Biomedical subjects

T Peters

Publications and source records attributed to T Peters.

At least 199 records · Page 11Linked to original sources

PubMed1990

Family stress and childhood asthma.

Eighty-six families, each with an asthmatic child, were studied in their normal environment. The relationships between the physical severity of asthma and the families' knowledge and feelings about the asthma were measured. The mean peak expiratory flow rate recorded prospectively for one week correlated (R = 0.33) with the symptom score. In the 73 families who knew their child had asthma, there was a significant relationship (R = +0.28) between the knowledge of physical signs of attack severity and knowledge of the drugs available for emergency therapy. The mean peak expiratory flow rate was inversely related to the practical effectiveness of the inhaler technique (R = 0.62) only when the 12 families in whom the child's mean peak expiratory flow rate was less than 90 per cent of predicted were examined. The parents' feelings of worry and fear, measured independently, related to the family's knowledge of physical indications of the severity of asthma attacks. Although the families' overall knowledge scores were poor, they were apparently adjusting appropriately to asthma as a psychological stress as it appeared that they sought more information if they were worried. Their comprehension should improve if such knowledge was correctly delivered. There is a need to explore more effective techniques for the education of such families.

Adult↗

PubMed1990

Tumor necrosis factor alpha stimulates prostaglandin but not superoxide synthesis in rat Kupffer cells.

Recombinant mouse TNF-alpha (TNF) stimulated the synthesis of prostaglandin E2, prostaglandin D2 and thromboxane in primary cultures of rat Kupffer cells. Compared to the unstimulated control the 24 h output of these three prostanoids was increased three- to four-fold in a concentration-dependent manner. PGD2-like immunoreactivity was the predominant product, while HPLC analysis of all the prostanoids produced by prelabelled Kupffer cells after TNF stimulation revealed thromboxane and PGE2 (37% each) as the main products. PGD2 was degraded during the incubation period to less polar products, probably PGJ2 and delta 12-PGJ2 that cross-react with the anti-PGD2 antiserum. TNF did not trigger superoxide generation in rat Kupffer cells but it does in neutrophils. The TNF-elicited PGE2 production together with the previously described [Karck, Peters & Decker (1988) J. Hepatol. 7:352-361] inhibition of TNF release by PGE2 in rat Kupffer cells establishes a regulatory circuit of self-limiting TNF production in liver macrophages.

Animals↗

PubMed1990

Uptake of catamphiphilic drugs into erythrocytes and muscular tissue correlates to membrane enrichment and to 45Ca displacement from phosphatidylserine monolayers.

The uptake of the catamphiphilic drugs flunarizine, R 56865 [N-1-4-(4-fluorophenoxy)butyl-4-piperidinyl-N-methyl-2- benzothiazolamine], verapamil, diltiazem, lidocaine and the noncatamphiphilic drug nitrendipine into erythrocytes and erythrocyte membranes was measured at pH 7.2 in a Ringer's solution at 22 degrees C. The uptake was concentration proportional between 10(-8) and 10(-6) mol/l for all drugs investigated; the erythrocyte/medium ratio (E/M) was constant after 20 min in all experiments. In rat aortas and left atria drug uptake was measured in a 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffered medium (pH 7.2, 32 degrees C). Equilibrium was reached after 360 min and the tissue/medium ratio (T/M) was concentration proportional between 10(-8) and 10(-6) mol/l for all drugs. E/M or T/M ratios, respectively, increased in the order: erythrocytes less than aortas less than left atria. However, the particular drug/phospholipid ratios were relatively constant for the drugs investigated, indicating that the membranes were a major distribution phase for these drugs. For the catamphiphilic drugs, the E/M or T/M ratios correlated linearly with the EC50 for 45Ca displacement from phosphatidylserine monolayers, but were poorly correlated with the octanol-water coefficient of the unchanged molecules. The EC50 for 45Ca displacement from phosphatidylserine monolayers is a measure for the uptake of the protonated species of catamphiphilic drugs into erythrocytes or tissue and may be a good estimate of tissue uptake of these drugs in general.

