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Biomedical subjects

B M Taylor

Publications and source records attributed to B M Taylor.

At least 37 records · Page 2Linked to original sources
PubMed1995

Lack of effect of postinjury treatment with methylprednisolone or tirilazad mesylate on the increase in eicosanoid levels in the acutely injured cat spinal cord.

Methylprednisolone (MP) improves motor recovery in spinal cord-injured patients when administered in a 24 h intensive high dose regimen beginning within 8 h after spinal cord injury (SCI). The rationale for this regimen has been based upon the need for high doses (i.e., 30 mg/kg initial IV dose) to inhibit posttraumatic lipid peroxidation (LP) in the injured spinal segment. However, injury also triggers the immediate calcium-mediated activation of phospholipase A2 (PLA2), the release of arachidonic acid, and the enzymatic formation of potentially deleterious prostaglandins (PGE2 alpha, PGE2), thromboxane A2 (TXA2), and leukotrienes (LTs). Thus, in view of the glucocorticoid receptor-mediated inhibition of PLA2 that underlies much of MP's antiinflammatory actions, an additional neuroprotective mechanism may relate to an inhibition of eicosanoid formation. Using the cat spinal cord compression model (180g x 5 min at L3; Na pentobarbitol anesthesia), we examined whether 30 min postinjury dosing with MP (30 mg/kg IV) could attenuate spinal tissue eicosanoid levels measured by enzyme immunoassay at 1 h (Experiment 1). Pial blood flow was measured over the dorsal columns at the injury site using laser doppler flowmetry to monitor posttraumatic hyperperfusion as an index of the microvascular pathophysiology of acute SCI. In vehicle treated animals at 1 h postinjury, there was a significant increase in the tissue levels of PGF2 alpha (+290%), PGE2 (+260%), TXB2 (stable analog of TXA2, +126%), and LTB4 (+73%) in comparison to sham, uninjured animals. However, 6-keto-PGF1 alpha (stable analog of prostacyclin or PGI2) and LTC4 did not increase. Methylprednisolone did not reduce the increase in eicosanoid production. In the case of LTB4 and LTC4, MP actually increased the levels further. In addition, we examined the effects of a double dose MP regimen (30 mg/kg IV at 30 min plus 15 mg/kg IV at 2.5 h postinjury) on spinal cord eicosanoid levels at 4 h postinjury (Experiment 2). At 4 h postinjury, significant increases in PGF2 alpha, PGE2, TXB2, and 6-keto-PGF1 alpha were observed, and with the exception of PGE2, no MP attenuation of the increased eicosanoids was seen. These results fail to provide evidence that postinjury administration of high dose MP exerts a significant anti-PLA2 action. On the other hand, MP effectively inhibited secondary spinal cord pial hyperperfusion, which is believed to be largely mediated by free radical-lipid peroxidative mechanisms. Thus, it seems likely that the protective action of MP on the acute microvascular pathophysiology of SCI is mediated by its well-documented effects on posttraumatic LP.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Effects of the lipid peroxidation inhibitor tirilazad mesylate (U-74006F) on gerbil brain eicosanoid levels following ischemia and reperfusion.

The present study measured the production of eicosanoids in the gerbil brain during early reperfusion after either a 3-h unilateral carotid occlusion (UCO, model of focal ischemia) or a 10-min bilateral carotid occlusion (BCO, model of global ischemia). Arachidonic acid (AA) metabolites were examined to determine if pretreatment with the 21-aminosteroid lipid peroxidation inhibitor U-74006F (tirilazad mesylate) could influence postreperfusion synthesis of brain eicosanoids. In the 3-h UCO focal ischemia model, there was an early (5-min) postreperfusion elevation in brain levels of PGF2 alpha, TXB2 and LTC4 (P < 0.05 vs. sham for all three eicosanoids). LTB4 also rose but not significantly. On the other hand, PGE2 and 6-keto-PGF1 alpha tended to decrease during ischemia and at 5-min postreperfusion (P < 0.05 vs. sham for PGE2). Pretreatment with known neuroprotective doses of U-74006F in this model (10 mg/kg i.p. 10 min before and again immediately upon reperfusion) did not affect the increase in PGF2 alpha or TXB2 but significantly blunted the elevations in LTC4 and LTB4. The postreperfusion decrease in PGE2 was also attenuated. In the 10-min BCO global ischemia model, there was also an increase in each of the measured eicosanoids, except LTB4, at 5 min after reperfusion. Pretreatment with U-74006F (10 mg/kg i.p. 10 min before ischemia) selectively decreased the rise in LTC4 but did not significantly affect the other eicosanoids. In contrast, the antioxidant actually caused a significant enhancement of the postreperfusion increase in PGE2 vs. vehicle-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Degradation of membrane phospholipids in the cultured human astroglial cell line UC-11MG during ATP depletion.

