards and only 50% of the graft surface remained endothelialized on day 16. When the grafts were exposed to 3 dyn/cm2 only small cell-free areas less than 1000 micron in diameter were found after 4 hours of perfusion. In contrast, exposure to 6 dyn/cm2 produced discouraging results: as early as 4 hours after the onset of perfusion 50% of the graft surface was cell free. After 16 hours only 20% endothelial cell coverage was seen under the stereo microscope. However, assuming that an ideal precoating substratum can be found, the two stage technique of in vitro endothelialization of vascular grafts with autologous endothelial cells may offer a promising clinical method. Moreover, the fact that our grafts were lined with cryopreserved EC implies the possible prospect of cell banks supplying unlimited numbers of EC for subsequent bypass operations.

Blood Vessel Prosthesis↗
PubMed1987

A prevention armamentarium for aeromedical practitioners.

Recent advances in preventive medicine offer practitioners exceptional opportunities to help patients and their families have longer, healthier, and more enjoyable lives. Those involved in aerospace medicine are uniquely qualified by their training and experience to apply this enhanced prevention armamentarium. The discussion considers a number of activities and techniques which can provide important patient benefits at acceptable costs.

Aerospace Medicine↗
PubMed1986

Possible inhibitory function of endogenous 15-hydroperoxyeicosatetraenoic acid on prostacyclin formation in bovine aortic endothelial cells.

Arachidonic acid is metabolized via the cyclooxygenase pathway to several potent compounds that regulate important physiological functions in the cardiovascular system. The proaggregatory and vasoconstrictive thromboxane A2 produced by platelets is opposed in vivo by the antiaggregatory and vasodilating activity of prostacyclin (prostaglandin I2) synthesized by blood vessels. Furthermore, arachidonic acid is metabolized by lipoxygenase enzymes to different isomeric hydroxyeicosatetraenoic acids (HETE's). This metabolic pathway of arachidonic acid was studied in detail in endothelial cells obtained from bovine aortae. It was found that this tissue produced 6-ketoprostaglandin F1 alpha as a major cyclooxygenase metabolite of arachidonic acid, whereas prostaglandins F2 alpha and E2 were synthesized only in small amounts. The monohydroxy fatty acids formed were identified as 15-HETE, 5-HETE, 11-HETE and 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT). The latter two compounds were produced by cyclooxygenase activity. Nordihydroguaiaretic acid (NDGA), a rather selective lipoxygenase inhibitor and antioxidant blocked the synthesis of 15- and 5-HETE. It also strongly stimulated the cyclooxygenase pathway, and particularly the formation of prostacyclin. This could indicate that NDGA might exert its effect on prostacyclin levels by preventing the synthesis of 15-hydroperoxyeicosatetraenoic acid (15-HPETE), a potent inhibitor of prostacyclin synthetase. 15-HPETE could therefore act as an endogenous inhibitor of prostacyclin production in the vessel wall.

Animals↗
PubMed1986

Preparation of 18O-labelled standards of hydroxy-eicosatetraenoic acids and thromboxanes for quantitative measurement by gas chromatography/mass spectrometry.

A study on the extent of 18O incorporation into various hydroxy-eicosatetraenoic acids, thromboxane B2 and 2,3-dinor-thromboxane B2 by base-catalysed hydrolysis of their methyl ester derivatives is presented. The amount as well as the position of the inbuilt 18O atoms were determined by gas chromatography/mass spectrometry, utilizing electron impact and positive and negative ion chemical ionization.

Gas Chromatography-Mass Spectrometry↗
PubMed1986

Organized intracerebral hematoma with acute hemorrhage: CT patterns and pathologic correlations.

Five cases of pathologically proven organized intracerebral hematoma with recent hemorrhage are reported. The hemorrhages were spontaneous, were located in deep structures of the brain, and presented without a clinical history of hypertension or trauma. No underlying causes of the hematomas were identified histologically. Various computed tomographic (CT) patterns of recurrent hemorrhage in an organized hematoma were observed. A hyperdense, well demarcated mass with minimal contrast enhancement but no surrounding edema was observed when rehemorrhage was confined within a late-organizing hematoma. A "target" sign of a ring-enhancing mass was observed when the new hemorrhage developed within an early-organizing hematoma. When a new hemorrhage occurred outside a solid-enhancing organized hematoma, the CT appearance suggested a possible tumoral hemorrhage. Close clinical and CT follow-up is desirable for initial management of a suspicious rehemorrhaging organized hematoma situated in the deep-seated or superficial sensitive structures if the symptomatology has stabilized or improved. Tissue diagnosis and surgical evacuation are indicated when the clinical course fluctuates or progresses and CT demonstrates an interval increase of lesion.

