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Biomedical subjects

S Ellis

Publications and source records attributed to S Ellis.

At least 127 records · Page 7Linked to original sources

Prediction of risk of anterior myocardial infarction by lesion severity and measurement method of stenoses in the left anterior descending coronary distribution: a CASS Registry Study.

To assess the 3 year risk of anterior myocardial infarction in patients with left anterior descending coronary artery territory disease (30 to 100% stenosis), National Heart, Lung, and Blood Institute (NHLBI) Coronary Artery Surgery Study (CASS) registry patients were identified who were 1) medically treated, and 2) had evidence of viable anterior myocardium at the time of baseline angiography. Prospectively, 118 patients having an anterior infarction within 3 years of baseline angiography were identified from annual follow-up of 4,535 medically treated patients who had left anterior descending coronary artery disease and viable anterior myocardium. From the large residual pool of patients without infarction, 141 were randomly selected from a stratified matrix to represent the entire group. The maximal percent stenosis was estimated by the CASS multiple angiographers, by a current single observer rereading and by contemporary computer measurement techniques. Absolute lumen dimension was assessed by computer measurement. The 3 year risk of anterior infarction was 2% for patients with their most severe left anterior descending stenosis less than 50%, 6% for patients with one such stenosis greater than or equal to 50% and 11% for patients with two or more such stenoses greater than or equal to 50% (p less than 0.02). Stenoses of 90 to 98% had the highest (15%) 3 year risk of anterior myocardial infarction. The three methods used to measure maximal percent stenosis differed little with regard to their predictiveness. Absolute lumen dimension was less predictive of risk. These results may provide a more rational basis on which to base coronary revascularization decisions.

Clinical Trials as Topic↗

Quantitation and immunocytochemical localization of ubiquitin conjugates within rat red and white skeletal muscles.

We employed solid-phase immunochemical methods to probe the dynamics of ubiquitin pools within selected rat skeletal muscles. The total ubiquitin content of red muscles was greater than that of white muscles, even though the fractional conjugation was similar for both types of muscle. The specificity for conjugated ubiquitin in solid-phase applications, previously demonstrated for an affinity-purified antibody against SDS-denatured ubiquitin, was retained when used as a probe for ubiquitin-protein adducts in tissue sections. Immunohistochemical localization revealed that differences in ubiquitin pools derived from the relative content of red (oxidative) vs white (glycolytic) fibers, with the former exhibiting a higher content of ubiquitin conjugates. Subsequent immunogold labeling demonstrated statistically significant enhanced localization of ubiquitin conjugates to the Z-lines in both red and white muscle fiber types.

Animals↗

Catalase-positive microperoxisomes in rat soleus and extensor digitorum longus muscle fiber types.

The size, distribution, and content of catalase-reactive microperoxisomes were studied cytochemically in slow-twitch oxidative (SO), fast-twitch oxidative glycolytic (FOG), and fast-twitch glycolytic (FG) fibers of soleus and extensor digitorum longus (EDL) rat muscles. Fiber types were classified on the basis of mitochondrial content and distribution, Z-band widths, and myofibril size and shape. Microperoxisomes were generally located between myofibrils at the I-bands. The absence of crystalloid inclusions prevented positive identification of microperoxisomes in nonreacted and aminotriazole-inhibited muscles. EDL and soleus SO fibers possessed the largest microperoxisomes, whereas FOG and FG fibers of the EDL contained small- to medium-sized microperoxisomes. Comparing either microperoxisome number per muscle fiber area or microperoxisome area per fiber area revealed significant differences between fiber types with this ranking: soleus SO greater than EDL SO greater than EDL FOG greater than EDL FG. The present observations demonstrate that the content of catalase-positive microperoxisomes is greatest in the oxidative muscle fiber types. These cytochemical findings account for the higher catalase activity in homogenates of soleus muscles as compared to that of EDL muscles, because the soleus contains more oxidative fibers than EDL.

Animals↗

Species variation in bladder cell and liver cell activation of acetylaminofluorene.

The metabolism and mutagenicity of 2-acetylaminofluorene were measured using freshly prepared intact bladder and liver cells from the cow, dog and rat. High pressure liquid chromatography was used to separate 2-acetylaminofluorene metabolites, and Salmonella typhimurium, strain TA98, was used to detect mutagenic intermediates. Species differences as well as animal-to-animal variation within a species were observed. Mutagenic activity with 2-acetylaminofluorene was greater with cow bladder cells than with dog or rat bladder cells. However, dog bladder cells were most active in metabolizing 2-acetylaminofluorene, and rat bladder cells were least active. Liver cells from all three species metabolized 2-acetylaminofluorene to mutagens for Salmonella, with dog and cow cells being more active than rat liver cells. However, cow liver cells were the most active in metabolizing 2-acetylaminofluorene, followed by rat and dog cells. With all cell types studied, except rat bladder cells, aminofluorene was the major metabolite detected. Carbon and N-hydroxylated products were produced by liver and bladder cells of the three species and glucuronide and sulfate conjugates of the metabolites were detected from both cell types. Correlations between mutagenic activity and the level of metabolism or any individual metabolite were not apparent. The data suggest that the relative contribution of bladder cell metabolism in aromatic amine induced bladder cancer may vary with the species.