The exposure of brain cells to adverse conditions, such as ATP depletion, induces the degradation of membrane phospholipids and the accumulation of free fatty acids. We have investigated the mechanism of membrane breakdown in an in vitro cell injury model. Confluent cells from the human astroglial cell line UC-11MG were treated with sodium iodoacetate to deplete their intracellular ATP. Large amounts of saturated (palmitic acid) and unsaturated (oleic, linoleic and arachidonic acid) free fatty acids as well as diacylglycerols containing prelabeled fatty acids were released from the cells prior to the loss of plasma membrane integrity. The capacity of the cells to reincorporate free fatty acid into membrane phospholipids decreased in parallel with the loss of intracellular ATP, indicating the failure of the acyltransferase pathway. The addition of the phospholipase A2 inhibitors manoalide, mepacrine, or U-26384, or the phospholipase C inhibitor U-73122, reduced the severity of cell injury, but did not maintain cell viability. The addition of a battery of protease inhibitors with or without the phospholipase inhibitors had no protective effect. These results suggest that the activation of phospholipases A2 and C coupled with the loss of the reacylation process lead to the breakdown of membrane components during lethal cell injury.

Adenosine Triphosphate↗
PubMed1993

Metabolism of leukotriene B4 by guinea pig eosinophils.

The metabolism of leukotriene B4 (5(S),12(R)-dihydroxy-6-cis-8,10-trans-14-cis-eicosatetraenoic acid) by isolated guinea pig eosinophils was investigated. Incubation of guinea pig eosinophils with [3H]-leukotriene B4 resulted in the rapid conversion of leukotriene B4 to several more polar metabolites. Two of these metabolites were identified by ultraviolet spectroscopy and gas chromatography-mass spectrometry as the omega oxidation products 5(S),12(R),20-trihydroxy-6,8,10,14-eicosatetraenoic acid (20-hydroxy-leukotriene B4) and 5(S),12(R),19-trihydroxy-6,8,10,14- eicosatetraenoic acid (19-hydroxy-leukotriene B4). Two novel metabolites, 5(S),12(R),18,19-tetrahydroxy-6,8,10,14 eicosatetraenoic acid (18,19-dihydroxy-leukotriene B4) and 5(S),12(R)-dihydroxy-1,18-dicarboxylic-6,8,10,14,16-octadecapentaenoi c acid (delta 16,17-18-carboxy-19,20-dinor-leukotriene B4) were tentatively identified. The identification of these compounds indicates that guinea pig eosinophils are capable of metabolizing leukotriene B4 by both omega and beta oxidation. This catabolic activity may play a role in modulating inflammatory reactions by removing the chemoattractant leukotriene B4 from inflammatory sites.

Animals↗
PubMed1992

Deep pelvic abscesses: transrectal drainage with radiologic guidance.

