A chimeric EGFR/neu receptor in functional analysis of the neu oncoprotein.

As the factor binding to the neu protein has been unknown, it has not been possible to confirm experimentally the proposed growth-factor receptor like functions of the neu protein. To approach this problem we constructed a recombinant receptor which enabled ligand regulation of the neu tyrosine kinase. The hybrid receptor consisted of the extracellular ligand binding, transmembrane and protein kinase C-substrate domains joined to the intracellular tyrosine kinase and carboxyl-terminal domains of the neu protein. Several properties of NIH3T3 cells carrying this construct were tested. We obtained the first experimental evidence that the neu proto-oncogene has mitogenic and transforming activities only in the presence of a ligand stimulating its tyrosine kinase activity. Various cellular and molecular biological parameters indicated that the chimeric receptor behaved very similarly to the EGFR. Also, this chimeric receptor has allowed us to compare the constitutive oncogenic and the ligand-activated non-oncogenic activities of the neu tyrosine kinase. In the future we plan to focus on characterization of possible differences between EGFR and neu signalling in more differentiated cellular backgrounds.     

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.     

Urethral blood circulation during cardiopulmonary bypass

The haemodynamic changes induced by extracorporeal circulation (ECC) are thought to be important in the induction of urethral strictures in open heart surgery when indwelling latex catheters are used. In the present study, 6 piglets were cannulated and connected to extracorporeal perfusion apparatus. Pump flows correlated with human ECC values with non-haemic prime were used. The mucosal and submucosal blood circulation in the urethra reduced by 66% during ECC (P less than 0.05). The brain and hepatic arterial flows increased. A significant reduction was seen in renal blood circulation. The changes in the urethral blood circulation during ECC correlated with previous findings. The reduced wash out levels of chemicals leaching from the indwelling latex catheters as a result of reduced local blood circulation are the main trigger for the induction of urethral strictures during ECC and in other shock-like circulatory disturbances in the human body.     

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.     

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.     

Periodontitis is associated with a low concentration of vitamin C in plasma

This study aimed to clarify how concentrations of vitamin C in plasma relate to the serology of periodontitis. The random sample used comprised 431 men, 194 from Finland and 237 from Russia. The plasma vitamin C concentration was determined by o-phtaldialdehyde-fluorometry, and serum immunoglobulin G antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were determined by a multiserotype enzyme-linked immunosorbent assay (ELISA). The mean plasma vitamin C concentration was higher (P < 0.001) in Finnish subjects (mean +/- standard deviation, 4.5 +/- 2.8 mg/liter) than in Russian subjects (1.4 +/- 1.8 mg/liter). Mean antibody levels to both A. actinomycetemcomitans (4.7 +/- 3.6 versus 5.2 +/- 3.1 ELISA units [P = 0.05]) and P. gingivalis (5.7 +/- 2.5 versus 7.6 +/- 2.9 ELISA units [P < 0.001]) were lower in Finnish men than in Russian men. In the combined Finnish and Russian population, the antibody levels to P. gingivalis were negatively correlated with vitamin C concentrations (r = -0.22; P < 0.001); this association remained statistically significant (P = 0.010) in a linear regression model after adjustment for confounding factors. The proportion of P. gingivalis-seropositive subjects decreased with increasing vitamin C concentrations (P for trend, <0.01), but no trend was seen among A. actinomycetemcomitans-seropositive subjects. In conclusion, P. gingivalis infection is associated with low concentrations of vitamin C in plasma, which may increase colonization of P. gingivalis or disturb the healing of the infected periodontium.