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In working with mothers' responses to the total or partial loss of their child, it becomes evident that, at one level, they experience such a loss as an injury to the integrity of their body ego, which includes the child. Their capacity to invest the child as a bodily part of themselves as well as to release him and transfer bodily ownership to him in the course of personality growth necessitates flexible body boundaries. This characteristic of the female body ego is both gratifying and threatening to the mother as well as to others. It also has a profound impact on the growing boy's and girl's attempts to differentiate themselves from the mother bodily and to delineate their own sex-specific body ego. The nature and outcome of this difficult process has a significant effect on women's and men's attitudes to motherhood. These attitudes contain many defensive measures against the primitive anxieties of this early level, contributing perhaps also to the frequent neglect of motherhood in theories of female psychology.

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.

Magnetic resonance imaging at high spatial resolution, dynamic-contrast enhanced imaging, and localized 31P magnetic resonance spectroscopy were applied to monitor in vivo growth and tamoxifen treatment of MCF7 human breast tumors implanted in athymic mice. Correlation of the imaging data with histological findings demonstrated significant differences between viable carcinoma, fibrous, and necrotic regions on T2 weighted images. At an early stage after tamoxifen treatment rapid necrosis preceded tumor regression suggesting tamoxifen inhibition of angiogenesis. The necrosis was followed by growth of reperative fibrous tissue at the boundary of the viable cancer cells and the necrotic regions. The dynamic of contrast enhancement after tamoxifen treatment revealed high permeability of microvessels at this boundary cord. In parallel to the induction of the repair process the tumor energy profile changed, showing a significant increase in the ratio of ATP to inorganic phosphate. Initial attempts to use MRI for evaluating the response of breast cancer patients to treatment are also described.

The intrinsic stimulatory potential or potency of a eukaryotic gene activator is controlled by the interaction between the activation domain and the transcriptional machinery. To further understand this interaction, we undertook a biochemical study to identify parameters that could be used to modulate activator potency. We considered how varying the number of activation domains, their flexibility, and the number of promoter sites affects potency in a yeast nuclear extract. The effects of GAL4 derivatives bearing either one, two, or four herpes simplex virus VP16 activation domains (amino acids 413 to 454) were measured on DNA templates containing one or two GAL4 sites in a Saccharomyces cerevisiae nuclear extract. We found that multimerized VP16 activation domains acted synergistically to increase the potency of the activators. The spacing between the activation domains was critical, such that the increased flexibility imparted by a protein linker contributed to increased activator potency. With highly potent activators, the levels of transcription stimulated on a single site were saturating, whereas the stimulatory effect of weaker activators increased with the number of sites. We discuss how these biochemical studies relate to the mechanism of gene activation and synergy in a yeast in vitro system.

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.

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.

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.

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.

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.

The upper and lower limits of the electrostrictive constants, dielectric permittivities, spontaneous polarizations, and piezoelectric coefficients were calculated for ceramic PbTiO(3) from theoretical single-crystal constants. Experimental ceramic data fall between these upper and lower limits. The large piezoelectric anisotropy d(33)/d(31) of ceramic PbTiO(3 ) was shown to be related to the single-crystal PbTiO(3) electrostrictive anisotropies Q(11)/Q(12 ) and Q(44)/Q(12). The possibility of a change in sign of the ceramic d(31) coefficient due to a slight variation in the single-crystal electrostrictive anisotropies was discussed. The single-crystal and predicted ceramic hydrostatic electrostrictive constants were found to be equal. Using this result the ceramic hydrostatic g(h ) coefficient is always smaller than the single-crystal g (h), but the ceramic hydrostatic d(h) coefficient can be either larger or smaller than the single-crystal d(h) depending on the dielectric anisotropy (epsilon (11)/epsilon(33)) of the single-crystal.

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.

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.

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.

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.

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.

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.