Acute Disease↗
PubMed1986

Isolation of pure LpB from human serum.

Low density lipoproteins (LDL), even after isolation from a narrow density cut and after several washes by preparative ultracentrifugation, are contaminated by 3-5% non-apoB proteins. Incubation of these LDL with artificial triglyceride-rich lipid emulsions (TGRP) removed all contaminating apoC and also, under certain conditions, apoA proteins. TGRP treatment did not, however, change the lipid composition and the flotation behavior of LDL. Residual apoE and albumin, amounting up to 0.5% of the apoB mass, were resistant to removal by TGRP treatment as well as by heparin-Sepharose column chromatography. ApoE and albumin could only be removed by immunoabsorption.

Apolipoproteins↗
PubMed1985

Slim disease (AIDS)

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Qualitative and quantitative measurement of hydroxy fatty acids, thromboxanes and prostaglandins using stable isotope dilutions and detection by gas chromatography-mass spectrometry.

Methods for measurement of the metabolites of arachidonic acid (AA), namely prostaglandins (PGs), thromboxanes (TXs) and hydroxy fatty acids, using stable isotope dilution gas chromatography--mass spectrometry are described. With a few exceptions, labelled species of the various AA metabolites are not commercially available and were therefore synthesized in our laboratory. [2H8]AA, produced by deuteration of eicosatetraynoic acid, was used for comparing the metabolism of exogenously added and endogenously present AA in fibroblast cultures. After derivatization and catalytic hydrogenation, structure elucidation and quantification of the different hydroxy fatty acids was carried out by determination of the fragment ions resulting from alpha-cleavage at the site of the hydroxy function. During catalytic hydrogenation a significant hydrogen--deuterium exchange was observed. To eliminate this problem, 18O-labelled standards were prepared by exchanging the oxygen of the carboxylic acid group. The preparation and the use of hydroxy fatty acids, PGs and TXs labelled with 18O is described.

Fatty Acids↗
PubMed1985

Cardiolipin is the membrane receptor for mitochondrial creatine phosphokinase.

Treatment of rat heart mitochondria with phosphate or mersalyl releases a number of proteins, including the mitochondrial creatine kinase (mt-CK). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the released proteins showed that phosphate is more selective than mersalyl in releasing mt-CK. The rebinding of mt-CK to mitochondria was selectively inhibited by adriamycin, which complexes membrane-bound cardiolipin. mt-CK activity and binding experiments have shown that intact mitochondria are able to bind approximately twice the amount of mt-CK they originally contain. Liver mitochondria bound heart mitochondria mt-CK to the same extent as creatine kinase-depleted heart mitochondria. mt-CK was bound by liposomes but only if they contained cardiolipin. The binding of mt-CK to cardiolipin-containing liposomes was inhibited by adriamycin. Phosphatidylcholine liposomes reconstituted with the purified ADP/ATP translocator failed to bind mt-CK.

Animals↗
PubMed1985

Antiadhesive properties of biological surfaces are protective against stimulated granulocytes.

Despite the fact that a series of endogenous and exogenous inflammatory mediators are potent activators of circulating granulocytes, damage of vascular endothelium, a primary target tissue, is a rather unusual event in systemic inflammatory states. Since mediator-induced neutrophil hyperadhesiveness on plastic tissue culture dishes is invariably accompanied by intense release of lysosomal granule constituents and respiratory burst activation, thus representing a powerful model to investigate neutrophil cytotoxic states, comparative studies with neutrophils suspended in autologous plasma in the presence or absence of N-formyl-Met-Leu-Phe (2.5 microM), the most potent adhesion inducer, were performed on different biologic surfaces. On optimally adherent closed monolayers of cultured endothelial cells or fibroblasts we observed poor stimulation of adhesion as well as minimal granule release and hexose monophosphate pathway activation. Functional behavior of neutrophils on single molecular components of basal laminas such as fibronectin and collagen (type IV) coats was intermediate, with positive adhesion promotion but markedly reduced metabolic activation. When tested on endothelial cell-derived extracellular matrices, neutrophils again showed functional nonresponsiveness to N-formyl-Met-Leu-Phe. Scanning electron microscopy revealed an impressive congruency between the degree of cellular spreading and metabolic activation in the presence of N-formyl-Met-Leu-Phe, with maximally flattened neutrophils on plastic vs. nonspread, polarized cells on monolayers. Identical results were obtained by using other adhesion inducers such as complement-activated plasma or endotoxin. Lack of cell injury by N-formyl-Met-Leu-Phe-exposed neutrophils was corroborated by the absence of tracer release from [111In]tropolonate-labeled endothelium. These results indicate that biologic surfaces possess antiadhesive properties that protect them from cytotoxic damage by stimulated angry phagocytes.

Cell Adhesion↗