The development of a new information model for a pediatric cancer registry on late treatment sequelae in The Netherlands.

Worldwide, the need is felt for life time follow up of survivors of childhood cancer and for the establishment of registries of the late effects of pediatric oncology treatments. There is however little consensus about how this all should take place. For example, agreement on the nature of this follow up and the type of data to be collected in view of the earlier diagnosis and treatment of the patient is lacking.

IPHIE: an International Partnership in Health Informatics Education.

Medical informatics contributes significantly to high quality and efficient health care and medical research. The need for well educated professionals in the field of medical informatics therefore is now worldwide recognized. Students of medicine, computer science/informatics are educated in the field of medical informatics and dedicated curricula on medical informatics have emerged.

Transcriptional organization and dynamic expression of the hbpCAD genes, which encode the first three enzymes for 2-hydroxybiphenyl degradation in Pseudomonas azelaica HBP1.

Pseudomonas azelaica HBP1 degrades the toxic substance 2-hydroxybiphenyl (2-HBP) by means of three enzymes that are encoded by structural genes hbpC, hbpA, and hbpD. These three genes form a small noncontiguous cluster. Their expression is activated by the product of regulatory gene hbpR, which is located directly upstream of the hbpCAD genes.

Suppressive interactions between mutations located in the two nucleotide binding domains of CFTR.

The S1235R locus in CFTR was studied in combination with alleles found at the M470V and G628R loci. While R628 caused a maturational defect, R1235 did not. The impact of R1235 was found to be influenced by the alleles present at the G628R and M470V loci.

HbpR, a new member of the XylR/DmpR subclass within the NtrC family of bacterial transcriptional activators, regulates expression of 2-hydroxybiphenyl metabolism in Pseudomonas azelaica HBP1.

The regulation of 2-hydroxybiphenyl and 2,2'-dihydroxybiphenyl degradation in Pseudomonas azelaica is mediated by the regulatory gene, hbpR. The hbpR gene encodes a 63-kDa protein belonging to the NtrC family of prokaryotic transcriptional activators and having the highest homology to members of the XylR/DmpR subclass. Disruption of the hbpR gene in P.

Functional characterization of the CFTR R domain using CFTR/MDR1 hybrid and deletion constructs.

To improve our insight into the structure and function of the CFTR R domain, deletion and hybrid constructs in which different parts of the R domain were deleted or replaced by the MDR1 linker domain, and vice versa, were made. Replacement of the linker domain by the R domain did not result in a decrease and replacement of the CFTR R domain by the linker domain did not result in an increase of maturation efficiency, when compared to the respective wild-type proteins. This indicates that the R domain is not responsible for the high degree of degradation observed for CFTR translation products in the ER, but rather the overall structure or sequences located outside the R domain.

Mutation analysis in adenylosuccinate lyase deficiency: eight novel mutations in the re-evaluated full ADSL coding sequence.

The deficiency of adenylosuccinate lyase (ADSL, also termed adenylosuccinase) is an autosomal recessive disorder characterized by the accumulation in body fluids of succinylaminoimidazole-carboxamide riboside (SAICA-riboside) and succinyladenosine (S-Ado). Most ADSL-deficient children display marked psychomotor delay, often accompanied by epilepsy or autistic features, or both, although some patients may be less profoundly retarded. Occasionally, growth retardation and muscular wasting are also present.

Characterization of mutations located in exon 18 of the CFTR gene.

In order to get a better insight into the function of amino acid residues located in the second transmembrane domain of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, all exon 18 mutations found in cystic fibrosis (CF) patients were characterized at the protein and at the electrophysiological level. Of the different mutations present in transmembrane helix 12 (M1137V, M1137R, I11139V and deltaM1140), and the intracytoplasmic loop connecting TM12 and NBD2 (D1152H and D1154G), only M1137R interfered with the proper maturation of the protein. Permeability studies performed after injection of the different wild-type and mutant cRNAs in Xenopus laevis oocytes indicated that the mutations did not alter the permeability sequence of the CFTR channels.

