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J Gustafsson

Publications and source records attributed to J Gustafsson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Structural basis for calcium binding by uteroglobins.

Uteroglobins, i.e. proteins with similar three-dimensional structure and ligand binding specificity to uteroglobin from rabbit uterus, have been found in rat, mouse and human lung. We have recently demonstrated the binding of calcium by human uteroglobin, and we have therefore tried to find potential binding sites for metals in the three-dimensional structure of uteroglobin by the use of two different computational procedures. A putative binding site for calcium in uteroglobin was identified by means of a hydrophobic contrast function. The spatial disposition of atoms that could ligand calcium in the putative calcium-binding site appears similar to that of the primary calcium-binding site of secretory phospholipase A2 enzymes, consisting of the carboxyl group of an aspartic acid residue and a loop providing three backbone carbonyl oxygens. From inspection of their primary sequences and three-dimensional structures, it became clear that this putative calcium-binding motif is conserved among uteroglobins from different species. The potential significance of the predicted site was investigated by site-directed point mutagenesis of human uteroglobin in which Asp46 was replaced by Asn or Lys. In both mutants, the ruthenium red and 45Ca2+ binding was significantly reduced. Sodium dodecyl sulphate/polyacrylamide gel electrophoresis under non-reducing conditions indicated that the mutant proteins had the expected molecular masses and that their ability to dimerize was not disturbed by these mutations. Valence calculations also identified the putative calcium-binding site, but only after optimization of its conformation by the use of molecular dynamics with a restrained calcium ion. Our results support the notion that Asp46 of uteroglobins acts as a "cap" residue in a calcium-binding site structurally similar to the primary calcium binding sites of phospholipases A2.

Amino Acid Sequence↗
PubMed1996

Chromatographic fractionation and analysis by mass spectrometry of conjugated metabolites of bis(2-ethylhexyl)phthalate in urine.

Mono(2-ethylhexyl)phthalate (MEHP), the primary metabolite of the plasticizer bis(2-ethylhexyl)phthalate (DEHP), was given to guinea pigs and mice and the methods for the isolation, separation and analysis of its metabolites in urine were developed. Following solid-phase extraction with octadecylsilane-bonded silica, individual metabolites were purified and separated using a combination of ion-exchange chromatography on lipophilic gels and reversed-phase high-performance liquid chromatography. Analysis of intact conjugates, as well as nonconjugated metabolites, was performed by fast atom bombardment mass spectrometry (FAB-MS) and, after derivatization, by gas chromatography-mass spectrometry. Enzymatic methods were used for further characterization. The study confirms glucuronidation as the major conjugation pathway for MEHP in the investigated species. Although less important quantitatively, glucosidation is shown to be an alternative conjugation pathway in mice. The methods developed were applied to a sample of urine from a hyperbilirubinemic newborn infant subjected to DEHP-exposure in conjunction with an exchange transfusion. It was demonstrated that metabolites of DEHP were excreted in amounts which could be analyzed by FAB-MS.

Animals↗
PubMed1996

Glycerol carbon contributes to hepatic glucose production during the first eight hours in healthy term infants.

The newborn infant must mobilize endogenous substrate stores to meet the requirements of glucose-dependent organs. High concentrations of free fatty acids and glycerol, and a rapid decrease in the respiratory quotient, indicate that lipids are an important fuel soon after birth. The purpose of the present study was to determine the onset of lipolysis and gluconeogenesis from glycerol in healthy, term, unfed infants. Eight infants were studied from a postnatal age of 3.5 +/- 0.5 h to 7.4 +/- 0.2 h using [6,6-2H2] glucose and [2-13C]glycerol analysed by gas chromatography/mass spectrometry. Plasma concentrations of glucose, glycerol and insulin averaged 2.9 +/- 0.4 mM, 369 +/- 89 microM and 9.4 +/- 9.4 +/- 3.7 microU.ml-1, respectively. The hepatic glucose production rate averaged 25.0 +/- 3.5 mumol.kg-1 min-1 (4.5 +/- 0.6 mg.kg-1.min-1) and the endogenous plasma appearance rate of glycerol 8.7 +/- 1.2 mumol.kg-1.min. On average, 57.9 +/- 8.4% of the glycerol was converted to glucose, representing 11.1 +/- 2.3% of hepatic glucose output. Thus, lipolysis and gluconeogenesis from glycerol are established within the first 8 h of life in term infants.