Transrectal catheter drainage was performed under radiologic guidance in eight patients with deep pelvic abscesses during a 7-month period. One patient underwent two procedures. In five patients, the abscess could not be palpated at rectal examination. Seven procedures were performed with fluoroscopic guidance. Transrectal ultrasound was performed in conjunction with fluoroscopy for two procedures. Medium to large (8-14-F) locking catheters were used in seven procedures, and small (5-F) nonlocking pigtail catheters were used in two. The catheter was left in place for 3 days or less in all but one patient, in whom the catheter was left in place for 20 days. Five abscesses were drained through the anterior or anterolateral rectal wall and four, including one repeat drainage, through the posterior rectal wall. No complications occurred as a direct result of transrectal drainage. Successful initial drainage was established with clinical improvement in all cases. Two patients eventually required surgery, one for continued bleeding into an infected hematoma and one for abscess recurrence after tube dislodgment. Transrectal drainage performed with radiologic guidance is a safe, feasible procedure; is well tolerated by patients; and is relatively easy to perform with the techniques described.

Abscess↗
PubMed1991

Functional properties of guinea pig eosinophil leukotriene B4 receptor.

It is currently thought that pulmonary eosinophils play a proinflammatory role in bronchial asthma. Leukotriene B4 (LTB4) is being considered as an important mediator in regulating eosinophil function because of its potent activities in inducing leukocyte chemotaxis, chemokinesis, degranulation, and aggregation. Because the LTB4 receptor has not been characterized in eosinophils, we report in this study the presence of a functional high affinity receptor for LTB4 on guinea pig (GP) eosinophils. Scatchard analysis of saturation binding studies yielded a Kd of 1.4 +/- 0.2 nM (mean +/- SEM, n = 3) and a Bmax of 1.6 +/- 0.4 pmol/mg of protein for LTB4 in GP eosinophil membranes. A linear Scatchard plot was obtained, suggesting that GP eosinophil membranes expressed only a single high affinity LTB4 receptor population. Saturation binding studies in whole cells also yielded a linear Scatchard plot, with a Kd of 2.8 +/- 0.96 nM (mean +/- SEM, n = 4) and a Bmax of 4 x 10(4) +/- 6 x 10(3) receptors/cell. Competitive binding studies using several compounds with structures similar to that of LTB4 showed that these agents bound to the receptor in the following descending order of affinity (Ki, nM): LTB4 (0.96) less than TB3 (1.0) greater than 20-hydroxy-LTB4 (3.5) greater than 12(R)-hydroxy-5,8,14-cis,10-trans-eicosatetraenoic acid (20) greater than 12(S)-hydroxy-5,8,14-cis,10-trans-eicosatetraenoic acid (231) greater than 20-carboxy-LTB4 (350) greater than 5(S),12(S)-dihydroxy-6,10-trans,8,14-cis-eicosatetraenoic acid (541). This rank order of potency in binding affinity correlates closely with the ability of these compounds to induce both chemotaxis and superoxide anion generation. Analysis of the structure-activity relationship suggests that the 12R-hydroxyl group and a cis double bond at the C-6 position are important for optimal agonist binding to the LTB4 receptor present in GP eosinophil membranes. The results suggest that LTB4 may be an important chemoattractant for eosinophils in GP and may induce the release of reactive oxygen species from this cell.

Animals↗
PubMed1991

Biochemical and functional differences between eosinophils from animal species and man.

Eosinophils were isolated from peritoneal lavages of repeated horse serum-injected guinea pigs or rhesus monkeys and from peripheral blood of normal human donors. Eicosanoid metabolism and chemotaxis by these cells were studied by in vitro techniques. Upon calcium ionophore stimulation guinea pig eosinophils released thromboxane B2 (TXB2) and leukotriene B4 (LTB4) while monkey and human cells produced LTC4, LTB4, and 5-HETE. Guinea pig cells do not synthesize sulfidopeptide LTs, because they lack the specific LTA4 glutathione S-transferase. Guinea pig eosinophils exhibit maximal chemotactic responses to LTB4, zymosan activated plasma, and human recombinant C5a, while producing only a negligible response to platelet activating factor (PAF). Monkey and human cells responded maximally to PAF, but exhibit only a weak response to LTB4. These results suggest that the guinea pig eosinophils differ from monkey and human eosinophils in both the synthetic capacity and functional chemotaxis responses to lipid mediators.

