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L Smith

Publications and source records attributed to L Smith.

At least 487 records · Page 27Linked to original sources
PubMed1988

Combined monitoring of thoracic duct and lung lymph during E. coli sepsis in awake sheep.

A thoracic duct lymph fistula in combination with a lung lymph fistula in the awake sheep was used to evaluate effects of thoracic lymph diversion during a septic insult and to monitor systemic and local changes in the lung and gastrointestinal tract. Live Escherichia coli 10(9) kg-1 b.w. were infused in 9 sheep. After sepsis, arterial pressure, cardiac output, partial pressure of oxygen, leukocytes and platelets decreased significantly compared to baseline values. Pulmonary arterial pressure increased significantly throughout the experiment with peak values at 44 +/- 4 mmHg after 15 minutes. Lung lymph flow (QL) (n = 6) increased from 23 +/- 0.5 to 11.2 +/- 2.4 ml/30 minutes after 60 minutes. QL then decreased but remained elevated. Lymph to plasma protein concentration ratio (L/P) in lung lymph decreased from 0.62 +/- 0.02 during baseline to 0.47 +/- 0.04 after 60 minutes. L/P then increased and was, after 150 minutes, no longer different from baseline. These lung lymph data favor increased pulmonary microvascular permeability during sepsis. Lymph flow in the thoracic duct (QT) (n = 9) increased from 34.2 +/- 6 to 58.3 +/- 9 ml/30 minutes during the first 30 minutes after bacterial infusion. QT was, after 90 minutes, back to baseline but then progressively increased. L/P in thoracic lymph steadily increased from 0.56 +/- 0.03 to 0.78 +/- 0.04. Thromboxane B2 and 6-keto PGF1 alpha in thoracic duct and lung lymph increased significantly after bacterial infusion and remained elevated thereafter. Combined monitoring of thoracic duct and lung lymph enabled comparison of systemic and pulmonary reactions in septic sheep.

Animals↗
PubMed1987

Extracellular Na+ dependence of changes in free Ca2+, 45Ca2+ efflux, and total cell Ca2+ produced by angiotensin II in cultured arterial muscle cells.

Angiotensin II (ANG II) evoked a rapid efflux of 45Ca2+ which was largely, but not completely, prevented by the removal of extracellular Na+. ANG II had little, if any, effect on a fast component of 45Ca2+ uptake, although the hormone increased a slow component of 45Ca2+ uptake by 2.5-fold. ANG II decreased total cell Ca2+ by about 40% within 1 min of hormone addition. The replacement of extracellular Na+ with N-methyl-D-glucamine or K+ nearly prevented ANG II from decreasing total cell Ca2+. ANG II caused a 5-fold increase in free Ca2+ which reached a peak about 10 s after hormone addition. Free Ca2+ decreased rapidly from the peak to a plateau phase which lasted for several min. Free Ca2+ during the plateau phase was about 1.5 times the basal level. Removing extracellular Na+ caused a more than 2-fold increase in the free Ca2+ concentration that was maintained during the plateau phase, and Na+, added during the plateau phase, rapidly decreased free Ca2+. These findings suggest that the transient nature of the increase in free Ca2+ produced by ANG II is due in part to a net efflux of Ca2+ which is largely dependent on external Na+ and probably mediated by Na+/Ca2+ exchange.

Angiotensin II↗
PubMed1987

Na+/Ca2+ antiport in cultured arterial smooth muscle cells. Inhibition by magnesium and other divalent cations.

Cultured smooth muscle cells from rat aorta were loaded with Na+, and Na+/Ca2+ antiport was assayed by measuring the initial rates of 45Ca2+ influx and 22Na+ efflux, which were inhibitable by 2',4'-dimethylbenzamil. The replacement of extracellular Na+ with other monovalent ions (K+, Li+, choline, or N-methyl-D-glucamine) was essential for obtaining significant antiport activity. Mg2+ competitively inhibited 45Ca2+ influx via the antiporter (Ki = 93 +/- 7 microM). External Ca2+ or Sr2+ stimulated 22Na+ efflux as would be expected for antiport activity. Mg2+ did not stimulate 22Na+ efflux, which indicates that Mg2+ is probably not transported by the antiporter under the conditions of these experiments. Mg2+ inhibited Ca2+-stimulated 22Na+ efflux as expected from the 45Ca2+ influx data. The replacement of external N-methyl-D-glucamine with K+, but not other monovalent ions (choline, Li+), decreased the potency of Mg2+ as an inhibitor of Na+/Ca2+ antiport 6.7-fold. Other divalent cations (Co2+, Mn2+, Cd2+, Ba2+) also inhibited Na+/Ca2+ antiport activity, and high external potassium decreased the potency of each by 4.3-8.6-fold. The order of effectiveness of the divalent cations as inhibitors of Na+/Ca2+ antiport (Cd2+ greater than Mn2+ greater than Co2+ greater than Ba2+ greater than Mg2+) correlated with the closeness of the crystal ionic radius to that of Ca2+.

