Biomedical subjects

Andrea-Romana Prusa

Publications and source records attributed to Andrea-Romana Prusa.

7 recordsLinked to original sources

PubMed2006

Immaturity of infection control in preterm and term newborns is associated with impaired toll-like receptor signaling.

The impaired infection control related to the functional immaturity of the neonatal immune system is an important cause of infection in preterm newborns. We previously reported that constitutive Toll-like receptor (TLR) 4 expression and cytokine secretion on lipopolysaccharide (LPS) stimulation increases with gestational age. Here, we analyzed constitutive monocyte TLR2 expression and evaluated the expression profiles of the proximal downstream adapter molecule myeloid differentiation factor 88 (MyD88). We further investigated activation of protein kinases p38 and extracellular regulated kinsase (ERK) 1/2 in CD14 monocytes after ex vivo stimulation with bacterial TLR ligands (LPS and lipoteichoic acid [LTA]). The functional outcome of the stimulation was determined by cytokine secretion. Monocytes from 31 preterm newborns (<30 weeks of gestation, n=16; 30-37 weeks of gestation, n=15), 10 term newborns, and 12 adults were investigated. In contrast to TLR4 expression, TLR2 levels did not differ between age groups. However, MyD88 levels were significantly lower in preterm newborns. Activation of p38 and ERK1/2 was impaired in all newborn age groups after stimulation with TLR-specific ligands. Accordingly, after LTA stimulation, the levels of interleukin (IL)-1 beta , IL-6, and IL-8 cytokine production were substantially lower (P<.001) in preterm newborns than in adults. The reduced functional response to bacterial cell wall components appears to be part of the functional immaturity of the neonatal immune system and might predispose premature newborns to bacterial infection.

Adult↗

PubMed2005

Umbilical vein plasma concentrations of asymmetrical dimethylarginine are increased in male but not female neonates delivered preterm: a pilot study.

BACKGROUND: Infants born term have substantially elevated plasma concentrations of the endogenous nitric oxide synthase antagonist asymmetrical dimethylarginine (ADMA) that normalize with growth. The plasma levels of ADMA in preterm newborns are unknown. SUBJECTS AND METHODS: Plasma concentrations of ADMA, symmetrical dimethylarginine (SDMA) and L-arginine were analyzed from venous umbilical cord blood samples of 19 preterm and 21 term infants by high performance liquid chromatography. RESULTS: Male preterm newborns (n=11) had higher ADMA (median [95% confidence interval (CI)]: 1.90 [1.73-2.10] micromol/l) than females born preterm (n=8; 1.57 [1.24-1.69] micromol/l; p<0.005). In term born males (n=10) and females (n=11) ADMA was significantly lower than in preterm male infants (all p<0.005), and without sex differences. SDMA and L-arginine concentrations were comparable between all groups. ADMA correlated inversely with body weight in male preterm newborns (r=-0.67; p<0.03). CONCLUSION: Male neonates delivered preterm have significantly higher umbilical cord venous plasma concentrations of ADMA compared to female neonates and infants born term. The sex difference and the time course of elevated ADMA may play a role in development and warrant further investigation.

Arginine↗

PubMed2004

Neurogenic cells in human amniotic fluid.

OBJECTIVE: The purpose of this study was to determine whether human amniotic fluid contains cells that harbor the potential to differentiate into neurogenic cells. STUDY DESIGN: Amniotic fluid cells (uncultivated or cultivated in standard or in neurogenic differentiation medium) were analyzed for morphologic neurogenic differentiation and for expression of cluster of differentiation 133 (marker for neuronal stem cells), nestin (neuronal progenitor cells), neurofilament (neurons), the p75 common neurotrophin receptor, the brain-derived neurotrophic factor and neurotrophin-3 and cyclic nucleotide phosphodiesterase (oligodendrocytes). RESULTS: The appearance of neurogenic cells was not detected in uncultivated cells, was sporadic after cultivation in standard medium but strongly increased in neurogenic differentiation medium, and was accompanied by the induction of the expression of the analyzed marker genes. CONCLUSION: For the first time, this study provides evidence that human amniotic fluid contains cells that express markers for neuronal stem and progenitor cells, which harbor the potential to differentiate into neurogenic cells.

AC133 Antigen↗

PubMed2004

Patient with partial trisomy 9q and learning disability but no pyloric stenosis.

