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L Paulesu

Publications and source records attributed to L Paulesu.

At least 55 records · Page 3Linked to original sources
PubMed1985

The physiological interferon response: IV. Production of interferon by the perfused human placenta at term.

Human placentas at term, free of bacterial and viral diseases, have been perfused and maintained sterile for up to 13 hr. Several parameters indicate that the organs remained viable and released interferon into the perfusate in a progressive fashion. The amount of interferon was small and the individual variations indicate that there are "poor" and "good" placenta producers. Both interferons -alpha and -beta were produced with a prevalence of the latter type. The partial acid lability and the type heterogeneity suggest that under physiological conditions the placentas produce unusual interferons, the function of which remains speculative.

Amnion↗
PubMed1985

The physiologic interferon response. VI. Interferon activity in human plasma after a meal and drinking.

Interferon activity in plasma was found negligible in the morning and slightly increased in the afternoon. However, because of the wide variability of the results, the difference was not statistically significant even though the existence of a circadian rhythm appears possible. The afternoon increase of IFN activity could be at least in part due to increased abdominal lymphatic drainage following digestion and absorption. In fact, it has been shown that there is a significant transient increase in IFN plasma level 2 hours after a fat-rich meal or drinking 700 ml of water. IFN activity was due to acid-labile IFN-alpha. This is another, yet indirect, indication of the existence of the physiologic IFN response that entails a localized production of lymphomonokines with limited spillover in the circulation.

Adult↗
PubMed1985

The physiological interferon response. V. Antiviral activity present in rat lymph is neutralized by anti-mouse interferon-gamma antibodies.

By neutralization tests using anti-rat and mouse interferon (IFN) antibodies, we tested whether the antiviral activity present in abdominal lymph but absent in plasma of healthy rats, could be ascribed to IFN. Antimouse IFN-gamma antibodies neutralized the inhibitor completely while anti-rat IFN-alpha/beta antibodies did not. We conclude that rat lymph contains traces of IFN-gamma and that the antiviral activity is not due to low-density lipoproteins, immunoglobulins, or to cell-produced viral inhibitors. This finding extends previous observations on rabbit lymph and further supports the existence of a physiological low-level interferon response.

Animals↗
PubMed1984

Pulmonary catabolism of interferons: alveolar absorption of 125I-labeled human interferon alpha is accompanied by partial loss of biological activity.

The catabolism of interferon was examined in isolated rabbit lungs which were ventilated and perfused with homologous blood. Natural human interferon-alpha (HuIFN-alpha) from lymphoblastoid Namalwa cells or recombinant DNA-derived HuIFN-alpha 2 were labeled with 125I, mixed with an excess of the respective cold interferons and added to the perfusion blood. Protein-bound and acid-soluble radioactivity, as well as antiviral activity, were measured at regular time intervals. During the first 3 h of perfusion, only very small fractions of the interferons disappeared from the perfusate, irrespective of whether lungs were inserted in the perfusion system. This indicated that catabolism of interferons in the pulmonary circulation was negligible. On the other hand, when the interferons were instilled into the bronchial-alveolar tree, absorption of antiviral activity differed from that of acid-precipitable protein-associated radioactivity. While most of the radioactivity was transferred into the perfusate, only 2% of antiviral activity of natural HuIFN-alpha and 30% of that of HuIFN-alpha 2 were recovered in the perfusate. In both cases acid-soluble radioactivity in the system reached about 10%. Since radioiodide, instilled in the bronchial-alveolar tree, was transported rapidly into the perfusate, this type of analysis did not help in locating the site(s) of degradation. Alveolar macrophages did not catabolize or inactivate interferons in vitro.

Animals↗
PubMed1984

The physiological interferon response. II. Interferon is present in lymph but not in plasma of healthy rabbits.

If interferon is produced by the gut-associated lymphoid tissue of healthy rabbits under normal conditions and is not all bound in situ, it may spill over and be detectable in lymph. We therefore measured antiviral activity in lymph and plasma simultaneously. We found that antiviral activity was consistently measurable in abdominal and thoracic lymph but not in plasma or in the lymph collected from the hind leg duct. The antiviral activity was neither due to lipoproteins, nor immunoglobulins, nor to cell-produced viral inhibitors other than interferons. Extensive characterization of the antiviral activity indicated that the inhibitor is either rabbit interferon gamma or an acid-labile interferon alpha or a mixture; appropriate antisera will be necessary to resolve this uncertainty. The results support the view of the existence of a physiological interferon response.

Abdomen↗
PubMed1983

Degradation of human 125I-interferon alpha by isolated perfused rabbit kidney and liver.

Rabbit livers and kidneys were isolated and perfused with homologous blood. After equilibration, human IFN alpha labeled with 125I and an excess of cold IFN alpha were added, and blood samples were withdrawn at predetermined times. Protein-bound and acid-soluble radioactivity together with biological (antiviral) activity were measured. Our results show that although liver exerts a minimal catabolism, the kidney filters and breaks down a considerable amount of IFN alpha. The parallelism between protein-bound radioactivity and biological activity decay curves indicates that IFN carefully labeled with 125I can be reliably used for metabolic investigations.

