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Biomedical subjects

J Ross

Publications and source records attributed to J Ross.

At least 451 records · Page 25Linked to original sources

Metabolism of benz[j]aceanthrylene (cholanthrylene) and benz[l]aceanthrylene by induced rat liver S9.

The metabolites of benz[j]aceanthrylene (B[j]A) produced by incubation with liver S9 proteins from rats induced with Aroclor-1254 and phenobarbital have been identified as: trans-B[j]A-1,2-dihydrodiol, B[j]A-9,10-dihydrodiol, B[j]A-11,12-dihydrodiol, and 10-hydroxy-B[j]A. The major metabolite formed (58-60%) by both induced S9 preparations was trans-B[j]A-1,2-dihydrodiol, the cyclopenta-ring dihydrodiol while oxidation at the k-region or the proximal-bay region was minor. There were no statistical differences in individual or total B[j]A metabolite rates between the 2 induced S9 preparations. B[l]A was metabolized by Aroclor-1254 and phenobarbital induced rat liver S9 preparations to trans-B[l]A-1,2-dihydrodiol, B[l]A-7,8-dihydrodiol, and B[l]A-4,5-dihydrodiol. The major B[l]A metabolite formed (28-40%) by both induced S9 preparations was B[l]A-7,8-dihydrodiol, the k-region dihydrodiol. Cyclopenta-ring oxidation to trans-B[l]A-1,2-dihydrodiol was approximately 50% of that observed for k-region oxidation. Both induced S9s produced similar rates of B[l]A metabolites except for B[l]A-7,8-dihydrodiol formation which was higher for Aroclor-1254-induced S9.

Animals↗

Late clinical outcome in patients with early ventricular fibrillation after myocardial infarction.

Whether ventricular fibrillation occurring within 48 h after acute myocardial infarction is associated with particular clinical features and poor prognosis, especially in patients with anterior myocardial infarction, is still debated. Therefore, clinical variables and in-hospital and 1 year mortality rates were analyzed in 2,088 patients, aged 18 to 95 years (mean +/- SD 64 +/- 12), admitted to the hospital with acute myocardial infarction between 1979 and mid 1984. One hundred forty-seven patients (7%) had at least one episode of ventricular fibrillation occurring within 48 h of hospital admission. Of these, 25% died during their initial hospitalization compared with 13% of patients without early ventricular fibrillation (p less than 0.001). In greater than 50% of patients with early ventricular fibrillation, the immediate cause of death was left ventricular failure or cardiogenic shock. In contrast, the 1 year mortality rate after hospital discharge was not significantly greater in patients with than in those without early ventricular fibrillation (15 versus 11%, respectively), particularly in the subgroup of patients with anterior myocardial infarction in which the mortality rate tended to be lower in patients with early ventricular fibrillation (8 versus 14%, respectively). Similar mortality results were found when only primary (not associated with left ventricular failure) ventricular fibrillation was analyzed. The left ventricular ejection fraction and the incidence of complex ventricular arrhythmias from 24 h ambulatory electrocardiographic monitoring obtained at hospital discharge were not different in survivors with or without early ventricular fibrillation (0.45 +/- 0.13 versus 0.49 +/- 0.14 and 41 versus 41%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Electron dose distributions in an anthropomorphic phantom--verification of Theraplan treatment planning algorithm.

As part of a Quality Assurance program, the performance of Theraplan (Version 4.0) for electron beam calculations was checked versus experiments carried out with an anthropomorphic (Rando) phantom. Large disagreements (up to 40%) between measured and calculated dose distributions were discovered which could not be explained in terms of the assumptions inherent in the code. Analysis of this data has led to discovery of an error in the software. AECL is working at present on a new software version with this error corrected.

Algorithms↗

Long-term outcome in patients with inferior myocardial infarction and complete atrioventricular block.

Some studies have reported increased short-term mortality and higher incidence of multivessel coronary artery disease in patients with inferior myocardial infarction and complete heart block, but information is lacking on clinical outcome after hospital discharge. Therefore, data were obtained and analyzed in 749 patients who were admitted with inferior myocardial infarction to four different centers and followed up for 1 year. Six hundred fifty-four patients (Group 1) did not have complete heart block and 95 (Group 2) had complete heart block during their hospital stay (incidence rate 12.8%). Compared with Group 1, Group 2 patients were older (66 versus 61 years, p less than 0.01), more often had signs of left ventricular failure (p less than 0.001) and had higher peak creatine kinase values (1,840 versus 1,322 IU/liter, p less than 0.001). The in-hospital mortality rate was higher in Group 2 than in Group 1 (24.2 versus 6.3%, p less than 0.001). However, at discharge there was no difference between Group 1 and Group 2 in clinical characteristics, left ventricular ejection fraction (0.52 +/- 0.12 versus 0.52 +/- 0.11) or incidence of complex ventricular arrhythmias on ambulatory electrocardiographic monitoring. Furthermore, during the year after hospital discharge, patients in Groups 1 and 2 did not have significantly different mortality rates (6.4 versus 10.1%, p = NS). The incidence rate of reinfarction (4%) was the same in Groups 1 and 2. The incidence of coronary artery bypass surgery was slightly but not significantly higher in Group 1 compared with Group 2 (11 versus 4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of long-term, alternate day feeding on renal function in aging conscious rats.

