| 1. |
- Gehlen, J., et al.
(författare)
-
First genome-wide association study of esophageal atresia identifies three genetic risk loci at CTNNA3, FOXF1/FOXC2/FOXL1, and HNF1B
- 2022
-
Ingår i: Human Genetics and Genomics Advances. - : Elsevier BV. - 2666-2477. ; 3:2
-
Tidskriftsartikel (refereegranskat)abstract
- Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 × 10−8; odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10–5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 × 10−10; OR = 1.47; 95% CI, 1.38–1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 × 10−16; OR = 1.75; 95% CI, 1.64–1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% ± 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes. © 2022 The Authors
|
|
| 2. |
- Rudnicka, W., et al.
(författare)
-
A potential double role of anti-Lewis X antibodies in Helicobacter pylori-associated gastroduodenal diseases
- 2001
-
Ingår i: Pathogens and Disease. - 2049-632X. ; 30:2, s. 121-125
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, we found Lewis X (Le(X)) determinants on 68% of Helicobacter pylori isolates from patients with chronic gastroduodenal diseases. Anti-Le(X) IgG were detected more frequently in the sera from dyspeptic children and adults (45 and 46%), with or without proved (culture) H. pylori infection, than in the sera from healthy individuals (14%, and 25%). In contrast, the prevalence of anti-Le(X) IgM was higher in the groups of healthy individuals than in the groups of dyspeptic patients. Moreover. anti-Le(X) monoclonal antibody of IgM class enhanced the uptake of Le(X)(+) but not Le(X)(-) H. pylori isolates by phagocytes. In the sera from some dyspeptic patients, we detected Le(X)-anti-Le(X) IgG immune complexes (Le(X) ICs). There was a great difference between children and adults as regards the presence of Le(X) ICs. The immune complexes were found in the sera from nine out of 29 (27%) H. pylori-infected and three out of eight (37%) uninfected adult dyspeptic patients. In comparison, Le(X)-anti-Le(X) IgG ICs were detected only for two out of 18 (11%) H. pylori-infected children. Le(X) ICs were not found in the sera from healthy individuals. Our results suggest that anti-Le(X) IgM may play a protective role in H. pylori infections. In contrast, anti-Le(X) IgG and particularly Le(X)-anti-Le(X) IgG ICs might contribute to the pathogenesis of chronic H. pylori infections.
|
|
| 3. |
- Socha-Banasiak, A., et al.
(författare)
-
Gut response to pasteurized donor human milk in a porcine model of the premature infant
- 2020
-
Ingår i: Journal of Biological Regulators and Homeostatic Agents. - 0393-974X. ; 34:6, s. 2003-2015
-
Tidskriftsartikel (refereegranskat)abstract
- This study investigated the tolerance and safety of pasteurized donor human milk (PDHM) given either alone or together with commercially-used supplements in a porcine model of premature infants. A porcine model, mimicking human neonates at 30-32 weeks of gestational age, was used. The 7-day experiment was performed on 20 piglets. After birth, the piglets were infused with porcine immunoglobulins via the umbilical artery and surgically fitted with a stomach port. The piglets were then randomized into five groups and fed either PDHM, different variants of fortified PDHM or 'raw' human milk (RHM). Preterm piglets fed PDHM showed signs of gastrointestinal intolerance. Four piglets across the various PDHM-fed groups died, none of them were from the group fed PDHM supplemented with long-chain polyunsaturated fatty acids (LC PUFA). In all groups fed PDHM, macroscopic features of enterocolitis were observed, however, these pathological gut changes were less manifested in piglets receiving PDHM supplemented with LC PUFA. The piglets fed RHM had no specific signs of gut damage. The poor tolerance to PDHM suggests changes in milk composition caused by the Holder pasteurization. The supplementation with LC PUFA probably improves tolerance to PDHM.
|
|
| 4. |
- Socha-Banasiak, A., et al.
(författare)
-
The pig as a model for premature infants - The importance of immunoglobulin supplementation for growth and development
- 2017
-
Ingår i: Journal of Biological Regulators and Homeostatic Agents. - 0393-974X. ; 31:1, s. 87-92
-
Tidskriftsartikel (refereegranskat)abstract
- Preterm human neonates, contrary to preterm piglets, obtain immunoglobulins from their mothers via the placenta during intrauterine development. However, one should note that the majority of trans-placental transfer of immunoglobulins in humans takes place during the last trimester of pregnancy. It is also known that the feeding of limited amounts of colostrum or systemic infusion of small amounts of serum improves the survival of preterm and full-term piglets. Full-term piglets deprived of their mother's immunoglobulins exhibit strong apathy and develop watery diarrhoea, often resulting in death. The aim of the current study was to determine if provision of immunoglobulins using different approaches would be beneficial for survival outcomes. To reach the immunological sufficient level we infused immunoglobulins intravenously in amount mimicking the blood level in piglets fed with sow colostrum. Intravenous infusion of immunoglobulins in both preterm and full-term newborn piglets fully ensured their survival, growth and blood immunoglobulin G and protein levels similar to those observed in piglets fed colostrum. Piglets completely deprived of immunoglobulins exhibited significantly lower blood levels of immunoglobulins and protein compared to colostrum-fed animals. Piglets infused with only serum exhibited significantly lower blood immunoglobulin G level compared to those infused with immunoglobulins. In conclusion, based on the data obtained, we suggest that passive immune support provided by colostrum intake or early systemic infusion of Ig's in sufficient amounts is key to ensuring the general well-being of preterm and full-term new born piglets, used as an animal model for the human infant.
|
|
