DNAxs/DNAStatistX: Development and validation of a software suite for the data management and probabilistic interpretation of DNA profiles.

The data management, interpretation and comparison of sets of DNA profiles can be complex, time-consuming and error-prone when performed manually. This, combined with the growing numbers of genetic markers in forensic identification systems calls for expert systems that can automatically compare genotyping results within (large) sets of DNA profiles and assist in profile interpretation. To that aim, we developed a user-friendly software program or DNA eXpert System that is denoted DNAxs.

Cell cycle/apoptosis molecule expression correlates with imatinib response in patients with advanced gastrointestinal stromal tumors.

Purpose: Altered expression of cell cycle/apoptosis key regulators may promote tumor progression, reflect secondary genetic/epigenetic events, and impair the effectiveness of therapy. Their expression pattern might then identify gastrointestinal stromal tumor (GIST) patient subgroups with different response to imatinib and elucidate novel therapeutic targets.

Experimental Design: Immunohistochemical evaluation of expression of p53, p16, p21, CHK2, CCND1, BCL2, CDK4, and MDM2 was done on 353 histologically validated GIST patients enrolled into a European/Australasian phase III trial.

Multidrug resistance mediated by ABC transporters in osteosarcoma cell lines: mRNA analysis and functional radiotracer studies.

Drug resistance remains a significant impediment to successful chemotherapy and constitutes a major prognostic factor in osteosarcoma (OS) patients. This study was designed to identify the role and prognostic significance of multidrug-resistance (MDR)-related transporters, such as multidrug resistance protein 1 (MDR1), multidrug-resistance-associated protein (MRP1) and breast-cancer-related protein (BCRP), in OS using cationic lipophilic radiotracers. We evaluated the chemosensitivity of four OS cell lines (Saos-2, 143B, MNNG/HOS and U-2OS) to doxorubicin (DOX), cisplatin (CIS) and methotrexate.

Oral pulsed dexamethasone therapy in early rheumatoid arthritis: a pilot study.

Pulse therapy with high-dose glucocorticoids (GCs) is widely used as "bridging therapy" for the treatment of patients with active rheumatoid arthritis (RA). Oral pulsed dexamethasone therapy has never been used for this purpose. We determined the clinical efficacy of oral pulsed dexamethasone treatment in patients with early active RA, concomitantly starting with disease-modifying anti-rheumatic drugs (DMARDs).

Problematic and positive support in relation to depression in people with rheumatoid arthritis.

This study focuses on the associations of both positive and problematic aspects of social support with depression in patients with rheumatoid arthritis. In a hierarchical multiple regression analysis we found that stressors such as functional limitations and pain are strongly related to depression. Positive and problematic support each explain an additional significant portion of the variance in depression.

[Paget's disease of the bones: diagnosis and treatment].

Paget's disease of bone affects one or more bones and is characterized by increased bone turnover (remodelling) with hypertrophy and abnormal bone structure with diminished strength leading to deformity and fracture. The cause of the disease is not known, possibly is a slow virus infection. For diagnosis and follow-up the conventional bone markers, serum alkaline phosphatase and urine hydroxyproline, are still useful.

The supply of and demand for informal and professional care for patients with rheumatoid arthritis.

The objective of this study is to determine supply of, and demand for, informal care for rheumatoid arthritis (RA) patients and to evaluate the factors that contribute to the amounts of help needed and received from professional and informal care providers at home. Data were collected by questionnaire from 229 RA patients and 174 informal caregivers. Most of the help required is also received, though 24% of the patients did not receive help for one or more tasks.

Evaluation of a Dutch version of the AIMS2 for patients with rheumatoid arthritis.

DUTCH-AIMS2, a Dutch version of AIMS2 and successor to DUTCH-AIMS, is an instrument to assess health status among patients with rheumatic diseases. It provides measurements of 12 areas of health status on scales for health status proper, satisfaction, attribution and arthritis impact. We assessed the reliability of its scales in terms of internal consistency and their validity according to both internal standards and external standards.

[The remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome].

RS3PE syndrome was diagnosed in a 83-year-old man with seronegative symmetrical polysynovitis with pitting oedema, which presented after a vehement acute beginning a remarkably favourable course. RS3PE syndrome, recently described, is characterized by a transient seronegative symmetrical synovitis with pitting oedema. The syndrome appears mainly in the aged.

Increased bone mass with pamidronate treatment in rheumatoid arthritis. Results of a three-year randomized, double-blind trial.

Objectives: Osteoporosis is a frequent complication of rheumatoid arthritis (RA). We therefore investigated the effect of oral pamidronate therapy as a specific bone-sparing agent in RA.

Methods: The study design was a 3-year randomized, double-blind trial of 300 mg oral pamidronate/day compared with placebo in 105 RA patients.

Presence of bacterial flora-derived antigen in synovial tissue macrophages and dendritic cells.

In previous studies using and animal model human bacterial flora-derived peptidoglycan Polysaccharides were shown to be arthropathic after a single subcutaneous injection. A prerequisite for proof of the hypothesis that bacterial products from the normal resident flora are involved in the immune reaction of human chronic polyarthritis of unknown aetiology is the presence of these antigens in synovial tissue. 2E9, a monoclonal antibody we developed against intestinal peptidoglycan polysaccharides was used in a histochemical study in rats and stained macrophages in the spleen red pulp.

Clinical and biochemical response to single infusion of pamidronate in patients with active rheumatoid arthritis: a double blind placebo controlled study.

