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Biomedical subjects

E F Smith

Publications and source records attributed to E F Smith.

At least 91 records · Page 5Linked to original sources
PubMed1985

The protection given by pilus and whole cell vaccines of Bacteroides nodosus strain 198 against ovine foot-rot induced by strains of different serogroups.

A highly purified pilus vaccine prepared from cells of Bacteroides nodosus strain 198 provided a high level of protection against homologous challenge and small, not statistically significant, levels of protection against challenge with 4 other strains each from different serogroups. In a second experiment, a partially purified pilus vaccine from strain 198 induced significant immunity to 1 of 4 heterologous strains which were different from those used in the first experiment. In a third experiment a strain 198 whole cell vaccine produced significant immunity against 3 of 6 heterologous strains used in the first 2 experiments. There was no obvious relationship between the colony type, degree of piliation and level of cross-protection obtained against a particular strain. The results provide further evidence that immunogens associated with, but distinct from, the pilus are involved in cross-protection and that cross-protective antigens are common to some, but not all, strains.

Agglutination Tests↗
PubMed1985

Experimental endotoxemia in the rat: efficacy of prostacyclin or the prostacyclin analog iloprost.

The purpose of this study was to examine the effects of PGI2 and iloprost, a prostacyclin analog, on the sequelae of experimental endotoxic shock. Endotoxemia was produced in rats by IV injection of 20 mg/kg Salmonella enteritidis (LPS). Mean arterial blood pressure fell from 117 +/- 5 mmHg (N = 22) to 92 +/- 5 mmHg and 71 +/- 10 mmHg at 30 and 180 min post-LPS, respectively. In LPS vehicle-treated rats, blood glucose levels fell from 100 +/- 10 mg/dl to 36 +/- 8 mg/dl at 180 min. Plasma glutamate-oxaloacetate transaminase and lactate dehydrogenase (liver fraction) activities were significantly elevated above concentrations in nonshocked animals, increasing to 426 +/- 86 IU/ml and 1,019 +/- 339 IU/ml, respectively. Infusion of PGI2 or iloprost (0.5 micrograms/kg/min) did not alter the blood pressure response to LPS compared to vehicle controls. PGI2 significantly prevented the LPS-induced hypoglycemia while neither treatment significantly reduced the elevations in plasma enzymes nor prevented the lethality of LPS. Thus, the hemodynamic and biochemical indices of shock severity were not significantly improved by either prostacyclin or iloprost. It is suggested that the beneficial effects of PGI2 or prostacyclin analogs observed in other species during endotoxemia does not extend to the rat.

Animals↗
PubMed1984

Omega-halofatty acids: a probe for mitochondrial membrane integrity. In vitro investigations in normal and ischaemic myocardium.

Long-chain omega-halofatty acids, especially omega-123I-iodoheptadecanoic acid (IHA), are widely used clinically as radiopharmaceuticals for functional heart imaging. The metabolic interpretation of the various elimination rates, however, remains in dispute. It has been previously shown (Kloster and Stöcklin 1982) that in isolated perfused guinea-pig hearts halide diffusion from the mitochondrion to the blood is the rate-determining step of IHA pharmacokinetics in normal myocardium. We have now extended these in vitro experiments to normal and globally ischaemic isolated perfused rabbit hearts. Again, in normal hearts a single phase iodide elimination half-time (14.3 +/- 2.1 min) was observed. In hearts made globally ischaemic for 90 min, the iodide elimination was biphasic with a first fast phase (T 1/2 = 3.8 +/- 0.49 min) and a late slow phase (T 1/2 = 60.5 +/- 14.0 min). The first fast phase is attributed to iodide ion released by residual beta-oxidation (more rapid than in normal hearts due to damaged membranes in ischaemia), while the late slow phase is explained by beta-oxidation of IHA slowly released by hydrolysis of intracellular lipid stores. These data were compared with published data from investigations in patients which seem to support our interpretation.

Animals↗
PubMed1984

Early and late administration of a PGI2-analogue, ZK 36 374 (iloprost): effects on myocardial preservation, collateral blood flow and infarct size.

