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K Jansson

Publications and source records attributed to K Jansson.

At least 37 records · Page 2Linked to original sources

Characterization of a new in vitro model for studies of reepithelialization in human partial thickness wounds.

Reepithelialization of artificial partial thickness wounds made in biopsies of human skin was determined after 3, 5, or 7 d of incubation, submerged or elevated to the air-liquid interface. The biopsies were reepithelialized within 5-7 d, with a more complete epidermal healing in wounds exposed to air. Both types of wounds showed similar time-course in deposition of basement membrane components, as detected by immunofluorescence labeling. Laminin and collagen type VII were deposited underneath the migrating tips, whereas collagen type IV was detected after reepithelialization. Markers of terminal differentiation showed a pattern close to normal in the air-liquid incubated wounds after reepithelialization. Involucrin was detected in the suprabasal regions of the migrating epidermis and thereafter in the upper half of neo-epidermis in the air-liquid incubated wound. Filaggrin could not be detected in the submerged wounds at any time during healing, whereas wounds exposed to air showed a well-differentiated epidermis by Day 7. Tritiated thymidine-incorporation indicated proliferation of epidermal and dermal cells during reepithelialization and a maintained viability, as shown by cultivation of endothelial- and fibroblast-like cells obtained from the dermis 7 d after wounding. Reepithelialization in this human in vitro model is supported by a matrix close to normal with the possibility of extracellular influences and cell-cell interactions and, in addition, the technique is simple and reproducible. Therefore, we suggest this model for studies of regeneration in culture and as a complement to in vivo studies on epidermal healing.

Basement Membrane↗

Mortality related to coronary angiography.

Coronary angiography is in general regarded as a safe investigation with a low risk of serious complications. Unfortunately, a risk of serious complications exists, especially in patients with left main coronary artery disease or 3-vessel disease. The mortality rate ranges in different studies between 0.10% to 0.25%. The present series, reflecting nine years experience, shows an overall mortality of 0.16%. This figure is influenced by the relatively high mortality rate in the first year of the study. The recent mortality rate of 0.07% has not changed in the last 3 years and almost all deaths occurred in the patients known to be at higher risk.

Aged↗

Kinds of mutations induced by 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in the hprt gene of Chinese hamster ovary cells.

The kinds of mutations induced by 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in the protein coding region of the hprt gene of Chinese hamster ovary (CHO) cells were determined by direct sequencing of polymerase chain reaction (PCR)-amplified cDNA. Primary mutations were found in 15 of 19 of the mutants: 11 were G:C-->T:A transversions, two were A:T-->T:A transversions and two were deletions of single G:C base pairs (-1 frameshifts). The remaining four mutants had large alterations in the cDNA that were explained by mRNA splicing errors. A group of control mutants had more diverse hprt cDNA alterations than MX-induced mutants. Transversions yielding an A:T base pair were the predominant type of MX-induced mutations, in agreement with previous findings in bacteria. This specificity may be explained by the 'A rule', that DNA polymerases preferentially insert adenine nucleotides opposite non-instructional lesions.

Animals↗

Mutagenicity in vitro of 3,4-dichloro-5-hydroxy-2(5H)-furanone (mucochloric acid), a chlorine disinfection by-product in drinking water.

The mutagenicity of chlorinated humic drinking waters is accounted for mainly by a single contaminant, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), as assessed in Salmonella typhimurium strain TA100. In the present study 3,4-dichloro-5-hydroxy-2(5H)-furanone (mucochloric acid, MA), another drinking water contaminant much less potent as a mutagen in TA100 than MX, was tested in Chinese hamster ovary (CHO) cells for the induction of mutation at the hypoxanthine phosphoribosyl transferase (hprt) locus to 6-thioguanine resistance (TGr). Unexpectedly, MA induced TGr mutants in CHO cells with a potency comparable to that reported previously for MX. In subsequent experiments with S. typhimurium, the presence of pKM101 plasmid in strain TA100 increased susceptibility to the mutagenicity of MA, but much less than to that of MX, relative to the parental strain TA1535 lacking pKM101. The difference between the two compounds in TA100 thus appears to be due to a higher enhancement of the mutagenicity of MX than that of MA by pKM101 mediated error-prone DNA repair.