Amiloride↗
PubMed1987

Throwing money at AIDS.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Thrombospondin promotes cell-substratum adhesion.

The physiological role of the platelet-secreted protein thrombospondin (TSP) is poorly understood, although it has been postulated to be involved in platelet aggregation and cellular adhesion. In this report, TSP isolated from human platelets was found to promote, in vitro, the cell-substratum adhesion of a variety of cells, including platelets, melanoma cells, muscle cells, endothelial cells, fibroblasts, and epithelial cells. The adhesion-promoting activity of TSP was species independent, specific, and not due to contamination by fibronectin, vitronectin, laminin, or platelet factor 4. The cell surface receptor for TSP is protein in nature and appears distinct from that for fibronectin.

Animals↗
PubMed1987

Recombinant human interleukin 1-stimulated Na+/H+ exchange is not required for differentiation in pre-B lymphocyte cell line, 70Z/3.

Interleukin-1 a polypeptide hormone produced by activated macrophages is a mixture of at least two proteins, interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta). We have previously shown that macrophage-derived interleukin-1 induced new kappa light chain synthesis for surface IgM expression in a murine pre-B like cell line 70Z/3, a finding associated with an early amiloride-sensitive rise in the total intracellular sodium concentration. Because IL-1 alpha and IL-1 beta are structurally quite different, in this study their effect on 70Z/3 was examined separately. The results show that both human rIL-1 alpha and rIL-1 beta induce the differentiation of 70Z/3, but a higher concentration of rIL-1 beta compared to rIL-1 alpha is needed for a maximal response. At saturating concentrations, both rIL-1 alpha and rIL-1 beta induce a simultaneous rise in intracellular pH and sodium concentration. Because rIL-1 mediated intracellular alkalinization and sodium rise are amiloride sensitive, they likely occur through stimulation of the Na+/H+ exchanger across the cell membrane. Inhibition of the Na+/H+ antiport with an amiloride analog did not have an effect on rIL-1 induced surface IgM expression or the rIL-1-mediated increase in kappa light chain specific mRNA level. Therefore, these results indicate that an increase in pHi or [Na]i is not required for IL-1 induced 70Z/3 differentiation.

Animals↗
PubMed1987

Na+/K+/Cl- cotransport in cultured vascular smooth muscle cells: stimulation by angiotensin II and calcium ionophores, inhibition by cyclic AMP and calmodulin antagonists.

The specific activity of the Na+/K+/Cl cotransporter was assayed by measuring the initial rates of furosemide-inhibitable 86Rb+ influx and efflux. The presence of all three ions in the external medium was essential for cotransport activity. In cultured smooth muscle cells furosemide and bumetanide inhibited influx by 50% at 5 and 0.2 microM, respectively. The dependence of furosemide-inhibitable 86Rb+ influx on external Na+ and K+ was hyperbolic with apparent Km values of 46 and 4 mM, respectively. The dependence on Cl was sigmoidal. Assuming a stoichiometry of 1:1:2 for Na+/K+/Cl-, a Km of 78 mM was obtained for Cl. In quiescent smooth muscle cells cotransport activity was approximately equal to Na+ pump activity with each pathway accounting for 30% of total 86Rb+ influx. Growing muscle cells had approximately 3 times higher cotransport activity than quiescent ones. Na+ pump activity was not significantly different in the growing and quiescent cultures. Angiotensin II (ANG) stimulated cotransport activity as did two calcium-transporting ionophores. A23187 and ionomycin. The removal of external Ca2+ prevented A23187, but not ANG, from stimulating the cotransporter. Calmodulin antagonists selectively inhibited 86Rb+ influx via the cotransporter. Beta-adrenoreceptor stimulation with isoproterenol, like other treatments which increase cAMP, inhibited cotransport activity. Cultured porcine endothelial cells had 3 times higher cotransport activity than growing muscle cells. Calmodulin antagonists inhibited cotransport activity, but agents which increase cAMP or calcium had no effect on cotransport activity in the endothelial cells.

Angiotensin II↗
PubMed1987

Lung damage following lymph fistula preparation in sheep.

