PubMed Health⌕ Search

Biomedical subjects

R H Fertel

Publications and source records attributed to R H Fertel.

At least 55 records · Page 3Linked to original sources
PubMed1985

Failure of percutaneous transluminal coronary angioplasty to stimulate platelet and prostaglandin activity.

Platelet function and prostaglandin activity were evaluated in nine patients with coronary artery disease undergoing percutaneous left anterior descending coronary artery angioplasty (PTCA) and compared to nine normal controls. Transcoronary measurements (arterial-coronary sinus) of platelet counts, mean platelet volume, platelet factor 4 (PF4), beta thromboglobulin, thromboxane (B2), and 6-keto-PGF 1 alpha were made. When compared to normal controls, the patients with coronary artery disease had higher circulating baseline levels of PF4 in the coronary sinus. There was no transcardiac production of any factor at baseline or immediately after infusion of nitroglycerin or performance of PTCA. These results suggest that PTCA does not grossly alter arachidonic acid metabolism or platelet activity.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Reversal of feline retroviral suppression by indomethacin.

The immunosuppressive effect of feline leukemia virus (FeLV) and its 15,000 dalton envelope protein (p15E) were studied to determine if the mechanism of action was due to an increase in prostaglandin production. We examined the effects of exogenous PGE1 and PGE2 on the normal Con A response of feline peripheral blood lymphocytes (PBL) and found them to be inhibitory. The addition of the cyclooxygenase inhibitor indomethacin to cells incubated with FeLV or FeLV p15E and Con A completely abrogated the viral suppressive effects. This reversal was titratable and time-dependent. Other non-steroidal anti-inflammatory (NSAI) drugs were found to have similar actions. Indomethacin was also able to increase the suppressed Con A response of PBL from FeLV-infected cats. Upon measurement of PGE2 levels from PBL cultured with FeLV, we found a decrease in PGE2 accumulation associated with FeLV presence during the first 24 h of culture. These findings indicate that FeLV does not cause its immunosuppressive effects by increasing PG production and suggests that indomethacin and the other tested NSAI drugs do not produce their effect by PG inhibition.

Animals↗
PubMed1985

The reversal of feline retroviral-induced suppression of lymphocyte Con A receptor mobility by indomethacin and PGE2.

Ultraviolet light-inactivated feline leukemia virus (FeLV) and its 15,000 dalton envelope protein (p15E) inhibited concanavalin A receptor motility of feline peripheral lymphocytes (PBL). In contrast, the virus had no effect on immunoglobulin capping of feline PBL. The inhibitory action of FeLV and FeLV p15E was reversed by the addition of indomethacin. The indomethacin effect was titratable and gave significant reversal between 1 X 10(-5) and 1 X 10(-10) M. The indomethacin inhibition of the prostaglandin synthesis does not appear to be the mechanism of action in its ability to reverse FeLV suppression of Con A receptor mobility. Since the addition of prostaglandin E2 (PGE2) (1.0 microM) was also able to reverse the FeLV-induced inhibition and neither indomethacin nor PGE2 had an observable effect on Con A receptor mobility of normal PBL without FeLV present. PBL from FeLV-infected cats were sensitive to indomethacin (1.0-10.0 microM) and an indomethacin-related increase in cap formation was observed. Since both indomethacin and PGE2 were able to reverse the FeLV-induced suppression it was concluded that their mechanism of action may be through a common site. In addition, indomethacin may prove useful as an immune response modifier for therapy in FeLV-infected cats.

Animals↗
PubMed1985

Psoralens increase the concentration of cyclic AMP in human cells in vitro.