Binding Sites↗

PubMed1989

Independent regulation of thromboxane and prostaglandin synthesis in liver macrophages.

Incubation of liver macrophages with zymosan, phorbol ester and calcium ionophore A 23187 led to the formation of thromboxane, prostaglandin E2 and prostaglandin D2, whereas after external addition of arachidonic acid prostaglandin E2 and prostaglandin D2 only were found. This was confirmed by the use of labeled arachidonic acid given together with the stimuli. When the liver macrophages were prelabeled with [3H]arachidonic acid, and zymosan and [14C]arachidonic acid were added simultaneously, [3H]-label only was found in thromboxane whereas both [3H]- and [14C]-labeled PGE2 and PGD2 were detected in the cell medium. These data suggest that in cultured rat liver macrophages externally added arachidonic acid is accessible to the cyclooxygenase supplying prostaglandin H2 for prostaglandin E2 and D2 synthesis but not for thromboxane synthesis.

Animals↗

PubMed1989

Protein metabolism in the small intestine of the ethanol-fed rat.

The effects of chronic ethanol feeding on the small intestine were investigated in young rats. Rats were fed a nutritionally-adequate liquid diet, containing 36 per cent of total energy as ethanol (treated, n = 7), or isovolumetric amounts of the same diet in which ethanol was substituted by isocaloric glucose (controls, n = 7). After six weeks the wet weight and total tissue contents of protein, RNA and DNA were significantly reduced by 21 per cent, 23 per cent, 16 per cent and 28 per cent respectively, (p less than 0.014). Rates of protein synthesis were measured with L[4(3H)]phenylalanine and fractional rates (defined as the percentage of constituent tissue protein synthesised each hour, i.e. ks, % h-1) were calculated from the specific radioactivity of free phenylalanine in both tissue homogenates and plasma. Ethanol-feeding reduced ks by approx 10 per cent (p less than 0.181). The amount of protein synthesized unit-1 RNA was also reduced by approx 15 per cent (p less than 0.059) but the amount of protein synthesis unit-1 DNA was unaffected by ethanol-feeding (p less than 1.000). In contrast, the absolute rates of protein synthesis were reduced by approximately 30 per cent (p less than 0.022). It was concluded that, as the small intestine contributes to approx. 20-25 per cent of whole body synthesis these results may have an important effect on whole body nitrogen homeostasis and may have implications for the gastrointestinal effects of ethanol seen during chronic alcoholic abuse.

Animals↗

PubMed1989

Comparative study of cytotoxicity, tumor necrosis factor, and prostaglandin release after stimulation of rat Kupffer cells, murine Kupffer cells, and murine inflammatory liver macrophages.

Macrophages (Mphi) and Mphi-depleted (nonadherent) nonparenchymal cells (NPC) of the liver were examined for their cytotoxic potential against tumor cells, production of tumor necrosis factor (TNF), and release of prostaglandins (PG) following stimulation by lipopolysaccharide (LPS), interferon-gamma (IFN gamma), and zymosan. Resident murine liver macrophages had no natural cytotoxicity for the TNF-resistant target cell line P815. Activation of these cells was only obtained by a combination of IFN gamma and LPS. Inflammatory murine macrophages were in a primed stage and could be activated by LPS alone in the absence of IFN gamma. Rat resident macrophages resembled functionally the inflammatory macrophages of the mouse liver rather than the resident macrophages. They displayed natural cytotoxicity against all targets tested and were further activated by LPS in the absence of IFN gamma. Similar results were obtained with respect to macrophage-depleted nonadherent NPC: Mouse NPC had a low level of NK activity against Yac-1 cells. Treatment with pyran copolymer resulted in a strong increase of cytotoxicity against Yac-1; furthermore, a TNF-dependent killing of Wehi 164 and TNF-independent cytotoxicity against P815 cells were now acquired. In the rat NPC prepared from unstimulated animals expressed high levels of natural cytotoxicity against all targets. No major differences could be observed between inflammatory Mphi and Kupffer cells of rat and mouse liver with regard to TNF production and TNF-dependent killing of Wehi 164 tumor cells. The same was true for the spectrum of secreted prostanoids. Upon activation of all cell populations a marked shift toward the production of PGE2 occurred. Experiments involving the cyclooxygenase inhibitor indomethacin showed enhanced TNF-dependent tumor cell killing by nonactivated Mphi in the absence of prostanoid production.

