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.     

Polymeric genes MEL8, MEL9 and MEL10 — new members of α-galactosidase gene family in Saccharomyces cerevisiae

Summary We used a combination of genetic hybridization analysis and electrokaryotyping with radioactively labelled MEL1 gene probe hybridization to isolate and identify seven polymeric genes for the fermentation of melibiose in strain CBS 5378 of Saccharomyces cerevisiae (syn. norbensis). Four of the MEL genes, i.e. MEL3, MEL4, MEL6 and MEL7, were allelic to those found in S. cerevisiae strain CBS 4411 (syn. S. oleaginosus) whereas three genes, i.e. MEL8, MEL9 and MEL10 occupied new loci. Electrokaryotyping showed that all seven MEL genes in CBS 5378 were located on different chromosomes. The new MEL8, MEL9 and MEL10 genes were found on chromosomes XV, X/XIV and XII, respectively.     

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.     

Palliative treatment at home for patients with haematological disorders

 Supportive treatment of patients with haematological disorders mainly takes the form of transfusions of blood and platelets, and sometimes palliative chemotherapy is given. Most patients are treated in hospital or at the outpatient clinic. However, it is often difficult for the patients to arrange to come to the hospital, as they need transport by ambulance or taxi and sometimes a relative to help them. Throughout 1996 we offered such patients supportive treatment at home. A nurse was employed on the project, who was supplied with a car and a mobile telephone. Treatment was given at home. In all, 17 patients were treated, with a total of 90 blood and 40 platelet transfusions. At three visits chemotherapy was administered. No complications were seen, and the patients felt safe and content. We conclude that supportive treatment at home is safe and well accepted by patients and their relatives. In addition, the costs for transportation and hospital care of this patient group were reduced.     

CABG and PTCA patients' expectations of informational support in health- related quality of life themes and adequacy of information in 1-year follow-up.

The purpose of this study was to describe coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA) patients' need for nursing informational support in health-related (HRQoL) items before and after coronary artery procedures. As well we present the adequacy of informational support from patients' viewpoint. The study sample (N=625) consisted of consecutive male (N=439) and female (N=176) patients with CAD who were treated with elective CABG or PTCA. The data were collected by structured interview before coronary artery procedures and by mailed questionnaires 6 and 12 months afterwards in 1999-2001. Patients in both groups reported needing the most information about recovery and psychosocial functioning before and after the treatments. Single HRQoL items identified that the expectations of women and men differed during the follow-up period. Women in the PTCA group needed more informational support than men before procedures, while men needed more support afterwards. Our results suggest that the content of informational support is different for male and female patients before and after the coronary artery procedures. The effects of nursing interventions and instruments for measuring change in patients' outcome resulting from nursing interventions should be developed further.     

L-selectin ligands in rat high endothelium: multivalent sialyl Lewis x glycans are high-affinity inhibitors of lymphocyte adhesion

Lymphocyte homing is initiated by their tethering to and rolling on the high endothelium and is followed by extravasation into the lymph nodes. We show here that glycosylated cell adhesion molecule-1 (GlyCAM-1), CD34, and sialyl Lewis x (sLex) are present on rat lymph node high endothelium analyzed by using monoclonal antibodies. α(1,3)fucosyltransferase VII (Fuc-TVII), the last enzyme involved in the synthesis of the sLex sequence is also expressed on the rat lymph node high endothelium. We have synthesized a family of sLex-decorated oligosaccharide structures and used them to inhibit lymphocyte binding to high endothelium in the Stamper-Woodruff assay. Monovalent sLex, branched di- and tetravalent sLex, as well as a linear tetravalent sLex significantly reduce lymphocyte binding to endothelium. The branched and linear forms of tetravalent sLex were clearly superior inhibitors of the L-selectin-dependent lymphocyte adhesion, with IC50 values in low nanomolar range. In contrast, the fucose-free analogs having the same charge and approximately the same size as the corresponding sLex glycans had no effect on lymphocyte binding and served as negative controls. Taken together, these data show the crucial importance of sLex in the endothelial ligands for L-selectin. Furthermore, we suggest that L-selectin acts as an oligomer on the lymphocyte surface as it binds multivalent sLex glycans.     

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.     

Interleukin 1-induced lymphocyte binding to endothelial cells. Role of cAMP as a second messenger

Interleukin 1 (IL 1) is a potent protein mediator of inflammation. Among other things it increases the number of lymphocytes adhering to endothelial cell monolayers. We analyzed the signal transduction during IL 1-induced lymphocyte binding. Dibutyryl cyclic AMP, which is a cAMP analog able to penetrate into the cytosol, increased lymphocyte binding to the same extent as IL 1. Direct activation of adenylate cyclase by forskolin enhanced also lymphocyte binding. IL 1 increased the level of cytosolic cAMP in a time- and dose-dependent manner measured with radioimmunoassay. 2',5'-Dideoxyadenosine, which is an inhibitor of adenylate cyclase, decreased both the IL 1-induced lymphocyte binding to endothelial cells and elevation in cytosolic cAMP levels. Lymphocyte binding increased with cytosolic cAMP levels in accordance with elevation of IL 1 concentration. These results suggest that cAMP is essential in signal transduction during IL 1-induced lymphocyte binding to cultured endothelial cell monolayers.     

Temperament as a potential predictor of mortality: Evidence from a 41-year prospective study

Psychological factors were hypothesized to influence mortality, in particular, early versus later mortality. To explore the relationship between temperament, a psychological factor, and mortality in a prospective study of 1337 medical students, we constructed a measure portraying three temperament types, using latent class analysis. Death occurred in 113 subjects over 25–41 years of follow-up. In univariate survival analysis, subjects tending to direct tension inward when under stress (Tension-In) had a higher risk of mortality than Tension-Out or Stable types. These associations persisted after adjustment for age, smoking, cholesterol level, and Quetelet Index. The relative risk (RR) of mortality for Tension-In was 1.56 (95% confidence interval, 1.00–2.44) compared with the Stable group. The risk was due entirely to the excess risk in persons under 55 years of age (RR, 2.59; 95% confidence interval, 1.46–4.62); the corresponding risk of death in older persons was 0.66 (0.30–1.48). Thus temperament is a significant risk factor for mortality, in particular, premature death.