Blood Glucose↗
PubMed1996

Growth and pubertal development in Down syndrome.

Growth retardation and gonadal insufficiency are well-known features of Down syndrome. In this longitudinal study, 44 home-reared children and adolescents with Down syndrome, aged 10-24 years, living in the county of Uppsala, were followed yearly. The male patients had a mean final height above that reported previously, and a close correlation between target and final heights was found. The mean final height in the female patients was below that reported earlier. Mean peak height velocities in males and females were 8.5 and 7.3 cm year-1, respectively, significantly lower than in healthy children. The mean ages at peak height velocity were 12.3 and 10.8 years, respectively, indicating early growth spurts. The serum follicle-stimulating hormone concentrations, the small testes and the negative correlation between luteinizing hormone and testicular volume in the males may indicate some primary gonadal insufficiency. For the girls, mean menarcheal age corresponded closely to that of their mothers.

Adolescent↗
PubMed1996

Increased perinatal intracranial pressure and prediction of early puberty in girls with myelomeningocele.

An increased risk of developing precocious puberty has been reported in children with myelomeningocele. In order to evaluate this further and to study factors associated with early or precocious puberty the medical records of all girls with myelomeningocele, born from 1970 onwards (n = 64), who were admitted to our unit were reviewed. Early/precocious puberty (E/PP) was defined as breast development or pubic hair corresponding to Tanner stage 2 before the age of 9.2 years. In 32 out of 62 cases data were sufficient for evaluation of the timing of puberty. Twenty girls had E/PP and 12 girls normal timing of puberty. In the girls who had reached the age of 9.2 years the incidence of E/PP was at least 52%. Girls with E/PP had a higher incidence of hydrocephalus, were treated with intraventricular shunts more often, and had significantly higher frequency of increased intracranial pressure during the perinatal period (p < 0.05, p < 0.01, and p < 0.001, respectively). The group of girls developing E/PP was also more severely disabled with respect to motor and urological function and had more shunt revisions. In conclusion, E/PP in girls with myelomeningocele is strongly associated with increased intracranial pressure particularly during the perinatal period.

Child↗
PubMed1996

Extremely preterm infants (< 28 weeks) are capable of gluconeogenesis from glycerol on their first day of life.

Extremely preterm infants have been shown capable of producing glucose at a rate comparable to that of term infants, but virtually no data are available on their capacity for lipolysis and gluconeogenesis. To address this issue, we studied the flux of glycerol and its gluconeogenic contribution to hepatic glucose output by determining the endogenous plasma appearance rate of glycerol (glycerol Ra) and its conversion to glucose in 10 newborn infants, 24-27 wk of gestational age. The study was performed during the 1st d of life by tracer dilution technique using [6,6-2H2]glucose and [2-13C]glycerol given as constant rate i.v. infusions. Plasma isotopic enrichments of the tracers were obtained by gas chromatography/mass spectrometry. Endogenous glycerol Ra ranged from 2.4 to 21.6 (median 5.0) mumol.kg-1.min-1, of which 31.5% (25.6-64.4%) was converted to glucose. The glucose production rate averaged 17.5 +/- 5.4 mumol.kg-1.min-1 (3.2 +/- 1.0 mg.kg-1.min-1), of which 5.0% (1.6-37.6%) was derived from glycerol. The results show that extremely preterm infants, despite limited fat stores, are capable of generating glycerol at a rate within the range reported for term and near term newborns. The infants were also capable of converting part of this glycerol to glucose, providing a contribution to hepatic glucose production comparable to that found in more mature newborns.

Birth Weight↗
PubMed1996

Improved final height in girls with Turner's syndrome treated with growth hormone and oxandrolone.

