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K O Raivio

Publications and source records attributed to K O Raivio.

At least 37 records · Page 2Linked to original sources
PubMed1998

Xanthine oxidoreductase gene expression and enzyme activity in developing human tissues.

Xanthine oxidoreductase (XOR) has been implicated in tissue injury following ischemia-reperfusion because of its ability to generate reactive oxygen species under these conditions. In order to elucidate its role in various organs, we quantified the levels of XOR mRNA expression and activity in developing human tissues. XOR gene expression was highest in the intestine and in the liver, which also showed the highest enzyme activities. By a sensitive RNA-PCR assay, low levels of the transcript were detected in the kidney, lung, cardiac muscle, and brain of all subjects studied. XOR activities followed the mRNA distribution, being low or undetectable in tissues other than the liver and the intestine.

Brain↗
PubMed1998

Manganese superoxide dismutase in healthy human pleural mesothelium and in malignant pleural mesothelioma.

We hypothesized that manganese superoxide dismutase (MnSOD), known to be induced in rat mesothelial cells by asbestos fibers, cytokines, and hyperoxia, may also be induced in asbestos-related pleural diseases such as mesothelioma. MnSOD was assessed in healthy human pleural mesothelium (n = 6), in biopsy samples of human pleural mesothelioma (n = 7), in transformed nonmalignant human mesothelial cells (Met5A), and in two human mesothelioma cell lines (M14K and M38K) established from the tumor tissue of mesothelioma patients. There was no MnSOD immunoreactivity in five of the six samples of healthy pleural mesothelium, whereas MnSOD immunoreactivity was high in the tumor cells in all the mesothelioma samples. Northern blotting, immunohistochemistry, Western blotting, and specific activity measurements showed lower MnSOD in the nonmalignant Met5A mesothelial cells than in the M14K and M38K mesothelioma cells. In additional experiments the mesothelial and mesothelioma cells were exposed to menadione, which generates superoxide intracellularly, and to epirubicin, a cytotoxic drug commonly used to treat mesothelioma. The M38K mesothelioma cells were most resistant to menadione and epirubicin when assessed by LDH release or by adenine nucleotide (ATP, ADP, and AMP) depletion. These same cells showed not only the highest MnSOD levels, but also the highest mRNA levels and activities of catalase, whereas glutathione peroxidase and glutathione reductase levels did not differ significantly. We conclude that MnSOD expression is low in healthy human pleural mesothelium and high in human malignant mesothelioma. The most resistant mesothelioma cells contained coordinated induction of MnSOD and catalase.

Adult↗
PubMed1998

Antioxidant enzyme regulation and resistance to oxidants of human bronchial epithelial cells cultured under hyperoxic conditions.

Bronchial epithelial cells are the first cells to encounter high concentrations of inspired oxygen, and their damage is a typical feature in many airway diseases. The direct effect of oxygen on the expression of the main antioxidant enzymes (AOEs) in human bronchial epithelial cells is unknown. We investigated the messenger RNA (mRNA) levels of manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), catalase (CAT), and glutathione peroxidase (GPx), as well as the specific activities of MnSOD, CuZnSOD, CAT, GPx, and glutathione reductase, in BEAS-2B bronchial epithelial cells exposed to hyperoxia (95% O2, 5% CO2) for 16 to 48 h. We also assessed the resistance of cells preexposed to hyperoxia to subsequent oxidant stress. Significant cell injury was observed after 72 h exposure to hyperoxia; release of lactate dehydrogenase (LDH) from control cells and cells exposed to hyperoxia for 72 h was 7.0 +/- 1.0% and 22.0 +/- 1.0%, respectively. Hyperoxia for 16 h, 24 h, or 48 h had no effect on the mRNA levels or specific activities of any of these enzymes. Despite their unchanged AOE levels, cells exposed to hyperoxia for 48 h showed increased resistance to H2O2 and menadione. Total glutathione content of the cells increased by 55% and 58% after 24 h and 48 h, respectively, compared with normoxic controls. However, glutathione depletion with buthionine sulfoximine (BSO) did not diminish the oxidant resistance of hyperoxia-exposed cells. We conclude that AOEs in human bronchial epithelial cells are not directly upregulated by high oxygen tension, and that increases in AOE-specific activities or glutathione are not necessary for the development of increased oxidant resistance in these cells.

Antioxidants↗
PubMed1998

Expression and developmental profile of antioxidant enzymes in human lung and liver.

