Reduced DNA binding and uptake in the absence of DsbA1 and DsbA2 of Neisseria meningitidis due to inefficient folding of the outer-membrane secretin PilQ.

DsbA ensures the correct folding of many exported bacterial proteins by forming intramolecular disulphide bonds in the bacterial periplasm. The pathogen Neisseria meningitidis is unusual in its possession of three different dsbA genes (dsbA1, dsbA2 and dsbA3), encoding two membrane-anchored (DsbA1 and DsbA2) and one periplasmic (DsbA3) thiol-disulphide oxidoreductase enzymes. In this study, the involvement of DsbA1 and DsbA2 in natural competence was confirmed and attributed to events in the early stages of the transformation process.

Distinct functions of H-Ras and K-Ras in proliferation and survival of primary hepatocytes due to selective activation of ERK and PI3K.

Ras proteins mediate signals both via extracellular signal-regulated kinase 1 and 2 (ERK), and phosphoinositide 3-kinase (PI3K). These signals are key events in cell protection and compensatory cell growth after exposure to cell damaging and pro-apoptotic stimuli, thus maintaining homeostasis. By transfection techniques, we found that both H-Ras and K-Ras were expressed and appeared functionally active in primary hepatocytes.

Contextual learning to improve health care and patient safety.

Context: Two unmatched blood units were transfused to a patient undergoing surgery. In order to learn from this kind of error, the department had to report the adverse event, the staff had to discuss the situation of what went wrong and why and how to improve their routines to prevent such errors in the future. In health care, learning to improve quality and safety needs to occur at the individual, team and organisational levels.

Identification of prostate cancer antigens by automated high-throughput filter immunoscreening.

There is a need for earlier and more accurate cancer diagnostics as well as new targets for cancer immunotherapy. To this end, it is important to identify sets of tumour antigens specific for different cancer forms. Several methods that identify potential tumour antigens in an arrayed and high-throughput format have been developed during the last years of SEREX (serological identification of antigens by recombinant expression cloning) related research.

Extracellular matrix signature identifies breast cancer subgroups with different clinical outcome.

Prediction of the clinical outcome of breast cancer is multi-faceted and challenging. There is growing evidence that the complexity of the tumour micro-environment, consisting of several cell types and a complex mixture of proteins, plays an important role in development, progression, and response to therapy. In the current study, we investigated whether invasive breast tumours can be classified on the basis of the expression of extracellular matrix (ECM) components and whether such classification is representative of different clinical outcomes.

The epigenome of testicular germ cell tumors.

Gene expression is tightly regulated in normal cells, and epigenetic changes disturbing this regulation are a common mechanism in the development of cancer. Testicular germ cell tumor (TGCT) is the most common malignancy among young males and can be classified into two main histological subgroups: seminomas, which are basically devoid of DNA methylation, and nonseminomas, which in general have methylation levels comparable with other tumor tissues, as shown by restriction landmark genome scanning (RLGS). In general, DNA methylation seems to increase with differentiation, and among the nonseminomas, the pluripotent and undifferentiated embryonal carcinomas harbor the lowest levels of DNA promoter hypermethylation, whereas the well-differentiated teratomas display the highest.

Genes harbouring susceptibility SNPs are differentially expressed in the breast cancer subtypes.

Recently, genome-wide association studies of breast cancer revealed single nucleotide polymorphisms (SNPs) in five genes with novel association to susceptibility. While there is little doubt that the novel susceptibility markers produced from such highly powered studies are true, the mechanisms by which they cause the susceptibility remain undetermined. We have looked at the expression levels of the identified genes in tumours and found that they are highly significantly differentially expressed between the five established breast cancer subtypes.

Activation of the p53-p21(Cip1) pathway is required for CDK2 activation and S-phase entry in primary rat hepatocytes.

p53 plays a major role in the prevention of tumor development. It responds to a range of potentially oncogenic stresses by activating protective mechanisms, most notably cell-cycle arrest and apoptosis. The p53 gene is also induced during normal liver regeneration, and it has been hypothesized that p53 serve as a proliferative 'brake' to control excessive proliferation.

Follow-up interviews of 12 living kidney donors one yr after open donor nephrectomy.

Very few studies have prospectively followed living kidney donors the first year after donor surgery. In 2003, we in-depth interviewed living kidney donors one wk after donation to explore their immediate experiences of going through nephrectomy. The aim of the current investigation was to explore experiences regarding physical and psychosocial health during the first year after donor surgery.

The Gcn2 kinase as a cell cycle regulator.

Cell cycle progression through G1 phase is of particular importance because this is the phase where the decision to embark on another cell cycle is made. An aberrant G1/S transition often leads to cell cycle deregulation and cancer development. Therefore, there is a complex regulatory network to ensure timely entry into S phase, coordinating initiation of DNA replication with growth and stress signals.

Radiation-induced gene expression in human subcutaneous fibroblasts is predictive of radiation-induced fibrosis.

Background And Purpose: Breast cancer patients show a large variation in normal tissue reactions after ionizing radiation (IR) therapy. One of the most common long-term adverse effects of ionizing radiotherapy is radiation-induced fibrosis (RIF), and several attempts have been made over the last years to develop predictive assays for RIF. Our aim was to identify basal and radiation-induced transcriptional profiles in fibroblasts from breast cancer patients that might be related to the individual risk of RIF in these patients.

Cytokine patterns after tourniquet-induced skeletal muscle ischaemia reperfusion in total knee replacement.

