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Biomedical subjects

D de Bruijn

Publications and source records attributed to D de Bruijn.

14 recordsLinked to original sources
PubMed2005

Disruption of the gene Euchromatin Histone Methyl Transferase1 (Eu-HMTase1) is associated with the 9q34 subtelomeric deletion syndrome.

BACKGROUND: A new syndrome has been recognised following thorough analysis of patients with a terminal submicroscopic subtelomeric deletion of chromosome 9q. These have in common severe mental retardation, hypotonia, brachycephaly, flat face with hypertelorism, synophrys, anteverted nares, thickened lower lip, carp mouth with macroglossia, and conotruncal heart defects. The minimum critical region responsible for this 9q subtelomeric deletion syndrome (9q-) is approximately 1.2 Mb and encompasses at least 14 genes. OBJECTIVE: To characterise the breakpoints of a de novo balanced translocation t(X;9)(p11.23;q34.3) in a mentally retarded female patient with clinical features similar to the 9q- syndrome. RESULTS: Sequence analysis of the break points showed that the translocation was fully balanced and only one gene on chromosome 9 was disrupted--Euchromatin Histone Methyl Transferase1 (Eu-HMTase1)--encoding a histone H3 lysine 9 methyltransferase (H3-K9 HMTase). This indicates that haploinsufficiency of Eu-HMTase1 is responsible for the 9q submicroscopic subtelomeric deletion syndrome. This observation was further supported by the spatio-temporal expression of the gene. Using tissue in situ hybridisation studies in mouse embryos and adult brain, Eu-HMTase1 was shown to be expressed in the developing nervous system and in specific peripheral tissues. While expression is selectively downregulated in adult brain, substantial expression is retained in the olfactory bulb, anterior/ventral lateral ventricular wall, and hippocampus and weakly in the piriform cortex. CONCLUSIONS: The expression pattern of this gene suggests a role in the CNS development and function, which is in line with the severe mental retardation and behaviour problems in patients who lack one copy of the gene.

Abnormalities, Multiple↗
PubMed2000

Construction of a 350-kb sequence-ready 11q13 cosmid contig encompassing the markers D11S4933 and D11S546: mapping of 11 genes and 3 tumor-associated translocation breakpoints.

Previously, we located three novel human tumor-associated translocation breakpoints in the chromosome 11q13 region between the markers D11S4933 and D11S546. To facilitate the molecular analysis of these breakpoints, we have constructed a continuous sequence-ready cosmid and PAC contig of approximately 350 kb, including the markers D11S4933 and D11S546. In addition, a detailed transcript map was generated. This resulted in the precise positioning of 11 genes and ESTs within the contig, including 4 genes already known to map in the 11q13 region. Three other genes that we positioned within the contig showed homologies to unmapped genes from human and/or other species. Three ESTs were novel. Partial cosmid sequencing resulted in the establishment of the direction of transcription of several of the reported genes. This contig will be instrumental for the detailed characterization of the tumor-associated chromosomal breakpoints and the identification of other 11q13-associated disease genes.

Animals↗
PubMed1998

Double chambered right ventricle: delineation by multiplane transoesophageal echocardiography.

Three consecutive patients (median age 5 years; median weight 15 kg) with double chambered right ventricle (DCRV) were studied by multiplane transoesophageal echocardiography (TOE), using a specially designed paediatric probe. Using a 30 degrees angulation from the longitudinal plane, the body and outflow tract of the right ventricle could be imaged with minimal foreshortening, allowing detailed description of the level and nature of obstruction. In all cases, angiography and subsequent surgical inspection confirmed the TOE findings. Multiplane TOE should avoid the necessity for angiography in the preoperative assessment of this unusual lesion.

Cardiac Catheterization↗
PubMed1998

Human growth-differentiation factor 3 (hGDF3): developmental regulation in human teratocarcinoma cell lines and expression in primary testicular germ cell tumours.

