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Biomedical subjects

U Nilsson

Publications and source records attributed to U Nilsson.

At least 109 records · Page 6Linked to original sources

The oxidation of p-phenetidine by horseradish peroxidase and prostaglandin synthase and the fate of glutathione during such oxidations.

The oxidation of p-phenetidine by horseradish peroxidase and prostaglandin synthase was investigated. The existence of a free radical intermediate formed during enzymatic oxidation was supported by a ratio of hydrogen peroxide: p-phenetidine consumed of 1:2 in the horseradish peroxidase system. Furthermore in both enzyme systems a rapid oxidation of added glutathione was observed and in the presence of the thiol there was a decreased removal of p-phenetidine. This suggests the reduction of a p-phenetidine radical by glutathione generating p-phenetidine and a thiyl radical. The latter react with oxygen and a rapid oxygen uptake was observed during enzymic oxidation in the presence of thiols. That p-phenetidine radicals were produced during horseradish peroxidase catalyzed oxidation of p-phenetidine was supported by experiments using the spin probe OXANOH. This was oxidized to its stable free radical form (OXANO.) in an enzyme- and substrate-dependent reaction and the EPR signal obtained was not decreased by SOD (80 micrograms/ml) or benzoate (10-100 mM). TLC characteristics of the products of the oxidation of p-phenetidine by both enzymes were almost identical inferring a similar mechanism of oxidation. Two of the metabolites were characterized by mass spectrometry and by comparison with reference compounds prepared by chemical oxidation. One metabolite was identified as 4,4'-diethoxyazobenzene, which further supports a radical mechanism, and the other was a p-phenetidine trimer which could exist in both oxidized and reduced forms. On the basis of these observations a mechanism for the oxidation of p-phenetidine and the fate of glutathione during such oxidations is proposed.

Aminophenols↗

Thiyl radicals--formation during peroxidase-catalyzed metabolism of acetaminophen in the presence of thiols.

We confirm using EPR spectroscopy in conjunction with the spin probe 2-ethyl-1-hydroxy-2,5,5-trimethyl-3-oxazolidine (OXANOH) that horseradish peroxidase catalyzed metabolism of the analgesic acetaminophen occurs via a one electron mechanism. When either glutathione cysteine or N-acetylcysteine were included in the reaction the thiols reduced the acetaminophen-derived radicals to generate thiyl radicals which were trapped with the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and observed using EPR spectroscopy. Similarly, DMPO-thiyl radical adducts were observed during prostaglandin synthase catalyzed oxidation of acetaminophen in the presence of either glutathione or N-acetylcysteine. This is a mechanism of removal of reactive xenobiotic free radicals generated in metabolic systems but whether it represents a true detoxification reaction depends on the subsequent fate of the thiyl radicals generated.

Acetaminophen↗

Increased erythrocyte sodium efflux during overfeeding without evidence of mediation by circulating catecholamines or thyroid hormone.

Ten slightly obese middle-aged men were instructed to increase their energy intake 25% during a period of 1 week, which was preceded by a control period of seven days. Body weight increased by 0.67 kg (SD 0.60) indicating good compliance with the regimen. Transmembrane sodium fluxes were determined with the use of 22Na. The pre-diet erythrocyte sodium content was 9.7 mmol/L (SD 0.8) decreasing to 8.9 mmol/L (SD 1.1) (P less than 0.05) during overfeeding. The Na-efflux rate constant increased from 0.40 h-1 to 0.54 h-1 (P less than 0.05). Urinary excretion of catecholamines and concentrations of catecholamines and insulin in plasma and of thyroxine, triiodothyronine, and reverse T3 in serum did not change. Thus, overfeeding seems to enhance the total Na efflux in erythrocytes from slightly obese men. There were no measurable changes in thyroid hormone or catecholamine levels leaving the regulatory mechanisms unexplained.

Adult↗

Weight-reducing diets: role of carbohydrates on sympathetic nervous activity and hypotensive response.

Two groups of obese, normotensive men were put on weight-reducing diets in an outpatient study. The groups were comparable with regard to age, weight, heart rate, blood pressure, energy and salt intake during a four-week control period. In a four-week dieting period, Gp I (n = 12) received an energy-reduced diet (1370 kcal, 5.7 MJ) with 24 energy per cent carbohydrates. Group II (n = 11) had an isocaloric diet (1400 kcal, 5.8 MJ) with 59 energy per cent carbohydrates consisting of mainly mono- and disaccharides. Significant decreases in systolic blood pressure, heart rate, plasma noradrenaline and urinary excretion of noradrenaline were observed in Gp I but not in Gp II. Weight reduction and decrease of urinary sodium output was equal in both groups. No difference in alcohol consumption was recorded. We conclude that in obese normotensive patients a high proportion of mono- and disaccharides counteracts the expected hypotensive response of weight reduction. On the other hand, and judged from the present data, the blood pressure decrease observed in the group on a low carbohydrate diet seems to be secondary to an effect on the sympathetic nervous system.