A number of investigations have reported that prostacyclin or prostacyclin analogues protect the ischaemic myocardium when administered early after myocardial ischaemia. Thus far, there are no reports describing whether these substances exert a cardioprotective effect when administered later than 0.5 h after coronary artery occlusion. Adult cats were subjected to acute coronary artery ligation for 5 h and administered the vehicle or ZK 36 374 (iloprost) (1.19 micrograms X kg-1 X min-1), a prostacyclin analogue, beginning at 0.5, 2 or 4 h. Compared with the MI-vehicle cats, ZK 36 374 prevented a decrease in myocardial creatine kinase specific activity, the loss of free amino nitrogen and the fall in percentage bound cathepsin D in the ischaemic area when infusion was started at 0.5 or 2 h (P less than 0.05). In addition ZK 36 374 started at 4 h still showed a significant protective effect against myocardial creatine kinase specific activity and amino nitrogen concentrations but not against cathepsin D. In a separate group of animals, regional myocardial blood flow and late coronary resistance were determined with radioactive labelled 15 +/- 1 micron microspheres. ZK 36 374 consistently reduced late diastolic coronary vascular resistance and increased coronary blood flow in nonischaemic regions of the myocardium (P less than 0.05) but only attenuated the further increase in late coronary resistance in the ischaemic myocardial regions. The infarcted area (NTB-staining) amounted to 9% of the total left ventricle after 5 h and was not reduced by ZK 36 374 (P greater than 0.05). In conclusion, ZK 36 374 exerted a significant biochemical cardioprotective effect when administered to 0.5, 2 or 4 h. The mechanism of cardioprotection does not appear to be due to increased myocardial perfusion but rather to some direct cellular action whose exact nature has yet to be elucidated.

Animals↗
PubMed1984

Aberrant polyadenylation by a vesicular stomatitis virus mutant is due to an altered L protein.

TsG16(I) is a temperature-sensitive mutant of vesicular stomatitis virus, Indiana serotype. Our stocks of this mutant overproduce polyadenylic acid in an in vitro transcription system. The overproduction of polyadenylic acid occurs at all temperatures tested (27, 31, 35, and 39 degrees C) and is apparently not due to an alternation in the N protein-RNA template. To characterize the altered moiety in tsG16(I) responsible for this phenotype, virions were fractionated and the polyadenylation phenotype in homologous and heterologous reconstitution assays was determined. The aberrant polyadenylation phenotype correlated with the presence of ts L protein but not ts NS or ts M protein fractions. Results of experiments in which solubilized tsG16(I) and wild-type virion components were mixed indicated that the altered moiety behaved as if present in stoichiometric amounts relative to active L protein. The effects of raising the temperature from 31 to 39 degrees C in such mixes were as would be predicted upon the assumption that the polyadenylation phenotype was associated with a thermosensitive transcriptase component [the L protein of tsG16(I) is known to be thermosensitive]. We conclude that the data strongly support the hypothesis that L is the altered protein responsible for the aberrant polyadenylation phenotype of tsG16(I).

Animals↗
PubMed1984

Effect of iloprost (ZK 36 374) on membrane integrity in ischemic rabbit hearts.

The hypothesis that prostacyclins exert a membrane stabilizing action on the ischemic myocardium was examined in isolated rabbit hearts by measuring the elimination half-time of labelled catabolites after injection of 17-(131I)-heptadecanoic acid. During normoxia, a rapid washout of labelled lipids was observed along with a slower exponential elimination of I- from beta-oxidation. After 90 min of ischemia, lipid washout was increased over 6-fold. Infusion of iloprost (1.1 nmol/min) significantly reduced the lipid washout half-time. Iloprost preserved functional myocardial integrity as evidenced by a greater recovery of left ventricular pressure and attenuation of the increase in coronary resistance after reperfusion. These results indicate that the poor recovery of the heart after ischemia is associated with significant changes in membrane integrity and permeability. These data support the hypothesis that the biochemical and functional myocardial preservation by prostacyclin(s) is by a membrane stabilizing mechanism.

Animals↗
PubMed1984

Acyanotic obstructive lesions. Coarctation of the aorta and congenital aortic stenosis.

The primary physiologic effect of coarctation of the aorta and aortic stenosis is impedence of blood flow out of the left ventricle, producing left ventricular strain. If unchecked, this progresses on a continuum leading to left-sided failure. Patients are asymptomatic in their younger years. With time, both defects progressively worsen, and may require surgical intervention in the teenage or adult years. While early and late postoperative results are quite good, these patients with obstructive lesions need continued medical and nursing follow-up throughout their adult years.

Adolescent↗
PubMed1983

RCS from human platelets: is it only thromboxane?

To determine if inhibition of a rabbit aorta contracting substance (RCS) corresponds to inhibition of thromboxane synthetase human washed platelets were stimulated with thrombin. RCS formation was bioassayed on rabbit aorta strips in Tyrode solution containing selective blocking agents and thromboxane (TX)B2 in the same probes by specific radioimmunoassay. Dazoxiben inhibited the formation of TXB2 but not of RCS, whereas indomethacin inhibited both RCS and TX formation. The data indicate that the rabbit aorta cannot be used alone to predict inhibition of TX formation with specific TX synthetase inhibitors.

