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Biomedical subjects

E Furman

Publications and source records attributed to E Furman.

At least 19 recordsLinked to original sources
PubMed1995

Purification of the spliceosome A-complex and its visualization by electron microscopy.

Pre-mRNA splicing occurs on spliceosomes, a family of ribonucleoprotein particles. Spliceosome assembly on exogenous adenovirus pre-mRNA was blocked at the A-complex (or pre-spliceosome) stage, either by destruction of the small nuclear ribonucleoproteins (snRNPs) that comprise the U4/U5/U6 tri-snRNP complex, or by interference in tri-snRNP assembly and interactions. The A-complex was isolated by size exclusion chromatography; homogeneity was shown by electrophoresis in nondenaturing polyacrylamide gels, gradient sedimentation, and electron microscopy. Northern hybridization showed U1 and U2 snRNAs to be present in the preparation, but not U4, U5, or U6. Antibodies specific for a component of the U1 snRNP or for a component that is common to all snRNPs (except U6) each precipitated an A-complex containing pre-mRNA, U1 and U2 snRNPs. Electron micrographs showed 230 x 270-A particles whose two components appear similar to individual U1 and U2 snRNPs. Electron micrographs of an A-complex-5'-biotinyl oligonucleotide-streptavidin-gold composite allowed identification of the U2 snRNP within the structure and the localization of the 5'-segment of U2 snRNA at a unique site in the A-complex. This region of U2 RNA is adjacent to the developing catalytic center of the spliceosome.

Base Sequence↗
PubMed1992

Tamoxifen induced changes in MCF7 human breast cancer: in vitro and in vivo studies using nuclear magnetic resonance spectroscopy and imaging.

The effects of 17 beta-estradiol versus tamoxifen on the growth and metabolism of MCF7 human breast cancer cells, in culture and in tumors implanted in nude mice, were studied by 31P and 13C nuclear magnetic resonance spectroscopy and by proton magnetic resonance imaging. In culture, the content of the phosphate metabolites including nucleoside triphosphates (NTP), phosphomonoesters, phosphodiesters and inorganic phosphate (Pi) were not affected by tamoxifen treatment. However, in the presence of estrogen the rate of glucose consumption and lactate production via glycolysis (270 and 280 fmol/cell.h, respectively) were twice that of tamoxifen treated cells. Estrogen rescue of tamoxifen treated cells indicated that glycolysis induction occurs at the early stages of the hormonal response. The in vivo studies included recording of proton images that provided an accurate measure of tumor size and distribution of tumor cells, necrotic regions and stromal tissue. Tamoxifen caused enhanced necrosis extending from the center of the tumor during the first two days of treatment (12 h to 6 days). This was followed by growth of reparative tissue along with tumor regression. Tamoxifen also modified the content of the phosphate metabolites, increasing markedly (P less than 0.0002) the ratio of NTP to Pi from 0.41 before treatment to 1.75 9-19 days after treatment. This change was attributed to the enhanced growth of repair tissue. The results provide new information regarding the response of human breast cancer to hormonal treatment and suggest a mechanism for the induction of tumor regression by tamoxifen.

Animals↗
PubMed1992

On feeling and being felt with.

The development of feelings in early childhood is traced, with special emphasis on the mother's role during the toddler phase when she facilitates her child's transition from sensorimotoric discharge to the mental experience, ownership, and use of modulated affects. Many child analytic patients use defenses to ward off feelings, many have not even reached the developmental level of experiencing feelings. How this difficulty manifests itself, the reasons for the developmental lag, and the analytic means of helping such patients are discussed and illustrated.

Child Behavior Disorders↗
PubMed1991

In vivo studies by magnetic resonance imaging and spectroscopy of the response to tamoxifen of MCF7 human breast cancer implanted in nude mice.

Magnetic resonance 1H-imaging and 31P-localized spectroscopy were utilized to monitor, noninvasively, MCF7 human breast cancer tumors implanted in immunodeficient mice. The tumors were followed during estrogen dependent growth and tamoxifen induced remission. Early after tamoxifen administration enhanced necrosis developed, extending to most of the tumor volume. This was followed by growth of repair tissue along with tumor regression. The short-term tamoxifen treatment also modified the content of the phosphate metabolites, increasing the nucleoside triphosphate to inorganic phosphate ratio from 0.41 +/- 0.15 (n = 14) before treatment to 1.10 +/- 0.70 (n = 8, P less than 0.025) and to 1.75 +/- 0.66 (n = 9, P less than 0.0002) 4-7 days and 9-19 days, respectively, after treatment. This change was attributed to the growth of reparative tissue. The results provide new information regarding the response and the mechanism of action of tamoxifen.

Animals↗
PubMed1987

Specific effects of nitroprusside on myocardial O2 balance following coronary ligation in the dog heart.