To examine the renal effects of lifelong intermittent feeding, we performed clearance and pathologic studies in 86 week old, awake male Sprague-Dawley rats fed on alternate days (N = 9) or ad libitum (N = 8) since the age of four weeks. Alternate day-fed rats were studied on both feeding and fasting days, and the values averaged. In the alternate day group the clearances of inulin (Cinulin) and PAH (CPAH), factored by body wt, were higher by 23% and 27%, respectively (P less than 0.05); albumin excretion (UalbV) was two orders of magnitude lower (P less than 0.001) and the percentage of glomeruli with lesions was eightfold lower (P less than 0.02) than in the ad libitum-fed group. The fractional clearances of neutral dextrans ranging in radii from 20 A to 42 A did not differ between the two groups. Compared to a previously published study of 30 week old, alternate day-fed rats, values for Cinulin and CPAH were similar while UalbV was higher (P less than 0.025) in the 86 week old alternate day-fed rats. Cinulin, however, was lower (P less than 0.005) while UalbV was much higher (P less than 0.001) in 86 week old, ad libitum-fed rats than in 30 week old, ad libitum-fed rats. The results indicate that long-term alternate day feeding preserves glomerular filtration rate (GFR) and renal plasma flow (RPF), while glomerular permselectivity is not completely preserved, as evidenced by an increase in microalbuminuria in aging awake male rats. Conversely, ad libitum feeding results in a significant decline in GFR and probably in RPF, in association with massive albuminuria and segmental glomerular sclerosis.

Aging↗

The nucleotide sequence of the LPD1 gene encoding lipoamide dehydrogenase in Saccharomyces cerevisiae: comparison between eukaryotic and prokaryotic sequences for related enzymes and identification of potential upstream control sites.

The complete nucleotide sequence of the LPD1 gene, which encodes the lipoamide dehydrogenase component (E3) of the pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase multienzyme complexes of Saccharomyces cerevisiae, has been established. The flanking region 5' to the LPD1 gene contains DNA sequences which show homology to known control sites found upstream of other yeast genes. The primary structure of the protein, determined from the DNA sequence, shows strong homology to a group of flavoproteins including Escherichia coli lipoamide dehydrogenase and pig heart lipoamide dehydrogenase. The amino acid sequence also reveals the presence of a potential targeting sequence at its N-terminus which may facilitate transport to and entry into mitochondria.

Amino Acid Sequence↗

Trichinella pseudospiralis larvae express natural killer (NK) cell-associated asialo-GM1 antigen and stimulate pulmonary NK activity.

Natural killer (NK) cell function was evaluated in mice infected with either Trichinella pseudospiralis or T. spiralis larvae. T. pseudospiralis-infected mice consistently demonstrated augmented pulmonary NK cell-mediated clearance of YAC-1 tumor cells in vivo but failed to display enhanced splenic NK cell-mediated lysis of the same tumor cells in vitro. Attempts to alter NK cell function in vivo by the injection of anti-asialo-GM1 antibody resulted in anaphylaxis and death of the hosts infected with T. pseudospiralis but not of mice infected with T. spiralis. Immunofluorescence studies demonstrated that larvae of both species bound large quantities of anti-asialo-GM1 antibody but did not react with another NK-associated antibody, anti-NK-1.1. Even though anti-asialo-GM1 antibody reacted with larvae of both species, intravenous injection of antibody elicited anaphylaxis only in hosts that were infected with T. pseudospiralis.

Adrenal Cortex Hormones↗

Poly(A) shortening and degradation of the 3' A+U-rich sequences of human c-myc mRNA in a cell-free system.

The early steps in the degradation of human c-myc mRNA were investigated, using a previously described cell-free mRNA decay system. The first detectable step was poly(A) shortening, which generated a pool of oligoadenylated mRNA molecules. In contrast, the poly(A) of a stable mRNA, gamma globin, was not excised, even after prolonged incubation. The second step, degradation of oligoadenylated c-myc mRNA, generated decay products whose 3' termini were located within the A+U-rich portion of the 3' untranslated region. These products disappeared soon after they were formed, consistent with rapid degradation of the 3' region. In contrast, the 5' region, corresponding approximately to c-myc exon 1, was stable in vitro. The data indicate a sequential degradation pathway in which 3' region cleavages occur only after most or all of the poly(A) is removed. To account for rapid deadenylation, we suggest that the c-myc poly(A)-poly(A)-binding protein complex is readily dissociated, generating a protein-depleted poly(A) tract that is no longer resistant to nucleases.

Adenine↗

Intracoronary alpha 2-adrenergic receptor blockade attenuates ischemia in conscious dogs during exercise.

