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Biomedical subjects

S I Said

Publications and source records attributed to S I Said.

At least 217 records · Page 12Linked to original sources
PubMed1968

Surface tension, metabolic activity, and lipid composition of alveolar cells in washings from normal dog lungs and after pulmonary artery ligation. Importance of a highly surface-active acellular layer.

Lung-washings from mammalian species are a rich source of surfactant and of cells, predominantly alveolar macrophages, that could be important in the metabolism of the surfactant. We obtained washings from normal dogs, and from dogs that had had one pulmonary artery (PA) ligated 1 or 2 days earlier. Centrifugation of wash (400 x g for 20 min) separated a sediment, made up of cells at the bottom and a white layer, largely acellular, from the supernatant. The volume of sediment averaged 2.1 +/- 1.4 ml,. 75% of which was white layer. The cells resembled the large alveolar (type II) cells found in the lung; however they differed by at least one major histochemical reaction. The white layer had greater surface activity than the cells or the supernate, and was richest in phospholipids and lecithin. The cells lost their surface activity when rinsed and resuspended. These observations suggest that surfactant is normally present, mainly in an acellular fraction and possibly at the surface of the alveolar cells. The alveolar macrophages may either store surfactant, rather than synthesize it, or simply acquire a coat of surfactant during sedimentation. After PA ligation, the earliest abnormality was a decrease in the white layer; the cells were fewer, smaller, and weaker in metabolic activity.

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PubMedDate not supplied

In vivo depression of lymphocyte traffic in sheep by VIP and HIV (AIDS)-related peptides.

Core pentapeptides and an octapeptide (Peptide T) computer deduced from amino acid sequences from vasoactive intestinal peptide (VIP) and the 120 gp external envelope of the HIV (AIDS) virus and synthesized have been reported to have important in vitro and in vivo activity including inhibition of HIV binding to CD4 surface antigens of brain cells and lymphocytes and limitation of HIV infectivity. Two of these core pentapeptides, peptide TTNYT (Peptide T [4-8]) and peptide TDNYT (VIP [7-11]), are reported here, on acute infusion into cannulated afferent popliteal lymphatics of sheep, to produce prompt and marked depressions in the output of both small recirculating and blast lymphocytes into popliteal lymph node efferent lymph. As with a prior VIP infusion study, there appeared to be a selective effect on T4 (CD4) lymphocytes, with a marked predominance of T4 (CD4) lymphocytes in the lymphocyte depleted efferent lymph.

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PubMedDate not supplied

Prompt elevations of PGE2 and thromboxane A2 metabolites in peripheral node efferent lymph of sheep following drainage area immunization.

In the past decade, the main interest in the involvement of prostaglandin E2 (PGE2) in the immune response has been concerned with its role in immunomodulation (suppression) both in vitro and in vivo. Comparatively little attention has been devoted to its immunostimulatory role. It has been suggested that PGE2, like histamine, may function as a 'double agent', initially triggering, facilitating and augmenting a stimulatory immune response and later modulating, limiting and contributing to the turning off of this response. We here report an early (within minutes) immunostimulatory involvement of PGE2 (and thromboxane A2) in the sheep, with prompt elevations in levels of PGE2 and thromboxane B2 in popliteal lymph node efferent lymph following drainage area immunization with killed Salmonella muenchen bacteria. These elevations were associated with an increase in efferent lymph flow and an equally prompt but limited depression of lymphocyte outputs into efferent lymph ('shutdown', 'recruitment'). Local increases in blood flow and vascular permeability probably play important roles in these events.

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PubMedDate not supplied

Substance P increases and prolongs increased output of T4 (CD4) lymphocytes from lymph nodes of sheep in vivo: is it a mediator of immunological memory?

There are receptors on lymphocytes for substance P which are found both on small recirculating and on blast lymphocytes. The principal effect of substance P on lymphocytes appears to be a stimulating one, both in vitro and in vivo. The in vivo administration of substance P to sheep by acute infusion into cannulated afferent lymphatics of peripheral lymph nodes has been found to stimulate efferent lymph flow and the output into efferent lymph of both small recirculating and blast lymphocytes. We here report that substance P both enhances and prolongs the enhancement of the output of T4 (CD4) lymphocytes from lymph nodes of sheep in vivo. This output-stimulating effect appears to be specific to T4 (CD4) lymphocytes and is associated with a depressant effect on the output of T8 (CD8) and B lymphocytes. The output-stimulating effect on small T4 (CD4) lymphocytes is quite prolonged, lasting in excess of 96 h after a single 50 micrograms acute infusion. A brief post-infusion depression in T4 (CD4) lymphocyte output is associated with an equally brief, but marked, elevation in the output into efferent lymph of the arachidonic acid metabolite, thromboxane B2. The output-stimulating effect of substance P on blast T lymphocytes is confined to the T4 (CD4) blast lymphocytes. Substance P or a similar molecule may be of value when a specific T4 (CD4) lymphocyte output stimulant effect is desired. A single prior (6 days) acute infusion of substance P into a popliteal lymph node via its cannulated afferent lymphatic produced profound changes in the response to nodal drainage area immunization with killed S. muenchen bacteria. The latent period prior to increased antibody production was abolished, as was the standard post-immunization 'shutdown' period of decreased output of lymphocytes into efferent lymph. These changes were accompanied by a marked and progressive increase in antibody production. The findings reported here suggest substance P-induced long-term potentiation (LTP) of the immune response and raise the question of an involvement of substance P as a major mediator of immunological memory.

