The predictive value of steroid hormone receptor analysis in breast, endometrial and ovarian cancer

The predictive value of female sex steroid, estrogen and progesterone, receptor (ER and PR, respectively) assays in breast, endometrial and ovarian cancer is reviewed with emphasis on comparative aspects of these malignant tumors in relation to their hormone dependency. The endocrine etiology of these three tumor types seems to be at least partly different, and so is the expression of these receptors in normal and malignant tissues of the breast, endometrium and ovary. There is a tendency for decreased receptor concentrations and disappearance of these receptors in association with advancement of these malignancies. There is also a decrease in the presence and concentrations of ER and PR in relation to loss of differentiation in breast and endometrial cancer. Receptor analyses have an established position in the selection of patients with advanced breast cancer for endocrine treatment, and they give promise of a similar application in endometrial cancer and in endometrioid cancer of the ovary. It is not clear whether the disease-free interval is related to the presence or concentrations of ER or PR as such in the tumor tissue. There is better survival in breast cancer patients with receptor-positive tumors, which might be due to a response to endocrine treatment. The same seems to be true for patients with endometrial cancer. Future progress in the application of female sex steroid receptor analyses in breast, endometrial and ovarian cancer needs additional controlled clinical trials and more highly developed receptor assays.     

Mutant ryanodine receptors in catecholaminergic polymorphic ventricular tachycardia generate delayed afterdepolarizations due to increased propensity to Ca2+ waves.

AIMS: Mutations in cardiac ryanodine receptors (RyR2s) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), characterized by risk of polymorphic ventricular tachyarrhythmias and sudden death during exercise. Arrhythmias are caused by gain-of-function defects in RyR2, but cellular arrhythmogenesis remains elusive. METHODS AND RESULTS: We recorded endocardial monophasic action potentials (MAPs) at right ventricular septum in 15 CPVT patients with a RyR2 mutation (P2,328S, Q4,201R, and V4,653F) and in 12 control subjects both at baseline and during epinephrine infusion (0.05 microg/kg/min). At baseline 3 and during epinephrine infusion, four CPVT patients, but none of the control subjects, showed delayed afterdepolarizations (DADs) occasionally coinciding with ventricular premature complexes. In order to study the underlying mechanisms, we expressed two types of mutant RyR2 (P2,328S and V4,653F) causing CPVT as well as wild-type RyR2 in HEK 293 cells. Confocal microscopy of Fluo-3 loaded cells transfected with any of the three RyR2s showed no spontaneous subcellular Ca(2+) release events at baseline. Membrane permeable cAMP analogue (Dioctanoyl-cAMP) triggered subcellular Ca(2+) release events as Ca(2+) sparks and waves. Cells expressing mutant RyR2s showed spontaneous Ca(2+) release events at lower concentrations of cAMP than cells transfected with wild-type RyR2. CONCLUSION: CPVT patients show DADs coinciding with premature action potentials in MAP recordings. Expression studies suggest that DADs are caused by increased propensity of abnormal RyR2s to generate spontaneous Ca(2+) waves in response to cAMP stimulation. Increased sensitivity of mutant RyR2s to cAMP may explain the occurrence of arrhythmias during exercise or emotional stress in CPVT.     

MRI Of the Brain, EEG Sleep Spindles and SPECT in the Early Diagnosis of Infantile Neuronal Ceroid Lipofuscinosis

Two patients with infantile neuronal ceroid lipofuscinosis are presented whose clinical diagnosis was based on the typical clinical picture, together with absent sleep spindles and MRI findings (hypointense thalami and hyperintense periventricular white matter) as early as 18 months in one girl. In addition to a flat cortical SEP, these abnormalities appeared earlier than the typical ERG and VEP findings used previously for clinical diagnosis of this condition. MRI of the other patient showed the same changes and EEG sleep spindles were absent by two years.     

Children and work‐related stress among physicians

The aim of this study was to analyse the influence of gender and children on physicians' stress and burnout and to obtain information on the compromises physicians make between family and work. The study was based on a nationwide survey of 3313 Finnish physicians. The results showed that work was the commonest reason for stress for both male and female physicians. If physicians had children, combining work and family was the commonest reason for stress among the women, but work still remained the commonest reason for stress among the men. The female physicians had made compromises between family and work more often than the male physicians (limited the number of children, delayed having children, given up postgraduate or continuing medical education, worked part‐time because of family, and given up a job because of a spouse's need to move). The female physicians—with or without children—were more likely than the male physicians to experience severe or moderate exhaustion and less likely than the male physicians to experience cynicism as components of burnout. Among both genders of physicians, having children was associated with less cynicism and reduced personal accomplishment, but the children did not affect exhaustion. In conclusion, having children is associated with a lower level of some burnout symptoms. Additional studies are needed to explain the health effects of work–family balance for physicians. Copyright © 2004 John Wiley & Sons, Ltd.     

