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Biomedical subjects

S Andersson

Publications and source records attributed to S Andersson.

At least 163 records · Page 9Linked to original sources

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↗

Early protein oxidation in the neonatal lung is related to development of chronic lung disease.

Free radical-mediated oxidation of proteins may impair their function and cause cellular damage. We studied pulmonary protein oxidation and its association with the development of chronic lung disease in 61 newborn infants (mean gestational age 31.1 +/- 4.0, range 24-41 weeks) requiring intensive care with oxygen therapy. Protein oxidation was quantified as protein carbonylation in tracheal aspirates recovered daily during the first week of life. Mean carbonyl concentration was 3.5 +/- 1.6 mumol/mg protein. Negative correlations existed between protein carbonylation during days 2-4 and gestational age (day 2: r = -0.37, p = 0.01; day 3: r = -0.48, p = 0.001; and day 4: r = -0.33, p = 0.03). Patients who developed bronchopulmonary dysplasia showed significantly higher protein carbonylation on days 1-6 (all p < 0.05). In multiple regression analysis explaining bronchopulmonary dysplasia, using gestational age, inspired oxygen on days 1-3 and protein carbonylation on day 3 as independent variables, only protein carbonylation remained significant. We conclude that immaturity is the most important factor explaining free radical-mediated pulmonary protein oxidation in newborn infants and that oxidation of proteins is related to the development of chronic lung disease.

Bronchopulmonary Dysplasia↗

Effect of branched-chain amino acid and carbohydrate supplementation on the exercise-induced change in plasma and muscle concentration of amino acids in human subjects.

Five male endurance-trained subjects performed exhaustive exercise on a cycle ergometer at a work rate corresponding to 75% of their VO2max after reduction of their muscle glycogen stores. During exercise the subjects were given in random order a 6% carbohydrate solution continuing 7 g L-1 of branched-chain amino acids (BCAA), a 6% CHO solution and flavoured water. The physical performance was lowered in four of the five subjects when they were given flavoured water during exercise as compared with the two conditions when CHO was supplied. No difference in performance was found when the subjects were given CHO + BCAA or only CHO during exercise. When CHO + BCAA was supplied the plasma and muscle (vastus lateralis) concentrations of BCAA increased during exercise by 120 and 35%, respectively. In the other conditions there was no change or a slight decrease in the plasma concentrations of BCAA, but the muscle concentrations of BCAA were decreased after exercise. The plasma concentration of glutamine over the whole exercise period and 5 min after exercise was higher when CHO + BCAA were supplied during exercise compared with a supply of CHO alone or water. However, exercise caused no change in the muscle concentration of glutamine, whereas that of glutamate decreased in all three conditions. A supply of CHO + BCAA or CHO alone did not affect the exercise-induced increase in the plasma and muscle concentration of aromatic amino acids, indicating that neither BCAA nor CHO influenced the net protein degradation during exercise.

Administration, Oral↗

Closure of patent ductus arteriosus decreases pulmonary myeloperoxidase in premature infants with respiratory distress syndrome.

The aim of the study was to determine whether in premature infants with respiratory distress syndrome (RDS), an interrelationship existed between patent ductus arteriosus (PDA) and pulmonary neutrophil content. Thirteen premature infants with PDA (gestational age 26.9 +/- 2.4 weeks, birth weight 903 +/- 300 g) were pair-matched with infants without PDA (gestations age 27.1 +/- 2.5 weeks, birth weight 1,041 +/- 430 g) with regard to gestational age, birth weight and severity of RDS. The myeloperoxidase (MPO) contents of tracheal aspirates were analyzed before (age 2.8 +/- 1.7 days, MPO I) and after closure of PDA with indomethacin (5.5 +/- 1.9 days, MPO II), and at corresponding time points in controls (2.6 +/- 1.6 and 4.8 +/- 1.8 days). In PDA patients closure of PDA decreased MPO from 14.7 (range 2.1-27.4) to 4.6 (1.2-8.0) micrograms/mg protein (p = 0.0008), whereas in controls it remained unchanged: 5.4 (2.9-7.8) and 5.3 (2.9-7.8; p = 0.58). A significant difference existed in the change in MPO contents between the infants with PDA and the controls. In premature infants with RDS, closure of PDA decreases the neutrophil content of the lungs. The effect may be caused by closure of PDA as such, or by indomethacin. The high pulmonary neutrophil content in PDA may exacerbate inflammatory processes and contribute to the development of chronic pulmonary disease.

Birth Weight↗

Prenatal muscle relaxation in congenital diaphragmatic hernia.

An infant with congenital diaphragmatic hernia was given 2 mg vecuronium bromide intramuscularly in utero 40 min before vaginal delivery at 40 weeks gestation. At birth the infant had complete muscle relaxation, which facilitated decompression of the bowel and surgical correction. Prenatal muscle relaxation may improve the care of infants with congenital diaphragmatic hernia.

Adult↗

HTLV infections among Swedish intravenous drug users in 1992.

