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Biomedical subjects

B Jansson

Publications and source records attributed to B Jansson.

At least 19 recordsLinked to original sources

Thomsen-Friedenreich oncofetal antigen in Schistosoma mansoni : localization and immunogenicity in experimental mouse infection.

Our preliminary observation, that sera from schistosomiasis patients react with carcinomas, raised the possibility of antigenic cross-reactivity. We here extend this observation to show that mice experimentally infected with Schistosoma mansoni react with human urothelial and transitional bladder carcinomas and also with a gastric carcinoma cell line, AGS. To identify cross-reacting epitopes, we looked for the expression of carcinoma markers in schistosome worms and eggs using monoclonal antibodies against tumour antigens MUC1, Tn and TF (also known as the oncofetal Thomsen-Friedenreich antigen or T antigen). Immunohistochemical staining showed that the TF-epitope is present in adult intravascular S. mansoni worms and eggs deposited in tissues of infected animals. The localization of TF-immuno-reactive material in schistosomes was seen at the parasite surface between male and female worms and around trapped eggs in the liver. This localization is consistent with the antigen being secreted. Mice experimentally infected with S. mansoni, developed circulating antibodies against the TF-epitope (identified as Gal(beta1-3) GalNAc-O-R) as seen in ELISA using TF-expressing asialoglycophorin (AGP) as antigen. The observed anti-TF response in S. mansoni-infected mice reflects the complexity of host-parasite interactions in this infection.

Animals↗

Polybrominated diphenyl ethers (PBDEs) and their methoxylated derivatives in pike from Swedish waters with emphasis on temporal trends, 1967-2000.

Temporal trends of five tetra- to hexabromodiphenyl ethers [BDE47, BDE99, BDE100, BDE153 and BDE154) and two methoxy-tetraBDEs [6-methoxy-2,2',4,4'- tetraBDE (6-MeO-BDE47) and 2'-methoxy-2,3',4,5'- tetraBDE (2'-MeO-BDE68)] in pike from Lake Bolmen for the years 1967-2000, are presented. All BDE congeners show increasing trends up to the mid-1980s (Sigma5PBDE from 60 to 1600 pg/g wet weight in 1989, i.e. a more than 25-fold increase), and then decrease or level off. The decreasing trends of PBDEs after the 1980s were considerably slower in the present study than was found in a study of an environmental matrix from the Baltic Proper covering the same time period. This difference suggests local sources near Lake Bolmen. The MeO-BDEs show initially decreasing concentrations, which for 6-MeO-BDE47 continues until the early 1990s. The concentrations of 6-MeO-BDE47 in herring from five locations along the Swedish coast increased from south to north in the Baltic Sea. No correlation between the concentrations of the BDE congeners and the MeO-BDEs was observed, indicating sources other than PBDEs for these compounds. The presence of MeO-BDEs in fish from lakes with different characteristics suggests a natural production not favoured by eutrophication, or dependent on sampling season and geographical location.

Animals↗

Methods for atom probe analysis of microgradients in functionally graded cemented carbides.

Methods to prepare needle-shaped specimens for atom probe field ion microscopy from near surface regions have been developed. The material used was a cemented carbide with a composition gradient towards the surface, but the method is equally applicable for other materials. The preparation technique involves dimple grinding, electropolishing and focused ion beam (FIB) milling. The use of FIB milling allows for specimen preparation of materials which due to the preferential etching of different phases are difficult to electropolish. The technique also allows for preparation of specimens at well defined depth from the sample surface, selection of phase to be analysed, and to sharpen and re-use already analysed specimens. Atom probe analyses of the near surface zone region in a gradient sintered WC-Ti(C,N)-TaC-Co cemented carbide are presented.

Journal Article↗

A prospective study of fatal occupational accidents -- relationship to sleeping difficulties and occupational factors.