8-Methoxypsoralen (8-MOP) and 4,5',8-trimethylpsoralen (TMP) were assessed for their effects on cyclic AMP (cAMP) accumulation in normal human fibroblasts, epithelial cells, and mononuclear leukocytes in vitro. In the absence of ultraviolet A radiation, 8-MOP and TMP caused an increase in the concentration of cAMP, but not cyclic GMP, in all of these cells. The effect was seen within 1 min and was sustained over control levels for at least 6 h. At 15 min, the highest dose of 8-MOP or TMP increased the cAMP concentration of fibroblasts by 52% and 69%, respectively. In mononuclear leukocytes, 8-MOP led to a 142% increase in cAMP after 20 min. Several analogs of 8-MOP and TMP had no effect on the cyclic nucleotide system of the cells. The pattern of the time-dependent increase in cAMP indicated that the effect was probably due to an inhibition of phosphodiesterase, rather than an activation of adenylyl cyclase. These results demonstrate that clinically effective psoralens, in the absence of UV radiation, can alter the cAMP concentration of human fibroblasts, epithelial cells, and mononuclear leukocytes in vitro.

Cyclic AMP↗
PubMed1984

Atrial fibrillation in mitral stenosis: histologic, hemodynamic and metabolic factors.

We examined the histologic, hemodynamic and metabolic factors associated with rheumatic mitral stenosis. Eighteen patients comprised three groups: Group I - 7 patients in sinus rhythm; Group II - 5 patients in intermittent atrial fibrillation; Group III - 6 patients in chronic atrial fibrillation. The left atrial dimension was determined by echocardiography. Left atrial pressure, mitral valve gradient, mitral valve area and the presence or absence of calcium in the mitral valve were determined at catheterization. The left atrial appendage was removed during open heart surgery and the tissue was analyzed for cell size, percent fibrosis and content of cyclic AMP and GMP. There was no difference between the groups in pulmonary capillary wedge pressure, mitral valve gradient, mitral valve area or the presence of calcium. The Group I left atrial dimension (51 +/- 2 mm, means +/- SE) was significantly smaller than that of Group III (56 +/- 2 mm, P less than 0.05). Group II was not different from Groups I or III. Although the concentration of cyclic AMP did not differ among the groups, the cyclic GMP was significantly depressed in Group III (0.15 +/- 0.02 fmol/microgram protein) when compared to Group I (0.24 +/- 0.05 fmol/microgram protein, P less than 0.01). Group II had intermediate values which did not differ from Groups I or III. The percent fibrosis was greatest in Group III (34.8 +/- 1.8%) and least in Group I (27.2 +/- 2.8%, P less than 0.05). There was no difference in cell size among the groups. Although atrial fibrillation may lead to some of these irregularities, a depressed cyclic GMP, increased fibrosis and increased left atrial dimension may play a role in the pathogenesis of irreversible atrial fibrillation.

Adult↗
PubMed1984

Change in levels of cyclic AMP and cyclic GMP during pregnancy and larval development of the tsetse fly, Glossina morsitans.

Cyclic AMP and cyclic GMP levels change very little in response to feeding and mating, but during pregnancy and at parturition major changes can be detected in both the mother and larva. In both the female head and larva (whole body) cyclic AMP levels reach a peak at parturition. In the larval brain and ring gland cyclic AMP is at its lowest at parturition but rises sharply, reaching a peak 1.5 hr later at the time of pupariation . Though cyclic AMP levels in the head and thorax are consistently 10-60 times greater than levels of cyclic GMP, both the female abdomen and larva contain high concentrations of cyclic GMP with a ratio of cyclic AMP:cyclic GMP approaching 1:1. In the abdomen, the pattern of high cyclic GMP closely parallels the activity cycle of the female's milk gland.

Animals↗
PubMed1984

The evolution of beta-adrenergic dysfunction during the induction of canine cobalt cardiomyopathy.