Animals↗

PubMed1989

Definition of Brucella A and M epitopes by monoclonal typing reagents and synthetic oligosaccharides.

The paradigm that Brucella A and M epitopes are simultaneously expressed on single cells and within one antigen molecule was reinvestigated by using polysaccharide-specific murine monoclonal antibodies. Monoclonal antibodies were generated to the M antigen of Brucella melitensis 16M. Chemically defined lipopolysaccharides and O polysaccharides from Brucella abortus 1119-3, B. melitensis 16M, and Yersinia enterocolitica O:9 were used to dissect the binding profiles of the B. melitensis antibodies and an additional set of antibodies available from a B. abortus fusion experiment. Binding specificities were rationalized in terms of prototype A- and M-antigen structures, an interpretation supported by competitive binding studies with O polysaccharides and synthetic oligosaccharide analogs of the A and M antigens. Three binding patterns were characterized. Antibodies specific for the A antigen required five contiguous alpha 1,2-linked 4,6-dideoxy-4-formamido-D-mannopyranosyl residues, while antibodies with equal affinities for A or M epitopes were effectively inhibited by alpha 1,2-linked tri- or tetrasaccharides. Specificity for the M epitope correlated with binding of a critical disaccharide element alpha-D-Rha4NFo(1----3)alpha-D-Rha4NFo bracketed by alpha 1,2-linked residues. The binding profiles of Brucella monoclonal antibodies were consistent with the concept of simultaneous expression of A and M epitopes within a single molecule. A epitopes were present in the M antigen, and the discovery of isolated alpha 1,3 linkages in the A antigen suggests that M epitopes occur in all A antigens. Three monoclonal antibodies are proposed as standard reagents for the detection and identification of Brucella A and M antigens.

Animals↗

PubMed1989

R 56865 differentiates between contractile agents with respect to the nifedipine-sensitive component in the isolated rat aorta.

The interaction of the benzothiazolamine R 56865 with the nifedipine-sensitive component of the serotonin (5-HT)-, angiotensin II (AII)- and arginine-vasopressin (AVP)-induced contractions was studied in the isolated rat aorta. Nifedipine caused concentration-dependently (10(-9)-10(-6) mol/l) a slight rightward shift accompanied by a limited depression of the maximum of the concentration-response curves for 5-HT-, AII- and AVP-induced contractions. R 56865 (10(-5) mol/l) antagonized the contraction elicited by 5-HT and AII in a similar manner as nifedipine. The effect of R 56865 on 5-HT- and AII-induced contractions was no longer observed after pretreatment with nifedipine. The AVP-induced contraction was not affected by R 56865 (10(-5) mol/l). As shown previously, R 56865 is a weak inhibitor of potential-operated channels but inactive on Ca2+ channels activated by NA. In conclusion, R 56865 does not only differentiate between depolarization and receptor-stimulation, but also between the activation of Ca2+ channels by different types of receptors. We propose that R 56865 may interact with Ca2+ channels at a site which plays a role in their activation.

Angiotensin II↗

PubMed1989

Effect of calmodulin antagonists on contraction and 45Ca movements in rat aorta.

