Sven Gustafsson - Academia.edu (original) (raw)

Papers by Sven Gustafsson

Cancer, Apr 15, 1980

This report provides a histological review of 264 female primary breast cancers analyzed for estr... more This report provides a histological review of 264 female primary breast cancers analyzed for estrogen receptor protein (ER). We also describe 5 cases of male breast cancer all of which bound estradiol specifically. Generally the ER concentrations were lower in the tumors of premenopausal women than in those of postmenopausal women. Three types of cancer with specific morphological features were shown to have ER concentrations that differed significantly from the other types of cancer. Medullary and comedo carcinoma had very low and papillary carcinoma very high levels of ER. No obvious trend in ER concentration was found in unspecified ductal carcinoma, colloid carcinoma, nor in lobular carcinoma. A positive correlation was demonstrated between ER content and degree of differentiation in ductal carcinoma. Cancer with lymphoid infiltration generally showed low ER levels.

Eur J Biochem, 1970

The 3/?-hydroxy-A5-steroid oxidoreductase inhibitor 2ol-cyano-4,4,17ol-trimethyl-5-androsten-1715... more The 3/?-hydroxy-A5-steroid oxidoreductase inhibitor 2ol-cyano-4,4,17ol-trimethyl-5-androsten-1715-01-3-0ne was administered intramuscularly to germfree and conventional, male and female, rats. Under the experimental conditions used, no steroids were found in faeces and urine from the male rats, but a large number of steroids were identified in excreta from female rats. The following 3/?-hydroxy-A6-steroids, none of which is present in normal rats, appeared in urine and faeces from germfree and conventional cyanoketone treated female rats (chiefly as monosulphates) : 5-androstene-38, 17p-dio1, 38, 7a(and 7/?)-dihydroxy-5-androsten-17-one, 5-androstene-38, 7a(and 7/?), 17/?-trioI, 38, 16a-dihydroxy-5-androsten-l7-one, 38, 17/?-dihydroxy-5androsten-l6-one, 3&hydroxy-5,16-pregnadien-20-one, 3/?-hydroxy-l7ol-pregn-5-en-2O-one, 3/?-hydroxy-5-pregnen-20-one, 3/?,7a(and 78)-dihydroxy-5-pregnenen-20-one, 38, 17ol-dihydroxy-5pregnen-20-one, 38, 16~-dihydroxy-5-pregnen-2O-one, 5-pregnene-3j3, 1601, 2Oa-triol, 5-pregnene-3/?,17a,20a-triol and 38,2l-dihydroxy-5-pregnen-20-one. In addition, several saturated steroids were identified which were identical with steroids excreted by normal germfree and conventional female rats.

Nature communications, 2016

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of ... more Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integratin...

British journal of cancer, Jan 10, 2016

Germline mutations within DNA-repair genes are implicated in susceptibility to multiple forms of ... more Germline mutations within DNA-repair genes are implicated in susceptibility to multiple forms of cancer. For prostate cancer (PrCa), rare mutations in BRCA2 and BRCA1 give rise to moderately elevated risk, whereas two of ∼100 common, low-penetrance PrCa susceptibility variants identified so far by genome-wide association studies implicate RAD51B and RAD23B. Genotype data from the iCOGS array were imputed to the 1000 genomes phase 3 reference panel for 21 780 PrCa cases and 21 727 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. We subsequently performed single variant, gene and pathway-level analyses using 81 303 SNPs within 20 Kb of a panel of 179 DNA-repair genes. Single SNP analyses identified only the previously reported association with RAD51B. Gene-level analyses using the SKAT-C test from the SNP-set (Sequence) Kernel Association Test (SKAT) identified a significant association with PrCa for...

Acta obstetricia et gynecologica Scandinavica, 2015

To evaluate the performance and cost efficacy of different first-trimester contingent screening s... more To evaluate the performance and cost efficacy of different first-trimester contingent screening strategies based on an initial analysis of biochemical markers. Retrospective study. Swedish National Quality Register for prenatal diagnosis. 35 780 women with singleton pregnancies. Serum values from first trimester biochemistry were re-analyzed in a contingent approach. For risks between 1:40 and 1:1000, risk estimates from nuchal translucency measurements were added and outcomes were compared using either a final cut-off risk of 1:200 to proceed with invasive testing or offering non-invasive prenatal testing. In a subgroup of 12 836 women with regular menstrual cycles the same analyses were performed using data on the last menstrual period for determining gestational age. The costs of detecting one case of aneuploidy were compared. Comparison of screening strategies. The detection rate was the same (87%) in the contingent group as in complete combined screening, with only 41% requirin...

