Acute early allograft failure and the C3/macrophage phenomenon.
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Biomedical subjects
Publications and source records attributed to U Nilsson.
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A peroxide of dehydroabietic acid was isolated from rosin using flash chromatography and preparative HPLC. It was identified by 1H-NMR and MS. In animal experiments, this peroxide cross-reacted with a previously identified allergen in rosin, 15-hydroperoxyabietic acid (15-HPA), despite differences in molecular weight and unsaturation. Both substances are able to react via a radical mechanism generating structurally similar molecules. In patch testing of patients, no reactions were observed to the peroxide. Low skin penetration of the peroxide could be the explanation for this. The peroxide seems of little clinical importance. The observed cross-reactivity is an indication of antigen generation via a radical mechanism. Only a few compounds that react with radical mechanisms to form antigens are described in the literature.
The purpose of this study was to compare three measures of the availability of dietary Zn and Fe in order to test their validity. Thirty-six 5-wk-old rats were fed deionized water and wheat crispbread made from endosperm flour, whole-grain flour, or endosperm flour supplemented with Zn and Fe to the whole-grain levels ad libitum for 14 d. The retention of 65Zn and 59Fe from test meals of the same breads after 1 wk and the sum of the excretion of endogenous Zn and Fe (injected 65Zn and 59Fe) with the Zn and Fe balances, respectively, were used as independent measures of Zn and Fe absorption. Measurements of Zn absorption, Zn balance, and serum Zn concentration gave quite different results with regard to the availability of Zn in the three breads, presumably because of the homeostatic regulation of the absorption and excretion of Zn when the Zn in the diet is in excess of the body's needs. Measurements of Fe absorption, Fe balance, and Fe concentrations in liver and serum were consistent in demonstrating overloading of Fe in the group given wheat-endosperm crispbread supplemented with Zn and Fe, but there was evidence that the isotope retention method overestimated iron absorption.
Extracts of pure cotton and jeans fabrics were tested for mutagenicity in Salmonella typhimurium strains TA98 and TA100. The vat dye indigo, technical grade as well as 98% and greater than 99.5% pure, was also tested for mutagenicity. Synthetic indigo, indirubin and isatin were tested for TCDD receptor affinity in competition experiments in vitro. The mutagenicity of the extracts was associated with the cotton denim and nondyed cotton gave only marginal effects. The mutagenicity of the indigo dyed fabrics was dependent on type and treatment of the fabrics. Extracts of both bleached and nonbleached jeans gave mutagenic effects on TA98 +/- S9 and TA100 +/- S9. The greatest effects were seen in the presence of S9. Bleaching gave an additional increase in the mutagenicity in the absence of S9. Normal washing of the fabrics after bleaching reduced the mutagenicity. Synthetic indigo of technical grade or 98% pure showed mutagenic effects, especially on TA98 + S9. Further purification to 99.5% reduced the mutagenicity to 24 revertants/mg (6.2 rev/mu mole). Considering the amount of indigo in the extracts and its low mutagenicity, the genotoxicity of jeans extracts must be caused by other unknown components. However, indigo showed a high (Kd = 1.9 nM) affinity for the Ah or TCDD receptor. Indigo can therefore still be a potential health risk either by eliciting toxic effects of other compounds or by being a nongenotoxic carcinogen. The worldwide use of jeans with a possible exposure of a large population to genotoxic and biologically active components emphasizes the need for a more thorough characterization of these effects.
Knowledge of the body burden of a metal is important for evaluation of exposure and risk. Traditionally, the burden has been estimated through levels in blood, urine, hair, or shed teeth, or by mobilization tests. However, all these methods have limitations. In vivo methods for determination of cadmium in kidney by neutron activation analysis or X-ray fluorescence (XRF) reflect the burden, long-term exposure, and risk of toxic effect. In vivo determination by XRF of lead in fingerbone, tibia, or calcaneus reflect the long-term exposure, and should become a valuable tool in epidemiological studies, especially of chronic effects.
Cylindrical gel phantoms of 2% agarose concentration were used as wall-less phantoms of arbitrary shape for calibration purposes in non-destructive measurements of bone mineral and heavy metal concentration using XRF. The counts of the coherently and incoherently scattered photons with no sample present should be subtracted as "background" to get a linear relationship between the ratio of the coherently and incoherently scattered photons and the bone mineral concentration for phantoms of arbitrary diameters.