Serum samples collected in 1992 from 1158 intravenous drug users (IVDUs) in Stockholm, Sweden, were tested retrospectively for antibodies to human T-lymphotropic virus type I and II (HTLV-I and II). The overall prevalence rate of HTLV infections was 2.4% (28/1158). A majority of the HTLV infections were caused by HTLV-II (27/28). A significant association between HTLV-II and HIV-1 seropositivity was found, the prevalence of HTLV-II infection being 11.4% (11/96) in HIV-seropositive individuals compared with 1.5% (16/1062) in HIV-seronegative persons (p < 0.001). All the HTLV-infected individuals were of Scandinavian origin. No significant differences in age and sex distribution were observed in HTLV-infected persons compared to seronegative individuals. This study confirms that HTLV-II infection is present in the Swedish IVDU population and the findings provide baseline information for future epidemiological studies.

Adolescent↗

Does transurethral resection of a clinically benign prostate gland increase the risk of developing clinical prostate cancer? A 10-year follow-up study.

BACKGROUND: Theoretical considerations have raised the suspicion that transurethral resection of the prostate (TURP) may increase the risk of developing prostate cancer in clinically benign prostate glands. Previous studies have not shown an increased risk among men who had undergone TURP for benign prostatic hyperplasia compared with the risk in age-matched control subjects. However, in all of these studies, all men with stage T1 prostate cancer in the TURP-group were excluded, possibly creating a bias, because no similar exclusion could be made for the controls. METHODS: The incidence and mortality of clinical prostate cancer were studied in 198 patients who had TURP and in 203 age-matched male control subjects. In both groups, all patients with known prostate cancer and patients with suspected cancer by digital rectal examination were excluded from the study. However, patients with stage T1 cancer found by the TURP were included in the comparison between the groups. RESULTS: The mean age in the two groups was 67 +/- 6 years. The patients were followed for an average of 10.2 +/- 1.2 years and 10.4 +/- 1.8 years in the TURP group and the control group, respectively. Clinical prostate cancer developed in six patients who had TURP and subsequently in five control (odds ratio, 0.8 [0.2-3.1]; P < 0.97). Before follow-up, three men in each group died because of prostate cancer (odds ratio, 1.3 (0.24-7.45); P < 0.97). CONCLUSIONS: The results of this study suggest that neither benign prostatic hyperplasia nor TURP increased the risk of developing clinical prostate cancer over the next 10 years in patients with a benign prostate gland determined by rectal examination before TURP.

Aged↗

Male pseudohermaphroditism caused by mutations of testicular 17 beta-hydroxysteroid dehydrogenase 3.

Defects in the conversion of androstenedione to testosterone in the fetal testes by the enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) give rise to genetic males with female external genitalia. We have used expression cloning to isolate cDNAs encoding a microsomal 17 beta-HSD type 3 isozyme that shares 23% sequence identity with other 17 beta-HSD enzymes, uses NADPh as a cofactor, and is expressed predominantly in the testes. The 17 beta HSD3 gene on chromosome 9q22 contains 11 exons. Four substitution and two splice junction mutations were identified in the 17 beta HSD3 genes of five unrelated male pseudohermaphrodites. The substitution mutations severely compromised the activity of the 17 beta-HSD type 3 isozyme.

17-Hydroxysteroid Dehydrogenases↗

A Drosophila third chromosome Minute locus encodes a ribosomal protein.

Minutes (M) are a group of over 50 phenotypically similar Drosophila mutations widely believed to affect ribosomal protein genes. This report describes the characterization of the P element-induced M(3)95A(Plac92) mutation [allelic to M(3)95A]. This mutation can be reversed by the mobilization of the P element, demonstrating that the mutation is caused by insertion of this transposable element. The gene interrupted by insertion of the P element was cloned by use of inverse polymerase chain reaction. Nucleotide sequence analysis revealed a 70-75% identity to the human and rat ribosomal protein S3 genes, and to the Xenopus ribosomal protein S1a gene. At the amino acid level, the overall identity is approximately 78% for all three species. This is only the second time that a Minute has been demonstrated to encode a ribosomal protein.

Amino Acid Sequence↗

Free-radical-induced lipid peroxidation during the early neonatal period.

The effect of gestational age on postnatal free-radical-mediated lipid peroxidation was studied in 19 term (gestational age 37-42 weeks) and 21 healthy preterm (gestational age 31-36 weeks) infants by measurement of expired ethane and pentane during the first 7 days of life. Ethane (11.9 versus 5.7 pmol/kg/min; p = 0.0001) and pentane (11.4 versus 7.5 pmol/kg/min; p = 0.01) were significantly higher in preterm than in term infants. Correlations were found between gestational age and ethane (r = 0.60, p = 0.0001) for days 1-7 and pentane (r = 0.54, p = 0.0003) for days 3-7; and between birth weight and ethane (r = 0.58, p = 0.0001) and pentane (r = 0.55, p = 0.0003). These results indicate that during the postnatal period, immaturity is a major factor determining the rate of free-radial-mediated lipid peroxidation.

Age Factors↗

17 beta-Hydroxysteroid dehydrogenase type 2: chromosomal assignment and progestin regulation of gene expression in human endometrium.