To study the selectivity of calmodulin antagonists it was assumed that they should inhibit noradrenaline (NA)- and K(+)-induced contractions similarly without an accompanying inhibition of 45Ca uptake. Therefore, in isolated rat aorta the effects of W-7, calmidazolium and trifluoperazine on contraction and 45Ca uptake elicited by K+ and NA were investigated. Calmidazolium (10(-5)-10(-4) mol/l) elicited an incomplete inhibiton of K(+)- and NA-induced contraction and 45Ca uptake. Trifluoperazine inhibited the NA-induced contractions at lower concentrations (10(-8)-10(-6) mol/l) than the K(+)-induced contraction (10(-6)-10(-4) mol/l). The K(+)- and NA-induced 45Ca uptake was blocked by trifluoperazine (10(-5) mol/l). W-7 (10(-5)-10(-4) mol/l) inhibited the K(+)- and NA-induced contraction, however, in the same concentration range W-7 diminished the K(+)- and NA-induced 45Ca uptake. In conclusion, the results indicate that calmidazolium and trifluoperazine are hardly useful as calmodulin antagonists because of their additional properties, whereas W-7 seems to be the least unspecific of the calmodulin antagonists studies.

Animals↗

PubMed1989

Effect of prostaglandin on indomethacin-induced increased intestinal permeability in man.

This study examines whether NSAID induced disruption of small intestinal integrity is preventable by concomitant prostaglandin administration, and whether prostaglandins themselves interfere with intestinal permeability and absorption. Twelve subjects underwent testing following treatment as indicated: baseline, no treatment rioprostil, 300 micrograms, at -9 and -1 h indomethacin, 75 mg and 50 mg, at -9 and -1 h respectively rioprostil plus indomethacin, regimen as above. At 0800 h (0 h) subjects drink a solution containing 51CrEDTA 100 microCi, L-rhamnose 0.5 g, D-xylose 0.5 g and 3-O-methyl-glucose 0.2 g; this is followed by a 5-h urine collection. The amount of test substance in the urine reflects non-mediated intercellular and transcellular permeability, and passive and active carrier mediated transport systems, respectively. Permeation of L-rhamnose, D-xylose and 3-O-methyl-glucose is unaffected by rioprostil and/or indomethacin. Indomethacin significantly increases intestinal permeability to 51CrEDTA; coadministration of rioprostil, however, significantly decreases this detrimental effect of indomethacin. These findings suggest that prostaglandins are essential for maintaining small intestinal integrity in man and lend further support to the suggestion that NSAIDs damage the small intestine by reducing mucosal prostaglandin synthesis.

3-O-Methylglucose↗

PubMed1988

Different effects of R 56865 and calcium entry blockers on K+- and noradrenaline-induced contractions and 45Ca uptake in rat aorta.

The effects of R 56865, nifedipine, verapamil, diltiazem and flunarizine on K+- and NA-induced contractions and K+-induced 45Ca uptake were compared in the isolated rat aorta. The calcium entry blockers concentration dependently inhibited the K+-induced contraction and 45Ca uptake over the same dose-range. R 56865 inhibited the K+-induced 45Ca uptake, but only partly inhibited the K+-induced contraction. The calcium entry blockers caused a slight rightward shift and a depression of the maximum of the concentration-response curve for the NA-induced contraction. In contrast, R 56865 caused a strong, dose-dependent rightward shift and a depression of the maximum, 10(-6) and 10(-5) M being equieffective. The effects of R 56865 and nifedipine were independent of each other. Nevertheless, the NA-induced increase in 45 Ca uptake, a putative model for Ca influx, was attenuated by R 56865. In conclusion, R 56865 is a weak inhibitor of the K+-induced Ca influx but is without effect on the NA-induced Ca influx. The discrepancy between its effects on K+-induced contractions and 45Ca uptake may be explained by an inhibition of the uptake of 45Ca from the cytosol into the 45Ca pool. The interaction between R 56865 and the alpha 1-adrenoceptor-mediated contractions may be explained by an action at a site that is distinct from the NA-binding-site on the alpha 1-adrenoceptor.

Animals↗

PubMed1988

pH-dependent influence of membrane-incorporated flunarizine on Ca-binding to phosphatidylserine monolayer membranes.

