Biomedical subjects

Jan Gustafsson

Publications and source records attributed to Jan Gustafsson.

16 recordsLinked to original sources

PubMed2007

Pituitary autoantibodies in autoimmune polyendocrine syndrome type 1.

Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene. High titer autoantibodies (Aabs) toward intracellular enzymes are a hallmark for APS1 and serve as diagnostic markers and predictors for disease manifestations. In this study, we aimed to identify pituitary autoantigens in patients with APS1. A pituitary cDNA expression library was screened with APS1 sera and a tudor domain containing protein 6 (TDRD6) cDNA clone was isolated. Positive immunoreactivity against in vitro translated TDRD6 fragments was shown in 42/86 (49%) APS1 patients but not in patients with other autoimmune diseases or in healthy controls. By using immunohistochemistry, sera from 3/6 APS1 patients with growth hormone (GH) deficiency showed immunostaining of a small number of guinea pig anterior pituitary cells, and 40-50% of these cells were GH-positive. No such immunostaining was seen with sera from healthy controls. The APS1 Aab-positive, GH-negative cells may represent a novel subpopulation of anterior pituitary cells. In addition, 4/6 patient sera showed staining of a fiber-plexus in the pituitary intermediate lobe recognizing enzymes of monoamine and GABA synthesis. Thus, we have identified TDRD6 as a major autoantigen in APS1 patients and shown that several sera from GH-deficient patients stain specific cell populations and nerves in the pituitary gland.

Adolescent↗

PubMed2007

Energy substrate production in infants born small for gestational age.

AIM: To investigate energy substrate production and its hormonal regulation in infants born small for gestational age. METHODS: Eleven infants, aged 24.4 +/- 5.3 hour, were studied following a fast of 4.0 +/- 0.6 hour. Gestational age was 35.4 +/- 2.8 weeks and birth weight 1804 +/- 472 g (<-2 SD). Rates of glucose production and lipolysis were analyzed using [6,6-(2)H(2)]-glucose and [2-(13)C]-glycerol. RESULTS: Plasma levels of glucose and glycerol were 4.1 +/- 1.1 mmol x L(-1) and 224 +/- 79 micromol x L(-1), respectively. Glucose appearance averaged 30.3 +/- 8.2 and glucose production rate 21.1 +/- 6.1 micromol x kg(-1) x minutes(-1). Glycerol production rate was 5.6 +/- 1.6 micromol x kg(-1) x minutes(-1), correlating strongly to birth weight (r = 0.904, p < 0.001). Of the glycerol produced, 55 +/- 22% was converted to glucose, corresponding to 8 +/- 3% of the glucose production. CONCLUSIONS: Even though the infants could produce energy substrates, lipolysis was reduced and the glucose production was in the low end of the normal range compared with infants born appropriate for gestational age. The correlation between glycerol production and birth weight indicates that lipolysis depends on the amount of stored fat. Data on insulin and insulin-like growth factor binding protein 1 support the view that insulin sensitivity in these infants is reduced in the liver but increased peripherally.

Blood Glucose↗

PubMed2006

Autoantibodies linked to autoimmune polyendocrine syndrome type I are prevalent in Down syndrome.

BACKGROUND: Patients with Down syndrome are prone to autoimmune diseases which also occur in the recessive disease autoimmune polyendocrine syndrome type I (APS I). Since this disease is caused by mutations in the gene AIRE on chromosome 21, one might speculate that altered expression of AIRE contributes to autoimmune disease in Down syndrome. AIM: To study the prevalence of 11 well-defined autoantibodies, five of which are specific for APS I, associated with various manifestations of APS I in patients with Down syndrome. METHODS: Sera from 48 patients with Down syndrome were analysed. Autoantibodies against 21-hydroxylase, 17alpha-hydroxylase, side-chain cleavage enzyme, aromatic L-amino acid decarboxylase, cytochrome P4501A2, tyrosine hydroxylase, tryptophan hydroxylase, glutamic acid decarboxylase 65, tyrosine phosphatase IA-2 and transglutaminase were analysed using an immunoprecipitation assay, and thyroid peroxidase autoantibodies were measured using a haemagglutination assay. RESULTS: Seven of 48 patients had elevated titres of autoantibodies: one against 21-hydroxylase, three against aromatic L-amino acid decarboxylase, one against cytochrome P4501A2, one against glutamic acid decarboxylase 65 and one against tyrosine phosphatase IA-2. None of the patients had clinical or laboratory signs of disease coupled to the respective autoantibody. CONCLUSION: Four patients with Down syndrome had autoantibodies hitherto regarded as unique for APS I, which may suggest a dysregulation of AIRE.