The effect of preparative trauma on lung microvascular permeability during lung lymph fistula preparation in sheep was investigated. Two groups of anesthetized sheep were used. In group I (controls: n = 3) the lymph fistula was prepared 3 to 4 days before the experiment. In group II (experimental group: n = 13): left atrial and lymph catheters were introduced on the day of the experiment. All animals had catheters in the aorta and pulmonary artery. The stable prostanoid metabolites thromboxane B2 (TxB2) and 6-keto-PGF1 alpha (6-keto) were measured in lymph. In group I systemic (Psa) and pulmonary pressures (Ppa) remained constant. Leukocytes and platelets were unchanged as was pulmonary lymph flow (QL) and the lymph to plasma total protein concentration ratio (L/P). In group II Psa and Ppa remained constant. All sheep developed a temporary leukopenia and thrombocytopenia. TxB2 and 6-keto were low and stable during anesthesia in group I but were elevated immediately following surgery in group II but values normalized during a 4-hr observation period. QL during the first half hour was 1.9 +/- 0.3 ml/30 min and increased over 5 hr to 3.1 +/- 0.7 ml/30 min corresponding to 60 +/- 15% over baseline (P less than 0.01). L/P did not change. These changes could be due either to changing permeability or surface area. These effects of preparative trauma indicated that the model was not in a steady state. This observation should be kept in mind when evaluating studies using the lung lymph fistula in acute experiments.

Animals↗
PubMed1987

Progress in T cell biology.

We outline recent work in our laboratories on thymus progenitors, lineages within the thymus, interactions between regulatory and effector lymphocytes, splitting the CD4 (T4) T cell subset, and Ir and Is genes. We highlight the possibilities for future research opened up by the demonstration that certain marrow-derived cell lines can repopulate thymic lobes in culture, and also the deep insight into the logical structure of the lymph node provided by our ability to make an exact comparison between two-cell-type and three-cell-type immunoregulatory clusters.

Animals↗
PubMed1987

Lysosomal enzyme pattern in lung lymph and blood during E. coli sepsis in sheep.

Systemic release of lysosomal enzymes and local release in the pulmonary microcirculation from sequestrated and activated leucocytes could be an important factor in the development of the lung microvascular injury seen after septicaemia. The maximal activities of 11 lysosomal acid hydrolases (acid phosphatase, alpha- and beta-glucosidase, alpha- and beta-galactosidase, alpha-mannosidase, beta-acetylglucosaminidase, beta-glucuronidase, arylamidase and cathepsins B and C) were measured in serum and lung lymph from seven sheep before and after infusion of live E. coli bacteria. In the early phase of septicaemia (the first hour) the activities of eight enzymes were increased in serum and/or lung lymph (1.1 to 2X pre-infusion values). In the late phase, 3-4 h after sepsis, there were significantly elevated serum activities of beta-glucosidase (5.4X), alpha- and beta-galactosidases (2.7X, 1.5X), beta-acetylglucosaminidase (2.0X) arylamidase (1.2X) and cathespin B (1.7X). In lymph acid phosphatase (1.7X), alpha- and beta-glucosidases (1.6X, 6.4X), alpha- and beta-galactosidases (2.1X, 1.7X). Beta-acetylglucosaminidase (2.6X), and beta-glucuronidase (4.0X pre-infusion) were elevated. The findings of a heterogenicity of changes in serum and lymph activities, as well as the large molecular sizes of some of the enzymes with changed activities indicated to us that permeability changes were not major causes of increased lymph enzyme activities. The results could indicate a local release of enzymes either from sequestrated leucocytes or lung tissue due to local reactions in the lung or lung microvessels. The heterogenous changes in activities for the various lysosomal enzymes as found in the present study indicated that measurement of only one enzyme could be misleading.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Prolongation of murine skin allograft survival by the systemic effects of 8-methoxypsoralen and long-wave ultraviolet radiation (PUVA).

Systemic administration of the photoactive drug 8-methoxypsoralen to a group of mice bearing cutaneous allografts, followed by exposure to long-wave ultraviolet radiation (UVA, 320-400 nm) (PUVA) daily for 14 days at a site distant from the allograft, significantly increased the survival time of the allografts. This effect was seen both in donor-recipient combinations that differ at the major histocompatibility complex and in those differing only at minor histocompatibility loci. Treatment with 8-methoxypsoralen or long-wave UV radiation alone was ineffective in prolonging allograft survival, as were doses of mid-wave UV radiation (UVB, 280-320 nm) that produced greater inflammation than the PUVA protocol. Allografted, PUVA-treated animals also demonstrated decreased alloantigen reactivity against donor-strain spleen cells during the period of treatment by cytotoxicity assays. Allografts of skin in the murine system are highly immunogenic and are generally rejected faster than organ allografts; thus PUVA treatment appears to exert a potent effect on prolonging allograft survival. The systemic nature of the effect and the fact that adverse side effects from PUVA are largely limited to the skin suggest that PUVA might have a role in clinical organ transplantation management.

