| 1. |
- Ghazi, Sam, et al.
(författare)
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Colorectal cancer susceptibility loci in a population-based study : associations with morphological parameters
- 2010
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 177:6, s. 2688-2693
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association studies have identified multiple genetic loci and single nucleotide polymorphisms (SNPs) associated with either increased or decreased risk of colorectal cancer (CRC). In the present study, our objective was to determine whether 11 of the new susceptibility CRC loci are associated with tumor morphology and to confirm these loci as distinct and etiologically different risk factors in the development of CRC. The following clinical and morphological parameters were analyzed in 1572 samples: tumor size, T-stage, lymph node metastases, degree of differentiation, mucin production, Crohn-like peritumoral lymphocytic infiltration, tumor-infiltrating lymphocytes, desmoplastic reaction, necrosis, invasion of blood or lymph vessels, perineural growth, medullary type, budding, and tumor margin. One SNP from each of the 11 loci (rs6983267 on 8q24.21, rs16892766 on 8q23.3, rs719725 on 9p24.1, rs10795668 on 10p14, rs3802842 on 11q23.1, rs4444235 on 14q22.2, rs4779584 on 15q13.3, rs9929218 on 16q22.1, rs4939827 on 18q21.1, rs10411210 on 19q13.11, and rs961253 on 20p12.3) was genotyped for all cases. Odds ratios, 95% confidence intervals, and the corresponding P values were calculated for the 11 SNPs identified above. A cross tabulation between SNPs and morphology was performed. Several loci showed statistically significant associations with specific phenotypes. The findings are consistent with pathogenic variants in several loci that act in distinct CRC and morphogenetic pathways. Further large-scale studies are required to validate these findings.
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| 2. |
- Holste, Carola, et al.
(författare)
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Mothers' attitudes towards perinatal autopsy after stillbirth
- 2011
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 90:11, s. 1287-90
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Tidskriftsartikel (refereegranskat)abstract
- We investigated mothers' attitudes to autopsy of their stillborn baby and their experiences concerning information and treatment in relation to their loss in an observational study. Data were collected by postal questionnaires and telephone calls. Fifty-four of 72 mothers (76%) replied. Fifty-one (94%) received information from a physician about the possibility of having an autopsy; three (6%) did not get any information. The autopsy rate was 83% (n= 45). Thirty-six of 45 (80%) received adequate information about results. Twenty-five (56%) were pleased with how results were presented. Eleven (24%) were positive about individual contact with the pathologist who performed the autopsy. Fifty-one (94%) stated that their decision concerning autopsy was right. Mothers do not regret their decision concerning perinatal autopsy but they do not always receive thorough and timely information concerning autopsy and its results. Personal contact with the perinatal pathologist might help with specific questions both before and after autopsy.
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| 3. |
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| 4. |
- Hulten, Maj A., et al.
(författare)
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On the paternal origin of trisomy 21 Down syndrome
- 2010
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Ingår i: Molecular Cytogenetics. - London, UK : BioMed Central (BMC). - 1755-8166. ; 3, s. 4-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Down syndrome (DS), characterized by an extra free chromosome 21 is the most common genetic cause for congenital malformations and learning disability. It is well known that the extra chromosome 21 originates from the mother in more than 90% of cases, the incidence increases with maternal age and there is a high recurrence in young women. In a previous report we have presented data to indicate that maternal trisomy 21 (T21) ovarian mosaicism might provide the major causative factor underlying these patterns of DS inheritance. One important outstanding question concerns the reason why the extra chromosome 21 in DS rarely originates from the father, i.e. in less than 10% of T21 DS cases. We here report data indicating that one reason for this parental sex difference is a very much lower degree of fetal testicular in comparison to ovarian T21 mosaicism. Results: We used fluorescence in situ hybridisation (FISH) with two chromosome 21-specific probes to determine the copy number of chromosome 21 in fetal testicular cell nuclei from four male fetuses, following termination of pregnancy for a non-medical/social reason at gestational age 14-19 weeks. The cells studied were selected on the basis of their morphology alone, pending immunological specification of the relevant cell types. We could not detect any indication of testicular T21 mosaicism in any of these four male fetuses, when analysing at least 2000 cells per case (range 2038-3971, total 11.842). This result is highly statistically significant (p < 0.001) in comparison to the average of 0.54% ovarian T21 mosaicism (range 0.20-0.88%) that we identified in eight female fetuses analysing a total of 12.634 cells, as documented in a previous report in this journal. Conclusion: Based on these observations we suggest that there is a significant sex difference in degrees of fetal germ line T21 mosaicism. Thus, it would appear that most female fetuses are T21 ovarian mosaics, while in sharp contrast most male fetuses may be either very low grade T21 testicular mosaics or they may be non-mosaics. We further propose that this sex difference in germ line T21 mosaicism may explain the much less frequent paternal origin of T21 DS than maternal. The mechanisms underlying the DS cases, where the extra chromosome 21 does originate from the father, remains unknown and further studies in this respect are required.
