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S Andersson

Publications and source records attributed to S Andersson.

At least 181 records · Page 10Linked to original sources
PubMed1993

Expression cloning and characterization of human 17 beta-hydroxysteroid dehydrogenase type 2, a microsomal enzyme possessing 20 alpha-hydroxysteroid dehydrogenase activity.

17 beta-Hydroxysteroid dehydrogenase (17 beta-HSD) is an enzyme crucial to the regulation of intracellular levels of biologically active steroid hormones in a variety of tissues. Here, we report the isolation, structure, and characterization of a cDNA encoding the human 17 beta-HSD type 2. A 1.4-kilobase cDNA was identified, and DNA sequence analysis indicated that 17 beta-HSD type 2 was a protein of 387 amino acids with a predicted molecular weight of 42,782. The protein contained an amino-terminal type II signal-anchor motif and a carboxyl-terminal endoplasmic reticulum retention motif, which suggested that 17 beta-HSD type 2 was associated with the membranes of the endoplasmic reticulum. 17 beta-HSD type 2 was capable of catalyzing the interconversion of testosterone and androstenedione as well as estradiol and estrone. The enzyme also demonstrated 20 alpha-HSD activity toward 20 alpha-dihydroprogesterone. The amount of 17 beta-HSD type 2 mRNA in placenta was found to be high. The data suggest that the 17 beta-HSD type 2 cDNA encodes the microsomal 17 beta-HSD of human placenta, described by several laboratories.

17-Hydroxysteroid Dehydrogenases↗
PubMed1993

LY191704: a selective, nonsteroidal inhibitor of human steroid 5 alpha-reductase type 1.

Androgens, in particular dihydrotestosterone (DHT), play a key role in differentiation, growth, and maintenance of the mammalian prostate. Production of DHT from testosterone is catalyzed by two distinct membrane-bound steroid 5 alpha-reductase [5 alpha-reductase; 3-oxo-5 alpha-steroid delta 4-dehydrogenase; 3-oxo-5 alpha-steroid:(acceptor) delta 4-oxidoreductase, EC 1.3.99.5] isozymes designated types 1 and 2. Benign prostatic hyperplasia (BPH), a disease that occurs almost universally in males, is characterized by obstructive and irritative urinary voiding symptoms and has been associated with an overproduction of DHT. Recently, steroidal inhibitors of 5 alpha-reductase type 2 have been used successfully for treatment of BPH. Described here is a nonsteroidal inhibitor of 5 alpha-reductase type 1, LY191704 (8-chloro-4-methyl-1,2,3,4,4a,5,6,10b-octaahydro-benzo[f]quinol in-3(2H)-one). This compound was identified based on its capacity to inhibit 5 alpha-reductase activity in a human genital skin fibroblast cell line (Hs68). Surprisingly, LY191704 is inactive when tested in freshly isolated prostate cells obtained from subjects with BPH, whereas previously described 4-azasteroids are active. LY191704 is, however, a potent inhibitor of the 5 alpha-reductase activity of BPH cells that have been maintained in culture. Analysis of human and rat 5 alpha-reductases expressed from transfected cDNAs in simian COS cells indicates that LY191704 is a specific noncompetitive inhibitor of the human 5 alpha-reductase type 1. Taken together, the results suggest that prostate cells have the capacity to express both 5 alpha-reductase isozymes and that LY191704 may be useful in treatment of human endocrine disorders associated with overproduction of DHT by 5 alpha-reductase type 1.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1993

Estimation of the number of enantioselective sites of bovine serum albumin using frontal chromatography.

On a column with bovine serum albumin (BSA) immobilized covalently to silica, the adsorption isotherms of the enantiomers of mandelic acid, tryptophan, 2-phenylbutyric acid, and N-benzoylalanine are measured using a buffered mobile phase. Knowing the amount of BSA immobilized on the column (36 mg), the ratio of the number of enantiomer molecules needed to saturate the enantioselective retention mechanism to the number of BSA molecules is determined. The mean of the set of eight enantiomers is 0.28. These data confirm that at most one enantioselective site exists for each BSA molecule for the kind of enantiomers studied.

Adsorption↗
PubMed1993

Disposition of olsalazine and metabolites in breast milk.

This study examined the disposition of olsalazine and its metabolites into breast milk after the ingestion of a single dose of 500 mg olsalazine. Blood and serum samples were obtained for 48 hours after the ingestion of 500 mg olsalazine in a 39-year-old lactating woman. Blood samples were obtained at .0, .5, 1, 2, 4,6, 24.5, 26, and 48 hours. Maternal milk samples were obtained at .0, .5, 2, 4, 6, 14, 24, 28, 36, and 48 hours. Olsalazine and olsalazine-S underwent high-pressure liquid chromatography analysis, and 5-ASA and Ac 5-ASA underwent fluorometric detection. Acetylated-5-ASA achieved concentrations of .8, .86, and 1.24 mumol/L in breast milk at 10, 14, and 24 hours, respectively. Olsalazine, olsalazine-S, and 5-ASA were undetectable in the breast milk for 48 hours after drug administration. Clinically significant drug exposure in the breast-fed infant is unlikely after a maternal single dose of olsalazine. Idiosyncratic hypersensitivity, however, remains a possibility even if the infant is exposed to only minute quantities.

