Modulation of dendritic cell maturation and function with mono- and bifunctional small interfering RNAs targeting indoleamine 2,3-dioxygenase.

Antigen-presenting cells expressing indoleamine 2,3-dioxygenase (IDO) play a critical role in maintaining peripheral tolerance. Strategies to inhibit IDO gene expression and enhance antigen-presenting cell function might improve anti-tumour immunity. Here we have designed highly effective anti-IDO small interfering (si) RNAs that function at low concentrations.

Checkpoint regulation of DNA replication.

We discuss the mechanisms regulating entry into and progression through S phase in eukaryotic cells. Methods to study the G1/S transition are briefly reviewed and an overview of G1/S-checkpoints is given, with particular emphasis on fission yeast. Thereafter we discuss different aspects of the intra-S checkpoint and introduce the main molecular players and mechanisms.

Seasonal variation of 1,25-dihydroxyvitamin D and its association with body mass index and age.

Under most normal conditions the serum level of 1,25-dihydroxyvitamin D is constant throughout the year, due to tight biochemical regulation. In contrast to this, the level of 25-hydroxyvitamin D is variable through the year, being largest in late summer, due to photosynthesis in the skin. The vitamin D status is usually assessed by measuring the level of the latter vitamin D derivative, rather than that of the presumably most active derivative 1,25(OH)2 vitamin D.

Parecoxib and indomethacin delay early fracture healing: a study in rats.

Nonsteroidal antiinflammatory drugs (NSAIDs) are used to reduce inflammatory response and pain. These drugs have been reported to impair bone metabolism. Parecoxib, a specific COX-2 inhibitor, exerts an inhibitory effect on the mineralization of fracture callus after a tibial fracture in rats.

Automatic segmentation and recognition of lungs and lesion from CT scans of thorax.

In this study, a fully automated texture-based segmentation and recognition system for lesion and lungs from CT of thorax is presented. For the segmentation part, we have extracted texture features by Gabor filtering the images, and, then combined these features to segment the target volume by using Fuzzy C Means (FCM) clustering. Since clustering is sensitive to initialization of cluster prototypes, optimal initialization of the cluster prototypes was done by using a Genetic Algorithm.

Two brothers with a microduplication including the MECP2 gene: rapid head growth in infancy and resolution of susceptibility to infection.

Microduplications in chromosome Xq28, which include the methyl-CPG binding protein (MECP2) gene, cause severe X-linked mental retardation. Serious recurrent infections are a feature of this condition. Affected males are micro or normocephalic.

Dipeptidyl peptidase IV expression in cancer and stromal cells of human esophageal squamous cell carcinomas, adenocarcinomas and squamous cell carcinoma cell lines.

Dipeptidyl peptidase IV (DPPIV) is a transmembrane serine protease which is involved in the process of tumor invasion and development of metastases in human cancers. The aim of this study was to investigate the expression of DPPIV in cancer and stromal cells of both esophageal adenocarcinoma and squamous cell carcinoma (SCC). Tissue material from 159 patients was analyzed using immunohistochemistry.

Therapy in a subtropical climate for children with cerebral palsy. Evidence of physical and psychosocial effects?

Aim: To assess a possible therapeutic effect in children and adolescents with cerebral palsy of a habilitation programme in a warm sunny climate.

Methods: Fifty-seven children and adolescents with cerebral palsy, all integrated with normal functioning children through mainstream schooling, received an individualized four-week habilitation programme at a habilitation centre in Lanzarote in the Canary Islands. They were clinically assessed before and after treatment, and again after three and six months.

Seprase, dipeptidyl peptidase IV and urokinase-type plasminogen activator expression in dysplasia and invasive squamous cell carcinoma of the esophagus. A study of 229 cases from Anyang Tumor Hospital, Henan Province, China.

Objective: Seprase, dipeptidyl peptidase IV (DPPIV) and urokinase-type plasminogen activator (uPA) play a crucial role in the degradation of the extracellular matrix and in the progression of various human tumors. However, their pathophysiologic significance in esophageal carcinoma has not yet been fully elucidated.

Methods: The expression of seprase, DPPIV and uPA in esophageal dysplasia, squamous cell carcinoma (SCC) and normal epithelium was examined by immunohistochemistry.

