[Must psychiatry sell its soul?].
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Biomedical subjects
Publications and source records attributed to B Jansson.
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Human monoclonal antibodies specific for tumour-associated Thomsen-Friedenreich (TF) [Gal(beta 1-3)GalNAc(alpha)-O-] and Tn [GalNAc(alpha)-O-] glycoproteins were prepared using peripheral blood lymphocytes from healthy blood donors. The B lymphocytes were either directly transformed with Epstein-Barr virus (EBV) or transformed after an in vitro stimulation period with synthetic glycoproteins. The EBV-transformed lymphocytes were subsequently fused with a mouse-human heteromyeloma to secure antibody production and stability. IgM antibodies exhibiting different patterns of specificity for synthetic TF and Tn antigens were obtained, including antibodies specific for the alpha and beta forms of different Gal(beta 1-3)GalNAc-O- and GalNAc-O- conjugates and antibodies agglutinating neuraminidase-treated erythrocytes. Several of the human monoclonal antibodies showed an increased binding to cultured carcinoma cells as compared to melanoma cells. This straightforward approach for the production of human monoclonal antibodies demonstrates the possibility of investigating the reactivity pattern of tumour-binding antibodies from peripheral blood lymphocytes. The binding patterns of these monoclonal antibodies show that healthy donors carry different fine specificities against synthetic TF/Tn antigens and that these antibodies react with different tumour cells.
Low body weight is a characteristic symptom of Parkinson's disease (PD), but the mechanism is unknown. To determine whether bulbar involvement is responsible for the weight loss, we compared the mean body weight (MBW), height, and body mass index (BMI) of 281 patients with PD and 86 patients with progressive supranuclear palsy (PSP). Although the patients with PSP had significantly worse dysphagia and dysarthria than the patients with PD, their MBW and BMI were not appreciably different. We conclude that bulbar dysfunction is not the reason for weight loss in PD.
Surface plasmon resonance, i.e. detection of changes in refractive index on a surface, was used in a biosensor to evaluate the dissociation/association rate and affinity constants of human monoclonal IgG and IgM antibodies and Fab fragments. The results showed that an observed difference in affinity constants between intact and fragmented IgG anti-tetanus antibody was related to approximately 10-fold differences in dissociation rate constants, since the association rate constants were in the same range, i.e. 2-3 x 10(5) (M-1 s-1). Affinity constants, as determined by conventional solid phase enzyme immunoassay, were substantially higher than the constants produced by the biosensor. Human monoclonal IgM anti-Tn alpha antibodies showed, furthermore, one order of magnitude higher association rate constants, as compared with the IgG antibodies, but since the dissociation rate constants were more than ten times higher, the resulting affinity constants of the anti-carbohydrate IgM antibodies were still somewhat lower than those of the IgG antibodies.
This study aimed to investigate the origin of the free cells in the lumen of the endolymphatic sac (ES). Activation of the cells was accomplished through osmotic induction using glycerol. The ES and the perisaccular tissue were analyzed with special reference to the activity of periaqueductal bone marrow cells after different time intervals following the injection of hyperosmotic agents. The results show that the perisaccular or periaqueductal bone marrow space may constitute a source of some of the free cells occurring in the ES. Osmotic challenging of the inner ear may cause activation of the periaqueductal bone marrow, initiating the locomotion and migration of cells (mostly monocytes, neutrophils and eosinophilic leukocytes) along bone marrow sinusoids that frequently anastomose with the ES vessels. The free cells show signs of transepithelial diapedesis and, in the lumen of the ES, cells may develop into phagocytes which initiate the ingestion and degradation of secreted macromolecular aggregates. It is thought that osmotic alterations in the inner ear may give rise to local changes in or around the ES, leading to the chemotactic attraction of bone marrow cells. The results verify the existence of a complex sugar/protein aggregate metabolism over the wall of the ES, which is linked to the turnover of free cells. The findings may indicate that ES macrophages are important in the regulation of inner ear fluid homeostasis.
A time sequence study was performed on experimental animals to investigate long-term effects of intravenously administered glycerol on the epithelial cell activity in the endolymphatic sac (ES) and on the ES volume. Fifteen to 60 min after systemic glycerol administration, the ES volume decreased. During this time, the ES lumen was often obliterated. Subsequently, the lumen dilated. Meanwhile, many light epithelial cells showed granules with floccular and/or lamellar contents. Concomitant deposition of floccular material into the luminal space suggested secretion of macromolecular substances, presumably from these transformed light cells. The number of granule-containing cells was significantly increased 2 h (p < 0.01) and 4 h (p < 0.01) after glycerol administration. The ES was significantly dilated after 4 h (p < 0.01) and 6 h (p < 0.05). Thus systemic alterations in osmotic pressure led to a reversible change in ES volume, with initial collapse followed by dilation and normalization after 8 h. The secretory response of the ES preceded the volume increase. A great variability in ES volume indicated high compliance of this organ system. A secretion/degradation system or turnover of osmotically active macromolecular complexes in the epithelial lining and ES lumen seems to be linked to the ability of the ES to hold fluid volumes within a wide range. This may serve as a micromechanical pressure-volume-regulating device for monitoring endolymph fluid homeostasis.
