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Background: We investigated whether individual differences in baseline executive control capacity could predict state anxiety during a potentially life-threatening situation., Methods: 19 Swedish military conscripts were assessed during two measurement occasions. During a baseline measurement, data regarding performance on a letter fluency task and state anxiety were assessed. During a second measurement, performed immediately prior to participation in a live hand-grenade throwing exercise, data regarding state anxiety was assessed. All participants were male, right-handed and had fulfilled 12 years of education., Results: The level of state anxiety was significantly increased between the two measurement occasions (p < .01). Both the number of words produced (beta = -.37; p < .05) and the number of perseveration made (beta = .43; p < .05) on the verbal fluency task predicted, while controlling for state anxiety at baseline, the level of experienced state anxiety during the threatening situation., Conclusion: Although more research is needed the present finding suggests that individual differences in executive control capacity might be related to emotion regulation ability during acute stressor exposure.

The epithelial mucin MUC1 is a high molecular weight membrane glycoprotein frequently overexpressed and aberrantly glycosylated in adenocarcinoma. Mucins normally contain high amounts of O-linked carbohydrate structures that may influence immune reactions to this antigen. During malignant transformation, certain glyco-epitopes of MUC1, such as Tn-antigen, TF-antigen and their sialylated forms become exposed. The role of these glycan structures in tumor biology is unknown, but their presence is known to correlate with poor prognosis in several adenocarcinomas. We analyzed the potency of MUC1 containing Tn-antigens (MUC1-Tn) to target C-type lectins that function as carbohydrate recognition and uptake molecules on dendritic cells (DC). We identified the macrophage galactose type C-type lectin (MGL), expressed by both DC and macrophages, as the receptor for recognition and binding of MUC1-Tn. To validate the occurrence of MGL-MUC1 interactions in situ, we studied the binding of MGL to MUC1 in primary colon carcinoma tissue. Isolation of MUC1 out of colon carcinoma tissue showed strong binding activity to MGL. Interestingly, MGL binding to MUC1 was highly correlated to binding by the lectin Helix pomatia agglutinin (HPA), which is associated with poor prognosis in colorectal cancer. The detection of MGL positive cells in situ at the tumor site together with the modified glycosylation status of MUC1 to target MGL on DC suggests that MGL positive antigen presenting cells may play a role in tumor progression.

Objectives: The aim of the study was to assess long-term state and trait anxiety in cardiac surgical risk patients., Design: Thirty two patients with serum S100B>0.3 microg/l 48 hours after cardiac surgery with cardiopulmonary bypass were matched according to age, gender, type, date and length of surgery with 35 operated patients without elevated S100B. They completed Spielberger's Anxiety Inventory (STAI)., Results: Patients with elevated S100B reported more state anxiety and trait anxiety. S100B was an independent predictor of both state and trait anxiety when controlling for perioperative variables., Conclusions: Patients with elevated S100B reported more anxiety 3-6 years after cardiac surgery. A postoperative blood sample can identify risk patients and facilitate appropriate follow-up.

Perceived control has been found to be of significance for patients with psychiatric disorders and may be regarded as an aspect of empowerment. Moreover, a sense of control has been identified as important for occupational performance, both in empirical research and in occupational therapy theory. This study aimed at investigating factors that might be of importance for perceived control: sociodemographic, clinical, and well-being variables. Another aim was to investigate whether perceived control served as a mediator between clinical variables, in terms of psychopathology, and well-being variables, in terms of perceived health. Sociodemographic data were collected from 177 subjects, most of them with psychosis diagnoses. They were also assessed regarding perceived control (locus of control and self-mastery) and different aspects of health and well-being. The findings showed that both clinical and well-being variables were consistently related to both aspects of perceived control. Moreover, the roles of self-mastery and locus of control as mediators of perceived health were identified. The results also identified some important sociodemographic factors that might promote a sense of control and empowerment, mainly educational level and friends. This study provided detailed knowledge of the role of perceived control for well-being among people with mental disorders. Strategies for how occupational therapists may promote a sense of control in this group are discussed.

The functional properties of glycoproteins are strongly influenced by their profile of glycosylation, and changes in this profile are seen in malignancy. In mucin-type O-linked glycosylation these changes can result in the production of mucins such as MUC1, carrying shorter sialylated O-glycans, and with different site occupancy. Of the tumor-associated sialylated O-glycans, the disaccharide, sialyl-Tn (sialic acid alpha2,6GalNAc), is expressed by 30% of breast carcinomas and is the most tumor-specific. The ST6GalNAc-I glycosyltransferase, which can catalyze the transfer of sialic acid to GalNAc, shows a highly restricted pattern of expression in normal adult tissues, being largely limited to the gastrointestinal tract and absent in mammary gland. In breast carcinomas, however, a complete correlation between the expression of RNA-encoding ST6GalNAc-I and the expression of sialyl-Tn is evident, demonstrating that the expression of sialyl-Tn results from switching on expression of hST6GalNAc-I. Endogenous or exogenous expression of hST6GalNAc-I (but not ST6GalNAc-II) always results in the expression of sialyl-Tn. This ability to override core 1/core 2 pathways of O- linked glycosylation is explained by the localization of ST6GalNAc-I, which is found throughout the Golgi stacks. The development of a Chinese hamster ovary (CHO) cell line expressing MUC1 and ST6GalNAc-I allowed the large scale production of MUC1 carrying 83% sialyl-Tn O-glycans. The presence of ST6GalNAc-I in the CHO cells reduced the number of O-glycosylation sites occupied in MUC1, from an average of 4.3 to 3.8 per tandem repeat. The availability of large quantities of this MUC1 glycoform will allow the evaluation of its efficacy as an immunogen for immunotherapy of MUC1/STn-expressing tumors.