Molecular genetic analysis of long QT syndrome in Norway indicating a high prevalence of heterozygous mutation carriers.

Mutations in the KCNQ1, HERG, SCN5A, minK and MiRP1 genes cause long QT syndrome (LQTS), of which there are two forms: the Romano Ward syndrome and the Jervell and Lange-Nielsen syndrome. We have performed DNA sequencing of the LQTS-associated genes in 169 unrelated patients referred for genetic testing with respect to Romano Ward syndrome and in 13 unrelated patients referred for genetic testing with respect to Jervell and Lange-Nielsen syndrome. A total of 37 different mutations in the 5 genes, of which 20 were novel, were identified.

The efficacy of rehabilitation for patients with rheumatoid arthritis: comparison between a 4-week rehabilitation programme in a warm and cold climate.

Objectives: To investigate the long-term effect (week 16) of a 4-week rehabilitation programme for patients with rheumatoid arthritis (RA) and to compare the effect of this intervention given in a Mediterranean or a Norwegian climate.

Methods: A randomized, controlled, parallel group design, where 124 RA patients applying for rehabilitation were randomized to a rehabilitation programme either in Norway or in a Mediterranean climate. The participants were examined clinically immediately before (week 0) and after (week 4) the rehabilitation period as well as in week 16 and answered a mailed questionnaire in week 28.

Long term physical sequelae after adult-onset cancer.

Introduction: With two thirds of cancer patients living for at least 5 years, clinical research has increasingly focused on the long-term health of cancer survivors. Contrary to the amount of knowledge on long-term consequences observations on late effects after childhood cancer in adult-onset cancer are sparse. Only limited literature is available recommending guidelines for long-term follow-up of cancer patients and their implementation in the delivery of health care.

FAP-alpha and uPA show different expression patterns in premalignant and malignant esophageal lesions.

Fibroblast activation protein-alpha (FAP-alpha) and urokinase-type plasminogen activator (uPA) are serine proteases involved in cancer invasion and metastasis. The authors examined FAP-alpha and uPA expression in premalignant and malignant stages of esophageal adenocarcinoma by immunohistochemistry. Additionally, Western blotting was performed on fresh-frozen tissue samples.

Vector-based delivery of siRNAs: in vitro and in vivo challenges.

RNA interference (RNAi) induced by small interfering RNAs (siRNAs) has recently become a powerful tool to knock-down gene expression in a sequence-specific manner. In addition to chemically made siRNAs, stable expression of siRNA in the form of short hairpin RNAs (shRNAs) expressed from an RNA polymerase III (pol III) promoter is now widely used approach for the application of RNAi in mammalian cells. However, long-term suppression using constitutive promoters can be problematic and emerging evidence indicates that siRNAs can cause several side effects in human cells.

Glioma grading by using histogram analysis of blood volume heterogeneity from MR-derived cerebral blood volume maps.

Purpose: To retrospectively compare the diagnostic accuracy of an alternative method used to grade gliomas that is based on histogram analysis of normalized cerebral blood volume (CBV) values from the entire tumor volume (obtained with the histogram method) with that of the hot-spot method, with histologic analysis as the reference standard.

Materials And Methods: The medical ethics committee approved this study, and all patients provided informed consent. Fifty-three patients (24 female, 29 male; mean age, 48 years; age range, 14-76 years) with histologically confirmed gliomas were examined with dynamic contrast material-enhanced 1.

Rapid regulation of protein activity in fission yeast.

Background: The fission yeast Schizosaccharomyces pombe is widely-used as a model organism for the study of a broad range of eukaryotic cellular processes such as cell cycle, genome stability and cell morphology. Despite the availability of extensive set of genetic, molecular biological, biochemical and cell biological tools for analysis of protein function in fission yeast, studies are often hampered by the lack of an effective method allowing for the rapid regulation of protein level or protein activity.

Results: In order to be able to regulate protein function, we have made use of a previous finding that the hormone binding domain of steroid receptors can be used as a regulatory cassette to subject the activity of heterologous proteins to hormonal regulation.

Systemic administration of enamel matrix derivative to lipopolysaccharide-challenged pigs: effects on the inflammatory response.