Administration, Oral↗
PubMed1993

Atrial natriuretic factor and pulmonary status in premature infants with respiratory distress syndrome: preliminary investigation.

We studied the correlation of atrial natriuretic factor (ANF) with lung compliance in a series of 16 premature infants with respiratory distress syndrome (RDS). The infants were followed during the first week of life by sequential Doppler echocardiography, lung compliance, and ANF measurements. Plasma ANF concentration varied between 38 and 2220 pg/mL; mean concentrations of 393 and 123 pg/mL with the ductus open and with it closed, respectively (P < 0.01). The arteriolar/alveolar oxygen-tension ratio showed an inverse correlation with the logarithm (In) of the ANF concentration (r = -0.55, P = 0.0002). Both mean airway pressure and In ANF showed an inverse correlation with the arteriolar/alveolar oxygen tension ratio (R = -0.77, F = 20.5 and 13.8, respectively). Plasma ANF was inversely correlated to lung compliance (r = -0.64, P < 0.0001). In infants with RDS, plasma ANF concentrations increase with the severity of respiratory distress. Because ANF increases endothelial permeability, in this preliminary investigation lead to the hypothesis that it may contribute to respiratory distress by causing extravasation of fluid from the pulmonary circulation in these patients.

Atrial Natriuretic Factor↗
PubMed1993

Evolution of the dec-1 eggshell locus in Drosophila. II. Intraspecific DNA sequence analysis reveals length mutations in a repetitive region in D. melanogaster.

The dec-1 eggshell gene in Drosophila melanogaster encodes follicle cell proteins required for proper eggshell assembly. As shown by Southern and Northern analyses the dec-1 gene occurs in four alleles (Fc1-4) among wild-type strains. Its second exon has a distinct feature in the form of 12 repeats with 78-91 nucleotides; the first five show nearly 100% homology. DNA sequence comparison of the repeated region of the alleles revealed that the length polymorphisms are caused by changes in the numbers of the first five repeats. The results suggest that the alleles have been generated by unequal intragenic crossing-over and/or slippage during DNA replication and that the allelic length variants have arisen independently. The possibility that the most common allele, FC1, has a selective advantage over the other alleles is discussed.

Alleles↗
PubMed1993

Methacholine reactivity and asthma. Report from the Northern Sweden Obstructive Lung Disease Project.

Methacholine tests were used in an epidemiologic study of the prevalence of asthma and chronic bronchitis in northern Sweden. Of 6610 subjects in three age groups from eight representative geographic areas in the northernmost province of Sweden, 5698 (86%) completed a postal questionnaire on respiratory symptoms, and 1506 underwent a structured interview and a lung function test. A total of 292 (5%) were diagnosed as having asthma. A subsample of 284 subjects (of 320 invited) classified at the interview as having asthma (n = 98) or as having respiratory symptoms that might be due to asthma but not fulfilling the interview criteria for the diagnosis of asthma (n = 186) underwent a methacholine test. Subjects who, before the interview study, already had a well-defined asthma diagnosis were not invited to the methacholine testing. Of those 98 subjects classified as having asthma, 61% reacted to methacholine doses < or = 4 mg/ml and 79% to doses < or = 8 mg/ml, while the corresponding figures in the symptomatic but nonasthma group were 20% and 34%, respectively. The results show that a carefully performed structured interview accurately diagnoses asthma in epidemiologic studies. The methacholine tests provide important diagnostic information primarily in subjects in whom the medical history is equivocal.

Adult↗
PubMed1993

Haemolysis in adult and neonatal erythrocytes caused by autoxidation of lipid emulsion (Intralipid).

