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Biomedical subjects

M Isaksson

Publications and source records attributed to M Isaksson.

71 records · Page 4Linked to original sources

Quinine and quinidine photoproducts can be identical.

Quinine and its d-isomer quinidine can both cause contact allergy as well as photoallergy. Contact allergic cross-reactions between quinine and quinidine are uncommon. In allergic photosensitization the two isomers cross-react, suggesting the possibility that quinine and quinidine after UV exposure are converted to one or more common sensitizing photoproducts. Solutions of quinine and quinidine at 0.1% in ethanol 99.5% were exposed to UVA for 14 h (total dose 201.6 J/cm2). Using thin-layer chromatography, we identified 8 and 6 photoproducts from irradiated quinine and quinidine, respectively. Five of these photoproducts were seen in both chromatograms. An identical pattern with four photoproducts was found for both irradiated solutions when these were subjected to analysis in a high-performance liquid chromatography system. This study indicates that photoproducts from irradiated quinine and quinidine can be identical. This would explain the differences in the cross-reactivity pattern between contact and photocontact sensitization clinically.

Chromatography, High Pressure Liquid↗

Contact allergy to Duraphat.

Skin-sensitizing rosin is present in Duraphat, a fluoride varnish used all over the world. Two cases of hypersensitivity to Duraphat are presented: a dental nurse with dermatitis of the hand and a patient with allergic contact stomatitis.

Dermatitis, Allergic Contact↗

Insulin-like growth factor binding protein-1 from Hep G2 cells is potently inhibited by the truncated IGF-I analogue des-(1-3) IGF-I.

Des-(1-3) insulin-like growth factor-I (IGF-I) is an IGF analogue lacking aminoacid 1 to 3 which displays reduced binding to insulin-like growth factor binding protein-1 (IGFBP-1). A greater inhibition of immunoreactive IGFBP-1 was obtained with des-(1-3) IGF-I (10 ng/ml) in Hep G2 medium when incubated in Eagle's Modified Essential Medium (EMEM) without phenolred compared to EMEM with phenolred; EMEM without phenolred was chosen for further experiments. Des-(1-3)IGF-I decreases dose dependently the concentration of IGFBP-1, with a maximal effect at 3-10 micrograms/l when incubated for 24 h; 10 micrograms/l of des-(1-3)IGF-I caused a small but significant inhibition of IGFBP-1 after 8 h incubation and this inhibition was 41% and 33% of controls after 14 and 19 h incubation. The relative potencies at 16 h of incubation of IGF-I and insulin in suppressing IGFBP-1 in comparison to des-(1-3)IGF-I were 0.41 (0.25-0.78) and 0.08 (0.01-0.26), respectively. A dose-dependent decrease of IGFBP-1 mRNA to 30% of control was observed after 4 h incubation with 0.1-10 micrograms/l des-(1-3)IGF-I. Changes of glucose concentration (0-20 mmol/l) in the medium did not affect the IGFBP-1 concentration in the medium. In summary: Des-(1-3)IGF-I was tenfold more potent than insulin, and threefold more potent than IGF-I in decreasing IGFBP-1 concentration in medium conditioned by Hep G2 cells.

Analysis of Variance↗

Systemic quinine photosensitivity with photoepicutaneous cross-reactivity to quinidine.

A 75-year-old man developed an eczematous eruption on the face and dorsal aspects of the hands one July after 3 weeks' treatment with quinine, 0.25 g nightly, for nocturnal leg cramps. The photoreaction cleared within a week of quinine being stopped. UVA and UVB erythema threshold determinations, after the acute episode had subsided, were normal. A photopatch test was positive for irradiated quinine down to a concentration of 0.01% and for unirradiated quinine to 0.5%. The test with the isomer quinidine was positive only when irradiated, down to a concentration of 0.01%. Preirradiated samples of quinine and quinidine were negative. Whereas in contact allergy quinine and quinidine usually do not cross-react, after systemic photosensitization, the 2 isomers probably form a common photoproduct, accounting for the cross-reactivity.

Aged↗

Modification of transplasma membrane oxidoreduction by SV40 transformation of 3T3 cells.

Transformation of 3T3 cells by SV40 virus changes the properties of the transplasma membrane electron transport activity which can be assayed by reduction of external ferric salts. After 42 h of culture and before the growth rate is maximum, the transformed cells have a much slower rate of ferric reduction. The change in activity is expressed both by change in Km and Vmax for ferricyanide reduction. The change in activity is not based on surface charge effect or on tight coupling to proton release or on intracellular NADH concentration. With transformation by SV40 virus infection the expression of transferrin receptors increases, which correlates with greater diferric transferrin stimulation of the rate of ferric ammonium citrate reduction in transformed SV40-3T3 cells than in 3T3 cells.

3T3 Cells↗

Ultraviolet B irradiation inhibits the induction of photoallergy to systemically administered quinidine in the mouse.

In albino mice photosensitized to quinidine, 100 mg/kg by intraperitoneal injection, pretreatment of the induction area with ultraviolet B (UVB) on 3 consecutive days was shown to significantly reduce the inflammatory response when the mice were challenged at a distant site 1 week later. Mice controlled for phototoxicity did not react. The inhibition was dose-dependent within the UVB dose range tested (0.05-1.0 J/cm2 x 3), being almost complete with the highest doses. Inhibition, although somewhat less pronounced, was also seen when an area on the back, distant from the induction site, was preirradiated following a similar protocol. The reduced response at elicitation persisted when the time to challenge was increased up to 4 weeks. At 5 weeks, a second attempt to photosensitize the previously inhibited animals failed, suggesting that a state of tolerance had been acquired. The timing of the UV exposure in relation to the photoactive chemical is critically important in determining whether an exposure promotes or inhibits photoallergic sensitization.