Animals↗
PubMed1987

Sepsis in sheep reduces pulmonary microvascular sieving capacity.

The changes in pulmonary microvascular permeability in sheep, after infusion of live Escherichia coli, were studied using estimations of the osmotic reflection coefficients (sigma) for total protein, albumin, immunoglobins (Ig) G and M and based on these estimations equivalent pore dimensions were calculated. A chronic lung lymph fistula was prepared in seven sheep. After a base-line period, left atrial pressure (Pla) was increased. E. coli (10(9) X kg body wt) were given after attaining filtration independent L/P values. The sigma's for the normal lung were calculated to 0.73 for total protein and to 0.65, 0.76, and 0.91 for albumin, IgG, and IgM, respectively. The equivalent pore radii were determined to 50 and 175 A with 35% of the filtration accounted for by the large pores. After bacterial infusion, the sigma's for total protein, albumin, IgG, and IgM decreased significantly from preseptic values to 0.58, 0.50, 0.64, and 0.83, respectively. After sepsis the small pores were 50 A and the large pores 200 A with 49% of total volume flow at maximum lymph flows occurring through the large pores. Assuming a constant small-pore population the large-pore number increased 32% after bacterial infusion. These results indicate that pulmonary microvascular permeability may have increased due to the sepsis.

Animals↗
PubMed1987

Estimation of equivalent pore radii in pulmonary microvasculature after lung lymph fistula preparation.

The effect of lung lymph fistula preparation on pulmonary microvascular permeability was investigated in sheep. Acutely prepared animals (n = 9) were compared with animals with a chronic lung lymph fistula (n = 5). The osmotic reflection coefficients (sigma) for total protein, albumin, immunoglobins (Ig) G and M, and the equivalent pore dimensions were calculated. Data were achieved at maximal possible lymph flows (QL) following elevation of left atrial pressure. In sheep with a chronic lung lymph fistula sigma's for total protein, albumin, IgG, and IgM at maximal lymph flows were 0.76 +/- 0.01, 0.65 +/- 0.09, 0.79 +/- 0.03, and 0.91 +/- 0.01, respectively. In the acutely prepared group the minimum lymph-to-plasma protein concentration for total protein was 0.39 +/- 0.06, corresponding to a sigma of 0.61 +/- 0.01. The sigma for albumin, IgG, and IgM were 0.48 +/- 0.04, 0.64 +/- 0.02, and 0.87 +/- 0.01, respectively. The equivalent pore radii in the chronic group were determined to be 54 and 190 A with 29% of the filtration accounted for by large pores. In the acute group the small pores were 56 A and the large pores 175 A with 53% of total volume flow at maximum lymph flows occurring through the large pores. Assuming a constant small-pore population the large pore number increased 4.5 times after surgery. For total protein, IgG, and IgM, sigma's in the acutely prepared group were significantly lower than in the control group. These results thus indicate that surgical preparation of a lung lymph fistula in sheep may cause acute increases in pulmonary microvascular permeability.

Animals↗
PubMed1987

Lipid peroxidation is not a major factor involved in the edema formation in perfused lungs.

Perfusion of isolated rat lungs was previously found to induce edema formation, which was considered to be mediated by oxygen-free radicals as scavengers reduced the edema. In the present study we elaborated upon these findings by measuring products found by O2-radical generation. We measured reduced and oxidized glutathione as well as conjugated dienes as an estimate of lipid peroxidation. Amount of water was also measured. Perfusion with oxygenated dextran/Tyrode solution increased edema as compared to nonoxygenated dextran/Tyrode and to nonperfused control lungs. Induction of oxygen radical formation by addition of xanthine and xanthine oxidase to the nonoxygenated dextran/Tyrode perfusate significantly increased the amount of edema as measured by the percentage of water in the lung to 87.0% as compared to the control value of 78.2%. Addition of the radical scavenger superoxide dismutase and catalase to this perfusate prevented edema accumulation. Levels of conjugated dienes as well as those of reduced and oxidized glutathione in lung tissue were measured before the start of perfusion and after 5 and 30 min of perfusion. No significant changes were seen in any of these parameters, indicating that lipid peroxidation may not be a major factor contributing to the edema formation during perfusion of isolated lungs.

Animals↗