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Biomedical subjects

C J Peterson

Publications and source records attributed to C J Peterson.

17 recordsLinked to original sources

A rodent model of focally evoked self-sustaining status epilepticus.

We describe a novel model of status epilepticus produced by the focal application of bicuculline methiodide into the deep prepiriform cortex of rats pretreated with lithium chloride. Three out of eight rats pretreated with one dose of lithium (3 mmol/kg) 24 h prior to induction of seizures by focal bicuculline, and eight out of 12 rats pretreated with two doses of lithium (at 24 and 48 h) prior to seizure induction, exhibited continual uninterrupted convulsive seizure activity (status epilepticus) lasting between 10 min and > 2 h. This status epilepticus which was manifest both behaviorally and electroencephalographically, was sensitive to reversal by diazepam (5 mg/kg i.p.) given as long as 2 h after the onset of sustained status epilepticus. Pilocarpine (25 mg/kg) pretreatment also predisposed to status epilepticus in response to the focal application of bicuculline, but diazepam (5 or 10 mg/kg i.p.) was ineffective in suppressing the status epilepticus in the presence of pilocarpine.

Animals

Transvalvular left ventricular pressure measurement in the isolated working rat heart.

A method of continuously measuring left ventricular (LV) pressure in an isolated buffer-perfused working rat heart is described. Transvalvular placement of a micromanometer through the aorta is the unique feature of this procedure. Advantages include catheter stability and lack of myocardial trauma. Changes in cardiac function were quantified by exposing hearts to either isoproterenol (10(-9) M) or halothane (1.5% vol/vol). To examine if any obstruction to LV outflow was caused by the micromanometer, cardiac performance was assessed during pullback from the ventricle to the aorta. Complications such as aortic insufficiency and ventricular arrhythmias were also studied. The results indicate that the transvalvular placement of a micromanometer can provide continuous, high-fidelity reproduction of LV pressure in this small-organ preparation. The presence of the micromanometer did not significantly alter cardiac performance, and proper catheter placement was achieved easily in a high percentage (> 90%) of cases.

Animals

Activation of uteroglobin gene expression by progesterone is modulated by uterine-specific promoter-binding proteins.

In a previous study specific protein binding to the uteroglobin (UG) promoter was detected in gel retardation assays using progesterone-dominated rabbit uterine nuclear extract proteins. Those findings have now been extended to reveal the components within that specific shifted band. Southwestern blotting and photoaffinity cross-linking of protein-DNA complexes by UV irradiation demonstrate binding of two proteins with apparent molecular masses of 94 and 115 kDa to a 126-basepair UG gene fragment (UG126-194/-68). To further investigate the tissue- and hormone-specific expression of the UG gene and to relate that specificity to promoter binding, RNA was prepared from rabbit uterus, kidney, and lung after 5 consecutive days of progesterone treatment. Northern blots of total RNA showed an absence of UG expression in kidney, while UG message was detected in uterus and lung. Protein binding to UG promoter DNA was absent in extracts from nuclei of kidney and HeLa cells, where the gene is not expressed, and from lung, where the gene is expressed but not regulated by progesterone. Digestion of the uterine protein-DNA complex using the nuclease activity of phenanthroline-copper ion and DNAase-I revealed two footprints. Protection was similar on both DNA strands, indicating no preference of protein binding to one DNA strand over the other. Taken together, the results provide strong indirect evidence that transcriptional activation of UG gene expression by progesterone requires binding of two additional proteins to UG promoter elements.

Animals

Uterus-like mass of the small intestine. Heterotopia or monodermal teratoma?

A 12-year-old girl with multiple lower-intestinal and urogenital tract anomalies and a past history of sacrococcygeal teratoma had an intramural mass of the ileum discovered as an incidental finding at surgery. The predominant mass had the features of the uterine fundus and two smaller contiguous nodules resembled the fallopian tube. A normal uterus and ovaries were observed at surgery. Somewhat similar lesions have been reported in the past in the ovary, ileum, scrotum, and possibly the bladder. Neither the metaplastic nor malformational theories are entirely satisfactory, yet they can be stated for most examples of heterotopias or choristomas.

Abnormalities, Multiple

Accelerated ribosome formation and growth in neonatal pig hearts.