Analysis of Variance↗

The Linköping-Lund surgical experience with the HeartMate left ventricular assist system.

Four transplant candidates fulfilling the Food and Drug Administration criteria for a permanent left ventricular assist device received a pneumatic HeartMate system as a bridge to heart transplantation. All patients survived and were fully rehabilitated at the time of transplantation, which was carried out 2 to 6 months after the initial operation. There were no major complications associated with the procedures. We are impressed by the effectiveness and safety of the device.

Adult↗

Cytogenetic effects in the peripheral lymphocytes and kidney cells of rats exposed to 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) orally on three consecutive days.

We reported previously that 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)- furanone (MX), a chlorine disinfection by-product in drinking water, induces sister-chromatid exchanges (SCEs) in the peripheral lymphocytes of male and female rats after subchronic exposure. In the present study, we found that the peripheral lymphocytes of male rats exposed to MX (25-150 mg/kg) by gavage on three consecutive days showed a significant dose-related increase in chromosomal damage measured as micronuclei, in addition to SCEs. Moreover, MX produced a significant dose-related increase in SCEs in the kidney cells of the exposed rats. The magnitude of the genotoxic responses observed was relatively weak. The finding is, however, consistent with the known pharmacokinetic distribution of MX in the rat after oral dosing.

Administration, Oral↗

PM2 DNA damage induced by 3-chloro-4-(dichloromethyl)-5-hydroxy-2 (5H)-furanone (MX).

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) is a potent direct-acting mutagen found in chlorinated drinking water. In the present study, the induction of DNA strand breaks and apurinic/apyrimidinic (AP) sites by MX in supercoiled PM2 DNA was examined using exonuclease III, which specifically cleaves the DNA at AP sites. The results showed that MX induced AP sites in great excess of direct strand breaks. In view of the known mutagenicity of AP sites, these results provide insight into the mechanism of MX-induced mutagenesis.

Apurinic Acid↗

Salmonella and mammalian-cell mutagenicity of 3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone.

3-Chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone (CMCF), a chlorine disinfection by-product in drinking water, was mutagenic in the Salmonella/his (Ames) assay for both base-pair substitution strains (TA1535, TA100, TA102) and frameshift strains (TA97, TA98) with the highest mutagenic response observed in strain TA100 (1292 revertants/microgram). The presence in TA100 of pKM101 plasmid, which enhances error-phone DNA repair, greatly increased susceptibility to CMCF mutagenicity relative to the isogenic strain TA1535 lacking pKM101. In the Chinese hamster ovary (CHO) cell hprt (6-thioguanine resistance) locus assay, the mutagenicity of CMCF (1.04 mutants/10(6) clonable cells per microgram/ml) was barely detectable because of the low mutagenicity/cytotoxicity ratio. From the present experiments it appears that CMCF acts in a manner similar to that of another drinking water mutagen, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX). However, CMFC appears to be a less potent mutagen in vitro than MX.

Animals↗

Subchronic toxicity of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in Wistar rats.