The spontaneous growth process in Turner's syndrome is characterized by a progressive decline in height velocity during childhood and no pubertal growth spurt. Therefore, therapy aimed at improving height during childhood as well as increasing final height is desirable for most girls with Turner's syndrome. Forty-five girls with Turner's syndrome, 9-16 yr of age (mean age, 12.2 yr), were allocated to three study groups. Group 1 (n = 13) was initially treated with oxandrolone alone; after 1 yr of treatment, GH without (group 1a; n = 6) or with (group 1b; n = 7) ethinyl estradiol was added. Group 2 (n = 17) was treated with GH plus oxandrolone. Group 3 (n = 15) was treated with GH, oxandrolone, and ethinyl estradiol. The dosage were: GH, 0.1 IU/kg.day; oxandrolone, 0.05 mg/kg.day; and ethinyl estradiol, 100 ng/kg.day. A height of 150 cm or more was achieved in 61%, 75%, and 60% of the girls in groups 1, 2, and 3, respectively. The most impressive increase in height was seen in group 2. In this group the mean final height was 154.2 cm (SD = 6.6), which is equivalent to a mean net gain of 8.5 cm (SD = 4.6) over the projected final height. In group 3, in which ethinyl estradiol was included from the start of therapy, the initially good height velocity decelerated after 1-2 yr of treatment. Their mean final height was 151.1 (SD = 4.6) cm, equivalent to a mean net gain of 3.0 cm (SD = 3.8). A similar growth-decelerating effect of ethinyl estradiol was seen in group 1b. We conclude that in girls with Turner's syndrome who are older than 9 yr of age, treatment with GH in combination with oxandrolone results in significant growth acceleration, imitating that in normal puberty, leading to a more favorable height during childhood. This mode of treatment also results in a significantly increased final height, permitting a great number of the girls to attain a final height of more than 150 cm. However, early addition of estrogen decelerates the height velocity and reduces the gain in height.

Adolescent↗
PubMed1995

Complexes between cationic liposomes and DNA visualized by cryo-TEM.

The association structures formed by cationic liposomes and DNA-plasmids have been successfully employed as gene carriers in transfection assays. In the present study such complexes was studied by cryo-TEM (cryo-transmission electron microscopy). Cationic liposomes made up by DOPE (dioleoylphosphatidylethanolamine) and various amounts of three different cationic surfactants were investigated. The cryo-TEM analysis suggests that an excess of lipid in terms of charge, leads to entrapment of the DNA molecules between the lamellas in clusters of aggregated multilamellar structures. With increasing amounts of DNA free or loosely bound plasmids were found in the vicinity of the complexes. The importance of the choice of surfactant, as reported from many transfection assays, was not reflected in changes of the type of DNA-vesicle association. A tendency towards polymorphism of the lipid mixtures is reported and its possible implications are discussed.

Cations↗
PubMed1995

Thyroid antibodies are not a risk factor for pregnancies with Down syndrome.

The observation that thyroid disease is frequent in mothers of children with Down syndrome (DS) has suggested that maternal thyroid antibodies could be a factor predisposing to trisomy 21 in their offspring. In this study, the incidences of thyroglobulin (Tg) and thyroid peroxidase (TPO) antibodies were analysed with a sensitive solid-phase immunosorbent radioassay in sera from 29 mothers giving birth to children with trisomy 21 and 87 control mothers. The serum samples were collected at delivery. There was no statistical difference regarding the proportion of thyroid antibodies (against Tg and/or TPO) in the two groups. Thyroid antibodies were detected in 6/29 (20.7 per cent) of the DS mothers and in 23/87 (26.4 per cent) of the control mothers. Among the women with thyroid antibodies, 4/6 (66.7 per cent) of the DS mothers and 12/23 (52 per cent) of the control mothers had antibodies against both Tg and TPO. There was no increase in the relative risk of having a child with DS if the titre of either Tg or TPO antibodies or both were positive, i.e. > or = 1/5. The results indicate that the presence of thyroid antibodies in the serum of a pregnant women has no prognostic value for the birth of an infant with DS.

