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Biomedical subjects

A Hedin

Publications and source records attributed to A Hedin.

At least 19 recordsLinked to original sources
PubMed1991

Effects on driving performance of visual field defects: a driving simulator study.

To elucidate the possible traffic safety risks induced by visual field defects, a method was developed based on a driving simulator. The capacity to detect stimuli of different sizes appearing in 24 different positions on the screen in front of the driver was measured. Two groups of normal subjects and a number of subjects with different visual field defects were studied. In the groups of normals, the median reaction times were fairly homogenous. There was a slight difference between central and peripheral stimuli, which was somewhat larger for the older subjects. Among the subjects with field defects, the individual variations were very dominant. Very few of these showed a capacity to compensate for their deficiency. In order to gain insight into possible compensatory mechanisms of these persons, eye movement recordings were made. The results indicate that the visual search pattern may be of importance in this respect. Some comparisons with respect to detection capacity were also made with one-eyed subjects and with optically generated field restrictions (spectacles and spectacle frames).

Adult↗
PubMed1991

Radioimmunolocalization of human colonic cancer xenografts; aspects of extensive purification of monoclonal anti-CEA-antibodies.

Tumour-to-normal tissue ratios of i.p. injected 125I-labelled monoclonal antibodies (MAbs), reacting with CEA were determined in nude rats xenografted with human colonic cancer cells (LS 174 T). Two MAbs, I-38S1 and II-16, reactive with the GOLD 1-epitope on CEA were tested. MAb I-38S1 was also tested after additional purification using anion exchange chromatography (thereafter named AEC 38). In the external activity measurements, MAb AEC 38 showed significantly better tumour-to-liver ratios than did MAb II-16 on all 4 days after injection. MAb I-38S1 gave intermediate ratios but was significantly better than II-16 only on day 3. The mean tumour-to-blood ratios were 3.0, 2.6 and 1.5 and the mean tumour-to-liver ratios were 6.6, 4.8 and 3.5 for MAbs AEC 38, I-38S1 and II-16 respectively. Gamma camera registrations in 3 animals on 4 days showed good imaging properties for all three MAbs and the patterns of tissue uptake were consistent with those seen in the external measurements. Furthermore, histopathological and immunohistochemical determinations were performed, showing that MAb II-16 gave about the same spatial binding as the previously analysed MAb I-38S1. The results indicate that additional purification of MAbs using anion exchange chromatography may potentiate tumour uptake in this model.

Carcinoembryonic Antigen↗
PubMed1990

An immunoassay for histamine based on monoclonal antibodies.

Monoclonal antibodies with high specificity for histamine as well as for 1-methylhistamine were obtained after immunization of mice with a conjugate where the histamine was coupled via its ring 1-nitrogen to dog serum albumin. An immunoassay was developed for the quantitation of histamine release from basophils and 1-methylhistamine release from mast cells after provocation. The test method is based on competitive inhibition between histamine and a labelled histamine conjugate for the antigen binding sites of the antibodies. The separation step is performed by the addition of solid phase bound anti-mouse subclass specific antibodies. The sensitivity of the assay is 2 micrograms/l for histamine and 0.1 micrograms/l for 1-methylhistamine. No cross-reactivity was obtained with other metabolites of histamine or with histidine. Serotonin and dopamine were detectable, but only in doses (mg/l) well above the normal concentration found in the circulation. The immunoassay has been evaluated for its capacity to measure histamine release in vitro. A good correlation with the conventional fluorometric assay was obtained when histamine released from allergen stimulated leucocytes from allergic patients was tested. Urinary samples from patients undergoing hyposensitization showed a mean excretion of 1-methylhistamine at a level of 131 mumol MeHi/mol creatinine. The release of histamine and 1-methylhistamine in vivo was examined in plasma samples taken during a bronchial provocation test. A significant elevation above the basal analyte level occurred ten minutes after provocation.

Animals↗
PubMed1990

Tumor specificity of monoclonal antibodies to carcinoembryonic antigen. Immunohistochemical analysis.