The effect of gradual infusion of nitroprusside was studied in healthy and in ischemic hearts. In two areas of the left ventricular surface (ischemic and non-ischemic) local coronary blood flow was measured by a thermistor technique. Isometric contractile tension was recorded with strain gauge arches, and nicotinamide-adenine-dinucleotide (NADH) redox state was measured simultaneously in both regions using a two-channel fluorometer. Aortic blood pressure was also recorded. It was found that at an infusion rate of 1.0 microgram/kg/min, nitroprusside increased regional coronary blood supply in the healthy heart as well as in the ischemic and nonischemic areas of left anterior descending artery (LAD)-ligated hearts. Flow elevation was similar in all regions (37.0 +/- 6.1, 42.5 +/- 13.5 and 45.36 +/- 14.8%, respectively). At higher doses, a decrease of 6-10% in blood pressure had a detrimental effect on the coronary flow to the ischemic region without reducing flow to the nonischemic region. The NADH redox level was not significantly improved by nitroprusside in spite of elevated coronary blood supply to all regions examined. Moreover, higher doses of nitroprusside resulted in a significant elevation in NADH levels that could be correlated to the decrease in blood pressure. It is concluded that the effect of nitroprusside on coronary blood supply and myocardial O2 balance may be strongly dependent on the magnitude of its effect on blood pressure.

Animals↗
PubMed1986

Variations in left and right ventricular oxygen balance produced by paired electrical stimulations.

The possible differential effect of positive inotropic stimulation upon regional myocardial oxygen balance in the two ventricles was investigated during tachycardia and paired electrical stimulation. Isometric contractile force was measured by strain gauge arches; local coronary blood supply was measured by thermistor probes and intracellular NADH redox level was recorded using surface fluorometry. It was found that when contractility was increased by paired stimulation at a basic rate of 140 bpm, the inotropic response was more pronounced in the right ventricle (97.2 +/- 11.5%) than in the left (63.1 +/- 12.6%). Coronary blood supply to the left ventricle increased by 117.8 +/- 30.4% and the corresponding NADH redox level increased by 54.3 +/- 19.9%. When the contractile force was increased to the same extent (64.1 +/- 8.9%) by single stimulation at a rate of 210 bpm, the coronary flow to the left ventricle was increased by only 36.4 +/- 11.0% and the NADH state rose by 67.1 +/- 12.1%. It is concluded that paired stimulation reduced the mechanical limitation to flow during tachycardia, thus allowing coronary blood supply to increase in response to positive inotropic stimulation, thereby preserving a relatively improved oxygen state. It was also observed that the ratio contractile force/blood supply (contraction efficiency) was usually proportional to the NADH redox level (oxygen balance). Nevertheless, variations observed in the force/supply ratio for the left ventricle indicate that the NADH redox level cannot be predicted quantitatively by the force/supply ratio.

Animals↗
PubMed1986

Effect of coronary vasodilators and pacing upon regional oxygen balance of the ischaemic myocardium.

In anaesthetized open-chest dogs, regional contractile force, epicardial tissue blood flow, and local NADH redox levels were recorded during graded ventricular pacing in the range 150-285 bpm. These parameters were measured before, and 30 min following LAD coronary artery occlusion. It was found that during pacing, blood supply to the untreated ischaemic region was reduced by 65.4 +/- 11% of control values at a rate of 150 bpm, and fell to -105 +/- 40.2% at a rate of 225 bpm. Hypopneic respiration prevented this pacing induced flow reduction. Pacing in the presence of nitroglycerin resulted in a marked increase in regional flow. Similarly, the vasodilator treatments prevented the marked elevation in NADH levels (77.5 +/- 15.6%) produced by pacing in the untreated ischaemic myocardium. The reduction in regional contractile force in the ischaemic region produced following pacing (-30.5%) was reversed during both vasodilator treatments (+47.2% during nitroglycerin and +23.4% during hypopnea). It was concluded that vasodilation improves regional ischaemic myocardial oxygen balance, thus expanding the functional reserve of the ischaemic muscle. Nitroglycerin is more active.

Animals↗
PubMed1986

Relation between myocardial substrate utilization, oxygen consumption and regional oxygen balance in the dog heart in vivo.

The interaction between myocardial function, oxygen consumption and energy production was examined in the left ventricular myocardium during various physiological conditions. Myocardial function was measured by both LV dP/dTmax and by local contractile tension. Coronary blood flow was measured from the coronary sinus; regional coronary blood supply was recorded using a thermistor placed on the epicardial surface. Intracellular oxygen balance was estimated using NADH fluorescence. Myocardial oxygen consumption and utilization of glucose, pyruvate, lactate and free fatty acids were calculated from their concentrations in the arterial and coronary sinus blood. The effects of tachycardia at 180 and 240 bpm, noradrenaline infusion (25 micrograms kg-1 min-1), and increased coronary blood flow caused by hypopneic respiration were examined. During pacing, contractile force, coronary flow and NADH fluorescence increased. At 240 bpm, the lactate/pyruvate ratio increased from 5.98 +/- 0.92 to 8.76 +/- 1.41 and NADH fluorescence increased from 50 to 71.7 +/- 3.73 (as compared to control), indicating impairment of myocardial oxygenation. Hypopneic respiration produced a marked elevation of coronary blood flow. Both noradrenaline infusion and hypopnea produced a decrease in both NADH fluorescence and the lactate/pyruvate ratio. No significant difference was found between the FORCE/ATP, FORCE/MVO2 and ATP/MVO2 ratios during pacing and noradrenaline. However, during hypopnea, the amount of ATP apparently formed (as calculated by substrate utilization assuming the formation of 3 ATP molecules per oxygen) was disproportionately greater than contractile force and oxygen consumption. It is suggested that this discrepancy may be due to the uncoupling of oxidative phosphorylation.