Air breathing, especially oxygen therapy, exposes the lung to reactive oxygen species (ROS). Antioxidant enzymes (AOEs) may protect the lung from ROS-mediated injury. Because expression of the key AOEs increases in several animal species during gestation, we investigated (1) the messenger RNA (mRNA) and activity levels of the key AOEs manganese and copper-zinc superoxide dismutases (MnSOD and CuZnSOD, respectively), catalase (CAT), and glutathione peroxidase (GPx) in adult lung samples and during ontogenesis; and (2) the difference in AOE expression between lung and liver. In the lung, the mRNA expression of MnSOD, CuZnSOD, and CAT increased toward adulthood, and GPx was unchanged. Pulmonary activities of MnSOD and CuZnSOD were unchanged, whereas CAT increased 3-fold from fetuses to adults. In the liver, the mRNA expression of MnSOD, CuZnSOD, and GPx increased, whereas that of CAT decreased toward adulthood. Hepatic activities of MnSOD and CuZnSOD increased 2-fold and 4-fold, respectively, whereas CAT was similar in fetuses and adults. Neonatal GPx activity was 2-fold higher in the lung and 6-fold higher in the liver compared with adults. The mRNA levels of MnSOD correlated positively with those of CuZnSOD and CAT in the lung, and GPx with those of MnSOD and CuZnSOD in the liver. Activities of MnSOD and CuZnSOD correlated positively in the liver. We conclude that the regulation of AOEs differs between human lung and liver, and is not tightly coordinated in either tissue.

Adult↗
PubMed1997

Reperfusion injury as the mechanism of brain damage after perinatal asphyxia.

Upon reperfusion of ischemic tissues, reactive oxygen metabolites are generated and are responsible for much of the organ damage. Experimental studies have revealed two main sources of these metabolites: 1) the oxidation of hypoxanthine to xanthine and on to uric acid by the oxidase form of xanthine oxidoreductase and 2) neutrophils accumulating in ischemic and reperfused tissue. Blocking either source will reduce reperfusion damage in a number of experimental situations. Although xanthine oxidoreductase activity may be unmeasurably low in organs other than liver and intestine, it may be involved in reperfusion injury elsewhere because of its localization in capillary endothelial cells. Time course considerations suggest that substrate accumulation and NADH inhibition of dehydrogenase activity may be more important in the pathogenesis than conversion of xanthine dehydrogenase into the oxidase form. Neutrophil accumulation may be partly due to oxidants in the first place, suggesting a link between the two sources of reactive oxygen metabolites. In the clinical context, many of the sequelae of perinatal asphyxia may be accounted for by reperfusion damage to organs such as brain, kidney, heart, liver, and lungs. During asphyxia, substrates of xanthine oxidase accumulate, upon resuscitation the cosubstrate oxygen is introduced, and evidence for oxidant production and effects has been obtained. In the pathogenesis of brain damage after asphyxia, both microvascular injury and parenchymal cell damage are important. Oxygen metabolites are involved in the former, but in the latter process their role is less clear because ischemia-reperfusion triggers not only oxidant production but many other phenomena, including gene activation, ATP depletion, glutamate accumulation, and increase of intracellular calcium. A severe insult results in cell necrosis, but more moderate asphyxia may cause delayed neuronal death through apoptosis. The time course of the changes in high energy phosphates as well as of selective neuronal death suggest that in the first hours of life there is a "therapeutic window," with future possibilities for prevention of permanent damage.

Animals↗
PubMed1997

Assessment of xanthine oxidase in human lung and lung transplantation.

Oxygen free radical generation by xanthine oxidase (XO) is a possible mechanism in the injury following reperfusion of transplanted organs. This study was undertaken to investigate XO in human lung, and to investigate whether XO is released into the blood stream during the immediate postoperative period after lung transplantation. XO activity was measured in healthy human lung tissue, and XO protein and the adenine nucleotide catabolic products hypoxanthine, xanthine and uric acid were analysed in the plasma samples collected during human heart-lung transplantation (n=4), double lung transplantation (n=2), and single lung transplantation (n=1). Neutrophil degranulation was assessed by plasma lactoferrin measurements. The results indicated that XO activity (detection limit 5 pmol x min(-1) x mg(-1) protein) and protein (detection limit 5 ng x mg-1 protein) were undetectable in the lungs of five healthy individuals. Similarly, no XO protein could be found in the plasma samples from the right ventricle or left atrium during and after the transplantation in any of the cases. Plasma xanthine and hypoxanthine concentrations were elevated 2-10 fold immediately after the reperfusion of the transplant, indicating washout of high-energy phosphate degradation products from the ischaemic lung. Plasma uric acid decreased rather than increased immediately after the surgery and during the following 24 h. Lactoferrin was elevated during the surgery. In conclusion, these results show that XO activity in human lung is low, it is not released into the blood stream during human heart-lung transplantation, and it is unlikely to contribute to postoperative complications in these patients.

