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C A Barnett

Publications and source records attributed to C A Barnett.

36 records · Page 2Linked to original sources

Activation of the glucocorticoid-receptor complex.

A crucial step in the interaction of glucocorticoids with target cells is the activation step, which involves a conformational change in the cytoplasmic glucocorticoid-receptor protein complexes and facilitates their binding to the cell nucleus. Activation can be quantified by measuring the ability of glucocorticoid-receptor complexes to bind to polyanions, such as DNA-cellulose, and unactivated complexes can be separated from activated complexes by rapid ion exchange chromatography using diethylaminoethyl (DEAE)-Sephadex or DEAE-cellulose. Activation occurs in vivo under physiological conditions and the rate of activation of cytoplasmic glucocorticoid-receptor complexes can be enhanced in vitro by physical manipulations (elevated temperature, increased ionic strength, dilution). In vitro studies suggest that activation is a regulated process and a low molecular weight component termed modulator, which has been identified in rat hepatic cytosol, inhibits activation. Additional studies employing phosphatase inhibitors, such as molybdate, and purified calf intestinal alkaline phosphatase suggest that either the receptor protein or a regulatory component is dephosphorylated during activation. Results obtained with specific chemical probes suggest that activation results in the exposure of basic amino acid residues consisting minimally of lysine, arginine, and histidine. Pyridoxal 5'-phosphate, a specific probe for lysine residues, exerts dual effects on glucocorticoid-receptor complexes, since it stimulates the rate of activation and also inhibits the binding of previously activated complexes to nuclei or DNA-cellulose. The ability of 1,10-phenanthroline, a metal chelator, to inhibit the DNA-cellulose binding of activated complexes suggests that a metal ion(s) located at or near the DNA binding site may become exposed as a consequence of activation. Collectively, the results of these various experiments suggest that activation is a regulated biochemical phenomenon with physiological significance.

Alkaline Phosphatase↗

Electrophoretic variation of aconitase and phosphoglucomutase detected in Microtus californicus.

Four electrophoretic variants of cytoplasmic aconitase (citrate (isocitrate) hydro-lyase, EC 4.2.1.3) were detected in a population of Microtus californicus when samples were screened by starch gel electrophoresis using Tris/citrate buffers at pH 7.0 and pH 8.7. Variation at what is presumed to be the phosphoglucomutase-3 locus (alpha-D-glucose-1,6-diphosphate:alpha-D-glucose-1-phosphate phosphotransferase, EC 2.7.5.1) was also detected with liver samples but was not detected in kidney samples or red blood cells lysates. This nongenetic variation is due to oxidation of free sulfhydryl groups.

Aconitate Hydratase↗

Selection of a dexamethasone-resistant H-4-IIE-C3 rat hepatoma tissue-culture line.

Exposure of H-4-IIE-C3 rat hepatoma cell cultures to the synthetic glucocorticoid, dexamethasone, results in an inhibition of cellular proliferation which is not the result of steroid-induced cytolysis. A significant decrease in both the rate of DNA synthesis and DNA content precedes a detectable effect on cell number. Continuous culture of H-IIE-C3 cells in medium containing 10(-5) M dexamethasone results in the selection of a steroid-resistant cell population that has the growth characteristics of unselected sensitive cultures and shows normal steroid induction of tryosine transaminase. Selection is a slow process requiring 24 to 36 months to obtain a phenotypically stable resistant cell line, and can be subdivided into three phases--a sensitive phase, adaptation and resistance. A comparison of the karyotypes of unselected and resistant cultures shows that the selection process enriches for a dexamethasone-resistant subpopulation.

Animals↗

Ventricular visualization on brain scan with intracranial hemorrhage in disseminated phycomycosis.

Infections with fungi of the class Phycomycetes result in distinctive tissue changes characterized by growth of hyphae in and around blood vessels, causing necrosis and hemorrhagic infarction of tissue. A brain scan on a patient with a phycomycotic intracranial aneurysm demonstrated ventricular visualization at a time when there was clinical and autopsy evidence of rupture of the aneurysm.