Animals↗
PubMed1991

Biological activity of leukotriene B4 analogs: inhibition of guinea pig eosinophil migration in vitro by the 2,6-disubstituted pyridine analogs U-75,302 and U-75,485.

A "late phase" antigen-induced bronchoalveolar eosinophilia has been demonstrated in ovalbumin sensitized guinea pigs (1,2). This in vivo response to antigen inhalation can be inhibited by a 2,6-disubstituted pyridine analog of LTB4, U-75,302(2) (3). In the present study, the mechanism of the drug action was studied by assessing the activity of U-75,302 and a second analog, U-75,485 to displace [3H]-leukotriene B4 binding at the guinea pig eosinophil membrane, as well as their action as chemoattractants or inhibitors of the directional migration of guinea pig eosinophils in vitro. Radioligand competition experiments demonstrated that both analogs interacted strongly with the high affinity LTB4 binding sites on guinea pig eosinophil membrane. Both analogs are powerful chemoattractants for guinea pig eosinophils since they induced directional migration of guinea pig eosinophils when administered alone. In addition, when the cells were treated with either analog and their chemotaxis response was measured in response to a natural chemoattractant, both U-75,302 and U-75,485 at concentrations of 0.1 to 100 microM dose dependently inhibited the LTB4 induced chemotaxis response. The EC50s obtained for U-75,302 and U-75,485 as inhibitors of LTB4 induced guinea pig eosinophil chemotaxis were estimated to be 11.5 +/- 5.5 microM and 5.4 +/- 2.5 microM respectively. Under the same conditions, they had no significant effect upon eosinophil migration induced by zymosan activated plasma at concentrations below 100 microM. We suggest that the inhibition of antigen-induced eosinophil infiltration in guinea pig airway in vivo by U-75,302 or U-75,485 may be a result of partial antagonism or desensitization at the LTB4 receptor level of guinea pig eosinophils.

Animals↗
PubMed1991

Contribution of leukotriene B4 to airway inflammation and the effect of antagonists.

Inhalation of aerosols of ovalbumin in sensitized guinea pigs produced a marked, bronchoalveolar eosinophilia 24 hr after challenge. The lung eosinophilia was not prevented by the cyclooxygenase inhibitors, indomethacin or PAF antagonists (WEB-2086 and L-652731) but was inhibited by methylprednisolone, the 5-LO inhibitor, U-66858 and a series of structural analogs of LTB4, U-75302, U-77692, U-75485 and U-78489. The effectiveness of LTB4 antagonists but not PAF antagonists in vivo was consistent with in vitro studies in which LTB4 was shown to be far more chemotactic than PAF for guinea pig eosinophils. LTB4 elicited maximal directional migration of guinea pig eosinophils at concentrations from 10(-7) M to 10(-9) M while PAF showed no effect over the same concentration range. The structural analogs of LTB4 were shown to inhibit LTB4 induced chemotaxis of guinea pig eosinophils and produced a dose-related inhibition of binding of LTB4 to guinea pig eosinophil membranes. To add further proof to the hypothesis that LTB4 contributed to the antigen-induced lung eosinophilia we attempted to measure LTB4 release into BAL fluid immediately after and at various time points up to 24 hr after antigen inhalation. However, using a sensitive radioimmunoassay (detection limit 10 pg/ml) very low levels of LTB4 (24.9-67.9 pg/ml) or its metabolite, 20-OH LTB4 (24.9-98.2 pg/ml) were detected in BAL fluid and these levels did not increase significantly following antigen provocation. Inhalation of LTB4 aerosols in unsensitized Brown-Norway rats or inhalation of aerosols of ovalbumin in sensitized Brown-Norway rats also produced a marked "late-phase" eosinophil-rich influx of inflammatory cells into the lungs. The lung eosinophilia in the rat was prevented by two structurally unrelated leukotriene B4 (LTB4) antagonists, U-75302 and Ly255283. These data implicate LTB4 as a mediator of allergen-induced bronchopulmonary eosinophilia. Leukotriene B4 antagonists may provide leads for the development of compounds which inhibit the chronic airway inflammation associated with asthma in man.