2-Acetylaminofluorene↗

Morphological transforming activity and metabolism of cyclopenta-fused isomers of benz[a]anthracene in mammalian cells.

4 isomeric cyclopenta-derivatives of benz[e]anthracene (benz[a]aceanthrylene, benz[j]aceanthrylene, benz[l]aceanthrylene, and benz[k]acephenanthrylene) were examined for their ability to morphologically transform C3H10T1/2CL8 mouse-embryo fibroblasts. All of these polycyclic aromatic hydrocarbons studied except benz[k]acephenanthrylene transformed C3H10T1/2CL8 cells to both type II and type III foci in a concentration-dependent fashion. Benz[j]aceanthrylene was the most active, equivalent in activity to benzo[a]pyrene on a molar basis, in producing dishes of cells with transformed foci (94% at 1.0 microgram/ml). Benz[e]aceanthrylene, and benz[l]aceanthrylene produced 58% and 85% of the dishes with foci respectively at 10 micrograms/ml. Metabolism studies with [3H]benz[j]aceanthrylene in C3H10T1/2CL8 cells in which unconjugated, glucuronic acid conjugated, and sulfate conjugated metabolites were measured indicated that the dihydrodiol precursor to the bay-region diol-epoxide, 9,10-dihydroxy-9,10-dihydrobenz[j]aceanthrylene, was the major dihydrodiol formed (55%). Smaller quantities of the cyclopenta-ring dihydrodiol, 1,2-dihydroxy-1,2-dihydrobenz[j]aceanthrylene (14%), and the k-region dihydrodiol, 11,12-dihydroxy-11,12-dihydrobenz[j]aceanthrylene (5%) were also formed. Similar studies with [14C]benz[l]aceanthrylene indicated that the k-region dihydrodiol, 7,8-dihydroxy-7,8-dihydrobenz[l]aceanthrylene was the major metabolite formed (45%). The cyclopenta-ring dihydrodiol, 1,2-dihydroxy-1,2-dihydrobenz[l]aceanthrylene and 4,5-dihydroxy-4,5-dihydrobenz[l]aceanthrylene were formed in minor amounts (less than 6%). Therefore, metabolism at the cyclopenta-ring of B(j)A and B(l)A is a minor pathway in C3H10T1/2CL8 cells in contrast to previously reported studies with cyclopenta[cd]pyrene in which the cyclopenta-ring dihydrodiol was the major metabolite. These results suggest that routes of metabolic activation other than oxidation at the cyclopenta-ring such as bay region or k-region activation may play an important role with these unique polycyclic aromatic hydrocarbons in C3H10T1/2CL8 cells.

Animals↗

Idiotype-anti-idiotype interactions of VHIX-coded anti-progesterone and anti-arsonate antibodies. Comparison of passive haemagglutination and radioimmunoassays.

The reactivity and specificity of polyclonal and monoclonal anti-idiotypic antibodies raised against monoclonal anti-progesterone and anti-arsonate antibodies have been studied by solid phase radioimmunoassay (RIA) with immobilized idiotype and by passive haemagglutination with idiotype-coupled red cells. The sensitivity of the two methods was comparable, though some cross-reactions were only detected by RIA. Passive haemagglutination was found to be especially suitable in screening for monoclonal anti-idiotypes in hybridoma supernatants and ascites, and had advantages over RIA in detection of syngeneic anti-idiotypes. Demonstration of binding site-associated idiotopes was possible by haemagglutination inhibition. RIA and haemagglutination were used to investigate the idiotypic relationships between BALB/c antiprogesterone and anti-arsonate monoclonal antibodies which share heavy chains encoded by VHIX variable region genes.

Amino Acid Sequence↗

Morphological criteria for comparing effects of X-rays and neon ions on mouse small intestine.

Several techniques have been used to assess changes in different parts of mouse small intestine three days after a single dose of either 16.5 Gy X-rays or 11 Gy neon beam. The doses were chosen to be approximately equivalent in terms of their effect on the number of microcolonies present. In qualitative terms, villous damage was seen after both types of radiation exposure: collared crypts, similar to those seen in biopsies taken from patients suffering from coeliac disease, were conspicuous after neon irradiation. In semi quantitative terms the doses used, although estimated from previous work to give biologically equivalent damage, produced a greater drop in microcolony numbers after X-irradiation. This makes all the more important the fact that significantly greater changes were seen after neon irradiation-a greater drop was seen in the number of villous profiles and the number of goblet cells per villus. There was also greater breakdown in the integrity of the villous basement membrane. Different responses after the two types of irradiation are therefore seen in the cryptal and villous compartment. Progress is being made towards identifying and quantitating radiation induced changes in different populations of cells or tissues in the small intestine.