Objective: To assess the effects of 3-amino-1-hydroxypropylidine-1,1-bisphosphonate (pamidronate) in rheumatoid arthritis (RA).

Methods: Thirty patients with active RA were randomly allocated to receive a single intravenous infusion of placebo, 20 mg pamidronate, or 40 mg pamidronate.

Results: Pamidronate treatment resulted in a rapid and sustained reduction in urinary calcium and hydroxyproline excretions.

Bone metabolism in rheumatoid arthritis; relation to disease activity.

Biochemical parameters of bone metabolism were investigated in 105 ambulant, non-steroid treated patients with RA and compared with parameters of disease activity. Urinary calcium (Ca) and hydroxyproline (OHP) excretions, as parameters of bone resorption and serum alkaline phosphatase (AP), as a parameter of bone formation, were positively related to parameters of disease activity. Serum osteocalcin, another parameter of bone formation, was not related to parameters of disease activity.

Construction of dystrophin fusion proteins to raise targeted antibodies to different epitopes.

For the study of the structure and function relationship of dystrophin, defective in DMD, and for diagnostic purposes it is important to dispose of antibodies against different parts of the protein. We have made five different constructs for the expression of fusion proteins containing parts of the four domains of dystrophin. Two different recombinant expression vectors, pATH2 and pEX1, were used.

Physical mapping of 14 new DNA markers isolated from the human distal Xp region.

We have isolated 14 new DNA markers from the human Xpter-Xp21 region distal to the Duchenne muscular dystrophy gene by targeted cloning, employing two somatic cell hybrids containing this region as their sole human material. High-resolution physical localization of these markers within this region was obtained by hybridization to two mapping panels consisting of DNA from patients carrying various translocations and deletions in distal Xp. Five markers were assigned to the pseudoautosomal region where their position on the long-range map of this region was further determined by pulsed-field gel electrophoresis.

Topography of the Duchenne muscular dystrophy (DMD) gene: FIGE and cDNA analysis of 194 cases reveals 115 deletions and 13 duplications.

We have studied 34 Becker and 160 Duchenne muscular dystrophy (DMD) patients with the dystrophin cDNA, using conventional blots and FIGE analysis. One hundred twenty-eight mutations (65%) were found, 115 deletions and 13 duplications, of which 106 deletions and 11 duplications could be precisely mapped in relation to both the mRNA and the major and minor mutation hot spots. Junction fragments, ideal markers for carrier detection, were found in 23 (17%) of the 128 cases.

High resolution deletion breakpoint mapping in the DMD gene by whole cosmid hybridization.

The locus DXS269 (P20) defines a deletion hotspot in the distal part of the Duchenne Muscular Dystrophy gene. We have cloned over 90 kilobase-pairs of genomic DNA from this region in overlapping cosmids. The use of whole cosmids as probes in a competitive DNA hybridization analysis proves a fast and convenient method for identifying rearrangements in this region.

A Pro----Leu substitution in codon 369 of the alpha-1-antitrypsin deficiency variant PI MHeerlen.

The molecular defect has been elucidated in the alpha-1-antitrypsin (PI) gene of a patient with a serum level of only 5 mg/100 ml and a PI M-like phenotype, designated PI MHeerlen. The restriction fragment patterns obtained by probes covering the whole gene and flanking sequences were normal, suggesting no major rearrangements. The nucleotide sequence of the exons, intron/exon junctions, and a part of the promoter region is similar to that of a PI M1(Ala213) gene except for an C----T mutation in codon 369, causing a Pro----Leu substitution.

Detection of alpha-1-antitrypsin deficiency variants by synthetic oligonucleotide hybridization.

Oligonucleotide probes, specific for the two most common deficiency variants, Z and S, of alpha-1-antitrypsin have been successfully applied for the diagnosis at the DNA-level. The possible presence of silent alleles necessitates a careful study of the parents both at the protein- and DNA-level in prenatal diagnostic cases.

Failure of anterior cruciate-ligament reconstruction using tendon xenograft.

From January 1981 to September 1983 forty knees had replacement of a torn anterior cruciate ligament with a tendon xenograft. In six of the first thirty knees that were operated on severe synovitis developed within eight months after the operation, and total synovectomy and removal of the graft was required. Because of this complication we changed the recommended rinsing procedure for the graft in the last ten knees, and no synovitis occurred in these.

Oestrogens and bone metabolism: a hypothesis.

The explanations so far proposed for the effects of oestrogens on bone metabolism in post-menopausal women have been based on the changes seen in calciotrophic hormones. However, we demonstrated in a previous study [6] that there is a decrease in the concentration of somatomedin (an insulin-like growth factor) and an increase in that of growth hormone (GH) in oestrogen-treated post-menopausal women. On the basis of those findings and the relevant data published in the literature, we advance a hypothesis to the effect that the bone-metabolism changes that occur in post-menopausal women following oestrogen replacement therapy come about via changes in serum somatomedin and growth hormone concentrations.

Changes in serum somatomedin and growth hormone concentrations after 3 weeks oestrogen substitution in post-menopausal women; a pilot study.

Oestrogens have a preventive effect on bone loss in post-menopausal women; however, little is known about their mechanism of action. The aim of this study was to investigate the changes in somatomedins (SM) and growth hormone (GH) concentrations in serum in post-menopausal women after 3 weeks of substitution with 20 micrograms ethinyloestradiol. A significant decrease was observed in the mean serum levels of SM, measured by bioassay (0.