Tumors exploit several strategies to evade immune recognition, including the production of a large number of immunosuppressive factors, which leads to reduced numbers and impaired functions of dendritic cells (DCs) in the vicinity of tumors. We have investigated whether a mucin released by tumor cells could be involved in causing these immunomodulating effects on DCs. We used a recombinant purified form of the MUC1 glycoprotein, an epithelial associated mucin that is overexpressed, aberrantly glycosylated, and shed during cancer transformation. The O-glycosylation profile of the recombinant MUC1 glycoprotein (ST-MUC1) resembled that expressed by epithelial tumors in vivo, consisting of large numbers of sialylated core 1 (sialyl-T, ST) oligosaccharides. When cultured in the presence of ST-MUC1, human monocyte-derived DCs displayed a modified phenotype with decreased expression of costimulatory molecules (CD86, CD40), Ag-presenting molecules (DR and CD1d), and differentiation markers (CD83). In contrast, markers associated with an immature phenotype, CD1a and CD206 (mannose receptor), were increased. This effect was already evident at day 4 of DC culture and was dose dependent. The modified phenotype of DCs corresponded to an altered balance in IL-12/IL-10 cytokine production, with DC expressing an IL-10(high)IL-12(low) phenotype after exposure to ST-MUC1. These DCs were defective in their ability to induce immune responses in both allogeneic and autologous settings, as detected in proliferation and ELISPOT assays. The altered DC differentiation and Ag presentation function induced by the soluble sialylated tumor-associated mucin may represent a mechanism by which epithelial tumors can escape immunosurveillance.

This study investigated predictors of quality of life among persons with schizophrenia and other psychoses. On the basis of previous research, it was hypothesised that objective life circumstances, self-variables, psychopathology, activity level, satisfaction with daily activities, and satisfaction with medical care would be determinants of quality of life. 134 persons were investigated, and the analysis was based on Structural Equation Modelling (SEM). A model with two quality of life variables, General quality of life and Security, fitted the data best. A self-variable, Sense of self, and Satisfaction with daily activities, Psychopathology, and Satisfaction with medical care served as mediators and explained the variation in the quality of life variables. External to the mediators, and related to these, were Activity level, Educational level, and Independent living. In conclusion, a self-variable showed the strongest association with quality of life, but two aspects that should be feasible to influence in mental health care, daily activity and medical care, contributed to the subjects' self-rated quality of life. These results render a somewhat optimistic view on how to accomplish a better self-perceived quality of life among people with severe mental illness.

A recombinant mucin O-glycosylation reporter protein, containing 1.7 tandem repeats (TRs) from the transmembrane mucin MUC1, was constructed. The reporter protein, MUC1(1.7TR)-IgG2a, was produced in CHO-K1 cells to study the glycosylation of the MUC1 TR and the in vivo role of polypeptide-GalNAc-T4 glycosyltransferase. N-terminal sequencing of MUC1(1.7TR)-IgG2a showed that all five potential O-glycosylation sites within the TR were used, with an average density of 4.5 glycans per repeat. The least occupied site was Thr in the PDTR motif, where 75% of the molecules were glycosylated, compared to 88-97% at the other sites. This glycan density was confirmed by an alternative liquid chromatography-mass spectrometry (LC-MS) based approach. The O-linked oligosaccharides were released from MUC1(1.7TR)-IgG2a and analyzed by nano-LC-MS and LC-MS/MS. Four oligosaccharides were present, NeuAcalpha2-3Galbeta1-3GalNAcol, NeuAcalpha2-3Galbeta1-3(NeuAcalpha2-6)GalNAcol, Galbeta1-3(NeuAcalpha2-6)GalNAcol, and Galbeta1-3GalNAcol, the two first being most abundant. Coexpression of the human polypeptide-GalNAc-T4 transferase with MUC1(1.7TR)-IgG2a increased the glycan occupancy at Thr in PDTR, Ser in VTSA, and Ser in GSTA, supporting the function of GalNAc-T4 proposed from previous in vitro studies. The expression of GalNAc-T4 with a mutation in the first lectin domain (alpha) had no glycosylation effect on PDTR and GSTA but surprisingly gave a dominant negative effect with a decreased glycosylation to around 50% at the Ser in VTSA. The results show that introduction of glycosyltransferases can specifically alter the sites for O-glycosylation in vivo.