Animals↗

Chromosome localization of the human oncogene INT1 to 12q13 by in situ hybridization.

The human oncogene INT1 has been mapped to chromosome band 12q13 by in situ hybridization. The precise localization of this gene is of particular interest, since the region 12q13----q14 has been reported to be involved in chromosomal rearrangements in lipomas, myxoid liposarcomas, pleomorphic adenomas, and myomas. The involvement of this region in both benign and malignant tumors suggests a common pathogenetic pathway in which changes affecting INT1 may be an important step.

Chromosome Mapping↗

DNA cloning and hybridization in deer species supporting the chromosome field theory.

The Cervidae show the largest variation in chromosome number found within any mammalian family. The eight species of deer which are the subject of this study vary in chromosome number from 2n = 70 to 2n = 6. Three species of Bovidae are also included since they belong to a closely related family. Digestion of nuclear DNAs with the restriction endonucleases Hae III, Hpa II, Msp I, Eco RI, Xba I, Pst I and Bam HI reveals that there is a series of highly repetitive sequences forming similar band patterns in the different species. There are two bands (1100 and 550 base pairs) which are common to all species although the two families separated more than 40 million years ago. To obtain information on the degree of homology among these conserved sequences we isolated a Bam HI restriction fragment of approximately 770 base pairs from red deer DNA. This sequence was 32P labeled and hybridized by the Southern blot technique with DNAs cleaved with Bam HI, Eco RI, Hpa II and Msp I. Moreover, the same sequence was cloned in the plasmid vector pBR322 nick translated with 32P and hybridized with the DNAs of 8 species of Cervidae and 3 of Bovidae. The same cloned probe was labeled with 3H and hybridized in situ with the metaphase chromosomes of red deer (2n = 68) and Muntiacus muntjak (2n = 7 male). Homologies are still present between the highly repetitive sequences of the 8 species of Cervidae despite the drastic reorganization that led to extreme chromosome numbers. Moreover, the cloned DNA sequence was found to occupy the same position, in the proximal regions of the arms, in both red deer (2n = 68) and M. muntjak (2n = 7 male) chromosomes. The ribosomal RNA genes and the centromeres in these species have also maintained their main territory despite the drastic chromosome reorganization. These results are experimental confirmation of the chromosome field theory which predicted that each DNA sequence has an optimal territory within the centromere-telomere field and tends to occupy this same territory following chromosome reorganization.

Animals↗

The somatomedin-binding protein isolated from a human hepatoma cell line is identical to the human amniotic fluid somatomedin-binding protein.

Serum-free medium conditioned by the human hepatoma cell line HEP G2 was shown to contain a somatomedin-binding protein with a relative molecular mass of about 35,000. This binding protein was purified to homogeneity by the use of immunoaffinity chromatography and subsequent size exclusion chromatography. Antibodies for the immunoaffinity step were raised in rabbits against a previously isolated human amniotic fluid somatomedin-binding protein. The total composition and N-terminal amino acid sequence showed the protein to be identical to the binding protein from human amniotic fluid. Both have the N-terminal structure Ala-Pro-Trp-Gln-. The HEP G2 cell line offers a useful model to study the regulation of the synthesis and secretion of human somatomedin-binding proteins.

Amino Acid Sequence↗

Conservation of repetitive DNA sequences in deer species studied by southern blot transfer.

The Cervidae show one of the largest variations in chromosome number found within a mammalian family. The five species of the deer family which are the subject of this study vary in chromosome number from 2n = 70 to 2n = 6. Digestion with the restriction enzymes EcoRI, HpaII, HaeIII and MspI reveals that there is a series of highly repetitive sequences forming similar band patterns in the different species. To obtain information on the degree of homology among these conserved sequences we isolated a HpaII restriction fragment of approximately 990 base pairs from reindeer DNA. This DNA sequence was 32P-labelled and hybridized by the Southern blot technique to DNAs cleaved with HpaII and HaeIII from the reindeer and four other Cervidae species. Hybridization to specific restriction fragments was recorded in all species. The patterns of hybridization showed a higher degree of similarity between reindeer, elk and roe deer than between reindeer and the Asiatic species (fallow deer and muntjac). Homologies are still present between the highly repetitive sequences of the five species despite the drastic reorganization that led to a change in chromosome number from 6 to 70.

Animals↗

Photopatch testing.

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Allergens↗

Patch-testing with serial dilutions of tixocortol pivalate and potential cross-reactive substances.

Of patch-tested patients with dermatitis, 4-5% are allergic to corticosteroids. Four groups of corticosteroids are recognized (A-D), where substances from the same group may cross-react. We investigated the potential cross-reactivity pattern and dose-response relationship for several corticosteroids from group A. We also included the corresponding aldehyde to hydrocortisone, as this degradation product has been proposed to be immunogenic. Eleven patients shown to be allergic to tixocortol pivalate were patch-tested with several corticosteroids from group A, as well as with the aldehyde, all in serial dilutions. All 11 reacted to both tixocortol pivalate and hydrocortisone. The dose-response relationship for the corticosteroids tended to be similar to sensitizers lacking anti-inflammatory potential. Patients with simultaneous reactions to many substances had high patch-test reactivity to tixocortol pivalate and hydrocortisone, while patients with few such reactions showed low reactivity (p=0.001 and 0.003, respectively). Several patients reacted to the aldehyde, supporting the theory that it is an intermediate in sensitization.

Administration, Topical↗