Adult↗

Percutaneous transhepatic cholangiography and drainage. Risks and complications.

An analysis of 237 consecutive PTC/PTD procedures revealed radiographically demonstrable complications in 21 per cent (50/237 cases: bile-contrast medium leakage 24 cases, haemobilia 18 cases) and clinically registered complications in 11% (26/237 cases: bile or blood leakage with or without peritonitis in 10 cases). Two deaths occurred. When possible, a drainage catheter was inserted for decompression. This was performed on 184 occasions in 139 patients--failure rate was 5 per cent. Unsuccessful attempt to introduce a drainage catheter constituted a major complication risk occurring in 5/13 cases (38%). Signs of infection were frequent though these complications were not a major problem in this series. Various possibilities to reduce complications and infections are discussed.

Adenoma, Bile Duct↗

Computed tomography in pulmonary pseudotumors and their relation to asbestos exposure.

Twelve patients, nine of whom had histories of exposure to asbestos, were evaluated by chest roentgenography and computed tomography because of a pulmonary mass lesion. The lesion consisted of condensed atelectatic lung parenchyma surrounded by marked thickening of the pleura--a pulmonary pseudotumor. In most patients, the mass lesion was only part of a more extensive disease process with pleural plaques and parenchymal fibrosis. Computed tomography demonstrated the full extent of disease better than chest roentgenograms. Asbestos is stressed as a possible causative factor of these mass lesions.

Aged↗

Computed tomography of iatrogenic hepatic lesions following percutaneous transhepatic cholangiography and portography.

Computed tomography (CT) was performed after percutaneous transhepatic cholangiography (PTC) in 22 patients and after percutaneous transhepatic portography (PTP) in 10 patients in order to find possible iatrogenic hepatic lesions. The interval between the transhepatic examinations and CT was usually less than 10 days. Hepatic lesions of low attenuation were demonstrated in four patients following PTC and in four patients following PTP. In one patient, bile leakage following PTC and transhepatic bile duct intubation necessitated laparotomy. In all other patients, the complications were considered clinically insignificant.

Adult↗

Intrahepatic vascular lesions following nonsurgical percutaneous transhepatic bile duct intubation.

Hepatic angiography was performed following nonsurgical percutaneous transhepatic intubation of the bile ducts in patients with extrahepatic cholestasis. Vascular lesions of the liver (aneurysm, hematoma, arterioportal venous fistula, arteriohepatic venous fistula) were demonstrated in 27 of 83 patients. No clinical complications were observed in 22 of these cases. One patient with an arterioportal venous fistula developed marked hemobilia necessitating blood transfusion. In four patients with severe hemorrhage from an intrahepatic aneurysm, transcatheter embolization was performed. Two of these patients died within 72 h because of liver insufficiency.

Adult↗

Malakoplakia: evidence for monocyte lysosomal abnormality correctable by cholinergic agonist in vitro and in vivo.

We studied monocyte function in a case of malakoplakia in an attempt to characterize the immune defect in this condition. Our patient's intracellular cyclic-GMP levels were abnormally low (mean +/- S.D. of 0.17 +/- 0.05 pmol per 10(7) malakoplakia cells, versus 0.79 +/- 0.12 in normals) p less than 0.001). After phagocytosis, his monocytes failed to release beta-glucuronidase. In the bactericidal assay, incubation of the patient's monocytes with Escherichia coli allowed growth of 542 +/- 46 colonies, normal monocytes allowed 95 +/- 22 (p less than 0.001). The percentage of monocytes with large lysosomal granules was 23 +/- 4 in the patient and 4 +/- 2 in normal controls. After in vitro incubation of the patient's cells or in vivo treatment with bethanechol chloride, the cyclic-GMP levels, bactericidal ability and lysosomal granules of the cells returned to normal levels. Low levels of cyclic-GMP could impair lysosomal function and bacterial killing in this condition. Cholinergic agonists correct the in vitro abnormalities and are beneficial in vivo.

Adult↗

Lethality and EROD-inducing potency of chlorinated chrysene in chick embryos.

Chrysene was non-specifically chlorinated and the toxic potency of the mixture formed was studied. The chlorinated mixture was considerably more potent than the parent compound in terms of embryolethality and EROD and AHH induction in a 2-week test in chick embryos. The chlorinated chrysene caused anomalies, including edema and beak defects, similar to those previously found after treatment of chick embryos with coplanar PCBs. Chlorinated chrysene was also much more potent than chrysene as an inducer of EROD in a 72-hour test in chick embryos in ovo and in chick embryo liver in vitro. It seems that the mechanism of toxicity of chlorinated chrysene in chick embryos is similar to that of the coplanar PCBs and other Ah receptor ligands. The effects of the chlorinated mixture were mainly accounted for by 6- chlorochrysene and 6,12-dichlorochrysene.