Adolescent↗

PubMed2006

Bile acid metabolism in extrahepatic biliary atresia: lithocholic acid in stored dried blood collected at neonatal screening.

Lithocholic acid (LCA) is a potent hepatotoxic compound. Fetal LCA may have a role in the pathogenesis of neonatal cholestasis/extrahepatic biliary atresia (EHBA). Fetal liver efficiently hydroxylates LCA in several positions. This may represent a detox-ification mechanism. In the present study LCA, cholic acid (CA) and chenodeoxycholic acid (CDCA) were quantitated by gas chromatography-mass spectrometry using selected ion monitoring in small amounts of stored dried blood from six newborn infants with EHBA and fourteen con-trols. The blood was collected at neonatal metabolic screening. Mean blood levels (+/- S.E.M.) of LCA were 0.11 +/- 0.04 microM in the in-fants with EHBA and 0.08 +/- 0.02 microM in the control infants. The correspon-ding levels for CA and CDCA were 15.6 +/- 3.6 microM and 7.4 +/- 2.5 microM in the infants with EHBA and 1.7 +/- 0.3 microM and 1.8 +/- 0.4 microM in the controls. The increased levels of CA and CDCA in the infants with liver disease can be explained by cholestasis. The low blood levels of LCA indicate a normal fetal metabolism of this bile acid in EHBA.

Biliary Atresia↗

PubMed2005

Patient information leaflets--patients' comprehension of information about interactions and contraindications.

OBJECTIVE: To determine how well patients could correctly recognize and comprehend the various information items on patient information leaflets, and to explore the reasons underlying poor comprehensibility. METHODS: Leaflets from 30 randomly selected, commonly prescribed medicines were examined by experts using protocols to evaluate leaflet layout, language and content. The same leaflets were also evaluated by patients who had their medicines dispensed at 24 randomly selected Swedish pharmacies. A questionnaire was used for the patients' examination. RESULTS: The results showed that most information on the leaflets is sound and is well comprehended by the patients. For two information items regarding 'risks of interactions' and 'contraindications' the patient scores were low, indicating poor comprehensibility. CONCLUSION: Leaflets with low scores on warnings of interactions and contraindications were found to deliver more complex messages to older patients as compared to leaflets with high scores for these items.

Adult↗

PubMed2005

Increased lipolysis in non-obese pregnant women studied in the third trimester.

BACKGROUND: During pregnancy, metabolic adaptation takes place in the mother to provide for the supply of substrates to the growing fetus. OBJECTIVE: To determine rates and endocrine regulation of lipolysis and glucose production (GPR) in late pregnancy. DESIGN: Energy substrate production was measured in healthy pregnant women by use of stable isotope-labelled compounds. SETTING: University Hospital, Uppsala, Sweden. SAMPLE: Eight healthy non-obese, non-smoking women with normal pregnancies were studied at 33-36 weeks of gestation after an overnight (12-14 hours) fast. METHODS: Rates of glycerol and glucose production were analysed by gas chromatography/mass spectrometry following constant rate infusion of [1,1,2,3,3-(2)H(5)]-glycerol and [6,6-(2)H(2)]-glucose. MAIN OUTCOME MEASURE: Glycerol and glucose production in the third trimester. RESULTS: The mean rate of glycerol production, reflecting lipolysis, was 3.06 (0.66) and the mean GPR was 13.2 (1.5) micromol kg(-1) minute(-1) [2.38 (0.27) mg kg(-1) minute(-1)]. There was a correlation between rate of glycerol production and GPR (r = 0.75, P = 0.033). Fasting insulin levels correlated inversely with both the rate of glycerol production (r = -0.85, P = 0.008) and GPR (r = -0.78, P= 0.021). CONCLUSIONS: Our results show that lipolysis is markedly increased during late pregnancy compared with reported data for non-pregnant women. The data also confirm the occurrence of an increased GPR in pregnant women. The finding of a correlation between rate of glycerol production and GPR corroborates the view that lipolysis promotes gluconeogenesis. Although late gestation is associated with insulin resistance, the results show that insulin plays a regulatory role both in lipolysis and glucose production.

Adult↗

PubMed2005

Normal spontaneous cortisol secretion in children after autologous bone marrow transplantation.