Aerosols↗
PubMed1989

Arachidonic acid metabolism in guinea pig eosinophils: synthesis of thromboxane B2 and leukotriene B4 in response to soluble or particulate activators.

The arachidonic acid metabolism of guinea pig eosinophils isolated from either peritoneal cavity or bronchoalveolar lavages was studied by reverse-phase high-performance liquid chromatography. The purified eosinophils (95-100%) from either source released thromboxane B2 (TxB2), luekotriene B4 (LTB4) and 5-hydroxy eicosatetraenoic acid (5-HETE) following calcium ionophore A23187 stimulation. Quantification by radioimmunoassay indicated that maximal mediator output from the stimulated peritoneal cells was reached at 3 min after stimulation. The increase in production of TxB2 and LTB4 was correlated to increasing calcium ionophore A23187 concentration up to 1.0 micrograms/ml. In addition to calcium ionophore, the guinea pig peritoneal cells were also activated by f-met-leu-phe, phorbol 12-myristate, 13-acetate (PMA), and to lesser extent platelet-activating factor (PAF) to produce TxB2. LTB4 synthesis was stimulated by calcium ionophore, by f-met-leu-phe, as well as by unopsonized glucan, a particulate phagocytotic stimulus. The guinea pig eosinophils do not synthesize sulfidopeptide leukotrienes because of the absence of the specific LTA4 glutathione S-transferase. These results suggest that the guinea pig eosinophils differ from the human circulating eosinophils in the synthetic capacity of lipid mediators derived from arachidonic acid metabolism. This difference may be important in the understanding of the role of the eosinophils in inflammatory reactions such as that which occurs in the bronchial tissues of asthmatics.

Animals↗
PubMed1988

Epidural anesthesia for acute pseudo-obstruction of the colon (Ogilvie's syndrome).

With the theory that Ogilvie's syndrome is caused by sympathetic inhibition of contractility in the colon as a basis, 18 patients with acute colonic pseudo-obstruction were enrolled in a treatment program assessing the safety and efficacy of sympathetic blockade, by epidural anesthesia, in those who failed conservative management. In some cases colonoscopy had been performed initially and, if unsuccessful, these patients were referred for treatment with epidural anesthesia. Seven patients recovered with conservative treatment alone. One patient refused further treatment and died of her underlying disease. Five of eight patients treated by epidural anesthesia responded. There were no recurrences following successful epidural anesthesia. Five of eight patients treated by colonoscopic decompression responded. No patients required surgical intervention. One patient suffered a subendocardial infarction during colonoscopy. There were no significant complications from epidural anesthesia. Epidural anesthesia is safe, effective, simple, and well tolerated in the management of Ogilvie's syndrome.

Acute Disease↗
PubMed1988

Effect of antibiotic and fluid resuscitation upon survival time in experimental intestinal ischemia.

Acute massive intestinal ischemia is an abdominal catastrophe. Prompt diagnosis and restoration of blood flow is essential; otherwise, massive intestinal resection occurs, leading to death or, in the survivors, intestinal cripples. In this study, the time of warm reversible ischemia in the canine intestine was explored. After this time was established, fluids and antibiotics were administered to note change in survival times. Massive intestinal ischemia (superior mesenteric artery was clamped) was tolerated without death for five hours (20 dogs in each group). With six hours of ischemia, a 10 per cent mortality rate occurred; with seven hours of ischemia, a 90 per cent mortality rate occurred. These dogs had a maintenance of 75 milliliters of fluid administered per hour. Using this group of dogs as the control (that is, the group with seven hour clamping time of the superior mesenteric artery with maintenance intravenously administered replacement), fluids were given to dogs in the experimental group to keep the pulmonary artery wedge pressure at a normal value (average of 300 milliliters per hour). This group of dogs had an increased survival rate of 40 per cent (ten dogs). Antibiotics were given to the dogs in the experimental group both before and after clamping, increasing the over-all survival rate to more than 80 per cent (46 dogs). Aggressive fluid replacement and antibiotic coverage may lengthen the so-called golden period in which intestinal ischemia may be reversed by revascularization.