Background: Periodontitis is the primary clinical indication for enamel matrix derivative (EMD). Recent investigations, showing that EMD inhibits the production of tumor necrosis factor-alpha (TNF-alpha) when added to human whole blood, indicate a novel role for EMD as a modulator of systemic inflammation. In the present study, we investigated the systemic effects of EMD in lipopolysaccharide (LPS)-challenged pigs.

Cytokine Responses to Glucocorticoids and Surgery : A Randomized Controlled Trial.

Purpose: This prospective randomized study was designed to evaluate the implication of high preoperative doses of glucocorticoids on the cytokine responses after surgical correction in patients with ankylosing spondylitis.

Patients And Methods: In 20 consecutive patients an extending osteotomy of the lumbar spine was done by a wedge excision. In a random manner, 10 of the patients were given 10 mg/kg of methylprednisolone ("Solum-Medrol", Pharmacia & Upjohn, Stockholm, Sweden) preoperatively.

Increased expression of LIGHT/TNFSF14 and its receptors in experimental and clinical heart failure.

Background: Clinical and experimental studies suggest a pathogenic role for inflammation in chronic heart failure (HF). LIGHT is a member of the tumour necrosis factor superfamily involved in innate and adaptive immune responses.

Aims: We sought to investigate a potential pathogenic role of LIGHT in chronic HF.

Hip arthroplasty in patients younger than 30 years: excellent ten to 16-year follow-up results with a HA-coated stem.

It is well accepted that youth and high activity levels are among the factors that increase the risk of mechanical failure of total hip prostheses. However, there are few reports of long-term results in very young patients. In this study, we evaluated the results of total 49 hip replacements (THRs) using an uncemented total hip prosthesis in 44 patients (28 females) who were 30 years or younger (range: 15-30 years).

Estimated risk for secondary cancer in the contra-lateral breast following radiation therapy of breast cancer.

Purpose: To facilitate a discussion about the impact of dose heterogeneity on the risk for secondary contralateral breast (CB) cancer predicted with linear and non linear models associated with primary breast irradiation.

Methods And Materials: Dose volume statistics of the CB calculated for eight patients using a collapsed cone algorithm were used to predict the excess relative risk (ERR) for cancer induction in CB. Both linear and non-linear models were employed.

Impact of MHC mismatch and freezing on bone graft incorporation: an experimental study in rats.

Cortical bone graft failure develops for poorly defined reasons, and the effects of the immune responses on the incorporation of an allograft are less clear. In a rat model of tibial allotransplantation, we have studied biometric and histological changes of the graft and the humoral immune response against it. We have also compared fresh with prefrozen grafts to study putative effects of freezing on the healing of the graft and the immune response against it.

Bronchial response pattern of antigen presenting cells and regulatory T cells in children less than 2 years of age.

Background: In early childhood, the ability to mount protective immune responses in the airways is impaired, with increased risk of allergic sensitisation to inhaled allergens. Antigen presenting cells (APC) and regulatory T cells (Treg) are important modifiers of T cell immunity but little is known about their distribution in bronchial mucosa at this age. Here the subset distribution of APC and the appearance of Foxp3(+) Treg and bronchus associated lymphoid tissue (BALT) were examined immunohistochemically in children less than 2 years of age with chronic asthma-like symptoms of the lower airways.

Consistent numerical chromosome aberrations in thecofibromas of the ovary.

Sex cord-stromal tumors of the ovary comprise 8% of all ovarian neoplasms. Because they consist of cells that resemble embryonic sex cord and/or specialized ovarian stroma cells, their cytologic and histologic features can be viewed as reflecting a continuum from fibromas to thecomas with thecofibromas in between. Existing cytogenetic knowledge about ovarian thecomas-thecofibromas-fibromas is restricted to 44 cases with chromosomal abnormalities.

Is it possible to predict outcome in cardiac ECMO? Analysis of preoperative risk factors.

Background: Serious heart failure may be treated with extracorporeal membrane oxygenation (ECMO) when other treatment fails. The aim of the present study was to analyse preoperative risk factors of early mortality in patients treated with veno-arterial (VA)-ECMO.

Methods: We studied a total of 18 possible risk factors in 80 patients with severe cardiac insufficiency treated with VA-ECMO.