Objective: Extremity surgery performed under tourniquet control causes one of the most common forms of skeletal muscle ischaemia-reperfusion injury in clinical practice. The aim of this study was to investigate the systemic and local inflammatory response after tourniquet-induced skeletal muscle ischaemia-reperfusion injury in patients undergoing total knee replacement. It was our hypothesis that local inflammatory responses in a surgical wound under tourniquet-induced ischaemia cause an excessive overflow of cytokines to the systemic circulation in the reperfusion phase.

Pharmacokinetic analysis of two different docetaxel dose levels in patients with non-small cell lung cancer treated with docetaxel as monotherapy or with concurrent radiotherapy.

Background: Previous pharmacokinetic studies with docetaxel have mostly used 3-weekly (75 mg/m2 and 100 mg/m2) or weekly regimens (35-40 mg/m2). The pharmacokinetics and radiosensitizing efficacy of weekly 20 mg/m2 docetaxel, has however not been well characterized. We examined the pharmacokinetics of weekly docetaxel when administered with concurrent radiotherapy and compared the results with a 3-weekly 100 mg/m2 regimen.

Pairwise comparison of genomic imbalances between primary and recurrent well differentiated liposarcomas.

Well-differentiated liposarcomas (WDL) are intermediate malignant, locally aggressive mesenchymal neoplasms. The cytogenetic hallmarks of WDL are supernumerary rings and giant marker chromosomes containing material mainly from chromosome arms 1q and especially 12q, but also occasionally from other chromosomes. WDL are typical examples of tumors that may become more aggressive with time.

MEK1 and MEK2 regulate distinct functions by sorting ERK2 to different intracellular compartments.

In this study, we provide novel insight into the mechanism of how ERK2 can be sorted to different intracellular compartments and thereby mediate different responses. MEK1-activated ERK2 accumulated in the nucleus and induced proliferation. Conversely, MEK2-activated ERK2 was retained in the cytoplasm and allowed survival.

Impaired motor competence in school-aged children with complex congenital heart disease.

Objective: To explore the extent and type of motor problems in children with complex congenital heart disease (CHD) compared with schoolchildren without any documented heart failure.

Design: Cohort study.

Setting: Biomechanical Laboratory, Rikshospitalet-Radiumhospitalet Medical Centre.

Inhibitory effects and target genes of bone morphogenetic protein 6 in Jurkat TAg cells.

Bone morphogenetic proteins (BMP) are multifunctional cytokines that belong to the TGF-beta superfamily. BMP have been shown to regulate haematopoietic stem cells, B lymphopoiesis and early thymocyte differentiation. In the present study we explored the role of BMP-6 in Jurkat TAg cells.

Clinical and psychosocial follow-up study of children treated with extracorporeal membrane oxygenation.

Background: Serious heart and pulmonary failure may be treated with extracorporeal membrane oxygenation (ECMO). The aim of this follow-up study was a multimodal assessment of outcome in children surviving ECMO at our hospital from 1991 to 2004.

Methods: Twenty-two children were, on average, 1.

High expression of CD7 on CD34+ cells is not linked to deletion of derivative chromosome 9 or lack of dendritic cells in chronic myeloid leukaemia.

Objective: High expression of CD7 on CD34+ cells (>20 %) has been shown to be associated with inferior prognosis in chronic myeloid leukaemia (CML), but the reason has not been unravelled. We set out to investigate whether lack of dendritic cells or der(9)t(9;22)(q34;q11) deletions might be correlated with increased CD7 expression on CD34+ cells in CML.

Material And Methods: We identified 43 patients in our cohort of CML patients in the first chronic phase in whom we were able to assess the expression of CD7 on CD34+ cells.

Reliability of an automatic ultrasound system for detecting postpartum urinary retention after vaginal birth.

Background: Urinary retention is a common postpartum condition which may lead to short- and long-term complications.Objective. To assess the reliability of a commercially available automatic bladder volume scanner in the puerperium, and to specifically identify women with a post-void residual volume of 400 ml or more.

Characterization of early stages of human B cell development by gene expression profiling.

We have characterized several stages of normal human B cell development in adult bone marrow by gene expression profiling of hemopoietic stem cells, early B (E-B), pro-B, pre-B, and immature B cells, using RNA amplification and Lymphochip cDNA microarrays (n = 6). Hierarchical clustering of 758 differentially expressed genes clearly separated the five populations. We used gene sets to investigate the functional assignment of the differentially expressed genes.

Presence of bone marrow micrometastasis is associated with different recurrence risk within molecular subtypes of breast cancer.

Expression profiles of primary breast tumors were investigated in relation to disseminated tumor cells (DTCs) in bone marrow (BM) in order to increase our understanding of the dissemination process. Tumors were classified into five pre-defined molecular subtypes, and presence of DTC identified (at median 85 months follow-up) a subgroup of luminal A patients with particular poor outcome (p=0.008).

Quality assurance of dosimetry and the impact on sample size in randomized clinical trials.

Background And Purpose: The aim of this study was to investigate the impact of appropriate dosimetry quality assurance (QA) on patient number required in radiotherapy randomized control trials (RCT).

Materials And Methods: The steepness of clinical dose-response curves, gamma(clin.), was calculated by a convoluting a biological dose-response distribution and the distribution of technical and dosimetrical factors.

Liver X receptor is a key regulator of cytokine release in human monocytes.

Aberrant regulation of innate immune responses and uncontrolled cytokine bursts are hallmarks of sepsis and endotoxemia. Activation of the nuclear liver X receptor (LXR) was recently demonstrated to suppress inflammatory genes. Our aim was to investigate the expression of LXR in human monocytes under normal and endotoxemic conditions and to study the influence of LXR activation on endotoxin-induced cytokine synthesis and release.