Products containing as much as 95% of d-limonene are used for, e.g., degreasing metal before industrial painting and for cleaning assemblies. Experimental studies on the sensitizing potential of limonene show diverging results. In a previous study, we found that the sensitizing potential of d-limonene increased with prolonged air exposure. The aim of this study was to make further chemical analyses, to identify compounds formed by air exposure of d-limonene and to study their allergenic potential. d-limonene was found to be a sensitizer after prolonged exposure to air according to 2 Freund's complete adjuvant test (FCAT) experiments and 1 guinea pig maximization test (GPMT) study. No significant response was obtained to d-limonene not air exposed, even if the animals were sensitized to oxidized d-limonene. 5 main oxidation products of d-limonene were identified. (R)-(-)-carvone and a mixture of cis and trans isomers of (+)-limonene oxide were found to be potent sensitizers, while no significant reactions were obtained in the animals induced with a mixture of cis and trans isomers of (-)-carveol. It can be concluded that air oxidation of d-limonene is essential for its sensitizing potential, and that potent allergens are created.
This study describes a spin trap technique to determine production of oxygen radicals in rabbit kidneys after ischaemia and reperfusion. OXANOH was infused intra-arterially. When exposed to oxygen free radicals OXANOH is oxidized to the stable radical OXANO(.). The concentration of OXANO. in samples of renal venous blood was determined by ESR. Production of oxygen radicals was calculated from the amount of OXANO. in the venous blood and the blood flow which was determined by an ultrasound technique. The radical production at reperfusion after ischaemia was expressed as a per cent of the pre-ischaemic value. A drastic increase in radical production was observed during (60 min) reperfusion after 60 min of ischaemia. Pretreatment with oxypurinol (20 mg kg-1) before ischaemia and before recirculation almost completely abolished the rise in radical production at recirculation. Similar results were obtained when oxypurinol was given before recirculation only.
In this study a close correlation [correlation coefficient (r) = 0.86, P less than 0.001] was found between the blood lead level of 20 lead workers and their urinary excretion of lead for 24 h after intravenous infusion with 1 g of the chelating agent calcium disodium edetate. In addition, there were significant associations between lead levels in different bones (tibia/calcaneus: r = 0.93, P less than 0.001; tibia/phalanx: r = 0.67, P less than 0.002; calcaneus/phalanx: r = 0.80, P less than 0.001), as measured by in vivo X-ray fluorescence. Chelation produced no significant change in the lead level in either tibia or calcaneus. There was a significant correlation between chelated lead and bone lead (eg, for calcaneus, r = 0.62) in currently exposed workers. However, there was no significant relationship when a retired worker and an inactive worker were included (r = 0.14). It was concluded that chelatable lead mainly reflects the blood and soft-tissue lead pool, which is only partly dependent upon the skeletal lead content that comprises the biggest share of the total body burden.
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The porcine complement proteins C3 and C4 have been isolated and then characterized using small-angle scattering methods. Within the limits of experimental errors, the porcine proteins are virtually identical with the corresponding human proteins as measured in terms of mol. wt, Mr and radius of gyration, R,: Mr(C3) = 198,000, Mr(C4) = 207,000, and R(C3) = 4.4 nm, R(C4) = 4.5 nm. The C3 and C4 proteins from pigs show cross-immunity with monoclonal antibodies (mAbs) raised against human C3 and C4, respectively. Using the Fab fragments of these mAbs as markers, it is indicated that porcine C3 and C4 undergo a conformational change after reaction with methylamine. The relatively large increase in the radius of gyration observed, delta R = 1.0-1.2 nm, going from the Fab complexes to the Fab complexes of the methylamine derivatives, is similar to that observed for human C3 under similar conditions. This may indicate that methylamine cleaves a labile thiol ester bond supposed to be present within the porcine proteins and that the epitopes interacting with the Fab fragments are very similar to those of the human proteins. Porcine C3 also resembles the human analogue by forming dimers after being subjected to methylamine and dilute lauryl sulphate: Mr = 404,000 and R = 7.9 nm.
In 14 retired lead workers, followed for over 18 years after end of exposure, repeated analyses of lead levels in finger bone by an in vivo X-ray fluorescence method revealed a decrease of lead concentration. The data were analysed using an exponential retention model. For the whole group the biological half-time was 16 (asymptotic 95% confidence interval, CI 12,23) years. The median of the estimated bone lead levels at the end of exposure was 85 micrograms.g-1 above the "background" (3 micrograms.g-1). A simultaneous follow-up of blood lead levels displayed a decrease, which could be described by a tri-exponential retention model with group half-times of 34 (CI 29,41) days, 1.2 (CI 0.9,1.8) years, and 13 (CI 10,18) years, respectively. The median of the estimated blood lead levels at the end of exposure for the three components were 0.49, 0.61, and 1.1 mumol.l-1 above the "background" (0.38-0.56 mumol.l-1), respectively. The well-documented decrease of lead exposure in the general population over the years, urged the use of a decreasing "background" of blood lead during the time of the study. The slowest of the three components represented the skeleton (probably mainly cortical bone), as did mainly probably also the intermediate one (trabecular bone). The data show the rather slow turnover of lead in the skeleton, the usefulnes of in vivo skeletal lead measurements as a long-term exposure index, and the importance of bone as a source of "endogenous" lead exposure.