European journal of cancer, 1980

The conversion of [3H] oestrone sulphate into [3H] oestrone and [3H] oestradiol-17t~ by homogenat... more The conversion of [3H] oestrone sulphate into [3H] oestrone and [3H] oestradiol-17t~ by homogenates of mammary carcinoma tissue in vitro and the oestrogen receptor levels in the tumor cytosol was studied in 23 breast cancer patients with low peripheral serum levels of oestradiol-171~ (<150pM). Sixteen of the patients had 9,tosol oestrogen receptor values above 0.3 fmole/#g of DNA (receptor rich) and seven patients receptor values below this level (receptor poor). [3H] oesterone sulphate was converted into [3HI oestrone and [3H] oestradiol-17t~ by all tumor homogenates. No significant difference between the receptor poor and receptor rich groups were found in the total hydrolysis of [3HI oesterone sulphate. The transformation of [3H] oesterone sulphate into [3H] oestradiol-17 [l was significantly higher in the receptor poor group than in the receptor rich group (35.95 ___ 11.06 vs 5.33 -t-1.37 fmole [3H] oestradiol-17[l formed per min and per mg of protein, P < 0.001 ). The mean age of the receptor poor group was significantly lower than that of the receptor rich group (58.0_+5.5 vs 73.1 _+2.1 yr, P<0.01 ). No significant difference was found in the peripheral serum levels of oestradiol-1713 in the two groups.

European Journal of Biochemistry, 1970

European Journal of Endocrinology, 1972

Page 1. Departments of Chemistry and Germfree Research, Karolinska Institutet and Department of P... more Page 1. Departments of Chemistry and Germfree Research, Karolinska Institutet and Department of Paediatrics, S:t Goran's Hospital, Stockholm STEROID EXCRETION PATTERNS IN URINE FROM TWO BOYS IN THE NEONATAL ...

Acta Obstetricia et Gynecologica Scandinavica, 2012

Objective. To evaluate the performance of a new first trimester web-based software for the detect... more Objective. To evaluate the performance of a new first trimester web-based software for the detection of chromosomal anomalies using a combination of ultrasound and biochemistry. Design. Registry-based cohort study. Setting. Ultrasound units in the Stockholm region. Population. 20 710 women with singleton pregnancies were examined at 11 +0 to 13 +6 weeks' gestational age during a three-year period 2006-2009. Methods. The risks for trisomy 21, 13 and 18 were calculated using a combination of maternal age, serum markers and nuchal translucency. Individual risk estimates were calculated and then reported to a web-based system using a new algorithm based on likelihood ratios of each marker derived from Gaussian distributions in normal and affected pregnancies. Main outcome measures. The impact on rates of invasive testing and the incidence of children born with Down's syndrome after implementing the method. Results. Approximately a third of all pregnant women in the region were examined with the combined test. The detection and test positive rates for Down's syndrome was 90 and 6.8%, respectively. Invasive testing among pregnant women decreased from 15 to 8% after introducing the method but the incidence of children born with Down's syndrome did not decrease during the study period. Conclusion. The new web-based software is an effective method for the detection of trisomy 21 with similar performance compared to other programs. However, it needs to be offered to all pregnant women to have an impact on the incidence of Down's syndrome.

Acta Obstetricia et Gynecologica Scandinavica, 1981

Scandinavian Journal of Urology and Nephrology, Feb 1, 1991

The plasma vasopressin and serum cortisol concentrations were recorded in 7 healthy volunteers re... more The plasma vasopressin and serum cortisol concentrations were recorded in 7 healthy volunteers receiving an intravenous infusion of 1 l of isosmotic (2.2%) glycine solution during 20 min. The infusion elicited a significant increase in the plasma vasopressin level by a mean of 60% (SEM 13) above baseline level. The serum cortisol level increased only in the patient who developed signs of glycine toxicity. These results suggest that a glycine solution has water-retaining properties by stimulating the vasopressin secretion but usually not by increasing cortisol secretion.