Very little is known about the association between sleep and (fatal) occupational accidents. This study investigated this relationship using register data of self-rated sleep difficulties, together with occupational and demographic characteristics. The variables were related to subsequent occupational fatal accidents. A national sample of 47,860 individuals was selected at regular intervals over a period of 20 years, and interviewed over the phone on issues related to work and health. The responses were linked to the cause of death register (suicides excluded) and the data set was subjected to a (multivariate) Cox regression survival analysis. One hundred and sixty six fatal occupational accidents occurred, and the significant predictors were: male vs. female: relative risk (RR)=2.30 with a 95% confidence interval (CI) of 1.56-3.38; difficulties in sleeping (past 2 weeks): RR=1.89 with CI=1.22-2.94; and non-day work: RR=1.63 with CI=1.09-2.45. No significant effect was seen for age, socio-economic group, hectic work, overtime (>50 h per week), or physically strenuous work. It was concluded that self-reported disturbed sleep is a predictor of accidental death at work, in addition to non-day work and male gender.

Accidents, Occupational↗

Epilepsy and injury mortality in Sweden--the importance of changes in coding practice.

We analysed national mortality trends of injuries and poisoning in patients with epilepsy to establish the importance of changes in coding practice. Patients where epilepsy was a syndrome, either as an underlying or contributing cause-of-death at any time of life, throughout Sweden during 1975-1995 were included. All conditions mentioned on each death certificate were examined, and epilepsy and injury diagnoses were separated according to underlying, contributing or multiple cause-of-death. Annual mortality rates, case-fatality rates, and linear regression coefficients were computed. The most common underlying cause-of-death (UCD) was diseases of the circulatory system (34.4%) followed by epilepsy (31.7%). Injury and poisoning were coded as UCDs for 5.8% of the patients. Injury and poisoning as a contributory cause-of-death increased significantly, but not as an underlying cause during the study period. The proportion of each diagnostic group as an underlying cause decreased by 35% for epilepsy and 18% for injury from 1981 and onwards. These changes should be interpreted with caution since changes of coding practice are more likely to be the cause of these apparent changes. The most frequent specific external causes of injury deaths in epileptic patients were falls and drowning. Intracranial fatal injuries in connection with fall accidents predominated, especially among elderly persons. Deaths related to accidental poisoning were caused by the toxic effect of non-medicinal substances. Cause-of-death statistics from different countries must be interpreted with caution when making international comparisons. Both underlying and contributing cause-of-death statistics should be considered in analyses of mortality trends.

Adolescent↗

Work-related acute injuries from mandatory fitness training in the Swedish Police Force.

Acute injuries in the Swedish Police Force from on-duty fitness training were selected retrospectively from the Information System of Occupational Injuries (ISA) at the National Board of Occupational Safety and Health and, if having caused a sick-leave exceeding 2 weeks, to the Labour Market Insurance (AMF Insurance). The latter included injuries from 1995 only. During the seven-year period 1992 to 1998, 920 injuries (80 % in males) from fitness training involving police officers were reported to the ISA-register. The total incidence was 1.6 for policemen per 10 000 hours of exposure and 2.2 for policewomen, which is 1.4 times higher than in men. Around 50 % of the injuries occurred in team and contact sports, with a slightly higher percentage for males, 54 % versus 49 % in females. The percentage of injuries from self-defense training was twice as high as in women than in men, 29 % versus 15 %. In 1995, 42 of the 72 injuries in males and 6 of the 21 injuries in females caused more than 14 days of sick-leave and were announced to the Occupational No Fault Liability Insurance. The major part, 32 of 48 injuries, came from team or contact sports (mainly floorball and soccer). Six policemen incurred injuries that were classified with a degree of disability ranging from 2 to 5 %. The total cost for medical treatment and production loss for the 48 injuries was Euro 248 448 and 99 336, respectively. Team and contact sports accounted for 89 % of the costs and 77 % of the production loss through sick-leave.

Accidents, Occupational↗

Visualization of in vivo olfactory uptake and transfer using fluorescein dextran.

Nasal administration of a 3 kDa fluorescein dextran (FD3) solution to rats resulted in transcellular absorption across the olfactory epithelium and transfer to the olfactory bulb within 15 min. After entering the lamina propria, FD3 was transferred in the connective tissue surrounding the olfactory nerve bundles to the olfactory bulb of the brain. More FD3 was absorbed across the olfactory epithelium than across the respiratory epithelium and to the nasal associated lymphoid tissue. Further, the amount of FD3 crossing the olfactory epithelium was region-dependent, with higher amounts absorbed in the turbinates than in the nasal septum. Plastic embedding and sectioning followed by fluorescence microscopy, enabled simultaneous visualization of FD3 in the mucosa and olfactory bulb, as well as the opportunity to store the tissue blocks for a prolonged period of time.