Chromatography, High Pressure Liquid↗
PubMed1996

Cloning and expression in vitro of human xanthine dehydrogenase/oxidase.

To study the expression of human xanthine dehydrogenase/oxidase (hXDH/XO), we cloned the cDNA covering its complete coding sequence and characterized it by translation in vitro in rabbit reticulocyte lysates and by transient expression in COS-1 cells. Two specific protein products with approximate molecular masses of 150 and 130 kDa were detected in both expression systems. These products are compatible with the molecular sizes of XDH/XO, and these peptides also showed immunoreactivity with polyclonal anti-hXDH antibodies. Significant XDH/XO enzyme activity (277 +/- 54 pmol/min per mg of protein) was measured in lysates of transfected COS cells, whereas in control transfections the activities were below the detection limit of our assay (0.2 pmol/min per mg of protein). The COS cells expressed the enzyme predominantly (89.8 +/- 0.3%) in the dehydrogenase form.

Amino Acid Sequence↗
PubMed1996

Differential effects of tumor necrosis factor and asbestos fibers on manganese superoxide dismutase induction and oxidant-induced cytotoxicity in human mesothelial cells.

We compared induction of manganese superoxide dismutase (MnSOD) by asbestos fibers and tumor necrosis factor alpha (TNF) using cultured human mesothelial cells. Transformed pleural mesothelial cells (MET 5A) were exposed for 48 h to amosite asbestos fibers (2 micrograms/cm2), to TNF (10 ng/ml), and to the combination of these two. TNF and amosite+TNF caused significant MnSOD mRNA upregulation. Similarly MnSOD specific activity was increased by TNF (290% increase) and the amosite+TNF combination (313% increase) but not by amosite alone. In cell injury experiments, amosite and amosite+TNF exposures caused significant cell membrane injury when assessed by lactate dehydrogenase release, which was 31% and 57% higher than in the unexposed cells. However, only the amosite+TNF combination caused significant depletion of cellular high-energy nucleotide when expressed as percentage of [14C]adenine labeling in cellular high-energy nucleotides. The nucleotide levels were 91.5 +/- 2.0% in the unexposed cells, 89.9 +/- 3.9% in amosite-exposed cells, 90.1 +/- 2.2% in TNF-exposed cells, and 79.8 +/- 9.4% in amosite+TNF-exposed cells. Amosite+TNF-exposed cells were also most sensitive to menadione (20 mumol/L, 2 h), a compound which generates superoxide radicals intracellularly. In conclusion, our data suggests that in human mesothelial cells inflammatory cytokines but not asbestos fibers alone can cause MnSOD induction. In this study, however amosite asbestos+TNF treatment rendered these cells more vulnerable to oxidant-induced cell damage despite elevated MnSOD activity.

Asbestos, Amosite↗
PubMed1996

Prolonged granulocyte activation, as well as hypoxanthine and free radical production after open heart surgery in children.

OBJECTIVE: To investigate granulocyte activation, as well as hypoxanthine and free radical production in children during the first day after cardiopulmonary bypass. DESIGN: A prospective study of pediatric patients undergoing either cardiac surgery with a cardiopulmonary bypass or thoracotomy and extracardiac vascular surgery not requiring a cardiopulmonary bypass. SETTING: Operative and intensive care units, Children's Hospital, University of Helsinki, Finland. PATIENTS: Seven consecutive patients undergoing elective correction of a ventricular septal defect and six patients undergoing extracardiac surgery for ligation of a patent ductus arteriosus or repair a coarctation of the aorta. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of myeloperoxidase (140-334 micrograms/l preoperatively, 460-1692 micrograms/l at 0.2 h after declamping, 471-1386 micrograms/l at 0.5 h after declamping) and lactoferrin (77-258 micrograms/l preoperatively, 533-1783 at 0.2 h, 404-1482 micrograms/l at 0.5 h) as markers of granulocyte activation, and hypoxanthine (0-5.7 mumol/l preoperatively, 4.3-17.0 mumol/l at 0.2 h, 6.5-17.9 mumol/l at 0.5 h) increased in a biphasic manner at 0.2-0.5 h and 6-10 h postoperatively (all p < 0.05). Expired ethane, as an index of free radical activity, increased at 10 h postoperatively (36-119 pmol/kg per min preoperatively, 72-152 pmol/kg per min, p < 0.005). CONCLUSION: Granulocyte activation, and hypoxanthine and free radical production occur at least 10 h after cardiopulmonary bypass. In children undergoing open heart surgery, attempts to reduce free radical activity should be extended to the postoperative period.