Adult↗
PubMed1995

Thyroid autoantibodies, Turner's syndrome and growth hormone therapy.

The prevalence of thyroid autoantibodies, i.e. thyroglobulin antibodies and antibodies to thyroid peroxidase, was analyzed in 89 girls, aged 3-16 years (mean age 10 years), with Turner's syndrome. The analyses were performed before the start of growth-promoting treatment and during a follow-up period of 1-5 years. The patients were divided into four groups according to karyotype as follows: group 1, 45, X (n = 63); group 2 with structural abnormalities of the X chromosome (n = 10); group 3 with mosaicism but no structural abnormalities of the X chromosome (n = 10); and group 4, with isochromosome X of the long arm (n = 12): 199 healthy girls aged 12 years, served as controls. Thyroid autoantibodies were demonstrated in 46 of 89 (52%) patients with Turner's syndrome compared with 34 of 199 (17%) age-matched control girls (p < 0.001), thus confirming the relationship between thyroid abnormalities and Turner's syndrome. There was also an increase in the prevalence of thyroid antibodies with age. Simultaneous presence of both autoantibodies was significantly more frequent in group 1 (45, X) and group 4 (isochromosome X of the long arm) than in group 3 (mosaicism) (p = 0.04 and p < 0.002, respectively) and significantly more frequent in group 4 than in group 1 (p < 0.05). During 12-60 months of growth-promoting treatment, no increase in the prevalence of thyroid antibodies was observed. The findings demonstrate the importance of continuous monitoring of thyroid function in girls with Turner's syndrome.

Adolescent↗
PubMed1995

Identification of the main gonadal autoantigens in patients with adrenal insufficiency and associated ovarian failure.

Autoimmune adrenal insufficiency is associated with premature ovarian failure at frequencies of 10-20%. In these patients a reactivity against an unknown steroid cell antigen in both the adrenal glands and gonads has been described. We have recently identified the cytochrome P450 enzyme 21-hydroxylase and the side-chain cleavage enzyme (SCC) as the major adrenal autoantigens in Addison's disease and the rare autoimmune polyendocrine syndrome type I (APS-I), respectively. In an attempt to identify the steroid cell antigen, sera from patients with Addison's disease (n = 13) and APS-I (n = 7) that reacted with Leydig cells were selected. Preparations of isolated human granulosa cells, isolated rat Leydig cells, and fractions of human placenta were used in Western blots. All sera were also tested against bacterially expressed 21-hydroxylase, SCC, and 17 alpha-hydroxylase. The SCC was recognized by sera from patients with Addison's disease and those with APS-I. In addition, a majority of the sera (n = 12) reacted with a novel 51-kilodalton autoantigen present in granulosa cells and placenta. The results show that the steroid cell autoantigen consists mainly of the SCC and a novel protein of unknown function.

Addison Disease↗
PubMed1994

Autoantibodies against a novel 51 kDa islet antigen and glutamate decarboxylase isoforms in autoimmune polyendocrine syndrome type I.

Beta-cell function and islet cell antibodies were studied in six patients with autoimmune polyendocrine syndrome type I. All suffered from mucocutaneous candidiasis, five had adrenocortical insufficiency and three hypoparathyroidism. All sera contained high titres of antibodies staining islets of Langerhans. Reactivity against glutamate decarboxylase, predominantly the 65 kDa isoform, was detected by immunoprecipitations and Western blots in five of the six sera, and all six sera immunoprecipitated a 51 kDa antigen from [35S]-methionine labelled rat islet cell lysates. No reactivity against this latter antigen was found in sera of patients with Type 1 (insulin-dependent) diabetes mellitus (n = 9), Graves' disease (n = 5), autoimmune gastritis (n = 4), idiopathic Addison's disease (n = 7), or stiff-man syndrome (n = 2). The 51 kDa antigen was also detected by Western blots using homogenates of rat islets and autoimmune polyendocrine syndrome type I patient sera, whereas no such reactivity was found with homogenates of testes, adrenals, small intestine, spleen, exocrine pancreas or brain. Moreover, the 51 kDa antigen was present in the rat insulinoma cell line RINm 5F but not in the SV-40 transformed, monkey kidney cell line COS, when examined by immunoprecipitations of [35S]-methionine labelled cell lysates and by Western blots. None of the patients with autoimmune polyendocrine syndrome type I had symptoms of diabetes and their insulin responses to glucose challenge were normal. The data illustrate that patients with autoimmune polyendocrine syndrome type I present an autoimmune response against islets of Langerhans, which is apparently different from that associated with classic Type 1 diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Inter-relationship between serum concentrations of glucose, glucagon and insulin during the first two days of life in healthy newborns.