Scandinavian Journal of Clinical and Laboratory Investigation, Feb 1, 2001

Reference values are usually based on blood samples from healthy men or non-pregnant women. Blood... more Reference values are usually based on blood samples from healthy men or non-pregnant women. Blood samples from pregnant women may be compared with these reference values. Correct references for pregnancy can be extremely important for clinical decisions such as ablatio placentae, appendicitis, premature rupture of membranes and preeclampsia. Previous studies of normal variations during third-trimester pregnancy are incomplete. Blood samples during pregnancy weeks 33, 36 and 39 as well as 1-3 h postpartum were collected from pregnant women with dietary iron supplement and at least one previous pregancy without a history of hypertension or preeclampsia. When the sampled values were compared with the present reference values from men and non-pregnant women, the following differences were found during normal pregnancy: Haemoglobin and ferritin were reduced, CRP was slightly elevated, WBC (white blood cell count) and HNL (human neutrophilic lipocalin) were elevated during pregnancy and significantly increased postpartum. Albumin was reduced. ALT and AST were slightly elevated and GGT was unchanged during pregnancy. ALP, D-dimer and fibrinogen were elevated. Uric acid increased during the third trimester and thrombocyte count decreased. Separate reference values for pregnant women are essential for correct diagnostic decisions during third-trimester pregnancy. Elevated levels of D-dimer do not necessarily indicate ablatio placentae. A diagnosis of progressive preeclampsia cannot be based on increasing uric acid levels and reduced platelet count in a stable clinical condition. HNL signals activation of neutrophilic granulocytes and can thereby offer a helpful tool for diagnosing infection during pregnancy and postpartum.

Int J Androl, 1985

Peripheral serum levels of testosterone, immnunoreactive oestrogens (Ez), FSH, LH, prolactin and ... more Peripheral serum levels of testosterone, immnunoreactive oestrogens (Ez), FSH, LH, prolactin and growth hormone (hGH) and two steroid-sensitive proteins, 'pregnancy-associated az-glycoprotein' (az-PAG) and sex hormone binding globulin (SHBG), were measured in patients with prostatic cancer before treatment and after orchidectomy or during combined oral and intramuscular oestrogen treatment. Following orchidectomy, the serum levels of testosterone and EZ decreased whilst the levels of FSH and LH increased significantly. No changes were noted in the serum levels of az-PAG, SHBG or prolactin. Oestrogen treatment significantly decreased the serum levels of testosterone, FSH and LH whilst levels of a2-PAG, SHBG and prolactin were increased significantly. Serum levels of hGH during oestrogen treatment were significantly higher than in patients subjected to orchidectomy. These data are at variance with the established dogma of the oestrogeniandrogen balance as a physiological regulator or liver protein synthesis, and indicate that factors other than the endogenous steroids may be operative. hGH may play an important role in this respect.

Acta Paediatrica, Apr 1, 2011

Sweden is situated between latitude 55-69°N, resulting in only a short period of the year when su... more Sweden is situated between latitude 55-69°N, resulting in only a short period of the year when sunlight, specifically UVB range 280-315 nm, is available. The dominating endogenous source of vitamin D is synthesis of prohormones in the skin via UVB-mediated reactions.

Objective: We examined the relationships of serum 25-hydroxyvitamin D (25(OH)D) concentration to ... more Objective: We examined the relationships of serum 25-hydroxyvitamin D (25(OH)D) concentration to established and emerging cardiovascular risk factors and risk of myocardial infarction (MI) in a population-based caseecontrol study of MI before the age of 60 years. Methods: A total of 387 survivors of a first MI and 387 sex-and age-matched controls were included. Fasting blood samples drawn three months after the MI in cases and at the same time in the matched controls were used for biochemical analyses. Results: Serum concentrations of 25(OH)D, adjusted for seasonal variation, were lower in cases than controls (55.0 (40.0e71.0) nmol/L vs 60.5 (47.0e75.0) nmol/L; median (interquartile range); standardized odds ratio (OR) for MI with 95% confidence interval in univariable analysis: 0.80 (0.69e0.93); p ¼ 0.003). The 25(OH)D association with MI disappeared after adjustment for established and emerging risk factors (OR: 1.01 (0.82e1.25)). Current smoking and plasma levels of proinsulin and PAI-1 activity were independently associated with 25(OH)D in controls, whereas waist circumference, plasma triglycerides, proinsulin, PAI-1 activity and cystatin C, and non-Nordic ethnicity were independently associated with 25(OH)D in patients. Serial measurements of 25(OH)D (samples drawn <4 h and 3 months after the onset of MI) in 57 patients showed no systematic differences between sampling times. Conclusion: Vitamin D insufficiency, which is associated with a multitude of metabolic, procoagulant and inflammatory perturbations, is not independently related to premature MI. This suggests that vitamin D insufficiency either constitutes an epiphenomenon or increases the risk of MI by promoting established risk factor mechanisms that predispose to atherothrombosis.