Animals↗

Quantitative analysis of the metabolism of benzo(a)pyrene by transformable C3H10T1/2CL8 mouse embryo fibroblasts.

The metabolism of benzo(a)pyrene [B(a)P] to organic soluble and water soluble metabolites by transformable C3H10T1/2CL8 mouse embryo fibroblasts was studied as a function of time, B(a)P concentration, and cell density. The total formation of organic-soluble and water-soluble metabolites increased with incubation time from 4 to 48 h and with B(a)P concentration from 4 to 40 microM. As cell density increased, the metabolic rate decreased for organic-soluble and water-soluble products between 6,300 and 54,000 cells/cm2 probably due to decreases in B(a)P concentrations to values below saturation. Specific organic-soluble metabolites identified were B(a)P-pre-9,10-diols, B(a)P-9,10-diol, B(a)P-7,8-diol, B(a)P-3,6-quinone, B(a)P-3-phenol, and B(a)P-9-phenol. Water-soluble metabolites were subjected to enzymatic hydrolysis with beta-glucuronidase and aryl sulfatase to identify specific conjugated products. The sulfate conjugated metabolites identified were B(a)P-7,8-diol, B(a)P-pre-9,10-diols, B(a)P-9,10-diol, and B(a)P-3,6-quinone. The beta-glucuronic acid metabolites identified were B(a)P-pre-9,10-diols, B(a)P-3,6-quinone, and B(a)P-3-phenol. Patterns of metabolite formation rates are discussed as to their possible effect on morphological transformation rates in C3H10T1/2 cells with respect to incubation time and cell density.

Animals↗

Optimal detection of the progression of coronary artery disease: comparison of methods suitable for risk factor intervention trials.

To assess the best method of quantitating progression of coronary disease, we studied four measurements in 114 coronary segments from 35 medically treated patients from whom angiograms were obtained 5 years apart. Only stenoses of less than 70% that were visualized in nearly identical projections on both angiograms were evaluated. Vessel edges were measured by use of catheter calibration and an automated computer algorithm yielding two "absolute dimensions" (mean and minimum diameters) and two measurements (percent stenosis and atheroma area) that required a "normal reference" diameter. The coefficient of variation for repeated segment measurements was less for mean and minimum diameter than for percent stenosis and area of atheroma. The best measure of progression of coronary disease as determined by t test comparison of different methods was the change in mean diameter over time (6.7 +/- 14.1% decrease), whether calculated on a per coronary segment or per patient basis (p less than .001). Based on this measurement and its standard deviation of progression of coronary disease in this patient subset with relatively benign disease, it is estimated that 470 patients per group would be required for an interventional study to demonstrate a 33% reduction in disease progression (207 patients for 50% reduction) at a 95% confidence level and 90% power.

Cardiac Catheterization↗

Anti-idiotypic sera against monoclonal anti-progesterone antibodies: production in rabbits and rats and characterization of specificity.

Antisera were raised in rabbits and rats against three mouse monoclonal anti-progesterone IgG1 antibodies. Anti-idiotypic antibodies were isolated from rabbit sera by successive passage over immunoadsorbent columns of normal mouse Ig and the specific immunizing monoclonal, with elution from the latter. Radioimmunoassays for anti-idiotype and free idiotype were established, enabling detection of idiotype in sera of mice immunized with progesterone-BSA conjugate. Binding of rabbit anti-idiotype to anti-progesterone monoclonals was partially inhibitable by free progesterone-hemisuccinate or progesterone-ovalbumin conjugate. While showing considerable specificity for their respective inducing monoclonals, the anti-idiotypes also cross-reacted in varying degrees with the other anti-progesterone monoclonals, demonstrating the presence of IdI and IdX determinants. The patterns of cross-reactivity showed some correlation with the relative isoelectric points and combining-site specificities of the anti-progesterones. The specificities of rat and rabbit anti-idiotypes were similar, but not identical.

Animals↗

Behavioral and neurochemical evaluation of phenylpropanolamine.

