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Biomedical subjects

D D Brown

Publications and source records attributed to D D Brown.

At least 145 records · Page 8Linked to original sources
PubMed1977

The isolation and characterization of a second oocyte 5s DNA from Xenopus laevis.

A second and minor DNA component containing 5s RNA genes has been purified from the genomic DNA of Xenopus laevis (XIt 5S DNA). Some of its physical and chemical characteristics are described. It contains a 5S RNA gene sequence which has some oocyte and some somatic-specific residues, as well as nucleotides which differ from both types of 5S RNA. There are about 2000 of these 5S RNA genes per haploid complement of DNA compared to about 24,000 of the principal oocyte 5S RNA genes. The multiple repeating units of XIt 5S DNA are homogeneous in length (about 350 base pairs). We present evidence that XIt 5S RNA is transcribed in ovaries but not in somatic cells; XIt 5S DNA may therefore be under the same control as the major oocyte 5S DNA.

Animals↗
PubMed1977

High-fidelity transcription of 5S DNA injected into Xenopus oocytes.

Purified DNA, from Xenopus erythrocytes, containing genes for 5S ribosomal RNA (58 DNA) is transcribed faithfully when it is injected into the nucleus of a Xenopus oocyte. Full length 5S RNA of the correct sequence is transcribed from the injected DNA, and the newly synthesized transcripts hybridize predominantly with the coding strand of 5S DNA. The majority of transcripts hybridize with the gene region as opposed to the spacer region of the coding strand. Accurate transcription starts within the first 3 hr and continues for up to 4 days after injection of 5S DNA. Radioactive 5S RNA is detected in as short a labeling time as 1 hr.

Animals↗
PubMed1976

Decreased bioavailability of digoxin due to antacids and kaolin-pectin.

Employing a Latin-square design and single-dose studies of bioavailability in 10 normal human volunteers, we tested the hypothesis that antacids and kaolin-pectin might interfere with the bioavailability of orally administered digoxin. Cumulative six-day urinary digoxin excretion (expressed as the percentage of a 0.75-mg dose recovered) was: control, 40.1+/-3.0 (S.E.); aluminum hydroxide, 30.7+/-2.9; magnesium hydroxide, 27.1+/-2.4; magnesium trisilicate, 29.1+/-1.7; and kaolin-pectin 23.4+/-2.0. The differences in means were highly significant (F = 10.47, P less than 0.005). Further analysis (multiple comparison test) revealed that control differed significantly from each of the other treatments (alpha = 0.05), but there was no such difference between any of the other treatment groups. The decreased cumulative excretion produced by antacids and kaolin-pectin reflected a striking reduction in digoxin absorption associated with these compounds that was not related to alteration of gut transit time or to adsorption of digoxin to these gastrointestinal medications.

Administration, Oral↗
PubMed1976

Effect of sulfasalazine on digoxin bioavailability.

Low levels of digoxin were noted in a patient receiving digoxin and sulfasalazine (SSA). Discontinuation of SSA resulted in a significant increase in serum digoxin levels. To determine whether or not SSA consistently interfered with the therapeutic effect of digoxin, both drugs were administered to 10 normal subjects in a crossover study. Each received 2 doses of digoxin (0.5 mg, elixir): one dose given alone, and a second dose after 6 days of treatment with SSA. When digoxin was given with SSA, the average area under the serum digoxin curve fell from the control value of 8.79 ng-hr-ml(-1) to 6.66 ng-hr-ml(-1) (p less than 0.05), fell and total urinary excretion decreased from 278 mcg/10 days to 228 mcg/10 days (p less than 0.025). These changes suggest interference with the bioavailability of digoxin by SSA. Studies were conducted to determine whether SSA inhibited digoxin absorption by physically absorbing the glycoside from solution. In vitro tests failed to reveal any significant adsorptive properties for SSA.

Absorption↗
PubMed1976

Effect of furosemide on the renal excretion of digoxin.

Digoxin serum and urine levels were determined by radioimmunoassay in 6 subjects (4 patients with heart disease and 2 volunteers without heart disease) who had been maintained on oral digoxin (0.25 or 0.5 mg daily). Observations were made during a 3-day control period and then during 8 days of concomitant digoxin and oral furosemide (40 mg daily) therapy. Serum digoxin levels determined 10 and 24 hr after each dose of digoxin averaged 1.2+/-0.1 ng/ml (M+/-SE) during control and 1.3+/-0.1 during the last 3 days on digoxin and furosemide. The daily urinary excretion of digoxine averaged 51+/-6% of the oral dose during control and 52+/-6 during the entire period of furosemide administration. The renal clearance of digoxin and creatinine averaged 94+/-7 and 87+/-11 ml/min, respectively, during control; corresponding values were 88+/-8 and 85+/-9 for urine collections demonstrating a distinct diuretic effect of furosemide and 87+/-8 and 75+/-10 for urine collections not demonstrating such an effect during diuretic therapy. The results suggest that the diuretic effect of furosemide does not significantly affect the excretion of digoxin

Adult↗
PubMed1976

Repeating units of Xenopus laevis oocyte-type 5S DNA are heterogeneous in length.