Background: The brain-derived protein S100B has been shown to be a useful marker of brain injury of different etiologies. Cognitive dysfunction after cardiac surgery using cardiopulmonary bypass has been reported to occur in up to 70% of patients. In this study we tried to evaluate S100B as a marker for cognitive dysfunction after coronary bypass surgery with cardiopulmonary bypass in a model where the inflow of S100B from shed mediastinal blood was corrected for., Methods: 56 patients scheduled for coronary artery bypass grafting underwent prospective neuropsychological testing. The test scores were standardized and an impairment index was constructed. S100B was sampled at the end of surgery, hourly for the first 6 hours, and then 8, 10, 15, 24 and 48 hours after surgery. None of the patients received autotransfusion., Results: In simple linear analysis, no significant relation was found between S100B levels and neuropsychological outcome. In a backwards stepwise regression analysis the three variables, S100B levels at the end of cardiopulmonary bypass, S100B levels 1 hour later and the age of the patients were found to explain part of the neuropsychological deterioration (r = 0.49, p < 0.005)., Conclusions: In this study we found that S100B levels 1 hour after surgery seem to be the most informative. Our attempt to control the increased levels of S100B caused by contamination from the surgical field did not yield different results. We conclude that the clinical value of S100B as a predictive measurement of postoperative cognitive dysfunction after cardiac surgery is limited.

A computerised test termed the Stroop Strategy Test, utilising the Stroop effect, is described. To assess the test's usefulness and discriminant power, it was given to three military groups adjudged on the basis of interview and a test of intelligence to differ in their qualifications (61 men of Level 1, 41 of Level 2, and 17 of Level 3, in descending order) and a group of 16 men imprisoned or put in detention school for violent behaviour. In a discriminant analysis in which the eight measures the test provided were included and the four groups were compared yielded a discriminant power of 52.6% for the group as a whole, highest (56%) for the military Level 1 group. The potential usefulness of the test is discussed.

The seasonal variations of some selected heavy metals (Cd, Cu, Pb and Zn) and principal anions in soil solutions were monitored as a function of distance from the road at two field sites in Sweden. During the winter, the conductivity, concentrations of dissolved sodium and chloride increased dramatically due to the application of deicing agents (i.e. NaCl). Due to ion exchange, the pH decreased one unit in the soil solutions, whereas the concentrations of total organic carbon decreased due to coagulation and/or sorption to stationary solids. The heavy metal concentrations increased during the winter, but through different mechanisms. Cadmium concentrations in the aqueous phase increased as a response to ion exchange, possibly also enhanced by the formation of chloride complexes. Similarly, the concentrations of zinc increased, due to ion exchange, with calcium and protons. The mechanisms of mobilisation for copper and lead were not that clear probably due to association with coagulated or sorbed organic matter in combination with colloid dispersion.

We examined multi-objective environmental management as applied to pursuing concurrent goals of water treatment, biodiversity and promotion of recreation in constructed wetlands. A case study of a wetland established to treat landfill leachate, increase biodiversity, and promote recreation was evaluated. The study showed that attempts to combine pollution management with activities promoting biodiversity or recreation are problematic in constructed wetlands. This could be because the typical single-objective focus of scientific research leads to contradictions when planning, implementing and assessing the multi-objective use of wetlands. In the specific case of wetland filters for landfill leachate treatment, biodiversity, and recreation, there is a need for further research that meet practical needs to secure positive outcomes.

Several roadside soil samples were collected at two field sites in Sweden. They were analysed for total elemental content (using both ICP-MS and XRF) and stable lead isotopes. Extraction with deicing salt solution and sequential extraction were performed in order to elucidate the potential mobility due to the use of deicing agents. The total concentrations of elements, especially lead, have decreased and lead is presently almost at background concentrations (15-51 ppm for surface samples). However, the isotopic signature indicates that old gasoline lead still is left at the site constructed prior to 1975. The field site constructed in 1992 showed, however, no 206Pb/207Pb ratio below 1.14. Only minor amounts were leached using deicing salt solutions; for lead only 0.29%, on average, was extracted indicating that the mobile fraction already was released. Sequential extraction indicated that lead mainly was associated with reducible (34.4%) and oxidisable (35.4%) fractions. Exchangable and acid soluble fractions contained 20.3% while 10.0% was found in the residual fraction. The salt extraction released, however, very low concentrations indicating that most in fraction 1 is acid soluble (e.g. carbonates). Tungsten was also found at high concentrations indicating a possible impact from studded tires. For tungsten the following composition was obtained: residual (48.0%) > oxidisable (47.6%) > reducible (3.3%) > exchangeable/acid soluble (1.1%). From the isotopic studies it was also suggested that the order for incorporating anthropogenic lead into soils is exchangeable/carbonates > (hydr)oxides > organic matter > residual. The multivariate technique principal component analysis (PCA) seems promising for evaluating large sequential extraction datasets.