Scandinavian Journal of Clinical and Laboratory Investigation, Oct 1, 2004

Cardiac troponin T (cTnT) is a highly sensitive and specific marker of acute myocardial infarctio... more Cardiac troponin T (cTnT) is a highly sensitive and specific marker of acute myocardial infarction. Serum cTnT is also slightly elevated in patients with severe heart failure and is associated with left ventricular hypertrophy (LVH) in patients treated with haemodialysis. In this study serum cTnT concentrations and echocardiographic findings were investigated in heart failure patients without acute coronary syndrome. cTnT was also compared with other cardiac markers and plasma levels of brain natriuretic peptide (BNP). Twenty-six patients hospitalized with heart failure were included in the study. Echocardiographic measurements and blood sampling were carried out 12-36 h after admission. Serum cTnT (3rd generation assay), cardiac troponin I (cTnI), creatine kinase MB (CKMB) and CK were measured. Plasma BNP was analysed using the Shionoria assay. LVH was defined as left ventricular mass index (LVMI) &amp;gt; 125 g/m for males and &amp;gt; 110 g/m for females. Left ventricular systolic function was estimated from the mitral annulus motion (AV-mean LV). Median cTnT was 0.012 (&amp;lt; 0.010-0.032) microg/L. Sixty-two percent of the patients (16 of 26) had elevated serum cTnT &amp;gt;or= 0.010 micro/L. cTnT was positively correlated with CKMB (rho = 0.40, p = 0.04) and BNP (rho = 0.43, p = 0.03), but not with cTnI and CK. A negative correlation was found between cTnT and AV-mean LV (rho = -0.58, p = 0.007), and there was a positive correlation between cTnT and LVMI (rho = 0.44, p = 0.03). No other analyte was correlated to LVMI. Serum cTnT but not cTnI was associated with left ventricular dysfunction and LVH in patients hospitalized with heart failure. This explains why cTnT tends to be slightly elevated in patients with heart failure without symptoms of acute myocardial ischaemia.

Nephrology Dialysis Transplantation Official Publication of the European Dialysis and Transplant Association European Renal Association, Aug 1, 1999

was a positive correlation between cTnT levels and LVMI. Background. Cardiac troponin T (cTnT ) i... more was a positive correlation between cTnT levels and LVMI. Background. Cardiac troponin T (cTnT ) is a highly sensitive marker for the detection of myocardial Conclusion. These findings suggest that circulating cTnT may reflect left ventricular hypertrophy and/or damage. However, patients maintained on chronic dialysis often have increased serum cTnT concentra-myocardial ischaemia in dialysis patients, and indicate that ET-1 and big ET-1 might be associated with these tions without evidence of acute myocardial injury. The reason for this is unclear. In chronic haemodialysis conditions. patients, elevated plasma concentrations of big

Acta obstetricia et gynecologica Scandinavica, Jan 17, 2015

We aimed to determine the relation between vitamin D deficiency in early pregnancy and preeclamps... more We aimed to determine the relation between vitamin D deficiency in early pregnancy and preeclampsia. In a nested case-control study out of 2496 pregnant women, we identified the 39 women who developed preeclampsia and 120 non-preeclamptic controls. Blood was sampled in 12(th) gestational week and analyzed for serum vitamin D. Vitamin D levels were similar in women who developed preeclampsia, 52.2 ± 20.5 nmol/L, and controls, 48.6 ± 20.5 nmol/L, p = 0.3. In addition, vitamin D deficiency (< 50 nmol/L) was found in similar proportion of control group (51.7%) as those with severe preeclampsia (41.2%). Women with vitamin D deficiency were 3 cm shorter than those with normal vitamin D levels (p = 0.002). Our data do not support the hypothesis that vitamin D deficiency in early pregnancy is associated with preeclampsia, but we cannot rule out a relation later in gestation. This article is protected by copyright. All rights reserved.