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| 5. |
- Vinnars, Marie-Therese, et al.
(författare)
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Association between placental pathology and neonatal outcome in preeclampsia: a large cohort study
- 2014
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Ingår i: Hypertension in Pregnancy. - : Informa Healthcare. - 1064-1955 .- 1525-6065. ; 33:2, s. 145-158
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study associations between placental histopathology and neonatal outcome in preeclampsia (PE).Study design: The cohort consisted of 544 singleton pregnancies complicated by PE and managed at Karolinska University Hospital, Stockholm, Sweden during 2000–2009. Evaluation of placental histopathology was made by one senior perinatal pathologist, blinded to outcome. Clinical outcome was obtained from prospectively collected medical registry data and medical records. Main outcome measures were intrauterine fetal death, smallness for gestational age, admission to neonatal unit, major neonatal morbidity (defined as presence of intraventricular hemorrhage ≥grade 3, retinopathy of prematurity ≥grade 3, necrotizing enterocolitis, cystic periventricular leucomalacia and/or severe bronchopulmonary dysplasia) and neonatal mortality. Logistic regression analyses including gestational age were performed.Results: Abnormal placental weight, both low (adjusted odds ratio (OR) [95% confidence interval] 5.2 [1.1–24], p = 0.03) and high (adjusted OR 1048 [21–51 663], p < 0.001) for gestational age, was associated with major neonatal morbidity in preterm infants. Accelerated villous maturation was less prevalent in intrauterine fetal death pregnancies (adjusted OR 0.18 [0.04–0.77], p = 0.02). Decidual arteriopathy increased the odds for admission to neonatal care (adjusted OR 2.7 [1.1–6.5], p = 0.03). Infarction involving ≥5% of the placenta was associated with intrauterine fetal death and small for gestational age infants (adjusted OR’s 75 [5.5–1011], p = 0.001 and 3.2 [1.7–5.9], p < 0.001; respectively). No relations between histological variables and neonatal mortality could be found. Conclusion: Placental pathology in PE reflects adverse perinatal events and deviant placental weight predicts adverse neonatal outcome in preeclamptic women delivering preterm. Placental investigation without delay can contribute to neonatal risk assessment.
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| 6. |
- Vinnars, Marie-Therese N., et al.