Brain↗

Quantitative hepatic scintiangiography.

A new method has been developed which quantitatively assesses the relative arterial and portal venous blood flow in both normal and diseased liver tissue. Using a standard dedicated computer and routine clinical programs, the hepatic blood flow time/activity curve was analyzed. Specific indices were calculated: alpha1 represents aortic blood flow; alpha2, portal blood flow; alpha1/alpha2, the ratio of arterial to portal blood flow; and delta T, the difference in time between the peak of the arterial curve and the junction of the arterial and portal phases of the hepatic curve. Student's t-tests showed that these indices may be used to differentiate between the normal population and patients who have metastases or moderate to severe hepatocellular disease. Patients with early hepatocellular disease could not be differentiated from the normal population, but they could be separated from patients with more advanced hepatocellular disease. Patients with severe hepatocellular disease could not be separated from those with metastases. The most important uses of this technique may be in following a patient and determining when hepatocellular disease has become irreversible, and in following the course of treatment of a patient with metastatic disease to the liver.

Humans↗

Assessment of conventional criteria for the early diagnosis of thrombophlebitis with the 125I-fibrinogen uptake test.

Analysis of 55 positive tests of a total of 300 tests by conventional criteria revealed that 125I-fibrinogen provides useful information early enough for clinical management. Of the tests which were ultimately interpreted as positive by conventional criteria, at least one was positive at 3-4 hours in 67% of the tests and 98% of the tests were positive at 24 hours after the administration of 125I-fibrinogen. A 20% difference between contralateral identical locations of the legs and a 20% difference between adjacent locations of the ipsilateral leg were found with almost equal frequency in the positive tests, whereas a 20% increase at the same location was less sensitive. The 125I-fibrogen uptake test is a simple and accurate technique for early diagnosis of active thrombophlebitis.

Fibrinogen↗

Banded karyotypes of H-4-IIE-C3 rat hepatoma cells grown in vitro.

Mitotic cells from the H-4-IIE-C3 rat hepatoma tissue culture line showed a range of 45 to 53 chromosomes per cell with 75% of the cells displaying a chromosome mumber between 49 and 52. Analysis of Wright's-Giemsa banded karyotypes of 22 cells revealed considerable cell to cell variation. Twenty-one structurally abnormal chromosomes were identified in these cells; the origin of nine of the 21 chromosomes were identified in these cells; the origin of nine of the 21 chromosomes could be determined. Of the structurally abnormal chromosomes detected, only one (M-1) occurred with a sufficiently high frequency to be of general use as a marker for these cells. This marker appears to be a Robertsonian translocation involving chromosome number 2 and chromosome number 10.

Animals↗

Quantitative gated blood pool SPECT for the assessment of coronary artery disease at rest.

BACKGROUND: Planar gated blood pool imaging (GBPI) has long proven to be useful for the noninvasive assessment of ventricular function. From a practical viewpoint, gated blood pool single photon emission computed tomography (GBPS) acquisition can be accomplished in the same time as a three-view planar series, with the benefit of a tomographic perspective that avoids chamber overlap. METHODS AND RESULTS: Quantitative gated blood pool SPECT was applied to 10 patients who underwent coronary arteriography, contrast ventriculography, and planar gated blood pool imaging. For each patient, the mid-short axis oblique slice was divided into 4 discrete segments using 4 different reference models and 2 forms of segmentation. A center of mass (counts) fixed in the end-diastolic frame and segmentation that bisected the ventricular septum proved to have the highest sensitivity and specificity for determining regional wall motion abnormalities at rest in myocardium supplied by severely diseased coronary arteries (>75 %). GBPS correctly identified 19 of 21 abnormal segments (90%), with good specificity (95%), whereas ventriculography identified 12 (57%) and planar GBPI identified 9 (43%) of the segments supplied by diseased coronaries. CONCLUSION: Quantitative GBPS appears to be a sensitive method for assessing coronary artery disease at rest in myocardium perfused by severely diseased coronary arteries.

Aged↗