The subchronic (14-18 wk) toxicity of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a mutagenic by-product in chlorinated drinking water, was evaluated in Wistar rats. In a range-finding study, MX was administered daily for 14 days by gavage in deionized water to male rats (five animals per group) at doses of 12.5, 25, 50, 100 or 200 mg/kg body weight. The doses above 50 mg/kg were lethal and three out of five animals also died during treatment at 50 mg/kg. The range-finding study was repeated with doses of 5, 10 and 20 mg MX/kg, given on 5 days a week, to both males and females (10 animals per group). These doses were not overtly toxic but caused several changes in plasma clinical chemistry at 10 and 20 mg MX/kg in comparison with the controls. These included increased urea, creatinine and bilirubin and decreased inorganic phosphate and potassium in females and increased cholesterol in males. In the subchronic toxicity study, rats (15 per group, were given MX by gavage, on 5 days a week, at doses of 0 (controls) or 30 md/kg (low dose) for 18 wk, or, in the high-dose group, at doses increasing from 45 to 75 mg/kg over 14 wk. The high dose was finally lethal (two males and one female died) and caused hypersalivation, wheezing respiration, emaciation and tangled fur in animals. The body weights of the high-dose males decreased by 15%, and food consumption was decreased by 15 to 20%, but the water consumption increased by 15% to 60%. Plasma cholesterol and triglycerides were elevated and urine excretion was increased. Urine specific gravity was decreased and the relative weights of the liver and kidneys were increased in both sexes at both doses in comparison with the controls. At both doses, duodenal hyperplasia occurred in males and females, and slight focal epithelial hyperplasia in the forestomach was observed in males. Splenic atrophy and haemosiderosis were seen in two high-dose females, and epithelial cell atypia in the urinary bladder of one high-dose male and female. The frequency of bone marrow polychromatic erythrocytes with micronuclei was slightly increased in low-dose males. The results indicate that repeated administration of MX disturbs the fluid-electrolyte balance and induces diuresis, causes mucosal hyperplasia in the gastro-intestinal tract as a local effect, and affects lipid metabolism.

Animals↗

Lack of uniformity in the mutational spectra of chlorohydroxyfuranones in Salmonella typhimurium strain TA100.

The mutational specificity of three chlorohydroxyfuranones found in chlorinated drinking water, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), 3-chloro-4(chloromethyl)-5-hydroxy-2(5H)-furanone (CMCF) and 3,4-dichloro-5-hydroxy-2(5H)-furanone (mucochloric acid, MCA), was examined in Salmonella typhimurium strain TA100. DNA colony-hybridization of TA100 revertants showed that MX and CMCF both induced predominantly G:C-->T:A transversions (87 and 75% of total, respectively) with a 3:1 preference for the second position of the hisG46 (CCC) target codon. By contrast, MCA produced primarily G:C-->A:T transitions (66% of the total) with a 4:1 preference for the second position of the CCC codon. The mutational specificity of MCA is consistent with the idea that chloroacetaldehyde, a degradation product of MCA, is responsible for the observed mutations. The chemical mechanism by which either MX or CMCF induces G:C-->T:A transversions remains unknown.

Base Composition↗

Keratinocyte conditioned medium stimulates type IV collagenase synthesis in cultured human keratinocytes and fibroblasts.

We have previously shown that conditioned medium from cultured human keratinocytes stimulates proliferation of a variety of cell types involved in wound healing, as well as re-epithelialization of wounds in human skin in vitro. We now present evidence for an autocrine/paracrine control of the synthesis of type IV collagenases in human keratinocytes and fibroblasts. During wound healing, keratinocytes migrate over the wound bed, an activity coupled with lysis of basement membranes, and hence requiring the presence of collagenases. Collagenases are also needed for the production and remodelling of the granulation tissue. In order to study the autocrine/paracrine control of collagenase production in keratinocytes and fibroblasts, we stimulated these cells in culture with conditioned medium from cultured keratinocytes. Protease synthesis was determined by affinity labelling with 3H-diisopropylfluorophosphoridate (DFP) and by zymography. Keratinocyte-conditioned medium was found to increase the expression of 72 and 92 kDa type IV collagenase in human keratinocytes, and the 72 kDa collagenase in human fibroblasts, indicating that an autocrine/paracrine control mechanism is involved in collagenase production in these cell types during wound healing. This increased expression of collagenases could be partly responsible for the stimulated healing seen in wounds treated with sheets of cultured keratinocytes.

Cells, Cultured↗

Induction of mutation, sister-chromatid exchanges, and chromosome aberrations by 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone in Chinese hamster ovary cells.