This study was designed to investigate the changes in the beta adrenergic system during the induction of cobalt cardiomyopathy in dogs. Cobalt sulphate, at a dose of 5 mg X kg-1 X day-1 was administered intravenously with a low protein, low thiamine diet to 13 dogs. The percentage change of the left ventricular minor axis with systole by echocardiogram (% delta D) and dP/dtmax were used to monitor left ventricular function. Noradrenaline (NA) was measured in 24 h urine samples. Left ventricular (LV) free wall biopsies were assayed for noradrenaline (LV-NA), cyclic AMP, cyclic GMP and dopamine beta hydroxylase (LV-DBH). Lymphocytes were assayed for beta-receptor density. All dogs were studied at baseline and seven were studied after a midpoint cumulative dose of 60 to 90 mg X kg-1 of cobalt; the remaining six dogs were studied when they were in heart failure and had received more than 110 mg X kg-1. During the induction of heart failure the heart rate rose from 112 +/- 6 (means +/- SE) at baseline to 154 +/- 9 at the midpoint and 153 +/- 9 (both P less than 0.05) at the final measurement while the % delta D fell from 35 +/- 2% to 31 +/- 3% and 23 +/- 2% (P less than 0.05) and dP/dt fell from 333 +/- 40 kPa X s-1 at baseline to 254 +/- 46 kPa X s-1 (P less than 0.05) and 207 +/- 33 kPa X s-1 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Production of arachidonic acid metabolites by operationally defined macrophage subsets.

The antitumor activity and arachidonic acid metabolism of operationally defined macrophage populations was examined. Macrophages from mice injected with Mycobacterium bovis (strain BCG) or with pyran-copolymer were cytotoxic for tumor cells. The major arachidonic acid metabolite of these cells was PGE2. Neither resident nor elicited macrophages were cytotoxic. However, elicited macrophages as well as macrophages from BCG injected mice inhibited tumor cell growth. The production of arachidonic acid metabolites by elicited cells, while low initially, was followed by a rapid increase in PGE2. The major metabolites of resident cells were PGE2 and prostacyclin. The cAMP:cGMP ratio correlated with the metabolic activity of the cells.

Animals↗
PubMed1983

Nitroglycerin tolerance and cyclic GMP generation in the longitudinal smooth muscle of the guinea-pig ileum.

The effects of in vitro nitroglycerin tolerance and methylene blue pretreatment on the ability of nitroglycerin and nitroprusside to promote relaxation and tissue accumulation of cyclic GMP were examined in the carbachol-contracted longitudinal smooth muscle of the guinea-pig ileum. Nitroglycerin and nitroprusside produced concentration-dependent increases in cyclic GMP levels. However, only nitroglycerin increased cyclic GMP levels before the onset of relaxation. Nitroglycerin tolerance produced approximately 200- and 5-fold shifts to the right of nitroglycerin and nitroprusside relaxation curves, respectively. Methylene blue pretreatment produced approximately 5-fold shifts to the right of both nitroglycerin and nitroprusside relaxation curves. Whenever there was an inhibition of nitroglycerin- or nitroprusside-induced relaxation, there was a corresponding reduction of cyclic GMP generation. Methylene blue inhibited the ability of 8-bromoguanosine 3',5'-monophosphoric acid to promote smooth muscle relaxation, suggesting that it also may impair the subsequent actions of cyclic GMP. This study provides the first demonstration of nitroglycerin tolerance in a nonvascular smooth muscle and provides evidence that cyclic GMP mediates the relaxant effects of nitroglycerin in the longitudinal smooth muscle of the guinea-pig ileum. However, because nitroprusside promoted tissue accumulation of cyclic GMP subsequent to relaxation, an exclusive role for cyclic GMP-mediated relaxation for this drug in the longitudinal smooth muscle appears unlikely.

Animals↗
PubMed1983

The role of reactive oxygen species in thromboxane b2 generation by polymorphonuclear leukocytes.

These studies evaluated further the relationship between the metabolism of reactive oxygen species (ROS) and prostaglandins in human granulocytes. Our experiments examined (1) the effects of several scavengers of ROS on thromboxane B2 (TXB2) production by zymosan-stimulated PMNs, (2) the capacity of the granulocytes of patients with chronic granulomatous disease (CGD) to produce TXB2, and finally (3) the generation of oxygen radicals in PMNs stimulated to produce TXB2 by the enzyme phospholipase A2. Our results confirm that both zymosan- and PMA-stimulated PMNs release increased amounts of TXB2. This enhanced production of TXB2 by normal PMNs could not be impaired and, in fact, appeared to be enhanced by scavengers of ROS. The PMNs of one patient with CGD produced TXB2 in an amount similar to those of healthy persons, whereas the TXB2 produced by the PMNs of a second patient was markedly increased. Finally, the enzyme phospholipase A2 stimulated TXB2 production in PMNs without stimulating the production of ROS. These data indicate that the activation of prostaglandin metabolism in PMNs is not dependent on the simultaneous production of ROS by these cells. However, the simultaneous production of ROS may be associated with an alteration of prostaglandin metabolism.