Sixty-six consecutive patients treated at the Prosthodontic Clinic in Uppsala, Sweden, received implant-supported fixed prostheses of the Brånemark type. The prosthesis frameworks were made of cobalt-chromium alloys. Different techniques for attaching the gold cylinders to the frameworks were used. Mechanical attachment with self-curing polymethyl methacrylate (PMMA), partial soldering combined with PMMA attachment, and soldering only were used. No abnormal tissue reactions were seen. Radiographic examination of the fixtures was performed at the time of prosthesis placement and at the 1- and 3-year follow-ups. A few cases of minor bone loss were detected but not related to the materials used in the superstructures.
Magnification angiography was compared with histology in order to assess the value of each of the two techniques for the evaluation of microvascular anastomoses. At postmortem, angiography of 108 end-to-end anastomoses of the rat carotid artery (4.5 X magnification) was performed, followed by histological examination. Each method assessed the degree of stenosis or aneurysmal dilatation independently, expressing it as a percentage of lumen change compared to a noninvolved vessel segment of the same artery. Results were plotted for each carotid separately. Both methods were found to be equally useful, but were of rather low sensitivity and specificity. Each failed to diagnose roughly one-third of all stenoses and even more aneurysms. A possibility for further improvement of the results is discussed. Both methods proved to be complementary; at least one-third of the vascular changes would have been missed if only one method had been used. A combination of both techniques should therefore be used in studies of microvascular anastomoses.
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9-0 absorbable polydioxanone (PDS) has been compared to 9-0 nonabsorbable Prolene in order to evaluate any advantages of either suture in microvascular surgery. In each of 29 rats, one carotid artery was anastomosed end-to-end with PDS and the other with Prolene. Specimens were harvested 48 hr, 14 days, and three, and five months postoperatively. Histologic examination of the carotids followed postmortem using 4.5 x magnification angiography. Histologic analysis of inflammation, fibrosis, and medical necrosis of the anastomoses revealed no significant differences between the two materials. There was no difference as regards stenosis and aneurysm formation, when evaluated independently by the two methods. It was observed that saccular aneurysms formed as a result of medial necrosis and could develop at any time. Fusiform aneurysms formed where the media was replaced by bulging fibrosis and they appeared late. External support of adherent skeletal muscle prevented aneurysm formation. It can be concluded that the amount of inflammation and fibrosis leading to stenosis is related to the amount of trauma at the time of surgery and not to the type of suturing material used.
Complement activation was studied during cardiopulmonary bypass (CPB) in the pig. One group of animals was perfused for 2 h using a standard extracorporeal circuit including a hollow fiber membrane oxygenator with full systemic heparinization. Another group was treated in the same way, except that bypass was performed through a heparin-coated CPB circuit (Carmeda Bio-Active Surface, CBAS) and systemic heparinization was reduced by 75%. It was found that complement activation during CPB, measured as changes in the ratio C3d/C3, was significantly less in the CBAS group, most probably reflecting a better biocompatibility.
As the exposure of blood to foreign material during cardiopulmonary bypass (CPB) leads to triggering of inflammatory systems, the inflammatory response was used as an indicator of the biocompatibility of oxygenators. Activation of complement and neutrophil granulocytes during CPB was studied in 96 patients undergoing coronary bypass, with randomized comparisons between four different oxygenators, two of bubble and two of membrane type. Seven patients undergoing thoracotomy without CPB served as controls. During CPB there was significant complement activation, measured as changes in the ratio C3d/C3, with no demonstrable difference between the bubble and membrane oxygenator groups. Such change was not seen in the controls. Neutrophil granulocytes released significant amounts of the granule proteins lactoferrin and myeloperoxidase during CPB, but not during thoracotomy without CPB. The plasma concentrations of lactoferrin and myeloperoxidase were significantly lower in the membrane oxygenator groups, possibly indicating better biocompatibility. The strong inflammatory response with both oxygenator types, however, indicates that presently used CPB devices have unsatisfactory biocompatibility.