The strong bacterial mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) was tested for the induction of mutation at the Na/K ATPase locus to ouabain resistance (OuaR), sister-chromatid exchanges (SCEs), and chromosome aberrations (CAs) in Chinese hamster ovary (CHO) cells without metabolic activation. MX increased the frequency of OuaR mutants in CHO cells when the cells were treated with it in PBS (effective dose range 2-3 micrograms/ml) or in medium (McCoy's 5A) without serum (effective dose range 20-30 micrograms/ml). MX also induced SCEs in CHO cells, at 0.19-1.5 microgram/ml, exposure in PBS; at 6-24 micrograms/ml, exposure in medium; and at 3-24 micrograms/ml, exposure in medium plus 2.5% fetal calf serum. The maximum induction of SCEs was about 1.5-2.5-fold compared with control level, irrespective of exposure conditions (PBS, medium or medium plus serum). The most pronounced genotoxic effect of MX was observed in CAs (100% aberrant cells at the dose level of 4 micrograms/ml, exposure in PBS) which were mainly of the chromatid type. In general, MX was more toxic to CHO cells treated in PBS compared with exposure in medium or medium plus 2.5% serum.

Animals↗

Induction of gene mutation in mammalian cells by 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a chlorine disinfection by-product in drinking water.

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a potent direct-acting Salmonella mutagen found in chlorinated drinking water, was tested in Chinese hamster ovary (CHO) cells for the induction of mutation at the hypoxanthine phosphoribosyl transferase locus to 6-thioguanine resistance (TGr). MX treatment of CHO cells for 3 h at 37 degrees C resulted in significant dose-related increases in mutant frequency. The lowest observed effective dose was 2.5 micrograms/ml, where the cloning efficiency estimated on the day after treatment was not affected. The relationship between the dose of MX and the frequency of TGr mutants was approximately linear over the range of 0-5 micrograms/ml with an estimated slope (+/- 95% confidence limits) of 7.2 +/- 2.6 mutants per 10(6) clonable cells per microgram/ml.

Animals↗

Cytogenetic effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in rat peripheral lymphocytes in vitro and in vivo.

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) is a potent direct-acting Salmonella mutagen found in wood pulp chlorination effluents and chlorinated drinking water. In cultured rat peripheral lymphocytes, MX induced significant dose-related increases in sister-chromatid exchanges (SCEs) and chromosome aberrations at doses of 20-60 micrograms/ml and of 60-80 micrograms/ml, respectively. MX produced primarily chromatid-type as opposed to chromosome-type aberrations. The peripheral lymphocytes of male and female rats exposed to MX by gavage 5 days a week for 14-18 weeks showed significant dose-related increases in SCEs at both levels of exposure (30 and 45-75 mg/kg) in both sexes. The present results demonstrate for the first time that MX is genotoxic in vivo.

Animals↗

The toxicity of chlorophenols in V79 Chinese hamster cells.

The toxicity of nine chlorophenols to V79 Chinese hamster cells was determined in a survival assay which gives a direct measure of reproductive cell death by measuring single-cell cloning efficiency. Quantitative analyses of the structure-activity relationships showed that the toxicity was linearly related not only to hydrophobicity, as suggested by previous mammalian-cell studies, but also to electronic (electron-withdrawing) substituent effects. The extent electronic factors were related to the toxicity was assessed apart from their influence on partition and transport. The results suggest a relationship between the toxicity and the well-known ability of chlorophenols to induce proton permeability in membranes.

Animals↗

Induction of micronuclei in V79 Chinese hamster cells by tetrachlorohydroquinone, a metabolite of pentachlorophenol.

Tetrachlorohydroquinone, a metabolite of the fungicide pentachlorophenol, induced significant dose-related increases in micronuclei in V79 Chinese hamster cells without exogenous metabolic activation. The lowest observed effective dose was 10 microM, where the relative survival was about 62%. At the highest dose tested, 20 microM, the relative survival was about 8% and the frequency of cells with micronuclei was about 6 times the solvent control frequency. The induction of micronuclei by tetrachlorohydroquinone was significantly inhibited by the hydroxyl radical scavenger dimethyl sulfoxide at 5% (v/v).

Animals↗