Ethylene–Propylene Copolymerisations: Effect of Metallocene Structure on Termination Reactions and Polymer Microstructure

Summary: Ethylene–propylene (EP) copolymerisations were performed with two sterically different metallocenes activated by methylaluminoxane (MAO) in an attempt to better understand the effect of catalyst structure on termination reactions and polymer microstructure. The metallocene precursors under investigation were rac‐dimethylsilylbis(2‐methyl‐4‐phenyl‐1‐indenyl)zirconium dichloride ( 1 ) and a more sterically hindered counterpart rac‐dimethylsilylbis(2‐isopropyl‐4‐[3,5‐dimethylphenyl]indenyl) zirconium dichloride ( 2 ). For both catalyst systems, the most common termination mechanism was chain transfer to aluminium. In addition, for polymer samples polymerised with 1 /MAO, chain growth was terminated by chain transfer to Zr metal in propylene‐rich polymerisations and by chain transfer to ethylene monomer in ethylene‐rich polymerisations. The steric hindrance of 2 was able to suppress the chain transfer to the ethylene monomer, and chain transfer to Zr metal was also found in the ethylene‐rich polymerisations. The greater steric hindrance of 2 also affected the EP copolymer microstructure: regioregularity in the propylene‐rich copolymers was greater and isotacticity less with 2 /MAO than with 1 /MAO.

The catalyst precursors used: rac‐dimethylsilylbis(2‐methyl‐4‐phenyl‐1‐indenyl)zirconium dichloride ( 1 ) and rac‐dimethylsilylbis(2‐isopropyl‐4‐[3,5‐dimethylphenyl]indenyl) zirconium dichloride ( 2 ).     

Molecular identification of T cell-specific antigens on human T lymphocytes and thymocytes

We have identified membrane glycoproteins which carry T cell-specific antigens on human T lymphocytes and thymocytes. Purified cells were surface-labeled with NaB³H₄ after treatment with neuraminidase and galactose oxidase. Immunoprecipitations were performed with rabbit anti-human T cell-specific antibodies using co precipitation with protein A-containing staphylococci strain Cowan I. The labeled membrane glycoproteins and the precipitates were subjected to polyacrylamide slab gel electrophoresis and visualized by fluorography. The antibodies specifically precipitated 4 proteins called GP200, GP180, GP165 and GP160 (mol. wts. = 200000, 180000, 165000 and 160000) from surface-labeled T lymphocytes and low-density (medullary) thymocytes. The GP200 and GP180 were not labeled on high-density (cortical) thymocytes. A protein with a mol. wt. of 45000 was precipitated from thymocytes. Another glycoprotein on T lymphocytes and thymocytes with a mol. wt. similar to that of mouse and rat Thy-1 or Θ antigen (mol. wt. 25000) reacted with the antibodies.     

Effect of endurance training on the capacity of red and white skeletal muscle of mouse to oxidize carboxyl-14C-labelled palmitate.

Three groups of mice were trained for 1, 4 and 5 months according to different running programs on a motor driven treadmill and the fatty acid oxidation capacity (FAO) and the activities of some enzymes of energy metabolism (cytochrome c oxidase, malate dehydrogenase, triosephosphate dehydrogenase, and lactate dehydrogenase) were determined from m. quadriceps femoris (MQF). Endurance training increased the FAO [5-month training 4 days/week, 30 min/day 22% (p less than 0.05); 1-month training, 7 days/week, 150 min/day 37% (p less than 0.001); 4-month training, 5 days/week, 60 min/day 24% (p less than 0.05)]. The activities of cytochrome c oxidase and malate dehydrogenase increased approx. 30% (p less than 0.001) whereas triosephosphate dehydrogenase and lactate dehydrogenase activities were not prominently influenced by training. The predominantly red part of MQF of untrained animals oxidized palmitate four times faster than the predominantly white part. The activities of cytochrome c oxidase and malate dehydrogenase were two times higher showing pronounced FAO in the red part. Endurance training increased the FAO and activities of oxidative enzymes in the red and white parts and in the whole muscle relatively equally resulting in similar differences between the muscle types after training. The absolute increase in the FAO of the red muscle was, however, manyfold when compared in chemical units to the white muscle.     

Lipid metabolism during exercise I: Physiological and biochemical characterization of normal healthy male subjects in relation to their physical fitness

Summary On the basis of maximal oxygen uptake ( O₂ max) 18 normal, healthy men were divided into two groups of equal size: moderately trained subjects (MTR) each having O₂ max below 65.0 ml·min^–1·kg^–1 body weight (54.0±8.3) and well trained subjects (WTR), whose O₂ max exceeded 65.0 ml·min^–1·kg^–1 body weight (69.2±4.1). The WTR group had slightly (non significant, n.s.) higher percentage of slow twitch, oxidative (SO) fibers in M. vastus lateralis and higher (n.s.) activities of cytochrome c oxidase (CytOx), succinate dehydrogenase (SDH), 3-hydroxyacyl-CoA-dehydrogenase (HADH), and citrate synthase (CS), while lactate dehydrogenase (LDH) activity was lower (n.s.). In the MTR group only, the SO-%, and the activities of CytOx, SDH and HADH correlated positively with O₂ max, and LDH negatively with O₂ max. These correlations were not significant in the WTR group possibly because of the adaptations produced by training in this group. Multiple regression analysis was used to elucidate the best combination of variables to explain the variance in O₂ max. The best model consisted of the sum of relative activities of oxidative muscle enzymes (CytOx, SDH, HADH, CS), muscle LDH activity, body fat content (% F) and lean body mass. This model explained 69% of the variance in O₂ max; and of the individual variables % F was of utmost importance.