The pH-dependent 45Ca binding to phosphatidylserine monolayers was investigated. Ca binding increased with increasing pH. Between pH 10 and pH 11 a steep increase of Ca binding could be observed. This increase was interpreted to be due to complex Ca binding opposed to ionic binding at low pH. Flunarizine added to the spreading solution of the monolayer dose dependently displaced up to 100% Ca at pH 5 independently of phospholipid packing. At pH 11 less than 20% of Ca could be displaced by flunarizine. Intermediate results were found at pH 7. Flunarizine displaced less Ca from dense than from loosely packed monolayers at pH 7. The results suggest two binding states of flunarizine: ionic binding at low pH and apolar binding at high pH. The latter is much less effective in displacing Ca from phosphatidylserine monolayers. The Ca displacing properties of charged flunarizine may prevent a deleterious phospholipid reorientation within the membrane induced by the intracellular Ca rise during ischemia.

Binding Sites↗

PubMed1988

Synthesis of antigenic determinants of the Brucella A antigen, utilizing methyl 4-azido-4,6-dideoxy-alpha-D-mannopyranoside efficiently derived from D-mannose.

A strategy for the synthesis of Brucella O-antigenic determinants containing 2-linked 4,6-dideoxy-4-formamido-alpha-D-mannopyranosyl residues is described. The approach adopted also permits the N-acyl moiety to be varied. A high-yield synthesis of methyl 4-azido-4,6-dideoxy-alpha-D-mannopyranoside from D-mannose on the 10-20-g scale provided the key intermediate. Regioselective acetylation of 7 gave the 2-acetate 8, which, on treatment with benzyl trichloroacetimidate, provided methyl 2-O-acetyl-4-azido-3-O-benzyl-4,6-dideoxy-alpha-D-mannopyranoside. This compound served as a common precursor to the glycosyl donor 12 and acceptor 10 molecules. Silver trifluoromethanesulphonate-promoted glycosylation of 10 by 12 gave a disaccharide derivative, hydrogenolysis of which gave methyl 4-amino-2-O-(4-amino-4,6-dideoxy-alpha-D-mannopyranosyl)-4,6-dideoxy- alpha-D-mannopyranoside from which the N-formyl and N-acetyl derivatives were obtained. Deacetylation of 13 followed by glycosylation with 12 gave a trisaccharide derivative. The N-formylated disaccharide 17 inhibited the binding of Brucella O-polysaccharide to Brucella-specific monoclonal antibodies.

Antigens, Bacterial↗

PubMed1988

Iron-binding properties and amino acid composition of marsupial transferrins: comparison with eutherian mammals and other vertebrates.

1. Some physicochemical properties of transferrin from three marsupials, viz a possum (Trachosurus vulpecula), a kangaroo (Macropus fuliginosus) and the quokka (Setonix brachyurus) were studied and compared with those of transferrins from mammalian and non-mammalian vertebrate species. 2. The molecular weight of the marsupial transferrins fell within the range of 76,000-79,000 daltons. 3. The marsupial transferrins were similar to the transferrins of eutherian mammals with respect to optical spectral properties, iron binding capacity and the pH-dependence of iron binding, and iron release mediated by 2,3-DPG. 4. The amino acid compositions of the marsupial transferrins were compared with each other and with the transferrins from the other vertebrate species. The compositions of the marsupial transferrin were closely related to each other, and also showed similarities with transferrins from eutherian mammals and chicken ovotransferrin.

Amino Acids↗

PubMed1988

The release of tumor necrosis factor from endotoxin-stimulated rat Kupffer cells is regulated by prostaglandin E2 and dexamethasone.