The tumor specificity of twelve different monoclonal antibodies (Mabs) against carcinoembryonic antigen (CEA) was assessed by immunohistochemistry. The Mabs had previously been classified into three specificity groups (I-III) on the basis of their reactivity with purified CEA-related antigens by ELISA. Mabs belonging to specificity group III (n = 4) did not cross-react with any CEA-related antigen, including normal cross-reactive antigen of 160 kD molecular weight (NCA-160 = meconium antigen). All Mabs, except one, gave positive immunohistochemical staining of 75-100% of individual tissue samples of colorectal carcinomas and gastric adenocarcinomas. However, when tested against different normal adult tissues, the Mabs displayed marked differences in reactivity. Group III Mabs stained normal colon epithelium, but not parenchymal cells in other organs or, with one exception, cells belonging to the granulocyte and/or macrophage series. Group I and II Mabs, in contrast, stained parenchymal cells in normal colon, submandibular salivary gland, placenta, and pancreas (group I Mab only). They also stained infiltrating and circulating granulocytes and/or macrophages. Lack of cross-reactivity with NCA-160 is the single-best criterion for selecting anti-CEA Mabs with a high degree of tumor specificity. To ensure tumor specificity, CEA-positive, NCA-160-negative Mabs should be checked by immunohistochemistry against cryostat sections of colorectal carcinoma, normal pancreas, submandibular salivary gland, spleen, and liver and for reactivity against circulating granulocytes.

Antibodies, Monoclonal↗
PubMed1989

Laser-induced desorption of proteins.

Laser-induced desorption mass spectrometry has been applied to a number of proteins in the mass range 5000-150,000 u. The beam from an excimer-laser-pumped dye-laser at 266 nm has been focused to a spot of about 50 microns in diameter with irradiances in the 10(7) W/cm2 region. A linear time-of-flight mass spectrometer has been used for mass spectrometric measurements, where positive and negative secondary ions of large proteins have been studied. The effect of different experimental parameters on the protein ion-signal intensities are discussed.

Lasers↗
PubMed1989

Homogeneous penetration but heterogeneous binding of antibodies to carcinoembryonic antigen in human colon carcinoma HT-29 spheroids.

The monoclonal antibodies 38S1, directed against the carcinoembryonic antigen (CEA), were tested for penetration and binding in human colon carcinoma HT-29 spheroids. Penetration was studied with a method which has not previously been used in immunological investigations. The method, which allows unbound substances to be visualized, is based on freeze drying, vapour fixation, dry sectioning and dry autoradiography. The antibodies penetrated easily and all parts of the HT-29 spheroids seemed to be reached within 15 min. The penetration was even faster than in control glioma U-118MG spheroids that did not express CEA. Binding of the 38S1 antibodies was demonstrated after processing with conventional histology and autoradiography. The binding in the HT-29 spheroids was, after a 1-h incubation period, extremely heterogeneous and occurred mainly in the peripheral parts. More cells were binding the antibodies after 8-h and 32-h incubations and these cells were arranged in peripheral clusters. No binding at all was seen in the CEA-negative glioma spheroids. The distribution of CEA antigens in monolayers and in frozen sections of spheroids of HT-29 cells was analysed with immunohistochemical staining using polyclonal CEA antibodies. The CEA antigens were heterogeneously distributed in both spheroids and monolayers and were as heterogenous as the binding of the monoclonal antibodies in the living spheroids. Thus, the heterogeneous binding in the living spheroids was not due to penetration barriers, but instead to the heterogeneity in the CEA antigen expression.

Adenocarcinoma↗
PubMed1988

In vitro studies of the biological effects of cigarette smoke condensate. III. Induction of SCE by some phenolic and related constituents derived from cigarette smoke. A study of structure-activity relationships.

Since our earlier studies of 23 individual weakly acidic constituents of cigarette smoke indicated that benzenes having vicinal oxygenation or a conjugated double bond induce sister-chromatid exchanges (SCE), we have now selected and examined a complementary set of 27 smoke constituents for their SCE-inducing properties. Of the 50 compounds tested in all, 23 were found to induce SCE, and these include all benzaldehydes but one and the majority of the compounds having a conjugated carbon-carbon double bond as well as several of the guaiacols. These groups of active compounds comprise important flavourants such as vanillin, ethylvanillin, isoeugenol and guaiacol. The structure-activity relationships encountered here may be useful in predicting the SCE-inducing activity of related compounds.

Benzaldehydes↗
PubMed1988

Eyelid surgery in dysthyroid ophthalmopathy.

Dysthyroid ophthalmopathy often gives rise to functional and cosmetic problems due to eyelid retraction. There are several causes of this state which are usually most obvious in the upper lid. Surgery should be delayed until the condition is stable and other operations have been done. A number of operative procedures have been used. In the upper eyelid, the traction of the Müller muscle and, most often, the levator is released; in the lower eyelid, the retractors are recessed or excised. Spacers have been used especially in the lower lid. The retractors can be reached either through the skin or the conjunctiva. Both methods give good results. In the upper lid, the risk of damaging other structures is lower with a skin incision; in the lower lid the conjunctival incision gives easier access to the tissues. The complications most frequently seen are over- or undercorrection both of which may necessitate a reoperation.

Autoimmune Diseases↗
PubMed1987

An experimental model for pharmacokinetic studies of monoclonal antibodies in human colonic cancer.