AIM: To describe spontaneous cortisol secretion in children after autologous bone marrow transplantation (BMT) for acute leukaemia and lymphoma. METHODS: Spontaneous cortisol secretion was analysed in 39 children before and after BMT. Thirteen patients were conditioned with chemotherapy only (group 1), and 26 patients also with total body irradiation (TBI). In the TBI group, 14 patients had received no additional irradiation (group 2), whereas 12 patients had received cranial irradiation (CRT) previously (group 3). RESULTS: Before BMT, in comparison with group 1, mean morning cortisol was significantly lower in group 2 (252 vs 415 mmol/l, p = 0.004), but not in group 3 (vs 312 mmol/l, p = 0.12). There was no change in group 1 six months after BMT (to 379 nmol/l), whereas morning cortisol increased significantly in group 2 and group 3 (to 386 and 343 nmol/l, respectively; p < 0.05). The change in mean morning cortisol correlated negatively with pretransplant morning cortisol (r = -0.63, p < 0.001). Neither TBI nor CRT were associated with changes in morning cortisol. CONCLUSION: Spontaneous cortisol secretion is maintained after BMT irrespective of whether cranial or total body irradiation has been given or not.

Adolescent↗

PubMed2005

Postnatal peer counselling on exclusive breastfeeding of low-birthweight infants: a randomized, controlled trial.

AIM: Exclusive breastfeeding increases survival and optimizes growth of low-birthweight (LBW) infants. If supported, mothers can overcome the unique difficulties associated with breastfeeding from birth to 6 mo. We tested the efficacy of postnatal peer counselling among first-time mothers that aimed to increase exclusive breastfeeding of term LBW infants. METHODS: In a Manila hospital, 204 mothers were randomized into three groups. Two intervention groups receiving home-based counselling visits, one by counsellors trained in breastfeeding counselling (n=68), the other by counsellors trained in general childcare (n=67), were compared with a control group of mothers (n=69) who did not receive counselling. RESULTS: Eighty-eight per cent of the participating pairs completed the trial. At 6 mo, 44% of the breastfeeding counselled mothers, 7% childcare-counselled mothers and none of the mothers in the control group were exclusively breastfeeding. More mothers in the breastfeeding counselled group than in the other groups were still breastfeeding at 6 mo. Twenty-four infants who were exclusively breastfed for 6 mo did not have any diarrhoea. All groups had improved mean weight-for-age Z-scores at 6 mo. CONCLUSION: This study has provided fundamental evidence of successful intervention to achieve 6 mo of exclusive breastfeeding among term LBW infants. By improving health outcomes, enhanced breastfeeding offers a distinct possibility of disrupting the intergenerational cycle of undernourished women giving birth to LBW infants.

Body Weight↗

PubMed2004

Electroacoustics in low-temperature ionic liquids.

Titanium dioxide was used as a model colloid to demonstrate the possibility of obtaining reliable values of the electrophoretic mobility in low-temperature ionic liquids. Mobilities as low as -0.98 +/- 0.16 x 10(-10) and -1.25 +/- 0.33 x 10(-10) m2 V(-1) s(-1) were found in dry and wet 1-butyl-3-methylimidazolium triflate, respectively. These values are lower by two orders of magnitude than typical mobilities in stable aqueous dispersions due to a high viscosity of the ionic liquids.

Journal Article↗

PubMed2004

[APS I--a severe autoimmune disease with endocrine and non-endocrine symptoms].

Autoimmune polyglandular syndrome type I (APS I) is an autosomal recessive disorder characterized by a combination of autoimmune manifestations affecting endocrine and non-endocrine organs. APS I usually presents in childhood. The three most common manifestations are chronic mucocutaneous candidiasis, hypoparathyroidism and Addison's disease. At least two of these must be present to fulfill the diagnostic criteria of this syndrome. The spectrum of other associated diseases includes gonadal insufficiency, alopecia, vitiligo and chronic active hepatitis. APS I is caused by a mutation in the AIRE-gene (autoimmune regulator) located on chromosome 21. Analysis of specific autoantibodies against intracellular enzymes, particularly enzymes in the synthesis of steroids and neurotransmittors, can be used in the diagnosis of APS I and to predict different manifestations of the disease.

Addison Disease↗

PubMed2004

Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type I.