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PubMedDate not supplied

In vivo influences of phorbol ester and calcium ionophore on lymphocyte traffic, lymph flow and efferent lymph levels of thromboxane B2 in sheep.

In vitro systems have provided increasing evidence of significant lymphocyte transmembrane signalling by plasma membrane receptors which utilize antigen and other ligand activation of the inositol phosphate dual second messenger system of intracellular signalling. Elevation of intracellular Ca2+ and activation of protein kinase C are important products of these signals and appear to provide a complete set of mitogenic signals for both T and B cells. Calcium inophore and phorbol ester have been found to mimic these events in vitro and are here employed in vitro to study their effects on lymphocyte traffic and efferent lymph flow through primary peripheral lymph nodes of sheep and on the output into efferent lymph of the arachidonic acid metabolite, thromboxane B2. Calcium ionophore and phorbol ester were given alone or in combination to popliteal lymph nodes of sheep by drainage area injection or by acute infusion into cannulated afferent lympatics of study popliteal lymph nodes whose efferent lymphatic was chronically cannulated for study. The findings resembled those of drainage area immunization with an early increase in efferent lymph flow and prompt and marked depressions in the output into efferent lymph of both small recirculating and blast lymphocytes ('shutdown', 'recruitment'), followed by a marked increase in the output into efferent lymph of both small recirculating and blast lymphocytes. The greatest elevation in both small recirculating and blast lymphocyte outputs was at 24 and 48 h following phorbol ester and calcium ionophore administration. Acute phorbol ester and calcium ionophore administration was associated with a prompt and marked elevation in efferent lymph levels of thromboxane B2 which were of short duration. The findings observed here with lymph node drainage area infusion/injection of both phorbol ester and calcium ionophore are quite similar to those encountered in this sheep lymphocyte traffic model following popliteal lymph node drainage area immunization with killed Salmonella muenchen antigen.

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PubMedDate not supplied

Purification of [125I]-vasoactive intestinal peptide by reverse-phase HPLC.

VIP was labeled with sodium 125iodide, and 125I-VIP was purified by reverse-phase high performance liquid chromatography. Optimal separations of 125I-VIP and unlabeled VIP were obtained using two C18-Novapak columns in series and a gradient of acetonitrile in triethylamine phosphate for elution. The specific activity of the 125I-VIP was 1.99 +/- 0.21 Ci/mumole, approaching the maximum specific activity of monoiodinated VIP (2.26 Ci/mumole). Radioimmunoassay and radioreceptorassay for VIP were more sensitive (2.6-fold, and 2.5-fold, respectively) using 125I-VIP purified by HPLC compared to 125I-VIP obtained from an open-end cellulose column. These results demonstrate the advantage of preparing purified 125I-VIP by HPLC for the accurate assay of VIP and VIP-receptors in tissues and biological fluids.

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PubMedDate not supplied

Vasoactive intestinal polypeptide (VIP): current status.

Research on VIP continues at a rapid pace. Recent progress includes: insights into its biosynthesis (and that of a closely related PHI-like peptide) and its neuronal localization, discovery of novel biological actions, new data on its release and binding to specific receptors, and additional evidence for its roles in physiological regulation and in the pathogenesis of disease.

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PubMedDate not supplied

VIP elevates platelet cyclic AMP (cAMP) levels and inhibits in vitro platelet activation induced by platelet-activating factor (PAF).

Platelet-activating factor (PAF), a potent endogenous phospholipid released by a variety of mammalian cells, induces platelet activation in vivo and in vitro. Little is known, however, about the physiological modulation of its actions. We have examined the ability of two naturally occurring compounds which stimulate cAMP production, vasoactive intestinal peptide (VIP) and prostacyclin (PGI2), to inhibit PAF-induced platelet aggregation and secretion in vitro. Washed, [3H]serotonin-labeled, rabbit platelets were incubated 60 sec in the presence of VIP, PGI2 or 3-isobutyl-1-methylxanthine (IBMX) and subsequently stimulated with PAF. In separate studies, cAMP levels were determined in similar aliquots of platelets incubated for 30 sec with VIP, PGI2 or IBMX. VIP, PGI2 and IBMX inhibited platelet aggregation and secretion in a dose-dependent manner. Fifty percent inhibition was achieved at final concentrations of 1.7 X 10(6) M VIP, 3.6 X 10(6) M PGI2 and 6.5 X 10(5) M IBMX. IBMX potentiated the inhibitory effects of VIP and PGI2 on PAF-induced platelet activation. VIP and PGI2 elevated platelet cAMP levels four-fold and 50-fold, respectively, in the presence of 10(3) M IBMX. These findings demonstrate that VIP inhibits PAF-induced platelet activation, with a potency comparable to that of PGI2.

1-Methyl-3-isobutylxanthine↗