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Biomedical subjects

T Wilson

Publications and source records attributed to T Wilson.

At least 145 records · Page 8Linked to original sources
PubMed1994

Decrease in human plasma gravidin levels after medical abortion.

The aim of this study was to determine if loss of pregnancy is associated with a decrease in plasma levels of gravidin, a phospholipase inhibitor thought to maintain pregnancy. Blood was taken from 28 women in the first trimester of pregnancy who had requested an abortion. The progesterone receptor antagonist, RU-486 was given on Day 0 for termination of pregnancy. Plasma gravidin levels were measured on day 0 and on day 2 just before the patients were given misoprostol, a prostaglandin E1 analogue (600 micrograms). In a small group of patients, plasma measurements were continued up to 42 days. By day 2, plasma gravidin levels had fallen significantly (100% to 94%, p = 0.010 in a paired t-test). Following treatment with prostaglandins and pregnancy loss, plasma gravidin levels continued to fall until day 14 when the non pregnant level was reached at 80% of the pregnant level. We conclude that a decrease in plasma gravidin levels is associated with loss of pregnancy. This may occur because progesterone action is blocked.

Abortion, Induced↗
PubMed1994

Lazaroid pretreatment preserves gas exchange in endotoxin-treated dogs.

PURPOSE: The lazaroids are a new class of potent free-radical scavengers. We tested whether U-74389G, a lazaroid, could attenuate some of the adverse cardiopulmonary effects of sepsis. METHODS: Dogs were randomized to receive either 10 mg/kg U-74389G (n = 10), or a saline control (n = 11). After baseline measurements of hemodynamics and gas exchange, they were then randomized to receive either 0.2 mg/kg endotoxin or a saline infusion. Measurements of hemodynamics and gas exchange were repeated. The study was concluded 70 minutes after endotoxin infusion and the lungs were then removed for histologic evaluation. RESULTS: In endotoxin-treated control animals, PO2 decreased (278 +/- 123 mm Hg to 67 +/- 13 mm Hg, P < .05) and intrapulmonary shunt increased (12.9% +/- 1.1% to 28.2% +/- 11.4%, P < .05) after endotoxin. Pretreatment with U-74389G attenuated the decrease in PO2 (476 +/- 61 mm Hg to 226 +/- 143) and the increase in intrapulmonary shunt (12.6% +/- 6.1% to 14.3% +/- 6.8%) observed after endotoxin. The extent of lung injury and systemic hemodynamics were similar between control or U-74389G-treated dogs. CONCLUSIONS: A free-radical-scavenger can attenuate the gas exchange defect commonly associated with endotoxin but it does not improve the derangement of systemic hemodynamics.

Analysis of Variance↗
PubMed1994

Potential role for phosphatidic acid in mediating the inflammatory responses to TNF alpha and IL-1 beta.

Tumor necrosis factor alpha (TNF alpha), interleukin 1 beta (IL-1 beta), and endotoxin (LPS) are potent pro-inflammatory mediators which induce multiple and diverse biological responses in a wide variety of cell types. However, these pro-inflammatory mediators also have significant overlap and redundancy in their biological effects. This suggests that there is significant diversity in second messenger signal transduction systems induced by these stimuli to explain the diversity in biological responses, as well as significant redundancy. Here we show that one such second messenger common to several proinflammatory stimuli may be phosphatidic acid (PA). Intracellular PA species, which may have intracellular signaling functions, are rapidly induced in P388 monocytic leukemia cells by TNF alpha, IL-1 beta, or LPS. These PA species vary according to the bond type (i.e., sn-1 ester vs. ether vs. vinyl ether), acyl chain length, and the degree of saturation in the sn-1 and sn-2 positions. Although PA itself may have direct second messenger activities, many of the PA species induced are converted to diacylglycerol species (DG), which are structurally distinct from the DGs generated by phosphatidylcholine-specific phospholipase C (PC-PLC). Lisofylline [(R)-1-(5-hydroxyhexyl)-3,7-dimethylxanthine; LSF] selectively inhibits generation of selected species of PA in P388 cells induced by TNF alpha, IL-1 beta or LPS. TNF alpha-induced sphingomyelin hydrolysis, PLC-mediated PC hydrolysis, and DG kinase-mediated PA formation or TNF alpha-induced NF-kappa B activation and apoptosis are not inhibited by LSF. LSF has a marked protective effect in a variety of acute inflammatory animal models that may be due to inhibition of this shared second messenger pathway involving PA.