(+/-)-Phenylpropanolamine (PPA), a widely available anorectic and decongestant, was evaluated in several behavioral paradigms in rhesus monkeys and for central nervous system neurotoxicity in rats. PPA (1-30 mg/kg intragastric) reduced food intake in rhesus monkeys but was not self-administered i.v. (0.3-10 mg/kg/injection) by monkeys experienced in drug self-administration. PPA (30-100 mg/kg intragastric) resulted in amphetamine-like responding in two of four monkeys trained in a drug discrimination paradigm to discriminate d-amphetamine from saline. In rats, a 4-day injection regimen of high doses of PPA (200 and 400 mg/kg/day) resulted in approximately a 20% depletion of dopamine in the frontal cortex but failed to deplete dopamine, norepinephrine or serotonin in any other brain region studied. Thus, PPA is an effective anorectic in rhesus monkeys that, based upon drug discrimination results, would be expected to have limited amphetamine-like subjective effects and only at doses well in excess of effective anorectic doses. However, based upon self-administration results, PPA would not be predicted to have amphetamine-like dependence potential. Moreover, repeated administration of PPA did not produce the severe central nervous system neurotoxicity associated with many other amphetamine congeners.

Animals↗

Metabolism of benzo(a)pyrene in monolayer cultures of human bronchial epithelial cells from a series of donors.

Benzo(a)pyrene [B(a)P] metabolism was measured in monolayer cultures of human bronchial epithelial cells derived from 18 specimens of explanted tissue. Bronchial epithelial cells converted B(a)P to dihydrodiols, phenols, quinone derivatives, and polyhydroxylated forms. Sulfate and glucuronide conjugates of B(a)P metabolites were also detected. Both total metabolism and distribution of metabolites showed a 10-fold or greater variation in cultures from different specimens. When the data were divided according to smoking status, however, no differences in total metabolism, extent of conjugation, or distribution of metabolites could be demonstrated between the two groups. Wide variation (over 1000-fold) in the cytotoxicity of B(a)P towards cells derived from different specimens was demonstrated but could not be directly correlated to the extent of metabolic activation. The results suggest that human bronchial epithelial cells which are newly grown from explanted tissue of smokers in culture do not demonstrate enzymatic induction. Variation among individuals observed in these studies probably represents basal differences in metabolic capability.

Benzo(a)pyrene↗

Surface studies of duodenal lesions induced by thoracic irradiation.

Acute duodenal ulcers are produced in mice as a remote ("abscopal") effect of irradiation to the lower mediastinum. Such lesions have been examined with scanning electron microscopy at 5, 8 and 28 days after irradiation with 18 Gy of X-rays. All the ulcers occur within the first 1 cm long segment of the duodenum which is endowed with Brunner's glands. The single lesions vary in size, shape and position. The damaged area often includes much of the duodenal circumference and is distinguished by conical or rudimentary villi, or even by the complete absence of villi. In contrast, around the periphery of the ulcer the villi are mostly vertical. Although the floor of these lesions appears to be covered with a continuous epithelial layer, during the first 4 weeks after irradiation the severity of the focal duodenal damage seems to increase gradually with time. The lesions have been compared with specimens from unirradiated mice and also with samples taken 3 days after partial thoracic irradiation when little damage is seen. The pattern of fully developed duodenal lesions differs greatly from that seen after direct irradiation where damage has not included localised ulceration in the samples of jejunum so far examined. The lesions induced by partial thoracic irradiation may be related to radiation injury to vascular or autonomic nerve targets in the lower mediastinum. Such injury could result in malfunction of the pyloric sphincter or could alter the secretion by Brunner's glands and thus lead to duodenal ulceration.

Animals↗

Stretch-induced growth in chicken wing muscles: role of soluble growth-promoting factors.

The involvement of soluble growth-promoting factors in stretch-induced hypertrophy of the Patagialis muscle (PAT) in the chicken wing was investigated. Soluble extracts were prepared from young chicken PAT muscles made hypertrophic by passive stretch and from unstretched contralateral controls. Extracts were tested for their ability to stimulate cell proliferation and creatine phosphokinase (CPK) activity in primary monolayer cultures of chick embryo muscle cells. Factors were present in muscle extracts which showed a dose-dependent stimulation of cell proliferation and CPK activity in vitro. Passive stretch for 5 days produced a rapid hypertrophy of the PAT which was accompanied by a dramatic increase in the activity of the growth factor(s). Release of stretch resulted in an arrest of growth and an immediate fall in growth factor activity. The difference in growth-stimulating activity between control and stretched PAT extracts could be demonstrated in chicken transferrin-sensitive chick myoblast cultures. Stretch thus induces an increase in a class-specific growth factor, possibly Transferrin, in the PAT. Stretched PAT extracts stimulated: (a) chick myoblast proliferation to a greater extent than an optimum concentration of chick embryo extract, and (b) CPK activity in vitro to a greater extent than excess Transferrin. Both control and stretched PAT extracts supported the growth of rat myoblasts. We conclude that PAT muscle extracts also contain unknown growth factor(s) which are different from Transferrin.

Animals↗