Administration, Intranasal↗

Levels of dopamine in blood and brain following nasal administration to rats.

The aim of this study was to investigate the levels of [(3)H]dopamine in blood, the cerebrospinal fluid (CSF) and brain tissue samples in rats and to find out whether the drug is transferred along the olfactory pathway to the central nervous system following nasal administration. [(3)H]Dopamine (50 microCi) was given to male Sprague-Dawley rats either intravenously or nasally to the right nostril. For the absorption study, blood samples were withdrawn from the carotid artery. The CSF samples were taken by cisternal puncture and then brain tissue samples were excised. The presence of unchanged dopamine in the samples was ascertained using thin layer chromatography (TLC). The radioactivity in the samples was measured using liquid scintillation. The greatest amount of the total radioactivity absorbed from the nasal mucosa into the systemic circulation was observed at the first sampling point 15 min after administration. The bioavailability of the total radioactivity was 68+/-30%. The uptake of [(3)H]dopamine in the brain was significantly higher 30 min after nasal administration than after intravenous administration (P<0.01). TLC data showed that approximately 59%, 14% and 68% of the radioactivity in the olfactory bulb, CSF and olfactory mucosa, respectively, coeluted with dopamine. In conclusion, these results show that unchanged dopamine is transferred into the olfactory bulb via the olfactory pathway in rats.

Administration, Intranasal↗

Tanning habits and sunburn in a Swedish population age 13-50 years.

As part of a skin cancer control programme, we studied the occurrence of self-reported outdoor tanning, sunbed use and ultraviolet (UV)-induced erythema in an urban area. A cross-sectional questionnaire study of 6000 adolescents aged 13-19 years, and 4000 adults aged 20-50 years was applied. Non-response was analysed for outdoor tanning and sunbed use. Results, in general, did not differ between responders and non-responders. Females aged 17-29 years tanned outdoors most frequently. Sunbed use and related erythema was twice as common in young females. In males, outdoor tanning was not age-related. In the past 12 months, 55% reported sunburn and/or burn from sunbed use, one-third were burned in Sweden, one-quarter on sunny resorts abroad. Sunburn occurs frequently. Compliance with recommendations for sunbed use is poor, especially among adolescents and young adults. To reduce the occurrence of erythema, the influence of risk settings upon behaviours is a critical issue for exploration.

Adolescent↗

Correlative fine specificity of several Thomsen-Friedenreich disaccharide-binding proteins with an effect on tumor cell proliferation.

Epithelial cancer cells show increased cell surface expression of mucin antigens with aberrant O-glycosylation, notably type I core (Galbeta1-3GalNAcalpha), termed Thomsen-Friedenreich disaccharide (TFD), a chemically well-defined carbohydrate antigen with a proven link to malignancy. Several TFD-binding proteins influence the proliferation of cells to which they bind. We studied the fine specificity of TFD-binding proteins and its relationship with epithelial tumor cell proliferation. Competitive binding assays against asialoglycophorin showed that Agaricus bisporus lectin (ABL) and human anti-TFD monoclonal antibody (mAb) TF1 were inhibited only by TFD and its alpha-derivatives. Peanut agglutinin (PNA), mAb TF2, and mAb TF5 were also inhibited by other carbohydrates such as lacto-N-biose (Galbeta1-3GlcNAc), lactose, and (Mealpha or beta) Gal, indicating lower recognition of the axial C-4 hydroxyl group position of GalNAc from TFD, and the major relevance of the terminal Gal on interaction of these three TFD-binding proteins. In the direct glycolipid-binding assay, ABL bound mostly to alpha-anomeric TFD-bearing glycolipids, whereas PNA interacted mainly with beta-linked TFD. Of the three anti-TFD mAbs analyzed, all bound N5b (terminal beta-TFD), but only TF2 interacted with N6 (terminal alpha-TFD). These findings indicate that TFD-binding proteins that stimulate the proliferation of epithelial tumor cell lines recognize mainly a terminal beta-Gal region of beta-linked TFD, whereas ABL, which inhibits the proliferation of these tumor cells, binds mainly to subterminal GalNAc of alpha-anomeric TFD.