The prevalence of autoantibodies against nine intracellular enzyme autoantigens, namely 21-hydroxylase, side-chain cleavage enzyme (SCC), 17 alpha-hydroxylase, glutamic acid decarboxylase 65, aromatic L-amino acid decarboxylase, tyrosine phosphatase-like protein IA-2, tryptophan hydroxylase (TPH), tyrosine hydroxylase, cytochrome P450 1A2, and against the extracellular calcium-sensing receptor, was assessed in 90 patients with autoimmune polyendocrine syndrome type I. A multivariate logistic regression analysis was performed for the presence of autoantibodies as independent predictors for different disease manifestations. Reactivities against 21-hydroxylase and SCC were associated with Addison's disease with odds ratios (ORs) of 7.8 and 6.8, respectively. Hypogonadism was exclusively associated with autoantibodies against SCC with an OR of 12.5. Autoantibodies against tyrosine phosphatase-like protein IA-2 were associated with insulin-dependent diabetes mellitus with an OR of 14.9, but with low sensitivity. Reactivities against TPH and, surprisingly, glutamic acid decarboxylase 65, were associated with intestinal dysfunction, with ORs of 3.9 and 6.7, respectively. TPH reactivity was the best predictor for autoimmune hepatitis, with an OR of 27.0. Hypoparathyroidism was not associated with reactivity against any of the autoantigens tested. No reactivity against the calcium-sensing receptor was found. Analysis of autoantibodies in autoimmune polyendocrine syndrome type I patients is a useful tool for establishing autoimmune manifestations of the disease as well as providing diagnosis in patients with suspected disease.

Adolescent↗

PubMed2004

Analysis of antibody reactivity against cysteine sulfinic acid decarboxylase, a pyridoxal phosphate-dependent enzyme, in endocrine autoimmune disease.

The structurally related group II pyridoxal phosphate (PLP)-dependent amino acid decarboxylases glutamic acid decarboxylase (GAD), aromatic L-amino acid decarboxylase (AADC), and histidine decarboxylase (HDC) are known autoantigens in endocrine disorders. We report, for the first time, the prevalence of serum autoantibody reactivity against cysteine sulfinic acid decarboxylase (CSAD), an enzyme that shares 50% amino acid identity with the 65- and 67-kDa isoforms of GAD (GAD-65 and GAD-67), in endocrine autoimmune disease. Three of 83 patients (3.6%) with autoimmune polyendocrine syndrome type 1 (APS1) were anti-CSAD positive in a radioimmunoprecipitation assay. Anti-CSAD antibodies cross-reacted with GAD-65, and the anti-CSAD-positive sera were also reactive with AADC and HDC. The low frequency of anti-CSAD reactivity is in striking contrast to the prevalence of antibodies against GAD-65, AADC, and HDC in APS1 patients, suggesting that different mechanisms control the immunological tolerance toward CSAD and the other group II decarboxylases. Moreover, CSAD may be a useful mold for the construction of recombinant chimerical antigens in attempts to map conformational epitopes on other group II PLP-dependent amino acid decarboxylases.

Addison Disease↗

PubMed2003

Consolidation behavior in sedimentation of TiO(2) suspensions in the presence of electrolytes.

The consolidation of TiO(2) suspensions (anatase and rutile) due to gravity sedimentation in the presence of electrolytes has been investigated as a function of pH. Sodium and barium nitrate were used as flocculating electrolytes. The particle interaction was related to the zeta potential and the thickness of the electrical double layer, kappa(-1), by utilizing the repulsive barrier in the classical DLVO theory. The stability of the suspensions was represented as the average final solids content of the sediment cake, phi(fin). The batch sedimentation process was followed by scanning the sample cell with X-rays, from which the solids content and the particle size were calculated. Generally, dense sediments, with phi(fin) up to volume fractions of 0.5, were found for stable suspensions. Flocculated suspensions produced sediments with low phi(fin). The phi(fin) was observed to increase linearly with increasing repulsive barrier. However, at pH values only slightly higher than the isoelectric point (pH(iep)) the phi(fin) remained low until it returned to linearity at a pH much higher than pH(iep). This was attributed to the stronger affinity of sodium than of nitrate for the particle surface, which may be explained by the higher negative hydration energy of sodium. The stronger affinity of sodium was also shown as unsymmetrical distribution of phi(fin) around pH(iep), with stronger flocculation at pH>pH(iep). The interpretation of phi(fin) as a function of the repulsive barrier (or kappa(-1)) also made it possible to distinguish between the adsorption mechanisms of ions from solution. Addition of electrolyte at a fixed low and high pH (surface positively and negatively charged, respectively) clearly showed the specificity in adsorption and consequent flocculation of the barium ion from the indifferent nitrate. Sodium was, however, again observed to flocculate the TiO(2) suspensions slightly more strongly than nitrate.