Cardiopulmonary Bypass↗
PubMed1996

Intracellular high energy metabolite depletion and cell membrane injury with antioxidant enzymes during oxidant exposure in vitro.

We compared oxidant-induced intracellular adenine nucleotide catabolism and cell membrane injury in 4 different human cell types. Responses to oxidant exposure were correlated with endogenous antioxidant enzyme activities in these cells. Blood monocytes, amniotic fibroblasts, umbilical vein endothelial cells in primary culture, and transformed bronchial epithelial cells (BEAS 2B) were exposed to 0.1-5 mM hydrogen peroxide (H2O2) for 4 h. Some experiments were conducted in cells pretreated with 3-amino 1:2,4-triazole (ATZ) to inactivate catalase or with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to inactivate glutathione (GSH) reductase. Depletion of adenine nucleotides and accumulation of their catabolic products (hypoxanthine, xanthine and uric acid) occurred to varying extent, monocytes being the most resistant. There was a mutual relationship between catalase and GSH reductase activities and maintenance of cellular adenine nucleotide levels during H2O2 exposure. GSH reductase inhibition rendered BEAS 2B cells susceptible to lytic injury by H2O2, assessed by release of lactate dehydrogenase and intact nucleotides into the medium, there was no correlation between these markers of such injury and endogenous antioxidant enzymes. We conclude that adenine nucleotide depletion and nucleotide catabolite accumulation relate closely with the antioxidant enzyme activities, whereas the lack of a similar correlation between the enzyme levels and markers of lytic cell injury suggest that intracellular antioxidant enzymes do not protect cells from membrane damage due to extracellular oxidants.

Adenine Nucleotides↗
PubMed1996

Serum cortisol, dehydroepiandrosterone sulfate, and steroid-binding globulins in preterm neonates: effect of gestational age and dexamethasone therapy.

Our aim was to assess adrenocortical function in very low birth weight infants, specifically to evaluate the impact of gestational age and dexamethasone (DEX) therapy on serum concentrations of total and free cortisol, dehydroepiandrosterone sulfate (DHEAS), and steroid-binding globulins. Twelve moderately preterm or full-term neonates of 38 +/- 4 (mean +/- SD) wk of gestation and 36 ill preterm neonates of 26 +/- 2 (mean +/- SD) wk of gestation were studied. Twenty-three of the 36 ill preterm neonates participated in a randomized neonatal DEX trial for the treatment of early chronic lung disease and received a 1-wk treatment of DEX or placebo. Serum concentrations of cortisol, corticosteroid-binding globulin (CBG), sex hormone-binding globulin (SHBG), and DHEAS were measured, and an ACTH test was performed. Gestational age correlated with the umbilical cord concentrations of total cortisol (r = 0.702, p < 0.01), free cortisol (r = 0.489, p < 0.05), DHEAS (r = 0.608, p < 0.01), and SHBG (r = 0.831, p < 0.01), but not significantly with the concentration of CBG (r = 0.428, p = 0.076). One-week DEX therapy decreased the serum concentrations of CBG (DEX 295 nmol/L, placebo 504 nmol/L; p < 0.01), DHEAS (DEX 6.5 mumol/L, placebo 11.8 mumol/L; p < 0.05), and the basal (DEX 81 nmol/L, placebo 176 nmol/L; p < 0.01) and ACTH-stimulated cortisol levels (DEX 458 nmol/L, placebo 817 nmol/L; p < 0.05). One week after discontinuation of DEX or placebo, basal cortisol concentrations did not differ significantly, but ACTH-stimulated cortisol levels were lower in the DEX-treated than in the placebo-treated infants. DEX therapy decreased the serum CBG and DHEAS concentrations and caused a transient suppression in the adrenocortical function. Despite severe illness, the very preterm neonates had relatively low basal cortisol concentrations, suggesting their reduced ability to respond adequately to stress during intensive care.