Animals↗

A central core structure in an antibody variable domain determines antigen specificity.

Antibody binding sites provide an adaptable surface capable of interacting with essentially any molecular target. Using CDR shuffling, residues important for the assembly of mucin-1 specific paratopes were defined by random recombination of the complementarity determining regions derived from a set of mucin-1 specific clones, previously selected from an antibody fragment library. It was found that positions 33 and 50 in the heavy chain and 32, 34, 90, 91 and 96 in the light chain were conserved in many of the clones. These particular residues seem to be located centrally in the binding site as indicated by a structure model analysis. The importance of several of these conserved residues was supported by their presence in a mouse monoclonal antibody with a known structure and the same epitope specificity. Several of these corresponding residues in the mouse monoclonal antibody are known to interact with the antigen. In conclusion, critical residues important for maintaining a human antigen-specific binding site during the process of in vitro antibody evolution were defined. Furthermore, an explanation for the observed restricted germline gene usage in certain antibody responses against protein epitopes is provided.

Animals↗

Ecology. The value of nature and the nature of value.

Ecosystems are capital assets: When properly managed, they yield a flow of vital goods and services. Relative to other forms of capital, however, ecosystems are poorly understood, scarcely monitored, and--in many important cases--undergoing rapid degradation. The process of economic valuation could greatly improve stewardship. This potential is now being realized with innovative financial instruments and institutional arrangements.

Australia↗

Transfer of dopamine in the olfactory pathway following nasal administration in mice.

PURPOSE: The aim of the study was to investigate whether dopamine is transferred along the olfactory pathway to the brain following nasal administration to mice. METHODS: [3H]-Dopamine was administered nasally or intravenously to female mice. Brain tissue samples were excised and the radioactive content was measured. The precise localisation of dopamine radioactivity in the brain was studied using autoradiography. The presence of dopamine or its metabolites in the olfactory bulb and mucosa was ascertained using thin layer chromatography (TLC). RESULTS: After administration of [3H]-dopamine into the right nostril, the amount of dopamine in the right bulb increased with time until. after 4 h, it was 27 times higher than in the left bulb. Among the other brain tissue samples, significantly higher amount of radioactivity was detected in the lateral olfactory tract. Radioactivity in the right olfactory bulb was shown by autoradiography to be selectively located in the peripheral layers 1 to 4 h after administration. Selective uptake of radioactivity was not seen in other regions of the brain. TLC data indicated that approximately 75% and 10% of the radioactivity in the olfactory bulb and mucosa, respectively, coeluted with dopamine. CONCLUSIONS: The results indicate that unchanged dopamine is transferred into the olfactory bulb following nasal administration of [3H]-dopamine.

Administration, Intranasal↗

Recombining germline-derived CDR sequences for creating diverse single-framework antibody libraries.

We constructed a single-chain Fv antibody library that permits human complementarity-determining region (CDR) gene fragments of any germline to be incorporated combinatorially into the appropriate positions of the variable-region frameworks VH-DP47 and VL-DPL3. A library of 2 x 109 independent transformants was screened against haptens, peptides, carbohydrates, and proteins, and the selected antibody fragments exhibited dissociation constants in the subnanomolar range. The antibody genes in this library were built on a single master framework into which diverse CDRs were allowed to recombine. These CDRs were sampled from in vivo-processed gene sequences, thus potentially optimizing the levels of correctly folded and functional molecules, and resulting in a molecule exhibiting a lower computed immunogenicity compared to naive immunoglobulins. Using the modularized assembly process to incorporate foreign sequences into an immunoglobulin scaffold, it is possible to vary as many as six CDRs at the same time, creating genetic and functional variation in antibody molecules.

Germ-Line Mutation↗

Global analysis of transcription kinetics during competence development in Streptococcus pneumoniae using high density DNA arrays.