Adenosine Triphosphate↗
PubMed1985

Effect of global vs regional ischaemia upon myocardial contractility and oxygen balance.

The possible role of catecholamines upon the nature of myocardial response to regional and global left ventricular ischaemia was investigated. Global ischaemia was accomplished by temporary occlusion of the left main coronary artery and regional ischaemia by temporary ligation of the left anterior descending coronary artery. Isometric force of contraction was measured with strain gauge arches, regional blood flow by a thermistor technique and intracellular NADH redox level by a fluorometric technique. These measurements were made simultaneously in two areas on the left ventricular myocardium: one immediately below the bifurcation of the LAD and the other immediately below the circumflex coronary artery. Following LAD occlusion a variable inotropic response was observed in the ischaemic area. A decrease in contractile tension was found in 19 of the dogs (44%), no change in 23% and an increase was found in 33%. Global ischaemia invariably resulted in a decrease in contractile tension. NADH redox state was markedly higher during global than during regional ischaemia. Propranolol administration blocked the positive inotropic response to regional ischaemia. It is concluded that endogenous catecholamine release may be responsible for increased contractile force during regional ischaemia. This response is apparently limited by the oxygen availability to the tissue.

Animals↗
PubMed1985

Preservation of myocardial oxygen balance and functional reserve by coronary vasodilators.

Reduced myocardial function at very high heart rates may be due to limited coronary blood supply. The effects of the vasodilators nitroglycerin (10 micrograms kg-1 min-1) and elevated CO2 upon regional function during tachycardia were studied. In open-chest anaesthetized dogs, regional contractile force, epicardial tissue blood flow and local NADH redox level were recorded during graded ventricular pacing. It was found that the vasodilating action of nitroglycerin in the unpaced heart was much lower than produced by CO2 (23.6 +/- 5.8% vs. 137.6 +/- 33.5%). Maximal pacing at 275 bpm caused only a moderate flow elevation in control (20 +/- 6.8%) and CO2 conditions (20.3 +/- 4.03%), but marked vasodilation during nitroglycerin infusion (85.2 +/- 14.6%). Regional function during tachycardia was improved similarly by both vasodilators. NADH levels increased with heart rates under all experimental conditions, but the absolute NADH levels were consistently lower following vasodilator treatments. The lowest NADH levels were observed during nitroglycerin treatment at all heart rates. It is suggested that nitroglycerin augments myocardial functional reserve by preserving oxygen balance more than predicted by its vasodilatory effect alone.

Animals↗
PubMed1984

Intermittent decathexis--a type of parental dysfunction.

This paper describes a type of parental dysfunction--intermittent decathexis--which apparently has not previously been reported although it occurs frequently, to varied extent. The dysfunction is introduced by some of the clinical material that originally brought it to the author's attention, is contrasted with the more usual parental investment in their children. Its relationship to depression and then to aggression is next clarified. Examples of the manifestations of having been intermittently decathected are offered from both child and adult analyses as well as the impediments it provides for a child's progressive emotional development. Finally, the evidence is presented which led the authors to conclude that metapyschologically intermittent decathexis is a primitive defensive manoeuvre.

Aggression↗
PubMed1983

Studies in childhood bereavement.

A group of child psychoanalysts, associated with the Cleveland Center for Research in Child Development and the Hanna Perkins Therapeutic Nursery School and Kindergarten, studied 23 children who had lost a parent through death. These children varied greatly in socio-economic, religious, racial and ethnic background and had suffered bereavement at different points in their development, as early as a few weeks old and as late as 13 years of age. The majority were in individual psychoanalytic treatment, seen 5 times weekly over several years. Some were treated by way of the parent while attending the Hanna Perkins Therapeutic School. The research group compared and discussed the multitude of data with a view to understanding mourning and the effects of bereavement on the personality, with a view to developing techniques in assisting children and families cope with the stress, and with a view to developing some prophylactic measures to minimize pathological resolutions. The results of the research were published in "A Child's Parent Dies" (1). This paper focuses on sharing those findings which might be helpful to the clinician in the assessment of bereaved patients and in assisting them and their families in the crucial period of parental loss or shortly following it.

Adaptation, Psychological↗