Lipid emulsion (Intralipid) causes free radical-mediated damage to human cells in vitro. Incubation with 0.44% Intralipid for 17 h caused 40.3 +/- 3.8% haemolysis in adult human erythrocytes and 26.5 +/- 8.1% in erythrocytes from term newborns (p = 0.0001). In adult erythrocytes mean corpuscular volume increased 68.7 +/- 8.2% and in newborn erythrocytes 54.8 +/- 10.4% (p = 0.0012). Initial concentrations of reduced glutathione in adult and newborn erythrocytes were 65.1 +/- 2.5 and 62.1 +/- 4.0 mg/dl, respectively (ns); after incubation, glutathione concentrations were 21.0 +/- 4.0 and in 25.7 +/- 5.2 mg/dl in adult and newborn erythrocytes, respectively (p = 0.0004). After incubation the concentrations of thiobarbituric acid reactive material and conjugated dienes in newborn erythrocytes (2.8 +/- 0.2 microM and 0.223 +/- 0.019 OD 233, respectively) were higher than those of adult erythrocytes (2.1 +/- 0.4 microM and 0.138 +/- 0.012 OD 233) (p = 0.0001). In both adult and newborn erythrocytes, the effects of Intralipid were significantly inhibited by 0.6 mM deferroxamine or 8 mM sodium etidronate. Despite higher susceptibility to lipid peroxidation of the cell membrane, newborn erythrocytes are more resistant than adult erythrocytes to free radical-mediated effects such as depletion of intracellular glutathione, cell swelling and haemolysis.

Adult↗
PubMed1993

Somatostatin regulation of beta-cell function in the normal human fetuses and in neonates with persistent hyperinsulinemic hypoglycemia.

To investigate the insulin-inhibitory effects of somatostatin during fetal development, and the defective regulation of insulin release in persistent hyperinsulinemic hypoglycemia of infancy (PHHI), we made perifusion experiments with islet-like cell clusters obtained from 14 human fetal pancreases (HFP) before 20 weeks of gestation and 6 neonates pancreatectomized because of PHHI (5 cases of diffuse and 1 adenomatous islet cell hyperplasia). Somatostatin-14 (600 nmol/L) suppressed insulin release only marginally (20% and 25% suppression in 2 and 20 mmol/L glucose, respectively) in HFP, whereas supplementation of the perifusate with 14 nmol/L glucagon potentiated the suppression to 57%. Somatostatin-28 (600 nmol/L) caused a 35% inhibition in insulin release from the HFP. In static incubation of HFP, somatostatin-14 caused a weak dose-dependent inhibition of insulin release, but had no effect on (pro)insulin biosynthesis. In the PHHI infants, somatostatin infusion suppressed hyperinsulinemia effectively before pancreatectomy. In vitro, 600 nmol/L somatostatin-14 suppressed insulin release clearly better than in the HFP experiments (35-61% inhibition). Glucose (20 mmol/L) induced a 2- to 3-fold increase in insulin release in two clinically mild cases of PHHI, but no response at all in the four others. We conclude that human fetal beta-cells are relatively insensitive to somatostatin, possibly because of low cellular cAMP levels. Furthermore, insulin release from PHHI cells is poorly stimulated by glucose but effectively blocked by somatostatin, supporting the concept of somatostatin deficiency in PHHI.

Abortion, Induced↗
PubMed1993

ScrippsHealth: quality planning for clinical processes of care.

UNLABELLED: Project Overview: In 1991, Scripps Memorial Hospital developed clinical pathways (called CareTracs) for four DRGs in cardiovascular surgery (DRGs 104, 105, 106, and 107) in order to stabilize those clinical processes, collect data on them, and make improvements. KEY FINDINGS: In the first six months the CareTracs were in place, lengths of stay decreased by 20 to 30 percent and charges were reduced by approximately 20 percent. Patients in DRG 107 (coronary artery bypass graft without cardiac catheterization), on average, now spend less time in ICU and are extubated sooner -- improvements that have, in turn, reduced the incidence of nosocomial pneumonia.

California↗
PubMed1993

Randomized double-blind study of liposomal amphotericin B (Ambisome) prophylaxis of invasive fungal infections in bone marrow transplant recipients.

Invasive fungal infection is a problem in patients undergoing bone marrow transplantation (BMT). To determine if a liposomal formulation of amphotericin B (Ambisome) is safe and can prevent fungal infection we performed a placebo controlled double-blind randomized prophylactic trial. Study drug was administered from when neutrophil count had decreased to < 0.5 x 10(9)/l and was continued until neutrophils recovered to this level or an infection or toxicity end-point was reached. Thirty-six patients received 1 mg/kg/day of ambisome and 40 patients received placebo daily. There were no statistical differences in characteristics or clinical course between the two groups. Fungal colonization decreased in the ambisome group while it increased in the placebo group. By the end of prophylaxis 8 of 24 (33%) patients receiving ambisome were colonized compared with 18 of 29 (62%) placebo patients (p = 0.05). Five and 7 patients on ambisome or placebo, respectively, were withdrawn due to a presumed fungal infection (NS). There was no statistical reduction of autopsy-proven fungal infection. Proven fungal infection occurred in one patient receiving ambisome (C. guillermondi) compared with three patients receiving placebo (C. guillermondi, 2; C. albicans, 1). Ambisome was well tolerated at the dose of 1 mg/kg/day but in three patients allergic reactions were observed.

Adolescent↗
PubMed1993

A prospective study of vertical transmission of HIV-2 in Bissau, Guinea-Bissau.