Studies on the role of alpha-adrenergic constrictor tone in the coronary vascular bed during ischemia were performed in dogs running on a treadmill. The animals were instrumented with a left ventricular pressure transducer, and regional systolic wall thickening (%WTh) was assessed by sonomicrometry in the anterior and posterior walls of the left ventricle. An intracoronary catheter was implanted chronically in the circumflex coronary artery, and a hydraulic cuff was placed proximally around the artery. After beta-adrenergic blockade with propranolol (0.8 mg/kg i.v.), acute stenosis of the coronary artery was performed during running in five dogs to induce severe regional myocardial dysfunction in the posterior wall. Intracoronary infusion of the selective alpha 2-adrenergic blocking agent idazoxan (80 micrograms/kg) improved %WTh in the ischemic region from 5.1 +/- 1.6 to 10.8 +/- 2.8% (p less than 0.05), without any significant effect on the anterior wall. Blood flow to the subendocardium of the posterior wall (radioactive microspheres) increased from 0.17 +/- 0.05 to 0.45 +/- 0.30 (ml/min)/g (p less than 0.05). It is concluded that in exercising dogs subjected to beta-adrenergic blockade, significant postjunctional alpha 2-adrenergic receptor-mediated coronary vasoconstriction exists, even during severe ischemia. Regional alpha 2-adrenergic receptor blockade can reduce regional ischemia and improve contractile function by attenuating exercise-induced sympathetic vasoconstriction in this conscious animal model.

Adrenergic alpha-Antagonists↗

Effect of insulin therapy on established diabetic nephropathy in rats.

The effectiveness of insulin therapy on early diabetic nephropathy has not been established. In this study we examined the influence of continuous subcutaneous insulin on the progression of established nephropathy in streptozocin-induced diabetic rats. Normal controls and diabetic rats were studied for 11 mo. During the first 6 mo, all the diabetic rats received 2 U protamine zinc insulin s.c. twice weekly. During the last 5 mo of study, diabetic rats either continued on the occasional subcutaneous insulin regimen or received regular insulin by continuous subcutaneous infusion. Six months after the initiation of the study, the diabetic rats were severely hyperglycemic, and their relative mesangial areas had increased. Continued poor glycemic control in the rats receiving occasional insulin was associated with relative increased mesangial area (25.2 +/- 1.0% of glomerular area) and significant proteinuria (148 +/- 17 mg/24 h) compared with normal controls. In contrast, the use of continuous subcutaneous insulin therapy with improved glycemic control arrested mesangial changes (19.5 +/- 1.4% of glomerular area) and prevented the excessive proteinuria (71 +/- 13 mg/24 h). Indeed, these parameters did not differ from age-matched controls. We conclude that in the rat, continuous subcutaneous insulin therapy instituted after the development of early glomerular pathology is effective in arresting the disease process.

Animals↗

Modified aerobic walking program: effect on patients with postpolio syndrome symptoms.

Modified aerobic exercise may have a role in the management of patients with symptoms of postpolio syndrome by improving biomechanical efficiency, alleviating secondary cardiorespiratory and muscular deconditioning, and avoiding some risks associated with traditional strengthening exercises. The effects of a walking program on the functional capacity of patients with symptoms of postpolio syndrome were studied. Three patients participated in full oxygen consumption studies during submaximal treadmill exercise tests before and after an eight-week period. Two patients participated in an eight-week program designed to prolong walking duration while maintaining perceived exertion and discomfort/pain at minimal levels. A third patient was tested before and after eight weeks but did not receive training. The untrained patient showed some reduction in the retest compared with the initial test at all workloads with respect to oxygen consumption, heart rate, and systolic blood pressure, but ratings of perceived exertion and discomfort/pain were comparable for the two tests. Reductions in metabolic responses during the retest could be explained by the effect of habituation to the testing situation. In contrast, the trained patients showed relatively marked reductions in both metabolic and subjective responses after training. These results suggest that patients with symptoms of postpolio syndrome can increase their functional work capacity after a modified aerobic walking program. This improvement reflects improved biomechanical efficiency and possible training effects at the cardiorespiratory and muscular levels. Further research is needed to elucidate the role and interactions of these mechanisms in improving the functional work capacity of patients with chronic neuromuscular dysfunction.

Adult↗

Properties of the exonuclease activity that degrades H4 histone mRNA.

We have described a cell-free system for studying mRNA degradation (Ross, J., and Kobs, G. (1986) J. Mol. Biol. 188, 579-593). Using that system we found that human H4 histone mRNA was degraded in a 3' to 5' direction by an exonucleolytic activity. Here we investigate several properties of the crude system and of the exonuclease. A RNase inhibitor, such as that from placenta, was required to block nonspecific ribonucleases and thereby to permit different mRNAs to be degraded at different rates. The histone mRNA exonuclease required divalent cation (magnesium) but not exogenously added ATP or GTP. It functioned efficiently at monovalent cation concentrations ranging from 0.5 to 200 mM. It was bound to ribosomes isolated from cells lysed in low salt buffers. However, it was eluted in active form from the ribosomes by exposing them to 0.3 M KCl. The enzyme rapidly degraded deproteinized, 32P-labeled histone mRNA prepared enzymatically.

Cell-Free System↗