Animals↗
PubMed1994

Pulmonary vascular effects of endotoxin in canine lobes pretreated with dapsone.

Endotoxin results in a granulocyte mediated loss of hypoxic pulmonary vasoconstriction (HPV). Dapsone blocks the granulocyte respiratory burst and might, therefore, preserve HPV following endotoxin. Isolated-perfused canine lobes (n = 6) were pretreated with 18 mg/kg dapsone (dapsone group), and compared to six lobes which did not receive dapsone (control group). Total pulmonary vascular resistance (Rtot) and arterial, middle (Rm), and venous segmental resistances were calculated by a vascular occlusion technique. We then administered endotoxin (2 mg/kg) and repeated measurements at 5, 30, and 90 min. The increase in Rm during 3% O2 compared to 35% O2 ventilation was used to define the presence of HPV. In the control group, following endotoxin, values of Rm did not change (P > 0.05) during 3% O2 ventilation (0.011 +/- 0.006 cm H2O/ml/min) compared with 35% O2 ventilation (0.014 +/- 0.005 cm H2O/ml/min). In the dapsone group, following endotoxin, values of Rm increased (P < 0.05) during 3% O2 ventilation (0.06 +/- 0.026 cm H2O/ml/min) compared with 35% O2 ventilation (0.03 +/- 0.015 cm H2O/ml/min). Changes in 6-keto PGF1 alpha or thromboxane B2 do not explain these observations. We conclude that in this experimental preparation, pretreatment with dapsone prevents the loss of HPV associated with endotoxin.

Animals↗
PubMed1994

Neutrophil-mediated acute lung injury after extracorporeal perfusion.

A pulmonary injury of varying severity occurs routinely after cardiopulmonary bypass. We studied the pulmonary complications of partial cardiopulmonary bypass in four groups of dogs to better define the injury and to evaluate the efficacy of two interventions (addition of a leukocyte filter or cyclooxygenase inhibition) on preservation of systemic oxygenation. All animals received a standard anesthetic (pentobarbital, morphine, and vecuronium) and, after sternotomy, three groups of animals received 3 hours of partial cardiopulmonary bypass. The animals were randomized to receive partial bypass alone (n = 6), indomethacin and bypass (n = 5), or a leukocyte filter and bypass (n = 5). A fourth group (n = 5) did not receive bypass and served as a time control. We measured blood gases and also obtained histologic samples to assess the degree of lung injury. We found that bypass alone caused a significant reduction (p < 0.05) in arterial oxygen tension 1 hour after the conclusion of bypass (175 +/- 53 mm Hg) compared with prebypass values (357 +/- 41 mm Hg). Pretreatment with indomethacin ameliorated the decrease in arterial oxygen tension from prebypass to postbypass values (477 +/- 50 mm Hg versus 339 +/- 57 mm Hg, respectively). Similarly use of a leukocyte filter reduced the decline in arterial oxygen tension from prebypass to postbypass values (440 +/- 71 mm Hg versus 311 +/- 73 mm Hg, respectively). We believe that indomethacin ameliorates the decline in systemic oxygenation associated with bypass by augmentation of hypoxic pulmonary vasoconstriction and that the leukocyte filter acted to reduce pulmonary edema and thereby minimized intrapulmonary shunt.

Animals↗
PubMed1993

Arachidonic acid, a growth signal in murine P815 mastocytoma cells.