Characterization of 19 disease-associated missense mutations in the regulatory domain of the cystic fibrosis transmembrane conductance regulator.

In order to gain a better insight into the structure and function of the regulatory domain (RD) of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, 19 RD missense mutations that had been identified in patients were functionally characterized. Nine of these (I601F, L610S, A613T, D614G, I618T, L619S, H620P, G628R and L633P) resulted in aberrant processing. No or a very small number of functional CFTR proteins will therefore appear at the cell membrane in cells expressing these mutants.

The graduate training in medical information sciences in the Academic Medical Centre at the University of Amsterdam.

Since its inception in 1987, the 4-year Medical Information Sciences (MIS) curriculum at the Academic Medical Centre (AMC), Amsterdam has gone through several major changes. The present curriculum started in 1994. The course takes 4 years, the first 3 years are programmed in integrated modules of 7 weeks in duration each.

[Alleviation of inoperable malignant colon stenosis using endoscopic placement of an endoprosthesis].

Treatment modalities for patients with an obstruction due to an irresectable malignant stenosis of the colon are: a palliative colostomy proximal of the obstruction, radiotherapy, laser therapy, cryosurgery, and photodynamic therapy. In 4 patients, 3 men and 1 woman of 70, 66, 74, and 38 years respectively with obstruction ileus caused by an irresectable distal colonic carcinoma, a self-expanding wallstent was successfully placed endoscopically in the stenosis of the latter three as a palliative measure, resulting in the unimpeded passage of faeces and intestinal gas.

Polyvariant mutant cystic fibrosis transmembrane conductance regulator genes. The polymorphic (Tg)m locus explains the partial penetrance of the T5 polymorphism as a disease mutation.

In congenital bilateral absence of the vas deferens patients, the T5 allele at the polymorphic Tn locus in the CFTR (cystic fibrosis transmembrane conductance regulator) gene is a frequent disease mutation with incomplete penetrance. This T5 allele will result in a high proportion of CFTR transcripts that lack exon 9, whose translation products will not contribute to apical chloride channel activity. Besides the polymorphic Tn locus, more than 120 polymorphisms have been described in the CFTR gene.

Development and characterization of a whole-cell bioluminescent sensor for bioavailable middle-chain alkanes in contaminated groundwater samples.

A microbial whole-cell biosensor was developed, and its potential to measure water-dissolved concentrations of middle-chain-length alkanes and some related compounds by bioluminescence was characterized. The biosensor strain Escherichia coli DH5 alpha(pGEc74, pJAMA7) carried the regulatory gene alkS from Pseudomonas oleovorans and a transcriptional fusion of PalkB from the same strain with the promoterless luciferase luxAB genes from Vibrio harveyi on two separately introduced plasmids. In standardized assays, the biosensor cells were readily inducible with octane, a typical inducer of the alk system.

The genomic structure of the murine alpha 4 integrin gene.

The VLA-4 (alpha 4 beta 1) integrin is a leukocyte glycoprotein involved in both cell-extracellular matrix and cell-cell interactions. We report here the cloning of the murine alpha 4 gene whose protein product is antigenically related to the human VLA-4 alpha chain. The alpha 4 m gene is about 75 kb long and consists of 28 exons, ranging in size from 46 bp (exon 13) to 437 bp (exon 1).

Sumatriptan in clinical practice: a 2-year review of 453 migraine patients.

The long-term and within-patient consistency of the efficacy and tolerability of subcutaneous and oral sumatriptan in migraine was studied by retrospective survey of 2 years with mailed self-administered questionnaires in our neurology outpatient clinic. Subjects were migraine patients with or without aura (N = 869). We measured long-term use of sumatriptan and within-patient consistency and change over time of headache relief, headache recurrence, and chest symptoms after sumatriptan.

A 68-kD antigen, which is probably an N-terminal fragment of the VLA-5 alpha 5-subunit, is specific for differentiating keratinocytes.