Evidence is presented that upon stimulation with endotoxin (lipopolysaccharide, LPS), Kupffer cells, the body's largest pool of sessile macrophages, synthesize and liberate a factor whose immunological, cytotoxic and chemical properties are those described for tumor necrosis factor (TNF)-alpha. Hepatocytes and sinusoidal endothelial cells do not produce detectable amounts of this protein. Ten nanograms of LPS per ml medium are sufficient to stimulate a substantial release of this mediator. Recombinant interferon-gamma (rIFN gamma) per se is a poor inducer of TNF release. Costimulation with endotoxin and rIFN gamma shows only a slight increment in the release of this cytotoxic factor, relative to LPS alone. Exposure of Kupffer cells to the Ca2+ ionophore A23187 or to elicitors of the oxidative burst and superoxide production, e.g. zymosan or phorbol 12-myristate 13-acetate, stimulates only a fraction (20%) of the TNF release seen after endotoxin challenge. Prostaglandin E2, the synthesis of which is strongly enhanced after challenge of rat Kupffer cells with LPS, suppresses the release of TNF by these cells. This autoregulatory mechanism may explain the kinetics of TNF production by stimulated Kupffer cells. Dexamethasone is another important mediator capable of reducing the LPS-elicited TNF formation. An effect of the glucocorticoid hormone can still be provoked if it is added simultaneously with or shortly after LPS. This rapid action requires a mechanism that is different from the time-consuming one leading to the inhibition of prostaglandin synthesis in Kupffer cells.

Animals↗

PubMed1988

Involvement of tumor necrosis factor in endotoxin-triggered neutrophil adherence to sinusoidal endothelial cells of mouse liver and its modulation in acute phase.

Tumor necrosis factor (TNF) has been shown to mediate lipopolysaccharide-induced neutrophil adhesion to liver sinusoidal endothelium in vivo. Female NMRI mice received either 5 micrograms lipopolysaccharide (R595) per animal alone (model A) or together with 116 mumol D-galactosamine (model B). One hour after injection, TNF activity in the serum was detectable to an equal extent in both models. Neutrophils in the liver, which had been identified by chloroacetate esterase staining of liver sections and quantitated by light microscopy, started to increase at 1 h and were elevated 10-fold above baseline at 6 h after application in (A) and (B). If 0.5 micrograms TNF instead of lipopolysaccharide was injected alone (model C) or together with D-galactosamine (model D), neutrophil influx into the liver was comparable to that observed in (A) or (B). Alanine aminotransferase activity in the serum was nearly normal in (A) and (C) 6 h after injection, while it reached levels up to 50-fold above baseline in models (B) and (D). This reflects the well-known D-galactosamine sensitization against lipopolysaccharide or TNF. Furthermore, degranulation of a large number of intrasinusoidal neutrophils could be observed 9 h after lipopolysaccharide-galactosamine injection. The administration of 116 mumol D-galactosamine per animal alone led neither to a measurable TNF activity in the serum nor to an increase in alanine aminotransferase activity or number of liver neutrophils. If the animals had received 50 microliter turpentine subcutaneously 24 h prior to lipopolysaccharide, TNF or D-galactosamine injection, the induced acute-phase reaction suppressed the increase of liver neutrophils in all models. Acute-phase reaction also prevented neutrophil degranulation and the rise of alanine aminotransferase in (B) to a great extent, while serum TNF activity was only minimally affected. It is concluded that TNF mediates neutrophil adhesion to the sinusoidal endothelium in vivo and that acute-phase reactants prevent lipopolysaccharide- or TNF-induced neutrophil influx into the liver.

Adjuvants, Immunologic↗

PubMed1988

Measurement of slowly exchanging 45Ca in rat aorta without using EGTA or lanthanum and its application to quantify the effects of the calcium entry blockers nifedipine and verapamil.

In rat aortic strips a method was developed to measure a fraction of slowly exchanging 45Ca, which correlates with contraction and the cytosolic Ca pool that is enhanced by K+-induced depolarization. In this method no EGTA or lanthanum are used, but the strips are washed for 45 min with a Tyrode solution at 4 degrees C. The K+ depolarization induced increase in 45Ca and contraction was concentration-dependently inhibited by verapamil and nifedipine. Since lanthanum and EGTA affect cellular membranes, this method may allow a more physiological approach to the measurements of slowly exchanging 45Ca.

Animals↗

PubMed1988

Basic mechanisms of cellular calcium homeostasis.

This contribution summarizes some basic principles of calcium distribution and calcium movements in eukaryotic cells. Emphasis is placed upon modes of calcium entry into cells, routes of calcium extrusion from cells, subcellular distribution of calcium, and the regulatory role of calcium for the control of membrane permeability to calcium itself and to other ions.

Calcium Channels↗