Radon (222Rn) accumulation in water in relation to stable elements was studied for the purpose of determining factors influencing the transfer of 222Rn to and from water. In 72 groundwater samples, 222Rn and about 70 analytical parameters were analysed using radiometric and ICP-MS techniques. Using multivariate statistics (partial least squares), it was observed that 222Rn has a positive correlation with fluoride and uranium. The correlation with fluoride was further investigated by a laboratory time-scale experiment to measure the emanation of 222Rn from water as a function of fluoride, pH and carbonate. The transfer of 222Rn from water was measured by continuous monitoring in air in a closed loop set-up. It was observed that fluoride in water adhere or trap 222Rn preferably in acidic water (pH 3). It is suspected that natural physical processes (such as diffusion and microbubble phenomenon) are less effective to transport 222Rn in the presence of fluoride.

We have developed an expression system for the production of large quantities of recombinant MUC1 mucin in CHO-K1 (Chinese-hamster ovary K1) cells. The extracellular part of human MUC1, including 16 MUC1 tandem repeats, was produced as a fusion protein with murine IgG Fc, with an intervening enterokinase cleavage site for the removal of the Fc tail. Stable MUC1-IgG-producing CHO-K1 clones were generated and were found to secrete MUC1-IgG into the culture medium. After adaptation to suspension culture in protein-free medium in a bioreactor, the fusion protein was secreted in large quantities (100 mg/l per day) into the culture supernatant. From there, MUC1 could be purified to homogeneity using a two-step procedure including enterokinase cleavage and ion-exchange chromatography. Capillary liquid chromatography MS of released oligosaccharides from CHO-K1-produced MUC1 identified the main O-glycans as Galbeta1-3GalNAc (core 1) and mono- and di-sialylated core 1. The glycans occupied on average 4.3 of the five potential O-glycosylation sites in the tandem repeats, as determined by nano-liquid chromatography MS of partially deglycosylated Clostripain-digested protein. A very similar O-glycan profile and site occupancy was found in MUC1-IgG produced in the breast carcinoma cell line T47D, which has O-glycosylation typical for breast cancer. In contrast, MUC1-IgG produced in another breast cancer cell line, MCF-7, showed a more complex pattern with both core 1- and core 2-based O-glycans. This is the first reported production of large quantities of recombinant MUC1 with a breast cancer-like O-glycosylation that could be used for the immunotherapy of breast cancer.

The icosahedral protein scaffold (1.5MDa) generated by self-assembly of the catalytic domains of the dihydrolipoyl acetyltransferase core of the pyruvate dehydrogenase multienzyme complex from Bacillus stearothermophilus has been engineered to display 60 copies of one or more peptide epitopes on a single molecule (E2DISP). An E2DISP scaffold displaying pep23, a 15-residue B- and T-helper epitope from the reverse transcriptase of HIV-1, was able to induce a pep23-specific T-helper response in cell lines in vitro. The same scaffold displaying both pep23 and peptide RT2, a nine-residue CTL epitope from HIV-1 reverse transcriptase, was able to prime an RT2-specific CD8(+) T-cell response in human cell lines in vitro and in HLA-A2 transgenic mice in vivo. This was accompanied by a humoral antibody response specific for E2DISP-presented epitopes. Thus, the icosahedral acetyltransferase core constitutes a simple and flexible scaffold for multiple epitope display with access to both cellular and humoral immune response pathways.

The effects of an aquatic fulvic acid on the pH-dependent adsorption of Hg(II) and Cd(II) to particulate goethite (alpha-FeOOH) were studied in batch systems. The ionic medium consisted of 0.01 M HClO(4) and the total concentrations of mercury and cadmium were maintained at 10(-8) M with 203Hg and 109Cd as tracers. pH In the systems was varied in the range 3-10 by addition of HClO(4) and NaOH. All commercial chemicals were of analytical grade or better. An aquatic fulvic acid (20 ppm), previously isolated and characterised in detail, was used as a model for humic substances and its adsorption to goethite is included in this study. The adsorption of the fulvic acid (20 ppm) onto goethite decreased slowly from 90% at pH 3-7.5 to 10% at pH 10. In systems without fulvic acid the adsorption of mercury increased in a linear fashion from 10% at pH 3 to 70% at pH 10. In the presence of fulvic acid (20 ppm), the adsorption was almost quantitative in the intermediate pH range (pH 5-7), and exceeded 92% over the entire pH range. Thus, association between mercury and the fulvic acid enhanced adsorption in general although the largest impact was found at low pH. Adsorption of cadmium increased from nearly 0 to almost 100% at approximately pH 6. In the presence of fulvic acid, the adsorption increased below pH 7 and decreased above pH 7. The adsorption isotherm for mercury when the concentration was increased from 10(-8) to 1.8 x 10(-4) M showed a corresponding increase of K(d) (l/g) up to a total concentration at 10(-6) M. At higher mercury concentrations K(d) was lowered. In the presence of fulvic acid the corresponding relationship of K(d) was bi-modal, i.e. high values at low and intermediate concentrations of mercury. This behaviour suggests that in the absence of fulvic acid the adsorption follow the expected behaviour, i.e. adsorption sites with similar affinity for mercury. In the presence of fulvic acid, additional adsorption sites are available by the organic molecule (possibly sulfur groups) when it is associated to the goethite. The adsorption isotherm for cadmium indicates a lowering of K(d) at 10(-4) M. Cadmium had no competitive effect on mercury and vice versa. Zinc, however, affected the adsorption of cadmium but not the adsorption of mercury.