Evidence is presented that inducing P815 murine mastocytoma cells to grow with serum activates a Ca(2+)-stimulated phospholipase A2 and the rapid release of arachidonic acid by the cells. Slower growth was also maintained by arachidonic acid or its immediate precursors or by diacylglycerols when bovine serum albumin replaced the serum. Together, arachidonic acid and 1-oleoyl-2-acetylglycerol stimulated growth at the same rate as 10% serum consistent with a role for both arachidonic acid and protein kinase C in the response to serum. Arresting cell growth with N6,O2'-dibutyryladenosine 3',5'-cyclic phosphate and theophylline inhibited the release of arachidonic acid in response to serum, suggesting that cyclic AMP prevents phospholipase activation as one of its pleiotypic effects on growth. Attempts to demonstrate metabolism of [3H]arachidonic acid to eicosanoids in serum-treated P815 cells by high-performance liquid chromatography or thin layer chromatography were unsuccessful, with the major products being phospholipids and triacylglycerol. Incubating digitonin-permeabilized P815 cells with [gamma-32P]ATP and arachidonic acid rapidly increased the phosphorylation of some proteins in the cells, especially the M(r) 135,000 and M(r) 44,000 proteins which were considerably more phosphorylated than the rest. Phosphorylation of these proteins was not prevented by several inhibitors of protein kinase C, nor was it increased by diacylglycerols or phorbol ester, suggesting that arachidonic acid activates a growth-related protein kinase other than protein kinase C in P815 cells. The possibility that some polyunsaturated fatty acids may promote tumor cell growth by stimulating protein phosphorylation is considered.

Animals↗
PubMed1993

Thymic microenvironmental abnormalities and thymic selection in NZB.H-2bm12 mice.

We have taken advantage of an extensive panel of mAb directed to thymic epithelial and nonepithelial stromal cells to examine the expression of these Ag from day 16 of gestation through 6 mo of age in NZB(H-2d), NZB.H-2b, NZB.H-2bm12, C57BL/6(H-2b), and C57BL/6.H-2bm12 mice. In addition, by triple color flow cytometry we have examined the expression of cell surface markers defining distinct stages of intrathymic T cell maturation. New Zealand mice demonstrated three abnormalities. MTS 10 normally stains thymic medullary and subcapsular epithelium. However, New Zealand mice demonstrated striking irregular medullary epithelial cell shape whereas their subcapsular epithelium remained normal. Moreover, New Zealand mice, unlike controls, were found to have MTS 10+ epithelial cells within the cortex. Additionally, MTS 39 and MTS 44, which normally stain reticular cortical epithelium, produced a striking different staining pattern in New Zealand mouse thymus, including the presence of large cortical epithelial cellfree regions, so-called "cortical holes." MTS 33 normally stains cortical thymocytes but in New Zealand mice, there was a severe decrease of MTS 33+ cells. There was also an increase of CD3lowCD4+CD8+ cells in NZB mice, which may include many predeletion thymocytes. Finally, there was a significant increase of CD3highCD4+CD8- cells in NZB.H-2bm12 and C57BL/6.H-2bm12 mice compared with NZB.H-2b and C57BL/6(H-2b) mice. We postulate that these microenvironmental alterations in NZB mice contribute to and reflect altered T cell differentiation, thereby predisposing them to autoimmune disease. Moreover, the increased proportion of CD3highCD4+CD8- cells associated with the H-2bm12 mutation may be involved in the remarkably different profiles of disease between NZB.H-2b and NZB.H-2bm12 mice.

Animals↗
PubMed1993

Gravidin: an endogenous inhibitor of phospholipase A2.

Gravidin is a recently discovered protein inhibitor of phospholipase A2 and therefore prostaglandin synthesis. Transformed or rapidly growing cells are unaffected by gravidin, but in slow-growing cells arachidonate release is inhibited. Gravidin may play a physiological role in pregnancy maintenance. This review summarizes our current knowledge of the properties and activity of gravidin.

Animals↗
PubMed1993

Raised serum gravidin levels are associated with pregnancy-induced hypertension.

It has recently been reported that synthesis of the vasodilatory prostaglandin, prostacyclin, is decreased in human pregnancy-induced hypertension (PIH). Prostaglandin production is regulated mainly by the enzyme phospholipase A2. We report here that serum levels of a potent phospholipase A2 inhibitor (gravidin) were elevated during early pregnancy in women who later developed PIH compared with those who remained normotensive throughout pregnancy. It is suggested that high circulating levels of this potent phospholipase inhibitor may account for the reported decrease in prostacyclin synthesis and contribute to the development of pregnancy-induced hypertension.

Female↗
PubMed1993

Laparoscopic management of acute small bowel obstruction.

Acute small bowel obstruction is commonly due to band adhesions. In the past it has had an overall mortality rate of up to 11% for elderly patients. In this paper we report three cases of small bowel obstruction, treated by laparoscopic division of the causative bands. All patients recovered rapidly and were discharged within 5 days of surgery.