The kinetics of global changes in transcription patterns during competence development in Streptococcus pneumoniae was analysed with high-density arrays. Four thousand three hundred and one clones of a S. pneumoniae library, covering almost the entire genome, were amplified by PCR and gridded at high density onto nylon membranes. Competence was induced by the addition of CSP (competence stimulating peptide) to S. pneumoniae cultures grown to the early exponential phase. RNA was extracted from samples at 5 min intervals (for a period of 30 min) after the addition of CSP. Radiolabelled cDNA was generated from isolated total RNA by random priming and the probes were hybridized to identical high density arrays. Genes whose transcription was induced or repressed during competence were identified. Most of the genes previously known to be competence induced were detected together with several novel genes that all displayed the characteristic transient kinetics of competence-induced genes. Among the newly identified genes many have suggested functions compatible with roles in genetic transformation. Some of them may represent new members of the early or late competence regulons showing competence specific consensus sequences in their promoter regions. Northern experiments and mutational analysis were used to confirm some of the results.

Base Sequence↗

Perceived future in chronic pain: the relationship between outlook on future and empirically derived psychological patient profiles.

Perceived (subjective) future has been found to be a significant factor in explaining the relationship between pain and pain-related distress. The present study is based on the assumption that chronic pain patients with the three psychological profiles introduced by Turk and Rudy in 1988 could also be found in a sample of chronic pain patients and if so, these profiles have different perspectives on the future. The Multidimensional Pain Inventory (MPI) and The Future Scale were used to collect data from 569 patients with heterogeneous non-malignant chronic pain. A cluster analysis was conducted, where the resulting clusters closely resembled the profiles labelled by Turk and Rudy as 'dysfunctional', 'interpersonally distressed' and 'adaptive coper'. The results indicated that patients with adaptive coper profile have a more positive perception, while those with an interpersonally distressed profile have a more negative perception of the future. With an increased duration of pain, the proportion of the adaptive coper category decreased linearly, while an opposite trend was noted for the interpersonally distressed category. These results may better enable profiled psychological interventions in clinical pain treatment, e.g. by providing patients with therapies focused on positive future orientation, resulting in increased motivation for health-seeking behaviour and better abilities to cope with pain.

Adaptation, Psychological↗

How to act--implementing health and safety promotion in organizations.

This interdisciplinary review focuses on strategies for implementing health and safety promotion activities in organizations. Theories are summarized in a checklist and illustrated by some practical examples from Sweden and abroad. The points illustrated appear obvious and logical, but they are seldom applied in practise.

Accident Prevention↗

Pharmacokinetics and safety of single oral doses of sirolimus (rapamycin) in healthy male volunteers.

A phase I study was conducted to determine the pharmacokinetics, safety, and tolerability of sirolimus, a new immunosuppressive drug, in 45 healthy men between 19 and 36 years of age. Nine subjects in each group were randomly assigned to receive single oral doses of either sirolimus (n = 6) or placebo (n = 3) in group I (0.3 mg/m2), group II (1 mg/m2), group III (3 mg/m2), group IV (5 mg/m2) and group V (8 mg/m2). No serious adverse events occurred during the study. Twenty-eight of the 45 volunteers (62%) reported an adverse event; 19 of 30 (63%) were in the sirolimus group and 9 of 15 (60%) were in the placebo group (ns). Asthenia was the most common adverse event, occurring in 7 of 30 (23%) in the sirolimus group compared with 6 of 15 (40%) in the placebo group (ns). Absorption occurred within 1 hour in all volunteers. Whole blood peak concentration and area under the concentration-time curve increased proportionally with dose. Mean (+/- SD) whole blood terminal disposition half-life (t1/2), apparent oral dose clearance (Cl/F), and volume of distribution (Vss/F) were 82 +/- 12 hours, 278 +/- 117 mL/h x kg and 23 +/- 10 L/kg, respectively. Distribution of sirolimus into formed blood elements was extensive, with a mean whole blood-to-plasma ratio of 36. Single oral doses of sirolimus (0.3 to 8 mg/m2) solution were well tolerated in healthy male volunteers.

Administration, Oral↗