We have constructed and efficiently produced and purified a candidate vaccine against schistosomiasis consisting of a novel hybrid protein in which two dominant T- and B-cell epitopes from Schistosoma mansoni 28 kDa glutathione-S-transferase (Sm28GST) antigen (a.a 24-43 and 191-212) are fused to cholera toxin B subunit (CTB). Intranasal treatment of S. mansoni-infected mice with the hybrid protein, which similar to native CTB was assembled into receptor binding pentamers, significantly reduced total worm burden and liver egg counts due to the induction of Sm28GST-specific antibodies. Immunopathologic granuloma formation in the liver was also significantly suppressed and there was an almost complete suppression of delayed-type hypersensitivity reactions to both Sm28GST and to total soluble egg antigen in infected animals. The results suggest that this type of hybrid protein could be used as a combined anti-immunopathology and anti-infection vaccine against schistosomiasis.

Background: Long-term outcome in patients who suffered stroke after undergoing a cardiac operation has been investigated sparingly, but increased long-term mortality has been reported. S100B is a biochemical marker of brain cell ischemia and blood-brain barrier dysfunction. The aim of this investigation was to record the long-term mortality in consecutive patients undergoing cardiac operations and to explore whether increased concentrations of S100B in blood had a predictive value for mortality., Methods: Prospectively collected clinical variables, including S100B, in 767 patients who survived more than 30 days after a cardiac operation, were analyzed with actuarial survival analysis and 678 patients were analyzed with Cox multiple regression analysis., Results: Forty-nine patients (6.4%) were dead at follow-up (range, 18 to 42 months); 11.5% (88 of 767 patients) had elevated S100B 2 days after operation (range, 38 to 42 hours). The probability for death at follow-up was 0.239 if the S100B level was more than 0.3 microg/L, and 0.041 if it was less than 0.3 microg/L. The clinical variables independently associated with mortality were preoperative renal failure, preoperative low left ventricular ejection fraction, emergency operation, severe postoperative central nervous system complication, and elevated S100B values, which turned out to be the most powerful predictor., Conclusions: Even slightly elevated S100B values in blood 2 days after cardiac operation imply a bad prognosis for outcome, and especially so in combination with any central nervous system complication.

During 24 h, water samples were taken for determination of a number of key parameters in a water system containing high concentrations of FeII at circumneutral pH. None of the major constituents (Ca, Mg, Na, K and sulfate) showed diurnal variations, while dissolved oxygen and pH increased during the night. This increase could entirely be explained by the decrease in water temperature. However, the concentration of FeII slightly increased at constant concentration of total Fe during the night, opposite to earlier observations in other systems where the presence of FeII was shown to be controlled by photoreduction. Nocturnal peaks of FeII have also been observed in other systems with high iron concentrations, however, at acidic pH, but without obvious explanation. The mechanisms for this process therefore need further investigation.

Background: The study aimed to investigate patient and spouse perception of cognitive functioning 1 to 2 years after coronary artery bypass grafting., Methods: Seventy-six married patients who had undergone coronary artery bypass grafting were selected and sex- and age-matched with 75 concurrent married patients who had undergone percutaneous transluminal coronary angioplasty. Couples received a letter of explanation and then completed telephone interviews. Forty-seven questions assessed memory, concentration, general health, social functioning, and emotional state. Response choices were: improved, unchanged, or deteriorated function after coronary artery bypass grafting/percutaneous transluminal coronary angioplasty., Results: Patients who had undergone coronary artery bypass grafting did not differ in subjective ratings on any measure from patients who had undergone percutaneous transluminal coronary angioplasty. There were no differences between spouses in the respective groups; spouse ratings also did not differ from patient ratings. Only in memory function did patients and spouses report a postprocedural decline., Conclusions: No subjective differences were found in patients who had undergone either coronary artery bypass grafting or percutaneous transluminal coronary angioplasty. Spouse ratings agreed with each other and with patient ratings. Positive correlations were found between the questionnaire factors, suggesting that perceived health and well-being are associated with subjective cognition.