Animals↗
PubMed1986

Coloanal anastomosis: indications and surgical technique.

The coloanal anastomosis has evolved from the older "sleeve" pull through techniques and is used as a sphincter-saving procedure in those patients requiring excision of the rectum where adequate removal of all disease necessitates transection of the rectum close to the dentate line. For very low rectal carcinomas, however, abdominoperineal resection remains the procedure of choice for curative treatment. The appropriate choice of low anterior resection, coloanal pull through anastomosis, or abdominoperineal resection depends on many other variables besides the location of the tumor, and the correct choice may not be apparent until the rectum has been mobilized at surgery. The coloanal procedure requires wide excision of the lesion; full mobilization of the splenic flexure, distal transverse colon, and descending colon; precise transanal removal of the rectum; accurate suturing of the descending colon to the anus; and a temporary defunctioning colostomy. With careful technique, longterm results are good in most patients.

Anal Canal↗
PubMed1985

Disappearance and metabolism of leukotriene B4 during carrageenan-induced pleurisy.

Leukotriene B4 (LTB4) has been implicated as a mediator in the inflammatory process by virtue of its potent chemotactic activity. At present, very little is known of the stability of this compound in vivo; therefore, the present study was designed to determine the half-life and metabolic fate of radiolabeled LTB4 during a 2-hr intrapleural incubation in rats with acute carrageenan pleurisy. After injection of 0.2 ml of 1% sodium carrageenan (Viscarin), inflammation was allowed to develop for 4 hr. A small polyethylene cannula was then inserted into the chest, and 0.1 microCi of [14C]LTB4 was injected into the chest. Samples for radioactivity determination were taken at 0, 1, 2, 3, 4, 5, 7, 10, 15, 20, 30, 45, 60, 90 and 120 min via the cannula, and at 120 min the entire content of the chest was collected. The half-life for the disappearance of radioactivity from the chest was 45.8 +/- 3.5 min. The 120-min samples were treated with acetone to precipitate protein and extracted with Sep-Paks. The extracts were analyzed by reversed phase high performance liquid chromatography using an ultraviolet detector set at 269 nm and a radioactivity detector. An additional experiment was run using multi-[3H]LTB4, and the only major metabolites detected were omega-hydroxylated compounds. It can be concluded from these results that LTB4 is relatively stable in vivo and could be present for long enough at the inflammatory site to have an influence upon inflammatory cell migration.

Animals↗
PubMed1985

Epoxidation of prostacyclin in the rabbit kidney.

In the isolated Tyrode's perfused rabbit kidney, metabolism of [9-3H]prostacyclin was examined. In addition to 7,9-dihydroxy-4,13-diketo-dinor-prostanoic acid, dinor-6-keto-prostaglandin F1 alpha, and pentanorprostaglandin (PG)F1 alpha gamma-lactone, a new, previously unreported, metabolite was isolated and identified by radio-gas chromatography and gas chromatography-mass spectrometry as 5-hydroxy-6-keto-PGF1 alpha. The structure of this metabolite was further confirmed by comparison of the mass spectra to that of the synthetic standard. The formation of 5-hydroxy-6-keto-PGF1 alpha in the kidney suggested epoxidation of prostacyclin via the renal epoxygenase pathway.

Animals↗
PubMed1985

Alternatives to ileostomy after colectomy for inflammatory bowel disease.

Proctocolectomy and Brooke ileostomy have long been the standard surgical procedure for patients with refractory ulcerative colitis or colonic Crohn's disease. Ileorectal anastomosis, ileoanal anastomosis, the continent ileostomy, and the continent ostomy valve are now being used in selected patients as options to the Brooke ileostomy. The indications for and advantages of these procedures and their potential disadvantages and contraindications are discussed in this chapter.

Anal Canal↗