An experimental model consisting of athymic rats carrying human colonic tumours from cell line LS 174T in both hind legs was used. 125I-labelled anti-carcinoembryonic antigen (anti-CEA) monoclonal antibodies were injected intra-arterially (i.a.), either alone (21 rats) or together with degradable starch microspheres (6 rats). As a control, an irrelevant antibody was injected i.a., alone (6 rats) or together with microspheres (3 rats). An intra-arterial injection was given on the side bearing one tumour in each rat, while the contralateral tumour served as an 'intravenous' control. The rats were submitted to external gamma measurements daily for four days. On the fourth day they were killed and pieces from the tumours and from various organs were examined by in vitro measurements. The results indicate strong expression of CEA in LS 174T cells grafted to athymic rats. No lasting enhancement of the tumour uptake was achieved by intra-arterial injection of antibodies as compared with the control tumours.

Animals↗
PubMed1987

Enhanced uptake of intra-arterially injected anti-CEA monoclonal antibodies in human colonic cancer after mannitol infusion in an experimental model.

In a previous report athymic rats carrying transplanted human colonic tumours from cell line LS 174T in both hind legs were injected intra-arterially (i.a.) with 125I-labelled anti-carcinoembryonic (anti-CEA) monoclonal antibodies. The i.a. injection was given on one side bearing a tumour in each rat, while the contralateral tumour served as an 'intravenous' control. In the same experimental model and treated in the same way, 10 rats were injected i.a. with anti-CEA monoclonal antibodies after an i.a. mannitol infusion. In both groups of rats external gamma measurements were performed daily for four days. On the fourth day the rats were killed and pieces of the tumours and of various organs were weighed and the activity was determined with a gamma-counter. The tumour uptake of antibodies was significantly enhanced after mannitol infusion.

Animals↗
PubMed1986

Epitope specificity and cross-reactivity pattern of a large series of monoclonal antibodies to carcinoembryonic antigen.

Monoclonal antibodies (MAbs) were produced against purified carcinoembryonic antigen (CEA) from liver metastases of colo-rectal and lung adenocarcinoma. Three and eight anti-CEA MAbs from the two groups were analyzed in detail. All antibodies were IgG1. With one exception they recognized epitopes present on all eight individual CEA preparations investigated irrespective of whether they were from colo-rectal or lung carcinoma. The exceptional MAb reacted with an epitope present on most but not all CEA preparations. With two, or possibly three, exceptions the MAbs recognized conformation dependent epitopes in the peptide moiety of CEA. One MAb reacted strongly with reduced and carboxymethylated CEA but only weakly with native CEA. Four MAbs appeared to be CEA-specific in that they did not react with any of the known CEA-cross-reactive substances including nonspecific cross-reactive antigen of 160,000 mol. wt (NCA-160). A total of nine different epitopes were detected in native CEA using this and our previous series [Hedin A., Hammarström S. and Larsson A. (1982) Molec. Immun. 19, 1641] of anti-CEA MAbs. With one exception practically all molecules (70-90%) in purified CEA preparations contained these epitopes.

Antibodies, Monoclonal↗
PubMed1986

In vitro studies of biological effects of cigarette smoke condensate. II. Induction of sister-chromatid exchanges in human lymphocytes by weakly acidic, semivolatile constituents.

Cigarette smoke condensate is known to enhance the frequency of sister-chromatid exchanges (SCE) in human lymphocytes in vitro and some of the activity has been found in the most volatile part of the particulate phase, the semivolatile fraction. In this study we have investigated the chemical composition and the SCE-inducing activity of the weakly acidic, semivolatile fraction of a cigarette smoke condensate. A number of individual weakly acidic compounds were also tested for their SCE-inducing effects. The weakly acidic fraction was separated by preparative gel chromatography into 11 subfractions (F1-F11). The chemical composition was determined by gas chromatography and gas chromatography-mass spectrometry. Measurements of the effects on SCE in human lymphocytes were used to evaluate the genotoxic effects. All fractions except F11 induced SCE in a dose-dependent way. The most active fraction was F4 which contained mainly alkyl-2-hydroxy-2-cyclopenten-1-ones. The individual compounds to be tested for induction of SCE were selected on the basis of their abundance in the weakly acidic subfractions and on the basis of their occurrence in the environment. Of 23 tested compounds, most of which were alkylphenols, 7 induced SCE, i.e., catechol, 2-(1-propenyl)phenol, cyclotene, maltol, isoeugenol, 2-methoxyphenol (guaiacol) and vanillin. Many of these are important flavor components that occur not only in tobacco and tobacco smoke but also in food, candies, beverages and perfumes.

Acids↗