Purpose: To assess the occurrence and pattern of adverse drug reactions as a cause for acute hospital admission., Methods: In 681 randomly selected patients, acutely admitted to a clinic of internal medicine at a Swedish university hospital, information was collected from their medical records about current symptoms and use of drugs, previous diseases and the results of medical investigations and tests. In addition, a standardized interview according to a questionnaire was carried out. A group of experts in clinical pharmacology assessed the data obtained from the patients' case records and the results of the interviews, and then, according to WHO criteria, judged the probability that an adverse drug reaction could have caused or contributed to the actual admission to hospital., Results: Out of the 681 cases included, 94 (13.8%) had symptoms and signs that were judged as drug-related and that had caused or contributed to the admission. Eighty-two patients (12.0%) had altogether 99 symptoms that were classified as adverse drug reactions. Of these, 91% were type A reactions. The relationship between the medication and the reaction was judged certain in eight, probable in 17, and possible in 74 cases. The most common adverse drug reactions were cardiovascular (36.3%). Twelve patients (1.8%) had symptoms indicating intoxications., Conclusions: The prevalence of drug-related problems causing or contributing to admission to a clinic of internal medicine is high and is dominated by type A reactions, i.e. reactions in principle predictable and preventable. This implies a possibility to increase drug safety by preventive measures.

This study reports the Swedish construct validation of two translated attachment style scales. The factor structure of the attachment construct was investigated via exploratory and confirmatory factor analyses of attachment scores from 515 students of a Swedish university. Results supported the expected two-factor solution, but found a three-factor solution to be a viable alternative. In addition, the attachment scales were compared with the Big Five personality inventory (NEO-PI), using a sample of 87 Swedish students, and found to have expected correlation to this scale.

Objectives: This study was designed to investigate attitudes of general practitioners (GPs) and hospital physicians in Sweden towards spontaneous reporting of adverse drug reactions (ADRs)., Method: Two areas in the northern region of Sweden were selected for the study. A knowledge and attitude questionnaire followed by a reminder letter 2 weeks later was addressed to all GPs and hospital physicians in the study areas., Result: The total response rate from the study areas was 748 of the 1274 questionnaires sent out (58.7%). Of those who responded, 236 were GPs, 433 were hospital physicians and 79 had other positions. Of the responders, 252 stated that they had never reported any ADR and 488 that they had reported at least once in their career. Issues that came out as important in the decision to report or not to report were whether the reaction was considered well-known or not, the severity of the reaction, hesitance to report only on suspicion, lack of knowledge of existing rules, giving priority to other matters and lack of time to report ADRs. Only minor differences in these regards were observed between male and female physicians., Conclusion: Our investigation shows that the physicians in northern Sweden have a fairly good knowledge about the existing rules for reporting ADRs in Sweden. However, the attitudes leave room for considerable under-reporting due to matters related mainly to the medical impact of the reaction and of reporting it, but also to the scientific "paradox" of reporting only on suspicion and of course due to lack of time in the health care setting.

The use of UV/Vis spectroscopy in combination with partial least squares (PLS) regression for the simultaneous prediction of nitrate and non-purgeable organic carbon (NPOC) in groundwaters was evaluated. A model of high quality was obtained using first order derivative spectra in the range 200-300 nm. Inclusion of non-UV-absorbing constituents in the modeling procedure, i.e., chloride, sulfate, fluoride, total carbon (TC), inorganic carbon (IC), alkalinity, pH and conductivity was also evaluated. This model seemed to be useful for prediction of chloride, TC, IC, alkalinity and conductivity, while its ability to predict sulfate, fluoride and pH was poor. In conclusion, application of PLS regression, which requires neither filtration of samples nor addition of chemicals, is a promising alternative for fast interpretation of geochemical patterns of groundwater quality.

Background: S100beta has been suggested as a marker of brain damage after cardiac operation. The aim of this study was to characterize the early S100beta release in detail and relate it to neuropsychological outcome., Methods: Three groups of patients were investigated. All patients underwent coronary artery bypass surgery (CABG) with extracorporeal circulation. In group A, 110 patients had sampling of S100beta for the first 10 postoperative hours and also underwent neuropsychological testing. In group B, 14 patients were examined for the effect of autotransfusion on S100beta levels. Eight patients in group C had their intraoperative bleeding processed with a cell-saving device., Results: Group A had a heterogeneous release pattern with several rapid elevations in S100beta concentration. In group B, high concentrations of S100beta were found in the autotransfusion blood (range 0.2 to 210 microg/L) with a concurrent elevation of serum S100beta levels after transfusion of shed blood. In group C, high levels of S100beta were found in the blood from the surgical field (12.0+/-6.0 microg/L) and decreased (1.1+/-0.64 microg/L) after wash. Group C had significantly lower S100beta values at the end of cardiopulmonary bypass compared to group A (0.53+/-0.35 microg/L versus 2.40+/-1.5 microg/L). S100beta values were corrected for extracerebral contamination with a kinetic model. With this correction, an association was found between adverse neuropsychological outcome and S100beta release in group A (r = 0.39, p < 0.02)., Conclusions: A significant amount of S100beta is found both in the blood from the surgical field and in the shed mediastinal blood postoperatively. Infusion of this blood will result in infusion of S100beta into the blood and interfere in the interpretation of early systemic S100beta values.