Adrenal Cortex↗
PubMed1996

Organ distribution and molecular forms of human xanthine dehydrogenase/xanthine oxidase protein.

Xanthine dehydrogenase/xanthine oxidase (XDH/XO) is a major cytoplasmic source of superoxide radicals and hydrogen peroxide, and it is considered important in the pathogenesis of ischemia-reperfusion damage. Because little is known about the enzyme in human tissues, the aims of this study were to purify human XDH/XO and to produce Ab for detection of the protein in Western blots and for quantification by ELISA. We purified human milk XDH/XO, produced Ab for Western blotting and ELISA of the protein, and evaluated the molecular forms and activity-protein relationships in human tissues. The molecular size of the purified protein under nondenaturing conditions was approximately 300 kd. On SDS-PAGE, it was fragmented into four main bands of 143, 125, 87, and 59 kd. Ab recognized bands of similar size in Western blots of the purified preparation and human milk. In fresh liver homogenates treated with anti-proteases, the three largest bands were observed; in the intestine, only the two largest were observed. Serum, brain, heart, and skeletal muscle were negative, whereas some lung and kidney samples showed one faint band of 143 kd. Trypsin treatment of the enzyme converted the large molecular-weight bands into smaller bands, as did incubation of a liver homogenate without anti-proteases. XDH/XO protein concentrations (ng/mg total protein) were 146 +/- 70 in liver and 556 +/- 320 in intestine and less than 5 ng/ml in serum. The relationship of activity to protein (2.7-3.0 mumol/min/mg XDH/XO protein) was constant in liver and intestine during development. We conclude that 1) human XDH/XO has molecular size and subunit structure similar to other mammalian enzymes; 2) the polypeptide chain is unstable, also in the intact cell, despite retained activity; and 3) the amount of inactive XDH/XO in human liver and intestine is apparently small.

Adult↗
PubMed1995

Neutrophil and asbestos fiber-induced cytotoxicity in cultured human mesothelial and bronchial epithelial cells.

This study investigates reactive oxygen species generation and oxidant-related cytotoxicity induced by amosite asbestos fibers and polymorphonuclear leucocytes (PMNs) in human mesothelial cells and human bronchial epithelial cells in vitro. Transformed human pleural mesothelial cells (MET 5A) and bronchial epithelial cells (BEAS 2B) were treated with amosite (2 micrograms/cm2) for 48 h. After 24 h of incubation, the cells were exposed for 1 h to nonactivated or amosite (50 micrograms) activated PMNs, washed, and incubated for another 23 h. Reactive oxygen species generation by the PMNs and the target cells was measured by chemiluminescence. Cell injury was assessed by cellular adenine nucleotide depletion, extracellular release of nucleotides, and lactate dehydrogenase (LDH). Amosite-activated (but also to a lesser degree nonactivated) PMNs released substantial amounts of reactive oxygen metabolites, whereas the chemiluminescence of amosite-exposed mesothelial cells and epithelial cells did not differ from the background. Amosite treatment (48 h) of the target cells did not change intracellular adenine nucleotides (ATP, ADP, AMP) or nucleotide catabolite products (xanthine, hypoxanthine, and uric acid). When the target cells were exposed to nonactivated PMNs, significant adenine nucleotide depletion and nucleotide catabolite accumulation was observed in mesothelial cells only. In separate experiments, when the target cells were exposed to amosite-activated PMNs, the target cell injury was further potentiated compared with the amosite treatment alone or exposure to nonactivated PMNs. In conclusion, this study suggests the importance of inflammatory cell-derived free radicals in the development of amosite-induced mesothelial cell injury.

Adenine Nucleotides↗
PubMed1995

Regional generation of free oxygen radicals during cardiopulmonary bypass in children.