Journal Article↗

PubMed2003

Histidine decarboxylase, a pyridoxal phosphate-dependent enzyme, is an autoantigen of gastric enterochromaffin-like cells.

Patients with autoimmune polyendocrine syndrome type 1 often have autoantibodies against neurotransmitter synthesizing enzymes, including the pyridoxal phosphate-dependent enzymes glutamic acid decarboxylase and aromatic L-amino acid decarboxylase. Using a candidate approach, we have identified the histamine-synthesizing enzyme histidine decarboxylase, also pyridoxal phosphate dependent, as an autoantigen in this disorder. Anti-histidine decarboxylase antibodies reacting with in vitro translated antigen were found in 36/97 (37%) of autoimmune polyendocrine syndrome type 1 patients studied. The antibodies also reacted with the native enzyme in HMC-1 cell lysates and did not cross-react with the highly homologous aromatic L-amino acid decarboxylase. Anti-histidine decarboxylase antibodies were associated with a history of intestinal dysfunction (P = 0.017). Gastric and duodenal biopsies from a patient with anti-histidine decarboxylase antibodies were studied by immunohistochemistry. The oxyntic mucosa was found to lack the histamine producing enterochromaffin-like cells, suggestive of an autoimmune destruction. To our knowledge, this is the first report of autoantibodies against histidine decarboxylase and absence of gastric enterochromaffin-like cells.

Adult↗

PubMed2002

Suppression of puberty in girls with short-acting intranasal versus subcutaneous depot GnRH agonist.

BACKGROUND/AIM: Central precocious puberty (CPP) is more common in females than in males. During the last few decades a new group of patients with CPP has been seen frequently in Northern Europe, namely children adopted from developing countries. GnRH analogue preparations, administered either as intranasal spray or as depot preparations, are the drugs of choice for inhibiting the release of gonadotropins. The aim of this study was to compare the effect of buserelin given by intranasal spray with that of the same compound given as a subcutaneous depot preparation. METHODS: The study group comprised 46 pubertal girls below the age of 9.5 years, adopted from a developing country. During the first 2 years, the treatment used was buserelin acetate 300 microg 6 times daily as a nasal spray. During the third year the treatment was changed to Suprefact Depot, 6.3 mg, given as a subcutaneous implant every 8 weeks. Half of the girls were randomized to growth hormone treatment in addition to the pubertal inhibition. RESULTS: GnRH provocation tests after 6 weeks, 1 year and 2 years of treatment with intranasal GnRH analogue showed suppression of gonadotropin secretion except in 1 case of noncompliance. During the third year, when the long-acting depot preparation was used, suppression was more pronounced. The peak LH response, especially, was considerably lower than during treatment with the nasal spray preparation. In all cases the clinical inhibition of puberty was adequate both during the first two years and during the third year. CONCLUSION: Even though the clinical suppression of puberty was adequate with both modes of administration, the effect of the depot preparation, in this study Suprefact Depot, was more pronounced in terms of gonadotropin suppression and less dependent on patient compliance.

Administration, Intranasal↗

PubMed2002

Patients' relationship episodes and therapists' feelings.

The idea that psychotherapists' feelings may reflect some aspect of the content in the patients' material has long been clinically accepted but on the whole poorly systematically studied. The aim of this study was to analyse associations between relationship episodes told by patients at evaluation interviews, and therapists' subsequent feelings towards the patients. In total, 28 psychotherapies with nine psychotherapists were studied. Before therapy started, the clients were interviewed separately by the eventual therapist and a second interviewer and six relationship episodes were written down by the interviewers. During the therapy, the therapists reported their feelings on a 'feeling checklist' after each therapy session. In a first analysis, the relationship episodes were categorized according to the CCRT system. The results indicated only scattered associations between CCRT categories and therapist feelings. The results were, however, difficult to interpret as it was found that the therapists' feeling patterns were quite homogenous for each therapist. Considering this, qualitative analyses were made of six therapies carried out by two therapists. These analyses revealed different but theoretically plausible patterns between the feelings attributed to the persons in the patients' relationship episodes and the therapists' subsequent feelings towards the patients. The results were interpreted as a confirmation of the purported relations between patient relationship episodes and therapist feelings, but also as pointing to the need to develop the understanding of these patterns. It seems particularly important to emphasize the importance of the therapist's own habitual feeling patterns when the impact of the patient's internalized relationship patterns on countertransference reactions is evaluated.

Adult↗