Acute Disease↗
PubMed1993

NG-monomethyl-L-arginine does not restore loss of hypoxic pulmonary vasoconstriction induced by TNF-alpha.

Tumor necrosis factor-alpha (TNF-alpha) causes systemic hypotension, pulmonary vasodilation, and loss of hypoxic pulmonary vasoconstriction. NG-monomethyl-L-arginine (L-NMMA) inhibits nitric oxide (NO) production and prevents some systemic manifestations of TNF-alpha. We tested using an isolated perfused canine lobe whether NO also mediates the pulmonary vascular effects of TNF-alpha. Total resistance (RT) was measured during control and hypoxic ventilation over a 90-min period in six control lobes, five lobes treated with TNF-alpha (250 micrograms), six lobes treated with L-NMMA (200 mg), and five lobes treated with L-NMMA (200 mg) + TNF-alpha (250 micrograms). In the control lobes RT increased (P < 0.02) from 0.0474 +/- 0.0105 to 0.0677 +/- 0.0133 cmH2O.ml-1 x min during normoxic and hypoxic ventilation, respectively. RT decreased (P < 0.05) from a baseline of 0.0593 +/- 0.0133 to 0.0449 +/- 0.0176 cmH2O.ml-1 x min 30 min after TNF-alpha administration and did not further change during hypoxic ventilation (0.0475 +/- 0.0107 cmH2O.ml-1 x min). L-NMMA pretreatment did not prevent the TNF-alpha-induced loss of hypoxic pulmonary vasoconstriction, with values of RT unchanged from normoxic (0.0541 +/- 0.0067 cmH2O.ml-1 x min) to hypoxic (0.0545 +/- 0.0078 cmH2O.ml-1.min) ventilation (P > 0.10) in the L-NMMA + TNF-alpha group after TNF-alpha administration. We conclude that NO is not the mediator responsible for the acute pulmonary vascular effects of TNF-alpha.

Animals↗
PubMed1993

Effect of aflatoxin-contaminated feed on morbidity and residues in walleye fish.

The effect of aflatoxin in the feed on the morbidity and toxin residue in the musculature of walleye fish was studied. The fish were divided into 3 groups of 12 each; group 1 served as controls, groups 2 and 3 received feed treated with 50 or 100 ppb toxin for 30 d respectively. Fish were kept in glass aquaria, 4 fish/aquarium, with aerator and solids-waste filter system. Fish were observed for morbidity and mortality. Six fish from each group were sacrificed after 30 d and examined for gross pathological lesions and histopathological changes. In addition, fish musculature were analyzed for aflatoxin. One out of 16 (8%) of the fish fed 100 ppb aflatoxin in 48 h. Pale livers and significant degenerative changes were observed in both toxin-treated groups. Aflatoxin B1, G1 and G2 were detected in the musculature of both groups at a concentration of 5, 10, 15, 20 ppb respectively. After 2 w of aflatoxin withdrawal, no aflatoxin was detectable in the fish muscle. However, marked histopathological lesions were still observed.

Aflatoxins↗
PubMed1992

A proposed function for spermine and spermidine: protection of replicating DNA against damage by singlet oxygen.

Like all aliphatic amines, the polyamines spermine and spermidine are physical quenchers of singlet molecular oxygen (1O2*). The rate constants of these processes were determined in vitro with photochemically generated 1O2* and the hydrocarbon rubrene as substrate, in pyridine. At millimolar concentration, spermine and spermidine should quench 1O2* in vivo and prevent it from damaging DNA. It is proposed that a biological function of polyamines is the protection of replicating DNA against oxidative damage.

DNA↗
PubMed1992

Spermine and spermidine protection of plasmid DNA against single-strand breaks induced by singlet oxygen.

Oxidative damage to DNA induced by singlet molecular oxygen (1O2*) includes single-strand breaks, which the biologically occurring 1O2* quenchers spermine and spermidine are shown to prevent. These polyamines at a physiological concentration (10 mM) reduce the percentage of the open circular form of pBR322 plasmid DNA, which is generated at the expense of the native supercoiled form when the plasmids are incubated with a chemical source of 1O2*, the water-soluble endoperoxide of 3,3'-(1,4-naphthylidene)dipropionate. Spermine and spermidine can be expected to protect DNA against other damaging effects of 1O2*.

DNA↗