The cDNAs for two separate human 17 beta-hydroxysteroid dehydrogenases (17 beta-HSD) have been isolated and sequenced. The well-studied human placental cytosolic 17 beta-HSD (also referred to as estradiol dehydrogenase) preferentially catalyzes the reduction of estrone to estradiol-17 beta and the reduction of the C-20-ketone of progesterone to 20 alpha-dihydroprogesterone. This isoform of the enzyme has been referred to as 17 beta-HSD type 1 and localized to chromosome 17. A second 17 beta-HSD isoform (referred to as type 2) is localized in the endoplasmic reticulum of human trophoblast and is characterized by the preferential oxidation of the C-17 beta-hydroxyl group of C18- and C19-steroids and the C-20 alpha-hydroxyl group of 20 alpha-dihydroprogesterone. In this study, we determined the chromosomal localization of human 17 beta-HSD type 2, the expression of this gene in human endometrium, and the tissue distribution of the mRNA. We found that the human 17 beta-HSD type 2 gene is localized on chromosome 16, 16q24. 17 beta-HSD type 2 mRNA (approximately 1.5 kb) was identified in human endometrial tissues by Northern analysis of total RNA (10 micrograms). The highest levels of 17 beta-HSD type 2 mRNA were found in endometrial tissues obtained during the mid- to late secretory phase of the ovarian cycle (i.e., during the time of high plasma levels of progesterone). 17 beta-HSD type 2 mRNA levels were much greater in glandular epithelium than in the stromal cells isolated from secretory phase endometrium. The levels of 17 beta-HSD type 2 mRNA in secretory phase endometrium were approximately one-tenth that in villous trophoblast tissue from human placenta. We did not detect 17 beta-HSD type 1 mRNA in endometrial tissue by Northern analysis of total (10 micrograms) RNA. These findings are consistent with the view that the progestin-regulated 17 beta-HSD of the glandular epithelium of the human endometrium is primarily, if not exclusively, the product of the 17 beta-HSD type 2 gene. 17 beta-HSD type 2 mRNA was present in human placenta, liver, and small intestine; much smaller amounts, barely detectable by Northern analysis of poly(A)+ RNA, were present in prostate, kidney, pancreas, and colon, but not in heart, brain, skeletal muscle, spleen, thymus, ovary, or testis.

17-Hydroxysteroid Dehydrogenases↗

Immaturity-dependent free radical activity in premature infants.

To examine the role of immaturity in the free radical-mediated rate of lipid peroxidation in premature infants, we studied 27 infants [gestational age, 27.1 (SD 2.4) wk; birth weight, 970 (SD 330) g]. Ethane and pentane were quantitated in expired air during the first 18 d of life. During the first 2 postnatal d ethane [24.1 (SEM 7.8) pmol x kg-1 x min-1] and pentane [24.2 (SEM 4.1) pmol x kg-1 x min-1] were stable but increased during d 5 to maxima of 79.1 (15.8) pmol x kg-1 x min-1 and 62.1 (8.1) pmol x kg-1 x min-1, respectively. Maximum ethane and pentane correlated with gestational age (r = -0.42, p = 0.03 and r = -0.52, p = 0.005, respectively) and birth weight (r = -0.38, p = 0.05 and r = -0.59, p = 0.001, respectively). Infants with high maximum expired ethane and pentane (exceeding 40 pmol x kg-1 x min-1) had higher odds of dying or having bronchopulmonary dysplasia than those with low ethane and pentane (odds ratio, 6.5; 95% confidence interval, 1.1 to 38.5; p < 0.05 for ethane and odds ratio, 5.6; 95% confidence interval, 1.1 to 29.3; p < 0.05 for pentane). We conclude that degree of prematurity is the single most important factor explaining free radical-mediated lipid peroxidation in premature infants. A therapeutic intervention to limit the effects of free radicals should be started during the 1st postnatal d in premature infants to be effective.

Ethane↗

RK2, a glial-specific homeodomain protein required for embryonic nerve cord condensation and viability in Drosophila.

We report the identification of RK2, a glial-specific homeodomain protein. RK2 is localized to the nucleus of virtually all embryonic and imaginal glial cells, with the exception of midline glia. Embryos mutant for the gene encoding RK2 are embryonic lethal but normal for early gliogenesis (birth, initial divisions and migration of glia) and axonogenesis (neuronal pathfinding and fasciculation). However, later in development, there are significantly fewer longitudinal glia that are spatially disorganized; in addition, there is a slight disorganization of axon fascicles and a defective nerve cord condensation. This suggests that RK2 is not required for early glial determination, but rather for aspects of glial differentiation or function that are required for embryonic viability.

Amino Acid Sequence↗

Successful treatment of ARDS with two doses of synthetic surfactant.

A 50-year-old man with adult respiratory distress syndrome (ARDS) was successfully treated with synthetic surfactant. The therapy rapidly improved the respiratory function; it also increased the release of endogenous surfactant. Synthetic surfactant may thus be of value in the treatment of ARDS.

Drug Combinations↗