We describe the cloning and initial characterization of a novel cDNA from human embryonal carcinoma (EC) cells. This cDNA, which we named human growth differentiation factor 3 (hGDF3), encodes the homologue of mouse GDF3, a TGFbeta superfamily member belonging to the Growth/Differentiation Factors. We have analysed the expression of hGDF3 in human embryonal carcinoma cell lines and in primary testicular germ cell tumours of adolescents and adults (TGCTs). Expression of hGDF3 in human EC cell lines is stem cell-specific, is down-regulated upon RA-mediated differentiation and is increased upon culture of the cells in the presence of activin A. In TGCTs, hGDF3 expression is low in seminomas, while expression in non-seminomas is readily detectable and appears to be associated with the EC and yolk sac components in the tumours. We have also mapped the hGDF3 locus to the short arm of human chromosome 12, a region consistently overrepresented in human testicular germ cell tumours. Thus, hGDF3 represents an embryonal carcinoma stem cell-associated marker both in vitro and in vivo.

Activins↗
PubMed1998

Masked t(X;18)(p11;q11) in a biphasic synovial sarcoma revealed by FISH and RT-PCR.

The initial cytogenetic analysis of a biphasic synovial sarcoma showed an apparently normal karyotype. After FISH using chromosome X- and 18-specific probes and RT-PCR using SYT- and SSX-specific primer sets, a cryptic synovial sarcoma-associated t(X;18)(p11;q11) could be revealed. The "masked" nature of the translocation may best be explained by a two-step scenario in which a genuine t(X;18)(p11;q11) has occurred as a first step and a reverse reciprocal X;18 translocation as a second step, leaving the synovial sarcoma-associated SYT-SSX1 fusion intact. The findings further underline our previous suggestion that SYT-SSX1 fusions may correlate with a biphasic nature of the tumor. In addition, our findings indicate that, in analogy to, e.g., the Philadelphia translocation in chronic myeloid leukemia, "masked" translocations may occur in soft tissue tumors and that, as a standard, RT-PCR and/or FISH analyses should be carried out in order to provide karyotypic information that may be relevant to tumor diagnosis and/or prognosis.

Adult↗
PubMed1998

Demonstration of a new pathogenic mutation in human complex I deficiency: a 5-bp duplication in the nuclear gene encoding the 18-kD (AQDQ) subunit.

We report the cDNA cloning, chromosomal localization, and a mutation in the human nuclear gene encoding the 18-kD (AQDQ) subunit of the mitochondrial respiratory chain complex I. The cDNA has an open reading frame of 175 amino acids and codes for a protein with a molecular mass of 23.2 kD. Its gene was mapped to chromosome 5. A homozygous 5-bp duplication, destroying a consensus phosphorylation site, in the 18-kD cDNA was found in a complex I-deficient patient. The patient showed normal muscle morphology and a remarkably nonspecific fatal progressive phenotype without increased lactate concentrations in body fluids. The child's parents were heterozygous for the mutation. In 19 other complex I-deficient patients, no mutations were found in the 18-kD gene.

Amino Acid Sequence↗
PubMed1998

Towards the isolation of a human malignant extragonadal germ cell tumour-associated breakpoint in chromosome 11q13.

In a previous study we have defined a subgroup of human malignant extragonadal germ cell tumours that is characterized by complex translocations involving chromosomes 6 and 11 (Echten et al. 1995). Here we report (i) the use of fluorescent in situ hybridization, pulsed field gel electrophoresis and direct visual hybridization techniques to localize the tumour-associated breakpoint within band 11q13, and (ii) the construction of a phage library enriched for this region to facilitate genomic walks towards the breakpoint. Extensive breakpoint-flanking contigs were generated and within these contigs six candidate genes could be identified.

Adult↗
PubMed1997

The human TRIDENT/HFH-11/FKHL16 gene: structure, localization, and promoter characterization.

We recently identified the winged-helix/fork head transcription factor Trident in mouse and described its expression in cycling cells. Here we report the isolation and characterization of the human TRIDENT (HGMW-approved symbol FKHL16) cDNA and gene. Homology between the human and the mouse Trident proteins was 79%. The gene consists of 10 exons and is located on chromosome 12 band p13. The winged-helix DNA-binding domain is encoded on three exons. Analysis of the promoter in synchronized Rat-1 fibroblasts revealed a fragment of 300 bases responsible for the cell cycle-specific expression of the TRIDENT gene.

Amino Acid Sequence↗
PubMed1997

Identification and characterization of interactions between the vertebrate polycomb-group protein BMI1 and human homologs of polyhomeotic.