Partial trisomy of the long arm of chromosome 9 represents a very rare and heterogeneous group of chromosomal aberrations. Associated clinical features include learning disability and pyloric stenosis. We present the first patient to be reported with a duplication of the chromosome region 9q22.1-->q33. The patient (female, age 17 years) presented with growth retardation, microcephaly, facial dysmorphia, oesophageal atresia, aortic stenosis, ventricular septal defect, atrial septal defect II, hypothyroidism, and learning disability, but no pyloric stenosis. A review of all cases of partial trisomy 9q reported in the literature demonstrates that learning disability is a characteristic feature of this group of chromosomal aberrations. However, there are cases of duplications of the same chromosome 9 material, with and without pyloric stenosis. This study provides new information for future genetic counselling, especially in cases of prenatal diagnosis of partial trisomy 9q.

Abnormalities, Multiple↗

PubMed2003

Oct-4-expressing cells in human amniotic fluid: a new source for stem cell research?

BACKGROUND: It is the hope of investigators and patients alike that in future the isolation of pluripotent human stem cells will allow the establishment of therapeutic concepts for a wide variety of diseases. A major aim in this respect is the identification of new sources for pluripotent stem cells. Oct-4 is a marker for pluripotent human stem cells so far known to be expressed in embryonal carcinoma cells, embryonic stem cells and embryonic germ cells. METHODS: Cells from human amniotic fluid samples were analysed for mRNA expression of Oct-4, stem cell factor, vimentin and alkaline phosphatase via RT-PCR. Oct-4 protein expression was investigated by Western blot analysis and immunocytochemistry. Oct-4-positive cells were also analysed for the expression of cyclin A protein via double immunostaining. RESULTS: Performing RT-PCR, Western blot and immunocytochemical analyses revealed that in human amniotic fluid in the background of Oct-4-negative cells a distinct population of cells can be found, which express Oct-4 in the nucleus. Oct-4-positive amniotic fluid cell samples also express stem cell factor, vimentin and alkaline phosphatase mRNA. The Oct-4-positive amniotic fluid cells are actively dividing, proven by the detection of cyclin A expression. CONCLUSIONS: The results presented here suggest that human amniotic fluid may represent a new source for the isolation of human Oct-4-positive stem cells without raising the ethical concerns associated with human embryonic research.

Amniotic Fluid↗

PubMed2002

Brca1 and differentiation.

Breast cancer is one of the most frequent malignancies affecting women. The human breast cancer gene 1 (BRCA1) gene is mutated in a distinct proportion of hereditary breast and ovarian cancers. Tumourigenesis in individuals with germline BRCA1 mutations requires somatic inactivation of the remaining wild-type allelle. Although, this evidence supports a role for BRCA1 as a tumour suppressor, the mechanisms through which its loss leads to tumourigenesis remain to be determined. Neither the expression pattern nor the described functions of human BRCA1 and murine breast cancer gene 1 (Brca1) can explain the specific association of mutations in this gene with the development of breast and ovarian cancer. Investigation of the role of Brca1 in normal cell differentiation processes might provide the basis to understand the tissue-restricted properties.

Animals↗

PubMed2002

Amniotic fluid cells and human stem cell research: a new connection.

Currently it is the hope of both patients and investigators that human progenitor cells and stem cells can be widely used to replace dysfunctional cells within a tissue. It is speculated that such cells may prove to have the potential to treat or cure a myriad of diseases, including Parkinson's and Alzheimer's diseases, heart disease, diabetes, stroke, spinal cord injuries, and burns. A major goal in this area of research is to identify potential new sources for the isolation of progenitor cells or stem cells, without raising the ethical issues involved in embryonic stem cell research. Despite the widespread and well-established use of amniotic fluid cells in routine prenatal genetic testing, current knowledge about the origin and properties of these cells is limited. A wide variety of different origins has been suggested for the mixture of cells within amniotic fluid. Recent observations on cell cultures from amniotic fluid and on amniotic epithelial cells provide evidence that they may represent new sources for the isolation of cells with the potency to differentiate into different cell types. Are these cells suitable for use as primary cell systems for basic research? Do these cells provide a new source for research on stem cell biology? Can amniotic fluid cells be used to develop new approaches in tissue engineering? In this article the authors review the current state of knowledge about these cells, focusing on these questions.

Amniocentesis↗