Animals↗

Contact allergy to resin acid hydroperoxides. Hapten binding via free radicals and epoxides.

For a better understanding of the mechanisms of contact allergic reactions, the patterns of cross-reactivity between different resin acid oxidation products were studied. The 13,14(alpha)-epoxide and the 13,14(beta)-epoxide of abietic acid and 15-hydroperoxydehydroabietic acid (15-HPDA) were shown in experimental sensitization studies to be contact allergens. Cross-reactivity was observed between the alpha- and beta-epoxides and also between the epoxides and the previously identified rosin allergen 15-hydroperoxyabietic acid (15-HPA). This indicates that 15-HPA may form an epoxide which then reacts with skin protein to generate the complete antigen. 15-HPA and 15-HPDA cross-reacted as well. This can be explained by the formation of similar alkoxy radicals from both hydroperoxides which further react with skin protein. Cross-reactivity patterns of the resin acid oxidation products indicate that 15-HPA may react with skin proteins either as a radical or as an epoxide, thus generating different antigens. The presence in rosin of the epoxides of abietic acid was also studied. The beta-epoxide was detected in gum rosin. Moreover, the epoxides elicited reactions in rosin-allergic individuals. Thus, the 13,14(beta)-epoxide of abietic acid was identified as a new, important rosin allergen.

Abietanes↗

Report of studies on monoclonal anti-IgG antibodies.

Eleven monoclonal anti-IgG antibodies were evaluated by ten laboratories for possible AHG reagent use by the ISBT/ICSH protocol. Three of the anti-IgGs were selected by tests with weak Fya sensitized cells as this represents the best screening test. One of the IgM class anti-IgGs (205) equalled ISBT/ICSH reference reagents (R3P and RIIIM) against weak anti-D, -K and Fya sensitized cells and it reacted with all four subclasses of IgG. Thus, subject to satisfactory stability and extended trials with a wide range of weak antibodies, monoclonal anti-IgGs for AHG reagent use are now a possible alternative to conventional rabbit anti-IgG.

Antibodies, Anti-Idiotypic↗

Report of studies on monoclonal antibodies (MABS) to complement components.

Twenty-five monoclonal antibodies (MABS) to complement components were evaluated according to the ISBT/ICSH protocol by twelve laboratories. Seven detected some form of C3c, but one of them, 174, did not react with EiC3b, although it was positive with 'EC3b' (Fruitstone). 174 may detect some form of enzyme sensitive C3b antigen, but C3a was not evaluated (present on 'EC3b' Fruitstone). Twelve of the antibodies were anti-C3d, one was an anti-C3g and five were anti-C4c.

Antibodies, Monoclonal↗

Teletransmission of radiographic images. Preliminary report.

A digital system for transmission of images over telephone lines using a 256 X 256 X 6 bits matrix provided for communication between a county hospital and a university hospital is presented. During a three-month period radiologic diagnostic problems encountered in 62 patients (computed tomography in 46 and conventional radiography in 16) were referred by transmitting selected images from each examination. Transmission of computed tomograms was performed without significant degradation of image quality and there was no loss of diagnostic information. Deterioration of image quality was noticed when conventional films especially those of the chest, were digitized and transmitted, though in no instance were they non-diagnostic. The consultations gave valuable information to the transmitting radiologist in approximately 50 per cent of the cases. Review by the consulted radiologists of all original films in each of the examinations 6 months later did not improve the diagnostic results. Thus, a few carefully selected images, digitized and transmitted over telephone lines, may be sufficient for adequate consultation.

Electronics, Medical↗

Magic Lite Chlamydia immunoassay in urogenital samples and urine versus chlamydial culture.

Magic Lite Chlamydia assay (commercial test kit for the identification of Chlamydia trachomatis) was evaluated on urogenital samples and urine with chlamydial culture as the reference method. The sediment of the transportation buffer of specimens which were Magic Lite positive but culture negative or toxic was investigated for elementary bodies with fluorescein-labelled anti-chlamydial antibodies. The prevalence of chlamydial infection among the 577 men investigated was 13.7% as estimated by culture and direct immunofluorescence and 6.4% among the 173 women. In order to improve the sensitivity a cut-off value below that recommended by the manufacturer was used. The sensitivity of Magic Lite in male urethral specimens was then 60.8% and that in female urethral/cervical specimens 90.9%. The specificity was 99.6% and 100%, respectively. In urine specimens the sensitivity of Magic Lite was 63.3% (men) and 63.6% (women). The specificity was 99.4% and 100%, respectively. The sensitivity of Magic Lite on male urethral specimens was related to the number of inclusion bodies per well in culture and it was higher among men attending with clinical findings of urethritis (69%) than among asymptomatic men sampled as a screening procedure (36%) (P < 0.05). Corresponding differences between the sexes and between those with and without symptoms were not noted for Magic Lite applied on urine samples.

Adolescent↗