(författare)
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The Number of CD68+ (Hofbauer) Cells is Decreased in Placentas with Chorioamnionitis and with Advancing Gestational Age
- 2010
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Ingår i: Pediatric and Developmental Pathology. - : Sage Publications. - 1093-5266 .- 1615-5742. ; 13:4, s. 300-304
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Tidskriftsartikel (refereegranskat)abstract
- Hofbauer cells are placental macrophages found in chorionic villous stroma; they express classic monocyte/macrophage markers, such as CD68. Little is known about their participation in placental disease and immunologic interactions at the placental interface. The aim of this study was to quantify the amount of Hofbauer cells in placentas complicated, or not, by chorioamnionitis and in placentas from different gestational ages. Fifty-eight 2nd-and 3rd-trimester placentas with the histologic diagnosis of acute chorioamnionitis were compared with 42 control placentas matched according to gestational age. Immunohistochemistry evaluation was performed with a monoclonal anti-CD68 antibody. Five areas of each placenta were photographed and 5 investigators, with the help of a computerized image analysis program, independently evaluated the number of CD68+ cells. Our results showed that there are significantly fewer CD68+ cells per villous area in placentas diagnosed with chorioamnionitis than in those of controls (P < 0.001). Moreover, there was a significant overall decrease in the number of these cells in 3rd as compared with 2nd trimester placentas (P = 0.02), as well as in placentas from term as compared to preterm pregnancies (P = 0.004). Our data indicate that CD68+ Hofbauer cells may be involved in placental infection and possibly associated with the developmental maturation of the fetoplacental unit.
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| 7. |
- Vinnars, Marie-Therese, et al.
(författare)
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The severity of clinical manifestations in preeclampsia correlates with the amount of placental infarction
- 2010
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Nordic Federation of Societies of Obstetrics and Gynecology. - 0001-6349 .- 1600-0412. ; 90:1, s. 19-25
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To correlate placental histopathology, in particular ischemic changes, with the clinical severity of preeclampsia.Design: A blinded retrospective study.Setting: One Swedish hospital.Sample: One hundred and fifty-seven women with severe (n= 116) or mild (n= 41) preeclampsia and 157 normotensive women matched according to gestational-age.Methods: One senior pathologist, blinded to clinical data and group, examined all histological slides. In the statistical analyses, adjustment for gestational week was done when appropriate.Main outcome measures: Placental histopathological findings. Results: Amount of infarction increased with the severity of preeclampsia (p < 0.001). Infarction involving ≥5% of the placental tissue was seen in 39.7% of severe preeclampsia, 17.1% of mild preeclampsia and 5.1% of non-preeclampsia. When comparing placentas in severe preeclampsia, mild preeclampsia and non-preeclampsia, there was an increase in the presence of any infarction (80.2%, 61.0%, vs. 20.4%). Also, there was a difference in the presence of decidual arteriopathy (35.3%, 22.0%, vs. 3.8%) and accelerated villous maturation (71.6%, 53.3%, vs. 12.6%). We found no difference in intervillous thrombosis, abruption placenta or placental weight in relation to gestational week.Conclusions: In pregnancies with mild or severe preeclampsia, a large proportion of the placentas had histological signs of pathology, in particular signs of ischemia. The pathology was similar, but more pronounced in severe compared to mild preeclampsia, suggesting mild and severe preeclampsia to have similar underlying etiology.
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| 8. |
- Winberg, Johanna, et al.
(författare)
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Mutation Screening and Array Comparative Genomic Hybridization Using a 180K Oligonucleotide Array in VACTERL Association
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:1, s. e85313-
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Tidskriftsartikel (refereegranskat)abstract
- In order to identify genetic causes of VACTERL association (V vertebral defects, A anorectal malformations, C cardiac defects, T tracheoesofageal fistula, E esophageal atresia, R renal anomalies, L limb deformities), we have collected DNA samples from 20 patients diagnosed with VACTERL or with a VACTERL-like phenotype as well as samples from 19 aborted fetal cases with VACTERL. To investigate the importance of gene dose alterations in the genetic etiology of VACTERL association we have performed a systematic analysis of this cohort using a 180K array comparative genomic hybridization (array-CGH) platform. In addition, to further clarify the significance of PCSK5, HOXD13 and CHD7 genes in the VACTERL phenotype, mutation screening has been performed. We identified pathogenic gene dose imbalances in two fetal cases; a hemizygous deletion of the FANCB gene and a (9;18)(p24;q12) unbalanced translocation. In addition, one pathogenic mutation in CHD7 was detected, while no apparent disease-causing mutations were found in HOXD13 or PCSK5. Our study shows that although large gene dose alterations do not seem to be a common cause in VACTERL association, array-CGH is still important in clinical diagnostics to identify disease cause in individual cases.
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