Background: During terminal differentiation, basal keratinocytes lose gradually contact with the basement membrane, a process accompanied by the progressive functional down-regulation and loss of integrin expression. Understanding the molecular nature of this complex mechanism will eventually lead to insight into the pathogenesis of differentiation disorders of the epidermis, e.g.

Localization of alpha 4m integrin at sites of mesenchyme condensation during embryonic mouse development.

The expression and distribution of the murine alpha 4 (alpha 4m) integrin subunit and of one of its ligands, VCAM-1, were examined in the developing mouse embryo at different development stages. Transcription of the mRNA was investigated by in situ hybridization using single-stranded sense and anti-sense cDNA probes and by Northern blotting. In parallel sections integrin was identified by immunohistochemistry using the alpha 4m-specific antibody R1/2.

Stable expression of VLA-4 and increased maturation of the beta 1-integrin precursor after transfection of CHO cells with alpha 4m cDNA.

A full-length cDNA coding for the murine alpha 4 integrin subunit (alpha 4m) was transfected into CHO-K1 cells and cell lines that expressed VLA-4 at their surface as a result of the association of transfected alpha 4m with endogenous hamster beta 1 were selected. Functionality of the expressed alpha 4m beta 1 was shown by adhesion assays on VCAM-1 and antibody (anti-VCAM-1) inhibition. Pulse chase experiments indicated that transfection of the murine alpha 4 cDNA into CHO cells led to an increase in maturation and a decrease in degradation of the beta 1 precursor subunit compared to control CHO-K1 cells.

Cloning and characterization of the promoter region of the murine alpha-4 integrin subunit.

To study the differential expression of the murine VLA-4 (alpha 4 beta 1) integrin, the 5'-flanking region of the gene for the alpha subunit (alpha 4m) was isolated and a cDNA for alpha 4m was obtained with reverse transcriptase polymerase chain reaction (RT-PCR). The cDNA sequence contained a difference in the signal peptide region compared to the previously described cDNA (Neuhaus et al., 1991).

A monoclonal antibody to the alpha 2 integrin subunit cross-reacts with RGD-dependent epitopes in fibrinogen.

Monoclonal antibodies were raised against platelet integrins purified by affinity chromatography. Two monoclonal antibodies (5C5 and 3H8) reacted with the purified alpha 2 subunit of VLA-2 in Western blotting. The monoclonal antibody 3H8 also reacted with fibrinogen in Western blots and in ELISA tests.

Inhibition of the degradation of the precursor and of the mature beta 1 integrin subunit by different protein synthesis inhibitors and by ATP depletion.

A stabilization of both the precursor and the mature beta 1 integrin subunit was observed in metabolically labeled human skin fibroblasts and Molt-4 T lymphocytes upon addition of protein synthesis inhibitors or by ATP depletion. Differential effects of protein synthesis inhibitors are reported since the slow degradation of the mature beta 1 subunit was sensitive to cycloheximide but not to puromycin. We also show that the half-life of the mature subunit was not dependent on intracellular lysosomal degradation or on ubiquitination suggesting that VLA turn-over occurs at the cell surface and might involve proteins or proteases with short half-life.

Oral caliber-persistent artery. Unusual presentations of unusual lesions.

Two cases of oral caliber-persistent artery are reported. Both cases were different from the five previously reported oral examples of this unusual entity. One case is the first reported instance of a caliber-persistent artery not associated with spontaneous hemorrhage, inflammation, or ulceration.

Assignment of three rat integrin genes to chromosome 19 (ITGB1), chromosome 3 (ITGA4), and chromosome 7 (ITGA5).

By means of somatic cell hybrids segregating rat chromosomes, we determined the chromosome localization of three rat beta 1 family integrin genes. ITGB1 was assigned to Chromosome (Chr) 19, ITGA4 to Chr 3, and ITGA5 to Chr 7. These chromosome assignments reveal or confirm homology between two pairs of rat and human chromosomes (rat Chr 3-human Chr 2; rat Chr 7-human Chr 12).