The relationship between serum concentrations of glucose, insulin and glucagon during the first two days of life was studied in healthy newborns. The first capillary blood sample was obtained at 3-15 h of age (median 6 h; day 0) and a second sample approximately 24 h later (day 1). Serum glucose concentrations in the first sample averaged 2.1 +/- 0.07 mmol/l (mean +/- SEM; n = 60) and were positively correlated with postnatal age (p < 0.01). Serum glucagon concentrations in the first sample averaged 570 +/- 32 pg/ml and were inversely correlated with glucose concentrations (p < 0.0001). At the second sampling, serum glucose concentrations had increased to 2.9 +/- 0.07 mmol/l (p < 0.001; n = 57) and serum glucagon concentrations had decreased to 403 +/- 22 pg/ml (p < 0.001). Serum insulin concentrations were 11.7 +/- 0.3 microU/ml and 10.2 +/- 0.3 microU/ml at the two samplings and did not correlate with serum glucose concentrations. The relationship of serum glucose and hormone concentrations to maternal and infant characteristics was studied by stepwise regression analysis. Serum glucose concentration on day 0 was positively correlated with postnatal age (p < 0.01) and birth weight (p < 0.05) but inversely correlated with duration of labour (p < 0.05). Serum glucose concentration on day 1 was positively correlated with birth weight (p < 0.0001) and inversely correlated with maternal prep-pregnancy weight (p < 0.05). Similar analyses of serum hormone concentrations did not demonstrate any relationships with maternal or infant characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1994

Very immature infants (< or = 30 Wk) respond to glucose infusion with incomplete suppression of glucose production.

Small substrate stores and immature enzyme systems make preterm infants prone to develop hypoglycemia. Hyperglycemia may also occur, particularly when these infants are given i.v. glucose. To evaluate the capacity for regulation of glucose production in response to glucose infusion, 10 newborn infants, born after 25-30 wk of gestation, were studied. Their glucose production rates (GPR) were calculated and the concentrations of glucose, insulin, and glucagon in plasma were measured during infusion of glucose at a rate of first 1.7 +/- 0.2 and then 6.5 +/- 0.3 mg.kg-1.min-1 (9.4 +/- 1.1 and 36.1 +/- 1.7 mumol.kg-1.min-1) (mean +/- SD). GPR was determined by use of D-6,6-2H2-glucose. When the rate of infusion of glucose was increased, GPR decreased from 4.3 +/- 1.3 to 1.4 +/- 1.1 mg.kg-1.min-1 (23.9 +/- 7.2 to 7.8 +/- 6.1 mumol.kg-1.min-1) (mean +/- SD) (p = 0.00006). In addition, the plasma insulin concentration increased from 6 +/- 2 to 11 +/- 4 microU.mL-1 (p = 0.006) and the plasma glucose concentration from 3.6 +/- 1.1 to 6.1 +/- 1.3 mM (mean +/- SD) (p = 0.0002), whereas the glucagon concentration remained unchanged. Only the insulin concentration in plasma was significantly related to GPR. The results show that very immature newborn infants have an incomplete and varying capacity to respond to glucose infusion with suppression of glucose production. Insulin seems to be more important than plasma glucose in the regulation of glucose homeostasis in these infants.

Analysis of Variance↗