OBJECTIVES: To determine the vertical transmission rate of HIV-2 and clinical findings associated with vertically transmitted HIV-2 infection. DESIGN: A prospective study of HIV-2 transmission in children of HIV-2-seropositive mothers, and a comparison of clinical findings between children of seropositive and seronegative mothers. SETTING: Recruitment of women delivering at the national hospital in Bissau, Guinea-Bissau. Follow-up by home visits. SUBJECTS AND METHODS: Eighty-six newborns of 82 HIV-2-seropositive mothers and a control group of 102 newborns of HIV-seronegative mothers were followed-up clinically and by HIV serology until the children reached the age of 20 months. RESULTS: Of the 86 children of seropositive mothers, 51 had a complete follow-up, 22 died and 13 were lost due to change of residence. Of the 102 children of seronegative mothers, 63 had a complete follow-up, 13 died and 26 were lost due to change of residence. None of 51 children of seropositive mothers had serological evidence of HIV-2 infection at the end of the follow-up period. There was no significant difference in the frequency of clinical symptoms between the children in the study group and the children in the control group. The mortality during the first year of life was not significantly different between the children of seropositive and seronegative mothers (13 out of 80 and 11 out of 94, respectively, P > 0.05, excluding children lost to follow-up). Only three of the dead children of seropositive mothers and one of the dead children of seronegative mothers had any symptoms that might be related to HIV-2 infection (diarrhoea > 1 month). CONCLUSION: Vertical transmission of HIV-2 appears to be rare.

Child, Preschool↗
PubMed1992

Determination of coenzyme Q by non-aqueous reversed- phase liquid chromatography.

A non-aqueous reversed-phase liquid chromatographic method for determination of coenzyme Q10 in pharmaceutical formulations has been developed. The reversed-phase system provides better reproducibility and better selectivity for the separation of coenzyme Q10 analogues and degradation products than studied normal-phase systems. Furthermore, the non-aqueous mobile phase showed a very good solubility and provides a greater variety of work-up solvents for the lipophilic formulations than aqueous mobile phases. Validation studies showed detector response linearity over a concentration range of 0.2-100 micrograms/ml. The lower limit of detection was 2 ng on-column. The intra-assay precision (relative standard deviation) for a soybean oil formulation was 2.0% (n = 11).

Chromatography, High Pressure Liquid↗
PubMed1992

[Amantadine in cognitive failure in patients with traumatic head injuries].

In patients with severe cerebral injuries, attentional dysfunction may cause greater difficulties for rehabilitation than neurological deficits. These functions seem to be controlled by catecholaminergic neural systems in the central nervous system. Dopamine agonists have therefore been recently introduced in the treatment of these patients. We describe two patients treated with amantadine in daily doses of 200-400 mg. We observed improvement of cognitive functions such as visual attention, speed of information processing, attentional span, learning capacity and alertness. We stress the value of amantadine as a treatment adjuvant in patients with severe attentional deficits following injury of the brain.

Adult↗
PubMed1992

The enzymatic synthesis of membrane glucolipids in Acholeplasma laidlawii.

In membranes of the prokaryote Acholeplasma laidlawii, the physiological regulation of the two major membrane lipids, monoglucosyldiacylglycerol (MGlcDAG) and diglucosyldiacylglycerol (DGlcDAG), is governed by factors affecting the equilibria between lamellar and non-lamellar phases of the membrane lipids. The synthesis of the glucolipids is considered to be a two-step glucosylation: (i) DAG+UDP-Glc----MGlcDAG+UDP; and (ii) MGlcDAG+UDP-Glc----DGlcDAG+UPD. This was corroborated by in vivo pulse labelling experiments showing turnover of MGlcDAG but not DGlcDAG. The enzymatic synthesis of MGlcDAG was localized to fresh or freeze-dried membranes in vitro. Synthesis of DGlcDAG was minor in such membranes but of substantial magnitude in intact cells. Synthesis of MGlcDAG was stimulated by small amounts of SDS but completely inhibited upon solubilization of the membranes by a variety of detergents. The inhibitory effect of several UDP-Glc analogs on glucolipid synthesis demonstrated the importance of UDP-Glc as the sugar donor. Synthesis of both glucolipids was lost in freeze-dried plus lipid-extracted cells but restored when lipids were transferred back to the extracted cell membrane. By selectively adding specific lipids, a strong dependence on the acceptor lipid DAG, as well as the need for general matrix lipids for enzyme activity, was established. In addition, the anionic phosphatidylglycerol (PG), but not the other phospholipids, had a strong stimulatory effect. The presence of different phosphorylating agents stimulated the synthesis of DGlcDAG and partially inhibited that of MGlcDAG. This, together with the lipid dependency, may constitute mechanisms for the regulation of the enzyme activities in vivo.

Acholeplasma laidlawii↗