Studies on free radical generation during cardiopulmonary bypass have focused mainly on the heart and the lungs. However, low pumping pressure, nonpulsatile perfusion, and hypothermia affect the entire circulation, resulting in decreased splanchnic blood flow, increased intestinal permeability, and endotoxemia. To evaluate regional phenomena, we studied 16 children undergoing cardiopulmonary bypass. Free radical production, granulocyte activation, and hypoxanthine metabolism were assessed separately in the circulations drained by the inferior and superior venae cavae, as well as in the oxygenator. Three minutes after the onset of cardiopulmonary bypass, significant gradients between the inferior vena cava and the arterial line of the oxygenator existed in malondialdehyde (+0.60 +/- 0.12 mumol/L, lactoferrin (+18.21 +/- 7.65 micrograms/L), myeloperoxidase (+53.75 +/- 16.50 micrograms/L), hypoxanthine (-0.62 +/- 0.15 mumol/L), and urate (+8.87 +/- 4.03 mumol/L). These gradients decreased in parallel with decreasing body temperature. Except for a transient gradient in malondialdehyde at 3 minutes after the onset of cardiopulmonary bypass (+0.23 +/- 0.08 mumol/L), no changes were detected between the superior vena cava and the arterial line. In the oxygenator, granulocyte activation was observed only after aortic declamping. We conclude that during cardiopulmonary bypass, significant free radical generation, granulocyte activation, hypoxanthine elimination, and urate production take place in the region drained by the inferior vena cava. In the oxygenator, granulocyte activation occurs only after aortic declamping.

Body Temperature↗
PubMed1995

Outcome of children after maternal primary Toxoplasma infection during pregnancy with emphasis on avidity of specific IgG. The Study Group.

Congenital toxoplasmosis results from maternal primary infection during pregnancy. In our serologic screening study 42 of 16,733 pregnant women had findings suggestive of primary infection. Here we document the outcome of their offspring, 37 of 39 liveborn children. After 12 months postnatally, serologically verified congenital toxoplasmosis appeared in 4 children. All these children had persisting IgG at the age of 12 months by both the dye test and the IgG enzyme-linked immunosorbent assay. All the congenitally infected infants had also specific IgM and IgA and showed significant increases in avidity of specific IgG during the 12-month follow-up. One of them had a unilateral retinal scar and intracranial calcifications. An additional 3 infants of the mothers with primary infection during early pregnancy presented with unilateral retinal scars but without seroresponses during the first 12 months of life. Maternal high avidity of IgG during the first trimester is a strong indicator against primary infection during pregnancy; the fetuses of such mothers are at low risk for congenital toxoplasmosis.

Base Sequence↗
PubMed1995

Mitochondrial superoxide dismutase induction does not protect epithelial cells during oxidant exposure in vitro.

The significance of manganese superoxide dismutase (MnSOD) induction in cells and tissues during oxidant stress is still poorly understood. In this study, transformed human bronchial epithelial cells (BEAS 2B) were treated with interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), or with combination of these cytokines (10 ng/ml concentrations) for 48 or 72 h and exposed to selected oxidants. TNF-alpha and IFN-gamma + TNF-alpha combination resulted in a marked increase of MnSOD protein and MnSOD activity. When cells pretreated with the cytokines were exposed to hyperoxia (95% O2, 72 h), menadione (5-50 microM, 4 h), or H2O2 (0.5 and 5 mM, 4 h), in all cases IFN-gamma and TNF-alpha enhanced oxidant-related cell injury. The effect was most significant with cells pretreated with a combination of IFN-gamma and TNF-alpha. Antioxidant enzymes such as total SOD, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase did not change significantly during the cytokine treatment. Catalase activity was not changed by IFN-gamma or TNF-alpha but it decreased significantly (34%) in IFN-gamma + TNF-alpha-treated cells. Free radical generation was not changed by these cytokines in acute (30 min) experimental conditions or after 48-h treatment. These results suggest that cytokine-induced MnSOD does not protect bronchial epithelial cells against endogenously or exogenously generated oxidants in vitro. In fact, cells that contained the highest MnSOD activity were the most sensitive to subsequent oxidant damage.

Bronchi↗
PubMed1995

The human gene for xanthine dehydrogenase (XDH) is localized on chromosome band 2q22.

Mutations in the xanthine dehydrogenase gene (XDH), which codes for the last enzyme of the purine catabolic pathway in man, cause the autosomal recessive disease xanthinuria. We obtained cDNA clones from a human breast cDNA library and confirmed one of the two different sequences proposed for human XDH. Using a somatic cell hybrid mapping panel and specific primers for human XDH, we assigned the gene to chromosome 2. By fluorescence in situ hybridization, the gene was localized to bands 2p22.3-->p22.2. The FLpter probe location was 0.135 (SD = 0.016), as determined by digital image analysis.

Base Sequence↗