Catalase↗
PubMed1982

Potentiating effects of clofibrate on prostaglandin-dependent and -independent pathways of human platelet activation: evidence for involvement of cyclic AMP.

Although clofibrate has been shown to inhibit platelet aggregation that is caused by thrombin, ADP and epinephrine, by blocking the release of arachidonic acid from platelet phospholipids [8], here we have demonstrated that clofibrate enhanced platelet aggregation by arachidonic acid and PLC and reversed the effects of PGE1 on platelet cAMP concentration and on PLC-induced secretion of [14C]-5HT in similar, concentration-dependent manners. Taken together, these findings strongly suggest that the proaggregatory effect of clofibrate is mediated by a lowering of cAMP in platelets.

Arachidonic Acid↗
PubMed1982

Vascular tolerance to nitroglycerin and cyclic GMP generation in rat aortic smooth muscle.

Recent reports have suggested that cyclic guanosine 3', 5'-monophosphate (cGMP) may mediate drug-induced vascular smooth muscle relaxation. This hypothesis was examined by correlating increases in cGMP formation with vascular smooth muscle relaxation after sensitivities to nitroglycerin and nitroprusside were altered. Both nitroglycerin and nitroprusside produced a concentration-dependent increase in rat aortic cGMP levels, which preceded relaxation. A specific inhibition of nitroglycerin relaxation was accomplished by pretreating helical rat aortic strips with 5.5 X 10(-4) M nitroglycerin for 1 hr (in vitro nitroglycerin tolerance). Both nitroglycerin and nitroprusside were inhibited by pretreating tissues with 10(-5) M methylene blue for 1 hr. Whenever nitroglycerin or nitroprusside relaxation was inhibited, there was a corresponding inability to generate cGMP. Vascular tissues derived from nitroglycerin-tolerant animals (in vivo tolerance) exhibited a profile of cGMP reduction that closely resembled that of the in vitro model. Vascular smooth muscle relaxation induced by 8-bromoguanosine-3', 5'-monophosphoric acid was not inhibited by either in vitro nitroglycerin tolerance or methylene blue, suggesting that the subsequent action of cGMP, once formed, is not impaired. The results of this study support the contention that cGMP generation may be an important step in the promotion of vascular smooth muscle relaxation by nitroglycerin and nitroprusside.

Animals↗
PubMed1981

Biochemical measurements of endomyocardial biopsies.

The purpose of this study is to investigate the validity of performing biochemical analyses on human endomyocardial biopsies. One problem of such analyses is the decay of metabolites between the time of biopsy and the analyses. This was addressed by varying the time delay from biopsy to submersion in liquid nitrogen (-200 degree C). Neither cyclic AMP or cyclic GMP changed significantly up to 90 seconds after biopsy. The reproducibility of the assays in human heart biopsies was determined by submitting paired samples from each procedure. The ATP content was determined by a fluorescent technique and was related to the protein and creatine content. The average ATP of 25 paired samples was 12.3 nm per mg protein; the average difference between the paired samples was -0.6, and the 95% confidence interval was 5.6 nm/mg protein. The average ATP-to-creatine ratio was 0.25; the 95% confidence interval was 0.12. The cyclic AMP and cyclic GMP were found to average 3.3 and 0.25 femtomoles/mcg protein, respectively. The 95% confidence intervals were 1.8 and 0.12 fmoles/mcg protein. The problems of sampling error and blood and connective tissue contamination decrease the reliability of the biochemical analyses. Reproducibility is adequate, however, to acquire meaningful biochemical information on the human heart.

Adenosine Triphosphate↗