Animals↗
PubMed1983

Effect of pilus dose and type of Freund's adjuvant on the antibody and protective responses of vaccinated sheep to Bacteroides nodosus.

Groups of sheep were immunised twice with one or other of six vaccines consisting of purified pili from Bacteroides nodosus at three dose levels (10, 38 and 154 micrograms) and emulsified with either complete (CFA) or incomplete Freund's adjuvant (IFA). Beginning one month after vaccination the sheep were homologously challenged on irrigated pasture, with naturally transmitted foot rot for a period of 26 weeks. Statistical analyses of the number of feet per sheep with severe foot rot demonstrated that there was a significant effect of vaccinal dose but neither an adjuvant effect nor an interaction between dose and adjuvant. Similar conclusions were reached when the titres of antipilus agglutinins in the serum were analysed. By both criteria the responses to doses of 154 and 38 micrograms of pili were significantly better than to 10 micrograms, but not significantly different from each other. The IFA vaccines caused less reaction at the sites of injection than the CFA vaccines and within the former the vaccines containing 10 and 38 micrograms pilus produced less reaction than those containing 154 micrograms. Hence a vaccine containing 38 micrograms of purified pili in IFA is nearly optimal for homologous protection against severe foot rot and is acceptable in terms of the reaction at the injection site.

Agglutination Tests↗
PubMed1982

Infarct size restriction in cats by the beta-adrenergic blocker timolol.

The beta-adrenergic antagonist, timolol, was previously shown to exert a protective effect in cats subjected to 5 h of myocardial ischemia. The present study was designed to determine the effect of timolol on infarct size in cats 24 h after coronary occlusion. Timolol (25 microgram/kg) or vehicle (0.9% NaCl) was administered 0.5, 5, 10, 15 and 20 h after acute ligation of the left anterior descending coronary artery. There was no significant difference in arterial blood pressure or heart rate in MI cats receiving timolol or vehicle. Timolol markedly decreased S-T segment elevation at 2-12 h (P less than 0.05). Left ventricular weights in MI + vehicle cats (8.5 +/- 0.7 g, n = 6) were similar to timolol-treated MI cats (8.9 +/- 0.4 g, n = 7). However, the percent of the left ventricular myocardium infarcted, determined by nitroblue tetrazolium staining, was significantly less (P less than 0.001) in timolol MI cats compared to saline-treated cats, 9.8 +/- 1.2% (n = 7) vs. 18.9 +/- 1.8% (n = 6), respectively. Hemodynamic or cytoprotective actions of timolol do not appear to explain these results. Rather, the mechanism of infarct size reduction by timolol is probably explained by antagonism of beta-receptor-mediated metabolic effects.

Animals↗
PubMed1982

Importance of pilus-associated antigen in Bacteroides nodosus vaccines.

The performances of two cellular vaccines, one sparsely piliated and the other well piliated, were compared on irrigated pasture with those of vaccines containing their respective, purified pili. There were statistically significant differences among the four vaccines in the mean numbers of feet per sheep which developed severe foot rot during 27 weeks of exposure. The incidence of severe foot rot was significantly lower in the two pili-vaccinated groups than in the group vaccinated with well-piliated cells, which were in turn substantially more effective than the sparsely piliated. However, the two pili vaccines did not prevent infection of the interdigital skin so that the differences in vaccine performance were much less marked when interdigital skin lesions were included. The number of feet affected by blowfly strike was closely associated with the presence of the most severe lesions and consequently there were far fewer struck feet in the two pili vaccine groups than in the two cellular vaccine groups. Analysis of serum agglutinin titres led to the same assessment of vaccinal efficacy as that derived from the analysis of severe foot rot lesions. Individually the agglutinin response to vaccination was not universally associated with resistance or susceptibility to severe foot rot but mean titres were significantly higher in the two pili vaccine groups than in the highly piliated-cell vaccine group, which were all in turn significantly higher than in the poorly piliated-cell vaccine group.

Animals↗
PubMed1981

Thromboxane synthetase inhibitors differentially antagonize thromboxane receptors in vascular smooth muscle.