The restriction enzymes Hind III and Hae III cleave Xenopus laevis 5S DNA at one and three sites, respectively, in each repeating unit of approximately 700 base pairs. The cleavage sites for both enzymes have been located within the repeating unit by denaturation mapping of the restriction fragments. The Hind III products and one of the Hae III fragments are variable in length, indicating heterogeneity in the length of the repeating unit in 5S DNA. This length heterogeneity is confined to the major A + T-rich spacer region. Repeating units differ from each other by discrete quanta of approximately 15 base pairs. The A + T-rich spacer has been shown to consist largely of tandem subrepeats of just this size (Brownlee, Cartwright, and Brown, 1974). We suggest that the repeat-length heterogeneity is due to variable numbers of these subrepeats in the spacer regions of the major repeating units.

Adenine↗
PubMed1976

Adjacent repeating units of Xenopus laevis 5S DNA can be heterogeneous in length.

The distribution of length heterogeneity in adjacent repeating units of X. laevis 5S DNA has been examined by "cloning" 5S DNA in bacteria. Fragments of 5S DNA produced by partial digestion with Hind III and containing 1, 4, and 5 repeating units have been inserted at the single Hind III site of the tetracycline-resistance plasmid, pSC101, and the hybrid plasmids cloned in E. coli. Adjacent 5S DNA repeats in the cloned multi-repeat fragments can differ in length. This finding rules out some mechanisms which have been proposed to account for the parallel evolution of tandem repeated DNAs. The results are consistent with an unequal crossing-over mechanism and place some constraints on the molecular processes in this recombinatory event.

Animals↗
PubMed1976

Echocardiography in Wolff-Parkinson-White syndrome.

Twenty-six patients with Wolff-Parkinson-White (WPW) syndrome were studied by echocardiography. They were classified into the following WPW types: anterior right ventricular pre-excitation (Type I) - six patients; posterior right ventricular pre-excitation (Type II) - six patients; posterior left ventricular pre-excitation (Type III) - fourteen patients. Twenty-three patients were in WPW at the time of study. Four patients with Type I WPW had abnormal systolic motion of the interventricular septum: three paradoxical and one flat. Patients with Type II and Type III WPW had no septal motion abnormalities related to pre-excitation. Three patients had intermittent WPW, Type III; in all three only minor changes in normal septal motion were apparent on WPW beats. Associated cardiac abnormalities were evident in six patients: two mitral prolapse (one Type II WPS and one Tpe III); one idiopathic hypertrophic subaortic stenosis (Type III); one congestive cardiomyopathy (Type III); one hypertrophic nonobstructive cardiomyopathy (Type I); and one atrial septal defect (Type II). We conclude that abnormal interventricular septal motion may occur with Type I WPW abnormality. Other abnormalities are detectable by echocardiography in a high proportion of WPW patients, but do not appear to be associated with any single Wolff-Parkinson-White type.

Cardiomegaly↗
PubMed1976

Relationships between myocardial perfusion, myocardial necrosis, and technetium--99m pyrophosphate uptake in dogs subjected to sudden coronary occlusion.

The quantitative relationship between abnormalities seen on technetium-99m pyrophosphate (99mTc-PYP) infarct scintigrams and the size of the myocardial infarction is unclear. We evaluated two possible determinants of 99mTc-PYP accumulation: myocardial perfusion measured with 7-10 mu microspheres and the extent of necrosis determined histologically. Hemodynamics and myocardial perfusion to small segments of the left ventricle were measured prior to, 5-10 min, and 44-48 hours following sudden occlusion of the left anterior descending coronary artery in ten awake dogs. 99mTc-PYP was injected i.v. following the third injection of microspheres and the animals were killed 2 hours later. The important findings were as follows: 1) there is a close relationship between the extent of myocardial necrosis observed and the perfusion of segments 5-10 min following coronary occlusion; and 2) that segmental myocardial perfusion is an important determinant of 99mTc-PYP accumulation by myocardial segments which contain areas of necrosis. Although the present data preclude statistical analysis of the relationship between the level of necrosis in a segment and the accumulation of 99mTc-PYP by that segment, the two do not appear to be related, a finding which would discourage use of intensity of 99mTc-PYP images for infarct size. The distribution of an abnormality on the scintigram may provide an estimate of infarct size. However, the geometry of the infarct and the resolving power of the scanning equipment will significantly limit this in many clinical situations.

Animals↗
PubMed1976

Model ecosystem evaluation of the environmental impacts of the veterinary drugs phenothiazine, sulfamethazine, clopidol, and diethylstilbestrol.

Four veterinary drugs of dissimilar chemical structures were evaluated for environmental stability and penchant for bioaccumulation. The techniques used were (1) a model aquatic ecosystem (3 days) and (2) a model feedlot ecosystem (33 days) in which the drugs were introduced via the excreta of chicks or mice. The model feedlot ecosystem was supported by metabolism cage studies to determine the amount and the form of the drug excreted by the chicks or mice. Considerable quantities of all the drugs were excreted intact or as environmentally short-lived conjugates. Diethylstilbestrol (DES) and Clopidol were the most persistent molecules, but only DES bioaccumulated to any appreciable degree. Phenothiazine was very biodegradable; sulfamethazine was relatively biodegradable and only accumulated in the organisms to very low levels. Data from the aquatic model ecosystem demonstrated a good correlation between the partition coefficients of the drugs and their accumulation in the fish.

Animals↗