In Drosophila melanogaster, the Polycomb-group (PcG) genes have been identified as repressors of gene expression. They are part of a cellular memory system that is responsible for the stable transmission of gene activity to progeny cells. PcG proteins form a large multimeric, chromatin-associated protein complex, but the identity of its components is largely unknown. Here, we identify two human proteins, HPH1 and HPH2, that are associated with the vertebrate PcG protein BMI1. HPH1 and HPH2 coimmunoprecipitate and cofractionate with each other and with BMI1. They also colocalize with BMI1 in interphase nuclei of U-2 OS human osteosarcoma and SW480 human colorectal adenocarcinoma cells. HPH1 and HPH2 have little sequence homology with each other, except in two highly conserved domains, designated homology domains I and II. They share these homology domains I and II with the Drosophila PcG protein Polyhomeotic (Ph), and we, therefore, have named the novel proteins HPH1 and HPH2. HPH1, HPH2, and BMI1 show distinct, although overlapping expression patterns in different tissues and cell lines. Two-hybrid analysis shows that homology domain II of HPH1 interacts with both homology domains I and II of HPH2. In contrast, homology domain I of HPH1 interacts only with homology domain II of HPH2, but not with homology domain I of HPH2. Furthermore, BMI1 does not interact with the individual homology domains. Instead, both intact homology domains I and II need to be present for interactions with BMI1. These data demonstrate the involvement of homology domains I and II in protein-protein interactions and indicate that HPH1 and HPH2 are able to heterodimerize.

Amino Acid Sequence↗
PubMed1996

Air travel and adults with cyanotic congenital heart disease.

BACKGROUND: Concern has been expressed that a reduction of partial oxygen pressure during flight in commercial aircraft may induce dangerous hypoxemia in patients with cyanotic congenital heart disease. METHODS AND RESULTS: To evaluate the validity of this concern, the transcutaneous SaO2 was measured in 12 adults with this type of heart disease and 27 control subjects during simulated commercial flights of 1.5 and 7 hours in a hypobaric chamber. Ten of those patients and 6 control subjects also were evaluated during two actual flights of approximately 2.5 hours in a DC-10 and an A-310, respectively. During the prolonged simulated and actual flights, the capillary blood pH, gases, and lactic acid were analyzed in the patients and during one of the actual flights also in the control subjects. During the simulated flights the SaO2 was at all times lower in the patients than in the control subjects. However, the maximal mean actual percentage decrease, as compared with sea level values, did not exceed 8.8% in either patients or control subjects. During the actual flights, this maximal decrease in the patients was 6%. In-flight reduction of the capillary PO2 was considerable in the control subjects but not in the patients. It is our hypothesis that the lack of a significant decrease of the PO2 in the patients might possibly be due to a high concentration of 2.3 diphosphoglycerate in the red cells. The flights had no influence on the capillary blood pH, PCO2, bicarbonate, or lactic acid levels in either patients or control subjects. CONCLUSIONS: Atmospheric pressure changes during commercial air travel do not appear to be detrimental to patients with cyanotic congenital heart disease.

2,3-Diphosphoglycerate↗
PubMed1983

Simultaneous bilateral fluorescein angiography of the retina and the iris in central retinal vein occlusion.

Twenty-two patients with a recently developed C.R.V.O. (central retinal vein occlusion) (symptoms: less than four weeks) are discussed. A delay in A.R.C.T. (arm to retina circulation time) in the affected eye was found in two patients with an ischaemic type of C.R.V.O. and in 3 patients with a non-ischaemic type of C.R.V.O. No side difference could be demonstrated in A.I.C.T. (arm to iris circulation time). Leakage of radial iris vessels on fluorescein angiography was found in 6 out of 7 patients with an ischaemic type of C.R.V.O. and in 2 out of 15 patients with a non-ischaemic type of C.R.V.O. Radial iris vessel leakage may be a helpful prognostic sign in C.R.V.O.

Adult↗
PubMed1977

Simultaneous bilateral fluorescein angiography.

Two fundus cameras were used in the development of a setup for bilateral fluorescein angiography. The indications for this method are listed and examples of simultaneous fluoroangiograms are given. This technique allows the simultaneous study of hemodynamics in the carotid artery, the study of intraocular and anterior eye segment circulatory disturbances, and it is time-saving in bilateral pathology.

Adult↗