A number of thromboxane (Tx) synthetase inhibitors have been found to prevent thromboxane release in acute cardiopulmonary disorders. However, little is known about Tx receptor antagonism by these substances. Imidazole, UK-37,248 and pinane thromboxane A2 (PTA2) were tested in isolated perfused cat coronary arteries, spirally cut rabbit pulmonary artery strips, and in rabbit and cat platelets for their ability to antagonize vasoconstrictor and aggregatory effects of a stable Tx agonist, carbocyclic thromboxane A2 (CTA2). Imidazole, at concentrations that completely inhibit thromboxane synthesis, failed to antagonize the vasoconstrictor effects of CTA2 in both systems. UK-37,248, at 10 to 1000 micrograms/ml, failed to inhibit CTA2-induced coronary constriction but at 1 microgram/ml reduced rabbit pulmonary artery constriction by 80 +/- 8% (P less than 0.0005). In comparison, 1 micro M PTA2 completely prevented PTA2-induced constriction in both coronary and pulmonary arteries. PTA2 did not antagonize KCl and angiotensin II responses. In platelets, PTA2 but not UK-37,248 prevented arachidonate induced aggregation in rabbit and cat platelets. Some of the beneficial effects of thromboxane synthetase inhibitors may be associated with thromboxane receptor antagonism. Inhibitors structurally similar to TxA2 appear to have greater thromboxane receptor antagonistic activity. This additional activity may be of importance in therapeutics of coronary and pulmonary disorders.

Animals↗
PubMed1981

Stabilization of cardiac lysosomal and cellular membranes in protection of ischemic myocardium due to coronary occlusion:efficacy of the nonsteroidal anti-inflammatory agent, naproxen.

The combined cellular membrane stabilizing and prostaglandin-inhibiting agent, naproxen, administered either 30 minutes before or after left coronary occlusion, induced significant preservation of the acutely ischemic experimental animal myocardium. A consistent extent of myocardial protection was provided as measured by ST segment elevation, plasma accumulation of CK activity, tissue CK activities, and amino-nitrogen concentrations, and ultrastructural integrity. Protection did not appear to be via hemodynamic mechanisms since naproxen neither altered pressure-rate product nor decreased coronary resistance. While the degree that inhibition of platelet thromboxane A2 generation contributes to these salutary results requires clarification due to possible simultaneous decrease of coronary endothelial PGI2 formation, the present study emphasizes the value of the concomitant special lysosomal and cellular stabilizing actions of naproxen. In contrast to acetylsalicylic acid, meclofenamate, and indomethacin which do not effect such benefit in the same experimental conditions, our results indicate that naproxen resembles the nonsteroidal anti-inflammatory agents which also possess membrane stabilizing properties, such as ibuprofen and flurbiprofen, and protects ischemic myocardium in similar adverse circumstances.

Animals↗
PubMed1981

Carbocyclic thromboxane A2: aggrevation of myocardial ischemia by a new synthetic thromboxane A2 analog.

In vitro experiments indicate that thromboxane A2 (TA2) is a potent platelet aggregator and vascular constrictor. However, it is unclear what roles these specific actions may contribute in the pathophysiology of myocardial ischemia. Carbocyclic thromboxane A2 (CTA2), a TA2 analog, constrict isolated perfused cat coronary arteries, but does not aggregate platelets, and thus appeared useful to clarify these separate actions of TA2. In anesthetized cats, radioactive labeled microspheres were injected into the left atrium for measurement of cardiac output and tissue blood flows. Compared to control measurements, CTA2 infusion (4.8 microgram.kg-1.min-1 for 10 min) significantly decreased cardiac output from 347 to 16 ml.min-1 to 248 +/- 16 ml.min-1 (p less than 0.025). Furthermore, CTA2 also significantly reduced blood flow to the left ventricle by 33 +/- 7%, but did not alter heart rate or MABP in the intact cat. In cats subjected to left anterior descending coronary artery occlusion, infusion of CTA2 (1 microgram.min-1 for 120 minutes) 30 min after ligation resulted in a significantly reduced myocardial cellular integrity as measured by myocardial creatine kinase activity (p less than 0.01) or percent bound myocardial cathepsin D (p less than 0.01). Thus, these data suggest that activation of vascular thromboxane receptors as well as direct cellular damage may play a role in the pathophysiology of myocardial ischemia.

Animals↗
PubMed1981

Effects of arachidonic acid hydroperoxides on vascular and non-vascular smooth muscle.

The omega-6 and omega-9 hydroperoxides of arachidonic acid (AA) caused dose-dependent contraction of rabbit aortic strip (RAS) and guinea pig ileum (GPI) at concentrations between 5 and 200 microM. At these concentrations, arachidonic acid had no effect in these preparations. The contractions could not be blocked by indomethacin, methysergide, phenoxybenzamine, propranolol, diphenhydramine, scopolamine, or the SRS-A antagonist FPL-55712, but were abolished by the calcium channel blocker nimodipine. In both tissues, the hydroperoxides initiated a sustained contraction. The onset of GPI contraction however, was much faster than the response of RAS to these hydroperoxides. 15-HPETE produced a more sustained contraction than 12-HPETE in both RAS and GPI. These results suggest that hydroperoxides generated from AA by the action of lipoxygenase can directly induce smooth muscle contraction and this effect is probably mediated through altering calcium fluxes in these smooth muscle preparations.

Animals↗