In a series of 83 patients undergoing coronary artery bypass grafting for angina, perceived QOL (quality of life) was rated by the patients and their spouses, preoperatively and at two and 12 months postoperatively, using the SWED-QUAL instrument. One year after surgery, QOL had improved to a level which might be expected of a normal population comparable in age and gender distribution. Good correlation existed between patient and spouse ratings, especially on physical measures.

The closely related B-subunits of cholera toxin (CTB) and Escherichia coli heat-labile enterotoxin (LTB) both bind strongly to GM1 ganglioside receptors but LTB can also bind to additional glycolipids and glycoproteins. A number of mutant CT B-subunits were generated by substituting CTB amino acids with those at the corresponding positions in LTB. These were used to investigate the influence of specific residues on receptor-binding specificity. A mutated CTB protein containing the first 25 residues of LTB in combination with LTB residues at positions 94 and 95, bound to the same extent as native LTB to both delipidized rabbit intestinal cell membranes, complex glycosphingolipids (polyglycosylceramides) and neolactotetraosylceramide, but not to non-GM1 intestinal glycosphingolipids. In contrast, when LTB amino acid substitutions in the 1-25 region were combined with those in the 75-83 region, a binding as strong as that of LTB to intestinal glycosphingolipids was observed. In addition, a mutant LTB with a single Gly-33-->Asp substitution that completely lacked affinity for both GM1 and non-GM1 glycosphingolipids could still bind to receptors in the intestinal cell membranes and to polyglycosylceramides. We conclude that the extra, non-GM1 receptors for LTB consist of both sialylated and non-sialylated glycoconjugates, and that the binding to either class of receptors is influenced by different amino acid residues within the protein.

The non-toxic B-subunit of cholera toxin (CTB) is a powerful immunogen and has been investigated as a carrier for foreign peptide epitopes, with peptides genetically fused to either the N- or C terminus of CTB. In the present study, we have constructed a plasmid encoding a novel intrachain CTB fusion protein with a peptide epitope inserted into an internal region of CTB: eight amino acids (aa) in CTB (56-63) were substituted with a 10-aa peptide from the third variable (V3) loop of the HIV-1 envelope protein gp120. The resulting chimeric protein retained important functional characteristics of the native CTB including pentamerization and GM1 ganglioside receptor binding. The internal hybrid protein was also shown to be resistant to proteolytic degradation during production in Vibrio cholerae, whereas a terminal hybrid protein, where the same gp120-epitope was fused to the N terminus of CTB, was rapidly cleaved during culture. The inserted epitope, which is known to give rise to HIV-1 neutralizing Ab, could be detected with a V3 loop-specific monoclonal Ab when the chimeric protein was analyzed in ELISA and immunoblot, indicating that the epitope inserted at this site is presented on the surface of the protein. Consistent with these observations, immunization of mice with the CTB::HIV hybrid protein elicited a high titered serum Ab response to the CTB moiety and also, in some but not all animals, a detectable response to the inserted gp120 epitope.

A form of combination anaesthesia using ketamine, diazepam, alcuronium and nitrous oxide was used in 41 patients over 65 years requiring abdominal surgery. The patients were premedicated with droperidol 2.5-7.5 mg im. At induction the patients received diazepam 5 mg. ketamine 2 mg/kg and alcuronium 0.2 mg/kg. Anaesthesia was maintained with a continuous, steady injection of ketamine 2.5 mg/kg/h and nitrous oxide-oxygen with controlled ventilation. Four minutes before incision the patients received 1 ml of coded solution and at the end of anaesthesia the same solution, which contained either 5 mg/ml diazepam or its solvent only. There were no statistically significant differences between the two groups, i.e. patients receiving either 15 or 5 mg of diazepam. The incidence of bad dreams was 5 per cent, i.e. one patient in each group. Only one patient vomited and one had pronounced nausea in group D5. According to the anaesthesiologist's, the anaesthesia nurse's and the patient's subjective evaluations this type of combination anaesthesia was found to be highly acceptable. Despite there being no statistically significant differences between the patients who received 5 + 5 + 5 mg of diazepam compared to those receiving 5 + 0 + 0 mg, the figures in results per se incline in favour of the use of 5 + 5 + 5 of diazepam.

A method was developed for the separation by thin-layer chromatography of 14C-labelled 3-methoxy, 4-hydroxyphenethylamine, 3-hydroxy, 4-methoxyphenethylamine and 3,4-dimethoxyphenethylamine (DMPEA) after incubation of dopamine with catechol-O-methyltransferase (COMT) in lysates of human red blood cells (RBC). 14 C-methyl-S-adenosyl-menthionine was used as the methyl donor. Total COMT activity with noradrenaline or dopamine as substrates, respectively, and the pattern of 14C-methylated metabolites of dopamine were measured in RBC of 47 schizophrenic patients and in 34 control subjects. There were no differences between patients and controls. DMPEA was not formed by RBC in schizophrenic patients (or in controls), a finding which argues against the "pnk spot"/DMPEA hypothesis of schizophrenia. The methods used seem suitable for studies of other human disorders where COMT might be involved.