Animals↗
PubMed1982

Cyclic changes of sialidase in human cervical mucus.

1. Sialidase activity is detectable in whole cervical mucus of normal women throughout the menstrual cycle and presents cyclic variations toward endogenous and exogenous substrates. 2. The level of sialic acid bound to the mucus increases progressively till mid-cycle and declines in the post-ovulatory phase. 3. The sialidase of the mucus probably derives from different sources and its role remains speculative.

Adult↗
PubMed1982

The kidney is the main site of interferon catabolism.

The fate of human natural interferons alpha and beta and of recombinant (R) alpha 2 has been investigated by using an isolated and perfused rabbit kidney preparation with a normal physiological performance. A remarkable amount of IFN is filtrated in a monoexponential fashion, reabsorbed and very likely degraded in tubular cells with negligible excretion in the urine. The disappearance rate of HuRIFN-alpha 2 is higher than natural HuIFNs-alpha and beta and is in keeping with the lower molecular weight of RIFN-alpha 2. Differences in molecular charge or shape are probably responsible for the slightly reduced filtration of IFN-beta. Pharmacokinetic studies in animal models appear instructive and useful for devising improved dosage schedules in clinical trials.

Animals↗
PubMed1982

The role of liver in the catabolism of human alpha- and beta-interferon.

The susceptibility of human leukocyte (alpha), fibroblast (beta) and recombinant alpha-2-interferons to clearance by the isolated and perfused rabbit liver has been evaluated. Human leukocyte and recombinant alpha-2-interferons were stable and their initial levels were maintained in the perfusate even if they had been treated with neuraminidase, thus suggesting that alpha-interferons have no exposed sugars recognizable by hepatic binding proteins. On the other hand, native, and particularly desialylated human beta-interferon, underwent marked hepatic uptake confirming the importance of the liver as a catabolic site for glycosylated interferons.

Animals↗
PubMed1981

Renal filtration, absorption and catabolism of human alpha interferon.

The renal handling of human interferon-alpha has been evaluated by using an isolated and perfused rabbit kidney. IFN-alpha disappears from plasma with a t1/2 of 81 min and the fractional turnover rate is 0.84%/min. About 47 molecules of IFN-alpha are filtrated with 100 molecules of creatinine but most of the IFN is absorbed by tubular cells. This is the first report showing that human IFN-alpha is filtrated by the kidney, largely absorbed, most probably catabolized within tubular epithelium and excreted in negligible amounts with the urine.

Animals↗
PubMed1981

Renal metabolism of rabbit serum infection.

Three different approaches have been used to evaluate the catabolism of rabbit serum interferon (IFN) by the kidneys. Firstly, in normal rabbits the disappearance of exogenous IFN from plasma was very rapid, whereas it was significantly slower after bilateral nephrectomy. Secondly, the IFN level in arterial blood was always higher than in renal venous blood: the mean renal extraction rate of IFN in the rabbit, with a renal plasma flow of 9 ml/min, was about 1 ml/min. Thirdly, a selective and reversible tubular damage induced by maleate before intravenous administration of IFN significantly inhibited luminal uptake of IFN and markedly increases the interferonuria. All of these results support the view that the kidneys have a preponderant role in IFN filtration, catabolism and excretion.

Animals↗
PubMed1980

Studies of factors regulating the ageing of human erythrocytes--III. Metabolism and fate of erythrocytic vesicles.

1. Ageing erythrocytes release vesicles the metabolism of which is unknown. 2. Human and rat erythrocytic vesicles labelled with 51Cr and injected into rats, disappear very rapidly from the circulation with half-lives from 2 to 8 min. 3. Their lifetime resembles that of liposomes encapsulating [51Cr]haemoglobin (Hb) and in both cases, liver and spleen take up considerable amounts of radioactivity. 4. These results indicate, for the first time, that vesicles released from erythrocytes are cleared at very fast rates from the circulation and suggest that this may be the reason for the absence of vesicles in the plasma in vivo.

Animals↗
PubMed1979

Studies of factors regulating the ageing of human erythrocytes. II. Metabolic depletion of erythrocytes is not accompanied by a decrease of their sialic acid content during blood bank storage.

Erythrocytes from human blood stored at 5 degrees C in anticoagulant-preservative solutions are considered, after a period from 21 to 24 days, unsuitable for transfusion. The nonviability of the cells appears due to metabolic impairment accompanied by a change of the biophysical properties of the cell but surprisingly not to a decrease of sialic acid of the membrane. The absence of proteolysis can be attributed to calcium chelation and to the stable levels of plasma protease inhibitors throughout the storage period. In fact, when erythrocytes are incubated for several days at 5 degrees C in protein-free media, release of sialopeptides from the membrane increases slowly and steadily, particularly if the medium is without glucose and adenine but contains divalent cations. Moreover, this phenomenon is strikingly amplified when incubation in protein-free media is carried out at 37 degrees C and once the ATP level has fallen below 5% of its initial value.

Adenine↗