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Recent studies have shown that technetium 99m mercaptoacetyltriglycine (MAG-3) is a suitable replacement for iodine 131 or 123 hippurate in gamma-camera renography. Also, the determination of its clearance is of value, since it correlates well with that of hippurate and thus may be an indirect measure of renal plasma flow. In order to simplify the clearance method we developed formulas for the estimation of plasma clearance of MAG-3 based on a single plasma sample and compared them with the multiple sample method based on 7 plasma samples. The correlation to effective renal plasma flow (ERPF) (according to Tauxe's method, using iodine 123 hippurate), which ranged from 75 to 654 ml/min per 1.73 m2, was determined in these patients. Using the developed regression equations the error of estimate for the simplified clearance method was acceptably low (18-14 ml/min), when the single plasma sample was taken 44-64 min post-injection. Formulas for different sampling times at 44, 48, 52, 56, 60 and 64 min are given, and we recommend 60 min as optimal, with an error of estimate of 15.5 ml/min. The correlation between the MAG-3 clearances and ERPF was high (r = 0.90). Since normal values for MAG-3 clearance are not yet available, transformation to estimated ERPF values by the regression equation (ERPF = 1.86 x CMAG-3 + 4.6) could be of clinical value in order to compare it with the normal values for ERPF given in the literature.
Malignant melanoma is the most rapidly increasing tumor in Sweden. Sunburns in childhood are considered a major risk factor. In the spring of 1989, a health education program was therefore initiated in Stockholm County in cooperation with the local preschool authorities in the area. Lectures on malignant melanoma, hazards of sunburns in childhood, and the importance of sun awareness were arranged for the nursery school matrons in the preschool sector. Thirty-five of 42 authorities (83%) wanted a lecture for their nursery school matrons, whereas 17% of the authorities wanted to spread information on their own. Of 1,991 nursery schools, 1,783 (90%) took part in the information program. These, the Stockholm nonparticipants, and the rest of the country received written information from the Federation of Swedish Municipalities by initiative of the Department of Cancer Prevention. A questionnaire distributed to 574 randomly selected nursery schools in Stockholm county and to 100 in a reference area outside Stockholm showed that sun awareness was reported high in both places. Face-to-face information disseminated by an established organization was more effective in increasing sun awareness in the preschool sector than mailed information alone. In the areas where lectures were given, the message of sun awareness practice was passed on to nursery school staff and parents twice as effectively as in the reference area (p less than 0.01).
Hyaluronan (HA) 0.5, 1, 1.9 and 4% was instilled into the round window niche in mice. Six hours after the 1.9% HA and 4, 6 and 8 h after the 4% HA deposition there was a significant increase in the proportion of granule-containing light epithelial cells in the endolymphatic sac. This indicated an increase in secretory activity. This activity could be a response to lowered intralabyrinthine pressure due to the osmotic capacity of HA. Secretion of high molecular substances can serve to keep the sac lumen patent and/or to regulate labyrinthine volume and pressure.
The aim of this article is to provide politicians with alternative ways of reducing health care expenditures through injury prevention. One way to do this is to present examples of how rationalisation gains resulting from injury prevention can be calculated and how this can be used to influence the direction of health policy. The calculations in the example are based on an estimated incidence of 113 patients per 1,000 population for outpatients and the number of hospitalised patients reported in the patient statistics. The costs of medical and surgical treatment and care have been calculated with the aid of Karolinska Hospital's contract for care of patients from other counties. Based on experience from the Falköping project, the preventive effect has been estimated to be 28 per cent. The approach has also been reviewed according to eight key features of health policy analysis in order to demonstrate new ways of increasing communication. The calculations show that under ideal conditions 316 hospital beds in Stockholm county can be released for other purposes. A dialogue has been started with politicians and administrators for continued discussions in the respective counties. Experience shows that data for calculation of rationalisation gains can be obtained rapidly. For more detailed health economic analyses, a comprehensive injury surveillance system and more detailed patient statistics are necessary.
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A rapid and simple liquid chromatographic method for the isolation of toxic planar polychlorinated biphenyls from their formulations by electron donor-acceptor high-performance liquid chromatography using a 2-(1-pyrenyl)ethyldimethylsilylated silica column is described. The separation takes less than 15 min and a complete analysis, including quantitation by gas chromatography-mass spectrometry or gas chromatography with electron-capture detection, may be completed in 60 min. Retention data for 105 individual polychlorinated biphenyl congeners are presented and the retention behaviour, as well as the mechanisms of separation, are discussed.
Monoclonal antibodies (MAbs) were derived from rats immunized against allo- and syngeneic rat colon carcinomas. Screening was performed by immunohistochemistry modified for MAbs of the same species as the tissue used for frozen sections. From 2 fusions, several MAbs were found that bound to syngeneic tumor tissue but showed little or no staining of normal adult tissues. Another group of MAbs demonstrated an intracellular staining of tumor cells and staining of mucus and goblet cells in the distal 2/3 of the normal colon. A third group of MAbs showed staining of both tumor and normal colon tissue. Staining patterns were reproduced with 6 MAbs selected from the first 2 groups after purification and biotinylation. One MAb, 10B12, recognized an antigen expressed in 10/11 colon carcinomas, the lowest parts of colonic crypts, intracellularly in a subpopulation of pancreatic acinar cells and mucus in antrum. It was used for affinity purification of a high-molecular-weight antigen, to which 3 of the other rat MAbs also bound. This antigen was also bound by antibodies to blood group A and isogloboseries carbohydrate determinants. Competition with the labelled 10B12 MAb for binding to the purified antigen was demonstrated in sera of tumor-bearing and immune rats. Thus, this high-molecular-weight glycoprotein expressed both auto-antigenic, tumor-associated and tissue-type-restricted epitopes. The 10B12 MAb homogeneously stained the majority of colorectal carcinomas and the antigenic determinant was expressed on the cell surface of 12/13 tissue-cultured colon-carcinoma clones. Modulation of the cell-surface antigen phenotype by recombinant rat interferon-gamma markedly increased expression of this determinant.