Somatomedin levels in cerebrospinal fluid (CSF) were determined in patients with acromegaly, pituitary deficiency, prolactinoma, and Cushing's disease by radioimmunoassay (RIA) for insulin-like growth factor 1 (IGF-1) and for IGF-2 as well as a radioreceptor assay (RRA) with adult human brain plasma membranes and IGF-2 as ligand. The mean value of RIA-IGF-2 (31 +/- 1.6 ng/ml) predominated over that of RIA-IGF-1 (5.8 +/- 0.3 ng/ml), but 10 times higher levels were found by RRA-IGF-2. Patients with acromegaly were not found to have higher values than those with GH deficiency even after corrections were made for possible leakage across the blood-CSF barrier. No correlations were found between CSF somatomedin levels determined by different techniques and immunoreactive IGF-1 or GH in the peripheral circulation except for a positive correlation between CSF RIA-IGF-2 and serum IGF-1 in patients with acromegaly. These findings suggest that somatomedins in CSF consist primarily of IGF-2-like peptides which are derived from production within the central nervous system or pituitary gland rather than from transport across the blood-CSF barrier.

Transplantations were made of fetal pineal glands (crown-rump length, CRL, 19-30 mm) or pineal glands from adult male rats to the anterior chamber of the eye of the rat. Studies were performed with regard to the importance of the age of the donor animal (and thereby the degree of maturation and innervation of the gland to be transplanted) for the possible development of denervation supersensitivity. The transplants were cultured in a medium containing 14C-serotonin. Increased production of 14C-N-acetylserotonin (NAcS) was used as the main criterion for beta-adrenergic stimulation. 4 experimental groups were obtained by transplanting fetal or adult pineals to intact or sympathetically denervated eyes. In all 4 groups beta1-stimulation (KWD 2033 10(-6) M) increased 14C-NAcS formation. The response to beta-stimulation was significantly higher in denervated fetal pineal transplants than in innervated fetal transplants and thus demonstrating beta-receptor supersensitivity. It was concluded that a) the ability to respond to beta-adrenoreceptor stimulation with increased 14C-NAcS formation develops between the 18th and 20th day of gestation, b) transplants derived from fetal as well as from adult rats can respond to beta-adrenergic stimulation, c) this sensitivity also develops in oculo in transplants that at the time of transplantation lacked the capacity to increase their 14C-NAcS formation in response to treatment with beta-agonist, d) denervation supersensitivity occurs in fetal transplants that became mature in sympathetically denervated eyes.

Immature rat pineal grafts were transplanted bilaterally to the anterior eye chamber of adult male rats. The transplants matured and became sympathetically innervated from the host iris and synthesized 5-hydroxytryptamine as revealed by fluorescence histochemistry. Transplants were used to investigate whether the newly formed nerve terminals were functional and thus could induce a rhythm in pineal N-acetyltransferase (NAT) enzyme activity and hydroxyindole-O-methyl transferase (HIOMT) enzyme activity. The in situ pineal glands from the recipient animals exhibited NAT and HIOMT levels and diurnal variations of enzyme activities no different from control rats without transplants. Sympathetically innervated transplants showed lower NAT enzyme activity than the in situ pineals but did yield a highly significant increase in darkness NAT activity as compared to light NAT activity (20:1). Sympathetically denervated transplants showed a much smaller rise in darkness NAT enzyme activity as compared to light values (1.8:1) but the rhythm was still statistically significant (p less then 0.01). Sympathetically innervated transplants had a higher HIOMT activity in darkness than in light (2.7:1)9 The HIOMT activity of the sympathetically denervated grafts was invariably low. Protein contents of transplants were found to be significantly lower than in situ pineal protein content but failed to show a diurnal variation.

8-Methoxypsoralen (10(-4) M) added to the medium of rat pineal glands in organ culture induces a five-fold increase of 14C-labelled N-acetylserotonin and melatonin formation when serotonin is used as 14C-labelled precursor. Addition of d-amphetamine (10(-5) M) to pineal glands also results in an increase of N-acetylserotonin and melatonin formation. This increase is enhanced by the addition of 8-methoxypsoralen (10(-5) M). In pineal glands pre-incubated for 24 h 8-methoxypsoralen (10(-4) M) caused an increased production of N-acetylserotonin and melatonin. This indicates that the effect of 8-methoxypsoralen is mediated through a postsynaptic event and not by release of noradrenaline or blocked re-uptake of amines to nerve terminals in the pineal gland. Further studies of the clinical significance of the effect of psoralen on pineal gland metabolism seems warranted.