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A Karlsson

Publications and source records attributed to A Karlsson.

278 records · Page 16Linked to original sources

New ultrasensitive 32P-postlabelling method for the analysis of 3,N4-etheno-2'-deoxycytidine in human urine.

Etheno-DNA adducts are generated from exogenous carcinogens such as vinyl chloride and urethane and also from endogenous lipid peroxidation products such as trans-4-hydroxy-2-nonenal (HNE). The present authors and others have established that 1,N6-ethenodeoxyadenosine (epsilondA) and 3,N4-ethenodeoxycytidine (epsilondC) are present in human urine and could be explored as biomarkers for monitoring whole-body oxidative stress. The present study reports on a new ultrasensitive 32P-postlabelling/thin-layer chromatography (TLC) method for the analysis of epsilondC as deoxynucleoside in human urine. The urine samples were purified and enriched on a solid-phase silica C-18 column followed by a semi-preparative reverse-phase high-performance liquid chromatography. The purified sample was labelled with a multisubstrate deoxyribonucleoside kinase from Drosophila melanogaster (Dm-dNK) in the presence of 5'-bromo-2'-deoxyuridine (BrdU) as internal standard. The absolute sensitivity of the method was 0.1 fmol epsilondC detectable in 500 microl of human urine. The analysis of human urine samples from 15 healthy volunteers revealed a mean epsilondC level of 2.49+/-1.76 (SD) fmol micromol-1 creatinine (range 0.66-6.42). By this non-invasive method, epsilondC in human urine could be explored as a biomarker for oxidative stress-related human diseases.

Animals↗

Synthesis, cytostatic activity and inhibition of ribonucleotide reductase by 5'-phosphoramidates and 5'-diphosphates, of 2'-O-allyl-arabinofuranosyl nucleosides.

The diphosphates of a series of 2'-O-allyl-1-beta-D-arabinofuranosyl derivatives, previously obtained by us, have been prepared and tested for their inhibitory activity in an in vitro assay using R1 and R2 subunits of the purified recombinant mouse ribonucleotide reductase (RNR). 2'-O-Allyl-araU diphosphate proved to be inhibitory, with an IC50 of 100 microM. The 5'-phosphoramidate pronucleotide of 2'-O-allyl-araU was also prepared and tested for inhibition of tumor cell proliferation.

Animals↗

Cultured rat and purified human Pneumocystis carinii stimulate intra- but not extracellular free radical production in human neutrophils.

The production of free radicals in human neutrophils was studied in both Pneumocystis carinii derived from cultures of L2 rat lung epithelial-like cells and Pneumocystis carinii purified from human lung. Using the cytochrome C technique, which selectively measured extracellular superoxide generation, hardly any free radical production was observed after stimulation with cultured rat-derived P. carinii. A chemiluminescence technique, which separately measured intra- and extracellular free radical production, was subsequently employed to differentiate the free radical generation. It was established that 1) P. carinii stimulated intra- but not extracellular free radical production in human neutrophils, 2) opsonized cultured rat-derived P. carinii stimulated human neutrophils to a strong intracellular response of superoxide production, and 3) opsonized P. carinii, purified from human lung also stimulated human neutrophils to produce intracellular free radicals.

Animals↗

Considerations in the corticosteroid treatment of bone cysts.

To be effective in treating bone cysts, intracavital injections of corticosteroids must be able to run freely over their lining membrane. Free movement may be prevented by complete or partial osseous or fibrous septa or by the cyst contents. This report illustrates such situations. To solve the problem, the interior anatomy of the cyst should be evaluated by a contrast study and then, when necessary, several corticosteroid injections should be made in different cyst compartments. The volume of corticosteroid should be modified according to the size of the cyst.

Bone Cysts↗

Radioimmunolocalisation of bladder tumors xenotransplanted in nude mice.

We have previously reported on the derivation of mouse monoclonal antibodies (Mabs), identifying several cell surface antigens selectively associated with cancer of the urinary bladder (TCC) (1-4). Three of these Mabs (4E8, SK4H and 8F4) have now been assessed for their ability to localise TCC-tumor xenografts in nude mice. The biodistribution of 125I-labeled intact Mabs as well as the corresponding Fab and F(ab')2 fragments from two of them were investigated in animals carrying TCC tumors or antigen negative control tumors. Using direct measurements of excised tissues, all three antibodies were seen to accumulate specifically in the TCC tumors, giving tumor to normal tissue ratios of between 3 and 20 depending on the Mab used and the time after injection. Antibody fragments were generally more efficient in their localisation, mainly due to a dramatic reduction in the blood background as compared to intact Ig. One of the antibodies, 4E8, was also employed for external imaging with gamma camera scintigraphy using 111In or 131I as tracers. Excellent visualisation of the tumor sites could be obtained both with Fab fragments and intact antibody within 12-24 hours after injection. As expected, background radioactivity was significantly lower with fragments than with whole molecules. 111In labeled antibodies appeared in all instances to be superior to the corresponding 131I conjugates. In conclusion, the present study indicates that the three anti TCC antibodies may become useful for the in vivo diagnosis of bladder cancer in man.

Animals↗

[Anniversary report].

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History, 17th Century↗

Beta2-microglobulin excretion and autoimmune phenomena in endemic Balkan nephropathy.

Quantitative determinations of beta2-microglobulins were carried out in 335 urinary samples collected from 335 subjects living in villages with a high rate of morbidity and mortality from endemic Balkan nephropathy. Three months after the first determination of beta2-microglobulin excretion, blood and urine samples were obtained from 19 patients with high values and from 19 with normal values of beta2-microglobulins. The results of the biochemical and immunological investigations performed on these samples suggest that the tubular alteration is the first lesion. The autoimmune phenomena elicited by the tubular alteration may contribute, by an antigen-antibody complex disease mechanism, to the appearance of glomerular secondary lesions.

Antigen-Antibody Complex↗