Rapid growth (5 mg dry heart/h) of the left ventricular free wall (LVFW) in the newborn pig heart accompanied by lack of growth of the right ventricular free wall (RVFW) represents a unique natural model of cardiac enlargement that is free of pathophysiological influences. By 3 days of life, LVFW was 71% larger than at 4 h of age. Rates of protein synthesis were measured during perfusion of isolated pig hearts with bicarbonate buffer containing glucose, lactate, insulin, and plasma concentrations of amino acids of an aortic pressure of 60 mmHg. In hearts from pigs that were 18 h of age, rates of protein synthesis were the same in RVFW and LVFW, but in 2-day-old pigs the rate was 52% greater in LVFW than RVFW. During the first 3 days of life, RNA content (mg/g) increased 3.4-fold faster in LVFW than RVFW. When RNA content was expressed per total heart portion, the increase was 7.9-fold greater. Because approximately 85% of total RNA is rRNA, these values indicated much more rapid formation of ribosomes in the LVFW than RVFW. When ribosome formation was measured in vitro in hearts from 48-h-old pigs, rates of formation were 39% greater in LVFW than RVFW, and at 18 h of age, ribosome formation was 40% faster in LVFW than RVFW. These findings indicated that formation of new ribosome preceded accelerated synthesis of total heart proteins. These findings indicated that rapid growth of LVFW compared with no growth of RVFW was associated with a 67% faster rate of ribosome formation and a 32% greater rate of protein synthesis.

Aging

Direct effects of myocardial depressant drugs on coronary vascular tone: anesthetic vasodilation by halothane and isoflurane.

Because certain vasoactive drugs also possess negative myocardial inotropic properties, it is difficult to determine their direct pharmacological actions on coronary resistance vessels in situ. Thus, a drug's myocardial effects may induce indirect physiological changes in coronary vascular tone that confound measuring its direct action. To separate the direct from indirect drug actions on vascular tone, the authors describe an experimental system utilizing the isolated perfused rat heart arrested with tetrodotoxin. The direct effects of the volatile anesthetics halothane and isoflurane on coronary vascular tone were examined in this preparation, using the concept of minimum alveolar concentration as the measure of potency. Both anesthetics demonstrated a dose-dependent direct coronary vasodilation that was reversible, with the median effective dose being 1.31 +/- 0.08 (mean +/- S.E.) for halothane, and 1.53 +/- 0.12 for isoflurane (P = 0.06; units of measure are the fraction of minimum alveolar concentration for each anesthetic). Further studies indicated that maximal vasodilation by adenosine was diminished after 90 min of perfusion, independent of anesthetic administration. Myocardial oxygen consumption was decreased significantly from the beating state by arrest, but neither anesthetic nor adenosine affected myocardial oxygen consumption further. These data indicate that halothane and isoflurane are equipotent for inducing direct dilation of coronary resistance vessels in the isolated perfused arrested rat heart.

Adenosine

Mechanisms of differential growth of heart ventricles in newborn pigs.

The left ventricular free wall (LVFW) grew approximately three times faster than the right ventricular free wall (RVFW) during the first 10 days of life in neonatal pigs. Faster growth was associated with proportional increases in total RNA and messenger RNA. These findings indicated that greater capacity for protein synthesis was a major factor in accelerated growth. Despite faster growth, heart content of ribosomal subunits was higher in piglets than in 60-day-old pigs or adult rats, suggesting a relatively slower rate of peptide chain initiation than elongation. When hearts from 5-day-old pigs were perfused in vitro, protein synthesis was more rapid in the LVFW than in the RVFW. In the absence of added insulin, the higher rate was due to both greater efficiency and greater capacity for protein synthesis. In the presence of the hormone, greater capacity was responsible for the increased rate of protein synthesis in the LVFW as compared with the RVFW.

Animals

Biochemical mechanisms of cardiac hypertrophy.

Rapid cardiac growth in adult rats and neonatal pigs involves more efficient use of existing components of the protein synthesis pathway and synthesis of new ribosomes and mRNA to increase the capacity for protein synthesis. Greater efficiency of synthesis can be induced by mechanical perturbations that stretch the ventricular wall, including increased cardiac work and increased ventricular pressure development in beating hearts, and increased aortic and intraventricular pressure in arrested-drained hearts. The biochemical signal linking stretch to more efficient protein synthesis has not been identified. Preferential synthesis of new ribosomes occurs in the first two hours of exposure of Langendorff preparations to high aortic pressure or within four hours after injection of thyroid hormone into normal rats. The rate of protein degradation is either accelerated or unchanged in hypertrophing hearts but is inhibited by induction of cardiac work or high aortic pressure in Langendorff preparations. Overall, increased capacity for, and efficiency of, protein synthesis are the major factors accounting for cardiac growth.

Aging